Generation of 4'-Carbon Radicals via 1,5-Hydrogen Atom Transfer for the Synthesis of Bridged Nucleosides.

The rapid and facile generation of 4'-carbon radicals from oxime imidates of nucleosides via 1,5-hydrogen atom transfer induced by iminyl radicals was developed. The cyclization of 4'-carbon radicals with olefins, followed by the hydrolysis of imidate residues, provided various 2'-,4'-- and 3'-,4'--bridged nucleosides. This operationally simple approach can be applied to the few-step syntheses of 6'-methyl-2'-,4'--ethylene-bridged 5-methyluridine (6'-Me-ENA-T) and -constrained ethyl-bridged 5-methyluridine (-cEt-T).