DOCSLIB.ORG

Elucidating the Mechanism of the Photo-Favorskii Rearrangement

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Elucidating the Mechanism of the Photo-Favorskii Rearrangement INVESTIGATIVE PHOTOCHEMISTRY: ELUCIDATING THE MECHANISM OF THE PHOTO-FAVORSKII REARRANGEMENT By C2008 Kenneth F. Stensrud Submitted to the Department of Chemistry and the Faculty of the Graduate School of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy ______________________________ Chairperson ______________________________ ______________________________ ______________________________ ______________________________ Date Defended: ________________ The dissertation committee for Kenneth F. Stensrud certifies that this is the approved version of the following dissertation: INVESTIGATIVE PHOTOCHEMISTRY: ELUCIDATING THE MECHANISM OF THE PHOTO-FAVORSKII REARRANGEMENT Dissertation Committee: ______________________________ Chairperson ______________________________ ______________________________ ______________________________ ______________________________ Date Approved: ________________ ii Abstract Kenneth F. Stensrud, Ph.D. Department of Chemistry, April 2008 University of Kansas The p-hydroxyphenacyl chromophore (pHP) is a versatile phototrigger for an assortment of biological nucleofuges, such as γ-aminobutyric acid (GABA). The photochemistry is trenchant; irradiation discharges the nucleofuge and induces rearrangement of pHP, analogous to the ground state Favorskii rearrangement. Structure-reactivity relationships were explored with pHP GABA’s. Electron donating groups lowered the release efficiency, Φdis, relative to the unsubstituted analog. Electron withdrawing carbonyl groups attenuated Φdis. Fluoro moieties modulated the pKa of pHP; protonated pHP manifested higher Φdis than their conjugate base counterparts. The reactive excited states were determined as triplets by Stern-Volmer quenching and laser flash photolysis studies. The triplet lifetimes were ~ 10-9 s with release rate constants of 107 to 108 s-1. Auxochrome substitutions lengthened the λmax of pHP but lowered Φdis. Added perchlorate salts markedly improved Φdis for pHP GABA’s, imputing intermediate ion-radical pairs. Comprehensive photo-Favorskii mechanisms were posited for protonated and conjugate base forms of pHP GABA. iii Acknowledgements There have been frequent comments regarding my use of flowery, poetic words instead of those deemed appropriate for scientific writing. Though I have learned to distinguish one from the other while composing this dissertation, I find it truly risible that, at this time, words fail me when appositely expressing my gratitude to my advisor, Professor Richard Givens. Dr. Givens equanimity in dealing with my oft hair-brained ideas and digressions cannot be understated. My motivations to work long hours at solving our research problems originated from his encouragements and well considered proposals. Honestly, I shouldn’t continue to indite a synopsis of his qualities, as they will present as mere platitudes. I can only state with certainty that Dr. Givens will always remain close to my heart for everything he has passed on to me both as a scientist and a man of utmost integrity. My parents, Ken and Donna, have sacrificed more than I can fathom to ensure that their son, the opsimath, would succeed in his endeavors. I am grateful for your closeness and support. Mom and dad, my love for you will transcend this life. My brother Dan has always been there for me irrespective of the difficulty of the times. Dan, I look forward to growing old with you as both my brother and best friend. My wife, Beth Stensrud, was the linchpin in my success as a graduate student. The single greatest event in my life was meeting you my first semester at KU. You were my foundation, my stimulus to endure time of tumult. I am dubious that I would iv have persevered without you. Beth, from you I have recognized the existence of angels. I owe a debt of gratitude to Dr. Todd Williams