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Diastereo- and Enantioselective Reductive Mannich-type Reaction of α,β-Unsaturated Carboxylic Acids to Ketimines: A Direct Entry to Unprotected β^2,3,3 -Amino Acids.

ABSTRACT: Stereoselective construction of unprotected β-amino acids is a significant challenge owing to the lack of methods for the catalytic generation of highly enantioenriched carboxylic acid enolates. In this study, a novel copper-catalyzed diastereo- and enantioselective reductive Mannich-type reaction of α,β-unsaturated carboxylic acids was developed, which provides a direct and scalable synthetic method for enantioenriched β^2,3,3 -amino acids with vicinal stereogenic centers. The protocol features in situ generation of transiently protected carboxylic acids by a hydrosilane and their diastereo- and enantioselective reductive coupling with ketimines. The synthetic utility of this process was demonstrated by a gram-scale reaction and the transformation of β-amino acids.

SUBMITTER: Suzuki H

PROVIDER: S-EPMC10107894 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Diastereo- and Enantioselective Reductive Mannich-type Reaction of α,β-Unsaturated Carboxylic Acids to Ketimines: A Direct Entry to Unprotected β2,3,3 -Amino Acids.

Suzuki Hirotsugu H Kondo Sora S Yamada Koichiro K Matsuda Takanori T

Chemistry (Weinheim an der Bergstrasse, Germany) 20221208 4

Stereoselective construction of unprotected β-amino acids is a significant challenge owing to the lack of methods for the catalytic generation of highly enantioenriched carboxylic acid enolates. In this study, a novel copper-catalyzed diastereo- and enantioselective reductive Mannich-type reaction of α,β-unsaturated carboxylic acids was developed, which provides a direct and scalable synthetic method for enantioenriched β2,3,3 -amino acids with vicinal stereogenic centers. The protoco ...[more]

PMID: 36341524

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