Ring Contraction of Bicyclic Lactams: A Molecular Editing Aza-Favorski-Type Approach to Tetrahydroquinoline-2-carboxylic Acids

Abstract

Development of skeletal editing methods offers new horizons for the acceleration of drug discovery. An original aza-Favorski-type approach is described for the ring contraction of benzazepine-2-ones, providing versatile tetrahydroquinoline-2-carboxylic acids. The sequence employing silylation and Pb(OAc)4-promoted oxidative ring contraction affords variously substituted N-protected derivatives in ≤67% yields. The approach can also be applied to higher homologues, although with a lower efficiency.