DOCSLIB.ORG

Durham E-Theses

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Durham E-Theses Durham E-Theses Some studies of polyuorinated polycyclic polyenes Hughes, Roger R. How to cite: Hughes, Roger R. (1975) Some studies of polyuorinated polycyclic polyenes, Durham theses, Durham University. Available at Durham E-Theses Online: http://etheses.dur.ac.uk/8213/ Use policy The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in Durham E-Theses • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Please consult the full Durham E-Theses policy for further details. Academic Support Oce, Durham University, University Oce, Old Elvet, Durham DH1 3HP e-mail: [email protected] Tel: +44 0191 334 6107 http://etheses.dur.ac.uk SOME STUDIES OF POLYFLUORINATED POLYCYCLIC POLYENES by Roger R. Hughes, B.Sc. (Van Mildert College) The copyright of this thesis rests with the author. No quotation from it should be published without his prior written consent and information derived from it should be acknowledged. A thesis submitted to the University of Durham for the Degree of Doctor of Philosophy 1975 ABSTRACT The attempted addition of difluorocarbene, which was generated from hexafluoropropene epoxide, to polyfluorinated cyclic olefins was largely unsuccessful, although perfluorobicyclo[4,l,0]hept-3-ene was isolated from the addition to perfluorocyclohexa-1,4-diene. It seems that difluorocarbene adds to the polyfluorinated cyclic olefins to form cyclopropanes, which readily eliminate difluorocarbene under the reaction conditions required for their formation. The attempted photochemical isomerisations of pplyfluorobicyclo[2,2,2]octa- 2,5-dienes, via the [2TI;+2TI;] ring closures to their corresponding tetracycles, were also unsuccessful. However, on irradiation dimethyl 1,4,5>6,7,7>8,8- octafluorobicycloC2,2,2]octa-2,5-diene-2,3-dicarboxylate formed a tricyclic biradical, which abstracted a hydrogen from the a methylene group of the diethyl ether solvent to give isomers of dimethyl 2-(3'-oxa-2'-pentyl)-l,4,5>6,7,7,8,8- octafluorotricycloC2,2,2,0-^''^]octane-2,3-dicarboxylate. The tricyclic biradical intermediate is similar to that proposed for the photochemical isomerisation of hydrocarbon bicyclo[2,2,2]hepta-2,5-dienes and their analogues. In contrast to their .corresponding hydrocarbon analogues the tricyclic biradical intermediates formed on irradiation of polyfluorobicyclo[2,2,2]octa-2,5-dienes do not appear to form tetracycles. 2 7 Perfluorotricyclo[6,2,2,0 ' ]dodeca-2,6,9-triene reacted as a diene in the Diels-Alder reactions with ethylene, but-2-yne, acetylene dicarboxylic acid dimethyl ester, perfluoroacetonitrile, tetrafluoroethylene and lH,2H-hexafluoro- cyclopentene. As a consequence imposed by the carbocyclic framework of the diene, the addition of lH,2H-hexafluorocyclopentene gave the exo adduct. The 1,4- alkyne adducts were pyrolysed to give 2,3-disubstituted hexafluoronaphthalenes. 2 7 The pyrolysis of perfluorotricycloC6,2,2,0 ' ]dodeca-2,6,9-triene proceeds 2 7 via a 1,3-alkyl migration to give perfluorotricyclo[8,2,0,0 ' ]dodeca-2,6,8-triene which subsequently eliminates tetrafluoroethylene to give perfluoro-l,2-dihydro- 2 7 naphthalene as the major product. The reaction of perfluorotricyclo[6,2,2,0 ' ]- dodeca-2,6,9-triene with lithium methyl in ether proceeded preferentially at the 2 7 diene moiety. The pyrolysis of the monomethyltridecafluorotricyclo[6,2,2,0 ' ]- dodeca-2,6,9-trienes gave monomethylnonafluoro-1,2-dihydronaphthalenes which had the methyl label in the non-aromatic ring. Nucleophilic substitution in perfluoro-1,2-dihydronaphthalene was found to occur only at the vinylic C3 position with sodium borohydride whereas with lithium methyl four monomethyl substitution products