DOCSLIB.ORG

Hydrogen Bond-Directed Stereospecific Interactions in (A) General Synthesis of Chiral Vicinal Diamines and (B) Generation of Helical Chirality with Amino Acids

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Hydrogen Bond-Directed Stereospecific Interactions in (A) General Synthesis of Chiral Vicinal Diamines and (B) Generation of Helical Chirality with Amino Acids HYDROGEN BOND-DIRECTED STEREOSPECIFIC INTERACTIONS IN (A) GENERAL SYNTHESIS OF CHIRAL VICINAL DIAMINES AND (B) GENERATION OF HELICAL CHIRALITY WITH AMINO ACIDS by Hyunwoo Kim A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Graduate Department of Chemistry University of Toronto © Copyright by Hyunwoo Kim, 2009 Hydrogen Bond-Directed Stereospecific Interactions in (A) General Synthesis of Chiral Vicinal Diamines and (B) Generation of Helical Chirality with Amino Acids Hyunwoo Kim Doctor of Philosophy 2009 Department of Chemistry University of Toronto ABSTRACT Hydrogen bonding interactions have been applied to the synthesis of chiral vicinal diamines and the generation of helical chirality. A stereospecific synthesis of vicinal diamines was developed by using the diaza-Cope rearrangement reaction driven by resonance-assisted hydrogen bonds (RAHBs). This process for making a wide variety of chiral diamines requires only a single starting chiral diamine, 1,2-bis(2-hydroxyphenyl)-1,2-diaminoethane (HPEN) and aldehydes. Experimental and computational studies reveal that this process provides one of the simplest and most versatile approaches to preparing chiral vicinal diamines including not only C2 symmetric diaryl and dialkyl diamines but also unsymmetrical alkyl-aryl and aryl-aryl diamines with excellent yields and enantiopurities. Weak forces affecting kinetics and thermodynamics of the diaza-Cope rearrangement were systematically studied by combining experimental and computational approaches. These forces include hydrogen bonding effects, electronic effects, steric effects, and oxyanion effects. As an example of tuning diamine catalysts, a vicinal diamine-catalyzed synthesis of warfarin is described. Detailed mechanistic studies lead to a new mechanism involving diimine intermediates. Decreasing the NCCN dihedral angle by varying the diamine structure results in an increase of the enantioselectivity up to 92% ee. Hydrogen bonds have been used to generate helical chirality in a highly stereospecific manner with a single amino acid and 2,2′-dihydroxybenzophenone. DFT computational and experimental data including circular dichroism (CD), X-ray crystallography and 1H NMR data provide insight into the origin of the stereospecificity. A signalling dizao group can be attached to the receptor for general sensing of amino acid enantiopurity. ii ACKNOWLEDGEMENTS I would like to express my sincere gratitude to my supervisor, Professor Jik Chin, for his mentorship, guidance, and encouragement throughout my studies. His scientific insight and unbounded enthusiasm will always be a source of inspiration for me. I would also like to thank Professors Andrei Yudin, Vy Dong, Mark Lautens, and Peter Guthrie for their discussions and suggestions while serving as members of my thesis defense committee. I extend my gratitude to Dr. Tim Burrow (NMR) and Dr. Alan Lough (X-ray) for their technical assistance. The financial support from Government of Canada Awards, University of Toronto, and DiaminoPharm Inc. is greatly acknowledged. My time spent in the Chin group has been enjoyable and memorable. I would like to thank Professor Hae-Jo Kim, Dr. Soon Mog So, Dr. Woosung Kim, Cindy Yen, Yen Nguyen, and Leo Mui for their support and friendship. I wish to thank Cindy once again for helping my departmental seminar and for reading all my rough writing. I would like to express my deepest gratitude to my parents. They have supported me in every way imaginable throughout my life and I could not have done this without them. This work is dedicated to them. My final thanks are reserved for my beautiful wife Eunha. Everything that I have accomplished during my time here would definitely not be possible without the constant love, understanding, and support from her. iii TABLE OF CONTENTS Chapter 1: Introduction to Vicinal Diamines ....................................................................... 1 1.1. Introduction ............................................................................................................ 1 1.2. Synthesis of chiral, vicinal diamines ...................................................................... 2 1.2.2. Production of DACH and DPEN .............................................................. 3 1.2.2. Enantioselective synthesis of vicinal diamines ......................................... 4 1.3. Vicinal-diamine-based catalysts ............................................................................. 6 1.3.1. Steric and electronic tuning of catalyst structure ...................................... 