EFFICIENT SYNTHESIS OF BICYCLIC LACTONES VIA TUNGSTEN-MEDIATED INTRAMOLECULAR CYCLOALKENATION

A series of tungsten-η1-alkynols tethered with a dimethylacetal, methyl ketone, or trimethoxymethane group are prepared. Treatment of these functionalized tungsten-alkynols with BF3·Et2O leads to intramolecular cycloalkenation, producing bicyclic tungsten-oxacarbeniums in high yields. Air oxidation of these oxacarbenium salts produces unsaturated bicyclic lactones in good yields. The lactone products include δ- and e-lactones fused with five-, six- and seven-membered carbocyclic rings. The preceding bicyclic tungsten-η1-oxacarbeniums are highly reactive toward organocuprates, Grignard reagents, and diazomethane, leading to demetalation to give various derivatives of bicyclic lactones. A short synthesis of (±)-mitsugashiwalactone is developed based on this method.