On the Mechanism of Cyclopropanation Reactions Catalyzed by a

Article pubs.acs.org/Organometallics

On the Mechanism of Cyclopropanation Reactions Catalyzed by a Rhodium(I) Catalyst Bearing a Chelating Imine-Functionalized NHC Ligand: A Computational Study Marianne L. Rosenberg,† Andreas Krapp,‡ and Mats Tilset*,‡ †

Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, N-0315 Oslo, Norway Centre for Theoretical and Computational Chemistry (CTCC), Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, N-0315 Oslo, Norway

‡

S Supporting Information *

ABSTRACT: A computational study at the DFT level using BP86 and dispersion-corrected D-BP86 methods has been performed on the mechanism of a highly cis-diastereoselective cyclopropanation reaction between ethyl diazoacetate and styrene, catalyzed by a Rh(I) complex bearing a chelating imine-functionalized NHC ligand. The key steps in the mechanism have been elucidated. The favored mechanistic pathway was found to be a stepwise mechanism involving the formation of a Rh metallacyclobutane intermediate. The results from the theoretical study indicate that the diastereoselectivity is determined in the step where styrene coordinates to the Rh(I) carbenoid and that the high cis-diastereoselectivity can be attributed to an unfavorable steric interaction between styrene and the substituents on the N-aryl ring in the ligand system, which disfavors the formation of the trans cyclopropanation product.

■

We have recently reported the use of new Rh(I) catalysts with chelating imine-functionalized N-heterocyclic carbene (NHC) ligands in cyclopropanation reactions.26−28 Among the complexes tested by us, 1 (Scheme 1) has been best studied. This Rh(I) complex displays a remarkably high reactivity and cis-selectivity in the cyclopropanation reaction between ethyl diazoacetate (EDA) and styrene. This is among the highest cis-selectivities that have been reported in this reaction and the highest cis-selectivity reported to date using a Rh catalyst. The catalyst also gives similarly excellent to good results with a range of different alkenes. It was therefore of significant interest to learn more about the mechanism of these Rh(I)-catalyzed cyclopropanation reactions in order to improve the catalytic system by design. While Rh(II) catalysts bearing carboxylate and carboxamidate ligands are the most extensively studied and employed catalysts in cyclopropanation reactions, there are only a few reports on Rh(I)-catalyzed cyclopropanation reactions.7,8,29 Some of these

INTRODUCTION Cyclopropanes are important substructures in many synthetic and naturally occurring biologically active compounds. 1,2 Among their reported biological activities are enzyme inhibition, antimicrobial, antibiotic, antitumor, and antiviral activities.2 Cyclopropanes are also interesting starting materials and intermediates in organic synthesis, as they can undergo a range of synthetically useful transformations.3,4 Metal-catalyzed cyclopropanation reactions are well known, and the most common way of obtaining cyclopropanes is the transfer of a carbene moiety from a diazo carbonyl compound to an olefin. In such a reaction, up to three new stereocenters can be formed. One challenge in intermolecular cyclopropanation reactions is the achievement of good diastereocontrol. As a result, considerable efforts have been made to develop methods and catalysts that are highly diastereoselective. Many catalysts are known that are highly efficient and selective for formation of the thermodynamically favored trans isomer.5−8 However, there are only a few reports on highly cis-diastereoselective catalysts for these types of reactions.8−25 © 2011 American Chemical Society

Received: July 5, 2011 Published: December 1, 2011 6562

dx.doi.org/10.1021/om200594q | Organometallics 2011, 30, 6562−6571

Organometallics

Article

the most stable form in each case will be discussed here. The energies discussed in the text are Gibbs free energies calculated at 298.15 K, unless otherwise stated. The geometry optimization and IRC algorithms implemented in the Gaussian03 program43 were used. All energy, gradient, and Hessian calculations were performed using the Turbomole program package.44 This coupling of Gaussian and Turbomole is possible due to the EXTERNAL option in Gaussian. The cyclopropanation reactions were conducted experimentally in CH2Cl2. The solvent effects were investigated by using the COSMO scheme45 on important steps in the mechanism. No significant effects were observed on the relative energies or selectivities. All structures and energies discussed in the text are therefore without solvent corrections. The possible involvement of triplet transition states has not been considered, although it is known that singlet−triplet crossing may sometimes be involved in organorhodium chemistry.46,47 In order to investigate the importance of dispersive forces, the empirical dispersion correction of Grimme48 was used in connection with the BP86 functional using the def2-SVP basis. This level of theory will be denoted D-BP86/def2-SVP. Single-point calculations on the BP86/def2-SVP-optimized structures were performed using Møller− Plesset perturbation theory of second order in combination with the def2-TZVPP basis, making use of the resolution of the identity (denoted MP2/def2-TZVPP).49−51 All computations were performed on the Stallo supercomputer located at the University of Tromsø, Norway.

Scheme 1. Highly cis-Selective Cyclopropanation Reaction Catalyzed by the New Rh(I) Complex 1

give promising results, but none of them give high diastereoselectivities, and they have not been extensively investigated.30−33 Hence, little is known about the mechanism of Rh(I)-catalyzed cyclopropanation reactions. In this contribution we present a computational mechanistic study on the cyclopropanation reaction between EDA and styrene catalyzed by Rh(I) complex 1. This is, to the best of our knowledge, the first report of a computational mechanistic study on Rh(I)-catalyzed cyclopropanation reactions.

