Zhu Mengqi, Wang Qiao-Lin, Huang Huawen, Mao Guojiang, Deng Guo-Jun
Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China.
College of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China.
J Org Chem. 2024 Sep 6;89(17):12591-12609. doi: 10.1021/acs.joc.4c01531. Epub 2024 Aug 14.
The incorporation of gem-difluoromethylene units into organic molecules remains a formidable challenge. Conventional methodologies for constructing aryldifluoromethyl derivatives relied on the use of high-functional fluorinating regents under harsh conditions. Herein, we report general and efficient photoredox catalytic systems for defluoroalkylation of readily available trifluoromethylarenes through selective C-F cleavage to deliver gem-difluoromethyl radicals which proceed through reductive addition to both electron-donating and withdrawing alkenes under transition-metal free conditions. Mechanistic studies reveal that thiol serves as both photocatalyst and HAT reagent under visible light irradiation. This synergistic photocatalysis and HAT catalysis protocol exhibits ample and salient features such as high chemo- and regioselectivity, broad substrate scope, amenable gram-scale synthesis and late-stage modification of bioactive molecules.
将偕二氟亚甲基单元引入有机分子仍然是一项艰巨的挑战。构建芳基二氟甲基衍生物的传统方法依赖于在苛刻条件下使用高官能度的氟化试剂。在此，我们报道了通用且高效的光氧化还原催化体系，用于通过选择性C-F裂解将易得的三氟甲基芳烃进行脱氟烷基化，以生成偕二氟甲基自由基，该自由基在无过渡金属条件下通过向供电子和吸电子烯烃的还原加成反应进行反应。机理研究表明，硫醇在可见光照射下既是光催化剂又是氢原子转移（HAT）试剂。这种协同光催化和HAT催化方案具有丰富且显著的特点，如高化学和区域选择性、广泛的底物范围、适合克级规模合成以及生物活性分子的后期修饰。
