The role of nucleophilic catalysis in chemistry and stereochemistry of ribonucleosideH-phosphonate condensation

Abstract

The efficiency and stereoselectivity of condensation of ribonucleoside 3′-H-phosphonates with alcohols were investigated as a function of amines used for the reaction. It was found that irrespective of the presence or absence of nucleophilic catalysts, the Dynamic Kinetic Asymmetric Transformation (DYKAT) was the major factor responsible for the stereoselective formation of the D_P(S_P) isomers of the H-phosphonate diesters, and a mechanistic rationalization of this observation was proposed. In addition, studies on the reactions carried out in the presence of various bases led to the conclusion that certain sterically hindered pyridines, e.g.2,6-lutidine, may act as nucleophilic catalysts in the condensation of ribonucleoside 3′-H-phosphonates with alcohols.