8 1.3.2. New diamine designs .............................................................................. 13 1.3.3. Diamines on solid support ....................................................................... 15 1.3.4. Water-soluble diamine catalysts ............................................................. 16 1.4. Diamine drugs ...................................................................................................... 16 1.4.1. Acyclic diamines ..................................................................................... 17 1.4.2. Imidazolines ............................................................................................ 18 1.4.3. Piperazines .............................................................................................. 19 1.4.4. Other diamines ........................................................................................ 19 1.5. Summary .............................................................................................................. 21 1.6. Plan of Study ........................................................................................................ 22 Chapter 2: Stereospecific Synthesis of Vicinal Diamines by the Diaza-Cope Rearrangement ................................................................................................... 24 2.1. Introduction .......................................................................................................... 24 2.2. Diaryl vicinal diamines ........................................................................................ 25 2.3. Dialkyl vicinal diamines ...................................................................................... 37 2.3.1. Imidazolidine-dihydro-1,3-oxazines ....................................................... 38 2.3.2. Synthesis of dialkyl vicinal diamines ...................................................... 45 2.3.1. Origin of synthetic challenge .................................................................. 50 2.3.2. Transition state geometries ..................................................................... 54 2.4. Unsymmetrical vicinal diamines .......................................................................... 56 2.4.1. Unsymmetrical diaryl diamines .............................................................. 57 2.4.2. Unsymmetrical alkyl-aryl diamines ........................................................ 59 2.5. Diastereoselective diaza-Cope Rearrangement .................................................... 62 2.6. Conclusions .......................................................................................................... 68 2.7. Experimental ........................................................................................................ 69 iv Chapter 3: Controlling Diaza-Cope Rearrangements with weak forces .......................... 87 3.1. Introduction .......................................................................................................... 87 3.2. The electronic effect ............................................................................................. 89 3.3. The hydrogen bonding effect ............................................................................... 94 3.4. The steric effect .................................................................................................. 102 3.5. The oxyanion effect ............................................................................................ 112 3.6. Interplay of weak forces on the thermodynamics .............................................. 117 3.7. Effect of weak forces on the kinetics ................................................................. 121 3.8. Conclusions ........................................................................................................ 123 3.9. Experimental ...................................................................................................... 124 Chapter 4: Organocatalytic Synthesis of Warfarin ......................................................... 128 4.1. Introduction ........................................................................................................ 128 4.2. Revision of imidazolidine catalyzed warfarin synthesis .................................... 129 4.3. Vicinal diamine-catalyzed synthesis of warfarin ............................................... 134 4.4. Conclusions ........................................................................................................ 140 4.5. Experimental ...................................................................................................... 140 Chapter 5: Highly Stereospecific Generation of Helical Chirality by Imprinting with Amino Acids ..................................................................................................... 141 5.1. Introduction .......................................................................................................
