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

• Published in: Nature communications Vol. 11; no. 1; pp. 5372 - 11
• Main Authors: Wen, Wei, Luo, Ming-Jing, Yuan, Yi, Liu, Jian-Hua, Wu, Zhu-Lian, Cai, Tian, Wu, Zhao-Wei, Ouyang, Qin, Guo, Qi-Xiang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.10.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/935; 639/638/549/933; 639/638/77/883; 639/638/77/888; Aldehydes; Amino acids; Aromatic compounds; Asymmetry; Catalysis; Conjugates; Humanities and Social Sciences; Imines; Methyl compounds; multidisciplinary; Quinones; Science; Science (multidisciplinary); Stereoselectivity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-19245-3

Chiral aldehyde catalysis is a burgeoning strategy for the catalytic asymmetric α-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 α-functionalization of both amino acids and aryl methylamines, and holds potential to promote a range of asymmetric transformations diastereoselectively. Chiral aldehyde catalysis is a useful strategy in the catalytic asymmetric α-functionalization of amino methyl compounds but these reaction types are limited. Here, the authors report two chiral aldehyde-catalysed diastereodivergent reactions, namely, a 1,6-conjugate addition and a bio-inspired Mannich reaction.