Conformational Flexibility of Hoveyda-Type and Grubbs-Type

Jan 16, 2015 - In this contributione density functional theory was used to gain insight into the conformational flexibility of acyclic diaminocarbenes...
0 downloads 0 Views 3MB Size
Download PDF
Article pubs.acs.org/Organometallics

Conformational Flexibility of Hoveyda-Type and Grubbs-Type Complexes Bearing Acyclic Carbenes and Its Impact on Their Catalytic Properties Aleksandra Pazio,†,‡ Krzysztof Woźniak,‡ Karol Grela,‡ and Bartosz Trzaskowski*,† †

Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097 Warszawa, Poland Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Ż wirki i Wigury 101, 02-089 Warszawa, Poland

‡

S Supporting Information *

ABSTRACT: In this contributione density functional theory was used to gain insight into the conformational flexibility of acyclic diaminocarbenes and their corresponding Hoveyda- and Grubbs-class ruthenium complexes. Remarkably, all known crystal structures of acyclic carbenes and their Hoveyda-type Ru complexes show only one specific conformer. We demonstrate that rotation about the C−N bonds in the free acyclic diaminocarbenes is thermally accessible (∼20 kcal/mol), but is relatively restricted upon coordination, primarily due to steric constraints. As a consequence, the capacity of the ADC ligands to sample multiple conformations is reduced following coordination. In addition, we show that the alkylidene proton has little contribution to the stabilization of the precatalysts, but has a non-negligible impact on the stabilization and energy barriers of both the transition states and products of the initiation phase of the metathesis.

■

INTRODUCTION Acyclic diamino carbenes (ADCs) constitute a group of ligands alternative to the widely used N-heterocyclic carbenes (NHCs) in the second-generation Hoveyda-type (Hov) metathesis catalysts,1 as well as other types of catalysts containing transition metals.2,3 The high conformational flexibility of these systems, as compared to standard NHC ligands, result in better σ-donor properties.4,5 The σ-donicity of ADCs, which strongly depends on their conformation6 (see Chart 1), may be controlled by the steric hindrance of N,N′-substituents attached to the ligand. Moreover, flexible ADCs may in some cases facilitate creation of a chiral environment at the catalytic center and enable enantioselective catalysis.7,8 The importance of the π-face donation through the Cipso atom on the stability of NHC Hoveyda catalysts has also been established recently.9−11 It requires, however, a specific geometry of the alkylidene ligand, where the hydrogen atom is not directed toward the mesityl ring, to allow a shorter distance between two carbon atoms: Cipso and Calkylidene (further in this contribution denoted as C(4) and C(22), respectively). Replacing NHCs by ACDs offers a unique possibility of further exploration of this interaction due to the multiple conformations available for ADCs. The intrinsic flexibility of acyclic carbenes may also affect the mechanism of the initiation step of the olefin metathesis, which is the ratelimiting step of the entire catalytic cycle for this reaction.12 Until now, only two ADC analogues of Hoveyda-type catalysts13 have been synthesized, and they both were found to adopt the amphi-L conformation.14 In this work we compared four conformers of ADC 4 (N,N′-dimesityl-N,N′-dimethylformamidin-2-ylidene) before and after coordination to form © XXXX American Chemical Society

Chart 1. Hoveyda Catalyst 1, Its ADC Derivatives 2 and 3, and ADC Ligands 4 and 5

Received: June 18, 2014

A

DOI: 10.1021/om5006462 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

the Ru(1)−O(1) bond, and the second one is the addition of the olefin. In all known cases the first transition state is, however, the ratedetermining step of the entire process. Therefore, in our studies we only evaluated the energy barriers of the first step of the dissociative mechanism.

Hoveyda-class Ru catalyst 2 and analyzed the structural and energetic differences versus the Hoveyda catalyst 1. For all conformers we evaluated the impact of the ADC conformation on the initial step of the metathesis catalytic cycle. We also compared these results with a computationally designed system, 3. Additionally we also performed similar analysis for a computationally designed Grubbs catalyst bearing the same ADC carbene.

■

■

RESULTS AND DISCUSSION The main difference in the ADC ligands, as compared to the NHC, is the possibility of rotation of the N-substituents along the C(1)−N(1) and C(1)−N(2) bonds. The geometry comparison between the DFT-optimized conformers of system 2 and the structure of 1 (both DFT-optimized and X-ray crystal structure) shows that the geometry around the ruthenium center is rather conserved (see Figure 1 for atom labeling and

