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Catalytic C-H activation by cyclometallated iridium hydroxo complexes in aqueous media
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Catalytic C-H activation by cyclometallated iridium hydroxo complexes in aqueous media
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Content
CATALYTIC C-H ACTIVATION BY CYCLOMETALLATED
IRIDIUM HYDROXO COMPLEXES IN AQUEOUS MEDIA
by
Steven Karl Meier
A Dissertation Presented to
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(CHEMISTRY)
August 2008
Copyright 2008 Steven Karl Meier
ii
Acknowledgements
As this chapter of my life closes, there are some people that I would like to
thank. First I would like to thank my advisor, Prof. Roy Periana, for teaching me
how to think about science, how to do science rigorously, and for taking the time to
educate me about life in general. I would also like to thank the Department of
Energy, that National Science Foundation, the Loker Hydrocarbon Institute, the
University of Southern California, and most importantly Chevron for funding, which
allowed me to practice this chemistry over the last four years.
To the Periana group, I would like to thank all of you for making the group so
competitive yet dysfunctional. Even though we had some bitter times together, at
least we can all say we came out stronger because of it. I would like to thank Dr.
Kenneth J. H. Young for teaching me how to synthesize and characterize ligands and
complexes. I appreciate all the time you have invested in me. I would also like to
thank Dr. Oleg Mironov for his selfless sacrifice to the group by maintaining the lab
over the years. While at times we didn’t get along, I actually turned out very similar
to you, and I am proud to say that. I would also like to thank Brian Conley, Bill
Tenn, and Somesh Ganesh for keeping me sane over the last 3 years. It was a lot of
fun. Someday, we should all meet up and reminisce. I would like to thank Steve
“Richie” Bischof for educating me about the finer things in life like lightweight fly
wheels, expensive dinners, and buying a house.
iii
I would like to thank the following Periana group members and Caltech
Goddard group members for their contributions to my science: Dr. Xiang-Yang Liu,
Dr. Gaurav Bhalla, Dr. C. J. Jones, Dr. Vadim Ziatdinov, Dr. Joo-Ho Lee, Dr. Claas
Hövelmann, Dr. Joyanta Choudhury, Dr. Chinnappan Sivasankar, Dr. Daniel Ess,
Dr. Robert Nielsen, Dr. Jonas Oxgaard, Dr. Marten Alhquist, Professor Bill
Goddard, and Dr. Jason Gonzales. I would also like to thank Professor William
Kaska for helpful discussions. I would like to thank various members of the
chemistry department that keep the department running like a well oiled machine:
Michele, Heather, Jaime, Bruno, Carole, David, Jessy, Allan, and Ross. I would like
to thank Professor Robert Bau, Dr. Muhammed Yousufuddin, and Mr. Timothy for
solving the various crystal structures that are presented in this thesis. I would not
have been able to do this without you.
I would also like to thank the professors that have served on my thesis and
Ph. D. candidacy exam committees: Prof. Surya Prakash, Prof. Nicos A. Petasis,
Prof. Roy A. Periana, Prof. Amy M. Barrios, Prof. John A. Petruska, and Prof. Travis
J. Williams. Thank you for sacrificing your invaluable time by serving on my
committee and for educating me so that I may become a better scientist. I would like
to thank Professor Travis J. Williams and Professor John A. Petruska for their
helpful corrections of this manuscript, which also allowed me to become a better
writer.
I would like to thank my parents: Mom, Dad and Jolene for their support and
encouragement during this period. I would also like to thank my brother, Danny
iv
Meier, and our friends: Walter Sobchak, Theodore Donald “Donny” Kerbatsos, and
Jeffery Lebowski for the great times. Thank you, Athena and Jaeya, for making my
last year so memorable.
Last but not least, I would like to thank all of the synthetic organic chemists
who have helped me by providing synthetic advice on how to synthesize and protect
water soluble ligands. I would like to thank the following Petasis group members:
Mr. Kalyan Nagulapalli, Dr. Jasim Uddin, Ms. Myslinska “Gosia” Malgorzata. I
would like to thank the following Roush group members at Scripps Florida: Dr. Josh
Dunetz, Dr. Tamara Hopkins, Dr. Etzer Derout, Dr. Joshua Roth, Dr. Ricardo Lira,
Dr. Rajan Pragani, Mr. John Whitaker, Dr. Mariola Tortosa, and Ms. SusAnn
Winbush.
v
Table of Contents
Acknowledgements ...................................................................................................... ii
List of Tables ............................................................................................................. vii
List of Figures ............................................................................................................. ix
List of Schemes ......................................................................................................... xvi
Abstract ................................................................................................................... xviii
Chapter 1: Introduction to C-H Activation .................................................................. 1
1.1: Background ....................................................................................................... 1
1.2: C-H Activation .................................................................................................. 5
1.3: C-H activation in Strongly Acidic Media: Catalyst Inhibition by Ground
State Stabilization .............................................................................. 18
1.4: Development of Systems that are Not Inhibited by Water ............................. 27
1.5: References ....................................................................................................... 34
Chapter 2: Heterolytic C-H activation by a Cyclometallated Pt(NNC)X
Complex. .................................................................................................................... 39
2.1: Introduction ..................................................................................................... 39
2.2: Results and Discussion ................................................................................... 42
2.3: Conclusion ...................................................................................................... 55
2.4: Experimental ................................................................................................... 56
2.5: References ....................................................................................................... 84
Chapter 3: Synthesis and Reactivity of a Water Soluble Cyclometallated Iridium
Bishydroxo Complex ................................................................................................. 86
3.1: Introduction ..................................................................................................... 86
3.2: Results and Discussion ................................................................................... 90
3.3: Conclusion .................................................................................................... 120
3.4: Experimental ................................................................................................. 121
3.5: References ..................................................................................................... 187
Chapter 4: Related Ir(I) and Ir(III) Chemistry ......................................................... 189
4.1: Synthesis and Reactivity of an Iridium(III) Hydroxo Bridged Dinuclear
Complex ........................................................................................... 189
4.1.1: Introduction ...................................................................................... 189
4.1.2: Results and Discussion ..................................................................... 191
4.1.3: Conclusion ....................................................................................... 200
vi
4.1.4: Experimental .................................................................................... 201
4.2: Analysis of Iridium(I) as an Active Catalyst for C-H activation in Water ... 209
4.2.1: Introduction ...................................................................................... 209
4.2.2: Results and Discussion ..................................................................... 211
4.2.3: Conclusion ....................................................................................... 216
4.3: Attempted Synthesis of a Sterically Hindered Cyclometallated Ir(NNC)
Complex ........................................................................................... 217
4.3.1: Introduction ...................................................................................... 217
4.3.2: Results and Discussion ..................................................................... 218
4.3.3: Conclusion ....................................................................................... 222
4.3.4: Experimental .................................................................................... 223
4.4: References ..................................................................................................... 227
Bibliography ............................................................................................................. 230
vii
List of Tables
Table 1. Data obtained from the H/D exchange studies of 1 with
CH
4
and sulfuric acid-d
2
. 64
Table 2. Comparison of the percent deuterated isotopologs of
benzene with time for the “catalytic reaction” and the
“control reaction.” 68
Table 3. Crystal data and structure refinement for C
36
H
38
N
2
Pt. 77
Table 4. Atomic coordinates ( x 10
4
) and equivalent isotropic
displacement parameters (Å
2
x10
3
) for C
36
H
38
N
2
Pt. U(eq) is
defined as one third of the trace of the orthogonalized Uij
tensor. 78
Table 5. Bond lengths [Å] for C
36
H
38
N
2
Pt. 79
Table 6. Bond angles [
o
] for C
36
H
38
N
2
Pt. 80
Table 7. Anisotropic displacement parameters (Å
2
x 10
3
) for
C
36
H
38
N
2
Pt. The anisotropic displacement factor exponent
takes the form: -2 π
2
[ h
2
a*
2
U
11
+ ... + 2 h k a* b* U
12
]. 81
Table 8. Hydrogen coordinates ( x 10
4
) and isotropic displacement
parameters (Å
2
x 10
3
) for C
36
H
38
N
2
Pt. 82
Table 9. Percentage of benzene isotopologs in the control reaction
(left) and the catalytic reaction (right). This reaction was
performed at 180
o
C, the concentrations listed are based on
total volume of solution present. 167
Table 10. Molar Volume determination by approximation method
using the Van der Waals equation to determine what
concentration of benzene must be used in order to prevent
the condensation of benzene in the reactor. 170
Table 11. Crystal data and structure refinement for C
60
H
66
Ir
2
N
4
O
2
. 174
viii
Table 12. Atomic coordinates ( x 10
4
) and equivalent isotropic
displacement parameters (Å
2
x 10
3
)for C
60
H
66
Ir
2
N
4
O
2
.
U(eq) is defined as one third of the trace of the
orthogonalized U
ij
tensor. 175
Table 13. Bond lengths [Å] for C
60
H
66
Ir
2
N
4
O
2
. 176
Table 14. Bond angles [
o
] for C
60
H
66
Ir
2
N
4
O
2
. 177
Table 15. Anisotropic displacement parameters (Å
2
x 10
3
) for
C
60
H
66
Ir
2
N
4
O
2
. The anisotropic displacement factor
exponent takes the form: -2 π
2
[ h
2
a
*2
U
11
+ ... + 2 h k a* b*
U
12
]. 178
Table 16. Hydrogen coordinates ( x 10
4
) and isotropic displacement
parameters (Å
2
x 10
3
) for C
60
H
66
Ir
2
N
4
O
2
. 179
Table 17. Crystal data and structure refinement for C
22
H
16
F
6
IrN
3
O
6
. 181
Table 18. Atomic coordinates ( x 10
4
) and equivalent isotropic
displacement parameters (Å
2
x 10
3
) for C
22
H
16
F
6
IrN
3
O
6
.
U(eq) is defined as one third of the trace of the
orthogonalized U
ij
tensor. 182
Table 19. Bond lengths [Å] for C
22
H
16
F
6
IrN
3
O
6
. 183
Table 20. Bond angles [
o
] for C
22
H
16
F
6
IrN
3
O
6
. 184
Table 21. Anisotropic displacement parameters (Å
2
x 10
3
) for
C
22
H
16
F
6
IrN
3
O
6
. The anisotropic displacement factor
exponent takes the form: -2 π
2
[ h
2
a*
2
U
11
+ ... + 2 h k a*
b* U
12
]. 185
Table 22. Hydrogen coordinates ( x 10
4
) and isotropic displacement
parameters (Å
2
x 10
3
) for C
22
H
16
F
6
IrN
3
O
6
. 186
ix
List of Figures
Figure 1. Oxidative conversion of fossil fuels is a foundational
technology. 1
Figure 2. Examples of products potentially impacted by next
generation, low temperature, selective, hydrocarbon
oxidation catalysts. 3
Figure 3. Incorporating the “C-H activation” reaction into a catalytic
system requires integration with a functionalization
reaction and stable systems. 4
Figure 4. Many complexes capable of C-H activation have now been
reported. However, relatively few have been utilized in
catalytic reactions for the conversion of alkanes to useful
products. 6
Figure 5. Greater selectivity is observed in the C-H activation
reaction than in classical chemistry, which gives it an
advantage. 7
Figure 6. Key requirements for any efficient catalyst. 8
Figure 7. Several pathways for the C-H cleavage in the C-H
activation reaction. 9
Figure 8. Catalytic cycle for alkane metathesis. 13
Figure 9. Electrophilic activation of methane by “soft” electrophiles. 14
Figure 10. Orbital interaction between the relatively low lying
compact HOMO of a C-H bond and the LUMO of a “soft”
(polarizable) electrophile. 15
Figure 11. Proposed mechanism for the electrophilic C-H activation
and oxidation of methane to methanol by the
mercury(II)/H
2
SO
4
system. 17
Figure 12. Generalized energy diagram for C-H activation via alkane
coordination and C-H cleavage showing ground state
stabilization. 20
x
Figure 13. Comparison of the likely active catalyst in the
Pt(bipyrimidine)Cl
2
/H
2
SO
4
system with the weakly
coordinating BARF anion. 25
Figure 14. Correlation of C-H activation Rates (measured by H/D
exchange rates between CH
4
and D
2
SO
4
) with solvent
acidity, H
0.
Hammett Acidity scale is expressed as H
0
. At
98 wt% H
2
SO
4
, the H
0
= -10.4, and 85 wt% H
2
SO
4
has a
Hammett acidity constant of H
0
= -8 on the. 27
Figure 15. Inhibition of the Pt(bipyrimidine)Cl
2
system by water in
sulfuric acid. 28
Figure 16. Proposed ground state destabilization of C-H activation. 30
Figure 17. Energy diagram for Pt(bipyrimidine)TFA
2
and
Pt(picolinate)TFA
2
, where N-N = bipyrimidine and N-O =
picolinate, for the activation of benzene in trifluoroacetic
acid. 32
Figure 18. Generalized energy diagram emphasizing the two key steps
involved in the C-H activation reaction: R-H coordination
and C-H cleavage. 40
Figure 19. Plot of ln(k) versus 1/(Temperature (K)) for the H/D
exchange of CF
3
CO
2
D and C
6
H
6
using 3 as a catalyst. 50
Figure 20. Thermal ellipsoid plot of 4 with 50 % probability.
Hydrogens and benzene co-solvent were removed for
clarity. Selected bond distances (Å) and angles (º) are as
follows: Pt(1)-C(16), 1.990(4); Pt(1)-N(1), 2.116(3); Pt(1)-
N(2), 2.006(3); Pt(1)-C(25), 2.014(4); N(2)-Pt(1)-C(25),
179.65(15); C(16)-Pt(1)-N(1), 159.50(13). 51
Figure 21. Energy diagram (calculated enthalpies) for the C-H
activation of benzene by the Pt(NNC)TFA system in
trifluoroacetic acid. 52
Figure 22. Energy diagram for Pt(NNC)TFA and
Pt(bipyrimidine)TFA
2
systems. 54
xi
Figure 23. (Top NMR)
1
H NMR of 3 in deuterated dichloromethane.
(Bottom NMR)
1
H NMR after 1.2 eq of
tris(pentafluorophenyl)borane was mixed with 3 in
deuterated dichloromethane. 63
Figure 24. Plot of turnover number vs. time for the H/D exchange
reaction between benzene-H
6
and trifluoroacetic acid-d
1
using 4 as the catalyst. Correction for background H/D
exchange has already been taken into account prior to
plotting the data. (Conditions: 10.26 mM of 4, 0.25 mL of
benzene-H
6
, 1 mL of deuterated trifluoroacetic acid, heated
at 180
o
C). 66
Figure 25. Plot of the percent benzene-H
6
that has reacted versus time
in minutes for the “catalytic reaction” and the “control
reaction.” 67
Figure 26. Eyring plot for the H/D exchange of benzene-H
6
and
trifluoroacetic acid-d
1
with the Pt(NNC)TFA catalyst. 70
Figure 27. View of the aromatic region of the
1
H NMR spectrum of
protonation of complex 4 with trifluoroacetic acid in
deuterated chloroform. 71
Figure 28. a)
1
H NMR spectrum of 3 in CD
2
Cl
2
. b)
1
H NMR spectrum
of 3 with 3.8 eq of HTFA in CD
2
Cl
2
. c)
1
H NMR spectrum
of 3 with 3.8 eq of HTFA in CD
2
Cl
2
. 72
Figure 29. (top NMR):
1
H NMR of complex 3 in CDCl
3
. (bottom
NMR):
1
H NMR of recovered product from “catalyst
recovery experiment.” 74
Figure 30. Thermal ellipsoid plot of 4 with 50 % probability.
Hydrogens and benzene co-solvent were removed for
clarity. 76
Figure 31. Energy diagram for Pt(NNC)TFA and
Pt(bipyrimidine)TFA
2
systems. 83
Figure 32. Catalytic sequence for the functionalization of
hydrocarbons via a non-redox catalytic cycle. 88
Figure 33. Stability of 1-(OH)
2
Py in D
2
O over time. 94
xii
Figure 34. Stability of 1-(OH)
2
Py in D
2
O over time in the presence of
4 eq of KOD. 95
Figure 35. Stirring rate study for H/D exchange between benzene-H
6
and D
2
O using 1-OH
2
Py as a catalyst. 97
Figure 36. Eyring Plot for H/D exchange by 1-OH
2
Py with benzene-
H
6
and D
2
O. 99
Figure 37. ORTEP of 1-Ph(µ-OH). (Thermal ellipsoids at 50 %
probability, and a molecule of water and CH
2
Cl
2
omitted
for clarity). Selected bond distances (Å): Ir(1)-O(1),
2.093(8); Ir(1)-C(1) = 1.99(14); Ir(1)-N(1) = 2.150(9);
Ir(1)-N(2) = 1.964(10). Selected bond angles (degrees):
Ir(1)-O(1)-Ir(2), 101.7(3); N(2)-Ir(1)-O(1), 170.7(4). 101
Figure 38. Proposed catalytic cycle for water and benzene H/D
exchange. 102
Figure 39.
1
H NMR of 2-TFA
2
NCMe after heating in KOD/D
2
O to
hydrolyze the esters and a produce a water soluble
complex. 107
Figure 40. Comparison of 2-TFA
2
NCMe (top) and 2-Cl
2
NCMe
(bottom) heated in KOD/D
2
O to yield similar NMR’s
suggesting that the (TFA and Cl) groups have been
displaced by deuteroxide. 108
Figure 41. Conditions for the catalytic H/D exchange reaction between
water and benzene using 2-TFA
2
NCMe as the catalytic
precursor. 109
Figure 42. ORTEP of 3-TFA
2
NHCOMe. (Thermal ellipsoids at 50 %
probability). Selected bond distances (Å): Ir(1)-N(3),
2.073(5); Ir(1)-O(3), 2.040(5); Ir(1)-N(1), 2.158(4); Ir(1)-
N(2), 1.983(5); Ir(1)-C(16), 2.010(5); N(30)-C(17),
1.266(8); C(17)-O(2), 1.322(8). Selected bond angles
(degrees): C(16)-Ir(1)-N(1), 160.8(2). No counterion could
be found. 114
Figure 43. Plot of TON vs. time for a 13.3 mM solution of 3-
TFA
2
NHCOMe in 0.15 M KOD/D
2
O solution with 50 μL
of benzene-H
6
at 160
o
C with the reaction sampled over
time. 117
xiii
Figure 44. Preparation of 1-EtClC
2
H
4
and 1-EtClNCMe. 122
Figure 45. Preparation of 1-Ph( μ-Cl). 125
Figure 46. Preparation of 1-PhClPy. 126
Figure 47. Preparation of 1-EtTFANCMe. 127
Figure 48. Preparation of 1-TFA
2
NCMe. 128
Figure 49. Preparation of 1-TFA
2
Py. 129
Figure 50. Preparation of 1-OMe
2
Py. 130
Figure 51. Preparation of 1-(OH)
2
Py. 132
Figure 52. Preparation of 1-Ph( μ-OH). 133
Figure 53. Preparation of 1-PhTFAPy. 134
Figure 54. Preparation of 6-phenyl-4,4’-dimethoxy-2,2’-bipyridine. 135
Figure 55. Preparation of 6-phenyl-4,4’-dimethyl-2,2’-bipyridine. 137
Figure 56. Preparation of 2. 138
Figure 57. Preparation of 2-EtClC
2
H
4
and 2-EtClNCMe. 140
Figure 58. Preparation of 2-EtTFANCMe. 143
Figure 59. Preparation of 2-TFA
2
NCMe. 144
Figure 60. Preparation of 4’-hydroxy-3-(dimethylamino)-
propiophenone hydrochloride. 145
Figure 61. Preparation of NNC
pOH
. 146
Figure 62. Preparation of NNC
pOTf
. 147
Figure 63. Preparation of NNC
pOAc
. 148
Figure 64. Preparation of 3-EtClC
2
H
4
. 149
Figure 65. Preparation of 3-EtClNCMe. 151
Figure 66. Preparation of 3-EtTFANCMe. 152
xiv
Figure 67. Preparation of 3-TFA
2
NCMe. 153
Figure 68. Preparation of 3-TFA
2
NHCOMe. 154
Figure 69.
1
H NMR of 3-TFA
2
NCMe in acetone-d
6
. 156
Figure 70. Preparation of 3-(OH)
2
NHCOMe. 156
Figure 71. Preparation of 3’-hydroxy-3-(dimethylamino)-
propiophenone. 157
Figure 72. Preparation of NNC
mOH
. 158
Figure 73. Preparation of NNC
mOAc
. 159
Figure 74. Preparation of 4-EtClC
2
H
4
. 160
Figure 75. Preparation of 4-EtClNCMe. 162
Figure 76. Preparation of 4-EtTFANCMe. 163
Figure 77.
1
H NMR of a 5.0 mM solution of 1-OH
2
Py in D
2
O. 164
Figure 78. Plot of TON vs. time for a 2.13 mM solution of 1-OH
2
Py
in 0.5 mL benzene-H
6
and 0.5 mL D
2
O with 78 eq (0.16 M)
KOD at 180
o
C. 165
Figure 79. ORTEP of 1-Ph(µ-OH). (Thermal ellipsoids at 50%
probability, and a molecule of water and CH
2
Cl
2
omitted
for clarity). 172
Figure 80. ORTEP of 1-Ph(µ-OH) asymmetric unit for clarity of atom
naming. (Thermal ellipsoids at 50 % probability, and a
molecule of water and CH
2
Cl
2
omitted for clarity). 173
Figure 81. ORTEP of 3-TFA
2
NHCOMe. (Thermal ellipsoids at 50 %
probability). 180
Figure 82. Thermodynamics (enthalpies in kcal/mol) at pH =14 for the
C-H activation using the phenylpyridine Ir(III) system. 192
Figure 83. Preparation of NC
pOH
. 202
Figure 84. Preparation of NC
mOH
. 203
xv
Figure 85. Preparation of NC
pOTf
. 204
Figure 86. Preparation of 2. 205
Figure 87. Preparation of NC
mOTBDMS
. 206
Figure 88. Preparation of NC
mOTIPS
. 207
Figure 89. Preparation of 1. 208
Figure 90. DFT Calculations for Ir
I
bipyridine, bipyrimidine, and
bipyrazine. The values in each box correspond to the
following: (bipyridine)Ir
I
, (bipyrimidine)Ir
I
, (bipyrazine)Ir
I
,
respectively. 213
Figure 91. DFT analysis of (PNP)Ir
I
OH dissociation of hydroxide and
the protonation by water. The values shown are the
following (respectively): (2,6-(CH
2
P(F)
2
)
2
)-pyridine)Ir,
(2,6-(CH
2
P(OMe)
2
)
2
)-pyridine)Ir, and (2,6-(CH
2
P(Me)
2
)
2
)-
pyridine)Ir. 215
Figure 92. Stack’s Complex and the desired Ir(NNC) sterically
hindered complex. 219
Figure 93. Chemdraw structure (top) for 3-Ir(H)(Cl) and
(PCP)Ir(H)(Cl) and their respective DFT geometry
optimized space filling models (bottom). 222
Figure 94. Preparation of 3. 223
Figure 95: Ball and spoke structure for the gas phase geometry
optimized (PCP)Ir(H)(Cl). 225
Figure 96: Ball and spoke structure for the gas phase geometry
optimized 3-Ir(H)(Cl). 226
xvi
List of Schemes
Scheme 1: C-H activation of methane by a scandium methyl complex
via sigma bond metathesis. 11
Scheme 2. Methane to methanol stoichiometry for the
mercury(II)/H
2
SO
4
system. 15
Scheme 3. Synthesis of Pt(NNC)X complex 3. 43
Scheme 4. The stoichiometric C-H activation of benzene with 3. 48
Scheme 5. Synthesis of 1, Pt(NNC)Cl. 57
Scheme 6. Synthesis of Pt(NNC)OAc. 58
Scheme 7. Synthesis of 3, Pt(NNC)TFA, from 1 and AgTFA. 59
Scheme 8. Synthesis of 4, Pt(NNC)Ph, from 1 and Ph
2
Zn. 60
Scheme 9. Synthesis of 1-(OH)
2
Py. 92
Scheme 10. Synthesis of possible phenyl intermediate. 100
Scheme 11. Synthesis of 6-phenyl-2,2’-bipyridine-4,4’-diyl diacetate. 105
Scheme 12. Synthesis of 2. 105
Scheme 13. Synthesis of 2-TFA
2
NCMe. 106
Scheme 14. Synthesis of NNC
pOH
ligand. 110
Scheme 15. Synthesis of 3-(OH)
2
NHCOMe. 112
Scheme 16. Synthesis of 3-(OH)
2
NHCOMe. 115
Scheme 17. Synthesis of NNC
mOH
. 118
Scheme 18. Resonance structures for deprotonated NNC
mOH
and
NNC
pOH
bound to iridium. 119
Scheme 19. Stoichiometric benzene C-H activation reaction with 1-
OH
2
Py and benzene under catalytic conditions. 169
Scheme 20. Synthesis of NC
pOH
and NC
mOH
. 195
xvii
Scheme 21. Resonance structures for NC
pOH
and NC
mOH
bound to an
iridium center indicating that only in the NC
mOH
case does
the negative charge ever reside at the 1 position. This
added charge may increase the catalytic rate for C-H
activation. 195
Scheme 22. Synthesis of NC
pOTf
and [(NC
pOTf
)
4
Ir(µ-Cl)]
2
. 197
Scheme 23. Synthesis of silyl protected phenylpyridine ligands. 198
Scheme 24. Synthesis of [(NC
mOTIPS
)
4
Ir(µ-Cl)]
2
. 199
Scheme 25. Projected route to get to [(NC
pOH
)
4
Ir(µ-OH)]
2
. 200
Scheme 26. Synthesis of 3, a sterically hindered NNC derivative. 219
xviii
Abstract
The first chapter is an introduction to the development of carbon-hydrogen
bond, (C-H), activation. The use of acidic solvents for C-H activation is addressed,
and catalyst inhibition by water or methanol is discussed as one of the major
problems in creating active catalysts. New approaches for designing C-H activation/
functionalization catalysts that operate in water are discussed.
Chapter two is the study of an electron rich platinum complex, Pt(NNC)TFA
where NNC = 6-phenyl-4,4’-di-tert-butyl-2,2’-bipyridine and TFA = trifluoroacetate,
designed to overcome the water inhibition of the Pt(bipyrimidine)Cl
2
catalyst. The
mechanism for the H/D exchange between benzene and trifluoroacetic acid is studied
using this catalyst. The energetics for C-H activation (both coordination and
cleavage of the C-H bond) by the Pt(bipyrimidine)(TFA)
2
complex and the
Pt(NNC)TFA complex are calculated and compared by DFT.
Chapter three is the synthesis and reactivity of a water soluble
cyclometallated (NNC)Ir(OH)
2
Py complex that is competent for the H/D exchange
of benzene and water. This complex was insoluble in water at elevated temperatures
(150
o
C), which hindered its use as a catalyst. To overcome the insolubility in water
at elevated temperatures, I designed water soluble (NNC derivatives) ligands.
Several of these water soluble iridium complexes were synthesized and tested.
Further work is ongoing in this area to determine if there is a pH dependence on rate
of C-H activation using these catalysts.
xix
Chapter 4 is a collection of related work. The first section is the synthesis of a
water soluble cyclometallated bisphenylpyridine iridium µ-OH bridged dinuclear
complex. This complex is being synthesized for the C-H activation of hydrocarbons
in basic aqueous media and to gain further understanding about μ-hydroxo bridged
dinuclear complexes. The second section contains DFT calculations of an iridium(I)
bipyridine hydroxo aquo complex for the C-H activation of hydrocarbons in water.
Protonation of the electron rich iridium(I) center by water is found to be highly
exothermic, which results in a ground state stabilization. Calculations were also
performed on Goldberg’s cyclometallated (PNP) iridium hydroxo complex, and the
protonation by water is calculated to be endothermic. Lastly, a sterically hindered
NNC ligand is synthesized. Attempts have been made to cyclometallate it to iridium
for the purpose of generating a five coordinate complex that could show interesting
chemistry.
1
Chapter 1: Introduction to C-H Activation
1.1: Background
The conversion of hydrocarbons to energy and materials is a foundational
technology.
1
While we work towards solutions to alternative forms of renewable
energy like wind, solar, and hydrogen, we must develop short term solutions to
address the current energy crisis. As a result, we need to develop more
environmentally benign, greener technologies for the hydrocarbon based processes
currently being used. As shown in Figure 1, the key objectives of these future
processes must be to minimize emissions and capital costs while maximizing energy
and product output. By reducing the dependence on petroleum and increasing the
use of abundant natural gas, the lifetime of the fossilized resources will be extended.
ENERGY
$$$
EMISSIONS
-$$
MATERIALS
$$$
FOSSIL FUELS
+
AIR
CAPITAL
-$$
Minimize
Maximize
Minimize
Maximize
Global warming
Lessen dependence
on oil
Currently:
Primarily oil
Future:
Natural gas
Figure 1. Oxidative conversion of fossil fuels is a foundational technology.
2
Alkanes from natural gas and petroleum are among the world’s most
abundant and low-cost feedstocks. Currently technologies to convert these materials
to energy, chemicals, and fuels operate at high temperatures and utilize multi-step
processes that are inefficient and capital intensive. The development of low-
temperature, selective, direct alkane oxidation catalysts could lead to a new paradigm
in the petrochemical industry that is environmentally cleaner, economically superior,
and allows the large reserves of untapped remote natural gas to be used as primary
building blocks for fuels and chemicals.
2
Alcohols are among the highest volume
commodity chemicals and most versatile feedstocks.
2b
A primary reason that
technologies for the direct, selective hydroxylation of alkanes to alcohols remain a
challenge is that the current commercial catalysts for alkane oxidation (typically
solid metal oxides) are not sufficiently active for the functionalization of alkane C-H
bonds. As a result, high temperatures and harsh conditions must be employed that
lead to low reaction selectivity.
2a
One way to ultimately impact the petrochemical industry is to develop new
catalysts that selectively convert methane and higher alkanes to alcohols or other
chemical commodities at low temperatures (approximately 200 to 250
o
C), in small
process reactors, and in high yields. Examples of products that could be
dramatically impacted by such low temperature conversion catalysts are shown in
Figure 2.
3
R-H R-X
Phenol
1,4-Butane Diol
Propylene Glycol
t-Butanol
1,3-Propane Diol
Ethanol
Ethylene Glycol
Methanol
(DMM)
Low Temperature
Fuel Cells
Acetic Acid
Lower
Temperatures
~200
o
C
Higher efficiencies
Lower capital
Today
High Temperatures
>600
o
C
High capital
Lower atom and
energy efficiency
Cinnamates
Linear Alkyl Benzene
MSA
Methyl Chloride
Divinyl Benzene
Cyclohexanol
Neoacids
Diphenyl Carbonates
Hydrogen peroxide
Liquid Fuels
Styrene
Isobutyl Benzene
Figure 2. Examples of products potentially impacted by next generation, low
temperature, selective, hydrocarbon oxidation catalysts.
The primary basis for direct alkane conversion chemistry impacting the
petrochemical industry is that, unlike the fine chemical industry, the bulk of the
expense in production are process costs as opposed to material costs. Depending on
the process, as much as 50 to 75 % of these process costs can be related to the price
of the plant itself, the capital costs. Consequently, in addition to improvements
related to environmental considerations, (green chemistry) key improvements to
developing new petrochemical technologies must involve significant reductions in
capital expenses in order to warrant the risks of developing new processes. This is
because in general, petrochemical technologies involve enormously large capital on
the order of hundreds of millions of dollars. One key to reducing the capital costs in
4
new processes is to reduce the number of steps in the process since this is related to
the number of process units in the plant.
An alternative process that has been proposed is the use of transition metals
for the well known C-H activation reaction followed by functionalization. C-H
activation can be defined as a two step process by which 1) coordination of the
substrate C-H bond to the inner-sphere of an metal, M-X, species followed by 2) the
facile cleavage of the C-H bond by the M-X species to generate an M-C intermediate
and H-X. Functionalization of the resulting M-C intermediate by reactions at the
inner-sphere of the metal or through an attack on or by the carbon bound to the metal
results in the functionalized product. This process could be carried out in a small
inexpensive reactor, which would reduce the capital costs associated with the multi-
step Fisher-Tropsch process.
C H
C-M + X-H C-M + H-X
C
H
X-M
MX
1/2 O
2
C-OH
+
Functionalization
CH Activation
<250
o
C
Stable
Catalysis!
Stable
Catalysis!
MX +
Electrophilic
Substitution
Insertion
Sigma bond
metathesis
Figure 3. Incorporating the “C-H activation” reaction into a catalytic system
requires integration with a functionalization reaction and stable
systems.
5
1.2: C-H Activation
From its early inception C-H activation has gained significant attention
throughout the scientific community. As can be seen in Figure 4,
3,4,5,6,7
many
systems have been developed that are competent for C-H activation. Through the
mechanistic study of some of these systems it was observed that the C-H activation
reaction (C-H bonds cleavage favors: 1
o
> 3
o
and aromatic > aliphatic) has a unique
selectivity.
5
It is well understood that the C-H bond in methanol (~90 kcal/mol) is
more reactive than the parent alkane (methane ~105 kcal/mol). Therefore, the
method chosen for the functionalization of C-H bonds must be one that shows
selectivity.
6
Pt
OH
2
Cl
Cl OH
2
Ir
H
H
Me
3
P
Ir
CO
CO
Lu CH
3
W
H
H
Ir
Me
3
P
CH
3
Re
Me
3
P
H
PMe
3
H
Zr
RHN
RHN
NR
[(Porphyrin)Rh
II
]
2
Os
R
3
P
R
3
P PR
3
H
PR
3 t
Bu
Ir
P(
t
Bu)
2
P(
t
Bu)
2
H
H
N M
P(
t
Bu)
2
P(
t
Bu)
2
OH
M=Rh
I
,Ir
I
NN
NN
Pt
Cl
Cl
Pd(II) Hg(II)
N
N N
N
N
N
Ru
B
H
Ph
3
P
NCCH
3
X
X = H, OH
NN
N
N
N N
Pt
B H
CH
3
Rh
Et
2
P
P
Et
2
Pt
H
t
Bu
N
N
Pt
OH
2
Me
N
N
M
H
O
M=Pd
II
,Pt
II
N Ir
N
N
CH
3
Aryl
Aryl
Aryl
Aryl
Aryl
Aryl
N Ru
P(
t
Bu)
2
P(
t
Bu)
2
H
H
H
2
N
N N
N
N
N
Ir
B
H
H
2
H
H
W
NO
t
Bu
Ir
O O
O O
CH
3
N
Sc CH
3
N
N
N
N
Pd
Br
Br
Herrmann
CH
3
CH
3
Tilley
Shilov Bergman Graham Watson W. D. Jones Green
Wolczanski
Wayland
Flood Whitesides Sen
Periana Bergman Kaska, Goldman,
Jensen, Brookhart
(Me)
6
N
N N
N
N
N
Ru
B
H
Me
3
P
L
X
X= Ph, OH
L=NCCH
3
,PMe
3
N Ir
N
Cl
t
Bu
t
Bu
Gunnoe Burger Carmona
Periana
Legzdins
Goldberg
Milstein and Leitner Bercaw
Periana
Lau
Goldberg
Hartwig
Periana Bercaw
N
Pt N
N
OTf
Peters
Figure 4. Many complexes capable of C-H activation have now been reported.
However, relatively few have been utilized in catalytic reactions for
the conversion of alkanes to useful products.
The fundamental basis for the higher efficiency of C-H activation based
catalysts is that the C-H activation reaction can be made to occur without the
involvement of high energy intermediates as shown in Figure 5. As can be seen, the
classical chemistry of the C-H bond typically involves the generation of
intermediates such as free radicals, carbocations, carbanions, and carbenes. These
7
intermediates are highly energetic species generated under very reactive conditions,
like high temperatures, or in the presence of reactive species like superacids or
peroxides. As a result, this ultimately leads to impractical chemistry. The key
advantage of the C-H activation reaction is that it is, to our knowledge, the only
reaction that can cleave the C-H bond of alkanes using moderately energetic
conditions and reagents.
1
C + H C + H C + H
zz
+ - -
+
C H C H
C-M + H-X C-M + H-X
C
H
X-M
MX
Electrophilic Substitution Insertion
Sigma bond metathesis
C
H
C
Classical Chemistry
High Energy Intermediates
Classical Chemistry
High Energy Intermediates
CH Activation
Low Energy Intermediates
CH Activation
Low Energy Intermediates
Highly Selective
Highly Selective
Non Free Radical
Non Free Radical
Figure 5. Greater selectivity is observed in the C-H activation reaction than in
classical chemistry, which gives it an advantage.
From the list of catalysts shown in Figure 4,
4,5
only a few have been shown to
generate functionalized products.
8,9
The reason for the limited number of catalysts
capable of generating functionalized products can likely be attributed to what some
8
call “the devil’s triangle,” Figure 6. Three successive criteria must be met for any
catalyst to be efficient in any catalytic reaction. These three criteria are rate, life, and
selectivity.
3
For example, a highly reactive catalyst might not be stable under the
specified reaction conditions and thus have a short lifetime, or even display low
selectivity. Vice versa, a relatively stable catalyst might have a sufficiently long
lifetime but will likely have slow rates. Therefore, all three criteria must be met
simultaneously in order to generate an efficient catalyst.
These requirements
should be simultaneously
considered for efficient
catalyst design
Figure 6. Key requirements for any efficient catalyst.
Another advantage to the C-H activation reaction is the ability to keep the
reactants coordinated to the inner-sphere of the metal during the reaction. This is
characteristic of many of the successful homogeneous catalytic reactions such as
hydrogenations, hydroformylation, polymerization, and metathesis. The advantage
of keeping the reactive species coordinated to the inner-sphere of the metal means
9
the metal can effectively mediate the rate and selectivity for the conversion of the
reactants to the products.
There are several different classifications for the transition state in the C-H
cleavage step, Figure 7. As shown, all of these classifications are related in that they
require the substrate R-H be coordinated to the inner-sphere of the metal either as
intermediate or via a transition state leading to the formation of a M-C intermediate.
The specifics of the actual mode of cleavage depend on the electronic configuration
of the metal, the X group and variations of these classifications have been observed.
Of these, the most common modes are electrophilic substitution (ES), oxidative
addition (OA) and sigma bond metathesis and in all cases unique C-H cleavage
selectivity patterns are observed.
5
Figure 7. Several pathways for the C-H cleavage in the C-H activation reaction.
10
Metalloradical pathways were discovered and popularized by Wayland et
al.
10
These reactions occur via a rhodium(II) porphyrin complex. The rhodium(II)
porphyrin complexes exist in a dimeric-monomeric equilibrium, and the C-H
activation occurs when two monomeric rhodium(II) centers interact with the C-H
bond of methane via a termolecular reaction. Experimental evidence does not
suggest that the reaction is free radical based. Furthermore, analysis of the Rh-H
bond strength (~60 kcal/mol) compared to the C-H bond strength (~105 kcal/mol)
suggest that a free radical hydrogen atom abstraction would be highly endothermic.
11
No functionalization pathways have been observed for these systems.
Patricia Watson discovered sigma bond metathesis in 1983.
12
These
reactions are characteristic of early group 3 metals, scandium, lanthanides and
actinides, Scheme 1. After analysis of the reaction, the reaction appears to be an
interchange reaction with no net alkane activation. To my knowledge only one form
of functionalization has been observed via a sigma bond metathesis pathway:
recently, the Tilley group showed that Cp*
2
ScCH=C(CH
3
)
2
is competent for the
hydromethylation of isobutylene to neopentane. However, the conversions were low
(TON ~2), and side reactions such as polymerization were competitive.
6c,d
11
Sc
H
3
C
C
H
3
H
Sc
CH
3
H
3
C
H
Sc
H
3
C
CH
3
H
+
+
Scheme 1: C-H activation of methane by a scandium methyl complex via sigma
bond metathesis.
A more recent pathway that has been given consideration is alkane activation
by 1,2-addition. Such additions have typically been reported for group 4 and 5
metals in high oxidation states, usually containing amido, or imido ligands.
11
Bergman and Wolczanksi studied 1,2-addition of C-H bonds to early transition metal
imido complexes, zirconium and titanium.
13
The appeal of this pathway is that the
resulting metal alkyl is one step away from functionalized products through a
reductive elimination/functionalization pathway. However, to date there have been
no reported examples of functionalization using this pathway.
While some of the previous C-H cleavage pathways have failed to show
functionalized products catalytically, there are predominantly two pathways that
have generated functionalized products in catalytic reactions. The first pathway to be
discussed is oxidative addition. Oxidative addition reactions are usually observed
for low oxidation state, electron rich, late transition metals, group VII-X metals.
Oxidative addition can be described as a loss of two electrons by the metal center
changing the electron count about the metal while increasing the coordination
12
number of the metal. Recent work by Hartwig has shown that alkanes can be
functionalized by boron reagents to generate alkylboron products.
14
Mechanistic
work; however, failed to distinguish whether the pathway for C-H cleavage was
oxidative addition or sigma bond metathesis with the iridium-boron complex.
However, Brookhart and Goldman recently published a work in Science where they
used the well known Ir(POCOP)H
2
pincer complex, where POCOP = C
6
H
4
-2,6-(O-
P(t-Bu)
2
)
2
, to dehydrogenate alkanes, which are then coupled via Schrock olefin
metathesis catalysts to generate higher and lower olefin products. These olefins are
then hydrogenated by iridium dihydride intermediates to regenerate the iridium
catalyst and the higher and lower alkane products. This process is called alkane
metathesis and the C-H cleavage step to generate the metal alkyl proceeds through
oxidative addition.
15
A simplified catalytic cycle can be seen in Figure 8.
13
PR
2
PR
2
Ir
H
H
PR
2
PR
2
Ir
H
H
PR
2
PR
2
Ir
H
PR
2
PR
2
Ir
+ 2 2
C
2
H
4
2
2
2
2
2
2
2
Metathesis
Reaction
(metathesis
catalyst)
Alkane dehydrogenation
Figure 8. Catalytic cycle for alkane metathesis.
The other predominantly utilized pathway is electrophilic substitution. In
electrophilic substitution a hydrocarbon substitutes a hydrogen ion for an
electrophilic metal. This hydrogen ion is abstracted by a weak base which, results in
H-X and a metal carbon intermediate, M
E
-C, where M
E
denotes the electrophilic
metal. Periana et al. developed several complexes that operate by electrophilic
substation such as palladium(II), thallium(I), iodine
+
, mercury(II), and platinum(II),
which all generate methane functionalized products in strongly acidic media, H
2
SO
4
.
A generic electrophilic substitution pathway for the conversion of methane to
methanol can be seen in Figure 9.
14
CH ACTIVATION
H
+
1/2 O
2
+ 2 H
+
H
2
O
CH
3
OH + H
+
[CH
3
-E
N
]
(n-1)
CH
4
[E
N
]
n
H
2
O
FUNCTIONALIZATION
OXIDATION
[E
(N-2)
]
(n-2)
C
H
H
H
H
E
Sol
[E
N
sol]
n
CH
4
sol
CH Cleavage
CH coordination
sol-H
+
Figure 9. Electrophilic activation of methane by “soft” electrophiles.
The coordination of the C-H bond of the methane to an electrophilic metal
center, [E
N
]
n
, followed by loss of a proton can also be described as attack of a
nucleophile, “sol”, on the coordinated C-H bond that leads to C-H cleavage and
generation an intermediate [E
N
-CH
3
]
(n-1)
species. Frontier orbital considerations of
this interaction between the C-H bond and electrophiles indicate (given the low
energy, σ-symmetry, and low polarizability of the HOMO
C-H
) that “soft”,
electrophiles (characterized by a relatively low lying, polarizable LUMO with σ-
symmetry) would be effective for this mode of C-H activation, Figure 10.
3
15
CH
CH
E
+
E
+
LUMO of a
“soft”
electrophile
HOMO of a
C-H bond
Figure 10. Orbital interaction between the relatively low lying compact HOMO
of a C-H bond and the LUMO of a “soft” (polarizable) electrophile.
This has been found to be the case with the “soft,” powerful electrophilic
species, [XHg]
+
, generated by dissolving HgX
2
salts in a strongly acidic solvent such
as sulfuric acid or trifluoromethanesulfonic acid. These species have been found to
react readily with methane via C-H activation, and they are among the most effective
catalysts for the conversion of methane to methanol in 96 % sulfuric acid solvent.
Thus at 180
o
C with a 20 mM concentration of Hg(HSO
4
)
2
in sulfuric acid, methanol
concentration of 1 M with yields of over 40 % based on added methane, at methanol
selectivities > 90 % have been observed by the reaction shown in Scheme 2.
9b
Scheme 2. Methane to methanol stoichiometry for the mercury(II)/H
2
SO
4
system.
16
As shown in Figure 11, the reaction mechanism is proposed to occur by an
electrophilic substitution (ES) pathway that involves coordination of methane to the
inner sphere of the poorly coordinated [X-Hg]
+
species (solvated by liquid sulfuric
acid) followed by subsequent loss of a proton to generate a [CH
3
-Hg]
+
intermediate.
The [CH
3
-Hg]
+
intermediate is converted to methanol and the reduced catalyst,
mercury(0), is reoxidized to mercury(II) by H
2
SO
4
.
Interestingly, given the poor basicity of the intermolecular base, bisulfate, the
coordination of the C-H bond to [X-Hg]
+
followed by “nucleophilic attack” of the
bisulfate shows that the coordinated methane must be considered quite an acidic
species.
3
Similarly the increase in acidity of hydrogen upon coordination to
electrophilic metal centers has also been reported.
16
17
H
2
X
+
X
-
C-H Cleavage
Functionalization
Oxidation
XHg Sol
+
Sol
H
CH
3
+
X
-
Methane
Coordination
X
-
CH
4
+ 3HX
CH
3
OH
2HX
XHg
XHg CH
3
Hg
2
X
2
2 H
2
O + SO
2
+ HgX
2
HgX
2
+ H
2
O
+ HX
CH
4
X = HSO
4
Electrophilic
CH Activation
Figure 11. Proposed mechanism for the electrophilic C-H activation and
oxidation of methane to methanol by the mercury(II)/H
2
SO
4
system.
One of the early pioneers for the direct conversion of methane to
functionalized products is George Olah at the University of Southern California. His
approach was based upon the use of acidic catalysts such as superacids for the direct
conversion of methane to methylhalides through a selective halogenation process. He
also showed that methane was converted to higher hydrocarbons through the
condensation of methanol or methyl halides. The methanol and methyl halides used
for the condensation could ultimately be generated from methane via the superacid
catalysts.
17
This work is very similar to the mercury(II) C-H activation system
which operates in sulfuric acid. Both systems operate by electrophilic substitution of
18
methane. The electrophile interacts with the C-H bond via a three centered two
electron interaction. Olah et al. indicate that the methanol generated likely becomes
protonated, CH
3
OH
2
+
, which further prevents over oxidation of the methanol
product. This protection is also what likely occurs in sulfuric acid either in the form
of CH
3
OH
2
+
or CH
3
OSO
3
H. In either case the C-H bond has become electron
deficient relative to methane and thus less reactive towards electrophiles. The
primary difference between the superacid and mercury systems is the fact that the
mercury(II) system has alternative orbitals open to it like (s) and (p) orbitals. It is
also a 6
th
row metal, which is very polarizable, and thus less sensitive to the presence
of water. On the other hand, it is known that in the presence of water a superacid
will level to H
3
O
+
, which is less acidic and thus less reactive.
1.3: C-H activation in Strongly Acidic Media: Catalyst Inhibition
by Ground State Stabilization
The C-H activation reaction is typically a facile reaction only when it is
carried out by the generation of highly energetic species and when the alkane is the
most (or only) reactive species present. However, in a medium that consists of
materials other than neat alkane, most of these highly reactive systems would suffer
poor rates due to side reactions with these other reagents. One reason for this is that
alkane C-H bonds, unlike C=C double bonds of olefins or other functional groups,
are poorly ligating and are unlikely to compete with the more coordinating species in
the reaction. Consistent with the poor ligating capability of alkanes, only by
spectroscopic studies has an alkane complex been observed.
18
The coordination of
19
an alkane to the first coordination sphere of a metal center in the C-H activation
reaction (either leading to an intermediate alkane complex or to a transition state that
leads directly to C-H cleavage) can be viewed as inner sphere ligand displacement
either through an associative, dissociative or interchange mechanism.
