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'-<i>O</i>,4'-<i>C</i>- and 3'-<i>O</i>,4'-<i>C</i>-bridged nucleosides. This operationally simple approach can be applied to the few-step syntheses of 6'<i>S</i>-methyl-2'-<i>O</i>,4'-<i>C</i>-ethylene-bridged 5-methyluridine (6'<i>S</i>-Me-ENA-T) and <i>S</i>-constrained ethyl-bridged 5-methyluridine (<i>S</i>-cEt-T).