Robert H Grubbs

Publications of Robert H Grubbs

• Cis-selective ring-opening metathesis polymerization with ruthenium catalysts.

  Authors: Benjamin K Keitz, Alexey Fedorov, Robert H Grubbs

  Journal of the American Chemical Society. 02/2012; 134(4):2040-3.

  Cis-selective ring-opening metathesis polymerization of several monocyclic alkenes as well as norbornene and oxanorbornene-type monomers using a C-H activated, ruthenium-based metathesis catalyst isCis-selective ring-opening metathesis polymerization of several monocyclic alkenes as well as norbornene and oxanorbornene-type monomers using a C-H activated, ruthenium-based metathesis catalyst is reported. The cis content of the isolated polymers depended heavily on the monomer structure and temperature. A cis content as high as 96% could be obtained by lowering the temperature of the polymerization.

• Z-Selectivity in olefin metathesis with chelated Ru catalysts: computational studies of mechanism and selectivity.

  Authors: Peng Liu, Xiufang Xu, Xiaofei Dong, Benjamin K Keitz, Myles B Herbert, Robert H Grubbs, K N Houk

  Journal of the American Chemical Society. 01/2012; 134(3):1464-7.

  The mechanism and origins of Z-selectivity in olefin metathesis with chelated Ru catalysts were explored using density functional theory. The olefin approaches from the "side" position of theThe mechanism and origins of Z-selectivity in olefin metathesis with chelated Ru catalysts were explored using density functional theory. The olefin approaches from the "side" position of the chelated Ru catalysts, in contrast to reactions with previous unchelated Ru catalysts that favor the bottom-bound pathway. Steric repulsions between the substituents on the olefin and the N-substituent on the N-heterocyclic carbene ligand lead to highly selective formation of the Z product.

• Thermally Stable, Latent Olefin Metathesis Catalysts.

  Authors: Renee M Thomas, Alexey Fedorov, Benjamin K Keitz, Robert H Grubbs

  Organometallics. 12/2011; 30(24):6713-6717.

  Highly thermally stable N-aryl,N-alkyl N-heterocyclic carbene (NHC) ruthenium catalysts were designed and synthesized for latent olefin metathesis. These catalysts showed excellent latent behaviorHighly thermally stable N-aryl,N-alkyl N-heterocyclic carbene (NHC) ruthenium catalysts were designed and synthesized for latent olefin metathesis. These catalysts showed excellent latent behavior toward metathesis reactions, whereby the complexes were inactive at ambient temperature and initiated at elevated temperatures, a challenging property to achieve with second generation catalysts. A sterically hindered N-tert-butyl substituent on the NHC ligand of the ruthenium complex was found to induce latent behavior toward cross-metathesis reactions, and exchange of the chloride ligands for iodide ligands was necessary to attain latent behavior during ring-opening metathesis polymerization (ROMP). Iodide-based catalysts showed no reactivity toward ROMP of norbornene-derived monomers at 25 °C, and upon heating to 85 °C gave complete conversion of monomer to polymer in less than 2 hours. All of the complexes were very stable to air, moisture, and elevated temperatures up to at least 90 °C, and exhibited a long catalyst lifetime in solution at elevated temperatures.

• EPR study of spin labeled brush polymers in organic solvents.

  Authors: Yan Xia, Yongjun Li, Alan O Burts, M Francesca Ottaviani, David A Tirrell, Jeremiah A Johnson, Nicholas J Turro, Robert H Grubbs

  Journal of the American Chemical Society. 12/2011; 133(49):19953-9.