COMPUTATIONAL METHODS

In this work, we used density functional theory (DFT) calculations to study all possible pathways of the initiation mechanism of investigated complexes and show the impact of the rotation of the mesityl ring in the ADC ligand on the energetic profile of the reaction. The calculations have been performed using a computational protocol similar to our previous studies.15,16 To summarize the most important points of the calculations, we have used an all-atom model for the catalyst and the cis-2-butene molecule to model the substrate of olefin metathesis. Starting models for systems 2 and 3 were prepared on the basis of available CSD crystal structures of Hoveyda catalyst derivatives.14 We have modeled the initiation step of studied systems using the M06 density functional with the 6-31G** basis set for all atoms except the Ru atom, which was described by the Los Alamos angular momentum projected effective core potential (ECP) using the double-ζ contraction of valence functions (denoted as LACVP**).17−19 We have chosen this particular density functional since it was also shown to perform particularly well for rutheniumbased catalysts, giving accurate energies for a number of Grubbs and Hoveyda systems.20−22 Additionally, the M06 functional is known to accurately describe the noncovalent interactions and particularly the weak interaction and π−π complexes. This feature makes the M06 functional very suitable to use in the case of ACDs with a number of weak, methyl−phenyl and π−π interactions. We have used the standard energy convergence criterion of 5 × 10−5 hartree. Solvation energies were calculated using the Poisson− Boltzmann self-consistent polarizable continuum method (PBF)23 as implemented in Jaguar v.7.9 (Schrodinger, 2013) to represent dichloromethane, using the dielectric constant of 8.93 and the effective radius 2.33 Å. The solvation calculations were performed using the M06/LACVP** level of theory and the gas-phase-optimized structures. For each structure frequencies were calculated to verify the nature of each stationary point. For all stationary points (i.e., all calculations not involving rotational scans) we have also performed single-point energy calculations using the same M06 functional, but with a larger basis set: here Ru was described with the triple-ζ contraction of valence functions augmented with two f functions, and the core electrons were described by the same ECP; the other atoms were described with the 6-311++G** basis set. Energies discussed in this work for stationary points are free energies, calculated as the sum of electronic energy (single-point, using the larger 6-311++G** basis set), solvation energy, zero-point energy correction, thermal correction to enthalpy, and the negative product of temperature and entropy (at 298 K). In the case of bond dissociation energies we used the same 6-311++G** basis set and counterpoise correction using the standard Boys−Bernardi scheme.24 Recent computational studies concluded that there are three theoretically possible mechanisms of the olefin metathesis initiation for Hoveyda-type catalysts: dissociative, associative, and interchange.25 In that work it was found that for NHC Hoveyda complexes the interchange mechanism is the most plausible one from the energetic point of view. Experimental investigations of the initiation mechanisms performed for a number of different Hoveyda catalysts and using different olefins as substrates showed, however, that this reaction may simultaneously follow two parallel pathways, dissociative and interchange, depending on the electronic/steric properties of both the catalyst and the substrate.26,27 In view of these results we have evaluated energy barriers for both the dissociative and interchange mechanisms for all four conformers of 2. Moreover, the dissociative mechanism consists of two steps. The first step is the dissociation of

Figure 1. Catalyst 1 and 2 atom-numbering scheme. A similar atomlabeling scheme is preserved in all investigated structures.

Table 1 for numerical values). In all four conformers of 2 only the systematic elongation of the Ru(1)−O(1) bond is observed: it is longer by 0.037 Å for the anti conformation and by 0.052 Å for the syn conformation. In the case of 1 the bond in the crystallographic structure is ca. 0.07 Å shorter than in the DFT-optimized one. Also the Ru(1)−C(22)−C(23)− C(28)−O(1) ring is more tilted from the plane for 1 with respect to 2. In all DFT-optimized structures the geometry around the C(1) atom in NHC is clearly different from the ADC one, where the N(1)−C(1)−N(2) angle (N−Ccarbene−N) is 8.2−13.0° wider. On the basis of the N(1)−C(1)−N(2) angle in all conformations of system 2 we can show the steric repulsion between C(4) and C(13) mesitylene rings: the widest angle is present in conformer 2-anti (see Figure 2). For all N,N′-methyl substituents the torsion angles (Ru(1)−C(1)−N(1)−C(2) and Ru(1)−C(1)−N(1)−C(3)) vary to a relatively large degree (up to 27.95°), suggesting that the carbene part of the catalyst is fairly flexible and attaining different geometry than the rigid Hoveyda catalyst. On the other hand the angles and bond lengths around the ruthenium catalyst center are similar for all four conformers, except in the Cl(1)−Ru(1)−Cl(2) angle case, whose value is increased when the C(13) mesitylene ring is directed downward, toward the chlorine atoms. Plane angles of the benzylidene ring are conserved, and all torsion angles are strongly dependent on the type and conformation of the carbene ligand. In the case where the mesitylene ring C(4) is directed toward the H atom bound to C(22) (further labeled as the H(22) atom), N(1)−C(4) and Ru(1)−C(22) bonds are almost planar (see Table 1 for C(4)− N(1)−Ru(1)−C(22) torsion angles for 1, 2-syn, and 2-amphiL). However, when the C(4) ring is directed upward (as in conformers 2-anti and 2-amphi-R), the deviation from the plane is large (C(2)−N(1)−Ru(1)−C(22) torsion angles are equal to −37° and −42°, respectively). We can also see that the geometry of this moiety confirms the previously described interaction between the H(22) atom B