for his willingness to instruct me on the applications of the QQQ and furthermore permit me to utilize the instrument without restrictions over the past two years. I can honestly state that I would have completed a tenth of the amount of work if I did not have access to instrument and your exhortations. Todd, your succor will always be remembered and revered. Professor Abraham Yousef was my antecedent in the laboratory. Your forbearance and willingness to instruct when I was maladroit will never be forgotten. Abraham, I owe much of my success in the laboratory to you, your mundane disposition was appreciated more than you can know. I hope we can stay in touch throughout the years. To Dr. Elizabeth Cope, you were a friend and lab colleague. Beth, I will never forget the long hours and weekends we spent in the laboratory, imbued with successes, failures, and insightful talks. I appreciated this. It is eerie now when I come into lab on the weekends and I don’t see you. To Dr. Gerry Lushington, Professor Jakob Wirz, Dr. Dominik Heger and Professor Karl Kandler, thank you for your collaborative efforts. The information that you gleaned facilitated the solution of my research problems. v John Hershberger - we came in together and we will go out together. Through good and bad times, times of confusion and consumption, our experiences will never be forgotten. vi Table of Contents page Abstract iii Acknowledgements iv List of Figures xi List of Schemes xvii List of Tables xxi List of Equations xxiv Glossary of Chemical Compounds Studied xxv Introduction 1 I. Early Investigations of The Favorskii Rearrangement 1 II. Bordwell’s Contributions 5 A. Rate, Isotope and Nucleofuge Studies 6 B. Substituent, LFER, Salt, Media Studies 11 C. Ramberg-Backland Analogy-Role of Orbital Overlap 17 D. Influence of α-Substituents 21 E. Evidence for a Dipolar Intermediate 29 F. Studies in Stereochemistry 32 III. Computational Investigations 37 IV. Variations to the Classical Favorskii Rearrangement 44 vii V. The Photochemical Version of the Favorskii Rearrangement 46 Statement of Problem 92 Results 94 I. Synthetic Methodologies 94 A. pHP GABA Series and 4-Fluorophenacyl GABA 94 B. pHP Glu Series 101 C. Other pHP Caged Amino Acids 102 D. pHP Deoxycholic Acid 104 E. pHP Diethyl Phosphonate 106 F. pHP F 106 G. 5-Acetylsalicylic Acid and Salicylamide GABA Series 107 H. 5-Acetylsalicylic Acid Alkanoyl Compounds 113 I. α-alkyl-pHP diaseteromers 114 J. FITC-DOC 116 II. Exploratory Photochemistry 117 A. 1H NMR Analysis, pHP GABA Series 119 B. 1H NMR Analysis, α-Alkyl-pHP GABA Series 125 C. 1H NMR Analysis, pHP Glu Series 128 D. 1H NMR Analysis, Other pHP-Caged Amino Acids 130 E. 1H NMR Analysis, pHP Deoxycholic Acid 131 F. 1H NMR Analysis, pHP Diethyl Phosphonate 133 G. 1H NMR Analysis, pHP F 133 viii H. 1H NMR Analysis, 5-Acetylsalicylic acid GABA Series 135 I. 1H NMR Analysis, 5-Acetylsalicylic Acid Alkanoyls 137 J. 1H NMR Analysis, α-Alkyl pHP Diastereomers 140 K. 19F NMR Analysis, pHP and 5-Acetylsalicylic Acid GABA’s 142 III. UV-Vis Spectroscopic Studies 145 A. pHP GABA Series and 4-Fluorophenacyl GABA 145 B. pHP Glu Series 153 C. Other pHP-Caged Amino Acids, DOC and Fluoride 154 D. 5-Acetylsalicylic Acid GABA Series and Alkanoyls 154 E. α-Alkyl-pHP Diastereomers 156 IV. Fluorescence Spectroscopic Studies 156 V. Time Correlated Single Photon Counting Studies 158 VI. Quantitative Photochemical Analysis 159 A. pHP GABA Series at 300 nm 160 B. pHP GABA Series at 350 nm 168 C. pHP Glu Series 169 D. Other pHP-Caged Amino Acids 170 E. pHP DOC and Fluoride 171 F. 5-Acetylsalicylic Acid GABA Series and Alkanoyls 171 G. α-Alkyl-pHP Diastereomers 173 VII. Stern-Volmer Quenching Studies 174 VIII. Computational Studies 176 ix A. ClogP Calculations 177 B. Energies and Geometries of Triplet Biradicals 179 C. Spin and Charge Density Calculations 181 IX. Laser Flash Photolysis Studies 183 Discussion 198 A. Synthetic Strategies 198 B. General Photochemistry 201 C. Preliminary Mechanistic