Alkoxyl radical addition to acceptor-substituted carbon–carbon double bonds

Alkoxyl radicals add 5-exo-trig selectively to cyano- and methoxycarbonyl-substituted carbon–carbon double bonds, to afford α-acceptor-α-tetrahydrofuryl-2-methyl radicals. Trapping of cyclized radicals by Bu3SnD furnishes products of site-specific deuterium-labeling in α-position to the acceptor group. In intramolecular competition experiments, alkoxyl radicals add similarly fast to a cyano-substituted double bond than to a terminal alkene, but by a factor >25 faster to an enol ether. The nucleophilic component of alkoxyl radical reactivity opens an interesting new access to tetrahydrofuryl amino acids via C,O-cyclization, as shown by synthesis of a N,O-protected 5-phenyltetrahydrofuryl-2-methyl glycine.