were obtained, both the vinylic, the C6 and C? fluorines being replaced. The gas phase photochemical reaction of perfluoro-1,2-dihydronaphthalene produces the perfluoro-1- and -2- methylenindanes possibly via the perfluorovinyl-o-quinodimethane. ACKNOWLEDGEMENTS I would like to thank Dr. W.J. Feast for his advice and help during the supervision of this work and Professor W.K.R. Musgrave for his interest. Assistance from the technical staff is appreciated and in particular, thanks* are due to Mr. D. Hunter for some practical assistance, I am also indebted to Mrs. E. McGauley for the presentation of the typescript and to Miss H. White for considerable help in the final preparation of this thesis. J . MEMORAr>IDUM The work in this thesis was cairried out in the Chemistry Laboratories of the University of Durham between October 1972 and July 1975. This work has not been submitted for any other degree and is the original work of the author except where acknowledged by reference. NOTF.S TO READER In this thesis compounds previously unreported in the literature are designated by large Roman numbers. [(XIX) and (XXI) have been reported but all of their spectral parameters are not available in the literature]. Other compounds are designated by Arabic numerals. The diagrams in the Introduction to all Chapters have unmarked bonds to hydrogen and in all Discussion Sections urmiarked bonds are to fluorine, unless otherwise stated. A reminder of this is given at the beginning of each Discussion. Tliroughout this thesis a number of abbreviations have been used regularly, these are: infrared spectroscopy (i.r.); ultra-violet spectroscopy (u.v.); mass spectroscopy (m.s.); nuclear magnetic resonance spectroscopy (n.m.r.); photoelectron spectroscopy (PES); gas-liquid chromatography (g.l.c); Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO). Generally the percentage composition of product mixtures has been determined from analytical g.l.c. peak areas which were obtained either by calibration or more usually by direct measurement from the gas density balance. 19 Many of the compounds reported in this thesis have very broad F n. m.r. signals that contain many coupling constants, however, in certain cases the actual width of an unresolved resonance has been helpful in ascertaining the presence or absence of large coupling constants and obviously for these systems it is the base line width that is necessgirily quoted. The chemical shift positions are quoted with respect to internal CFCl^ and internal T.M.S., unless otherwise stated and refer to the centres of bands. Integrated intensities are given in parentheses and coupling constants in Hz. The names of the compounds (I) —> (XXXXIV) are to be found in Appendix C, which also contains the infrared spectra. Appendix B contains the mass spectra 19 and structures of compounds in numerical order. The F n.m.r. data and the structures of compounds are generally to be found in Tables in the Discussions with the exceptions being (I), (V) and (Vl) whose structures are to be found 19 on pages 22, 53 and 95 respectively. The F n.m.r. data for the compounds (I) —>(XXXXIV) are to be found on: Page (I) 26 (II) (IV) Table 1 49 (V) 53 54 (VI) 119 (VII) —> (XII) Table 9 lOO 7-^ lOi (XIII) —^(XV) Table lO IO7 (XVI) and (XVII) Table 14 l4l (XVIII) Table 15 l44 (XIX) —(XXI) Table 16 l48 (XXII) Table 15 144 (XXIII) (XXVIII) Table 17 153 —^ 154 (pCX) (XXXVI) Table 21 191 192 (XXXVII) and (XXXVIII) Table 11 113 (XXXIX) -^(XXXXI) Table 23 2O3 (XXXXII) —^ (XXXXIV) Table 22 20i CONTENTS Abstract Acknowledgements Memorandum Notes to reader Page CHAPTER 1. The addition of difluorocarbene to polyfluorinated cyclic olefins INTRODUCTION 1.1 Methods of generating difluorocarbene 1 1.2 Generation of