DOCSLIB.ORG

Ligand Effects on Cobalt-Catalyzed Hydrofunctionalization of Olefins

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Ligand Effects on Cobalt-Catalyzed Hydrofunctionalization of Olefins Ligand Effects on Cobalt-Catalyzed Hydrofunctionalization of Olefins THESIS Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Bryan F. Cunningham Graduate Program in Chemistry The Ohio State University 2016 Master's Examination Committee: Professor T. V. RajanBabu, Advisor Professor Jon R. Parquette Copyright by Bryan F. Cunningham 2016 ABSTRACT With a significant amount of early chemistry focusing on the stoichiometric hydrofunctionalization of olefins, it has not been until recent years that chemists have had access to the powerful metal-catalyzed equivalents. With its advent, metal-catalyzed hydrofunctionalization has broadened the scope of reactivity and made strides towards the ultimate goals of atom-economy and multiplication of chirality in the synthesis of useful molecules. In its simplest form, metal-centered catalysis can be described as reactions catalyzed with a metal M, which must be stabilized in a useful conformation and electronic configuration with ligand L. The M(L) combination can be varied by the metal and the ligand, with the ligand having a large effect on the reactivity of the complex through sterics and electronics. Herein we discuss ligand effects on a variety of metal-catalyzed hydrofunctionalizations, including hydrosilylation, hydroboration and hydrovinylation. Ligands explored include Nishiyama’s Bis(oxazolinyl)pyridine, and Schmalz’s Phosphine-Phosphite ligands. The details of the synthesis and application of these ligands is described, as well improvements to previously described methods. ii Dedicated to Violet Mae Fagan - Chemist and Maverick iii ACKNOWLEDGMENTS Dr. Diana L. Fagan (Mother) Rich M. Cunningham (Father) Dr. T.V. RajanBabu (Advisor) Dr. John A. Jackson (Mentor) OSU Chemistry Faculty (Professors) Babu Group Members (Friends) S.B. (Koala) iv VITA July 27th, 1989………........................................................ Born – Los Angeles, California May 2013 ..................................................................................................... B.S. Chemistry Youngstown State University 2013-2016 ............................................................................................. Teaching Associate The Ohio State University FIELDS OF STUDY Major Field: Chemistry v TABLE OF CONTENTS Abstract……………………………………………………………………………………ii Dedication………………………………………………………………………...………iii Acknowledgments……………………………………………………………………...…iv Vita………………………………………………………………………………………...v Fields of Study…………………………………………………………………………….v Table of Contents…………………………………………………………………………vi List of Schemes…………………………………………………………………………...ix List of Tables……………………………………………………………………………...x List of Figures…………………………………………………………………………….xi List of Abbreviations…………………………………………………………………….xii Chapter 1: Bis(oxazolinyl)pyridine Ligands………………………………………………1 1.1 Background and Significance…………………………………………………………1 vi 1.2 Synthesis………………………………………………………………………………5 1.3 Hydrosilyation…………………………………………………………………………6 1.4 Conclusion…………………………………………………………………………….9 1.5 Experimental Procedures……………………………………………………………...9 1.5.1 General Methods…………………………………………………………….9 1.5.2 Synthesis of Bis(oxazolinyl)pyridine (PyBox) Ligands…………………...10 Chapter 2: Phosphine-Phosphite Ligands………………………………………………..16 2.1 Background and Significance………………………………………………………..16 2.2 Synthesis and a Novel Alternative…………………………………………………...22 2.3 Hydroboration of Simple, Linear 1,3-Dienes………………………………………..26 2.4 Hydrovinylation of Simple, Linear 1,3-Dienes………………………………………32 2.5 Conclusion…………………………………………………………………………...38 2.6 Experimental Procedures…………………………………………………………….39 2.6.1 General Methods…………………………………………………………...39 2.6.2 Synthesis of Phosphine-Phosphite Ligands………………………………..41 2.6.3 