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Updated: Jun 23, 2025

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
Decarboxylative Aldol Reaction of α,α-Difluoro-β-keto Esters: Easy Access to Difluoroenolate
Atsushi Tarui1, Hiroshi Shimomura1, Yohei Yasuno1
1Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
Abstract:
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 CF2-containing bioactive GABAB agonists, contributing to drug design.
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