Estimation of the stereoselectivity of reduction of 3,3,5,5-tetramethylcyclohexanone by sodium borohydride

Abstract

4-(1-Hydroxyethyl)-3,3,5,5-tetramethylcyclohexanone has been prepared to serve as a model for 3,3,5,5-tetramethylcyclohexanone on which the reduction stereochemical product ratio may be experimentally determined. Reduction with sodium borohydride in 2-propanol gives two epimers in a 95.5:4.5 ratio. The major isomer is shown to be the less stable by equilibration over Raney nickel. Proton and 13C nmr spectra confirm that this major epimer is cis-4-(1-hydroxyethyl)-3,3,5,5-tetramethylcyclohexanol and show that this compound exists predominantly in the conformation with an axial hydroxyethyl group and an equatorial hydroxyl group. It is concluded that reduction of this model compound proceeds at least 95.5% by equatorial attack.