Origin of π-facial stereoselection in nucleophilic additions of adamantanones. A new interpretation based on the exterior frontier orbital extension model

Abstract

The experimental data of π-facial stereoselection of 5-substituted adamantan-2-ones, 5-aza-adamantan-2-ones, and nor- and homo-adamantanones have been successfully rationalized by the exterior frontier orbital extension model (EFOE model). The values of π-plane-divided accessible space (PDAS), which represents simple summation of the π-plane-divided exterior three-dimensional space nearest to the reaction center outside the van der Waals surface, showed that the adamantanone system is sterically biased and sterically much more demanding than cyclohexanone. The PDAS values indicated that in most cases steric effects are responsible for π-facial stereoselection except for a series of 5-aryladamantan-2-ones, the facial stereoselection of which was found to be orbital-controlled. In most cases, the facial differences in the frontier orbital (LUMO) extension as quantified by the EFOE density were marginal, but were consistent with experimental stereoselectivity except for a few cases with electron-withdrawing substituents. The structures of the transition states of a few 5-substituted adamantan-2-ones with LiAlH4 (B3LYP/6−31+G(d)) have shown that (1) hyperconjugative anti-periplanar stabilization effects involving an incipient bond (AP effects) are much larger in adamantan-2-one than in cyclohexanone, in spite of enhanced reactivity with hydride of the latter, (2) the facial differences of AP effects are marginal and (3) they often operate against observed stereoselectivity.