Li Lian-Jie, Zhang Jun-Chun, Tang Jia-Yu, Yu Hui, Yang Ze-Peng
Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200092, P.R China.
Angew Chem Int Ed Engl. 2025 Jun 10;64(24):e202506883. doi: 10.1002/anie.202506883. Epub 2025 Apr 17.
While significant advancements have been made in creating quaternary stereocenters (all-carbon substituents) within cyclic frameworks, generating acyclic quaternary stereocenters poses a more formidable task due to increased conformational flexibility. Herein, we report an enantioselective synthesis of compounds containing acyclic quaternary stereocenters through an iron-catalyzed alkylation reaction between an acyclic tertiary alkyl source and an unactivated primary alkyl source. This method not only facilitates the rapid construction of sterically hindered motifs but also effectively enhances the saturation level of the molecule. Key to this method is an outer-sphere C─C bond formation mechanism, where enantioselectivity is governed by a cooperative triple catalysis system that combines photoredox, chiral Lewis acid, and iron catalysis. A series of compounds featuring acyclic quaternary stereocenters is produced under mild reaction conditions, and various transformations are presented to illustrate the potential applications of this approach. A comprehensive mechanistic study supports the crucial S2 (bimolecular homolytic substitution) mechanism.
虽然在环状骨架内创建季碳立体中心（全碳取代基）方面已取得重大进展，但由于构象灵活性增加，生成非环状季碳立体中心是一项更艰巨的任务。在此，我们报告了通过铁催化的非环状叔烷基源与未活化的伯烷基源之间的烷基化反应，对含有非环状季碳立体中心的化合物进行对映选择性合成。该方法不仅有助于快速构建空间位阻基团，还能有效提高分子的饱和度。该方法的关键是外层球C─C键形成机制，其中对映选择性由光氧化还原、手性路易斯酸和铁催化相结合的协同三催化体系控制。在温和的反应条件下制备了一系列具有非环状季碳立体中心的化合物，并展示了各种转化反应以说明该方法的潜在应用。全面的机理研究支持关键的S2（双分子均裂取代）机制。
