Asymmetric synthesis of lactams mediated by copper(I) complexes

The asymmetric synthesis of β- and γ-lactams is a center of interest for chemists due to their biological and pharmaceutical applications. The asymmetric and diastereoselective synthesis of β-lactams through Kinugasa reaction, a (3+2) cycloaddtion reaction between a nitrone and a terminal alkyne and catalyzed by copper(I) complexes is studied. A diastereoselective version of this reaction is developed using NHC copper catalysts. An asymmetric version of this reaction is studied as well. Furthermore, a double Michael domino cyclization process catalyzed by a copper(I) catalyst is examined. This methodology allows the formation of γ-and δ-lactams in one step. Starting from substrates comprising two Michael acceptors, a double Michael addition mechanism is expected to form the desired products. The same substrates are also subjected to Morita-Baylis-Hilman reaction conditions to provide α-methylene-γ-lactams which present an interesting class of compounds with important biological activities. Besides, an illustration of a synthetic pathway to produce unprecedented dinuclear copper acetylide diphosphine complexes is demonstrated. These complexes are present with one phosphine of a given ligand bridging to one copper atom while the other phosphine bridges to the other copper atom.(SC - Sciences) -- UCL, 201