■

COMPUTATIONAL DETAILS

■

All structures (minima and transition states) were fully optimized at the gradient-corrected density functional theory (DFT) level using the exchange functional of Becke34 in conjunction with the correlation functional of Perdew35 (denoted BP86), making use of the resolution of the identity approximation.36 The basis sets that were used were the Weigend−Ahlrichs basis sets, denoted def2-SVP and def2-TZVPP,37 and the corresponding fitting basis.38 The influence of the basis set size on the structures and relative energies for significant steps in the mechanism was tested, and it was found that the influence was minor. Therefore all structures presented were obtained using the def2-SVP basis set in combination with the BP86 functional (denoted as BP86/ def2-SVP). The applicability of gradient-corrected functionals as BP86 for the structural prediction of transition metal compounds is well documented;39 it was also asserted that BP86 outperforms hybrid functionals as B3LYP for second-row transition metal compounds. In combination with the resolution of the identity (RI) technique and medium-sized basis sets, this level of theory allows for an efficient exploration of potential energy hypersurfaces. Such an efficient method was needed in the present mechanistic study. As will be discussed, BP86 and D-BP86 were tested against MP2, and good performance was observed. Thus, we evaluate BP86 as being efficient as well as sufficiently accurate for the purpose of the present investigation. Analytic Hessians were used to characterize the nature of the stationary points on the potential energy surface and to obtain thermodynamic contributions.40 The Hessian eigenvalues were scaled by 0.9 in the calculation of the thermodynamic contributions. The connectivities of minima and transition structures were verified by intrinsic reaction coordinate (IRC) following calculations.41,42 The possibility of different conformations was taken into account, but only

RESULTS AND DISCUSSION 1. Formation of the Rh(I) Carbenoid. The mechanistic study was initiated by a geometry optimization of the Rh(I) complex 1 at BP86/def2-SVP. The calculated bond lengths and angles were compared with the ones observed in an X-ray crystal structure of complex 1.26 As shown in Table 1, the bond distances and angles from the geometry optimization are in good agreement with the data obtained from the crystal structure. Scheme 1 summarizes the experimental conditions for the cyclopropanation reactions catalyzed by complex 1. The target in this mechanistic study is the cyclopropanation reaction between EDA and styrene. The first step in the reactions is the activation of the catalyst, presumably by abstraction of the chloride ligand from Rh, using an activating agent such as AgOTf26 or, preferably,27 NaBArf (where Barf− = [B(3,5(CF3)2C6H3)4]−). It is assumed that a cationic Rh(I) species with a vacant coordination site is then formed (2, Figure 2). Dichloromethane was used as a solvent in the experiments; thus it is likely that dichloromethane may coordinate to the cationic Rh(I) metal center (3). The next step in the experimental cyclopropanation procedure is the addition of styrene, and this gives the possibility for formation of a Rhstyrene complex (4). The styrene complex 4 was found to be 5.5 kcal/mol lower in energy than the dichloromethane adduct 3, indicating that 4 might be the preferred complex present in

Table 1. Selected Bond Lengths and Angles for 1 from the X-ray Structurea and Calculated Structure at the BP86/def2-SVP Level

a

bond

X-ray (Å)

calculated (Å)

angle

X-ray (deg)

calculated (deg)

Rh−N(1) Rh−Cl Rh−C(1) Rh−C(20) C(5)−N(1) C(5)−N(2)

2.131(2) 2.367(6) 1.953(2) 1.813(3) 1.293(3) 1.386(3)

2.159 2.351 1.942 1.821 1.311 1.397

C(1)−Rh−C(20) C(20)−Rh−Cl Cl−Rh−N(1) N(1)−Rh−C(1)

97.39(11) 90.38(8) 93.40(6) 78.53(9)

97.46 91.75 92.93 77.91

From ref 26. 6563


Organometallics

Article

part of the ligand system has been observed for neutral Pd complexes that bear related chelating imine-functionalized NHC ligands in a six-membered chelate ring,58 but so far this behavior has not been observed for ligands that form fivemembered chelate rings such as that which is present here. 59 A four-coordinated complex in which styrene and EDA are both coordinated, and not the imine, was actually found (complex 9, Figure 3). This complex adopts a strongly distorted squareplanar geometry. The styrene and the CO ligands are trans to each other with the CO ligand bent out of the plane by 25°. Complex 9 was found to be as much as 24.6 kcal/mol higher in energy than free styrene and complex 5, in which the imine and EDA are coordinated. It is therefore likely that the imine does not dissociate and, hence, that styrene is not coordinated to the metal center at this stage in the mechanism. It is generally accepted that metal-catalyzed cyclopropanation reactions between diazo compounds and alkenes proceed through the formation of metal carbenoid species. 29,60 Supporting this notion, some Ru carbenoid complexes that were formed from diazo compounds have been isolated and characterized by X-ray crystallography, and their use in cyclopropanation reactions has been demonstrated.61−63 A Cu carbenoid intermediate involved in cyclopropanation reactions has also been detected by NMR spectroscopy. 64 Rh(I) carbenoid 11 is presumably involved in the cyclopropanation reactions catalyzed by Rh(I) complex 1, and calculated structures that have been located in the pathway for formation of Rh(I) carbenoid 11 are presented in Scheme 2. Formation of the Rh(I) carbenoid 11 starts with a precoordination of the diazo compound via the carbon atom (5) followed by loss of N2 (TS-10) to generate the Rh(I) carbenoid 11 (Scheme 2). In the transition state for loss of N2 (TS-10), the bond between Rh(I) and the EDA carbon atom is shortened from 2.235 to 2.021 Å, and the carbon−nitrogen bond is elongated from 1.364 to 1.870 Å compared to complex 5. The Rh−C bond is somewhat bent out of the chelate ring plane by 5.4°. In the Rh(I) carbenoid 11, the Rh−C(carbenoid) bond is bent somewhat further out of the chelate ring plane by 6.7°, causing a slight deviation from the square-planar geometry normally expected for symmetrically substituted four-coordinate d 8 complexes. Considerable distortions from the expected square-planar geometry caused by electronic effects have been reported even in simple metal carbonyl complexes.65,66 The ester carbonyl group in EDA is almost perpendicular to the Rh(I) carbenoid. The Rh−C−CO dihedral angle is 110°, suggesting that the Rh(I) carbenoid and the ester carbonyl