DOI: 10.1021/om5006462 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Table 1. Comparison of the Experimental (1) and Computational Geometries in Investigated Compounds and Bond Dissociation Energies 1 X-ray Ru(1)−C(22) Ru(1)−C(1) Ru(1)−Cl(1) Ru(1)−Cl(2) Ru(1)−O(1) C(4)−C(22) C(2)−C(22) O(1)−C(28) O(1)−C(29) N(1)−C(1)−N(2) C(1)−N(1)−C(4) C(1)−N(1)−C(13) C(1)−N(1)−C(2) C(1)−N(1)−C(3) C(1)−Ru(1)−C(22) Cl(1)−Ru(1)−Cl(2) Ru(1)−C(22)−C(23) C(22)−C(23)−C(28) Ru(1)−C(1)−N(1)−C(2) Ru(1)−C(1)−N(1)−C(3) Ru(1)−C(1)−N(1)−C(4) Ru(1)−C(1)−N(2)−C(13) C(4)−N(1)−Ru(1)−C(22) C(2)−N(1)−Ru(1)−C(22) C(22)−Ru(1)−O(1)−C(28) Ru(1)−C(22)−C(23)−C(28) C(22)−C(23)−C(28)−O(1) O(1)−Ru(1)−C(22)−C(23) C(1)−Ru(1)−O(1)−C(29) Ru(1)−C(1) bond dissociation energy a

1

2-syn

2-amphi-L

1.829(1) 1.979(1) 2.3379(5) 2.3278(5) 2.256(1) 3.072(2)

1.8328 1.9721 2.3964 2.4004 2.3278 3.167

1.8380 1.9775 2.4072 2.4166 2.3794 3.069

1.8347 2.0113 2.4116 2.4082 2.3683 3.040

1.370(2) 1.469(2) 107.2(1) 126.9(1) 126.6(1) 113.6(1) 113.5(1) 101.34(6) 156.25(1) 118.5(1) 118.5(1) −173.3(1) ↑a 171.0(1) ↑a 17.7(2) ↓a −22.4(2) ↓a −2.91(9)

1.3519 1.4486 106.71 127.77 124.58 112.97 113.40 102.68 160.26 119.32 119.31 −174.13 ↑a −174.91 ↑a 3.48↓a 5.28↓a 1.60

1.3491 1.4474 114.91 122.60 119.43 124.20 124.25 105.39 162.65 120.35 119.73 155.96 ↑a 145.06 ↑a −18.05 ↓a −28.38 ↓a −6.49

1.3532 1.4471 119.76 120.64 129.02 128.13 119.14 107.50 157.65 120.21 119.63 177.01 ↑a 2.85 ↓a −1.92 ↓a 175.90 ↑a −1.76

7.1(1) 4.1(2) 2.7(2) −5.8(1) 90.4(8)

0.99 1.56 −0.53 −1.30 18.36 −80.86 kcal/mol

1.87 2.92 −0.92 −2.42 42.70 −74.34 kcal/mol

−3.82 −4.72 0.72 4.32 −23.47 −74.81 kcal/mol

2-anti

2-amphi-R

1.8311 1.9837 2.3908 2.4209 2.3646

1.8323 1.9754 2.4002 2.4280 2.3752

3.059 1.3524 1.4482 119.10 125.29 127.66 121.24 118.44 102.91 159.06 120.51 119.18 −20.26 ↓a 5.65 ↓a 148.84 ↑a 173.71 ↑a

3.014 1.3493 1.4484 116.08 123.07 118.08 122.35 125.96 99.82 162.57 120.63 119.06 −20.33 ↓a 161.78 ↑a 144.61 ↑a −0.43 ↓a

−37.52 0.92 2.08 −1.05 −1.52 77.09 −72.00 kcal/mol

−42.34 5.13 4.78 0.55 −5.07 145.49 −69.32 kcal/mol

Arrows in the table indicate the position of the substituent in the carbene ligand (↑ for upward, ↓ for downward).

Figure 2. Molecular overlay of investigated structures: (a) front view 1 (red) vs 2-syn (gray) and 2-anti (yellow), (b) side view 1 vs 2-syn and 2-anti, (c) front view 1 vs 2-amphi-L (pink) vs 2-amphi-R (blue), (d) side view 1 vs 2-amphi-L vs 2-amphi-R.

and the C(4) mesityl ring,16 present in all Hoveyda-type catalysts due to the constraints imposed by the isopropoxy group. We can visualize the interaction using a Hirshfeld surface,28 by introducing the dnorm value (Figure 3).29 This value is the sum of the two quantities normalized by the van der Waals radius: de, which is the distance from the Hirshfeld surface to the nearest nucleus outside of the surface, and di, which is the corresponding distance to the nearest nucleus inside the surface. Interatomic contacts closer than the sum of

their van der Waals radii are highlighted in red on the dnorm surface. Although ADC ligands should exhibit higher flexibility in comparison to the NHC, both known crystallographic structures of Hoveyda-type derivatives adopt the amphi-L conformation (although for similar Grubbs-like catalysts the conformation of the ADC may be either amphi-L or anti).13 The most straightforward explanation of this phenomenon is that all other conformations are not crystallizing. Such an C

