Asymmetric Synthesis of (<i>S</i>)‐5,5,5,5′,5′,5′,5′‐Hexafluoroleucine

Abstract

Abstract ( S )‐5,5,5,5′,5′,5′‐Hexafluoroleucine (( S )‐ 13 ) of 81 % ee is prepared from hexafluoroacetone ( l ) and ethyl bromopyruvate (= ethyl 2‐oxopropanoate) in 7 steps with an overall yield of 18% ( Schemes 1 and 2 ). Key step in this sequence is the highly enantioselective reduction of the carbonyl group in α‐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 determined by X‐ray analysis of the HCl adduct ( S,R )‐ 9b of (2 S )‐ N ‐[( R )‐ l‐phenylethyl]‐5,5,5,5′,5′,5′‐hexafluoroleucine ethyl ester.