perfluoroalkylcarbenes 3 1.3 The preparation of polyfluorinated cyclopropanes from difluorocarbenes 4 1.4 Structure and reactivity of difluorocarbene 5 1.5 Structure and reactivity of perfluoroalkylcarbenes lO 1.6 Pyrolysis of highly fluorinated cyclopropanes 11 1.7 Cyclopropyl-allyl rearrangements , 13 DISCUSSION ' Experimental 1.8 Preparation of starting materials 24 1.9 Reaction of hexafluoropropene epoxide with polyfluorinated cyclic olefins 24 1.10 Pyrolysis of perfluorobicyclo[4,1,0]hept-3-ene 26 CHAPTER 2. The photochemistry of polyfluorobicyclo[2,2,2]octa- 2,5-dienes INTRODUCTION 2.1 The photochemistry of norbornadienes 27 2.2 Photochemistry of bicyclo[2,2,2]octa-2,5-dienes 33 Page 2.3 Photochemistry of bicyclo[2,2,0]hexa-2,5-dienes 36 2.4 Photochemistry of bicycloC3,2,2]nona-6,8-dienes 37 2.5 The effect of fluorine on the stability of the cyclopropane ring 38 2.6 The interaction of TC orbitals in non-conjugated bicyclic dienes 43 DISCUSSION 2.7 Preparation of starting materials and spectral parameters of the Diels Alder adducts of perfluorocyclohexa-1,3-diene 48 2.8 The photochemistry of polyfluorobicyclo[2,2,2]octa-2,5-dienes 5O EXPERIMENTAL 2.9 Preparation of starting materials 63 2.10 Photochemical reactions 65 2.11 Irradiation of polyfluorinated bicyclo[2,2,2]octa-2,5-diene systems (a) Gas phase irradiation of 1,2,3,4,7>7>8,8-octafluorobicyclo- [2,2,2]octa-2,5-diene (III) ' 65 (b) Gas phase photolysis of perfluoro-2,3-dimethylbicyclo- [2 ,2 ,2]octa-2 ,5-diene 66 (c) Irradiation of dimethyl l,4,5>6,7,7,8,8-octafluorobicyclo- [2,2,2]octa-2,5-diene-2,3-dicarboxylate 66 (d) The photolysis of perfluoro-2,3-dimethylbicyclo[2,2,2]octa- 2,5-diene in CFCl^ 70 CHAPTER 3. Diels-Alder reactions of tetradecafluorotricyclo- p 7 [6,2,2,0"^'
Load more

Recommended publications
  • American Chemical Society Division of Organic Chemistry 243Rd ACS National Meeting, San Diego, CA, March 25-29, 2012
    American Chemical Society Division of Organic Chemistry 243rd ACS National Meeting, San Diego, CA, March 25-29, 2012 A. Abdel-Magid, Program Chair; R. Gawley, Program Chair SUNDAY MORNING Ralph F. Hirschmann Award in Peptide Chemistry: Symposium in Honor of Jeffery W. Kelly D. Huryn, Organizer; D. Huryn, Presiding Papers 1-4 Biologically-Related Molecules and Processes A. Abdel-Magid, Organizer; T. Altel, Presiding Papers 5-16 New Reactions and Methodology A. Abdel-Magid, Organizer; N. Bhat, Presiding Papers 17-28 Asymmetric Reactions and Syntheses A. Abdel-Magid, Organizer; D. Leahy, Presiding Papers 29-39 Material, Devices, and Switches A. Abdel-Magid, Organizer; S. Thomas, Presiding Papers 40-49 SUNDAY AFTERNOON James Flack Norris Award in Physical Organic Chemistry: Symposium to Honor Hans J. Reich G. Weisman, Organizer; G. Weisman, Presiding Papers 50-53 Understanding Additions to Alkenes D. Nelson, Organizer; D. Nelson, Presiding Papers 54-61 Biologically-Related Molecules and Processes A. Abdel-Magid, Organizer; B. C. Das, Presiding Papers 62-73 New Reactions and Methodology A. Abdel-Magid, Organizer; T. Minehan, Presiding Papers 74-85 Asymmetric Reactions and Syntheses A. Abdel-Magid, Organizer; A. Mattson, Presiding Papers 86-97 Material, Devices, and Switches A. Abdel-Magid, Organizer; Y. Cui, Presiding Papers 98-107 SUNDAY EVENING Material, Devices, and Switches, Molecular Recognition, Self-Assembly, Peptides, Proteins, Amino Acids, Physical Organic Chemistry, Total Synthesis of Complex Molecules R. Gawley, Organizer Papers 108-257 MONDAY MORNING Herbert C. Brown Award for Creative Research in Synthetic Organic Chemistry: Symposium in Honor of Jonathan A. Ellman S. Sieburth, Organizer; S. Sieburth, Presiding Papers 258-261 Playing Ball: Molecular Recognition and Modern Physical Organic Chemistry C.
