Enantioselective Cu-Catalyzed Nucleophilic Substitutions of Polyfluoroarenes: Synthesis of Chiral Polyfluoroaryl Diarylmethanes

作者：Huaxin Lin, Xiang Huang, Wei Jiao, Dongmei Fang, Min Wang, Jian Liao · 发表于：Organic Letters · 年份：2023 · DOI：10.1021/acs.orglett.3c00948 · 被引用次数：11 · 研究领域：Fluorine in Organic Chemistry、Asymmetric Synthesis and Catalysis、Catalytic C–H Functionalization Methods

Optically pure diarylmethanes are frequently presented in pharmaceuticals and bioactive molecules. However, minor efforts have been devoted to chiral polyfluoroarene-containing diarylmethanes, and their synthesis is still challenging. Herein, we describe an enantioselective Cu/sulfoxide phosphine ( SOP ) catalyzed nucleophilic substitution reaction by using polyfluoroarenes as the polyfluoroaryl reagent. Under mild conditions, this protocol enables the efficient synthesis of chiral polyfluoroaryl diarylmethanes with fluorinated quaternary stereogenic center in good yields (up to 93%), high regioselectivties, and excellent enantioselectivities (up to 99% ee). Moreover, gram-scale experiments, product derivations, and late-stage diversifications were performed to demonstrate the utility of this method.