ARTICLE pubs.acs.org/Organometallics
Carbene Rotamer Switching Explains the Reverse Trans Effect in Forming the Grubbs Second-Generation Olefin Metathesis Catalyst Hsiao-Ching Yang,*,† Yen-Chin Huang,‡ Yi-Kang Lan,† Tien-Yau Luh,‡ Yan Zhao,^ and Donald G. Truhlar*,§ †
Department of Chemistry, Fu-Jen Catholic University, New Taipei City, Taiwan, Republic of China Department of Chemistry, National Taiwan University, Taipei, Taiwan, Republic of China ^ Commercial Print Engine Lab., HP Laboratories, Hewlett-Packard Co., Palo Alto, California, United States § Department of Chemistry and Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota, United States ‡
bS Supporting Information ABSTRACT: As a long-standing puzzle, experimental observations reveal faster organophosphine dissociation in the olefin metathesis by Grubbs’s first-generation precatalyst (Gen I) than by the secondgeneration precatalyst (Gen II), but Gen I shows less catalytic activity. Here we show by electronic structure calculations with the M06-L density functional that carbene rotamer energetic effects are responsible for the inverse relation between organophosphine dissociation rate and catalytic activity. The carbene rotamer acts as a toggle switch, triggering the dissociative mechanism that produces the active catalyst. The slower catalyst production in Gen II as compared to Gen I is not a pure electronic effect but results from rotameric coupling to the dissociation coordinate speeding up Gen I dissociation more than Gen II dissociation. If organophosphine dissociation were to occur with fixed rotamer orientation, Gen II would be produced faster than Gen I, as originally expected. The rotameric energetics also contributes to the higher catalytic activity of the Gen II catalyst.
’ INTRODUCTION Olefin metathesis catalyzed by ruthenium carbenes is a powerful tool for forming organic carbon carbon double bonds,1 making it useful for the synthetic applications of olefin crossmetathesis, ring-opening metathesis polymerization (ROMP), acyclic diene metathesis polymerization, and ring-closing metathesis. The mechanisms of such catalytic reactions have been explored extensively, and it is widely appreciated that dissociation of an organophosphine ligand is a critical step in forming a 14-electron ruthenacarbene intermediate (denoted as B in Scheme 1) that serves as the active species with trans-olefin coordination to form a ruthenacyclobutane. ’ RESULTS AND DISCUSSION The ligand L (see Scheme 1) differentiates first-generation (1, also called Grubbs-I or Gen I) and second-generation (2, also called Grubbs-II or Gen II) catalysts. Changing the L ligand from an organophosphine to an N-heterocyclic carbene (NHC) dramatically increases the reactivity. This was originally attributed to the increased labilization of the organophosphine group of the 16-electron precatalyst A due to the large trans influence of the more bulky and basic H2IMes ligand.2 4 However, subsequent investigation of the kinetics found that the enthalpy of activation for dissociation of the organophosphine ligand in 2 is higher than in 1, which slows the dissociation process in the former.5,6 Sanford et al.5 attributed this to a two-stage kinetic r 2011 American Chemical Society
process in which, although the rate constant for loss of organophosphine is 2 orders of magnitude greater for Grubbs catalyst 1 than for 2, the 14-electron ruthenacarbene 1B is rapidly removed from the catalytic cycle by trapping with free organophosphine. The NHC-ligated 2B, although formed more slowly than 1B, remains longer in the catalytic cycle because recoordination of free organophosphine is less favorable. The ratio of rate constants k 1/k2, defined in Scheme 1, is 4 orders of magnitude greater for 1B than for 2B.5 Gas-phase experiments also indicated that the 14-electron species 2B has more favorable partitioning toward the product-forming step than does 1B.7 Thus, catalyst 2 initiates the catalytic cycle more slowly, but propagation is much faster, leading to an overall increase in metathesis activity of a hundred to a thousand times. The kinetic results indicate that organophosphine dissociation is the rate-determining step for 2, but not for 1.5 7 However, the slow initiation rate of 2 remains a serious problem because only a small fraction of the catalyst may initiate before the substrate is consumed, such that one cannot control the molecular weight of the polymer.5,8 The conventional way to speed up the initiation is to employ a stronger σ donor as ligand L. The H2IMes ligand, being a strong electron donor, should favor dissociation of trans ligands as compared to L = PCy3. This is called the trans effect. It has three aspects, the structural and thermodynamic trans effects Received: June 21, 2011 Published: July 08, 2011 4196