5,19
This
depends on the binding constant of the ligand being displaced by the alkane, but
given the poor binding characteristics of alkanes, it is reasonable that there will be
substantial dissociative character to the displacement reaction in all cases except
when poorly coordinating ligands are competing with the C-H bond for the
coordination site. The ligand that is to be displaced by the alkane can be represented
as “X” in Figure 12. This ligand “X” will likely be the most nucleophilic or
coordinating reagent in the medium, and it can either be a reactant, a product, a
solvent molecule, or a ligand. The main point to make is that this ligand “X” will be
more coordinating than the alkane substrate.
20
Figure 12. Generalized energy diagram for C-H activation via alkane
coordination and C-H cleavage showing ground state stabilization.
The poorly coordinating abilities of alkanes demonstrate a fundamental
challenge in performing C-H activation that must be overcome. Inner sphere ligand
displacement mechanisms with alkanes (whether associative or dissociative) lead to
weakly bound, intermediate alkane complexes, or directly to a transition state leading
to C-H cleavage. As a result, it can be expected that there will likely be severe
ground state inhibition in most media that would be useful for catalytic C-H
functionalization. This ground state stabilization arises from strong binding of other
ligands to the catalyst in the reaction system, which leads to an exothermic formation
of the catalyst resting state. As can be seen from Figure 12, the more stable the
resting state is the higher the activation barrier will be for the C-H activation
reaction.
Coordination
Alkane Complex
C-H Cleavage
Cleavage TS
M
X L
L L
M
CH
4
L
L L
M
C
H
3
L
L L
H
X
M
C H
3
L
L L
+HX
+CH 4
Activation
Barrier for
C-H Activation
+X
-
21
For example, it is challenging to imagine how methane coordination could
occur to sufficient extent to allow efficient catalysis in a solvent such as liquid water,
given the excellent coordinating properties of water, which would lead to stable M-
H
2
O complexes and extensive ground state inhibition. The challenge is heightened
by the poor solubility of methane in most useful media and the high concentration of
the solvent. Of course, it isn’t a requirement that the reaction be carried out in
solvents as ligating as water. However, if the objective is the hydroxylation of C-H
bonds to C-OH functional groups, then at a minimum, (the catalyst is expected to
operate at high turnover numbers before separation of product) the alcohol, which is
expected to bind more tightly to the catalyst than the alkane will be present in the
system and catalyst inhibition may be observed.
As anticipated, this issue of ground state inhibition is observed in many
catalytic alkane functionalization systems that operate by the C-H activation
reaction. The systems that are known to activate and hydroxylate alkanes by the C-H
activation reaction, the Shilov, Sen and Periana systems, this issue of ground state
inhibition is present. The Sen (palladium(II)) and Periana (mercury(II) and
Pt(bipyrimidine)Cl
2
) systems shown in Figure 4, independent of stabilities, the slow
rates or eventual inhibition of these catalyst systems prevent their utility, which can
be traced to water (or methanol) binding. This binding leads to ground state
inhibition. Other C-H activation/functionalization systems that operate by other
mechanisms such as the Ir(PCP)(H)
2
system for the dehydrogenation of alkanes to
olefins inhibition is observed through coordination of the olefin to the metal.
8e-g
The
22
slow rates of the Shilov system that is proposed to operate through an oxidative
addition mechanism is also likely due to strong ground state inhibition from water
binding.
3
The idea behind using acidic solvents (Lewis, or Brønsted) is that in
principle, the strongest base that can exist in such a solvent is the conjugate base of
the acid solvent. In the case of a strong acid, the conjugate base should be weakly
basic and poorly coordinating. As a result, ground state stabilization by the solvent
and the conjugate base will be minimized. The solvent is the reagent in the largest
quantity in the reaction medium; therefore, it only makes sense to use the acid as a
solvent rather than as a stoichiometric reagent. It can also be expected that in
catalysis other reactants and products will exists in larger than stoichiometric
amounts.
The general use of Lewis or Brønsted acids to facilitate coordination of
reactants is a well-known fact in coordination chemistry.
20
Thus, one of the most
active complexes known for catalytic C-H activation was developed by Professor
Bergman at Berkley,
21
[Cp
*
Ir(PMe)
3
Me(CH
2
Cl
2
)]
+
[MeB(C
6
F
5
)
3
]
-
. This complex is
generated by reaction of the Lewis acid, B(C
6
F
5
)
3
, with Cp
*
Ir(PMe)
3
Me
2
in the
poorly coordinating solvent dichloromethane. One reason that this complex is quite
reactive with methane (C-H activation occurs at -10
o
C) is that all of the possible
competing ligands in the reaction system [MeB(C
6
F
5
)
3
]
-
and CH
2
Cl
2
, are poorly
coordinating. Therefore, the coordinating ability of methane becomes more
comparable to these ligands. The use of a stoichiometric weakly coordinated
23
complex leads to very active catalysts; however, in the presence of more
coordinating species such as reactants or products, including methanol, these systems
would likely be greatly inhibited. Consequently, this approach of the stoichiometric
use of weakly coordinating groups would not be suitable for catalytic systems where
the desired product is methanol and many catalyst turnovers are required.
An alternative approach would be to run the reaction in a solvent such as
molten BARF, B(C
6
F
5
)
3
. Under these conditions any methanol produced would
form a strong acid-base adduct with the excess B(C
6
F
5
)
3
. The methanol produced
would be unavailable for coordination to the metal preventing inhibition or ground
state stabilization. The key issue with this strategy is that B(C
6
F
5
)
3
is expensive and
the cost of separating methanol from the MeOH:B(C
6
F
5
)
3
adduct to recycle the
B(C
6
F
5
)
3
solvent
would be too expensive. However, if the Lewis acid utilized is
inexpensive and thermally robust, this could be a useful strategy.
This was the idea behind the use of an inexpensive solvent like sulfuric acid
for facilitating the selective functionalization of methane.
9b
By definition an acid,
liquid sulfuric acid, is polar, strongly acidic, and weakly nucleophilic. The strongest
nucleophile or ligand that can exist in this solvent is the conjugate base bisulfate,
HSO
4
-
. Bisulfate is a poorly coordinating substrate which is less coordinating that
water or methanol. At high concentrations of acid solvent (> 85 wt% sulfuric acid),
any water or methanol generated (or any other species more basic than HSO
4
-
) is
essentially fully protonated and not available for coordination to the metal center.
As a result, this helps to minimize catalyst inhibition by ground state stabilization.
24
As the sulfuric acid concentration drops below 85 wt% the acidity
17b
rapidly
decreases, and water or methanol can become available for coordination to the metal
center, which should lead to inhibition of the C-H activation reaction.
The key challenge to utilizing this strategy is the identification of catalysts,
reactants and products that are thermally stable in such a medium. Both methane and
methanol are thermally stable in sulfuric acid at temperature below 250
o
C, and
Periana et. al. have identified several catalyst systems that are stable in this media for
the selective oxidation of methane to methanol. Consistent with the concept of
basicity leveling, theoretical studies indicate that, at sulfuric acid concentrations
greater than 90 wt%, the ground states of the Pt(bipyrimidine)Cl
2
and mercury(II)
catalysts, [(H-bipyrimidine)PtCl(HSO
4
)]
+
and Hg(HSO
4
)
2
, are coordinated to the
weakly binding bisulfate ligand, HSO
4
-
. The coordinated bisulfate ligand is most
likely extensively hydrogen bonded to solvent H
2
SO
4
molecules as shown in Figure
13 for the Pt(bipyrimidine)Cl
2
/H
2
SO
4
system. As can be seen, this poor coordination
of HSO
4
-
in sulfuric acid leads to a highly dispersed anion that is similar to the
weakly coordinating anion, [B(C
6
F
5
)
3
Me]
-
, which can be expected to be displaced by
methane more readily than water.
25
BARF anion
Weak coordinating
Ligands that can be
displaced by methane
Likely active Pt(II) Catalyst
NN
HN N
S
O
O
OH
OH
H
S
O
O
O
O
H
S
O
O
O
OH
H
S
O
OH
O
O
Pt
Cl
+
F
F
F
F
F
B
F
F
F F
F
F
F
F
F
F
F
F
F
F
F
-
Figure 13. Comparison of the likely active catalyst in the
Pt(bipyrimidine)Cl
2
/H
2
SO
4
system with the weakly coordinating
BARF anion.
Calculations show that replacement of the HSO
4
-
ligand by methane in the
Pt(bipyrimidine)Cl
2
/H
2
SO
4
system is endothermic (24 kcal/mol) with an activation
barrier of 33 kcal/mol for C-H cleavage. The calculated activation barrier is
comparable to the approximately 28-30 kcal/mol activation barrier obtained
experimentally for the C-H activation step. The experimental activation barrier was
measured by carrying out the reaction in D
2
SO
4
and monitoring the rate of H/D
exchange between methane and the solvent in the presence of catalyst.
Interestingly, the calculations as well as experimental results indicate that in the
Pt(bipyrimidine)X
2
system, where X = Cl
-
or HSO
4
-
, the coordination of methane is
the rate determining step rather than C-H cleavage. Due to the large excess of the
solvent, sulfuric acid (the catalyst concentration is typically 5 – 50 mM),
substantially more than one equivalent of methanol can be generated in this reaction
before catalyst inhibition due to water or methanol binding slows reaction to
impractical rates. At a catalyst concentration of 50 mM, and starting with 100 %
sulfuric acid solvent, approximately 300 turnovers have been demonstrated with the
26
generation of greater than 1.5 M methanol at 80 % conversion of methane and
greater than 90 % selectivity to methanol. At these high levels of water and
methanol concentrations, the activity of water and methanol are considerably higher
because the sulfuric acid concentration is reduced. Experimental studies show that at
acid concentrations below 80 % sulfuric acid the reaction rates are too low to be
useful (catalyst turnover frequency = ~10
-7
s
-1
) at 200
o
C. In this acid concentration
range, the C-H activation step is rate limiting and is at least 1000 times slower than
at 96 wt% sulfuric acid concentration. The basis for this large difference in rate can
be explained by theoretical calculations, which shows that the Pt-H
2
O complex
(which is expected to be formed at lower concentrations of acid),
[(Hbpym)PtCl(H
2
O)]
2+
is ~7 kcal/mol more stable than the [(Hbpym)PtCl(HSO
4
)]
+
complex. Consistent with the expected dependence on solvent acidity, as can be
seen from Figure 14 the decrease in rate below 85 wt% sulfuric acid solvent
correlates well with the solvent acidity.
27
Figure 14. Correlation of C-H activation Rates (measured by H/D exchange rates
between CH
4
and D
2
SO
4
) with solvent acidity, H
0.
Hammett Acidity
scale is expressed as H
0
. At 98 wt% H
2
SO
4
, the H
0
= -10.4, and 85
wt% H
2
SO
4
has a Hammett acidity constant of H
0
= -8 on the.
22
Critically, while the use of sulfuric acid allows the catalytic reaction to
proceed efficiently, the rapid inhibition of the catalysts by water or methanol below
90 wt% sulfuric acid leads to uneconomical catalyst rates (for the platinum(II)
system) and high separation costs for the methanol (for both the platinum and
mercury systems). Calculations show that if catalyst inhibition can be minimized to
allow a five molar solution of methanol to be obtained, with an overall catalyst
turnover of frequency of ~1 s
-1
that a process based on the use of sulfuric acid could
potentially be useful.
3
1.4: Development of Systems that are Not Inhibited by Water
Theoretical and experimental studies show, Figure 15, that inhibition of the
Pt(bipyrimidine)Cl
2
system results from the ground state stabilization (~10 kcal/mol
relative to the HSO
4
-
complex) of the platinum complex by reversible binding to
0.0
0.5
1.0
1.5
2.0
67 8 9 10 11
D
2
SO
4
acidity, –H
0
k
H/D
x10
4
, s
-1
0.0
0.5
1.0
1.5
2.0
67 8 9 10 11
D
2
SO
4
acidity, –H
0
k
H/D
x10
4
, s
-1
NN
NN
Pt
Cl
Cl
28
water or methanol. Consequently, the key to developing improved systems is to
develop C-H activation systems that are not inhibited by water and are stable to the
conditions required for functionalization to occur.
0.0; A
1
3 8.0 , T S
1
36 .0 , T S
2c
32 .1 ; B
20 .9; C
3
Δ H (sol, 0K ) in kcal/m ol
-2.6
6.4
Water complex
HSO
4
-
complex
dichloride
Figure 15. Inhibition of the Pt(bipyrimidine)Cl
2
system by water in sulfuric acid.
While many think of the C-H activation reaction as the breaking of the C-H
bond, it is instructive to think of C-H activation as composed of two steps, 1)
coordination of the C-H bond and 2) cleavage of the C-H bond. This is shown
schematically in Figure 12. Indeed, studies by Periana et al. have shown that in
some cases (particularly in systems that activate by electrophilic substitution) that the
bulk of the activation barrier for the overall C-H activation reaction (and formation
29
of the M-C intermediate) can be associated with coordination of the C-H bond to the
metal center rather than with the actual breaking of the C-H bond. In the case of the
Pt(bipyrimidine)Cl
2
system the thermodynamics associated with coordination of the
alkane to the platinum center contributes approximately 32 kcal/mol while the
activation barrier for cleavage from the resulting alkane complex is only 4 kcal/mol,
Figure 15.
23
It is useful to distinguish between the steps because it is likely that the stereo-
and electronic requirements for binding of the alkane and cleavage of the C-H bond
are different. As shown in Figure 16, the key challenge in designing complexes that
would not be inhibited by water is to destabilize the catalyst ground state (e.g., the
water complex) without proportionately destabilizing the transition state for the C-H
cleavage step. While this would be expected to be challenging, it should be possible
given the differences in bonding between the states.
30
Figure 16. Proposed ground state destabilization of C-H activation.
To address the issue of water inhibition, the Periana group has been focused
on developing systems that are capable of the following: A) stable to the conditions
required for product formation, B) operate at a turnover frequency, TOF, of ~1 s
-1
, C)
not inhibited by water or other desired products and D) the M-C intermediate can
readily be functionalized to products.
3
Periana plans to do this by working with
more electropositive metals. Low valent metals to the left of platinum, such as
iridium, on the periodic table should be less electronegative than platinum, and thus
show decreased binding to water. The use of stronger donor ligands will also assist
by increasing the electron density at the metal. This serves to make the metal more
electron rich such that water binding should be more repulsive than in a less electron
Coordination Alkane Complex
C-H Cleavage
Cleavage TS
M
X L
L L
M
CH
4
L
L L
M
C
H
3
L
L L
H
X
M
C H
3
L
L L
+H X
+CH
4
Activation
Barrier for
C-H Activation
+X
-
Can we destabilize the ground state
without destabilizing the transition
state to a greater extent
Is it possible to destabilize the ground
state while simultaneously stabilizing
the transition state.
Can we destabilize the ground state
without destabilizing the transition
state to a greater extent?
Is it possible to destabilize the ground
state while simultaneously stabilizing
the transition state?
31
rich metal. A direct way to make the metal more electron rich is to modify the
ligand set such that stronger donor ligands are present. In the case of
Pt(bipyrimidine)Cl
2
, we propose that by changing the bipyrimidine ligand set to
bipyridine and by further placing a phenyl group on the platinum should ultimately
make the platinum(II) center more electron rich, see chapter 2.
One of the major limitations to the Pt(bipyrimidine)Cl
2
system was that it
operated in strongly acidic media, H
2
SO
4
. As a result, it was not cost effective to
separate the product methanol from the solvent. Therefore, we have also been trying
to work in less acidic media. Preliminary work by Ziatdinov et al. in our group has
shown that by using picolinate, a monoanionic ligand, in place of bipyrimidine
allowed for the synthesis of a more active H/D exchange catalyst. Whereas the
Pt(bipyrimidine)TFA
2
, where TFA = trifluoroacetate, was not active for H/D
exchange between benzene and trifluoroacetic acid, the Pt(picolinate)(TFA)
2
complex was competent for the H/D exchange of benzene in trifluoroacetic acid.
Calculations for the Pt(picolinate)TFA
2
system also predicted that the barrier for
coordination of the C-H bond of benzene is lower by ~9 kcal/mol and the barrier for
cleavage of the C-H bond is lower by ~6 kcal/mol relative to the
Pt(bipyrimidine)TFA
2
complex, Figure 17.
24
32
Figure 17. Energy diagram for Pt(bipyrimidine)TFA
2
and Pt(picolinate)TFA
2
,
where N-N = bipyrimidine and N-O = picolinate, for the activation
of benzene in trifluoroacetic acid.
As new systems are created that are capable of activating the C-H bond, it is
also possible that other pathways for functionalization of the resulting M-C
intermediates will be discovered. Our group has been investigating alternative
pathways by which these low valent metal alkyls could be functionalized to generate
new products. Early work by Conley et al. of our group showed that methyl
trixoxorhenium, MTO, can be functionalized by a wide variety of O-atom donor
reagents to generate methanol. Mechanistic studies suggest that the functionalization
occurs by insertion of the oxygen into the Re-Me bond via Bayer-Villiger type
transition state.
25
The rhenium center in MTO is rhenium(VII), which is in its
highest oxidation state, whereas we believe that the C-H activation by metals similar
to rhenium will occur in the lower oxidation states. As a result, it is important that
we look for functionalization possibilities with low valent metal alkyls.
33
To address this issue of functionalizing a low valent metal alkyl our group
found another pathway in the process of functionalizing a Re
I
-Me complex,
Re(CO)
5
Me. Preliminary results show that the methyl is being transferred to
Se
IV
O(OH)
2
to yield CH
3
Se
IV
O(OH) in a quantitative fashion. The CH
3
Se
IV
O(OH)
is then further functionalized by periodate to yield methanol. Further work is
ongoing to investigate the mechanism of this reaction.
26
We believe that by coupling
the C-H activation to these new functionalization pathways it should be possible to
convert alkanes to functionalized products by catalysts that are not inhibited by the
products.
The following chapters will detail work related to the synthesis of platinum
and iridium complexes with cyclometallated NNC ligands, where NNC = 6-phenyl-
2,2’-bipyridine, for the activation of hydrocarbons in acidic media and water.
Mechanistic studies were done on these complexes to better understand them with
the goal of designing more active catalysts. Eventually, I address water solubility of
catalysts by synthesizing water soluble NNC ligands and studying these water
soluble cyclometallated iridium(III) complexes in basic aqueous media.
34
1.5: References
1
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2
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3
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6
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7
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Yu. S.; Moravsky, A. P.; Shilov, A. E . New J. Chem. 1983, 7. (q) Sakakura, T.;
Sodeyama, T.; Sasaki, K.; Wada, K.; Tanaka, M. J. Am. Chem. Soc. 1990, 112,
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9
(a) Periana, R. A.; Taube, D. J.; Gamble, S.; Taube, H.; Satoh, T.; Fuji, H.
Science 1998, 280, 560. (b) Periana, R. A.; Taube, D. J.; Evitt, E. R.; Loffler, D.
G.; Wentrcek, P. R.; Voss, G.; Masuda, T. Science 1993, 259, 340. (c) Periana,
R. A.; Mironov, O.; Taube, D. J.; Bhalla, G.; Jones, C. J. Science 2003, 301,
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Oxgaard, J.; Goddard, W. A., III Angew. Chem., Int. Ed. 2004, 43, 4626. (e)
Periana, R. A.; Taube, D. J.; Evitt, E. R.; Loffler, D. G.; Wentrcek, P. R.; Voss,
G.; Masuda, T. Stud. Surf. Sci. Catal. 1994, 81, 533. (f) Periana, R. A. Adv.
Chem. Ser. 1997, 253, 61.
10
(a) Sherry, A. E.; Wayland, B. B. J. Am. Chem. Soc. 1990, 112, 1259. (b)
Wayland, B. B.; Ba, S.; Sherry, A. E. J. Am. Chem. Soc. 1991, 113, 5305.
11
Labinger, J. A.; Bercaw, J. E. Nature 2002, 417, 507.
12
(a) Watson, P. L. J. Am. Chem. Soc. 1983, 105, 6491. (b) Thompson, M. E.;
Baxter, S. M.; Bulls, A. R.; Burger, B. J.; Nolan, M. C.; Santarsiero, B. D.;
Schaefer, W. P.; Bercaw, J. E. J. Am. Chem. Soc. 1987, 109, 203.
13
Gunnoe, T. B. Eur. J. Inorg. Chem. 2007, 1185; and citations therein.
14
(a) Boller, T. M.; Murphy, J. M.; Hapke, M.; Ishiyama, T.; Miyaura, N.;
Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 14263; and references therein.
15
Goldman, A. S.; Roy, A. H.; Huang, Z.; Ahuja, R.; Schinski, W.; Brookhart, M.
Science 2006, 312, 257.
16
(a) Jessop, P. G.; Morris, R. H. Coord. Chem. Rev. 1992, 121, 155. (b)
Heinekey, D. M.; Oldham, W. J., Jr. Chem. Rev. 1993, 93, 913. (c) Kubas, G. J.
Acc. Chem. Res. 1988, 21, 120. (d) Huhmann-Vincent, J.; Scott, B. L.; Kubas,
G. J. J. Am. Chem. Soc. 1998, 120, 6808. (e) Kubas, G. J. J. Organomet. Chem.
2001, 635, 37.
17
a) Olah, G. A. Acc. Chem. Res. 1987, 20, 422. b) Olah, G. A.; Prakash, G. K. S.
Sommer, J. Superacids, Wiley & Sons: New York, USA, 1985.
18
(a) Geftakis, S.; Ball, G. E. J. Am. Chem. Soc. 1998, 120, 9953. (b) Gross, C.
L.; Girolami, G. S. J. Am. Chem. Soc. 1998, 120, 6605. (c) Gould, G. L.;
Heinekey, D. M. J. Am. Chem. Soc. 1989, 111, 5502. (d) Northcutt T. O.; Wick
D. D.; Vetter A. J.; Jones W. D. J. Am. Chem. Soc. 2001, 123, 7257.
19
Johansson, L.; Tilset, M. J. Am. Chem. Soc. 2001, 123, 739.
38
20
Basolo, F.; Pearson, R. G. Mechanisms of Inorganic Reactions, 2
nd
Ed.; Wiley,
John and Sons: New York, USA, 1967.
21
(a) Klei, S. R.; Golden, J. T.; Burger, P.; Bergman, R. G. J. Mol. Catal. A. 2002,
189, 79. (b) Tellers, D. M.; Yung, C. M.; Arndtsen, B. A.; Adamson, D. R.;
Bergman, R. G. J. Am. Chem. Soc. 2002, 124, 1400. (c) Burger, P.; Bergman, R.
G. J. Am. Chem. Soc. 1993, 115, 10462.
22
Mironov, O. A. Ph.D. Thesis, University of Southern California, Los Angeles,
CA, Aug 2006.
23
(a) Kua, J.; Xu, X.; Periana, R. A.; Goddard, W. A., III Organometallics 2002,
21, 511. (b) Muller, R. P.; Phillipp, D. M.; Goddard, W. A., III Top. Catal.
2003, 23, 81.
24
Ziatdinov, V. R.; Oxgaard, J.; Mironov, O. A.; Young, K. J. H.; Goddard, W.
A., III; Periana, R. A. J. Am. Chem. Soc. 2006, 128, 7404; and references
therein.
25
(a) Conley, B. L.; Ganesh, S. K.; Gonzales, J. M.; Tenn, W. J., III; Young, K. J.
H.; Oxgaard, J.; Goddard, W. A., III; Periana, R. A. J. Am. Chem. Soc. 2006;
128, 9018. (b) Gonzales, J. M.; Distasio, R., Jr.; Periana, R. A.; Goddard, W. A.,
III; Oxgaard, J. J. Am. Chem. Soc. 2007, 129, 15794.
26
Tenn, W. J., III; Conley, B. L.; Ahlquist, M. L.; Oxgaard, J.; Goddard, W. A.,
III; Periana, R. A. manuscript in preparation.
39
Chapter 2: Heterolytic C-H activation by a Cyclometallated
Pt(NNC)X Complex.
2.1: Introduction
Homogeneous catalysts that operate by C-H activation currently show the
greatest potential for the development of new, selective, hydrocarbon oxidation
chemistry.
27
Many of the new systems currently being studied utilize neutral
bidentate nitrogen ligands with platinum.
28
Recently a monoanionic bidentate
nitrogen ligated platinum(II) system has been reported by Baker and Bercaw and
shown to undergo C-H activation.
29
Peters et al. have recently reported a
monoanionic tridentate amido NNN platinum(II) pincer complex that activates the
C-H bond of benzene in the presence of a bulky organic base.
30
We previously
reported a bidentate, nitrogen ligated, electrophilic platinum(II) bipyrimidine
catalyst, Pt(bpym)Cl
2
(bpym = κ
2
-2,2'-bipyrimidine), for the direct conversion of
methane to methylbisulfate in 70 % yield and greater than 90 % selectivity in
concentrated sulfuric acid.
27a
Studies indicated that this catalyst system operates via
a C-H activation/functionalization reaction sequence involving a Pt-CH
3
intermediate.
27a,31
The key limitation of this system is inhibition of the catalyst with
decreasing acidity of the sulfuric acid solvent as the reaction products, H
2
O and
CH
3
OH increase beyond 1 M.
Consistent with the inhibition of the Pt(bpym)Cl
2
system by weaker acid
solvents, the related Pt(bpym)(TFA)
2
complex (TFA = trifluoroacetate) shows no
H/D exchange with methane in CF
3
CO
2
D (Hammett acidity, H
0
= -2.6). As with
40
most systems examined in detail,
33g,34b,37b
theoretical and experimental studies show
that the overall activation energy for C-H activation with the Pt(bpym)Cl
2
/H
2
SO
4
system results from two key barriers: A) hydrocarbon (R-H) coordination and B)
C-H cleavage defined as shown in, Figure 18. Of these two contributions, the ΔH for
methane coordination (27 kcal mol
-1
, L = X = HSO
4
-
) far outweighs the ΔH
‡
for C-H
cleavage (5 kcal mol
-1
).
31, 32
Further, calculations show that the inhibition by H
2
O
results from ground state stabilization, L = H
2
O in Figure 18, that increases the ΔH
for methane coordination by 7 kcal mol
-1
, rather than from destabilization of the
transition state (TS) for C-H cleavage.
31b
M
X
L
+ R ‐H
M
X
H
R
L +
M
R
L
H ‐X +
ΔH for C-H Coordination
ΔH
‡
for C-H Cleavage
L
M
X
H
R
+
Figure 18. Generalized energy diagram emphasizing the two key steps involved in
the C-H activation reaction: R-H coordination and C-H cleavage.
41
One strategy that Periana et al. are exploring to increase the rate of C-H
activation and overcome water inhibition is to develop more electron rich platinum
catalysts that are sufficiently stable to protic, oxidizing media. Conceptually,
increasing electron density at the platinum(II) center is expected to reduce H
2
O or
CH
3
OH binding to the sigma acceptor orbitals on platinum(II) since H
2
O and
CH
3
OH are good σ- or π-donors but not π-acids, thereby minimizing inhibition by
destabilizing the ground state.
32
Assuming that binding of the hydrocarbon, R-H, (as
shown in Figure 18) is not the rate determining step, then the activation barrier for
the overall C-H activation reaction will depend on the energy differences between
the ground state, L-M-X, and the C-H cleavage transition state (i.e. the energetics for
binding R-H is not relevant to the overall activation barrier). Under these
circumstances, the key to obtaining a net reduction in the barrier for C-H activation
in weakly acidic solvents is to ensure that the degree of destabilization of the ground
state brought about by ligand modifications is greater than the destabilization for the
C-H cleavage transition state.
Significantly, unlike non-transition metal ions such as mercury(II),
platinum(II) can potentially interact in the TS for C-H cleavage with both σ-acceptor
and π-donor orbitals.
33
In the Pt(bpym)Cl
2
/H
2
SO
4
system, the C-H bond was shown
theoretically to be cleaved by an electrophilic substitution (ES) pathway that
involves C-H donor interactions to σ-acceptor orbitals on platinum(II).
31
Increasing
electron density at the metal center in a weaker acid solvent, H-X, could be expected
42
to destabilize the transition state for this mode of cleavage assuming that the metal
center still behaves as an electrophile. If the C-H cleavage continues to proceed via
an ES pathway, increasing electron density at the platinum center could lead to an
increase in the C-H cleavage transition state (either minor or significant). However,
if the dominant pathway for C-H cleavage switches to an insertion (oxidative
addition (OA)) pathway (by interactions between the C-H σ*-bonding orbitals and
π-donor orbitals on platinum(II)), followed by rapid proton loss, then a net decrease
in the overall barrier for C-H activation might be possible by ligand modifications
that increase electron density at the platinum center. Therefore, it should be possible
to stabilize the C-H cleavage by insertion as well as destabilize water coordination
by increasing the electron density at platinum(II). Herein, I report on the synthesis
of an electron rich, thermally stable, monoanionic, tridentate, pincer, platinum NNC
complex, Pt(NNC)TFA (NNC = κ
3
-6-phenyl-4,4’-di-tert-butyl-2,2’-bipyridine), and
experimental and theoretical comparison of the reactivity for C-H activation relative
to the Pt(bpym)(TFA)
2
system.
2.2: Results and Discussion
It is now well established that the tridentate pincer ligand motif can impart
both thermal stability and reactivity to transition metal complexes.
34
This has been
demonstrated with the thermally stable PCP-Ir systems of Kaska, Jensen and
Goldman
35
that catalyzes the thermal dehydrogenation of alkanes. The tridentate
ligand 6-phenyl-2,2’-bipyridine and its derivatives have been shown to readily form
43
stable, cyclometallated complexes with platinum.
36
However, most of the interest in
these complexes has been focused on the photoluminescent properties, and to our
knowledge no catalysis studies have been reported. The corresponding
cyclometallated NNC platinum(II) chloride complex, 1, Pt(NNC)Cl, was prepared
following the procedures previously published by Lu et al.
36c
Complex 1 was
synthesized by heating the NNC ligand with K
2
PtCl
4
in glacial acetic acid. In order
to create a potentially active catalyst, the chloride was replaced with a more labile
leaving group using silver trifluoroacetate to obtain the corresponding
trifluoroacetate complex (3), Pt(NNC)TFA in good yields, Scheme 3. Complex 3 is
air stable and was fully characterized by
1
H and
13
C NMR, mass spectrometry and
elemental analysis. All expected, nine, aromatic resonances were observed, and
platinum satellites (J
Pt-H
= 33 Hz) were observed for the ortho-proton on the
cyclometallated phenyl ring of 3.
Scheme 3. Synthesis of Pt(NNC)X complex 3.
To ensure that complex 3 was acid and thermally stable, it was heated in
trifluoroacetic acid for eleven hours at 200
o
C under argon. The resulting clear,
44
homogeneous solution was evaporated, washed with water followed by extraction
with CH
2
Cl
2
and evaporation. The residue was dissolved in CDCl
3
containing 1,3,5-
trimethoxybenzene as an internal standard. No insoluble platinum metal was visible,
and analysis by
1
H NMR showed no significant decomposition of 3. Complex 3 was
recovered with 91 % mass balance with minor amounts of what is believed to be the
ion pair or solvent coordinated, solvento, complex.
Dissolution of 3, an orange solid, in CH
2
Cl
2
results in an orange solution.
Consistent with the desired destabilization of the ground state and lability of the
trifluoroacetate by use of the more electron rich NNC ligand, solvation of 3 in
CF
3
CO
2
H leads to a blue solution that we believe is due to acid-assisted dissociation
of the trifluoroacetate ligand and formation of [Pt(NNC)]
+
TFA
-
complex either as a
three-coordinate ion-pair or solvento complex. Evidence for this is that removal of
the CF
3
CO
2
H in vacuo leads to a blue residue. Treatment of the residue with a
mixture of water and CH
2
Cl
2
, and subsequent evaporation of the CH
2
Cl
2
layer leads
to quantitative recovery of 3 as a yellow-orange solid. Additional evidence that the
blue solution results from dissociation of the TFA
-
ligand is the observation that
when orange CD
2
Cl
2
solutions of 3 are treated with the poorly coordinating, strong
Lewis acid, B(C
6
F
5
)
3
, a dark blue-black solid is generated. Consistent with the
expected lability of the TFA
-
, reaction of the blue solution of 3 in CF
3
CO
2
H with
excess LiCl leads to immediate formation of the yellow-orange chloride derivative,
Pt(NNC)Cl, 1. While, a three-coordinate ion-pair or solvento complex best fits these
observations, another possibility is that the complex becomes protonated in the
45
presence of added CF
3
CO
2
H to generate a platinum(IV) hydride. However,
1
H NMR
studies in which CF
3
CO
2
H (3.8 equivalents) was added to a solution of 3 in CD
2
Cl
2
at –70
o
C did not show any evidence of a protonated platinum species.
The formation of the ion-pair can be rationalized as the acidic media
competes with the electrophilic platinum center for the Lewis basic trifluoroacetate
ligand. It has been suggested that the blue residue was occurring through
protonation of the TFA ligand bound to the platinum center. This in essence is what
we believe is occurring through the ion-pair formation. The acidic media would
rather share the proton, H
+
, between two weak bases, CF
3
CO
2
-
, to generate the more
stable adduct, [(CF
3
CO
2
-
)
2
H
+
]. It is not known whether this is an intimate ion-pair or
loose ion-pair. Furthermore, comments were made suggesting that the protonation of
the acid ligand would create an electrophilic Lewis acid in which the H/D exchange
is all acid mediated by the Lewis acid. Similar arguments were made concerning the
Hg(HSO
4
)
2
/H
2
SO
4
system. One would expect that Zn(HSO
4
)
2
would be a better
Lewis acid; however, in the presence of sulfuric acid and methane no H/D exchange
is observed using Zn(HSO
4
)
2
as the catalyst. Therefore, we would propose that if the
complex were acting merely as a Lewis acid, then the use of any better but similar
Lewis acid should generate more facile rates for H/D exchange.
Having established that 3 is thermally stable under protic conditions and the
trifluoroacetate ligand was labile in CF
3
CO
2
H solvent, the efficiency for catalyzing
the H/D exchange reactions between methane and CF
3
CO
2
D or D
2
SO
4
was
investigated and compared to the reference system, Pt(bpym)(TFA)
2
. As was the
46
case for the Pt(bpym)(TFA)
2
system, 3 was also found to be inactive for catalyzing
the H/D exchange between methane and CF
3
CO
2
D at temperatures as high as 200
o
C. Significantly, however, while solutions of the Pt(bpym)(TFA)
2
in CF
3
CO
2
D are
stable in both the presence and absence of methane, 3 decomposed at 200
o
C to
colloidal platinum in the presence of methane. Since the control studies showed that
trifluoroacetic acid solutions of 3 are thermally stable at 200
o
C in the absence of
methane, these results suggest that a reaction between methane the Pt(NNC)TFA
complex occurred in CF
3
CO
2
D. This potentially interesting result could not further
be investigated due to the instability of 3 in trifluoroacetic acid.
Interestingly, catalytic H/D exchange between methane and sulfuric acid
could be observed with the Pt(NNC)Cl, 1, without obvious decomposition, but at a
rate 10 times slower than the Pt(bpym)Cl
2
system. Thus, heating 1 in D
2
SO
4
with
methane (500 psi) for 10 hours at 180
o
C resulted in 14 % conversion of methane to
the deuterated methane isotopologs, (CH
3
D 5.39 %, CH
2
D
2
2.53 %, CHD
3
2.3 %,
CD
4
4.2 %), with a turnover-number (TON) of 61.70 and a turnover-frequency
(TOF) of 1.61 x 10
-3
s
-1
. However, unlike the Pt(bpym)Cl
2
, which was efficient for
methane functionalization, only a small amount of methylbisulfate production (TON
of ~2) was observed. This suggests that 1 may not undergo efficient
functionalization of the Pt-CH
3
intermediate in sulfuric acid, an oxidizing acid.
To further investigate the chemistry of this, (NNC)PtTFA, system I turned to
benzene as a substrate as the barriers for C-H activation could be expected to be
lower. The system should also be more stable and amenable to fundamental study in
47
the less acidic, non-oxidizing acid solvent, CF
3
CO
2
H, than in sulfuric acid. Complex
3 is soluble in benzene at elevated temperatures; therefore, I investigated whether the
stoichiometric C-H activation, Scheme 4, would proceed to generate the phenyl
complex, Pt(NNC)Ph, 4. In situ
1
H NMR analyses showed that no reaction was
observed after heating 3 in C
6
D
6
for 12 hours at 180
o
C. To investigate whether this
was due to unfavorable thermodynamics or kinetics I used DFT to calculate the
ΔH
rxn
for the formation of 4 from reaction of benzene with 3 as shown in Scheme 4.
All theoretical calculations were performed with the B3LYP
37,38
density functional,
in combination with the Jaguar 6.0
39,40
computational package. Platinum was
described with the effective core potential of Hay and Wadt
41
while all other atoms
used the 6-31G**
39
all electron basis set. The effects of diffuse functions were
included with single point calculations. Solvation effects in trifluoroacetic acid
(computed via single point corrections) were modeled implicitly with the PCM
42,43
model ( ε = 8.55, solvent radius = 2.451 Å). The calculations show that the C-H
activation reaction, Scheme 4, (assuming trifluoroacetic acid as solvent) is
unfavorable by 18 kcal mol
-1
(vide infra) and that the equilibrium concentration of
the likely C-H activation product, Pt(NNC)Ph, 4, would be too low to observe. In an
attempt to shift the equilibrium of the reaction towards formation of the C-H
activation product, 3 was heated in neat benzene at 160
o
C with Hunig’s base (N,N-
diisopropylethyl amine) with the belief that this base would accept the proton in the
C-H cleavage further stabilizing the products. However, no phenyl product was
observed in this reaction and 3 was recovered.
48
Scheme 4. The stoichiometric C-H activation of benzene with 3.
To examine whether 4 could be reversibly generated by C-H activation, I
investigated whether 3 could catalyze the H/D exchange between benzene and
trifluoroacetic acid. When the reaction was carried out at 180
o
C with a 1:4 by
volume mixture of benzene (C
6
H
6
) and deuterated trifluoroacetic acid (CF
3
CO
2
D),
respectively, catalytic incorporation of deuterium into benzene was observed to
generate C
6
H
5
D with a TOF of 8.18 x 10
-3
sec
-1
(TON of 14.7 after 30 minutes).
Almost no other benzene isotopologs, e.g. C
6
H
4
D
2
or higher, are observed at TON
below 60 suggesting that H/D exchange occurs via sequential, as opposed to parallel
formation of the isotopologs C
6
H
5
D
1
Æ C
6
H
4
D
2
Æ etc.
33g,34c,44
At these
temperatures, control experiments in the absence of 3 show that some H/D exchange
occurs between C
6
H
6
and CF
3
CO
2
D and the reported H/D exchange rates are
corrected for this background activity (see experimental section).
A plot of TON versus time shows a linear increase (see experimental
section), which suggests that the catalytic system is stable over time. Complex 3
could also be isolated from the C
6
H
6
/CF
3
CO
2
H reaction mixtures by quenching the
49
reaction with water followed by extraction with CH
2
Cl
2
and evaporation. Both
1
H
and
19
F NMR analyses of the solid residue confirmed that 3 could be recovered in
92 % yield based on internal standardization with 1,3,5-trimethoxybenzene.
Consistent with the theoretical calculations showing that the expected phenyl
complex, 4, is less stable than 3, complex 4 was never isolated in these experiments.
The H/D exchange reactions were carried out at several temperatures between 160
and 190
o
C and the activation barrier was determined to be E
a
= 32.4 ( ± 2.5) kcal
mol
-1
(Figure 19). Significantly, under similar conditions, the related system,
Pt(bpym)(TFA)
2
was found to be more active for H/D exchange between C
6
H
6
and
CF
3
CO
2
D with an activation barrier of E
a
= 27 kcal mol
-1
.
32a
50
R
2
= 0.9766
-7.3
-6.3
-5.3
-4.3
0.00214 0.00222 0.0023
1/T (1/K)
ln(k)
Figure 19. Plot of ln(k) versus 1/(Temperature (K)) for the H/D exchange of
CF
3
CO
2
D and C
6
H
6
using 3 as a catalyst.
Given the central importance of the phenyl complex, Pt(NNC)Ph, 4, in the
expected mechanism for H/D exchange, I synthesized this material for study. The
phenyl complex was obtained by heating the chloro complex, 1, with diphenyl zinc
in THF at 80
o
C. The compound was fully characterized by
1
H and
13
C NMR, mass
spectrometry, elemental analysis, and X-ray crystallography. Suitable crystals of 4
were grown by slow vapor diffusion of pentane into a benzene solution. As can be
seen in the thermal ellipsoid plot in Figure 20, the ligand binds in a tridentate fashion
with the phenyl ring [C(26)-C(25)-Pt(1)-C(16)] at a 60.9
o
angle to the plane of the
ligand. Consistent with the phenyl complex as an intermediate in the proposed
mechanism for H/D exchange, complex 4 was found to catalyze the H/D exchange
51
between benzene and trifluoroacetic acid at 180
o
C with a similar TOF (9.1 x 10
-3
s
-1
)
as that of 3 (8.18 x 10
-3
s
-1
). Treatment of 4 with an equivalent of trifluoroacetic acid
results in the formation of benzene-H
6
and the trifluoroacetate complex, 3. The
instability is consistent with calculations that suggest that 4 is unstable with respect
to 3, Scheme 4. Significantly, when CF
3
CO
2
D was used for the protonolysis only
C
6
H
5
D was observed, no other isotopologs of benzene were observed. This is
consistent with the observed sequential isotopolog formation from the H/D exchange
with CF
3
CO
2
D/C
6
H
6
mixtures, vide supra.
Figure 20. Thermal ellipsoid plot of 4 with 50 % probability. Hydrogens and
benzene co-solvent were removed for clarity. Selected bond
distances (Å) and angles (º) are as follows: Pt(1)-C(16), 1.990(4);
Pt(1)-N(1), 2.116(3); Pt(1)-N(2), 2.006(3); Pt(1)-C(25), 2.014(4);
N(2)-Pt(1)-C(25), 179.65(15); C(16)-Pt(1)-N(1), 159.50(13).
52
Figure 21. Energy diagram (calculated enthalpies) for the C-H activation of
benzene by the Pt(NNC)TFA system in trifluoroacetic acid.
To further understand how the C-H activation occurs at the platinum center
of 3, I turned to DFT calculations, Figure 21. Significantly, the calculations show
that stabilization of the trifluoroacetate, TFA
-
, anion with an explicit CF
3
CO
2
H,
HTFA, solvent molecule, [TFA-H-TFA]
-
, is required to correlate the theoretical data
with the experimental data. The calculations show that the global ground state is a
solvent coordinated species, [Pt(NNC)(HTFA)]
+
[TFA]
-
, 2, that is 1.8 kcal mol
-1
lower in energy than 3. The -1.8 kcal/mol value listed for the solvento complex is
the relative energy with respect to the reference reactant computed using solvent
optimized structures and energetics. All other values are enthalpies using gas-phase
structures with single point solvation corrections. The calculations showing that 2
and 3 differ by a small amount of energy, -1.8 kcal mol
-1
, is consistent with the
4 5
4 0
3 5
3 0
2 5
2 0
1 5
1 0
5
0
- 5
Pt
O
O
C F
3
N
N
- 1 . 8
P t O
O
C F
3
H
O
O
C F
3
0
Pt TFA
34.3
9.1
Pt
28.2
18.7
2 6. 4
Pt
O
O
CF
3
H
Pt
H
Pt Pt H
Pt H
O
O
CF
3
3 9 . 8
Ox id a t iv e addition
E l ec t r o ph ilic Substitution
[2 ]
[3]
[5]
[4]
[TS4]
[TS3]
[TS2]
[6]
53
experimental observations. Upon heating the blue CF
3
CO
2
H solutions (believed to
be due to TFA
-
ionization) of 3 (an orange solid) the color reversibly changes to
reddish-orange.
In order to make better use of the energies listed in Figure 21, I decided to
compare calculations of the Pt(bpym)(TFA)
2
system with those in Figure 21 to
understand why 3 was slower for C-H activation. The comparison between the
Pt(NNC)TFA system and the Pt(bpym)(TFA)
2
system can be seen in Figure 22 As
can be seen, in accordance with experimental results, the calculations predict that the
Pt(NNC)TFA system has a higher overall barrier for the C-H activation reaction
compared to the Pt(bpym)(TFA)
2
system. C-H activation can be defined as a two
step process; 1) hydrocarbon coordination, and 2) C-H cleavage, and the barrier for
this process is the sum of these two steps. As observed in earlier theoretical studies
with methane in sulfuric acid,
31
the lowest energy pathway identified for the
Pt(bipyrimidine)TFA
2
system
32a
involves benzene coordination ( ΔH = 14.1 kcal mol
-
1
) via a dissociative process (that can be considered an upper limit for this step),
followed by C-H cleavage via electrophilic substitution (ES), TS-1, ( ΔH
‡
= 13.2
kcal mol
-1
), Figure 22. The predicted value (which is the sum of these two steps) of
the overall C-H activation barrier, ΔH
‡
= 27.3 kcal mol
-1
for the Pt(bpym)(TFA)
2
system is consistent with the experimental activation barrier of ~27 kcal mol
-1
.
54
Figure 22. Energy diagram for Pt(NNC)TFA and Pt(bipyrimidine)TFA
2
systems.
Interestingly, contrary to our expectations that C-H cleavage by
Pt(NNC)TFA could proceed by a lower energy pathway involving an insertion (as
opposed to ES) pathway followed by rapid proton loss, the pathway that best fits the
experimental activation energy of ~32 kcal mol
-1
is one involving C-H activation via
benzene coordination, 5, ( ΔH = 9.1 kcal mol
-1
via an upper limit dissociative
process) and cleavage via electrophilic substitution (ES), TS-2, ( ΔH
‡
= 25.2 kcal
mol
-1
) for an overall barrier of ΔH
‡
= 34.3 kcal mol
-1
. The calculations do show, as
expected, that C-H cleavage by insertion (TS-3, ΔH
‡
= 19.1 kcal mol
-1
) is lower than
the ES pathway, TS-2. However, the energy diagram shows that reversible proton
loss from the product of C-H cleavage by insertion, [Pt
IV
(NNC)(Ph)(H)]
+
, 6, is a
higher energy pathway, TS-4, than the electrophilic substitution, TS-2, pathway.
Thus, the calculations and experiment show that our expectations were met that the
Pt(NNC)TFA would be: A) thermally stable to protic media, B) able to catalyze the
C-H activation reaction and C) able to reduce the ΔH for substrate coordination from
55
~14 for the Pt(bpym)(TFA)
2
system to ~9 kcal mol
-1
for the Pt(NNC)TFA system.
However, the expected reduction in the ΔH
‡
for
C-H cleavage with the Pt(NNC)TFA
system (~25 kcal mol
-1
and ~19 kcal mol
-1
via the ES and insertion pathways,
respectively) relative to the Pt(bpym)(TFA)
2
system (~13 kcal mol
-1
via an ES
pathway) was not realized and this accounts for the slower rates for C-H activation
using the Pt(NNC) system.
2.3: Conclusion
In conclusion, I report the synthesis of a new acid and thermally stable
cyclometallated 6-phenyl-4,4’-di-tert-butyl,-2,2’-bipyridine platinum(II)
trifluoroacetate complex, (3), that is more electron rich than the Pt(bpym)(TFA)
2
system. The results suggest that this complex, unlike Pt(bpym)(TFA)
2
, reacts with
methane in trifluoroacetic acid but decomposes. The complex catalyzes H/D
exchange with methane in sulfuric acid at a lower activity than the Pt(bpym)Cl
2
system and only low levels of methylbisulfate are generated. In a comparison to the
Pt(bpym)TFA
2
system for H/D exchange between C
6
H
6
and CF
3
CO
2
D I found that
the Pt(bpym)TFA
2
system is faster. Thus, my expectation that the more electron-rich
Pt(NNC)TFA system would minimize inhibition by H
2
O by ground state
destabilization did not lead to a more effective catalyst. Theoretical studies show
that while I was successfully able to lower the energetics for substrate coordination,
the concomitant increase in the C-H cleavage barrier was greater, which led to an
overall increase in the barrier for C-H activation. These results show that modifying
the Pt(bpym)Cl
2
system to increase the overall activity for methanol generation in
56
the presence of water will require a more detailed understanding and greater
predictability of the various structure-function relationships for coordination, C-H
cleavage, and oxidative functionalization.
