Observations on the stereochemistry of reduction of 2,6-dimethylcyclohexanones

Abstract

The reduction of cis-2,6-dimethylcyclohexanone with NaBH4 in methanol is shown to produce predominantly the axial alcohol, an unexpected result based upon prior reports and current paradigms for similar cyclohexanone reductions. This finding prompted a careful and systematic investigation of the NaBH4 and LiAlH4 reductions of cis- and trans-2,6-dimethylcyclohexanones in various solvents, with additional results contrary to literature reports. Possible explanations for these discrepancies are given, an unusual solvent effect is noted, the rate of epimerization versus reduction is examined, molecular modeling results are reported, and an important caveat is offered for future stereochemical studies of this nature.Key words: cyclic ketone reduction, stereochemistry, molecular modeling.