Difluoromethylation of Aryl Halides via Palladium-Catalyzed Redox-Neutral Deacylation

Organic Letters 2026

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Authors: Shihao Li, Mingming Li, Yan Liu, Jingwen Hao, Shaojun Zheng, Zitong Rong, Yi‐Si Feng, Nai-Dong Chen, Pan Pan
DOI: 10.1021/acs.orglett.5c04966
Cited by: 2
References: 51

Abstract

A novel difluoromethylating reagent was developed via the dehydration condensation between 1,1-difluoroacetone and N'-methylpicolinohydrazonamide (MPHA). This reagent is suitable for palladium-catalyzed coupling reactions, offering a broad substrate scope (43 examples) and excellent scalability (gram-scale synthesis), and can be efficiently employed for the modification of drug molecules to enable the facile synthesis of difluoromethylated (hetero)arenes. Mechanistic studies indicate that the successful release of the difluoromethyl radical results from aromatization-driven C-C bond cleavage.

Fields of Study & Subjects

Fluorine in Organic Chemistry Catalytic C–H Functionalization Methods Radical Photochemical Reactions

Publication details

Journal / source
Organic Letters
Publisher
American Chemical Society (ACS)
Volume
28
Issue
2
Pages
806–812
Publication date
5 January 2026
Language
EN