Removal of the acyl donor residue allows the use of simple alkyl esters as acyl donors for the dynamic kinetic resolution of secondary alcohols

The dynamic kinetic resolution of secondary alcohols using a lipase and a ruthenium catalyst as developed by Backvall required some improvements to make it suitable for its use in all industrial process. The use of p-chlorophenyl acetate as acyl donor is not desirable in view of the toxicity of the side product. We herein report that simple alkyl esters call be used as acyl donors if the alcohol or ketone residue formed during the enzymatic acylation is continuously removed during the reaction. The addition of a ketone speeds up the racemisation process and allowed us to reduce the amounts of enzyme and ruthenium catalyst. The scope of this method was explored and a suitable range of acyl donors found. Various benzylic and aliphatic alcohols were reacted using isopropyl butyrate or methyl phenylacetate as acyl donor and in most cases the ester was isolated in >95% yield and 99% ee. Furthermore, it was demonstrated that the alcohol by-products of the enzymatic resolution Could be used as the hydrogen Source in the asymmetric reductive transesterification of ketones. (C) 2005 Elsevier Ltd. All rights reserved.