DOCSLIB.ORG

DFT Study of the Mechanism and Stereoselectivity of the 1,3-Dipolar Cycloaddition Between Pyrroline-1-Oxide and Methyl Crotonate

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
DFT Study of the Mechanism and Stereoselectivity of the 1,3-Dipolar Cycloaddition Between Pyrroline-1-Oxide and Methyl Crotonate J. Chem. Sci. Vol. 126, No. 1, January 2014, pp. 283–292. c Indian Academy of Sciences. DFT study of the mechanism and stereoselectivity of the 1,3-dipolar cycloaddition between pyrroline-1-oxide and methyl crotonate KHADIJA MARAKCHIa,∗, RACHIDA GHAILANEb, OUM KALTOUM KABBAJa and NAJIA KOMIHAa aLaboratoire de Spectroscopie, Modélisation Moléculaire, Matériaux et Environnement (LS3ME) Université Mohammed V-Agdal Faculté des Sciences, BP 1014 Rabat, Maroc bLaboratoire de Synthèse Organique, Organométallique et Théorique. Faculté des Sciences, Université Ibn Tofail, BP 13314 Kénitra, Maroc e-mail: [email protected] MS received 22 May 2013; revised 8 October 2013; accepted 23 October 2013 Abstract. A theoretical study of the regio- and stereoselectivities of the 1,3-dipolar cycloaddition reaction between methyl crotonate and pyrroline-1-oxide has been carried out using density functional theory (DFT) at the B3LYP/6-31G(d) level of theory. The reaction has been followed by performing transition state opti- mization, calculations of intrinsic reaction coordinate and activation energies; the molecular mechanism of the reactions is concerted and asynchronous. The regio- and exo/endo-selectivity have been explained in terms of frontier molecular orbital interactions, local and global electrophilicity and nucleophilicity indices and an analysis of the Wiberg bond indices in the transition state. The FMO analysis and DFT-based reactivity indices showed that the regioselectivity of this reaction is controlled by the HOMOdipole–LUMOdipolarophile interaction. The activation parameters indicated favoured endo approach along the meta-pathway in agreement with the experimental results. Keywords. Pyrroline-1-oxide; dipolar cycloaddition; optimized structures; stereoselectivity; DFT-based reactivity indices. 1. Introduction levels together with the 6-31G* basis set. Activation energies and asynchronicity are dependent on the com- 1,3-Dipolar cycloaddition (1,3-DC) is one of the sim- putation level. Thus, while HF calculations gave large plest approaches for the construction of five-membered barriers, MP2 calculations tend to underestimate them. heterocyclic rings.1 Reactions between nitrones and DFT calculations gave reasonable values.8 Liu et al.9 alkenes leading to isoxazolidines are well-known have performed DFT calculations at B3LYP/6-31G* construction processes.1,2 Substituted isoxazolidines level on the 1,3-dipolar cycloaddition reaction of the are interesting biological active compounds3 and could simplest nitrone to dipolarophiles containing electron- be used as enzyme inhibitors.4,5 They are also fre- releasing substituents. Here, the endo approach is quently used as intermediates for the synthesis of a kinetically favoured because of stabilization of the variety of compounds after cleavage of the N–O bond.6 secondary orbital interactions. In another study, In the context of the cycloadditions of nitrones Cossó et al.10 have used B3LYP/6-31G* calculations to with several dipolarophiles, we have reported a den- study the 1,3-dipolar cycloaddition reaction of unsub- sity functional theory (DFT) study of 1,3-dipolar stituted nitrone with nitroethene. Asynchronicity in cycloaddition reaction between simple nitrone with the bond formation process in the two regioisomeric three-fluorinated dipolarophiles, analysis of the results approaches of the two reactants is found to be controlled on different reaction pathways shows that the reac- by the electron-deficient dipolarophile. Domingo tion occurs through a concerted process and proceed et al. have studied the 1,3-dipolar cycloaddition reac- more or less synchronously.7 We have also studied the tion of nitrones with several dipolarophiles using DFT molecular mechanism for the 1,3-dipolar cycloaddi- methods at the B3LYP/6-31G* and B3LYP/6-31+G* tion of nitrone with sulphonylethene chloride using ab levels.11,12 Their