DOCSLIB.ORG

Novel Process Windows: Reactions Using Tricky Reagents

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Novel Process Windows: Reactions Using Tricky Reagents Novel Process Windows: Reactions Using Tricky Reagents A Thesis Submitted to Cardiff University in Fulfilment of the Requirements for the Degree of Doctor of Philosophy by Matthew John Hutchings PhD Thesis October 2016 Cardiff University I II DECLARATION This work has not been submitted in substance for any other degree or award at this or any other university or place of learning, nor is being submitted concurrently in candidature for any degree or other award. Signed ................................................ (Matthew Hutchings) Date .............................. STATEMENT 1 This thesis is being submitted in partial fulfillment of the requirements for: the Degree of Doctor of Philosophy Signed ................................................ (Matthew Hutchings) Date .............................. STATEMENT 2 This thesis is the result of my own independent work/investigation, except where otherwise stated. Other sources are acknowledged by explicit references. The views expressed are my own. Signed ................................................ (Matthew Hutchings) Date .............................. STATEMENT 3 I hereby give consent for my thesis, if accepted, to be available for photocopying and for inter- library loan, and for the title and summary to be made available to outside organisations. Signed ................................................ (Matthew Hutchings) Date ............................ III CANDIDATES LAST NAME HUTCHINGS CANDIDATES FIRST NAME(S) MATTHEW CANDIDATES ID NUMBE R 0704493 SCHOOL CHEMISTRY Please circle appropriate degree title TITLE OF DEGREE EdD, EngD, DSW, DClinPsy, DHS, MCh, MD, MPhil, MScD by Research, PhD Novel process windows: reactions using tricky FULL TITLE OF THESIS reagents IS THIS A RESUB MISSION? YES / NO Permanent binding [ ] THESIS SUBMITTED FOR EXAMINATION IN Temporary binding [ ] CANDIDATES DATE SIGNATURE IV Acknowledgments Firstly, I would like to thank my supervisor Professor Thomas Wirth who gave me the opportunity to research the field of flow chemistry within his group. His guidance and tutorship has been invaluable. Furthermore, I would like to thank the members of my research group Dr. Fateh, Dr Munawwer, Dr Ravi, Dr Pushpak, Dr. Kenta, Dr Nida, Dr Mike, Dr Umar, Dr Kevin, Dr Guillaume, Richard, Alastair, Simon, Florence, Ana, Filipa, Mohammad. I would further like to acknowledge the technical support staff at the Cardiff School of Chemistry, Dr Rob Jenkins, Sham Ali, Robin Hicks, Dave Walker and Simon Waller. Lastly I would like to give a big thanks to the engineering department Alun Davies and Steven Morris for their help in repairs of flow equipment within my time here. V List of Abbreviations Å Angstrøm Ac Acetyl AIBN Azobisisobutyronitrile Ar Aryl BPR Back Pressure Regulator CV Column volumes DBN 1,5-Diazabicyclo(4.3.0)non-5-ene DBU 1,8-Diazabicycloundec-7-ene (DHQ) 2PHAL Hydroquinine 1,4 -phthalazinediyl diether DIAD Diisopropyl azodicarboxylate DIB Diacetoxyiodobenzene DMF Dimethylformamide DMP Dess –Martin periodinane DPPA Diphenylphosphoryl azide dppp 1,3-Bis(diphenylphosphino)propane DMSO Dimethylsulfoxide Et Ethyl FIBX (2,4,5,6-Tetra -fluoro) 2-iodoxybenzoic acid GPR Gas Pressure Regulator h Hour/hours HPLC High pressure liquid chromatography HRMS High resolution mass spectrometry IBX 2-Iodoxybenzoic acid iNOC isonicotinyloxycarbonyl IR Infra-red Hz Hertz mA milliamp µm micrometre m-CPBA m- Chloroperoxybenzoic acid VI Me Methyl MFC Mass Flow Control MHz Megahertz min Minute m.p. Melting point m/z Mass over charge ratio NIS N-iodosuccinimide NMR Nuclear magnetic resonance o.n. overnight PET Positron emission tomography PIFA [Bis(trifluoroacetoxy)iodo]benzene pKa Acid dissociation constant ppm parts per million Ph Phenyl Pr Propyl PTC phase transfer catalysis/catalyst Re Reynold’s Number rt Room temperature T3P Propylphosphonic anhydride TBD 1,5,7-Triazabicyclo[4.4.0]dec-5-ene t-Bu t-Butyl TEA Triethylamine TEMPO 2,2,6,6-Tetramethyl-1-piperidinyloxyl TFA Trifluoroacetic acid THF Tetrahydrofuran TMEDA N,N,N′,N′ -Tetramethylethylenediamine TMS Trimethylsilyl TTMS Tetramethylsilane VII Abstract Flow chemistry has been increasingly used in the last decade as an alternative method to batch chemistry. This methodology allows for conditions that would be unattainable under batch techniques due to the high temperature control, selectivity and safety that flow chemistry allows. The diazidation of styrenes has been investigated under continuous flow conditions, where the inherent safety of flow chemistry allows the use of azides without the concerns usually associated with these reagents. Secondly, the nitroaldol reaction has been transferred to flow conditions. This highlights the safety of continuous flow procedures, as the use of a highly energetic reagent such as nitromethane is easily possible.. The Koch-Haaf carbonylation reaction was investigated to demonstrate the use of gases in flow chemistry and the safe handling of toxic gases such as carbon monoxide. Finally the Ritter reaction was used to further demonstrate the suitability of flow chemistry for highly exothermic reactions using concentrated acids; where the temperature control allows for high selectivities. VIII 2.1 Contents Acknowledgments ......................................................................................................................... 