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-dosing 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.