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36
2.2.3 Strecker Reaction of Ketones and their Fluorinated Analogs.
One of the most important multicomponent reactions is the Strecker
reaction to synthesize -amino acids via the intermediacy of -
aminonitriles.45,46,47,48,49,50,51,52,53,54,55 However, successful three component Strecker
reactions using ketones and fluorinated ketones are rare. Fluorinated amino acids
are becoming increasingly important in pharmaceuticals and other biological
applications56,57,58,59,60,61,62 such as the development of anticancer drugs for the
control of tumor growth, drugs for the control of blood pressure and allergies.63
Also, recent studies with fluorinated amino acids have shown the possibilities for
the design and construction of hyperstable protein folds and studies of the protein-protien
interaction for unnatural amino acids.64,65,66,67,68,69,70 Fluorinated amino
acids are also a valuable tool for the screening of protein dynamics by NMR
studies.64,65,66,67,68,69,70 Consequently, fluorinated amino acids have become the
object of intense synthetic activity and scrutiny in recent years.
The Strecker reaction with aldehydes has been studied extensively with a
variety of catalysts71,72,73,74,75,76,77,78,79,80 including a number of metal triflates.81,82,83
Efficient, clean and direct three component Strecker reaction using ketones is
difficult. Quite often these reactions have to be carried out stepwise (preparation of
imines first followed by the cyanide addition)46,47 or under high pressure
conditions.50,51 Use of ammonia or ammonium salts in the presence of cyanides has
been described.52-54
Object Description
| Title | Synthesis of organofluorine compounds via Lewis/Bronsted acid and base catalysed reactions and related chemistry |
| Author | Vaghoo, Habiba Ebrahim |
| Author email | vaghoo@usc.edu; vaghoo@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program |
Chemistry vinyl fluorides |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2008-06-24 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-10-31 |
| Advisor (committee member) |
Olah, George A. Shing, Katherine S. |
| Abstract | This dissertation describes the development of new and practical methodologies for the synthesis of a broad variety of fluorinated heterocycles and vinyl fluorides via acid and base catalysis, respectively. It also describes efficient cyanosilylation of carbonyl compounds using a variety of nucleophilic catalysts.; Chapter 1 explores the rich history of fluorine and its compounds. Important milestones that have made a significant contribution to the field of chemistry are highlighted with emphasis on fluorine's role in medicinal chemistry. Methods to introduce fluorine are also included in this chapter.; Chapter 2 deals with the use of gallium (III) triflate as a versatile Lewis acid for the synthesis of different fluorinated heterocycles and α-aminonitriles. The condensation-cyclization reactions of various aromatic amino derivatives with fluorinated ketones to afford the corresponding fluorinated benzimidazolines, benzothiazolines, benzoxazolines, and dihydrobenzoxazinones, as well as fluorinated 1, 5 benzodiazepines and quinoxaline derivatives is described. Also included in this chapter are the syntheses of α-aminonitriles and their fluorinated analogs via the multicomponent Strecker reaction using gallium (III) triflate. Monofluoro-, difluoro-, or trifluoromethyl groups have been incorporated into both heterocycles and the α-aminonitrile products by varying the nature of the fluorinated ketones.; In Chapter 3, Nafion^®-H, a perfluoroalkanesulfonic acid resin, is shown to be a suitable solid acid catalyst with high selectivity and catalytic activity for the one-pot synthesis of fluorinated heterocycles. The Nafion-H mediated reactions are easily achieved under mild conditions in high yields and purity. Monofluoro, difluoro and trifluoromethylated derivatives can be prepared and its advantage as a solid superacid is highlighted by the recyclability studies.; Chapter 4 describes a new approach for the stereoselective synthesis of vinyl fluorides using α-substituted fluoro(phenylsulfonyl)methane derivatives under mildly basic reaction conditions. A variety of fluorovinyl sulfones as well as α-fluoro-α,β-unsaturated carbonyls can be synthesized to afford the E-isomer.; Finally, in Chapter 5, cyanosilylation of aldehydes and ketones using various nucleophilic catalysts under mild conditions is portrayed. Use of dimethylformamide (DMF) as solvent, afforded the trimethylsilylated cyanohydrins in good to excellent yields. K2CO3 and (MeO)2P(O)(O^-)(N^+Bu4)3 have been employed as the nucleophilic catalysts for the cyanosilylation using trimethylsilyl cyanide (TMSCN). |
| Keyword | fluorine chemistry; fluorinated heterocycles; fluorinated aminonitriles; cyanosilylation |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m1729 |
| Contributing entity | University of Southern California |
| Rights | Vaghoo, Habiba Ebrahim |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@lib.usc.edu |
| Filename | etd-Vaghoo-2053 |
| Archival file | uscthesesreloadpub_Volume44/etd-Vaghoo-2053.pdf |
Description
| Title | Page 50 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 36 2.2.3 Strecker Reaction of Ketones and their Fluorinated Analogs. One of the most important multicomponent reactions is the Strecker reaction to synthesize -amino acids via the intermediacy of - aminonitriles.45,46,47,48,49,50,51,52,53,54,55 However, successful three component Strecker reactions using ketones and fluorinated ketones are rare. Fluorinated amino acids are becoming increasingly important in pharmaceuticals and other biological applications56,57,58,59,60,61,62 such as the development of anticancer drugs for the control of tumor growth, drugs for the control of blood pressure and allergies.63 Also, recent studies with fluorinated amino acids have shown the possibilities for the design and construction of hyperstable protein folds and studies of the protein-protien interaction for unnatural amino acids.64,65,66,67,68,69,70 Fluorinated amino acids are also a valuable tool for the screening of protein dynamics by NMR studies.64,65,66,67,68,69,70 Consequently, fluorinated amino acids have become the object of intense synthetic activity and scrutiny in recent years. The Strecker reaction with aldehydes has been studied extensively with a variety of catalysts71,72,73,74,75,76,77,78,79,80 including a number of metal triflates.81,82,83 Efficient, clean and direct three component Strecker reaction using ketones is difficult. Quite often these reactions have to be carried out stepwise (preparation of imines first followed by the cyanide addition)46,47 or under high pressure conditions.50,51 Use of ammonia or ammonium salts in the presence of cyanides has been described.52-54 |