5 List of Abbreviations ..................................................................................................................... 6 Abstract ......................................................................................................................................... 8 1.1 Advantages of Flow Chemistry...................................................................................... 1 1.2 Organic s ynthesis promoted by flow chemistry’s properties ....................................... 4 1.1.1 Single Phase Reactions .......................................................................................... 4 1.1.2 Liquid-Liquid Biphasic Reactions ........................................................................... 6 1.3 Heterogeneous conditions ............................................................................................ 8 1.1.3 Gas liquid conditions ............................................................................................. 8 1.1.4 Solid liquid conditions ......................................................................................... 11 1.4 Miscellaneous techniques ........................................................................................... 13 1.5 Multi-Step Synthesis ................................................................................................... 16 1.6 In-line Analysis and automated control ...................................................................... 18 1.7 Scaling up .................................................................................................................... 21 2.1 Introduction to diazidation reactions ............................................................................. 23 2.1.1 Azides in organic synthesis.................................................................................. 23 2.1.2 Azide chemistry in microreactors ....................................................................... 25 2.1.3 Iodine reagents and their use in diamination reactions ..................................... 31 2.1.4 Hypervalent iodine compounds in combination with azides.............................. 36 2.1.5 Aims of project .................................................................................................... 44 2.2 Results and Discussions .................................................................................................. 46 2.2.1 Initial diazidation conditions ............................................................................... 46 2.2.2 Stereoselective diazidations ............................................................................... 50 2.2.3 Catalytic diazidations .......................................................................................... 54 2.2.4 Flow conditions ................................................................................................... 56 2.2.5 Azido thiocyanation. ........................................................................................... 61 2.2.6 Results ................................................................................................................. 65 IX 2.3 Concluding remarks and Future work ............................................................................. 67 3.1 Introduction to nitroaldol reactions ............................................................................... 68 3.1.1 Nitromethane: A highly energetic chemical ........................................................... 68 3.1.2 Synthesis of compounds containing nitro groups................................................... 70 3.1.3 The Nitroaldol Reaction .......................................................................................... 72 3.1.4 Utilization of the nitro group .................................................................................. 76 3.2 Results and Discussion .................................................................................................... 77 3.2.1 Initial Flow Conditions ............................................................................................. 77 3.2.2 Chiral synthesis ......................................................................................................
