DOCSLIB.ORG

Metathesis Applications in API Synthesis October 18Th, 2016

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Metathesis Applications in API Synthesis October 18Th, 2016 Metathesis Applications in API Synthesis October 18th, 2016 2016 AGENDA Materia’s Catalyst Business Model Metathesis and Applications Maximizing Reaction Efficiency Macrocyclizations on Scale Capabilities, Services, and Support 2 MATERIA MATERIA’S BUSINESS MODEL 1. Catalyst Sales • IP included in purchase price • No license fees or royalties • No restrictions on patenting API composition or route • Transferable to 3rd party CMO/CRO 2. Technical Services • Process guidance (free) • Catalyst screening • Catalyst development • Process development and optimization • Intermediate synthesis (non-GMP) …our mission is to accelerate Grubbs’ catalyst use in the pharmaceutical industry MATERIA 3 Metathesis and Applications PRIMARY OLEFIN METATHESIS REACTIONS Ring-Closing Metathesis (RCM): makes ring structures Cross Metathesis (CM): creates new olefins (large or small molecules) Ring-Opening Metathesis Polymerization (ROMP): makes polymers Metathesis mechanism: Sanford, M. S.; Love, J. L.; Grubbs, R. H. J. Am. Chem. MATERIA Soc. 2001, 123, 6543. 5 POLYMER APPLICATIONS: ADVANCED MATERIALS Auto Composites • Developmental Lightweight Pressure Vessels • Developmental Electronic Materials • Developmental Subsea Insulation Subsea Buoyancy Chlorinated Fluid Handling • Commercial Downhole Tools • Commercial MATERIA 6 CHEMICAL APPLICATIONS: BIORENEWABLES 1-butene Olefins Metathesis Specialty Natural Grubbs Chemicals Oil Catalyst® Oleochemicals • Flexible feedstock process (palm, soy, rapeseed, canola, etc.) • Elevance was spun off as a JV between Cargill and Materia • Announced over 1.9 billion lbs+ / year of bio refinery capacity • Commercial-scale natural feedstock available for new product development and mass production using Grubbs Catalyst® based metathesis MATERIA 7 PHARMA APPLICATIONS: MACROCYCLES Ciluprevir Simeprevir HCV NS3-4A Protease Inhibitor HCV NS3-4A Protease Inhibitor Carbon-carbon bonds formed by olefin metathesis Horvath, A. et al (Janssen Pharmaceuticals, Inc., USA). Improved Farina, V.; Shu, C.; Zeng, X.; Wei, X.; Yee, N. K.; Senanayake, C. H. Org. Proc. process for preparing an intermediate of the macrocyclic protease MATERIA Res. Dev. 2009, 13, 250. 8 inhibitor TMC 435. PCT Int. Appl. 2013061285, May 2, 2013. WHY MACROCYCLES? Potential to Hit “Undruggable” Targets • May replace larger molecules (e.g. biologics) for difficult targets1 • Large, saturated ring balances preorganization with flexibility2 Oral Bioavailabity Beyond Rule of 5 (bRo5) Space • Better diffusion across membranes in studies of matched acyclic/macrocyclic pairs (both peptide and non-peptide)3 • “Chameleon-like behavior” - exposed polar surface area in aqueous media, conformational changes (e.g. internal H-bonding) enable membrane permeability4 Unexplored Intellectual Property Space • Tying ends of pharmacophore into a macrocycle may lead to new, patentable composition 1. Espada, A.; Broughton, H.; Jones, S.; Chalmers, M. J.; Dodge, J. A. J. Med. Chem. General reviews: 2016, 59, 2255. Giordanetto, F.; Kihlberg, J. J. Med. Chem. 2014, 57, 278. 2. Mallinson, J.; Collins, I. Future Med. Chem. 2012, 4, 1409. Villar, E. A.; Beglov, D.; Chennamadhavuni, S.; Porco Jr., J. A.; Kozakov, D.; 3. Bogdan, A. R.; Davies, N. L.; James, K. Org. Biomol. Chem. 2011, 9, 7727. Vajda, S.; Whitty, A. Nature Chemical Biology, 2014, 10, 723. 