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Updated: Mar 31, 2026

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions
Published on: July 28, 2022
Difluorocarbene-Promoted Regioselective Ring-Opening of Benzimidazoles
Jingyu Wei1, Huanhuan Liu1, Bingxian Liu1
1Pingyuan Laboratory, State Key Laboratory of Antiviral Drugs, School of Pharmaceutical Sciences, Henan Normal University, Xinxiang, Henan 453007, China.
None:
This study presents a regioselective ring-opening method for 2-substituted benzimidazoles, utilizing in situ-generated difluorocarbene as a key electrophile. Employing sodium chlorodifluoroacetate as the carbene precursor and Na2CO3 as the base, the reaction directly affords valuable 2-carbonyl phenyl isocyanides. Mechanistic studies, including HRMS (using 18O-labeled water) and Hammett analysis, confirm that the reaction proceeds via a difluorocarbene-derived N-CF2 ylide intermediate, followed by water nucleophilic attack at the C2 position. This cascade process results in the simultaneous introduction of an isocyanide and a carbonyl group, demonstrating a novel hydrolysis/functionalization strategy. The methodology features a broad substrate scope, successful gram-scale synthesis, and versatile downstream derivatization of the isocyanide products, offering a new and practical approach for heterocycle editing and drug synthesis.
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