南开大学叶萌春团队报道了带C-H键烯烃的对映选择性羰基环化合成含α-季碳的γ-内酰胺。相关研究成果于2024年12月19日发表在国际顶尖学术期刊《美国化学会杂志》。

开发有效的从相对惰性的C（O）-H键与烯烃构建带有手性α-季碳的γ-内酰胺的合成方法，一直是一个难以捉摸的挑战。

该文中，研究人员使用萘胺衍生的氧化膦连接镍和铝双金属催化剂，实现了甲酰基C-H键与烯烃的羰基化环化，高度区域和对映选择性地构建了带有手性α-季碳的γ-内酰胺，产率高达99%，ee高达98%。这些γ-内胺被证明是许多生物活性分子的通用合成前体。

附：英文原文

Title: Enantioselective Carbonylative Cyclization of Alkenes with C–H Bonds for Synthesis of γ-Lactams Bearing an α-Quaternary Carbon

Author: Weiwei Xu, Yanan Sun, Yuqing Jiang, Xueyuan Yan, Zhixuan Gao, Haorui Wang, Genping Huang, Qi-Lin Zhou, Mengchun Ye

Issue&Volume: December 19, 2024

Abstract: The development of effective synthetic methods to construct γ-lactams bearing a chiral α-quaternary carbon from relatively inert C(O)–H bonds with alkenes has been an elusive challenge. Herein, we used a naphthylamine-derived phosphine oxide ligating Ni and Al bimetallic catalyst to realize a carbonylative cyclization of formyl C–H bonds with alkenes, highly regio- and enantioselectively constructing γ-lactams bearing a chiral α-quaternary carbon in up to 99% yield and 98% ee. These γ-lactams proved to be versatile synthetic precursors for many biologically active molecules.

DOI: 10.1021/jacs.4c15875

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c15875