Controlling the Cleavage of Carbon–Carbon Bonds To Generate α,α-Difluorobenzyl Carbanions for the Construction of Difluoromethylbenzenes

Controlling
the cleavage of carbon–carbon bonds during a
chemical reaction is a substantial challenge; however, synthetic methods
that accomplish this objective produce valuable and often unexplored
reactivity. We have designed a mild process to generate α,α-difluorobenzyl
carbanions in the presence of potassium carbonate by exploiting the
cleavage of C–C bonds during the release of trifluoroacetate.
The initiating reagent is potassium carbonate, which represents an
improvement over existing protocols that require a strong base. Fragmentation
studies across substituted arenes and heteroarenes were conducted
along with computational analyses to elucidate reactivity trends.
Furthermore, the mildly generated α,α-difluorobenzyl carbanions
from electron-deficient aromatics and heteroaromatic rings can react
with aldehydes to create derivatives of difluoromethylbenzenes, which
are valuable synthetic targets.