2.4: Experimental
General Considerations: Unless otherwise noted all reactions were performed
using standard Schlenk techniques (argon) or in a MBraun glove box (nitrogen).
GC-MS analysis were performed on a Shimadzu GC-MS QP5000 (ver. 2) equipped
with a cross-linked methyl silicone gum capillary column (DB5) and GS-gaspro
column.
1
H and
13
C NMR spectra were collected on a Varian 400 Mercury plus
Spectrometer. Chemical shifts were referenced to TMS using residual protiated
solvent. All coupling constants are reported in hertz, Hz. Mass spectrometry
analyses were performed at the UCLA mass spec lab. Elemental analyses were
performed by Desert Analytical Laboratory, Inc.; Arizona. X-ray data was collected
on a Bruker SMART APEX CCD diffractometer.
Materials: K
2
PtCl
4
(Strem), 4,4’-di-tert-butyl-2,2’-dipyridyl (Aldrich),
phenyllithium (1.8 M in butyl ether, Aldrich) were used as received. All solvents
were reagent grade or better. Trifluoroacetic acid-d
1
(CIL) was used as received and
was degassed by freeze-pump-thaw cycles prior to use. Diethyl ether was dried over
sodium/benzophenone ketyl and distilled under argon. Dichloromethane (stabilizer
removed with sulfuric acid) was dried over P
2
O
5
and distilled under argon.
6-phenyl-4,4’-di-tert-butyl-2,2’-bipyridine was prepared following literature
57
procedures.
45
Hunig’s base (N,N-diisopropylethyl amine) was distilled and degassed
by several freeze-pump-thaw cycles prior to use.
Scheme 5. Synthesis of 1, Pt(NNC)Cl.
Synthesis of Pt(4,4’-tBu
2
(NNC))Cl (1): Complex 1 was prepared following
a modified procedure reported by Lu and coworkers.
45
A suspension of K
2
PtCl
4
(398 mg, 0.958 mmol) and 6-phenyl-4,4’-di-tert-butyl)-2,2’-bipyridine (300 mg,
0.870 mmol) in glacial acetic acid (10 mL) was heated at 120
o
C for 3 days. The
resulting orange suspension was allowed to cool to room temperature, and then
filtered over celite. The orange solid was washed with water (4 x 20 mL), ether (3 x
20 mL), and extracted with CH
2
Cl
2
. The product was then precipitated from CH
2
Cl
2
with pentane. Yielding 412 mg, 82.5 %
1
H NMR (CDCl
3
, 400 MHz): δ = 8.82 (d,
1H,
3
J = 5.8 Hz,
3
J
Pt-H
= 7.0 Hz, H-1), 7.75 (d, 1H,
4
J = 1.8 Hz, H-4), 7.62 (dd, 1H,
3
J
= 7.6 Hz,
4
J = 1.4 Hz,
3
J
Pt-H
= 21.6 Hz, H-15), 7.49 (dd, 1H,
3
J = 5.7 Hz,
4
J = 1.9 Hz,
H-2), 7.46 (d, 1H,
4
J = 1.6 Hz, H-7), 7.41 (d, 1H,
4
J = 1.6 Hz, H-9), 7.26 (dd, 1H,
3
J
= 7.7 Hz,
4
J = 1.4 Hz, H-12), 7.13 (dt, 1H,
3
J = 7.5 Hz,
4
J = 1.4 Hz, H-14), 7.00 (dt,
1H,
3
J = 7.5 Hz,
4
J = 1.4 Hz, H-13), 1.43 (s, 9H, -C(CH
3
)
3
), 1.41 (s, 9H, -C(CH
3
)
3
).
58
13
C {
1
H} NMR (CDCl
3
, 100 MHz): δ = 166.3 (C-16, J
Pt-C
= 53 Hz), 163.9 (C-8),
163.1 (C-3), 157.4 (C-5, J
Pt-C
= 26 Hz), 154.4 (C-6, J
Pt-C
= 17 Hz), 148.7(C-1, J
Pt-C
=
9 Hz), 147.1(C-10, J
Pt-C
= 36 Hz), 142.8 (C-11), 135.3 (J
Pt-C
= 25 Hz), 130.9 (J
Pt-C
=
22 Hz), 124.4 (J
Pt-C
= 5 Hz), 124.1 (J
Pt-C
= 23 Hz), 123.9 (J
Pt-C
= 13 Hz), 119.2 (J
Pt-C
=
8 Hz), 115.8 (J
Pt-C
= 24 Hz), 115.0 (J
Pt-C
= 19 Hz), 36.1 (-C(CH
3
)
3
), 35.9 (-C(CH
3
)
3
),
30.7 (-C(CH
3
)
3
), 30.6 (-C(CH
3
)
3
).
Scheme 6. Synthesis of Pt(NNC)OAc.
Synthesis of Pt(4,4’-tBu
2
(NNC))OC(O)CH
3
(2): A solution of 1 (24.6 mg,
4.29 x 10
-2
mmol) and silver acetate (20.9 mg, 0.125 mmol) in CH
2
Cl
2
(8 mL) was
stirred in the dark for 2 days. The resulting orange-brown solution was filtered over
celite, washed with CH
2
Cl
2
, and evaporated to dryness. The product was
recrystallized from CH
2
Cl
2
and pentane in a 96.8 % (24.8 mg) yield.
1
H NMR
(CDCl
3
, 400MHz): δ = 8.62 (d, 1H,
3
J = 5.8 Hz, H-1), 7.81 (d, 1H,
4
J = 1.7 Hz, H-4),
7.52 (dd, 1H,
3
J = 5.7 Hz,
4
J = 1.8 Hz, H-2), 7.45 (d, 1H,
4
J = 1.5 Hz, H-7), 7.36 (d,
1H,
3
J = 1.5 Hz, H-9), 7.23 (d, 1H,
3
J = 7.5 Hz, H-15), 7.14 (d, 1H,
3
J = 7.3 Hz, H-
12), 7.08 (t, 1H,
3
J = 7.3 Hz, H-14), 6.99 (dt, 1H,
3
J = 7.3 Hz,
4
J = 1.3 Hz, H-13),
2.19 (s, 3H, -OOCCH
3
), 1.40 (s, 9H, -C(CH
3
)
3
), 1.39 (s, 9H, -C(CH
3
)
3
).
13
C NMR
59
{
1
H} (CDCl
3
, 100 MHz): δ = 177.99, 166.80, 164.13, 163.56, 156.96, 155.08,
150.44, 146.99, 133.52, 130.66, 124.53, 124.22, 123.99, 119.23, 115.40, 114.72,
36.09 (-C(CH
3
)
3
), 35.88 (-C(CH
3
)
3
), 30.65 (-C(CH
3
)
3
), 30.52 (-C(CH
3
)
3
),
24.03(OOCCH
3
). ESI-MS: 598.2 (M+H)
+
.
Scheme 7. Synthesis of 3, Pt(NNC)TFA, from 1 and AgTFA.
Synthesis of Pt(4,4’-tBu
2
(NNC))OC(O)CF
3
(3): A solution of 1 (310.0 mg,
0.5400 mmol) and silver trifluoroacetate (125.2 mg, 0.5670 mmol) in CH
2
Cl
2
(30
mL) was stirred in the dark for 4 days. The resulting red solution was filtered over
celite to remove the silver chloride then evaporated to dryness. The solid was
redissolved in a minimal amount of CH
2
Cl
2
and precipitated with pentane, and
filtered to give an orange-red solid in 77.93% yield.
1
H NMR (CDCl
3
, 400 MHz): δ
= 8.30 (d, 1H,
3
J = 6 Hz, H-1), 7.69 (d, 1H,
4
J = 2 Hz, H-4), 7.45 (dd, 1H,
3
J = 6 Hz,
4
J = 2 Hz, H-2), 7.30 (d, 1H,
4
J = 2 Hz, H-7), 7.19 (d, 1H,
4
J = 2 Hz, H-9), 7.02 (d,
1H,
3
J = 8 Hz, H-15), 6.94 (m, 1H,
3
J = 7 Hz, H-14), 6.93 (m, 2H,
3
J = 7 Hz, H-13),
6.62 (d, 1H,
3
J = 7 Hz, H-12), 1.40 (s, 9H, -C(CH
3
)
3
), 1.39 (s, 9H, -C(CH
3
)
3
).
13
C
NMR {
1
H} (CDCl
3
, 100 MHz): δ = 166.1 (C-16), 164.1 (C-3), 163.8 (C-8), 162.3
60
(C(O)CF
3
, J
C-F
= 36.8 Hz), 156.6 (C-5), 155.1 (C-6), 150.1 (C-1), 146.9 (C-11),
132.8 (C-15), 130.5 (C-14), 124.5 (C-2), 124.4 (C-13), 124.0 (C-12), 119.6 (C-4),
115.7 (C(O)CF
3
, J
C-F
= 290.0 Hz), 115.4 (C-9), 115.1 (C-7), 35.8 (C-17), 35.6 (C-
21), 30.4 (C-18,19,20), 30.3 (C-22,23,24).
19
F NMR (CDCl
3
, 376 MHz): δ = -73.8
(s). Anal. Calc’d for C
26
H
27
F
3
N
2
O
2
Pt: C, 47.93 %; H, 4.18 %; F, 8.75 %; N, 4.30
%. Found: C, 47.64 %; H, 4.27 %; F, 8.51 %; N, 4.22 %. ESI-MS: 674.1 (M+Na)
+
,
652.2 (M+H)
+
.
Scheme 8. Synthesis of 4, Pt(NNC)Ph, from 1 and Ph
2
Zn.
Synthesis of Pt(4,4-tBu
2
-[NNC])phenyl (4): A solution of 1 (490.0 mg,
0.8536 mmol) and diphenylzinc (300.0 mg, 1.366 mmol) in THF (30ml) was heated
at 40
o
C for 2 h, then at 80
o
C for 8 h. The reaction was quenched with methanol,
and the solvent was removed in vacuo. The residue was extracted with CH
2
Cl
2
then
filtered over celite. The product was obtained as an orange solid after passing
through neutral alumina with a 1: 3 mixture of CH
2
Cl
2
: hexanes as the eluent
resulting in a 51.29 % yield.
1
H NMR (CDCl
3
, 400 MHz): δ = 8.54 (d, 1H,
3
J = 6
Hz, J
Pt-H
= 9 Hz, H-1), 7.87 (d, 1H,
4
J = 2 Hz, H-4), 7.74 (dd, 2H,
3
J = 6 Hz,
4
J = 1
61
Hz, J
Pt-H
= 27.9 Hz, H-18), 7.67 (s, 1H, H-7), 7.63 (d, 1H,
4
J = 1.2 Hz, H-9), 7.51
(dd, 1H,
3
J = 6 Hz,
4
J = 1 Hz, H-15), 7.44 (dd, 1H,
3
J = 4 Hz,
4
J = 2 Hz, H-2), 7.38
(d, 1H,
3
J = 8 Hz, H-12), 7.22 (t, 2H,
3
J = 7 Hz, H-19), 7.13 (dt, 1H,
3
J = 7 Hz,
4
J = 1
Hz, H-13), 7.07 (m, 2H, H-20), 1.46 (s, 9H, -C(CH
3
)
3
), 1.42 (s, 9H, -C(CH
3
)
3
).
13
C
NMR {
1
H} (CDCl
3
, 100 MHz): δ = 164.3 (C-16, J
Pt-C
= 50 Hz), 163.4 (C-8), 163.1
(C-3), 159.2 (J
Pt-C
= 11 Hz, C-5), 155.3 (C-25), 153.6 (J
Pt-C
= 14 Hz, C-6), 150.4 (J
Pt-
C
= 12 Hz, C-1), 148.0 (J
Pt-C
= 15 Hz, C-10), 144.3 (C-11), 138.9 (J
Pt-C
= 10 Hz, C-
26), 137.5 (J
Pt-C
= 45 Hz, C-12), 130.9 (J
Pt-C
= 39 Hz, C-13), 127.4 (J
Pt-C
= 32 Hz, C-
27), 124.4 (C-15), 124.2 (C-2), 123.3 (C-14), 122.1 (J
Pt-C
= 5 Hz, C-28), 119.3 (J
Pt-C
= 6 Hz, C-4), 115.4 (J
Pt-C
= 11 Hz, C-9), 114.3 (J
Pt-C
= 6 Hz, C-7), 36.1 (C-17), 35.8
(C-21), 30.8 (C-18,19,20), 30.5 (C-22,23,24). Anal. Calc’d for C
30
H
32
N
2
Pt: C, 58.53
%; H, 5.24 %; N, 4.55 %. Found: C, 58.06 %; H, 5.28 %; N, 4.58 %. APCI-MS:
616.3 (M+H)
+
, 556.3 (M-Ph+H
2
O)
+
, 538 (M-Ph)
+
.
Stability tests for 3: A Schlenk tube was charged with 3 (37.1 mg) in
trifluoroacetic acid (1.5 mL). The blue homogenous solution was then heated at 200
o
C for 11 hours. The solvent was removed under reduced pressure, extracted with
dichloromethane and washed with water. After removal of the solvent under reduced
pressure, 45 μL of a 0.3389 M solution of 1,3,5-trimethoxybenzene in CDCl
3
was
added to the mixture in CDCl
3
.
1
H NMR analysis showed that 3 was the major
species (with minor amounts of what is believed to be the ion-pair) and was
recovered with 91 % mass balance.
62
Reaction of Pt(4,4-tBu
2
-[NNC])TFA (3) with
tris(pentafluorophenyl)borane: In a J-young NMR tube 3 (16.9 mg, 0.0259 mmol)
was dissolved in CD
2
Cl
2
. A
1
H NMR spectrum was obtained, followed by the
addition of tris(pentafluorophenyl)borane (15.7 mg, 0.0306 mmol). Upon addition
of the borane complex, the solution immediately changed color from a reddish-
orange solution to a dark blue solution. After addition of the borane, a
1
H NMR
spectrum was obtained verifying that 3 completely reacted. There was primarily one
species present in the
1
H NMR in roughly 48 % mass balance (based on comparison
to residual solvent). After allowing the J-young NMR tube to set overnight, needle-
like microcrystals could be seen on the on the walls of the NMR tube; however,
these crystals were not suitable for X-ray diffraction.
63
Figure 23. (Top NMR)
1
H NMR of 3 in deuterated dichloromethane. (Bottom
NMR)
1
H NMR after 1.2 eq of tris(pentafluorophenyl)borane was
mixed with 3 in deuterated dichloromethane.
General Procedure for H/D exchange studies with methane: In a typical
reaction, approximately 6.5 to 9.0 mg of complex (1 or 3) was added to a 1.5 mL vial
along with a teflon stir bar, which was then placed into resealable metal reactor.
Under argon, 1.0 mL of solvent (sulfuric acid-d
2
or trifluoroacetic acid-d
1
) was
added to the metal reactor. The reactor was then stirred and pressurized with 500 psi
of methane. After pressurization, the reactor was stirred and heated to 180 or 200
o
C
for various times. A control reaction was also prepared without any catalyst in the
reaction mixture. The control was prepared to account for any H/D exchange
between the acid solvent and methane. Analysis of the H/D exchange with methane
was performed by analyzing the head space using GC-MS. The reactor was removed
NNC aromatic
protons
Residual NMR
solvent
tert ‐butyls
tert ‐butyls
Residual NMR
solvent
NNC aromatic
protons
The reaction initially starts our as a reddish ‐
orange solution, and addition of the borane
generates a blackish colored solution. Analysis
by
1
H NMR indicates that the aromatic protons
have shifted, which suggests that a reaction
occurred.
64
from the heating block and a vial with a septum (2 mL, flushed with argon prior to
being placed under vacuum) was pressurized with the head space from the metal
reactor. A 2.0 µL sample of the headspace was taken from the vial and analyzed by
GC-MS. Observation of methanol was performed by
1
H NMR analysis. A 10 µL
amount of glacial acetic acid was added to the reaction mixture and the mixture was
stirred to achieve homogeneity. This mixture was then placed in a NMR tube
containing and analyzed by
1
H NMR using the acetic acid as an internal standard.
Table 1. Data obtained from the H/D exchange studies of 1 with CH
4
and
sulfuric acid-d
2
.
Catalytic Reaction defined as 6.7 mg ( 0.012 mmol ) of 1 in 1 mL of D
2
SO
4
with 500 psi methane. Control reaction defined as 1 mL D
2
SO
4
and 500 psi
methane. Both reactions were heated for 640 minutes.
Methane
isotopologs
Catalytic
Reaction
Control
Reaction
"Control Reaction" subtracted
from "Catalytic Reaction"
CH
4
81.90% 96.34% 85.56%
CH
3
D 9.05% 3.66% 5.39%
CH
2
D
2
2.53% 0.00% 2.53%
CHD
3
2.30% 0.00% 2.30%
CD
4
4.22% 0.00% 4.22%
Stoichiometric benzene activation studies: To a resealable Schlenk tube
14.2 mg (0.0218 mmol) of 3 and 5.0 µL (0.029 mmol) of Hunig’s base was added to
1 mL of benzene. The tube was sealed and heated at 180
o
C for 6 hours. The
benzene was pumped off and the remaining yellow solid was dissolved in CDCl
3
. A
1
H NMR spectrum was obtained and only afforded complex 3.
General Procedure for H/D exchange studies with benzene: In a typical
reaction, approximately 6.5 to 9.0 mg of complex 3 or 4 and 0.25 mL of benzene-H
6
65
was added to a resealable Schlenk tube. Under argon, 1.0 mL of deuterated
trifluoroacetic acid was added to the Schlenk tube. The tube was sealed and heated
at temperatures ranging from 160 to 190
o
C. A control reaction was also prepared
with 1.0 mL deuterated trifluoroacetic acid and 0.25 mL of benzene-H
6
under argon.
At various times, the control and catalyst tubes were removed from the oil bath, and
under argon a 0.2 µL sample was obtained from each Schlenk tube and analyzed by
GC-MS. The tubes were resealed and placed back into the oil bath for further
heating.
66
y = 0.4136x + 8.9854
R
2
= 0.9805
13
23
33
43
53
25 65 105
Time (mins)
Turnover Number
Figure 24. Plot of turnover number vs. time for the H/D exchange reaction
between benzene-H
6
and trifluoroacetic acid-d
1
using 4 as the
catalyst. Correction for background H/D exchange has already been
taken into account prior to plotting the data. (Conditions: 10.26 mM
of 4, 0.25 mL of benzene-H
6
, 1 mL of deuterated trifluoroacetic acid,
heated at 180
o
C).
67
y = 0.0635x - 1.0546
R
2
= 0.9986
y = 0.2527x + 3.0982
R
2
= 0.9911
y = 0.1893x + 4.1528
R
2
= 0.9811
0
5
10
15
20
25
30
35
40
0 20 40 60 80 100 120 140
Time (mins)
% of Benzene-H
6
that has reacted.
10.26mM of complex 3 in 0.25mL Benz-H6
and 1 mL of D-TFA (Catalytic Reaction)
0.25mL Benz-H6 and 1mL D-TFA (Control
Reation)
(Catalytic Reaction) - (Control Reaction)
Figure 25. Plot of the percent benzene-H
6
that has reacted versus time in
minutes for the “catalytic reaction” and the “control reaction.”
68
Table 2. Comparison of the percent deuterated isotopologs of benzene with
time for the “catalytic reaction” and the “control reaction.”
Percent Deuterated Isotopologs from "Catalytic Reaction"
Time (mins) % D
1
% D
2
% D
3
% D
4
% D
5
% D
6
30 9.42 0.44 0.02 0.00 0.00 0.01
59 17.01 1.59 0.09 0.01 0.01 0.01
90 23.14 3.33 0.27 0.03 0.01 0.01
120 27.08 4.92 0.51 0.06 0.02 0.01
Percent Deuterium Isotopologs from "Control Reaction"
Time (mins) % D
1
% D
2
% D
3
% D
4
% D
5
% D
6
30 0.85 0.06 0.00 0.00 0.00 0.01
59 2.50 0.09 0.01 0.00 0.00 0.00
90 4.34 0.17 0.04 0.01 0.00 0.01
120 6.19 0.33 0.07 0.02 0.01 0.01
Percent Deuterium Isotopologs from [“Catalytic Rxn” – “Control Rxn”]
Time (mins) % D
1
% D
2
% D
3
% D
4
% D
5
% D
6
30 8.57 0.38 0.02 0.00 0.00 0.00
59 14.51 1.50 0.07 0.01 0.01 0.00
90 18.79 3.16 0.23 0.02 0.01 0.00
120 20.89 4.59 0.43 0.04 0.01 0.01
Reaction of 3 with benzene-H
6
and toluene-d
8
: In a resealable Schlenk
tube 10.1 mg (0.0164 mmol) of complex 3 was added to 0.50 mL of benzene-H
6
and
0.50 mL of toluene-d
8
. The reaction was heated at 180
o
C for 28 hours, after which a
sample was taken and analyzed by GC-MS. After deconvolution, it was found that
no H/D exchange was observed. A control reaction consisting of only 0.50 mL
benzene-H
6
and 0.50 mL of toluene-d
8
did not show any H/D exchange.
Analysis of H-D exchange: Catalytic H/D exchange reactions were
quantified by monitoring the increase of deuterium into C
6
H
6
by GC-MS analyses.
This was achieved by deconvoluting the mass fragmentation pattern obtained from
the MS analysis, using a program developed with Microsoft EXCEL. An important
69
assumption made with this method is that there are no isotope effects on the
fragmentation pattern for the various benzene isotopologs. Fortunately, because the
parent ion of benzene is relatively stable towards fragmentation, it can be used
reliably to quantify the exchange reactions. The mass range from 78 to 84 (for
benzene) was examined for each reaction and compared to a control reaction where
no metal catalyst was added. The program was calibrated with known mixtures of
benzene isotopologs. The results obtained by this method are reliable to within 5 %.
Thus, analysis of a mixture of C
6
H
6
, C
6
D
6
and C
6
H
5
D
1
prepared in a molar ratio of
40: 50: 10 resulted in a calculated ratio of 41.2(C
6
H
6
): 47.5(C
6
D
6
): 9.9(C
6
H
5
D
1
).
Catalytic H/D exchange reactions were thus run for sufficient reaction times to be
able to detect changes > 5 % exchange. Methane was analyzed in the same way as
benzene using methane isotopologs. Turnover numbers for the catalytic reactions
with methane and benzene were defined as (moles of deuterated isotopologs of
methane or benzene) divided by (moles of catalyst).
70
Figure 26. Eyring plot for the H/D exchange of benzene-H
6
and trifluoroacetic
acid-d
1
with the Pt(NNC)TFA catalyst.
Protonation Studies of Complex 4: In a NMR tube, 8.0 mg (0.013 mmol) of
4 was dissolved in CDCl
3
, and a
1
H NMR spectrum was obtained of the solution.
Trifluoroacetic acid (3 µL) was added to the solution, and a new
1
H NMR spectrum
was obtained. The
1
H NMR spectrum indicated the presence of free benzene and the
formation of complex 3.
Enthalpy of Activation= 31.5 (± 2.5) kcal / mol
y = -15862x + 23.594
R
2
= 0.9752
-13.5
-12.5
-11.5
-10.5
0.00214 0.00222 0.0023
1/T (1/K)
ln(k/T)
71
Figure 27. View of the aromatic region of the
1
H NMR spectrum of protonation
of complex 4 with trifluoroacetic acid in deuterated chloroform.
Protonation Studies of Complex 3: In a J-young NMR tube 11.1 mg
(0.0170 mmol) of 3 was dissolved in approx. 0.75 mL of CD
2
Cl
2
. The NMR tube
was then placed into the NMR probe and the probe was cooled to -70
o
C. After
obtaining an initial
1
H NMR spectrum of starting material, the NMR tube was
removed from the probe, and approximately 5 µL (0.065 mmol) of trifluoroacetic
acid was injected into the NMR tube. The solution rapidly changed color from an
orange solution to a blue solution. The NMR tube was reinserted into the probe, and
a
1
H NMR spectrum was obtained with a spectral window of -40 to 15 ppm. No
hydride peak was observed.
72
a)
b)
c)
Figure 28. a)
1
H NMR spectrum of 3 in CD
2
Cl
2
. b)
1
H NMR spectrum of 3
with 3.8 eq of HTFA in CD
2
Cl
2
. c)
1
H NMR spectrum of 3 with 3.8
eq of HTFA in CD
2
Cl
2
.
73
Procedure for Catalyst recovery experiment: Inside a nitrogen filled box,
10.8 mg of 4 and 0.25 mL of benzene-H
6
was added to a resealable Schlenk tube.
Under argon, 1.0 mL of trifluoroacetic acid-H
1
was added to the Schlenk tube. The
tube was sealed and heated to 190
o
C for 100 minutes. The tube was open under air,
and deionized water was added to the reaction mixture. The catalyst was extracted
with methylene chloride. The methylene chloride was washed with water to remove
any residual amounts of acid. The methylene chloride was removed under vacuum,
and the sample was dissolved in CDCl
3
. In a vial, 3.9 mg of 1,3,5-
trimethoxybenzene was added to 1.0 mL of CDCl
3
. From this internal standard
solution 100 µL (2.3 x 10
-3
mmol) was added to the previously prepared NMR tube.
A
1
H NMR spectrum was obtained with a relaxation delay of 60 seconds.
Integration obtained from the
1
H NMR spectrum showed that complex 3’s ortho-
proton having an integration of 7.01 and the protons from 1,3,5-trimethoxybenzene
were set as the reference with an integration of 3.00. A 92 % yield (1.6 x 10
-2
mmol)
was obtained for the amount of catalyst recovered. The fluorine NMR only showed
one fluorine peak at δ -73.9 ppm.
74
Figure 29. (top NMR):
1
H NMR of complex 3 in CDCl
3
. (bottom NMR):
1
H
NMR of recovered product from “catalyst recovery experiment.”
75
X-ray structure determination of Pt(4,4-tBu
2
-[NNC])phenyl (4). Suitable
crystals (amber) of 4 for X-ray analysis were grown from vapor diffusion of pentane
in to a benzene solution. Diffraction data was collected at 143 K with graphite-
monochromatic Mo K α radiation ( λ = 0.71073 Å). The cell parameters were
obtained from the least-squares refinement of the spots (collected 60 frames) using
the SMART program. A hemisphere of data was collected up to a resolution of 0.75
Å, and the intensity data was processed using the Saint Plus program. All
calculations for the structure determination were carried out using the SHELXTL
package (version 5.1).
46
Initial atomic positions were located by direct methods
using XS, and the structure was refined by least-squares methods using SHELX with
11750 independent reflections and within the range of Φ 1.39 to 25.68 (completeness
99.7 %). Absorption corrections were applied by using SADABS.
47
Calculated
hydrogen positions were input and refined in a riding manner along with the attached
carbons. The thermal ellipsoid plot is shown in Figure 30. There are 2 molecules in
the unit cell, and they co-crystallized with one benzene solvent molecule. Crystal
data and refinement parameters can be found in Table 3. Selected bond lengths and
angles can be found in Table 5 and Table 6.
76
Figure 30. Thermal ellipsoid plot of 4 with 50 % probability. Hydrogens and
benzene co-solvent were removed for clarity.
77
Table 3. Crystal data and structure refinement for C
36
H
38
N
2
Pt.
Identification code steveptm
Empirical formula C
36
H
38
N
2
Pt
Formula weight 693.77
Temperature 143(2) K
Wavelength 0.71073 Å
Crystal system Monoclinic
Space group P2(1)/c
Unit cell dimensions a = 13.002(2) Å α= 90°.
b = 16.534(3) Å β= 95.971(3)°.
c = 13.345(2) Å γ = 90°.
Volume 2853.3(8) Å
3
Z 4
Density (calculated) 1.615 Mg/m
3
Absorption coefficient 4.945 mm
-1
F(000) 1384
Crystal size 0.17 x 0.12 x 0.03 mm
3
Theta range for data collection 1.57 to 27.49°.
Index ranges -15 < = h < = 16; -19 < = k < = 21; -17 < = l < = 10
Reflections collected 17411
Independent reflections 6457 [R(int) = 0.0406]
Completeness to theta = 27.49° 98.6 %
Transmission factors min/max ratio: 0.739
Refinement method Full-matrix least-squares on F
2
Data / restraints / parameters 6457 / 0 / 358
Goodness-of-fit on F
2
1.002
Final R indices [I>2sigma(I)] R1 = 0.0298, wR2 = 0.0638
R indices (all data) R1 = 0.0417, wR2 = 0.0677
Largest diff. peak and hole 1.531 and -0.732 e.Å
-3
78
Table 4. Atomic coordinates ( x 10
4
) and equivalent isotropic displacement
parameters (Å
2
x10
3
) for C
36
H
38
N
2
Pt. U(eq) is defined as one third of the trace of
the orthogonalized Uij tensor.
x y z U(eq)
Pt(1) 6077(1) 1270(1) 5725(1) 17(1)
N(2) 6681(2) 186(2) 6124(2) 17(1)
N(1) 4763(2) 619(2) 6086(2) 19(1)
C(16) 7551(3) 1521(2) 5581(3) 19(1)
C(15) 8051(3) 2237(2) 5360(3) 24(1)
C(14) 9110(3) 2279(2) 5342(3) 28(1)
C(13) 9728(3) 1607(2) 5539(3) 25(1)
C(12) 9270(3) 879(2) 5761(3) 24(1)
C(11) 8210(3) 831(2) 5784(3) 18(1)
C(10) 7701(3) 80(2) 6069(3) 19(1)
C(9) 8133(3) -679(2) 6283(3) 20(1)
C(8) 7521(3) -1316(2) 6561(3) 19(1)
C(7) 6466(3) -1171(2) 6619(3) 20(1)
C(6) 6067(3) -409(2) 6408(3) 17(1)
C(5) 4982(3) -138(2) 6450(3) 16(1)
C(4) 4251(3) -605(2) 6874(3) 19(1)
C(3) 3243(3) -322(2) 6894(3) 18(1)
C(2) 3019(3) 427(2) 6453(3) 21(1)
C(1) 3786(3) 870(2) 6070(3) 22(1)
C(17) 7976(3) -2163(2) 6758(3) 22(1)
C(18) 7804(4) -2643(2) 5764(4) 37(1)
C(19) 7452(4) -2596(3) 7579(4) 45(1)
C(20) 9140(3) -2132(2) 7098(3) 29(1)
C(21) 2449(3) -782(2) 7454(3) 20(1)
C(22) 1347(3) -547(3) 7058(3) 30(1)
C(23) 2568(3) -1701(2) 7343(3) 26(1)
C(24) 2646(3) -562(2) 8576(3) 28(1)
C(25) 5464(3) 2357(2) 5330(3) 21(1)
C(26) 5520(3) 2716(2) 4385(3) 26(1)
C(27) 5076(3) 3469(2) 4122(3) 29(1)
C(28) 4564(3) 3893(2) 4824(3) 30(1)
C(29) 4489(3) 3553(2) 5759(3) 28(1)
C(30) 4923(3) 2805(2) 5995(3) 24(1)
C(31) 7700(4) 1022(3) 8395(3) 35(1)
C(32) 8725(4) 1155(3) 8316(4) 40(1)
C(33) 9439(4) 567(3) 8595(4) 47(1)
C(34) 9130(4) -170(3) 8953(4) 50(1)
C(35) 8088(4) -307(3) 9032(3) 44(1)
C(36) 7378(4) 292(3) 8752(3) 35(1)
79
Table 5. Bond lengths [Å] for C
36
H
38
N
2
Pt.
Atom-Atom Angstroms Atom-Atom Angstroms
Pt(1)-C(16) 1.990(4) C(17)-C(18) 1.543(6)
Pt(1)-N(2) 2.006(3) C(21)-C(22) 1.525(5)
Pt(1)-C(25) 2.014(4) C(21)-C(23) 1.536(5)
Pt(1)-N(1) 2.116(3) C(21)-C(24) 1.537(5)
N(2)-C(6) 1.347(4) C(25)-C(30) 1.400(5)
N(2)-C(10) 1.347(5) C(25)-C(26) 1.403(5)
N(1)-C(1) 1.334(5) C(26)-C(27) 1.402(5)
N(1)-C(5) 1.362(4) C(27)-C(28) 1.393(6)
C(16)-C(15) 1.397(5) C(28)-C(29) 1.382(6)
C(16)-C(11) 1.436(5) C(29)-C(30) 1.382(5)
C(15)-C(14) 1.381(6) C(31)-C(32) 1.367(6)
C(14)-C(13) 1.380(6) C(31)-C(36) 1.378(6)
C(13)-C(12) 1.388(5) C(32)-C(33) 1.369(7)
C(12)-C(11) 1.385(5) C(33)-C(34) 1.383(7)
C(11)-C(10) 1.475(5) C(34)-C(35) 1.388(7)
C(10)-C(9) 1.392(5) C(35)-C(36) 1.380(6)
C(9)-C(8) 1.394(5) C(4)-C(3) 1.395(5)
C(8)-C(7) 1.402(5) C(3)-C(2) 1.390(5)
C(8)-C(17) 1.531(5) C(3)-C(21) 1.537(5)
C(7)-C(6) 1.380(5) C(2)-C(1) 1.377(5)
C(6)-C(5) 1.486(5) C(17)-C(19) 1.527(6)
C(5)-C(4) 1.389(5) C(17)-C(20) 1.535(5)
80
Table 6. Bond angles [
o
] for C
36
H
38
N
2
Pt.
Atom’s Angle (Degrees) Atom’s Angle (Degrees)
C(16)-Pt(1)-N(2) 81.83(14) C(9)-C(10)-C(11) 129.0(3)
C(16)-Pt(1)-C(25) 98.47(15) C(10)-C(9)-C(8) 120.4(3)
N(2)-Pt(1)-C(25) 179.65(15) C(9)-C(8)-C(7) 118.3(3)
C(16)-Pt(1)-N(1) 159.50(13) C(9)-C(8)-C(17) 121.0(3)
N(2)-Pt(1)-N(1) 77.80(12) C(7)-C(8)-C(17) 120.6(3)
C(25)-Pt(1)-N(1) 101.89(13) C(6)-C(7)-C(8) 119.7(3)
C(6)-N(2)-C(10) 122.4(3) N(2)-C(6)-C(7) 120.2(3)
C(6)-N(2)-Pt(1) 120.0(2) N(2)-C(6)-C(5) 112.5(3)
C(10)-N(2)-Pt(1) 117.5(2) C(7)-C(6)-C(5) 127.3(3)
C(1)-N(1)-C(5) 117.1(3) N(1)-C(5)-C(4) 121.9(3)
C(1)-N(1)-Pt(1) 128.9(2) N(1)-C(5)-C(6) 115.3(3)
C(5)-N(1)-Pt(1) 113.9(2) C(4)-C(5)-C(6) 122.7(3)
C(15)-C(16)-C(11) 115.6(3) C(5)-C(4)-C(3) 120.4(3)
C(15)-C(16)-Pt(1) 132.2(3) C(2)-C(3)-C(4) 116.5(3)
C(11)-C(16)-Pt(1) 112.1(3) C(2)-C(3)-C(21) 121.7(3)
C(14)-C(15)-C(16) 122.2(4) C(4)-C(3)-C(21) 121.6(3)
C(13)-C(14)-C(15) 121.1(4) C(1)-C(2)-C(3) 120.2(3)
C(14)-C(13)-C(12) 119.0(4) C(31)-C(36)-C(35) 120.2(5)
C(11)-C(12)-C(13) 120.3(4) N(1)-C(1)-C(2) 123.6(3)
C(12)-C(11)-C(10) 121.9(3) C(19)-C(17)-C(8) 111.0(3)
C(16)-C(11)-C(10) 116.3(3) C(33)-C(34)-C(35) 119.4(5)
N(2)-C(10)-C(9) 119.0(3) C(19)-C(17)-C(20) 107.6(3)
N(2)-C(10)-C(11) 112.0(3) C(32)-C(33)-C(34) 120.4(5)
C(8)-C(17)-C(20) 111.8(3) C(31)-C(32)-C(33) 120.3(5)
C(19)-C(17)-C(18) 109.9(4) C(32)-C(31)-C(36) 120.1(4)
C(8)-C(17)-C(18) 107.7(3) C(29)-C(30)-C(25) 123.3(4)
C(20)-C(17)-C(18) 108.7(3) C(30)-C(29)-C(28) 120.3(4)
C(22)-C(21)-C(23) 108.6(3) C(29)-C(28)-C(27) 119.1(4)
C(22)-C(21)-C(3) 111.1(3) C(28)-C(27)-C(26) 119.5(4)
C(23)-C(21)-C(3) 111.4(3) C(27)-C(26)-C(25) 122.9(4)
C(22)-C(21)-C(24) 109.4(3) C(26)-C(25)-Pt(1) 123.9(3)
C(23)-C(21)-C(24) 108.7(3) C(30)-C(25)-Pt(1) 121.2(3)
C(3)-C(21)-C(24) 107.7(3) C(30)-C(25)-C(26) 115.0(3)
81
Table 7. Anisotropic displacement parameters (Å
2
x 10
3
) for C
36
H
38
N
2
Pt.
The anisotropic displacement factor exponent takes the form: -2 π
2
[ h
2
a*
2
U
11
+ ...
+ 2 h k a* b* U
12
].
U
11
U
22
U
33
U
23
U
13
U
12
Pt(1) 16(1) 15(1) 20(1) 1(1) 3(1) 0(1)
N(2) 15(2) 17(2) 18(2) 2(1) 0(1) 1(1)
N(1) 20(2) 16(2) 21(2) -2(1) 2(1) 2(1)
C(16) 17(2) 22(2) 17(2) -1(2) 4(2) -2(1)
C(15) 31(2) 18(2) 24(2) 3(2) 1(2) -1(2)
C(14) 31(2) 23(2) 31(2) 4(2) 2(2) -11(2)
C(13) 17(2) 35(2) 24(2) -1(2) 4(2) -9(2)
C(12) 19(2) 29(2) 22(2) 0(2) 1(2) 0(2)
C(11) 16(2) 20(2) 18(2) 2(2) 2(2) -2(1)
C(10) 19(2) 23(2) 15(2) -1(2) 0(2) 0(2)
C(9) 12(2) 24(2) 23(2) 4(2) 3(2) 1(1)
C(8) 21(2) 21(2) 16(2) 2(2) 4(2) 4(2)
C(7) 20(2) 15(2) 25(2) 5(2) 4(2) -2(1)
C(6) 14(2) 20(2) 16(2) 0(2) 0(1) -2(1)
C(5) 13(2) 19(2) 17(2) -1(2) 1(1) 0(1)
C(4) 19(2) 17(2) 22(2) -2(2) 2(2) 1(1)
C(3) 15(2) 20(2) 18(2) -5(2) 2(2) -3(1)
C(2) 17(2) 20(2) 26(2) -2(2) 5(2) 3(1)
C(1) 24(2) 16(2) 24(2) 1(2) 2(2) 5(2)
C(17) 17(2) 21(2) 29(2) 4(2) 3(2) 3(2)
C(18) 41(3) 24(2) 46(3) -8(2) -3(2) 2(2)
C(19) 31(3) 39(3) 66(4) 31(3) 17(2) 14(2)
C(20) 20(2) 26(2) 41(3) 3(2) -2(2) 2(2)
C(21) 16(2) 25(2) 19(2) -2(2) 2(2) -1(2)
C(22) 14(2) 38(2) 38(3) 5(2) 4(2) -4(2)
C(23) 28(2) 23(2) 28(2) -3(2) 7(2) -5(2)
C(24) 28(2) 34(2) 23(2) -5(2) 4(2) -6(2)
C(25) 15(2) 19(2) 28(2) 1(2) -2(2) -1(1)
C(26) 22(2) 24(2) 31(2) 3(2) 2(2) -1(2)
C(27) 25(2) 28(2) 33(3) 10(2) -5(2) -1(2)
C(28) 28(2) 13(2) 47(3) 2(2) -4(2) 3(2)
C(29) 20(2) 24(2) 39(3) -6(2) 2(2) 4(2)
C(30) 16(2) 26(2) 28(2) 3(2) 1(2) 0(2)
C(31) 42(3) 30(2) 33(3) -3(2) 5(2) 2(2)
C(32) 44(3) 39(3) 38(3) -9(2) 14(2) -13(2)
C(33) 26(3) 60(3) 54(3) -21(3) 3(2) -1(2)
C(34) 50(3) 54(3) 42(3) -17(3) -15(3) 18(3)
C(35) 61(4) 37(3) 32(3) -5(2) 1(2) -5(2)
C(36) 35(3) 40(3) 30(3) -6(2) 10(2) -4(2)
82
Table 8. Hydrogen coordinates ( x 10
4
) and isotropic displacement
parameters (Å
2
x 10
3
) for C
36
H
38
N
2
Pt.
x y z U(eq) x y z U(eq)
H(15) 7649 2711 5217 29 H(24B) 3335 -749 8844 42
H(14) 9419 2780 5192 34 H(24C) 2123 -821 8946 42
H(13) 10455 1642 5522 30 H(26) 5876 2438 3903 31
H(12) 9686 412 5898 28 H(27) 5123 3688 3471 35
H(9) 8850 -763 6239 24 H(28) 4271 4409 4661 36
H(7) 6029 -1595 6801 24 H(29) 4137 3834 6243 33
H(4) 4440 -1119 7153 23 H(30) 4852 2584 6641 28
H(2) 2335 635 6415 25 H(31) 7208 1433 8203 42
H(1) 3610 1382 5779 26 H(32) 8944 1658 8067 48
H(18A)7062 -2670 5542 56 H(33) 10151 665 8542 56
H(18B)8078 -3192 5871 56 H(34) 9626 -578 9144 60
H(18C)8163 -2372 5247 56 H(35) 7866 -810 9276 53
H(19A)7507 -2262 8190 67 H(36) 6664 202 8805 41
H(19B)7793 -3117 7729 67 H(24A) 2605 27 8653 42
H(19C)6721 -2686 7346 67 H(23C) 2505 -1844 6627 39
H(20A)9508 -1929 6545 44 H(23B) 3248 -1869 7661 39
H(20B)9388 -2677 7285 44 H(23A) 2026 -1977 7672 39
H(20C)9266 -1772 7681 44 H(22C) 857 -864 7407 45
H(22A)1235 -656 6333 45 H(22B) 1242 30 7180 45
83
Figure 31. Energy diagram for Pt(NNC)TFA and Pt(bipyrimidine)TFA
2
systems.
Another possible mechanism for the H/D exchange reaction shown in Figure
31, is the concerted exchange of D for H in the intermediate platinum phenyl hydride
complex, [(NNC)Pt
IV
(Ph)(H)]
+
, to generate [(NNC)Pt
IV
(Ph)(D)]
+
followed by a
reductive elimination to form C
6
H
5
D
1
. However, all attempts to find the transition
state for this exchange were unsuccessful.
84
2.5: References
27
(a) Periana, R. A.; Taube, D. J.; Gamble, S.; Taube, H.; Satoh, T.; Fuji, H. Science
1998, 280, 560. (b) Shilov, A. E.; Shul’pin, G. B. Activation and Catalytic
Reactions of Saturated Hydrocarbons in the Presence of Metal Complexes,
Kluwer Academic: Dordrecht, The Netherlands, 2000. (c) Jia, C. G.; Kitamura,
T.; Fujiwara, Y. Acc. Chem. Res. 2001, 34, 633; and references therein. (d)
Crabtree, R. H. J. Chem. Soc., Dalton Trans. 2001, 17, 2437. (e) Labinger, J. A.;
Bercaw, J. E. Nature 2002, 417, 507. (f) Jones, W. D. Acc. Chem. Res. 2003, 36,
140. (g) Periana, R. A.; Mironov, O.; Taube, D. J.; Bhalla, G.; Jones, C. J.
Science 2003, 301, 814. (h) Conley, B. L; Tenn, W. J., III; Young, K. J. H.;
Ganesh, S. K.; Meier, S. K; Ziatdinov, V. R.; Mironov, O.; Oxgaard, J.;
Gonzales, J.; Goddard, W. A., III; Periana, R. A. J. Mol. Catal. A. 2006, 251, 8.
28
(a) Heyduk, A. F.; Zhong, H. A.; Labinger, J. A.; Bercaw, J. E. C-H activation at
Pt(II): A route to selective alkane oxidation. In Activation and Functionalization
of C-H Bonds; Goldberg, K. I.; Goldman, A. S. Eds.; ACS Symposium Series
No. 885; American Chemical Society: Washington D.C., 2004; pp. 250-263. (b)
Tilset, M.; Lersch, M. Chem. Rev. 2005, 105, 2471. (c) Johansson, L.; Tilset, M.;
Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc. 2000, 122, 10846.
29
Iverson, C. N.; Carter, C. A. G.; Baker, T.; Scollard, J. D.; Labinger, J. A.;
Bercaw, J. E. J. Am. Chem. Soc. 2003, 125, 12674.
30
Harkins, S. B.; Peters, J. C. Organometallics 2002, 21, 1753.
31
(a) Kua, J.; Xu, X.; Periana, R. A.; Goddard, W. A., III Organometallics 2002,
21, 511. (b) Muller, R. P.; Phillipp, D. M.; Goddard, W. A., III Top. Catal. 2003,
23, 81.
32
(a) Ziatdinov, V. R.; Oxgaard, J.; Mironov, O. A.; Young, K. J. H.; Goddard, W.
A., III; Periana, R. A. J. Am. Chem. Soc. 2006, 128, 7404; and references therein.
(b) Zhong, H. A.; Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc. 2002, 124,
1378.
33
Collman, J. P.; Hegedus, L. S. Principles and Applications of Organotransition
Metal Chemistry; University Science Books: Mill Valley, CA, 1980.
34
van der Boom, M. E.; Milstein, D. Chem. Rev. 2003, 103, 1759.
35
(a) McLoughlin, M. A.; Flesher, R. J.; Kaska, W. C.; Mayer, H. A.
Organometallics 1994, 13, 3816. (b) Liu, F; Pak, E. B.; Singh, B.; Jensen, C. M.;
Goldman, A. S. J. Am. Chem. Soc. 1999, 121, 4086.
85
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(a) Constable, E. C.; Henney, R. P. G.; Leese, T. A.; Tocher, D. A. J. Chem. Soc.,
Dalton Trans. 1990, 443. (b) Jahng, Y.; Park J. G. Inorg. Chim. Acta 1998, 267,
265. (c) Lu, W.; Mi, B-X.; Chan, M. C. W.; Hui, Z.; Che, C-M.; Zhu, N.; Lee, S-
T. J. Am. Chem. Soc. 2004, 126, 4958.
37
Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
38
Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B. 1988, 37, 785.
39
Jaguar 6.0, Schrodinger, LLC, Portland, Oregon, 2005.
40
Harihara, P. C.; Pople, J. A. Theor. Chim. Acta 1973, 28, 213.
41
Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299.
42
Tannor, D. J.; Marten, B.; Murphy, R.; Friesner, R. A.; Sitkoff, D.; Nichlolls, A.;
Ringnalda, M.; Goddard, W.A., III; Honig, B. J. Am. Chem. Soc. 1994, 116,
11775.
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Marten, B.; Kim, K.; Cortis, C.; Friesner, R. A.; Murphy, R.; Ringnalda, M.;
Sitkoff, D.; Honig, B. J. Phys. Chem. 1996, 100, 9098.
44
Gerdes, G.; Chen, P. Organometallics 2004, 23, 3031.
45
Lu, W.; Mi, B-X.; Chan, M. C. W.; Hui, Z.; Che, C-M.; Zhu, N.; Lee, S-T. J. Am.
Chem. Soc. 2004, 126, 4958.
46
Sheldrick, G. M. SHELXTL, version 5.1; Bruker Analytical X-ray Systems, Inc.:
Madison, WI, 1997.
47
Blessing, R. H. Acta Crystallogr. 1995, A51, 33.
86
Chapter 3: Synthesis and Reactivity of a Water Soluble
Cyclometallated Iridium Bishydroxo Complex
3.1: Introduction
The selective functionalization of C-H bonds is considered one of the holy
grails in the scientific community, and it has been proposed that the C-H activation
reaction can be utilized towards the cleavage and functionalization of C-H bonds.
48
Several systems have been shown to convert methane into functionalized products.