Studies 203 D. Substituent Effects on the Photo-Favorskii Rearrangement 209 E. Miscellaneous Substituent Effects on pHP GABA Photochemistry 216 F. Substituent Effects on 5-acetylsalicylic acid GABA derivatives 221 G. Nucleofuge Effects on the Photo-Favorskii Rearrangement 221 H. Nucleofuge Effects - Linear Free Energy Relationships 223 I. Media Effects on the Photo-Favorskii Rearrangement 226 J. Salt and Ionic Strength Effects 231 K. Rationalized Mechanism of the Photo-Favorskii Rearrangement 240 L. Biological Studies 244 M. Future Studies 248 Conclusion 251 Experimental 255 x List of Figures Figure 1. Diphenylcyclohexanones examined in the Favorskii reaction. 6 Figure 2. A potential energy illustration of the semibenzilic rearrangement process, revealing relative energies (in kcal/mol) of stationary points on the reactive surface that were calculated at the HF/6-31G* level. 40 Figure 3. A potential energy surface diagram of the cyclopropanone rearrangement mechanism, revealing relative energies (in kcal/mol) of stationary points on the reactive surface that were calculated at the HF/6-31G* level. 43 Figure 4. Left: Time dependent decay profile of pHP diethyl phosphate (3114) band ~1600 cm-1 with ns 3TR. Right: Time dependent decay profile of 3114 band ~1600 cm-1 with ns 3TR. 70 Figure 5. Time dependent decay profile of 3110 at ~1600 cm-1 in ns-3TR spectra. Circles indicate degassed, triangles open air, and squares oxygen. 72 Figure 6. Left: 1) Bottom - psTR3 spectrum of 115 in water. 2) Top - psTR3 spectrum of 115 in water. Right: 1) Bottom - psTR3 spectrum of 115 in buffer, pH = 9.00. 2) Top - psTR3 spectrum of 115 in buffer, pH = 9.00. 75 Figure 7. DFT determined, optimized geometry and bond distances (Ǻ) of 3115 in water. 77 Figure 8. Stern Volmer analysis of 3114 lifetimes as a function of water concentration, in percentage. 81 Figure 9. Phillips’ proposed structure of unknown, M, as a solvation/contact ion pair complex. 84 Figure 10. Step-scan FTIR of 121 in CD3CN (2% D2O) at 50 ns (red) and 1µs (blue) delay. 89 3 Figure 11. Plot of kobs of 114 vs. mole fraction of deuterium in degassed, o 10% aq. CH3CN at 25 C. 90 xi Figure 12.
Load more

Recommended publications
  • Cubane and Triptycene As Scaffolds in the Synthesis of Porphyrin Arrays
    Cubane and Triptycene as Scaffolds in the Synthesis of Porphyrin Arrays Submitted by Gemma M. Locke B.A. (Mod.) Medicinal Chemistry Trinity College Dublin, Ireland A thesis submitted to the University of Dublin, Trinity College for the degree of Doctor of Philosophy Under the Supervision of Prof. Dr. Mathias O. Senge University of Dublin, Trinity College September 2020 Declaration I declare that this thesis has not been submitted as an exercise for a degree at this or any other university and it is entirely my own work. I agree to deposit this thesis in the University’s open access institutional repository or allow the Library to do so on my behalf, subject to Irish Copyright Legislation and Trinity College Library conditions of use and acknowledgement. I consent to the examiner retaining a copy of the thesis beyond the examining period, should they so wish. Furthermore, unpublished and/or published work of others, is duly acknowledged in the text wherever included. Signed: ____________________________________________ March 2020 Trinity College Dublin ii Summary The primary aim of this research was to synthesise multichromophoric arrays that are linked through rigid isolating units with the capacity to arrange the chromophores in a linear and fixed orientation. The electronically isolated multichromophoric systems could then ultimately be tested in electron transfer studies for their applicability as photosynthesis mimics. Initially, 1,4-diethynylcubane was employed as the rigid isolating scaffold and one to two porphyrins were reacted with it in order to obtain the coupled product(s). Pd-catalysed Sonogashira cross-coupling reactions were used to try and achieve these bisporphyrin complexes.
