Grela, Karol

Harutyunyan, Syuzanna

Michrowska, Anna

ARTS repository - University of Groningen

   University of GroningenA Highly Efficient Ruthenium Catalyst for Metathesis ReactionsGrela, Karol; Harutyunyan, Syuzanna; Michrowska, AnnaPublished in:Angewandte Chemie International EditionDOI:10.1002/1521-3773(20021104)41:21<4038::AID-ANIE4038>3.0.CO;2-0IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2002Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Grela, K., Harutyunyan, S., & Michrowska, A. (2002). A Highly Efficient Ruthenium Catalyst for MetathesisReactions. Angewandte Chemie International Edition, 41(21), 4038-4040. https://doi.org/10.1002/1521-3773(20021104)41:21<4038::AID-ANIE4038>3.0.CO;2-0CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 16-07-2023A Highly Efficient Ruthenium Catalyst forMetathesis Reactions**Karol Grela,* Syuzanna Harutyunyan, andAnna MichrowskaThe development of accessible metathesis catalysts thatcombine high activity with excellent tolerance to a variety offunctional groups has been key to the widespread applicationof olefin metathesis in organic synthesis. In spite of thegeneral superb application profile of the ruthenium carbene1a, its limited thermal stability and the low activity towardssubstituted double bonds are major drawbacks.[1]Specifically, the preparation of substituted olefins withelectron-withdrawing functionality (such as a,b-unsaturatedcarbonyl compounds, nitriles, sulfones, etc.) through crossmetathesis (CM) with terminal alkenes remains a difficulttask. The newly introduced highly active ruthenium alkyli-dene complexes with sterically demanding N-heterocycliccarbene (NHC)[3] ligands have dramatically alleviated thislimitation.[2] Compounds of type 1b and 1c were found to beefficient catalysts in the reactions of previously metathesis-inactive substrates, including a,b-unsaturated olefins(Scheme 1).[2,4]Hoveyda and co-workers have recently established 2 as aremarkably robust complex, which promotes olefin meta-thesis by a ™release±return∫ mechanism.[5] Despite the factthat phosphane-free catalyst 2 was found to be more sluggishthan 1b,[6] it has a superior general reactivity toward electron-deficient olefins.[7] The fact that the ruthenium carbene 2 isair-stable and can be easily purified by standard silica-gelchromatography and recycled after the reaction is a partic-ularly appealing facet of this chemistry.[5,8]Blechert and Wakamatsu have shown recently that thereplacement of the isopropoxystyrene ™ligand∫ in 2 by binol-or biphenyl-based styrene results in a large improvement inthe activity of the catalyst, as complexes 4 and 5 are muchmore reactive than both 2 and the ™second-generation∫Grubbs catalyst 1b.[9]During our project aimed at the preparation of theimmobilized metathesis catalyst, we prepared the bromoanalogue 3 of Hoveyda©s catalyst 2.[10] Although the reactivitypatterns of complexes 2 and 3 were in general similar, thelatter system was visibly less reactive in some modelreactions.[4b] This result once again shows that even a smallvariation in the isopropoxystyrene ™ligand∫ can result in achange in the activity of the catalyst. Impressed by resultspublished recently by Blechert and Wakamatsu,[9] we decidedto investigate the electronic effects in the isopropoxystyrene™ligand∫ sphere of complex 2 which are not fully under-stood.[11] At first, we decided to test whether a decrease in theelectron density of the styrene part of 2 would result inincreased catalyst reactivity.As illustrated in Scheme 2, we used commercially available6 as a starting material for preparation of the correspondingruthenium carbene 9. The green microcrystalline complex 9was easily obtained in good yield (83%) by the reaction of 1b(1 equiv) and CuCl (1 equiv) with styrene 8 (1 equiv),followed by routine flash chromatography. Having securedan efficient method for the preparation of complex 9, wetested its catalytic activity. As the reactions of standard modelsubstrates diallyltosylamide or diallylmalonate are too fast foran accurate measurement of their conversions,[12] we decidedto use more challenging ring-closing metathesis of 10a. Thismodel reaction showed that precatalyst 9 is significantly morereactive than 2 and 3 in the formation of trisubstituted doublebonds (Figure 1). Notably, 9 is not only highly active but alsostable, as it can be stored in air (þ 4 8C) for more than fourweeks without decomposition or loss of activity.The metathesis of selected benchmark substrates was thenexamined. The results compiled in Table 1 illustrate theremarkably wide scope of this catalyst: 1) The RCM andenyne variant of the metathesis reaction can be performedefficiently at 0 8C (Table 1, entries 2±4); 2) Various degrees ofsubstitution of the double bond are tolerated, and eventrisubstituted olefins can be synthesized in good yields atambient temperature (Table 1, entries 1 and 5); 3) The CMreaction of terminal alkenes and a,b-unsaturated compoundsCOMMUNICATIONS4038 ¹ 2002 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim 0044-8249/02/4121-4038 $ 20.00+.50/0 Angew. Chem. Int. Ed. 2002, 41, No. 21[*] Dr. K. Grela, S. Harutyunyan, A. MichrowskaInstitute of Organic Chemistry, Polish Academy of SciencesKasprzaka 44/52, P.O.B. 58, 01-224 Warsaw (Poland)Fax: (þ 48)22-632-6681E-mail: grela@icho.edu.pl[**] This work was supported by the State Committee of ScientificResearch (Grant No. 4 T09A 136 22). The authors wish to thank theAlexander von Humboldt foundation for a donation of books andequipment, and Professor Mieczys¯aw MaŒkosza for helpful advice andencouragement.MesN NMesRuPCy3PhClClLMesN NMesiPrORuClClXiPrORuClCliPrO iPrORuClClMesN NMes MesN NMesMesN NMesa: L= b: L= c: L=1a–c: PCy32 (X=H)3 (X=Br)4 5Activity: 2<1b<4<5Scheme 1. Evolution of ruthenium precatalysts for alkene metathesis. Cy¼cyclohexyl; Mes¼ 2,4,6-trimethylphenyl.ORNO2O ONO2ORuClClMesN NMesNO2a)6: R = H7: R = iPrb) c)8 9Scheme 2. Synthesis of catalyst 9. a) iPrI, K2CO3, Cs2CO3 (cat.), DMF,2 days, room temperature, 86%; b) Ph3P¼CH2, THF, 78 8C!RT, 1 h,57%; c) 1b, CuCl, CH2Cl2, 30 8C, 1 h, 83%.can be also performed at room temperature (Table 1, entries6±9). The more demanding CM reactions of phenyl vinylsulfone[4] (Table 1, entry 8) and acrylonitrile[7a] (Table 1,entry 9) show that also in this particular case complex 9 issuperior to 1b and 2. Most remarkably, the new precatalyst 9can be used for CM of methacrylonitrile; the transformation isbeyond the scope of the ™second generation∫ Grubbs© carbene1b (Table 1, entry 10).In conclusion, we have shown that the catalysts related tothat of Hoveyda can be significantly improved by changingnot only the steric[11] but also the electronic character of theRu-chelating isopropoxy fragment. For example, introductionof a strong electron-withdrawing group at the 2-isopropoxy-styrene ring of 2 leads to complex 9, which is equally stablebut dramatically more reactive than the parent catalyst 2. Weassume that the decrease in the electron density[13] of theoxygen atom of the isopropoxy fragment reduces its chelatingability, thus facilitating formation of the catalytically active14-electron Ru±carbene species, and suppressing repeatedreassociation to the metal center. Therefore, this mode ofcatalyst activation is, in fact, similar to that of 4 and 5, in whichthe increase in steric bulk improves the leaving-group abilityof the styrene ™ligand∫ (Scheme 3).