Enantioselective Construction of 1,3-Nonadjacent Stereocenters via 1,2-Difunctionalization of Alkenes Under Visible Light

IF 9.2 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

CCS Chemistry Pub Date : 2026-07-03 DOI:10.31635/ccschem.026.202607790

Xue-Song Zhou, Wen-Yuan Qu, Wen-Jing Xiao, Ying Cheng & Jia-Rong Chen1Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, College of Chemistry, Central China Normal University, Wuhan, Hubei 4300792Wuhan Institute of Photochemistry and Technology, Wuhan, Hubei 430083

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Abstract

CCS Chemistry, Ahead of Print.
Achieving simultaneous chemo-, regio-, and stereocontrol in the 1,2-difunctionalization of alkenes represents a formidable challenge in organic synthesis. While significant advances have enabled access to products bearing a single stereocenter, catalytic enantioselective methods that forge nonadjacent stereocenters through this transformation remain largely unexplored. Here, we report a synergistic photoredox-nickel-copper triple catalytic platform that enabled the enantioselective 1,2-difunctionalization of alkenes to construct 1,3-nonadjacent stereocenters. This protocol operated through a sequential radical process: photoredox-generated β-ketocarbonyl radicals add to alkenes to generate a benzylic radical and establish the first quaternary stereocenter, which subsequently underwent copper-catalyzed enantioselective cyanation to install the second stereocenter with high fidelity. This modular approach provided direct access to valuable chiral architectures featuring 1,3-nonadjacent stereocenters from readily available starting materials. Mechanistic investigations revealed that the differential oxidation potentials of nickel- and copper-enolate complexes played a decisive role in orchestrating this triple catalytic cascade.

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可见光下1,2-二官能化烯烃对映选择性构建1,3-非相邻立体中心

CCS化学，领先于印刷。在烯烃的1,2-二官能化中实现同时的化学、区域和立体控制是有机合成中一个艰巨的挑战。虽然取得了重大进展，可以获得具有单一立体中心的产物，但通过这种转化形成非相邻立体中心的催化对映选择方法在很大程度上仍未被探索。在这里，我们报道了一个协同光氧化还原-镍-铜三重催化平台，使烯烃的1,2-对映选择性双官能化能够构建1,3-非相邻的立体中心。该方案通过一个连续的自由基过程进行操作：光氧化还原生成的β-酮羰基自由基加入到烯烃中生成苯基自由基并建立第一个季立体中心，随后进行铜催化的对映选择性氰化以高保真度安装第二个立体中心。这种模块化方法提供了从现成的起始材料直接获得具有1,3-非相邻立体中心的有价值的手性结构的途径。机理研究表明，镍和铜烯酸酯配合物的不同氧化电位在协调这种三重催化级联反应中起决定性作用。

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来源期刊

CCS Chemistry Chemistry-General Chemistry

CiteScore

13.60

自引率

13.40%

发文量

475

审稿时长

10 weeks

期刊介绍： CCS Chemistry, the flagship publication of the Chinese Chemical Society, stands as a leading international chemistry journal based in China. With a commitment to global outreach in both contributions and readership, the journal operates on a fully Open Access model, eliminating subscription fees for contributing authors. Issued monthly, all articles are published online promptly upon reaching final publishable form. Additionally, authors have the option to expedite the posting process through Immediate Online Accepted Article posting, making a PDF of their accepted article available online upon journal acceptance.