Toward a computational tool predicting the stereochemical outcome of asymmetric reactions. 1. Application to Sharpless asymmetric dihydroxylation.

A reliable and computationally tractable protocol directed at the study of the stereochemical outcome of asymmetric reactions and its application to the Sharpless asymmetric dihydroxylation reaction are proposed. This method, based on a genetic algorithm and molecular mechanics, effectively provides qualitative as well as semiquantitative results and explains the origin of the observed enantioselectivity. For instance, the method reliably predicts reversal of selectivity between similar substrates, unexpected isomers, and even enantio- and diastereoisomeric excess with good accuracy. Two binding modes, closely related to those proposed by Sharpless and Corey, are favored. After comparison with Sharpless' mnemonic device, we propose two alternative interpretations.