美国罗格斯大学Michal Szostak团队基于C-O/C-H偶联实现双金属协同催化羧酸脱羰基杂芳基化反应。 相关研究成果于2021年2月17日发表于国际顶尖学术期刊《德国应用化学》。

协同双金属催化是现代合成化学的一种基本方法，它解决了许多与该领域发展相关的挑战。

该文中，研究人员报道了双金属协同催化通过酰基C–O/C–H偶联实现普遍存在的羧酸的直接脱羰基杂芳基化反应。该新的催化体系利用了铜催化剂和钯催化剂在脱羰基体系下的协同作用，在无序预先活化、导向官能团条件下，使得在有机合成领域中通过羧酸与杂芳烃的偶合而高度化学选择性地合成重要的杂二芳基基序成为可能。该协同脱羰基平台得益于普通羧酸的直接使用，并且显示出非常广泛的支持底物范围（>70例），包括药物的后期修饰和生物活性剂的合成。

为了深入了解双金属脱羰平台的机理，研究人员进行了大量的机理和计算研究。关键步骤是通过氧化加成/脱羰生成的钯（II）中间物与铜芳基物种的转移，将两个催化循环交叉。

研究人员希望多功能的双金属协同脱羰基框架将对规划协同催化、脱羰基偶联和合成双芳基物种的合成方法产生影响。

附：英文原文

Title: Bimetallic Cooperative Catalysis for Decarbonylative Heteroarylation of Carboxylic Acids via C–O/C–H Coupling

Author: Chengwei Liu, Chong-Lei Ji, Tongliang Zhou, Xin Hong, Michal Szostak

Issue&Volume: 2021-02-17

Abstract: Cooperative bimetallic catalysis represents a fundamental approach in modern synthetic chemistry that addresses many challenges associated with the evolution of the field. Herein, we report bimetallic cooperative catalysis for the direct decarbonylative heteroarylation of ubiquitous carboxylic acids via acyl C–O/C–H coupling. This novel catalytic system exploits the cooperative action of a copper catalyst and a palladium catalyst under decarbonylative regimen, which enables for the highly chemoselective synthesis of important heterobiaryl motifs that enjoy a privileged role in the realm of organic synthesis through the coupling of carboxylic acids with heteroarenes in the absence of prefunctionalization or directing groups. This cooperative decarbonylative platform benefits from the direct use of common carboxylic acids and shows a remarkably broad substrate scope (>70 examples), including late‐stage modification of pharmaceuticals and streamlined synthesis of bioactive agents. Extensive mechanistic and computational studies were conducted to gain insight into the mechanism of the bimetallic decarbonylative platform. The key step involves intersection of the two catalytic cycles via transmetallation of the copper‐aryl species with the palladium(II) intermediate generated by oxidative addition/decarbonylation. We envision the versatile bimetallic cooperative decarbonylative framework will have an impact on planning synthetic approaches in cooperative catalysis, decarbonylative coupling and synthesis of biaryl motifs .

DOI: 10.1002/anie.202100949

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202100949