DOI: 10.1021/om5006462 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

groups in the anti conformations (see Supporting Information). Such specific orientation is probably the result of an attractive π−π stacking interaction between the mesityl groups, which is stronger than either the mesityl−phenyl or phenyl−phenyl interaction. A similar arrangement of the mesityl groups in the carbene can be observed for the model of catalyst 3. Two interesting questions arising in the case of these systems is (a) whether the conformation of the ADC group is established before or after the formation of the C(1)−Ru(1) bond and the synthesis of the ADC-Hov system and (b) how flexible is the ADC group after being attached to the remaining part of the catalyst. To answer these questions, we performed rotation scans for two types of carbenes in ADC-Hov derivatives 2 (N,N′-dimesityl-N,N′-dimethylformamidin-2-ylidene) and 3 (N,N′-dimesityl-N,N′-diphenylformamidin-2ylidene) ligands (see Chart 1 and Figure 5). We have used the same computational approach as in the free carbenes case, but since these systems are asymmetric, we performed the scans for both the “right”, C(4), and “left”, C(13), mesityl rings. To provide a complete picture of the dynamics of the systems, we also performed a rotational scan of the entire carbene moiety around the Ru(1)−C(1) bond and evaluated the bond dissociation energy for this bond for each of the four conformations of 2. As expected, in the case of system 2 the energy barriers for rotations around the C(1)−N(1) and C(1)−N(2) bonds are quite similar (see Figure 4). The rotation of the C(4) mesityl ring has an energy barrier comparable to the free carbene case 4 (ca. 20 kcal/mol), while the rotation of the C(13) mesityl ring shows a slightly higher energy barrier (ca. 23 kcal/mol). The slightly higher energy barrier for the C(13) ring is probably a result of the presence of the two chlorine atoms, which are not positioned in a symmetric way, but shifted away from the isopropoxy-styrene part of the molecule (the values of the C(22)−Ru(1)−Cl(1) and C(22)−Ru(1)−Cl(2) angles are 100.9° and 98.7°, respectively, for the DFT-optimized structure of 2). As a result, the chlorine atoms are partially blocking the rotation of the “left” C(13) mesityl moiety due to a steric effect. Interestingly, the rotation barriers of the entire ADC around the Ru(1)−C(1) bond seem to have very similar barriers. In the most interesting case the energy barrier for going from the 2amphi-R to the 2-amphi-L conformation (or vice versa) is approximately 23 kcal/mol. A nearly equal value has been

Figure 3. Interaction between the H(22) atom and the C(4) mesitylene ring for 1 (bottom view).

argument is, however, not in accordance with experimental data since the solution NMR/NOESY studies show also only selected conformations.13 In order to explain these findings, we decided to estimate the rotation barriers for 4 and 5 and analyze the interactions between N-substituents. We performed computational rotational scans of two carbene ligands 4 and 5 (see Chart 1) around the C(1)−N(1) or C(1)−N(2) bonds with 15° increments (24 points in total for each case). We used a relaxed scan, which allowed for the optimization of the remainder of the molecule in each step (Figure 4). Such an approach allowed us to obtain lower limits of the energy barriers for such rotations. In the case of carbene 4 the amphi geometry has the lowest energy, which is consistent with the experimental data.13 It seems that the crucial feature for the stabilization of this particular conformer is the interaction between the methyl group and the benzene ring. It is worth noting that this interaction is fairly weak, ca. −1.5 kcal/mol,30 so it is weaker than the interaction between two aromatic rings (π−π stacking), which is estimated to be almost −3 kcal/mol,31 but stronger than the interaction between two methyl groups, estimated to be around −0.5 kcal/mol. On the other hand, the benzene−benzene type of interaction needs a specific geometry,31 which cannot be accomplished in system 4 due to the constraints imposed by the carbene part of this system and particularly the geometry of the N−Ccarbene−N bond. In the case of system 5 the lowest energy structure is the one with the mesityl groups oriented toward each other, with the phenyl

Figure 4. Rotational scan energies for ADC-containing Hoveyda derivative 2 and carbene 4, with the syn conformation as the starting point. D

DOI: 10.1021/om5006462 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

Figure 5. Rotational scan energies for ADC-containing Grubbs derivative, with the syn conformation as the starting point.

