Rational Design and Evaluation of Upgraded Grubbs/Hoveyda Olefin Metathesis Catalysts: Polyfunctional Benzylidene Ethers on the Test Bench

The series of upgraded Grubbs/Hoveyda second-generation catalysts (H2IMes)(Cl)2Ru═C(H)(C6H4OR) (E2 (71% yield), R = CH(Me)(C(O)OMe); M2 (58% yield), R = CH(C(O)OMe)2; Kme2 (88% yield), R = CH2C(O)Me; Ket2 (63% yield), R = CH2C(O)Et); C2 (58% yield), R = C(Me)CN) were prepared by the reaction of the Grubbs second-generation catalyst (H2IMes)(Cl)2Ru(CHPh)(PCy3) (G2) with the appropriate ortho-substituted ether H(Me)C═CHC6H4OR in the presence of CuCl as a phosphine scavenger. The X-ray structures of these complexes reveal that the terminal oxygen of the ester, ketone, or malonate group installed as the terminal substituent of the benzylidene ether is coordinated to the metal, giving an octahedral structure. In contrast, the nitrile group of the complex C2 remains uncoordinated. Even more sophisticated complexes, incorporating both a coordinating group R (ester or ketone) as a terminal substituent of the ether and an electron-withdrawing group X (NO2 or C(O)Me) on the aromatic ring, were synthesized: (H2IMes)...

[1]  P. D. Weghe,et al.  Metathesis of heteroatom-substituted olefins and alkynes: Current scope and limitations , 2006 .

[2]  R. Grubbs,et al.  Rate acceleration in olefin metathesis through a fluorine-ruthenium interaction. , 2006, Journal of the American Chemical Society.

[3]  Volodymyr Sashuk,et al.  [(NHC)(NHC(ewg))RuCl(2)(CHPh)] complexes with modified NHC(ewg) ligands for efficient ring-closing metathesis leading to tetrasubstituted olefins. , 2010, Chemistry.

[4]  H. Plenio,et al.  How important is the release-return mechanism in olefin metathesis? , 2010, Chemistry.

[5]  M. Sodupe,et al.  DFT mechanistic study on diene metathesis catalyzed by Ru-based Grubbs-Hoveyda-type carbenes: the key role of pi-electron density delocalization in the Hoveyda ligand. , 2010, Chemistry.

[6]  Anatoly Chlenov,et al.  Ruthenium-catalyzed ring-closing metathesis to form tetrasubstituted olefins. , 2007, Organic letters.

[7]  Patricio E. Romero,et al.  Rapidly initiating ruthenium olefin-metathesis catalysts. , 2004, Angewandte Chemie.

[8]  S. Nolan,et al.  Towards Long‐Living Metathesis Catalysts by Tuning the N‐Heterocyclic Carbene (NHC) Ligand on Trifluoroacetamide‐Activated Boomerang Ru Complexes , 2009 .

[9]  R. Grubbs,et al.  Olefin metathesis catalyst: stabilization effect of backbone substitutions of N-heterocyclic carbene. , 2008, Organic letters.

[10]  Par Jean‐Louis Hérisson,et al.  Catalyse de transformation des oléfines par les complexes du tungstène. II. Télomérisation des oléfines cycliques en présence d'oléfines acycliques , 1971 .

[11]  K. Wagener,et al.  Metathesis Activity and Stability of New Generation Ruthenium Polymerization Catalysts , 2003 .

[12]  Volodymyr Sashuk,et al.  Nitro-substituted Hoveyda-Grubbs ruthenium carbenes: enhancement of catalyst activity through electronic activation. , 2004, Journal of the American Chemical Society.

[13]  Alexander Deiters,et al.  Synthesis of oxygen- and nitrogen-containing heterocycles by ring-closing metathesis. , 2004, Chemical reviews.

[14]  R. Grubbs,et al.  Ruthenium-based heterocyclic carbene-coordinated olefin metathesis catalysts. , 2010, Chemical reviews.

[15]  I. Goldberg,et al.  Photoactivation of Ruthenium Olefin Metathesis Initiators , 2009 .

[16]  Dennis G. Gillingham,et al.  Chiral Ru-based complexes for asymmetric olefin metathesis: enhancement of catalyst activity through steric and electronic modifications. , 2003, Journal of the American Chemical Society.

