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Mechanism of Intermolecular Ene-yne Metathesis Promoted by the Grubbs First-Generation Catalyst: An Alternative Entry Point to Catalysis Jennifer E. Marshall, Jerome B. Keister,* and Steven T. Diver* Department of Chemistry, University at Buffalo, the State University of New York, Buffalo, New York 14260-3000, United States
bS Supporting Information ABSTRACT: The kinetics of intermolecular alkene-alkyne (ene-yne) metathesis promoted by the first generation Grubbs catalyst (Cy3P)2Cl2RudCHPh (1) were investigated. The dissociated tricyclohexylphosphine plays an important kinetic role during the initial exchange with the terminal alkyne, resulting in a half-order rate dependence on 1 and first-order dependence on the alkyne.
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ne-yne metathesis has emerged as an important catalytic method for 1,3-diene synthesis.1 Like alkene metathesis, ene-yne metathesis is promoted by the Grubbs carbene complexes 1 and 2 (Scheme 1). Recent studies have tended to focus on use of the second-generation Grubbs carbene complex 2 because of its greater reactivity and thermal stability; however, the first-generation Grubbs carbene complex 1 is still widely used for applications such as ring-closing ene-yne metathesis. Ene-yne metathesis is unique because it involves a net insertion of an alkyne into the ruthenium-carbene bond, eventually producing the vinyl carbene intermediate C (Scheme 2). Our previous work,2 and the work of the Grubbs group in alkene metathesis,3 led us to consider not only the coordinatively unsaturated, active intermediates in the catalytic cycle but also the tricyclohexylphosphine-bound “resting states”, as these intermediates control the entry of active catalyst into the cycle. Our previous study with the second-generation Grubbs complex 2 suggested that the phosphine-bound resting state D was important to explain observed rate differences for different alkyne substitution. In that study, the phosphine equilibrium D = C served as a critical entry point to catalytic ene-yne metathesis (Scheme 2). In this communication, we investigate ene-yne metathesis reaction kinetics using the first-generation Grubbs complex 1 and find a different ratedetermining step due to phosphine equilibrium in the catalytic entry point A = B. The similarities with alkene metathesis will also be discussed. The ene-yne metathesis reactivity of the first-generation Grubbs complex 1 is significant, because it provides a way to compare ene-yne to alkene metathesis and reveals fundamental properties of the reactive metal carbene. In alkene metathesis, the Grubbs group made a surprising conclusion regarding the reactivity difference between the second- and first-generation catalysts— the phosphine exchange rate is faster for 1, but the selectivity of the 14-electron intermediate B for alkene vs phosphine is more favorable for 2.4 For the equilibrium step A = B using carbene 1, the intrinsic rate constants favor the Cy3P binding over alkene by 15 000:1. This equilibrium favors resting state A. For ene-yne r 2011 American Chemical Society
Scheme 1. Ene-yne Metathesis and the Grubbs Catalysts
metathesis, these data hint that a difference in catalyst resting state (16-electron complex with Cy3P bound) might manifest itself through a change in the rate-determining step. How do differences in phosphine exchange rate affect the ene-yne metathesis mechanism where alkyne bonding is involved? The ene-yne metathesis catalytic activity of 1 may also provide a valuable benchmark for mechanistic comparison, since Grubbs has completely defined the behavior of this catalyst family for alkene metathesis.3 Each of the catalysts 1 and 2 are widely available, and the Grubbs catalyst 1 is still used synthetically for ring-closing applications and for reactions where high temperatures are not needed. An improved understanding of reactivity differences will aid in the selection of catalysts for a particular application and may help the chemist avoid poor reactant combinations, avoid unwanted secondary metathesis reactions,5 and limit problematic decomposition. To answer these questions, we studied the kinetics of the ene-yne metathesis catalyzed by complex 1 (eq 1 in Scheme 1). Ene-yne metathesis (cross ene-yne metathesis) catalyzed by 1 is generally slower than that catalyzed by 2, which led to experimental difficulties associated with longer reaction times. Received: February 11, 2011 Published: March 02, 2011 1319
dx.doi.org/10.1021/om200133j | Organometallics 2011, 30, 1319–1321
