Dissertation/Thesis Abstract

Development of Palladium-Catalyzed Allylation Reactions of Alkylidene Malononitriles and Stereospecific Nickel-Catalyzed Cross-Coupling Reactions of Alkyl Electrophiles
by Swift, Elizabeth Claire, Ph.D., University of California, Irvine, 2013, 337; 3592019
Abstract (Summary)

Transition-metal catalysis has enabled the development of an unprecedented number of mild and selective C-C bond-forming reactions. We sought to access the reactivity of palladium and nickel catalysts for two types of transformations: conjugate allylations and sp3-sp 3 cross-coupling reactions.

Conjugate allylation of malononitriles was evaluated with N-heterocyclic carbene-ligated palladium complexes. The allylation was found to yield a variety of mono-allylated products. These results are in contrast to the bis-allylation of malononitriles using other palladium-based catalysts. Additionally, conjugate addition of α,β-unsaturated N-acylpyrroles was found to be accelerated in the presence of sulfoxide substitution on the pyrrole ring. These substrates are lead compounds for the development of an enantioselective allylation reaction.

Transition metal-catalyzed cross-coupling reactions have become standard practice in organic synthesis. Recent advances in alkyl-alkyl couplings have been transformative in the way organic chemists approach the construction of target molecules. This dissertation focuses on the development of stereospecific sp3-sp3 cross-coupling reactions. We discovered that in the presence of nickel catalysts, secondary benzylic ethers were found to undergo stereospecific substitution reactions with Grignard reagents. Reactions proceeded with inversion of configuration and high stereochemical fidelity. This reaction allows for facile enantioselective synthesis of biologically active diarylethanes from readily available optically enriched carbinols.

Subsequently, this reaction was expanded to dialkylzinc reagents and the first stereospecific Negishi cross-coupling reaction of secondary benzylic esters was developed. A series of traceless directing groups were evaluated for their ability to promote cross-coupling with dimethylzinc. Esters with a chelating thioether derived from commercially-available 2-(methylthio)acetic acid were found to be the most effective. The products were formed in high yield and with excellent stereospecificity. A variety of functional groups were tolerated in the reaction including alkenes, alkynes, esters, amines, imides, and O-, S-, and N-heterocycles. The utility of this transformation was highlighted in the enantioselective synthesis of a retinoic acid receptor (RAR) agonist.

Indexing (document details)
Advisor: Jarvo, Elizabeth R.
Commitee: Rychnovsky, Scott D., Van Vranken, David L.
School: University of California, Irvine
Department: Chemistry
School Location: United States -- California
Source: DAI-B 74/12(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Chemistry, Inorganic chemistry, Organic chemistry
Keywords: Alkyl electrophiles, Alkylidene malononitriles, Cross-coupling reactions, Nickel catalysis, Palladium catalysis
Publication Number: 3592019
ISBN: 9781303328121
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