Organometallics 2010, 29, 3007–3011 DOI: 10.1021/om100310f
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Ruthenium Complexes Bearing Two N-Heterocyclic Carbene Ligands in Low Catalyst Loading Olefin Metathesis Reactions Xavier Bantreil, Rebecca A. M. Randall, Alexandra M. Z. Slawin, and Steven P. Nolan* EaStCHEM School of Chemistry, University of St. Andrews, St. Andrews KY16 9ST, U.K. Received April 17, 2010
The synthesis of ruthenium indenylidene complexes containing mixed N-heterocyclic carbene ligands featuring one sterically small NHC [IMeMe (1,3,4,5-tetramethylimidazol-2-ylidene), IiPrMe (1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene), and ICy (1,3-dicyclohexylimidazol-2-ylidene)] and one larger congener SIMes (1,3-bis-(2,4,6 trimethylphenyl)imidazolin-2-ylidene) is described. Characterization by X-ray diffraction allowed for calculation of percent buried volume of the small NHCs in these complexes and for speculation on the relationship NHC/catalytic activity. In addition, these complexes displayed an enhanced stability but also a high ability to promote ring-closing metathesis reactions at catalyst loadings as low as 0.05 mol %. Introduction Olefin metathesis is now recognized as one of the most valuable tools in organic chemistry.1 Indeed, its versatility is highlighted by its use in an ever-increasing number of applications ranging from the synthesis of biologically active compounds to polymers.2 Since the initial report of the firstgeneration ruthenium catalyst,3 numerous studies have aimed at developing long-living and more active precatalysts. Replacing a phosphine ligand by an N-heterocyclic carbene (NHC) increased the reactivity as well as the stability of
the corresponding complex.4 Even more stable bis-NHC ruthenium complexes were reported earlier by Herrmann5 and Grubbs6 (Figure 1), showing increased stability but moderate activity in RCM and ROMP, probably because of the strong binding of the carbene to the metal center. The same tendency was observed more recently by Verpoort and co-workers in [(NHC)2RuCl2(CHPh)] (NHC = N,N0 -aryl,alkyl-imidazol-2-ylidene) complexes7 and Zhang et al. for [(NHC)2RuCl2(CHPh)] (NHC = N,N0 -diarylimidazol-2-ylidene) complexes.8 However, Plenio and co-workers recently revealed that introducing an electron-poor NHC in bis-NHC benzylidene-type complexes improved their efficiency in elevated temperature ring-closing metathesis (RCM) reactions.9 In a follow-up study, they have demonstrated that [(NHC)(NHCewg)RuCl2(CHPh)] complexes, in which NHCewg is sterically small and was shown to act as the leaving ligand, could be highly efficient in the RCM of hindered substrates.10 We wanted to investigate the behavior of analogous bis-NHC indenylidene-type complexes, especially at low catalyst loadings. Indeed, indenylidene complexes are more stable precatalysts than their benzylidene counterparts,11 and these have already been shown to be excellent precatalysts.12 Thus, generating