    [Show full text]
  • Cumulative Chapter Titles by Volume
    bindcom.tex 4/18/06 12:24 PM Page 659 CUMULATIVE CHAPTER TITLES BY VOLUME Volume 1 (1942) 1. The Reformatsky Reaction: Ralph L. Shriner 2. The Arndt-Eistert Reaction: W. E. Bachmann and W. S. Struve 3. Chloromethylation of Aromatic Compounds: Reynold C. Fuson and C. H. McKeever 4. The Amination of Heterocyclic Bases by Alkali Amides: Marlin T. Leffler 5. The Bucherer Reaction: Nathan L. Drake 6. The Elbs Reaction: Louis F. Fieser 7. The Clemmensen Reduction: Elmore L. Martin 8. The Perkin Reaction and Related Reactions: John R. Johnson 9. The Acetoacetic Ester Condensation and Certain Related Reactions: Charles R. Hauser and Boyd E. Hudson, Jr. 10. The Mannich Reaction: F. F. Blicke 11. The Fries Reaction: A. H. Blatt 12. The Jacobson Reaction: Lee Irvin Smith Volume 2 (1944) 1. The Claisen Rearrangement: D. Stanley Tarbell 2. The Preparation of Aliphatic Fluorine Compounds: Albert L. Henne 3. The Cannizzaro Reaction: T. A. Geissman 4. The Formation of Cyclic Ketones by Intramolecular Acylation: William S. Johnson 5. Reduction with Aluminum Alkoxides (The Meerwein-Ponndorf-Verley Reduction): A. L. Wilds 659 bindcom.tex 4/18/06 12:24 PM Page 660 660 CUMULATIVE CHAPTER TITLES BY VOLUME 6. The Preparation of Unsymmetrical Biaryls by the Diazo Reaction and the Nitrosoacetylamine Reaction: Werner E. Bachmann and Roger A. Hoffman 7. Replacement of the Aromatic Primary Amino Group by Hydrogen: Nathan Kornblum 8. Periodic Acid Oxidation: Ernest L. Jackson 9. The Resolution of Alcohols: A. W. Ingersoll 10. The Preparation of Aromatic Arsonic and Arsinic Acids by the Bart, Béchamp, and Rosenmund Reactions: Cliff S.
    [Show full text]
  • Photoremovable Protecting Groups Used for the Caging of Biomolecules
    1 1 Photoremovable Protecting Groups Used for the Caging of Biomolecules 1.1 2-Nitrobenzyl and 7-Nitroindoline Derivatives John E.T. Corrie 1.1.1 Introduction 1.1.1.1 Preamble and Scope of the Review This chapter covers developments with 2-nitrobenzyl (and substituted variants) and 7-nitroindoline caging groups over the decade from 1993, when the author last reviewed the topic [1]. Other reviews covered parts of the field at a similar date [2, 3], and more recent coverage is also available [4–6]. This chapter is not an exhaustive review of every instance of the subject cages, and its principal focus is on the chemistry of synthesis and photocleavage. Applications of indi- vidual compounds are only briefly discussed, usually when needed to put the work into context. The balance between the two cage types is heavily slanted to- ward the 2-nitrobenzyls, since work with 7-nitroindoline cages dates essentially from 1999 (see Section 1.1.3.2), while the 2-nitrobenzyl type has been in use for 25 years, from the introduction of caged ATP 1 (Scheme 1.1.1) by Kaplan and co-workers [7] in 1978. Scheme 1.1.1 Overall photolysis reaction of NPE-caged ATP 1. Dynamic Studies in Biology. Edited by M. Goeldner, R. Givens Copyright © 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30783-4 2 1 Photoremovable Protecting Groups Used for the Caging of Biomolecules 1.1.1.2 Historical Perspective The pioneering work of Kaplan et al. [7], although preceded by other examples of 2-nitrobenzyl photolysis in synthetic organic chemistry, was the first to apply this to a biological problem, the erythrocytic Na:K ion pump.