4. Whitty, A.; Zhong, M.; Viarengo, L.; Beglov, D.; Hall, D. R.; Vajda, S. Drug Discovery MATERIA Today, 2016, 21, 712. 9 PHARMA APPLICATIONS: STAPLED PEPTIDES Small Stapled Drug Properties Biologics Peptides Metathesis-enabled peptide staples hold peptides Molecules Peptides in helical conformation to enhance stability and Cell Penetration ++ -- -- ++ cell penetration while maintaining specificity. Specificity + ++ ++ ++ Stability ++ ++ -- ++ 1. Drahl, C. C&E News vol. 86, no. 22. pp.18-23 (June 2, 2008). 2. http://aileronrx.com/science_stapled-peptide-technology.php MATERIA 3. Image: Kim, Y.-W.; Grossman, T. N.; Verdine, G. L. Nature Protocols 2011, 6, 761. 10 PHARMA APPLICATIONS: OTHER SP3-RICH STRUCTURES Saturated N-Heterocyclic Spirocyclic NK-1 Cathepsin K Inhibitor Receptor Antagonist Carbon-carbon bonds formed by olefin metathesis Wu, G. G.; Werne, G.; Fu, X.; Orr, R. K.; Chen, F. X.; Cui, J. Sprague, V. Wang, H.; Goodman, S. N.; Dai, Q.; Stockdale, G. W.; Clark, W. M. Jr. Org. M.; Castellanos, L. P.; Chen, Y.; Piorier, M.; Mergelsberg, I. (Schering- MATERIA Process Res. Dev. 2008, 12, 226. 11 Plough, USA) WO2010028232, 2010 Maximizing Reaction Efficiency CATALYST SELECTION General RCM General CM C848 C627 C949 Grubbs II Hoveyda-Grubbs II Nolan-Grubbs II RCM to Trisubstituted CM to Trisubstituted Z-selective (CM or RCM) C571 C711 C633 MATERIA 13 GENERAL PURPOSE CATALYSTS IN ACTION Ring-Closing Metathesis1,2 C627 Hoveyda-Grubbs II Cross Metathesis3 C848 Grubbs II 1. Wang, H.; Goodman, S. N.; Dai, Q.; Stockdale, G. W.; Clark, W. M. Jr. Org. Proc. Res. Dev. 2008, 12, 226. 2. Wang, H.; Matsuhashi, H.; Doan, B. D.; Goodman, S. N.; Ouyang, X.; Clark, W. M. Jr. Tetrahedron 2009, 65, 6291. MATERIA 3. Wang, G.; Krische, M. J. J. Am. Chem. Soc. 2016, 138, 8088. 14 STERIC SPECIALIST CATALYSTS IN ACTION Ring-Closing Metathesis1 C823 (Grubbs I): 0% C627 (Hoveyda-Grubbs II): 0% C571 C571: 82% Cross Metathesis2 C571: 60% C627 (Hoveyda-Grubbs II): 78% C711 C711: 98% 1. Allen, C. E.; Chow, C. L.; Caldwell, J. J.; Westwood, I. M.; van Montfort, R. L. M.; Collins, I. Bioorg. Med. Chem. 2013, 21, 5707 MATERIA 2. Stewart, I. C.; Douglas, C. D.; Grubbs, R. H. Org. Lett. 2008, 10, 441. 15 Z-SELECTIVE CATALYST IN ACTION Ring-Closing Metathesis1 2 Cross Metathesis C633 1. Mangold, S. L.; Grubbs, R. H. Chem. Sci. 2015, 6, 4561. 2. Herbert, M. B.; Marx, V. M.; Pederson, R. L.; Grubbs, R. H. Angew. Chem. MATERIA Int. Ed. 2013, 52, 310. 16 TEMPERATURE AND CONCENTRATION Ring-Closing Metathesis Heat Necessary? Temperature (°C) Concentration (M) No, unless there is ring strain No, unless there is ring strain Possibly, if there is an entropic barrier Yes, entropic barrier and high dilution are likely Yes, to overcome sterics MATERIA 17 TEMPERATURE AND CONCENTRATION Cross Metathesis Heat Necessary? Temperature (°C) Concentration (M) No, Type I CM is fast Yes, electron deficient olefins are slow to react Yes, to overcome sterics No, selectivity may suffer at higher temperature MATERIA 18 SOLVENT SELECTION Preferred Solvents Tolerated Solvents Avoid if Possible (non-coordinating) (coordinating/nucleophilic) (strongly coordinating) hexane, heptane MeOH, EtOH, i-PrOH MeCN toluene, xylene Acetone, HOAc DMSO, DMF, NMP TBME, 2-MeTHF Et2O, THF Pyridine and other amines DCM, DCE, PhCl water (neutral/acidic) water (basic) EtOAc, i-PrOAc Perfluoroalkanes http://allthingsmetathesis.com/solvent-considerations-in-ruthenium-catalyzed-metathesis-reactions MATERIA 19 WATCH FOR SOLVENT IMPURITIES . Inconsistent results on scale-up − Catalyst deactivation − Olefin isomerization − Epimerization of vinylcyclopropane . Identified morpholine as an impurity in toluene (<20 ppm) − [morpholine] ~ [catalyst] . Purification of toluene led to consistent results MATERIA Nicola, T.; Brenner, M.; Donsbach, K.; Kreye, P. Org. Process Res. Dev. 2005, 9, 513. 