Hui Gao; Shuang Lin; Shunning Zhang; Weijie Chen; Xiawen Liu; Guang Yang; Richard A. Lerner; Hongtao Xu; Zhi Zhou; Wei Yi
Angew. Chem. Int. Ed., 2021, 60(4), 1959-1966
https://doi.org/10.1002/anie.202013052

Abstract

Using gem ‐difluoromethylene alkynes as effectors, unprecedented diverse C−H activation/[4+2] annulations of simple benzoic acids are reported here. Remarkably, the chemodivergent reaction outcomes are well‐tuned by Rh/Ir‐catalyzed system; in the Rh(III) catalysis, 3‐alkenyl‐1 H ‐isochromen‐1‐one and 3,4‐dialkylideneisochroman‐1‐one skeletons are afforded in a solvent‐dependent manner whereas difluoromethylene‐substituted 1 H ‐isochromen‐1‐ones are generated under the Ir(III)‐catalyzed system. Mechanistic studies revealed that unusually double β‐F eliminations and fluorine effect‐induced regioselective reductive elimination are independently involved to enable distinct reaction modes for divergent product formations. Besides, synthetic application in both the derivatization of obtained diene products and the on‐DNA synthesis of DNA‐tagged difluorinated isocoumarin have been demonstrated, which manifested great potential for synthetic utility of the developed protocols.