Asymmetric Synthesis of ß-Lactams through Copper-Catalyzed Alkyne-Nitrone Coupling with a Prolinol-Phosphine Chiral Ligand.

Prolinol-phosphine chiral ligands enabled highly enantioselective copper-catalyzed intermolecular alkyne-nitrone coupling (Kinugasa reaction) to produce 1,3,4-trisubstituted chiral ß-lactams. A high level of enantiocontrol was achieved not only with aryl- or alkenylacetylenes but also with alkylacetylenes, which were important but unfavorable substrates in the previously reported protocols. Two-point hydrogen bonding between the chiral ligand and the nitrone oxyanion consisting of O-H⋅⋅⋅O and C(sp3 )-H⋅⋅⋅O hydrogen bonds is proposed.