[9] Complex 9 is attractiveCOMMUNICATIONSAngew. Chem. Int. Ed. 2002, 41, No. 21 ¹ 2002 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim 0044-8249/02/4121-4039 $ 20.00+.50/0 4039Figure 1. RCM of 10a with precatalysts 1b (~, 1 mol%), 2 (*, 2.5 mol%),3 (&, 2.5 mol%), and 9 (^, 1 mol%). a) cat. (1±2.5 mol%), CH2Cl2, roomtemperature, x ¼ conversion.Table 1. Comparative investigation of 9.Entry Substrate 10 Product 11 Yield using 9 [%][a] Yield using ref. catalyst [%][a]1 10a 11a 99%[b] (1 mol%, RT, 2 h) 2 : 50%[b] (2.5 mol%, RT, 18 h)2 98% (1 mol%, 0 8C, 1 h) 1c : 85%[c] (1 mol%, 80 8C, 1 h)3 99% (1 mol%, 0 8C, 1 h) 1b : 99%[d] (1 mol%, RT, 1 h)4 78% (2.5 mol%, 0 8C, 8 h) 1b : 99%[d] (1 mol%, RT, 1.5 h)5 99%[b] (2.5 mol%, RT, 4 h)6[e] 82% (2.5 mol%, RT, 30 min) 5 : 90%[d] (1 mol%, RT, 40 min)7[f] 10 f 95% (1 mol%, RT, 30 min) 5 : 91%[d] (2.5 mol%, RT, 20 min)8[g] 10 f 90% (2.5 mol%, RT, 16 h) 1b : 85%[h] (5 mol%, 40 8C, 16 h)9[i] 87%[b] (5 mol%, RT, 30 min) 2 : 79%[j] (8 mol%, 40 8C, 6 h)10[k] 10 f 58% (5 mol%, 408, 16 h) 1b : 0%[b] (5 mol%, 80 8C, 24 h)[a] Yield of isolated product, unless stated otherwise. [b] Yield determined by GC. [c] Ref. [2g]. [d] Ref. [9b]. [e] Reaction with methyl vinyl ketone(2 equiv). [f] Reaction with methyl acrylate (2 equiv). [g] Reaction with phenyl vinyl sulfone (2 equiv). [h] Ref. [4]. [i] Reaction with acrylonitrile (2 equiv).[j] E/Z¼ 1:3, ref. [7a]. [k] Reaction with methacrylonitrile (4 equiv).from a practical point of view as it is active and easy to obtainin a three-step synthesis. This catalyst operates under verymild conditions (0 8C to room temperature) and can besuccessfully applied in various types of metathesis reactions(RCM, CM, enyne). Further investigations to determine thefull scope and limitations of 9 and similar systems are underway.Experimental Section9 : Carbene complex 1b (153 mg. 0.18 mmol), CuCl (18 mg, 0.18 mmol),and CH2Cl2 (10 mL) were placed in a Schlenk tube. A solution of 8 (38 mg,0.18 mmol) in CH2Cl2 (4 mL) was then added and the resulting solution wasstirred under argon at 30 8C for 1 h. After this step, all manipulations werecarried out in air with reagent-grade solvents. The reaction mixture wasconcentrated in vacuo, and the resulting material was purified by columnchromatography on silica. Elution with cyclohexane/EtOAc (5:2) led to theisolation of 9 as a green band. The solvent was evaporated, the residue waswashed with n-pentane and dried under vacuum to afford 9 as a greenmicrocrystalline solid (100 mg, 83%). Rf¼ 0.30 (cyclohexane/EtOAc 8:2);1H NMR (500 MHz, CD2Cl2): d¼ 16.42 (s, 1H; 1-H), 8.46 (dd, J¼ 9.1,2.5 Hz, 1H; 5-H), 7.80 (d, J¼ 2.5 Hz, 1H; 3-H), 7.10 (s, 4H; 16-H), 6.94 (d,J¼ 9.1 Hz, 1H; 6-H), 5.01 (sept, J¼ 6.1 Hz, 1H; 8-H), 4.22 (s, 4H; 11-H,11’-H), 2.47 (2 î s, 18H; 12-H, 13-H), 1.30 ppm (d, J¼ 6.1 Hz, 6H; 9-H, 9’-H); 13C NMR (125 MHz, CD2Cl2): d¼ 289.1 (C1), 208.2 (C10), 156.8 (C7),150.3, 145.0 (C2), 143.5 (C4), 139.6 (C15), 139.3, 129.8 (C16), 124.5 (C5),117.2 (C3), 113.3 (C6), 78.2 (C8) 52.0 (C11, C11’), 21.3 (C9, C9’), 21.2 (C12),19.4 ppm (C13) (where assignments of the NMR signals are given (basedon 2D 1H,13C-chemical shift correlated spectra: GHSQC, GHMBC), theyare unambiguous and refer to the arbitrary numbering shown in Scheme 3);IR (KBr): ñ¼ 2924, 2850, 1606, 1521, 1480, 1262, 1093, 918, 745 cm1;HRMS (IE): m/z calcd for C31H37N3O335C12102Ru: [MþC] 671.1255, found671.1229; elemental analysis (%) calcd for C31H37N3O3Cl2Ru (671.63): C55.44, H 5.55, N 6.26; found: C 55.35; H 5.70, N 6.09.Received: July 19, 2002 [Z19778][1] For relevant reviews, see: a) T. M. Trnka, R. H. Grubbs, Acc. Chem.Res. 2001, 34, 18; b) A. F¸rstner, Angew. Chem. 2000, 112, 3140;Angew. Chem. Int. Ed. 2000, 39, 3012; c) R. H. Grubbs, S. Chang,Tetrahedron 1998, 54, 4413; d) M. Schuster, S. Blechert,Angew. Chem.1997, 109, 2124; Angew. Chem. Int. Ed. Engl. 1997, 36, 2037; e) A.F¸rstner, Top. Catal. 1997, 4, 285; f) S. K. Armstrong, J. Chem. Soc.Perkin Trans. 1 1998, 371; g) M. E. Maier, Angew. Chem. 2000, 112,2153; Angew. Chem. Int. Ed. 2000, 39, 2073.[2] a) W. A. Herrmann, M. Speigler, W. C. Schattenmann, T. Westcamp,Angew. Chem. 1998, 110, 2631; Angew. Chem. Int. Ed. 1998, 37, 2490;b) W. A. Herrmann, T. Westcamp, L. Ackermann, F. J. Kohl, A.F¸rstner, Tetrahedron Lett. 1999, 40, 4787; c) J. Huang, E. D. Stevens,S. P. Nolan, J. L. Pedersen, J. Am. Chem. Soc. 1999, 121, 2674; d) M.Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1, 953;e) M. S. Sanford, M. Ulman, R. H. Grubbs, J. Am. Chem. Soc. 2001,123, 749; f) M. S. Sanford, J. A. Love, R. H. Grubbs, J. Am. Chem. Soc.2001, 123, 6543; g) A. F¸rstner, L. Ackermann, B. Gabor, R. Goddard,C. W. Lehmann, R. Mynott, F. Stelzer, O. R. Thiel, Chem. Eur. J. 2001,7, 3236.[3] For a comprehensive survey of N-heterocyclic carbenes, see: a) W. A.Herrmann, Angew. Chem. 2002, 114, 1342; Angew. Chem. Int. Ed.2002, 41, 1290; b) D. Bourissou, O. Guerret, F. P. Gabbai:, G.Bertrand, Chem. Rev. 2000, 100, 39; c) A. J. A. Arduengo, Acc. Chem.Res. 1999, 32, 913.[4] a) For a recent example from our laboratory, see: K. Grela, M.Bieniek, Tetrahedron Lett. 2001, 42, 6425; b) for screening of thecatalytic performance of Ru- and Mo-based catalysts in cross-meta-thesis reactions of a,b-unsaturated sulfones and sulfoxides, see: K.Grela, M. Bieniek, M. Kim, R. Klajn, unpublished results.[5] S. B. Garber, J. S. Kingsbury, B. L. Gray, A. H. Hoveyda, J. Am. Chem.Soc. 2000, 122, 8168.[6] For a comparative study of the performance of precatalysts 1b and 2 inthe RCM reaction of diallyltosylamide, see: ref. [9a].[7] a) S. Randl, S. Gessler, H. Wakamatsu, S. Blechert, Synlett 2001, 430;b) S. Imhof, S. Randl, S. Blechert, Chem. Commun. 2001, 1692; c) S.Randl, S. J. Connon, S. Blechert, Chem. Commun. 2001, 1796.[8] Catalysts 1a, 1b, and 2 are available from Aldrich Chemical Co.[9] a) H. Wakamatsu, S. Blechert, Angew. Chem. 2002, 114, 832; Angew.Chem. Int. Ed. 2002, 41, 794; b) H. Wakamatsu, S. Blechert, Angew.Chem. 2002, 114, 2509; Angew. Chem. Int. Ed. 2002, 41, 2403.[10] K. Grela, M. Tryznowski, M. Bieniek, Tetrahedron Lett. , in press.[11] Extensive studies described in ref. [9a,b] suggest that a stericbulk adjacent to the chelating isopropoxy moiety of 4 and 5 is thecrucial factor required for the unusually high activity of thesecomplexes.[12] For example, see footnote 32 in ref. [2g].[13] We thank Mr. Michal Barbasiewicz for carrying out some preliminaryAM1 calculations.COMMUNICATIONS4040 ¹ 2002 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim 0044-8249/02/4121-4040 $ 20.00+.50/0 Angew. Chem. Int. Ed. 2002, 41, No. 21ORuClClPhORuClClNO2N NN N5 912 34567899'1011 11'121314151617Scheme 3.

