Department of Chemistry and Institute of Chemical Biology and Drug Discovery, The State University of New York at Stony Brook, Stony Brook, NY, 11794, USA.
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
Angew Chem Int Ed Engl. 2019 May 27;58(22):7318-7323. doi: 10.1002/anie.201901874. Epub 2019 Apr 17.
Late-stage synthesis of α,β-unsaturated aryl ketones remains an unmet challenge in organic synthesis. Reported herein is a photocatalytic non-chain-radical aroyl chlorination of alkenes by a 1,3-chlorine atom shift to form β-chloroketones as masked enones that liberate the desired enones upon workup. This strategy suppresses side reactions of the enone products. The reaction tolerates a wide array of functional groups and complex molecules including derivatives of peptides, sugars, natural products, nucleosides, and marketed drugs. Notably, addition of 2,6-di-tert-butyl-4-methyl-pyridine enhances the quantum yield and efficiency of the cross-coupling reaction. Experimental and computational studies suggest a mechanism involving PCET, formation and reaction of an α-chloro-α-hydroxy benzyl radical, and 1,3-chlorine atom shift.
α,β-不饱和芳基酮的晚期合成仍然是有机合成中的一个未满足的挑战。本文报道了一种通过 1,3-氯原子迁移的光催化非链自由基芳基氯代反应，将烯烃转化为β-氯代酮作为掩蔽的烯酮，在后处理时释放出所需的烯酮。该策略抑制了烯酮产物的副反应。该反应可以容忍广泛的官能团和复杂分子，包括肽、糖、天然产物、核苷和市售药物的衍生物。值得注意的是，添加 2,6-二叔丁基-4-甲基吡啶可以提高交叉偶联反应的量子产率和效率。实验和计算研究表明，该反应涉及质子-电子转移（PCET）、α-氯-α-羟基苄基自由基的形成和反应以及 1,3-氯原子迁移。
