美国波士顿大学Zhang, X. Peter团队报道了同时控制分子间自由基烯丙基C−H胺化的金属自由基方法。相关研究成果发表在2023年1月12日出版的国际知名学术期刊《自然—化学》。

尽管自由基化学具有巨大的潜力，但其高反应性和多种途径给有机合成中的应用带来了难题。除了多种竞争途径的分化之外，控制自由基反应中的各种选择性也带来了巨大的挑战和机遇。为了调节化学选择性和区域选择性，以及非对映选择性和对映选择性，需要制定概念上的新方法和根本不同的控制原则。

该文中，研究表明，基于Co（II）的金属自由基催化能够通过使用模块化设计的D2对称手性酰胺基卟啉，以可调口袋状环境作为支持配体，实现烯丙基CH键的自由基化学选择性分子间胺化。该反应在单一催化操作中表现出区域选择性、非对映选择性和对映选择性的显著收敛。除了证明了金属自由基催化在控制均裂自由基反应中的独特机会外，Co（II）催化的聚合C–H胺化提供了直接从烯烃异构体混合物合成有价值的手性α-叔胺的途径。

附：英文原文

Title: Metalloradical approach for concurrent control in intermolecular radical allylic C−H amination

Author: Xu, Pan, Xie, Jingjing, Wang, Duo-Sheng, Zhang, X. Peter

Issue&Volume: 2023-01-12

Abstract: Although they offer great potentials, the high reactivity and diverse pathways of radical chemistry pose difficult problems for applications in organic synthesis. In addition to the differentiation of multiple competing pathways, the control of various selectivities in radical reactions presents both formidable challenges and great opportunities. To regulate chemoselectivity and regioselectivity, as well as diastereoselectivity and enantioselectivity, calls for the formulation of conceptually new approaches and fundamentally different governing principles. Here we show that Co(II)-based metalloradical catalysis enables the radical chemoselective intermolecular amination of allylic CH bonds through the employment of modularly designed D2-symmetric chiral amidoporphyrins with a tunable pocket-like environment as the supporting ligand. The reaction exhibits a remarkable convergence of regioselectivity, diastereoselectivity and enantioselectivity in a single catalytic operation. In addition to demonstrating the unique opportunities of metalloradical catalysis in controlling homolytic radical reactions, the Co(II)-catalysed convergent C–H amination offers a route to synthesize valuable chiral α-tertiary amines directly from an isomeric mixture of alkenes.

DOI: 10.1038/s41557-022-01119-4

Source: https://www.nature.com/articles/s41557-022-01119-4