Nucleoside H-phosphonates. Part 16.31P NMR studies on the transformation of nucleoside H-phosphonate monoesters into a monofunctional tervalent intermediate, nucleoside acyl silyl phosphite

Abstract

Transformation of nucleoside 3′-H-phosphonate monoester 1 into the corresponding nucleoside pivaloyl; trimethylsilyl phosphite 3 by silylation of the in situ formed phosphonic–acyl mixed anhydride 2 with trimethylsilyl chloride (TMSCl), has been investigated using 31P NMR spectroscopy. The conversion was found to be a complex process and its efficiency, due to the involvement of several reversible reactions, depended strongly on the ratio of the reagents used. The tervalent intermediate 3 was found to be unstable under the reaction conditions and underwent at least three parallel reactions, i.e. to the nucleoside trimethylsilyl chlorophosphite 6, the nucleoside pivaloyl chlorophosphite 7 and to the monosilylated nucleoside H-phosphonate 5. On the basis of the 31P NMR data the most important factors affecting the stability of 3 were delineated and new reaction conditions for the efficient formation of the monofunctional phosphite derivative 3 from H-phosphonate monoesters 1 were developed.