Prediction of facial diastereoselection with the exterior frontier orbitalextension model (EFOE model)

Based on the simple assumption that pi -facial diastereoselection should be originated from the difference in the magnitude of the reaction driving fo rce over the two faces of the pi -plane, a new theoretical model is propose d for the prediction of faical diastereoselection. According to the Salem-K lopman equation, two quantities - steric effects (Ist term) and the spatial extension of frontier orbital of a substrate ketone (3rd term) - are quant itatively evaluated as the pi -plane-divided accessible space (PDAS) and th e exterior frontier orbital extension density (EFOE density). The latter is obtained by integrating the frontier orbital (LUMO of a ketone) extension over one side of the pi -plane in the exterior area of the van der Waals su rface of the ketone under the specific criteria that the driving force vect or located on the hydride should be maximally directed toward the carbonyl carbon. Numerous cases of facial diastereoselectivity of hydride reduction including ketones with polar substituents, heterocyclic systems, symmetric bi- or tricyclic ketones, imines, iminium ion are successfully explained by these two new simple quantities. These results as well as quantitative eva luation of transition effects (mainly the antiperiplanar hyperconjugative s tabilization involving the incipient bond) strongly suggest that the orbita l interaction between reactants generated in the initial stage rather than transition state effects must be the essential process of diastereoselectio n.