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).

Photoredox-Catalyzed Deformylative 1,4-Addition of 2'-Deoxy-5'- O-phthalimidonucleosides for Synthesis of 5'-Carba Analogs of Nucleoside 5'-Phosphates.

A concise approach for the synthesis of the 5'-carba analogs of nucleoside 5'-phosphates from 2'-deoxy-5'- O-phthalimidonucleosides by a visible-light-mediated deformylative 1,4-addition was developed. This method enabled rapid and facile generation of 4'-carbon radicals of nucleosides. Moreover, this synthetic strategy was applicable to the 5'-carba analogs of nucleoside 5'-phosphates as well as other 5'-carba nucleosides bearing methoxycarbonyl, cyano, and N-methylsulfamoyl groups.