Load more

Recommended publications
  • Strategic Applications of Tandem Reactions in Complex Natural Product Synthesis
    Strategic Applications of Tandem Reactions in Complex Natural Product Synthesis: Rapid Access to the (Iso)Cyclocitrinol Core Christopher W. Plummer Submitted in partial fulfillment of the Requirement for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences Columbia University 2012 © 2012 Christopher Wainwright Plummer All Rights Reserved Abstract Strategic Applications of Tandem Reactions in Complex Natural Product Synthesis: Rapid Access to the (Iso)Cyclocitrinol Core Christopher W. Plummer This thesis describes the efforts of Professor James Leighton and myself toward the synthesis of the tetracyclic core of a class of steroidal natural products known as the cyclocitrinols. Our initial work in this area was performed on racemic model systems in order to validate our ring contraction-Cope rearrangement strategy. Novel chemistry was then identified to access the functionalized core in enantio-enriched form. Finally, in line with our efforts to probe the transition state of our key tandem Claisen-Cope reaction, additional substrates were prepared supporting our proposed transition state and improving the efficiency of this transformation. Table of Contents Chapter I. Background………………………………………………………....……………1 1.1: Isolation and Characterization of the Cyclocitrinols 1 1.2: Biosynthesis and Previous Synthetic Approach 2 1.3: Retrosynthetic Analysis 5 1.4: Previous Synthetic Efforts in the Leighton Laboratory 9 Chapter II. Model Studies……………………………………………………………….….13 2.1: 1st Generation Macrolactone Approach 13 2.2:
    [Show full text]
  • Anion Relay Cyclopropanation and Aryl Vinyl Cyclopropane Cope Rearrangements By
    Anion Relay Cyclopropanation and Aryl Vinyl Cyclopropane Cope Rearrangements By Kevin Michael Allegre B.Sc., The University of Kansas, 2013 Submitted to the graduate degree program in Chemistry and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. Chair: Jon A. Tunge Paul R. Hanson Helena Malinakova Michael Rubin Ryan A. Altman Date Defended: 18 July 2019 The dissertation committee for Kevin M. Allegre certifies that this is the approved version of the following dissertation: Anion Relay Cyclopropanation and Aryl Vinyl Cyclopropane Cope Rearrangements Chair: Jon A. Tunge Date Approved: 24 July 2019 ii Abstract Kevin M. Allegre and Jon A. Tunge Department of Chemistry, July 2019 University of Kansas Anion Relay Chemistry is a powerful tool for the rapid development of molecular complexity in an operationally simple manner. Much of the work in this field has been pioneered and developed by the Smith group, whose work has primarily focused on silicon and phosphorus Brook rearrangements to effect anion relay. Presented herein is the development of a retro-Claisen condensation protocol to effect anion relay in the synthesis of vinyl cyclopropanes, and subsequent aromatic Cope rearrangement of those vinyl cyclopropanes. This protocol provides a supplementary method of anion relay utilizing readily accessible nucleophiles, which obviates the need for synthesis of alkyl silanes or phosphines as starting materials. Chapter 1 is a review of anion relay chemistry, which focuses on through-space anion relay over 3 or more bonds. It covers both new developments and applications to total synthesis of through-space anion relay more than three bonds since the field was last reviewed by Smith in 2008.
    [Show full text]
  • Elimination Reactions Are Described
    Introduction In this module, different types of elimination reactions are described. From a practical standpoint, elimination reactions widely used for the generation of double and triple bonds in compounds from a saturated precursor molecule. The presence of a good leaving group is a prerequisite in most elimination reactions. Traditional classification of elimination reactions, in terms of the molecularity of the reaction is employed. How the changes in the nature of the substrate as well as reaction conditions affect the mechanism of elimination are subsequently discussed. The stereochemical requirements for elimination in a given substrate and its consequence in the product stereochemistry is emphasized. ELIMINATION REACTIONS Objective and Outline beta-eliminations E1, E2 and E1cB mechanisms Stereochemical considerations of these reactions Examples of E1, E2 and E1cB reactions Alpha eliminations and generation of carbene I. Basics Elimination reactions involve the loss of fragments or groups from a molecule to generate multiple bonds. A generalized equation is shown below for 1,2-elimination wherein the X and Y from two adjacent carbon atoms are removed, elimination C C C C -XY X Y Three major types of elimination reactions are: α-elimination: two atoms or groups are removed from the same atom. It is also known as 1,1-elimination. H R R C X C + HX R Both H and X are removed from carbon atom here R Carbene β-elimination: loss of atoms or groups on adjacent atoms. It is also H H known as 1,2- elimination. R C C R R HC CH R X H γ-elimination: loss of atoms or groups from the 1st and 3rd positions as shown below.