However, all of these systems rely on electrophilic metals (platinum(II),
palladium(II), mercury(II), and gold(I)/gold(III)), and all of these operate in strongly
acidic media, sulfuric acid.
49
The most well known of these systems is the Catalytica
system, Pt(bipyrimidine)Cl
2
developed by Periana et al., which converts methane to
methylbisulfate in a 72 % one-pass yield at 90 % selectivity.
49a
The functionalized
product, methanol, is protected as methylbisulfate by the sulfuric acid. It is believed
that the formation of methylbisulfate prevents the methanol from being over-
oxidized to CO
2
. However, the separation of the product, methanol, from the
sulfuric acid is expensive at the concentrations the catalyst generates, 1 M. The
water produced in the functionalization step also inhibits the reaction rate by
coordinating to the electrophilic platinum(II) center.
50
My research efforts have been
directed towards developing more electron rich C-H activation catalysts that are
thermally stable to protic and oxidizing media. The catalysts should efficiently and
selectively activate C-H bonds to generate metal alkyls, which can be coupled with
functionalization reactions to generate useful products, such as alcohols, Figure 32.
87
While there has been a significant amount of work on C-H activation, the
functionalization of metal alkyls is less well understood. The functionalization of an
iridium alkyl through an iridium(V) pathway is not likely due the rarity of iridium(V)
species. Therefore, it might be possible for the iridium alkyl intermediates to be
functionalized via an oxygen atom insertion into the iridium-carbon bond, similar to
a Bayer-Villiger reaction. The use of this pathway for functionalizing metal alkyls
has recently been shown by our group using a rhenium(VII) methyl complex,
CH
3
Re
VII
O
3
and oxygen atom transfer reagents, abbreviated as YO, to generate a
(CH
3
O)Re
VII
O
3
intermediate and Y. From Figure 32, the resulting metal methoxo
product can then be hydrolyzed through a subsequent C-H activation step. The
methoxo acts as a base abstracting the proton from the hydrocarbon substrate in the
C-H cleavage transition state. This concept has recently been shown by our group by
heating a ( κ
2
-O,O-acac)
2
Ir(OMe)Py complex, where Py = pyridine, in the presence
of benzene, which cleanly converts the Ir-OMe to an Ir-Ph product with the
formation of methanol. Using these two results, a catalytic cycle can be proposed for
the functionalization of C-H bonds through a non-redox pathway, Figure 32.
88
LM
n
-OR
LM
n
-R
YO
Y
RH
ROH
Non-Redox
Catalysis
Oxidation
CH Activation
and Functionalization
Figure 32. Catalytic sequence for the functionalization of hydrocarbons via a
non-redox catalytic cycle.
Water is a cheap, environmentally friendly solvent, which can be used as a
solvent for the selective functionalization of C-H bonds. Although the field of C-H
activation has been around for years, there are still only a handful of systems that are
capable of activating C-H bonds in the presence of water. The earliest example of C-
H activation in water was done by Shilov
51
and Garnett,
52
working separately, using
K
2
PtCl
4
. The use of ruthenium for C-H activation in aqueous media has also been
demonstrated recently by several groups. Gunnoe
53
and Lau
54
in separate work
demonstrated that ruthenium hydro(trispyrazolyl)borate complexes are competent for
H/D exchange between water and various organic substrates. Milstein and Leitner
55
have shown that a ruthenium pincer complex exchanges hydrogen and deuterium
between various C-H bonds and water under the mildest conditions reported to date,
50
o
C. Iridium has also been used by several groups to activate C-H bonds in the
89
presence of water. Bergman
56
showed that an iridium(III) complex, CpIr(PMe
3
)Cl
2,
incorporates deuterium from D
2
O into various organic substrates. Carmona and
Poveda
57
have also shown that H/D exchange occurs between THF and water using a
(Tp
Me2
)IrH
4
catalyst. Recently, Periana published work on an ( κ
2
-O,O-
acac)
2
Ir(OH)OH
2
complex that catalyzes the H/D exchange between benzene and
water.
58
This shows that within the past ten years there has been a significant
interest in developing C-H activation catalysts that operate in water.
Our group has been studying a (NNC
(tBu2)
)Ir(Et)(TFA)(C
2
H
4
) complex, where
(NNC
(tBu2)
) = 6-phenyl-4,4’-di-tert-butyl-2,2’-bipyridine and TFA = trifluoroacetate,
that shows H/D exchange between hydrocarbons (methane and benzene) and
trifluoroacetic acid.
59
With the ability for (NNC
(tBu2)
)Ir(Et)(TFA)(C
2
H
4
) to activate
methane in acidic solvents, I decided to investigate whether a similar complex could
activate the C-H bond of methane under less acidic conditions, in water. I believe
that by synthesizing a bishydroxo (NNC
(tBu2)
)Ir(OH)
2
L complex (where L is a labile
group) that the hydroxo ligands will assist in increasing the solubility of the complex
in water, and the labile L group would provide the open coordination site needed for
the coordination and activation of the C-H bond. Herein I report, the synthesis and
reactivity of an ((NNC
(tBu2)
)Ir(OH)
2
Py complex, 1-(OH)
2
Py, that is competent for
the H/D exchange between benzene and water. I also report the synthesis of several
base, water soluble ligands that can be used to make water soluble cyclometallated
iridium complexes. One of these ligands is explored in the form of an
90
(NNC
pOH
)Ir(OH)
2
NHCOMe complex, where NNC
pOH
= 6-(para-hydroxyphenyl)-
2,2’-bipyridine.
3.2: Results and Discussion
To synthesize the (NNC
(tBu2)
)Ir(OH)
2
L, Scheme 9, I decided to start with the
previously published (NNC
(tBu2)
)Ir(Et)(TFA)NCCH
3
, 1-Et(TFA)NCMe, complex
that is competent for the H/D exchange reaction between various hydrocarbons and
acids. The stereochemistry of this complex, shown in Scheme 9, was identified by X-
ray crystallography.
59
The ethyl was replaced with a more labile trifluoroacetate by
protonolysis with trifluoroacetic acid, as this provided a convenient precursor for the
synthesis of (NNC
(tBu2)
)Ir(OH)
2
NCCH
3
complex. Complex 1-Et(TFA)NCMe was
stirred under argon in neat trifluoroacetic acid for 12 hours at room temperature.
After removing the acid under reduced pressure and purification by column
chromatography, a yellow, air-stable solid was obtained in 60 % yield as the
(NNC
(tBu2)
)Ir(TFA)
2
NCCH
3
complex, 1-TFA
2
NCMe. Fluorine NMR analysis
shows only one fluorine resonance, and this suggests that the trifluoroacetate groups
are trans to each other. Initial attempts to produce (NNC
(tBu2)
)Ir(OH)
2
L were carried
out using 1-TFA
2
NCMe; however, direct routes to the hydroxo complex were
unsuccessful due to the insolubility of 1-TFA
2
NCMe in water. This led me to try
and replace the trifluoroacetate ligands with methoxo ligands, since I knew that 1-
TFA
2
NCMe was soluble in methanol. The synthesis of the bismethoxo complex
was advantageous because the product can easily be identified by
1
H NMR. The –
OMe groups are easily seen in the
1
H NMR, whereas the –OH groups are more
91
difficult to observe. The reaction of 1-TFA
2
NCMe in methanol with 16 eq of
NaOMe was followed by
1
H NMR. After the addition of the sodium methoxide, the
Ir-NCCH
3
peak could no longer be observed by
1
H NMR. Additional heating at 70
o
C led to multiple intractable products. This indicates that the base is reacting with
the NCCH
3
, which results in the failure to isolate a discrete bismethoxo complex. To
my detriment, the NCCH
3
had to be substituted for a more stable ligand. Complex 1-
TFA
2
NCMe was heated in neat pyridine for ten hours at 120
o
C. Afterwards the
pyridine was removed under reduced pressure, and purification of the product by
column chromatography produced an air-stable orange solid in 94 % yield as the
Ir(NNC
(tBu2)
)(TFA)
2
Py, 1-TFA
2
Py. Complex 1-TFA
2
Py, was not soluble in water;
therefore, 1-TFA
2
Py was heated at 70
o
C for 24 hours in methanol containing 16 eq
of sodium methoxide. The product was obtained by removal of the excess sodium
methoxide and methanol, and the product, Ir(NNC)(OMe)
2
Py, 1-OMe
2
Py, was
purified by column chromatography resulting in a black solid in 35 % yield.
Complex 1-OMe
2
Py was slightly moisture sensitive and could not be stored for very
long periods of time. Due to the instability of 1-OMe
2
Py, it was immediately
converted to 1-(OH)
2
Py after purification. Complex 1-(OH)
2
Py was obtained by
heating 1-OMe
2
Py in a 1:1 mixture of THF:H
2
O at 85
o
C for 2 days. Complex 1-
(OH)
2
Py, was obtained as a black, slightly moisture sensitive (vide infra) solid by
removal of the solvent and purification using column chromatography to yield 1-
(OH)
2
Py in 21 %. Each complex was fully characterized by
1
H and
13
C NMR, high-
resolution mass spectrometry, and elemental analysis. Attempts to obtain a crystal
92
structure of 1-(OH)
2
Py were unsuccessful. Furthermore, the –OH protons for 1-
(OH)
2
Py were observed at δ -2.71 ppm in CD
2
Cl
2
.
Scheme 9. Synthesis of 1-(OH)
2
Py.
Next, the stability of 1-(OH)
2
Py in water was tested by heating a 3 mM
solution of 1-(OH)
2
Py in D
2
O, under argon, inside of a J-Young NMR tube. As the
93
solution was heated at 100
o
C over a period of 8 hours, two new species formed,
which were observed by
1
H NMR, Figure 33. No free pyridine was observed, which
would rule out the formation of a dinuclear species of the type [(NNC
tBu2
)Ir(OH)( μ-
OH)]
2
. However, I could not rule out the loss of hydroxo to produce a dinuclear
species of the type [(NNC
(tBu2)
)IrPy( μ-OH)]
2
2+
. Therefore, the reaction was repeated
with added pyridine, 2 eq, to see if added pyridine would stabilize the complex and
inhibit the rate of formation of these new intermediates. In the presence of added
pyridine, the rate of formation of the two new species was the same. It was then
speculated whether loss of hydroxo was resulting in the formation of these
byproducts; therefore, I repeated the experiment in the presence of 4 eq of KOD.
The reaction was monitored over time and no other products other than the starting
material, 1-(OH)
2
Py, are observed in the
1
H NMR, Figure 34.
94
Stability in Aqueous Media
130
o
C 2h
100
o
C 3.5h
Multiple sets of tert-Butyls
indicates multiple species;
therefore it is not stable.
T0
Ext.
Std.
Ext.
Std.
D 2 O
NNC and pyridyl protons
tButyls
Test for
stability
D
2
O, heat, time
Ir(NNC)(OH)
2
Py
Figure 33. Stability of 1-(OH)
2
Py in D
2
O over time.
The complex was stable up in the KOD/D
2
O solution at 130
o
C over a period
of two hours. At 150
o
C, it was observed that the concentration of 1-(OH)
2
Py was
decreasing relative to an external standard, and small amounts of solid could be seen
on the walls of the NMR tube.
95
Stability in Aqueous Media with 4eq of KOD
100
o
C 3.5h
130
o
C 2h
T0
Only 2 tert-Butyl peaks,
so complex is stable.
Complex is stable in basic, aqueous media
up to 130
o
C for at least 2 hours. At 150
o
C
the complex precipitates from solution
Test for
stability 4eq of KOD, D
2
O,
heat, time
Ir(NNC)(OH)
2
Py
Figure 34. Stability of 1-(OH)
2
Py in D
2
O over time in the presence of 4 eq of KOD.
Similar studies were also carried out in Schlenk-tubes to confirm that the charred
material was not produced from the inability to stir the solution in the NMR tube.
The thermal stability tests carried out in Schlenk-tubes resulted in precipitation of a
tan solid within several hours of heating the solution at 180
o
C.
1
H NMR analysis of
the tan solid, using deuterated acetone, only revealed a broad range of aromatic and
tert-butyl NMR peaks. I attempted the C-H activation of methane using an
approximately 3.5 mM solution of 1-(OH)
2
Py in D
2
O with 16 eq of KOD and 500
psi of CH
4
. After the reaction, the methane was analyzed by GC-MS, and no H/D
exchange had occurred. Therefore, I turned my attention towards a more easily
96
studied substrate, benzene, which could act as a cosolvent keeping 1-(OH)
2
Py in
solution.
The reaction conditions for benzene/water H/D exchange were carried out
using a 1:1 mixture of benzene-H
6
and D
2
O resulting in an approximately 2 mM
solution of catalyst, 1-(OH)
2
Py. A temperature range of 160 – 190
o
C was used.
The deuterium incorporation into benzene was monitored over time by analysis of
the benzene phase by GG-MS using a deconvolution program. Initial H/D exchange
studies between water and benzene using 1-(OH)
2
Py as a catalyst without added
KOD showed little to no H/D exchange over a 48 hour period, less than 10 turnovers
at 180
o
C. Earlier studies using
1
H NMR revealed that an added amount of base was
needed to stabilize 1-(OH)
2
Py, vide supra. Therefore, when 20 eq of KOD was
added to the reaction mixture, H/D exchange was observed to be steady over time
with a turnover-frequency, TOF, of 2.0 x 10
-3
s
-1
at 180
o
C. Control reactions were
carried out with the same amount of KOD as the catalytic reaction, and all H/D
exchange results are reported with background corrections already performed. An
analysis of the catalytic H/D exchange compared to the background can be observed
in the experimental section.
Stirring studies were performed at 190
o
C to determine if the reaction was
mass transfer limited, Figure 35. The highest temperature at which the H/D
exchange studies were carried out was chosen because this would result in the fastest
chemical rate for H/D exchange. Consequently, this chemical rate would be most
competitive with the rate of diffusion. The stirring studies revealed that in the range
97
of 300 - 1000 rpm the catalyst did not appear to be mass transfer limited. However,
these stirring studies were performed using PTFE stir bars rather than an overhead-
driven stirrer with an impeller. As a result, at high stir rates it is possible that the
solution is vortexing rather than efficiently mixing.
Mass Transfer Study
1
3
5
7
9
0 200 400 600 800 1000 1200 1400
Revolutions per minute
TOF x 10
-3
(s
-1
)
C
6
H
6 ~3.5 mM cat
1 mL D
2
O, ~60eqKOD,
180
o
C.
5.56 M
1 mL
C
6
H
n
D
6-n
Figure 35. Stirring rate study for H/D exchange between benzene-H
6
and D
2
O
using 1-OH
2
Py as a catalyst.
When benzene/water H/D exchange reactions were conducted with a varying
amount of KOD, similar TOF were observed indicating that there is no dependence
on the amount of added KOD. However, [KOD] dependence can not be ruled out
because it appears that the catalyst is operating in the benzene phase of the reaction
98
where the amount of base is likely constant (saturated) throughout the reactions.
When the reaction is loaded into the Schlenk bomb, the aqueous phase is red due to
the presence of the catalyst and the benzene phase is colorless. Once the reaction is
heated at 180
o
C, the color of the benzene layer turns black. Stopping the reaction
after a short period of time, the benzene phase is black and the aqueous phase is
colorless. This indicates that the catalyst is likely residing in the benzene phase.
H/D exchange studies with 1-(OH)
2
Py showed an inverse dependence of pyridine
through a 1/[Py] study conducted at 190
o
C. An Eyring plot, Figure 36, was obtained
for the H/D exchange of benzene and water using 1-(OH)
2
Py as the catalyst over a
temperature range of 160-190
o
C. The experimental enthalpy of activation was
determined to be ΔH
‡
= 33 (± 2) kcal/mol. DFT calculations predict that the
enthalpy of activation for the C-H activation of benzene with a cis-1-(OH)
2
Py
should be ΔH
‡
= 36 kcal/mol, whereas the trans-1-(OH)
2
Py has an enthalpy of
activation of ΔH
‡
= 42 kcal/mol. Since 1-(OH)
2
Py starts out in a trans configuration,
a cis to trans isomerization must occur prior to the transition state. However, it is not
expected that this isomerization step will be the rate limiting step as only one ligand
needs to rearrange in order to go from the five coordinate trans-1-(OH)
2
-opensite to
the cis-1-(OH)
2
-opensite.
99
y = -17505x + 26.487
R
2
= 0.9826
Delta H
‡
= 33 (± 2)
Delta S
‡
= 5 (± -18)
-13.5
-13
-12.5
-12
-11.5
-11
-10.5
-10
0.00212 0.00216 0.0022 0.00224 0.00228
1/T (K
-1
)
ln(k
obs
/T)
Figure 36. Eyring Plot for H/D exchange by 1-OH
2
Py with benzene-H
6
and
D
2
O.
The focus of the work was then shifted to see whether I could get a
stoichiometric product from the C-H activation of benzene by 1-(OH)
2
Py. Carrying
out the stoichiometric reaction under the catalytic conditions used for H/D exchange
yielded multiple products. To help identify some of these products I decided to try
and synthesize the products that I would expect to obtain from the stoichiometric
reaction. One of the possible products from the stoichiometric C-H activation of
benzene with 1-(OH)
2
Py would be the (NNC
(tBu2)
)Ir(Ph)(OH)Py, 1-PhOHPy;
therefore, I explored several routes by which 1-PhOHPy could be synthesized. My
group previously reported an (NNC
(tBu2)
)Ir(Ph)(Cl)Py complex,
59
1-PhClPy, which
was used as a precursor for the attempted synthesis of 1-PhOHPy. Complex 1-
100
PhClPy was heated in THF at 70
o
C for 8 hours with 4 eq of CsOH. However, I did
not obtain 1-PhOHPy from this reaction, instead I obtained, after recrystallization,
the µ-hydroxo dinuclear complex [(NNC
(tBu2)
)IrPh(µ-OH)]
2
, 1-Ph(µ-OH).
Scheme 10. Synthesis of possible phenyl intermediate.
An alternative prep for 1-Ph(µ-OH) was devised that yielded 1-Ph(µ-OH)
with much less side products from a μ-chloro bridged dinuclear complex which was
previously reported by the Periana group, [(NNC
(tBu2)
)IrPh(µ-Cl)]
2
, 1-Ph(µ-Cl).
59
The alternative prep required that 1-Ph(µ-Cl) be heated at 70
o
C for 8 hours with 4
eq of CsOH in THF, and after recrystallization from CH
2
Cl
2
and pentane the product,
1-Ph(µ-OH), was obtained as a black, air-stable solid in 38 % yield. Complex
1-Ph(µ-OH) was characterized by
1
H and
13
C NMR, high-resolution mass
spectrometry, elemental analysis, and X-ray crystallography. The ORTEP structure
of 1-Ph(µ-OH) can be seen in Figure 37.
101
N1
C1
O1
Ir1
N2
Figure 37. ORTEP of 1-Ph(µ-OH). (Thermal ellipsoids at 50 % probability, and
a molecule of water and CH
2
Cl
2
omitted for clarity). Selected bond
distances (Å): Ir(1)-O(1), 2.093(8); Ir(1)-C(1) = 1.99(14); Ir(1)-N(1)
= 2.150(9); Ir(1)-N(2) = 1.964(10). Selected bond angles (degrees):
Ir(1)-O(1)-Ir(2), 101.7(3); N(2)-Ir(1)-O(1), 170.7(4).
It was then suspected that if the chloro group could be replaced with a more
labile group such as trifluoroacetate, it might be possible to synthesize 1-PhOHPy
under milder conditions. Therefore, I synthesized (NNC
(tBu2)
)Ir(Ph)(TFA)Py, 1-
PhTFAPy, from 1-PhClPy using silver trifluoroacetate in CH
2
Cl
2.
This reaction was
sluggish at room temperature taking approximately seven days to go to completion.
The silver chloride and solvent were removed, and 1-PhTFAPy was obtained by
recrystallization as a reddish-orange, air-stable solid in 85 % yield. My attempts to
102
synthesize 1-PhOHPy proved unsuccessful. Reacting 1-PhTFAPy in THF-d
8
with 4
eq of CsOH at room temperature over 2 days produced 1-Ph(µ-OH) in 49 % yield,
by internal standardization. These reactions indicate that the ∆G for formation of 1-
Ph(µ-OH) from 1-PhOHPy is favorable, and under catalytic conditions 1-Ph(µ-
OH) could be an intermediate or even the resting state of the catalyst. Therefore, I
decided to test whether 1-Ph(µ-OH) was active for H/D exchange between benzene
and water. The TOF for 1-Ph(µ-OH) at 190
o
C was observed to be 7.0 x 10
-3
s
-1
,
which is similar to the TOF observed for 1-(OH)
2
Py, 6.4 x 10
-3
s
-1
. These similar
TOF support the claim that 1-Ph(µ-OH) may be present as an intermediate in the
catalytic reactions. A proposed catalytic cycle can be seen in Figure 38.
Figure 38. Proposed catalytic cycle for water and benzene H/D exchange.
103
Further support for a dinuclear species as an intermediate in the catalytic
cycle comes from analysis of the stoichiometric C-H activation of benzene by 1-
(OH)
2
Py. Analysis of the
1
H NMR spectrum of the stoichiometric reaction doesn’t
reveal any presence of 1-(OH)
2
Py, and the presence of 1-Ph(µ-OH) is difficult to
determine due to the large number of aromatic peaks from the multiple products
produced in the reaction. However, the furthest downfield chemical shift in the
1
H
NMR is at δ 8.5 ppm. Every mononuclear complex reported in this chapter or used
as a precursor for the synthesis of a molecule in this chapter has a characteristic
chemical shift for the ortho-proton on the pyridyl (NNC
(tBu2)
) ligand that appears at
9 ppm or further downfield. On the other hand, three dinuclear complexes, 1-Ph( μ-
OH), 1-Ph(µ-Cl), and [(NNC
(tBu2)
)Ir(Et)(µ-Cl)]
2
59
that all have their most downfield
chemical shift no greater than δ 8.5 ppm in the
1
H NMR. This indicates that the
products formed in the stoichiometric reaction are most likely dinuclear species. To
determine how much of the products in the stoichiometric reaction contain a
phenylated species, I decided to react the products with trifluoromethanesulfonic
acid. Therefore, a small excess of trifluoromethanesulfonic acid, 3 eq, was used for
protonolysis of any phenyl groups resulting in free benzene-H
6
. The benzene was
quantified by using mesitylene as an internal standard, and the benzene produced
was determined to be 40 % based on the amount of 1-(OH)
2
Py used. No
decomposition of the (NNC
(tBu2)
) ligand has ever been observed in the presence of
trifluoromethanesulfonic acid nor has decomposition of the ligand been observed in
104
the attempted synthesis of (NNC
(tBu2)
)Ir(OTf)
2
C
2
H
4
by protonolysis of the ethyl
group of (NNC
(tBu2)
)IrEt(OTf)C
2
H
4
with trifluoromethanesulfonic acid.
To overcome the inability to operate in water and to determine the kinetic
dependence of C-H activation on the concentration of base, Dr. Young and I decided
to synthesize ligands that would make the catalyst soluble in water. We believed that
ligands with –OH and –COOH groups should assist in solubilizing the catalyst in a
basic aqueous medium. My group ruled out the use of –SO
3
H groups due to their
tendency to desulfonate at elevated temperatures. The first derivative that was
sought after was based on Dr. Young’s synthetic procedure for 1, the (NNC
(tBu2)
)
ligand. The reaction of 4,4’-dimethoxy-2,2’-bipyridine with phenyllithium followed
by oxidation with MnO
2
generates 6-phenyl-4,4’-dimethoxy-2,2’-bipyridine,
Scheme 11. The methoxy groups are then converted to hydroxy groups following
the previously published procedure for converting 4,4’-dimethoxy-2,2’-bipyridine to
4,4’-dihydroxy-2,2’-bipyridine using aqueous hydrobromic acid in acetic acid.
60
The
dihydroxylated organic ligands are generally insoluble in most common organic
solvents. To enable the dihydroxylated ligand to be used in common organic
solvents for the synthesis of the iridium complex I attempted to esterify the hydroxyl
groups with acetylchloride to yield 6-phenyl-2,2’-bipyridine-4,4’-diyl diacetate.
However, due to the low yields and long reaction times required for the synthesis of
this ligand I decided to look for an alternative water soluble ligand.
105
Scheme 11. Synthesis of 6-phenyl-2,2’-bipyridine-4,4’-diyl diacetate.
As previously mentioned, the use of –COOH should also help make the
catalyst soluble in a basic aqueous medium. Therefore, I synthesized 6-phenyl-2,2’-
bipyridine-4,4’-dicarboxylic acid. Knowing that phenyllithium undergoes side
reactions in the presence of carboxyl groups, I was not able to react phenyllithium
with dimethyl 2,2’-bipyridine-4,4’-dicarboxylate. However, by synthesizing 6-
phenyl-4,4’-dimethyl-2,2’-bipyridine the methyl groups could be oxidized using
KMnO
4
in a pyridine/water mixture to generate 6-phenyl-4,4’-dicarboxylate-2,2’-
bipyridine.
61
Esterification using a catalytic amount of sulfuric acid in methanol
followed by chromatographic purification yielded dimethyl 6-phenyl-2,2’-
bipyridine-4,4’-dicarboxylate, (NNC
(COOMe)2
) 2, in 22 % yield, Scheme 12. While a
low yield of 2 was obtained, unreacted starting material and monooxidized products
were recycled in future preparations of 2.
Scheme 12. Synthesis of 2.
An iridium catalyst precursor using 2 as a ligand was synthesized similarly
to the conditions in which iridium complexes containing ligand 1 were synthesized,
Scheme 13. Both the (NNC
(COOMe)2
)Ir(Et)(Cl)C
2
H
4
, 2-EtClC
2
H
4
and
106
(NNC
(COOMe)2
)Ir(Et)(Cl)NCMe, 2-EtClNCMe are produced in the reaction. I chose
to maximize my yield of 2-EtClNCMe. As a result, the initial reaction was heated
with NCCH
3
for 2 hours at 60
o
C to convert most of the product to 2-EtClNCMe, a
greenish solid in 25 % yield. The chloride was then removed through chloride
abstraction using silver trifluoroacetate, AgTFA, to yield a green solid,
(NNC
(COOMe)2
)Ir(Et)(TFA)NCMe, 2-EtTFANCMe, in 84% yield. The ethyl group
was removed by protonolysis with trifluoroacetic acid to yield a bright red solid,
(NNC
(COOMe)2
)Ir(TFA)
2
NCMe, 2-TFA
2
NCMe, in a 44 % yield, after purification.
Scheme 13. Synthesis of 2-TFA
2
NCMe.
It was proposed that reaction of 2-TFA
2
NCMe in basic aqueous media
should hydrolyze the methyl esters to generate carboxylates. These carboxylates
should make the complex soluble in the basic aqueous medium. Indeed heating an
approximately 5 mM solution of 2-TFA
2
NCMe in 0.01 M KOD in D
2
O at 90
o
C for
107
one hour results in the insoluble reddish 2-TFA
2
NCMe solubilizing to form a dark
green solution. Analysis of the solution by
1
H NMR shows that 2 equiv of MeOH are
present from the hydrolysis of the esters, Figure 39. Analysis of this same reaction
by
19
F NMR reveals one fluorine resonance, which corresponds to unbound
trifluoroacetate. This was confirmed by spiking the solutions with sodium
trifluoroacetate, which resulted in only one fluorine peak in the
19
F NMR.
Consequently, this suggests that the trifluoroacetate groups have been displaced by
deuteroxide. To further confirm this result, a small amount of 2-EtClNCMe was
stirred overnight in CH
2
Cl
2
saturated with HCl (g). The reaction changed colors
from green to red producing the dichloro complex, (NNC
(COOMe)2
)Ir(Cl)
2
NCMe.
(NNC
(COOMe)2
)Ir(TFA)
2
(NCMe)
30 eq KOD
D
2
O, 80
o
C, 2hours
Figure 39.
1
H NMR of 2-TFA
2
NCMe after heating in KOD/D
2
O to hydrolyze
the esters and a produce a water soluble complex.
108
The solvent was removed, and the material was heated in D
2
O containing 0.01 M
KOD at 120
o
C for one hour. Higher temperatures were needed to solubilize the
dichloro precursor. The resulting solution was dark green in color and yielded a
similar
1
H NMR, Figure 40, to that of the reaction of KOD in D
2
O with 2-
TFA
2
NCMe. However, in both cases the Ir-NCMe peak was not observed in the
1
H
NMR, which was the case for the reaction of NaOMe with 1-TFA
2
NCMe, vide
supra. This suggests that the NCCH
3
peak is likely reacting in the presence of base.
2-TFA
2
NCMe in KOD/D
2
O
2-Cl
2
(NCMe) after further
heating to 100
o
C in KOD/D
2
O
Identical NMR’s from 2 different
complexes likely indicates that the (TFA
and Cl) groups have been displaced by
hydroxo groups
Figure 40. Comparison of 2-TFA
2
NCMe (top) and 2-Cl
2
NCMe (bottom) heated
in KOD/D
2
O to yield similar NMR’s suggesting that the (TFA and
Cl) groups have been displaced by deuteroxide.
Initial H/D exchange studies, using a 3.5 mM of 2-TFA
2
NCMe as a catalyst
precursor, showed that in 0.10 M KOD in 1 mL of D
2
O and 1 mL of benzene-H
6
H/D exchange was observed with a TOF = 6.0 x 10
-3
s
-1
at 150
o
C. Furthermore,
109
after the reaction was stopped, the benzene phase was colorless and the aqueous
phase was colored indicating that the catalyst is likely residing in the aqueous phase.
To eliminate any the possibility of the catalyst residing in any phase other than water
at the temperature under which catalysis occurs, I decided to only use 50 μL of
benzene-H
6
(~150 eq). At 130
o
C in a D
2
O solution with a 0.05 M concentration of
KOD, 50 μL of benzene-H
6
, and a 3.7 mM catalyst concentration (2-TFA
2
NCMe)
results in a TOF of 1.50 x 10
-3
s
-1
. Addition of pyridine to this reaction shows
inhibition by shutting down catalysis at 130
o
C, and resulting in the color change of
the solution from dark green to dark red. Addition of a mercury drop also showed
no affect on catalysis, which suggests that the colloidal iridium is not acting as the
catalyst.
62
I decided to look for an alternative ligand that could be made water
soluble under milder conditions due to the following: 1) difficulty in purifying 2-
TFA
2
NCMe, 2) the questions surrounding the fate of the acetonitrile originally
bound to iridium (Ir-NCCH
3
), and 3) the possibility of side reactions between the
methanol generated from the methyl esters and the iridium center.
Figure 41. Conditions for the catalytic H/D exchange reaction between water
and benzene using 2-TFA
2
NCMe as the catalytic precursor.
H
6
H
6 -n
D
n
~3.5 mM 2-TFA
2
NCMe
1 mL
0.10 M KOD, 1mL D
2
O
150
o
C, TOF = 6.0x10
-3
s
-1
110
An alternative route to synthesizing a water soluble ligand is by the use of the
Krönhke pyridine synthesis, Scheme 14. A postdoc in our group, Dr. Kenny Young,
discovered and explored this route for making water soluble NNC ligand derivatives,
where NNC = 6-phenyl-2,2’-bipyridine. Starting with a water soluble group on the
phenyl Mannich base allows for the placement of water soluble groups on the NNC
ligand. Dr. Young decided to use 4-hydroxyacetophenone as the precursor to the
Mannich base, which after the reaction results in 6-(para-hydroxyphenyl)-2,2’-
bipyridine. The placement of the hydroxy group on the phenyl ring was chosen such
that cyclometallation at either place on the phenyl ring would produce a symmetrical
cyclometallated iridium complex.
Scheme 14. Synthesis of NNC
pOH
ligand.
It was found that the ligand can be cyclometallated to the iridium center;
however, the resulting complex is only soluble in DMSO and KOH/H
2
O. To ease
with purification and further synthetic steps, I decided to esterify the hydroxy group
just as I had with (NNC
(COOMe2)
). Esterification by trifluoromethanesulfonic
anhydride was chosen such that hydrolysis of the aryltrifluoromethanesulfonate
under catalytic conditions, in the presence of base, would yield free
trifluoromethanesulfonate. Trifluoromethanesulfonate is known to be a very weakly
coordinating ligand, which should not affect the catalyst by being present in the
111
reaction. The (NNC
pOTf
)Ir(TFA)
2
NCMe was synthesized and heated in a mixture of
KOD/D
2
O and did not undergo facile hydrolysis of the trifluoromethanesulfonate
ester. Therefore, I found an alternative preparation for the hydrolysis of
aryltrifluoromethanesulfonates using Et
4
NOH (aq) in dioxane at room temperature.
63
This procedure appeared to work in good yields. In order to more easily observe the
esterification group, I decided to use an acetyl group as the protecting group. The
acetyl group would more easily be observed by
1
H NMR, whereas the triflate
protecting group could only be observed by
19
F NMR. The hydroxy ligand was
protected with acetic anhydride in pyridine to yield 6-(para-phenylacetate)-2,2’-
bipyridine in 90 % yield. The ligand was attached to the metal using the standard
procedure previously reported, Scheme 15. The ligated complex was synthesized
and isolated as an orange solid (NNC
pOAc
)Ir(Et)(Cl)C
2
H
4
, 3-EtClC
2
H
4
, in 37 %
yield. The ethylene complex was converted to the acetonitrile complex by heating
the ethylene complex in neat acetonitrile at 100
o
C for 12 hours to produce a red
solid (NNC
pOAc
)Ir(Et)(Cl)NCMe, 3-EtClNCMe, in 97 % yield. The chloride was
removed by halide abstraction using silver trifluoroacetate, AgTFA, to yield a red
solid (NNC
pOAc
)Ir(Et)(TFA)NCMe, 3-EtTFANCMe, in 81 % yield. Protonolysis of
the ethyl group by stirring 3-EtTFANCMe in neat trifluoroacetic acid overnight
results in a yellow solid (NNC
pOAc
)Ir(TFA)
2
NCMe, 3-TFA
2
NCMe, in 76 % yield.
112
N
N
[Ir(C
2
H
4
)
2
( Cl)]
2
CH
2
Cl
2
,
C
2
H
4
atmosphere, 37%
N
N
Ir
Cl
NCCH
3
,
100
o
C, 12hrs
97%
neat HTFA
rt,24h,76%
N
N
Ir
TFA TFA
NCMe
~8eq Et
4
NOH(aq)
dioxane, rt 12h, 76%
N
N
Ir
TFA TFA
HN
N
N
Ir
TFA
NCMe
3
3-EtClC
2
H
4
3-TFA
2
NCMe
3-EtTFANCMe
3-TFA
2
NHCOMe
OAc
OAc
O
Na
OH OAc
OAc
1.25 eq AgTFA
CH
2
Cl
2
,dark
24h, 82%
N
N
Ir
Cl
NCMe
3-EtClNCMe
OAc
N
N
Ir
HO OH
HN
3-(OH)
2
NHCOMe
O
Na
OH
N
N
Ir
TFA TFA
HN
3-TFA
2
NHCOMe
O
Na
OH
0.4M NaOH(aq)
60
o
C, 12 hours
Scheme 15. Synthesis of 3-(OH)
2
NHCOMe.
Using the previously described procedure for removal of the triflate
protecting group resulted in a yellowish-orange solid in 76% yield. During the
characterization of this new complex, it was discovered that the iridium bound
113
acetonitrile had reacted either with the water or hydroxide to generate an Ir-
acetamido complex. Previously Lau et al. reported that their
(Tp)Ru(PPh
3
)(H)(NCMe) complex undergoes reaction in the presence of water to
generate a Ru-acetamido complex.
54
Consequently, I expected that at some point I
might discover that the Ir-NCCH
3
complex had undergone a similar reaction. The
presence of the acetamide ligand was confirmed by HMBC experiments in which the
only methyl group present in the
1
H NMR at δ 2.5 ppm shows correlation to the most
downfield carbon in the
13
C NMR at δ 180 ppm. A carbon in that area of the
13
C
NMR is characteristic of a carbonyl carbon. On the other hand, in the previously
reported 1-Et(TFA)NCMe the nitrile carbon is at δ 116 ppm.
59
This iridium
acetamide complex, (NNC
pOH
)Ir(TFA)
2
NHCOMe, 3-TFA
2
NHCOMe, was
characterized by
1
H and
13
C NMR, high-resolution mass spectrometry, and X-ray
crystallography, Figure 42. Crystals suitable for X-ray crystallography were grown
by slow diffusion of methylene chloride into a solution of the acetamide complex
dissolved in acetone. I am currently trying to determine what the counter-ion is in
the complex. Elemental analysis results indicated that the elemental composition was
low in Na content, and X-ray crystallography was unable to determine the presence
of the counterion. It is possible that there is a mixture of Na and K as the counter-
ion, and the complex will likely have to be purified using cation exchange
chromatography.
114
C17
C16
C7
O3
O4
C19
O2
N3
N1
Ir1
N2
Figure 42. ORTEP of 3-TFA
2
NHCOMe. (Thermal ellipsoids at 50 %
probability). Selected bond distances (Å): Ir(1)-N(3), 2.073(5); Ir(1)-O(3), 2.040(5);
Ir(1)-N(1), 2.158(4); Ir(1)-N(2), 1.983(5); Ir(1)-C(16), 2.010(5); N(30)-C(17),
1.266(8); C(17)-O(2), 1.322(8). Selected bond angles (degrees): C(16)-Ir(1)-N(1),
160.8(2). No counterion could be found.
Complex 3-TFA
2
NHCOMe is soluble in basic water and produces an orange
colored solution. Heating 3-TFA
2
NHCOMe in a 0.04 M KOD/D
2
O solution at 60
o
C for 12 hours results in a dark green solution and the formation of a new species.
The
19
F NMR indicates that the only observable fluorine resonance corresponds to
unbound trifluoroacetate. This was confirmed by adding sodium trifluoroacetate to
the reaction, and analyzing the solution by
19
F NMR, which showed only one
fluorine resonance. This reaction was carried out on a preparative scale, and
115
purification over centrifugal thin-layer chromatography using silica resulted in the
isolation of (NNC
pOH
)Ir(OH)
2
NHCOMe, 3-(OH)
2
NHCOMe, in 65 % yield.
Complex 3-(OH)
2
NHCOMe has been characterized by
1
H NMR and high resolution
mass spectroscopy in negative mode. The bishydroxo complex reacted in the
presence of methanol overnight to produce several species. As a result, the
13
C NMR
could not be obtained by the time this manuscript was written.
Scheme 16. Synthesis of 3-(OH)
2
NHCOMe.
Further heating of the 3-(OH)
2
NHCOMe complex in 0.4 M KOD/D
2
O at
120
o
C results in a color change from dark green to a dark red. The peak
corresponding to coordinated acetamide moves in the
1
H NMR from δ 2.32 ppm to δ
1.92 ppm which corresponds to free acetamide. Furthermore, addition of acetamide
to this solution increases this proton resonance relative to the residual solvent peak.
This evidence suggests that the iridium bound trifluoroacetates and the iridium
bound acetamide are all removed by heating 3-TFA
2
NHCOMe in basic water.
However, the hydrolysis of the acetamide from 3-(OH)
2
NHCOMe results in several
species present by
1
H NMR. I am currently trying to identify them.
116
Using 3-TFA
2
NHCOMe as a catalyst precursor, H/D exchange between
water and benzene was performed at 160
o
C. In this reaction a 13.3 mM solution of
catalyst was used in a 0.15 M KOD/D
2
O solution. To prevent the formation of a
benzene phase, the partial pressure of benzene was kept below the known vapor
pressure of benzene at 160
o
C. Using the Van der Waals equation for gases the
values for “a” and “b” were obtained from the literature to calculate the molar
volume of benzene needed. The number of moles was calculated using the head
space volume of the reactor. It was determined that less than 54.4 μL of benzene-H
6
could be added in order to keep the partial pressure of benzene less than the known
vapor pressure of benzene, see experimental. Professor Periana and I consider these
calculations to be in our favor as we are not accounting for the solubility of benzene
in the aqueous phase. Using 50.0 μL of benzene-H
6
and sampling the reaction over
time it was determined that the reaction had a TOF of 5.0 x 10
-4
s
-1
. I am currently
trying to determine whether this reaction is mass transfer limited.
117
y = 0.0271x
R² = 0.9985
0
5
10
15
20
25
30
35
0 200 400 600 800 1000 1200
Turnover Number
Time (mins)
Figure 43. Plot of TON vs. time for a 13.3 mM solution of 3-TFA
2
NHCOMe in
0.15 M KOD/D
2
O solution with 50 μL of benzene-H
6
at 160
o
C with
the reaction sampled over time.
It was recently reported that having –OH groups at the -4,4’- positions in
bipyridine had a dramatic increase on the rate of hydrogenation of bicarbonate to
generate formic acid.
64
Therefore, I speculated whether the placement of the –OH
group in the NNC
pOH
ligand was the most beneficial place. For simplification if we
assume that the carbon bound to the metal is numbered 1, then the –OH group is in
the 3 position. As a result, when the –OH group becomes –O
-
in the presence of base,
the negative charge can be inducted into the aromatic ring; however, analysis of the
possible resonance structures shows that the negative charge never resides at the 1
118
position, the carbon bound to the metal, Scheme 18. Consequently, I wondered
what effect the hydroxyl placement on the phenyl ring has on the rate for H/D
exchange. I synthesized 6-(3-hydroxyphenyl)-2,2’-bipyridine, NNC
mOH
, using the
same method as above for the synthesis of NNC
pOH
, Scheme 17.
Scheme 17. Synthesis of NNC
mOH
.
Analysis of the possible resonance structures for the iridium bound NNC
mOH
ligand show that when the hydroxyl group becomes deprotonated to form –O
-
the
negative charge can be inducted into the phenyl ring. The negative charge in one of
the four possible resonances structures resides on the carbon bound to the metal. As a
result, this added charge on the metal might have an impact on the catalytic rates for
H/D exchange.
119
N
N
O
-
Ir
N
N
O Ir
N
N
O
Ir
N
N
O Ir
N
N
Ir
O
-
N
N
Ir
O
N
N
Ir
O
N
N
Ir
O
NNC
pOH
NNC
mOH
Scheme 18. Resonance structures for deprotonated NNC
mOH
and NNC
pOH
bound
to iridium.
I am currently synthesizing the (NNC
mOH
)Ir(TFA)
2
NHCOMe with the
purpose of comparing it’s catalytic rates for H/D exchange relative to 3-
120
TFA
2
NHCOMe. There are several other experiments that need to be performed in
order to better understand these systems.
1. Stirring studies to ensure that the reaction is not mass transfer limited
2. Eyring analysis for the H/D exchange in basic aqueous media
3. Determine what effect base has on the rate of catalysis
4. Determine what effect the acetamide hydrolysis has on the catalysis
5. Determine the effects of acetamide and acetate on the catalytic rate
6. Analyze a mixture of methane and benzene in the presence of the catalyst and
basic aqueous media to determine if the catalyst is not reacting with methane
or is the catalyst decomposing in the presence of methane
7. Determine the counterion in the 3-TFA
2
NHCOMe complex
8. Determine what effect the placement of the -OH group on the phenyl ring has
on the catalytic rates for H/D exchange
3.3: Conclusion
In conclusion, I have synthesized a water soluble bishydroxo complex, 1-
OH
2
Py, which is competent for the H/D exchange between benzene and water at
160–190
o
C. However, the complex is not stable at elevated temperatures in water,
which precludes its studies with methane. Mechanistic studies were performed using
1-OH
2
Py, and it was determined that the mechanism occurs by preequilibrium
pyridine loss prior to the rate determining step. The attempted synthesis of a
121
possible stoichiometric phenyl product was obtained as a μ-hydroxo bridged
dinuclear complex, 1-Ph( μ-OH). The stoichiometric benzene reaction, carried out
under catalytic conditions, revealed the likely presence of dinuclear complexes, as
suggested by
1
H NMR data. In order to overcome the instability in water at elevated
temperatures, I synthesized several water soluble derivatives of the NNC ligand. I
have currently been exploring the catalysis of one of these ligated complexes 3-
TFA
2
NHCOMe for the catalytic H/D exchange of benzene in a basic aqueous
medium. The catalysis appears to be stable over time; however, further studies are
needed to ensure that the reaction is not mass transfer limited. Experiments have
been designed to gain further understanding about this and related complexes.
3.4: Experimental
General Considerations: Unless otherwise noted all reactions were
performed using standard Schlenk techniques (argon) or in a MBraun glove box
(nitrogen). GC-MS analyses were performed on a Shimadzu GC-MS QP5000 (ver.
2) equipped with a cross-linked methyl silicone gum capillary column (DB5).
1
H
and
13
C NMR were collected on Varian 400 Mercury plus spectrometer and
referenced to residual protiated solvent. Fluorine resonances were referenced to
CFCl
3
or hexafluorobenzene. All coupling constants are reported in hertz, Hz. Mass
spectrometry analyses were performed at the UC Riverside mass spectrometry lab
and at the University of Florida. Elemental analyses were performed by Desert
Analytical Laboratory, Inc.; Arizona. X-ray crystallography data was collected on a
Bruker SMART APEX CCD diffractometer.
122
Materials: IrCl
3
•3H
2
O (Pressure Chemical), phenyllithium (1.8 M in n-butyl
ether, Aldrich), 4,4’-di-tert-butyl-2,2’-dipyridyl (98 %, Aldrich), Manganese(IV)
dioxide ( ≥ 90 %, Aldrich) were all used as received. All solvents were reagent grade
or better. Ether was dried over sodium/benzophenone ketyl and distilled under
argon. Dichloromethane (stabilizer removed with sulfuric acid) was dried over P
2
O
5
and distilled under argon. The ligand 6-phenyl-4,4’-di-tert-butyl-2,2’-bipyridine,
65
and N-[2-(2-pyridyl)-2-oxoethyl] pyridinium iodide were prepared according to
previously published procedures.
66
Chromatotron (centrifugal thin-layer
chromatography) plates were made using aluminum oxide neutral (type E) and silica
for thin layer chromatography, which were purchased from EMD.
Figure 44. Preparation of 1-EtClC
2
H
4
and 1-EtClNCMe.
Preparation of (NNC
(tBu2)
)Ir(Et)(Cl)C
2
H
4
59
(1-EtClC
2
H
4
), and
(NNC
(tBu2)
)IrEtCl(NCCH
3
) (1-EtClNCCH
3
).
59
[Ir(C
2
H
4
)
2
( μ-Cl)]
2
(1.03 g, 1.82
mmol) was dissolved in CH
2
Cl
2
(25 mL) in a Schlenk bomb. In a separate Schlenk
flask, 6-phenyl-4,4’-di-tert-butyl-2,2’-bipyridine (1.25 g, 3.63 mmol) was dissolved
in CH
2
Cl
2
(15 mL). Ethylene was bubbled through the iridium solution while
stirring at –50
o
C for 5 minutes. Under an ethylene atmosphere the dissolved ligand
was transferred (by cannula). The flask was then washed with CH
2
Cl
2
(15 mL) and
123
the solution was transferred to the Schlenk bomb. The resulting red solution was
stirred at –50
o
C for 15 minutes. The reaction was warmed to room temperature and
stirred for 16 hours. During the course of the reaction the bomb was opened
periodically to relieve excess ethylene pressure. After stirring for 16 hours, the
solvent was reduced to 20 mL under reduced pressure, and ethylene was bubbled
through the mixture for five minutes. A minor amount of what is believed to be the
cis-(NNC
(tBu2)
)Ir(Et)(Cl)C
2
H
4
was also observed; however, this complex is only
stable under an ethylene atmosphere. When placed under vacuum, the red solution
turns slightly greenish. The [(NNC
(tBu2)
)Ir(Et)( μ-Cl)]
2
was later characterized as a
greenish colored compound, which is what the cis-isomer likely forms when it
decomposes. Bubbling ethylene through the greenish solution results in what
appears to be an ethylene complex, and treatment with acetonitrile at 50
o
C for 30
minutes leads to the isolation of this side product as the acetonitrile adduct.
Complex 1-EtClC
2
H
4
can be converted to 1-EtClNCCH
3
by heating in acetonitrile.
Acetonitrile (20 mL) was added to the reaction, and the solution was heated at 50
o
C
for 30 minutes. The solvent was removed, and the resulting red residue was passed
through neutral alumina. An ethyl acetate/methanol gradient was used to remove 1-
EtClC
2
H
4
(orange band) and the acetonitrile complex 1-EtClNCCH
3
(red band).