Load more

Recommended publications
  • (Nitroaldol) Reaction
    MICROREVIEW DOI: 10.1002/ejoc.201101840 Biocatalytic Approaches to the Henry (Nitroaldol) Reaction Sinéad E. Milner,[a] Thomas S. Moody,[b] and Anita R. Maguire*[c] Keywords: Enzyme catalysis / Biocatalysis / C–C coupling / Nitroaldol reaction / Nitro alcohols Enantiopure β-nitro alcohols are key chiral building blocks approaches to the Henry (nitroaldol) reaction. The first for the synthesis of bioactive pharmaceutical ingredients. method is a direct enzyme-catalysed carbon–carbon bond The preparation of these target compounds in optically pure formation resulting in either an enantio-enriched or enantio- form has been the focus of much research and there has been pure β-nitro alcohol. The second approach describes the an emergence of biocatalytic protocols in the past decade. Henry reaction without stereocontrol followed by a biocata- For the first time, these biotransformations are the focus of lytic resolution to yield the enantiopure β-nitro alcohol. this review. Herein, we describe two principal biocatalytic Introduction The construction of carbon–carbon bonds is an essential element of synthetic organic chemistry. Among the various C–C bond forming reactions, the nitroaldol or Henry reac- tion[1] is one of the classical named reactions in organic synthesis. Essentially, this reaction describes the coupling of a nucleophilic nitro alkane with an electrophilic aldehyde or ketone to produce a synthetically useful β-nitro alcohol (Scheme 1).[2–5] Moreover, the Henry reaction facilitates the joining of two molecular fragments, under mild reaction conditions with the potential formation of two new ste- reogenic centres and a new C–C bond. The resulting β-nitro alcohols can undergo a variety of useful chemical transfor- mations which lead to synthetically useful structural motifs, e.g.
    [Show full text]
  • Nitroso and Nitro Compounds 11/22/2014 Part 1
    Hai Dao Baran Group Meeting Nitroso and Nitro Compounds 11/22/2014 Part 1. Introduction Nitro Compounds O D(Kcal/mol) d (Å) NO NO+ Ph NO Ph N cellular signaling 2 N O N O OH CH3−NO 40 1.48 molecule in mammals a nitro compound a nitronic acid nitric oxide b.p = 100 oC (8 mm) o CH3−NO2 57 1.47 nitrosonium m.p = 84 C ion (pKa = 2−6) CH3−NH2 79 1.47 IR: υ(N=O): 1621-1539 cm-1 CH3−I 56 Nitro group is an EWG (both −I and −M) Reaction Modes Nitro group is a "sink" of electron Nitroso vs. olefin: e Diels-Alder reaction: as dienophiles Nu O NO − NO Ene reaction 3 2 2 NO + N R h 2 O e Cope rearrangement υ O O Nu R2 N N N R1 N Nitroso vs. carbonyl R1 O O O O O N O O hυ Nucleophilic addition [O] N R2 R O O R3 Other reaction modes nitrite Radical addition high temp low temp nitrolium EWG [H] ion brown color less ion Redox reaction Photochemical reaction Nitroso Compounds (C-Nitroso Compounds) R2 R1 O R3 R1 Synthesis of C-Nitroso Compounds 2 O R1 R 2 N R3 3 R 3 N R N R N 3 + R2 2 R N O With NO sources: NaNO2/HCl, NOBF4, NOCl, NOSbF6, RONO... 1 R O R R1 O Substitution trans-dimer monomer: blue color cis-dimer colorless colorless R R NOBF OH 4 - R = OH, OMe, Me, NR2, NHR N R2 R3 = H or NaNO /HCl - para-selectivity ΔG = 10 Kcal mol-1 Me 2 Me R1 NO oxime R rate determining step Blue color: n π∗ absorption band 630-790 nm IR: υ(N=O): 1621-1539 cm-1, dimer υ(N−O): 1300 (cis), 1200 (trans) cm-1 + 1 Me H NMR (α-C-H) δ = 4 ppm: nitroso is an EWG ON H 3 Kochi et al.
