Zhang Boyi, Bai Hui, Zhan Beibei, Wei Kaihang, Nie Shenyou, Zhang Xiaheng
School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.
Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention (Ministry of Education), Institute of Life Sciences and Department of Urology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China.
Sci Adv. 2024 Apr 26;10(17):eado0225. doi: 10.1126/sciadv.ado0225.
Ketones are ubiquitous in bioactive natural products, pharmaceuticals, chemical feedstocks, and synthetic intermediates. Hence, deacylative coupling reactions enable the versatile elaboration of a plethora of chemicals to access complex drug candidates and natural products. Here, we present deacylative arylation and alkynylation strategies for the synthesis of a wide range of alkyl-tethered arenes and alkynes from cyclic ketones and methyl ketones under dual nickel/photoredox catalysis. This reaction begins by generating a pre-aromatic intermediate (PAI) through the condensation of the ketone and '-methylpicolino-hydrazonamide (MPHA), followed by the oxidative cleavage of the PAI α-C─C bond to form an alkyl radical, which is subsequently intercepted by a Ni complex, facilitating the formation of diverse C()-C()/C() bonds with remarkable generality. This protocol features a one-pot reaction capability, high regioselectivity and ring-opening efficiency, mild reaction conditions, and a broad substrate scope with excellent functional group compatibility.
酮类化合物广泛存在于生物活性天然产物、药物、化学原料和合成中间体中。因此，脱酰基偶联反应能够对大量化学品进行多功能修饰，以获得复杂的候选药物和天然产物。在此，我们展示了在双镍/光氧化还原催化下，从环酮和甲基酮合成多种烷基连接的芳烃和炔烃的脱酰基芳基化和炔基化策略。该反应首先通过酮与α-甲基吡啶甲酰肼（MPHA）缩合生成预芳香中间体（PAI），然后PAI的α-C─C键发生氧化裂解形成烷基自由基，随后该自由基被镍配合物捕获，促进形成具有显著通用性的各种C（芳基）-C（烷基）/C（炔基）键。该方法具有一锅反应能力、高区域选择性和开环效率、温和的反应条件以及广泛的底物范围和优异的官能团兼容性。