[17]  R. Grubbs,et al.  A tandem approach to photoactivated olefin metathesis: combining a photoacid generator with an acid activated catalyst. , 2009, Journal of the American Chemical Society.

[18]  A. Kirschning,et al.  Sustainable concepts in olefin metathesis. , 2007, Angewandte Chemie.

[19]  Ian C. Stewart,et al.  Conformations of N-heterocyclic carbene ligands in ruthenium complexes relevant to olefin metathesis. , 2009, Journal of the American Chemical Society.

[20]  César A. Urbina-Blanco,et al.  Olefin metathesis featuring ruthenium indenylidene complexes with a sterically demanding NHC ligand. , 2011, Chemistry.

[21]  R. Grubbs,et al.  Protonolysis of a ruthenium-carbene bond and applications in olefin metathesis. , 2011, Journal of the American Chemical Society.

[22]  H. Plenio,et al.  An [(NHC)(NHC(EWG))RuCl2(CHPh)] complex for the efficient formation of sterically hindered olefins by ring-closing metathesis. , 2009, Angewandte Chemie.

[23]  Dennis G. Gillingham,et al.  Chiral N-heterocyclic carbenes in natural product synthesis: application of Ru-catalyzed asymmetric ring-opening/cross-metathesis and Cu-catalyzed allylic alkylation to total synthesis of baconipyrone C. , 2007, Angewandte Chemie.

[24]  A. Slawin,et al.  Ruthenium complexes bearing two N-heterocyclic carbene ligands in low catalyst loading olefin metathesis reactions , 2010 .

[25]  S. Cramp,et al.  A RECYCLABLE 'BOOMERANG' POLYMER-SUPPORTED RUTHENIUM CATALYST FOR OLEFIN METATHESIS , 1999 .

[26]  Xudong Wei,et al.  Second-Generation Process for the HCV Protease Inhibitor BILN 2061: A Greener Approach to Ru-Catalyzed Ring-Closing Metathesis† , 2009 .

[27]  H. Mizutani,et al.  First diastereoselective chiral synthesis of (-)-securinine. , 2004, Organic letters.

[28]  R. Grubbs.  Olefin-metathesis catalysts for the preparation of molecules and materials (Nobel Lecture). , 2006, Angewandte Chemie.

[29]  M. Buchmeiser,et al.  Cationic versus neutral Ru(II)--N-heterocyclic carbene complexes as latent precatalysts for the UV-induced ring-opening metathesis polymerization. , 2010, Chemistry.

[30]  R. Grubbs,et al.  Latent Olefin Metathesis Catalysts Featuring Chelating Alkylidenes , 2006 .

[31]  J. P. Harrity,et al.  A Recyclable Ru-Based Metathesis Catalyst , 1999 .

[32]  C. Bielawski,et al.  Olefin Metathesis Catalysts Containing N,N′-Diamidocarbenes , 2011 .

[33]  X. Luan,et al.  Impact of NHC ligand conformation and solvent concentration on the ruthenium-catalyzed ring-closing metathesis reaction. , 2009, Journal of the American Chemical Society.

[34]  S. Kotha,et al.  Synthesis of Diverse Polycyclic Compounds via Catalytic Metathesis , 2007 .

[35]  A. Gradillas,et al.  Macrocyclization by ring-closing metathesis in the total synthesis of natural products: reaction conditions and limitations. , 2006, Angewandte Chemie.

[36]  P. Chen,et al.  Tuning the Steric Properties of a Metathesis Catalyst for Copolymerization of Norbornene and Cyclooctene toward Complete Alternation , 2010 .

[37]  I. Goldberg,et al.  Studies on electronic effects in O-, N- and S-chelated ruthenium olefin-metathesis catalysts. , 2010, Chemistry.

[38]  C. Diesendruck,et al.  A latent s‐chelated ruthenium benzylidene initiator for ring‐opening metathesis polymerization , 2009 .

[39]  W. Goddard,et al.  The isomerization equilibrium between cis and trans chloride ruthenium olefin metathesis catalysts from quantum mechanics calculations. , 2005, Journal of the American Chemical Society.

[40]  H. Plenio,et al.  Probing the mechanism of olefin metathesis in Grubbs-Hoveyda and Grela type complexes. , 2010, Angewandte Chemie.

