Theoretical insights into the role of a counterion in copper-catalyzed enantioselective cyclopropanation reactions.
The effect of a coordinating counteranion on the mechanism of Cu(I)-catalyzed cyclopropanation has been investigated extensively for a medium-sized reaction model by means of theoretical calculations at the B3LYP/6-31G(d) level. The main mechanistic features are similar to those found for the cationic (without a counteranion) mechanism, the rate-limiting step being nitrogen extrusion from a catalyst-diazoester complex to generate a copper-carbene intermediate. 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. However, the presence of the counteranion has a noticeable influence on the calculated geometries of all the intermediates and transition structures. Furthermore, the existence of a preequilibrium with a dimeric form of the catalyst, together with a higher activation barrier in the insertion step, explains the lower yield of cyclopropane products observed experimentally in the presence of chloride counterion. The stereochemical predictions of a more realistic model (made by considering a chiral bis(oxazoline)-copper(i) catalyst) have been rationalized in terms of the lack of significant steric repulsions, and the model shows good agreement with the low enantioselectivities observed experimentally for these kinds of catalytic systems.
Fraile
José M
JM
Departamento de Química Orgánica, Instituto de Ciencia de Materiales de Aragón, C.S.I.C.-Universidad de Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain.
García
José I
JI
Gil
María J
MJ
Martínez-Merino
Víctor
V
Mayoral
José A
JA
Salvatella
Luis
L