Enantioselective Synthesis of (+)-l-733,060 and (+)-CP-99,994: Application of an Ireland-Claisen Rearrangement/Michael Addition Domino Sequence

An efficient asymmetric synthesis of (+)-L-733,060, (-)(2S,3R)-1 and (+)-CP-99,994, starting from a Baylis-Hillman adduct, is described. The key steps include a novel domino reaction: stereoselective Ireland-Claisen rearrangement, asymmetric Michael addition, and piperidone ring formation through a one-pot reaction hydrogenolysis/lactamization and a stereoselective inversion of a hydroxy group.