EFFICIENT SYNTHESIS AND RESOLUTION OF TRANS-2-(1-ARYL-1-METHYLETHYL)CYCLOHEXANOLS - PRACTICAL ALTERNATIVES TO 8-PHENYLMENTHOL

A short synthesis and resolution of effective chiral auxiliaries of the 8-arylmenthol-type were achieved using inexpensive materials, a recyclable lipase, and easily applied procedures that are amenable to large-scale preparation. A variety of isopropylarenes were alpha-metalated with n-butyllithium/potassium tert-pentoxide and treated with cyclohexene oxide to provide racemic trans-2-(1-aryl-1-methylethyl)-cyclohexanols 6a-f in fair to high yield. Candida rugosa lipase and lauric acid were used to resolve these racemic alcohols by converting the (-)-enantiomer to its laurate ester. The enzymatic resolutions were carried out at 40-degrees-C and were faster in cyclohexane than in hexanes. The synthesis and resolution of racemic trans-2-(1-methyl-1-phenylethyl)cyclohexanol (6a) were performed on a 1 mol scale in 68% overall yield, requiring three steps for (+)-6a and five steps for (-)-6a.