title: Can the pi-facial selectivity of solvation be predicted by atomistic simulation?
abstract: This work is concerned with the rationalization and prediction 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 of (R)-2-phenyl-propionaldehyde in n-pentane and n-octane at a number of temperatures and compare it with experimental selectivity data for the nBuLi addition leading to syn- and anti-(2R)-2-phenyl-3-heptanol, which give nonlinear Eyring plots with the presence of inversion temperatures. We have found from simulations that the facial solvation changes with temperature and alkane. Moreover, by introducing a suitable molecular chirality index we have been able to predict break temperatures (T(CI)) 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 inversion temperatures and other subtle solvent effects in a number of stereoselective reactions.
authors.affiliation: Dipartimento di Chimica Fisica e Inorganica and Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali, Università di Bologna, Viale Risorgimento 4, 40136 Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Berardi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Cainelli
authors.forename: Paola
authors.initials: P
authors.lastname: Galletti
authors.forename: Daria
authors.initials: D
authors.lastname: Giacomini
authors.forename: Andrea
authors.initials: A
authors.lastname: Gualandi
authors.forename: Luca
authors.initials: L
authors.lastname: Muccioli
authors.forename: Claudio
authors.initials: C
authors.lastname: Zannoni