English

A Highly Efficient Ruthenium Catalyst for Metathesis Reactions

University of Groningen

   University of GroningenA Highly Efficient Ruthenium Catalyst for Metathesis ReactionsGrela, Karol; Harutyunyan, Syuzanna; Michrowska, AnnaPublished in:Angewandte Chemie International EditionDOI:10.1002/1521-3773(20021104)41:21<4038::AID-ANIE4038>3.0.CO;2-0IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2002Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Grela, K., Harutyunyan, S., & Michrowska, A. (2002). A Highly Efficient Ruthenium Catalyst for MetathesisReactions. Angewandte Chemie International Edition, 41(21), 4038-4040. https://doi.org/10.1002/1521-3773(20021104)41:21<4038::AID-ANIE4038>3.0.CO;2-0CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 25-04-2023A Highly Efficient Ruthenium Catalyst forMetathesis Reactions**Karol Grela,* Syuzanna Harutyunyan, andAnna MichrowskaThe development of accessible metathesis catalysts thatcombine high activity with excellent tolerance to a variety offunctional groups has been key to the widespread applicationof olefin metathesis in organic synthesis. In spite of thegeneral superb application profile of the ruthenium carbene1a, its limited thermal stability and the low activity towardssubstituted double bonds are major drawbacks.[1]Specifically, the preparation of substituted olefins withelectron-withdrawing functionality (such as a,b-unsaturatedcarbonyl compounds, nitriles, sulfones, etc.) through crossmetathesis (CM) with terminal alkenes remains a difficulttask. The newly introduced highly active ruthenium alkyli-dene complexes with sterically demanding N-heterocycliccarbene (NHC)[3] ligands have dramatically alleviated thislimitation.[2] Compounds of type 1b and 1c were found to beefficient catalysts in the reactions of previously metathesis-inactive substrates, including a,b-unsaturated olefins(Scheme 1).[2,4]Hoveyda and co-workers have recently established 2 as aremarkably robust complex, which promotes olefin meta-thesis by a ™release±return∫ mechanism.[5] Despite the factthat phosphane-free catalyst 2 was found to be more sluggishthan 1b,[6] it has a superior general reactivity toward electron-deficient olefins.[7] The fact that the ruthenium carbene 2 isair-stable and can be easily purified by standard silica-gelchromatography and recycled after the reaction is a partic-ularly appealing facet of this chemistry.[5,8]Blechert and Wakamatsu have shown recently that thereplacement of the isopropoxystyrene ™ligand∫ in 2 by binol-or biphenyl-based styrene results in a large improvement inthe activity of the catalyst, as complexes 4 and 5 are muchmore reactive than both 2 and the ™second-generation∫Grubbs catalyst 1b.[9]During our project aimed at the preparation of theimmobilized metathesis catalyst, we prepared the bromoanalogue 3 of Hoveyda©s catalyst 2.[10] Although the reactivitypatterns of complexes 2 and 3 were in general similar, thelatter system was visibly less reactive in some modelreactions.[4b] This result once again shows that even a smallvariation in the isopropoxystyrene ™ligand∫ can result in achange in the activity of the catalyst. Impressed by resultspublished recently by Blechert and Wakamatsu,[9] we decidedto investigate the electronic effects in the isopropoxystyrene™ligand∫ sphere of complex 2 which are not fully under-stood.[11] At first, we decided to test whether a decrease in theelectron density of the styrene part of 2 would result inincreased catalyst reactivity.As illustrated in Scheme 2, we used commercially available6 as a starting material for preparation of the correspondingruthenium carbene 9. The green microcrystalline complex 9was easily obtained in good yield (83%) by the reaction of 1b(1 equiv) and CuCl (1 equiv) with styrene 8 (1 equiv),followed by routine flash chromatography. Having securedan efficient method for the preparation of complex 9, wetested its catalytic activity. As the reactions of standard modelsubstrates diallyltosylamide or diallylmalonate are too fast foran accurate measurement of their conversions,[12] we decidedto use more challenging ring-closing metathesis of 10a. Thismodel reaction showed that precatalyst 9 is significantly morereactive than 2 and 3 in the formation of trisubstituted doublebonds (Figure 1). Notably, 9 is not only highly active but alsostable, as it can be stored in air (þ 4 8C) for more than fourweeks without decomposition or loss of activity.The metathesis of selected benchmark substrates was thenexamined. The results compiled in Table 1 illustrate theremarkably wide scope of this catalyst: 1) The RCM andenyne variant of the metathesis reaction can be performedefficiently at 0 8C (Table 1, entries 2±4); 2) Various degrees ofsubstitution of the double bond are tolerated, and eventrisubstituted olefins can be synthesized in good yields atambient temperature (Table 1, entries 1 and 5); 3) The CMreaction of terminal alkenes and a,b-unsaturated compoundsCOMMUNICATIONS4038 ¹ 2002 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim 0044-8249/02/4121-4038 $ 20.00+.50/0 Angew. Chem. Int. Ed. 2002, 41, No. 21[*] Dr. K. Grela, S. Harutyunyan, A. MichrowskaInstitute of Organic Chemistry, Polish Academy of SciencesKasprzaka 44/52, P.O.B. 58, 01-224 Warsaw (Poland)Fax: (þ 48)22-632-6681E-mail: grela@icho.edu.pl[**] This work was supported by the State Committee of ScientificResearch (Grant No. 4 T09A 136 22). The authors wish to thank theAlexander von Humboldt foundation for a donation of books andequipment, and Professor Mieczys¯aw MaŒkosza for helpful advice andencouragement.MesN NMesRuPCy3PhClClLMesN NMesiPrORuClClXiPrORuClCliPrO iPrORuClClMesN NMes MesN NMesMesN NMesa: L= b: L= c: L=1a–c: PCy32 (X=H)3 (X=Br)4 5Activity: 2<1b<4<5Scheme 1. Evolution of ruthenium precatalysts for alkene metathesis. Cy¼cyclohexyl; Mes¼ 2,4,6-trimethylphenyl.ORNO2O ONO2ORuClClMesN NMesNO2a)6: R = H7: R = iPrb) c)8 9Scheme 2. Synthesis of catalyst 9. a) iPrI, K2CO3, Cs2CO3 (cat.), DMF,2 days, room temperature, 86%; b) Ph3P¼CH2, THF, 78 8C!RT, 1 h,57%; c) 1b, CuCl, CH2Cl2, 30 8C, 1 h, 83%.can be also performed at room temperature (Table 1, entries6±9). The more demanding CM reactions of phenyl vinylsulfone[4] (Table 1, entry 8) and acrylonitrile[7a] (Table 1,entry 9) show that also in this particular case complex 9 issuperior to 1b and 2. Most remarkably, the new precatalyst 9can be used for CM of methacrylonitrile; the transformation isbeyond the scope of the ™second generation∫ Grubbs© carbene1b (Table 1, entry 10).In conclusion, we have shown that the catalysts related tothat of Hoveyda can be significantly improved by changingnot only the steric[11] but also the electronic character of theRu-chelating isopropoxy fragment. For example, introductionof a strong electron-withdrawing group at the 2-isopropoxy-styrene ring of 2 leads to complex 9, which is equally stablebut dramatically more reactive than the parent catalyst 2. Weassume that the decrease in the electron density[13] of theoxygen atom of the isopropoxy fragment reduces its chelatingability, thus facilitating formation of the catalytically active14-electron Ru±carbene species, and suppressing repeatedreassociation to the metal center. Therefore, this mode ofcatalyst activation is, in fact, similar to that of 4 and 5, in whichthe increase in steric bulk improves the leaving-group abilityof the styrene ™ligand∫ (Scheme 3).[9] Complex 9 is attractiveCOMMUNICATIONSAngew. Chem. Int. Ed. 2002, 41, No. 21 ¹ 2002 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim 0044-8249/02/4121-4039 $ 20.00+.50/0 4039Figure 1. RCM of 10a with precatalysts 1b (~, 1 mol%), 2 (*, 2.5 mol%),3 (&, 2.5 mol%), and 9 (^, 1 mol%). a) cat. (1±2.5 mol%), CH2Cl2, roomtemperature, x ¼ conversion.Table 1. Comparative investigation of 9.Entry Substrate 10 Product 11 Yield using 9 [%][a] Yield using ref. catalyst [%][a]1 10a 11a 99%[b] (1 mol%, RT, 2 h) 2 : 50%[b] (2.5 mol%, RT, 18 h)2 98% (1 mol%, 0 8C, 1 h) 1c : 85%[c] (1 mol%, 80 8C, 1 h)3 99% (1 mol%, 0 8C, 1 h) 1b : 99%[d] (1 mol%, RT, 1 h)4 78% (2.5 mol%, 0 8C, 8 h) 1b : 99%[d] (1 mol%, RT, 1.5 h)5 99%[b] (2.5 mol%, RT, 4 h)6[e] 82% (2.5 mol%, RT, 30 min) 5 : 90%[d] (1 mol%, RT, 40 min)7[f] 10 f 95% (1 mol%, RT, 30 min) 5 : 91%[d] (2.5 mol%, RT, 20 min)8[g] 10 f 90% (2.5 mol%, RT, 16 h) 1b : 85%[h] (5 mol%, 40 8C, 16 h)9[i] 87%[b] (5 mol%, RT, 30 min) 2 : 79%[j] (8 mol%, 40 8C, 6 h)10[k] 10 f 58% (5 mol%, 408, 16 h) 1b : 0%[b] (5 mol%, 80 8C, 24 h)[a] Yield of isolated product, unless stated otherwise. [b] Yield determined by GC. [c] Ref. [2g]. [d] Ref. [9b]. [e] Reaction with methyl vinyl ketone(2 equiv). [f] Reaction with methyl acrylate (2 equiv). [g] Reaction with phenyl vinyl sulfone (2 equiv). [h] Ref. [4]. [i] Reaction with acrylonitrile (2 equiv).[j] E/Z¼ 1:3, ref. [7a]. [k] Reaction with methacrylonitrile (4 equiv).from a practical point of view as it is active and easy to obtainin a three-step synthesis. This catalyst operates under verymild conditions (0 8C to room temperature) and can besuccessfully applied in various types of metathesis reactions(RCM, CM, enyne). Further investigations to determine thefull scope and limitations of 9 and similar systems are underway.Experimental Section9 : Carbene complex 1b (153 mg. 0.18 mmol), CuCl (18 mg, 0.18 mmol),and CH2Cl2 (10 mL) were placed in a Schlenk tube. A solution of 8 (38 mg,0.18 mmol) in CH2Cl2 (4 mL) was then added and the resulting solution wasstirred under argon at 30 8C for 1 h. After this step, all manipulations werecarried out in air with reagent-grade solvents. The reaction mixture wasconcentrated in vacuo, and the resulting material was purified by columnchromatography on silica. Elution with cyclohexane/EtOAc (5:2) led to theisolation of 9 as a green band. The solvent was evaporated, the residue waswashed with n-pentane and dried under vacuum to afford 9 as a greenmicrocrystalline solid (100 mg, 83%). Rf¼ 0.30 (cyclohexane/EtOAc 8:2);1H NMR (500 MHz, CD2Cl2): d¼ 16.42 (s, 1H; 1-H), 8.46 (dd, J¼ 9.1,2.5 Hz, 1H; 5-H), 7.80 (d, J¼ 2.5 Hz, 1H; 3-H), 7.10 (s, 4H; 16-H), 6.94 (d,J¼ 9.1 Hz, 1H; 6-H), 5.01 (sept, J¼ 6.1 Hz, 1H; 8-H), 4.22 (s, 4H; 11-H,11’-H), 2.47 (2 î s, 18H; 12-H, 13-H), 1.30 ppm (d, J¼ 6.1 Hz, 6H; 9-H, 9’-H); 13C NMR (125 MHz, CD2Cl2): d¼ 289.1 (C1), 208.2 (C10), 156.8 (C7),150.3, 145.0 (C2), 143.5 (C4), 139.6 (C15), 139.3, 129.8 (C16), 124.5 (C5),117.2 (C3), 113.3 (C6), 78.2 (C8) 52.0 (C11, C11’), 21.3 (C9, C9’), 21.2 (C12),19.4 ppm (C13) (where assignments of the NMR signals are given (basedon 2D 1H,13C-chemical shift correlated spectra: GHSQC, GHMBC), theyare unambiguous and refer to the arbitrary numbering shown in Scheme 3);IR (KBr): ñ¼ 2924, 2850, 1606, 1521, 1480, 1262, 1093, 918, 745 cm1;HRMS (IE): m/z calcd for C31H37N3O335C12102Ru: [MþC] 671.1255, found671.1229; elemental analysis (%) calcd for C31H37N3O3Cl2Ru (671.63): C55.44, H 5.55, N 6.26; found: C 55.35; H 5.70, N 6.09.Received: July 19, 2002 [Z19778][1] For relevant reviews, see: a) T. M. Trnka, R. H. Grubbs, Acc. Chem.Res. 2001, 34, 18; b) A. F¸rstner, Angew. Chem. 2000, 112, 3140;Angew. Chem. Int. Ed. 2000, 39, 3012; c) R. H. Grubbs, S. Chang,Tetrahedron 1998, 54, 4413; d) M. Schuster, S. Blechert,Angew. Chem.1997, 109, 2124; Angew. Chem. Int. Ed. Engl. 1997, 36, 2037; e) A.F¸rstner, Top. Catal. 1997, 4, 285; f) S. K. Armstrong, J. Chem. Soc.Perkin Trans. 1 1998, 371; g) M. E. Maier, Angew. Chem. 2000, 112,2153; Angew. Chem. Int. Ed. 2000, 39, 2073.[2] a) W. A. Herrmann, M. Speigler, W. C. Schattenmann, T. Westcamp,Angew. Chem. 1998, 110, 2631; Angew. Chem. Int. Ed. 1998, 37, 2490;b) W. A. Herrmann, T. Westcamp, L. Ackermann, F. J. Kohl, A.F¸rstner, Tetrahedron Lett. 1999, 40, 4787; c) J. Huang, E. D. Stevens,S. P. Nolan, J. L. Pedersen, J. Am. Chem. Soc. 1999, 121, 2674; d) M.Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1, 953;e) M. S. Sanford, M. Ulman, R. H. Grubbs, J. Am. Chem. Soc. 2001,123, 749; f) M. S. Sanford, J. A. Love, R. H. Grubbs, J. Am. Chem. Soc.2001, 123, 6543; g) A. F¸rstner, L. Ackermann, B. Gabor, R. Goddard,C. W. Lehmann, R. Mynott, F. Stelzer, O. R. Thiel, Chem. Eur. J. 2001,7, 3236.[3] For a comprehensive survey of N-heterocyclic carbenes, see: a) W. A.Herrmann, Angew. Chem. 2002, 114, 1342; Angew. Chem. Int. Ed.2002, 41, 1290; b) D. Bourissou, O. Guerret, F. P. Gabbai:, G.Bertrand, Chem. Rev. 2000, 100, 39; c) A. J. A. Arduengo, Acc. Chem.Res. 1999, 32, 913.[4] a) For a recent example from our laboratory, see: K. Grela, M.Bieniek, Tetrahedron Lett. 2001, 42, 6425; b) for screening of thecatalytic performance of Ru- and Mo-based catalysts in cross-meta-thesis reactions of a,b-unsaturated sulfones and sulfoxides, see: K.Grela, M. Bieniek, M. Kim, R. Klajn, unpublished results.[5] S. B. Garber, J. S. Kingsbury, B. L. Gray, A. H. Hoveyda, J. Am. Chem.Soc. 2000, 122, 8168.[6] For a comparative study of the performance of precatalysts 1b and 2 inthe RCM reaction of diallyltosylamide, see: ref. [9a].[7] a) S. Randl, S. Gessler, H. Wakamatsu, S. Blechert, Synlett 2001, 430;b) S. Imhof, S. Randl, S. Blechert, Chem. Commun. 2001, 1692; c) S.Randl, S. J. Connon, S. Blechert, Chem. Commun. 2001, 1796.[8] Catalysts 1a, 1b, and 2 are available from Aldrich Chemical Co.[9] a) H. Wakamatsu, S. Blechert, Angew. Chem. 2002, 114, 832; Angew.Chem. Int. Ed. 2002, 41, 794; b) H. Wakamatsu, S. Blechert, Angew.Chem. 2002, 114, 2509; Angew. Chem. Int. Ed. 2002, 41, 2403.[10] K. Grela, M. Tryznowski, M. Bieniek, Tetrahedron Lett. , in press.[11] Extensive studies described in ref. [9a,b] suggest that a stericbulk adjacent to the chelating isopropoxy moiety of 4 and 5 is thecrucial factor required for the unusually high activity of thesecomplexes.[12] For example, see footnote 32 in ref. [2g].[13] We thank Mr. Michal Barbasiewicz for carrying out some preliminaryAM1 calculations.COMMUNICATIONS4040 ¹ 2002 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim 0044-8249/02/4121-4040 $ 20.00+.50/0 Angew. Chem. Int. Ed. 2002, 41, No. 21ORuClClPhORuClClNO2N NN N5 912 34567899'1011 11'121314151617Scheme 3.