calculations predict an asynchronous initio and DFT methods at the HF, MP2 and B3LYP concerted mechanism and both stereo and regiose- lectivity were found dependent on the computational ∗For correspondence model and computational level. Nacereddine et al.13 283 284 Khadija Marakchi et al. have studied the regio- and stereoselectivities of the graphical interface GaussView3.08. The full geomet- 1,3-dipolar cycloaddition of C-diethoxyphosphoryl-N- rical optimization of all structures and transition states methylnitrone with substituted alkenes (allyl alcohol structures (TSs) were carried out with DFT by apply- and methyl acrylate) using DFT method. An ana- ing the Becke’s18 three-parameter hybrid functional lysis of potential energy surfaces (PESs) shows that and Lee-Yang-Parr’s19 correlation functional. The basis these 1,3-dipolar cycloaddition reactions favour the set 6-31G(d)20 has been employed for the prediction formation of the ortho-trans cycloadduct in agreement of activation energies of cycloaddition reactions and with experimental data. Stecko et al. have reported to provide geometries and electronic properties. The a DFT/B3LYP/6-31+G(d) study of the 1,3-dipolar stationary points were characterized by frequency cal- cycloaddition of cyclic nitrones with electron-poor and culations in order to check that the TSs had one and electron-rich cyclic dipolarophiles: α, β-unsaturated only one imaginary frequency with the corresponding lactones and vinyl ethers. Different reaction channels eigenvector involving the formation of the newly cre- and reactants approaches, effective in regio- and stereo- ated C–C and C–O bonds. Furthermore, the intrinsic chemical preferences are discussed; the results reaction coordinate (IRC)21,22 path was mapped to were compared to experimental data and found in authenticate the connection of a TS to the two asso- good agreement.14 Recently, Acharjee and Banerji15 ciated minima of the proposed mechanism. Electronic studied the 1,3-dipolar cycloaddition between C,N- structures of critical points were analysed by the natural diphenyl nitrone and an unsymmetrical disubstituted bond orbital (NBO) method.23 Global reactivity indices olefin at DFT/B3LYP/6-31G(d) level of theory. The were estimated according to the equations recom- analysis of FMO energies, reactivity indices and charge mended by Parr and Yang.24 In particular, the electronic transfer in the transition states indicates a normal chemical potentials (μ) and chemical hardness (η)of electron demand character for the reaction. the reactants studied were evaluated in terms of the The experimental investigations of Asrof et al.16 one-electron energies of the frontier molecular orbital implied that the cycloaddition between pyrroline-1- HOMO and LUMO, using the following equations: oxide 1 to dipolarophile 3b (methyl crotonate) gives μ = (E + E ) /2, (1) a mixture of substituted isoxazolidines 4b and 5b in HOMO LUMO a 93:7 ratio, respectively (scheme 1). In what follows, η = E − E . we present a DFT study on the cycloaddition reaction LUMO HOMO (2) involving cyclic 5-membered nitrone with methyl cro- The values of μ and η were then used for the calculation tonate. Our results are presented and discussed on the ω) basis of the generated trends in terms of detailed con- of global electrophilicity ( according to the formula: ceptual DFT-based reactivity indices and the analysis of ω = μ2/2η. (3) stationary points on the potential energy surfaces. This 25 analysis allows to elucidate the regio- and stereoselec- The global nucleophilicity (N) is referred to tetra- tivities of the 1,3-dipolar cycloaddition and to explain cyanoethylene (TCE) because it presents the lowest ω = the experimental observations. HOMO energy and a very large electrophilicity ( 5.95 eV) in a large series of molecules already investi- gated in the context of polar cycloadditions. The global nucleophilicity can then be expressed as: 2. Computational details N = EHOMO(nucleophile) − EHOMO(TCE). (4) 26 All calculations reported in this paper were performed The local electrophilicity (ωk) condensed to atom k using Gaussian 03 suite of programs17 along with the was calculated by projecting the indice ω onto any Scheme 1. 