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Organometallics (sometimes called trans influence) and the kinetic trans effect. The structural and thermodynamic trans effects imply that 2 should have longer and weaker Ru P bonds than 1, and the kinetic trans effect is that it should have a lower energy of activation for producing the catalyst. The experimental results on slow initiation of 2 are inconsistent with the expected trans effect of the H2IMes ligand in 2. Density functional studies showed that van der Waals attraction is the main contributor to the corresponding higher bond dissociation energies for Grubbs catalyst 2, but our mechanistic understanding of how ruthenacarbene ligands effect catalytic metathesis is still imperfect, and, in particular, the slow initiation of 2 and the associated inverse relation between organophosphine dissociation and catalytic activity is still not fully understood. This is an area where computations can be very useful because they can uncover structural and conformational features of intermediates and transition states that remain elusive when using only experimental techniques, but which can be of the utmost importance for fundamental understanding and for improved catalyst design. For many years, theory was not able to address quantitative issues in catalysis because of the high costs of studying realistic catalysts; calculations in which the catalyst was oversimplified (e.g., replacing organophosphines with unsubstituted phosphines) were untrustworthy because it is known experimentally that such substitutions have a profound effect on the chemistry. In recent years, however, density functional theory (DFT) has been used successfully for many problems in transition metal chemistry without such oversimplifications,9,10 and this leads to the hope that qualitatively correct and even semiquantitative descriptions of realistic catalysts are now practical. However, initial attempts to use DFT to study Grubbs catalysts yielded the incorrect prediction that 2 has a weaker Ru organophosphine bond than 1.11 A meta density functional called M06-L12 15 has been able to predict the correct ligand effect on the bond energy for real catalysts,16 and it shows excellent agreement with well-converged quantum mechanical calculations on small, model catalysts17 (for which they are affordable). Here we use the M06-L functional to examine the carbene orientation in the structural evolution accompanying catalysis. Straub18,19 provided qualitative molecular orbital explanations of how the relative stability of carbene orientations is regulated by the other ruthenium ligands; other authors also pointed out the importance of the carbene orientations in Grubbs catalysis.20 23 The carbene orientation is specified by the dihedral angle τ, which is the L Ru CR R torsion angle, where CR is the carbene carbon of the benzylidene (1 or 2) or methylidene ligand (1m or 2m); values of this dihedral angle close to 90 and 180 correspond, respectively, to active and inactive rotamers in that a torsion angle near 90 is required to make the metallacyclobutane. The energetics and kinetics of rotameric states of ligands are critical not just for understanding the mechanism but also for determining the microstructures of polymers formed in metathesis polymerization.24,25 Efficient production of stereoregular polymers with Grubbs catalytic ROMP is still an unattained goal.22 However, the key determining factor for synthesis of isotactic or syndiotactic polymers is the cis/trans ratio of the newly formed double bonds as determined by the clockwise or counterclockwise rotation of the benzylidene ligand in passing from an inactive structure to an active one, as illustrated in Figure 1. Consideration of the barriers to rotameric state interconversion therefore warrants attention and may open a new venue in understanding the stereochemistry of Grubbs olefin
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Figure 1. Carbene rotation toward an active carbene complex determines the trans/cis ratio of the double bond formed in ROMP. Structures shown are cis and trans isomers for 1Ca and 1D.