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Scheme 2. The Two Different Entry Points to the Catalytic Cycle Depend on Cy3P
Preliminary rate comparisons conducted in toluene led to poor kinetic data, due to significant decomposition in that solvent over lengthy reaction times (toluene was used in our previous study using complex 2). Solvent effects on alkene metatheses have previously been noted, with polar solvents accelerating the rate of ligand dissociation.4b Improved results were obtained in dichloromethane or 1,2-dichloroethane, the latter being the solvent of choice for our kinetic study. The kinetics of the reaction were determined by monitoring the disappearance of alkyne. The alkyne concentration was determined by IR spectroscopy via the absorbance of the alkyne CH bond stretch at 3300-3310 cm-1 (eq 1).6 During the 1-hexene-alkyne metathesis, 1-hexene and alkyne were converted to the diene product cleanly. It was observed that only after the alkyne had completely reacted by ene-yne metathesis did excess 1-hexene undergo alkene selfmetathesis to provide 5-decene and ethylene.7 Kinetic orders for alkene and alkyne were established for the metathesis of 1-hexene and alkyne 3a. The loss of alkyne under pseudo-first-order conditions (excess 1-hexene) showed a linear decrease of the natural logarithm of alkyne concentration with time; this indicates a first-order rate dependence on the alkyne concentration. This is in contrast to the rate law for the same reaction catalyzed by complex 2, which is zero order in [alkyne]. Experiments at varying 1-hexene concentrations showed that the rate was zero order in [alkene]. Again, this is in contrast to the rate law for the same reaction catalyzed by complex 2, which is first order in [alkene]. These data show a shift in the ratedetermining step to a different part of the catalytic cycle. With the orders in unsaturated reactants established, we turned our attention to the order in the Grubbs catalyst 1. To determine the dependence on catalyst concentration, we determined kobs from plots of ln[alkyne 3a] at varying catalyst concentrations of 2.9-30.1 mM and a 1-hexene concentration of 0.32 M and then plotted ln(kobs) vs ln[catalyst] (Figure 1). This plot gave a linear relationship with slope equal to the order n of the catalyst, which was found to be 0.55(0.02), consistent with approximate half-order dependence on [catalyst].8 This is in contrast to the rate law for the same ene-yne metathesis catalyzed by complex 2, which is first order in [catalyst].2 Approximate half-order dependence on catalyst concentration was shown previously by Grubbs et al. for ring-closing alkene metathesis catalyzed by complexes of the first-generation catalyst family, in the absence of added PCy3.3 The rate law is consistent with the mechanism shown in Scheme 3. The alkyne concentration dependence indicates that it is involved in the rate-determining step, which could be step II or
Figure 1. Plot of ln(kobs) vs ln[1] for metathesis of 3a with 1-hexene (0.32 M) with slope 0.55(0.02).
III (defined by the dotted-line box in Scheme 3). In step III, the high-energy ruthenacyclobutene transition state G9 is involved in the reorganization of E, and this is likely to be the slowest elementary step. The half-order dependence on [1] arises from the tricyclohexylphosphine dissociation step I, which generates equal concentrations of free PCy3 and reactive intermediate B from the carbene A. The active carbene B partitions between phosphine binding and alkyne binding; the latter step is catalytically productive (step II). The catalytic reaction depends on the concentration of the reactive intermediate B, which is derived from the Grubbs complex 1. The concentration of active alkylidene B is very low and can be related to the precatalyst 1 through the equilibrium expression Keq = ([B][PCy3])/[1]. Since [B] = [Cy3P], [B]µ[1]0.5. Importantly, the half-order dependence on Grubbs carbene complex 1 rules out the associative pathway in which alkyne reacts directly with 16electron alkylidene A, as this pathway should display a rate law first order in [alkyne] and first order in [catalyst].10 The results here are analogous to the Grubbs study of the alkene metathesis mechanism,3 where alkene (rather than alkyne) coordination would be involved in this step. Kinetic dependencies for alkynes 3b,c with 1-hexene were analogous, with a narrow range of observed rates. Plots of ln(kobs) vs ln[catalyst] gave linear relationships with slopes of 0.53(0.04) for 3b and 0.44(0.07) for 3c, consistent with approximate halforder dependence on [catalyst]. The calculated rate constants, 1320
