Difluoromethylation of Phenols and Thiophenols with the S‑(Difluo-romethyl)sulfonium Salt: Reaction, Scope, and Mechanistic Study

• Published in: Journal of organic chemistry Vol. 84; no. 24; pp. 15948 - 15957
• Main Authors: Liu, Guo-Kai, Qin, Wen-Bing, Li, Xin, Lin, Li-Ting, Wong, Henry N. C
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20-12-2019
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.9b02424

A facile and practical approach for the difluoromethylation of phenols and thiophenols was described. Making use of the recently developed bench-stable S-(difluoromethyl)­sulfonium salt as the difluorocarbene precursor, a wide variety of diversely functionalized phenols and thiophenols were readily converted to their corresponding aryl difluoromethyl ethers in good to excellent yields in the presence of lithium hydroxide. Chemoselectivity of various O,S-nucleophiles toward difluorocarbene was systematically studied, suggesting the reactivity order ArS– > RS–, ArO– > ROH > RO–, ArSH, ArOH, RSH.