Alternative Synthesis………………………………………………………48 vii 2.6.4 (L)CoCl2 Complexes……………………………………………………….49 2.6.5 Hydroboration and Oxidation……………………………………………...49 2.6.6 Hydrovinylation……………………………………………………………52 Bibliography……………………………………………………………………………..55 Appendix A: 1H and 13C NMR Spectra from Chapter 1…………………………………62 Appendix B: 31P, 1H, 13C NMR Spectra and Gas Chromatograms from Chapter 2……..71 viii LIST OF SCHEMES Scheme 1.1. Nishiyama Synthesis of PyBox (1989)……………………………………...2 Scheme 2.1. General Synthesis of Phosphine-Phosphite Ligand (2000)………………...17 Scheme 2.2. P-O to P-C Migration of Borane-Protected Phosphinite…………………...19 Scheme 2.3. General Synthesis of Phosphine-Phosphite Ligand (2002)………………...19 Scheme 2.4. General Synthesis of Phosphine-Phosphite Ligand (2012)………………...23 Scheme 2.5. General Synthesis of Phosphoramidite Ligand…………………………….25 Scheme 2.6. Novel General Synthesis of Phosphine-Phosphite Ligand (New Method)...25 Scheme 2.7. Possible Products of Metal-Catalyzed Hydrovinylation 1,3-Dienes……….32 Scheme 2.8. Schmalz Cobalt-Catalyzed 1,4-Hydrovinylation of 2,3-Dimethyl-1,3- Butadiene…………………………………………………………………..34 Scheme 2.9. Schmalz Cobalt-Catalyzed Hydrovinylation of Substituted Vinylarene…...36 ix LIST OF TABLES Table 1.1. Hydrosilylation of 4-Methylstyrene……………………………………………8 Table 2.1. Effect of Ligands on Rhodium-Catalyzed Hydroformylation………………..21 Table 2.2. Phosphorus NMR; Jpp Coupling Values of Phosphine-Phosphite Ligands…..21 Table 2.3. RajanBabu Cobalt-Catalyzed Hydroboration of Simple 1,3-Dienes…………29 Table 2.4. Cobalt Catalyzed Hydroboration of 1,3-Nonadiene………………………….31 Table 2.5. RajanBabu Cobalt-Catalyzed Hydrovinylation of Simple 1,3-Dienes……….33 Table 2.6. Cobalt-Catalyzed Hydroboration of 1,3-Nonadiene………………………….35 Table 2.7. Cobalt-Catalyzed Hydrovinylation of Styrene……………………………….37 x LIST OF FIGURES Figure 1.1. Neutral and Reduced Forms of PDI and PyBox………………………………4 Figure 1.2. Common Metal-Catalyzed Hydrosilylation Products………………………...7 Figure 2.1. Evolution of Metal-Catalyzed Hydroboration 1,3-Dienes…………………..28 xi LIST OF ABREVIATIONS atm atmospheres br broad (NMR) BINOL 1,1'-bi-2-naphthol n-Butyl normal-butyl t-Butyl tertiary-butyl ˚C degrees Celsius HBCat catechol borane conv conversion δ chemical shift in parts per million DABCO 1,4-diazabicyclo[2.2.2]octane DCM dichloromethane DIPA N,N-diisopropylamine xii DMAP 4-Dimethylaminopyridine DMF N,N-dimethylformamide d doublet (NMR) dd doublet of doublets (NMR) dt double of triplets (NMR) ee enantiomeric excess E entgegen (trans) Eq Equation equiv equivalent(s) Et ethyl EtOAc ethyl acetate g gram(s) h hour(s) Hz hertz i-Pr isopropyl IPO iminopyridine-oxazoline xiii J coupling constant in hertz (NMR) L ligand; liter(s) MAO methylaluminoxane m milli; multiplet (NMR) M mega; metal; molarity Me methyl min minute(s) mol mole(s) NBS N-bromosuccinimide NMR nuclear magnetic resonance PDI bis(imino)pyridine Ph phenyl PyBox bis(oxazolinyl)pyridine Pyr pyridine π pi HBPin Pinacolborane xiv q quartet (NMR) rt room temperature s singlet (NMR) TADDOL α,α,α',α'-tetraaryl-2,2-disubstituted 1,3-dioxolane-4,5-dimethanol TMA trimethylamine t triplet (NMR) THF tetrahydrofuran THP tetrahydropyranyl acetal TLC thin layer chromatography Z zusammen (cis) xv Chapter 1: Bis(oxazolinyl)pyridine Ligands 1.1 Background and Significance First synthesized in 1989 by Nishiyama and coworkers1, bis(oxazolinyl)pyridine (PyBox) ligands are well known to today’s chemists, and have proven themselves as flexible and selective ligands in metal-catalyzed asymmetric catalysis. Easy and cheap to produce, their modular synthesis allows for easy tuning of their unique electronic and steric characteristics. To date, PyBox has found use in more than thirty types of reactions2, including hydrofunctionalization, a well-studied class of reactions allowing for the functionalization of typically non-reactive olefins, and the focus later