Theoretical investigations of the influence of pressure on the selectivityof the Michael addition of biphenylmethaneamine to stereogenic crotonates

SIBFA (sum of interactions between fragments ab initio computed) molecular mechanics systematics has been modified to take into account the effect of pressure on intra- and intermolecular energies. The van der Waals radii are related to the pressure, using Bridgman results on the variation of crysta l volume, on one hand, and the relation between the volume of an atom and i ts van der Waals radius on the other. This procedure produces a decrease of the volume of the systems considered. The modified systematics is used for the study of the conformation at 1 atm and 15 kbar of two stereogenic crot onates and of the complexes formed by these two molecules with the diphenyl methaneamine and the three solvent molecules present in the experiment. The results obtained show that in the case of NMECC Pa the diastereoselectivit y induced by high pressure and by the presence of methanol proceeds from an important stabilization of the pro-R reactive complex in which the crotona te has a stacked-transoid conformation. This stabilization is mainly due to intermolecular interactions. In the case of the second crotonate considere d, NMCC Ib, our results indicate that pressure induces a stabilization of t he pro-R and pro-S complexes having the axial conformation for which the re action exhibits little diastereoselectivity in qualitative agreement with e xperimental data. This study tends to show that it is possible to account t heoretically for the influence of pressure on molecular conformation and/or complex structure, using a molecular mechanics method that is able to take into account the variation of volumes of the different entities present in the system studied.