Scheme 1.

General reaction scheme for the (associative) reverse of dianionic in-line methanolysis of ethylene phosphate: a model for RNA phosphate transesterification under alkaline conditions. “React.”, “ETS”, “Int.”, “LTS”, and “Prod.” stand for reactant, early transition state, intermediate, late transition state, and product, respectively. In the present work, the native reaction in the scheme is studied in both gas and solution phases as well as reactions that have single sulfur substitutions in the bridging 3′- (S3′) and leaving group 5′-positions (S5′). Note: as revealed by our calculations, not all of the states in the scheme exist for every reaction (see text for details).