A SIMPLE COMPUTATIONAL MODEL FOR PREDICTING PI-FACIAL SELECTIVITY IN REDUCTIONS OF STERICALLY UNBIASED KETONES - ON THE RELATIVE IMPORTANCE OF ELECTROSTATIC AND ORBITAL INTERACTIONS

Various factors controlling the preferred facial selectivity in the reductions of a number of sterically unbiased ketones have been evaluated using a semiempirical MO procedure. MNDO optimized geometries do not reveal any significant ground-state distortions which can be correlated with the observed face selectivities. Electrostatic effects due to an approaching reagent were modeled by placing a test negative charge at a fixed distance from the carbonyl carbon on each of the two faces. A second series of calculations was carried out using the hydride ion as a test nucleophile. The latter calculations effectively include orbital interactions involving the sigma and sigma* orbitals of the newly formed bond in the reaction. The computed energy differences with the charge model are generally much larger compared to those with the hydride ion. However, both models lead to predictions which are qualitatively consistent with the experimentally determined facial preferences for most of the systems. Thus, electrostatic interactions between the nucleophile and the substrate seem to effectively determine the face selectivities in these molecules. However, there are a few exceptions in which orbital interactions are found to contribute significantly and occasionally reverse the preference dictated by electrostatic effects. The remarkable success of the hydride model calculations, in spite of retaining the unperturbed geometries of the substrates, points to the unimportance of torsional effects and orbital distortions associated with the pyramidalized carbonyl unit in the transition state in most of the substrates considered. Additional experimental results are reported which provide useful calibration for the present computational approach.