[41]  A. Hoveyda,et al.  Regarding the mechanism of olefin metathesis with sol-gel-supported Ru-based complexes bearing a bidentate carbene ligand. Spectroscopic evidence for return of the propagating Ru carbene. , 2005, Journal of the American Chemical Society.

[42]  I. Goldberg,et al.  Widening the Latency Gap in Chelated Ruthenium Olefin Metathesis Catalysts , 2011 .

[43]  F. Totzke,et al.  Modular synthesis of radicicol A and related resorcylic acid lactones, potent kinase inhibitors. , 2007, Angewandte Chemie.

[44]  K. Woźniak,et al.  A dormant ruthenium catalyst bearing a chelating carboxylate ligand: in situ activation and application in metathesis reactions. , 2007, Angewandte Chemie.

[45]  K. Koide,et al.  Total synthesis of FR901464, an antitumor agent that regulates the transcription of oncogenes and tumor suppressor genes. , 2006, Journal of the American Chemical Society.

[46]  S. Nolan,et al.  Improving Grubbs' II type ruthenium catalysts by appropriately modifying the N-heterocyclic carbene ligand. , 2009, Chemical communications.

[47]  R. Schrock,et al.  Molybdenum and tungsten imido alkylidene complexes as efficient olefin-metathesis catalysts. , 2003, Angewandte Chemie.

[48]  Y. Chauvin,et al.  Olefin metathesis: the early days (Nobel Lecture). , 2006, Angewandte Chemie.

[49]  Richard L. Pederson,et al.  Low catalyst loadings in olefin metathesis: synthesis of nitrogen heterocycles by ring-closing metathesis. , 2010, Organic letters.

[50]  R. Grubbs,et al.  Ruthenium-based olefin metathesis catalysts coordinated with unsymmetrical N-heterocyclic carbene ligands: synthesis, structure, and catalytic activity. , 2008, Chemistry.

[51]  R. Grubbs.  Handbook of metathesis , 2003 .

[52]  K. Jarzembska,et al.  New air-stable ruthenium olefin metathesis precatalysts derived from bisphenol S , 2006 .

[53]  G. Erker,et al.  Ruthenium Carbene Complexes Featuring a Tridentate Pincer-type Ligand , 2005 .

[54]  R. Grubbs,et al.  A Standard System of Characterization for Olefin Metathesis Catalysts , 2006 .

[55]  I. Goldberg,et al.  Homodinuclear ruthenium catalysts for dimer ring-closing metathesis. , 2008, Angewandte Chemie.

[56]  R. Schrock.  Multiple metal-carbon bonds for catalytic metathesis reactions (Nobel Lecture). , 2006, Angewandte Chemie.

[57]  H. Plenio,et al.  Switched Stereocontrol in Grubbs−Hoveyda Complex Catalyzed ROMP Utilizing Proton-Switched NHC Ligands† , 2010 .

[58]  A. Hoveyda,et al.  The remarkable metal-catalysed olefin metathesis reaction , 2007, Nature.

[59]  F. Stelzer,et al.  Comparative investigation of ruthenium-based metathesis catalysts bearing N-heterocyclic carbene (NHC) ligands. , 2001, Chemistry.

[60]  Faustin Kamena,et al.  Synthesis and biological activity of largazole and derivatives. , 2008, Angewandte Chemie.

[61]  B. Plietker,et al.  Diastereoselective Ru-catalyzed cross-metathesis-dihydroxylation sequence. an efficient approach toward enantiomerically enriched syn-diols. , 2008, The Journal of organic chemistry.

[62]  H. Mizutani,et al.  Novel stereoselective synthesis of enantiopure (+)-N-Boc-norpandamarilactonine-A, the intermediate for pandamarilactonines , 2006 .

[63]  A. Hoveyda,et al.  Efficient and Recyclable Monomeric and Dendritic Ru-Based Metathesis Catalysts , 2000 .

[64]  I. Goldberg,et al.  Latent sulfur chelated ruthenium catalysts: Steric acceleration effects on olefin metathesis , 2008 .

[65]  A. Hoveyda,et al.  A recyclable chiral Ru catalyst for enantioselective olefin metathesis. Efficient catalytic asymmetric ring-opening/cross metathesis in air. , 2002, Journal of the American Chemical Society.