  Spin-labeled polylactide brush polymers were synthesized via ring-opening metathesis polymerization (ROMP), and nitroxide radicals were incorporated at three different locations of brush polymers:Spin-labeled polylactide brush polymers were synthesized via ring-opening metathesis polymerization (ROMP), and nitroxide radicals were incorporated at three different locations of brush polymers: the end and the middle of the backbone, and the end of the side chains (periphery). Electron paramagnetic resonance (EPR) was used to quantitatively probe the macromolecular structure of brush polymers in dilute solutions. The peripheral spin-labels showed significantly higher mobility than the backbone labels, and in dimethylsulfoxide (DMSO), the backbone end labels were shown to be more mobile than the middle labels. Reduction of the nitroxide labels by a polymeric reductant revealed location-dependent reactivity of the nitroxide labels: peripheral nitroxides were much more reactive than the backbone nitroxides. In contrast, almost no difference was observed when a small molecule reductant was used. These results reveal that the dense side chains of brush polymers significantly reduce the interaction of the backbone region with external macromolecules, but allow free diffusion of small molecules.

• One-pot synthesis of polyrotaxanes via acyclic diene metathesis polymerization of supramolecular monomers.

  Authors: Nebojša Momčilović, Paul G Clark, Andrew J Boydston, Robert H Grubbs

  Journal of the American Chemical Society. 11/2011; 133(47):19087-9.

  A one-pot synthesis of polyrotaxanes has been developed. The method employs a supramolecular monomer comprising a polymerizable ammonium salt and crown ether, in combination with dynamic ADMetA one-pot synthesis of polyrotaxanes has been developed. The method employs a supramolecular monomer comprising a polymerizable ammonium salt and crown ether, in combination with dynamic ADMet polymerization. Ultimately, highly efficient complexation, polymerization, and end-capping were accomplished in a single operation to yield polyrotaxanes with M(w) up to 19.3 kDa and >80% of the repeat units being complexed.

• Radical-mediated anti-Markovnikov hydrophosphonation of olefins.

  Authors: Christopher S Daeffler, Robert H Grubbs

  Organic letters. 11/2011; 13(24):6429-31.

  The radical-mediated addition of triphenylphosphonium tetrafluoroborate to olefins (hydrophosphonation) is reported. Both standard radical initiators and photochemical conditions are effective, up toThe radical-mediated addition of triphenylphosphonium tetrafluoroborate to olefins (hydrophosphonation) is reported. Both standard radical initiators and photochemical conditions are effective, up to the gram scale. The phosphonium salts are shown to serve as Z-selective Wittig olefination reagents, even without purification.

• Primary alcohols from terminal olefins: formal anti-Markovnikov hydration via triple relay catalysis.

  Authors: Guangbin Dong, Peili Teo, Zachary K Wickens, Robert H Grubbs

  Science (New York, N.Y.). 09/2011; 333(6049):1609-12.

  Alcohol synthesis is critical to the chemical and pharmaceutical industries. The addition of water across olefins to form primary alcohols (anti-Markovnikov olefin hydration) would be a broadlyAlcohol synthesis is critical to the chemical and pharmaceutical industries. The addition of water across olefins to form primary alcohols (anti-Markovnikov olefin hydration) would be a broadly useful reaction but has largely proven elusive; an indirect hydroboration/oxidation sequence requiring stoichiometric borane and oxidant is currently the most practical methodology. Here, we report a more direct approach with the use of a triple relay catalysis system that couples palladium-catalyzed oxidation, acid-catalyzed hydrolysis, and ruthenium-catalyzed reduction cycles. Aryl-substituted terminal olefins are converted to primary alcohols by net reaction with water in good yield and excellent regioselectivity.

• Probing the origin of degenerate metathesis selectivity via characterization and dynamics of ruthenacyclobutanes containing variable NHCs.

  Authors: Benjamin K Keitz, Robert H Grubbs

  Journal of the American Chemical Society. 09/2011; 133(40):16277-84.