20 COORDINATING GROUPS: ADD ACID Potential ligands Catalyst (10 mol%) Additive, Time Yield (trans:cis) C823 (Grubbs I) None, 16h n.d. C848 (Grubbs II) None, 16h n.d. C823 (Grubbs I) 5 equiv HCl in MeOH, 16h 10 %, 86:14 C848 (Grubbs II) 5 equiv HCl in MeOH, 4h 70 %, 94:6 C823 (Grubbs I) 5 equiv TFA in MeOH, 16h 8 %, 85:15 C848 (Grubbs II) 5 equiv TFA in MeOH, 4h 86 %, 94:6 MATERIA William, A. D.; Lee, A. C.-H. Chimia, 2015, 69, 142. 21 COORDINATING GROUPS: START WITH THE SALT Varubi®(rolapitant) FDA-approved September 2015 for treatment of chemotherapy-induced nausea and vomiting) Wu, G. G.; Werne, G.; Fu, X.; Orr, R. K.; Chen, F. X.; Cui, J. Sprague, V. M.; Castellanos, L. P.; Chen, Y.; Piorier, M.; Mergelsberg, I. (Schering-Plough, USA) MATERIA WO 2010028232, March 11, 2010 22 OLEFIN ISOMERIZATION Vaniprevir RCM Kong, J.; Chen, C-y.; Balsells-Padros, J.; Cao, Y.; Dunn, R. F.; Dolman, S. J.; Janey, MATERIA J.; Li, H.; Zacuto, M. J. J. Org. Chem. 2012, 77, 3820. 23 OLEFIN ISOMERIZATION - HYPOTHESES Hydride Formation Nanoparticles 1. http://allthingsmetathesis.com/inhibiting-olefin-isomerization/ 2. Ru-H formation: Dinger, M. B. Mol, J. C. Eur. J. Inorg. Chem. 2003, 15, 2827. 3. Ru-H isomerization (in)activity: Higman, C. S.; Plais, L.; Fogg, D. E. ChemCatChem 2013, 5, 3548. 4. RuNPs: Higman, C. S.; Lanterna, A. E.; Marin, M. L.; Sciano, J. C.; Fogg, D. E. MATERIA ChemCatChem 2016, 8, 2426. 24 OLEFIN ISOMERIZATION - PREVENTION C848 Grubbs II Additive Equiv A B none - <5% >95% AcOH 0.1 >95% none benzoquinone 0.1 >95% none galvinoxyl 0.2 80% 20% TEMPO 0.5 7% 93% 4-methoxyphenol 0.5 17% 83% BHT 0.5 4% 93% Hong, S. H.; Sanders, D. P.; Lee, C. W.; Grubbs, R. H. J. Am. Chem. Soc. 2005, MATERIA 127, 17160. 25 CATALYST STABILITY - INERT CONDITIONS Decomposition of C627, C848, C827, & C949 • Catalyst solutions were prepared 100 with rigorous exclusion of oxygen C627 and moisture (samples were 90 % C627 (C6D6) prepared in the glovebox using % C627 (CD2Cl2) 80 C949 freshly distilled and/or degassed % C627 (CDCl3) NMR solvent). 70 % C627 (C6D6 wet) C827 % C827 (C6D6) 60 • 0.02 M catalyst in NMR solvent % C827 (CD2Cl2) C848 % C827 (CDCl3) with internal standard 50 % C827 (C6D6 wet) % C848 (C6D6) • Wet Benzene contained 0.035 M 40 catalyst remaining (%) remaining catalyst % C848 (CD2Cl2) H O1 2 30 % C848 (CDCl3) % C848 (C6D6 wet) 20 • NMR samples were stored on % C949 (C6D6) bench top at room temp in the % C949 (CD2Cl2) 10 dark over the 8 days. % C949 (CDCl3) 0 % C949 (C6D6 wet) 0 20 40 60 80 100 120 140 160 180 200 time (h) Adam Johns MATERIA 26 CATALYST STABILITY - NON-INERT CONDITIONS Decomposition of C627, C827, C848 & C949 (Air) • Catalyst solutions were prepared 100 by sparging with oxygen, no C627 attempt to keep moisture out of 90 % C627 (C6D6) % C627 (CD2Cl2) the samples. (Samples were 80 prepared outside of the glovebox, % C627 (CDCl3) on the lab bench top with NMR 70 % C627 (C6D6 wet) solvents used as is).
