Can the p - facial selectivity of solvation be predicted by atomistic simulation?

This work is concerned with the rationalization and predicton of solvent and temperature effects in nucleophilic addition to alpha-chiral carbonyl compounds leading to facial diastereoselectivity. We study, using molecular dynamics simulations, the facial solvation ol (R)-2-phenyl-propionaldehyde in n-pentane and n-octane at a number ol temperatures and compare it with experimental selectivity data tor the nBuLi addition leading to syn- and anti-(2R)-2-phenyl-3-heptanol which give nonlinear Eyring plots with the presence ol inversion temperatures. We have found from simulations that the facial solvation changes with temperature and alkane. Moreover, by introducing a suitable molecular chiraiity index we have been able to predict break temperatures for the two solvents within less than 20 degrees of the inversion temperatures experimentally observed in the diastereoselective nBuLi addition. We believe this could lead to a viable approach for predicting inverson temperatures and other subtle solvent effects in a number of stereoselective reactions.