*Corresponding author. Fax: (þ44) 1334463808. E-mail: snolan@ st-andrews.ac.uk. (1) For reviews on metathesis, see: (a) F€ urstner, A. Angew. Chem., Int. Ed. 2000, 39, 3013–3043. (b) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18–29. (c) Handbook of Metathesis; Grubbs, R. H., Ed.; Wiley-VCH: Weinheim, 2003; p 1204. (d) Astruc, D. New J. Chem. 2005, 29, 42–56. (e) Deshmukh, P. H.; Blechert, S. Dalton Trans. 2007, 2479– 2491. (2) For reviews on synthetic applications of olefin metathesis, see: (a) Deiters, A.; Martin, S. F. Chem. Rev. 2004, 104, 2199–2238. (b) Mc Reynolds, M. D.; Dougherty, J. M.; Hanson, P. R. Chem. Rev. 2004, 104, 2239–2258. (c) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem., Int. Ed. 2005, 44, 4490–4527. (d) Van de Weghe, P.; Bisseret, P.; Blanchard, N.; Eustache, J. J. Organomet. Chem. 2006, 691, 5078–5108. (e) Donohoe, T. J.; Orr, A. J.; Bingham, M. Angew. Chem., Int. Ed. 2006, 45, 2664–2670. (f) Gradillas, A.; Perez-Castells, J. Angew. Chem., Int. Ed. 2006, 45, 6086–610. (g) Hoveyda, A. H.; Zhugralin, A. R. Nature (London) 2007, 450, 243–251. (h) Kotha, S.; Lahiri, K. Synlett 2007, 2767–2784. (i) Compain, P. Adv. Synth. Catal. 2007, 349, 1829–1846. (3) (a) Nguyen, S. T.; Johnson, L. K.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1992, 114, 3974–3975. (b) Schwab, P; France, M. B.; Ziller, J. W.; Grubbs, R. H. Angew. Chem. 1995, 107, 2179–2181; Angew. Chem., Int. Ed. Engl. 1995, 34, 2039-2041. (4) (a) Huang, J.; Stevens, E. D.; Nolan, S. P.; Petersen, J. L. J. Am. Chem. Soc. 1999, 121, 2674–2678. (b) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953–956. For recent reviews on NHCcontaining precatalysts: (c) Samojlowicz, C.; Bieniek, M.; Grela, K. Chem. Rev. 2009, 109, 3708–3742. (d) Vougioukalakis, G. C.; Grubbs, R. H. Chem. Rev. 2010, 110, 1746–1787. (5) Weskamp, T.; Schattenmann, W. C.; Spiegler, M.; Herrmann, W. A. Angew. Chem. 1998, 110, 2631–2633; Angew. Chem., Int. Ed. 1998, 37, 2490-2493. (6) Trnka, T. M.; Morgan, J. P.; Sanford, M. S.; Wilhelm, T. E.; Scholl, M.; Choi, T.-L.; Ding, S.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 2546–2558.
(7) Ledoux, N.; Allaert, B.; Linden, A.; Voort, P. V. D.; Verpoort, F. Organometallics 2007, 26, 1052–1056. (8) Zhang, W.; Bai, C.; Lu, X.; He, R. J. Organomet. Chem. 2007, 692, 3563–3567. (9) Vorfalt, T.; Leuth€ausser, S.; Plenio, H. Angew. Chem. 2009, 121, 5293–5296. Angew. Chem., Int. Ed. 2009, 48, 5191-5194. (10) Sashuk, V.; Peeck, L. H.; Plenio, H. Chem.—Eur. J. 2010, 16, 3983–3993. (11) For a review on ruthenium indenylidene complexes: (a) Dragutan, V.; Dragutan, I.; Verpoort, F. Platinum Met. Rev. 2005, 49, 33–40. (b) Boeda, F.; Clavier, H.; Nolan, S. P. Chem Commun. 2008, 2726–2740. See also for increased stability of such complexes: Clavier, H.; Petersen, J. L.; Nolan, S. P. J. Organomet. Chem. 2006, 691, 5444–5477, and references therein. (12) (a) Jafarpour, L.; Schanz, H.-J.; Stevens, E. D.; Nolan, S. P. Organometallics 1999, 18, 5416–5419. (b) Clavier, H.; Nolan, S. P. Chem.— Eur. J. 2007, 13, 8029–8036. (c) Boeda, F.; Bantreil, X.; Clavier, H.; Nolan, S. P. Adv. Synth. Catal. 2008, 350, 2959–2966. (d) Bieniek, M.; Microwska, A.; Usanov, D. L.; Grela, K. Chem.—Eur. J. 2008, 14, 806–818. (e) Clavier, H.; Urbina-Blanco, C. A.; Nolan, S. P. Organometallics 2009, 28, 2848– 2854. (f) Monsaert, S.; Canck, E. D.; Drozdzak, R.; Voort, P. V. D.; Verpoort, F.; Martins, J. C.; Hendrickx, P. M. S. Eur. J. Org. Chem. 2009, 655–665.
