An Asymmetric Aldol−Ring-Closing Metathesis Strategy for the Enantioselective Construction of Oxygen Heterocycles:  An Efficient Approach to the Enantioselective Synthesis of (+)-Laurencin

A strategy is described for the enantioselective construction of medium-ring cyclic ethers by merging the asymmetric aldol addition of glycolates with a ring-closing metathesis reaction. Cyclic ethers of seven-, eight-, and nine-membered rings are readily available through a ring-closing metathesis without cyclic conformational constraints, by exploiting the acyclic conformational bias of the gauche effect. A short formal synthesis of the eight-membered ether (+)-laurencin, a red algae metabolite, has been accomplished utilizing the aldol−metathesis combination.