    [Show full text]
  • Selenium Stabilized Carbanions. Preparation of A-Lithio Selenides and Applications to the Synthesis of Olefins by Reductive Elim
    6638 Journal of the American Chemical Society / 101:22 / October 24, I979 Selenium Stabilized Carbanions. Preparation of a-Lithio Selenides and Applications to the Synthesis of Olefins by Reductive Elimination of ,&Hydroxy Selenides and Selenoxide Syn Elimination Hans J. Reich,** Flora Chow, and Shrenik K. Shah Contribution from the Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706. Received May 10, 1979 Abstract: The deprotonation of several alkyl aryl selenides with lithium amide bases has been studied. The kinetic acidity of methyl m-trifluoromethylphenyl selenide was found to be 1/33 that of the sulfur analogue. The introduction of a m-trifluoro- methyl substituent into methyl phenyl sulfide increased the kinetic acidity by a factor of 22.4. A variety of @-hydroxy selenides have been prepared by the reduction of a-phenylseleno ketones and the addition of a-lithio selenides (prepared by deprotona- tion of benzyl phenyl selenide, bis(phenylseleno)methane, methoxymethyl m-trifluoromethylphenyl selenide, and phenylsele- noacetic acid, and by n-butyllithium cleavage of bis(pheny1seleno)methane) to carbonyl compounds. These @-hydroxyselen- ides are converted to olefins on treatment with rnethanesulfonyl chloride and triethylamine. This reductive elimination pro- ceeds exclusively or predominantly with anti stereochemistry. Simple olefins, styrenes, cinnamic acids, vinyl ethers, and vinyl selenides have been prepared using this technique. Attempts to carry out the syn reductive elimination of @-hydroxyselenox-
    [Show full text]
  • John Ulric N E F
    NATIONAL ACADEMY OF SCIENCES JOHN ULRIC N EF 1862—1915 A Biographical Memoir by M E L V I L L E L . W O L F R O M Any opinions expressed in this memoir are those of the author(s) and do not necessarily reflect the views of the National Academy of Sciences. Biographical Memoir COPYRIGHT 1960 NATIONAL ACADEMY OF SCIENCES WASHINGTON D.C. JOHN ULRIC NEF' June 14,1862-August 13,1915 BY MELVILLE L. WOLFROM OHN ULRIC NEF was a great pioneer in American chemistry. It was J he, along with Arthur Michael and Ira Remsen, who was mainly responsible for the transfer to the universities of the United States of the tenets of the actively growing science of organic chemistry from the laboratories of the great European universities of the time. Nef was a pioneer in theoretical organic chemistry, a great experimental- ist, and an inspiring trainer of men. His advanced students, the Ph.D. trainees, went into positions in the American universities, and espe- cially in the Middle West, determined to carry on the tradition of research. In the words of one: "We were determined to keep some research going if it were only to boil water." This establishment of chemical research in the American universities was carried out under the most difficult of conditions and with little support or understand- ing on the part of the administrators of these growing institutions, who mainly considered the science departments, in the liberal arts colleges, as units which cost a lot of money and produced results of doubtful cultural value.
    [Show full text]
  • Cu-Catalyzed Cross-Dehydrogenative Coupling: a Versatile Strategy for C–C Bond Formations Via the Oxidative Activation of Sp3 C–H Bonds
    Cu-catalyzed cross-dehydrogenative coupling: A versatile strategy for C–C bond formations via the oxidative activation of sp3 C–H bonds Zhiping Li, D. Scott Bohle*, and Chao-Jun Li† Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC, Canada H3A 2K6 Edited by Jack Halpern, University of Chicago, Chicago, IL, and approved April 12, 2006 (received for review February 28, 2006) Cu-catalyzed cross-dehydrogenative coupling (CDC) methodolo- gies were developed based on the oxidative activation of sp3 C–H bonds adjacent to a nitrogen atom. Various sp, sp2, and sp3 C–H bonds of pronucleophiles were used in the Cu-catalyzed CDC reactions. Based on these results, the mechanisms of the CDC reactions also are discussed. C–H activation ͉ catalysis ͉ Baylis–Hillman reaction ͉ Mannich reaction ͉ Friedel–Crafts reaction –C bond formation reactions are among the most important Cprocesses in organic chemistry. Transition metal-catalyzed Scheme 1. Various cross-coupling methods for the formation of C–C bonds. cross-coupling reactions of various reactive functional groups are newer and more powerful methods for the formation of C–C bonds tromethane serving as both the reagent and solvent. Various copper [Scheme 1, Path A (1)]. However, these well developed cross- catalysts, such as CuCl, CuBr, CuI, Cu(OTf), CuCl , CuBr , coupling reactions must use prefunctionalized starting materials. 2 2 Cu(OTf) , and Cu(OAc) ⅐H O, were examined at room tempera- Therefore, in the formation of a single chemical bond, an extra 2 2 2 ture (RT), and the desired product was obtained in all cases.