1,3-Dipolar cycloaddition of pyrroline-1-oxide with methylcrotonate. DFT study of the mechanism 285 where ρk(N+1), ρk(N) and ρk(N-1) are defined as the grosselectronic populations of the site k in the anionic, neutral and cationic species, respectively. 3. Results and discussions For this 1,3-DC reaction between cyclic nitrone: pyrroline-1-oxide and methyl crotonate, we first eva- luated the geometrical parameters and energies of all the stationary points (reactants, transition structures and cycloadducts) at DFT/B3LYP/6-31G(d). Popula- tion analysis at the transition structures in terms of bond orders and natural charges was performed, together with an analysis based on the global and local reac- tivity indices of the reactants involved during the cycloadditions. 3.1 Regiochemistry of 1,3-dipolar cycloaddition reaction based on FMOs and reactivity indices analysis Figure 1. Frontier molecular orbital (B3LYP/6-31G*)) 3.1a FMOs analysis: In this section, the frontier interaction in the 1,3-DC between pyrroline-1-oxide and molecular orbital theory30–39 was applied to explain the methyl crotonate. regioselectivity and reactivity in 1,3-dipolar cycloaddi- tion of methyl crotonate and the nitrone. reaction centre k of the molecule by using Fukui Analysis of the frontier molecular orbitals of the f + 27 function k . reactants show that in the nitrone, both HOMO and ω = ωf+. k k (5) LUMO are π molecular orbitals (MOs). However, in 28 the methyl crotonate, the HOMO is a nonbonding MO The local nucleophilicity (Nk) condensed to atom k was calculated using global nucleophilicity N and localized essentially on the oxygen of the carbonyl Fukui function f − according to the formula: group and, in consequence, it is expected that it will k not be directly involved in the 1,3-DC process. The N = Nf −. π k k (6) HOMO-1 of dipolarophile is a bonding molecular orbital with a large contribution of the atoms present For an atom k in a molecule, depending upon the type at the active sites, thus the relative reactivity can be of electron transfer, we have three different types of explained with analysis of this MO.
Load more

Recommended publications
  • Predicting Glycosylation Stereoselectivity Using Machine Learning† Cite This: Chem
    Chemical Science View Article Online EDGE ARTICLE View Journal | View Issue Predicting glycosylation stereoselectivity using machine learning† Cite this: Chem. Sci.,2021,12,2931 ab a ab All publication charges for this article Sooyeon Moon, ‡ Sourav Chatterjee, ‡ Peter H. Seeberger have been paid for by the Royal Society and Kerry Gilmore §*a of Chemistry Predicting the stereochemical outcome of chemical reactions is challenging in mechanistically ambiguous transformations. The stereoselectivity of glycosylation reactions is influenced by at least eleven factors across four chemical participants and temperature. A random forest algorithm was trained using a highly reproducible, concise dataset to accurately predict the stereoselective outcome of glycosylations. The steric and electronic contributions of all chemical reagents and solvents were quantified by quantum mechanical calculations. The trained model accurately predicts stereoselectivities for unseen nucleophiles, electrophiles, acid catalyst, and solvents across a wide temperature range (overall root mean square error 6.8%). All predictions were validated experimentally on a standardized microreactor platform. The model helped to identify novel ways to control glycosylation stereoselectivity and Creative Commons Attribution 3.0 Unported Licence. Received 11th November 2020 accurately predicts previously unknown means of stereocontrol. By quantifying the degree of influence Accepted 24th December 2020 of each variable, we begin to gain a better general understanding of the transformation, for example that DOI: 10.1039/d0sc06222g environmental factors influence the stereoselectivity of glycosylations more than the coupling partners in rsc.li/chemical-science this area of chemical space. Introduction retrosynthesis,9 reaction performance10 and products,11,12 the identication of new materials and catalysts,13–15 as well as Predicting the outcome of an organic reaction generally enantioselectivity16,17 have been addressed.
