Nucleophile Generation via Decarboxylation: Asymmetric Construction of Contiguous Trisubstituted and Quaternary Stereocenters through a Cu(I)-Catalyzed Decarboxylative Mannich-Type Reaction
- 25 June 2009
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 131 (28) , 9610-9611
Abstract
The first catalytic asymmetric decarboxylative Mannich-type reaction between aldimines and cyanocarboxylic acids was developed. α,α,β-Trisubstituted β-amino nitriles containing contiguous trisubstituted and all-carbon quaternary stereocenters were produced with moderate to high enantio- and diastereoselectivity using 5 mol % CuOAc−(R)-DTBM-SEGPHOS complex as an asymmetric catalyst. This reaction proceeds through Cu(I)-catalyzed decarboxylative nucleophile generation followed by the addition of the resulting chiral Cu ketenimide to imines. Because the reaction proceeds under very mild conditions at nearly neutral pH, the reaction is applicable to a wide range of substrate combinations, including both aromatic and aliphatic imines. The products were converted to β2,2,3-amino acid derivatives through simple acidic hydrolysis without any racemization or epimerization. Therefore, this is a general catalytic asymmetric method for the synthesis of β2,2,3-amino acid derivatives, a group of important chiral building blocks for pharmaceutical lead compounds.Keywords
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