Hydrolysis of Bifunctional Silyl Groups

Abstract

Hydrolysis of 3', 5'-0-(di-t-butylsilanediyl)deoxyribonucleosides and ribonucleosides was investigated in the presence of tetrabutylammonium fluoride in THF. The ribonucleoside derivatives were more smoothly converted to the parent nucleosides than the corresponding deoxyribonucleoside derivatives regardless of the kind of the base. A close ex amination of the desilylation reaction of the thymidine derivative revealed that the desilylation proceeded in two stages and partially hydrolyzed compounds, 5'- and 3'-O-(di-t-butylhydroxysilyl)thymidine, were found as by-products in the second stage. The masking of the 3'-hydroxyl function of 5'-O-(di-t-butylhydroxysilyl)thymidine by an acetyl group markedly facilitated the cleavage of the silyl group. This indicates that a hydrogen bonding between a fluoride anion and the 3'-hydroxyl group interferes with the fluoride attack at the 5'-silyl po sition. In the case of the ribonucleoside derivatives, 2'-O-hydroxysilyl derivatives were also found as well as 5'- and 3'-O-hydroxysilyl derivatives. The occurrence of the 2'-silyl compound suggests the existence of a 2', 3'-cyclic silyl intermediate which contains reactive 1, 3, 2dioxasilacyclopentane structure. The mechanism of desilylation via the 2', 3'-cyclic silanediyl intermediate has been proposed for the ribonucleoside derivatives.