Carbene-Catalyzed Esterification for the Synthesis of Inherently Chiral Saddle-Shaped Eight-Membered Lactones
Yao Chen, Xiaoqing Lai, Huan Gong, Han Zhuang, Yong Hu, Yang Xiao, Jianing An, Jianfeng Xu, Xingkuan Chen
Abstract
Inherently chiral molecules have found significant applications in various research fields, including asymmetric catalysis, host-guest chemistry, materials science, and molecular recognition. However, the enantioselective construction of these molecules, particularly through organic catalysis, remains a considerable challenge. Herein, we report a strategy for concise access to saddle-shaped eight-membered inherently chiral molecules via NHC-catalyzed esterification. In the presence of an NHC precatalyst, a base, and an oxidant, this protocol enables the facile synthesis of a series of inherently chiral saddle-shaped eight-membered lactones in high yields with excellent enantiocontrol. Compared with desymmetrization or resolution approaches, this direct construction strategy offers distinct advantages, including more straightforward substrate preparation and structurally simpler inherently chiral products.