Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling.
Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling.
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光驱动的对映选择性卡宾催化的自由基-自由基偶联。
DOI：
10.1002/anie.202312829
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Scheidt,KarlA
中科院分区：
文献类型：
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作者：
Byun,Seunghwan;Hwang,MeemieU;Wise,HenryR;Bay,AnnaV;Cheong,PaulH-Y;Scheidt,KarlA
公开了酰基咪唑和外消旋Hantzsch酯的对映选择性卡宾催化的自由基-自由基偶联。该方法涉及N-杂环卡宾衍生的酮基自由基和仲sp3-碳自由基的偶联，并且允许以中等至良好的产率和对映选择性获得手性α-芳基脂肪族酮，而没有任何竞争性差向异构化。该方案的实用性通过各种药物化合物的后期官能化而突出，并通过将对映体富集的产物转化为生物相关分子而进一步证明。计算研究表明，N-杂环卡宾分别控制了酮基自由基和烷基自由基的双面选择性。
An enantioselective carbene‐catalyzed radical‐radical coupling of acyl imidazoles and racemicHantzsch esters is disclosed. This method involves the coupling of an N‐heterocyclic carbene‐derived ketyl radical and a secondarysp3‐carbon radical and allows access to chiral α‐aryl aliphatic ketones in moderate‐to‐good yields and enantioselectivities without any competitive epimerization. The utility of this protocol is highlighted by the late‐stage functionalization of various pharmaceutical compounds and is further demonstrated by the transformation of the enantioenriched products to biologically relevant molecules. Computational investigations reveal the N‐heterocyclic carbene controls the double‐facial selectivity of the ketyl radical and the alkyl radicals, respectively.