University of Groningen Research Database

  
 University of Groningen
A Highly Efficient Ruthenium Catalyst for Metathesis Reactions
Grela, Karol; Harutyunyan, Syuzanna; Michrowska, Anna
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DOI:
10.1002/1521-3773(20021104)41:21<4038::AID-ANIE4038>3.0.CO;2-0
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A Highly Efficient Ruthenium Catalyst for
Metathesis Reactions**
Karol Grela,* Syuzanna Harutyunyan, and
Anna Michrowska
The development of accessible metathesis catalysts that
combine high activity with excellent tolerance to a variety of
functional groups has been key to the widespread application
of olefin metathesis in organic synthesis. In spite of the
general superb application profile of the ruthenium carbene
1a, its limited thermal stability and the low activity towards
substituted double bonds are major drawbacks.[1]
Specifically, the preparation of substituted olefins with
electron-withdrawing functionality (such as a,b-unsaturated
carbonyl compounds, nitriles, sulfones, etc.) through cross
metathesis (CM) with terminal alkenes remains a difficult
task. The newly introduced highly active ruthenium alkyli-
dene complexes with sterically demanding N-heterocyclic
carbene (NHC)[3] ligands have dramatically alleviated this
limitation.[2] Compounds of type 1b and 1c were found to be
efficient catalysts in the reactions of previously metathesis-
inactive substrates, including a,b-unsaturated olefins
(Scheme 1).[2,4]
Hoveyda and co-workers have recently established 2 as a
remarkably robust complex, which promotes olefin meta-
thesis by a ™release±return∫ mechanism.[5] Despite the fact
that phosphane-free catalyst 2 was found to be more sluggish
than 1b,[6] it has a superior general reactivity toward electron-
deficient olefins.[7] The fact that the ruthenium carbene 2 is
air-stable and can be easily purified by standard silica-gel
chromatography and recycled after the reaction is a partic-
ularly appealing facet of this chemistry.[5,8]
Blechert and Wakamatsu have shown recently that the
replacement of the isopropoxystyrene ™ligand∫ in 2 by binol-
or biphenyl-based styrene results in a large improvement in
the activity of the catalyst, as complexes 4 and 5 are much
more reactive than both 2 and the ™second-generation∫
Grubbs catalyst 1b.[9]
During our project aimed at the preparation of the
immobilized metathesis catalyst, we prepared the bromo
analogue 3 of Hoveyda©s catalyst 2.[10] Although the reactivity
patterns of complexes 2 and 3 were in general similar, the
latter system was visibly less reactive in some model
reactions.[4b] This result once again shows that even a small
variation in the isopropoxystyrene ™ligand∫ can result in a
change in the activity of the catalyst. Impressed by results
published recently by Blechert and Wakamatsu,[9] we decided
to investigate the electronic effects in the isopropoxystyrene
™ligand∫ sphere of complex 2 which are not fully under-
stood.[11] At first, we decided to test whether a decrease in the
electron density of the styrene part of 2 would result in
increased catalyst reactivity.
As illustrated in Scheme 2, we used commercially available
6 as a starting material for preparation of the corresponding
ruthenium carbene 9. The green microcrystalline complex 9
was easily obtained in good yield (83%) by the reaction of 1b
(1 equiv) and CuCl (1 equiv) with styrene 8 (1 equiv),
followed by routine flash chromatography. Having secured
an efficient method for the preparation of complex 9, we
tested its catalytic activity. As the reactions of standard model
substrates diallyltosylamide or diallylmalonate are too fast for
an accurate measurement of their conversions,[12] we decided
to use more challenging ring-closing metathesis of 10a. This
model reaction showed that precatalyst 9 is significantly more
reactive than 2 and 3 in the formation of trisubstituted double
bonds (Figure 1). Notably, 9 is not only highly active but also
stable, as it can be stored in air (þ 4 8C) for more than four
weeks without decomposition or loss of activity.
The metathesis of selected benchmark substrates was then
examined. The results compiled in Table 1 illustrate the
remarkably wide scope of this catalyst: 1) The RCM and
enyne variant of the metathesis reaction can be performed
efficiently at 0 8C (Table 1, entries 2±4); 2) Various degrees of
substitution of the double bond are tolerated, and even
trisubstituted olefins can be synthesized in good yields at
ambient temperature (Table 1, entries 1 and 5); 3) The CM
reaction of terminal alkenes and a,b-unsaturated compounds
COMMUNICATIONS
4038 ¹ 2002 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim 0044-8249/02/4121-4038 $ 20.00+.50/0 Angew. Chem. Int. Ed. 2002, 41, No. 21
[*] Dr. K. Grela, S. Harutyunyan, A. Michrowska
Institute of Organic Chemistry, Polish Academy of Sciences
Kasprzaka 44/52, P.O.B. 58, 01-224 Warsaw (Poland)
Fax: (þ 48)22-632-6681
E-mail: grela@icho.edu.pl
[**] This work was supported by the State Committee of Scientific
Research (Grant No. 4 T09A 136 22). The authors wish to thank the
Alexander von Humboldt foundation for a donation of books and
equipment, and Professor Mieczys¯aw MaŒkosza for helpful advice and
encouragement.
MesN NMes
Ru
PCy3Ph
Cl
Cl
L
MesN NMes
iPrO
RuCl
Cl
X
iPrO
RuCl
Cl
iPrO iPrO
RuCl
Cl
MesN NMes MesN NMes
MesN NMes
a: L= b: L= c: L=
1a–c
: PCy3
2 (X=H)
3 (X=Br) 4 5
Activity: 2<1b<4<5
Scheme 1. Evolution of ruthenium precatalysts for alkene metathesis. Cy¼
cyclohexyl; Mes¼ 2,4,6-trimethylphenyl.
OR
NO2
O O
NO2
O
Ru
Cl
Cl
MesN NMes
NO2
a) 6: R = H
7: R = iPr
b) c)
8 9
Scheme 2. Synthesis of catalyst 9. a) iPrI, K2CO3, Cs2CO3 (cat.), DMF,
2 days, room temperature, 86%; b) Ph3P¼CH2, THF, 78 8C!RT, 1 h,
57%; c) 1b, CuCl, CH2Cl2, 30 8C, 1 h, 83%.
can be also performed at room temperature (Table 1, entries
6±9). The more demanding CM reactions of phenyl vinyl
sulfone[4] (Table 1, entry 8) and acrylonitrile[7a] (Table 1,
entry 9) show that also in this particular case complex 9 is
superior to 1b and 2. Most remarkably, the new precatalyst 9
can be used for CM of methacrylonitrile; the transformation is
beyond the scope of the ™second generation∫ Grubbs© carbene
1b (Table 1, entry 10).
In conclusion, we have shown that the catalysts related to
that of Hoveyda can be significantly improved by changing
not only the steric[11] but also the electronic character of the
Ru-chelating isopropoxy fragment. For example, introduction
of a strong electron-withdrawing group at the 2-isopropoxy-
styrene ring of 2 leads to complex 9, which is equally stable
but dramatically more reactive than the parent catalyst 2. We
assume that the decrease in the electron density[13] of the
oxygen atom of the isopropoxy fragment reduces its chelating
ability, thus facilitating formation of the catalytically active
14-electron Ru±carbene species, and suppressing repeated
reassociation to the metal center. Therefore, this mode of
catalyst activation is, in fact, similar to that of 4 and 5, in which
the increase in steric bulk improves the leaving-group ability
of the styrene ™ligand∫ (Scheme 3).[9] Complex 9 is attractive
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Figure 1. RCM of 10a with precatalysts 1b (~, 1 mol%), 2 (*, 2.5 mol%),
3 (&, 2.5 mol%), and 9 (^, 1 mol%). a) cat. (1±2.5 mol%), CH2Cl2, room
temperature, x ¼ conversion.
Table 1. Comparative investigation of 9.
Entry Substrate 10 Product 11 Yield using 9 [%][a] Yield using ref. catalyst [%][a]
1 10a 11a 99%[b] (1 mol%, RT, 2 h) 2 : 50%[b] (2.5 mol%, RT, 18 h)
2 98% (1 mol%, 0 8C, 1 h) 1c : 85%[c] (1 mol%, 80 8C, 1 h)
3 99% (1 mol%, 0 8C, 1 h) 1b : 99%[d] (1 mol%, RT, 1 h)
4 78% (2.5 mol%, 0 8C, 8 h) 1b : 99%[d] (1 mol%, RT, 1.5 h)
5 99%[b] (2.5 mol%, RT, 4 h)
6[e] 82% (2.5 mol%, RT, 30 min) 5 : 90%[d] (1 mol%, RT, 40 min)
7[f] 10 f 95% (1 mol%, RT, 30 min) 5 : 91%[d] (2.5 mol%, RT, 20 min)
8[g] 10 f 90% (2.5 mol%, RT, 16 h) 1b : 85%[h] (5 mol%, 40 8C, 16 h)
9[i] 87%[b] (5 mol%, RT, 30 min) 2 : 79%[j] (8 mol%, 40 8C, 6 h)
10[k] 10 f 58% (5 mol%, 408, 16 h) 1b : 0%[b] (5 mol%, 80 8C, 24 h)
[a] Yield of isolated product, unless stated otherwise. [b] Yield determined by GC. [c] Ref. [2g]. [d] Ref. [9b]. [e] Reaction with methyl vinyl ketone
(2 equiv). [f] Reaction with methyl acrylate (2 equiv). [g] Reaction with phenyl vinyl sulfone (2 equiv). [h] Ref. [4]. [i] Reaction with acrylonitrile (2 equiv).
[j] E/Z¼ 1:3, ref. [7a]. [k] Reaction with methacrylonitrile (4 equiv).
from a practical point of view as it is active and easy to obtain
in a three-step synthesis. This catalyst operates under very
mild conditions (0 8C to room temperature) and can be
successfully applied in various types of metathesis reactions
(RCM, CM, enyne). Further investigations to determine the
full scope and limitations of 9 and similar systems are under
way.
Experimental Section
9 : Carbene complex 1b (153 mg. 0.18 mmol), CuCl (18 mg, 0.18 mmol),
and CH2Cl2 (10 mL) were placed in a Schlenk tube. A solution of 8 (38 mg,
0.18 mmol) in CH2Cl2 (4 mL) was then added and the resulting solution was
stirred under argon at 30 8C for 1 h. After this step, all manipulations were
carried out in air with reagent-grade solvents. The reaction mixture was
concentrated in vacuo, and the resulting material was purified by column
chromatography on silica. Elution with cyclohexane/EtOAc (5:2) led to the
isolation of 9 as a green band. The solvent was evaporated, the residue was
washed with n-pentane and dried under vacuum to afford 9 as a green
microcrystalline solid (100 mg, 83%). Rf¼ 0.30 (cyclohexane/EtOAc 8:2);
1H NMR (500 MHz, CD2Cl2): d¼ 16.42 (s, 1H; 1-H), 8.46 (dd, J¼ 9.1,
2.5 Hz, 1H; 5-H), 7.80 (d, J¼ 2.5 Hz, 1H; 3-H), 7.10 (s, 4H; 16-H), 6.94 (d,
J¼ 9.1 Hz, 1H; 6-H), 5.01 (sept, J¼ 6.1 Hz, 1H; 8-H), 4.22 (s, 4H; 11-H,
11’-H), 2.47 (2 î s, 18H; 12-H, 13-H), 1.30 ppm (d, J¼ 6.1 Hz, 6H; 9-H, 9’-
H); 13C NMR (125 MHz, CD2Cl2): d¼ 289.1 (C1), 208.2 (C10), 156.8 (C7),
150.3, 145.0 (C2), 143.5 (C4), 139.6 (C15), 139.3, 129.8 (C16), 124.5 (C5),
117.2 (C3), 113.3 (C6), 78.2 (C8) 52.0 (C11, C11’), 21.3 (C9, C9’), 21.2 (C12),
19.4 ppm (C13) (where assignments of the NMR signals are given (based
on 2D 1H,13C-chemical shift correlated spectra: GHSQC, GHMBC), they
are unambiguous and refer to the arbitrary numbering shown in Scheme 3);
IR (KBr): n˜¼ 2924, 2850, 1606, 1521, 1480, 1262, 1093, 918, 745 cm1;
HRMS (IE): m/z calcd for C31H37N3O335C12102Ru: [MþC] 671.1255, found
671.1229; elemental analysis (%) calcd for C31H37N3O3Cl2Ru (671.63): C
55.44, H 5.55, N 6.26; found: C 55.35; H 5.70, N 6.09.
Received: July 19, 2002 [Z19778]
[1] For relevant reviews, see: a) T. M. Trnka, R. H. Grubbs, Acc. Chem.
Res. 2001, 34, 18; b) A. F¸rstner, Angew. Chem. 2000, 112, 3140;
Angew. Chem. Int. Ed. 2000, 39, 3012; c) R. H. Grubbs, S. Chang,
Tetrahedron 1998, 54, 4413; d) M. Schuster, S. Blechert,Angew. Chem.
1997, 109, 2124; Angew. Chem. Int. Ed. Engl. 1997, 36, 2037; e) A.
F¸rstner, Top. Catal. 1997, 4, 285; f) S. K. Armstrong, J. Chem. Soc.
Perkin Trans. 1 1998, 371; g) M. E. Maier, Angew. Chem. 2000, 112,
2153; Angew. Chem. Int. Ed. 2000, 39, 2073.
[2] a) W. A. Herrmann, M. Speigler, W. C. Schattenmann, T. Westcamp,
Angew. Chem. 1998, 110, 2631; Angew. Chem. Int. Ed. 1998, 37, 2490;
b) W. A. Herrmann, T. Westcamp, L. Ackermann, F. J. Kohl, A.
F¸rstner, Tetrahedron Lett. 1999, 40, 4787; c) J. Huang, E. D. Stevens,
S. P. Nolan, J. L. Pedersen, J. Am. Chem. Soc. 1999, 121, 2674; d) M.
Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1, 953;
e) M. S. Sanford, M. Ulman, R. H. Grubbs, J. Am. Chem. Soc. 2001,
123, 749; f) M. S. Sanford, J. A. Love, R. H. Grubbs, J. Am. Chem. Soc.
2001, 123, 6543; g) A. F¸rstner, L. Ackermann, B. Gabor, R. Goddard,
C. W. Lehmann, R. Mynott, F. Stelzer, O. R. Thiel, Chem. Eur. J. 2001,
7, 3236.
[3] For a comprehensive survey of N-heterocyclic carbenes, see: a) W. A.
Herrmann, Angew. Chem. 2002, 114, 1342; Angew. Chem. Int. Ed.
2002, 41, 1290; b) D. Bourissou, O. Guerret, F. P. Gabbai:, G.
Bertrand, Chem. Rev. 2000, 100, 39; c) A. J. A. Arduengo, Acc. Chem.
Res. 1999, 32, 913.
[4] a) For a recent example from our laboratory, see: K. Grela, M.
Bieniek, Tetrahedron Lett. 2001, 42, 6425; b) for screening of the
catalytic performance of Ru- and Mo-based catalysts in cross-meta-
thesis reactions of a,b-unsaturated sulfones and sulfoxides, see: K.
Grela, M. Bieniek, M. Kim, R. Klajn, unpublished results.
[5] S. B. Garber, J. S. Kingsbury, B. L. Gray, A. H. Hoveyda, J. Am. Chem.
Soc. 2000, 122, 8168.
[6] For a comparative study of the performance of precatalysts 1b and 2 in
the RCM reaction of diallyltosylamide, see: ref. [9a].
[7] a) S. Randl, S. Gessler, H. Wakamatsu, S. Blechert, Synlett 2001, 430;
b) S. Imhof, S. Randl, S. Blechert, Chem. Commun. 2001, 1692; c) S.
Randl, S. J. Connon, S. Blechert, Chem. Commun. 2001, 1796.
[8] Catalysts 1a, 1b, and 2 are available from Aldrich Chemical Co.
[9] a) H. Wakamatsu, S. Blechert, Angew. Chem. 2002, 114, 832; Angew.
Chem. Int. Ed. 2002, 41, 794; b) H. Wakamatsu, S. Blechert, Angew.
Chem. 2002, 114, 2509; Angew. Chem. Int. Ed. 2002, 41, 2403.
[10] K. Grela, M. Tryznowski, M. Bieniek, Tetrahedron Lett. , in press.
[11] Extensive studies described in ref. [9a,b] suggest that a steric
bulk adjacent to the chelating isopropoxy moiety of 4 and 5 is the
crucial factor required for the unusually high activity of these
complexes.
[12] For example, see footnote 32 in ref. [2g].
[13] We thank Mr. Michal Barbasiewicz for carrying out some preliminary
AM1 calculations.
COMMUNICATIONS
4040 ¹ 2002 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim 0044-8249/02/4121-4040 $ 20.00+.50/0 Angew. Chem. Int. Ed. 2002, 41, No. 21
O
RuCl
Cl
Ph
O
RuCl
Cl
NO2
N NN N
5 9
1
2 3
4
56
7
8
9
9'
10
11 11'12
13
141516
17
Scheme 3.