    [Show full text]
  • 01Isinmain.Pdf (377.6Kb)
    STUDIES ON THE SYNTHESIS AND REARRANGEMENT OF INDAZOLYLPYRIDINIUM DERIVATIVES, PRECURSORS TO POTENTIAL NEUROPROTECTIVE PRODRUGS BEARING A 1,2,3,6-TETRAHYDROPYRIDINYL CARRIER By Emre M. Işın Dissertation submitted to the faculty of the Virginia Polytechnic Institute and State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY IN CHEMISTRY Professor Neal Castagnoli, Jr., Chairman Professor David R. Bevan Professor Paul R. Carlier Professor David G.I. Kingston Professor James M. Tanko March 22, 2004 Blacksburg, Virginia Keywords: Monoamine Oxidase, Bioactivation, Docking, Neuroprotection, Rearrangement, Regiospecific Synthesis Copyright 2004, Emre M. Isin STUDIES ON THE SYNTHESIS AND REARRANGEMENT OF INDAZOLYLPYRIDINIUM DERIVATIVES, PRECURSORS TO POTENTIAL NEUROPROTECTIVE PRODRUGS BEARING A 1,2,3,6-TETRAHYDROPYRIDINYL CARRIER By Emre M. Işın Professor Neal Castagnoli, Jr., Chairman ABSTRACT The neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI) protects against the neurotoxicity of MPTP in a mouse model of neurodegeneration. Since 7-NI also inhibits the monoamine oxidase-B (MAO-B) catalyzed bioactivation of MPTP, the role of nNOS inhibition as a mediator of 7-NI’s neuroprotective properties have been challenged. In order to examine in greater detail the neuroprotective effects of indazolyl derivatives, the synthesis of water soluble indazolyltetrahydropyridinyl derivatives as potential “prodrugs” that may undergo MAO bioactivation in the brain was undertaken. During the course of the studies on the synthesis of indazolylpyridinium derivatives, precursors to these “prodrugs”, an interesting reaction involving the rearrangement of 4-(2H-indazolyl)-1-methylpyridinium iodide to the corresponding 1H- isomer was encountered. A detailed investigation of this rearrangement reaction is reported in this thesis.
    [Show full text]
  • Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy Petr Klan,́*,†,‡ Tomaś̌solomek,̌ †,‡ Christian G
    Review pubs.acs.org/CR Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy Petr Klan,́*,†,‡ Tomaś̌Solomek,̌ †,‡ Christian G. Bochet,§ Aurelień Blanc,∥ Richard Givens,⊥ Marina Rubina,⊥ Vladimir Popik,# Alexey Kostikov,# and Jakob Wirz∇ † Department of Chemistry, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic ‡ Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Kamenice 3, 625 00 Brno, Czech Republic § Department of Chemistry, University of Fribourg, Chemin du Museé 9, CH-1700 Fribourg, Switzerland ∥ Institut de Chimie, University of Strasbourg, 4 rue Blaise Pascal, 67000 Strasbourg, France ⊥ Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, 5010 Malott Hall, Lawrence, Kansas 66045, United States # Department of Chemistry, University of Georgia, Athens, Georgia 30602, United States ∇ Department of Chemistry, University of Basel, Klingelbergstrasse 80, CH-4056 Basel, Switzerland 7.3. Arylsulfonyl Group 160 7.4. Ketones: 1,5- and 1,6-Hydrogen Abstraction 160 7.5. Carbanion-Mediated Groups 160 7.6. Sisyl and Other Silicon-Based Groups 161 7.7. 2-Hydroxycinnamyl Groups 161 7.8. α-Keto Amides, α,β-Unsaturated Anilides, CONTENTS and Methyl(phenyl)thiocarbamic Acid 162 7.9. Thiochromone S,S-Dioxide 162 1. Introduction 119 7.10. 2-Pyrrolidino-1,4-Benzoquinone Group 162 2. Arylcarbonylmethyl Groups 121 7.11. Triazine and Arylmethyleneimino Groups 162 2.1. Phenacyl and Other Related Arylcarbonyl- 7.12. Xanthene and Pyronin Groups 163 methyl Groups 121 o 7.13. Retro-Cycloaddition Reactions 163 2.2. -Alkylphenacyl Groups 123 8. Sensitized Release 163 2.3. p-Hydroxyphenacyl Groups 125 p 8.1.