Scheme 1. Structure Labels and Mechanism
metathesis as required for synthesis of polymers with spatially controlled properties.26 29 Here we examine the quantitative importance of the carbene orientation on the energetics of the organophosphine dissociation and olefin binding steps by calculating energies and rotameric energy differences at critical points in the three steps of the catalytic mechanism in Scheme 1. Structure. The molecular orbital considerations of Straub18 predict that the ligand pair that is orthogonal to the π-acceptor orbital of the R carbon will be significantly bent, and we find that this is true with Cl Ru Cl bond angles of 149 150 in the inactive carbene complexes Bi and to a lesser extent in the active rotamers with L Ru P bond angles of 155 165. Furthermore the L Ru CR angle differs significantly from 90, being 95 102 in the four B structures, which is consistent with increased back-bonding.18 The structural trans effect implies that 2 should have longer Ru P bonds than 1. We find that this is indeed the 4197
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Table 1. Relative Energiesa (kcal/mol) A
B
C
Lowest-Energy Rotamers 1
0
35.1
18.9
2
0
39.4b
19.2
1m
0
34.4
20.4
2m
0
39.2
25.5
1
0
48.5c
18.9
2
0
44.2c
19.2
1m 2m
0 0
48.7c 46.8c
25.3c 25.5c
Active Rotamers
Inactive Rotamers 1
10.1d
35.1
26.8c
2
d
39.4
24.7c
1m
c
2.3
34.4
20.4
2m
6.6c
39.2
27.7
16.8
a
Local minima except where noted otherwise. b From ref 17. c Saddle point. d Optimized with the constraint that τ = 180.
case; in the favored active conformation, the Ru P bond length in 1A is 2.43 Å, and that in 2A is 2.47 Å. Production of the Catalyst. The structural features do not translate into a simply understood stability pattern, as shown in Table 1, which shows that the carbene rotamer state plays a major role in the dissociative mechanism. Since there is little or no intrinsic barrier (j1 kcal/mol) to organophosphine dissociation, that is, no or hardly any barrier in the exoergic (associative) direction, the thermodynamic and kinetic trans effects are essentially the same, at least from a conventional transition-state-theory point of view, and they lead to the expectation that ΔE, defined as the energy of B minus that of A, should be smaller in 2 and in 1; but this is not true, as discussed in the Introduction. The present M06-L calculations confirm this experimentally observed breakdown of the trans effect, but Table 1 shows that this is a rotamer effect rather than a strictly electronic effect. In particular, if one proceeds from the lowest energy structure of A to the lowest energy structure of B, ΔE is larger in 2 (39.4 kcal/mol) than in 1 (35.1 kcal/mol), but if one conserves the rotamer state as the active state, then ΔE is 44.2 kcal/mol in 2 but 48.4 kcal/mol in 1m. The larger dissociation energy for the model 2 is a direct result of its smaller stabilization of the inactive rotamer and is not a pure electronic effect! We find that when 1 is used, the energy barrier for the direct formation of active carbene 1Ba is 48.5 kcal/mol, which is 13.4 kcal/mol higher than the energy of 35.1 kcal/mol required to transform 1Aa to the inactive carbene complex 1Bi. The latter value is in good agreement with the gas-phase activation energy7 of 33.4 kcal/mol for 1. For catalysis using 2, the relative energies calculated for the formation of active and inactive carbene complexes from the precatalyst are 44.2 and 39.4 kcal/mol, respectively. The latter result is again comparable with the experimentally observed7 activation energy of 36.9 kcal/mol for 2B. (When comparing the calculated bond dissociation energy to the gasphase experiments, note that the experimental results include zero point and thermal energy; if we remove these contributions, the agreement between calculations and experiments becomes better, as we have shown for the Gen II catalyst in ref 17.) The