NARCIS 

Grela

Crossref

A Highly Efficient Ruthenium Catalyst for Metathesis Reactions.

   University of GroningenA Highly Efficient Ruthenium Catalyst for Metathesis ReactionsGrela, Karol; Harutyunyan, Syuzanna; Michrowska, AnnaPublished in:Angewandte Chemie International EditionDOI:10.1002/1521-3773(20021104)41:21<4038::AID-ANIE4038>3.0.CO;2-0IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2002Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Grela, K., Harutyunyan, S., & Michrowska, A. (2002). A Highly Efficient Ruthenium Catalyst for MetathesisReactions. Angewandte Chemie International Edition, 41(21), 4038-4040. https://doi.org/10.1002/1521-3773(20021104)41:21<4038::AID-ANIE4038>3.0.CO;2-0CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 09-09-2023A Highly Efficient Ruthenium Catalyst forMetathesis Reactions**Karol Grela,* Syuzanna Harutyunyan, andAnna MichrowskaThe development of accessible metathesis catalysts thatcombine high activity with excellent tolerance to a variety offunctional groups has been key to the widespread applicationof olefin metathesis in organic synthesis. In spite of thegeneral superb application profile of the ruthenium carbene1a, its limited thermal stability and the low activity towardssubstituted double bonds are major drawbacks.[1]Specifically, the preparation of substituted olefins withelectron-withdrawing functionality (such as a,b-unsaturatedcarbonyl compounds, nitriles, sulfones, etc.) through crossmetathesis (CM) with terminal alkenes remains a difficulttask. The newly introduced highly active ruthenium alkyli-dene complexes with sterically demanding N-heterocycliccarbene (NHC)[3] ligands have dramatically alleviated thislimitation.[2] Compounds of type 1b and 1c were found to beefficient catalysts in the reactions of previously metathesis-inactive substrates, including a,b-unsaturated olefins(Scheme 1).[2,4]Hoveyda and co-workers have recently established 2 as aremarkably robust complex, which promotes olefin meta-thesis by a ™release±return∫ mechanism.[5] Despite the factthat phosphane-free catalyst 2 was found to be more sluggishthan 1b,[6] it has a superior general reactivity toward electron-deficient olefins.[7] The fact that the ruthenium carbene 2 isair-stable and can be easily purified by standard silica-gelchromatography and recycled after the reaction is a partic-ularly appealing facet of this chemistry.[5,8]Blechert and Wakamatsu have shown recently that thereplacement of the isopropoxystyrene ™ligand∫ in 2 by binol-or biphenyl-based styrene results in a large improvement inthe activity of the catalyst, as complexes 4 and 5 are muchmore reactive than both 2 and the ™second-generation∫Grubbs catalyst 1b.[9]During our project aimed at the preparation of theimmobilized metathesis catalyst, we prepared the bromoanalogue 3 of Hoveyda©s catalyst 2.[10] Although the reactivitypatterns of complexes 2 and 3 were in general similar, thelatter system was visibly less reactive in some modelreactions.[4b] This result once again shows that even a smallvariation in the isopropoxystyrene ™ligand∫ can result in achange in the activity of the catalyst. Impressed by resultspublished recently by Blechert and Wakamatsu,[9] we decidedto investigate the electronic effects in the isopropoxystyrene™ligand∫ sphere of complex 2 which are not fully under-stood.[11] At first, we decided to test whether a decrease in theelectron density of the styrene part of 2 would result inincreased catalyst reactivity.As illustrated in Scheme 2, we used commercially available6 as a starting material for preparation of the correspondingruthenium carbene 9. The green microcrystalline complex 9was easily obtained in good yield (83%) by the reaction of 1b(1 equiv) and CuCl (1 equiv) with styrene 8 (1 equiv),followed by routine flash chromatography. Having securedan efficient method for the preparation of complex 9, wetested its catalytic activity. As the reactions of standard modelsubstrates diallyltosylamide or diallylmalonate are too fast foran accurate measurement of their conversions,[12] we decidedto use more challenging ring-closing metathesis of 10a. Thismodel reaction showed that precatalyst 9 is significantly morereactive than 2 and 3 in the formation of trisubstituted doublebonds (Figure 1). Notably, 9 is not only highly active but alsostable, as it can be stored in air (þ 4 8C) for more than fourweeks without decomposition or loss of activity.The metathesis of selected benchmark substrates was thenexamined. The results compiled in Table 1 illustrate theremarkably wide scope of this catalyst: 1) The RCM andenyne variant of the metathesis reaction can be performedefficiently at 0 8C (Table 1, entries 2±4); 2) Various degrees ofsubstitution of the double bond are tolerated, and eventrisubstituted olefins can be synthesized in good yields atambient temperature (Table 1, entries 1 and 5); 3) The CMreaction of terminal alkenes and a,b-unsaturated compoundsCOMMUNICATIONS4038 ¹ 2002 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim 0044-8249/02/4121-4038 $ 20.00+.50/0 Angew. Chem. Int. Ed. 2002, 41, No. 21[*] Dr. K. Grela, S. Harutyunyan, A. MichrowskaInstitute of Organic Chemistry, Polish Academy of SciencesKasprzaka 44/52, P.O.B. 58, 01-224 Warsaw (Poland)Fax: (þ 48)22-632-6681E-mail: grela@icho.edu.pl[**] This work was supported by the State Committee of ScientificResearch (Grant No. 4 T09A 136 22). The authors wish to thank theAlexander von Humboldt foundation for a donation of books andequipment, and Professor Mieczys¯aw MaŒkosza for helpful advice andencouragement.MesN NMesRuPCy3PhClClLMesN NMesiPrORuClClXiPrORuClCliPrO iPrORuClClMesN NMes MesN NMesMesN NMesa: L= b: L= c: L=1a–c: PCy32 (X=H)3 (X=Br)4 5Activity: 2<1b<4<5Scheme 1. Evolution of ruthenium precatalysts for alkene metathesis. Cy¼cyclohexyl; Mes¼ 2,4,6-trimethylphenyl.ORNO2O ONO2ORuClClMesN NMesNO2a)6: R = H7: R = iPrb) c)8 9Scheme 2. Synthesis of catalyst 9. a) iPrI, K2CO3, Cs2CO3 (cat.), DMF,2 days, room temperature, 86%; b) Ph3P¼CH2, THF, 78 8C!RT, 1 h,57%; c) 1b, CuCl, CH2Cl2, 30 8C, 1 h, 83%.can be also performed at room temperature (Table 1, entries6±9). The more demanding CM reactions of phenyl vinylsulfone[4] (Table 1, entry 8) and acrylonitrile[7a] (Table 1,entry 9) show that also in this particular case complex 9 issuperior to 1b and 2. Most remarkably, the new precatalyst 9can be used for CM of methacrylonitrile; the transformation isbeyond the scope of the ™second generation∫ Grubbs© carbene1b (Table 1, entry 10).In conclusion, we have shown that the catalysts related tothat of Hoveyda can be significantly improved by changingnot only the steric[11] but also the electronic character of theRu-chelating isopropoxy fragment. For example, introductionof a strong electron-withdrawing group at the 2-isopropoxy-styrene ring of 2 leads to complex 9, which is equally stablebut dramatically more reactive than the parent catalyst 2. Weassume that the decrease in the electron density[13] of theoxygen atom of the isopropoxy fragment reduces its chelatingability, thus facilitating formation of the catalytically active14-electron Ru±carbene species, and suppressing repeatedreassociation to the metal center. Therefore, this mode ofcatalyst activation is, in fact, similar to that of 4 and 5, in whichthe increase in steric bulk improves the leaving-group abilityof the styrene ™ligand∫ (Scheme 3).