Theoretical Insights into the Role of a Counterion in Copper‐Catalyzed Enantioselective Cyclopropanation Reactions

Abstract

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.

Supported Ionic‐Liquid Films (SILF) as Two‐Dimensional Nanoreactors for Enantioselective Reactions: Surface‐Mediated Selectivity Modulation (SMSM)

“…The use of chloride as the counterion in cyclopropanation reactions carried out in molecular solvents leads to much worse results due to the influence of the counterion on the geometry of the transition state. [14] However, we have shown that, in ionic liquids, the anion of the solvent plays the role of counterion.…”

“…This phenomenon has been experimentally demonstrated in this reaction, as complexes prepared with copper triflate and copper chloride display the same results when used in ionic liquids, [6] but not in dichloromethane. [14,16] Surface effect in other cyclopropanation reactions: In an attempt to show the generality of this effect on selectivities, four different alkenes were tested. The results of these experiments are gathered in Table 3.…”

Stereoselectivity induced by support confinement effects. Aza-pyridinoxazolines: A new family of C1-symmetric ligands for copper-catalyzed enantioselective cyclopropanation reactions

“…An extensive study on the importance of the nature of the support has been recently reported, confirming the need of having a lamellar anionic support to observe such surface 55 confinement effects. 10 A simple model has been proposed to explain those results, taking into account the known cyclopropanation reaction mechanism [11][12][13][14][15][16][17][18][19][20] and the strong ionpair interaction between the key copper-carbene intermediate and the support surface, as well as the steric constraints of the 60 catalytic complex. From that model we proposed the synthesis of chiral ligands without C 2 symmetry as a method to enhance the surface-complex proximity and hence the support-complex interaction, allowing the surface to effectively shield one face of the complex.…”

“…15 With the aim of rationalizing the experimental results described above, and to have a better understanding of the geometries of the key intermediates and transition structures (TS), a theoretical study of the different reaction channels of the copper-catalyzed cyclopropanation reaction with C 1 -20 symmetric aza-pyox ligands was done. Apart from the wellknown drawbacks in modeling the cyclopropanation reaction with styrene due to the flatness of the potential energy surface, [11][12][13][14][15] our main interest in this work was to evaluate the enantioselectivity of the process; therefore, all the calculations 25 were carried out using ethylene as olefin. In addition, as in previous studies, methyl diazoacetate was used in the calculations instead of ethyl diazoacetate.…”

Ligand spheres in asymmetric hetero Diels–Alder reactions catalyzed by Cu(ii) box complexes: experiment and modeling

“…[19][20][21][22][23][24] However, not only the nature of the ligand but also the solvent and counterions play a decisive role in the efficiency and stereoselectivity of the catalytic reactions. [25][26][27][28][29][30] This is particularly reflected in the recent developments of ligand design and the involvement of alternative counterions. 31,32 Nevertheless, mechanistic details in terms of the arrangement of ligands are scarce.…”