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Scheme 3. Proposed Catalytic Cycle for Ene-yne Metathesis Promoted by Grubbs Catalyst 1
based on a rate law which is first order in alkyne and half order in catalyst, follow the trend 3b ([8.0(0.7)] 10-3 M-0.5 s-1) > 3c ([4.6(0.4)] 10-3 M-0.5 s-1) > 3a ([2.4(0.3)] 10-3 M-0.5 s-1). The faster rate for 3b in comparison to that for the more sterically hindered 3a is expected if alkyne coordination is involved in the rate-determining step (e.g., step II or III in Scheme 3). Interestingly, for ene-yne metathesis promoted by the second-generation Grubbs complex 2, the alkyne reactivities are reversed: 3a reacts about 20 times faster than 3b. In conclusion, the kinetics of ene-yne metathesis catalyzed by Grubbs first- and second-generation catalysts display different rate-determining steps. Phosphine binding influences the entry of active carbene into the catalytic cycle, which helps explain the reactivity difference between 1 and 2 for ene-yne metathesis. The first-generation catalyst does not have the same high affinity for unsaturated reactants as compared to Cy3P, as previously observed in the secondgeneration Grubbs catalyst. As a result, the carbene A serves as the entry point to catalysis, with the dissociable Cy3P ligand serving as the gatekeeper. Since the role of the phosphine is so prominent with these catalysts, we anticipate significant differences with catalysts of the “phosphine-free” type, where no such resting states exist. Further studies along these lines are continuing in our laboratories.
’ ASSOCIATED CONTENT Supporting Information. Text, figures, and tables giving experimental details and kinetic data. This material is available free of charge via the Internet at http://pubs.acs.org.
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’ AUTHOR INFORMATION Corresponding Author
*E-mail: diver@buffalo.edu (S.T.D.).
’ REFERENCES (1) Recent reviews: (a) Diver, S. T.; Giessert, A. J. Chem. Rev. 2004, 104, 1317. (b) Poulsen, C. S.; Madsen, R. Synthesis 2003, 1. The first examples of ene-yne cross-metathesis employed carbene catalyst 1: (c) Stragies, R.; Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. 1997, 36, 2518. (2) Galan, B. R.; Giessert, A. J.; Keister, J. B.; Diver, S. T. J. Am. Chem. Soc. 2005, 127, 5762. (3) Dias, E. L.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc. 1997, 119, 3887. (4) (a) Sanford, M. S.; Love, J. A.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 6543. (b) Love, J. A.; Sanford, M. S.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 10103. (5) For example, a less reactive catalyst might be preferred to achieve a kinetic result, where secondary cross-metathesis is intentionally minimized. For the rules of alkene reactivity for various Grubbs catalysts, see: Chatterjee, A. K.; Choi, T.-L.; Sanders, D. P.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 11360. (6) Using a GC assay, we verified the accuracy of the rate determination, showing that (1) the rate of alkyne disappearance was the same as that measured with the IR method and (2) the 1,3-diene product appeared concomitantly with the alkyne disappearance (see Figure S1 in the Supporting Information). (7) For this particular 1-alkene-alkyne combination, alkene (RCHdCH2) exchange with the catalyst 1 to form styrene and carbene complex B, where R = alkyl group, is much faster than ene-yne metathesis. (8) Plotting equation: ln kobs = n ln[1] þ ln k. See the Supporting Information. (9) Lippstreu, J. J.; Straub, B. F. J. Am. Chem. Soc. 2005, 127, 7444. (10) The kinetics of alkene vs alkyne binding to 16-electron complex 1 were recently reported; these data show that alkene coordination is ca. 10 times faster than alkyne coordination: Sohn, J.-H.; Kim, K. H.; Lee, H.-Y.; No, Z. S.; Ihee, H. J. Am. Chem. Soc. 2008, 130, 16506. Since the predominant pathway for alkene metathesis using 1 involves PCy3 dissociation to form a 14-electron intermediate, these data may not apply to the catalytic reaction. DFT calculations suggest that alkynes bind more strongly than alkenes with comparable steric properties to 14electron ruthenium carbene complexes.9
’ ACKNOWLEDGMENT We gratefully acknowledge Dr. Richard Pederson of Materia, Inc., for catalyst support and financial support of this work through research grants from the NSF (CHE-601206 and CHE-1012839 to S.T.D. and J.B.K.). 1321
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