discussion. Box ligands are that which contain two oxazoline rings, separated by a spacer, typically an alkyl chain. Building from previous success in the enantioselective hydrosilylation of ketones by Brunner’s group in 19843, Nishiyama and coworkers set out to design new chiral, C2-symmetric tridentate pyridine ligands for use in the rhodium(III) catalyzed hydrosilylation of ketones1. It would be remiss to continue without mentioning Brunner’s significant work with Schiff base4 and pyridine oxazoline ligands5 (1), which Nishiyama and coworkers clearly drew their inspiration from for the synthesis of PyBox (2). 1 PyBox’s distinction was in the two chiral oxazoline rings with bulky alkyl groups, making it chiral and C2 symetric axially. This allowed for chiral recognition at one face of the substrate coordinated to the metal, which was illustrated in the same paper as its synthesis, attaining a high enantioselectivity in the hydrosilylation of ketones (up to 95% ee)1. Another attraction of PyBox was it’s cheap, easy and modular synthesis starting from pyridine-2,6-dicarbozylic acid, allowing for easy screening of ligands. Scheme 1.1. Nishiyama Synthesis of PyBox (1989) 2 As described in Nishiyama’s original 1989 paper, PyBox can be obtained in just four steps from pyridine-2,6-dicarboxylic acid (Scheme 1.1). Much of the original derivation was first explored by Nishiyama using the rhodium(III) catalyzed hydrosilyation of ketones as a benchmark. Nishiyama went on to show a significant oxazoline substituent effect on the enantioselectivity and reaction rate of the rhodium catalyzed hydrosilylation of ketones6. In general, it can said that selectivity trends follows sterics (Me < Et ≈ Bn < iPr) 2. Furthermore, substitution at the 4-position of the pyridine ring with an electron withdrawing group was shown to increase reaction
Load more

Recommended publications
  • An Integrated Flow and Batch-Based Approach for the Synthesis of O-Methyl Siphonazole Amarcus Combined Flow and Batch Synthesis of O-Methyl Siphonazole Baumann, Ian R
    LETTER 1375 An Integrated Flow and Batch-Based Approach for the Synthesis of O-Methyl Siphonazole AMarcus Combined Flow and Batch Synthesis of O-Methyl Siphonazole Baumann, Ian R. Baxendale, Malte Brasholz, John J. Hayward, Steven V. Ley, Nikzad Nikbin Innovative Technology Centre, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK E-mail: [email protected] Received 21 February 2011 has transformed flow chemistry from an academic interest Abstract: The bisoxazole containing natural product O-methyl si- phonazole was assembled using a suite of microreactors via a flow- to a valuable enabling technology that overcomes several based approach in concert with traditional batch methods. The use of the bottlenecks traditionally faced by synthetic chem- 6 of a toolbox of solid-supported scavengers and reagents to aid puri- ists. As such the generation and immediate use of hazard- fication afforded the natural product in a total of nine steps. ous, toxic, or unstable intermediates7 has been reported as Key words: oxazoles, Claisen condensation, flow chemistry, well as the possibility to more reliably perform reaction microreactors, solid-supported reagents scale-up.8 Furthermore, flow reactors can be transformed into automated platforms by the addition of liquid han- dling and fraction collector modules expanding the work- As part of our ongoing interest in oxazole-containing nat- ing capabilities of the units and allowing for 24/7 working 9 ural products,1 we have devised a synthetic route to the regimes. Finally, individual reactions can be telescoped bisoxazole alkaloid O-methyl siphonazole (2), which was into one continuous flow sequence, thus avoiding the iter- discovered by König and co-workers in 2006, along with ative isolation, purification, and reprocessing of interme- 10 the C-21-demethylated parent compound siphonazole (1, diates.