    [Show full text]
  • Synthesis and Reactions of 4,5-Homotropone and 4,5-Dimethylenetropone Richard Anthony Fugiel Iowa State University
    Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1974 Synthesis and reactions of 4,5-homotropone and 4,5-dimethylenetropone Richard Anthony Fugiel Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Organic Chemistry Commons Recommended Citation Fugiel, Richard Anthony, "Synthesis and reactions of 4,5-homotropone and 4,5-dimethylenetropone " (1974). Retrospective Theses and Dissertations. 5986. https://lib.dr.iastate.edu/rtd/5986 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. INFORIVIATIOIM TO USERS This material was produced from a microfilm copy of the original document. While the most advanced technological means to photograph and reproduce this document have been used, the quality is heavily dependent upon the quality of the original submitted. The following explanation of techniques is provided to help you understand markings or patterns which may appear on this reproduction. 1.The sign or "target" for pages apparently lacking from the document photographed is "Missing Page(s)". If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting thru an image and duplicating adjacent pages to insure you complete continuity. 2. When an image on the film is obliterated with a large round black mark, it is an indication that the photographer suspected that the copy may have moved during exposure and thus cause a blurred image.
    [Show full text]
  • Gold Catalysis in Organic Synthesis
    SCI Review Meeting 2010 Gold Catalysis in Organic Synthesis Paul Davies [email protected] School of Chemistry University of Birmingham November 2010 111 Why use gold catalysis for organic synthesis? • Gold catalysed reactions show several characteristics that render them synthetically attractive: – Significant increases in molecular complexity; – Diverse set of reactions; – Mild reaction conditions (often room temperature); – Au(I) generally tolerant of oxygen; – Minimal use of additives; – Excellent chemoselectivity; – Asymmetric control possible; – Straightforward work-ups; – Robust readily accessible precatalysts; – Orthogonal reactivity to many other TM catalysed processes; – Au(I), Au(III) do not readily cycle between oxidation states (though see final section). 2 Talk Overview This talk is intended to give an overview of the breadth and depth of gold catalysis in the development of methodology for organic synthesis and its implementation. The talk is loosely broken down into sub-sections concerning particular types of overall reactivity: 1. Gold as a π–acid 2. X-H addition across π–systems 3. Indirect X-H addition 4. C-H addition across π–systems 5. Gold Intermediates 6. C-X addition across π–systems 7. Cycloadditions 8. Enyne cycloisomerisations 9. Propargylic carboxylates 10.Preparation of gold carbenoids 11.Recent advances in gold redox cycles 333 Gold as a π-acid catalyst • A diverse range of transformations have been developed based on the activation of alkynes by gold (and platinum) salts and complexes: • π-acids: – Metal fragments that bind to a C-C multiple bond – Deprive multiple bonds of a part of their electron density – Induce positive charge onto multiple bonds – “soft” counterparts to conventional Lewis acids • More electron density is lost than is gained through back donation, rendering the π- system electrophilic Reviews: Relativistic Effects: D.