    [Show full text]
  • Green Synthesis of Carboxylic Acids and Esters
    Molecules 2015, 20, 10496-10510; doi:10.3390/molecules200610496 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Article Selenium Catalyzed Oxidation of Aldehydes: Green Synthesis of Carboxylic Acids and Esters Luca Sancineto 1,†, Caterina Tidei 1,†, Luana Bagnoli 1, Francesca Marini 1, Eder J. Lenardão 2 and Claudio Santi 1,* 1 Group of Catalysis and Organic Green Chemistry, Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, Perugia 06100, Italy; E-Mails: sancineto.luca@gmail.com (L.S.); caterinatidei@libero.it (C.T.); luana.bagnoli@unipg.it (L.B.); francesca.marini@unipg.it (F.M.) 2 Laboratório de Síntese Orgânica Limpa (LASOL), Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Universidade Federal de Pelotas (UFPel), P.O. Box 354, Pelotas 96010-900, Brazil; E-Mail: lenardao@ufpel.edu.br † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: claudio.santi@unipg.it; Tel.: +39-75-585-5102; Fax: +39-75-585-5116. Academic Editor: Thomas G. Back Received: 30 April 2015 / Accepted: 3 June 2015 / Published: 8 June 2015 Abstract: The stoichiometric use of hydrogen peroxide in the presence of a selenium-containing catalyst in water is here reported as a new ecofriendly protocol for the synthesis of variously functionalized carboxylic acids and esters. The method affords the desired products in good to excellent yields under very mild conditions starting directly from commercially available aldehydes. Using benzaldehyde as a prototype the gram scale synthesis of benzoic acid is described, in which the aqueous medium and the catalyst could be recycled at last five times while achieving an 87% overall yield.
    [Show full text]
  • Nitroalkanes As Central Reagents in the Synthesis of Spiroketals
    Molecules 2008, 13, 319-330 molecules ISSN 1420-3049 © 2008 by MDPI www.mdpi.org/molecules Review Nitroalkanes as Central Reagents in the Synthesis of Spiroketals Roberto Ballini 1,*, Marino Petrini 1 and Goffredo Rosini 2 1 Dipartimento di Scienze Chimiche, Università di Camerino, via S.Agostino, 1, I-62032 Camerino, Italy; E-mail: marino.petrini@unicam.it. 2 Dipartimento di Chimica Organica ‘A. Mangini’, Alma Mater Studiorum–Università di Bologna, Viale del Risorgimento n. 4, 40136 Bologna, Italy; E-mail: goffredo.rosini@unibo.it. * Author to whom correspondence should be addressed; E-mail: roberto.ballini@unicam.it; Fax: +39 0737 402297 Received: 8 January 2008; in revised form: 2 February 2008 / Accepted: 4 February 2008 / Published: 7 February 2008 Abstract: Nitroalkanes can be profitably employed as carbanionic precursors for the assembly of dihydroxy ketone frameworks, suitable for the preparation of spiroketals. The carbon-carbon bond formation is carried out exploiting nitroaldol and Michael reactions, while the nitro to carbonyl conversion (Nef reaction) ensures the correct introduction of the keto group. Several spiroketal systems endowed with considerable biological activity can be prepared using this synthetic strategy. Keywords: Conjugate addition, Nef reaction, nitroaldol reaction, nitroalkanes, spiroketals. 1. Introduction The spiroketal moiety is a key motif embodied in a large number of natural products present in plants, fungi, insect secretions, shellfish toxins and other living organisms [1-5]. Many of these compounds also display a considerable biological activity as antibiotics and pheromones. From a synthetic standpoint, among various practical strategies currently available for the assembling of the spiroketal unit, the one based on the acid promoted intramolecular acetalization of dihydroxy ketone derivatives 1 firmly occupies a prominent position (Scheme 1).
    [Show full text]
  • Conjugate Additions of Nitroalkanes to Electron-Poor Alkenes: Recent Results
    Chem. Rev. 2005, 105, 933−971 933 Conjugate Additions of Nitroalkanes to Electron-Poor Alkenes: Recent Results Roberto Ballini,* Giovanna Bosica, Dennis Fiorini, Alessandro Palmieri, and Marino Petrini* Dipartimento di Scienze Chimiche, Universita` di Camerino, via S. Agostino, 1, I-62032 Camerino, Italy Received September 30, 2004 Contents Conjugate additions using highly stabilized carban- ions are still of interest since a growing number of 1. Introduction 933 these procedures can be carried out in environmen- 2. General Aspects of the Conjugate Addition of 934 tally benign solvents such as water and using cata- Nitroalkanes lytic amounts of the basic promoter. In addition, the 2.1. Multiple Additions 934 achievement of diastereo- and enantioselective pro- 2.2. Basic Catalysts 935 cesses is no longer an exclusive domain of highly 3. New Basic Catalysts for the Conjugate Addition 936 reactive carbanionic systems working in carefully 4. Diastereoselective Conjugate Additions 936 controlled conditions3 but can be nowadays conducted 4.1. Intermolecular Additions 936 even at room temperature using easily available 4.2. Intramolecular Additions 948 substrates and suitable base/solvent combinations. 5. Asymmetric Conjugate Additions Promoted by 949 Nitroalkanes are a valuable source of stabilized Chiral Catalysis carbanions since the high electron-withdrawing power 6. Conjugate Addition−Elimination Reactions 953 of the nitro group provides an outstanding enhance- R 7. Synthetic Applications 957 ment of the hydrogen acidity at the -position (cf. pka ) 4-8 7.1. Pyrrolidines and Derivatives 957 MeNO2 10). Nitronate anions 2 that can be generated from nitroalkanes 1 using a wide range of 7.2. Lactones and Oxygenated Heterocycles 960 bases act as carbon nucleophiles with common elec- 7.3.