Figure 1. Optimized structure of complex 1.

solution. The main contribution to the Rh−styrene interaction is the donation of the alkene π-electrons to the Rh center; however, there is some back-donation to the alkene from the metal center, as indicated by the CC bond distance (1.397 Å), which is close to that of free styrene (1.351 Å). The next step is the addition of the diazo compound. Several possible modes of coordination of EDA to the Rh(I) center are conceivable.52−55 Complexes where the diazo compound is coordinated to Rh via the carbon atom (5), the terminal diazo nitrogen (6), the carbonyl oxygen (7), or both nitrogen and oxygen (8) were computationally located (Figure 3). It is complex 5 with the diazo compound coordinated via the carbon atom that is presumed to be the product-forming complex. It is conceivable that the EDA-coordinated complexes 5−8 may alternatively form by styrene dissociation from the styrene complex 4 via the cationic Rh(I) complex 2, which has a vacant coordination site. Attempts were made to find a fivecoordinated structure in which both styrene and EDA were coordinated to the metal center, but no such structure could be located. It is therefore likely that such a process occurs through a dissociative ligand exchange mechanism, as also found in theoretical studies of some Cu and Ru complexes.56,57 The possibility of dissociation of the imine moiety of the ligand system was also explored, in order to examine whether the imine might dissociate to furnish a vacant coordination, such that styrene and EDA might both be coordinated to the Rh(I) center at the same time. Such dynamic behavior of the imine

Figure 2. Cationic complexes possibly formed after removal of the chloride. Energies in kcal/mol at the BP86/def2-SVP level. Energies are relative to an assembly of isolated 2, styrene, and EDA. 6564


Organometallics

Article

Figure 3. Possible coordination modes of EDA. Energies in kcal/mol at BP86/def2-SVP. Energies are relative to an assembly of isolated 2, styrene, and EDA.

Scheme 2. Formation of the Rh(I) Carbenoid 11a

a

Relative energies in kcal/mol at BP86/def2-SVP. Energies are relative to an assembly of isolated 2, styrene, and EDA.

group are not in conjugation. It has been suggested that this alignment of the carbonyl group allows for favorable interactions between the carbonyl π* and the Rh(I) carbenoid π orbital or between the carbonyl π orbital and the Rh(I) carbenoid σ orbital.52,54,67 It was observed that the transition state (TS-10), leading to the Rh(I) carbenoid with the ester group pointed away from the N-aryl ring, is favored by 5.8 kcal/mol over the alternative transition state, where the ester group is pointed toward the Naryl ring (TS-12, Figure 4). This difference is presumably caused by an unfavorable steric interaction between the ester group and the N-aryl ring in transition state TS-12 when compared to TS-10 (details of the structure of TS-12 are given in the Supporting Information). The energy diagram for formation of Rh(I) carbenoid 11 is displayed in Figure 5. The reaction is exothermic and can be considered to be irreversible. The barrier for loss of N 2 from 5 is 12.7 kcal/mol (ΔH‡298 = 13.9 kcal/mol), and this is close to

Figure 4. The sterically less congested transition state TS-10 is favored over TS-12. Relative energies are in kcal/mol at BP86/def2-SVP. Energies are relative to an assembly of isolated 2, styrene, and EDA.

the calculated barrier of 14.8 kcal/mol (ΔH) calculated for EDA with dirhodium(II) formate52 and the experimentally observed barrier of 15 kcal/mol (ΔH) reported for EDA with dirhodium(II) acetate.68 6565