    [Show full text]
  • PDF (Appendix 2: the Cope Rearrangement)
    65 APPENDIX TWO The Cope Rearrangement A2.1 The Cope Rearrangement In 1940, Arthur Cope discovered a thermal rearrangement of 1,5-diene 137a to a more conjugated isomeric 1,5-diene (137b, Scheme A2.1.1).1 Cope postulated that his rearrangement was an all-carbon analogue of the Claisen rearrangement,2 and was intramolecular. He speculated that the reaction proceeded through a six-membered transition state. Cope published these hypotheses 25 years before Woodward and Hoffman3 disclosed the first papers on conservation of orbital symmetry, a theory that explained the molecular orbital basis for synchronous Cope rearrangements, calling them [3,3] sigmatropic rearrangements. Scheme A2.1.1 The Cope rearrangement 150–160 °C NC NC Me 4 h Me EtO2C EtO2C Me Me 137a 137b A2.2 Transition State Geometry in Concerted Cope Rearrangements4 Thermal [3,3] sigmatropic rearrangements occur with suprafacial–suprafacial geometries3 through a six-membered cyclic transition state in either a chair or boat conformation. In 1962, Doering and Roth5 determined that in simple cases, the Cope rearrangement proceeded through a chair-like transition state (Scheme A2.2.1). On the basis of product ratios, Doering and Roth estimated that ΔΔG‡ (boat–chair) for meso 66 138a was 5.7 kcal/mol. Subsequent experiments by Hill excluded the twist (helix) arrangement,6 which had not been considered by Doering and Roth. Scheme A2.2.1 Feasible transition states for the Cope rearrangement Me Me Me Me ! Me Me Me Me (99.7% yield) 138b Me Me Me Me ! ! Me Me Me Me Me Me (0.3% yield) 138a 138c Me Me Me Me ! Me Me Me Me 138d While simple Cope rearrangements employ a chair transition state, the boat transition state is used when molecules are geometrically constrained, as is the case with 1,2-divinyl cyclopropanes in which the vinyl groups are nearly elipsed.7 Most 1,2- divinylcyclobutanes also proceed through boat transition states,8,9 but their larger ring size accompanies greater structural flexibility.
    [Show full text]
  • Progress Toward the Total Synthesis of Paclitaxel (Taxol®)
    PROGRESS TOWARD THE TOTAL SYNTHESIS OF PACLITAXEL (TAXOL®) DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Matthew M. Kreilein, M.S. * * * * * The Ohio State University 2005 Dissertation Committee: Approved by Professor Leo A. Paquette, Advisor Professor David J. Hart Professor T.V. RajanBabu _____________________________ Advisor Professor Pui-Kai Li Chemistry Graduate Program ABSTRACT Described herein is the continuation of efforts focused towards the synthesis of Taxol utilizing a route that is amenable to novel analog formation from advanced Taxol precursors. Elaboration of (1S)-(+)-10-camphorsulfonic acid to a highly functionalized taxane skeleton has been achieved in a total of twenty-two synthetic operations. Highlighting the brevity and efficiency of this series is the fact that only five operations thus far are protecting group manipulations, which tend to significantly increase the length and complexity of a synthetic route. Entry to a completed D-ring has been made by prevous researchers in a six-step sequence. After the revelation that formation of the densly functionalized A-ring in the presence of a completed D-ring was not possible, the focus became one of elaboration of the A-ring using the very useful diosphenol intermediate 3.1. Two areas of research have been explored and are described. First, the route to the bridge-migrated taxane 1.85 was reviewed and problems existing in the key alkenyl iodide coupling, dihydroxylation, C2 oxygenation, and bridge migration were investigated and resolved. ii With an efficient synthesis of 1.85 in hand, attention was focused on completion of the A-ring beginning with routes originating from 1.85.
    [Show full text]
  • Substituent Control in the Oxy-Cope Rearrangements of 1-Vinyl-Trans-Cyclotridec-3-En-1-Ol Systems
    AN ABSTRACT OF THE THESIS OF Khushroo Peshotan Daruwala for the degree of Doctor of Philosophy in Chemistry presented on July 18, 1986 Title: SUBSTITUENT CONTROL IN THE OXY-COPE REARRANGEMENTS OF 1-VINYL-TRANS-CYCLOTRIDEC-3-EN-1-0L SYSTEMS Abstract approved: Redacted for privacy (Richard W. Thies) The thermal and anionic rearrangements of substituted 1-vinyl- trans-cyclotridec-3-en-l-ol compounds have been studied to determine what effects substituents would have on the sigmatropic shift when placed on the two positions of the 1-vinyl group. For the thermal rearrangements, the a-substituted vinyl-trans- cyclotridecenols gave both the [3,3] and [1,3] shift products of rearrangement. On the other hand the 0-methyl and trimethylsilyl groups gave a high periselective control favoring the [1,3] shift siloxy-Cope ring expansion relative to the [3,3] shift. A rather unusual result was obtained for the 0-isopropyl case. The products obtained from its rearrangement were trienes resulting from loss of the trimethylsiloxy group. The effect of substituents on the control of periselectivity in the case of anionic rearrangements was much less than for the thermal ones. The m-substituted vinyl-trans-cyclotridecenols gave products of rearrangement comparable to that of the unsubstituted case, studied earlier. However the study of the anionic rearrangements of the 0-substituted alcohols were found to be of interest, since their products of rearrangement would throw considerable light on the nature of the mechanism as to whether it is concerted or non-concerted. Thus treatment of cis and trans 0-methyl vinyl-cyclotridecenols with KH in HMPA, gave along with the [1,3] shift product, both the [3,3] shift diastereomers.
