DOCSLIB.ORG

The Ireland-Claisen Rearrangement of 3

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Ireland-Claisen Rearrangement of 3 THE IRELAND‐CLAISEN REARRANGEMENT OF 3‐ ALKOXYPROPENOL AMINO ESTERS AS AN ENTRY TO SPHINGOLIPID AMINO ACID NATURAL PRODUCTS Nathan William George Fairhurst A thesis submitted for the degree of Doctor of Philosophy University of Bath Department of Chemistry July 2012 COPYRIGHT Attention is drawn to the fact that copyright of this thesis rests with its author. A copy of this thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with the author and they must not copy or use it or use material from it except as permitted by law or with the consent of the author. This thesis may be made available for consultation within the University Library and maybe photocopied or lent to other libraries for the purpose of consultation. [Signature] [Date] | ii Abstract ABSTRACT The Ireland-Claisen rearrangement is a powerful synthetic tool which allows predictable diasterocontrol and chirality transfer in the synthesis of γ,δ-unsaturated carboxylic acids. Previous work within the Carbery group has developed a novel protocol for the synthesis of β-alkoxy- and aryloxy-α-amino acids. Chapter 2 covers the initial volume of work on developing this methodology further to allow the synthesis of sterically congested α-quaternary carbon centres in β-alkyoxy- and aryloxy-α-amino acids. Individual substrate optimisation allowed improvement of both the yields and diastereoselectivity of this rearrangement, along with the isolation of a key degradation product. A series of heteroproline-based rearrangements laid the groundwork for remote chirality transfer within this Ireland-Claisen rearrangement. The principle of self-regeneration of stereocentres is applied in an Ireland-Claisen context in Chapter 3. Showing exceptional levels of remote stereocontrol the rearrangement is shown to be general, offering almost exclusively diastereoselectivities of >99:1. Allylic enol ether amino esters saw yields of 47 – 83% and provided functional handles allowing for further synthetic manipulations. Carbon substituted allyl amino esters allowed facile access into β-hydroxy-α-amino acid derivatives of proteinogenic amino acids leucine and isoleucine (amongst others) with excellent selectivity. The synthesis of both enantiomers of mycestericin G in Chapter 4 highlights the synthetic utility of this methodology, in addition to allowing a revision of absolute configuration of this natural product. The synthesis of a mycestericin G analogue, derived from threonine, is also presented. Finally, Chapter 5 exploits these rearrangement products as chiral diene ligands in rhodium-catalysed conjugate addition reactions. Both ligand and reaction condition optimisation led to a range of aryl boronic acids used in the 1,4-addition to 2- cyclohexenone with yields of 24 – 100% and enantioselectivities of 74 – 93% observed. | iii Contents CONTENTS ABSTRACT ..................................................................................................................... iii CONTENTS ..................................................................................................................... iv ACKNOWLEDGEMENTS ............................................................................................ vii ABBREVIATIONS ......................................................................................................... ix 1. INTRODUCTION 1 1.1 β-Hydroxy-α-Amino Acids ........................................................................................ 1 1.1.1 Synthesis of β-Hydroxy-α-Amino Acids ............................................................. 3 1.2 Sphingosine and Sphingosine-related Metabolites ..................................................... 7 1.2.1 Isolation and Biology of Sphingosine Analogues ................................................ 8 1.2.2 Synthesis of Sphingosine Analogues ................................................................. 10 1.3 Self-Regeneration of Stereocentres ........................................................................... 16 1.3.1 Endocyclic Enolates in SRS ............................................................................... 18 1.3.2 Bicyclic Enolates in SRS ................................................................................... 22 1.3.3 Exocyclic Enolates in SRS ................................................................................. 24 1.3.4 α,β-Unsaturated Carbonyl Compounds in SRS ................................................. 28 1.4 Pericyclic Reactions .................................................................................................. 30 1.4.1 Sigmatropic Rearrangements ............................................................................. 30 1.4.2 Claisen Rearrangement ...................................................................................... 31 1.4.3 Variants of the Claisen Rearrangement ............................................................. 36 1.5 Ireland-Claisen Rearrangement ................................................................................. 39 1.5.1 Diastereocontrol in the Ireland-Claisen Rearrangement .................................... 41 1.5.2 Glycinates in the Ireland-Claisen Rearrangement ............................................. 43 1.5.3 Quaternary Centres in the Ireland-Claisen Rearrangement ............................... 46 2. α-QUATERNARY CENTRES IN β-HYDROXY-α-AMINO ACIDS 49 2.1 Background ............................................................................................................... 