Stereoelectronic and conformational effects on the stereochemical course of reduction of bicyclo[3.3.1]nonane 1,3-diketones

Abstract

The stereoselectivity of the reduction of bicyclo[3.3.1]nonane 1,3-diketones was studied. The experimental data of π-facial stereoselection of the reduction of the carbonyl group were successfully rationalized by the application of the exterior frontier orbital extension (EFOE) model. The observed facial diastereoselectivity of the carbonyl reduction of bicyclo[3.3.1]nonane diketones could be reasonably explained by the ground-state facial anisotropy of the frontier orbital extension, steric effects, and the intrinsic reactivity of carbonyl groups. Although the EFOE density and PDAS values predicted the enhanced reactivity at the C-2 carbonyl compared to C-9 carbonyl, transition-state calculations at the B3LYP/6-31+G(d,p) level showed that the reactivity of C-9 and C-2 in a hydride addition to both carbonyl groups should be nearly the same. The EFOE analysis also strongly indicated that in the second hydride reduction step the corresponding oxobicyclononanolates are most likely to be involved in the reduction as the major species rather than the free hydroxyketones. The antiperiplanar effects in the transition states of the LiAlH4 reduction as measured by both the elongation and the natural bond population of the antiperiplanar bonds clearly indicated they should not be an essential factor of the facial diastereoselection of studied diketones.Key words: bicyclo[3.3.1]nonanedione, EFOE model, reduction, stereoselectivity, transition state.