    [Show full text]
  • Recent Syntheses of Steroidal Oxazoles, Oxazolines and Oxazolidines
    A Platinum Open Access Journal Review for Organic Chemistry Free to Authors and Readers DOAJ Seal Arkivoc 2021, part i, 471-490 Recent syntheses of steroidal oxazoles, oxazolines and oxazolidines Besma Bendif,a,b Malika Ibrahim-Ouali,*a and Frédéric Dumur c aAix Marseille Univ, CNRS, Centrale Marseille, iSm2, F-13397 Marseille, France bLaboratoire de Chimie Appliquée, Faculté des Sciences, Université du 08 mai 1945 Guelma, Algeria cAix Marseille Univ, CNRS, ICR, UMR 72 73, F-13397 Marseille, France Email: [email protected] Received 03-15-2021 Accepted 04-11-2021 Published on line 05-08-2021 Abstract It was found that the introduction of heterocycles to steroids often leads in a change of their physiological activity and the appearance of new interesting biological precursors. Recent developments in the syntheses of steroidal oxazoles, oxazolines, and oxazolidines are described herein. The biological activities of those steroidal derivatives for which data are available are given. Keywords: Steroids, oxazoles, oxazolines, oxazolidines DOI: https://doi.org/10.24820/ark.5550190.p011.512 Page 471 ©AUTHOR(S) Arkivoc 2021, i, 471-490 Bendif, B. et al. Table of Contents 1. Introduction 2. Synthesis of Steroidal Oxazoles 3. Synthesis of Steroidal Oxazolines 4. Synthesis of Steroidal Oxazolidines 5. Conclusions Acknowledgements References 1. Introduction Steroids constitute an extensive and important class of biologically active polycyclic compounds that are widely used for therapeutic purposes.1-3 Even after decades of research, the total synthesis of steroid nuclei by improved strategies continues to receive considerable attention. Numerous methods have been exploited for the total synthesis of steroids which are widely distributed in nature and which possess practical medical importance.
    [Show full text]
  • Block-Poly(2-Methyl-2-Oxazoline)
    ENGINEERING OF POLY(2-OXAZOLINE)S FOR A POTENTIAL USE IN BIOMEDICAL APPLICATIONS by Camille Legros A thesis presented to the University of Waterloo, Université de Liege and Université de Bordeaux in fulfillment of the thesis requirement for the degree of Doctor of Philosophy in Chemical Engineering (Nanotechnology) Waterloo, Ontario, Canada, 2015 © Camille Legros 2015 'I hereby declare that I am the sole author of this thesis. This is a true copy of the thesis, including any required final revisions, as accepted by my examiners. I understand that my thesis may be made electronically available to the public.' ii iii Abstract Résumé: Ce travail décrit d'abord l’élaboration de nanogels hydrophiles stimulables, sensibles à un changement de pH et à un environnement où les propriétés d’oxydo-réduction peuvent varier. Ils ont été synthétisés en milieu dilué, d’une part, et en émulsion inverse, d’autre part; dans les deux cas à partir d’un copolymère statistique composé d’unités 2-éthyl-2-oxazoline et éthylène imine. Ces nanogels n’ont pas montré d’interactions spécifiques avec des protéines telles que la BSA et se sont avérés non-toxiques in vitro. Une plateforme à base d’un copolymère POx statistique porteur de fonctions aldéhydes a par ailleurs permis d’accéder à une librairie de POx, incluant des structures greffées et réticulées. Enfin, l’auto-assemblage en solution d’un copolymère à blocs de type poly(2-methyl-oxazoline)-b-poly(2-isopropyl-2-oxazoline) (PMeOx- b-PiPrOx), a été étudié en détail. Des micelles ont été observées à des temps courts au-dessus du point trouble du PiPrOx.
