Decarboxylative Aldol Reaction of α,α-Difluoro-β-keto Esters: Easy Access to Difluoroenolate.

Yb(OTf) 3 promoted the Krapcho decarboxylation of 2,2-difluoro-3-oxopropanoate, and a subsequent aldol reaction was achieved. This process is the first example of generating difluoroenolates through a decarboxylation-type process, and a large number of carbonyl compounds are applicable to the aldol reaction. The protocol is a complete one-pot reaction that uses the bench-stable and nonhygroscopic 2,2-difluoro-3-oxopropanoate to generate the difluoroenolate. This strategy has been applied for the synthesis of CF 2 -containing bioactive GABA B agonists, contributing to drug design.