    [Show full text]
  • Stereoselective Reactions of Organoselenium Compounds
    Organoselenium Chemistry Authors: Fateh V. Singh, Thomas Wirth Address: VIT University, Chennai Campus, Vandalur-Kelambakkam Road, Chennai-600127, Tamil Nadu, India Cardiff University, School of Chemistry, Main Building, Park Place, Cardiff CF10 3AT, United Kingdom Email: wirth@cf.ac.uk 1 1. Introduction Organoselenium chemistry has been established as valuable research area in synthetic and medicinal chemistry.1-11 After the discovery of the selenoxide elimination reaction in early 1970s,12-14 organoselenium reagents received the great success in organic synthesis including asymmetric synthesis.15-18 More commonly, synthetic transformations such as selenenylations, selenocyclizations and 2,3-sigmatropic rearrangements have been successfully achieved using these reagents under mild reaction conditions.19-33 The application of these reagents in catalysis makes them more suitable reagents in organic synthesis.34-39 Several books,1-7, 41-43 book chapters8-11, 44-48 and review articles49-64 have been published to explain the utility of organoselenium reagents in synthesis. This chapter highlights the application of organoselenium reagents in organic synthesis including asymmetric synthesis. 2. Organoselenium Reagents As Electrophiles Organoselenium reagents play different roles in organic reactions but mainly known for their electrophilic behaviour. The electrophilic selenium species can be generated by the cleavage of the Se-Se bond of diselenides and can be used to activate the olefinic double bonds. Due to their electrophilic character, selenium electrophiles react with olefinic double bonds to form three membered seleniranium ion intermediate. Furthermore, the seleniranium ion intermediate can be employed to achieve various selenenylation reactions with different nucleophiles. 2.1. Selenenylation Reactions 2 Selenium electrophiles have been successfully used to achieve various selenylation reactions such as selenylation of olefins, arenes and other organic species.
    [Show full text]
  • Visible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic Synthesis Christopher K
    Review pubs.acs.org/CR Visible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic Synthesis Christopher K. Prier, Danica A. Rankic, and David W. C. MacMillan* Merck Center for Catalysis at Princeton University, Princeton, New Jersey 08544, United States References 5360 1. INTRODUCTION CONTENTS A fundamental aim in the field of catalysis is the development 1. Introduction 5322 of new modes of small molecule activation. One approach 2+ toward the catalytic activation of organic molecules that has 2. Photochemistry of Ru(bpy)3 5323 3. Net Reductive Reactions 5324 received much attention recently is visible light photoredox 3.1. Reduction of Electron-Poor Olefins 5324 catalysis. In a general sense, this approach relies on the ability of 3.2. Reductive Dehalogenation 5326 metal complexes and organic dyes to engage in single-electron- 3.3. Reductive Cleavage of Sulfonium and transfer (SET) processes with organic substrates upon Sulfonyl Groups 5328 photoexcitation with visible light. 3.4. Nitrogen Functional Group Reductions 5329 Many of the most commonly employed visible light 3.5. Radical Cyclizations 5330 photocatalysts are polypyridyl complexes of ruthenium and iridium, and are typified by the complex tris(2,2′-bipyridine) 3.6. Reductive Epoxide and Aziridine Opening 5331 2+ 3.7. Reduction-Labile Protecting Groups 5331 ruthenium(II), or Ru(bpy)3 (Figure 1). These complexes 4. Net Oxidative Reactions 5332 4.1. Functional Group Oxidations 5332 4.2. Oxidative Removal of the PMB Group 5334 4.3. Oxidative Biaryl Coupling 5335 4.4. Oxidative Generation of Iminium Ions 5335 4.5. Azomethine Ylide [3 + 2] Cycloadditions 5338 4.6.