49 2.2 Phthaloyl Protected Substrates .................................................................................. 50 2.2.1 Retrosynthetic Analysis ..................................................................................... 50 2.2.2 Forward Synthesis .............................................................................................. 51 2.2.3 Initial Rearrangement Attempts ......................................................................... 53 | iv Contents 2.2.4 Rearrangement Optimisation ............................................................................. 54 2.2.5 Optimal Rearrangements .................................................................................... 59 2.3 Boc-N-Me Protected Substrates ................................................................................ 61 2.3.1 Retrosynthetic Analysis ..................................................................................... 61 2.3.2 Forward Synthesis .............................................................................................. 62 2.3.3 Rearrangement Attempts .................................................................................... 64 2.4 Heteroproline Derived Substrates ............................................................................. 65 2.4.1 Substrate Genesis ............................................................................................... 65 2.4.2 Forward Synthesis of Heteroproline Allyl Esters .............................................. 66 2.4.3 Rearrangement of Heteroproline Allyl Esters .................................................... 68 3. SRS IN AN IRELAND-CLAISEN REARRANGEMENT 69 3.1 Concept Development ............................................................................................... 69 3.2 Reaction Development .............................................................................................. 72 3.2.1 Forward Synthesis of Chiral Oxazolidine .......................................................... 72 3.2.2 Rearrangement Optimisation ............................................................................. 73 3.3 Reaction Scope of Enol Ethers .................................................................................. 75 3.3.1 Substrate Synthesis ............................................................................................ 75 3.3.2 Substrate Rearrangement ................................................................................... 79 3.4 Reaction Scope of Crotyl Esters ............................................................................... 86 3.4.1 Substrate Synthesis ............................................................................................ 87 3.4.2 Substrate Rearrangement ................................................................................... 88 3.5 Rearrangement Product Derivatisation ..................................................................... 90 3.5.1 Derivatisation of Enol Ether Rearrangement Products ...................................... 90 3.5.2 Derivatisation of Crotyl Rearrangement Products ............................................. 97 3.6 Conclusions ............................................................................................................... 98 4. SYNTHESIS OF MYCESTERICIN G 100 4.1 Background ............................................................................................................. 100 4.2 Total Synthesis of Mycestericin G .......................................................................... 100 4.2.1 Retrosynthetic Analysis ................................................................................... 100 4.2.2 Initial Investigation .......................................................................................... 101 4.2.3 Completion of the Synthesis of Mycestericin G .............................................. 104 4.3 Total Synthesis of Threonine Analogue of
Load more

Recommended publications
  • Rearrangement Reactions
    Rearrangement Reactions A rearrangement reaction is a broad class of organic reactions where the carbon skeleton of a molecule is rearranged to give a structural isomer of the original molecule. 1, 2-Rearrangements A 1, 2-rearrangement is an organic reaction where a substituent moves from one atom to another atom in a chemical compound. In a 1, 2 shift the movement involves two adjacent atoms but moves over larger distances are possible. In general straight-chain alkanes, are converted to branched isomers by heating in the presence of a catalyst. Examples include isomerisation of n-butane to isobutane and pentane to isopentane. Highly branched alkanes have favorable combustion characteristics for internal combustion engines. Further examples are the Wagner-Meerwein rearrangement: and the Beckmann rearrangement, which is relevant to the production of certain nylons: Pericyclic reactions A pericyclic reaction is a type of reaction with multiple carbon-carbon bonds making and breaking wherein the transition state of the molecule has a cyclic geometry and the reaction progresses in a concerted fashion. Examples are hydride shifts [email protected] and the Claisen rearrangement: Olefin metathesis Olefin metathesis is a formal exchange of the alkylidene fragments in two alkenes. It is a catalytic reaction with carbene, or more accurately, transition metal carbene complexintermediates. In this example (ethenolysis, a pair of vinyl compounds form a new symmetrical alkene with expulsion of ethylene. Pinacol rearrangement The pinacol–pinacolone rearrangement is a method for converting a 1,2-diol to a carbonyl compound in organic chemistry. The 1,2-rearrangement takes place under acidic conditions.