Organometallics

Article

propanation reaction. It is also well known that Rh metallacyclobutanes can be prepared and isolated, and it has been shown that they can undergo reductive eliminations to form cyclopropanes.77,78 Despite an extensive computational search, no transition states could be located for a concerted pathway starting from Rh carbenoid 11. On the other hand, a well-defined pathway was found involving the formation of a Rh metallacyclobutane species. This general mechanism is depicted in Scheme 4. The first step in this mechanism is coordination of styrene to the Rh(I) carbenoid, giving a five-coordinate Rh(I) species a. Next, the Rh metallacyclobutane c is formed via transition state b. The metallacyclobutane c then undergoes a reductive elimination via transition state d to furnish the cyclopropane. There are eight different orientations by which the olefinic CC bond of styrene can coordinate at the Rh(I) carbenoid complex 11. All eight possibilities (and the pathways leading therefrom) were investigated, and all these structures are described in the Supporting Information. However, only the lowest energy pathways that lead to each of the cis and trans isomers will be discussed here. The calculated structures that are involved in these two lowest energy pathways are displayed in Scheme 5. The styrene complexes 13a and 13b adopt a slightly distorted square-pyramidal geometry. The styrene ligand is coordinated so that the olefinic CC bond is approximately parallel with the Rh(I)−C(carbenoid) bond. In styrene complex 13a, styrene is oriented such that the styrene phenyl ring and the ester group on the carbenoid are on the same side of the plane that is defined by the styrene olefinic CC bond and the Rh(I)−C(carbenoid) bond. This orientation will lead to the cis cyclopropane. In styrene complex 13b, the styrene phenyl ring and the carbenoid ester group are on the opposite sides of this plane, leading to the trans cyclopropane. The possible involvement of imine side arm dissociation was also explored for these styrene complexes in order to examine whether a four-coordinate complex with a noncoordinated imine might be more stable than the five-coordinated styrene complexes 13a and 13b. Dissociation of the imine side arm did, however, result in complexes that were significantly less stable (21.0−23.4 kcal/mol) than the five-coordinated complexes (calculated structures can be found in the Supporting Information). This strongly suggests that the imine is coordinated to the metal center throughout the entire catalytic cycle; the outcome of the reactions would then be expected to strongly depend on substituent patterns at the N-aryl group, which would always be in close proximity to the Rh center. The Rh−styrene bonding is primarily made up by donation of the alkene π electrons to the Rh(I) center with some backdonation from the metal center to the alkene (CC distances, 1.403−1.410 Å). Similarly to the situation in Rh(I) carbenoid 11, the Rh(I)−C(carbenoid) bond in both styrene complexes 13a and 13b are also bent out of the chelate ring plane by 19− 21°. The Rh(I)−C(carbenoid) bond is bent out of this plane to the opposite side of where styrene is coordinated. The Rh−C− CO dihedral angles in the carbenoid unit are smaller than those observed for Rh(I) carbenoid 11. In complex 13a the Rh−C−CO dihedral angle is 15°, and in complex 13b the ester carbonyl is nearly in the same plane as the Rh(I) carbenoid, as the dihedral angle is only 1°. Complex 13a, which leads to the cis isomer, is 2.4 kcal/mol lower in energy than complex 13b, which leads to the trans isomer. An unfavorable steric interaction between the styrene phenyl ring and the

Figure 5. Energy diagram for the formation of Rh(I) carbenoid 11. Relative energies are in kcal/mol at BP86/def2-SVP.

Even though it is only 5 that is the product formed by N2 expulsion, it may be argued that the other EDA-coordinated complexes 6−8 should also be taken into consideration.52,54 Pirrung et al.69 argued in the case of Rh(II) carboxylates that reversible, nonproductive binding of the substrate to the catalyst can affect the reaction rate by lowering the overall initial energy of the system. If these non-product-forming complexes were to be taken into account for our system, the barrier for loss of N2 starting from the species of lowest possible energy (8) would be the energy difference between this most stable complex (8) and TS-10, and the activation barrier would thereby increase to 21.4 kcal/mol. 2. Cyclopropanation. The next step in the catalytic cycle is the reaction between the metal carbenoid and the alkene to form the cyclopropane. Two possible mechanisms for this reaction have been proposed (Scheme 3). One is a concerted Scheme 3. Two Possible Mechanistic Pathways for Cyclopropanation of Alkenes with Metal Carbenoids

mechanism, where the alkene directly attacks the carbenoid carbon and the cyclopropane is formed through a threemembered ring transition state. This mechanism has been shown by calculations to be the favored pathway for the dimeric Rh(II) carboxylates52,54,70 and a number of Cu,57,71,72 Ru,56 and Fe73 catalysts. The other possibility is a stepwise mechanism involving the formation of a metallacyclobutane in which the metal has been formally oxidized. Further, the metallacyclobutane undergoes a reductive elimination and the cyclopropane is formed. This mechanism has been proposed to be the favored pathway for some Pd-74,75 and Fe73-catalyzed cyclopropanations. Hoffmann and co-workers76 prepared and isolated a palladacyclobutane, which was demonstrated to be involved in the cyclo6566


Organometallics

Article

Scheme 4. Metallacyclobutane Mechanism Found for the Cyclopropanation Reaction Catalyzed by Rh(I) Complex 1 a

a

[Rh] = (N−C)Rh(CO)+.

cyclopropane is lower in energy than the transition state leading to the trans cyclopropane, by 4.8 kcal/mol. The energy profile for reaction of the Rh(I) carbenoid 11 with styrene is depicted in Figure 7. The addition of styrene to the Rh(I) carbenoid 11 is endothermic according to this energy diagram. Despite an extensive search, no transition state could be located for the coordination of styrene to the Rh(I) carbenoid 11 to give 13a and 13b. The barriers for the formation of the metallacyclobutanes are as low as 2.5 kcal/mol from 13a leading to the cis isomer and 4.5 kcal/mol from 13b leading to the trans isomer. The formation of the metallacyclobutanes is highly exothermic, and the process can be considered to be irreversible. Metallacyclobutanes 15a and 15b are substantially stabilized compared to the Rh(I) carbenoid 11 and free styrene by 22.5 and 18.1 kcal/mol, respectively. The barriers for the reductive elimination (TS-16a, 10.8 kcal/mol and TS-16b, 11.2 kcal/mol) are considerably higher than for the formation of the metallacyclobutanes. This might reflect the higher stability of the metallacyclobutanes (15a and 15b) compared to the styrene complexes (13a and 13b). As mentioned, many metallacyclobutanes are sufficiently stable to be isolated. The extrusion of N2 in the formation of Rh(I) carbenoid 11 presents the highest barrier in the catalytic cycle (TS-10) and therefore represents the rate-determining step of the reaction. This has also been reported to be the case in theoretical studies of Rh(II)-catalyzed cyclopropanation reactions.52,54 We found it somewhat surprising that the coordination of styrene at the Rh(I) carbenoid 11 appeared to be endothermic. Considering that 11 is a 16-electron cationic species, and despite the fact that it is a four-coordinate square planar complex, one might envision that the coordination of styrene would have a stabilizing effect, rendering the process exothermic. It was observed that there were only very small changes in bond distances and angles around the metal center upon coordination of styrene, also indicating that the coordination of styrene would not be destabilizing. It is well known that standard DFT methods like the ones used in this study are not able to account for dispersion forces. 48 As the imine-functionalized NHC ligand system is quite large, one might expect the dispersion forces to be of considerable importance. In order to probe this, reoptimizations of the stationary structures of the key steps in the mechanism were

