The preparation of a series of β,β-difluoro-α-keto esters and corresponding acids RCF2COCO2R′ (R = Me, Et, i-Pr, Bn, and Ph; R′ = Et and H), designed as potential inhibitors of serine proteases, is described. The standard procedure developed consists in the initial formation of an α,α-difluoro ester from an α-keto ester, followed by a simple four-step sequence involving the synthesis of hemiacetal, cyanohydrin, and α-hydroxy ester difluorinated intermediates. This method provides an easy route to β,β-difluoro-α-keto esters and corresponding acids, via "formal" insertion of a difluoromethylene group between the R substituent and the α-carbonyl group of a generic α-keto ester.
ASJC Scopus subject areas
- Organic Chemistry