Theoretical (DFT) insights into the mechanism of copper-catalyzed cyclopropanation reactions. Implications for enantioselective catalysis

The mechanism of the copper(I)-catalyzed cyclopropanation reaction has been extensively investigated for a medium-size reaction model by means of B3LYP/6-31G(d) calculations. The starting ethylene complex of the N,N‘-dimethylmalonaldiimine−copper (I) catalyst undergoes a ligand exchange with methyl diazoacetate to yield a reaction intermediate, which subsequently undergoes nitrogen extrusion to generate a copper−carbene complex. The cyclopropanation step takes place through a direct carbene insertion of the metal−carbene species to yield a catalyst−product complex, which can finally regenerate the starting complex. The stereochemical predictions of a more realistic model (by considering a chiral bis(oxazoline)−copper (I) catalyst) have been rationalized in terms of steric repulsions, showing good agreement with experimental data.This work was made possible by the generous financial support of the Comisión Interministerial de Ciencia y Tecnología (Project MAT99-1176).Peer reviewe