Protection of Phosphonate Function by Means of Ethoxycarbonyl Group. A New Method for Generation of Reactive Silyl Phosphite Intermediates

Nucleoside ethoxycarbonylphosphonates were prepared by condensation of appropriately protected nucleosides with ethoxycarbonylphosphonic acid. They were easily converted by treatment with 1 M NaOH followed by trimethylsilylation to highly reactive bis(trimethylsilyl) nucleoside phosphite intermediates which were allowed in situ to react with water, diphenyl disulfide, 2,2′-dipyridyl disulfide, and aldehydes to afford the corresponding nucleoside phosphonates, nucleoside S-phenyl phosphorothioates, nucleoside phosphates, and nucleoside α-hydroxy phosphonates in good yields, respectively. The nucleoside phosphonates were further converted to nucleosides under mild acidic conditions. Thus, the ethoxycarbonyl group proved to serve as a versatile protecting group for not only H–P(O) but also HO–P(O) and hydroxyl groups of sugars.