Wagulde Sidhant, Rai Pramod, Gevorgyan Vladimir
Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080-3021, United States.
J Am Chem Soc. 2025 Sep 24;147(38):34211-34217. doi: 10.1021/jacs.5c10306. Epub 2025 Sep 9.
The direct transformation of C-H bonds into C-C bonds via cross-dehydrogenative coupling (CDC) represents a powerful strategy in synthetic chemistry, enabling streamlined bond construction without the need for prefunctionalized substrates. While traditional CDC approaches rely on polar mechanisms and preactivation of one of the C-H partners, recent advances have introduced radical-based strategies that employ a hydrogen atom transfer (HAT) approach to access carbon-centered radicals from unactivated substrates. Herein, we report a nickel-catalyzed CDC reaction between aldehydes and alkenes for the synthesis of skipped enones, leveraging aryl radicals as intermolecular HAT agents. The transformation proceeds via the generation of aryl radicals from aryl bromides, which mediates HAT from both the aldehydic and allylic C-H bonds to generate acyl and allylic radicals, respectively. These radicals are then engaged in a nickel-catalyzed radical-radical cross-coupling to deliver the skipped enone products. This method demonstrates a broad substrate scope, high chemoselectivity, and excellent tolerance to diverse functional groups, providing a versatile platform for late-stage functionalization and synthesis of valuable skipped enone scaffolds.
通过交叉脱氢偶联（CDC）将C-H键直接转化为C-C键是合成化学中的一种强大策略，能够在无需预官能化底物的情况下实现简化的键构建。虽然传统的CDC方法依赖于极性机制和其中一个C-H伙伴的预活化，但最近的进展引入了基于自由基的策略，该策略采用氢原子转移（HAT）方法从未活化的底物中获取碳中心自由基。在此，我们报道了一种镍催化的醛与烯烃之间的CDC反应，用于合成烯酮，利用芳基自由基作为分子间HAT试剂。该转化过程通过从芳基溴化物生成芳基自由基来进行，芳基自由基介导醛基和烯丙基C-H键的HAT，分别生成酰基和烯丙基自由基。然后这些自由基参与镍催化的自由基-自由基交叉偶联反应，生成烯酮产物。该方法展示了广泛的底物范围、高化学选择性以及对多种官能团的优异耐受性，为后期官能化和合成有价值的烯酮支架提供了一个通用平台。
