Asymmetric N—H Insertion Reaction ofα-Diazoesters and Carbamates Co-catalyzed by Dirhodium Acetate, Sufonic Acid and Chiral Sulfonamide Urea

The enantioselective N-H insertion of α-diazoesters and carbamates provides a potentially attractive approach to α-amino acid derivatives.Herein, a novel cooperative catalytic system of achiral dirhodium(II) acetates, chiral sulfonamide urea and achiral sulfonic acid was developed for asymmetric N-H insertion reactions.Prochiral ammonium ylide intermediates, generated in situ from α-diazoesters and carbamates initiated by dirhodium(II) acetate, underwent asymmetric protonation with a considerable enantioselectivity in the presence of chiral sulfonamide urea and achiral sulfonic acid as co-catalysts.The co-catalysts of chiral sulfonamide urea and achiral sulfonic acid were considered as a chiral proton shuttle assisting the asymmetric proton transfer process to control the enantioselectivity.This methodology provides an efficient and mild approach to α-amino acid derivatives in high yields (up to 84% yield) with moderate enantioselectivity (up to 77% ee).Keywords N-H insertion; chiral sulfonamide urea; ammonium ylide; co-catalysts; α-amino acid derivatives α-氨基酸是构成天然蛋白质的基本物质, 也是生物 体中不可缺少的营养成分之一.现有的 α-氨基酸衍生物 合成方法大多通过发酵法 [1] 得到. 这种方法最大缺陷是 只能得到消旋体 α-氨基酸衍生物.因此发展高效不对称 方法合成光学纯 α-氨基酸衍生物在现代有机合成中具 有重要意义 [2] .现代有机合成中, 不对称 N-H 官能团 化反应是一类高效构建手性新化学物质的方法 [3] .其中, α-重氮酯和胺类化合物的不对称 N-H 键插入反应是一 类快速、高效构建 α-氨基酸衍生物的有效方法 [4] , 因此 如何发展 α-重氮酯参与的不对称 N-H 插入反应引起了 化学工作者的广泛兴趣 [5] .