Mechanochemical difluoromethylation of (thio)phenols and N‐heterocycles

Abstract

Herein, we report a minimalistic protocol for the solvent‐free, mechanochemical difluoromethylation of (thio)phenols and N‐heteroarenes using non‐ozone depleting chlorodifluoromethyl phenyl sulfone as a difluorocarbene source. This mechanochemical difluoromethylation features a short reaction time, excellent functional group tolerance, and compatibility with complex biologically active scaffolds.

Mechanochemical Deoxyfluorination of Carboxylic Acids to Acyl Fluorides and Successive Mechanochemical Amide Bond Formation

“…25−32 A ball mill is a mechanochemical apparatus that employs the controlled movement of a ball at a specified frequency to exert mechanical force on a mixture of reagents, thereby expediting the reaction process. Although many mechanochemical reactions, including fluorination 33,34 and difluoromethylation, 35,36 have recently been reported, there is an absence of mechanochemical synthesis methods for acyl fluorides.…”

“…IUPAC has acknowledged mechanochemistry as one of the ten leading technologies in chemistry, responding to the growing need for environmentally friendly processes and sustainable reaction conditions. − A ball mill is a mechanochemical apparatus that employs the controlled movement of a ball at a specified frequency to exert mechanical force on a mixture of reagents, thereby expediting the reaction process. Although many mechanochemical reactions, including fluorination , and difluoromethylation, , have recently been reported, there is an absence of mechanochemical synthesis methods for acyl fluorides.…”