Gem‐Difluoromethylene Alkyne‐Enabled Diverse C−H Functionalization and Application to the on‐DNA Synthesis of Difluorinated Isocoumarins. (20th November 2020)

• Record Type: Journal Article
• Authors: Gao, Hui; Lin, Shuang; Zhang, Shuning; Chen, Weijie; Liu, Xiawen; Yang, Guang; Lerner, Richard A.; Xu, Hongtao; Zhou, Zhi; Yi, Wei
• Is Part Of: Angewandte Chemie. Volume 133:Number 4(2021)
• Page Start: 1987
• Page End: 1994
• Publication Date: 2020-11-20
• Subjects: C−H functionalization -- chemodivergence -- DNA-encoded libraries -- gem-difluoromethylene alkynes -- Rh/Ir catalysis; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202013052
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Using gem‐difluoromethylene alkynes as effectors, unprecedented diverse C−H activation/[4+2] annulations of simple benzoic acids are reported. The chemodivergent reaction outcomes are well‐tuned by Rh/Ir‐catalyzed system; in the Rh III catalysis, 3‐alkenyl‐1H‐isochromen‐1‐one and 3, 4‐dialkylideneisochroman‐1‐one skeletons are afforded in a solvent‐dependent manner whereas difluoromethylene‐substituted 1H‐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. Abstract : An unprecedented divergent C−H functionalization of simple benzoic acids with gem ‐difluoromethylene alkynes was realized in a controllable and chemoselective manner, which is tuned by Rh III /Ir III ‐catalyzed system. The derivatization of obtained diene products and synthetic applicability on‐DNA synthesis were feasible.