Complexes 1-EtClC
2
H
4
and 1-EtClNCCH
3
were obtained as crystalline material by
recrystallization from CH
2
Cl
2
/Pentane at –25
o
C, which yielded 1.32 g (57.9 %) of 1-
EtClC
2
H
4
and 301.5 mg (13.2 %) of 1-EtClNCCH
3
.
1
H NMR of 1-EtClC
2
H
4
:
(CDCl
3
, 400 MHz): δ = 9.21 (d, 1H,
3
J = 6.1 Hz), 8.04 (d, 1H,
4
J = 2.0 Hz), 7.94 (d,
124
1H,
4
J = 1.6 Hz), 7.80 (d, 1H,
4
J = 1.6 Hz), 7.73 (dd, 1H,
3
J = 8.0 Hz,
4
J = 1.0 Hz),
7.68 (dd, 1H,
3
J = 7.8 Hz,
4
J = 1.6 Hz), 7.56 (dd, 1H,
3
J = 6.1 Hz,
4
J = 2.1 Hz), 7.28
(dt, 1H,
3
J = 7.5 Hz,
4
J = 1.6 Hz), 7.13 (dt, 1H,
3
J = 7.5 Hz,
4
J = 1.0 Hz), 3.97 (s, 4H,
C
2
H
4
), 1.52 (s, 9H), 1.48 (s, 9H), 0.47 (dq, 1H,
2
J = 10.8 Hz,
3
J = 7.7 Hz, -CH
2
-),
0.25 (dq, 1H,
2
J = 10.8 Hz,
3
J = 7.7 Hz, -CH
2
-), -0.28 (t, 3H,
3
J = 7.7 Hz, -CH
3
).
13
C
{
1
H} NMR (CDCl
3
, 100 MHz): δ = 163.8, 163.0, 162.2, 158.4, 153.1, 151.2, 144.7,
144.3, 134.9, 131.6, 124.9, 124.6, 122.7, 119.6, 116.1, 115.1, 65.8(C
2
H
4
), 35.5
(CMe
3
), 35.4 (CMe
3
), 30.9 (CMe
3
), 30.6 (CMe
3
), 14.9 (-CH
3
), -7.5 (-CH
2
-). ESI-
MS: 593.2 m/z. [M-Cl]
+
, 565.2 [M-Cl-C
2
H
4
]
+
. Anal. Calc’d for C
28
H
36
N
2
ClIr: C,
53.53 %; H, 5.78 %; N, 4.46 %: Cl, 5.64 %. Found: C, 52.98 %; H, 5.52 %; N, 4.24
%; Cl, 5.59 %.
1
H NMR of 1-EtClNCCH
3
(CDCl
3
, 400 MHz): δ = 8.78 (d, 1H,
3
J
= 5.7 Hz, 7.91 (d, 1H,
4
J = 1.8 Hz), 7.66 (d, 1H,
4
J = 1.6 Hz), 7.61 (d, 1H,
4
J = 1.6
Hz), 7.55 (m, 2H), 7.48 (dd, 1H,
3
J = 5.7 Hz,
4
J = 1.8 Hz), 7.14 (dt, 1H,
3
J = 7.7 Hz,
4
J = 1.4 Hz), 6.98 (dt, 1H,
3
J = 7.6 Hz,
4
J = 1.3 Hz), 2.69 (s, 3H, NCCH
3
), 1.44 (s,
9H, -CMe
3
), 1.43 (s, 9H, -CMe
3
), 0.91 (m, 1H, Ir-CH
2
-CH
3
), 0.67 (m, 1H, Ir-CH
2
-
CH
3
), 0.21 (t, 1H,
3
J = 7.7 Hz, Ir-CH
2
-CH
3
);
13
C {
1
H} NMR (CDCl
3
, 100 MHz): δ =
167.7, 161.8, 160.8, 157.6, 155.5, 154.0, 149.9, 145.2, 133.6, 130.9, 124.9, 124.1,
120.7, 119.3, 115.0, 114.8, 114.0, 35.3 (CMe
3
), 31.0, 30.7, 16.0, 5.0, -9.4. ESI-MS:
647.2 m/z (M-Cl+NCCH
3
)
+
, 606.2 m/z [M-Cl]
+
, 565.2 m/z [M-Cl-NCCH
3
]
+
. Anal.
Calc’d for C
28
H
35
N
3
ClIr: C, 52.44 %; H, 5.50 %; N, 6.55 %; Cl, 5.53 %. Found: C,
52.03 %; H, 5.47 %; N, 6.23 %; Cl, 5.62 %.
125
Figure 45. Preparation of 1-Ph( μ-Cl).
Preparation of [(NNC
(tBu2)
)IrPh( μ-Cl)]
2
1-Ph( μ-Cl).
59
Complex
1-EtClC
2
H
4
(100 mg, 0.159 mmol) was heated at 160
o
C in benzene (100 mL) in a
Schlenk bomb for 2 hours. The solvent was removed under vacuum, and the residue
was redissolved in CH
2
Cl
2
and reprecipitated with pentane, which yielded 94.7 mg
(91.8 %).
1
H NMR (CD
2
Cl
2
, 400 MHz): δ = 8.57 (d, 1H,
3
J = 5.8 Hz), 8.05 (d, 1H,
4
J = 1.7 Hz), 7.80 (bs, 2H), 7.69 (dd, 1H,
3
J = 7.9 Hz,
4
J = 1.3 Hz), 7.43 (dd, 1H,
3
J =
5.8 Hz,
4
J = 1.7 Hz), 7.15 (dd, 1H,
3
J = 7.4 Hz,
4
J = 1.3 Hz), 7.10 (dt, 1H,
3
J = 7.5
Hz,
4
J = 1.3 Hz), 6.91 (dt, 1H,
3
J = 7.4 Hz,
4
J = 1.3 Hz), 6.40-6.28 (m, 5H, phenyl),
1.53 (s, 9H, -CMe
3
), 1.52 (s, 9H, -CMe
3
).
13
C {
1
H} NMR (CD
2
Cl
2
, 100 MHz): δ =
169.2, 162.2, 161.8, 157.4, 157.0, 154.3, 152.1, 147.6, 137.3, 133.7, 130.9, 125.3,
125.1, 124.7, 124.7, 121.3, 119.3, 115.2, 115.2, 35.6, 31.0, 30.6. Anal. Calc’d for
C
60
H
64
N
4
Cl
2
Ir
2
: C, 55.58 %; H, 4.98 %; N, 4.32 %; Cl, 5.47 %. Found: C, 55.19 %;
H, 4.69 %; N, 4.76 %; Cl, 5.20 %.
126
Figure 46. Preparation of 1-PhClPy.
Preparation of (NNC
(tBu2)
)Ir(Ph)(Cl)Py (1-PhClPy).
59
Complex 1-
EtClC
2
H
4
(52.0 mg, 8.28 x 10
-2
mmol) was heated at 160
o
C in benzene (80 mL) in
a Schlenk bomb for 2 hours. The solvent was removed under vacuum, and the
residue was redissolved in pyridine (10 mL). The pyridine was removed, and the
mixture was purified by alumina prep TLC with CH
2
Cl
2
,
yielding 55.7 mg (92.5 %).
1
H NMR (CDCl
3
, 400 MHz): δ = 9.30 (d, 1H,
3
J = 5.8 Hz), 8.32 (dd, 2H), 8.07 (dd,
1H,
3
J = 7.6 Hz,
4
J = 1.2 Hz), 7.87 (d, 1H,
4
J = 1.7 Hz), 7.72 (d, 1H,
3
J = 1.8 Hz),
7.63 (dd, 1H,
3
J = 5.7 Hz,
4
J = 1.9 Hz), 7.61 (d, 1H,
3
J = 1.7 Hz), 7.56 (dd, 1H,
3
J =
7.8 Hz), 7.47 (m, 1H), 7.19 (dt, 1H,
3
J = 7.6 Hz,
3
J = 1.3 Hz), 7.04 (dt, 1H,
3
J = 7.6
Hz,
3
J = 1.2 Hz), 6.97 (m, 2H), 6.88 (m, 2H), 6.62-6.54 (m, 3H), 1.47 (s, 9H, -
CMe
3
), 1.44 (s, 9H, -CMe
3
).
13
C {
1
H} NMR (CDCl
3
, 100 MHz): δ = 169.5, 162.4,
160.5, 158.4, 156.5, 156.4, 150.5, 149.5, 146.0, 136.5, 136.3, 135.7, 131.8, 127.7,
125.4, 124.9, 124.8, 121.5, 121.2, 119.1, 115.1, 114.6, 35.5, 35.5, 31.1, 30.8. ESI-
MS: 750.2 m/z [M+Na]
+
728.2 m/z [M+H]
+
. Anal. Calc’d for C
35
H
37
N
3
ClIr: C,
127
57.79 %; H, 5.13 %; Cl, 4.87 %; N, 5.78 %. Found: C, 56.97 %; H, 4.86 %; Cl, 4.87
%; N, 5.74 %.
Figure 47. Preparation of 1-EtTFANCMe.
Preparation of (NNC
(tBu2)
)Ir(Et)(TFA)NCCH
3
(1-EtTFANCMe). Under
an inert atmosphere, CH
2
Cl
2
(30 mL) was added to a Schlenk flask containing 1-
EtTFANCMe (620.4 mg, 0.9674 mmol) and silver trifluoroacetate (235.0 mg, 1.064
mmol). The mixture was filtered over celite to remove the silver chloride. The
solvent was removed under reduced pressure, and the product was obtained by
recrystallization from CH
2
Cl
2
and pentane at -30
o
C resulting in a 78.2 % (543.8 mg)
yield.
1
H NMR (CDCl
3
, 400MHz): δ = 8.87 (d, 1H,
3
J = 6.0 Hz), 7.85 (d, 1H,
4
J =
1.6 Hz), 7.63 (d, 1H,
4
J = 1.4 Hz), 7.58 (d, 1H,
4
J = 1.4 Hz), 7.53 (d, 1H,
3
J = 7.4
Hz), 7.50 (d, 1H,
3
J = 8.0 Hz), 7.46 (dd, 1H,
3
J = 6.0 Hz,
4
J = 1.9 Hz), 7.14 (t, 1H,
3
J
= 7.3 Hz), 6.99 (t, 1H,
3
J = 7.0 Hz), 2.58 (s, 3H, -NCCH
3
), 1.44 (s, 9H), 1.42 (s, 9H),
0.87 (m, 1H, Ir-CH
2
-CH
3
), 0.58 (m, 1H, Ir-CH
2
-CH
3
), 0.09 (t, 3H, -CH
2
CH
3
,
3
J =
7.9 Hz).
13
C {
1
H} NMR (CDCl
3
, 100MHz): δ = 168.4, 162.3, 161.5, 158.0, 156.6,
152.8, 151.0, 146.0, 134.0, 130.8, 124.7, 123.8, 121.1, 118.7, 116.4, 116.31
128
(CO(CF
3
) J
C-F
= 294 Hz), 114.7, 113.9, 35.51, 35.49, 31.07, 30.73, 16.6, 4.62, 15.42.
19
F NMR (CD
2
Cl
2
, 376 MHz): δ = -74.79 (s, 3F). Hi res ESI for C
30
H
35
N
3
O
2
F
3
Ir:
Calc’d Mass [M-TFA]
+
: (606.2460 m/z); Found (606.2400 m/z).
Figure 48. Preparation of 1-TFA
2
NCMe.
Preparation of (NNC
(tBu2)
)Ir(TFA)
2
NCCH
3
(1-TFA
2
NCMe). Under an
inert atmosphere, complex 1-EtTFANCMe (1.644 g, 2.289 mmol) was stirred
overnight with trifluoroacetic acid (60 mL) in a Schlenk flask. The solvent was
removed under reduced pressure, and the resulting brown, oily residue was
redissolved in CH
2
Cl
2
. Compound 1-TFA
2
NCMe was purified using column
chromatography (basic alumina), and it eluted as a yellow band with 95 % CH
2
Cl
2
/
5 % ethyl acetate in a 60.2 % (1.103 g) yield.
1
H NMR (CD
2
Cl
2
, 400MHz): δ =
9.32 (d, 1H,
3
J = 5.8 Hz), 8.08 (d, 1H,
4
J = 1.8 Hz), 7.88 (d, 1H,
4
J = 1.5 Hz), 7.85
(d, 1H,
4
J = 1.5 Hz), 7.72 (m, 3H), 7.32 (dt, 1H,
3
J = 7.7 Hz,
4
J = 1.4 Hz), 7.17 (dt,
1H,
3
J = 7.6 Hz,
4
J = 1.1 Hz), 2.81 (s, 3H), 1.55 (s, 9H), 1.51 (s, 9H).
13
C {
1
H}
NMR (CD
2
Cl
2
, 100MHz): δ = 168.5, 165.1, 164.6, 164.1 (CO(CF
3
)
2
J
C-F
= 35.7 Hz),
158.1, 157.6, 153.6, 147.3, 141.3, 135.8, 130.9, 125.2, 124.1, 123.9, 119.8, 118.8,
129
115.9, 115.6, 112.6 (CO(CF
3
) J
C-F
= 290.7 Hz), 36.0 (-C-(CH
3
)
3
), 35.9 (-C-(CH
3
)
3
),
31.1 (-C-(CH
3
)
3
), 30.8 (-C-(CH
3
)
3
), 4.5 (Ir-NCCH
3
).
19
F NMR (CD
2
Cl
2
, 376 MHz):
δ = -75.09 (s, 3F). Anal. Calc’d for C
30
H
30
N
3
O
4
F
6
Ir: C, 44.88 %; H, 3.77 %; N, 5.23
%; F, 14.20 %. Found: C, 44.96 %; H, 3.79 %; N, 5.16 %; F, 14.63 %. Hi-res FAB
+
(
191
Ir) for C
30
H
30
N
3
O
4
F
6
Ir: Calc’d Mass [M]
+
: (801.1746 m/z); Found: (801.1717
m/z).
Figure 49. Preparation of 1-TFA
2
Py.
Preparation of (NNC
(tBu2)
)Ir(TFA)
2
Py (1-TFA
2
Py). Complex 1-
TFA
2
NCMe (1.103 g, 1.374 mmol) was dissolved in degassed pyridine (40 mL).
The solution was heated overnight in a Schlenk bomb at 100
o
C. The pyridine was
removed under reduced pressure to give an orange solid, which was redissolved in
CH
2
Cl
2
. Complex 1-TFA
2
Py was purified by column chromatography (basic
alumina), and it was eluted from the column as an orange band with an eluent
mixture of 25 % pentane and 75 % CH
2
Cl
2
in a 94.2 % (1.088 g) yield.
1
H NMR
(CD
2
Cl
2
, 400 MHz): δ = 9.09 (dd, 2H,
3
J = 5.3 Hz,
4
J = 1.5 Hz), 8.53 (d, 1H,
3
J = 5.5
Hz), 8.20 (d, 1H,
4
J = 1.8 Hz), 8.08 (dt, 1H,
3
J = 7.6 Hz,
4
J = 1.6 Hz), 7.96 (d, 2H),
130
7.79 (dd, 1H,
3
J = 7.8 Hz,
4
J = 1.6 Hz), 7.66 (m, 3H), 7.22 (dt, 1H,
3
J = 7.6 Hz,
4
J =
1.8 Hz), 7.15 (dt, 1H,
3
J = 7.6 Hz,
4
J = 1.5 Hz), 6.96 (dd, 1H,
3
J = 7.6 Hz,
4
J = 1.2
Hz), 1.62 (s, 9H, t-Bu), 1.53 (s, 9H, t-Bu);
13
C {
1
H} NMR (CD
2
Cl
2
, 400 MHz): δ =
168.6, 164.5, 164.4, 163.6 (O
2
C-(CF
3
),
2
J
C-F
= 36.6 Hz), 160.0, 158.2, 155.0, 152.1,
150.1, 149.0, 141.5, 138.3, 133.6, 130.3, 126.3, 124.9, 124.0, 123.7, 119.7, 115.5,
115.1, 112.7 ((O
2
C-(CF
3
), J
C-F
= 291.3 Hz), 35.93 (-C-(CH
3
)
3
), 35.90 (-C-(CH
3
)
3
),
31.3 (-C-(CH
3
)
3
), 30.8 (-C-(CH
3
)
3
).
19
F NMR (CD
2
Cl
2
, 376 MHz): δ = -75.63 (s,
3F). Anal. Calc’d for C
33
H
32
N
3
O
4
F
6
Ir: C, 47.14 %; H, 3.84 %; N, 5.00 %; F, 13.56
%. Found: C, 46.73 %; H, 3.71 %; N, 4.83 %; F, 13.53 %. Hi-res FAB
+
(
191
Ir) for
C
33
H
32
N
3
O
4
F
6
Ir: Calc’d Mass [M]
+
: (839.1903 m/z); Found: (839.1878 m/z).
Figure 50. Preparation of 1-OMe
2
Py.
Preparation of (NNC
(tBu2)
)Ir(OMe)
2
Py (1-OMe
2
Py): Under an inert
atmosphere, 1-TFA
2
Py (313.3 mg, 0.3726 mmol) and sodium methoxide (330.7 mg,
6.122 mmol) were dissolved in methanol (30 mL) in a Schlenk bomb. The bomb
was sealed and heated at 70
o
C for 24 hours. The solvent was removed under reduced
131
pressure, and the resulting solid was dissolved in CH
2
Cl
2
. The solution was filtered
over celite to remove the excess sodium methoxide. The process of filtering out the
excess sodium methoxide was repeated until the solution could easily be filtered
through a pipette plug of celite. Complex 1-OMe
2
Py was purified by centrifugal
thin-layer chromatography (Chromatotron) using a neutral alumina Chromatotron
plate. The product was eluted as a blackish-green band with 4 % methanol / 96 %
ethyl acetate as the eluent to yield a black solid in 35.2 % (266.5 mg) yield.
1
H
NMR (CDCl
3
, 400 MHz): δ = 9.52 (dd, 1H,
3
J = 7.0 Hz,
4
J = 1.4 Hz), 8.27 (d, 1H,
3
J
= 5.8 Hz), 8.01 (d, 1H,
4
J = 1.8 Hz), 7.96 (dt, 1H,
3
J = 7.8 Hz,
4
J = 1.4 Hz), 7.80 (dd,
1H,
3
J = 6.4 Hz,
4
J = 1.8 Hz), 7.63 (m, 1H), 7.58 (dt, 2H,
3
J = 6.2 Hz,
4
J = 1.4 Hz),
7.49 (dd, 1H,
3
J = 6.0 Hz,
4
J = 1.8 Hz), 7.05 (m, 3H), 2.52 (s, 6H, Ir-OCH
3
), 1.55 (s,
9H), 1.44 (s, 9H);
13
C {
1
H} NMR (CDCl
3
, 100 MHz): δ = 168.6, 162.7, 162.3,
158.2, 156.3, 148.6, 146.5, 136.5, 132.5, 130.5, 125.7, 125.1, 124.0, 121.6, 119.6,
114.6, 114.0, 59.0 (Ir-OCH3), 35.4 (-C-(CH
3
)
3
), 35.3 (-C-(CH
3
)
3
), 31.2 (-C-(CH
3
)
3
),
30.6 (-C-(CH
3
)
3
). Anal. Calc’d for C
31
H
38
N
3
O
2
Ir: C, 55.01 %; H, 5.66 %; N, 6.21 %.
Found: C, 55.31; H, 6.01; N, 5.93. Hi-res FAB
+
(
191
Ir) for C
31
H
38
N
3
O
2
Ir: Calc’d
Mass [M]
+
: (675.2570 m/z); Found: (675.2594 m/z).
132
Figure 51. Preparation of 1-(OH)
2
Py.
Preparation of (NNC
(tBu2)
)Ir(OH)
2
Py (1-OH
2
Py): Under an inert
atmosphere, 1-OMe
2
Py (342.2 mg, 0.5055mmol) was dissolved in a 1:1 (24 mL)
mixture of THF: water in a Schlenk bomb. The bomb was sealed and heated at 85
o
C for 2 days. Pyridine (15 mL) was added to the reaction to break up the viscosity
of the solvent, and the solvent was removed under reduced pressure at 60
o
C. The
resulting reddish-black solid was then dissolved in CH
2
Cl
2
and purified over
centrifugal thin-layer chromatography (Chromatotron) using a neutral alumina
Chromatotron plate. Complex 1-OH
2
Py was eluted as a red band by a slow gradient
elution starting with 2 % methanol/ 98 % ethyl acetate and increasing the eluent
mixture up to 20 % methanol/ 80 % ethyl acetate. Complex 1-OH
2
Py was obtained
as a blackish-green solid in 21.4 % (70.2 mg) yield.
1
H NMR (CDCl
3
, 400 MHz): δ
= 9.57 (d, 1H,
3
J = 5.2 Hz), 8.28 (d, 1H,
3
J = 5.8 Hz), 7.95 (d, 1H,
3
J = 1.7 Hz), 7.88
(dt, 1H,
3
J = 7.6 Hz,
4
J = 1.8 Hz), 7.72 (d, 1H,
4
J = 1.7 Hz), 7.71 (d, 1H,
4
J = 1.5 Hz),
7.57 (dd, 1H,
3
J = 7.6 Hz,
4
J = 1.4 Hz), 7.49 (dt, 1H,
3
J = 6.9 Hz,
4
J = 1.5 Hz), 7.42
133
(dd, 1H,
3
J = 5.8 Hz,
4
J = 1.9 Hz), 7.01 (dt, 1H,
3
J = 7.2 Hz,
4
J = 1.5 Hz), 6.96 (dt,
1H,
3
J = 7.3 Hz,
4
J = 1.6 Hz), 6.85 (dd, 1H,
3
J = 7.0 Hz,
4
J = 1.1 Hz), 1.47 (s, 9H),
1.36(s, 9H)
13
C {
1
H} NMR (CDCl
3
, 100MHz): δ = 168.7, 162.4, 161.6, 158.4, 157.1,
151.3, 150.3, 148.9, 147.9, 136.0, 133.3, 130.5, 125.2, 124.8, 124.00, 121.9, 119.4,
114.7, 114.1, 35.3 (-C(CH
3
)
3
), 35.2 (-C(CH
3
)
3
), 31.3 ((-C(CH
3
)
3
), 30.8 ((-C(CH
3
)
3
),
Anal. Calc’d for C
29
H
34
N
3
O
2
Ir: C, 53.68 %; H, 5.28 %; N, 6.48 %. Found: C, 53.12
%; H, 5.19 %; N, 6.32 %. Hi-res FAB
+
(
191
Ir) for C
29
H
34
N
3
O
2
Ir: Calc’d. Mass [M]
+
:
(647.2257 m/z); Found: (647.2265 m/z).
Figure 52. Preparation of 1-Ph( μ-OH).
Preparation of [(NNC
(tBu2)
)IrPh(µ-OH)]
2
(1-Ph(µ-OH)): In a Schlenk
bomb, degassed THF (30 mL) was added to a mixture of 1-Ph(µ-Cl) (150.3 mg,
0.116 mmol) and cesium hydroxide (80.5 mg, 0.479 mmol). The bomb was sealed
under argon, and heated at 70
o
C for 8 hours. The solution was filtered over celite to
remove the cesium chloride and excess cesium hydroxide. The celite was washed
with CH
2
Cl
2
to dissolve any precipitated 1-Ph(µ-OH). The filtrate was then
evaporated to dryness. Complex 1-Ph(µ-OH) was obtained in 38 % yield (55.2 mg,
0.0436 mmol) as a black solid by recrystallization from CH
2
Cl
2
and pentane at -30
134
o
C.
1
H NMR (CDCl
3
, 400MHz): δ = 8.27 (d, 1H,
3
J = 5.8 Hz), 7.88 (d, 1H,
4
J = 1.5
Hz), 7.73 (d, 1H,
4
J = 1.3 Hz), 7.69 (d, 1H,
3
J = 7.7 Hz), 7.65 (d, 1H,
3
J = 1.5 Hz),
7.26 (dd, 1H,
3
J = 5.6 Hz,
4
J = 1.8 Hz), 7.03 (dt, 1H,
3
J = 7.3 Hz,
4
J = 1.5 Hz), 6.75
(dt, 1H,
3
J = 6.7 Hz), 6.73 (t, 1H,
3
J = 7.3 Hz), 6.35 (m, 3H), 6.28 (dd, 1H,
3
J = 3.7
Hz,
4
J = 2.0 Hz), 1.52 (s, 9H), 1.46 (s, 9H).
13
C {
1
H} NMR (CDCl
3
, 100MHz): δ =
169.8, 161.1, 158.4, 158.1, 157.4, 156.8, 151.5, 147.7, 135.9, 133.7, 130.0, 129.8,
124.9, 124.4, 123.8, 120.2, 117.9, 114.0, 113.9, 35.3 (-C(CH
3
)
3
), 35.2 (-C(CH
3
)
3
),
31.2 (-C-(CH
3
)
3
), 30.8 (-C-(CH
3
)
3
), Anal. Calc’d for C
60
H
66
N
4
O
2
Ir
2
: C, 57.21 %; H,
5.28 %; N, 4.45 %. Found: C, 55.64 %; H, 5.37 %; N, 4.41 %. Hi-res FAB
+
(
191
Ir)
for C
60
H
66
N
4
O
2
Ir
2
: Calc’d Mass [M+H]
+
: (1261.4517 m/z); Found (1261.4537 m/z).
N
N
Ir
Cl
N
tBu
tBu
1-PhClPy
AgOOCCF
3
CH
2
Cl
2
, dark, 1 week
N
N
Ir
F
3
CCOO
N
tBu
tBu
1-PhTFAPy
Figure 53. Preparation of 1-PhTFAPy.
Preparation of (NNC
(tBu2)
)IrPh(TFA)Py (1-PhTFAPy): Under an inert
atmosphere, CH
2
Cl
2
(30 mL) was added to a Schlenk bomb containing 1-PhClPy
(213.0 mg, 0.2928 mmol) and silver trifluoroacetate (101.8 mg, 0.4610 mmol). The
reaction was protected from light with aluminum foil and allowed to stir for one
135
week. The solvent was removed under reduced pressure, and the mixture was
redissolved in CH
2
Cl
2
. The mixture was filtered over celite to remove the silver
chloride. The filtrate was evaporated under reduced pressure to yield 1-PhTFAPy
(200.2 mg, 0.2488 mmol) as an orange solid in 85.2 % yield.
1
H NMR (CD
2
Cl
2
,
400MHz): δ = 8.99 (d, 1H,
3
J = 5.6 Hz), 8.06 (m, 4H), 7.87 (d, 1H,
4
J = 1.8 Hz),
7.83 (dd, 1H,
3
J = 7.4 Hz,
4
J = 1.1 Hz), 7.79 (dd, 1H,
3
J = 5.8 Hz,
4
J = 1.6 Hz), 7.71
(d, 1H,
4
J = 1.6 Hz), 7.66 (dt, 1H,
3
J = 7.3 Hz,
4
J = 1.4 Hz), 7.36 (dt, 1H,
3
J = 7.5 Hz,
4
J = 1.4 Hz), 7.28 (dt, 1H,
3
J = 7.0 Hz,
4
J = 1.4 Hz), 7.15 (t, 2H,
3
J = 6.0 Hz), 6.93
(t, 2H,
3
J = 7.0 Hz), 6.89 (t, 2H,
3
J = 7.0 Hz), 6.84 (dt, 1H,
3
J = 7.0 Hz,
4
J = 1.6 Hz),
1.50 (s, 9H), 1.38 (s, 9H).
13
C {
1
H} NMR (CD
2
Cl
2
, 100MHz): δ = 167.0, 164.5,
164.3 (-O
2
C-CF
3
,
2
J
C-F
= 35 Hz) 163.4, 156.4, 155.7, 149.0, 148.1, 147.8, 144.4,
137.9, 132.2, 131.6, 130.5, 127.2, 127.0, 126.6, 125.5, 123.0, 121.6, 120.3, 117.3,
116.6, 115.3, 114.5 (-O
2
C-CF
3
, J
C-F
= 287 Hz) 35.6 (-C(CH
3
)
3
), 35.5 (-C(CH
3
)
3
),
30.4 (-C-(CH
3
)
3
), 30.3 (-C-(CH
3
)
3
).
19
F NMR (CD
2
Cl
2
, 376 MHz): δ = -75.10 (s,
3F). Hi-res ESI/APCI MS for C
37
H
37
N
3
O
2
F
3
Ir: Calc’d Mass [M-Ph]
+
: (728.2076
m/z); Found: (728.2078 m/z).
Figure 54. Preparation of 6-phenyl-4,4’-dimethoxy-2,2’-bipyridine.
136
Preparation of 6-phenyl-4,4’-dimethoxy-2,2’-bipyridine. In a Schlenk
flask, 4,4’-dimethoxy-2,2’-bipyridine (4.97 g, 0.0230 mol) was added to 400 mL of
dry diethyl ether. The flask was cooled to -78
o
C, and phenyllithium (18.0 mL of
1.8 M in n-butyl ether, 0.0324 mol) was added in a drop wise fashion. The reaction
was then allowed to warm to room temperature and stirred for 5 days. The reaction
was quenched with water (50 mL), and the organic phase was extracted with
methylene chloride (100 mL) and separated. The organic phase was washed with
water (3 x 50 mL), saturated NaCl (aq) (3 x 30 mL), and dried over MgSO
4
. The
solvent was removed by rotary evaporation under reduced pressure to yield an
orange oil. The oil was dissolved in 100 mL of CH
2
Cl
2
and added to a round bottom
flask. MnO
2
(25g) was added to the flask in 5 g increments over the course of a 12
hour period, which resulted in a color change of the solution from orange to yellow.
The suspension was stirred for 2 days followed by filtration over celite. The solvent
was reduced by rotary evaporation under reduced pressure. The ligand was purified
using column chromatography on silica, and the product was eluted (80% CH
2
Cl
2
/
20% ethyl acetate) to yield a white solid in a 7.20 % (485.7 mg) yield. Some of the
starting material was recovered (37.4%, 1.857 g).
1
H NMR (CDCl
3
, 400MHz): δ =
8.51 (d, 1H,
3
J = 5.6 Hz), 8.21 (d, 1H,
4
J = 2.6 Hz), 8.14 (t, 1H,
4
J = 1.7 Hz), 8.12 (t,
1H,
4
J = 1.5 Hz), 7.97 (d, 1H,
4
J = 2.0 Hz), 7.50 (dt, 2H,
3
J = 7.0 Hz,
4
J = 1.8 Hz),
7.44 (dt, 1H,
3
J = 7.4 Hz,
4
J = 1.5 Hz), 7.30 (d, 1H,
4
J = 2.5 Hz), 6.86 (dd, 1H,
3
J =
5.7 Hz,
4
J = 2.6 Hz) 4.00 (s, 3H), 3.96 (s, 3H).
13
C {
1
H} NMR (CD
2
Cl
2
, 100MHz):
δ = 168.0, 167.1, 158.4, 158.2, 157.8, 150.6, 139.8, 129.6, 129.1, 127.4, 110.7,
137
107.8, 107.3, 105.2, 55.9, 55.8. Hi-res ESI/APCI MS for C
18
H
16
N
2
O
2
: Calc’d Mass
[M+H]
+
:
(293.1290 m/z); Found: (293.1295 m/z).
Figure 55. Preparation of 6-phenyl-4,4’-dimethyl-2,2’-bipyridine.
Preparation of 6-phenyl-4,4’-dimethyl-2,2’-bipyridine. In a Schlenk flask,
4,4’-dimethyl-2,2’-bipyridine (6.01 g, 0.0326 mol) was added to 250 mL of dry
diethyl ether. The flask was cooled to -78
o
C, and phenyllithium (21.7 mL of a 1.8
M solution in n-butyl ether, 0.0391 mol, 1.2 eq) was added in a drop wise fashion.
The reaction was then allowed to warm to room temperature and stirred overnight.
The reaction was quenched with water (50 mL). The organic phase was extracted
with methylene chloride (100 mL) and separated. The organic layer washed with
saturated NaCl (aq) (3 x 50 mL), and dried over MgSO
4
. The solvent was then
removed by rotary evaporation under reduced pressure to yield an orange oil. The
orange oil was dissolved in 100 mL of CH
2
Cl
2
and added to a 250 mL round bottom
flask. Over the course of a 12 hour period, MnO
2
(25g) was added in 5 g portions
every three hours. This resulted in a color change of the solution from orange to
yellow. The suspension was stirred for 2 days followed by filtration over celite. The
solvent was reduced by rotary evaporation under reduced pressure. The product was
obtained by purification over column chromatography using neutral alumina, the
138
product was eluted (90% CH
2
Cl
2
/ 10% ethyl acetate) from the column to yield a
white solid in 46.4 % (3.93 g) yield.
1
H NMR (CDCl
3
, 400 MHz): δ = 8.54 (d, 1H,
3
J = 4.9 Hz), 8.45 (m, 1H), 8.21 (d, 1H), 8.15 (t, 1H,
4
J = 2.0 Hz), 8.13 (t, 1H,
4
J =
1.4 Hz), 7.59 (dd, 1H), 7.51 (dt, 2H,
3
J = 7.0 Hz,
4
J = 1.6 Hz), 7.43 (dt, 1H,
3
J = 7.2
Hz,
4
J = 2.2 Hz), 7.14 (dd, 1H,
3
J = 5.4 Hz) 2.50 (s, 3H), 2.47 (s, 3H).
13
C {
1
H}
NMR (CDCl
3
, 100 MHz): δ = 156.7, 156.4, 155.9, 149.0, 148.9, 148.1, 139.7, 129.0,
128.8, 127.2, 124.9, 122.4, 121.5, 120.5, 21.6, 21.5. Hi-res ESI/APCI MS for
C
18
H
16
N
2
: Calc’d Mass [M+H]
+
: (261.1392 m/z); Found: (261.1399 m/z).
Figure 56. Preparation of 2.
Preparation of dimethyl 6-phenyl-2,2’-bipyridine-4,4’-dicarboxylate (2).
This preparation follows a previously published preparation for the oxidation of 4,4’-
dimethyl-2,2’-bipyridine.
61
In a three-neck round bottom flask, 6-phenyl-4,4’-
dimethyl-2,2’-bipyridine (1.01 g, 0.00388 mol) was added to a mixture of pyridine
(10 mL) and water (3 mL). The solution was heated to 100
o
C, and KMnO
4
(12 g)
was added in 1 g portions along with water (10 mL) over the course of a 12 hour
period. The reaction was heated for 24 hours at 100
o
C. The reaction was filtered,
while hot, over celite to remove the brown, insoluble MnO
2
. The celite was then
139
washed with pyridine (25 mL) and 2 M KOH (aq) (25 mL) solution. The filtrate was
then placed into a three-neck round bottom flask and heated to 100
o
C. Over the
course of a 12 hour period, KMnO
4
(12 g) was added portion wise (1 g increments)
with water (10 mL / 1 g KMnO
4
). The reaction was heated for 24 hours at 100
o
C.
The solution was filtered, while hot, over celite to remove the MnO
2
. The filtrate
was then slowly titrated with conc. HCl (aq) to remove any unreacted KMnO
4
,
(caution: Cl
2
gas evolution). The addition of conc. HCl (aq) was stopped once the
solution lost its purplish color. The solution was then brought to a basic pH with
KOH in order to extract the pyridine, while leaving the product in its dicarboxylate
form in the aqueous layer. After the solution had a basic pH, CH
2
Cl
2
(500 mL) was
used to extract the pyridine from the reaction mixture. From this organic layer, the
solvent was removed under reduced pressure and the solid material was recycled in
future preparative reactions, as this material contained product, mono-oxidized
products, and unreacted starting material. Ice was added to the aqueous solution, and
conc. HCl (aq) was slowly added to the solution. (Caution should be used in the
previous step as small portions of CH
2
Cl
2
resided on the bottom of the neutralization
flask, and the exothermic nature of the neutralization caused this to reflux
vigorously.) Once the solution reached an acidic pH, a white solid precipitated out
of solution. The white precipitate was collected by centrifugation using four (30
mL) vials. The precipitate was placed on a fine frit and washed with water (50 mL)
followed by drying over air. The white solid was then loaded into a round bottom
flask containing methanol (100 mL) and conc. H
2
SO
4
(aq) (1 mL). The mixture was
140
refluxed for 12 hours. The solution was cooled to room temperature followed by
pouring the solution into a beaker containing ice. Sodium bicarbonate was then
added to the reaction mixture, to neutralize the acid, until the solution had a pH of
7-8. The product was extracted into CH
2
Cl
2
(3 x 50 mL), and the organic layer was
washed with water (3 x 20 mL), sat. NaCl (aq) (3 x 20 mL), and dried over MgSO
4
.
The product was obtained by purification using centrifugal thin-layer
chromatography (Chromatotron) over a neutral alumina plate. The reaction mixture
was loaded onto the Chromatotron plate using a 1:1 mixture of CH
2
Cl
2
: hexanes, and
the product was eluted from the plate by slowly increasing the eluent mixture to neat
CH
2
Cl
2
. The product was obtained a white solid in 22.2 % (0.375 g) yield.
1
H NMR
(CDCl
3
, 400 MHz): δ = 9.11 (d, 1H), 8.45 (m, 1H), 8.21 (d, 1H), 8.15 (t, 1H,
4
J = 2.0
Hz), 8.13 (t, 1H,
4
J = 1.4 Hz), 7.59 (dd, 1H), 7.51 (dt, 2H,
3
J = 7.0 Hz,
4
J = 1.6 Hz),
7.43 (dt, 1H,
3
J = 7.2 Hz,
4
J = 2.2 Hz), 7.14 (dd, 1H,
3
J = 5.4 Hz), 2.50 (s, 3H), 2.47
(s, 3H).
13
C {
1
H} NMR (CDCl
3
, 100MHz): δ = 166.0, 165.9, 157.9, 156.9, 156.3,
150.2, 139.6, 138.6, 138.4, 129.8, 129.1, 127.3, 123.3, 120.9, 120.1, 119.0, 53.0,
52.9. Hi-res ESI/APCI MS for C
20
H
16
N
2
O
4
: Calc’d Mass [M+H]
+
: (349.1188 m/z);
Found: (349.1190 m/z).
Figure 57. Preparation of 2-EtClC
2
H
4
and 2-EtClNCMe.
141
Preparation of (NNC
(COOMe)2
)IrEtCl(C
2
H
4
) (2-EtClC
2
H
4
) and
(NNC
(COOMe)2
)IrEtCl(NCMe) (2-EtClNCMe). Under an inert atmosphere, CH
2
Cl
2
(10 mL) was added to a Schlenk flask containing 2 (70.6 mg, 0.202 mmol), and
CH
2
Cl
2
(15 mL) was added to Schlenk bomb containing [Ir(C
2
H
4
)
2
(µ-Cl)]
2
(57.0 mg,
0.100 mmol). Both reaction vessels were sealed. The bomb containing the
[Ir(C
2
H
4
)
2
(µ-Cl)]
2
was opened under argon, and ethylene was bubbled through the
solution for 5 minutes. The solution changed color to a deep red. The bomb was
then cooled to -78
o
C with continuous bubbling of ethylene. Next, the solution of 2
was cannulated over to the bomb containing the solution of [Ir(C
2
H
4
)
2
(µ-Cl)]
2
.
Ethylene was bubbled through the solution in the bomb for another five minutes, and
the bomb was sealed and allowed to slowly warm to room temperature. The reaction
was then stirred overnight which resulted in a dark green solution. The vessel was
slowly opened under argon. (Caution: Ethylene pressure vents during this step, so
the venting should be controlled by the PTFE valve to the Schlenk bomb). The
solvent was removed under reduced pressure. The bomb containing the residue was
charged with acetonitrile (30 mL) and heated at 60
o
C for 2 hours. The acetonitrile
was removed under reduced pressure, and the products were purified by column
chromatography using silica. The product, 2-EtClC
2
H
4
, was obtained as a dark red
solid by elution from a silica column using a 1:1 mixture of CH
2
Cl
2
: ethyl acetate as
the eluent resulting in 4.0 % (5.1 mg, 0.0081 mmol) yield. The product 2-
EtClNCMe was obtained as a green solid by elution with a 9:1 mixture of ethyl
acetate: methanol as the eluent in 25.2 % (32.8 mg, 0.0510 mmol) yield. 2-
142
EtClC
2
H
4
:
1
H NMR (CDCl
3
, 400 MHz): δ = 9.48 (d, 1H,
3
J = 5.8 Hz), 8.74 (d, 1H,
4
J = 1.8 Hz), 8.47 (d, 2H,
4
J = 2.0 Hz), 8.10 (dd, 1H,
3
J = 5.6 Hz,
4
J = 1.7 Hz), 7.73
(t, 2H,
3
J = 7.6 Hz), 7.31 (dt, 1H,
3
J = 7.7 Hz,
4
J = 1.8 Hz), 7.16 (t, 1H,
3
J = 7.6 Hz),
4.13 (s, 3H), 4.08 (s, 7H), 0.41 (m, 1H, Ir-CH
2
-CH
3
), 0.14 (m, 1H, Ir-CH
2
-CH
3
), -
0.34 (t, 3H,
3
J = 7.8 Hz, Ir-CH
2
-CH
3
).
13
C {
1
H} NMR (CDCl
3
, 100 MHz): δ = 165.5,
164.1, 163.5, 158.9, 153.1, 152.3, 144.0, 142.9, 139.5, 139.0, 134.8, 132.6, 126.8,
125.8, 123.2, 122.6, 118.9, 117.5, 68.3, 53.8, 53.4, 14.5, -6.6. Hi-res ESI/APCI MS
for C
24
H
24
N
2
O
4
ClIr: Calc’d Mass [M-Cl-C
2
H
4
]
+
:
(569.10528 m/z); Found: (569.1049
m/z). 2-EtClNCMe:
1
H NMR (CDCl
3
, 400 MHz): δ = 9.05 (d, 1H,
3
J = 5.8 Hz),
8.62 (s, 1H), 8.27 (d, 1H,
4
J = 1.4 Hz), 8.19 (d, 1H,
4
J = 1.1 Hz), 8.05 (dd, 1H,
3
J =
5.4 Hz,
4
J = 1.6 Hz), 7.61 (d, 1H,
3
J = 7.7 Hz), 7.53 (d, 1H,
3
J = 7.4 Hz), 7.21 (dt,
1H,
3
J = 7.5 Hz,
4
J = 1.4 Hz), 7.03 (dt, 1H,
3
J = 7.4 Hz,
4
J = 1.5 Hz), 4.06 (s, 3H),
4.04 (s, 3H), 2.78 (s, 3H, Ir-NCCH
3
), 0.82 (m, 1H, Ir-CH
2
-CH
3
), 0.59 (m, 1H, Ir-
CH
2
-CH
3
), 0.10 (t, 3H,
3
J = 7.7 Hz, Ir-CH
2
CH
3
).
13
C NMR (CDCl
3
, 100 MHz): δ =
169.8, 164.7, 164.2, 158.3, 156.0, 153.4, 150.8, 143.5, 138.7, 137.7, 133.5, 132.2,
127.2, 126.0, 122.1, 121.5, 117.5, 117.0, 116.8, 53.6, 53.3, 15.6, 5.1, -7.5. Hi-res
ESI/APCI MS for C
24
H
23
N
3
O
4
ClIr: Calc’d Mass [M-Cl]
+
: (610.1318 m/z); Found:
(610.1342 m/z).
143
Figure 58. Preparation of 2-EtTFANCMe.
Preparation of (NNC
(COOMe)2
)IrEtTFA(NCMe) (2-EtTFANCMe). Under
an inert atmosphere, CH
2
Cl
2
(30 mL) was added to a Schlenk bomb containing 2-
EtClNCMe (701.1 mg, 1.086 mmol) and silver trifluoroacetate (251.5 mg, 1.141
mmol, 1.05 eq). The reaction was sealed and allowed to stir overnight in the dark,
which resulted in a dark green reaction mixture. The reaction was filtered over celite
to remove the silver chloride. The solvent was then removed under reduced pressure
to yield a green solid in 84.3 % (661.2, 0.9149 mmol) yield.
1
H NMR (CDCl
3
, 400
MHz): δ = 9.08 (d, 1H,
3
J = 5.7 Hz), 8.57 (s, 1H), 8.25 (d, 1H,
4
J = 1.4 Hz), 8.13 (d,
1H,
4
J = 1.1 Hz), 8.03 (dd, 1H,
3
J = 5.5 Hz,
4
J = 1.5 Hz), 7.56 (d, 1H,
3
J = 7.9 Hz),
7.53 (d, 1H,
3
J = 7.3 Hz), 7.20 (dt, 1H,
3
J = 7.4 Hz,
4
J = 1.0 Hz), 7.02 (dt, 1H,
3
J =
7.4 Hz,
4
J = 1.2 Hz), 4.02 (s, 3H), 3.93 (s, 3H), 2.71 (s, 3H, Ir-NCCH
3
), 0.82 (m, 1H,
Ir-CH
2
-CH
3
), 0.55 (m, 1H, Ir-CH
2
-CH
3
), 0.52 (t, 3H,
3
J = 7.9 Hz, Ir-CH
2
-CH
3
).
13
C
{
1
H} NMR (CDCl
3
, 100 MHz): δ = 169.8, 164.3, 164.0, 162.9 (
2
J
C-F
= 37 Hz),
158.5, 157.4, 151.8 148.8, 145.2, 139.3, 138.8, 132.1, 130.6, 127.2, 126.1, 125.9 (J
C-
F
= 286 Hz), 122.6, 121.9, 119.2, 117.7, 117.3, 53.6, 53.3, 16.0, 4.3, -13.3.
19
F NMR
144
(CDCl
3
, 376 MHz): δ = -74.5 (s, 3F). Hi-res ESI/APCI MS for C
26
H
23
N
3
O
6
F
3
Ir:
Calc’d Mass [M-TFA]
+
:
(610.1318 m/z); Found: (610.1336 m/z).
Figure 59. Preparation of 2-TFA
2
NCMe.
Preparation of (NNC
(COOMe)2
)IrTFA
2
(NCMe) (2-TFA
2
NCMe). Using
Schlenk technique, degassed trifluoroacetic acid (20 mL) was added to a Schlenk
bomb containing 2-EtTFANCMe (661.2 mg, 0.9149 mmol). The reaction was then
allowed to stir for 12 hours at room temperature, which resulted in a bright red
reaction mixture. The solvent was removed under reduced pressure to yield a red
solid. The solid was dissolved in CH
2
Cl
2
, and the product was purified by column
chromatography using silica. Complex 2-TFA
2
NCMe eluted as a red band using a
1:1 CH
2
Cl
2
:
ethyl acetate mixture as the eluent. The product was obtained a bright
red solid in a 43.8 % (323.4 mg, 0.4009 mmol) yield.
1
H NMR (CD
2
Cl
2
, 400 MHz):
δ = 9.50 (dd, 1H,
3
J = 5.4 Hz,
4
J = 1.1 Hz), 8.74 (s, 1H), 8.44 (d, 1H,
4
J = 1.1 Hz),
8.35 (d, 1H,
4
J = 1.1 Hz), 8.22 (dd, 1H,
3
J = 5.7 Hz,
4
J = 1.5 Hz), 7.73 (dd, 1H,
3
J =
7.7 Hz,
4
J = 1.4 Hz), 7.65 (dd, 1H,
3
J = 7.6 Hz,
4
J = 1.1 Hz), 7.33 (dt, 1H,
3
J = 7.6
Hz,
4
J = 1.4 Hz), 7.18 (dt, 1H,
3
J = 7.4 Hz,
4
J = 1.6 Hz), 4.063 (s, 3H), 4.060 (s,
3H), 2.90 (s, 3H, Ir-NCCH
3
).
13
C {
1
H} NMR (CD
2
Cl
2
, 400 MHz): δ = 170.0, 164.3
145
(
2
J
C-F
= 37 Hz), 164.1, 159.0, 158.6, 154.5, 145.9, 141.8, 141.2, 140.6, 132.0, 126.8,
126.2, 124.5, 122.4, 119.6, 118.4, 117.9, 113.9, 112.5 (J
C-F
= 290 Hz).
19
F NMR
(CDCl
3
, 376 MHz): δ = -75.0 (s, 3F). Hi-res ESI/APCI MS for C
26
H
18
N
3
O
8
F
6
Ir:
Calc’d Mass [M-TFA]
+
: (694.0777 m/z); Found: (694.0769 m/z).