to be rather modest, since it only slightly affects the barrier of mesityl ring rotation in comparison to the free carbene case. On the other hand, the H(22)−C(4) interaction is definitely not negligible, as shown by the differences in the energy barriers of rotation for the 2-anti conformation versus the other three conformations. In view of these results it is difficult to explain without doubt the lack of the anti conformer for the Hoveyda-type catalysts 2. On one hand, this result is consistent with our computational results. The precatalyst 2 is synthesized from the corresponding carbene, for which the amphi-L conformation is the most favorable one. Additionally, the energy barriers of rotations around the C(1)−N(1)/N(2) bonds suggest that the rotation both prior to or after coordination has similar, rather low probability. This is also consistent with the experimental findings that the rotation around these bonds is relatively slow on the NMR scale.13 On the other hand the example of the anti conformation for a similar system ((N,N′-dimesityl-N,N′dimethylformamidin-2-ylidene)(SIMes)-Cl 2 RuCHPh), which is also synthesized from carbene 4, suggests that attaining a different conformation is indeed possible either before or after the coordination to the Ru center. For systems 3 and 5 one could expect slightly higher rotation energy barriers due to possible steric clashes. This is, however, not the case since for rotation energy profiles for both these systems are similar to those of 2 and 4 (see Supporting Information). On the other hand for both 3 and 5 the anti conformation is the lowest energy one and by a non-negligible margin (2−3 kcal/mol; see Supporting Information). The behavior of this system is probably a result of an attractive π−π interaction between the aromatic groups, which is stronger for mesityl moieties than for the phenyl moieties. This, however, may lead to different catalytic properties of such a system, due to the lack of the mesityl moiety in the vicinity of the C(22) atom. We can suggest that system 3 will possess a similar intrinsic flexibility to 2, but different catalytic properties. To better answer the second question (how flexible is the ADC group after being attached to the rest of the catalyst?), we have decided to perform additional calculations using different, though similar precatalyst 7, bearing a methylidene moiety (see Chart 2). A similar system with the SIMES moiety (6, see Chart 2), often used in various olefin metathesis reactions,36

obtained experimentally earlier for the Grubbs catalyst and the rotation of the N,N′-bis[2,4,6-(trimethyl)phenyl]imidazolidin2-ylidene (SIMES) ligand.32 Other works also suggest that the rotation around the Ru(1)−C(1) bond for Grubbs-like systems is either hindered or completely restricted at room temparatures.33−35 We obtained an almost identical value for the carbene rotation for the 2-syn conformation, but in the case of the 2-anti conformation it is noticeably lower, at ca. 15 kcal/ mol. This final value may suggest that the interaction between the H(22) and C(4) atoms, which is present in three conformations (2-syn, 2-amphi-L, 2-amphi-R) but not in the 2-anti one, is not negligible, and breaking it requires an additional 7 kcal/mol. On the other hand it may be argued that the π−π stacking of mesityl moieties alters the π-donation from the lone pairs of N(1)/N(2) atoms to the carbene C(1) atom, weakening the Ru(1)−C(1) bond. The second hypothesis may be tested by calculating the bond dissociation energy (BDE) of the Ru(1)−C(1) bond, which is presented in Table 1. We can see that the BDE is similar for the 2-anti and 2-syn conformers, suggesting that their effect connected to the π−π stacking of mesityl groups is rather small. These results are also consistent with previous experimental studies suggesting that the ADC ligands dissociate from the Ru center easier than SIMES, since for 1 we have obtained a BDE value higher by 6 kcal/mol than for 2 (see Table 1).28 All results presented up to this point lead us to two conclusions. First, since the rotation of the C(13) mesityl group as well as the rotation of the whole carbene group is not likely for the Hoveyda-type catalyst 2 due to relatively large rotation barriers, its amphi-L conformation has to be established for the free carbene, before the addition of the remaining part of the catalyst. The computational and experimental studies agree that the amphi conformation is the dominating one for carbene 4 in the solution. During complexation to Ru the amphi-L orientation of the carbene is chosen due to favorable interactions of the carbene mesityl group with the isopropoxy-styrene part of the Ru complex. While the energy barriers of approximately 20 kcal/mol for the free carbene rotations are still thermally accessible at ambient temperatures, the higher values for the catalysts make these rotations unlikely. Second, the interaction between the H(22) atom of the isopropoxystyrene part and the C(4) atom of the mesityl ring for 2 appears E

