Stereo- and Regioselective Introduction of 1- or 2-Hydroxyethyl Group via Intramolecular Radical Cyclization Reaction with a Novel Silicon-Containing Tether. An Efficient Synthesis of 4'alpha-Branched 2'-Deoxyadenosines(1)

Satoshi Shuto; Makiko Kanazaki; Satoshi Ichikawa; Noriaki Minakawa; Akira Matsuda

doi:10.1021/jo971703a

Stereo- and Regioselective Introduction of 1- or 2-Hydroxyethyl Group via Intramolecular Radical Cyclization Reaction with a Novel Silicon-Containing Tether. An Efficient Synthesis of 4'alpha-Branched 2'-Deoxyadenosines(1)

J Org Chem. 1998 Feb 6;63(3):746-754. doi: 10.1021/jo971703a.

Authors

Satoshi Shuto¹, Makiko Kanazaki, Satoshi Ichikawa, Noriaki Minakawa, Akira Matsuda

Affiliation

¹ Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060, Japan.

PMID: 11672069
DOI: 10.1021/jo971703a

Abstract

An efficient method for the synthesis of 4'alpha-branched 2'-deoxyadenosines 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 adeninenucleoside derivative 17 with Bu(3)SnH 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 conditions. With a lower Bu(3)SnH concentration, the reaction gave the 4'alpha-(2-hydroxyethyl) derivative 21, via a 6-endo-radical cyclized product 20, as the sole product in 72% yield. The reaction of 17 in the presence of excess Bu(3)SnH gave 19 quantitatively, via a 5-exo-cyclized product 18, as a diastereomeric mixture. The reaction mechanism was examined using Bu(3)SnD. The results demonstrated that the 5-exo cyclized (3-oxa-2-silacyclopentyl)methyl radical (C) was formed initially which was trapped when the concentration of Bu(3)SnH(D) was high enough. With lower concentrations of Bu(3)SnH(D), radical C rearranged into the ring-enlarged 4-oxa-3-silacyclohexyl radical (D) which was then trapped with Bu(3)SnH(D) to give endo-cyclized product F.