Computational studies on the copper(II) catalyzed Michael reaction

We report computational results on the mechanism of the copper(II) catalyzed Michael addition of enamines formed from β-diketones and amino acids. The results suggest that the enamine gets deprotonated upon coordination to Cu2+, and that it occupies three coordination sites of a square planar geometry. The formation of this coordinated aza-enolate is facilitated by basic co-ligands such as acetate which take over the enamine proton. In this rather rigid structure, the former amino acid side chain assumes an angular position which leads to preferred attack of the Michael acceptor from the non-hindered side of the coordination plane and the formation of a preferred enantiomer if one starts from a prochiral diketone. This discrimination becomes effective because the Michael acceptor, although only loosely bound to the complex before carbon-carbon bond formation, attaches itself to a “free” axial position of the copper centre during the reaction.

Graphical abstractThe copper(II) catalyzed Michael reaction of enamines derived from 1,3-diketones and amino acids most likely involves as a key intermediate an aza-enolate coordinated to three sites of a square planar copper centre.Figure optionsDownload full-size imageDownload as PowerPoint slide