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

Abstract

A method is described for the introduction of a tributylstannyl group to the 3′-position of 2′,3′-didehydro-2′,3′-dideoxyadenosine ( 2 : d4A). Transalkoxylation of Bu 3SnOMe with d4A and subsequent anionic O→C stannyl migration gave 3′- C-tributylstannyl-d4A ( 5 ), 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]- N 6-pivaloyladenine ( 14 ): ring opening with NaSPh, oxidation of the 3′- C-phenylthio group, removal of the N 6-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 14 . The synthetic utility of 5′- O-( tert-butyldimethylsilyl)-3′- C-tributylstannyl-d4A ( 18 ) thus obtained was briefly exemplified by the preparation of some 3′-substituted analogues ( 19– 23 : I, Br, Ph, vinyl, and phenylethynyl).