Gamma-Lactams and the Reformatsky Reaction: New Tricks for an Old Reaction

A large fraction of the world's antibiotic arsenal depends on the 4-membered beta-lactam ring as the active functional group. An alternative to the beta-lactam is the 5-membered gamma-lactam structure, which has formed the core of several compounds that have been reported to possess antibiotic activity. The use of Reformatsky-type chemistry to form beta-lactams has been known since the 1940's, but to date Reformatsky-type chemistry has not been reported for the preparation of gamma-lactams. In principle, the reaction between ketones or aldehydes based on alpha-amino acids and Reformatsky reagents should cyclize and afford gamma-lactams directly. In this talk we wish to report on our success to date.