    [Show full text]
  • Transannular Pericyclic Reactions
    Transannular Claisen Rearrangements of α-Sulfonyl Lactones Sophie Gore Julia Laboratory, Department of Chemistry, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom June 2009 A thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy, Imperial College London Abstract This thesis is divided into three sections. Section one is a review of transannular pericyclic reactions. It covers the four main types of pericyclic reaction and major contributions in the field to date. Recent applications of these reactions to natural product synthesis are also included. Section two discusses the results of research efforts into transannular Claisen rearrangements of α-sulfonyl lactones. The background to the project is discussed along with initial investigations into the transannular Claisen and decarboxylative Claisen rearrangements (dCr) of the 7-membered α-tosyl lactone to form vinyl cyclopropanes. Stereoselectivity from within the pericyclic array, by substitution at the lactone C7 position is examined. Efforts towards stereoinduction from outside of the pericyclic array are also detailed, along with aryl substitution at the lactone C5 position to form highly substituted vinyl cyclopropanes. Extension of this methodology to the unprecedented transannular Claisen rearrangement and dCr reaction of 8-membered α- tosyl lactones to give vinyl cyclobutanes is reported. Finally, efforts towards a novel synthetic route to (±)-grandisol utilising the transannular Claisen rearrangement chemistry
    [Show full text]
  • Msc-Chemistry.Pdf
    BHARATHIDASAN UNIVERSITY (Re-accredited with ‘A’ Grade by NAAC) CENTRE FOR DISTANCE EDUCATION PALKALAIPERUR, TIRUCHIRAPPALLI – 24 M.Sc., CHEMISTRY Major Paper -I Organic Chemistry - I I - Year Copy right reserved For Private Circulation only Lesson Writter Dr. T. Vimala, Associate Professor PG & Research Department of Chemistry Seethalakshmi Ramaswami College, Tiruchirappalli-620 002. 2 MAJOR PAPER I – ORGANIC CHEMISTRY UNIT – I Nomenclature, Reactive Intermediates, Methods of Determining Reaction Methods 1.1. Nomenclature of alicyclic, bicyclic and tricyclic compounds. Nomenclature of heterocycles having not more than two hetero atoms such as oxygen, nitrogen and sulphur. 1.2. Aromatic character: six-, five-, seven-, and eight-membered rings – Other systems with aromatic sextets Huckel’s theory of aromaticity, Concept of homoaromaticity and antiaromaticity, systems with 2,4,8 and 10 electrons, systems of more than 10 electrons, alternant and non-alternant hydrocarbons (azulene type). Bonding properties of systems with (4n + 2) electrons and 4n electrons, Heteraromatic molecules. Annulenes and sydnones and fullerenes. 1.3. Thermodynamic and kinetic aspects, Hammond’s postulate, isotope effects. Energy profile diagrams – Intermediate versus transition state, Product analysis and its importance, Crossover experiments, Kinetic methods, Stereochemical studies, Isotopic and substitutent effects. UNIT – II Stereochemistry 2.1 Fundamentals of Organic Stereochemistry: Principles of symmetry – Stereoisomerism – Optical isomerism – Definitions – Conventions used in stereochemistry: Newman, Sawhorse and Fischer notations and interconversions and representations. Nomenclature, correlation of configuration. Cahn – Ingold – Prelog rules for simple molecules. Optical activity and chirality – Types of molecules exhibiting optical activity – Fischer projection – Absolute configuration. Molecules with more than one chiral centre – Molecular chirality – Atropisomerism – Biphenyls, 3 allenes and spiranes.