Load more

Recommended publications
  • Olefin Metathesis in Aqueous Media Offers a New, Broad M
    Green Chemistry CRITICAL REVIEW View Article Online View Journal | View Issue Olefin metathesis in aqueous media Cite this: Green Chem., 2013, 15, 2317 Jasmine Tomasek and Jürgen Schatz* The worldwide undisputable and unattainable chemist is nature, using water as a solvent of choice in biosynthesis. Water as a solvent not only indicates “green chemistry” but is also inevitable in biochemical reactions as well as syntheses of several pharmaceutical products. In the last few decades, several organic reactions were successfully carried out under aqueous conditions, a powerful and attractive tool in Received 3rd June 2013, organic synthesis metathesis reaction. This review summarises advances made in metathesis reaction in Accepted 12th July 2013 aqueous media. Two main strategies can be distinguished: the design of water soluble catalysts to obtain DOI: 10.1039/c3gc41042k homogeneous conditions and using commercially available catalysts to utilize the advantages of hetero- www.rsc.org/greenchem geneous conditions. reactions, meaning coupling reactions of cyclic and acyclic Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Introduction alkenes or alkynes as well as polymerisation reactions In organic chemistry, C–C coupling reactions open a wide (Scheme 1).1 Accordingly, the metathesis has been of great range of applications for effective synthesis, which otherwise interest since its discovery in the mid-1950s3 and reveals a would be difficult or even hardly feasible. The olefin meta- powerful tool for both industrial applications,
    [Show full text]
  • Hoveyda–Grubbs Catalysts with an N→Ru Coordinate Bond in a Six-Membered Ring
    Hoveyda–Grubbs catalysts with an N→Ru coordinate bond in a six-membered ring. Synthesis of stable, industrially scalable, highly efficient ruthenium metathesis catalysts and 2-vinylbenzylamine ligands as their precursors Kirill B. Polyanskii1, Kseniia A. Alekseeva1, Pavel V. Raspertov1, Pavel A. Kumandin1, Eugeniya V. Nikitina1, Atash V. Gurbanov2,3 and Fedor I. Zubkov*1 Full Research Paper Open Access Address: Beilstein J. Org. Chem. 2019, 15, 769–779. 1Organic Chemistry Department, Faculty of Science, Peoples’ doi:10.3762/bjoc.15.73 Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation, 2Centro Received: 23 October 2018 de Química Estrutural, Instituto Superior Técnico, Universidade de Accepted: 25 February 2019 Lisboa, Av. Rovisco Pais, 1049–001 Lisbon, Portugal and 3Organic Published: 22 March 2019 Chemistry Department, Baku State University, Z. Xalilov Str. 23, Az 1148 Baku, Azerbaijan This article is part of the thematic issue "Progress in metathesis chemistry III". Email: Fedor I. Zubkov* - [email protected] Guest Editors: K. Grela and A. Kajetanowicz * Corresponding author © 2019 Polyanskii et al.; licensee Beilstein-Institut. License and terms: see end of document. Keywords: CM; cross metathesis; Hoveyda–Grubbs catalyst; olefin metathesis; RCM; ring-closing metathesis; ring-opening cross metathesis; ROCM; ruthenium metathesis catalyst; styrene; 2-vinylbenzylamine Abstract A novel and efficient approach to the synthesis of 2-vinylbenzylamines is reported. This involves obtaining 2-vinylbenzylamine ligands from tetrahydroisoquinoline by alkylation and reduction followed by the Hofmann cleavage. The resultant 2-vinylbenzyl- amines allowed us to obtain new Hoveyda–Grubbs catalysts, which were thoroughly characterised by NMR, ESIMS, and X-ray crystallography.
