Page 22 |
Save page Remove page | Previous | 22 of 181 | Next |
|
small (250x250 max)
medium (500x500 max)
Large (1000x1000 max)
Extra Large
large ( > 500x500)
Full Resolution
All (PDF)
|
This page
All
|
8
The building block method, on the other hand, involves use of already
fluorinated intermediates that are readily available and involves C-C bond
formation. For this approach there are four major types of reagents that can be used
to transform fluorine-containing building blocks, namely: fluorine-substituted
nucleophilic reagents, electrophilic reagents, radicals and carbenes.
Building blocks based on fluorine-substituted nucleophilic reagents include
fluoro-alkyl, alkneyl, alkynyl metals, and metal enolates. The former approach,
works well for introduction of perfluorinated moieties but is not effective for the
trifluoromethyl anion as the corresponding metal reagent is unstable.25 Kobayashi
and co-workers26,27 pioneered in preparing in-situ trifluoromethylcopper, which
they used to trifluoromethylated a variety of aromatic and alkenyl halides by
oxidative addition reductive elimination. Many ventured to improve this
methodology and consequently Burton and Wiemers28 reported the reaction of
difluorodihalomethanes with cadmium and zinc. These thermally stable
trifluoromethyl cadmium and zinc reagents transferred the trifluoromethyl group to
copper, generating the trifluoromethylcopper reagent in excellent yields. Prakash
and co-workers29,30 have developed methods to introduce the trifluoromethyl group
using Trifluoromethyl(trimethyl)silane as a versatile trifluoromethide equivalent.
The reagent is widely known as the “Ruppert-Prakash Reagent”. The metal enolates
prepared from the corresponding fluorinated carbonyls can also be used to
introduce monofluoro-, difluoro-, trifluoromethyl- and perfluoroalkyl groups.24
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 22 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 8 The building block method, on the other hand, involves use of already fluorinated intermediates that are readily available and involves C-C bond formation. For this approach there are four major types of reagents that can be used to transform fluorine-containing building blocks, namely: fluorine-substituted nucleophilic reagents, electrophilic reagents, radicals and carbenes. Building blocks based on fluorine-substituted nucleophilic reagents include fluoro-alkyl, alkneyl, alkynyl metals, and metal enolates. The former approach, works well for introduction of perfluorinated moieties but is not effective for the trifluoromethyl anion as the corresponding metal reagent is unstable.25 Kobayashi and co-workers26,27 pioneered in preparing in-situ trifluoromethylcopper, which they used to trifluoromethylated a variety of aromatic and alkenyl halides by oxidative addition reductive elimination. Many ventured to improve this methodology and consequently Burton and Wiemers28 reported the reaction of difluorodihalomethanes with cadmium and zinc. These thermally stable trifluoromethyl cadmium and zinc reagents transferred the trifluoromethyl group to copper, generating the trifluoromethylcopper reagent in excellent yields. Prakash and co-workers29,30 have developed methods to introduce the trifluoromethyl group using Trifluoromethyl(trimethyl)silane as a versatile trifluoromethide equivalent. The reagent is widely known as the “Ruppert-Prakash Reagent”. The metal enolates prepared from the corresponding fluorinated carbonyls can also be used to introduce monofluoro-, difluoro-, trifluoromethyl- and perfluoroalkyl groups.24 |