[9] Complex 9 is attractiveCOMMUNICATIONSAngew. Chem. Int. Ed. 2002, 41, No. 21 ¹ 2002 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim 0044-8249/02/4121-4039 $ 20.00+.50/0 4039Figure 1. RCM of 10a with precatalysts 1b (~, 1 mol%), 2 (*, 2.5 mol%),3 (&, 2.5 mol%), and 9 (^, 1 mol%). a) cat. (1±2.5 mol%), CH2Cl2, roomtemperature, x ¼ conversion.Table 1. Comparative investigation of 9.Entry Substrate 10 Product 11 Yield using 9 [%][a] Yield using ref. catalyst [%][a]1 10a 11a 99%[b] (1 mol%, RT, 2 h) 2 : 50%[b] (2.5 mol%, RT, 18 h)2 98% (1 mol%, 0 8C, 1 h) 1c : 85%[c] (1 mol%, 80 8C, 1 h)3 99% (1 mol%, 0 8C, 1 h) 1b : 99%[d] (1 mol%, RT, 1 h)4 78% (2.5 mol%, 0 8C, 8 h) 1b : 99%[d] (1 mol%, RT, 1.5 h)5 99%[b] (2.5 mol%, RT, 4 h)6[e] 82% (2.5 mol%, RT, 30 min) 5 : 90%[d] (1 mol%, RT, 40 min)7[f] 10 f 95% (1 mol%, RT, 30 min) 5 : 91%[d] (2.5 mol%, RT, 20 min)8[g] 10 f 90% (2.5 mol%, RT, 16 h) 1b : 85%[h] (5 mol%, 40 8C, 16 h)9[i] 87%[b] (5 mol%, RT, 30 min) 2 : 79%[j] (8 mol%, 40 8C, 6 h)10[k] 10 f 58% (5 mol%, 408, 16 h) 1b : 0%[b] (5 mol%, 80 8C, 24 h)[a] Yield of isolated product, unless stated otherwise. [b] Yield determined by GC. [c] Ref. [2g]. [d] Ref. [9b]. [e] Reaction with methyl vinyl ketone(2 equiv). [f] Reaction with methyl acrylate (2 equiv). [g] Reaction with phenyl vinyl sulfone (2 equiv). [h] Ref. [4]. [i] Reaction with acrylonitrile (2 equiv).[j] E/Z¼ 1:3, ref. [7a]. [k] Reaction with methacrylonitrile (4 equiv).from a practical point of view as it is active and easy to obtainin a three-step synthesis. This catalyst operates under verymild conditions (0 8C to room temperature) and can besuccessfully applied in various types of metathesis reactions(RCM, CM, enyne). Further investigations to determine thefull scope and limitations of 9 and similar systems are underway.Experimental Section9 : Carbene complex 1b (153 mg. 0.18 mmol), CuCl (18 mg, 0.18 mmol),and CH2Cl2 (10 mL) were placed in a Schlenk tube. A solution of 8 (38 mg,0.18 mmol) in CH2Cl2 (4 mL) was then added and the resulting solution wasstirred under argon at 30 8C for 1 h. After this step, all manipulations werecarried out in air with reagent-grade solvents. The reaction mixture wasconcentrated in vacuo, and the resulting material was purified by columnchromatography on silica. Elution with cyclohexane/EtOAc (5:2) led to theisolation of 9 as a green band. The solvent was evaporated, the residue waswashed with n-pentane and dried under vacuum to afford 9 as a greenmicrocrystalline solid (100 mg, 83%). Rf¼ 0.30 (cyclohexane/EtOAc 8:2);1H NMR (500 MHz, CD2Cl2): d¼ 16.42 (s, 1H; 1-H), 8.46 (dd, J¼ 9.1,2.5 Hz, 1H; 5-H), 7.80 (d, J¼ 2.5 Hz, 1H; 3-H), 7.10 (s, 4H; 16-H), 6.94 (d,J¼ 9.1 Hz, 1H; 6-H), 5.01 (sept, J¼ 6.1 Hz, 1H; 8-H), 4.22 (s, 4H; 11-H,11’-H), 2.47 (2 î s, 18H; 12-H, 13-H), 1.30 ppm (d, J¼ 6.1 Hz, 6H; 9-H, 9’-H); 13C NMR (125 MHz, CD2Cl2): d¼ 289.1 (C1), 208.2 (C10), 156.8 (C7),150.3, 145.0 (C2), 143.5 (C4), 139.6 (C15), 139.3, 129.8 (C16), 124.5 (C5),117.2 (C3), 113.3 (C6), 78.2 (C8) 52.0 (C11, C11’), 21.3 (C9, C9’), 21.2 (C12),19.4 ppm (C13) (where assignments of the NMR signals are given (basedon 2D 1H,13C-chemical shift correlated spectra: GHSQC, GHMBC), theyare unambiguous and refer to the arbitrary numbering shown in Scheme 3);IR (KBr): ñ¼ 2924, 2850, 1606, 1521, 1480, 1262, 1093, 918, 745 cm1;HRMS (IE): m/z calcd for C31H37N3O335C12102Ru: [MþC] 671.1255, found671.1229; elemental analysis (%) calcd for C31H37N3O3Cl2Ru (671.63): C55.44, H 5.55, N 6.26; found: C 55.35; H 5.70, N 6.09.Received: July 19, 2002 [Z19778][1] For relevant reviews, see: a) T. M. Trnka, R. H. Grubbs, Acc. Chem.Res. 2001, 34, 18; b) A. F¸rstner, Angew. Chem. 2000, 112, 3140;Angew. Chem. Int. Ed. 2000, 39, 3012; c) R. H. Grubbs, S. Chang,Tetrahedron 1998, 54, 4413; d) M. Schuster, S. Blechert,Angew. Chem.1997, 109, 2124; Angew. Chem. Int. Ed. Engl. 1997, 36, 2037; e) A.F¸rstner, Top. Catal. 1997, 4, 285; f) S. K. Armstrong, J. Chem. Soc.Perkin Trans. 1 1998, 371; g) M. E. Maier, Angew. Chem. 2000, 112,2153; Angew. Chem. Int. Ed. 2000, 39, 2073.[2] a) W. A. Herrmann, M. Speigler, W. C. Schattenmann, T. Westcamp,Angew. Chem. 1998, 110, 2631; Angew. Chem. Int. Ed. 1998, 37, 2490;b) W. A. Herrmann, T. Westcamp, L. Ackermann, F. J. Kohl, A.F¸rstner, Tetrahedron Lett. 1999, 40, 4787; c) J. Huang, E. D. Stevens,S. P. Nolan, J. L. Pedersen, J. Am. Chem. Soc. 1999, 121, 2674; d) M.Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1, 953;e) M. S. Sanford, M. Ulman, R. H. Grubbs, J. Am. Chem. Soc. 2001,123, 749; f) M. S. Sanford, J. A. Love, R. H. Grubbs, J. Am. Chem. Soc.2001, 123, 6543; g) A. F¸rstner, L. Ackermann, B. Gabor, R. Goddard,C. W. Lehmann, R. Mynott, F. Stelzer, O. R. Thiel, Chem. Eur. J. 2001,7, 3236.[3] For a comprehensive survey of N-heterocyclic carbenes, see: a) W. A.Herrmann, Angew. Chem. 2002, 114, 1342; Angew. Chem. Int. Ed.2002, 41, 1290; b) D. Bourissou, O. Guerret, F. P. Gabbai:, G.Bertrand, Chem. Rev. 2000, 100, 39; c) A. J. A. Arduengo, Acc. Chem.Res. 1999, 32, 913.[4] a) For a recent example from our laboratory, see: K. Grela, M.Bieniek, Tetrahedron Lett. 2001, 42, 6425; b) for screening of thecatalytic performance of Ru- and Mo-based catalysts in cross-meta-thesis reactions of a,b-unsaturated sulfones and sulfoxides, see: K.Grela, M. Bieniek, M. Kim, R. Klajn, unpublished results.[5] S. B. Garber, J. S. Kingsbury, B. L. Gray, A. H. Hoveyda, J. Am. Chem.Soc. 2000, 122, 8168.[6] For a comparative study of the performance of precatalysts 1b and 2 inthe RCM reaction of diallyltosylamide, see: ref. [9a].[7] a) S. Randl, S. Gessler, H. Wakamatsu, S. Blechert, Synlett 2001, 430;b) S. Imhof, S. Randl, S. Blechert, Chem. Commun. 2001, 1692; c) S.Randl, S. J. Connon, S. Blechert, Chem. Commun. 2001, 1796.[8] Catalysts 1a, 1b, and 2 are available from Aldrich Chemical Co.[9] a) H. Wakamatsu, S. Blechert, Angew. Chem. 2002, 114, 832; Angew.Chem. Int. Ed. 2002, 41, 794; b) H. Wakamatsu, S. Blechert, Angew.Chem. 2002, 114, 2509; Angew. Chem. Int. Ed. 2002, 41, 2403.[10] K. Grela, M. Tryznowski, M. Bieniek, Tetrahedron Lett. , in press.[11] Extensive studies described in ref. [9a,b] suggest that a stericbulk adjacent to the chelating isopropoxy moiety of 4 and 5 is thecrucial factor required for the unusually high activity of thesecomplexes.[12] For example, see footnote 32 in ref. [2g].[13] We thank Mr. Michal Barbasiewicz for carrying out some preliminaryAM1 calculations.COMMUNICATIONS4040 ¹ 2002 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim 0044-8249/02/4121-4040 $ 20.00+.50/0 Angew. Chem. Int. Ed. 2002, 41, No. 21ORuClClPhORuClClNO2N NN N5 912 34567899'1011 11'121314151617Scheme 3.