    [Show full text]
  • Keto Esters Vincent Bizet, Valérie Lefebvre, Jérôme Baudoux, Marie-Claire Lasne, Agathe Boulangé, Stéphane Leleu, Xavier Franck, Jacques Rouden
    Metal-Free SN2’ Decarboxylative Rearrangement of β-Keto Esters Vincent Bizet, Valérie Lefebvre, Jérôme Baudoux, Marie-Claire Lasne, Agathe Boulangé, Stéphane Leleu, Xavier Franck, Jacques Rouden To cite this version: Vincent Bizet, Valérie Lefebvre, Jérôme Baudoux, Marie-Claire Lasne, Agathe Boulangé, et al.. Metal- Free SN2’ Decarboxylative Rearrangement of β-Keto Esters. European Journal of Organic Chemistry, Wiley-VCH Verlag, 2011, 2011 (22), pp.4170-4175. 10.1002/ejoc.201100120. hal-01017341 HAL Id: hal-01017341 https://hal.archives-ouvertes.fr/hal-01017341 Submitted on 29 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. FULL PAPER DOI: 10.1002/ejoc.201100120 Ј Metal-Free SN2 Decarboxylative Rearrangement of β-Keto Esters Vincent Bizet,[a] Valérie Lefebvre,[a] Jérôme Baudoux,*[a] Marie-Claire Lasne,[a] Agathe Boulangé,[b] Stéphane Leleu,*[b] Xavier Franck,[b] and Jacques Rouden*[a] Keywords: Nucleophilic substitution / Reaction mechanisms / Organocatalysis / Rearrangement/ Decarboxylation Treatment of 2-methoxycarbonyl- (or 3-cyano-)allyl aceto- tested to elucidate the mechanism. The results of the study acetates with a tertiary amine or triphenylphosphane af- strongly suggest an intermolecular pathway involving a forded α-methylene γ-substituted δ-keto esters (or nitrile) in SN2Ј–decarboxylation–SN2Ј cascade.
    [Show full text]
  • The Claisen Condensation
    Lecture 19 The Claisen Condensation •• •• • • O • O • – • CH3COCH2CH3 • CH2 COCH2CH3 March 29, 2016 Chemistry 328N Exam Tomorrow Evening!! Review tonight 5PM -6PM Welch 1.316 Chemistry 328N Some “loose ends” before we go on Spectrosopy of acid derivatives A selective reduction for your tool box Chemistry 328N Reduction of Acid Derivatives Acids (page 679-681) Esters (page 738-739) Please work through the example on 738 Amides (page 739-742) Nitriles (page 742) Selective reductions with NaBH4 Chemistry 328N DIBAlH Diisobutylaluminum hydride (DIBAlH) at -78°C selectively reduces esters to aldehydes •at -78°C, the tetrahedral intermediate does not collapse and it is not until hydrolysis in aqueous acid that the carbonyl group of the aldehyde is liberated Stable at low temperature Chemistry 328N Infrared Spectroscopy C=O stretching frequency depends on whether the compound is an acyl chloride, anhydride, ester, or amide. C=O stretching frequency n O O O O O CH3CCl CH3COCCH3 CH3COCH3 CH3CNH2 1822 cm-1 1748 1736 cm-1 1694 cm-1 and 1815 cm-1 Chemistry 328N Infrared Spectroscopy Anhydrides have two peaks due to C=O stretching. One from symmetrical stretching of the C=O and the other from an antisymmetrical stretch. C=O stretching frequency n O O CH3COCCH3 1748 and 1815 cm-1 Chemistry 328N Infrared Spectroscopy Nitriles are readily identified by absorption due to carbon-nitrogen triple bond stretching that is “all alone” in the 2210-2260 cm-1 region. Chemistry 328N Hydrolysis and Decarboxylation Chemistry 328N t-Butyl esters Chemistry 328N t-Butyl esters Chemistry 328N t-Butyl ester hydrolysis Note which bond is broken in this hydrolysis !! Chemistry 328N Recall our discussion of the acidity of protons a to carbonyls The anion is stabilized by resonance The better the stabilization, the more acidic the a proton Acidity of a protons on“normal” aldehydes and ketones is about that of alcohols and less than water…pKa ~ 18-20 Some are far more acidic, i.e.
