TETRAHEDRON: ASYMMETRY Tetrahedron: Asymmetry 12 (2001) 2457–2462 Pergamon Humicola lanuginosa lipase-catalyzed enantioselective resolution of -hydroxy sulfides: versatile synthons for enantiopure -hydroxy sulfoxides Satwinder Singh, Subodh Kumar and Swapandeep Singh Chimni* Department of Chemistry, Guru Nanak Dev University, Amritsar 143 005, India Received 4 September 2001; accepted 1 October 2001 Abstract—Humicola lanuginosa lipase-catalyzed acylation of -hydroxy sulfides provides both the (R )- and (S )-enantiomers in high enantiomeric purity. In two cases the resolved hydroxy sulfides were oxidized to give -hydroxy sulfoxides in >99% e.e. The effect of substituents on enantioselectivity is discussed. © 2001 Elsevier Science Ltd. All rights reserved. 1. Introduction Enantiopure functionalized secondary alcohols are important synthetic intermediates and useful chiral aux- iliaries both for analytical and synthetic applications. 1 The presence of a sulfur atom placed at an appropriate position from the hydroxy group provides unique syn- thetic versatility. 2 Thus, enantiopure hydroxy sulfides serve as intermediates in the synthesis of naturally occurring spiroketal pheromones, 3 chiral oxiranes, 4 thi- iranes, 5 tetrahydrofurans, 6 and 4-acetoxyazetidinone. 7 The available synthetic approaches for obtaining enan- tiopure hydroxy sulfides involve stereoselective reduc- tion of phenylthio ketones using baker’s yeast 3,8 or asymmetric chiral ruthenium complexes 9 and are plagued with either the availability of only one enan- tiomer or moderate enantioselectivity. The lipase-cata- lyzed resolution of hydroxy sulfides or their esters provides an alternative approach 10 and have found that Humicola lanuginosa lipase (HLL), a cheap detergent lipase, rarely used for resolution of organic molecules resolves -hydroxy sulfides to give both the (R )- and (S )-enantiomers of 1a–1g in high enantiomeric purity. Furthermore, oxidation of the enzymatically-resolved enantiomers 1a–1b with m -CPBA, followed by frac- tional crystallization provides a convenient route to the enantiopure -hydroxy sulfoxides (Scheme 1), which find widespread application as chiral intermediates 11 and chiral catalysts. 12 Generally, -hydroxy sulfoxides are synthesized by the stereoselective reduction 13,14 of chiral -ketosulfoxides, which are obtained through an approach requiring several steps, starting with Andersen’s resolution. 15 This method, in addition to Scheme 1. (i) Lipase/VA; (ii) base; (iii) m-CPBA; (iv) fractional crystallization. * Corresponding author. Fax: +91-183-258820; e-mail: sschimni@angelfire.com 0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII:S0957-4166(01)00434-7