methyl groups in the ortho positions on the N-aryl ring in complex 13b (Figure 6) might explain the energy difference between these two complexes. In complex 13a the styrene phenyl ring is not in close proximity to any of the groups in the iminocarbene ligand system. The distance between Rh and the α olefinic carbon is somewhat elongated in complex 13b (2.645 Å) compared to 13a (2.481 Å). This difference in bond lengths might also be enforced by steric interactions between the styrene phenyl ring and the methyl groups in the ortho positions on the N-aryl ring. In the transition states leading from the styrene complexes to the metallacyclobutanes, the distances between the β olefinic carbon of styrene and the Rh-carbenoid carbon are shortened in both transition state TS-14a (2.994 → 2.434 Å) and TS-14b (3.237 → 2.393 Å), and the Rh−C(carbenoid) bonds are elongated (TS-14a (1.912 → 1.965 Å) and TS-14b (1.900 → 1.965 Å)). The double-bond character of the olefinic CC bond in styrene is reduced, as indicated by increasing C−C bond distances of 0.018 Å (TS-14a) and 0.025 Å (TS-14b). The Rh(I)−C(carbenoid) bond is still bent out of chelate ring plane (9−14°) but to a lesser extent than in the styrene complexes 13a and 13b. The transition state leading to the cis isomer (TS-14a) is also in this step lower in energy than transition state TS-14b, leading to the trans isomer, by 4.4 kcal/ mol. In the metallacyclobutanes the bond lengths of the C−C bonds that originate from styrene have increased further to 1.525 Å for 15a and 1.516 Å for 15b; these bond lengths correspond to single bonds. It is observed that in the metallacyclobutane 15b that leads to the trans cyclopropane, the four-membered ring is more twisted than in complex 15a, leading to the cis cyclopropane, and the bond length between Rh and the olefinic α carbon of styrene is greater in 15b than in 15a by 0.028 Å. This may again be attributed to the unfavorable steric interactions between the styrene phenyl ring and the methyl groups in the ortho positions on the N-aryl ring in metallacyclobutane 15b. Metallacyclobutane 15a is 4.4 kcal/mol lower in energy than metallacyclobutane 15b. In the final transition states (TS-16a and TS-16b) for the reductive elimination leading to the cyclopropanes, the Rh−C bonds that undergo cleavage are elongated and the C−C distance is shortened. The transition states have a strong product-like character with the cyclopropanes almost completely formed. Also in this case, the transition state leading to the cis 6567


Organometallics

Article

Scheme 5. Calculated Structures for the Pathways Leading to the cis and trans Cyclopropanes (17a and 17b)a

a

Relative energies in kcal/mol at BP86/def2-SVP. Energies are relative to an assembly of isolated 2, styrene, and EDA.

cyclopropane. This compares to the 2.4 kcal/mol energy difference at BP86/def2-SVP. It was found for both complexes (13a′ and 13b′) that the Rh−styrene distances were shorter than what was observed without dispersion correction. This indicates that the dispersion-corrected method predicts styrene to be more firmly bound to the metal center. The energy profile of the reaction between the Rh(I) carbenoid 11′ and styrene at the D-BP86/def2-SVP level is displayed in Figure 8. The most important and significant difference between the two methods is that the dispersion-corrected method in fact predicts the coordination of styrene to the Rh(I) carbenoid 11′ to be exothermic. Apart from this, there were only small changes in the overall energy profile. For all the steps in the mechanism, it

performed using a dispersion-corrected method (D-BP86/def2SVP). All reoptimized structures can be found in the Supporting Information. Only small changes in the structural parameters were found with this new method. The reoptimized structures of the Rh(I) carbenoid (11′) and styrene (13a′ and 13b′) complexes are shown in Scheme 6 (all new, or reoptimized, structures are given the same number as previously, but are denoted with an slanted prime ′). In the reoptimized styrene complexes, the Rh−C(carbenoid) bonds were bent out of the chelate ring plane by 4° less in 13a′ than in 13a and by 4° more in 13b′ than in 13b. Complex 13a′, which leads to the cis cyclopropane, was found to be 3.9 kcal/ mol lower in energy than 13b′, which leads to the trans 6568


Organometallics

Article

Figure 8. Energy profile for the cyclopropanation reaction between Rh(I) carbenoid 11′ and styrene at the D-BP86/def2-SVP level.