    [Show full text]
  • Part I Α,Β‑Dehydrogenation of Carbonyl Compounds Via Selenium Reagents Elimination Part II Indium Catalyzed Cyclization Reaction of Acrylate
    This document is downloaded from DR‑NTU (https://dr.ntu.edu.sg) Nanyang Technological University, Singapore. Part I α,β‑dehydrogenation of carbonyl compounds via selenium reagents elimination Part II Indium catalyzed cyclization reaction of acrylate Zhang, Qiuchi 2019 Zhang, Q. (2019). Part I α,β‑dehydrogenation of carbonyl compounds via selenium reagents elimination Part II Indium catalyzed cyclization reaction of acrylate. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/83381 https://doi.org/10.32657/10220/47601 Downloaded on 23 Sep 2021 15:44:23 SGT PART I: DEHYDRO OF THIOESTERS PART II: INDIUM CATALYZED CYCLIZATION. CYCLIZATION. CATALYZED II: INDIUM THIOESTERS PART I: DEHYDRO OF PART PART I: DEHYDROGENATION OF CARBONYL COMPOUNDS VIA SELENIUM REAGENTS ELIMINATION. PART II: INDIUM CATALYZED CYCLIZATION REACTION OF ACRYLATE. ZHANG QIUCHI ZHANG QIUCHI 2018 SCHOOL OF PHYSICAL ANDMATHEMATICAL SCIENCES 2019 i PART I: α,β-DEHYDROGENATION OF CARBONYL COMPOUNDS VIA SELENIUM REAGENTS ELIMINATION. PART II: INDIUM CATALYZED CYCLIZATION REACTION OF ACRYLATE. ZHANG QIUCHI School of Physical and Mathematical Sciences A thesis submitted to the Nanyang Technological University in partial fulfillment of the requirement for the degree of Doctor of Philosophy 2019 ii Statement of Originality I hereby certify that the work embodied in this thesis is the result of original research, is free of plagiarised materials, and has not been submitted for a higher degree to any other University or Institution. 3 Supervisor Declaration Statement I have reviewed the content and presentation style of this thesis and declare it is free of plagiarism and of sufficient grammatical clarity to be examined.
    [Show full text]
  • Nitrile N-Oxides and Nitrile Imines As Electrophilic Partners For
    Università degli Studi del Piemonte Orientale “Amedeo Avogadro” Dipartimento di Scienze del Farmaco Dottorato di Ricerca in Chemistry & Biology Curriculum Drug discovery and development (SSD CHIM/08) XXIX ciclo a.a. 2015-2016 Nitrile N-oxides and nitrile imines as electrophilic partners for the discovery of novel isocyanide multicomponent reactions: an innovative strategy for the synthesis of molecular scaffolds useful in medicinal chemistry Valentina Mercalli Supervised by Prof. Gian Cesare Tron PhD program coordinator Prof. Domenico Osella Contents Contents Chapter 1 . Introduction 1 1.1 Introduction 3 1.2 Multicomponent reactions (MCRs) 4 1.3 Isocyanides 9 1.4 Isocyanide based multicomponent reactions (IMCRs) 14 1.5 References 23 Chapter 2 . Outline of the thesis 29 2.1 Outline of the thesis 30 2.2 References 33 Chapter 3 . Prologue (I): Nitrile N-oxides as electrophilic 35 partners in IMCRs 3.1 Introduction 37 3.2 Reaction between Z-chlorooximes, isocyanides and 41 carboxylic acids 3.3 References 44 Chapter 4 . Isocyanide -mediated multicomponent synthesis of 47 C-oximinoamidines 4.1 Results and discussion 49 4.2 Conclusions 55 4.3 Experimental section 56 4.4 References 66 Chapter 5 . Reaction between Z‑arylchlorooximes and α‑isocyanoacetamides: a procedure for the 69 synthesis of aryl-α-ketoamide amides 5.1 Results and discussion 71 5.2 Conclusions 79 5.3 Experimental section 80 5.4 References 95 iii Contents Chapter 6 . Solution -phase parallel synthesis of aryloxyimino amides via a novel multicomponent reaction among aromatic Z‑chlorooximes, isocyanides, and 97 electron-deficient phenols 6.1 Results and discussion 99 6.2 Conclusions 109 6.3 Experimental section 110 6.4 References 133 Chapter 7 .
    [Show full text]