    [Show full text]
  • Recent Perspectives on Rearrangement Reactions of Ylides Via Carbene Transfer Reactions Sripati Jana, Yujing Guo, and Rene M
    Minireview Chemistry—A European Journal doi.org/10.1002/chem.202002556 & Organic Chemistry |Reviews Showcase| Recent Perspectives on Rearrangement Reactions of Ylides via Carbene Transfer Reactions Sripati Jana, Yujing Guo, and Rene M. Koenigs*[a] Chem. Eur. J. 2020, 26,1–13 1 2020 The Authors. Published by Wiley-VCH GmbH && These are not the final page numbers! ÞÞ Minireview Chemistry—A European Journal doi.org/10.1002/chem.202002556 Abstract: Among the available methods to increase the mo- between p-bond and negatively charged atom followed by lecular complexity, sigmatropic rearrangements occupy a simultaneous redistribution of p-electrons. This minireview distinct position in organic synthesis. Despite being known describes the advances in this research area made in recent for over a century sigmatropic rearrangement reactions of years, which now opens up metal-catalyzed enantioselective ylides via carbene transfer reaction have only recently come sigmatropic rearrangement reactions, metal-free photo- of age. Most of the ylide mediated rearrangement processes chemical rearrangement reactions and novel reaction path- involve rupture of a s-bond and formation of a new bond ways that can be accessed via ylide intermediates. Introduction In 1912, Rainer Ludwig Claisen reported on the reaction of allyl vinyl ether 1a under thermal reaction conditions to deliver g,d-unsaturated carbonyl compound 2a, which is now text- book knowledge in undergraduate course and commonly known as the Claisen reaction (Scheme 1a).[1] The Claisen rear- rangement is an example of a [3,3]-sigmatropic rearrangement reaction. Sigmatropic rearrangement reactions are character- ized by the migration of a s-bond, flanked by at least one p- system, to a new position and the order of rearrangement re- actions is determined by the original and terminal position of the migratory group.
    [Show full text]
  • Author(S) Ishida, Naoki
    Development of New Carbon-Carbon Bond Forming Reactions Title Catalyzed by palladium and Nickel( Dissertation_全文 ) Author(s) Ishida, Naoki Citation 京都大学 Issue Date 2008-03-24 URL https://doi.org/10.14989/doctor.k13848 Right Type Thesis or Dissertation Textversion author Kyoto University Development of New Carbon–Carbon Bond Forming Reactions Catalyzed by Palladium and Nickel Naoki Ishida 2008 Preface The studies described in this thesis have been carried out under the direction of Professor Masahiro Murakami from April 2002 to March 2008. These studies concern with novel carbon–carbon forming reactions catalyzed by palladium and nickel. This thesis is completed with the aid of so many people such as a supervisor, collaborators and colleagues. The author would like to show his appreciation them. First of all, the author would like to express his sincerest gratitude to Supervisor Professor Masahiro Murakami for providing an opportunity to study state-of-the-art organic chemistry. All the works in this thesis could be achieved with his constant supervisions. The author also would like to acknowledge to: Associate professor Ryoichi Kuwano and Assistant professor Tomoya Miura for their directions covered from guidance of the project to experimental procedures. Professor Michinori Suginome, Assistant professor Takanori Matsuda, and Assistant professor Toshimichi Ohmura for helpful discussions and advises. Dr. Yoshiyuki Miyake, Dr. Yuichiro Mutoh, Mr. Hideyuki Igawa, Dr. Akihiko Yamamoto, Dr. Sho Kadowaki, Dr. Munehiro Hasegawa, Dr Hiroyoshi Noguchi for their kind directions. the collaborators, Yusuke Takahashi, Tatsuo Shinmoto, and Mizuna Narumi for their support on the research. Their patience and earnest lead to the results described herein.