    [Show full text]
  • Alkyne-Nitrone Cycloadditions for Functionalizing Cell Surface Proteins
    Alkyne-Nitrone Cycloadditions for Functionalizing Cell Surface Proteins by Craig McKay Thesis Submitted to the Faculty of Graduate and Postdoctoral Studies In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Candidate Supervisor Craig McKay Dr. John Paul Pezacki Ottawa-Carleton Chemistry Institute Faculty of Science University of Ottawa © Craig McKay, Ottawa, Canada, 2012 Alkyne-Nitrone Cycloadditions for Functionalizing Cell Surface Proteins by Craig McKay Submitted to the Faculty of Graduate and Postdoctoral Studies On July 31, 2012 in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy In Organic Chemistry Abstract Over the past decade, bioorthogonal chemistry has emerged as powerful tools used for tracking biomolecules within living systems. Despite the vast number of organic transformations in the literature, only select few reactions meet the stringent requirements of bioorthogonality. There is increasing demands to develop biocompatible reactions that display high specificity and exquisitely fast kinetics under physiological conditions. With the goal of increasing reaction rates as a means for reducing the concentrations of labelling reagents used for bioconjugation, we have developed metal-catalyzed and metal-free alkyne- nitrone cycloadditions as alternatives to azide-alkyne cycloadditions and demonstrate their applications for imaging cell surface proteins. The copper(I)-catalyzed alkyne-nitrone cycloaddition, also known as the Kinugasa reaction, is typically conducted with a Cu(I) catalyst in the absence of air. We have developed highly efficient micelle promoted multicomponent Kinugasa reactions in aqueous media to make the reaction faster and more efficient. Despite good product yields, the slow kinetics, limited substrate scope and competing side-reaction pathways precludes its practical applicability for biological labelling.
    [Show full text]
  • Investigations Into the Ruthenium Catalyzed Ring Opening and Dimerization Reactions of Oxabicyclic Alkenes
    Investigations into the Ruthenium Catalyzed Ring Opening and Dimerization Reactions of Oxabicyclic Alkenes by Kelsey Jack A Thesis Presented to The University of Guelph In partial fulfilment of requirements for the degree of Master of Science in Chemistry Guelph, Ontario, Canada © Kelsey Jack, December 2012 ABSTRACT INVESTIGATIONS INTO THE RUTHENIUM CATALYZED RING OPENING AND DIMERIZATION REACTIONS OF OXABICYCLIC ALKENES Kelsey Jack Advisor: University of Guelph, 2012 Professor W. Tam Oxabicyclic alkenes have been the focus of many synthetic studies as they are versatile compounds which act as synthetic intermediates to produce a variety of useful heterocyclic, carbocyclic and acyclic products. The nucleophilic ring opening reaction of oxabenzonorbornadiene was studied. Methanol was the primary nucleophile used throughout the investigation, however various other alcohol nucleophiles were also tested for their efficacy. The effects of substitution were explored, providing ring opened products in yields of up to 81%. The [2+2] cyclodimerization reaction of oxanorbornadienes was also examined providing the first examples of dimers of this kind. The scope was expanded to include other 2,3-diester oxanorbornadienes as well as various C1 substitutions. Changing the ester moiety did not affect the reaction, however the addition of a C1 alkyl substituent did result in lower yields. Moderate yields of up to 66% were obtained. Additionally, a new ruthenium complex was discovered in the process. Acknowledgments First and foremost I would like to thank my advisor, Dr. William Tam for all of his support and guidance over the years. This Master’s would never have happened if it weren’t for your encouragement and faith in me as an undergraduate student.
