Nucleophilic difluoromethylation of epoxides with PhSO(NTBS)CF₂H by a preorganization strategy.
Unlike the facile synthesis of β-monofluoromethyl alcohols by nucleophilic monofluoromethylation of epoxides, the synthesis of β-difluoromethyl alcohols by nucleophilic difluoromethylation of epoxides still remains a challenge. Herein, studies on tackling this problem with PhSO(NTBS)CF2H (2; TBS=tert-butyldimethylsilyl) are reported. The preorganization of 2 and epoxides with BF3⋅Et2O was found to be crucial for the reaction. The reaction shows excellent regioselectivity and has a broad substrate scope. The facile transformation of the ring-opened products to β-difluoromethyl, γ-difluoromethyl, and β-difluoromethylenyl alcohols demonstrates the synthetic utility of the reaction.
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032 (P. R. China).
Xiao
X
Shen
Qinghe
Q
Liu
Tao
T
Luo
Jinbo
J
Hu
alcohols; difluoromethylation; nucleophilic substitution; preorganization; sulfoximines