Optical resolution of acyclic α-hydroxy ketone derivatives by inclusion complexation

A new method for the preparation of optically active acyclic alpha-hydroxy ketone derivatives by thermodynamic resolution using a chiral host compound is described. We examined the resolution of racemic 2-benzyloxy-3-pentanone with chiral host compounds in various solvents. After optimization of the reaction conditions, it has become apparent that the optical resolution could occur only under certain strict conditions about solvents, host compounds, and the concentration of the substrate. Stirring the suspension of the ketone with (-)-TADDOL bearing a cyclohexyl ring, derived from ethyl L-tartrate, in MeOH-H2O (1:1) at room temperature produces the inclusion complex with high enantioselectivity to give (S)-ketone with up to 99% ee. On the other hand, the ee of (R)-ketone obtained from the filtrate could be improved by the same procedure using (+)-TADDOL; finally, both enantiomers of the ketone as an almost optically pure form were afforded. Analysis of the formed complex by ESI-TOFMS supposed that the host-guest ratio would be 1:1. This resolution procedure was also applied to other substrates to afford the corresponding optically active ketones.