    [Show full text]
  • Recent Advances in Total Synthesis Via Metathesis Reactions
    SYNTHESIS0039-78811437-210X © Georg Thieme Verlag Stuttgart · New York 2018, 50, 3749–3786 review 3749 en Syn thesis I. Cheng-Sánchez, F. Sarabia Review Recent Advances in Total Synthesis via Metathesis Reactions Iván Cheng-Sánchez Francisco Sarabia* Department of Organic Chemistry, Faculty of Sciences, University of Málaga, Campus de Teatinos s/n. 29071- Málaga, Spain [email protected] Received: 16.04.2018 ly explained by the emergence, design, and development of Accepted after revision: 30.05.2018 powerful catalysts that are capable of promoting striking Published online: 18.07.2018 DOI: 10.1055/s-0037-1610206; Art ID: ss-2018-z0262-r transformations in highly efficient and selective fashions. In fact, the ability of many of them to forge C–C bonds be- Abstract The metathesis reactions, in their various versions, have be- tween or within highly functionalized and sensitive com- come a powerful and extremely valuable tool for the formation of car- pounds has allowed for the preparation of complex frame- bon–carbon bonds in organic synthesis. The plethora of available cata- lysts to perform these reactions, combined with the various works, whose access were previously hampered by the lim- transformations that can be accomplished, have positioned the me- itations of conventional synthetic methods. Among the tathesis processes as one of the most important reactions of this centu- myriad of recent catalysts, those developed and designed to ry. In this review, we highlight the most relevant synthetic contributions promote metathesis reactions have had a profound impact published between 2012 and early 2018 in the field of total synthesis, reflecting the state of the art of this chemistry and demonstrating the and created a real revolution in the field of total synthesis, significant synthetic potential of these methodologies.
    [Show full text]
  • Dissertation Reactivity and Selectivity in The
    DISSERTATION REACTIVITY AND SELECTIVITY IN THE POLYMERIZATION OF MULTIFUNCTIONAL ACRYLIC MONOMERS BY CHIRAL ZIRCONOCENIUM CATALYSTS Submitted by Fernando Vidal Peña Department of Chemistry In partial fulfillment of the requirements For the Degree of Doctor of Philosophy Colorado State University Fort Collins, Colorado Summer 2017 Doctoral Committee: Advisor: Eugene Y.-X. Chen Richard G. Finke Steven Strauss Ellen Fisher David Wang Copyright by Fernando Vidal Peña 2017 All Rights Reserved ABSTRACT REACTIVITY AND SELECTIVITY IN THE POLYMERIZATION OF MULTIFUNCTIONAL ACRYLIC MONOMERS BY CHIRAL ZIRCONOCENIUM CATALYSTS Described in this dissertation are the results of investigating the reactivity and selectivity in the polymerization of multifunctional acrylic monomers by chiral cationic zirconocenium catalysts. The unprecedented precision polymer synthesis method developed in this workthe polymerization of polar divinyl monomers that is not only living but also simultaneously chemoselective and stereoselectivehas enabled the synthesis of well-defined highly stereoregular functionalized polymers bearing reactive C=C bonds on every chiral repeat unit. Thus, under ambient conditions, chiral ansa-ziroconocenium catalysts of the appropriate symmetry (C2- vs CS-ligated) have afforded highly isotactic and highly syndiotactic double-bond- carrying polymers, respectively, with controlled molecular weights and narrow dispersities. The enantiomorphic-site controlled, conjugate-addition coordination polymerization mechanism is responsible for the observed
    [Show full text]
  • Ruthenium Olefin Metathesis Catalysts
    Ruthenium Olefin Metathesis Catalysts: Tuning of the Ligand Environment Ruthenium olefine metathese katalysatoren: Optimalisatie van de ligandsfeer Nele Ledoux Promotor: Prof. Dr. F. Verpoort Proefschrift ingediend tot het behalen van de graad van Doctor in de Wetenschappen: Scheikunde Vakgroep Anorganische en Fysische Chemie Vakgroepvoorzitter: Prof. Dr. S. Hoste Faculteit Wetenschappen 2007 ii Members of the Dissertation Committee: Prof. Dr. F. Verpoort Prof. Dr. Ir. C. Stevens Dr. V. Dragutan Dr. R. Drozdzak Dr. R. Winde Prof. Dr. Ir. D. Devos Prof. Dr. J. Van der Eycken Prof. Dr. P. Van Der Voort Prof. Dr. K. Strubbe This research was funded by the Fund for Scien- tific Research - Flanders (F.W.O.-Vlaanderen). Acknowledgments This dissertation is the final product of an educative and fascinating journey, which involved many contributors. First of all, I wish to express my gratitude to the people with whom I learned how to do research. There is my promotor Prof. Dr. Francis Verpoort who gave me the opportunity to join his ’Catalysis group’ and ensured the necessary funding. I’m especially grateful for his confidence and indulgence. In addition, I have been extremely lucky to work with several nice colleagues. Thank you, Thank you (= double thank you ♥) to Bart who helped me conquer many small and big difficulties, and by doing so, contributed a lot to the results reported here. Special thanks to Hans for many funny moments and support over the years. Of course, my acknowledgments also go to the other boys: Carl, Stijn, David, Jeroen, Prof. Dr. Pascal Van Der Voort and not to forget Siegfried, Steven, and Mike for the pleasant working atmosphere and supportive chats.