    [Show full text]
  • Biodegradable Protein Nanocarriers for Drug Delivery Dissertation
    Biodegradable Protein Nanocarriers for Drug Delivery Dissertation zur Erlangung des akademischen Grades „Doktor der Naturwissenschaften“ im Promotionsfach Chemie am Fachbereich Chemie, Pharmazie und Geowissenschaften der Johannes Gutenberg-Universität Mainz vorgelegt von Keti Piradashvili Mainz 2016 Für meine Eltern Declaration I hereby declare that I wrote the dissertation submitted without any unauthorized external assistance and used only sources acknowledged in the work. All textual passages which are appropriated verbatim or paraphrased from published and unpublished texts as well as all information obtained from oral sources are duly indicated and listed in accordance with bibliographical rules. In carrying out this research, I complied with the rules of standard scientific practice as formulated in the statutes of Johannes Gutenberg-University Mainz to insure standard scientific practice. Mainz, 2016 Keti Piradashvili Amtierender Dekan: Prof. Dr. Dirk Schneider Erster Gutachter: Prof. Dr. Katharina Landfester Zweiter Gutachter: Prof. Dr. Stephan Gehring Tag der mündlichen Prüfung: Content CONTENT ABSTRACT IV ZUSAMMENFASSUNG VI MOTIVATION 1 1. THEORETICAL BACKGROUND 3 1.1 INTERFACIAL REACTIONS 3 1.1.1 EMULSIFICATION TECHNIQUES 4 1.1.2 REACTIONS AT THE (DROPLET) INTERFACE 9 1.1.3 POLYMERIZATIONS AT THE DROPLET INTERFACE 23 1.1.4 CONCLUSION 33 1.2 BIOORTHOGONAL CHEMISTRY 34 1.2.1 1,3-DIPOLAR TETRAZOLE-ENE CYCLOADDITION 39 1.2.2 BIOORTHOGONAL CHEMISTRY FOR NANOCAPSULE SYNTHESIS 41 2. RESULTS AND DISCUSSION 46 2.1 ALBUMIN NANOCONTAINERS
    [Show full text]
  • Metabolic Labelling of Bacterial Isoprenoids Produced by the Methylerythritol Phosphate Pathway : a Starting Point Towards a New Inhibitor
    UNIVERSITÉ DE STRASBOURG ÉCOLE DOCTORALE DES SCIENCES CHIMIQUES UMR 7177 & 7199 THÈSE présentée par : Zoljargal BAATARKHUU soutenue le : 05 Septembre 2017 pour obtenir le grade de : Docteur de l’université de Strasbourg Discipline/ Spécialité : Chimie Bio-Organique Metabolic labelling of bacterial isoprenoids produced by the Methylerythritol phosphate pathway : A starting point towards a new inhibitor THÈSE dirigée par : Dr Alain WAGNER Directeur de recherche, CNRS Dr Myriam SEEMANN Directeur de recherche, CNRS RAPPORTEURS : Dr Joelle DUBOIS Directeur de recherche, Institut de Chimie des Substances Naturelles, Paris Dr Alain BURGER Professeur, Université de Nice, Nice (In memory of my beloved memory of my (In father Baatarkhuu Dugajii) Résumé de thèse en français 1) Introduction Les isopréonoïdes forment une famille de produits naturels parmi les plus diverses avec plus de 50000 composés connus. 1 Ils sont présents dans tous les organismes vivants. Ils ont de nombreux rôles biologiques, allant du transport d’électrons, à la biosynthèse des membranes cellulaires. Malgré la diversité des isoprénoïdes, ils sont synthétisés à partir de deux précurseurs : le diphosphate d’isopentényle (IPP) et le diphosphate de diméthylallyle (DMAPP). Deux voies de biosynthèse existent pour la formation de ces molécules : la voie du mévalonate et la voie du méthylérythritol phosphate (MEP), découverte plus récemment. 2, 3 Cette dernière voie de synthèse est utilisée par les micro-organismes dont des pathogènes comme Mycobacterium tuberculosis (bactérie responsable de la tuberculose), Vibrio cholerae (bactérie responsable du choléra) et Plasmodium falciparum (parasite responsable de la malaria). Elle est cependant absente chez l’humain et, par conséquent, est une cible de choix pour le développement d’un nouveau médicament antibactérien ou antiparasitaire.
