Lee Johnny W, Zheng Weijia, Morales-Rivera Cristian A, Liu Peng, Ngai Ming-Yu
Department of Chemistry , Institute of Chemical Biology and Drug Discovery , Stony Brook University , Stony Brook , NY 11794 , USA . Email:
Department of Chemistry , University of Pittsburgh , Pittsburgh , PA 15260 , USA . Email:
Chem Sci. 2019 Feb 11;10(11):3217-3222. doi: 10.1039/c8sc05390a. eCollection 2019 Mar 21.
Intermolecular C-H difluoromethoxylation of (hetero)arenes remains a long-standing and unsolved problem in organic synthesis. Herein, we report the first catalytic protocol employing a redox-active difluoromethoxylating reagent and photoredox catalysts for the direct C-H difluoromethoxylation of (hetero)arenes. Our approach is operationally simple, proceeds at room temperature, and uses bench-stable reagents. Its synthetic utility is highlighted by mild reaction conditions that tolerate a wide variety of functional groups and biorelevant molecules. Experimental and computational studies suggest single electron transfer (SET) from excited photoredox catalysts to forming a neutral radical intermediate that liberates the OCFH radical exclusively. Addition of this radical to (hetero)arenes gives difluoromethoxylated cyclohexadienyl radicals that are oxidized and deprotonated to afford the products of difluoromethoxylation.
（杂）芳烃的分子间C-H二氟甲氧基化在有机合成中仍然是一个长期未解决的问题。在此，我们报道了首个使用氧化还原活性二氟甲氧基化试剂和光氧化还原催化剂对（杂）芳烃进行直接C-H二氟甲氧基化的催化方法。我们的方法操作简单，在室温下进行，并且使用易于保存的试剂。其合成效用体现在温和的反应条件上，该条件能耐受多种官能团和与生物相关的分子。实验和计算研究表明，激发态的光氧化还原催化剂发生单电子转移（SET）生成 ，形成一个中性自由基中间体，该中间体仅释放出OCFH自由基。该自由基加成到（杂）芳烃上生成二氟甲氧基化的环己二烯基自由基，这些自由基被氧化并去质子化，从而得到二氟甲氧基化产物。