    [Show full text]
  • • Both Schrock and Grubbs Type Alkene Metathesis Catalysts Have a Low Coordination Number CN = 4 (After Dissociation of Pcy By
    • Both Schrock and Grubbs type alkene metathesis catalysts have a low coordination number CN = 4 (after dissociation of PCy 3 by Grubbs catalyst) • This allows facile access of the alkene to the central metal centre, where the decisive coordination step occurs. • Spectator ligands such as imido or oxo functions commonly found in metathesis catalysts promote formation of the metallacyclic intermediates. PCy 167o 3 Cl Ru P Cl Ph PCy3 Grubbs (1995) PCy3 Tolerance of functional groups in substrate (CO, OH, NH) Selectivity towards sterically unhindered olefins and strained olefins Tri- and tetra-substituted olefins are not attacked 16 Cross Metathesis (CM) • Cross metathesis has been used in industry in the form of the Shell higher olefin process (SHOP) since 1977. • This process is a combination of oligomerization, isomerization, and metathesis steps. α • First, linear C 4 to C 30+ -olefin chains are produced from ethylene. Enrichment of the C 8 – C18 fraction, which is of interest for application in various productions, is possible by a heterogeneous cross -metathesis reaction. 17 • Cross metathesis has only found limited applications however due to product “branching”. • Grubbs reported that heterodimers are obtained in high yield when one of the starting olefins first undergoes homodimerization. 18 Ring Closing Metathesis (RCM) • Ring closing metathesis is today considered a standard method in any organic synthesis laboratory (high dilution is required for diffusion controlled RCM to avoid CM). • Its suitability for the preparation of N-heterocycles has inspired natural product synthesis. • Assymetric ring closing metathesis (ARCM) has also been developed. 19 Ring Opening Metathesis (ROM) • Ring opening metathesis is the reversal of ring closing metathesis.
    [Show full text]
  • Hydrogenation of a Diene-Based Polymer Latex Hydrierung Eines Dien-Basierten Polymer-Latex Hydrogénation D’Un Latex Polymère À Base De Diène
    (19) TZZ __T (11) EP 2 676 971 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C08C 19/02 (2006.01) C08F 36/04 (2006.01) 08.04.2015 Bulletin 2015/15 C08F 236/12 (2006.01) C08F 8/04 (2006.01) (21) Application number: 12173165.7 (22) Date of filing: 22.06.2012 (54) Hydrogenation of a diene-based polymer latex Hydrierung eines dien-basierten Polymer-Latex Hydrogénation d’un latex polymère à base de diène (84) Designated Contracting States: (56) References cited: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB EP-A1- 2 289 621 US-A1- 2006 211 827 GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR • DATABASE COMPENDEX [Online] ENGINEERING INFORMATION, INC., NEW YORK, (43) Date of publication of application: NY, US; 3 October 2011 (2011-10-03), 25.12.2013 Bulletin 2013/52 KONGPARAKUL S ET AL: "Metathesis hydrogenation of natural rubber latex", (73) Proprietor: UNIVERSITY OF WATERLOO XP002689385, Database accession no. Waterloo, Ontario N2L 3G1 (CA) E20113714322330 -& KONGPARAKUL S ET AL: "Metathesis hydrogenation of natural rubber (72) Inventors: latex", APPLIED CATALYSIS A: GENERAL, vol. • REMPEL, Garry L. 405, no. 1-2, 3 October 2011 (2011-10-03), pages Waterloo, Ontario N2T 2H4 (CA) 129-136, XP002690182, ELSEVIER NLD DOI: • PAN, Qinmin 10.1016/J.APCATA.2011.07.039 Waterloo, Ontario N2T 2W9 (CA) • DATABASE COMPENDEX [Online] • Wu, Jialong ENGINEERING INFORMATION, INC., NEW YORK, Waterloo, Ontario N2L 4N2 (CA) NY, US; 15 April 2008 (2008-04-15), MINGOTAUD •LIU,Yin A-F ET AL: "Characterization of the micellar ring Mississauga, Ontario L5B 0E8 (CA) opening metathesis polymerization in water of a norbornene derivative initiated by Hoveyda- (74) Representative: Hollah, Dorothee Grubbs’ catalyst", XP002689386, Database Isenbruck Bösl Hörschler LLP accession no.