   University of GroningenA Highly Efficient Ruthenium Catalyst for Metathesis ReactionsGrela, Karol; Harutyunyan, Syuzanna; Michrowska, AnnaPublished in:Angewandte Chemie International EditionDOI:10.1002/1521-3773(20021104)41:21<4038::AID-ANIE4038>3.0.CO;2-0IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2002Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Grela, K., Harutyunyan, S., & Michrowska, A. (2002). A Highly Efficient Ruthenium Catalyst for MetathesisReactions. Angewandte Chemie International Edition, 41(21), 4038-4040. 3.0.CO;2-0"class="link">https://doi.org/10.1002/1521-3773(20021104)41:213.0.CO;2-0CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 12-11-2019A Highly Efficient Ruthenium Catalyst forMetathesis Reactions**Karol Grela,* Syuzanna Harutyunyan, andAnna MichrowskaThe development of accessible metathesis catalysts thatcombine high activity with excellent tolerance to a variety offunctional groups has been key to the widespread applicationof olefin metathesis in organic synthesis. In spite of thegeneral superb application profile of the ruthenium carbene1a, its limited thermal stability and the low activity towardssubstituted double bonds are major drawbacks.[1]Specifically, the preparation of substituted olefins withelectron-withdrawing functionality (such as a,b-unsaturatedcarbonyl compounds, nitriles, sulfones, etc.) through crossmetathesis (CM) with terminal alkenes remains a difficulttask. The newly introduced highly active ruthenium alkyli-dene complexes with sterically demanding N-heterocycliccarbene (NHC)[3] ligands have dramatically alleviated thislimitation.[2] Compounds of type 1b and 1c were found to beefficient catalysts in the reactions of previously metathesis-inactive substrates, including a,b-unsaturated olefins(Scheme 1).[2,4]Hoveyda and co-workers have recently established 2 as aremarkably robust complex, which promotes olefin meta-thesis by a ™release±return∫ mechanism.[5] Despite the factthat phosphane-free catalyst 2 was found to be more sluggishthan 1b,[6] it has a superior general reactivity toward electron-deficient olefins.[7] The fact that the ruthenium carbene 2 isair-stable and can be easily purified by standard silica-gelchromatography and recycled after the reaction is a partic-ularly appealing facet of this chemistry.[5,8]Blechert and Wakamatsu have shown recently that thereplacement of the isopropoxystyrene ™ligand∫ in 2 by binol-or biphenyl-based styrene results in a large improvement inthe activity of the catalyst, as complexes 4 and 5 are muchmore reactive than both 2 and the ™second-generation∫Grubbs catalyst 1b.[9]During our project aimed at the preparation of theimmobilized metathesis catalyst, we prepared the bromoanalogue 3 of Hoveyda©s catalyst 2.[10] Although the reactivitypatterns of complexes 2 and 3 were in general similar, thelatter system was visibly less reactive in some modelreactions.[4b] This result once again shows that even a smallvariation in the isopropoxystyrene ™ligand∫ can result in achange in the activity of the catalyst. Impressed by resultspublished recently by Blechert and Wakamatsu,[9] we decidedto investigate the electronic effects in the isopropoxystyrene™ligand∫ sphere of complex 2 which are not fully under-stood.[11] At first, we decided to test whether a decrease in theelectron density of the styrene part of 2 would result inincreased catalyst reactivity.As illustrated in Scheme 2, we used commercially available6 as a starting material for preparation of the correspondingruthenium carbene 9. The green microcrystalline complex 9was easily obtained in good yield (83%) by the reaction of 1b(1 equiv) and CuCl (1 equiv) with styrene 8 (1 equiv),followed by routine flash chromatography. Having securedan efficient method for the preparation of complex 9, wetested its catalytic activity. As the reactions of standard modelsubstrates diallyltosylamide or diallylmalonate are too fast foran accurate measurement of their conversions,[12] we decidedto use more challenging ring-closing metathesis of 10a. Thismodel reaction showed that precatalyst 9 is significantly morereactive than 2 and 3 in the formation of trisubstituted doublebonds (Figure 1). Notably, 9 is not only highly active but alsostable, as it can be stored in air (þ 4 8C) for more than fourweeks without decomposition or loss of activity.The metathesis of selected benchmark substrates was thenexamined. The results compiled in Table 1 illustrate theremarkably wide scope of this catalyst: 1) The RCM andenyne variant of the metathesis reaction can be performedefficiently at 0 8C (Table 1, entries 2±4); 2) Various degrees ofsubstitution of the double bond are tolerated, and eventrisubstituted olefins can be synthesized in good yields atambient temperature (Table 1, entries 1 and 5); 3) The CMreaction of terminal alkenes and a,b-unsaturated compoundsCOMMUNICATIONS4038 ¹ 2002 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim 0044-8249/02/4121-4038 $ 20.00+.50/0 Angew. Chem. Int. Ed. 2002, 41, No. 21[*] Dr. K. Grela, S. Harutyunyan, A. MichrowskaInstitute of Organic Chemistry, Polish Academy of SciencesKasprzaka 44/52, P.O.B. 58, 01-224 Warsaw (Poland)Fax: (þ 48)22-632-6681E-mail: grela@icho.edu.pl[**] This work was supported by the State Committee of ScientificResearch (Grant No. 4 T09A 136 22). The authors wish to thank theAlexander von Humboldt foundation for a donation of books andequipment, and Professor Mieczys¯aw MaŒkosza for helpful advice andencouragement.MesN NMesRuPCy3PhClClLMesN NMesiPrORuClClXiPrORuClCliPrO iPrORuClClMesN NMes MesN NMesMesN NMesa: L= b: L= c: L=1a–c: PCy32 (X=H)3 (X=Br) 4 5Activity: 2<1b<4<5Scheme 1. Evolution of ruthenium precatalysts for alkene metathesis. Cy¼cyclohexyl; Mes¼ 2,4,6-trimethylphenyl.ORNO2O ONO2ORuClClMesN NMesNO2a) 6: R = H7: R = iPrb) c)8 9Scheme 2. Synthesis of catalyst 9. a) iPrI, K2CO3, Cs2CO3 (cat.), DMF,2 days, room temperature, 86%; b) Ph3P¼CH2, THF, 78 8C!RT, 1 h,57%; c) 1b, CuCl, CH2Cl2, 30 8C, 1 h, 83%.can be also performed at room temperature (Table 1, entries6±9). The more demanding CM reactions of phenyl vinylsulfone[4] (Table 1, entry 8) and acrylonitrile[7a] (Table 1,entry 9) show that also in this particular case complex 9 issuperior to 1b and 2. Most remarkably, the new precatalyst 9can be used for CM of methacrylonitrile; the transformation isbeyond the scope of the ™second generation∫ Grubbs© carbene1b (Table 1, entry 10).In conclusion, we have shown that the catalysts related tothat of Hoveyda can be significantly improved by changingnot only the steric[11] but also the electronic character of theRu-chelating isopropoxy fragment. For example, introductionof a strong electron-withdrawing group at the 2-isopropoxy-styrene ring of 2 leads to complex 9, which is equally stablebut dramatically more reactive than the parent catalyst 2. Weassume that the decrease in the electron density[13] of theoxygen atom of the isopropoxy fragment reduces its chelatingability, thus facilitating formation of the catalytically active14-electron Ru±carbene species, and suppressing repeatedreassociation to the metal center. Therefore, this mode ofcatalyst activation is, in fact, similar to that of 4 and 5, in whichthe increase in steric bulk improves the leaving-group abilityof the styrene ™ligand∫ (Scheme 3).