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Figure 1. Previously reported ruthenium complexes in the context of the present study.
bis-NHC indenylidene complexes might afford longer-living precatalysts, resistant to high-temperature conditions. We envisioned an easy synthesis from commercially available ruthenium indenylidene pyridine adduct Ind-III (Figure 1).13
Scheme 1. Synthesis of Bis-NHC Indenylidene Complexes 1a-c
Results and Discussion Synthesis and Characterization of Complexes 1a-c. Direct reaction of Ind-III featuring SIMes ligand (1,3-bis-(2,4,6 trimethylphenyl)imidazolin-2-ylidene) with 1.1 equiv of the appropriate free NHC in toluene at room temperature afforded the expected complexes. Ind-III was reacted with three readily available small free NHCs, IMeMe (1,3,4,5-tetramethylimidazol-2-ilydene), I iPrMe (1,3-diisopropyl-4,5dimethylimidazol-2-ilydene), and ICy (1,3-dicyclohexylimidazol-2-ilydene), affording respectively complexes 1a, 1b, and 1c (Scheme 1). After 1 to 3 h reaction time, complexes 1a-c were isolated in high yields from 70% to 98% on a 1 g scale. In order to fully characterize those complexes, X-ray quality crystals were grown by slow evaporation of a solution of 1a-c in a mixture CH2Cl2/pentane (v/v 1:2). Compounds 1a and 1c gave suitable crystals for diffraction study. Ball and stick representations of 1a and 1c are provided in Figure 2, and selected bond lengths and angles are presented in Table 1. Both complexes present a slightly distorted square-pyramidal arrangement, the two NHCs being in mutually trans positions. However, the repulsion between the two NHCs was found to be higher in 1c, as indicated by metrical parameters (C(39)-Ru(1)-C(1) = 166.9°) compared to those found for 1a (C(39)-Ru(1)-C(1) = 159.05°), as ICy is known to be slightly more sterically demanding than IMeMe. In addition, Ru-NHCs bonds were found to be longer in 1c (Ru(1)C(1) = 2.137 A˚, Ru(1)-C(39) = 2.153 A˚) than in 1a (respectively 2.105 and 2.091 A˚). In each complex, the distances of the two NHCs to the metal center were found to be similar, although the bond Ru-ICy (Ru(1)-C(39)) was slightly longer than Ru-SIMes (Ru(1)-C(1)) in 1c. Steric and electronic properties of ICy might account for this observation. In order to evaluate the steric hindrance of the NHCs around the metal center, the measurement of the percent (13) (a) Burtscher, D.; Lexer, C.; Mereiter, K.; Winde, R.; Karch, R.; Slugovc, C. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 4630–4635. (b) Monsaert, S.; Drozdzak, R.; Dragutan, V.; Dragutan, I.; Verpoort, F. Eur. J. Inorg. Chem. 2008, 432–440.
buried volume (%VBur) was carried out using the SambVca calculation methodology developed by Cavallo and coworkers14 (Table 2). A detailed procedure of this method has already been reported.15 In this model, the %VBur value represents the portion of a sphere, centered around the metal atom, occupied by the ligand. Calculations were done using a fixed bond length Ru-Ccarbene = 2.10 A˚, and the radius of the sphere R chosen as 3.5 A˚, for each ligand examined.16 Electronic properties of the NHCs involved in this study are included in Table 2. These properties were estimated by examining the infrared bands associated with the CO stretching in the corresponding Ni(CO)3(NHC).17 IMeMe is the best donor of the small NHCs involved in this study. However, it shares the same steric hindrance as ICy in our ruthenium complexes (%VBur = 24.7 vs 24.4 for ICy). This observation is not surprising, as the higher donating ability of IMeMe induces a shorter Ru-(NHC) bond. This shorter bond length renders IMeMe slightly more sterically demanding. In comparison, IiPrMe is as donating as ICy and would be expected to be slightly more hindering because of its substituted backbone, which should push the isopropyl substituents toward the metal. (14) This free web application is available online: https://www. molnac.unisa.it/OMtools/sambvca.php. (15) Poater, A.; Cosenza, B.; Correa, A.; Giudice, S.; Ragone, F.; Scarano, V.; Cavallo, L. Eur. J. Inorg. Chem. 2009, 1759–1766. For a review on %VBur, see: Clavier, H.; Nolan, S. P. Chem. Commun. 2010, 46, 841–861. (16) Calculations using an average bond distance give the same trend. See Supporting Information for details. (17) Gusev, D. G. Organometallics 2009, 28, 6458–6461.