    [Show full text]
  • II.Pericyclic Reactions 7
    M.Sc. Semester-IV Core Course-9 (CC-9) Synthetic Organic Chemistry II.Pericyclic Reactions 7. Claisen Rearrangement, The Nazarov Reaction Dr. Rajeev Ranjan University Department of Chemistry Dr. Shyama Prasad Mukherjee University, Ranchi II Pericyclic Reactions 20 Hrs Molecular orbital symmetry, Frontier orbitals of ethylene, 1,3-butadiene, 1, 3, 5-hexatriene, allyl system, Classification of pericyclic reactions. FMO approach, Woodward-Hoffman correlation diagram method and PMO approach for pericyclic reaction under thermal and photochemical conditions. Electrocyclic reactions: Conrotatary and disrotatary motion, 4n and (4n+2) systems, Cycloaddition reaction: [2+2] and [4+2] cycloaddition reaction, Cycloaddition of ketones, Secondary effects in [4+2] cycloaddition. Stereochemical effects on rate of cycloaddition reaction, Diels-Alder reaction, 1,3-dipolar cycloaddition, Chelotropic reaction, The Nazarov reaction. Sigmotropic rearrangement: Suprafacial and antarafacial shift involving H and carbon-moieties, Peripatetic cyclopropane bridge, Retention and inversion of configuration, [3,3]-, [1,5]-, [2,3]-, [4,5]-, [5,5]-, and [9,9]- Sigmatropic rearrangements, Claisen rearrangements (including Aza-Claisen, Ireland-Claisen), Cope rearrangements (including Oxy-Cope, Aza-Cope), Sommelet-Hauser rearrangements, Group transfer reaction, Ene reaction, Mislow - Evans rearrangement, Walk rearrangement. Coverage: 1.Claisen Rearrangement 2.The Nazarov Reaction 2 Claisen Rearrangement : [3, 3] Sigmatropic Rearrangement How and Why? Claisen rearrangement: A thermal rearrangement of allyl phenyl ethers to form 2- allylphenols. Rainer Ludwig Claisen O OH 1851-1930 200-250°C Allyl phenyl ether 2-Allylphenol Dr. Rajeev Ranjan 3 Claisen Rearrangement : [3, 3] Sigmatropic Rearrangement Mechanism: O O heat Allyl phenyl Transition ether state O OH keto-enol tautomerism H A cyclohexadienone o-Allylphenol intermediate Dr.
    [Show full text]
  • Review Claisen, Cope and Related Rearrangements in The
    Molecules 2000, 5, 1033-1050 molecules ISSN 1420-3049 © 2000 by MDPI http://www.mdpi.org Review Claisen, Cope and Related Rearrangements in the Synthesis of Flavour and Fragrance Compounds Janusz Nowicki Institute of Heavy Organic Synthesis "Blachownia", ul. Energetyków 9, 47-225 . G]LHU]\Q.R(OH Poland Tel.: +48 77 487 35 51, Fax: +48 77 487 36 60, E-mail: [email protected] Received: 22 February 2000; revised form 21 July 2000 / Accepted: 8 August 2000 / Published: 23 August 2000 Abstract: A review of the use of the Claisen, Cope and related [3,3]-sigmatropic rearrange- ments, sequential ("tandem") sigmatropic rearrangements and the "ene" reaction in the syn- theses of flavour and fragrance compounds is presented. Keywords: Claisen rearrangements, Cope rearrangements, Caroll rearrangements, tandem sigmatropic rearrangements, "ene" reactions, flavour and fragrance compounds. 1. Introduction The Claisen rearrangement was discovered in 1912. Its mechanism was proposed in the 60's, just as the Cope rearrangement which involves a similar mechanism [1]. They are both [3,3]-sigmatropic rear- rangements and they have been the subject of numerous reviews [2-4]. The Claisen rearrangement is the sigmatropic conversion of allyl vinyl ethers (1) into homoallyl carbonyl compounds (2) (Scheme1). 2 2 1 2 Scheme 1. The majority of these rearrangements require high temperatures (100-350°C), although numerous examples of catalytic syntheses are also known [5]. The common feature of all [3,3]-sigmatropic rear- rangements is a six-membered transition state with a delocalised electronic structure (Scheme 2). Molecules 2000, 5 2 2 2 1 2 Scheme 2.