DOI: 10.1021/om5006462 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

from this interaction. If no mesityl group is present close to the methylidene moiety (as in conformer anti), the H(22) atom can interact with the C(2) methyl group of the ADC, but this interactions is at least a few kcal/mol weaker. The activation mechanisms for Hoveyda-type catalysts (including 1) have been studied earlier using theoretical methods,25,26,38 and usually three possible initiation pathways of olefin metathesis precatalysts are considered. A dissociative mechanism occurs when the Ru(1)−O(1) bond dissociation is followed by olefin association, while in the interchange mechanism both of these two events occur simultaneously and the mechanism is similar to the SN2-type reaction. The third mechanism, named the associative one, proceeds with the formation of the six-coordinated 18-electron intermediate followed by the Ru(1)−O(1) bond dissociation. Previous theoretical studies have shown, however, that for all investigated Hoveyda-like and Grubbs-like systems the associative mechanism is always characterized by the highest energy barrier. Additionally, in all known and stable crystallographic structures of six-coordinated precatalysts the Ru ion is coordinated by highly electronegative atoms (e.g., nitrogen16,39 or oxygen40,41 atoms). As a result, in this study we have only considered the dissociative and interchange mechanisms as valid initiation pathways for the ADC-Hoveyda catalysts. Even though catalyst 2 has only one stable conformation, it is worth noting that during the initiation it undergoes substantial structural changes, which may alter the conformation of ADC. Therefore, we decided to perform the calculations for all four conformations of 2. The results of our theoretical investigations are presented in Figures 6 and 7, which show the energy

Chart 2. Grubbs-Type Precatalysts and Their ADC Analogue Investigated for Carbene Flexibility: The Activation Scheme

can be characterized by a simple initiation mechanism: upon dissociation of the PCy3 group the active 14e species is formed and the methylidene group undergoes a 90-degree rotation.37 We undertook a computational assessment of the related system 7 with the SIMES group replaced by the same acyclic diamino carbene as in system 2 and performed a series of 15degree rotational scans of the entire carbene groups around the Ru(1)−C(1) bond and the N-mesityl(methyl) groups around the C(1)−N(1) and C(1)−N(2) bonds for both system 7 and its 14e active species 7a (see Figure 5). The final test of the flexibility of the Grubbs-like system was a series of rotational scans around the Ru(1)−C(1), C(1)− N(1)/N(2), and Ru(1)−C(22) bonds for species 7 and 7a. In the case of catalyst 7 our computational results suggest that the flexibility of the ADC is seriously diminished with respect to catalyst 2. The rotation around the C(1)−(N1) or C(1)−N(2) bonds is not likely due to a relatively large energy barrier of approximately 20 kcal/mol. The rotation of the whole carbene moiety around the Ru(1)−C(1) bond shows very large energy barriers of over 30 kcal/mol in the case of syn, amphi-L, and amphi-R conformers. Only in the case of the anti conformer is the energy barrier smaller (22.8 kcal/mol), but still large enough to hinder the possibility of the rotation around that bond. These results clearly show that the interaction between the methylidene group and the C(4) mesityl moiety stabilized the entire structure. As in the case of catalyst 2, we can see that the change of conformation of the carbene after its coordination to ruthenium has low probability. The rotational scan results for the 14e species 7a are quite different and suggest that the dissociation of the PCy3 group results in a much more flexible system. While the rotation around the C(1)−(N1) or C(1)−N(2) bonds gives similar values of energy barriers to the previous case (∼20 kcal/mol), the energy barriers for the rotation around the Ru(1)−C(1) bonds are much lower. Interestingly, however, these barriers remain relatively high for the two amphi conformations (21−22 kcal/mol), suggesting that the conversion between the amphi-L conformer and the amphi-R conformer is again not likely. For the 7a-syn and 7a-anti conformers these energy barriers are between 11 and 13 kcal/mol, suggesting that the entire carbene moiety may rotate rather freely around the Ru(1)−C(1) bond at ambient temperatures. The difference in the behavior of the pairs of conformers may be attributed again to the presence or absence of the H(22)−C(4) interaction, suggesting once more that there is certain stabilization of the entire molecule resulting

Figure 6. Free energies for the initiation step of the ADC-containing Hoveyda derivatives following the interchange mechanism.

barriers ΔG for conformers of 2 and the initiation phase using either the interchange or dissociative mechanism. The amphi-L conformation is always characterized by the lowest free energy in both mechanisms for transition states and products. As a result, even if the rotation around the Ccarbene−N bonds had been viable due to a low energy barrier, the system would still have stayed in the amphi-L conformation as the most energetically favorable one. The different conformations of the ADC part in Hoveyda analogues give us also more insight into the importance of the interaction between the C(4) atom of the mesityl ring and the C(22) atom of the isopropoxy-styrene part. In the previous part F

DOI: 10.1021/om5006462 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

The conformational flexibility of ADCs and their corresponding Hoveyda- and Grubbs-class ruthenium complexes was evaluated by estimating the energy barriers of rotations around the C−N and Ru−C bonds. In the free carbene case the rotation around the C−N bond is thermally accessible (∼20 kcal/mol), while for the Ru-based catalyst it becomes partially restricted due to steric constraints, particularly for the Grubbslike system. The rotation of the entire ADC around the Ru−C bond shows a similar energy barrier. Despite the relatively high flexibility of the carbene, the amphi conformation is favored in all cases due to the favorable benzene−methyl interaction mentioned above. The conformation of the carbene part of both the ADCHoveyda and ADC-Grubbs catalysts has a major impact on the energy barriers of the initiation step of metathesis reaction. First, we demonstrated the presence of the interaction between the H(22) atom of the isopropoxy-styrene part and the C(4) (Cipso) atom of the neighboring mesityl ring. Our results suggest that this interaction has little impact on the rotational energy barriers. On the other hand the importance of the previously described C(4)−C(22) interaction is immediately obvious when we consider the energetic outcome of the precatalyst activation. The amphi-L and syn conformers, both with the mesityl ring close to the C(22) atom, have substantially lower energy barriers and more stable products of the initiation step than those conformers with the mesityl ring rotated away from the Ru center (amphi-R and anti). As a result, the structures of both the dissociative and intermediate path transition states as well as the products are stabilized by this subtle, yet important interaction. These findings should provide inspiration for the future design of new ADC and NHC ligands for Ru-based metathesis catalysts.