[66]  J. L. Snelgrove,et al.  Highly efficient Ru-pseudohalide catalysts for olefin metathesis. , 2005, Journal of the American Chemical Society.

[67]  É. Cloutet,et al.  Cross olefin metathesis for the selective functionalization, ferrocenylation, and solubilization in water of olefin-terminated dendrimers, polymers, and gold nanoparticles and for a divergent dendrimer construction. , 2008, Journal of the American Chemical Society.

[68]  R. Grubbs,et al.  Improved ruthenium catalysts for Z-selective olefin metathesis. , 2012, Journal of the American Chemical Society.

[69]  Linda C Hsieh-Wilson,et al.  A 'molecular switchboard'--covalent modifications to proteins and their impact on transcription. , 2004, Organic & biomolecular chemistry.

[70]  A. Barrett,et al.  A simple, short, and flexible synthesis of viridiofungin derivatives. , 2006, The Journal of organic chemistry.

[71]  P. Compain.  Olefin Metathesis of Amine‐Containing Systems: Beyond the Current Consensus , 2007 .

[72]  Patricio E. Romero,et al.  Kinetic and thermodynamic analysis of processes relevant to initiation of olefin metathesis by ruthenium phosphonium alkylidene catalysts. , 2010, Journal of the American Chemical Society.

[73]  R. Mathieu,et al.  New Insight into the Reactivity of Pyridine-Functionalized Phosphine Complexes of Ruthenium(II) with Respect to Olefin Metathesis and Transfer Hydrogenation , 2008 .

[74]  M. Buchmeiser,et al.  Cationic Ru(II) complexes with N-heterocyclic carbene ligands for UV-induced ring-opening metathesis polymerization. , 2008, Angewandte Chemie.

[75]  R. Grubbs,et al.  The development of L2X2Ru=CHR olefin metathesis catalysts: an organometallic success story. , 2001, Accounts of chemical research.

[76]  S. Harutyunyan,et al.  A Highly Efficient Ruthenium Catalyst for Metathesis Reactions , 2002 .

[77]  K. Grela,et al.  Ruthenium-based olefin metathesis catalysts bearing N-heterocyclic carbene ligands. , 2009, Chemical reviews.

[78]  S. Collins,et al.  A Highly Active Chiral Ruthenium-Based Catalyst for Enantioselective Olefin Metathesis , 2007 .

[79]  Karol Grela,et al.  Advanced fine-tuning of grubbs/hoveyda olefin metathesis catalysts: a further step toward an optimum balance between antinomic properties. , 2006, Journal of the American Chemical Society.

[80]  C. Toniolo,et al.  Facile and E-selective intramolecular ring-closing metathesis reactions in 3(10)-helical peptides: a 3D structural study. , 2007, Journal of the American Chemical Society.

[81]  Alois Fürstner.  Olefin Metathesis and Beyond , 2000 .

[82]  B. Schmidt,et al.  Synthesis of Dihydrofurans and Dihydropyrans with Unsaturated Side Chains Based on Ring Size‐Selective Ring‐Closing Metathesis , 2007 .

[83]  R. Grubbs,et al.  Enantioselective ruthenium-catalyzed ring-closing metathesis. , 2001, Organic letters.

[84]  David A. Leigh,et al.  Cover Picture: Light‐Driven Transport of a Molecular Walker in Either Direction along a Molecular Track (Angew. Chem. Int. Ed. 1/2011) , 2011 .

[85]  Ian C. Stewart,et al.  Highly efficient ruthenium catalysts for the formation of tetrasubstituted olefins via ring-closing metathesis. , 2007, Organic letters.

[86]  L. Cavallo,et al.  The pivotal role of symmetry in the ruthenium-catalyzed ring-closing metathesis of olefins. , 2011, Chemistry.

[87]  P. van der Sluis,et al.  BYPASS: an effective method for the refinement of crystal structures containing disordered solvent regions , 1990 .

[88]  R. Grubbs,et al.  Ring-expansion metathesis polymerization: catalyst-dependent polymerization profiles. , 2009, Journal of the American Chemical Society.

[89]  H. Schanz,et al.  Reversible inhibition/activation of olefin metathesis: a kinetic investigation of ROMP and RCM reactions with Grubbs' catalyst. , 2007, Journal of the American Chemical Society.