preferred carbene orientation of each precatalyst differs from that of its dissociated product. The 14-electron species has the inactive structure, 1Bi, as a local minimum and the active one, 1Ba, as a saddle point. The barrier height to reach the saddle is 13.3 kcal/mol for 1 and 4.8 kcal/mol for 2. We also constructed truncated Grubbs-type catalysts to examine the effect of the phenyl group of the benzylidene on bond energetics. These models of the true Grubbs catalysts 1 and 2 have an unsubstituted methylidene rather than a benzylidene, and they are called 1m and 2m in Scheme 1, with 1m being a model of 1 and 2m being a model of 2. The trends are the same for the model systems; just as in the real catalysts, we see that were dissociation to occur at fixed rotamer torsion angle, 2m would dissociate more readily, as expected by the trans effect. In particular, if we consider the dissociative process proceeding from the favored rotamer to the favored rotamer, 1m has a lower dissociation energy by 4.8 kcal/mol, whereas if we consider the dissociative process proceeding from the active rotamer to the active rotamer, 2m has a lower dissociation energy by 1.9 kcal/mol. Additional studies show that, for 1m, cleavage of the Ru P bond and rotation of the carbene are nonsynchronous processes; the carbene rotates from 90 to 180 at a very early stage of the dissociation of the organophosphine ligand; this rotation seems to actuate liberation of the organophosphine ligand. On the other hand, the path for 2m shows synchronous dissociation of the P Ru bond and rotation of the carbene. Olefin Coordination. Mechanistic experimental results suggest that olefins coordinate to the bottom of the carbene complex before metallacycle generation.30,31 Figure 1 illustrates the attack of norbornene (bicyclo[2.2.1]hept-2-ene, to be abbreviated NBE) at the bottom coordination site of a 14-electron ruthenacarbene; this reaction step converts tetracoordinated B to pentacoordinated C. When NBE binds to B, the energy of binding is partially offset by the energy required to restore the active conformation, and since the inactive rotamer is more favored in 1 than in 2 (see Table 1, where there is a 13.3 kcal/mol difference between 1Ba and 1Bi vs a 4.8 kcal/mol difference between 2Ba and 2Bi), this contributes an 8.5 kcal/mol greater offset in 1 than in 2. This is reflected in the higher energy of 1(C) ( 16.2 kcal/mol, relative to the state B) than that of 2(C) ( 20.2 kcal/mol), a difference of 4.0 kcal/mol. The 8.5 kcal/mol offset (rotameric penalty) accounts for this difference, and the NBE coordination mitigates the rotameric penalty by about 1/2. The lower energy of structure 2C should lead to a lower energy for the critical transition state for forming the metallacyclobutane (structure D); this is the transition state of the rate-determining step for 1. To expose the underlying electronic effect of the relative orientation of the carbene to the two planes of ligands of Figure 2, we again considered the model catalysts 1m and 2m. Table 1 shows the dramatic result that the inactive state of 1mC is actually the favored rotamer, by the large margin of 4.9 kcal/mol, whereas for 2mC the active rotamer is favored. As mentioned above, this rotameric penalty is expected to carry over to the transition state for forming metallacyclobutane, and we confirmed this for 1m and 2m. In particular, we found that the energy of the transition state for converting C to metallacyclobutane (D) is 4.5 kcal/mol higher for 1m than for 2m, relative to C (but 0.6 kcal/mol lower, relative to A). In summary, for stage A (organophosphine (PCy3) ligation) in 1, 2, 1m, and 2m and for stage C (NBE ligation) in 1, 2, and 2m, the active rotamer is always lower in energy than the inactive one, 4198
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noncovalent interactions for the catalyst production step was demonstrated.16 Here we have quantitatively demonstrated the key role of carbene rotameric states in both catalyst production and olefin binding, thereby explaining the long-puzzling differences of first- and second-generation Grubbs catalysts on a unified basis. Dissociation of the precatalyst to form the catalyst is speeded up for both 1 and 2 by coupling to internal rotation. The speed-up in forming 1 is much greater, and so it actually is formed more readily than 2. But when the olefin coordinates to the more readily formed Gen I catalyst, Gen I must overcome the electronic effect that favors the inactive state, hindering catalysis, whereas in 2, the olefin binding more readily induces a transition back to the active form, promoting catalysis.
’ METHODS Figure 2. Comparison of the intrinsic rotameric energy barriers at three stages of reaction of the catalytic mechanism. These results are the absolute values of energy differences.
All energetic results are calculated with the M06-L density functional at geometries optimized by M06-L for 1 and 2 and optimized with the BP86 density functional33 for 1m and 2m except for the cis trans comparison of C and D structures, which was carried out with BP86.