Figure 60. Preparation of 4’-hydroxy-3-(dimethylamino)-propiophenone
hydrochloride.
Preparation of 4’-hydroxy-3-(dimethylamino)-propiophenone
hydrochloride. Under atmospheric conditions, a round bottom flask was charged
with 4-hydroxyacetophenone (5.02 g, 0.0368 mol), paraformaldehyde (1.21 g,
0.0405 mol, 1.1 eq), dimethylamine hydrochloride (3.31 g, 0.0405 mol, 1.1 eq),
ethanol (50 mL) and concentrated HCl (aq) (1 mL). The flask was then heated to
reflux for 36 hours. After heating, the flask was slowly cooled to room temperature
followed by cooling at -30
o
C overnight. A white solid recrystallized out of solution
and was collected by filtration. The solid was washed with cold ethanol (50 mL).
The product was obtained in a 46.0 % (3.89 g) yield.
1
H NMR (DMSO-d
6
, 400
MHz): δ = 10.81 (s, 1H), 10.76 (s, 1H), 7.88 (d, 2H,
3
J = 9.1 Hz), 6.92 (d, 2H,
3
J =
9.1 Hz), 3.52 (t, 2H,
3
J = 7.7 Hz), 3.36 (t, 2H,
3
J = 6.8 Hz), 2.78 (s, 6H).
13
C {
1
H}
NMR (DMSO-d
6
, 100 MHz): δ = 194.8, 162.7, 130.5, 127.5, 115.3, 52.1, 41.8, 32.7.
146
Hi-res ESI-TOF
+
for C
11
H
16
NO
2
Cl: Calc’d Mass [M-Cl]
+
:
(194.1176 m/z); Found:
(194.1177 m/z).
Figure 61. Preparation of NNC
pOH
.
Preparation of 6-(4-hydroxyphenyl)-2,2’-bipyridine (NNC
pOH
). Under
atmospheric conditions, acetic acid (15 mL) was added to a round bottom flask
containing N-[2-(2-pyridyl)-2-oxoethyl] pyridinium iodide (1.00 g, 3.10 mmol) and
ammonium acetate (6.738 g, 28.2 eq). The flask was then heated to reflux until
everything dissolved. Then 4’-hydroxy-3-(dimethylamino)-propiophenone
hydrochloride (0.726 g, 3.16 mmol) was added, and the solution was refluxed for 4
hours. The dark red-brown solution was concentrated under reduced pressure. Ice
was added to the solution, and the acidic solution was neutralized with NaHCO
3
.
The solution was filtered, and the resulting reddish-brown residue was extracted with
acetone. The solution was dried with saturated NaCl (aq) and anhydrous MgSO
4
.
The extract was then passed through an alumina plug with acetone. The product was
purified using a silica column with a 2:3 mixture of acetone: CH
2
Cl
2
as the eluent,
and the product was obtained as an off white solid in a 60.5 % (465.5 mg) yield.
1
H
NMR (DMSO-d
6
, 400 MHz): = δ 9.81 (s, 1H, -OH), 8.70 (dd, 1H,
3
J = 4.8 Hz,
4
J =
1.8 Hz), 8.57 (dt, 1H,
3
J = 8.0 Hz,
4
J = 1.1 Hz), 8.25 (dd, 1H,
3
J = 7.5 Hz,
4
J = 1.1
Hz), 8.10 (d, 2H,
3
J = 8.9 Hz), 7.98 (dt, 1H,
3
J = 7.8 Hz,
4
J = 1.9 Hz), 7.95 (t, 1H,
3
J
147
= 7.5 Hz), 7.90 (dd, 1H,
3
J = 7.9 Hz,
4
J = 1.2 Hz), 7.46 (dd, 1H,
3
J = 7.5 Hz,
4
J = 1.2
Hz), 6.92 (d, 2H,
3
J = 8.9 Hz).
13
C {
1
H} NMR (DMSO-d
6
, 100 MHz): δ = 158.7,
155.6, 155.5, 154.7, 149.2, 138.2, 137.3, 129.4, 128.1, 124.1, 120.6, 119.3, 117.9,
115.6. Anal. Calc’d. for C
16
H
12
N
2
O
2
: C, 77.40 %; H, 4.87 %; N, 11.28 %. Found:
C, 77.2 %, H, 4.63 %, N, 11.28 %. Hi-res EI-MS for C
16
H
12
N
2
O
2
: Calc’d Mass [M]
+
:
(248.094963 m/z); Found: (248.094619 m/z).
Figure 62. Preparation of NNC
pOTf
.
Preparation of 6-(4-trifluoromethyl-phenyl)-2,2’-bipyridine (NNC
pOTf
).
Under an inert atmosphere, anhydrous pyridine (30 mL) was added to a Schlenk
flask containing NNC
pOH
(433.4 mg, 1.745 mmol). The flask was then cooled to 0
o
C and opened under an argon flow. Trifluoromethanesulfonic anhydride (2.90 mL,
17.4 mmol, 10 eq) was added in a drop wise fashion. The reaction was then allowed
to stir at room temperature overnight. The solution was poured into a beaker
containing ice. The product was extracted with 100 mL of CH
2
Cl
2
, and the organic
phase was washed with 20 mL of each of the following: 1 M HCl (aq), water, and
saturated NaCl (aq). The mixture was then dried over anhydrous MgSO
4
. The
product was purified by column chromatography using a silica column, and the
product was obtained, using CH
2
Cl
2
as the eluent, as an off white solid in 88.5 %
148
(556.2 mg) yield.
1
H NMR (CDCl
3
, 400MHz): δ = 8.69 (d, 1H,
3
J = 4.5 Hz,
4
J = 1.1
Hz), 8.57 (dt, 1H,
3
J = 7.8 Hz,
4
J = 1.1 Hz), 8.41 (dd, 1H,
3
J = 8.20 Hz,
4
J = 1.1 Hz),
8.22 (dt, 2H,
3
J = 8.0 Hz,
4
J = 2.2 Hz), 7.90 (t, 1H,
3
J = 8.0 Hz), 7.85 (dt, 1H,
3
J = 7.6
Hz,
4
J = 1.6 Hz), 7.74 (dd, 1H,
3
J = 8.0 Hz,
4
J = 1.0 Hz), 7.39 (dt, 2H,
3
J = 8.7 Hz,
4
J
= 2.0 Hz), 7.33 (dd, 1H,
3
J = 7.4 Hz,
4
J = 1.1 Hz).
13
C {
1
H} NMR (CDCl
3
, 100
MHz): δ = 156.1, 156.0, 154.5, 150.2, 149.2, 139.7, 138.0, 137.0, 128.9, 124.1,
121.7, 121.3, 120.4, 120.1, 118.9 (J
C-F
= 325 Hz, CF
3
).
19
F NMR (CDCl
3
, 376
MHz): δ = -75.65 (s, 3F). Hi-res DART
+
MS for C
17
H
11
N
2
O
3
F
3
S: Calc’d Mass
[M=H]
+
: (381.0515 m/z); Found: (381.0527 m/z).
Figure 63. Preparation of NNC
pOAc
.
Preparation of 6-(4-phenylacetate)-2,2’-bipyridine (NNC
pOAc
). Under an
inert atmosphere, anhydrous pyridine (75 mL) was added to a Schlenk flask
containing NNC
pOH
(4.268 g, 0.01715 mol). The Schlenk flask was sealed and
cooled to 0
o
C. The flask was then opened under an argon flow, and acetic anhydride
(16.20 mL, 0.1719 mol, 10 eq) was added in a drop wise fashion. The reaction was
then stirred at room temperature overnight. After stirring, the reaction mixture was
poured into a beaker containing ice. The product was extracted with CH
2
Cl
2
(100
mL), and the organic phase was separated and subsequently washed with 40 mL of
149
each of the following: 1M HCl, water, and saturated NaCl (aq). The organic phase
was then dried over anhydrous MgSO
4
. The product was purified by silica column
chromatography, and the product was eluted with CH
2
Cl
2
to yield an off-white solid
in 90.0 % (4.494 g) yield.
1
H NMR (CDCl
3
, 400 MHz): δ = 8.76 (dd, 1H,
3
J = 5.20
Hz,
4
J = 1.1 Hz), 8.59 (dt, 1H,
3
J = 7.8 Hz,
4
J = 1.1 Hz), 8.35 (dd, 1H,
3
J = 8.0 Hz,
4
J = 1.0 Hz), 8.15 (dt, 2H,
3
J = 9.0 Hz,
4
J = 2.2 Hz), 7.86 (t, 1H,
3
J = 7.6 Hz), 7.83
(dt, 1H,
3
J = 8.0 Hz,
4
J = 1.9 Hz), 7.72 (dd, 1H,
3
J = 8.1 Hz,
4
J = 1.0 Hz), 7.30 (dd,
1H,
3
J = 7.7 Hz,
4
J = 1.4 Hz), 7.21 (dt, 1H,
3
J = 9.0 Hz,
4
J = 3.0 Hz), 2.32 (s, 3H, -
OOCCH
3
).
13
C {
1
H} NMR (CDCl
3
, 100 MHz): δ = 169.4, 156.2, 155.7, 155.5,
151.5, 149.0, 137.8, 137.0, 136.8, 128.1, 123.8, 121.8, 121.2, 120.1, 119.3, 21.1. Hi-
res DART
+
MS for C
18
H
14
N
2
O
2
: Calc’d Mass [M+H]
+
: (291.1128 m/z);
Found:
(291.1130 m/z).
Figure 64. Preparation of 3-EtClC
2
H
4
.
Preparation of (NNC
pOAc
)IrEtCl(C
2
H
4
) (3-EtClC
2
H
4
). Under an inert
atmosphere, CH
2
Cl
2
(35 mL) was added to a Schlenk flask containing NNC
pOAc
(502.7 mg, 1.733 mmol). A Schlenk bomb was charged with [Ir(C
2
H
4
)
2
(µ-Cl)]
2
(490.5 mg, 0.8664 mmol) and 50 mL of CH
2
Cl
2
. Both reaction vessels were sealed
and connected to a Schlenk line. The bomb, containing the [Ir(C
2
H
4
)
2
(µ-Cl)]
2
, was
150
opened under an argon flow, and ethylene was bubbled through the solution for
approximately 5 minutes. The solution changed in color to a deep red. The flask was
then cooled to -78
o
C and ethylene was continually bubbled through the solution,
which resulted in a color change from red to yellow. The solution of NNC
pOAc
was
cannulated over to the bomb containing the iridium precursor. Ethylene was bubbled
through the mixture for another five minutes, and then the bomb was sealed and
slowly warmed to room temperature. The reaction was stirred overnight, which
resulted in a dark red solution. The bomb was slowly vented under argon, and the
solvent was removed under reduced pressure. (Caution: ethylene pressure vents
during this step, so the venting should be controlled by the PTFE valve to the
Schlenk bomb). In similar cyclometallations with other NNC derivatives (1-
EtClNCMe / 1-EtClC
2
H
4
and 2-EtClNCMe / 2-EtClC
2
H
4
) the residue was
dissolved and heated in acetonitrile to trap other possible products as the Ir-NCCH
3
product. However, in this reaction heating the reaction mixture with acetonitrile
resulted in a red side product that was slightly soluble in CH
2
Cl
2
. This side product
by
1
H NMR and hi-res mass spectrometry indicated that the iridium center was
coordinated to 2 NNC
pOAc
ligands. Consequently, the residue was not heated in
acetonitrile, and only the Ir-C
2
H
4
product was isolated. The product was purified by
column chromatography using silica, and the product was isolated as an orange solid
in 37.2 % (370.4 mg) yield using an elution gradient from 1:1 CH
2
Cl
2
:
ethyl acetate
to 1:9 methanol: ethyl acetate.
1
H NMR (CDCl
3
, 400 MHz): δ = 9.36 (d, 1H,
3
J =
5.8 Hz), 8.13 (d, 1H,
3
J = 7.9 Hz), 7.98 (dt, 1H,
3
J = 7.9 Hz,
4
J = 1.0 Hz), 7.85 (d,
151
1H,
3
J = 8.2 Hz), 7.82 (d, 1H,
3
J = 8.4 Hz), 7.73 (t, 1H,
3
J = 8.5 Hz), 7.61 (d, 1H,
3
J =
8.2 Hz), 7.57 (dt, 1H,
3
J = 6.5 Hz,
4
J = 1.4 Hz), 7.35 (d, 1H,
4
J = 2.2 Hz), 6.93 (dd,
1H,
3
J = 8.4 Hz,
4
J = 2.0 Hz), 4.02 (s, 4H, Ir-C
2
H
4
), 2.35 (s, 3H, -OOCCH
3
), 0.47
(m, 1H, Ir-CH
2
-CH
3
), 0.21 (m, 1H, Ir-CH
2
-CH
3
), -0.31 (s, 3H, Ir-CH
2
-CH
3
).
13
C
{
1
H} NMR (CDCl
3
, 100 MHz): δ = 169.8, 163.5, 158.4, 153.4, 151.6, 147.3, 144.5,
140.3, 138.7, 138.3, 135.7, 127.4, 124.5, 123.4, 119.4, 118.6, 117.8, 66.9, 21.5, 14.7,
-7.0. Hi-res ESI-TOF
+
MS for C
22
H
22
N
2
O
2
Ir: Calc’d Mass [M-Cl-C
2
H
4
]
+
:
(511.0993
m/z); Found: (511.0991 m/z).
Figure 65. Preparation of 3-EtClNCMe.
Preparation of (NNC
pOAc
)IrEtCl(NCMe) (3-EtClNCMe). Under an inert
atmosphere, acetonitrile (30 mL) was added to a Schlenk bomb containing 3-
EtClC
2
H
4
(370.4 mg, 0.6452 mmol). The bomb was sealed and heated at 100
o
C for
12 hours, which resulted in a color change of the solution from orange to red. The
solvent was removed under reduced pressure, and the product was purified by
column chromatography using silica. The product was eluted from the column using
a 1:1 mixture of CH
2
Cl
2
:
ethyl acetate as the eluent. Complex 3-EtClNCMe was
obtained as a red solid in 97.0 % (367.7 mg) yield.
1
H NMR (CD
2
Cl
2
, 400 MHz): δ
152
= 8.88 (d, 1H,
3
J = 5.0 Hz), 8.05 (d, 1H,
3
J = 8.7 Hz), 7.93 (dt, 1H,
3
J = 7.7 Hz,
4
J =
1.2 Hz), 7.70 (d, 1H,
3
J = 7.5 Hz), 7.62 (d, 1H,
3
J = 8.2 Hz), 7.57 (dd, 1H,
3
J = 5.7
Hz,
4
J = 1.5 Hz), 7.54 (t, 2H,
3
J = 8.4 Hz), 7.18 (d, 1H,
4
J = 2.2 Hz), 6.73 (dd, 1H,
3
J
= 8.5 Hz,
4
J = 2.0 Hz), 2.75 (s, 3H), 2.31 (s, 3H), 0.84 (m, 1H, Ir-CH
2
-CH
3
), 0.63
(m, 1H, Ir-CH
2
-CH
3
), 0.14 (s, 3H, Ir-CH
2
-CH
3
).
13
C {
1
H} NMR (CD
2
Cl
2
, 100
MHz): δ = 170.3, 167.7, 158.0, 157.2, 156.5, 153.5, 150.6, 143.4, 138.2, 137.2,
127.4, 126.3, 123.2, 118.2, 118.2, 117.8, 116.5, 114.4, 21.86, 15.6, 5.4, -8.8. Hi-res
ESI-TOF
+
MS for C
22
H
21
N
3
O
2
ClIr: Calc’d Mass [M-Cl-NCCH
3
]
+
:
(511.0993 m/z);
Found: (511.1001 m/z).
Figure 66. Preparation of 3-EtTFANCMe.
Preparation of (NNC
pOAc
)IrEtTFA(NCMe) (3-EtTFANCMe). Under an
inert atmosphere, CH
2
Cl
2
(20 mL) was added to a Schlenk flask containing 3-
EtClNCMe (367.7 mg, 0.6263 mmol) and silver trifluoroacetate, AgTFA, (175.9
mg, 0.7925 mmol). The reaction was then stirred for 24 hours in the dark. The
silver chloride was removed by filtration over celite, and the solvent was removed
under reduced pressure. The product was purified by column chromatography using
153
silica, and the product was eluted using a 1:1 mixture of CH
2
Cl
2
: ethyl acetate as the
eluent. The product was obtained as a bright red solid in 81.8 % (340.9 mg) yield.
1
H NMR (CD
2
Cl
2
, 400 MHz): δ = 8.99 (d, 1H,
3
J = 5.0 Hz), 7.99 (m, 2H), 7.68 (dd,
1H,
3
J = 7.2 Hz,
4
J = 1.3 Hz), 7.63 (dd, 1H,
3
J = 7.6 Hz,
4
J = 1.9 Hz), 7.60 (d, 1H,
3
J
= 7.7 Hz), 7.56 (m, 2H), 7.20 (d, 1H,
4
J = 2.2 Hz), 6.77 (dd, 1H,
3
J = 8.8 Hz,
4
J =
2.5), 2.74 (s, 3H), 2.30 (s, 3H) 0.90 (m, 1H, Ir-CH
2
-CH
3
), 0.66 (m, 1H, Ir-CH
2
-CH
3
),
0.08 (s, 3H, Ir-CH
2
-CH
3
).
13
C {
1
H} NMR (CD
2
Cl
2
, 100 MHz): δ = 170.2, 168.3,
162.1 (-OOCCF
3
,
2
J
C-F
= 36 Hz), 158.5, 157.5, 154.9, 153.3, 151.7, 144.1, 138.7,
137.9, 127.2, 126.3, 126.2, 122.6, 119.6 (J
C-F
= 290 Hz), 118.0, 117.4, 115.1, 21.6,
16.1, 5.1, -14.5. Hi-res ESI-MS for C
24
H
21
N
3
O
4
F
3
Ir: Calc’d Mass [M]
+
:
(665.1109
m/z); Found: (665.1061 m/z).
Figure 67. Preparation of 3-TFA
2
NCMe.
Preparation of (NNC
pOAc
)IrTFA
2
(NCMe) (3-TFA
2
NCMe). Using Schlenk
technique, trifluoroacetic acid (25 mL) was added to a Schlenk flask containing 3-
EtTFANCMe (340.9 mg, 0.5125 mmol). The solution was then stirred for 24 hours,
which resulted in a color change of the solution from a brownish-yellow to a clear
yellow color. The trifluoroacetic acid was removed under reduced pressure, and
154
product was purified by column chromatography using silica. The product was
eluted as a yellow band using a 1:3 mixture of CH
2
Cl
2
: ethyl acetate. The product
was obtained as yellow solid in 76.4 % (239.3 mg) yield.
1
H NMR (DMSO-d
6
, 400
MHz): δ = 9.32 (d, 1H,
3
J = 5.4 Hz), 8.60 (d, 1H,
3
J = 8.7 Hz), 8.31 (d, 1H,
3
J = 8.7
Hz,
4
J = 1.1 Hz), 8.23 (dt, 1H,
3
J = 7.6 Hz,
4
J = 1.6 Hz), 8.12 (dd, 1H,
3
J = 7.9 Hz,
4
J
= 1.0 Hz), 7.93 (t, 1H,
3
J = 8.5 Hz), 7.87 (dd, 1H,
3
J = 5.4 Hz,
4
J = 1.5 Hz), 7.84 (d,
1H,
3
J = 8.6 Hz), 7.27 (d, 1H,
4
J = 2.2 Hz), 6.84 (dd, 1H,
3
J = 8.3 Hz,
4
J = 1.5 Hz),
3.32 (s, 3H), 3.05 (s, 3H).
13
C {
1
H} NMR (DMSO-d
6
, 100 MHz): δ = 169.1, 167.1,
162.2 (
2
J
C-F
= 36.8 Hz), 157.5, 157.4, 152.7, 151.1, 144.4, 142.0, 140.6, 140.4, 127.9,
127.2, 125.9, 123.2, 120.1, 118.6, 118.5, 116.7, 111.6 (J
C-F
= 289 Hz) 20.99, 3.47.
Hi-res ESI-TOF
+
for C
24
H
16
N
3
O
6
F
6
Ir: Calc’d Mass [M+Na]
+
:
(772.0465 m/z);
Found: (772.0466 m/z).
Figure 68. Preparation of 3-TFA
2
NHCOMe.
Preparation of (NNC
pOH
)IrTFA
2
(NHCOMe) (3-TFA
2
NHCOMe). Under
an inert atmosphere, degassed 1,4-dioxane (40 mL) was added to a Schlenk flask
containing 3-TFA
2
NCMe (1.001 g, 1.314 mmol). The flask was opened under an
argon flow, and Et
4
NOH (aq) (4.3 mL of a 35 wt% solution, 10.5 mmol, 8 eq) was
155
added. The reaction was then stirred overnight. After the reaction, a red aqueous
solution had separated from the dioxane. The solvent was removed under reduced
pressure to produce a reddish solid that was redissolved in acetone. The product was
purified by centrifugal thin-layer chromatography using silica, and the product was
eluted from the Chromatotron plate using a 1:1 mixture of CH
2
Cl
2
: ethyl acetate. The
product was obtained as a yellowish-orange solid in 76.7 % (765.0 mg) yield.
1
H
NMR (acetone-d
6
, 400 MHz): δ = 10.49 (s, 1H, -OH), 9.13 (d, 1H,
3
J = 5.4 Hz), 8.50
(d, 1H,
3
J = 7.8 Hz), 8.19 (dt, 1H,
3
J = 7.6 Hz,
4
J = 1.6 Hz), 8.08 (d, 1H,
3
J = 8.0 Hz),
7.85 (d, 1H,
3
J = 7.5 Hz), 7.82 (dd, 1H,
3
J = 6.0 Hz,
4
J = 1.4 Hz), 7.57 (t, 1H,
3
J =
8.4 Hz), 7.58 (d, 1H,
3
J = 9.0 Hz), 6.91 (d, 1H,
4
J = 2.1 Hz), 6.53 (dd, 1H,
3
J = 8.7
Hz,
4
J = 2.3 Hz), 2.58(s, 3H, Ir-HNCOCH
3
).
13
C {
1
H} NMR (acetone-d
6
, 100
MHz): δ = 178.0, 169.7, 164.0 (-OOCCF
3
2
J
C-F
= 36 Hz), 160.9, 159.6, 158.9, 152.8,
142.8, 140.9, 140.33, 140.30, 127.8, 127.6, 123.6, 122.8, 117.8, 117.4, 112.9 (J
C-F
=
290 Hz), 111.0, 23.01 (Ir-NHCOCH
3
). Hi-res ESI/APCI for C
22
H
15
N
3
O
6
F
6
Ir: Calc’d
Mass [M-TFA-Acetamide+Na]
+
: (553.0351 m/z); Found: (553.0378 m/z). Calc’d
Mass [2M+Na]
+
: (1471.1016 m/z); Found: (1471.0983 m/z).
156
Figure 69.
1
H NMR of 3-TFA
2
NCMe in acetone-d
6
.
Figure 70. Preparation of 3-(OH)
2
NHCOMe.
Preparation of (NNC
pOH
)Ir(OH)
2
NHCOMe (3-OH
2
NHCOMe). Using
Schlenk technique, 20 mL of a 0.4 M NaOH (aq) solution was added to a Schlenk
bomb containing 3-TFA
2
NHCOMe (602.4 mg, 0.7941 mmol). The bomb was
sealed and heated at 60
o
C for 12 hours. The solvent was then removed under
reduced pressure, and the mixture was redissolved in acetone. The product was
purified by centrifugal thin-layer chromatography using silica. The product was
157
eluted using a 1:1 mixture of ethyl acetate: methanol as the eluent, and the product
was obtained as maroon colored solid in 65.1 % (286.2 mg) yield.
1
H NMR
(CD
3
OD, 400 MHz): δ = 8.98 (dd, 1H,
3
J = 5.5 Hz,
4
J = 1.2 Hz), 8.47 (d, 1H,
3
J =
8.5 Hz), 8.18 (dt, 1H,
3
J = 7.8 Hz,
4
J = 1.8 Hz), 8.08 (d, 1H,
3
J = 8.3 Hz), 7.87 (d,
1H,
3
J = 8.0 Hz), 7.84 (dd, 1H,
3
J = 6.7 Hz,
4
J = 1.2 Hz), 7.70 (t, 1H,
3
J = 8.1 Hz),
7.63 (d, 1H,
3
J = 8.3 Hz), 7.03 (d, 1H,
4
J = 2.8 Hz), 6.57 (dd, 1H,
3
J = 8.3 Hz,
4
J =
2.7 Hz), 2.35 (s, 3H). Hi-res ESI (neg mode) for C
18
H
17
N
3
O
4
Ir
1
Na: Calc’d Mass [M-
H]
-
: (554.0674 m/z); Found: (554.0559 m/z).
Figure 71. Preparation of 3’-hydroxy-3-(dimethylamino)-propiophenone.
Preparation of 3’-hydroxy-3-(dimethylamino)-propiophenone
hydrochloride. A round bottom flask was charged with 3-hydroxyacetophenone
(5.00 g, 0.0368 mol), paraformaldehyde (1.21 g, 0.0405 mol), dimethylamine
hydrochloride (3.31 g, 0.0405 mol), ethanol (50 mL), and 1 mL of concentrated HCl
(aq). The flask was then heated to reflux for 36 hours. After heating, the flask was
slowly cooled to room temperature followed by cooling at -30
o
C overnight. During
cooling a white solid recrystallized out of solution. The white solid was collected by
filtration and washed with cold ethanol (50 mL). The product was obtained in a 46.0
% (3.89 g) yield and used without further purification.
1
H NMR (DMSO-d
6
, 400
158
MHz): δ = 10.84 (s, 1H), 10.01 (s, 1H), 7.45 (d, 1H,
3
J = 8.5 Hz), 7.38 (t, 1H,
4
J =
2.0 Hz), 7.35 (t, 1H,
3
J = 8.0 Hz), 7.11 (dd, 1H,
3
J = 7.9 Hz,
4
J = 2.5 Hz), 3.58 (t, 2H,
3
J = 7.1 Hz), 3.37 (t, 2H,
3
J = 7.4 Hz), 2.78 (s, 6H).
13
C {
1
H} NMR (DMSO-d
6
, 100
MHz): δ = 197.0, 158.3, 137.2, 130.3, 120.8, 118.5, 114.5. Hi-res ESI-TOF
+
for
C
11
H
16
NO
2
: Calc’d Mass [M+H]
+
:
(194.1176 m/z); Found: (194.1174 m/z).
Figure 72. Preparation of NNC
mOH
.
Preparation of 6-(3-hydroxyphenyl)-2,2’-bipyridine (NNC
mOH
). A round
bottom flask was charged with N-[2-(2-pyridyl)-2-oxoethyl] pyridinium iodide (6.04
g, 0.185 mmol), ammonium acetate (19.96 g, 14 eq), and acetic acid (100 mL). The
flask was then heated to reflux, until everything dissolved, then 3’-hydroxy-3-
(dimethylamino)-propiophenone hydrochloride (3.93 g, 0.0204 mol) was added. The
solution was refluxed overnight, and the dark red-brown solution was concentrated
under vacuum. Ice was added to the solution, and the solution was neutralized with
NaHCO
3
(s). The solution was filtered and the resulting reddish-brown residue was
redissolved in acetone. The solution was dried with saturated NaCl (aq) (100 mL)
and anhydrous MgSO
4
. The solution was then passed through an alumina plug with
acetone. The product was then purified by column chromatography using silica, and
the product was eluted with a 1:3 mixture of acetone: CH
2
Cl
2
as the eluent. The
product was obtained as an off-white solid in a 45.7 % (2.10 g) yield.
1
H NMR
159
(acetone-d
6
, 400 MHz): δ = 9.81 (s, 1H, -OH), 8.70 (dd, 1H,
3
J = 4.8 Hz,
4
J = 1.8
Hz), 8.57 (dt, 1H,
3
J = 8.0 Hz,
4
J = 1.1 Hz), 8.25 (dd, 1H,
3
J = 7.5 Hz,
4
J = 1.1 Hz),
8.10 (d, 2H,
3
J = 8.9 Hz), 7.98 (dt, 1H,
3
J = 7.8 Hz,
4
J = 1.9 Hz), 7.95 (t, 1H,
3
J =
7.5 Hz), 7.90 (dd, 1H,
3
J = 7.9 Hz,
4
J = 1.2 Hz), 7.46 (dd, 1H,
3
J = 7.5 Hz,
4
J = 1.2
Hz), 6.92 (d, 2H,
3
J = 8.9 Hz).
13
C {
1
H} NMR (acetone-d
6
, 100 MHz): δ = 158.9,
157.08, 157.01, 156.5, 150.1, 141.5, 138.8, 137.8, 130.7, 124.9, 121.5, 121.2, 120.1,
118.9, 116.9, 114.6. Hi-res ESI-TOF
+
for C
16
H
12
N
2
O: Calc’d Mass [M+H]
+
:
(249.1022 m/z); Found: (249.1028 m/z).
Figure 73. Preparation of NNC
mOAc
.
Preparation of 6-(3-phenylacetate)-2,2’-bipyridine (NNC
mOAc
). Under an
inert atmosphere, anhydrous pyridine was added to a Schlenk flask containing
NNC
mOH
(2.718 g, 0.01094 mol). The Schlenk flask was then cooled to 0
o
C and
opened under an argon flow. Acetic anhydride (10.3 mL, 0.109 mol, 10 eq) was
added to the reaction in a drop wise fashion. The reaction was then stirred at room
temperature overnight. After stirring, the reaction mixture was poured into a beaker
containing ice. The product was extracted with 100 mL of CH
2
Cl
2
, and the organic
phase was washed with 40 mL of each of the following: 1M HCl (aq), water, and
saturated NaCl (aq). The organic phase was then dried over anhydrous MgSO
4
.
160
The product was then purified over a silica column, and the product was eluted with
CH
2
Cl
2
to yield an off-white solid in 80.7 % (2.5606 g) yield.
1
H NMR (CDCl
3
,
400 MHz): δ = 8.66 (dd, 1H,
3
J = 4.8 Hz,
4
J = 1.2 Hz), 8.59 (dt, 1H,
3
J = 7.9 Hz,
4
J =
1.1 Hz), 8.36(dd, 1H,
3
J = 7.8 Hz,
4
J = 1.0 Hz), 7.96 (dt, 1H,
3
J = 7.9 Hz,
4
J = 1.3
Hz), 7.90 (t, 1H,
4
J = 1.9 Hz), 7.84 (t, 1H,
3
J = 7.9 Hz), 7.81 (dt, 1H,
3
J = 7.7 Hz,
4
J =
1.9 Hz), 7.72 (dd, 1H,
3
J = 7.9 Hz,
4
J = 1.0 Hz), 7.48 (t, 1H,
3
J = 7.9 Hz), 728 (dd,
1H,
3
J = 7.4 Hz,
4
J =1.3 Hz), 7.15 (dd, 1H,
3
J = 8.0 Hz,
4
J =1.1 Hz), 2.32 (s, 3H, -
OOCCH
3
).
13
C {
1
H} NMR (CDCl
3
, 100 MHz): δ = 169.6, 156.3, 155.8, 155.4,
151.5, 149.2, 141.2, 137.9, 137.0, 129.7, 124.4, 123.9, 122.3, 121.5, 120.4, 120.2,
119.7, 21.0. Hi-res ESI-TOF
+
for C
18
H
14
N
2
O
2
: Calc’d Mass [M+H]
+
:
(291.1128
m/z); Found: (291.1132 m/z).
Figure 74. Preparation of 4-EtClC
2
H
4
.
Preparation of (NNC
mOAc
)IrEtCl(C
2
H
4
) (4-EtClC
2
H
4
). Under an inert
atmosphere, CH
2
Cl
2
(20 mL) was added to a Schlenk flask containing NNC
mOAc
(449.8 mg, 1.722 mmol). In a glovebox, CH
2
Cl
2
(35 mL) was added to a Schlenk
bomb containing [Ir(C
2
H
4
)
2
(µ-Cl)]
2
(488.1 mg, 0.8600 mmol). Both reaction vessels
were sealed and opened under an argon flow. Ethylene was bubbled through the
solution, the bomb, containing the [Ir(C
2
H
4
)
2
(µ-Cl)]
2
for approximately 5 minutes.
161
The bomb was then cooled to -78
o
C, and ethylene was continually bubbled through
the solution, which resulted in the solution changing to a clear golden appearance.
The solution containing the NNC
mOAc
was cannulated over to the bomb containing
the iridium precursor. Ethylene was bubbled through the mixture for another five
minutes. The reaction was then stirred overnight at room temperature, which
resulted in a dark red solution. The reaction vessel was slowly vented under argon.
(Caution: ethylene pressure vents during this step, so the venting should be
controlled by the PTFE valve to the Schlenk bomb). The solvent was removed
under reduced pressure, and the product was purified over a silica column. The
product was isolated as an orange solid in 38.3 % (379.0 mg) yield using an eluent
mixture of 5 % methanol: 95 % ethyl acetate.
1
H NMR (CD
2
Cl
2
, 400 MHz): δ =
9.32 (d, 1H,
3
J = 5.3 Hz), 8.18 (d, 1H,
3
J = 7.7 Hz), 7.92 (m, 2H), 7.83 (d, 1H,
3
J =
8.2 Hz), 7.82 (d, 1H,
3
J = 8.4 Hz), 7.72 (m, 2H), 7.58 (t, 1H,
3
J = 6.0 Hz), 7.42 (t,
1H,
4
J = 2.0 Hz), 7.50 (dt, 1H,
3
J = 8.7 Hz,
4
J = 2.5 Hz), 4.00 (s, 4H, Ir-C
2
H
4
), 2.33
(s, 3H, -OOCCH
3
), 0.41 (m, 1H, Ir-CH
2
-CH
3
), 0.21 (m, 1H, Ir-CH
2
-CH
3
), -0.33 (s,
3H, Ir-CH
2
-CH
3
).
13
C {
1
H} NMR (CD
2
Cl
2
, 100 MHz): δ = 170.5, 163.4, 158.6,
153.9, 151.9, 147.7, 145.1, 141.2, 139.3, 138.8, 135.9, 127.9, 124.9, 123.9, 119.7,
119.3, 118.2, 67.3, 21.5, 14.7, -7.0. Hi-res ESI
+
for C
22
H
22
N
2
O
2
ClIr: Calc’d Mass
[M-Cl-C
2
H
4
]
+
:
(511.0993 m/z); Found: (511.0965 m/z).
162
Figure 75. Preparation of 4-EtClNCMe.
Preparation of (NNC
mOAc
)IrEtCl(NCMe) (4-EtClNCMe). Under an inert
atmosphere, acetonitrile (25 mL) was added to a Schlenk bomb containing 4-
EtClC
2
H
4
(379.0 mg, 0.6601 mmol). The bomb was sealed and heated at 100
o
C
for 12 hours, which resulted in a color change of the solution from orange to red.
The solvent was removed under reduced pressure, and the product was purified over
a silica column. The product was eluted using a 1:1 mixture of CH
2
Cl
2
: ethyl acetate
as the eluent, and the product was obtained as a red solid in 77.0 % (298.6 mg) yield.
1
H NMR (CD
2
Cl
2
, 400 MHz): δ = 8.95 (d, 1H,
3
J = 5.6 Hz), 8.03 (d, 1H,
4
J = 1.6
Hz), 8.02 (d, 1H,
4
J = 1.2 Hz), 7.75 (dd, 1H,
3
J = 7.0 Hz,
4
J = 1.8 Hz), 7.65 (t, 1H,
3
J
= 7.9 Hz), 7.62 (m, 2H), 7.58 (d, 1H,
3
J = 8.4 Hz), 7.31 (d, 1H,
4
J = 2.2 Hz), 7.01
(dd, 1H,
3
J = 8.0 Hz,
4
J = 2.6 Hz), 2.76 (s, 3H), 2.32 (s, 3H), 0.97 (m, 1H, Ir-CH
2
-
CH
3
), 0.73 (m, 1H, Ir-CH
2
-CH
3
), 0.46 (s, 3H, Ir-CH
2
-CH
3
); Hi-res ESI
+
for
C
20
H
18
N
2
O
2
Ir: Calc’d Mass [M-Cl-NCCH
3
]
+
:
(511.0993 m/z): Found: (511.0966
m/z).
163
N
N
Ir
OOCCF
3
NCMe
AgOOCCF
3
CH
2
Cl
2
,dark
24 h
N
N
Ir
Cl
NCMe
4-EtClNCMe
4-EtTFANCMe
OAc
OAc
Figure 76. Preparation of 4-EtTFANCMe.
Preparation of (NNC
mOAc
)IrEtTFA(NCMe) (4-EtTFANCMe). Under an
inert atmosphere, CH
2
Cl
2
(30 mL) was added to a Schlenk flask containing 4-
EtClNCMe (298.6 mg, 0.5086 mmol) and silver trifluoroacetate, AgTFA, (123.2
mg, 0.5595 mmol, 1.1 eq). The reaction was then stirred for 24 hours in the dark at
room temperature. The solution was filtered over celite to remove the silver
chloride. The solvent was removed under reduced pressure, and the product was
purified by separation over a silica column. The product was eluted using a 1:1
mixture of CH
2
Cl
2
: ethyl acetate as the eluent, and the product was obtained as a
bright red solid in 89.9 % (304.3 mg) yield.
1
H NMR (CDCl
3
, 400 MHz): δ = 8.95
(d, 1H,
3
J = 5.5 Hz), 7.95 (d, 2H,
3
J = 4.5 Hz), 7.66 (dd, 1H,
3
J = 6.6 Hz,
4
J = 2.6
Hz), 7.58 (t, 1H,
3
J = 8.4 Hz), 7.56 (m, 2H), 7.27 (d, 1H,
4
J = 2.4 Hz), 7.01 (dd, 1H,
3
J = 8.0 Hz,
4
J = 2.7 Hz), 2.75 (s, 3H), 2.30 (s, 3H) 0.94 (m, 1H, Ir-CH
2
-CH
3
), 0.69
(m, 1H, Ir-CH
2
-CH
3
), 0.02 (s, 3H, Ir-CH
2
-CH
3
). Hi-res ESI
+
for C
24
H
21
N
3
O
4
F
3
Ir:
Calc’d Mass [M-TFA-NCMe]
+
:
(511.0993 m/z); Found: (511.0975 m/z).
164
Figure 77.
1
H NMR of a 5.0 mM solution of 1-OH
2
Py in D
2
O.
Stability tests of 1-OH
2
Py in D
2
O: In 3 separate J-young NMR tubes, a 5.0
mM solution of 1-OH
2
Py was added. To one NMR tube 2 eq of pyridine was added
and to another NMR tube 4 eq of KOD was added. The tubes were all heated
simultaneously, and then analyzed by
1
H NMR. The
1
H NMR study for 1-OH
2
Py in
neat D
2
O can be seen in Figure 33 and in the presence of 4 eq of KOD, Figure 34.
General Procedure for H/D exchange studies of water/benzene by 1-
OH
2
Py: In a typical reaction, 0.50 mL of a 3.54 mM solution of 1-OH
2
Py in D
2
O,
14 eq of KOD, and 0.50 mL of benzene-H
6
were loaded into a resealable Schlenk
tube under argon. The tube was then heated anywhere from 2 to 24 hours depending
on the temperature used. After the desired heating, the Schlenk tube was removed
from the oil bath, and the benzene layer was analyzed by GC-MS to determine the
amount of deuterium incorporation into benzene. To determine if 1-OH
2
Py was
stable under catalytic conditions, the Schlenk tube was opened under argon and a 0.6
165
μL sample of the benzene layer was analyzed by GC-MS. The Schlenk tube was
then resealed and heated longer. This process was repeated several times to ensure
that a plot of TON vs. time was linear, Figure 78.
y = 0.112x
R² = 0.936
0
50
100
150
200
250
300
350
400
0 500 1000 1500 2000 2500 3000 3500
Turnover Number
Time (minutes)
Figure 78. Plot of TON vs. time for a 2.13 mM solution of 1-OH
2
Py in 0.5 mL
benzene-H
6
and 0.5 mL D
2
O with 78 eq (0.16 M) KOD at 180
o
C.
Analysis of H/D exchange: Catalytic H-D exchange reactions were
quantified by monitoring the increase of deuterium into C
6
H
6
by GC-MS analyses.
This was achieved by deconvoluting the mass fragmentation pattern obtained from
the MS analysis, using a program developed with Microsoft EXCEL.
67
An important
assumption made with this method is that there are no isotope effects on the
fragmentation pattern for the various benzene isotopologs. Fortunately, because the
166
parent ion of benzene is relatively stable towards fragmentation, it can be used
reliably to quantify the exchange reactions. The mass range from 78 to 84 m/z (for
benzene) was examined for each reaction and compared to a control reaction where
no metal catalyst was added. The program was calibrated with known mixtures of
benzene isotopologs. The results obtained by this method are reliable to within 5 %.
Thus, analysis of a mixture of C
6
H
6
, C
6
D
6
and C
6
H
5
D
1
prepared in a molar ratio of
50.6: 25.3: 24.1 resulted in a experimentally determined ratio of 49.4 (C
6
H
6
): 23.3
(C
6
D
6
): 27.3 (C
6
H
5
D
1
). Catalytic H/D exchange reactions were thus run for
sufficient reaction times to be able to detect changes > 5 % exchange. Methane was
analyzed in the same way as benzene using methane isotopologs. H/D exchange
reactions of benzene were carried out such that less than 10 % deuterium
incorporation had occurred. This allowed for the kinetics to remain pseudo-first
order. By keeping the deuterium incorporation to a small amount this also prevented
the statistical chance that degenerate deuterium/deuterium exchange would occur.
Background analysis: To ensure that catalysis was occurring I conducted
background reactions to account for the amount of H/D exchange that might be seen
from a reaction containing D
2
O, KOD, and benzene-H
6
. The reaction conditions
were conducted similar as to those described in the general procedure for H/D
exchange section, vide supra. However, the solution contained no added catalyst.
These solutions were analyzed as described above. Results of the control
(background) and the catalytic reaction can be seen in Table 9.
167
Table 9. Percentage of benzene isotopologs in the control reaction (left) and
the catalytic reaction (right). This reaction was performed at 180
o
C, the
concentrations listed are based on total volume of solution present.
0.16 M KOD, 0.5 mL D
2
O, 0.5
mL benzene-H
6
H/D Exchange
Analysis
2.13 mM catalyst, 0.16 M KOD, 0.5
mL D
2
O, 0.5 mL benzene-H
6
H/D
Exchange Analysis
277
mins
1980
mins
3060
mins
277
mins
1980
mins
3060
mins
C
6
H
6
99.9 99.7 99.04 C
6
H
6
99.81 90.67 87.62
C
6
H
5
D
1
0 0.24 0.93 C
6
H
5
D
1
0.15 8.91 11.77
C
6
H
4
D
2
0 0 0 C
6
H
4
D
2
0.01 0.38 0.55
C
6
H
3
D
3
0 0 0 C
6
H
3
D
3
0 0.01 0.04
C
6
H
2
D
4
0 0 0 C
6
H
2
D
4
0 0 0
C
6
H
1
D
5
0 0 0 C
6
H
1
D
5
0 0 0
C
6
D
6
0 0 0 C
6
D
6
0 0 0
General procedure for H/D exchange with methane: Using Schlenk
technique, 1.0 mL of a 3 mM solution of 1-OH
2
Py in D
2
O was added to a resealable
glass-walled metal reactor. The reactor was then pressurized with 500 psi of
methane. After pressurization, the reactor was stirred and heated at 180
o
C for 16
hours. For analysis of the H/D exchange with methane, the reactor was removed
from the heating block, and a 4 mL vial (flushed with argon prior to being placed
under vacuum) was pressurized with the headspace of the metal reactor. A 2.0 µL
sample of the headspace was taken from the vial and analyzed by GC-MS. A control
reaction was also performed to account for any H/D exchange that occurs in the
absence of catalyst. Analysis of the methane revealed no incorporation of deuterium.
In an alternative procedure, 1.0 mL of a 3 mM solution of 1-OH
2
Py in D
2
O was
loaded into a resealable Schlenk tube under argon. The solution was then degassed
through 3 cycles of freeze-pump-thaw, and the reactor was left under vacuum on the
last cycle. The Schlenk like was then connected to a methane cylinder, and methane
168
was allowed to refill the Schlenk tube. After having 1 atm of methane in the Schlenk
tube, the tube was sealed and heated at 180
o
C for 16 hours. However, within the
first several hours a tan colored solid could be seen precipitating from the solution.
After heating, the tube was cooled to room temperature and a rubber septum was
placed over the side arm of the Schlenk tube. Using a hose and needle the side arm
was evacuated and flushed with argon to remove the air in the side arm of the
Schlenk tube. The side arm was then placed under vacuum, and the valve to the
reactor was opened to allow the methane to flow into the side arm. A 2.0 μL sample
was obtained from the side arm and analyzed by GC-MS. Analysis of the methane
from this reaction revealed no H/D exchange.
Mass Transfer Study: Using the procedure described in the “General
procedure for H/D exchange with benzene” section, vide supra, separate Schlenk
tubes were analyzed under different stirring rates at the highest temperature that
would be used in my studies, 190
o
C. The turnover frequencies observed at the
various stirring rates were within error of what might be expected at 190
o
C.
Stoichiometric reaction of 1-OH
2
Py with benzene: Under argon, 6 mL of
a 2.12 mM stock solution of 1-OH
2
Py (0.0127 mmol) in H
2
O and 6 mL of benzene-
H
6
was added to a resealable Schlenk tube. Aqueous NaOH was added to make the
aqueous phase a 0.050 M NaOH (aq) solution. The Schlenk bomb was sealed and
heated at 160
o
C for 8 hours. The reaction was cooled to room temperature and 3
mL of pyridine was added to the reaction. The reaction was sealed and heated at 50
o
C for 1 hour prior to removal of the solvent under reduced pressure with gentle
169
heating. The mixture was redissolved in CD
2
Cl
2
and checked to ensure that there
was no observable benzene-H
6
by
1
H NMR. Trifluoromethanesulfonic acid (5 µL)
was added to proton ate any iridium phenyl complexes present in the solution. As an
internal standard, 1 µL of mesitylene (0.864 mg, 0.00718 mmol) was added
producing an integration of the mesityl-H protons of 3.00. Normalization of the 3
mesitylene protons per mole of mesitylene relative to the 6 benzene-H
6
protons per
mole of benzene (integration of 4.24) results in 0.00507 mmol of benzene-H
6
produced. This resulted in a 39.9 % of benzene-H
6
relative to the amount of iridium
starting material.
1:1 benzene-H
6
:
water, 0.050 M
NaOH,160
o
C,
8 h
Complex mixture of
aromatic protons
and t-butyls
Benzene-H
6
produced in 39.9%
yield based on [Ir]
3 eq of HOTf
CD
2
Cl
2
, rt
Scheme 19. Stoichiometric benzene C-H activation reaction with 1-OH
2
Py and
benzene under catalytic conditions.
Procedure for H/D exchange with 3-TFA
2
NHCOMe as the catalyst
precursor: In order to prevent the formation of a benzene phase from forming in
the reactor, I chose conditions such that partial pressure of benzene was kept below
the known vapor pressure of benzene at the reaction temperature. As long as the
partial pressure doesn’t exceed the known vapor pressure benzene will never
condense in the reactor. This method also allows for error because the solubility of
benzene in water is not taken into account. Therefore, using the Van der Waals
170
equation which is believed to be more rigorous than the ideal gas law I was able to
use the known values for the vapor pressure of benzene at various temps, see Table
10, the parameters a = 18.82 bar·L
2
·mol
-2
and b = 0.1193 L·mol
-1
for benzene and
the gas constant (R = 0.08314 L·atm·(mol·K)
-1
) to calculate the molar volume by the
approximation method of solving the Van der Waals equation for the known vapor
pressure of benzene at some temperature. Table 10 shows the results from the
approximation method.
Table 10. Molar Volume determination by approximation method using the Van
der Waals equation to determine what concentration of benzene must be used in
order to prevent the condensation of benzene in the reactor.
