A Systematic Study of the Synthesis of 2′-Deoxynucleosides by Mitsunobu Reaction

The Mitsunobu reaction has emerged as an important alternative for the preparation of synthetic 2'-deoxynucleosides, which have various biological and biotechnological applications. In this work, the Mitsunobu-based synthesis of 2'-deoxynucleosides was systematically studied. The effect of phosphine, azodicarbonyl reagent, and solvent on the product yield and alpha/beta ratio was investigated, and the highest yield and beta-selectivity were obtained using (n-Bu) 3P and 1,1'-(azodicarbonyl) dipiperidine in DMF. The reaction was successfully applied to various nucleobase analogues.