Copper-Catalyzed Remote C–H Functionalizations of Naphthylamides through a Coordinating Activation Strategy and Single-Electron-Transfer (SET) Mechanism

Achieving p-CAr–H site selectivity is one of the major challenges in direct carbon–hydrogen (C–H) functionalization reactions. Herein, the copper-catalyzed and picolinamide-assisted remote p-C–H sulfonylation of 1-naphthylamides was realized. The synthetic utility of this method was further examined by sequential functionalizations and the efficient synthesis of the pharmaceutically useful 5-HT6 serotonin receptor ligand. This approach also provided a general strategy for other p-C–H bond functionalization, such as highly selective constructions of C–O, C–Br, C–I, C–C, and C–N bonds. Control experiments and theoretical calculations suggested that this C–H sulfonylation reaction might proceed through a single-electron-transfer process.

实现芳环对位碳氢键（p-CAr–H）位点选择性，是直接碳氢键（C–H）官能化反应的主要挑战之一。本研究中，我们成功实现了铜催化、吡啶甲酰胺（picolinamide）辅助的1-萘甲酰胺类化合物的远程对位C–H磺酰化反应。通过连续官能化反应以及高效合成具有药用价值的5-HT6血清素受体配体，进一步考察了该方法的合成应用价值。该策略同时为其他对位C–H键官能化反应提供了通用方案，例如高选择性构建C–O、C–Br、C–I、C–C及C–N化学键。对照实验与理论计算结果表明，该C–H磺酰化反应可能通过单电子转移过程进行。