    [Show full text]
  • Bioorthogonal Bioconjugation
    Chemistry & Biology Review Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation Craig S. McKay1 and M.G. Finn1,* 1School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA *Correspondence: mgfi[email protected] http://dx.doi.org/10.1016/j.chembiol.2014.09.002 The selective chemical modification of biological molecules drives a good portion of modern drug develop- ment and fundamental biological research. While a few early examples of reactions that engage amine and thiol groups on proteins helped establish the value of such processes, the development of reactions that avoid most biological molecules so as to achieve selectivity in desired bond-forming events has revolution- ized the field. We provide an update on recent developments in bioorthogonal chemistry that highlights key advances in reaction rates, biocompatibility, and applications. While not exhaustive, we hope this summary allows the reader to appreciate the rich continuing development of good chemistry that operates in the bio- logical setting. Introduction: Bioorthogonal Click Chemistry oxygen and water (Kolb et al., 2001; Hawker and Wooley, Chemical biology involves the creation of nonbiological mole- 2005; Kolb and Sharpless, 2003; Wu et al., 2004). In vivo bio- cules that exert an effect on, or reveal new information about, orthogonal chemistry and click chemistry therefore overlap quite biological systems. Central to this field is the property of selec- a bit, reflecting the same underlying chemical principles applied tivity: ultimately, one wishes for molecules with perfectly selec- in somewhat different ways toward the discovery or develop- tive biological function, but in practice, one starts with as much ment of molecular function and information.
    [Show full text]
  • PDF Hosted at the Radboud Repository of the Radboud University Nijmegen
    PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/72445 Please be advised that this information was generated on 2021-10-09 and may be subject to change. Thrombin Generation Molecules and Tools Een wetenschappelijke proeve op het gebied van de Natuurwetenschappen, Wiskunde en Informatica Proefschrift ter verkrijging van de graad van doctor aan de Radboud Universiteit Nijmegen op gezag van de rector magnificus prof. mr. S.C.J.J. Kortmann, volgens besluit van het College van Decanen in het openbaar te verdedigen op maandag 3 november 2008 om 15:30 uur precies door Sander Sebastiaan van Berkel geboren op 19 juni 1979 te de Bilt Promotores: Prof. dr. F.P.J.T. Rutjes Prof. dr. H.C. Hemker (Universiteit Maastricht) Co-promotor: Dr. F.L. van Delft Manuscriptcommissie: Prof. dr. ir. J.C.M. van Hest Dr. ir. P.J.L.M. Quaedflieg (DSM Pharmaceutical Products, Geleen) Dr. ir. D.T.S. Rijkers (Universiteit Utrecht) Paranimfen: Stan Groothuys Ton Dirks The research described in this thesis was financially supported by the Council of the Technical Sciences (STW) of the Netherlands Organization for Scientific Research. van Berkel, S.S. (Sander) Thrombin Generation; Tools and Molecules Printing: PrintPartners Ipskamp ISBN: 90-9023540-0 Cover design: Remko van Vught No part of this book may be reproduced by any mechanical, photographic or electronic process, nor may it be stored in a retrieval system, transmitted, or otherwise copied for public or private use without the written permission of the author.
    [Show full text]
  • Site-, Enantio- and Stereo-Selectivities of the 1,3-Dipolar Cycloaddition Reactions of Oxanorbornadiene with C,N-Disubstituted N
    Theoretical Chemistry Accounts (2020) 139:16 https://doi.org/10.1007/s00214-019-2529-8 REGULAR ARTICLE Site‑, enantio‑ and stereo‑selectivities of the 1,3‑dipolar cycloaddition reactions of oxanorbornadiene with C,N‑disubstituted nitrones and dimethyl nitrilimines: a DFT mechanistic study Ernest Opoku1 · Grace Arhin1 · George Bafour Pipim1 · Anita Houston Adams1 · Richard Tia1 · Evans Adei1 Received: 9 September 2019 / Accepted: 15 December 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2020 Abstract 1,3-Dipolar cycloaddition of nitrones to oxanorbornadienes is an important method for the enantioselective synthesis of highly substituted 5-membered heterocycles such as furans and isoxazolidines, which have high utility in the chemical and pharmaceutical industries. The mechanism of the reaction and the efects of substituents on the (3 + 2) cycloaddition reactions (32CA) of C,N-dialkyl nitrones with a series of substituted oxanorbornadienes have been studied with focus on the site-selectivity (attack on the more substituted double bond of the oxanorbornadiene derivatives versus attack on the less substituted double bond), enantioselectivity and stereo-selectivity using density functional theory calculations at the M06/6-311++G(d,p) of theory. The results showed that the addition step to form the bicyclic isoxazolidines cycloadducts has generally low barriers compared to the cycloreversion step which converts the cycloadducts into furans and monocyclic isoxazolidines. Generally, electron-withdrawing substituents favour the nitrone attack on the highly substituted double bond, while electron-donating substituents favour the attack on less substituted double bond. The R enantiomers are generally favoured over the S enantiomers, and exo stereo-isomers are generally favoured over the endo stereo-isomers, irrespective of substituents.