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Figure 2. Ball and stick representations of complexes 1a and 1c. H atoms are omitted for clarity. Table 1. Selected Bond Distances (A˚) and Angles (deg) in Complexes 1a and 1c
Ru(1)-C(24) Ru(1)-C(39) Ru(1)-C(1) Ru(1)-Cl(1) Ru(1)-Cl(2) C(24)-Ru(1)-C(39) C(24)-Ru(1)-C(1) C(39)-Ru(1)-C(1) Cl(1)-Ru(1)-Cl(2) N(2)-C(3)-C(4)-N(5) N(40)-C(41)-C(42)-N(43)
1a
1c
1.866 (4) 2.091 (4) 2.105 (4) 2.4146 (11) 2.4004 (11) 98.35 (16) 102.32 (16) 159.05 (15) 162.78 (4) 2.7 (4) 1.5 (4)
1.848 (9) 2.153 (9) 2.137 (9) 2.370 (2) 2.375 (2) 91.0 (4) 101.9 (4) 166.9 (4) 167.02 (9) 15.3 (11) 0.4 (12)
Table 3. Comparison of Precatalysts 1a-c in RCM Reactionsa
Table 2. Electronic and Steric Properties of the NHCs Studied Entry
NHC
νCOa (cm-1)
1 2 3 4
IMeMe IiPrMe ICy SIMes (1a/1c)
2051.7 2049.6 2049.7 2051.2
%VBurb 24.7 24.4 30.6/30.1
a
Determined in Ni(CO)3(NHC). b Calculations were achieved using a fixed bond length of 2.10 A˚ for the Ru-Ccarbene bond and the sphere radius fixed at R = 3.5 A˚.
Catalytic Activity. Precatalysts 1a-c were then evaluated in catalysis. The test reaction was selected as a RCM reaction using N,N-diallyltosylamine 2 as prototypical substrate. Attempts to conduct the reaction in the presence of 1 mol % of 1c at rt, 40 °C, and 60 °C indicated that thermal activation of the catalyst was not efficient enough to promote a rapid RCM (no reaction detected after 30 min in all cases). However, at 80 °C, significant conversion was achieved in less than 2 h. The complexes 1a-c were thus compared at that temperature, and the reaction was stopped after 1.25 h, before complete conversion was reached. While 1a and 1c gave respectively an encouraging 87% and 83% conversion, 1b, featuring IiPrMe, was able to reach only 45% conversion (Table 3, entries 1-3). Low catalyst loading experiments were next targeted. As the rate of the reaction seemed particularly low, even with 1 mol % of precatalyst, the temperature was increased to 110 °C and reaction time set at 24 h. Such a long period could allow the fastest catalysts to perform the reaction but also slower catalysts such as 1b to reach complete conversion. Decreasing catalyst loadings to 0.02 mol % did not allow full conversion, although the same reactivity trend was observed as before: 1a > 1c > 1b (Table 3, entries 4-6). However, the difference in activity between 1b and 1c was found to be reduced, proving that a
a Reaction conditions: substrate (0.25 mmol), catalysts, toluene (0.5 M). b Average of 2 runs; conversions determined by NMR. c An unidentified side-product was observed, probably issued from doublebond isomerization.