Vm(390K) Press(390K Vm(400K) Press(400K) Vm(410K) Press(410K) Vm(420K) Press(420K) Known values
11 2.824473287 8.9 3.549801097 7.2 4.451088423 5.9 5.499934082 Temp (K) Vp (bar)
11.02 2.81956978 8.92 3.54225832 7.22 4.439537351 5.91 5.491330617 390 2.777
11.04 2.814683237 8.94 3.534747439 7.24 4.428045827 5.92 5.482753862 400 3.532
11.06 2.80981357 8.96 3.527268254 7.26 4.416613394 5.93 5.474203695 410 4.41
11.08 2.804960691 8.98 3.519820564 7.28 4.405239599 5.94 5.465679992 420 5.455
11.1 2.800124515 9 3.512404172 7.3 4.393923995 5.95 5.457182632 430 6.667
11.12 2.795304956 9.02 3.505018881 7.32 4.382666137 5.96 5.448711494 440 8.088
11.14 2.790501927 9.04 3.497664497 7.34 4.371465587 5.97 5.440266457 450 9.711
11.16 2.785715345 9.06 3.490340826 7.36 4.360321911 5.98 5.431847402
11.18 2.780945126 9.08 3.483047678 7.38 4.349234679 5.99 5.42345421
11.2 2.776191185 9.1 3.475784862 7.4 4.338203464 6 5.415086762
11.22 2.77145344 9.12 3.468552191 7.42 4.327227846 6.01 5.406744942 a 18.82 bar L
2
mol
-2
11.24 2.766731808 9.14 3.461349477 7.44 4.316307406 6.02 5.398428632 b 0.1193 L mol
-1
11.26 2.762026207 9.16 3.454176535 7.46 4.305441731 6.03 5.390137717 R 0.08314 bar L (atm K)
-1
Vm(430K) Press(430K) Vm(440K) Press(440K) Vm(450K) Press(450K)
4.8 6.820948942 4 8.250296757 3.4 9.775940984
4.81 6.808059002 4.01 8.231927617 3.41 9.750820387
4.82 6.795217245 4.02 8.213639032 3.42 9.725826263
4.83 6.782423403 4.03 8.195430482 3.43 9.700957681
4.84 6.769677213 4.04 8.17730145 3.44 9.67621372
4.85 6.756978412 4.05 8.159251425 3.45 9.651593467
4.86 6.744326738 4.06 8.141279901 3.46 9.627096018
4.87 6.731721932 4.07 8.123386375 3.47 9.602720477
4.88 6.719163738 4.08 8.105570347 3.48 9.578465957
4.89 6.7066519 4.09 8.087831324 3.49 9.554331579
4.9 6.694186164 4.1 8.070168814 3.5 9.530316472
4.91 6.681766279 4.11 8.052582333 3.51 9.506419774
4.92 6.669391995 4.12 8.035071397 3.52 9.482640631
4.93 6.657063065 4.13 8.017635528 3.53 9.458978195
4.94 6.644779241 4.14 8.000274252 3.54 9.435431628
4.95 6.632540279 4.15 7.982987099 3.55 9.412000099
Once the molar volume was determined, the volulme of the headspace in the reactor
was determined, and in my glass reactors the head space was determined to be 3 mL.
The glass reactor had an overall volume of 4 mL but 1 mL of D
2
O containing 13.3
mM of 3-TFA
2
NHCOMe and 0.15 M KOD was added to the reactor reducing the
head space volume to 3 mL. From the volume of the headspace and molar volume
171
the moles of benzene could be determined. In the case of 430 K, using a molar
volume of 4.92 L mol
-1
, the amount of millimoles was determined to be 0.609 mmol.
Converting that amount of millimoles to volume yields 54.4 μL of benzene.
Therefore, to a 4 mL Schlenk bomb with a resealable teflon valve a 13.3 mM
solution of 3-TFA
2
NHCOMe and 0.15 M KOD was added. To this reaction 50.0
μL of benzene-H
6
was added. The reaction was sealed and was heated at 160
o
C
over time, and the reactor was occasionally opened to sample the reaction. The
benzene was analyzed by GC-MS to determine the amount of deuterium
incorporation into the benzene. A plot of TON vs. time was obtained and can be
seen in Figure 43. It was not determined whether the reaction was mass transfer
limited.
X-ray structure determination of [(NNC
(tBu2)
)IrPh(µ-OH)]
2
(1-Ph( μ-
OH)). Suitable black crystals of 1-Ph( μ-OH) for X-ray analysis were grown from a
CH
2
Cl
2
/ pentane mixture at –20
o
C. Diffraction data was collected at 138 K with
graphite-monochromatic Mo K α radiation ( λ = 0.71073 Å). The cell parameters
were obtained from the least-squares refinement of the spots (collected 60 frames)
using the SMART program. A hemisphere of data was collected and the intensity
data was processed using the Saint Plus program. All calculations for the structure
determination were carried out using the SHELXTL package (version 5.1).
68
Initial
atomic positions were located by direct methods using XS, and the structure was
refined by least-squares methods using SHELX. Absorption corrections were
applied by using SADABS.
69
Calculated hydrogen positions were input and refined
172
in a riding manner along with the attached carbons. The thermal ellipsoid plots are
shown in Figure 79 and Figure 80. There are 2 molecules in the unit cell, and it co-
crystallized with a CH
2
Cl
2
(solvent) molecule and a molecule of water. Crystal data
and refinement parameters can be found in Table 11. Selected bond lengths and
angles can be found in Table 13 and Table 14.
Figure 79. ORTEP of 1-Ph(µ-OH). (Thermal ellipsoids at 50% probability, and
a molecule of water and CH
2
Cl
2
omitted for clarity).
173
Figure 80. ORTEP of 1-Ph(µ-OH) asymmetric unit for clarity of atom naming.
(Thermal ellipsoids at 50 % probability, and a molecule of water and
CH
2
Cl
2
omitted for clarity).
174
Table 11. Crystal data and structure refinement for C
60
H
66
Ir
2
N
4
O
2
.
Identification code irackx2m
Empirical formula C
60
H
66
Ir
2
N
4
O
2
Formula weight 1459.40
Temperature 138(2) K
Wavelength 0.71073 Å
Crystal system Triclinic
Space group P-1
Unit cell dimensions a = 10.009(2) Å α= 88.518(3)°.
b = 12.096(3) Å β= 88.768(4)°.
c = 12.500(3) Å γ = 81.758(4)°.
Volume 1497.0(6) Å
3
Z 1
Density (calculated) 1.619 Mg/m
3
Absorption coefficient 4.668 mm
-1
F(000) 722
Crystal size 0.30 x 0.15 x 0.20 mm
3
Theta range for data collection 1.63 to 27.54°.
Index ranges -11<=h<=13, -15<=k<=15, -14<=l<=16
Reflections collected 4975
Independent reflections 3378 [R(int) = 0.0321]
Completeness to theta = 27.54° 49.0 %
Absorption correction None
Refinement method Full-matrix least-squares on F
2
Data / restraints / parameters 3378 / 0 / 344
Goodness-of-fit on F
2
1.054
Final R indices [I>2sigma(I)] R1 = 0.0545, wR2 = 0.1534
R indices (all data) R1 = 0.0569, wR2 = 0.1562
Largest diff. peak and hole 3.265 and -0.921 e.Å
-3
175
Table 12. Atomic coordinates ( x 10
4
) and equivalent isotropic displacement
parameters (Å
2
x 10
3
)for C
60
H
66
Ir
2
N
4
O
2
. U(eq) is defined as one
third of the trace of the orthogonalized U
ij
tensor.
x y z U(eq)
Ir(1) 9965(1) 9670(1) 1295(1) 21(1)
N(1) 10978(9) 7988(8) 1144(7) 19(2)
N(2) 8756(11) 8819(9) 2129(8) 25(2)
O(1) 11073(8) 10522(7) 192(6) 24(2)
O(2) 5371(9) 8763(7) -28(7) 29(2)
Cl(1) 1461(8) 6664(7) 4626(8) 102(2)
Cl(2) -829(11) 6235(8) 5895(7) 116(3)
C(1) 8659(14) 10949(10) 1819(11) 28(3)
C(2) 8670(16) 12126(10) 1722(11) 33(3)
C(3) 7711(18) 12871(11) 2176(12) 41(3)
C(4) 6666(19) 12502(13) 2806(13) 46(4)
C(5) 6596(17) 11386(13) 2925(12) 40(3)
C(6) 7577(14) 10609(11) 2427(11) 30(3)
C(7) 7639(14) 9373(11) 2534(10) 26(2)
C(8) 6655(11) 8786(11) 3021(10) 26(2)
C(9) 6902(13) 7616(10) 3066(10) 27(2)
C(10) 8117(13) 7086(10) 2626(10) 27(2)
C(11) 9032(12) 7686(10) 2149(10) 25(2)
C(12) 5783(15) 6972(12) 3553(11) 34(3)
C(13) 5341(16) 7387(17) 4671(12) 49(4)
C(14) 6193(19) 5722(14) 3639(19) 55(5)
C(15) 4530(15) 7233(16) 2779(13) 48(4)
C(16) 10301(13) 7233(10) 1629(9) 24(2)
C(17) 10766(13) 6096(10) 1549(12) 29(3)
C(18) 11977(12) 5712(10) 988(12) 29(3)
C(19) 12695(14) 6521(11) 560(12) 33(3)
C(20) 12190(12) 7653(10) 660(11) 28(3)
C(21) 12493(13) 4492(11) 874(11) 32(3)
C(22) 13637(17) 4147(15) 1651(16) 50(4)
C(23) 13060(20) 4290(14) -317(15) 53(4)
C(24) 11356(16) 3765(12) 1062(15) 45(4)
C(25) 11087(12) 9918(9) 2545(9) 22(2)
C(26) 11120(30) 9390(30) 3506(16) 120(14)
C(27) 12050(50) 9510(40) 4290(20) 200(30)
C(28) 12806(15) 10343(14) 4274(13) 41(3)
C(29) 12880(20) 10850(30) 3330(16) 80(8)
C(30) 12030(20) 10670(30) 2448(16) 87(10)
C(31) 140(30) 7220(20) 5445(19) 78(7)
176
Table 13. Bond lengths [Å] for C
60
H
66
Ir
2
N
4
O
2
.
Ir(1)-N(2) 1.964(10)
Ir(1)-C(1) 1.991(14)
Ir(1)-C(25) 1.997(11)
Ir(1)-O(1) 2.093(8)
Ir(1)-N(1) 2.150(9)
Ir(1)-O(1)#1 2.182(8)
N(1)-C(16) 1.338(15)
N(1)-C(20) 1.358(15)
N(2)-C(7) 1.316(18)
N(2)-C(11) 1.358(16)
O(1)-Ir(1)#1 2.182(8)
Cl(1)-C(31) 1.72(2)
Cl(2)-C(31) 1.72(3)
C(1)-C(6) 1.413(19)
C(1)-C(2) 1.427(16)
C(2)-C(3) 1.35(2)
C(3)-C(4) 1.41(2)
C(4)-C(5) 1.37(2)
C(5)-C(6) 1.405(19)
C(6)-C(7) 1.491(18)
C(7)-C(8) 1.413(15)
C(8)-C(9) 1.402(18)
C(9)-C(10) 1.399(18)
C(9)-C(12) 1.558(17)
C(10)-C(11) 1.367(17)
C(11)-C(16) 1.456(18)
C(12)-C(14) 1.51(2)
C(12)-C(13) 1.532(18)
C(12)-C(15) 1.59(2)
C(16)-C(17) 1.393(17)
C(17)-C(18) 1.413(19)
C(18)-C(19) 1.385(19)
C(18)-C(21) 1.501(18)
C(19)-C(20) 1.398(18)
C(21)-C(22) 1.52(2)
C(21)-C(24) 1.546(18)
C(21)-C(23) 1.59(2)
C(25)-C(26) 1.34(2)
C(25)-C(30) 1.41(2)
C(26)-C(27) 1.40(3)
C(27)-C(28) 1.34(3)
C(28)-C(29) 1.32(3)
C(29)-C(30) 1.44(2)
177
Table 14. Bond angles [
o
] for C
60
H
66
Ir
2
N
4
O
2
.
Atom-Atom-Atom Degrees Atom-Atom-Atom Degrees
N(2)-Ir(1)-C(1) 81.6(5) N(2)-Ir(1)-C(25) 94.5(5)
C(1)-Ir(1)-C(25) 86.4(5) N(2)-Ir(1)-O(1) 170.7(4)
C(1)-Ir(1)-O(1) 99.5(5) C(25)-Ir(1)-O(1) 94.8(4)
N(2)-Ir(1)-N(1) 78.3(4) C(1)-Ir(1)-N(1) 159.6(5)
C(25)-Ir(1)-N(1) 91.4(4) O(1)-Ir(1)-N(1) 100.9(3)
N(2)-Ir(1)-O(1)#1 92.4(4) C(1)-Ir(1)-O(1)#1 95.9(4)
C(25)-Ir(1)-O(1)#1 173.0(4) O(1)-Ir(1)-O(1)#1 78.3(3)
N(1)-Ir(1)-O(1)#1 88.7(3) C(16)-N(1)-C(20) 119.9(10)
C(16)-N(1)-Ir(1) 112.7(8) C(20)-N(1)-Ir(1) 127.4(7)
C(7)-N(2)-C(11) 123.4(11) C(7)-N(2)-Ir(1) 117.8(8)
C(11)-N(2)-Ir(1) 118.4(9) Ir(1)-O(1)-Ir(1)#1 101.7(3)
C(6)-C(1)-C(2) 115.9(14) C(6)-C(1)-Ir(1) 113.0(9)
C(2)-C(1)-Ir(1) 131.1(12) C(3)-C(2)-C(1) 122.4(15)
C(2)-C(3)-C(4) 120.2(13) C(5)-C(4)-C(3) 120.1(14)
C(4)-C(5)-C(6) 119.6(16) C(5)-C(6)-C(1) 121.7(13)
C(5)-C(6)-C(7) 124.5(13) C(1)-C(6)-C(7) 113.7(12)
N(2)-C(7)-C(8) 120.0(11) N(2)-C(7)-C(6) 113.4(11)
C(8)-C(7)-C(6) 126.7(13) C(9)-C(8)-C(7) 118.6(12)
C(10)-C(9)-C(8) 118.1(11) C(10)-C(9)-C(12) 123.4(11)
C(8)-C(9)-C(12) 118.4(12) C(11)-C(10)-C(9) 121.3(11)
N(2)-C(11)-C(10) 118.6(12) N(2)-C(11)-C(16) 115.0(11)
C(10)-C(11)-C(16) 126.4(11) C(14)-C(12)-C(13) 107.8(15)
C(14)-C(12)-C(9) 114.0(13) C(13)-C(12)-C(9) 111.3(10)
C(14)-C(12)-C(15) 108.9(13) C(13)-C(12)-C(15) 108.6(13)
C(9)-C(12)-C(15) 106.2(12) N(1)-C(16)-C(17) 120.4(11)
N(1)-C(16)-C(11) 115.3(10) C(17)-C(16)-C(11) 124.1(11)
C(16)-C(17)-C(18) 121.2(11) C(19)-C(18)-C(17) 116.7(11)
C(19)-C(18)-C(21) 120.9(12) C(17)-C(18)-C(21) 122.5(11)
C(18)-C(19)-C(20) 120.1(13) N(1)-C(20)-C(19) 121.4(11)
C(18)-C(21)-C(22) 109.7(12) C(18)-C(21)-C(24) 111.5(10)
C(22)-C(21)-C(24) 110.6(13) C(18)-C(21)-C(23) 108.7(12)
C(22)-C(21)-C(23) 108.9(13) C(24)-C(21)-C(23) 107.4(12)
C(26)-C(25)-C(30) 112.5(13) C(26)-C(25)-Ir(1) 127.5(9)
C(30)-C(25)-Ir(1) 119.9(11) C(25)-C(26)-C(27) 123.9(16)
C(28)-C(27)-C(26) 123(2) C(29)-C(28)-C(27) 114.2(18)
C(28)-C(29)-C(30) 123(2) C(25)-C(30)-C(29) 121.0(19)
Cl(2)-C(31)-Cl(1) 112.5(14)
Symmetry transformations used to generate equivalent atoms: #1 -x+2,-y+2,-z
178
Table 15. Anisotropic displacement parameters (Å
2
x 10
3
) for C
60
H
66
Ir
2
N
4
O
2
.
The anisotropic displacement factor exponent takes the form: -2 π
2
[ h
2
a
*2
U
11
+ ... +
2 h k a* b* U
12
].
U
11
U
22
U
33
U
23
U
13
U
12
Ir(1) 23(1) 21(1) 18(1) 1(1) 0(1) -3(1)
N(1) 22(4) 21(4) 13(4) -3(3) 8(3) -4(4)
N(2) 26(5) 28(5) 20(5) 1(4) 11(4) -3(4)
O(1) 21(4) 36(4) 16(4) 4(3) 1(3) -8(3)
Cl(1) 78(4) 103(5) 128(7) -23(5) 17(4) -19(4)
Cl(2) 147(8) 116(6) 95(5) -21(5) 49(5) -58(6)
C(1) 37(7) 22(5) 25(6) -5(5) -11(5) -6(5)
C(2) 54(8) 20(5) 27(7) -2(5) -9(6) -8(5)
C(3) 68(10) 18(5) 34(7) -8(5) -3(7) 4(6)
C(4) 69(11) 34(7) 28(7) -6(6) 6(7) 19(7)
C(5) 52(9) 37(7) 26(7) -1(6) -1(6) 15(6)
C(6) 32(6) 30(6) 25(6) 1(5) 7(5) 2(5)
C(7) 32(6) 28(6) 19(6) 10(5) 1(5) -6(5)
C(8) 13(5) 41(6) 24(6) 6(5) 13(4) -5(5)
C(9) 33(6) 30(6) 17(6) 3(5) 2(5) -3(5)
C(10) 31(6) 20(5) 29(6) -1(5) 8(5) -2(5)
C(11) 28(6) 27(5) 21(6) 1(5) -5(4) -2(5)
C(12) 34(7) 42(7) 28(7) -2(6) 4(5) -16(6)
C(13) 38(8) 83(12) 32(8) -13(8) 14(6) -34(9)
C(14) 40(9) 33(8) 91(15) 4(8) 21(9) -8(7)
C(15) 34(8) 70(10) 45(9) -10(8) -9(6) -18(8)
C(16) 35(6) 23(5) 12(5) 0(4) 2(4) -2(5)
C(17) 25(6) 20(5) 43(8) 4(5) -7(5) -8(4)
C(18) 21(6) 27(6) 39(7) -1(5) -6(5) -2(5)
C(19) 28(6) 38(7) 33(7) -3(6) -6(5) 2(5)
C(20) 19(5) 24(5) 42(7) -5(5) -2(5) -9(4)
C(21) 25(6) 32(6) 36(7) 6(5) 16(5) 3(5)
C(22) 38(8) 41(8) 66(11) 2(8) -11(7) 12(7)
C(23) 66(11) 38(8) 53(11) -18(8) 5(8) 1(8)
C(24) 39(8) 25(6) 69(11) -7(7) 5(7) 1(6)
C(25) 23(5) 24(5) 20(5) -4(4) -5(4) -3(4)
C(26) 170(30) 190(30) 42(11) 42(14) -44(13) -170(30)
C(27) 340(60) 280(50) 51(15) 100(20) -120(30) -250(50)
C(28) 37(7) 58(9) 29(7) -7(7) -7(5) -4(7)
C(29) 53(11) 150(20) 44(11) 15(13) -16(8) -44(15)
C(30) 76(14) 170(30) 39(10) 8(13) -23(9) -90(18)
C(31) 85(16) 80(15) 65(14) -17(12) -15(12) 3(13)
179
Table 16. Hydrogen coordinates ( x 10
4
) and isotropic displacement
parameters (Å
2
x 10
3
) for C
60
H
66
Ir
2
N
4
O
2
.
x y z U(eq)
H(2) 9380 12393 1322 40
H(3) 7737 13649 2073 49
H(4) 6011 13030 3148 56
H(5) 5888 11136 3342 48
H(8) 5843 9177 3311 32
H(10) 8308 6294 2660 32
H(13A) 4551 7050 4913 73
H(13B) 5110 8202 4644 73
H(13C) 6081 7174 5170 73
H(14A) 6988 5554 4091 82
H(14B) 6409 5425 2924 82
H(14C) 5447 5375 3959 82
H(15A) 4843 7139 2035 72
H(15B) 4093 8003 2877 72
H(15C) 3881 6717 2950 72
H(17) 10259 5569 1878 34
H(19) 13532 6306 197 40
H(20) 12707 8200 385 33
H(22A) 14433 4480 1414 75
H(22B) 13859 3331 1672 75
H(22C) 13354 4409 2368 75
H(23A) 12460 4748 -818 80
H(23B) 13090 3499 -484 80
H(23C) 13967 4497 -381 80
H(24A) 11140 3723 1830 67
H(24B) 11656 3012 801 67
H(24C) 10550 4100 676 67
H(26) 10466 8908 3659 144
H(27) 12151 8985 4872 245
H(28) 13253 10548 4885 50
H(29) 13518 11351 3227 96
H(30) 12114 11074 1792 105
H(31A) 511 7557 6068 94
H(31B) -431 7819 5048 94
180
Figure 81. ORTEP of 3-TFA
2
NHCOMe. (Thermal ellipsoids at 50 %
probability).
181
Table 17. Crystal data and structure refinement for C
22
H
16
F
6
IrN
3
O
6
.
Identification code IrACm
Empirical formula C
22
H
16
F
6
IrN
3
O
6
Formula weight 722.56
Temperature 128(2) K
Wavelength 0.71073 Å
Crystal system Triclinic
Space group P-1
Unit cell dimensions a = 9.988(3) Å α= 104.908(4)
o
b = 10.100(3) Å β = 94.769(4)
o
c = 13.591(4) Å γ = 114.578(3)
o
Volume 1176.3(5) Å
3
Z 1
Density (calculated) 2.040 Mg/m
3
Absorption coefficient 5.768 mm
-1
F(000) 692
Crystal size 0.51 x 0.22 x 0.18 mm
3
Theta range for data collection 1.59 to 27.55
Index ranges -11<=h<=12, -13<=k<=13, -7<=l<=15
Reflections collected 4554
Independent reflections 3144 [R(int) = 0.0334]
Completeness to theta = 27.55 ̊ 58.0 %
Absorption correction Semi-Empirical
Refinement method Full-matrix least-squares on F
2
Data / restraints / parameters 3144 / 0 / 344
Goodness-of-fit on F
2
1.051
Final R indices [I>2sigma(I)] R1 = 0.0322, wR2 = 0.0793
R indices (all data) R1 = 0.0328, wR2 = 0.0805
Largest diff. peak and hole 1.947 and -1.761 e.Å
-3
182
Table 18. Atomic coordinates ( x 10
4
) and equivalent isotropic displacement
parameters (Å
2
x 10
3
) for C
22
H
16
F
6
IrN
3
O
6
. U(eq) is defined as one
third of the trace of the orthogonalized U
ij
tensor.
x y z U(eq)
Ir(1) 1723(1) 4779(1) 2191(1) 17(1)
N(1) 1834(6) 3053(6) 2810(4) 21(1)
N(2) 3907(6) 5721(6) 2814(4) 19(1)
N(3) -539(6) 3744(6) 1471(4) 22(1)
O(1) 1283(6) 9012(6) 556(4) 36(1)
O(2) -1485(6) 5085(7) 2532(4) 40(1)
O(3) 2048(5) 3918(5) 750(3) 22(1)
O(4) 2689(8) 2100(7) 944(4) 46(2)
O(5) 1202(5) 5768(5) 3518(3) 23(1)
O(6) 3130(6) 6402(8) 4828(4) 41(1)
F(1) 2350(7) 1108(5) -1119(4) 47(1)
F(2) 4112(5) 3415(7) -655(4) 46(1)
F(3) 1866(6) 2918(6) -1283(3) 45(1)
F(4) -244(5) 6415(6) 4992(4) 37(1)
F(5) 1541(8) 8552(6) 5059(5) 62(2)
F(6) 1776(6) 7469(8) 6178(3) 58(2)
C(1) 715(7) 1686(7) 2747(4) 25(1)
C(2) 971(8) 637(8) 3122(5) 31(1)
C(3) 2442(9) 1047(8) 3578(5) 33(2)
C(4) 3595(8) 2437(8) 3653(5) 29(1)
C(5) 3274(7) 3435(7) 3249(4) 22(1)
C(6) 4444(8) 4965(8) 3284(4) 26(1)
C(7) 5961(7) 5592(8) 3720(5) 28(1)
C(8) 6900(7) 7081(9) 3699(5) 28(1)
C(9) 6318(7) 7863(8) 3250(5) 26(1)
C(10) 4761(7) 7143(7) 2789(4) 21(1)
C(11) 3921(7) 7747(8) 2257(5) 23(1)
C(12) 4574(8) 9173(8) 2111(5) 30(1)
C(13) 3706(8) 9644(8) 1566(5) 31(1)
C(14) 2196(8) 8664(8) 1156(5) 27(1)
C(15) 1512(7) 7233(7) 1301(5) 24(1)
C(16) 2348(6) 6749(7) 1855(4) 19(1)
C(17) -1634(7) 4015(8) 1669(5) 26(1)
C(18) -3191(8) 3230(10) 967(6) 38(2)
C(19) 2416(7) 2858(8) 460(5) 23(1)
C(20) 2680(7) 2576(8) -666(5) 24(1)
C(21) 1980(7) 6387(7) 4464(5) 24(1)
C(22) 1269(8) 7217(8) 5184(5) 29(1)
183
Table 19. Bond lengths [Å] for C
22
H
16
F
6
IrN
3
O
6
.
Atom-Atom length [Å] Atom-Atom length [Å]
Ir(1)-N(2) 1.983(5) Ir(1)-C(16) 2.010(5)
Ir(1)-O(3) 2.040(5) Ir(1)-O(5) 2.045(4)
Ir(1)-N(3) 2.073(5) Ir(1)-N(1) 2.158(4)
N(1)-C(1) 1.342(9) N(1)-C(5) 1.361(7)
N(2)-C(10) 1.343(8) N(2)-C(6) 1.347(7)
N(3)-C(17) 1.266(8) O(1)-C(14) 1.383(6)
O(2)-C(17) 1.322(8) O(3)-C(19) 1.253(8)
O(4)-C(19) 1.223(7) O(5)-C(21) 1.290(7)
O(6)-C(21) 1.205(7) F(1)-C(20) 1.332(7)
F(2)-C(20) 1.321(8) F(3)-C(20) 1.324(7)
F(4)-C(22) 1.347(8) F(5)-C(22) 1.320(8)
F(6)-C(22) 1.322(7) C(1)-C(2) 1.390(8)
C(2)-C(3) 1.387(10) C(3)-C(4) 1.367(11)
C(4)-C(5) 1.394(7) C(5)-C(6) 1.485(10)
C(6)-C(7) 1.381(8) C(7)-C(8) 1.412(10)
C(8)-C(9) 1.381(9) C(9)-C(10) 1.415(8)
C(10)-C(11) 1.466(7) C(11)-C(12) 1.388(9)
C(11)-C(16) 1.428(8) C(12)-C(13) 1.395(8)
C(13)-C(14) 1.378(10) C(14)-C(15) 1.393(8)
C(15)-C(16) 1.389(7) C(17)-C(18) 1.515(8)
C(19)-C(20) 1.548(9) C(21)-C(22) 1.534(9)
184
Table 20. Bond angles [
o
] for C
22
H
16
F
6
IrN
3
O
6
.
Atom-Atom-Atom Angle [
o
] Atom-Atom-Atom Angle [
o
]
N(2)-Ir(1)-C(16) 82.3(2) N(2)-Ir(1)-O(3) 91.66(18)
C(16)-Ir(1)-O(3) 85.3(2) N(2)-Ir(1)-O(5) 94.36(18)
C(16)-Ir(1)-O(5) 88.7(2) O(3)-Ir(1)-O(5) 170.86(14)
N(2)-Ir(1)-N(3) 177.16(18) C(16)-Ir(1)-N(3) 97.7(2)
O(3)-Ir(1)-N(3) 85.52(19) O(5)-Ir(1)-N(3) 88.48(19)
N(2)-Ir(1)-N(1) 78.6(2) C(16)-Ir(1)-N(1) 160.8(2)
O(3)-Ir(1)-N(1) 96.70(17) O(5)-Ir(1)-N(1) 91.24(17)
N(3)-Ir(1)-N(1) 101.4(2) C(1)-N(1)-C(5) 119.5(5)
C(1)-N(1)-Ir(1) 128.5(4) C(5)-N(1)-Ir(1) 111.9(4)
C(10)-N(2)-C(6) 123.5(5) C(10)-N(2)-Ir(1) 116.8(3)
C(6)-N(2)-Ir(1) 119.7(5) C(17)-N(3)-Ir(1) 133.5(5)
C(19)-O(3)-Ir(1) 127.1(4) C(21)-O(5)-Ir(1) 129.3(4)
N(1)-C(1)-C(2) 122.2(6) C(3)-C(2)-C(1) 117.7(6)
C(4)-C(3)-C(2) 120.9(5) C(3)-C(4)-C(5) 118.9(6)
N(1)-C(5)-C(4) 120.8(6) N(1)-C(5)-C(6) 116.0(4)
C(4)-C(5)-C(6) 123.2(5) N(2)-C(6)-C(7) 120.8(7)
N(2)-C(6)-C(5) 113.7(5) C(7)-C(6)-C(5) 125.4(5)
C(6)-C(7)-C(8) 117.3(5) C(9)-C(8)-C(7) 121.0(6)
C(8)-C(9)-C(10) 119.1(6) N(2)-C(10)-C(9) 118.2(5)
N(2)-C(10)-C(11) 113.7(5) C(9)-C(10)-C(11) 128.1(6)
C(12)-C(11)-C(16) 120.3(5) C(12)-C(11)-C(10) 124.0(6)
C(16)-C(11)-C(10) 115.8(6) C(11)-C(12)-C(13) 120.5(6)
C(14)-C(13)-C(12) 119.2(6) C(13)-C(14)-O(1) 122.5(6)
C(13)-C(14)-C(15) 121.4(5) O(1)-C(14)-C(15) 116.1(6)
C(16)-C(15)-C(14) 120.5(6) C(15)-C(16)-C(11) 118.2(5)
C(15)-C(16)-Ir(1) 130.4(5) C(11)-C(16)-Ir(1) 111.4(3)
N(3)-C(17)-O(2) 121.3(6) N(3)-C(17)-C(18) 125.4(7)
O(2)-C(17)-C(18) 113.3(6) O(4)-C(19)-O(3) 130.3(6)
O(4)-C(19)-C(20) 116.1(5) O(3)-C(19)-C(20) 113.4(5)
F(2)-C(20)-F(3) 107.2(6) F(2)-C(20)-F(1) 107.4(5)
F(3)-C(20)-F(1) 106.8(5) F(2)-C(20)-C(19) 110.2(5)
F(3)-C(20)-C(19) 113.7(5) F(1)-C(20)-C(19) 111.2(5)
O(6)-C(21)-O(5) 129.8(6) O(6)-C(21)-C(22) 118.8(6)
O(5)-C(21)-C(22) 111.4(5) F(5)-C(22)-F(6) 108.1(7)
F(5)-C(22)-F(4) 105.7(6) F(6)-C(22)-F(4) 106.8(6)
F(5)-C(22)-C(21) 111.4(6) F(6)-C(22)-C(21) 111.9(5)
F(4)-C(22)-C(21) 112.6(6)
185
Table 21. Anisotropic displacement parameters (Å
2
x 10
3
) for C
22
H
16
F
6
IrN
3
O
6
.
The anisotropic displacement factor exponent takes the form: -2 π
2
[ h
2
a*
2
U
11
+ ... + 2 h k a* b* U
12
].
U
11
U
22
U
33
U
23
U
13
U
12
Ir(1) 19(1) 19(1) 15(1) 7(1) 3(1) 9(1)
N(1) 25(3) 21(3) 16(2) 10(2) 7(2) 9(2)
N(2) 22(2) 29(3) 12(2) 10(2) 10(2) 16(2)
N(3) 23(3) 26(3) 22(2) 10(2) 10(2) 14(2)
O(1) 44(3) 36(3) 36(3) 21(2) 2(2) 21(3)
O(2) 31(2) 61(4) 27(2) -1(3) 2(2) 29(3)
O(3) 25(2) 23(2) 19(2) 8(2) 5(2) 11(2)
O(4) 94(5) 47(3) 28(3) 20(3) 24(3) 53(4)
O(5) 26(2) 28(2) 15(2) 5(2) 3(2) 12(2)
O(6) 32(3) 64(4) 26(2) 7(3) 2(2) 26(3)
F(1) 80(4) 28(2) 26(2) -1(2) 13(2) 25(3)
F(2) 31(2) 61(4) 32(2) 9(3) 12(2) 11(3)
F(3) 60(3) 74(4) 24(2) 23(2) 12(2) 46(3)
F(4) 29(2) 42(3) 39(2) 8(2) 12(2) 17(2)
F(5) 89(4) 28(3) 74(4) 17(3) 47(3) 25(3)
F(6) 58(3) 97(5) 19(2) 1(3) 6(2) 47(4)
C(1) 31(3) 21(3) 15(3) 4(3) 3(2) 6(3)
C(2) 39(4) 22(3) 27(3) 10(3) 5(3) 9(3)
C(3) 46(4) 31(4) 28(3) 13(3) 8(3) 22(4)
C(4) 36(3) 36(4) 21(3) 15(3) 3(2) 18(3)
C(5) 29(3) 24(3) 14(3) 7(3) 3(2) 13(3)
C(6) 33(3) 41(4) 13(3) 11(3) 8(2) 24(3)
C(7) 24(3) 43(4) 23(3) 13(3) 3(2) 20(3)
C(8) 19(3) 36(4) 22(3) 5(3) 0(2) 10(3)
C(9) 22(3) 26(3) 24(3) 7(3) 4(2) 6(3)
C(10) 22(3) 23(3) 16(3) 5(3) 6(2) 10(3)
C(11) 23(3) 28(3) 21(3) 11(3) 6(2) 11(3)
C(12) 29(3) 27(4) 31(3) 10(3) 6(3) 11(3)
C(13) 42(4) 26(3) 32(3) 14(3) 10(3) 17(3)
C(14) 35(3) 30(3) 24(3) 15(3) 8(2) 19(3)
C(15) 24(3) 27(3) 25(3) 13(3) 9(2) 13(3)
C(16) 20(3) 20(3) 20(3) 9(3) 5(2) 9(3)
C(17) 26(3) 27(3) 25(3) 10(3) 3(2) 9(3)
C(18) 22(3) 48(5) 40(4) 12(4) 6(3) 14(4)
C(19) 24(3) 24(3) 19(3) 8(3) 2(2) 11(3)
C(20) 28(3) 25(3) 21(3) 7(3) 7(2) 12(3)
C(21) 25(3) 23(3) 17(3) 4(3) 2(2) 5(3)
C(22) 34(3) 30(4) 21(3) 8(3) 10(3) 13(3)
186
Table 22. Hydrogen coordinates ( x 10
4
) and isotropic displacement parameters
(Å
2
x 10
3
) for C
22
H
16
F
6
IrN
3
O
6
.
x y z U(eq)
H(3) -792 2950 910 26
H(1A) -286 1428 2435 30
H(2A) 167 -328 3069 37
H(3A) 2651 353 3842 39
H(4) 4598 2718 3974 35
H(7) 6358 5045 4022 34
H(8) 7947 7552 4000 33
H(9) 6955 8871 3249 31
H(12) 5620 9832 2384 35
H(13) 4149 10629 1478 38
H(15) 466 6584 1018 29
H(18A) -3217 3792 482 57
H(18B) -3939 3217 1393 57
H(18C) -3425 2172 573 57
187
3.5: References
48
(a) Shilov, A. E.; Shul’pin, G. B. Activation and Catalytic Reactions of Saturated
Hydrocarbons in the Presence of Metal Complexes, Kluwer Academic:
Dordrecht, The Netherlands, 2000. (b) Waltz, K. M.; Hartwig, J. F. Science 1997,
277, 211. (c) Sen, A. Acc. Chem. Res. 1998, 31, 550; and references therein. (d)
Labinger, J. A.; Bercaw, J. E. Nature 2002, 417, 507. (e) Conley, B. L.; Ganesh,
S. K.; Gonzales, J. M.; Tenn, W. J., III; Young, K. J. H.; Oxgaard, J.; Goddard,
W. A., III; Periana, R. A. J. Am. Chem. Soc. 2006; 128, 9018.
49
(a) Periana, R. A.; Taube, D. J.; Gamble, S.; Taube, H.; Satoh, T.; Fuji, H.
Science 1998, 280, 560. (b) Periana, R. A.; Mironov, O.; Taube, D. J.; Bhalla, G.;
Jones, C. J. Science 2003, 301, 814. (c) Periana, R. A.; Taube, D. J.; Evitt, E. R.;
Loffler, D. G.; Wentrcek, P. R.; Voss, G.; Masuda, T. Science 1993, 259, 340.
(d) Jones, C. J.; Taube, D.; Ziatdinov, V. R.; Periana, R. A.; Nielsen, R. J.;
Oxgaard, J.; Goddard, W. A., III Angew. Chem., Int. Ed. 2004, 43, 4626.
50
Muller, R. P.; Phillipp, D. M.; Goddard, W. A., III Top. Catal. 2003, 23, 81.
51
(a) Goldshleger, N. F.; Tyabin, M. B.; Shilov, A. E.; Sheinman, A. A. Zh. Fiz.
Khim. 1969, 43, 2174. (b) Shilov, A. E.; Shteinman, A. A. Coord. Chem. Rev.
1977, 24, 97.
52
(a) Garnett, J. L.; Hodges, R. J. J. Am. Chem. Soc. 1967, 89, 4546. (b) Garnett, J.
L.; Hodges, R. J. Chem. Commun. 1967, 1001. (c) Garnett, J. L.; West, J. C.
Aust. J. Chem. 1974, 27, 129.
53
(a) Feng, Y.; Lail, M.; Barakat, K. A.; Cundari, T. R.; Gunnoe, T. B.; Petersen, J.
L. J. Am. Chem. Soc. 2005, 127, 14174. (b) Feng, Y.; Lail, M.; Foley, N. A.;
Gunnoe, T. B.; Barakat, K. A.; Cundari, T. R.; Petersen, J. L. J. Am. Chem. Soc.
2006, 128, 7982.
54
Leung, C. W.; Zheng, W.; Wang, D.; Ng, S. M.; Yeung, C. H.; Zhou, Z; Lin, Z.;
Lau, C. P. Organometallics 2007, 26, 1924.
55
Prechtl, M. H. G.; Hölscher, M.; Ben-David, Y.; Theyssen, N.; Loshcen, R.;
Milstein, D.; Leitner, W. Angew Chem., Int. Ed. 2007, 46, 2269.
56
(a) Klei, S. R.; Golden, J. T.; Tilley, T. D.; Bergman, R. G. J. Am. Chem. Soc.
2002, 124, 2092. (b) Klei, S. R.; Tilley, T. D.; Bergman, R. G. Organometallics
2002, 21, 4905.
188
57
Gutiérrez-Puebla, E.; Monge, A.; Paneque, M.; Poveda, M. L.; Taboada, S.;
Trujillo, M.; Carmona, E. J. Am. Chem. Soc. 1999, 121, 346.
58
(a) Tenn, W. J., III; Young, K. J. H.; Bhalla, G.; Oxgaard J.; Goddard, W. A., III;
Periana, R. A. J. Am. Chem. Soc. 2005, 127, 14172. (b) Tenn, W. J., III; Young,
K. J. H.; Oxgaard, J.; Nielsen, R. J.; Goddard, W. A., III; Periana, R. A.
Organometallics 2006, 25, 5173.
59
Young, K. J. H.; Oxgaard, J.; Goddard, W. A., III; Periana, R. A.; manuscript in
preparation.
60
Hong, Y.-R.; Gorman, C. B. J. Org. Chem. 2003, 68, 9019.
61
Usui, M. Preparation of 4,4’-dicarboxy-2,2’-bipyridine. JP 2006193444, July 27,
2006.
62
Foley, P.; DiCosimo, R.; Whitesides, G. M. J. Am. Chem. Soc. 1980, 102, 6713.
63
Ohgiya, T.; Nishiyama, S. Tetrahedron Lett. 2004, 45, 6317.
64
(a) Himeda, Y.; Onozawa-Komatsuzaki, N.; Sugihara, H.; Arakawa. H. Kasuga,
K. Organometallics 2004, 23, 1480. (b) Himeda, Y.; Onozawa-Komatsuzaki, N.;
Sugihara, H.; Kasuga, K. Organometallics 2007, 26, 702.
65
Lu, W.; Mi, B-X.; Chan, M. C. W.; Hui, Z.; Che, C-M.; Zhu, N.; Lee, S-T. J. Am.
Chem. Soc. 2004, 126, 4958.
66
Soro, B.; Stoccoro, S.; Minghetti, G.; Zucca, A.; Cinellu, M. A.; Manassero, M.;
Gladiali, S. Inorg. Chim. Acta 2006, 359, 1879.
67
Young, K. J. H.; Meier, S. K.; Gonzales, J. M.; Oxgaard, J.; Goddard, W. A., III;
Periana, R. A. Organometallics 2006, 25, 4734, See supporting information.
68
Sheldrick, G. M. SHELXTL, version 5.1; Bruker Analytical X-ray Systems, Inc.:
Madison, WI, 1997.
69
Blessing, R. H. Acta Crystallogr. 1995, A51, 33.
189
Chapter 4: Related Ir(I) and Ir(III) Chemistry
4.1: Synthesis and Reactivity of an Iridium(III) Hydroxo Bridged
Dinuclear Complex
4.1.1: Introduction
The selective conversion of C-H bonds to functionalized products has been
an important area of chemistry over the last twenty years.
70
Specifically, the use of
transition metal hydroxo catalysts for C-H activation has been given a significant
effort in the scientific community. Work by Periana et al. and Gunnoe et al. have
shown that complexes such as ( κ
2
-O,O-acac)
2
Ir(OH)OH
2
and (Tp)Ru(PMe
3
)
2
OH are
capable of activating aromatic C-H bonds.
71
Recently work by Goldberg’s group has
shown that low valent cyclometallated iridium(I) and rhodium(I) hydroxo complexes
are capable of catalytic H/D exchange between benzene and water.
72
Bercaw’s
group has shown that a hydroxo bridged dinuclear complex, [( κ
2
-N,N-diimine)Pt(µ-
OH)]
2
, is competent for C-H activation of various allylic C-H bonds in the presence
of ( κ
2
-N,N-diimine)Pt(OH
2
)
2
; however, currently no catalytic H/D exchange has been
reported using this complex.
73
The significance of using late transition metal hydroxo complexes for C-H
activation is the hydroxo can act as an internal base in the cleavage of the C-H
bond.
74
Moreover, the resulting product, water, is benign resulting in minimal waste
byproducts. Bercaw’s work using a dinuclear complex demonstrates the importance
that since dinuclear complexes have the possibility of forming and existing as the
resting state, they can not be catalytically inactive species in catalysis.
73
The
190
possibility of being an inactive species increases because hydroxo bridging dinuclear
species are usually formed exothermically, which adds to the overall barrier for C-H
activation. It is known that hydroxo bridged dinuclear complexes are common place
for late transition metals.
75
Even with the current knowledge of science as is it today, very little
information exists as to why hydroxo bridged dinuclear complexes form. Currently,
work is being done by Goddard and Periana to determine the thermodynamic driving
force for the formation of hydroxo bridged dinuclear complexes. By understanding
the influence, we can better design complexes such that the formation of a dinuclear
complex has little to no impact on the rate for catalysis.
To further understand these hydroxo bridged dinuclear complexes, I decided
to investigate the [( κ
2
-NC)
2
Ir( μ-OH)]
2
complex, 1, where NC = phenylpyridine.
This complex was first reported by Watts at UC Santa Barbra in 1984.
76
Watts was
trying to studying the solvento species produced by the abstraction of the chloride.
However, he noticed that in the presence of base the complex immediately forms the
hydroxo bridged dinuclear complex that is a sparingly soluble orange solid. The
majority of work done using cyclometallated iridium phenylpyridine complexes is in
the area of luminescent studies; however, to my knowledge no one has used these
systems for the activation of C-H bonds.
77
191
4.1.2: Results and Discussion
Before investigating this complex for C-H activation, I turned to DFT studies
to understand what the energetics would be for the C-H activation, using 1 as a
catalyst. By using QM-RP, quantum mechanical rapid prototyping initially
developed by Muller and Goddard, calculations by Jonas Oxgaard, of the Goddard
group, showed that the ( κ
2
-NC)
2
Ir(OH)H
2
O complex had an enthalpy of activation of
36 kcal/mol for the C-H bond of methane and 32 kcal/mol for the C-H bond of
benzene, Figure 82.
78,79
The calculated resting state is the ( κ
2
-NC)
2
Ir(OH)H
2
O
complex; however, calculations also revealed that the hydroxo bridged dinuclear will
likely be the experimental resting state. While the overall barrier for the C-H
activation of methane is likely too great for any H/D exchange to be observed on the
time scale and temperatures under which I carry out the reactions, it should still be
possible to study this complex for the C-H activation of benzene.
192
Ir
C
C
N
N
OH
2
OH
0
‐4
4
7
8
5
32
5
12
1/2
Transition state for CH
cleavage via Internal
Electrophilic Substitution
ΔH Thermodynamics
LACVP**/B3LYP
Solvated in water
+ 2 H
2
O+ C
6
H
6
+ 2 H
2
O + C
6
H
6
+ C
6
H
6
+ H
2
O
+ C
6
H
6
+ H
3
O
+
+ OH
-
+ H
2
O+ C
6
H
6
+ C
6
H
6
+ OH
-
+ 2 H
2
O
+ 2 H
2
O
units = kcal/mol
(pH =14)
Figure 82. Thermodynamics (enthalpies in kcal/mol) at pH =14 for the C-H
activation using the phenylpyridine Ir(III) system.
From Figure 82, the dinuclear complex is only 4 kcal/mol more stable than
the ( κ
2
-NC)
2
Ir(OH)H
2
O complex, which results in an overall enthalpy of activation
of 36 kcal/mol for the C-H activation of benzene. It’s interesting to note that the
anionic [( κ
2
-NC)
2
Ir(OH)
2
]
-
complex is uphill in energy from the resting state
complex, which indicates that working in a basic medium (pH 14) the catalyst should
not be inhibited by the presence of hydroxide.
80
The resulting Ir-phenyl complex is
endothermic from the dinuclear resting state by 16 kcal/mol. When applying QM-
RP to catalyst selection two criteria are investigated: 1) the metal alkyl intermediate
should not be more than 10 kcal/mol more endothermic than the resting state, and 2)
193
the enthalpy of activation barrier shouldn’t be greater than 35 kcal/mol. In the case
of the 1
st
point the formation of the Ir-phenyl is endothermic by 16 kcal/mol from the
dinuclear resting state of the catalyst, and the metal-alkyl should be even more
endothermic. However, this can be viewed as a beneficial characteristic in that
previously our group reported that polarization of the M-R
( δ-)
bond dictates how
facile the functionalization is; therefore, a more polarized bond should allow for the
use of weaker oxidants.
81
Since the oxidants will be in the same reaction pot as the
catalyst, one has to assume that the catalyst can interact with the oxidant and
ultimately be oxidized by the oxidant. The use of weaker oxidants might prevent
the oxidation of the catalyst to an inactive species.
To test 1 as a catalyst for H/D exchange in basic aqueous media, I prepared 1
according to previously published procedures.
76
Initial studies of the known
complex 1 in a 1:1 mixture of benzene-H
6
and D
2
O with 0.010 M KOD resulted in
no observable H/D exchange between benzene and water. In these experiments a
large amount of the complex could be seen on the bottom of the reaction vessel, and
this is largely attributed to the insolubility of 1. The benzene was analyzed by
GC-MS in order to measure the amount of deuterium incorporation into the benzene.
I decided to use –OH functional groups on the ligand in order to address the
water solubility issue. In a basic aqueous medium these groups are generally known
to be more acidic than water (pKa phenol ~10, pka water ~16); as a result, the –OH
functional group will likely exits as –O
-
or that of a phenoxide rather than phenol.