    [Show full text]
  • Novel Functional Poly(2-Oxazoline)S As Potential Carriers for Biomedical Applications
    Technische Universität München Department Chemie WACKER-Lehrstuhl für Makromolekulare Chemie Novel Functional Poly(2-oxazoline)s as Potential Carriers for Biomedical Applications Robert Luxenhofer Vollständiger Abdruck der von der Fakultät für Chemie der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften (Dr. rer. nat.) genehmigten Dissertation. Vorsitzender: Univ.-Prof. Dr. Kai-Olaf Hinrichsen Prüfer der Dissertation: 1. Priv.-Doz. Dr. Rainer Jordan 2. Univ.-Prof. Dr. Horst Kessler 3. Univ.-Prof. Dr. Andreas Türler Die Dissertation wurde am 29.05.2007 bei der Technischen Universität München ein- gereicht und durch das Department Chemie am 26.06.2007 angenommen. In Vivo Veritas! Die vorliegende Arbeit wurde am WACKER-Lehrstuhl für Makromolekulare Chemie (zuvor Lehrstuhl für Makromolekulare Stoffe) im Department Chemie der Technischen Universität München in der Zeit von März 2004 bis Mai 2007 unter der Leitung von Herrn PD Dr. Rainer Jordan angefertigt. Insbesondere möchte ich mich bei meinem Mentor und Betreuer PD Dr. Rainer ´Ray´ Jordan sehr herzlich bedanken, dass er mir die Möglichkeit gegeben hat, an diesem Projekt zu arbeiten. Ich glaube das war die interessanteste Doktorarbeit die ich hätte finden können, selbst wenn ich gesucht hätte. Ich war sehr froh über all die Freiheit die ich hatte, wobei man immer vorbeikommen konnte, wenn man ein Problem hatte. Außerdem bin ich dankbar für die Arbeits- und Konferenzaufenthalte in New York, Flic en Flac, Budapest, San Francisco etc., die ich genießen konnte und die große Geduld mit mir. Prof. Dr.-Ing. Oskar Nuyken und Prof. Dr. Bernhard Rieger danke ich für die Auf- nahme bzw. die Möglichkeit meines Verbleibs am Lehrstuhl.
    [Show full text]
  • Goods-PDF-Brochures-Reducingagents.Pdf
    ᮣᮣᮣᮣ Gelest, Inc. Gelest Gelest, Inc. Telephone: General 215-547-1015 Order Entry 888-734-8344 FAX: 215-547-2484 Internet: www.gelest.com Correspondence: 11 East Steel Road Morrisville, PA 19067, USA In Europe: ABCR GmbH & Co. KG Im Schlehert D-76187 Karlsruhe Germany Tel: +49 - 721 - 950610 Fax: +49 - 721 - 9506180 e-mail: [email protected] on-line catalog: www.abcr.de In Japan: AZmax Co. Ltd. 1-6-13 Tamasaki Nishi Ichihara City Chiba, 290-0044 Japan Tel: 81-436-20-2660 Fax: 81-436-20-2665 email: [email protected] on-line catalog: www.azmax.co.jp For further information consult our web site at: www.gelest.com For technical advice contact: Gerald L. Larson, Ph.D. Vice-President, Research Products e-mail [email protected] ©2004 Gelest, Inc. Gelest, Inc. Silicon-Based Reducing Agents Edited by Gerald L. Larson, Ph.D. Vice President, Research Products Materials for the reduction of: Aldehydes Ketones Acetals Ketals Esters Lactones Thioesters Enamines Imines Acids Amides Halides Olefins Metal Halides Supplement to the Gelest Catalog, “Silicon, Germanium & Tin Compounds, Metal Alkoxides and Metal Diketonates” which is available on request. (215) 547-1015 FAX: (215) 547-2484 www.gelest.com 1 Gelest, Inc. SILICON-BASED REDUCING AGENTS Introduction The widely-used organometallic-based reducing agents can be broadly classified as either ionic, such as lithium aluminum hydride and sodium borohydride, or free-radical such as tri-n-butyltin hydride. The mechanistic differences between these two classes of reducing agents very often complement one another in their ability to reduce organic substrates.
