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

5 years ago

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

Yurie Takayama, Martin C. Schwarzer, Seiji Mori, Tomohiro Iwai, Takaoki Ishii, Hirohisa Ohmiya, Kenji Monde, Tohru Taniguchi, Masaya Sawamura

Prolinol–phosphine chiral ligands enabled highly enantioselective copper-catalyzed intermolecular alkyne–nitrone coupling (Kinugasa reaction) to produce 1,3,4-trisubstituted chiral β-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. β-Lactam synthesis: Prolinol–phosphine chiral ligands enabled highly enantioselective copper-catalyzed intermolecular alkyne–nitrone coupling (Kinugasa reaction) to produce 1,3,4-trisubstituted chiral β-lactams. 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.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201702070