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

J M Fraile; J I García; V Martínez-Merino; J A Mayoral; L Salvatella

doi:10.1021/ja003695c

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

J Am Chem Soc. 2001 Aug 8;123(31):7616-25. doi: 10.1021/ja003695c.

Authors

J M Fraile¹, J I García, V Martínez-Merino, J A Mayoral, L Salvatella

Affiliation

¹ Departamento de Química Orgánica, Instituto de Ciencia de Materiales de Aragón, C.S.I.C.-Universidad de Zaragoza, Pedro Cerbuna 12, E-50009 Zaragoza, Spain.

PMID: 11480983
DOI: 10.1021/ja003695c

Abstract

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.