    [Show full text]
  • Applications of Boronic Acids in Organic Synthesis
    Applications of Boronic Acids in Organic Synthesis A dissertation presented by Pavel Starkov in partial fulfilment of the requirements for the award of the degree of DOCTOR OF PHILOSOPHY at UNIVERSITY COLLEGE LONDON Department of Chemistry Christopher Ingold Laboratories University College London 20 Gordon Street WC1H 0AJ London Declaration This dissertation is the result of my own work. Where information has been derived from other sources it has been clearly indicated so and acknowledged accordingly. /Pavel Starkov/ ii Abstract This thesis describes progress on the application of boronic acids and borate esters as catalysts and reagents in synthetic organic synthesis, focusing on two areas: one-pot enolate formation/aldol reactions and amide bond formation. Chapter 1 introduces the reader to boronic acids and derivatives thereof, their methods of preparation and their use in synthetic organic chemistry as reactants, reagents and catalysts. Chapter 2 covers current chemical methods and cellular alternatives for amide bond formation. Here, we also discuss our use of boron reagents for the activation of carboxylic acids as well as amides. Chapter 3 introduces a new concept in catalytic aldol reactions, i.e. an alternative strategy to access boron enolates in situ. The work covers successful demonstration of the feasibility of such an approach on an intramolecular system. A novel variation of aerobic Chan–Evans– Lam coupling, an intramolecular coupling of an aliphatic alcohol with a boronic acid using catalytic copper, is also introduced Chapter 4 builds on our observations on gold catalysis and especially that in relation to electrophilic halogenations. Chapter 5 contains full details of the experimental procedures.
    [Show full text]
  • And Enantioselective Synthesis of P-Hydroxy-A-Amino Acids by Condensation of Aldehydes and Ketones with Glycine
    4252 J. Am. Chem. SOC.1985, 107, 4252-4259 mL and DMF and saturated with methylamine gas at 0 OC. The vessel mL volume) joined to the solvent distillation apparatus, waste, and was sealed and agitated for 1 day. The polymer was washed successively vacuum pump via Teflon tubing. in dioxane, ethanol, 2 N NaOH/i-PrOH (l:l), water (until eluate neu- In summary, we have shown for the first time the possibility to per- tral), ethanol, and ether. After drying in vacuo, the polymer (3.7 g/3.8 form highly efficient condensation reactions, by transferring polymer- mequiv of amino groups/l g of dry weight) was suspended in a mixture bound electrophiles (Le., active esters) via a mediator (shadchan) to of water (1.5 mL), ethanol (0.5 mL), triethylamine (7 mL), and 4- polymer-bound nucleophiles (i.e., amines). We have also shown the chloropyridine hydrochloride (4.7 g) in a glass pressure vessel, sealed and possibility of on-line monitoring which is relevant for automation. heated for 4 days at 140 OC. The polymer was washed as before, and The mediator methodology developed here is believed not to be limited unreacted amino groups were blocked by acetylation (acetic anhydride to acylation and related processes but to be expandable to other chemical in CH2C12,then base wash). The washed DMAP polymer was dried at processes that involve the creation of activated intermediates. These 150 OC in vacuo until constant weight. Incorporation of pyridine groups possibilities are currently under investigation. was determined by potentiometric chloride titration of the hydrochloride salt bound to the polymer: 2.53 mequiv/g compared to 3.15 mequiv/g Acknowledgment.