  The preparation of new phosphonium alkylidene ruthenium metathesis catalysts containing N-heterocyclic carbenes (NHCs) that result in a preference for degenerate metathesis is described. The reactionThe preparation of new phosphonium alkylidene ruthenium metathesis catalysts containing N-heterocyclic carbenes (NHCs) that result in a preference for degenerate metathesis is described. The reaction of the catalysts with ethylene or substrates relevant to ring-closing metathesis (RCM) produced ruthenacyclobutanes that could be characterized by cryogenic NMR spectroscopy. The rate of α/β methylene exchange in ethylene-only ruthenacycles was found to vary widely between ruthenacycles, in some cases being as low as 3.97 s(-1) at -30 °C, suggesting that the NHC plays an important role in degenerative metathesis reactions. Attempts to generate RCM-relevant ruthenacycles resulted in the low-yielding formation of a previously unobserved species, which we assign to be a β-alkyl-substituted ruthenacycle. Kinetic investigations of the RCM-relevant ruthenacycles in the presence of excess ethylene revealed a large increase in the kinetic barrier of the rate-limiting dissociation of the cyclopentene RCM product compared with previously investigated catalysts. Taken together, these results shed light on the degenerate/productive selectivity differences observed for different metathesis catalysts.

• Z-selective homodimerization of terminal olefins with a ruthenium metathesis catalyst.

  Authors: Benjamin K Keitz, Koji Endo, Myles B Herbert, Robert H Grubbs

  Journal of the American Chemical Society. 06/2011; 133(25):9686-8.

  The cross-metathesis of terminal olefins using a novel ruthenium catalyst results in excellent selectivity for the Z-olefin homodimer. The reaction was found to tolerate a large number of functionalThe cross-metathesis of terminal olefins using a novel ruthenium catalyst results in excellent selectivity for the Z-olefin homodimer. The reaction was found to tolerate a large number of functional groups, solvents, and temperatures while maintaining excellent Z-selectivity, even at high reaction conversions.

• Protonolysis of a Ruthenium-Carbene Bond and Applications in Olefin Metathesis.

  Authors: Benjamin K Keitz, Jean Bouffard, Guy Bertrand, Robert H Grubbs

  Journal of the American Chemical Society. 06/2011;

• Synthesis and direct imaging of ultrahigh molecular weight cyclic brush polymers.

  Authors: Yan Xia, Andrew J Boydston, Robert H Grubbs

  Angewandte Chemie (International ed. in English). 06/2011; 50(26):5882-5.

• Chelated ruthenium catalysts for Z-selective olefin metathesis.

  Authors: Koji Endo, Robert H Grubbs

  Journal of the American Chemical Society. 06/2011; 133(22):8525-7.

  We report the development of ruthenium-based metathesis catalysts with chelating N-heterocyclic carbene (NHC) ligands that catalyze highly Z-selective olefin metathesis. A very simple and convenientWe report the development of ruthenium-based metathesis catalysts with chelating N-heterocyclic carbene (NHC) ligands that catalyze highly Z-selective olefin metathesis. A very simple and convenient procedure for the synthesis of such catalysts has been developed. Intramolecular C-H bond activation of the NHC ligand, promoted by anion ligand substitution, forms the appropriate chelate for stereocontrolled olefin metathesis.

• Protonolysis of a ruthenium-carbene bond and applications in olefin metathesis.

  Authors: Benjamin K Keitz, Jean Bouffard, Guy Bertrand, Robert H Grubbs

  Journal of the American Chemical Society. 06/2011; 133(22):8498-501.

  The synthesis of a ruthenium complex containing an N-heterocylic carbene (NHC) and a mesoionic carbene (MIC) is described wherein addition of a Brønsted acid results in protonolysis of the Ru-MICThe synthesis of a ruthenium complex containing an N-heterocylic carbene (NHC) and a mesoionic carbene (MIC) is described wherein addition of a Brønsted acid results in protonolysis of the Ru-MIC bond to generate an extremely active metathesis catalyst. Mechanistic studies implicated a rate-determining protonation step in the generation of the metathesis-active species. The activity of the NHC/MIC catalyst was found to exceed those of current commercial ruthenium catalysts.

• Highly selective ruthenium metathesis catalysts for ethenolysis.

  Authors: Renee M Thomas, Benjamin K Keitz, Timothy M Champagne, Robert H Grubbs

  Journal of the American Chemical Society. 05/2011; 133(19):7490-6.