    [Show full text]
  • Ruthenium-Based Olefin Metathesis Catalysts Bearing Ph-Responsive Ligands: External Control of Catalyst Solubility and Activity" (2011)
    The University of Southern Mississippi The Aquila Digital Community Dissertations Spring 5-2011 Ruthenium-Based Olefin Metathesis Catalysts Bearing pH- Responsive Ligands: External Control of Catalyst Solubility and Activity Shawna Lynn Balof University of Southern Mississippi Follow this and additional works at: https://aquila.usm.edu/dissertations Part of the Chemistry Commons Recommended Citation Balof, Shawna Lynn, "Ruthenium-Based Olefin Metathesis Catalysts Bearing pH-Responsive Ligands: External Control of Catalyst Solubility and Activity" (2011). Dissertations. 693. https://aquila.usm.edu/dissertations/693 This Dissertation is brought to you for free and open access by The Aquila Digital Community. It has been accepted for inclusion in Dissertations by an authorized administrator of The Aquila Digital Community. For more information, please contact [email protected]. The University of Southern Mississippi RUTHENIUM-BASED OLEFIN METATHESIS CATALYSTS BEARING PH-RESPONSIVE LIGANDS: EXTERNAL CONTROL OF CATALYST SOLUBILITY AND ACTIVITY by Shawna Lynn Balof Abstract of a Dissertation Submitted to the Graduate School of The University of Southern Mississippi in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy May 2011 ABSTRACT RUTHENIUM-BASED OLEFIN METATHESIS CATALYSTS BEARING PH-RESPONSIVE LIGANDS: EXTERNAL CONTROL OF CATALYST SOLUBILITY AND ACTIVITY by Shawna Lynn Balof May 2011 Sixteen novel, Ru-based olefin metathesis catalysts bearing pH responsive ligands were synthesized. The pH-responsive groups employed with these catalysts included dimethylamino (NMe2) modified NHC ligands as well as N-donor dimethylaminopyridine (DMAP) and 3-(o-pyridyl)propylidene ligands. These pH- responsive ligands provided the means by which the solubility and/or activity profiles of the catalysts produced could be controlled via acid addition.
    [Show full text]
  • Pyridine-Stabilized Fast-Initiating Ruthenium Monothiolate Catalysts for Z-Selective Olefin Metathesis
    This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. Article pubs.acs.org/Organometallics Pyridine-Stabilized Fast-Initiating Ruthenium Monothiolate Catalysts for Z‑Selective Olefin Metathesis Giovanni Occhipinti,* Karl W. Törnroos, and Vidar R. Jensen* Department of Chemistry, University of Bergen, Allegateń 41, N-5007 Bergen, Norway *S Supporting Information ABSTRACT: Pyridine as a stabilizing donor ligand drastically improves the performance of ruthenium monothiolate catalysts for olefin metathesis in comparison with previous versions based on a stabilizing benzylidene ether ligand. The new pyridine- stabilized ruthenium alkylidenes undergo fast initiation and reach appreciable yields combined with moderate to high Z selectivity in self-metathesis of terminal olefins after only a few minutes at room temperature. Moreover, they can be used with a variety of substrates, including acids, and promote self- metathesis of ω-alkenoic acids. The pyridine-stabilized ruthe- nium monothiolate catalysts are also efficient at the high substrate dilutions of macrocylic ring-closing metathesis and resist temperatures above 100 °C during catalysis. ■ INTRODUCTION Chart 1. Examples of Z-Selective Catalysts Transition-metal-catalyzed olefin metathesis is a powerful, versatile, and green method for making carbon−carbon double bonds and is widely used in organic synthesis.1,2 This reaction is also exploited in several industrial processes ranging from value- added processes of simple alkenes to the synthesis of complex pharmaceuticals.3,4 Grubbs-type ruthenium-based catalysts have been the most widely used so far because, in addition to their high activity, they tolerate many functional groups, including alcohols and carboxylic acids.5 Moreover, they are relatively robust toward air and moisture and therefore also easy to handle and store.
    [Show full text]
  • Decomposition of Ruthenium Olefin Metathesis Catalyst
    catalysts Review Decomposition of Ruthenium OlefinOlefin Metathesis CatalystMetathesis Catalyst Magdalena Jawiczuk 1,, Anna Anna Marczyk Marczyk 1,21,2 andand Bartosz Bartosz Trzaskowski Trzaskowski 1,* 1,* 1 1 CentreCentre of of New New Technologies, Technologies, University University of of Warsaw, Warsaw, Banacha Banacha 2c, 2c, 02-097 02-097 Warsaw, Warsaw, Poland; [email protected]@cent.uw.edu.pl (M.J.); (M.J.); [email protected] [email protected] (A.M.) (A.M.) 2 Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland 2 Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland * Correspondence: [email protected] * Correspondence: [email protected] Received: 28 28 June 2020; Accepted: 02 2 AugustAugust 2020;2020; Published:Published: 5date August 2020 Abstract: RutheniumRuthenium olefin olefin metathesis metathesis catalysts catalysts are are one one of of the most commonly used class of catalysts. There There are are multiple multiple reviews reviews on on their their us useses in in various branches of chemistry and other sciences but a detailed review of their decomposition is missing, despite a large number of recent and important advances advances in in this this field. field. In In particular, particular, in in the the last last five five years years several several new new mechanism mechanism of decomposition,of decomposition, both both olefin-driven olefin-driven as well as well as induc as induceded by external by external agents, agents, have have been been suggested suggested and usedand usedto explain to explain differences differences in the decomposition in the decomposition rates and rates the metathesis and the metathesis activities activitiesof both standard, of both N-heterocyclicstandard, N-heterocyclic carbene-based carbene-based systems and systems the recently and the developed recently developed cyclic alkyl cyclic amino alkyl carbene- amino containingcarbene-containing complexes.
