Premium
gem ‐Difluoromethylene Alkyne‐Enabled Diverse C−H Functionalization and Application to the on‐DNA Synthesis of Difluorinated Isocoumarins
Author(s) -
Gao Hui,
Lin Shuang,
Zhang Shuning,
Chen Weijie,
Liu Xiawen,
Yang Guang,
Lerner Richard A.,
Xu Hongtao,
Zhou Zhi,
Yi Wei
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202013052
Subject(s) - isocoumarins , chemistry , isocoumarin , regioselectivity , combinatorial chemistry , alkyne , derivatization , catalysis , surface modification , stereochemistry , organic chemistry , high performance liquid chromatography
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.