    [Show full text]
  • Chimica Industriale “Toso Montanari”
    Alma Mater Studiorum - Università di Bologna SCUOLA DI SCIENZE Dipartimento di Chimica Industriale “Toso Montanari” Corso di Laurea Magistrale in Chimica Industriale Classe LM-71 - Scienze e Tecnologie della Chimica Industriale Supporting Cubane’s Renaissance: Metathesis reactions on 4-iodo-1-vinylcubane and Stetter reaction on 1-iodocubane-4-carboxaldehyde Tesi di laurea sperimentale CANDIDATO RELATORE Andrea Fasolini Chiar.mo Prof. Paolo RIghi CORRELATORE Prof. Mathias O. Senge ___________________________________________________________________________________________________________ _____________ Anno Accademico 2015-2016 ___________________________________________________________________________________________________________ _____________ 1 2 Abstract Cubane is a peculiar cube-shaped alkane molecule with a rigid, regular structure. This makes it a good scaffold, i.e. a molecular platform to which the substituents are arranged in a specific and fixed orientation. Moreover, cubane has a body diagonal of 2.72 Å, very similar to the distance across the benzene ring, i.e. 2.79 Å. Thus, it would be possible to use cubane as a scaffold in medicinal and material chemistry as a benzene isostere 1,2. This could lead to advantages in terms of solubility and toxicity and could provide novel properties. For this purpose, the possibility of performing “modern organic chemistry” on the cubane scaffold has to be studied. This project was entirely carried out in the framework of the Erasmus+ mobility programme at the Trinity College (Dublin, IRL) under the supervision of prof. M. O. Senge. The main goal of this project was to widen the knowledge on cubane chemistry. In particular, it was decided to test reactions that were never applied to the scaffold before, such as metathesis of 4-iodo-1-vinylcubane and Stetter reaction of 1-iodocubane-4- carboxaldehyde.
    [Show full text]
  • Design and Synthesis of Explosives: Polynitrocubanes and High Nitrogen Content Heterocycles Reported by Andrew L
    Design and Synthesis of Explosives: Polynitrocubanes and High Nitrogen Content Heterocycles Reported by Andrew L. LaFrate March 17th, 2005 Introduction In the ninth century, Chinese alchemists discovered black powder, a mixture of sulfur, charcoal, 1 and saltpeter (KNO3), while trying to invent a formula for immortality. Since then humans have been fascinated by explosives and have strived to develop more powerful formulations. In 1846, the Italian chemist Ascanio Sobrero, prepared nitroglycerine (1) by adding glycerine to concentrated HNO3 and H2SO4. Nitroglycerine was not used as an explosive until 1863 when Alfred Nobel stabilized it by adding a nitrocellulose binder, a mixture he termed “dynamite” (from Greek: dynamis meaning power).2 Dynamite and 2,4,6-trinitrotoluene (2) were the explosives of choice until the advent of the nitramine explosives RDX (3) and HMX (4) prior to the second World War. More than 60 years later, HMX (and its formulations) is still O N CH3 2 ONO the workhorse for most 2 O N NO NO N NO 2 2 2 N 2 N military and heavy duty ONO2 N O2N N N N civilian applications. ONO2 NO2 O2N NO2 NO2 Nitroglycerine (1) TNT (2) RDX (3) HMX (4) Background The two most common methods used to quantitate the performance of explosives are the velocity of detonation (VOD) and the detonation pressure (PD). VOD is the rate at which the chemical reaction propagates through the solid explosive or the velocity of the shockwave produced by an explosion. PD is a measure of the increase in pressure followed by detonation of an explosive.3 Despite the development of high explosives such as HMX, active efforts have continued within the military and scientific communities to produce better explosives to complement emerging weapons and space technologies.
