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112
In all cases, only the E-isomer was obtained based on 19 F NMR. Benzyl
halides with both electron donating and electron withdrawing groups on the phenyl
ring were tolerated. With electron withdrawing groups, the yields of the
corresponding fluorovinyl sulfones were considerably higher in most cases
compared to those with electron donating groups (Table 4.1, entry 7). Also the
reaction proceeded at room temperature in the case of benzyl halides containing
electron withdrawing groups, while the reaction with benzyl bromide and electron
rich benzyl systems required heating (120 ºC). Both substituted benzyl bromides
and chlorides work well in this reaction. However, in the case of benzyl chlorides, a
small amount of NaI is needed to make the reaction more facile. When we
compared the reactivity of ortho, meta, and para nitrobenyl bromides, we found
that ortho and para substituted nitrobenzyl bromides react immediately to give the
corresponding fluorovinyl sulfones in excellent yield. However, the meta
substituted nitrobenzyl bromide reacts sluggishly even when heated to 70 ºC to give
comparably lower yield than the ortho and para substituted derivatives.
The fluorovinyl sulfones act as versatile intermediates that can be
transformed to a variety of synthetically important compounds. To illustrate this,
we converted the fluorovinyl sulfone 1 to the corresponding tin compound 2
(Scheme 4.2). Compound 2 easily undergoes Stille coupling with an aryl halide
using a Pd(0) catalyst and CuI to afford the coupling product 3. Alternatively, the
tributyltin group can be replaced by an Iodo (or bromo) group using N-Iodosuccinimide
(or N-Bromosuccinimide) in dichloromethane. 30
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 126 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 112 In all cases, only the E-isomer was obtained based on 19 F NMR. Benzyl halides with both electron donating and electron withdrawing groups on the phenyl ring were tolerated. With electron withdrawing groups, the yields of the corresponding fluorovinyl sulfones were considerably higher in most cases compared to those with electron donating groups (Table 4.1, entry 7). Also the reaction proceeded at room temperature in the case of benzyl halides containing electron withdrawing groups, while the reaction with benzyl bromide and electron rich benzyl systems required heating (120 ºC). Both substituted benzyl bromides and chlorides work well in this reaction. However, in the case of benzyl chlorides, a small amount of NaI is needed to make the reaction more facile. When we compared the reactivity of ortho, meta, and para nitrobenyl bromides, we found that ortho and para substituted nitrobenzyl bromides react immediately to give the corresponding fluorovinyl sulfones in excellent yield. However, the meta substituted nitrobenzyl bromide reacts sluggishly even when heated to 70 ºC to give comparably lower yield than the ortho and para substituted derivatives. The fluorovinyl sulfones act as versatile intermediates that can be transformed to a variety of synthetically important compounds. To illustrate this, we converted the fluorovinyl sulfone 1 to the corresponding tin compound 2 (Scheme 4.2). Compound 2 easily undergoes Stille coupling with an aryl halide using a Pd(0) catalyst and CuI to afford the coupling product 3. Alternatively, the tributyltin group can be replaced by an Iodo (or bromo) group using N-Iodosuccinimide (or N-Bromosuccinimide) in dichloromethane. 30 |
