ASYMMETRIC-SYNTHESIS OF (S)-5,5,5,5',5',5'-HEXAFLUOROLEUCINE

(S)-5,5,5,5',5',5'-Hexafluoroleucine ((S)-13) of 81% ee is prepared fr om hexafluoroacetone (1) and ethyl bromopyruvate (= ethyl 2-oxopropano ate) in 7 steps with an overall yield of 18% (Schemes 1 and 2). Key st ep in this sequence is the highly enantioselective reduction of the ca rbonyl group in alpha-keto ester 4 either by bakers' yeast (91% ee) or by 'catecholborane' 6 utilizing an oxazaborolidine catalyst, yielding hydroxy ester (R)-5 with 99% ee. The absolute configuration was deter mined by X-ray analysis of the HCl adduct (S,R)-9b of R)-1-phenylethyl ]-5,5,5,5',5',5'-hexafluoroleucine ethyl ester.