    [Show full text]
  • Scheme 1. the Reaction Observed by Albrecht and Later by Diels and Alder
    Quinones as Dienophiles in the Diels–Alder Reaction; History and Applications in Total Synthesis Christopher C. Nawrat and Christopher J. Moody* In the canon of reactions available to the organic chemist engaged in total synthesis, the Diels–Alder reaction is among the most powerful and well understood. Its ability to generate rapidly molecular complexity through the simultaneous formation of two carbon-carbon bonds is almost unrivalled, and this is reflected in the great number of applications of it reported in the literature. Historically the use of quinones as dienophiles is highly significant being the very first example investigated by Diels and Alder. Herein we review the application of the Diels–Alder reaction of quinones in the total synthesis of natural products. The highlighted examples span some 60 years from the landmark syntheses of morphine and reserpine by Gates and Woodward respectively in 1952 and 1956, through to the present day examples such as the tetracyclines. 1. History and importance of the Diels–Alder reaction Although the [4 + 2]-cycloaddition reaction now bears the names of Professor Otto Diels and his student Kurt Alder for their seminal publication in 1928,[1] history could easily have been otherwise. Indeed, in the two decades preceding their work, some of the greatest organic chemists of the day, including Thiele, Zincke[2] and von Euler,[3] had already unknowingly observed the reaction occurring.[4] The reaction studied by Diels and Alder was that between cyclopentadiene and benzoquinone, which gave a mixture of mono- and di- adducts (1 and 2), and it was the successful identification of the products, the formation of which was inexplicable with the chemistry known at the time, that ensured them a place in history (Scheme 1).
    [Show full text]
  • Name Reactions
    Name Reactions A Collection of Detailed Reaction Mechanisms Bearbeitet von Jie Jack Li 1. Auflage 2002. Buch. xviii, 417 S. Hardcover ISBN 978 3 540 43024 7 Format (B x L): 15,5 x 23,5 cm Gewicht: 780 g Weitere Fachgebiete > Chemie, Biowissenschaften, Agrarwissenschaften > Chemie Allgemein Zu Leseprobe schnell und portofrei erhältlich bei Die Online-Fachbuchhandlung beck-shop.de ist spezialisiert auf Fachbücher, insbesondere Recht, Steuern und Wirtschaft. Im Sortiment finden Sie alle Medien (Bücher, Zeitschriften, CDs, eBooks, etc.) aller Verlage. Ergänzt wird das Programm durch Services wie Neuerscheinungsdienst oder Zusammenstellungen von Büchern zu Sonderpreisen. Der Shop führt mehr als 8 Millionen Produkte. Table of Contents Preface ................................................................................................................XIII Abbreviations.......................................................................................................XV 1. Abnormal Claisen rearrangement..............................................................1 2. Alder ene reaction......................................................................................2 3. Allan–Robinson reaction ...........................................................................3 4. Alper carbonylation...................................................................................5 5. Amadori glucosamine rearrangement........................................................7 6. Angeli–Rimini hydroxamic acid synthesis................................................8
    [Show full text]
  • The Design of Novel Benzoin Acetate Photolabile Protecting Groups
    The Design of Novel Benzoin Acetate Photolabile Protecting Groups by Laura J. McKay BSc, University of Victoria, 2018 Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science in the Department of Chemistry Faculty of Science © Laura McKay 2021 SIMON FRASER UNIVERSITY Spring 2021 Copyright in this work rests with the author. Please ensure that any reproduction or re-use is done in accordance with the relevant national copyright legislation. Declaration of Committee Name: Laura McKay Degree: Master of Science (Chemistry) Thesis title: The Design of Novel Benzoin Acetate Photolabile Protecting Groups Committee: Chair: Robert Britton Professor, Chemistry Neil Branda Supervisor Professor, Chemistry Peter Wilson Committee Member Associate Professor, Chemistry Andrew Bennet Committee Member Professor, Chemistry Vance Williams Examiner Professor, Chemistry ii Abstract Photoremovable protecting groups are powerful tools for the release or deprotection of a wide range of molecules. Benzoin type photoremovable protecting groups are renowned for their exceptional properties but have been significantly underdeveloped. This thesis concerns the design, synthesis, and evaluation of four molecules in the benzoin class. A review of the benzoin photolabile protecting group is presented in Chapter 2. The first study, featured in Chapter 3, revisits the fundamental photochemistry of the 3’,5’-dimethoxybenzoin acetate photolabile protecting group and explores that of two polyaromatic derivatives. In a second study, Chapter 4, the unique photochemistry of a donor acceptor 4- dimethylamino-3’,5’-dimethoxybenzoin photocage is examined. The implications of the deviation of this photorelease from all known mechanistic pathways are discussed. A second donor-acceptor derivative 4-methoxy-3’,5’-dimethoxybenzoin was designed to combine the traditional photochemistry of dimethoxybenzoin acetate with the advantageous properties of the previous donor acceptor species.
