Graduation Semester and Year

2011

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry

Department

Chemistry and Biochemistry

First Advisor

Christopher O'Brien

Abstract

The formation of carbon-carbon double bonds with stereocontrol is of great importance to synthetic chemistry. The Wittig olefination involves the treatment of an aldehyde or ketone with a phosphonium ylide; yielding an alkene product with concomitant phosphine oxide byproduct. Mechanistic studies have shown that structural and electronic properties of the phosphine and halide reagent greatly influence the stereochemical outcome (E:Z) of the olefination. However, a significant limitation of the reaction is the difficulty of removing the phosphine oxide. A process catalytic in phosphine would alleviate the aforementioned concern and allow enhanced stereocontrol. Preliminary results led to the development of the first Wittig reaction catalytic in phosphine. Initial optimization studies include: phosphine catalyst screening, reducing agent efficiency, solvent effect, temperature variation, and base evaluation. After the efficiency of the catalytic Wittig cycle was improved, a substrate study was performed to examine the scope of the protocol, and reasonable substrate diversity was achieved. These include 4-10 mol% phosphine oxide precatalyst loading and formation of stabilized ylides from cyano, ketyl, and ester activated bromides and chlorides. In one-pot the ylides were coupled to various aldehydes including benzaldehyde, thiophencarbaldehyde, electron rich and deficient aromatic, and alkyl aldehydes. An E selective olefination process is found when using methylbromoacetate as the halide component. Upon further investigation it was found that semi-stabilized ylides could also be used with good to moderate yields. For example, stilbene was produced in 96% yield with 2:1 E:Z selectivity as well as pharmaceutical active stilbene derivatives in one pot. The reaction is made catalytic by the regeneration of phosphine from the chemoselective reduction of the phosphine oxide by-product using a silane reducing agent.

Disciplines

Chemistry | Physical Sciences and Mathematics

Comments

Degree granted by The University of Texas at Arlington

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