Computational mechanistic studies on enantioselective pybox-ruthenium-catalyzed cyclopropanation reactions

The mechanism of the ruthenium(II)-catalyzed cyclopropanation reaction of olefins with diazo compounds has been extensively investigated for a medium-sized reaction model by means of DFT calculations. The starting ethylene complex of the dichloro[(E)-2-(methylimino)-N-(1E,2E)-2-(methyliminoethylidene)ethanamine]ruthenium(II) catalyst undergoes a ligand exchange with methyl diazoacetate to yield a reaction intermediate, which subsequently undergoes nitrogen extrusion to generate a ruthenium-carbene complex. The cyclopropanation step takes place through a direct carbene addition of the ruthenium carbene species to the olefin double bond to yield a catalyst-product complex, which can finally regenerate the starting complex. Stereochemical considerations on a "real-world" system-the cyclopropanation reaction of styrene with methyl diazoacetate, catalyzed by a chiral pyboxruthenium complex-have been investigated by means of full quantum-mechanical calculations on this reaction. The theoretical results show excellent agreement with the experimental observations and allow a mechanistic explanation to be advanced concerning the origin of the stereoselectivities observed. The explanation is based on the intermolecular steric interaction between the alkene and one of the isopropyl groups of the chiral ligand in the disfavored approaches. The model developed also provides an explanation for some particular stereoelectronic behavior of pybox ligands, such as the remote stereoelectronic effects and the good enantioselectivities described with C-1-pybox ligands.