    [Show full text]
  • The Ramberg-Bäcklund Reaction
    The Ramberg-Bäcklund Reaction Richard J. K. Taylor, University of York, Heslington, York, UK Guy Casy, Cambridge, UK 1. Introduction The base-mediated conversion of -halosulfones into regio-defined alkenes was first described by Ludwig Ramberg and Birger Bäcklund. (1) This transformation, generalized in Eq. 1, has proved to be of wide synthetic value and is now known as the Ramberg-Bäcklund reaction. (Also referred to as the Ramberg-Bäcklund rearrangement, and abbreviated herein as RBR). (1) The facile nature of the RBR is surprising given the difficulties encountered when attempting to carry out nucleophilic substitution reactions on -halosulfones. (2) In contrast to halogens adjacent to carbonyls and related electron-withdrawing groups, (3) polar, steric, and field effects appear to combine leading to the marked deactivation of -halosulfones. The stereochemical outcome of the reaction was also unexpected: a predominance of Z-alkenes is often observed with relatively weak bases (e.g. sodium hydroxide) whereas stronger bases [e.g. potassium tert-butoxide] tend to favor E-alkenes. The mechanism of the RBR was therefore the subject of intense interest, particularly in the 1950's and 1960's; mechanistic aspects are reviewed in the next section. From the synthetic viewpoint, the RBR is attractive for a number of reasons: i. The accessibility of the precursor sulfides and sulfones, ii. The conjunctive nature of the process, iii. The unambiguous location of the resulting double bond, iv. The absence of alkene rearrangement processes due to the alkaline reaction conditions, v. The applicability of the procedure to all alkene substitution patterns including tetra-substituted variants, vi.
    [Show full text]
  • Methods for Ring Contraction Chem 115
    Myers Methods for Ring Contraction Chem 115 Recent Reviews: • Chiral-pool starting materials have been much used as substrates for the Favorskii reaction, affording functionalized, optically active cyclopentanes. Song, Z.-L.; Fan, C.-A.; Tu, Y.-Q. Chem. Rev. 2011, 111, 7523–7556. O O O Silva, Jr. L. F. Tetrahedron 2002, 58, 9137–9161. H O Cl CH3 2 2 CH 1. TMSCl 3 CH3 • O Ring contraction reactions can be grouped into three general categories based on mechanism: NaOH 2. DHP, p-TsOH THPO 90% 81% (2 steps) O O Nu CH3 CH3 CH3 X Nu: Anionic (–)-Carvone NaOCH3 CH3OH O Nu O O CH CO3CH3 3 CH H Nu: 3 CH Carbenoid THPO 3 80% CH3 THPO M Lee, E.; Yoon, C. H. J. Chem. Soc., Chem. Commun. 1994, 479–481. O O R R • For example, the ring contraction of a (+)-pulegone derivative has been used in the synthesis of Cationic several terpenoid natural products. CH CH3 3 CH3 Anionic Ring Contractions Br2 NaOCH3 Favorskii Rearrangement CO2CH3 O O Et2O Br CH3OH • The Favorskii reaction leads to the rearrangement of an !-halo cycloalkanone upon treatment CH3 CH3 CH3 CH3 CH3 Br with base. This reaction proceeds through a cyclopropanone intermediate that is opened by CH3 60–67% (2 steps) nucleophilic attack. (+)-Pulegone O O O OCH3 NaOCH OCH3 Cl 3 Et2O, 35 °C, 2 h CH CH3 56–61% CH 3 3 H CH3 H Organic syntheses; Wiley & Sons: New York, 1963; Coll. Vol. No. 4, pp. 594. CH CH3 3 O H O CH3 CH • In some cases, enolization is not possible, precluding cyclopropanone formation.
    [Show full text]