  N-Aryl,N-alkyl N-heterocyclic carbene (NHC) ruthenium metathesis catalysts are highly selective toward the ethenolysis of methyl oleate, giving selectivity as high as 95% for the kinetic ethenolysisN-Aryl,N-alkyl N-heterocyclic carbene (NHC) ruthenium metathesis catalysts are highly selective toward the ethenolysis of methyl oleate, giving selectivity as high as 95% for the kinetic ethenolysis products over the thermodynamic self-metathesis products. The examples described herein represent some of the most selective NHC-based ruthenium catalysts for ethenolysis reactions to date. Furthermore, many of these catalysts show unusual preference and stability toward propagation as a methylidene species and provide good yields and turnover numbers at relatively low catalyst loading (<500 ppm). A catalyst comparison showed that ruthenium complexes bearing sterically hindered NHC substituents afforded greater selectivity and stability and exhibited longer catalyst lifetime during reactions. Comparative analysis of the catalyst preference for kinetic versus thermodynamic product formation was achieved via evaluation of their steady-state conversion in the cross-metathesis reaction of terminal olefins. These results coincided with the observed ethenolysis selectivities, in which the more selective catalysts reach a steady state characterized by lower conversion to cross-metathesis products compared to less selective catalysts, which show higher conversion to cross-metathesis products.

• Low pressure ethenolysis of renewable methyl oleate in a microchemical system.

  Authors: Chan Pil Park, Matthew M Van Wingerden, So-Yeop Han, Dong-Pyo Kim, Robert H Grubbs

  Organic letters. 04/2011; 13(9):2398-401.

  A microchemical system for ethenolysis of renewable methyl oleate was developed, in which the dual-phase, microfluidic design enabled efficient diffusion of ethylene gas into liquid methyl oleateA microchemical system for ethenolysis of renewable methyl oleate was developed, in which the dual-phase, microfluidic design enabled efficient diffusion of ethylene gas into liquid methyl oleate through an increased contact area. The increased mass transfer of ethylene favored the formation of desired commodity chemicals with significantly suppressed homometathesis when compared to the bulk system. In addition to higher selectivity and conversion, this system also provides the typical advantages of a microchemical system, including the possibility of convenient scale-up.

• Synthesis of Highly Stable 1,3-Diaryl-1H-1,2,3-triazol-5-ylidenes and their Applications in Ruthenium-Catalyzed Olefin Metathesis.

  Authors: Jean Bouffard, Benjamin K Keitz, Ralf Tonner, Vincent Lavallo, Gregorio Guisado-Barrios, Gernot Frenking, Robert H Grubbs, Guy Bertrand

  Organometallics. 03/2011; 30(9):2617-2627.

  The formal cycloaddition between 1,3-diaza-2-azoniaallene salts and alkynes or alkyne equivalents provides an efficient synthesis of 1,3-diaryl-1H-1,2,3-triazolium salts, the direct precursors ofThe formal cycloaddition between 1,3-diaza-2-azoniaallene salts and alkynes or alkyne equivalents provides an efficient synthesis of 1,3-diaryl-1H-1,2,3-triazolium salts, the direct precursors of 1,2,3-triazol-5-ylidenes. These N,N-diarylated mesoionic carbenes (MICs) exhibit enhanced stability in comparison to their alkylated counterparts. Experimental and computational results confirm that these MICs act as strongly electron-donating ligands. Their increased stability allows for the preparation of ruthenium olefin metathesis catalysts that are efficient in both ring-opening and ring-closing reactions.

• Ring-closing metathesis approaches for the solid-phase synthesis of cyclic peptoids.

  Authors: Sharaf Nawaz Khan, Arim Kim, Robert H Grubbs, Yong-Uk Kwon

  Organic letters. 03/2011; 13(7):1582-5.

  Cyclic peptoids were efficiently synthesized on a solid phase in high yields utilizing ring-closing metathesis (RCM). This method should be a valuable tool for easy access to cyclic peptoid librariesCyclic peptoids were efficiently synthesized on a solid phase in high yields utilizing ring-closing metathesis (RCM). This method should be a valuable tool for easy access to cyclic peptoid libraries and various cyclic compounds.