    [Show full text]
  • UCLA Electronic Theses and Dissertations
    UCLA UCLA Electronic Theses and Dissertations Title Computational Exploration of Reactivities and Catalysis of Pericyclic Reactions Permalink https://escholarship.org/uc/item/6st5r669 Author Fell, Jason Scott Publication Date 2018 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA Los Angeles Computational Exploration of Reactivities and Catalysis of Pericyclic Reactions A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Chemistry by Jason Scott Fell 2018 © Copyright by Jason Scott Fell 2018 ABSTRACT OF THE DISSERTATION Computational Explorations of Reactivities and Catalysis of Pericyclic Reactions By Jason Scott Fell Doctor of Philosophy in Chemistry University of California, Los Angeles, 2018 Professor Kendall N. Houk, Chair This dissertation describes research that delves into exploring puzzling chemical phenomena utilizing modern computational chemistry methods. Theoretical chemical models that are coupled with quantum mechanical (QM) calculations can dissect complex chemical reactions into many components that influence chemical reactivity and selectivity. Each chapter of this dissertation demonstrates that QM calculations can help predict and explain the complexities of chemical phenomena involving reaction mechanisms. The first section (hapters 1 thru 4) details computational explorations of reactivities and selectivities of pericyclic reactions. Pericyclic reactions are an important class of chemical reactions wherein the reacting species form a cyclic transition state with aromatic delocalization. ii Often these reactions occur with high degrees of regio- and stereoselectivity. Chapter 1 explores the large differences in reactivity between cyclic 1- and 2-azadienes in Diels-Alder reactions. Chapter 2 investigates how thiol addition to substituted oxanorbornadienes promotes a retro- Diels-Alder reaction, as well as how the substitution pattern on the norbornadiene affects the rates of fragmentation.
    [Show full text]
  • Organosulfur Compounds and Reactions
    Organosulfur compounds and reactions Key reactions of Organosulfur Compounds (Students references) Organosulfur compounds and reactions 2 2 6 2 4 Sulfur has the electronic configuration 1s 2s 2p 3s 3p . Sulfur exists in acyclic and cyclic Sn species or allotropic form owing to have a marked tendency to react with itself (catenation). The sulfur-sulfur bond in elemental sulfur is probably a resonance hybrid for which S8 ring exists in the energetically favoured crown shape. All the chain and ring forms of sulfur are thermodynamically less stable than cyclooctasulfur (S8) at 25°C. Saturated hydrocarbons can be dehydrogenated by heating with sulfur. For example, cyclohexane is converted to benzene. Sulfur, like most elements in the second and higher rows of the periodic table, is reluctant to form normal π-double bonds; thus, thiocarbonyl (C=S) compounds are comparatively rare and are usually unstable with a tendency to polymerise. This is a result of the relatively low effectiveness of pπ-dπ bonding involving lateral overlap of the 3p-orbitals and arising from the larger size of the sulfur atom as compared with carbon. The sulfur atom (atomic radius 1.02Å; 1 Å = 0.1 nm) is larger than oxygen (atomic radius 0.73 Å). Sulfur is consequently more polarisable than oxygen; the sulfur lone pairs of electrons are better nucleophiles but weaker bases in reactions with acids. The outer electronic shell in sulfur contains not only s-electrons and p- electrons but also vacant 3d-orbitals which can be utilised in bonding. The 3p orbitals of sulfur are too large to overlap effectively with 2p orbitals on oxygen or carbon.
    [Show full text]