Mukherjee Upasana, Shah Jagrut A, Musaev Djamaladdin G, Ngai Ming-Yu
Department of Chemistry, Purdue University, West Lafayette, Indiana 47906, United States.
Department of Chemistry, State University of New York, Stony Brook, New York 11794, United States.
J Am Chem Soc. 2024 Aug 7;146(31):21271-21279. doi: 10.1021/jacs.4c08984. Epub 2024 Jul 23.
1,2-Difunctionalization of styrenes, adding two distinct functional groups across the C═C double bond, has emerged as a powerful tool for enhancing molecular complexity. Herein, we report the development of a regioconvergent β-acyloxylation-α-ketonylation of styrenes through bromo/acyloxy transposition (BrAcT) and excited-state copper catalysis. This approach is amenable to gram-scale synthesis and tolerates a wide range of functional groups and complex molecular frameworks, including derivatives of natural products and marketed drugs. Our experimental and computational studies suggest a unique mechanism featuring a dynamic, ionic BrAcT process and excited-state copper-catalyzed redox reactions. We anticipate that this BrAcT process could serve as a broadly applicable and versatile strategy for β-acyloxylation-α-functionalization of styrenes, creating valuable intermediates for preparing new pharmaceuticals, agrochemicals, and functional materials.
苯乙烯的1,2-双官能团化，即在碳碳双键上引入两个不同的官能团，已成为提高分子复杂性的有力工具。在此，我们报道了一种通过溴/酰氧基转位（BrAcT）和激发态铜催化实现苯乙烯区域收敛性β-酰氧基化-α-酮基化的方法。该方法适用于克级规模的合成，并且能够耐受多种官能团和复杂的分子骨架，包括天然产物和市售药物的衍生物。我们的实验和计算研究表明，该反应具有独特的机理，其特征在于动态的离子型BrAcT过程和激发态铜催化的氧化还原反应。我们预计，这种BrAcT过程可作为一种广泛适用且通用的策略，用于苯乙烯的β-酰氧基化-α-官能团化，为制备新的药物、农用化学品和功能材料创造有价值的中间体。
