A versatile intermediate for the synthesis of 3′-substituted 2′,3′-didehydro-2′,3′-dideoxyadenosine (d4A): preparation of 3′-C-stannyl-d4A via radical-mediated desulfonylative stannylation

A method is described for the introduction of a tributylstannyl group to the 3′-position of 2′,3′-didehydro-2′,3′-dideoxyadenosine (: d4A). Transalkoxylation of Bu3SnOMe with d4A and subsequent anionic O→C stannyl migration gave 3′-C-tributylstannyl-d4A (), but only in a low yield. An alternative route involves several reactions starting from 9-[2,3-anhydro-5-O-(tert-butyldimethylsilyl)-β-d-ribofuranosyl]-N6-pivaloyladenine (): ring opening with NaSPh, oxidation of the 3′-C-phenylthio group, removal of the N6-pivaloyl group, 2′-O-mesylation, elimination of methanesulfonic acid, and tin radical-mediated substitution of the 3′-C-benzenesulfonyl group. The overall yield of this approach was 55% from . The synthetic utility of 5′-O-(tert-butyldimethylsilyl)-3′-C-tributylstannyl-d4A () thus obtained was briefly exemplified by the preparation of some 3′-substituted analogues (: I, Br, Ph, vinyl, and phenylethynyl).