Desymmetrisation of 4,4-disubstituted cyclohexanones by enzyme-catalysed resolution of their enol acetates

Abstract

Enol acetates 3–10 derived from prochiral 4,4-disubstituted cyclohexanones can be resolved with Pseudomonas fluorescens lipase to give enantiomerically pure (>99% ee) enol esters by transesterification with n-BuOH. The product ketones are prochiral and can easily be recycled giving an overall desymmetrisation of the ketone. Highest selectivity was obtained for substrates containing a 4-cyano and 4-aryl or a 4-benzyloxy substituent. The methodology was compared to asymmetric deprotonation–enolate trapping using the chiral base (S,S)-bis(α-methylbenzyl)amide which gave low (54–64%) ee’s for this class of ketones.