Stereoselective Synthesis of Medium-Sized Cyclic Ethers by Sequential Ring-Closing Metathesis and Tsuji–Trost Allylation

Fully functionalized medium-sized cyclic ethers, of the type found in fused polyether natural products, have been prepared by sequential ring-closing diene metathesis, conversion of the resulting cyclic enone into an allylic enol carbonate, and Tsuji-Trost allylation using a chiral palladium complex. Very high levels of diastereocontrol, favoring the diastereomer in which there is a cis relationship between the allyl group at C-2 of the medium-ring ether and the substituent at C-7/C-8, are obtained in cases where catalyst control and substrate control are matched.