1,1,1,3,3,3-Hexafluoro-2-Propanol-Promoted Friedel-Crafts Reaction: Metal-Free Synthesis of C3-Difluoromethyl Carbinol-Containing Imidazo[1,2-]pyridines at Room Temperature.

A facile and efficient method has been developed for the synthesis of C3-difluoromethyl carbinol-containing imidazo[1,2-]pyridines at room temperature via the HFIP-promoted Friedel-Crafts reaction of difluoroacetaldehyde ethyl hemiacetal and imidazo[1,2-]pyridines. This strategy could be applied to the direct C(sp)-H hydroxydifluoromethylation of imidazo[1,2-]pyridines and afford a series of novel difluoromethylated carbinols in good to satisfactory yields with 29 examples. Furthermore, gram-scale and synthetic transformation experiments have also been achieved, demonstrating its potential applicable value in organic synthesis. This green protocol has several advantages, including being transition metal- and oxidant-free, being carried out at room temperature, having high efficiency, and having a wide substrate scope.