NUCLEOSIDE H-PHOSPHONATES .16. P-31 NMR-STUDIES ON THE TRANSFORMATIONOF NUCLEOSIDE H-PHOSPHONATE MONOESTERS INTO A MONOFUNCTIONAL TERVALENT INTERMEDIATE, NUCLEOSIDE ACYL SILYL PHOSPHITE

Transformation of nucleoside 3'-H-phosphonate monoester 1 into the cor responding nucleoside pivaloyl dagger trimethylsilyl phosphite 3 by si lylation of the in situ formed phosphonic-acyl mixed anhydride 2 with trimethylsilyl chloride (TMSCl), has been investigated using P-31 NMR spectroscopy. The conversion was found to be a complex process and its efficiency, due to the involvement of several reversible reactions, d epended strongly on the ratio of the reagents used. The tervalent inte rmediate 3 was found to be unstable under the reaction conditions and underwent at least three parallel reactions, i.e. to the nucleoside tr imethylsilyl chlorophosphite 6, the nucleoside pivaloyl chlorophosphit e 7 and to the monosilylated nucleoside H-phosphonate 5. On the basis of the P-31 NMR data the most important factors affecting the stabilit y of 3 were delineated and new reaction conditions for the efficient f ormation of the monofunctional phosphite derivative 3 from H-phosphona te monoesters 1 were developed.