Acyl Radical Addition to Activated Olefins: A Stereocontrolled Route to Polysubstituted Tetrahydrofurans and Lactones, and Application to the Total Synthesis of (+)-No. 2106 A

The addition of acyl radicals to alpha,beta-unsaturated esters, followed by acetalization and reduction of the resulting hemiacetal was shown to provide a straightforward access to tetrahydrofurans, and fused tetrahydrofuran-lactones in good yield with high 1,3-stereocontrol. Similar addition reactions to five-and six-membered-ring alpha-methylenelactones led to trisubstituted lactones with high diastereocontrol, using (Me3Si)(3)SiH as hydrogen-atom-transfer agent. This strategy was applied to the first total synthesis of (+)-No. 2106 A, a fused THF-lactone produced by an endophytic fungus isolated from the seeds of the mangrove Avicennia marina.