    [Show full text]
  • Discovery of the Michael Reaction
    IN MEMORIAM DOI: 10.1002/ejoc.200901130 Discovery of the Michael Reaction Takashi Tokoroyama*[a] Keywords: Michael addition / History of science / Chemical creativity / Reminiscences This essay deals with the details of the discovery of the the Michael addition were observed prior to Michael’s crucial Michael addition reaction, focusing on Arthur Michael, an finding, and the validity of his credit as the discoverer is dis- American chemist, after whom it is named. Michael envis- cussed. At the same time, a general consideration is made on aged the possibility of an addition reaction of sodiomalonate chemical creativity with reference to the individuality in the ester or sodioacetoacetate ester to α,β-unsaturated acid esters career and the personality of A. Michael. and confirmed this by experimentation. Some instances of Introduction At classical school, Michael received private instruction in chemistry, and in his leisure time, he enjoyed performing [1–3] The Michael reaction, addition of stabilized anions chemical experiments in a home laboratory that his father (e.g., enolate) to α,β-unsaturated carbonyl and related com- had set up for him. Toward the end of his teens, he experi- pounds, is a prototype for the conjugate addition reactions enced a great trial: his plan to enter Harvard College was [4,5] of various nucleophiles that now find wide utility in or- foiled by a serious illness. After wavering about his future ganic syntheses (Scheme 1). career following his recovery, Michael decided to study chemistry in Germany. During a family sojourn in Ger- many in the summer of 1871 (the year of the establishment of the German Empire), Michael had the fortune to be ad- mitted to the Chemical Laboratory of Professor August W.
    [Show full text]
  • Unit – I - Carboxylic Acids and Their Derivatives - Scy1315
    SCHOOL OF SCIENCE AND HUMANITIES DEPARTMENT OF CHEMISTRY UNIT – I - CARBOXYLIC ACIDS AND THEIR DERIVATIVES - SCY1315 1 1. CARBOXYLIC ACIDS AND THEIR DERIVATIVES Structure and nomenclature - General methods of preparation of carboxylic acids – acidity – Effect of substituents on acidity – Physical and Chemical properties –Hell-Volhard-Zelinsky Reaction –Dicarboxylic acids - oxalic, malonic succinic, glutaric, adipic, phthalic, acrylic, crotonic and cinnamic acids – Stereospecific addition to maleic and fumaric acids – Derivatives of carboxylic acids – Acid halides, esters, anhydrides and amides – Preparation and Properties – Relative reactivity - Acid and alkaline hydrolysis of esters – trans-esterification. Organic compounds containing carboxylic group are known as carboxylic acids. Their general formulae is RCOOH. NOMENCLATURE H O O HO HO Ethanoic acid methanoic acid O O HO Propanoic acid HO Butanoic acid O (2Z)-3-phenylprop-2-enoic acid O HO Benzoic acid HO O O HO oxo(phenyl)acetic acid 2 ACID DERIVATIVES O O O O H2N Cl benzoyl chloride benzamide ethyl benzoate O O Cl H2N acetyl chloride acetamide O O O Cl H2N H2N butanamide propanoyl chloride propanamide O O O O O O ethyl acetate ethyl butanoate ethyl propanoate 3 DICARBOXILIC ACIDS O O O O HO OH HO OH oxalic acid propanedioic acid O O O O HO OH HO OH butanedioic acid (2E)-but-2-enedioic acid GENERAL PREPARATION METHODS 1. Oxidation of alcohols, aldehydes and ketones CH3CH2OH CH3CHO CH3COOH [O] [O] H [O] OH [O] O O + O HO HO 2. Hydrolysis of cyanides and amides H O+ + 3 H3O CH3CN CH3CONH2 CH3 COOH C H SO K + KCN C H CN 6 5 3 6 5 4 3.
    [Show full text]
  • Give Mechanism of the Following Reactions I) Wolf-Kishner Reduction Ii) Claisen Condensation Iii) Ozonolysis of 2-Butene
    Question #61068 – Chemistry – Organic Chemistry Question: Give mechanism of the following reactions i) Wolf-Kishner reduction ii) Claisen condensation iii) Ozonolysis of 2-butene i) In general, the reaction mechanism first involves the in situ generation of a hydrazone by condensation of hydrazine with the ketone or aldehyde substrate. Sometimes it is however advantageous to use a pre-formed hydrazone as substrate (see modifications). The hydrazone is deprotonated by alkoxide base followed by a concerted, rate-determining step in which a diimide anion is formed. Collapse of this alkyldiimde with loss of N2 leads to formation of an alkylanion which can be protonated by solvent to give the desired product. ii) The Claisen condensation is a carbon–carbon bond forming reaction that occurs between two esters or one ester and anothercarbonyl compound in the presence of a strong base, resulting in a β-keto ester or a β- diketone.[1] It is named after Rainer Ludwig Claisen, who first published his work on the reaction in 1887.[2][3][4] In the first step of the mechanism, an α-proton is removed by a strong base, resulting in the formation of an enolate anion, which is made relatively stable by the delocalization of electrons. Next, the carbonyl carbon of the (other) ester is nucleophilically attacked by the enolate anion. The alkoxy group is then eliminated (resulting in (re)generation of the alkoxide), and the alkoxide removes the newly formed doubly α-proton to form a new, highly resonance-stabilized enolate anion. Aqueous acid (e.g. sulfuric acid or phosphoric acid) is added in the final step to neutralize the enolate and any base still present.
