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

Enol acetates 3-10 derived from prochiral 4,4-disubstituted cyclohexanones can be resolved with Pseudomonas fluorescens lipase to give enantiomericall y pure (> 99% ee) enol esters by transesterification with n-BuOH. The produ ct ketones are prochiral and can easily be recycled giving an overall desym metrisation of the ketone. Highest selectivity was obtained for substrates containing a 4-cyano and 4-aryl or a 4-benzyloxy substituent. The methodolo gy was compared to asymmetric deprotonation-enolate trapping using the chir al base (S,S)-bis(alpha-methylbenzyl)amide which gave low (54-64%) ee's for this class of ketones.