This added charge build up should also provide added electronic effects which might
194
make the catalyst more reactive towards the C-H bond, and thus yield faster rates for
H/D exchange.
Suzuki coupling was used to make the hydroxylated phenylpyridine ligands
by coupling the hydroxyphenylboronic acid and 2-bromopyridine, Scheme 20. I
decided to make two versions of the hydroxylated phenylpyridine ligand: 2-(para-
hydroxyphenyl)-pyridine, NC
pOH
, and 2-(meta-hydroxyphenyl)-pyridine, NC
mOH
, so
that I could further test whether there are any added electronic effects from the –O
-
group on the ligand. In the case of NC
pOH
binding to the metal would theoretically
generate only one complex in which the –OH group is in the 3 position relative to the
carbon bound to the metal, the 1 position. Whereas in the case of NC
mOH
, binding to
the metal presents two possibilities where the –OH group can either be at the 4
position or the 2 position. Analysis of the possible resonance structures for the bound
NC
pOH
shows that the negative charge never resides at the 1 position; however, in
the case of NC
mOH
the negative charge does reside at 1 position, Scheme 21. Recent
work by other groups has shown that placing hydroxy groups at the 4,4’- positions of
2,2’-bipyridine increased the transition metal catalyzed rate for the hyhdrogenation
of carbonate.
82
195
Scheme 20. Synthesis of NC
pOH
and NC
mOH
.
Scheme 21. Resonance structures for NC
pOH
and NC
mOH
bound to an iridium
center indicating that only in the NC
mOH
case does the negative
charge ever reside at the 1 position. This added charge may increase
the catalytic rate for C-H activation.
Following the previously published synthesis of 1, I tried to react the NC
pOH
with IrCl
3
•3H
2
O; however, the reaction mixture needed further purification, and the
196
material did not run on silica, alumina, basic alumina and reversed phase silica.
Therefore, just as had been done in the NNC
pOH
work, see chapter 3, where NNC
pOH
= 6-(para-hydroxyphenyl)-2,2’-bipyridine, I decided to protect the hydroxy group as
this was the likely cause for the binding to the chromatographic support. Initially I
used acetyl as a protecting group by stirring the NC
pOH
with acetic anhydride in
pyridine to produce the acetylated phenylpyridine, 4-(2’-pyridine)-phenyl acetate.
Reactions of the acetylated phenylpyridine with IrCl
3
•3H
2
O only produced similar
products as the unprotected hydroxylated phenylpyridine, NC
pOH
. I then reasoned
that the HCl (aq) generated in the cyclometallation was causing the cleavage of the
acetyl group under the harsh reaction conditions (160
o
C). Therefore, I decided to
use the trifluoromethanesulfonyl as the protecting group for the hydroxy substituent.
Esterification with trifluoromethanesulfonic anhydride in pyridine at room
temperature produced the trifluoromethanesulfonate protected product, 4-(2’-
pyridine)-phenyl triflate, NC
pOTf
, in 63 % yield. Reaction of NC
pOTf
with
IrCl
3
•3H
2
O in 2-ethoxyethanol produced the cyclometallated product
[(NC
pOTf
)
4
Ir(µ-Cl)]
2
in 46 % yield as a bright yellow solid.
197
Scheme 22. Synthesis of NC
pOTf
and [(NC
pOTf
)
4
Ir(µ-Cl)]
2
.
To remove the trifluoromethanesulfonate groups I used a previously
published method that I had success with in the NNC
pOH
work, see chapter 3. The
use of Et
4
NOH (aq) in dioxane at room temperature has been shown to remove the
triflate from aryl triflates in high yields.
83
Therefore, I attempted to use this method;
however, I found that the products needed further purification. Just as in the above
procedure for the direct reaction of NC
pOH
with IrCl
3
•3H
2
O the products did not run
on most chromatographic supports. I began looking for alternative methods for the
protection of the phenolic groups that are stable to HCl (aq), but can cleanly be
removed in a later step. Following the long tradition of organic chemist’s use of
silation of –OH groups in the form of phenyl silyl ethers, I explored this route of
protection. I chose two of the most common silyl derivatives tert-butyl
dimethylsilylchloride, TBDMS-Cl, and triisopropylsilylchloride, TIPS-Cl. I chose to
198
use the NC
mOH
with each silyl protecting group in order to make the silated protected
ligands. Reaction of NC
mOH
with the each respective silyl protecting group in
CH
2
Cl
2
containing imidazole produced the silated phenylpyridine, see Scheme 23.
The rationale behind using the silyl groups is that in general they are easily removed
with tetrabutylammonium fluoride. After making the cyclometallated iridium
product, the silyl groups should easily be removed in a clean fashion with minimal
byproducts and side reactions, such that no further purification is needed.
Scheme 23. Synthesis of silyl protected phenylpyridine ligands.
The initial synthesis of NC
mOTBDMS
and IrCl
3
•3H
2
O produced several
products that have not been cleanly identified at this time. Due to the complex
199
mixture produced in a usually clean reaction I speculated that the –TBDMS
protecting group might not be sufficient to prevent cleavage at 160
o
C in the
presence of the HCl (aq) produced by the cyclometallation. I decided to use the
more stable –TIPS ligand. Reaction of NC
mOTIPS
and IrCl
3
•3H
2
O produced the
cyclometallated complex, [(NC
mOTIPS
)
4
Ir(µ-Cl)]
2
, in 35 % yield as an orange solid,
Scheme 24.
Scheme 24. Synthesis of [(NC
mOTIPS
)
4
Ir(µ-Cl)]
2
.
At this time, I am currently working to abstract the chlorides via halide
abstraction using silver trifluoromethanesulfonate, AgOTf, as Watts had previously
done followed by reaction with base to generate the hydroxo bridged dinuclear
complex. Once, I have each complex, [(NC
pOH
)
4
Ir(µ-OH)]
2
and [(NC
mOH
)
4
Ir(µ-
OH)]
2
, I will test these complexes for the H/D exchange of benzene and water in a
basic aqueous medium.
Cl
Ir
Cl
Ir
N
N
N
N
OTIPS
OTIPS
TIPSO
TIPSO
N
OTIP S
2 . 5 eq
IrCl
3
(H
2
O)
3
2-ethoxyethanol
reflux, 12 hours
35%yield
200
Cl
Ir
Cl
Ir
N
N
N
N
OTIPS
OTIPS
TIPSO
TIPSO
H
O
Ir
O
H
Ir
N
N
N
N
OTIPS
OTIPS
TIPSO
TIPSO
H
O
Ir
O
H
Ir
N
N
N
N
OTIPS
OTIPS
TIPSO
TIPSO
H
O
Ir
O
H
Ir
N
N
N
N
OH
OH
HO
HO
1) ~2 eq AgOSO
2
CF
3
MeOH, rt, 1hour
2) NaOH, rt
Bu
4
N
+
F
-
THF, rt
Scheme 25. Projected route to get to [(NC
pOH
)
4
Ir(µ-OH)]
2
.
4.1.3: Conclusion
It has been shown by DFT that 1 should be competent for the activation of
the C-H bond of benzene. Furthermore, DFT indicates that the iridium phenyl
complex is 16 kcal/mol more endothermic than the resting state hydroxo bridged
dinuclear complex. However, this might be beneficial as the iridium phenyl bond
will be more polarized and thus more reactive to oxidants. As a result, more facile
functionalization should be observed and the iridium phenyl will likely be
functionalized using weaker oxidants. I also found that using 1 in a basic aqueous
mixture of benzene and water resulted in a large amount of 1 being insoluble in the
reaction, and no observable H/D exchange. As a result, I set out to design water
soluble phenylpyridine ligands. Specifically, I designed two hydroxylated
phenylpyridine ligands, NC
mOH
and NC
pOH
. I later found that the resulting
cyclometallated iridium complex could not be purified on most common
201
chromatographic supports. Therefore, I protected the –OH groups using
trifluoromethanesulfonic anhydride, which resulted in the triflate protected
phenylpyridine, NC
pOTf
. Reaction of NC
pOTf
with IrCl
3
•3H
2
O resulted in a
cyclometallated complex [(NC
pOTf
)
4
Ir(µ-Cl)]
2
. However, deprotection of the
NC
pOTf
ligated complexes using Et
4
NOH (aq) wasn’t clean, and difficulty arose in
purifying the product. Therefore, I utilized protecting groups that should have
cleanver methods for removal of the protecting group, such as silyl protecting
groups. I protected the NC
mOH
with TBDMS-Cl and TIPS-Cl to generate the silyl
protected phenylpyridine ligands. Reaction of the NC
mOTBDMS
with IrCl
3
•3H
2
O did
not yield a clean reaction; however, reaction of NC
mOTIPS
resulted in the
cyclometallated product, [(NC
mOTIPS
)
4
Ir(µ-Cl)]
2
. I am currently moving forward
trying to prepare the [(NC
pOH
)
4
Ir(µ-OH)]
2
and [(NC
mOH
)
4
Ir(µ-OH)]
2
complexes in
order to test them for catalytic H/D exchange in a basic aqueous media.
4.1.4: Experimental
General Considerations: Unless otherwise noted all reactions and
manipulations were performed using standard Schlenk techniques (argon) or in a
MBraun LABmaster 130 glove box (nitrogen).
1
H (400 MHz),
13
C (100 MHz), and
19
F (376 MHz) NMR spectra were collected on a Varian 400 Mercury plus
spectrometer. Chemical shifts were referenced using residual protiated solvent, or in
the case of
19
F NMR using hexafluorobenzene or CFCl
3
. All coupling constants are
202
reported in hertz, Hz. Mass spectrometry analyses were performed at the University
of Florida mass spectrometry facility.
Materials: IrCl
3
•3H
2
O was purchased from Pressure Chemical. All solvents
were reagent grade or better, and were purchased from Sigma Aldrich or Alfa Aesar.
Anhydrous methanol was purchased from Acros Organics.
Figure 83. Preparation of NC
pOH
.
Preparation of 2-(4-hydroxyphenyl)-pyridine (NC
pOH
). Under an inert
atmosphere, methanol (125 mL) was added to a Schlenk bomb containing 4-
hydroxyphenylboronic acid (5.48 g, 0.0391 mol), CsCO
3
(15.10 g, 0.783 mol, 2 eq),
and Pd(PPh
3
)
4
(2.26 g, 0.00196 mol, 5 mol %). The bomb was opened under a flow
of argon, and 2-bromopyridine (3.74 mL, 0.0391 mol) was added. The bomb was
sealed and heated at 110
o
C in an oil bath for 12 hours, which produced a yellowish
colored solution. The solution was then filtered over celite, and the product was
purified by column chromatography using silica. The product was eluted from the
column using a 1:5 ethyl acetate: DCM mixture to yield a white solid in 58.0 % (3.88
g) yield.
1
H NMR (acteone-d
6
, 400MHz): δ = 8.68 (s, 1H, -OH), 8.59 (dd, 1H,
3
J =
4.9 Hz,
4
J = 1.0 Hz), 8.00 (dt, 1H,
4
J = 8.9 Hz,
4
J = 2.0 Hz), 7.78 (m, 2H), 7.20 (dd,
203
1H,
3
J = 4.9 Hz,
4
J = 1.6 Hz), 6.95 (dt, 1H,
3
J = 9.0 Hz,
4
J = 2.0 Hz).
13
C {
1
H} NMR
(acetone-d
6
, 100 MHz): δ = 159.4, 157.8, 150.2, 137.6, 131.8, 128.9, 122.1, 119.9,
116.4.
Figure 84. Preparation of NC
mOH
.
Preparation of 2-(3-hydroxyphenyl)-pyridine (NC
mOH
). To a Schlenk
bomb containing 3-hydroxyphenylboronic acid (5.16 g, 0.0374 mol), CsCO
3
(14.43
g, (0.748 mol, 2 eq), and Pd(PPh
3
)
4
(2.16 g, 0.00186 mol, 5 mol %) was added 125
mL of degassed, anhydrous methanol. The bomb was opened under an argon flow,
and 2-bromopyridine (3.56 mL, 0.0374 mol, 1 eq) was added. The reaction flask
was sealed and heated at 110
o
C in an oil bath for 12 hours, which produced a
yellowish colored solution. The solution was then filtered over celite, and the
product was purified by column chromatography using silica. The product was
eluted from the column using a 1:5 ethyl acetate: DCM mixture to yield a white solid
in 78.4 % (5.02 g) yield.
1
H NMR (acteone-d
6
, 400 MHz): δ = 8.86 (dd, 1H,
3
J = 4.6
Hz,
4
J = 1.1 Hz), 8.56 (s, 1H, -OH), 7.83 (m, 2H), 7.66 (t, 1H,
4
J = 2.4 Hz), 7.57 (dt,
1H,
3
J = 7.7 Hz,
4
J = 1.2 Hz), 7.31 (t, 1H,
3
J = 8.1 Hz), 7.28 (dd, 1H,
3
J = 5.6 Hz,
4
J
= 1.6 Hz), 6.92 (dd, 1H,
3
J = 8.1 Hz,
4
J = 1.0 Hz).
13
C {
1
H} NMR (acetone-d
6
, 100
204
MHz): δ = 158.8, 157.6, 150.4, 141.6, 137.7, 130.6, 123.2, 121.0, 118.8, 116.8,
114.4. Hi-res ESI-TOF
+
for C
11
H
10
NO: Calc’d Mass [M+]
+
: (172.0757 m/z); Found:
(172.0768 m/z).
Figure 85. Preparation of NC
pOTf
.
Preparation of 4-(2’-pyridine)-phenyltriflate (NC
pOTf
). Under an inert
atmosphere, pyridine (25 mL) was added to a Schlenk bomb containing NC
pOH
(537
mg, 3.14 mmol). The solution was chilled in an ice bath, and
trifluoromethanesulfonic anhydride (2.52 mL) was added drop wise. The reaction
was sealed and slowly warmed to room temperature followed by stirring overnight.
The solution was then poured into a 250 mL beaker containing ice. The product was
extracted with CH
2
Cl
2
(50 mL) and washed with 50 mL of each of the following: 1M
HCl (aq), water, sat. NaCl (aq). The organic mixture was then dried over anhydrous
MgSO
4
. The solvent was removed by rotary evaporation under reduced pressure.
The product was purified by column chromatography using silica, and eluted with
neat CH
2
Cl
2
to yield an off-white solid in 63.7 % (606 mg) yield.
1
H NMR (CDCl
3
,
400 MHz): δ = 8.68 (dd, 1H,
3
J = 5.0 Hz,
4
J = 1.0 Hz), 8.06 (dt, 2H,
3
J = 8.7 Hz,
4
J =
2.1 Hz), 7.76 (dd, 1H,
3
J = 7.5 Hz,
4
J = 1.8 Hz), 7.70 (dt, 1H,
3
J = 8.1 Hz,
4
J = 1.0
205
Hz), 7.36 (dt, 2H,
3
J = 8.5 Hz,
4
J = 1.8 Hz), 7.26 (dd, 1H,
3
J = 6.2 Hz,
4
J = 1.2 Hz).
19
F NMR (CDCl
3
, 376 MHz): δ = -72.74 (s, 3F).
Figure 86. Preparation of 2.
Preparation of [(NC
pOTf
)
4
Ir(µ-Cl)]
2
(2). Under atmospheric conditions, 2-
ethoxyethanol (30 mL) was added to a Schlenk bomb containing NC
pOTf
(606.2 mg,
1.998 mmol) and IrCl
3
(H
2
O)
3
(234.8 mg, 0.666 mmol). Nitrogen was bubbled
through the solution for 15 minutes, and the solution was then refluxed under
nitrogen for 12 hours. The solvent was removed under reduced pressure at 60
o
C to
yield a yellowish solid. The yellow solid was dissolved in dichloromethane, and the
product was purified by column chromatography using silica. The product was
eluted from the column with dichloromethane to yield a bright yellow solid in 46.2
% (256 mg) yield.
1
H NMR (acetone-d
6
, 400 MHz): δ = 9.22 (d, 1H,
3
J = 6.33 Hz),
8.34 (d, 1H,
3
J = 8.1 Hz), 8.15 (dt, 1H,
3
J = 8.1 Hz,
4
J = 1.5 Hz), 7.92 (d, 1H,
3
J = 8.8
Hz), 7.25 (dt, 1H,
3
J = 6.7 Hz,
4
J = 1.4 Hz), 6.89 (dd, 1H,
3
J = 8.6 Hz,
4
J = 2.5 Hz),
5.74 (d, 1H,
4
J = 2.6).
13
C {
1
H} NMR (acetone-d
6
, 100 MHz): δ = 166.6, 151.6,
149.6, 147.1, 145.5, 138.9, 126.0, 124.7, 121.9, 120.7, 119.0(J
C-F
= 322 Hz) 115.0.
206
19
F NMR (CD
2
Cl
2
, 376 MHz): δ = -73.92 (s, 3F). Hi-res ESI-TOF
+
for
C
48
H
28
N
4
O
12
F
12
Cl
2
S
4
Ir
2
: Calc’d Mass [M-Cl]
+
: (1628.9321 m/z); Found: (1628.9512
m/z).
Figure 87. Preparation of NC
mOTBDMS
.
Preparation of 2-(3-tert-butyl-dimethylsilyl phenylether)-pyridine
(NC
mOTBDMS
). Under an inert atmosphere, dichloromethane (25 mL) was added to a
Schlenk flask containing NNC
mOH
(201.0 mg, 1.168 mmol), tert-butyl-dimethyl-
silylchloride, TBDMS-Cl, (352.0 mg, 2.34 mmol, 2 eq), and imidazole (159.0 mg).
The reaction was then sealed and stirred overnight. The reaction was quenched with
water (10 mL), and the organics separated. The organic layer was washed with
saturated NaCl (aq) (30 mL) followed by drying over anhydrous MgSO
4
. The
product was purified by flash column chromatography using silica, and eluted with a
gradient from hexanes to methylene chloride, and small fractions were collected in
order to avoid collecting tert-butyl-dimethylsilanol in the product. The product was
isolated as an oil in a 93.3 % (311 mg) yield.
1
H NMR (CDCl
3
, 400 MHz): δ = 8.66
(d, 1H,
3
J = 4.6 Hz), 7.64 (m, 2H), 7.57 (d, 1H,
3
J = 8.0 Hz), 7.53 (t, 1H,
4
J = 2.5
207
Hz), 7.31 (t, 1H,
3
J = 7.6 Hz), 7.14 (m, 1H), 6.89 (dd, 1H,
3
J = 8.0 Hz,
4
J = 2.5 Hz),
1.01 (s, 9H), 0.23 (s, 6H).
13
C {
1
H} NMR (CDCl
3
, 100 MHz): δ = 157.2, 156.1,
149.6, 140.9, 136.6, 129.7, 122.1, 120.6, 120.0, 118.8, 26.0, 18.2, -4.0. Hi-res
DART
+
for C
17
H
23
NOSi: Calc’d Mass [M+H]
+
: (286.1627 m/z); Found: (286.1638
m/z).
Figure 88. Preparation of NC
mOTIPS
.
Preparation of 2-(3-triisopropylsilyl phenylether)-pyridine (NC
mOTIPS
).
Under an inert atmosphere, dichloromethane (20 mL) was added to a Schlenk bomb
containing NNC
mOH
(162 mg, 0.963 mmol), triisopropylsilylchloride, TIPS-Cl, (371
mg, 1.92 mmol, 2 eq), and imidazole (131.1 mg, 1.926 mmol, 2 eq). The reaction
was sealed and stirred overnight. The reaction was quenched with water (10 mL),
and the organics were separated from the water. The organic layer was washed with
saturated NaCl (aq) (30 mL) followed by drying over anhydrous MgSO
4
. The
product was purified by flash chromatography using silica, and the product was
eluted with a gradient from hexanes to methylene chloride. Fractions were collected
in small amounts to avoid collecting triisopropylsilanol in the product. The product
208
was obtained as an oil in 51.5 % (162 mg) yield.
1
H NMR (CDCl
3
, 400 MHz): δ =
8.57 (d, 1H,
3
J = 5.0 Hz), 7.58 (m, 2H), 7.47 (d, 1H,
3
J = 7.8 Hz), 7.44 (t, 1H,
4
J =
1.9 Hz), 7.21 (t, 1H,
3
J = 8.1 Hz), 7.07 (dd, 1H,
3
J = 6.1 Hz,
4
J = 1.9 Hz), 6.83 (dd,
1H,
3
J = 8.1 Hz,
4
J = 1.1 Hz), 1.19 (sept, 3H,
3
J = 8.3 Hz), 0.23 (d, 18H,
3
J = 7.9
Hz).
13
C {
1
H} NMR (CDCl
3
, 100 MHz): δ = 157.4, 156.6, 149.7, 141.0, 136.7,
129.7, 122.2, 120.6, 120.4, 119.8, 118.6, 18.1, 12.8. Hi-res DART
+
for C
20
H
29
NOSi:
Calc’d Mass [M+H]
+
: (328.2097 m/z); Found: (328.2094 m/z).
Figure 89. Preparation of 1.
Preparation of [(NC
mOTIPS
)
4
Ir( μ-Cl)]
2
(1). Under atmospheric conditions,
2-ethoxyethanol (30 mL) was added to a round bottom flask containing NC
mOTIPS
(162 mg, 0.496 mmol, 2.5 eq) and IrCl
3
•3H
2
O (69.9 mg, 0.198 mmol). The reaction
was then refluxed overnight under argon. Within the first 30 minutes, the color
changed from a golden-yellow suspension to a clear orange solution. The solvent
was removed under reduced pressure. The product was purified by flash
chromatography using silica, and the product was eluted with neat dichloromethane
to yield an orange solid in 35.0 % (61.2 mg) yield.
1
H NMR (CD
2
Cl
2
, 400 MHz) δ
209
9.19 (d, 1H,
3
J = 5.7 Hz,
4
J = 0.8 Hz), 7.82 (d, 1H,
3
J = 7.7 Hz), 7.76 (dt, 1H,
3
J =
7.4 Hz,
4
J = 1.9 Hz), 7.12 (d, 1H,
4
J = 2.89 Hz), 6.80 (dt, 1H,
3
J = 6.7 Hz,
4
J = 1.6
Hz), 6.28 (dd, 1H,
3
J = 8.0 Hz,
4
J = 2.9 Hz), 5.71 (d, 1H,
3
J = 8.3 Hz), 1.17 (sept, 3H,
3
J = 7.9 Hz), 1.05 (d, 18H,
3
J = 8.4 Hz).
13
C {
1
H} NMR (CD
2
Cl
2
, 100 MHz) δ
168.6, 152.2, 151.7, 144.7, 136.8, 135.2, 130.9, 123.1, 121.5, 119.1, 115.4, 18.3,
13.2.
4.2: Analysis of Iridium(I) as an Active Catalyst for C-H activation
in Water
4.2.1: Introduction
For many years scientists have been pursuing the C-H activation reaction as a
route for the functionalization of C-H bonds.
84
Several systems have been shown to
convert methane into functionalized products; however, all of these systems rely on
electrophilic metals, such as platinum(II), palladium(II), mercury(II), and
gold(I)/gold(III), and all of these operate in strongly acidic media, sulfuric acid.
85
The most well known of these systems is the Catalytica system, Pt(bipyrimidine)Cl
2
,
developed by Periana et al., which converts methane to methylbisulfate in a 72 %
one-pass yield at 90 % selectivity. However, the water produced in the
functionalization step as a byproduct inhibits the electrophilic platinum(II) center.
86
As a result, our research efforts have been directed towards developing more electron
rich C-H activation catalysts that operate in water and are thermally stable to protic
and oxidizing media. These more electron rich less electronegative metal complexes
(i.e. metals to the left of platinum) should bind water less tightly than the
210
Pt(bipyrimidine)Cl
2
system. Pathways for C-H cleavage other than electrophilic
substitution should also be viable. Therefore, the Periana group has been interested
in the use of low valent electron rich complexes for activation of hydrocarbons in
water.
One possible catalyst system could be the group IX metals in the +1
oxidation state, rhodium(I)/iridium(I). Many iridium(I) complexes are known;
however, a majority of these complexes contain phosphine ligands. The Periana
group has ruled out using phosphine ligands due to π-acidic nature of the phosphine,
which decreases the electron density at the metal and makes the metal less
nucleophilic towards the C-H bond. Phosphines also have the potential to undergo
side reactions in the presence of an oxidant. Our group has chosen to look at
aromatic heterocycles as potential ligands for these low oxidation state, late
transition metal catalysts. These aromatic heterocycles are tunable by placing various
substituent groups around the rings. The π-acidity of the heterocycle can also be
changed by placing other nitrogens within the aromatic ring system.
A literature search for known iridium(I) complexes containing our choice of
ligand set turned up the (κ
2
-bipyridine)Ir(C
2
H
4
)
2
Cl. This complex was reported in
the 1980s and was largely used for the transfer hydrogenation of ketones. Therefore,
I wondered if this system might be competent for C-H activation. The novel utility
of this system was that it would have been one of the first reported iridium(I)
catalysts for the H/D exchange of water and hydrocarbons. Using a low valent metal,
such as iridium(I), the activation of the C-H bond of methane should be facile. More
211
importantly the Periana group feels that by using a low valent metal to make the
metal alkyl should result in a more polarized M-R
( δ-)
bond, which should lead to
more facile functionalization.
81
4.2.2: Results and Discussion
Before I ran any experiments, I turned to Density Functional Theory, DFT, to
give me a better picture of what I might observe in solution. DFT calculations were
performed by using the B3LYP density functional. This functional is a combination
of the hybrid three parameter Becke exchange functional (B3)
87
and the Lee-Yang-
Parr correlation functional (LYP).
88
The basis sets used for iridium were the core-
valence effective core potential of Hay and Wadt,
89
while the Pople-style 6-31G**
90
basis set was utilized for all other atoms. Since some of the calculations contained
negatively charged species, the effects of diffuse functions were included by
computing single-point energies with the 6-31G**
++
basis set.
All calculations were corrected for the effect of solvent interactions by using
the polarizable continuum model (PCM) of solvation.
91,92
All calculations were
solvated with water which has a dielectric of 80.37 and a probe radius of 1.40 Å. All
calculations were computed with a combination of the Jaguar 6.0 and Jaguar 6.5
computation packages.
93
The nature of all stationary points was confirmed with a
normal mode analysis by confirming that all minima had zero imaginary frequencies.
The vibrational frequencies were used to compute the zero-point correction. The
total enthalpies were computed for each stationary point and used for relative
212
enthalpy calculations (at 298.15 K). No free energy calculations have been included
due to the difficulty in accurately predicting the changes in the entropy of the
translational and rotation entropy of the vibrational modes as molecular complexes
are associated or dissociated. All calculations are reported at pH =14, which implies
that 1 M hydroxide is present in the thermodynamic calculations.
I performed a variety of thermodynamic calculations, and one of the goals
was to determine what would be the resting state of the catalyst. I plan to operate in
a basic aqueous medium, so I proposed that the chloride would likely be displaced to
generate an Ir-OH species. The hydroxo would also be important in this system as it
will likely be the basic site that receives the proton from the hydrocarbon in the C-H
cleavage transition state. Work by Maestroni et al. has shown that the ethylene’s
bound to iridium are labile and are displaced in isopropanol to generate a solvento
species. Therefore, I started with (bipyridine)Ir(OH)OH
2
as the reference point.
DFT calculations were carried out on several proposed intermediate species, Figure
90. From this energy diagram several interesting points should be noted. The most
important point is that the protonation of the iridium(I) complex by water (insertion
into the O-H bond of water / oxidative addition of water) is exothermic by 11
kcal/mol. Therefore, DFT predicts that in the presence of water, the iridium(I)
complex will likely be oxidized to iridium(III).
213
Ir
N
N
OH
2
OH
Ir
N
N
OH
OH
Ir
N
N
CH
3
OH
Ir
N
N
OH
2
OH
2
Ir
N
N
OH
Ir
N
N OH
2
Ir
N
N
CH
3
OH
2
Ir
N
N
OH
CH
3
H
OH
2
Ir
N
N
OH
OH
H
OH
2
0, 0, 0
-11,-14, -16
8,10,12
12, 13, 13
25, 25, 27
4, -3, -2
14,13, 12
-11, -9, -7
-3, -3, -1
∆H for Ir(bipyridine) solvated in water
(pH=14); LACVP**/B3L YP
By adding electron
withdrawing ligands to the
metal, the protonation of Ir(I)
by water or (oxidative
addition of water) is
destabilized; however, the
binding of hydroxide over
water is stabilized.
-9, -10, -10
-1, 0, 1
CH cleavage
Transition state
Figure 90. DFT Calculations for Ir
I
bipyridine, bipyrimidine, and bipyrazine. The
values in each box correspond to the following: (bipyridine)Ir
I
,
(bipyrimidine)Ir
I
, (bipyrazine)Ir
I
, respectively.
This protonation to generate the higher oxidation state species is
fundamentally a problem. Since the protonation generates a more stable species by
10 kcal/mol, this adds to the overall barrier for C-H activation. Iridium(I) and
iridium(III) will likely have two different transition states for the C-H cleavage;
however, the iridium(I) pathway should have the lower overall barrier for C-H
activation. This assumption is based off of the precedence that iridium(I) has been
shown to rapidly cleave the C-H bond. Therefore, I wanted to keep the iridium in
the lower oxidation state such that facile rates for C-H activation could be achieved.
214
The increased electron density about the metal would also assist in the C-H
functionalization of the M-R species, vide supra. If the system operates in the +3
oxidation state, then the system is not as novel, as there have been several reported
iridium(III) systems that activate C-H bonds in water.
71,72,94
To gain further understanding as to how to prevent this oxidation from
occurring, I decided to perform the calculations with various other similar ligands
that contained nitrogens within the bipyridine ring system, i.e. bipyrimidine and
bipyrazine. Having the extra nitrogens within the ring system should increase the π-
acidity of the ligands and thus decrease the electron density at the metal. The results
of the comparison of iridium(I) using bipyridine, bipyrimidine, and bipyrazine can be
seen in Figure 90. From the results an interesting trend is observed. If one assumes
that the π-acidity of the ligands increases from bipyridine < bipyrimidine <
bipyrazine then it can be said that the protonation of the metal to go from iridium(I)
to iridium(III) should be less exothermic going from (bipyridine)Ir
I
to (bipyrazine)Ir
I
.
This is what is observed from Figure 90. The protonation of the
(bipyrazine)Ir
I
(OH)OH
2
is exothermic by 4 kcal/mol, which is less than in the case
of (bipyrimidine)Ir
I
(OH)OH
2
(exothermic = 10 kcal/mol). The use of the more π-
acidic ligands decreased the electron density at the iridium center such that
protonation was not as favorable. However, another product, the dihydroxo, appears
to be more stabilized by the increased π-acidity of the ligands. The increased π-
donation from the hydroxo ligand is stabilized by having ligands with increased π-
acceptance capabilities. This result is further compounded by the fact that during
215
this investigation Goldberg published work on a rhodium(I) and iridium(I) pincer
(PNP) hydroxo complex, where PNP = 2,6-(CH
2
P
t
Bu
2
)
2
)-pyridine, that is
competent for C-H activation. Her mechanistic studies were carried out using a Rh
I
-
acetate and Rh
I
-phenoxo complex, and the complexes were not exposed to a
significant amount of water, no greater than 10 equivalents in benzene. From the
mechanistic studies it was concluded that the mechanism was dissociative in the
phenoxo ligand. Therefore, assuming that the (bipyrazine)Ir
I
(OH)OH
2
went through
a similar mechanism for C-H activation there will likely be an inhibition by base.
+ H
2
O + OH
-
H
2
O +
0, 0, 0
8, 2.5, 0.3
37, 27, 24
Protonation of Ir(I)
by water (Oxidative
addition of water)
Hydroxide dissociation
from Ir(I)
,
,
LACVP**/B3LYP
Enthalpies
Solvation in water
Figure 91. DFT analysis of (PNP)Ir
I
OH dissociation of hydroxide and the
protonation by water. The values shown are the following
(respectively): (2,6-(CH
2
P(F)
2
)
2
)-pyridine)Ir, (2,6-(CH
2
P(OMe)
2
)
2
)-
pyridine)Ir, and (2,6-(CH
2
P(Me)
2
)
2
)-pyridine)Ir.
216
An analysis of the (PNP)Ir(OH) system by DFT shows that the protonation
by water to generate an iridium(III) species is endothermic. However, it is also
apparent that loss of hydroxo from the iridium(I) center is also quite endothermic.
The same general trend that was observed in the previous (bipyridine)Ir
I
is observed
in the (PNP)Ir
I
(OH) calculations. While the electron withdrawing ligands with
fluorine groups on the phosphine greatly disfavor the protonation (oxidative
addition) of water to the Ir(I) center( ΔH
rxn
= 8 kcal/mol), it also shows a very high
barrier for dissociation of the hydroxo from the metal center ( ΔH
rxn
= 37 kcal/mol).
On the other hand, using a more electron rich PNP ligand where the fluorine atoms
have been replaced by methyl groups shows that the protonation (oxidative addition)
of water to the iridium(I) center is approximately thermoneutral ( ΔH
rxn
= 0.3
kcal/mol); however, the dissociation of the hydroxo ligand by the more electron rich
iridium(I) center is more favorable ( ΔH
rxn
= 24 kcal/mol).
4.2.3: Conclusion
In the group’s effort to develop electron rich C-H activation catalysts I
thought that iridium(I) would be an electron rich C-H activation catalyst that could
ultimately yield facile H/D exchange rates in water. However, through DFT
calculations I observed that four coordinate electron rich systems, like iridium(I),
have the tendency to become protonated by water formally increasing the oxidation
state of the metal thereby decreasing the electron density at the metal center. The
use of π-acidic ligands destabilizes this protonation by water, but it also appears that
217
it stabilizes the binding of the π-donating hydroxo ligand. Furthermore, while it is
known that most d
8
complexes undergo associative substitution, Goldberg has
recently shown that a Rh
I
-phenoxo complex undergoes a dissociative pathway for C-
H activation. As a result, it is possible that in the presence of base that the iridium(I)
hydroxo will likely be inhibited by the basic medium. Therefore, the use of four
coordinate complexes over using similarly octahedral electron rich complexes may
not be the best choice due to the above stated reasons.
4.3: Attempted Synthesis of a Sterically Hindered Cyclometallated
Ir(NNC) Complex
4.3.1: Introduction
The use of sterically hindered pincer ligands have shown great importance
throughout catalysis. Schrock et al. used a bulky tetradentate nitrogenous based
[(HIPTCH
2
CH
2
N)
3
N]
3-
where HIPT = (3,5-(2,4,6-i-Pr
3
C
6
H
2
)
2
C
6
H
3
) for the catalytic
reduction of nitrogen to ammonia using a (HIPTN
3
N) Molybdenum complex. This
bulky ligand maximized the steric protection about the open coordination site.
95
One of the more well known sterically hindered pincer ligands is the PCP and PNP
pincer ligands, where PCP = (C
6
H
4
-2,6-(CH
2
P
t
Bu
2
)
2
) and PNP = 2,6-(CH
2
P
t
Bu
2
)
2
)-
pyridine. Both of these ligands have found extensive chemistry on many late
transition metals. The (PCP)Ir(H)
2
complex was found to be competent for catalytic
alkane dehydrogenation and alkane metathesis.
96,97
Recently our group reported an (NNC
(tBu2)
)IrEt(TFA)(C
2
H
4
) complex, where
(NNC
(tBu2)
) = 6-phenyl-4,4’-di-tert-butyl-2,2’-bipyridine and TFA = trifluoroacetate,
218
that shows H/D exchange between hydrocarbons (methane and benzene) and
trifluoroacetic acid.
98
With the ability for this motif to activate methane, I decided to
investigate whether a sterically hindered NNC derivative could yield some exciting
and interesting chemistry similar to that chemistry which has been observed with the
(PCP)Ir(H)
2
complex. The use of the sterically hindered NNC derivative might also
lead to the formation of the rare five coordinate Ir(III) complex.
4.3.2: Results and Discussion
A bulky NNO ligand, where NNO = 9-(3,5-di-tert-butyl-2-phenol)-2-tert-
butyl-1,10-phenanthroline, was recently reported by Stack et al. in his studies of a
(NNO)Cu
II
Cl complex, Figure 92.
99
The idea for a sterically hindered NNC
derivative came from this complex. By removing the coordinating oxygen and
directly bonding the metal to the aryl ring, the complex would be a NNC coordinated
complex with sterically hindering tert-butyl groups on either side of the metal,
Figure 92. These bulky groups should prevent the formation of dinuclear complexes,
which have been observed in the Ir(NNC
(tBu2)
) complexes, ( μ-Cl) and (µ-OH), see
chapter 3. Furthermore, the increased sterics might force the complex to go five
coordinate. The ability to form five coordinate d
6
complexes are rare, and are
usually only observed in the case of sterically hindered ligands such as PNP and
PCP. A five coordinate molecule such as this would be interesting to study and to
see what kind of chemistry it might generate. Therefore, I set out to synthesize the
sterically hindered NNC ligand.
219
Figure 92. Stack’s Complex and the desired Ir(NNC) sterically hindered complex.
I prepared one of the starting precursors following Stack’s procedure for the
preparation of 2-tert-butyl-1,10-phenanthroline. The other precursor 3,5-di-tert-
butyl-bromobenzene was obtained through commercial sources, and the two
substrates were coupled together to produce 9-(3,5-di-tert-butyl-phenyl)-2-tert-butyl-
1,10-phenanthroline, 3. The product was obtained in 16 % yield and was
characterized by
1
H and
13
C NMR and high resolution mass spectrometry.
Scheme 26. Synthesis of 3, a sterically hindered NNC derivative.
Once 3 was synthesized, I tried various routes to cyclometallate it to iridium.
Initial discussions with Professor Kaska led me to follow preparations similar to his
preparation for (PCP)Ir(H)(Cl), which called for the reaction of 3 and IrCl
3
·(H
2
O)
3
in
a 7:1 isopropanol: water mixture at 70
o
C for 24 hours. However, reactions carried
out under the same conditions using 3 only produced iridium black. Every reaction
220
was performed under argon due to the possibility of producing iridium(I), which
would be an air sensitive intermediate. I then decided to try the well known
precursors [Ir(COE)
2
(µ-Cl)]
2
and [Ir(C
2
H
4
)
2
(µ-Cl)]
2
, where COE = cyclooctene, as
starting materials, as these precursors were used to synthesize the parent NNC
ligated iridium complexes, where NNC = 6-phenyl-4,4’-di-tert-butyl-2,2’-bipyridine,
see chapter 3. I began using [Ir(C
2
H
4
)
2
(µ-Cl)]
2
as the starting material as it would
be the most reactive. Compound 3 and [Ir(C
2
H
4
)
2
(µ-Cl)]
2
were mixed in CD
2
Cl
2
,
and the reaction was followed by
1
H NMR. Analysis of the reaction at T
0
indicated
that a coordination complex was likely occurring with at least one of the nitrogens
bound to metal due to the shift in the
1
H NMR signals for 3, and the fact that the
ligand
1
H NMR signals had become broadened. Heating this solution at 40
o
C
produced a reaction as observed by
1
H NMR, and the color of the solution had
changed from light red to dark red. Excess [Ir(C
2
H
4
)
2
(µ-Cl)]
2
was used, and due to
the thermal sensitivity of this starting material decomposition, products could be
observed on the walls of the NMR tube. Several iridium hydride signals were
observed at δ -11 to -16 ppm in the
1
H NMR. However, the total yield of these
proton resonances was less than 25 % of the total material in solution. This same
reaction was also tried in toluene-d
8
and tetrahydrofuran-d
8
with similar results. This
starting material was not used for further reactions, which required heating due to the
thermal sensitivity of [Ir(C
2
H
4
)
2
(µ-Cl)]
2
. The cyclometallation of 3 to iridium is not
expected to be a facile reaction due to the steric hindrance in the transition state for
the cyclometallation and in the resulting product.
221
I also tried preparations similar to those reported by Brookhart et al. using
[Ir(COD)
2
(µ-Cl)]
2
, where COD = 1,5-cyclooctadiene. Brookhart successfully
cyclometallated his POCOP ligand, where POCOP = (C
6
H
4
-2,6-(O-PBu
t
2
)
2
), to
[Ir(COD)
2
(µ-Cl)]
2
to generate the five coordinate (POCOP)Ir(H)(Cl) complex.
Heating a 1:1 mixture of [Ir(COD)
2
(µ-Cl)]
2
and 3 yielded only starting materials
after 5 hours at 80
o
C in CD
2
Cl
2
. I am further investigating this reaction at higher
temperatures in higher boiling solvents, toluene, so the mixture can be heated to
higher temperatures. Due to the excessive sterics for the cyclometallation of 3 with
the metal, an extended reaction time may be needed. It might be possible to react 3
at room temperature in the presence of the thermally sensitive [Ir(COE)
2
(µ-Cl)]
2
and
[Ir(C
2
H
4
)
2
(µ-Cl)]
2
for an extended period of time (2 weeks) to achieve the
cyclometallated product.
To further understand the geometry of the proposed five coordinate complex
that might be generated by the cyclometallation of 3 with iridium, I decided to look
at the geometry of the 3-Ir(H)(Cl) complex and compare it to the (PCP)IrHCl five
coordinate complex, Figure 93. It is interesting to observe that in the case of 3-IrHCl
that the bulky tert-butyl substituents appear to force the hydride and chloride ligands
to go axial, (H)-(Ir)-(Cl) angle = 176
o
. The space filling model, Figure 93, for 3-
IrHCl shows that the equatorial open coordination site is filled by the methyl groups
of each tert-butyl substituent. It is not clear, but agnostic interactions may also be
present between the tert-butyl substituent and the iridium center. The tert-butyl
group might also cyclometallate to the metal center as occasionally has been
222
observed in the studies of the (PCP)Ir(H)(Cl) system; however, these reactions are
reversible and should not be a problem.
Figure 93. Chemdraw structure (top) for 3-Ir(H)(Cl) and (PCP)Ir(H)(Cl) and
their respective DFT geometry optimized space filling models
(bottom).
4.3.3: Conclusion
The use of sterically hindered pincer ligands have shown to be thermally and
protic stable and their related complexes have generated interesting chemistry such
as alkane dehydrogenation and alkane metathesis. I synthesized a sterically hindered
NNC derivative, 3, and I am currently pursuing various routes to make a 5
coordinate cyclometallated iridium complex. We will further pursue the use of this
ligand on other late transition metals such as platinum, osmium, and rhenium.
223
4.3.4: Experimental
General Considerations: Unless otherwise noted all reactions were
performed using standard Schlenk techniques (argon) or in a MBraun glove box
(nitrogen).
1
H and
13
C NMR were collected on Varian 400 Mercury plus
spectrometer, and chemical shifts were referenced to residual protiated solvent. All
coupling constants are reported in hertz, Hz. Mass spectrometry analyses were
performed at the University of Florida mass spectrometry facility.
Materials: IrCl
3
•3H
2
O was purchased from Pressure Chemical, and tert-
butyl lithium (1.5M in pentane) was purchased from Aldrich. All solvents were
reagent grade or better. Diethyl ether was dried over sodium/benzophenone ketyl
and distilled under argon. Dichloromethane (stabilizer removed with sulfuric acid)
was dried over P
2
O
5
and distilled under argon. The precursor, 2-tert-butyl-1,10-
phenanthroline, was prepared according to a previously published procedure.
99
Chromatotron (centrifugal thin-layer chromatography) plates were made using silica
gel for thin layer chromatography that was purchased from EMD.
Figure 94. Preparation of 3.
Preparation of 9-(3,5-di-tert-butyl-phenyl)-2-tert-butyl-1,10-
phenanthroline (3). Under an inert atmosphere, 3,5-di-tert-butyl-bromobenzene
224
(5.24 g, 0.0195 mol) was added to dried, degassed, diethyl ether (100 mL). The
solution was cooled to -78
o
C, and tert-butyllithium (26.0 mL of a 1.5 M solution,
0.0389 mol, 4 eq) was added in a drop-wise fashion. The solution was stirred for 2
hours before allowing it to warm to room temperature. The suspension was
cannulated over to a 100 mL solution of 2-tert-butyl-phenanthroline (2.30 g, 0.00973
mol) in toluene at room temperature. The reaction was stirred overnight followed by
slow quenching with ice water (50 mL). The organics were extracted with CH
2
Cl
2
(3
x 50 mL). The methylene chloride solution was then stirred with MnO
2
(25 g) for
one day followed by filtration over celite. The organic solution was then washed
with saturated NaCl (aq) (100 mL) followed by drying over MgSO
4
. The solvent
was evaporated by rotary evaporation under reduced pressure, and the mixture was
redissolved in pentane. The product was purified by centrifugal thin-layer
chromatography using a 4 mm silica Chromatotron plate. The product was eluted
using 3:10 CH
2
Cl
2
: pentane mixture to yield an oil in 15.7 % (0.650 mgs, 0.00153
mol).
1
H NMR (CDCl
3,
400 MHz): δ = 8.36 (d, 2H,
4
J = 1.9 Hz), 8.25 (d, 1H,
3
J =
8.5 Hz), 8.14 (dd, 2H,
3
J = 8.30 Hz), 7.72 (m, 3H), 7.54 (t, 1H,
4
J = 1.8 Hz), 1.63 (s,
9H), 1.44 (s, 18H).
13
C {
1
H} NMR (CDCl
3,
100 MHz): δ = 169.4, 157.3, 151.2,
146.1, 145.0, 138.9, 136.7, 136.0, 127.6, 127.0, 125.8, 125.4, 123.7, 122.0, 120.1,
38.9, 35.2, 31.7, 30.4. Hi-res ESI-TOF
+
MS for C
30
H
36
N
2
: Calc’d Mass [M+H]
+
:
(425.2957 m/z); Found: (425.2951 m/z).
Geometry Optimization Calculations: Density Functional Theory
calculations were performed by using the B3LYP density functional. This functional
225
is a combination of the hybrid three parameter Becke exchange functional (B3)
87
and
the Lee-Yang-Parr correlation functional (LYP).
88
The basis sets used for iridium
were the core-valence effective core potential of Hay and Wadt,
89
while the Pople-
style 6-31G**
90
basis set was utilized for all other atoms. The effects of diffuse
functions were included by computing single-point energies with the 6-31G**
++
basis set. All calculations were computed with a combination of the Jaguar 6.0 and
Jaguar 6.5 computation packages.
93
Figure 95: Ball and spoke structure for the gas phase geometry optimized
(PCP)Ir(H)(Cl).
226
Figure 96: Ball and spoke structure for the gas phase geometry optimized
3-Ir(H)(Cl).
227
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Abstract (if available)
Abstract
The first chapter is an introduction to the development of carbon-hydrogen bond, (C-H), activation. The use of acidic solvents for C-H activation is addressed, and catalyst inhibition by water or methanol is discussed as one of the major problems in creating active catalysts. New approaches for designing C-H activation/functionalization catalysts that operate in water are discussed.
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University of Southern California Dissertations and Theses
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Asset Metadata
Creator
Meier, Steven Karl
(author)
Core Title
Catalytic C-H activation by cyclometallated iridium hydroxo complexes in aqueous media
School
College of Letters, Arts and Sciences
Degree
Doctor of Philosophy
Degree Program
Chemistry
Publication Date
07/28/2008
Defense Date
06/03/2008
Publisher
University of Southern California
(original),
University of Southern California. Libraries
(digital)
Tag
C-H activation,hydroxo,iridium,OAI-PMH Harvest
Language
English
Advisor
Periana, Roy A. (
committee chair
), Petruska, John A. (
committee member
), Prakash, G.K. Surya (
committee member
), Williams, Travis J. (
committee member
)
Creator Email
meiersk78@yahoo.com
Permanent Link (DOI)
https://doi.org/10.25549/usctheses-m1427
Unique identifier
UC1301700
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etd-Meier-20080728 (filename),usctheses-m40 (legacy collection record id),usctheses-c127-201959 (legacy record id),usctheses-m1427 (legacy record id)
Legacy Identifier
etd-Meier-20080728.pdf
Dmrecord
201959
Document Type
Dissertation
Rights
Meier, Steven Karl
Type
texts
Source
University of Southern California
(contributing entity),
University of Southern California Dissertations and Theses
(collection)
Repository Name
Libraries, University of Southern California
Repository Location
Los Angeles, California
Repository Email
cisadmin@lib.usc.edu
Tags
C-H activation
hydroxo
iridium