Figure 6. Unfavorable steric interaction in styrene complex 13b.

without dispersion correction, the transition state for the loss of N2 (TS-10′) represents the highest barrier in the catalytic cycle (12.9 kcal/mol at D-BP86/def2-SVP) and is therefore the ratedetermining step. Interestingly, the energetic trends at the dispersion-corrected DFT level of theory, especially the exothermicity of the styrene addition, reproduce very well the behavior that was observed when single-point calculations at the MP2/def2-TZVPP level of theory were performed on BP86/def2-SVP structures (energies can be found in the Supporting Information). This indicates that the overall reaction profile is well described at the DFT level of theory and that dispersion-including methods are needed in order to describe the styrene addition step more correctly. The dispersion effects introduced at the D-BP86 level are quite large. Especially, and as might be anticipated, this is the case for the first step in Figures 7 and 8, the addition of styrene, which introduces numerous additional dispersive interactions, which serve to stabilize the addition product. From the results discussed in this contribution it appears that the cis/trans diastereoselectivity of the cyclopropanation reaction is determined by the orientation of the incoming styrene upon coordination at Rh. The diastereoselectivity is determined in the steps where the styrene complexes (13a′ and 13b′) are formed or in the following transition states (TS-14a′ and TS-14b′). The difference between the activation barriers for the two reactions 13b′ → 15b′ via 14b′ and 13a′ → 15a′ via 14a′ (Δ(ΔErel) = 1.4 kcal/mol) is not large enough to rationalize the very high cis-diastereoselectivity obtained in the laboratory; the observed >99.5:0.5 selectivity corresponds to a greater than 3.2 kcal/mol barrier difference at 298 K. (At the

Figure 7. Energy diagram for the cyclopropanation reaction between Rh(I) carbenoid 11 and styrene. Relative energies in kcal/mol at BP86/def2-SVP.

was found that the complexes leading to the cis cyclopropane were lower in energy than the complexes leading to the trans cyclopropane, also with the dispersion-corrected method. Again, no transition state for the addition of styrene could be identified. The barriers for the formation of the metallacyclobutanes 15a′ and 15b′ from the styrene complexes 13a′ and 13b′ were slightly lower at D-BP86/def2-SVP (3.3 and 1.9 kcal/mol) than at BP86/def2-SVP (4.5 and 2.5 kcal/mol, respectively). The barriers for the reductive elimination were also predicted to be somewhat lower (11.2 and 10.8 kcal/mol at BP86/def2-SVP and 10.6 and 9.7 at D-BP86/def2-SVP). As

Scheme 6. D-BP86/def2-SVP Structures of the Rh(I) Carbenoid (11′) and the Styrene-Coordinated Complexes (13a′ and 13b′)a

a

Energies are relative to an assembly of isolated 2, styrene, and EDA. 6569


Organometallics

Article

(4) Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-C.; Tanko, J.; Hudlicky, T. Chem. Rev. 1989, 89, 165−198. (5) Doyle, M. P. Angew. Chem., Int. Ed. 2009, 48, 850−852. (6) Langlotz, B. K.; Wadepohl, H.; Gade, L. H. Angew. Chem., Int. Ed. 2008, 47, 4670−4674. (7) Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B. Chem. Rev. 2003, 103, 977−1050. (8) Caballero, A.; Prieto, A.; Díaz-Requejo, M. M.; Pérez, P. J. Eur. J. Inorg. Chem. 2009, 1137−1144. (9) Suematsu, H.; Kanchiku, S.; Uchida, T.; Katsuki, T. J. Am. Chem. Soc. 2008, 130, 10327−10337. (10) Alexander, K.; Cook, S.; Gibson, C. L. Tetrahedron Lett. 2000, 41, 7135−7138. (11) Uchida, T.; Irie, R.; Katsuki, T. Synlett 1999, 1793−1795. (12) Uchida, T.; Irie, R.; Katsuki, T. Synlett 1999, 1163−1165. (13) Uchida, T.; Irie, R.; Katsuki, T. Tetrahedron 2000, 56, 3501− 3509. (14) Uchida, T.; Katsuki, T. Synthesis 2006, 1715−1723. (15) Bachmann, S.; Mezzetti, A. Helv. Chim. Acta 2001, 84, 3063− 3074. (16) Bachmann, S.; Furler, M.; Mezzetti, A. Organometallics 2001, 20, 2102−2108. (17) Bonaccorsi, C.; Mezzetti, A. Organometallics 2005, 24, 4953− 4960. (18) Bonaccorsi, C.; Santoro, F.; Gischig, S.; Mezzetti, A. Organometallics 2006, 25, 2002−2010. (19) Bonaccorsi, C.; Bachmann, S.; Mezzetti, A. Tetrahedron: Asymmetry 2003, 14, 845−854. (20) Casey, C. P.; Polichnowski, S. W.; Shusterman, A. J.; Jones, C. R. J. Am. Chem. Soc. 1979, 101, 7282−7292. (21) Hoang, V. D. M.; Reddy, P. A. N.; Kim, T.-J. Tetrahedron Lett. 2007, 48, 8014−8017. (22) Díaz-Requejo, M. M.; Caballero, A.; Belderrain, T. R.; Nicasio, M. C.; Trofimenko, S.; Pérez, P. J. J. Am. Chem. Soc. 2002, 124, 978− 983. (23) Lüning, U.; Fahrenkrug, F. Eur. J. Org. Chem. 2006, 916−923. (24) Kanchiku, S.; Suematsu, H.; Matsumoto, K.; Uchida, T.; Katsuki, T. Angew. Chem., Int. Ed. 2007, 46, 3889−3891. (25) Shitama, H.; Katsuki, T. Chem.Eur. J. 2007, 13, 4849−4858. (26) Rosenberg, M. L.; Krivokapic, A.; Tilset, M. Org. Lett. 2009, 11, 547−550. (27) Rosenberg, M. L.; Vlašaná, K.; Gupta, N. S.; Wragg, D.; Tilset, M. J. Org. Chem. 2011, 76, 2465−2470. (28) Rosenberg, M. L.; Langseth, E.; Krivokapic, A.; Gupta, N. S.; Tilset, M. New J. Chem. 2011, 35, 2306−2313. (29) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides; Wiley: New York, 1998. (30) Dias, E. L.; Brookhart, M.; White, P. S. Chem. Commun. 2001, 423−424. (31) Teixidor, F.; Núñez, R.; Flores, M. A.; Demonceau, A.; Viñas, C. J. Organomet. Chem. 2000, 614−615, 48−56. (32) Ç etinkaya, B.; Ö zdemir, I.; Dixneuf, P. H. J. Organomet. Chem. 1997, 534, 153−158. (33) Carmona, A.; Corma, A.; Iglesias, M.; San José, A.; Sánchez, F. J. Organomet. Chem. 1995, 492, 11−21. (34) Becke, A. D. Phys. Rev. A 1988, 38, 3098−3100. (35) Perdew, J. P. Phys. Rev. B 1986, 33, 8822−8824. (36) Eichkorn, K.; Treutler, O.; Ö hm, H.; Häser, M.; Ahlrichs, R. Chem. Phys. Lett. 1995, 242, 652−660. (37) Weigend, F.; Ahlrichs, R. Phys. Chem. Chem. Phys. 2005, 7, 3297−3305. (38) Weigend, F. Phys. Chem. Chem. Phys. 2006, 8, 1057−1065. (39) Waller, M. P.; Braun, H.; Hojdis, N.; Bühl, M. J. Chem. Theory Comput. 2007, 3, 2234−2242, , and references therein.. (40) Deglmann, P.; Furche, F.; Ahlrichs, R. Chem. Phys. Lett. 2002, 362, 511−518. (41) Gonzalez, C.; Schlegel, H. B. J. Phys. Chem. 1990, 94, 5523− 5527.

