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Photo-Induced Difluoromethylation-Cyclization and Domino Amination-Defluorination to 4-(Aminomethyl)-3-fluoro-quinolinones

Xin Wang, Dongyang Zhao, Jia-Bo Huang, Gangqing Shi, Er‐Jun Hao, Shao‐Fei Ni, Kai Sun

2024Organic Letters12 citationsDOI

Abstract

Herein, we report a visible light-induced difluoromethylation cyclization and subsequent amination-defluorination reaction. This protocol allows efficient to valuable 3-fluoro-quinolinones in moderate to excellent yields. A sequential difluoromethylation-cyclization-amination-defluorination mechanism was proposed based on a mechanism study. Further density functional theory (DFT) calculations revealed that the base K 2 HPO 4 could lower the energy due to the C═O···K + electrostatic interaction to assist the elimination process, while the six-membered transition state located in situ was essential for the cleavage of N–H and C–F bonds during this S N 2′-type process.

Topics & Concepts

ChemistryDominoAminationCombinatorial chemistryReductive aminationOrganic chemistryCatalysisFluorine in Organic ChemistrySynthesis and Reactions of Organic CompoundsRadical Photochemical Reactions
Photo-Induced Difluoromethylation-Cyclization and Domino Amination-Defluorination to 4-(Aminomethyl)-3-fluoro-quinolinones | Litcius