Use of bis[2-(trialkylsilyl)ethyl]N,N-dialkylphosphoramidites for the synthesis of phosphate monoesters

Abstract

The bis[2-(trimethylsilyl)ethyl]N,N-dialkylphosphoramidites 7a and b and bis[2-(methyldiphenylsilyl)ethyl]N,N-dialkylphosphoramidites 6a and b have been prepared by reaction of the N,N-dialkylphosphorochloridites 5a and b with the appropriate 2-(trialkylsilyl)ethanol. In the presence of 1H-tetrazole, the phosphoramidites 6a, b and 7a, b phosphorylated MeOH, PhCH₂OH, PhCH₂CH₂OH, Me(PhCH₂CH₂)CHOH, 2,3,4,5,6-penta-o-benzyl-myo-inositol and Bu^tOH, to give the phosphites 8a–h. Without isolation, these were oxidised to the corresponding phosphate triesters 9a–h with m-chloroperoxybenzoic acid. Treatment of the triesters 9a–h with tetrabutylammonium fluoride removes only one 2-(trialkylsilyl)ethyl group to give the diesters 10a–h, whereas treatment with a solution of hydrofluoric acid in acetonitrile–water gives the phosphate monoesters 11a–e.