Ling Bo, Yao Shunruo, Ouyang Shengmao, Bai Haonan, Zhai Xinyi, Zhu Chengjian, Li Weipeng, Xie Jin
State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Shanghai, 200032, China.
Angew Chem Int Ed Engl. 2024 Aug 5;63(32):e202405866. doi: 10.1002/anie.202405866. Epub 2024 Jul 9.
Controlling the cross-coupling reaction between two different radicals is a long-standing challenge due to the process occurring statistically, which would lead to three products, including two homocoupling products and one cross-coupling product. Generally, the cross-coupling selectivity is achieved by the persistent radical effect (PRE) that requires the presence of a persistent radical and a transient radical, thus resulting in limited radical precursors. In this paper, a highly selective cross-coupling of alkyl radicals with acyl radicals to construct C(sp)-C(sp) bonds, or with alkyl radicals to construct C(sp)-C(sp) bonds have been achieved with the readily available carboxylic acids and their derivatives (NHPI ester) as coupling partners. The success originates from the use of tridentate ligand (2,2' : 6',2''-terpyridine) to enable radical cross-coupling process to Ni-mediated organometallic mechanism. This protocol offers a facile and flexible access to structurally diverse ketones (up to 90 % yield), and also a new solution for the challenging double decarboxylative C(sp)-C(sp) coupling. The broad utility and functional group tolerance are further illustrated by the late-stage functionalization of natural-occurring carboxylic acids and drugs.
由于该过程是按统计学方式发生的，会产生三种产物，包括两种自偶联产物和一种交叉偶联产物，因此控制两个不同自由基之间的交叉偶联反应一直是一项长期挑战。一般来说，交叉偶联选择性是通过持久自由基效应（PRE）实现的，这需要存在一个持久自由基和一个瞬态自由基，从而导致自由基前体有限。在本文中，已实现了烷基自由基与酰基自由基的高度选择性交叉偶联以构建C(sp)-C(sp)键，或者与烷基自由基交叉偶联以构建C(sp)-C(sp)键，使用易于获得的羧酸及其衍生物（NHPI酯）作为偶联伙伴。成功源于使用三齿配体（2,2':6',2''-三联吡啶）使自由基交叉偶联过程转变为镍介导的有机金属机理。该方法为结构多样的酮提供了一种简便灵活的合成途径（产率高达90%），也为具有挑战性的双脱羧C(sp)-C(sp)偶联提供了一种新的解决方案。天然存在的羧酸和药物的后期官能团化进一步说明了该方法的广泛实用性和官能团耐受性。
