A COMBINED SYNTHETIC AND AB-INITIO STUDY OF CHIRAL OXAZABOROLIDINES STRUCTURE AND ENANTIOSELECTIVITY RELATIONSHIPS

Investigations into the relationship of oxazaborolidine structure to t he enantioselectivity obtained in the reduction of prochiral ketones r evealed the intrinsic power of the molecular recognition element in th e catalytic reduction. This molecular recognition, two-point binding o f borane and the ketonic oxygen atom by the oxazaborotidine, assembles a trimolecular complex which provides high enantiomeric excess. Enant iomeric excess was demonstrated to be dependent on the extent to which one oxazaborolidine face was precluded from attaining two-point bindi ng and on nonbonded interactions that developed during formation of th e borane-oxazaborolidine complex. As a result, erythro-substituted oxa zaborolidines were demonstrated to be useful catalysts for enantiosele ctive reduction of prochiral ketones. Ab initio molecular orbital calc ulations have been used to locate possible complexes and transition st ate assemblies that correspond to catalyst-borane and the trimolecular complex on a proposed reduction pathway. Geometry optimizations were carried out at the 3-21G, 6-31G(d), and MP2/6-31G(d) levels of theory. Correlation energies were computed via Moller-Plesset perturbation th eory to the second order (MP2). Relative activation energies establish correctly the observed enantioselectivity of the two best oxazaboroli dine catalysts in this study. Additionally, the diminished enantiosele ctivity of N-methyl-substituted catalysts was traced to conformational changes in the exo transition state. Though the relative energies obt ained from the various levels of theory are similar, absolute complexa tion and activation energies are found to vary considerably with the l evel of theory employed. The existence of key intermediates was found to depend on the level of theory.