Diastereospecific synthesis of 2'- or 3'-C-branched nucleosides through intramolecular free-radical capture by silicon-tethered acetylene

Abstract

The intramolecular free-radical trapping by a silicon tethered acetylene function in a ribonucleoside 2a, 2b, 2c, 8a, 8b or 8c gave only the [3.3.0]-cis-fused Z-vinylsiloxane 3a, 3b, 3c, 9a, 9b or 9c (> 90%) in a diastereospecific manner. The temporary silicon connection from the Z-vinylsiloxane was removed by the oxidation to give the 2'- or 3'-C-branched α-keto-β-D-ribonucleoside (~ 85%), which was diastereospecifically reduced to give 1,3-syn diol (> 90%, > 97% ee) [2'- or 3'-C-branched-α-substituted R or S-hydroxymethyl-β-D-ribonucleosides 5a, 5b, 5c, 11a, 11b or 11c]. These are the first examples of highly diastereospecific synthesis of 2'- or 3'-C-branched ribonucleosides, through a 5-trig-exo radical cyclization, using the silicon-tethered approach.