’ ASSOCIATED CONTENT whereas for stage B (the 14-electron catalyst) the inactive one is lower in energy in 1, 2, 1m, and 2m, and the active structure is a saddle point, not a local minimum. However for NBE ligation in 1m, the inactive rotamer is the lower-energy one, in contrast to the case of 2m. Thus, for NBE association, the carbene maintains its inactive rotameric state in passing from B to C in the 1m case, whereas it switches from inactive to active in the 2m case. These results indicate the organophosphine ligands and norbornene substrates possess disparate intrinsic electronic properties, and these findings demonstrate a previously unknown difference between the Gen II-type Gen I-type catalyst systems. Figure 2 shows the absolute values of the carbene rotameric energy difference at three critical stages of the overall reaction for 1 and 2. These energy differences can be called the intrinsic torsional barriers. The striking features of Figure 2 are that the torsional barrier is much higher in the precatalyst A for the Gen II system than for Gen I and that the torsional barrier is much higher in the uncrowded structure B than in the crowded structures A and C. The former is consistent with the carbene rotamer energetic effects being responsible for the inverse relation between organophosphine dissociation rate and catalytic activity, and the latter reveals that orbital interactions rather than repulsive steric effects dominate the torsional barriers. Stereochemistry of the Catalytic Step. Figure 1 illustrates the difference between the cis and trans isomer of the phenyl group in 1C. We find the trans isomer is lower in energy by 1.2 kcal/mol, which may be attributed to a steric clash as the smallest nonbonded H H distances decrease from 2.69 Å (trans) to 2.52 Å (cis). The energy difference increases to 2.9 kcal/mol for D, where the smallest nonbonded H H distances are 2.30 Å (trans) and 2.15 Å (cis). Thus the sterics favor production of the trans double bond.
’ CONCLUDING REMARKS The conventional explanations of ligand influence on the metathesis activity of organoruthenium carbene catalysts focus on σ basicity (electron-pair donating ability) and steric effects (size).32 In 2007, rotamer-state-dependent orbital interactions were emphasized,19 and the decisive importance of attractive
bS
Supporting Information. Geometries, absolute energies of structures, basis sets, and software. This material is available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION Corresponding Authors
*(H.-C.Y.) Tel: +886-2-29052534. E-mail: hcyang_chem@mail. fju.edu.tw. (D.G.T.) Tel: 1(612)624-7555. E-mail: truhlar@ umn.edu.
’ ACKNOWLEDGMENT This work was supported by the National Science Council of the ROC (grant NSC 96-2113-M-030-002-MY2), the National Science Foundation of the USA (grant no. CHE09-56776), and the Air Force Office of Scientific Research. We thank Fu-Jen Catholic University for support and the National Center for High-Performance Computing of the ROC and Minnesota Supercomputing Institute for computational resources. ’ REFERENCES (1) Grubbs, R. H. Angew. Chem., Int. Ed. 2006, 45, 3760. (2) Dias, E. L.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc. 1997, 119, 3887. (3) Weskamp, T.; Kohl, F. J.; Hieringer, W.; Gliech, D.; Herrmann, W. A. Angew. Chem., Int. Ed. 1999, 38, 2416. (4) Huang, J.; Stevens, E. D.; Nolan, S. P.; Peterson, J. L. J. Am. Chem. Soc. 1999, 121, 2674. (5) Sanford, M. S.; Love, J. A.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 6543. (6) Adlhart, C.; Chen, P. J. Am. Chem. Soc. 2004, 126, 3496. (7) Torker, S.; Merki, D.; Chen, P. J. Am. Chem. Soc. 2008, 130, 4808. (8) Dunbar, M. A.; Balof, S. L.; LaBeaud, L. J.; Yu, B.; Lowe, A. B.; Valente, E. J.; Schanz, H.-J. Chem.—Eur. J. 2009, 15, 12435. (9) Harvey, J. M. Annu. Rep. Prog. Chem. Sect. C 2006, 102, 203. (10) Cramer, C. J.; Truhlar, D. G. Phys. Chem. Chem. Phys. 2009, 11, 10757. (11) Tsipis, A. C.; Orpen, A. G.; Harvey, J. N. Dalton Trans. 2005, 34, 2849. (12) Zhao, Y.; Truhlar, D. G. J. Chem. Phys. 2006, 125, 194101. 4199
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