Enantioselective Synthesis of β-lactams

The group of Fu at MIT has improved a reaction known as the Kinugasa reaction, involving the cycloaddition of acetylenes with nitrones (Lo MCM et al, J Am Chem Soc, 2002, 124, 4572). By using a copper catalyst and a bisazo-ferrocene ligand, high yields and ee of the β-lactam product are produced. The process is generally cis-celective, and is quite versatile, although some yields are only in the 40-60% range.

An earlier communication from the same group (Hodous B L et al, J Am Chem Soc, 2002, 124, 1578) had shown that β-lactams can be made enantioselectively from ketenes and imines using a planar-chiral heterocycle as catalyst.