Rapid Dehydroxytrifluoromethoxylation of Alcohols

Wei Zhang; Jia Chen; Jin-Hong Lin; Ji-Chang Xiao; Yu-Cheng Gu

doi:10.1016/j.isci.2018.07.004

Rapid Dehydroxytrifluoromethoxylation of Alcohols

iScience. 2018 Jul 27:5:110-117. doi: 10.1016/j.isci.2018.07.004. Epub 2018 Jul 11.

Authors

Wei Zhang¹, Jia Chen¹, Jin-Hong Lin², Ji-Chang Xiao³, Yu-Cheng Gu⁴

Affiliations

¹ Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
² Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. Electronic address: jlin@sioc.ac.cn.
³ Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. Electronic address: jchxiao@sioc.ac.cn.
⁴ Syngenta, Jealott's Hill International Research Centre, Bracknell, Berkshire RG426EY, UK.

Abstract

The CF₃O functional group is a unique fluorinated group that has received a great deal of attention in medicinal chemistry and agrochemistry. However, trifluoromethoxylation of substrates remains a challenging task. Herein we describe the dehydroxytrifluoromethoxylation of alcohols promoted by a R₃P/ICH₂CH₂I (R₃P = Ph₃P or Ph₂PCH=CH₂) system in DMF. P-I halogen bonding drives the reaction of R₃P with ICH₂CH₂I in DMF to generate iodophosphonium salt (R₃P⁺I I^-) and a Vilsmeier-Haack-type intermediate, both of which could effectively activate alcohols, thus enabling a fast (15 min) trifluoromethoxylation reaction. A wide substrate scope and a high level of functional group tolerance were observed.

Keywords: Chemistry; Organic Chemistry; Organic Synthesis.