Matsumoto Akira, Maeda Natsumi, Maruoka Keiji
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo, Kyoto 606-8501, Japan.
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China.
J Am Chem Soc. 2023 Sep 20;145(37):20344-20354. doi: 10.1021/jacs.3c05337. Epub 2023 Jul 25.
Organic molecules that can be connected to multiple substrates by sequential C-C bond formations can be utilized as linchpins in multicomponent processes. While they are useful for rapidly increasing molecular complexity, most of the reported linchpin coupling methods rely on the use of organometallic species as strong carbon nucleophiles to form C-C bonds, which narrows the functional group compatibility. Here, we describe a metal-free, radical-mediated coupling approach using a formyl-stabilized phosphonium ylide as a multifunctional linchpin under visible-light photoredox conditions. The present method uses the ambiphilic character of the phosphonium ylide, which serves as both a nucleophilic and an electrophilic carbon-centered radical source. The stepwise and controllable generation of these radical intermediates allows sequential photocatalysis involving two mechanistically distinct radical additions, both of which are initiated by the same photocatalyst in one pot with high functional group tolerance. The methodology enables a bidirectional assembly of the linchpin with two electronically differentiated alkene fragments and thus offers rapid and modular access to 1,4-dicarbonyl compounds as versatile synthetic intermediates.
能够通过连续的C-C键形成连接到多个底物的有机分子可用作多组分过程中的关键组分。虽然它们有助于快速增加分子复杂性，但大多数已报道的关键组分偶联方法依赖于使用有机金属物种作为强碳亲核试剂来形成C-C键，这限制了官能团的兼容性。在此，我们描述了一种无金属、自由基介导的偶联方法，该方法在可见光光氧化还原条件下使用甲酰基稳定的鏻叶立德作为多功能关键组分。本方法利用了鏻叶立德的双亲性，它既是亲核的又是以碳为中心的亲电自由基源。这些自由基中间体的逐步可控生成允许进行涉及两种机制不同的自由基加成的连续光催化反应，这两种反应均由同一光催化剂在一个反应釜中引发，具有高官能团耐受性。该方法能够将关键组分与两个电子性质不同的烯烃片段进行双向组装，从而提供了快速且模块化地获得作为通用合成中间体的1,4-二羰基化合物的途径。
