We report the use of cross-linked enzyme aggregates (CLEAs 1 ) to catalyse the kinetic resolution of tetralol and 1-phenylethanol in a continuous supercritical carbon dioxide (scCO 2 ) system. We describe the performance of the CLEA from Candida antarctica lipase B (CALB) and compare this to the catalytic activity of Novozym 435 (CALB immobilised on a macroporous acrylic resin). In addition, we report a two-stage reaction with the kinetic resolution of 1-phenylethanol performed in series with the metal (Pd) catalysed hydrogenation of acetophenone. Reactions performed in series have a potential economic advantage as the second, and subsequent reactions do not require additional expenditure of energy for re-pressurization of solvent.

Continuous flow supercritical carbon dioxide (scCO 2 ) has previously been shown (P. Stephenson, P. Licence, S. K. Ross, M. Poliakoff, Green Chem. 2004, 6, 521) to be a viable medium for conducting continuous asymmetric hydrogenation when it is combined with an appropriate enantioselective catalyst. Here we examine the use of a composite catalyst immobilisation system modified with several different types of asymmetric bisphosphine ligands in continuous flow scCO 2 . In particular, proprietary ligands from Solvias AG were found to be the most successful, with Josiphos 001 improving the enantiomeric excess (ee) to> 80 % in the asymmetric hydrogenation of dimethyl itaconate (DMIT); this ee is higher than that reported for the batch hydrogenation of DMIT using a homogeneous catalyst fully dissolved in scCO 2 (S. Lange, A. Brinkmann, P. Trautner, K. Woelk, J. Bargon, W. Leitner, Chirality 2000, 12, 450).

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