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Synthesis 2011(18): 2921-2928  
DOI: 10.1055/s-0030-1260149
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© Georg Thieme Verlag Stuttgart ˙ New York

Lipase-Catalyzed Synthesis of Both Enantiomers of 3-Chloro-1-arylpropan-1-ols

Laura Ancua Popa, Andrea Czompab, Csaba Paizsa, Monica Ioana Toşaa, Elemér Vassc, Péter Mátyusb, Florin-Dan Irimie*a
a Babes-Bolyai University, Faculty of Chemistry and Chemical Engineering, Arany János street, Nr. 11, 400028 Cluj Napoca, Romania
Fax: +40(264)590818; e-Mail: irimie@chem.ubbcluj.ro ;
b Semmelweis University, Department of Organic Chemistry, Hőgyes Endre u. 7., 1092 Budapest, Hungary
c Eötvös Loránd University, Laboratory for Chiroptical Structure Analysis, Institute of Chemistry, PO Box 32, 1518 Budapest 112, Hungary
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Publication History

Received 4 March 2011
Publication Date:
02 August 2011 (online)

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Abstract

The lipase-catalyzed synthesis of both enantiomers of 3-chloro-1-(4-fluorophenyl)propan-1-ol, 3-chloro-1-(4-iodophenyl)propan-1-ol, and 3-chloro-1-phenylpropan-1-ol is described. The procedure is based on the enantiomer-selective acylation of the racemic alcohols in presence of lipase from Pseudomonas fluorescens (LAK) followed by the lipase from Candida rugosa (CRL) mediated hydrolysis of previously obtained enantiomerically enriched 1-aryl-3-chloropropyl esters. For the production of enantiopure (S)-1-aryl-3-chloropropan-1-ols (99% ee, 34-42% yield) the reactions were stopped at higher conversions than the theoretical optimum of 50%, while for enantiopure (R)-1-aryl-3-chloropropyl acetates (99% ee) the reactions were stopped at lower conversions. The latter compounds were enzymatically hydrolyzed into the corresponding (R)-1-aryl-3-chloropropan-1-ols (97-99% ee, 18-24% yield). The absolute configuration of the resolution products was determined by VCD measurements combined with quantum chemical calculations.

Key words

enzymes - kinetic resolution - enantioselectivity - chiral resolution - alcohols - halide