Synthesis of pyrimidine 2 '-deoxy ribonucleosides branched at the 2 '-position via radical atom-transfer cyclization reaction with a vinylsilyl groupas a radical-acceptor tether

Recently, we developed a regio- and stereoselective method for introducing a vinyl group at the position beta to a hydroxyl group in halohydrins or al pha -phenylselenoalkanols via a radical atom-transfer cyclization reaction with a vinylsilyl group as a temporary connecting radical-acceptor tether. The synthesis of 2'-deoxy-2'-C-vinyl- and 2'-deoxy-2'-C-hydroxymethyluridin es (7 and 8, respectively) and the corresponding 2'-deoxycytidine congeners (10 and 11, respectively), which were designed as potential antitumor and/ or antiviral agents, was achieved using this radical atom-transfer cyclizat ion as the key step. When the 2'-deoxy-2'-iodo-5'-O-monomethoxytrityl (MMTr ) uridine derivative 19a, bearing a vinylsilyl group at the 3'-hydroxyl gro up, was heated with (Me3Sn)(2) and AIBN in benzene, the corresponding radic al atom-transfer product was generated, which in turn was successively trea ted with tetrabutylammonium fluoride and TBSCl/imidazole to give the desire d 2'-deoxy-5'-O-MMTr-3'-O-TBS-2'-C-vinyluridine (25). Compound 25 was succe ssfully converted into the target 2'-deoxy-2'-branched pyrimidine ribonucle osides 7, 8, 10, and 11.