Mechanisms of reaction of sulfate esters: A molecular orbital study of associative sulfuryl group transfer, intramolecular migration, and pseudorotation

Molecular orbital calculations for the reactions of 2-hydroxyethyl sulfate in neutral and ionized forms were used to examine the free energy profiles for intramolecular sulfuryl group transfer in the gas phase. Detailed analysis of reaction dynamics yielded structures for trigonal bipyramidal pentacoordinate reaction intermediates and for transition states at the MP2/6-31+G*//HF/3-21+ G(*) and MP2/6-31+G*//HF/3-21G(*) levels of calculation for anionic and neutral species, respectively. Application of a continuum dielectric model to these structures provided estimated free energy profiles for reaction in aqueous solution. Comparison with the reactivity of phosphate esters suggests that the empirical guidelines for reactions of phosphates may, in large part, be extended to reactions of sulfate esters. It is predicted that the activation barriers to intramolecular sulfuryl group transfer will be large, in accord with experiment and in contrast with phosphoryl transfer. The explanation is based upon (1) the requirement for the energetically unfavorable protonation of the sulfate moiety for nucleophilic attack on sulfur; and (2) the relatively higher energy of the pentacoordinate relative to the tetracoordinate state for S over P species. However, Berry pseudorotation is facile and does not present a barrier to reaction. The calculations suggest that nucleophilic substitution of alkoxide on the protonated sulfate moiety has a low activation barrier and may occur with inversion or retention of stereochemistry at sulfur.