    [Show full text]
  • ECSOC-10 Hall A. General Organic Synthesis. A026
    10th International Electronic Conference on Synthetic Organic Chemistry (ECSOC-10). 1-30 November 2006. http://www.usc.es/congresos/ecsoc/10/ECSOC10.htm & http://www.mdpi.org/ecsoc-10/ [a026] Zagreb, Croatia University of Wollongong NSW Australia The Preparation of 7-Substituted Norbornadiene-2,3-dicarboxylic Anhydrides and a Theoretical and Experimental Study of their Thermolysis to 5-Membered Carbocyclic or Heterocyclic Anhydrides Davor Margetić*A, Ronald N. WarrenerB, Guangxing SunC and Douglas N. ButlerB A Laboratory for Physical Organic Chemistry, Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia (e-mail: [email protected]) B Intelligent Polymer Research Institute, The University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia C current address: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA Abstract. New substituted methano-bridged or heteroatom-bridged norbornadienomaleic anhydrides have been prepared and converted to sesquinorbornadiene anhydrides by reaction with cyclic 1,3-dienes. The versatility of parity reversal, in conjuction with N-substituent steric effects, has been used to produce stereoisomers of the N,O-sesquinorbornadiene anhydrides in separate, stereoselective cycloadditions. The anhydrides have been synthesized by cyclisation of their diacids (in situ production) or by flash vacuum pyrolysis of their furan adducts (yielding crystalline products); further fragmentation occurs at these or higher temperatures to produce five-membered carbocyclic or heterocyclic anhydrides. Activation energies have been evaluated for the two fragmentation processes and Diels-Alder reactions using DFT calculations (B3LYP/6-31G*) and these calculations correctly predict which reactions can be intercepted at the norbornadienomaleic anhydride stage.
    [Show full text]
  • Furan Denvatives and an Acetylenic Bis-Dienophile for the Rapid Construction of Bndged Polyoxacyclic Ring Systems
    The Development of New Oxabicyclic-Based Strategies for the Stereo- and Enantioselective Synthesis of Azepines, Thiepines and Thiocines, Polysubstituted Decalins and Related Fused Polycycles by Eric Fillion A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Graduate Department of Chemistry University of Toronto Q Copyright by Eric Fion (1998) National Library Bibliothèque nationale du Canada Acquisitions and Acquisitions et Bibliographie Services senrices bibliographiques 395 Wellington Street 395, rue Wellington OttawaON K1AW OttawaON KIAON4 Canada Canada The author has granted a non- L'auteur a accordé une licence non exclusive licence allowing the exclusive permettant B la National Library of Canada to ~ibliothé~uenationale du Canada de reproduce, loan, distriiute or sel1 reproduire, prêter, distribuer ou copies of this thesis in microform, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfiche/nlm, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantïal extracts f?om it Ni la thèse ni des extraits substantieIs may be printed or otherwise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation. 0 bjectives The synthesis and investigation of the reactivity of dioxatetra- and pentacycles, as weil as hetero-oxabicycles were the overall objectives. The utility of these rigid templates in the development of new enantio- and stereoselective synthetic strategies toward seven- and eight- membered nitrogen and sulfur heterocycles, polysubstituted decalins and related fused polyc ycles was defined.
