DELTA,EPSILON-UNSATURATED BETA,BETA-DIFLUORO-ALPHA-KETO ESTERS - NOVEL SYNTHESIS AND UTILITY AS PRECURSORS OF BETA,BETA-DIFLUORO-ALPHA-AMINO ACIDS

Treatment of the hemiketals 6 formed from ethyl trifluoropyruvate and primary allylic alcohols with SOCl2 and pyridine readily afforded a nu mber of alpha-chloro-beta,beta,beta-trifluorolactyl allyl ethers 2. Su bsequent reductive dechlorofluorination from 2 led to the formation of allyl-substituted difluoroenol pyruvyl ethers 3 whose Claisen rearran gement provided a convenient access to a variety of delta,epsilon-unsa turated beta,beta-difluoro-alpha-keto esters 4. As further transformat ion, direct conversion of beta,beta-difluoro-alpha-keto esters to the corresponding beta,beta-difluoro-alpha-amino acids was achieved by red uctive amination of the corresponding alpha-keto acids with NH3 . H2O/ NaBH4. Furthermore, use of the prepared beta beta-difluoro-alpha-keto ester 4a as a common precursor of other structurally related beta,beta -difluoro-alpha-amino acids was demonstrated by the synthesis of beta, beta-difluoroproline (18) and beta,beta-difluoroglutamic acid (23) thr ough synthetic elaboration of its inherent double bond.