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Title: Asymmetric Alkylation of Aldehydes via New Strategies in Organic Catalysis
Authors: Shih, Hui-Wen
Advisors: MacMillan, David W
Contributors: Chemistry Department
Keywords: aldehyde alkylation
enamine catalysis
photoredox catalysis
synergistic catalysis
Subjects: Chemistry
Organic chemistry
Issue Date: 2012
Publisher: Princeton, NJ : Princeton University
Abstract: The construction of carbonyl α-alkyl stereocenters is an important and long- standing challenge in organic synthesis. The chiral α-alkyl carbonyl is a common motif found in natural products and medicinal targets. However, general technologies do not exist for a direct asymmetric carbonyl α-alkylation protocol. The synergistic catalysis strategy, wherein the nucleophile and electrophile are simultaneously activated by separate catalysts, allows access to difficult transformations that are impossible to access via mono-catalysis strategies. The intersection of a chiral amine catalyzed nucleophile activation (enamine catalysis) and a metal-catalyzed electrophile activation has been applied to the development of direct methods for carbonyl α-(sp3)-carbon functionalization. This thesis describes our efforts to develop novel asymmetric aldehyde α-alkylation technologies via the merger of enamine and metal catalysis. Electron-deficient arenes and heteroarenes are incorporated in pharmaceutical compounds, yet a direct carbonyl α-benzylation employing electron-deficient benzyl electrophiles has not been achieved. The enantioselective α-benzylation of aldehydes employing electron-poor arenes and heteroarenes has been achieved via a synergistic enamine/photoredox catalysis strategy (chapter 2). Methyl stereogenicity is the most common chiral alkyl motif, yet no direct methods exist for asymmetric electrophilic methylation. A synergistic enamine/copper catalysis strategy has been applied towards the development of an asymmetric aldehyde α-methylation via the coupling of a chiral enamine with an electrophilic alkylcopper(III). Progress regarding the development of this novel transformation is detailed in chapter 3.
Alternate format: The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Chemistry

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