• Characterization and dynamics of substituted ruthenacyclobutanes relevant to the olefin cross-metathesis reaction.

  Authors: Anna G Wenzel, Garrett Blake, David G VanderVelde, Robert H Grubbs

  Journal of the American Chemical Society. 03/2011; 133(16):6429-39.

  The reaction of the phosphonium alkylidene [(H(2)IMes)RuCl(2)=CHP(Cy)(3))](+) BF(4)(-) with propene, 1-butene, and 1-hexene at -45 °C affords various substituted, metathesis-active ruthenacycles.The reaction of the phosphonium alkylidene [(H(2)IMes)RuCl(2)=CHP(Cy)(3))](+) BF(4)(-) with propene, 1-butene, and 1-hexene at -45 °C affords various substituted, metathesis-active ruthenacycles. These metallacycles were found to equilibrate over extended reaction times in response to decreases in ethylene concentrations, which favored increased populations of α-monosubstituted and α,α'-disubstituted (both cis and trans) ruthenacycles. On an NMR time scale, rapid chemical exchange was found to preferentially occur between the β-hydrogens of the cis and trans stereoisomers prior to olefin exchange. Exchange on an NMR time scale was also observed between the α- and β-methylene groups of the monosubstituted ruthenacycle (H(2)IMes)Cl(2)Ru(CHRCH(2)CH(2)) (R = CH(3), CH(2)CH(3), (CH(2))(3)CH(3)). EXSY NMR experiments at -87 °C were used to determine the activation energies for both of these exchange processes. In addition, new methods have been developed for the direct preparation of metathesis-active ruthenacyclobutanes via the protonolysis of dichloro(1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)(benzylidene) bis(pyridine)ruthenium(II) and its 3-bromopyridine analogue. Using either trifluoroacetic acid or silica-bound toluenesulfonic acid as the proton source, the ethylene-derived ruthenacyclobutane (H(2)IMes)Cl(2)Ru(CH(2)CH(2)CH(2)) was observed in up to 98% yield via NMR at -40 °C. On the basis of these studies, mechanisms accounting for the positional and stereochemical exchange within ruthenacyclobutanes are proposed, as well as the implications of these dynamics toward olefin metathesis catalyst and reaction design are described.

• Insights into the carbene-initiated aggregation of [Fe(cot)(2)].

  Authors: Vincent Lavallo, Amer El-Batta, Guy Bertrand, Robert H Grubbs

  Angewandte Chemie (International ed. in English). 01/2011; 50(1):268-71.

• Drug-loaded, bivalent-bottle-brush polymers by graft-through ROMP.

  Authors: Jeremiah A Johnson, Ying Y Lu, Alan O Burts, Yan Xia, Alec C Durrell, David A Tirrell, Robert H Grubbs

  Macromolecules. 12/2010; 43(24):10326-10335.

  Graft-through ring-opening metathesis polymerization (ROMP) using ruthenium N-heterocyclic carbene catalysts has enabled the synthesis of bottle-brush polymers with unprecedented ease and control.Graft-through ring-opening metathesis polymerization (ROMP) using ruthenium N-heterocyclic carbene catalysts has enabled the synthesis of bottle-brush polymers with unprecedented ease and control. Here we report the first bivalent-brush polymers; these materials were prepared by graft-through ROMP of drug-loaded polyethylene-glycol (PEG) based macromonomers (MMs). Anticancer drugs doxorubicin (DOX) and camptothecin (CT) were attached to a norbornene-alkyne-PEG MM via a photocleavable linker. ROMP of either or both drug-loaded MMs generated brush homo- and co-polymers with low polydispersities and defined molecular weights. Release of free DOX and CT from these materials was initiated by exposure to 365 nm light. All of the CT and DOX polymers were at least 10-fold more toxic to human cancer cells after photoinitiated drug release while a copolymer carrying both CT and DOX displayed 30-fold increased toxicity upon irradiation. Graft-through ROMP of drug-loaded macromonomers provides a general method for the systematic study of structure-function relationships for stimuli-responsive polymers in biological systems.