    [Show full text]
  • European Patent Office Office Europeenpeen Des Brevets EP 0 674 618 B1
    Europaisches Patentamt (19) European Patent Office Office europeenpeen des brevets EP 0 674 618 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) intci.6: C07C 317/32, C07C 233/22, of the grant of the patent: C07C 315/04, C07D 301/19, 09.09.1998 Bulletin 1998/37 C07D 263/14, A61K31/16 (21) Application number: 94903599.2 (86) International application number: PCT/US93/12071 (22) Date of filing: 15.12.1993 (87) International publication number: WO 94/14764 (07.07.1994 Gazette 1994/15) (54) ASYMMETRIC PROCESS FOR PREPARING FLORFENICOL, THIAMPHENICOL, CHLORAMPHENICOL AND OXAZOLINE INTERMEDIATES ASYMMETRISCHES HERSTELLUNGSVERFAHREN FUR FLORFENICOL, THIAMPHENICOL, CHLORAMPHENICOL UND OXAZOLIN-ZWISCHENPRODUKTE PROCEDE ASYMETRIQUE DE PREPARATION DE FLORFENICOL, THIAMPHENICOL, CHLORAMPHENICOL ET D'INTERMEDI AIRES OXAZOLINE (84) Designated Contracting States: (74) Representative: AT BE CH DE DK ES FR GB GR IE IT LI LU NL PT von Kreisler, Alek, Dipl.-Chem. et al SE Patentanwalte, von Kreisler-Selting-Werner, (30) Priority: 18.12.1992 US 993932 Bahnhofsvorplatz 1 (Deichmannhaus) 50667 Koln (DE) (43) Date of publication of application: 04.10.1995 Bulletin 1995/40 (56) References cited: EP-A- 0 423 705 EP-A- 0 472 790 (73) Proprietor: SCHERING CORPORATION WO-A-92/07824 US-A- 4 235 892 Kenilworth New Jersey 07033 (US) US-A- 4 876 352 US-A- 4 900 847 (72) Inventors: • CHEMICAL ABSTRACTS, vol. 107, no. 1, 06 July • WU, Guang-Zhong 1987, Columbus, Ohio, US; abstract no. 6859M, Somerville, NJ 08876 (US) JOMMI, GIANCARLO ET AL '2-Oxazolidinones • TORMOS, Wanda, I. as regioselective protection of beta-amino Elizabeth, NJ 07202 (US) alcohols in the synthesis of 2-amino-1-aryl-3-fluoro-1-propanols' page 632; column 1; & GAZZ.
    [Show full text]
  • Recent Advances in the Synthesis of Oxazole-Based Molecules Via Van Leusen Oxazole Synthesis
    molecules Review Recent Advances in the Synthesis of Oxazole-Based Molecules via van Leusen Oxazole Synthesis Xunan Zheng 1,2, Wei Liu 3,* and Dawei Zhang 1,* 1 College of Chemistry, Jilin University, Changchun 130012, China; [email protected] 2 College of Plant Science, Jilin University, Changchun 130062, China 3 Department of Pesticide Science, Plant Protection College, Shenyang Agricultural University, Shenyang 110866, China * Correspondence: [email protected] (W.L.); [email protected] (D.Z.); Tel.: +86-188-1775-2588 (W.L.); +86-431-8783-6471 (D.Z.) Academic Editors: Anna Carbone and Fabio Bertozzi Received: 2 March 2020; Accepted: 23 March 2020; Published: 31 March 2020 Abstract: Oxazole compounds, including one nitrogen atom and one oxygen atom in a five-membered heterocyclic ring, are present in various biological activities. Due to binding with a widespread spectrum of receptors and enzymes easily in biological systems through various non-covalent interactions, oxazole-based molecules are becoming a kind of significant heterocyclic nucleus, which have received attention from researchers globally, leading them to synthesize diverse oxazole derivatives. The van Leusen reaction, based on tosylmethylisocyanides (TosMICs), is one of the most appropriate strategies to prepare oxazole-based medicinal compounds. In this review, we summarize the recent advances of the synthesis of oxazole-containing molecules utilizing the van Leusen oxazole synthesis from 1972, aiming to look for potential oxazole-based medicinal compounds, which are valuable information for drug discovery and synthesis. Keywords: van Leusen; TosMICs; oxazole; synthesis 1. Introduction The oxazole ring, with one nitrogen atom and one oxygen atom, which are widely displayed in natural products and synthetic molecules, is known as a prime skeleton for drug discovery.
