TETRAHEDRON LETTERS Pergamon Tetrahedron Letters 40 (1999) 2863-2864 Diastereoselective Reduction of (S)-1-Chloro-3- silyloxybutan-2-one. Synthesis of Enantiopure (2S,3R) and (2S,3S) O-tert-Butyl dimethylsilyl- 3 ,4-epoxybutan-2-ol. Jos6 M. Concell6n,* Pablo L. Bemad, R. Alvarez, A. Rodriguez and B. Baragafia. Departammto de Quimitu Orgttrica elnorgtlnim, Juli6n Cknmla8, Uniu~sidzrl deOcmb, 33071Ovied~Spain Received 22 December 1998; revised 1 February 1999; accepted 9 February 1999 Abstract: (2S,3S)- And (2R,3S)-3-[(tert-butykYlmethyl)silyloxy]-1-chlorobutan-2-ol have been obtained with high diastereoseleetivity by reduction of enantiopure (S)-3-[(tert-butyldimethyl)silyloxy]-l-chlorobutan-2-one using different reducing agents. The ehiral alcohols were transformed into the corresponding (2R,3S)- and (2S,3S)-3-[(tert-butyldimethyl)silyloxy]-1,2-epoxybutane. © 1999 ElsevierScienceLtd. All rightsreserved. Keywords: chiral chloromethyl ketones;reduction; diastereoseleetion; I~,~-epoxy alcohols. We have reported the direct preparation of chiral (S)-3-alkoxy-l-chlorobutan-2-one 1 by reaction of (chloromethyl)lithium generated in situ with O-protected ethyl lactate, [ 1 ]. In the present communication we report some synthetic applications of 1. Thus, reduction of 1 with different reducing agents led to both diastereoisomeric 13-alkoxy alcohols syn-2 or anti-2 [2] with high diastereoselectivity; epoxidation of these diols provided both diastereoisomers of the 3-alkoxy-1,2-epoxides syn-3 and anti-3. The stereochemistry of the major diastereoisomers obtained in the reduction reactions was also established. OH 0 OH M e..,,i~.,jC' tH'] M ey.[~CI [H'] M e',,,I,,."Z",..,/C' + anti-2 . . syn-2 + ositBuMe2 O G p ositBuMe2 syn-2 ~ la Gp= Bn / anti-2 ositBuae2 MeYMe M'XMe OSitBuMe2 syn- 3 trans-4 cls.4 anti-3 Scheme 1 Reduction using ketone la and NaBH4, gave the desired O-monoprotected diol 2 in high yield, but no diastereoselectivity was observed. By contrast, reduction of lb with NaBH4 led to the anti-2 [~-silyloxy alcohol with high diastereoselectivity. Since O-tert-hutyl&methylsilylated ketone lb shows enhanced diastereoselectivity relative to the corresponding O-benzylated 0040-4039/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved. PII: S0040-4039(99)00313-5