Synthesis of oxygen-containing medium and large rings using one-pot combinations of sequential alkene, enyne and alkyne metathesis reactions

The first and second generation Grubbs' catalysts are shown to convert cyclohexane and cyclohexene bis-allyl and allyl propargyl ethers into 6,8-fused bicyclic derivatives by alkene and enyne metathesis reactions, respectively. The corresponding cyclohexane and cyclohexene bis-propargyl ethers are converted into 6,8-fused bicyclic trienes by enyne metathesis when treated with the second generation Grubbs' catalyst. Cyclohexene and norbornene esters bearing two alkyne units undergo alkyne metathesis when treated with molybdenum hexacarbonyl and 2-fluorophenol to give 12-membered ring containing alkynes which subsequently undergo alkene and enyne metathesis reactions when treated with first or second generation Grubbs' catalysts. Both Grubbs' catalysts are shown to be compatible with the reagents and conditions used for the molybdenum alkyne metathesis catalyst, thus allowing the two catalysts to be used in a one-pot process involving alkyne, enyne and alkene metathesis transformations.