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

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 o...

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Bibliographic Details
Published in:Chemistry : a European journal 2023-01, Vol.29 (4), p.e202202575
Main Authors: Suzuki, Hirotsugu, Kondo, Sora, Yamada, Koichiro, Matsuda, Takanori
Format: Article
Language:English
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Summary: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 -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.
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.202202575