近日，美国Scripps研究所余金权团队开发了催化剂控制的双羧酸位点选择性亚甲基C-H内酯化。这一研究成果发表在2022年5月26日出版的国际学术期刊《科学》上。

在这项研究中，团队通过把不同螯合环大小的喹啉-吡啶酮配体与一对钯催化剂组装在一起，可以催化许多双羧酸进行高度位点选择性的单内酯化反应，通过位点选择性β-或γ-亚甲基C-H活化，生成结构多样和有合成价值的γ-和δ-内酯。余下的未反应羧基则可作为后续合成应用的灵活出发点，团队通过从来源丰富的双羧酸实现了两种天然产物——myrociumone A和pedicellosine——的全合成验证了这一理念。

据了解，催化剂控制的自由羧基β-和γ-亚甲基C-H键的位点选择性活化是一个存在已久的挑战。

附：英文原文

Title: Catalyst-controlled site-selective methylene C–H lactonization of dicarboxylic acids

Author: Hau Sun Sam Chan, Ji-Min Yang, Jin-Quan Yu

Issue&Volume: 2022-05-26

Abstract: Catalyst-controlled site-selective activation of β- and γ-methylene C–H bonds of free carboxylic acids is a long-standing challenge. Here we show that with a pair of palladium catalysts assembled with quinoline-pyridone ligands of different chelate ring sizes, it is possible to perform highly site-selective monolactonization reactions with a wide range of dicarboxylic acids, generating structurally diverse and synthetically useful γ- and δ-lactones via site-selective β- or γ-methylene C–H activation. The remaining carboxyl group serves as a versatile linchpin for further synthetic applications as demonstrated by the total synthesis of two natural products, myrotheciumone A and pedicellosine, from abundant dicarboxylic acids.

DOI: abq3048

Source: https://www.science.org/doi/10.1126/science.abq3048