slow activator could still perform the reaction in view of its stability. To confirm that 1a was the best catalyst in this series, RCM of diethyldiallylmalonate 3 and hindered dimethallyltosylamine 4 were tested at low catalyst loading, respectively 0.02 and 0.1 mol %, in refluxing toluene. After 24 h of reaction, 3 was not fully converted, but, as seen before, 1a was found to give higher conversion than 1b and 1c (Table 3, entries 7-9). Interestingly, at such low catalyst loading, the activity of 1b was comparable to 1c. In the RCM of 4, the three precatalysts were found almost equivalent, 1b surprisingly giving comparable conversion to 1a and better than 1c (Table 3, entries 10-12). As the sterics of the NHCs involved in this study were found similar, it seems reasonable to attribute the better catalytic performance of 1a to the higher donor ability of IMeMe, affording a more stable precatalyst. These preliminary results set the stage for the evaluation of 1a in the RCM of other substrates at low catalyst loadings.
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Table 4. Experiments at Low Catalyst Loading in the Presence of 1aa
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were fully converted with 0.075 mol % (Table 4, entries 4 and 5). However, isolated yields were found poor compared to conversion. This was due to the concomitant formation of unidentified side-products that may result from isomerization of double bonds during the reaction; reducing the temperature of the experiment did not eliminate the formation of these side-products. Finally, ether 13 was converted in a highly efficient manner, giving bicyclic compound 14 in 96% yield (Table 4, entry 6). Slightly more hindered substrates affording trisubstituted olefins were next tested. Malonate 15 and ether 17 required only 0.075 mol % of 1a to furnish respectively 16 and 18 in excellent yields (Table 4, entries 7 and 8). Finally, hindered substrates affording tetrasubstituted double bonds were tested. If dimethallylmalonate 19, which is one of the most difficult substrates, did not allow for more than 36% conversion, even at 1.0 mol % of 1a (Table 4, entry 9), tosylamine-containing compounds 21 and 23 were isolated in quantitative yields with as low as 0.5 mol % of precatalyst, regardless of the ring size of the product (Table 4, entries 10 and 11). Ether 24 could also be cyclized to yield hindered 25 in 91% yield with 0.5 mol % of 1a (Table 4, entry 12).
Conclusion In conclusion, we report herein the easy synthesis of new bisNHC indenylidene ruthenium complexes 1a-c, featuring a small NHC as leaving group. This class of compounds recently regained interest for low catalyst loading experiments. Indeed, their increased stability due to the strong interaction between the NHCs and the metal center contributes to their good efficiency in low catalyst loading RCM experiments. With 1a featuring IMeMe as leaving group, loadings as low as 0.05 mol % for “unchallenging” substrates and 0.5 mol % for hindered ones were sufficient to allow for excellent yields of the desired products. Of interest, the NHC acting as leaving group does not require electron-deficient substituents to lead to complexes behaving quite effectively in RCM reactions.
Experimental Section
a Reaction conditions: substrate (0.25 mmol), 1a, toluene (0.5 M), reflux. b Average of 2 runs; conversions were determined by 1H NMR; isolated yields in brackets. c A concentration of 0.05 M was used. d Yield determined by 1H NMR with butadiene sulfone as internal standard because of the volatility of the product.
Low Catalyst Loading Study. Ruthenium-containing metathesis precatalysts are usually not significantly sensitive to air, but, as low catalyst loadings were employed, all reactions were prepared in a glovebox under Ar atmosphere to avoid any possible erosion of the conversion due to air contamination. RCM reactions were then conducted in refluxing toluene (0.5 M) and stopped after 24 h. Precatalyst 1a was first evaluated in the RCM of “easy” substrates, affording disubstituted cyclic olefins. RCM of diallylmalonate 3 was surprisingly troublesome, and full conversion could not be reached with very low catalyst loading (Table 4, entry 1). Nevertheless, increasing the ring size to six- or sevenmembered allowed for full conversion and high isolated yields of 7 and 9 with as low as 0.05 mol % of precatalyst 1a (Table 4, entries 2 and 3). Tosylamine-containing analogues 2 and 11
General Considerations. All reactions were carried out using standard Schlenk techniques or in an M-Braun glovebox (H2O< 0.1 ppm and O2