    [Show full text]
  • Organic & Biomolecular Chemistry PAPER
    View Article Online / Journal Homepage / Table of Contents for this issue Organic & Dynamic Article Links Biomolecular Chemistry Cite this: Org. Biomol. Chem., 2012, 10, 5547 www.rsc.org/obc PAPER Bioorthogonal metal-free click-ligation of cRGD-pentapeptide to alginate† Andreas Krause, Andreas Kirschning and Gerald Dräger* Received 22nd March 2012, Accepted 1st June 2012 DOI: 10.1039/c2ob25604e “Click” reactions have become very common and powerful ligation techniques, of which 1,3-dipolar cycloadditions have most frequently been employed. Since metal-mediated cycloadditions are incompatible in biomedical applications due to toxicity issues associated with transition metals like copper, metal-free variants provide important alternatives. The metal-free conjugation process is studied in detail with special emphasis put on the reaction progress. This report unfolds the first aqueous metal- free “click” conjugation of a cyclic RGD-pentapeptide with the biomacromolecule alginate, creating a “smart” bioactive polymer with potential applications in biomedicine. Introduction The last decade has seen the development of powerful synthetic methods to link or merge biomolecules with each other or other complex molecular entities. Terms like “click” reactions and chemical ligation are associated with this chemistry that has paved the way to specifically modify complex biological systems at will.1 In this context, the preparation of peptide–polymer bio- conjugates is a very important issue that can be realised by “grafting onto” or by “grafting from” approaches.2 The most “ ” popular grafting to technique is the copper-mediated Huisgen- Scheme 1 Structures of alginate 1 and azido-derivatised cyclic RGD- type 1,3-dipolar cycloaddition, first reported by Meldal and pentapeptide 2.
    [Show full text]
  • The Diels±Alder Reaction
    The Diels±Alder Reaction: Selected Practical Methods Edited by Francesco Fringuelli and Aldo Taticchi Copyright # 2002 John Wiley & Sons,Ltd ISBNs: 0-471-80343-X -Hardback); 0-470-84581-3 -Electronic) The Diels±Alder Reaction The Diels±Alder Reaction: Selected Practical Methods Edited by Francesco Fringuelli and Aldo Taticchi Copyright # 2002 John Wiley & Sons,Ltd ISBNs: 0-471-80343-X -Hardback); 0-470-84581-3 -Electronic) The Diels±Alder Reaction Selected Practical Methods Francesco Fringuelli UniversitaÁ degli Studi di Perugia, Italy Aldo Taticchi UniversitaÁ degli Studi di Perugia, Italy The Diels±Alder Reaction: Selected Practical Methods Edited by Francesco Fringuelli and Aldo Taticchi Copyright # 2002 John Wiley & Sons,Ltd ISBNs: 0-471-80343-X -Hardback); 0-470-84581-3 -Electronic) Copyright # 2002 John Wiley & Sons,Ltd Baffins Lane,Chichester, West Sussex,PO19 1UD,England National 01243 779777 International -44) 1243 779777 e-mail -for orders and customer service enquiries): [email protected] Visit our Home Page on http://www.wiley.co.uk or http://www.wiley.com All Rights Reserved. No part of this publication may be reproduced,stored in a retrieval system,or transmitted,in any form or by any means,electronic,mechanical,photocopying,recording, scanning or otherwise,except under the terms of the Copyright Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency Ltd,90 Tottenham Court Road,London W1P 0LP,UK,without the permission in writing of the Publisher. Other Wiley Editorial Offices John Wiley & Sons,Inc.,605 Third Avenue, New York,NY 10158±0012,USA WILEY-VCH Verlag GmbH Pappelallee 3,D-69469 Weinheim,Germany John Wiley & Sons Australia,Ltd 33 Park Road,Milton,Queensland 4064,Australia John Wiley & Sons -Canada) Ltd,22 Worcester Road Rexdale,Ontario,M9W 1L1,Canada John Wiley & Sons -Asia) Pte Ltd,2 Clementi Loop #02±01, Jin Xing Distripark,Singapore 129809 Library of Congress Cataloging-in-Publication Data Fringuelli,Francesco.
    [Show full text]