[90]  P. Hanson,et al.  Synthesis of phosphorus and sulfur heterocycles via ring-closing olefin metathesis. , 2004, Chemical reviews.

[91]  R. Grubbs,et al.  Decomposition of ruthenium olefin metathesis catalysts. , 2007, Journal of the American Chemical Society.

[92]  B. List,et al.  Concise synthesis of ricciocarpin A and discovery of a more potent analogue. , 2009, Nature chemistry.

[93]  Deryn E. Fogg and Jay C. Conrad.  Ruthenium-Catalyzed Ring-Closing Metathesis: Recent Advances, Limitations and Opportunities , 2006 .

[94]  G. Sheldrick.  A short history of SHELX. , 2008, Acta crystallographica. Section A, Foundations of crystallography.

[95]  Jennifer A Love,et al.  Synthesis, structure, and activity of enhanced initiators for olefin metathesis. , 2003, Journal of the American Chemical Society.

[96]  D. Usanov,et al.  In an attempt to provide a user's guide to the galaxy of benzylidene, alkoxybenzylidene, and indenylidene ruthenium olefin metathesis catalysts. , 2008, Chemistry.

[97]  Patricio E. Romero,et al.  Generation and spectroscopic characterization of ruthenacyclobutane and ruthenium olefin carbene intermediates relevant to ring closing metathesis catalysis. , 2008, Journal of the American Chemical Society.

[98]  S. Blechert,et al.  A highly efficient olefin metathesis initiator: improved synthesis and reactivity studies , 2003 .

[99]  J. Jiricek,et al.  Ruthenium olefin metathesis catalysts with modified styrene ethers: influence of steric and electronic effects , 2003 .

[100]  K. Nicolaou,et al.  Metathesis reactions in total synthesis. , 2005, Angewandte Chemie.

[101]  S. Blechert,et al.  A new highly efficient ruthenium metathesis catalyst. , 2002, Angewandte Chemie.

[102]  R. Grubbs,et al.  Effects of NHC-backbone substitution on efficiency in ruthenium-based olefin metathesis. , 2009, Journal of the American Chemical Society.

[103]  Javier Magano,et al.  Large-scale applications of transition metal-catalyzed couplings for the synthesis of pharmaceuticals. , 2011, Chemical reviews.

[104]  S. Blechert,et al.  Recent developments in olefin cross-metathesis. , 2003, Angewandte Chemie.

[105]  H. Plenio,et al.  Synthesis and RCM Activity of [(NHC)(NHCewg)RuCl2(3-phenylindenylid-1-ene)] Complexes , 2010 .

[106]  Anna Grela.  Initiation at Snails Pace: Design and Applications of Latent Olefin Metathesis Catalysts Featuring Chelating Alkylidene Ligands , 2008 .

[107]  I. Goldberg,et al.  A Thermally Switchable Latent Ruthenium Olefin Metathesis Catalyst , 2008 .

[108]  R. Grubbs,et al.  A practical and highly active ruthenium-based catalyst that effects the cross metathesis of acrylonitrile. , 2002, Angewandte Chemie.

[109]  Giovanni Luca Cascarano,et al.  Completion and refinement of crystal structures with SIR92 , 1993 .

[110]  Louis J. Farrugia,et al.  WinGX suite for small-molecule single-crystal crystallography , 1999 .

[111]  R. Grubbs,et al.  Ruthenium metallacycles derived from 14-electron complexes. New insights into olefin metathesis intermediates. , 2006, Journal of the American Chemical Society.

[112]  Robert H. Grubbs,et al.  A Versatile Precursor for the Synthesis of New Ruthenium Olefin Metathesis Catalysts , 2001 .

[113]  R. Grubbs,et al.  Chelated ruthenium catalysts for Z-selective olefin metathesis. , 2011, Journal of the American Chemical Society.

[114]  M. Dinger,et al.  High Turnover Numbers with Ruthenium-Based Metathesis Catalysts , 2002 .

[115]  K. Grela,et al.  Aqueous olefin metathesis. , 2009, Angewandte Chemie.

[116]  Timothy J Donohoe,et al.  Ring-closing metathesis as a basis for the construction of aromatic compounds. , 2006, Angewandte Chemie.