Figure 7. Free energies for the initiation step of the ADC-containing Hoveyda derivatives following the dissociative mechanism.

of this study we have confirmed that the interaction between C(4) and H(22) atoms is close to negligible from the point of view of the precatalyst starting structure, which is consistent with previous results,9,42 since the energetic outcome of the rotation of the mesityl group is similar for both the “right” C(4) ring (with the C(4)−H(22) interaction present) and the “left” C(13) ring (with no such interaction). On the other hand the results presented in Figures 6 and 7 suggest that the C(4)− C(22) interaction, which starts forming during the catalyst activation, is relatively important in the formation of the transition state and the products. It is clear from this data that syn and amphi-L conformers have significantly lower energies than the anti and amphi-R conformers, for both transition states and products, allowing for faster and more efficient catalyst activation. The difference between the energetic outcomes for the syn and amphi-L conformations (both with the C(4)− C(22) interaction present) is, however, a result of the favorable interaction between the methyl and phenyl groups, as in the free carbene case. It is also interesting to go back to the BDE for the conformers of catalyst 2 (see Table 1). It is clear that the amphi-R conformer, which gives the lowest free energy in the catalytic cycle, also has the highest BDE for the Ru(1)−C(1) bond. This finding is interesting since there have been attempts to connect the σ/π-donation with the strength of the Ru− carbene bond. There’s definitely not enough data in our work to draw any certain conclusions in this matter, but it would be interesting to see if the high BDE can be correlated with the low-energy barrier for this type of catalysts.

■

ASSOCIATED CONTENT

* Supporting Information S

Cartesian coordinates and energies of all investigated systems and rotational scans. This material is available free of charge via the Internet at http://pubs.acs.org.

■

AUTHOR INFORMATION

Corresponding Author

*(B. Trzaskowski) E-mail: [email protected]. Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS This work was supported by NCN grant UMO-2012/05/B/ ST5/00715. The calculations were partially performed at the Interdisciplinary Center for Mathematical and Computational Modeling of the University of Warsaw (grant no. G53-9).

■

CONCLUSIONS In conclusion, four different, theoretically possible conformers of ADC-Hoveyda analogue 2, ADC-Grubbs analogue 7, and free carbene 4 have been subject to computational studies elucidating their geometrical features as well as their impact on the energetic outcome of the metathesis initiation step. We have shown that the propensity of carbene 2 and catalysts 4 and 7 to adopt the amphi conformation is a result of a favorable benzene−methyl interaction and an example of a C−H···πdriven structure stabilization. Due to the specific geometry constraints in the ADC carbene, such interaction is stronger than the possible π−π stacking of two mesityl rings in the anti conformation.31

■

REFERENCES

(1) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168−8179. (2) Slaughter, L. M. ACS Catal. 2012, 2, 1802−1816. (3) Boyarskiy, V. P.; Luzyanin, K. V.; Kukushkin, V. Y. Coord. Chem. Rev. 2012, 256, 2029−2056. (4) Melaimi, M.; Soleilhavoup, M.; Bertrand, G. Angew. Chem., Int. Ed. 2010, 49, 8810−8849. (5) Vignolle, J.; Cattoën, X.; Bourissou, D. Chem. Rev. 2009, 109, 3333−3384. (6) Collins, M. S.; Rosen, E. L.; Lynch, V. M.; Bielawski, C. W. Organometallics 2010, 29, 3047−3053.

G

DOI: 10.1021/om5006462 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

́ (41) Bieniek, M.; Samojłowicz, C.; Sashuk, V.; Bujok, R.; Sledź , P.; Lugan, N.; Lavigne, G.; Arlt, D.; Grela, K. Organometallics 2011, 30, 4144−4158. (42) Fernández, I.; Lugan, N.; Lavigne, G. Organometallics 2012, 31, 1155−1160.

