Key Laboratory of Applied Chemistry of Chongqing Municipality, and Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, School of Chemistry and Chemical Engineering, Southwest University, 400715, Chongqing, China.
College of Pharmacy, Third Military Medical University, 400038, Chongqing, China.
Nat Commun. 2020 Oct 23;11(1):5372. 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.
手性醛催化是一种新兴的策略，可用于催化手性不对称的氨甲基化合物的α-功能化。然而，反应类型有限，迄今为止还没有立体发散催化的例子。在这项工作中，我们揭示了两种手性醛催化的非对映选择性发散反应：氨基酸对对醌甲醚的 1,6-共轭加成和吡啶基甲胺和亚胺的生物启发的曼尼希反应。这两个反应的顺式和反式产物都可以以中等至高产率、非对映选择性和对映选择性获得。通过 DFT 计算提出了四个潜在的反应模型来解释观察到的立体选择性控制。我们的工作表明，基于可逆亚胺形成原理的手性醛催化适用于氨基酸和芳基甲胺的α-功能化，并且有可能选择性地促进一系列不对称转化。
