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. 2009 Dec 23;131(50):18028-9.
doi: 10.1021/ja9094044.

N-heterocyclic carbene-catalyzed enantioselective Mannich reactions with alpha-aryloxyacetaldehydes

Yasufumi Kawanaka  1 , Eric M Phillips, Karl A Scheidt
Affiliations

N-heterocyclic carbene-catalyzed enantioselective Mannich reactions with alpha-aryloxyacetaldehydes

Yasufumi Kawanaka et al. J Am Chem Soc. .

Abstract

N-Heterocyclic carbenes (NHCs) catalyze a new Mannich-type reaction to form beta-amino acid derivatives in high yield and enantioselectivity. The reaction is initiated by the addition of an NHC to an alpha-aryloxyaldehyde followed by elimination of a phenoxide anion which generates an enol/enolate. A Mannich addition to a tosylimine proceeds with excellent control over enantioselectivity. In a new carbene catalysis concept, catalyst regeneration is promoted by return, or rebound, and acylation of the phenoxide group which served as the activating component in the first step of the catalytic cycle. The activated ester products formed in situ are manipulated to form a variety of useful compounds including beta-amino acids, beta-amino amides, and peptides.

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Figures

Scheme 1
Scheme 1
Proposed catalytic pathway
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