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.

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′-O,4′-C- and 3′-O,4′-C-bridged nucleosides. This operationally simple approach can be applied to the few-step syntheses of 6′S-methyl-2′-O,4′-C-ethylene-bridged 5-methyluridine (6′S-Me-ENA-T) and S-constrained ethyl-bridged 5-methyluridine (S-cEt-T).