(7) Handa, S.; Slaughter, L. M. Angew. Chem., Int. Ed. 2012, 51, 2912−2915. (8) Wang, Y.-M.; Kuzniewski, C. N.; Rauniyar, V.; Hoong, C.; Toste, F. D. J. Am. Chem. Soc. 2011, 133, 12972−12975. (9) Straub, B. F. Angew. Chem., Int. Ed. 2005, 44, 5974−5978. (10) Fernández, I.; Lugan, N.; Lavigne, G. Organometallics 2012, 31, 1155−1160. (11) Credendino, R.; Falivene, L.; Cavallo, L. J. Am. Chem. Soc. 2012, 134, 8127−8135. (12) Vorfalt, T.; Wannowius, K.-J.; Plenio, H. Angew. Chem. 2010, 122, 5665−5668. (13) Rosen, E. L.; Sung, D. H.; Chen, Z.; Lynch, V. M.; Bielawski, C. W. Organometallics 2010, 29, 250−256. (14) Allen, F. H. Acta Crystallogr. B 2002, 58, 380−388 REFCODES: USUTOS and USUTUY CSD ver. 5.35 Nov 2013. (15) Trzaskowski, B.; Grela, K. Organometallics 2013, 32, 3625− 3630. (16) Ż ukowska, K.; Szadkowska, A.; Trzaskowski, B.; Pazio, A.; Pączek, Ł.; Woźniak, K.; Grela, K. Organometallics 2013, 32, 2192− 2198. (17) Zhao, Y.; Truhlar, D. G. J. Phys. Chem. A 2005, 109, 5656−5667. (18) Hehre, W. J.; Ditchfield, R.; Pople, J. A. J. Chem. Phys. 2003, 56, 2257−2261. (19) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299−310. (20) Benitez, D.; Tkatchouk, E.; Goddard, W. A. Organometallics 2009, 28, 2643−2645. (21) Benitez, D.; Tkatchouk, E.; Goddard, W. A. Chem. Commun. 2008, 6194−6196. (22) Stewart, I. C.; Benitez, D.; O’Leary, D. J.; Tkatchouk, E.; Day, M. W.; Goddard, W. A.; Grubbs, R. H. J. Am. Chem. Soc. 2009, 131, 1931−1938. (23) Tannor, D. J.; Marten, B.; Murphy, R.; Friesner, R. A.; Sitkoff, D.; Nicholls, A.; Honig, B.; Ringnalda, M.; Goddard, W. A. J. Am. Chem. Soc. 1994, 116, 11875−11882. (24) Boys, S. F.; Bernardi, F. Mol. Phys. 1970, 19, 553−566. (25) Ashworth, I. W.; Hillier, I. H.; Nelson, D. J.; Percy, J. M.; Vincent, M. A. Chem. Commun. 2011, 47, 5428−5430. (26) Thiel, V.; Hendann, M.; Wannowius, K.-J.; Plenio, H. J. Am. Chem. Soc. 2012, 134, 1104−1114. (27) Vorfalt, T.; Wannowius, K.-J.; Plenio, H. Angew. Chem. 2010, 122, 5665−5668. (28) Spackman, M. A.; Jayatilaka, D. CrystEngComm 2009, 11, 19− 32. (29) McKinnon, J. J.; Spackman, M. A.; Mitchell, A. S. Acta Crystallogr. B 2004, 60, 627−668. (30) Zhao, Y.; Truhlar, D. G. J. Chem. Theory Comput. 2005, 1, 415− 432. (31) Sinnokrot, M. O.; Valeev, E. F.; Sherrill, C. D. J. Am. Chem. Soc. 2002, 124, 10887−10893. (32) Sanford, M. S. Synthetic and mechanistic investigations of ruthenium olefin metathesis catalysts. Ph.D. thesis, California Institute of Technology, 2001. (33) Weskamp, T.; Schattenmann, W. C.; Spiegler, M.; Herrmann, W. A. Angew. Chem., Int. Ed. 1998, 37, 2490−2493. (34) Gallagher, M. M.; Rooney, A. D.; Rooney, J. J. J. Organomet. Chem. 2008, 693, 1252−1260. (35) Leuthäußer, S.; Schmidts, V.; Thiele, C. M.; Plenio, H. Chem. Eur. J. 2008, 14, 5465−5481. (36) Vougioukalakis, G. C.; Grubbs, R. H. Chem. Rev. 2010, 110, 1746−1787. (37) Poater, A.; Ragone, F.; Correa, A.; Cavallo, L. Dalton Trans. 2011, 40, 11066−11069. (38) Urbina-Blanco, C. A.; Poater, A.; Lebl, T.; Manzini, S.; Slawin, A. M. Z.; Cavallo, L.; Nolan, S. P. J. Am. Chem. Soc. 2013, 135, 7073− 7079. (39) Szadkowska, A.; Ż ukowska, K.; Pazio, A. E.; Woźniak, K.; Kadyrov, R.; Grela, K. Organometallics 2011, 30, 1130−1138. (40) Szadkowska, A.; Makal, A.; Woźniak, K.; Kadyrov, R.; Grela, K. Organometallics 2009, 28, 2693−2700. H

DOI: 10.1021/om5006462 Organometallics XXXX, XXX, XXX−XXX