MP2/def2-TZVPP//BP86/def2-SVP level, the computationally predicted energy difference was even lower, at Δ(ΔErel) = 0.2 kcal/mol.) This suggests that the coordination of styrene to the Rh(I) carbenoid 11′ might be the diastereoselectivitydetermining step. No transition states for the coordination of styrene to Rh(I) carbenoid 11′ could be located. If this step is indeed barrierless, the reactivity must be controlled by reaction dynamics, e.g., different collision frequencies. 79 Realistic molecular dynamic simulations, however, lie far outside the scope of this work, and hence the details of this step are not clear at this point in time.

■

CONCLUSION A computational study of the mechanism of a cyclopropanation reaction between styrene and EDA catalyzed by Rh(I) catalyst 1 that bears a chelating imine-functionalized NHC ligand has been presented. This is, to the best of our knowledge, the first report of a computational study of a Rh(I) catalyzed cyclopropanation reaction. Density functional theory at the BP86/def2-SVP level and dispersion-corrected DFT (D-BP86/ def2-SVP) as well as ab initio theory (MP2/def2-TZVPP) were used in the investigations. The rate-determining step of the catalytic cycle was found to be extrusion of N2 in the formation of a Rh(I) carbenoid, representing a barrier of 12.9 kcal/mol (D-BP86/def2-SVP). The reaction was shown to proceed via a stepwise mechanism, which involves the formation of Rh metallacyclobutanes. The origin of the high cis-diastereoselectivity probably lies in an unfavorable steric interaction between the styrene phenyl ring and the methyl groups in the ortho positions on the ligand N-aryl ring in the complexes leading to the trans isomer. The results provide valuable information about the origin of the high cis-diastereoselectivity, which might prove useful in further developments of the Rh(I)-catalyzed cyclopropanations. In this respect, it is interesting to note that manipulation of the N-aryl ortho substituent of the iminocarbene ligand strongly influences catalyst performance and diastereoselectivities.28

■

ASSOCIATED CONTENT

S Supporting Information *

Optimized geometries, energies, and Cartesian coordinates for all the calculated species. This material is available free of charge via the Internet at http://pubs.acs.org.

■ ■

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]. ACKNOWLEDGMENTS The authors gratefully acknowledge financial support from the Norwegian Research Council (NFR) through the Centre of Excellence program (grant no. 179568/V30 to the Centre of Theoretical and Computational Chemistry) and through the KOSK program (grant no. 177325/V30, stipend to M.L.R.). We also thank NOTUR for providing generous computational resources and Dr. Ole Swang, SINTEF, for helpful discussions.