[9] Complex 9 is attractiveCOMMUNICATIONSAngew. Chem. Int. Ed. 2002, 41, No. 21 ¹ 2002 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim 0044-8249/02/4121-4039 $ 20.00+.50/0 4039Figure 1. RCM of 10a with precatalysts 1b (~, 1 mol%), 2 (*, 2.5 mol%),3 (&, 2.5 mol%), and 9 (^, 1 mol%). a) cat. (1±2.5 mol%), CH2Cl2, roomtemperature, x ¼ conversion.Table 1. Comparative investigation of 9.Entry Substrate 10 Product 11 Yield using 9 [%][a] Yield using ref. catalyst [%][a]1 10a 11a 99%[b] (1 mol%, RT, 2 h) 2 : 50%[b] (2.5 mol%, RT, 18 h)2 98% (1 mol%, 0 8C, 1 h) 1c : 85%[c] (1 mol%, 80 8C, 1 h)3 99% (1 mol%, 0 8C, 1 h) 1b : 99%[d] (1 mol%, RT, 1 h)4 78% (2.5 mol%, 0 8C, 8 h) 1b : 99%[d] (1 mol%, RT, 1.5 h)5 99%[b] (2.5 mol%, RT, 4 h)6[e] 82% (2.5 mol%, RT, 30 min) 5 : 90%[d] (1 mol%, RT, 40 min)7[f] 10 f 95% (1 mol%, RT, 30 min) 5 : 91%[d] (2.5 mol%, RT, 20 min)8[g] 10 f 90% (2.5 mol%, RT, 16 h) 1b : 85%[h] (5 mol%, 40 8C, 16 h)9[i] 87%[b] (5 mol%, RT, 30 min) 2 : 79%[j] (8 mol%, 40 8C, 6 h)10[k] 10 f 58% (5 mol%, 408, 16 h) 1b : 0%[b] (5 mol%, 80 8C, 24 h)[a] Yield of isolated product, unless stated otherwise. [b] Yield determined by GC. [c] Ref. [2g]. [d] Ref. [9b]. [e] Reaction with methyl vinyl ketone(2 equiv). [f] Reaction with methyl acrylate (2 equiv). [g] Reaction with phenyl vinyl sulfone (2 equiv). [h] Ref. [4]. [i] Reaction with acrylonitrile (2 equiv).[j] E/Z¼ 1:3, ref. [7a]. [k] Reaction with methacrylonitrile (4 equiv).from a practical point of view as it is active and easy to obtainin a three-step synthesis. This catalyst operates under verymild conditions (0 8C to room temperature) and can besuccessfully applied in various types of metathesis reactions(RCM, CM, enyne). Further investigations to determine thefull scope and limitations of 9 and similar systems are underway.Experimental Section9 : Carbene complex 1b (153 mg. 0.18 mmol), CuCl (18 mg, 0.18 mmol),and CH2Cl2 (10 mL) were placed in a Schlenk tube. A solution of 8 (38 mg,0.18 mmol) in CH2Cl2 (4 mL) was then added and the resulting solution wasstirred under argon at 30 8C for 1 h. After this step, all manipulations werecarried out in air with reagent-grade solvents. The reaction mixture wasconcentrated in vacuo, and the resulting material was purified by columnchromatography on silica. Elution with cyclohexane/EtOAc (5:2) led to theisolation of 9 as a green band. The solvent was evaporated, the residue waswashed with n-pentane and dried under vacuum to afford 9 as a greenmicrocrystalline solid (100 mg, 83%). Rf¼ 0.30 (cyclohexane/EtOAc 8:2);1H NMR (500 MHz, CD2Cl2): d¼ 16.42 (s, 1H; 1-H), 8.46 (dd, J¼ 9.1,2.5 Hz, 1H; 5-H), 7.80 (d, J¼ 2.5 Hz, 1H; 3-H), 7.10 (s, 4H; 16-H), 6.94 (d,J¼ 9.1 Hz, 1H; 6-H), 5.01 (sept, J¼ 6.1 Hz, 1H; 8-H), 4.22 (s, 4H; 11-H,11’-H), 2.47 (2 î s, 18H; 12-H, 13-H), 1.30 ppm (d, J¼ 6.1 Hz, 6H; 9-H, 9’-H); 13C NMR (125 MHz, CD2Cl2): d¼ 289.1 (C1), 208.2 (C10), 156.8 (C7),150.3, 145.0 (C2), 143.5 (C4), 139.6 (C15), 139.3, 129.8 (C16), 124.5 (C5),117.2 (C3), 113.3 (C6), 78.2 (C8) 52.0 (C11, C11’), 21.3 (C9, C9’), 21.2 (C12),19.4 ppm (C13) (where assignments of the NMR signals are given (basedon 2D 1H,13C-chemical shift correlated spectra: GHSQC, GHMBC), theyare unambiguous and refer to the arbitrary numbering shown in Scheme 3);IR (KBr): n˜¼ 2924, 2850, 1606, 1521, 1480, 1262, 1093, 918, 745 cm1;HRMS (IE): m/z calcd for C31H37N3O335C12102Ru: [MþC] 671.1255, found671.1229; elemental analysis (%) calcd for C31H37N3O3Cl2Ru (671.63): C55.44, H 5.55, N 6.26; found: C 55.35; H 5.70, N 6.09.Received: July 19, 2002 [Z19778][1] For relevant reviews, see: a) T. M. Trnka, R. H. Grubbs, Acc. Chem.Res. 2001, 34, 18; b) A. F¸rstner, Angew. Chem. 2000, 112, 3140;Angew. Chem. Int. Ed. 2000, 39, 3012; c) R. H. Grubbs, S. Chang,Tetrahedron 1998, 54, 4413; d) M. Schuster, S. Blechert,Angew. Chem.1997, 109, 2124; Angew. Chem. Int. Ed. Engl. 1997, 36, 2037; e) A.F¸rstner, Top. Catal. 1997, 4, 285; f) S. K. Armstrong, J. Chem. Soc.Perkin Trans. 1 1998, 371; g) M. E. Maier, Angew. Chem. 2000, 112,2153; Angew. Chem. Int. Ed. 2000, 39, 2073.[2] a) W. A. Herrmann, M. Speigler, W. C. Schattenmann, T. Westcamp,Angew. Chem. 1998, 110, 2631; Angew. Chem. Int. Ed. 1998, 37, 2490;b) W. A. Herrmann, T. Westcamp, L. Ackermann, F. J. Kohl, A.F¸rstner, Tetrahedron Lett. 1999, 40, 4787; c) J. Huang, E. D. Stevens,S. P. Nolan, J. L. Pedersen, J. Am. Chem. Soc. 1999, 121, 2674; d) M.Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1, 953;e) M. S. Sanford, M. Ulman, R. H. Grubbs, J. Am. Chem. Soc. 2001,123, 749; f) M. S. Sanford, J. A. Love, R. H. Grubbs, J. Am. Chem. Soc.2001, 123, 6543; g) A. F¸rstner, L. Ackermann, B. Gabor, R. Goddard,C. W. Lehmann, R. Mynott, F. Stelzer, O. R. Thiel, Chem. Eur. J. 2001,7, 3236.[3] For a comprehensive survey of N-heterocyclic carbenes, see: a) W. A.Herrmann, Angew. Chem. 2002, 114, 1342; Angew. Chem. Int. Ed.2002, 41, 1290; b) D. Bourissou, O. Guerret, F. P. Gabbai:, G.Bertrand, Chem. Rev. 2000, 100, 39; c) A. J. A. Arduengo, Acc. Chem.Res. 1999, 32, 913.[4] a) For a recent example from our laboratory, see: K. Grela, M.Bieniek, Tetrahedron Lett. 2001, 42, 6425; b) for screening of thecatalytic performance of Ru- and Mo-based catalysts in cross-meta-thesis reactions of a,b-unsaturated sulfones and sulfoxides, see: K.Grela, M. Bieniek, M. Kim, R. Klajn, unpublished results.[5] S. B. Garber, J. S. Kingsbury, B. L. Gray, A. H. Hoveyda, J. Am. Chem.Soc. 2000, 122, 8168.[6] For a comparative study of the performance of precatalysts 1b and 2 inthe RCM reaction of diallyltosylamide, see: ref. [9a].[7] a) S. Randl, S. Gessler, H. Wakamatsu, S. Blechert, Synlett 2001, 430;b) S. Imhof, S. Randl, S. Blechert, Chem. Commun. 2001, 1692; c) S.Randl, S. J. Connon, S. Blechert, Chem. Commun. 2001, 1796.[8] Catalysts 1a, 1b, and 2 are available from Aldrich Chemical Co.[9] a) H. Wakamatsu, S. Blechert, Angew. Chem. 2002, 114, 832; Angew.Chem. Int. Ed. 2002, 41, 794; b) H. Wakamatsu, S. Blechert, Angew.Chem. 2002, 114, 2509; Angew. Chem. Int. Ed. 2002, 41, 2403.[10] K. Grela, M. Tryznowski, M. Bieniek, Tetrahedron Lett. , in press.[11] Extensive studies described in ref. [9a,b] suggest that a stericbulk adjacent to the chelating isopropoxy moiety of 4 and 5 is thecrucial factor required for the unusually high activity of thesecomplexes.[12] For example, see footnote 32 in ref. [2g].[13] We thank Mr. Michal Barbasiewicz for carrying out some preliminaryAM1 calculations.COMMUNICATIONS4040 ¹ 2002 WILEY-VCH Verlag GmbH&Co. KGaA, Weinheim 0044-8249/02/4121-4040 $ 20.00+.50/0 Angew. Chem. Int. Ed. 2002, 41, No. 21ORuClClPhORuClClNO2N NN N5 912 34567899'1011 11'121314151617Scheme 3.

A Highly Efficient Ruthenium Catalyst for Metathesis Reactions

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