Deuterium Isotope Effects in the Reduction of Cyclohexanones. The Concepts of Steric Approach Control and Product Development Control

Abstract

Definitions for the terms stericapproachcontrol and productdevelopmentcontrol in relation to the degree of bonding in the transition state are put forward. Kinetic deuterium isotope effects in the reduction of a graded series of ketones by NaBH4 and NaBD4 have been measured. These effects are inverse, and show no systematic dependence on the degree of steric hindrance of the ketone. This evidence appears to invalidate the steric approach control – product development control explanation of the axial to equatorial product ratios (1). The primary isotope effect is very small, which is consistent with an early transition state in these reductions, as demanded by other explanations of product ratios, but since several other factors causing small isotope effects may be applicable, the evidence does not constitute proof of an early transition state.The main conclusions of this work have already been published in preliminary form (2).