    [Show full text]
  • Download Author Version (PDF)
    Dalton Transactions Accepted Manuscript This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. www.rsc.org/dalton Page 1 of 39 Dalton Transactions Chiral multidentate oxazoline ligands based on cyclophosphazene cores: Synthesis, characterization and complexation studies Dheeraj Kumar, Jatinder Singh and Anil J. Elias ,* ____________________________________________________________________ Chiral oxazoline based bi and hexadentate ligands built on cyclophosphazene cores have been synthesized and characterized. (NPPh 2)2[NP(m-OC 6H4C(O)OCH 3)2] (1) was prepared by the reaction of gem -(NPPh 2)2(NPCl 2) with methyl-3-hydroxy benzoate in presence of Cs 2CO 3. Compound 1 was converted to the dicarboxylic acid (NPPh 2)2[NP(m-OC 6H4C(O)OH)2] (2) Manuscript using base promoted hydrolysis with KO(t-Bu).
    [Show full text]
  • Intermolecular Reductive C–N Cross Coupling of Nitroarenes and Boronic Acids by P[Superscript III]/P[Superscript V]#O Catalysis
    Intermolecular Reductive C–N Cross Coupling of Nitroarenes and Boronic Acids by P[superscript III]/P[superscript V]#O Catalysis The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Nykaza, Trevor V. et al. "Intermolecular Reductive C–N Cross Coupling of Nitroarenes and Boronic Acids by P[superscript III]/ P[superscript V]#O Catalysis." Journal of the American Chemical Society 140, 45 (2018): 15200-15205 © 2018 American Chemical Society As Published http://dx.doi.org/10.1021/jacs.8b10769 Publisher American Chemical Society (ACS) Version Author's final manuscript Citable link https://hdl.handle.net/1721.1/123674 Terms of Use Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author J Am Chem Manuscript Author Soc. Author Manuscript Author manuscript; available in PMC 2019 November 14. Published in final edited form as: J Am Chem Soc. 2018 November 14; 140(45): 15200–15205. doi:10.1021/jacs.8b10769. Intermolecular Reductive C–N Cross Coupling of Nitroarenes and Boronic Acids by PIII/Pv=O Catalysis Trevor V. Nykaza#†, Julian C. Cooper#†, Gen Li†, Nolwenn Mahieu†, Antonio Ramirez‡, Michael R. Luzung‡,∥,*, and Alexander T. Radosevich†,* †Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States. ‡Chemical and Synthetic Development, Bristol-Myers Squibb Company, One Squibb Drive, New Brunswick, New Jersey 08903, United States. # These authors contributed equally to this work.
    [Show full text]
  • Synthesis, Biodistribution and Excretion of Radiolabeled Poly(2-Alkyl-2-Oxazoline)S ⁎ ⁎ Florian C
    Journal of Controlled Release 119 (2007) 291–300 www.elsevier.com/locate/jconrel Synthesis, biodistribution and excretion of radiolabeled poly(2-alkyl-2-oxazoline)s ⁎ ⁎ Florian C. Gaertner a,1, Robert Luxenhofer b,1, Birgit Blechert a, Rainer Jordan b, , Markus Essler a, a Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München, Germany b Lehrstuhl für Makromolekulare Stoffe, Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany Received 29 December 2006; accepted 19 February 2007 Available online 2 March 2007 Abstract Here we report on the preparation of well defined water-soluble poly(2-methyl-2-oxazoline) and poly(2-ethyl-2-oxazoline) terminally equipped with a chelator (N,N′,N″,N‴-tetraazacylododecane-1,4,7,10-tetraacetic acid (DOTA)) for radionuclide labeling. The tissue distribution and excretion of 111In-labeled poly(2-alkyl-2-oxazoline)s were studied in mice. We found that the hydrophilic polymers do not accumulate in tissues and are rapidly cleared from the blood pool, predominantly by glomerular filtration in the kidneys. In contrast only a small fraction is excreted via the hepatobiliary tract. Only minimal amounts of poly(2-alkyl-2-oxazoline)s are taken up by the reticuloendothelial system (RES). Scintigraphic studies revealed the feasibility of in vivo imaging of 111In-labeled poly(2-oxazoline)s. Since additional functionalities for targeting can readily be introduced into poly(2-oxazoline)s via functional monomer units, these compounds fulfill fundamental requirements for an application as carrier molecules in radionuclide therapy. © 2007 Elsevier B.V. All rights reserved.
    [Show full text]