STEREOSELECTIVE AND REGIOSELECTIVE INTRODUCTION OF 1-HYDROXYETHYL OR 2-HYDROXYETHYL GROUP VIA INTRAMOLECULAR RADICAL CYCLIZATION REACTION WITH A NOVEL SILICON-CONTAINING TETHER - AN EFFICIENT SYNTHESIS OF 4'ALPHA-BRANCHED 2'-DEOXYADENOSINES

An efficient method for the synthesis of 4'alpha-branched 2'-deoxyaden osines starting from 2'-deoxyadenosine has been developed utilizing a novel radical cyclization reaction with a silicon tether. The radical reaction of 4'beta-phenylseleno)-3'-O-diphenylvinylsilyl adeninenucleo side derivative 17 with Bu3SnH and AIBN, followed by Tamao oxidation, gave selectively either the 4'alpha-(2-hydroxyethyl) derivative 21 or 4'alpha-(1-hydroxyethyl) derivative 19, depending on the reaction cond itions. With a lower Bu3SnH concentration, the reaction gave the 4'alp ha-(2-hydroxyethyl) derivative 21, via a 6-endo-radical cyclized produ ct 20, as the sole product in 72% yield. The reaction of 17 in the pre sence of excess Bu3SnH gave 19 quantitatively, via a 5-exo-cyclized pr oduct 18, as a diastereomeric mixture. The reaction mechanism was exam ined using Bu3SnD. The results demonstrated that the 5-exo cyclized (3 -oxa-2-silacyclopentyl)methyl radical (C) was formed initially which w as trapped when the concentration of Bu3SnH(D) was high enough. With l ower concentrations of Bu3SnH(D), radical C rearranged into the ring-e nlarged 4-oxa-3-silacyclohexyl radical (D) which was then trapped with Bu3SnH(D) to give endo-cyclized product F.