Diastereodivergent chiral aldehyde catalysis for asymmetric 1,6-conjugated addition and Mannich reactions.

ABSTRACT: Chiral aldehyde catalysis is a burgeoning strategy for the catalytic asymmetric ?-functionalization of aminomethyl compounds. However, the reaction types are limited and to date include no examples of stereodivergent catalysis. In this work, we disclose two chiral aldehyde-catalysed diastereodivergent reactions: a 1,6-conjugate addition of amino acids to para-quinone methides and a bio-inspired Mannich reaction of pyridinylmethanamines and imines. Both the syn- and anti-products of these two reactions can be obtained in moderate to high yields, diastereo- and enantioselectivities. Four potential reaction models produced by DFT calculations are proposed to explain the observed stereoselective control. Our work shows that chiral aldehyde catalysis based on a reversible imine formation principle is applicable for the ?-functionalization of both amino acids and aryl methylamines, and holds potential to promote a range of asymmetric transformations diastereoselectively.

SUBMITTER: Wen W 

PROVIDER: S-EPMC7584650 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature