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Updated: Jan 12, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
NHC Precursor Catalyzed C3-Chloromethylation of Oxindole with Dichloromethane as C1 Synthon
Lijuan Liang1, Teck-Peng Loh1,2, Yaojie Li1
1Henan Linker Technology Key Laboratory, College of Advanced Interdisciplinary Science and Technology (CAIST), Henan University of Technology, Zhengzhou 450001, China.
Abstract:
The construction of sterically hindered all-carbon α-chloromethyl quaternary centers remains a major synthetic challenge due to both steric congestion and limited efficient methods. Herein, we report a mild and efficient protocol for the chloromethylation of oxindoles using dichloromethane (DCM) as a C1 synthon, mediated by an NHC precursor. This reaction proceeded under mild conditions with broad substrate scope, high chemoselectivity, and good to excellent yields across over 30 examples. Preliminary mechanistic studies suggested a unique pathway distinct from that of conventional NHC catalysis. The method demonstrated excellent scalability and offered a versatile and green approach to access α-chloromethyl quaternary centers, providing valuable intermediates for further transformations in pharmaceutical and organic synthesis.
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