    [Show full text]
  • Renewable Polymers from Itaconic Acid
    RENEWABLE POLYMERS FROM ITACONIC ACID A Dissertation Presented to the Faculty of the Graduate School of Cornell University In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy by Jacob Thomas Trotta August 2019 © 2019 Jacob Thomas Trotta ii RENEWABLE POLYMERS FROM ITACONIC ACID Jacob Thomas Trotta, Ph. D. Cornell University 2019 Itaconic acid (IA) is a biorenewable compound that is generated inexpensively and in large amounts by the fermentation of biomass. While a variety of structurally diverse polymers have been accessed from IA, continued exploration of efficient syntheses and polymerizations of novel monomers could lead to the development of sustainable materials that can help reduce society’s dependence of petroleum (Chapter 1). We show that from β-monomethyl itaconate, an IA derivative, we can utilize a selective addition strategy that allows access to both α-methylene-γ-butyrolactone (MBL, tulipalin A) and α-methylene-γ,γ-dimethyl-γ-butyrolactone (Me2MBL), which serve as high value biorenewable analogues to petroleum-derived methyl methacrylate. Subsequent polymerization of both Me2MBL and MBL through reversible addition- fragmentation chain-transfer (RAFT) polymerization generates well defined poly(Me2MBL) (PMe2MBL) and poly(MBL) (PMBL) polymers. Through physiochemical characterization, we show that PMe2MBL has desirable properties comparable with known PMBL materials (Chapter 2). We then extend our strategy to produce triblock polymers using PMBL end blocks with an IA-derived polyester mid- block. Using catalytic, solvent-free, and high yielding transformations from an itaconate source, we efficiently synthesize a saturated diol, a saturated diester, and an unsaturated diester. Subsequent step-growth polycondensation polymerizations of these monomers leads to polyesters with relatively high molar masses (> 10 kg/mol).
    [Show full text]
  • A Convenient Method for Removing All Highly-Colored Byproducts Generated During Olefin Metathesis Reactions
    ORGANIC LETTERS 2000 A Convenient Method for Removing All Vol. 2, No. 9 Highly-Colored Byproducts Generated 1259-1261 during Olefin Metathesis Reactions Leo A. Paquette,* Jeffrey D. Schloss, Ivan Efremov, Fabrizio Fabris, Fabrice Gallou, Jose´Me´ndez-Andino, and Jiong Yang EVans Chemical Laboratories, The Ohio State UniVersity, Columbus, Ohio 43210 [email protected] Received February 18, 2000 ABSTRACT Addition of a very modest amount of lead tetraacetate (1.50 equiv relative to the amount of Grubbs catalyst) to ring-closing metathesis reaction mixtures effectively removes all colored ruthenium and phosphine impurities to deliver colorless reaction products. The olefin metathesis reactions, in their cross-coupling, ring- employed, although its general ineffectiveness for producing opening, and particularly ring-closing modes,1,2 have devel- trisubstituted alkenes is generally recognized.7 oped into processes that are of considerable value to organic synthesis.3 The striking advances that have materialized in recent years stem largely from the availability of efficient molybdenum4 and ruthenium5 precatalysts having well- balanced electronic and coordinative unsaturation such that high turnover performance is manifested. Due to its increased stability, the Grubbs catalyst 16 has been most widely (1) Olefin Metathesis and Metathesis Polymerization; Ivin, K. J., Mol, J. C., Academic Press: New York, 1997. Despite the major advantages offered by this group of (2) Alkene Metathesis in Organic Synthesis;Fu¨rstner, A., Ed.; Springer: reactions, they share the same complication. Removal of the Berlin, 1998. (3) For recent reviews, consult: (a) Grubbs, R. H.; Miller, S. J.; Fu, G. darkly colored, metal-containing byproducts upon completion C.
    [Show full text]