Addressing regio- and stereo-specificity challenges in the synthesis of nucleoside 2',3'-cyclic monophosphate analogs - a rapid and facile synthesis of nucleoside-2',3'-O,O-phosphoro-thioate or -selenoate, and elucidation of the origin of the rare specificity.

A new facile, rapid, stereo- and regio-selective one-pot synthesis of nucleoside-2',3'-O,O-phosphorothioate and selenoate analogs has been developed. This method avoids the need for protection strategies and chiral reagents, chiral metal catalysts, or chiral separations. This synthetic method has been applied to all natural nucleosides (U/A/G/C/T). Furthermore, we have deciphered the origin of the stereo- and regio-selectivity of the reaction.