    [Show full text]
  • And Para-Substituted Allyl Phenyl Ethers Was Investigated
    Experimental and theoretical study of the regioselectivity of Claisen rearrangements of substituted allyl phenyl ethers William Thomas Möller Faculty of Physical Sciences University of Iceland 2020 Experimental and theoretical study of the regioselectivity of Claisen rearrangements of substituted allyl phenyl ethers William Thomas Möller 60 ECTS thesis submitted in partial fulfillment of a Magister Scientiarum degree in Organic Chemistry Advisor Benjamín Ragnar Sveinbjörnsson MS Committee Benjamín Ragnar Sveinbjörnsson Krishna Kumar Damodaran Master’s Examiner Haraldur Garðarsson Faculty of Physical Sciences School of Engineering and Natural Sciences University of Iceland Reykjavik, May 2020 Experimental and theoretical study of the regioselectivity of Claisen rearrangements of substituted allyl phenyl ethers Claisen rearrangement of substituted allyl phenyl ethers (50 characters including spaces) 60 ECTS thesis submitted in partial fulfillment of a Magister Scientiarum degree in Chemistry Copyright © 2020 William Thomas Möller All rights reserved Faculty of Physical Sciences School of Engineering and Natural Sciences University of Iceland Hjarðarhagi, 2-6 107, Reykjavik Iceland Telephone: 525 4000 Bibliographic information: William Thomas Möller, 2020, Experimental and theoretical study of the regioselectivity of Claisen rearrangements of substituted allyl phenyl ethers, Master’s thesis, Faculty of Physical Science, University of Iceland. Printing: Háskólaprent, Fálkagata 2, 107 Reykjavík Reykjavik, Iceland, June 2020 Abstract The regioselectivity of Claisen rearrangement with different meta-substituted and meta- and para-substituted allyl phenyl ethers was investigated. The main results were that in meta- substituent Claisen rearrangements the regioselectivity depends roughly on the electronic nature of the substituent. When the substituent is electron donating it favors the migration to unhindered side while when the substituent is electron withdrawing it favors migration towards the meta-substituent.
    [Show full text]
  • Pd-Catalyzed Domino Carbonylative/Decarboxylative Allylation Steven Giboulot
    Pd-catalyzed domino carbonylative/decarboxylative allylation Steven Giboulot To cite this version: Steven Giboulot. Pd-catalyzed domino carbonylative/decarboxylative allylation. Organic chemistry. Université Pierre et Marie Curie - Paris VI, 2012. English. NNT : 2012PAO66196. tel-00829489 HAL Id: tel-00829489 https://tel.archives-ouvertes.fr/tel-00829489 Submitted on 3 Jun 2013 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THESE DE DOCTORAT DE L’UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6 Spécialité CHIMIE ORGANIQUE Ecole Doctorale de Chimie Moléculaire de Paris Centre – ED 406 Présentée par Mr Steven GIBOULOT Pour obtenir le grade de DOCTEUR de l’UNIVERSITE PIERRE ET MARIE CURIE Sujet de la thèse : Pd-Catalyzed Domino Carbonylative / Decarboxylative Allylation Soutenue le 24 SEPTEMBRE 2012 Devant le jury composé de : Docteur Emmanuel ROULLAND Institut de Chimie des Substances Naturelles Rapporteur Professeur Bartolo GABRIELE Université de Calabria Rapporteur Professeur André MORTREUX Université de Lille 1 Examinateur Professeur Serge THORIMBERT Université Pierre et Marie Curie Examinateur Docteur Frédéric LIRON Université Pierre et Marie Curie Examinateur Professeur Giovanni POLI Université Pierre et Marie Curie Directeur de thèse Université Pierre & Marie Curie - Paris 6 Tél. Secrétariat : 01 42 34 68 35 Bureau d’accueil, inscription des doctorants et base de Fax : 01 42 34 68 40 données Tél.
    [Show full text]