■

REFERENCES

(1) Donaldson, W. A. Tetrahedron 2001, 57, 8589−8627. (2) Salaün, J. Top. Curr. Chem. 2000, 207, 1−67. (3) Rubin, M.; Rubina, M.; Gevorgyan, V. Chem. Rev. 2007, 107, 3117−3179. 6570


Organometallics

Article

(69) Pirrung, M. C.; Liu, H.; Morehead, A. T. Jr. J. Am. Chem. Soc. 2002, 124, 1014−1023. (70) Hansen, J.; Autschbach, J.; Davies, H. M. L. J. Org. Chem. 2009, 74, 6555−6563. (71) Fraile, J. M.; García, J. I.; Martínez-Merino, V.; Mayoral, J. A.; Salvatella, L. J. Am. Chem. Soc. 2001, 123, 7616−7625. (72) Suenobu, K.; Itagaki, M.; Nakamura, E. J. Am. Chem. Soc. 2004, 126, 7271−7280. (73) Wang, F.; Meng, Q.; Li, M. Int. J. Quantum Chem. 2008, 108, 945−953. (74) Berthon-Gelloz, G.; Marchant, M.; Straub, B. F.; Marko, I. E. Chem.Eur. J. 2009, 15, 2923−2931. (75) Bernardi, F.; Bottoni, A.; Miscione, G. P. Organometallics 2001, 20, 2751−2758. (76) Hoffmann, H. M. R.; Otte, A. R.; Wilde, A.; Menzer, S.; Williams, D. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 100−102. (77) Jennings, P. W.; Johnson, L. L. Chem. Rev. 1994, 94, 2241− 2290. (78) Tjaden, E. B.; Stryker, J. M. J. Am. Chem. Soc. 1990, 112, 6420− 6422. (79) Swiegers, G. F.; Huang, J.; Brimblecombe, R.; Chen, J.; Dismukes, G. C.; Mueller-Westerhoff, U. T.; Spiccia, L.; Wallace, G. G. Chem.Eur. J. 2009, 15, 4746−4759.

(42) Gonzalez, C.; Schlegel, H. B. J. Chem. Phys. 1989, 90, 2154− 2161. (43) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Rev. E.01; Gaussian Inc.: Wallingford, CT, 2004. (44) TURBOMOLE, V6.2, a development of University of Karlsruhe and Forschungszentrum Karlsruhe GmbH, 1989−2007, TURBOMOLE GmbH, since 2007; available from http://www.turbomole. com. (45) Klamt, A.; Schüürmann, G. J. Chem. Soc., Perkin Trans. 2 1993, 799−805. (46) Petit, A.; Richard, P.; Cacelli, I.; Poli, R. Chem.Eur. J. 2006, 12, 813−823. (47) Blake, A. J.; George, M. W.; Hall, M. B.; McMaster, J.; Portius, P.; Sun, X. Z.; Towrie, M.; Webster, C. E.; Wilson, C.; Zarić, S. D. Organometallics 2008, 27, 189−201. (48) Grimme, S. J. Comput. Chem. 2004, 25, 1463−1473. (49) Hellweg, A.; Hättig, C.; Höfener, S.; Klopper, W. Theor. Chem. Acc. 2007, 117, 587−597. (50) Weigend, F.; Häser, M.; Patzelt, H.; Ahlrichs, R. Chem. Phys. Lett. 1998, 294, 143−152. (51) Weigend, F.; Häser, M. Theor. Chem. Acc. 1997, 97, 331−340. (52) Bonge, H. T.; Hansen, T. J. Org. Chem. 2010, 75, 2309−2320. (53) Ö zen, C.; Tüzün, N. Ş. Organometallics 2008, 27, 4600−4610. (54) Nowlan, D. T. III; Gregg, T. M.; Davies, H. M. L.; Singleton, D. A. J. Am. Chem. Soc. 2003, 125, 15902−15911. (55) Demonceau, A.; Noels, A. F.; Hubert, A. J. Aspects Homogeneous Catal. 1988, 6, 199−232. (56) Cornejo, A.; Fraile, J. M.; García, J. I.; Gil, M. J.; MartínezMerino, V.; Mayoral, J. A.; Salvatella, L. Organometallics 2005, 24, 3448−3457. (57) Fraile, J. M.; García, J. I.; Gil, M. J.; Martínez-Merino, V.; Mayoral, J. A.; Salvatella, L. Chem.Eur. J. 2004, 10, 758−765. (58) Frøseth, M.; Dhindsa, A.; Røise, H.; Tilset, M. Dalton Trans. 2003, 4516−4524. (59) Frøseth, M.; Netland, K. A.; Rømming, C.; Tilset, M. J. Organomet. Chem. 2005, 690, 6125−6132. (60) Yates, P. J. Am. Chem. Soc. 1952, 74, 5376−5381. (61) Galardon, E.; Maux, P. L.; Toupet, L.; Simonneaux, G. Organometallics 1998, 17, 565−569. (62) Galardon, E.; Roué, S.; Le Maux, P.; Simonneaux, G. Tetrahedron Lett. 1998, 39, 2333−2334. (63) Park, S.-B.; Sakata, N.; Nishiyama, H. Chem.Eur. J. 1996, 2, 303−306. (64) Straub, B. F.; Hofmann, P. Angew. Chem., Int. Ed. 2001, 40, 1288−1290. (65) Ogasawara, M.; Macgregor, S. A.; Streib, W. E.; Folting, K.; Eisenstein, O.; Caulton, K. G. J. Am. Chem. Soc. 1995, 117, 8869− 8870. (66) Elian, M.; Hoffmann, R. Inorg. Chem. 1975, 14, 1058−1076. (67) Nakamura, E.; Yoshikai, N.; Yamanaka, M. J. Am. Chem. Soc. 2002, 124, 7181−7192. (68) Anciaux, A. J.; Hubert, A. J.; Noels, A. F.; Petiniot, N.; Teyssié, P. J. Org. Chem. 1980, 45, 695−702. 6571


On the Mechanism of Cyclopropanation Reactions Catalyzed by a

Recommend Documents