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. In the present work, the native reaction shown in the scheme is studied as well as reactions that incorporate single thio substitutions in the bridging 3′ (denoted S3′) and leaving group 5′ (denoted S5′) positions. Note: as revealed by the computational analysis herein, not all of the states shown in the scheme exist for every reaction (see text for details).