    [Show full text]
  • Aldol Reactions: E-Enolates and Anti-Selectivity
    Utah State University DigitalCommons@USU All Graduate Plan B and other Reports Graduate Studies 5-2005 Aldol Reactions: E-Enolates and Anti-Selectivity Matthew Grant Anderson Utah State University Follow this and additional works at: https://digitalcommons.usu.edu/gradreports Part of the Organic Chemistry Commons Recommended Citation Anderson, Matthew Grant, "Aldol Reactions: E-Enolates and Anti-Selectivity" (2005). All Graduate Plan B and other Reports. 1312. https://digitalcommons.usu.edu/gradreports/1312 This Report is brought to you for free and open access by the Graduate Studies at DigitalCommons@USU. It has been accepted for inclusion in All Graduate Plan B and other Reports by an authorized administrator of DigitalCommons@USU. For more information, please contact [email protected]. ALDOL REACTIONS: E-ENOLATES AND ANTI-SELECTIVITY Prepared By: MATTHEW GRANT ANDERSON A non-thesis paper submitted in partial fulfillment of the requirement for a Plan B Degree of Masters of Science in Organic Chemistry UTAH STATE UNIVERSITY Logan, Utah 2005 Contents Page CONTENTS ...................................................................................... .i LIST OF TABLES, FIGURES AND SCHEMES ....................................... ii,iii ABSTRACT .................................................................................... iv CHAPTER I. ALDOL REACTIONS:E-ENOLATES AND ANTI SELECTIVITY ......... 1 CHAPTER II. SECTION 1. MODELS OF E-ENOLATE FORMATION ...... .... ....... ... 12 SECTION 2. PATERSON ENOLATE PAPER ..... .........................
    [Show full text]
  • Stereoselectivity in Atmospheric Autoxidation Kristian H
    Subscriber access provided by Caltech Library Clusters, Radicals, and Ions; Environmental Chemistry Stereoselectivity in Atmospheric Autoxidation Kristian H. Møller, Eric Joseph Praske, Lu Xu, John D. Crounse, Paul O. Wennberg, and Henrik Grum Kjaergaard J. Phys. Chem. Lett., Just Accepted Manuscript • DOI: 10.1021/acs.jpclett.9b01972 • Publication Date (Web): 23 Sep 2019 Downloaded from pubs.acs.org on September 24, 2019 Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
    [Show full text]
  • Reactions of Alkenes and Alkynes
    05 Reactions of Alkenes and Alkynes Polyethylene is the most widely used plastic, making up items such as packing foam, plastic bottles, and plastic utensils (top: © Jon Larson/iStockphoto; middle: GNL Media/Digital Vision/Getty Images, Inc.; bottom: © Lakhesis/iStockphoto). Inset: A model of ethylene. KEY QUESTIONS 5.1 What Are the Characteristic Reactions of Alkenes? 5.8 How Can Alkynes Be Reduced to Alkenes and 5.2 What Is a Reaction Mechanism? Alkanes? 5.3 What Are the Mechanisms of Electrophilic Additions HOW TO to Alkenes? 5.1 How to Draw Mechanisms 5.4 What Are Carbocation Rearrangements? 5.5 What Is Hydroboration–Oxidation of an Alkene? CHEMICAL CONNECTIONS 5.6 How Can an Alkene Be Reduced to an Alkane? 5A Catalytic Cracking and the Importance of Alkenes 5.7 How Can an Acetylide Anion Be Used to Create a New Carbon–Carbon Bond? IN THIS CHAPTER, we begin our systematic study of organic reactions and their mecha- nisms. Reaction mechanisms are step-by-step descriptions of how reactions proceed and are one of the most important unifying concepts in organic chemistry. We use the reactions of alkenes as the vehicle to introduce this concept. 129 130 CHAPTER 5 Reactions of Alkenes and Alkynes 5.1 What Are the Characteristic Reactions of Alkenes? The most characteristic reaction of alkenes is addition to the carbon–carbon double bond in such a way that the pi bond is broken and, in its place, sigma bonds are formed to two new atoms or groups of atoms. Several examples of reactions at the carbon–carbon double bond are shown in Table 5.1, along with the descriptive name(s) associated with each.
    [Show full text]
  • [4 + 2] Annulation and Enyne Cross Metathesis
    Communication pubs.acs.org/JACS Gold-Catalyzed Intermolecular Reactions of Propiolic Acids with Alkenes: [4 + 2] Annulation and Enyne Cross Metathesis † † † ‡ ‡ ‡ Hyun-Suk Yeom, Jaeyoung Koo, Hyun-Sub Park, Yi Wang, Yong Liang, Zhi-Xiang Yu,*, † and Seunghoon Shin*, † Department of Chemistry and Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Korea ‡ Beijing National Laboratory of Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry, Peking University, Beijing 100871, China *S Supporting Information Scheme 1. Propiolic Acid as a Functional Equivalent of 1,4- ABSTRACT: A gold-catalyzed intermolecular reaction of C,O-Dipole or Biscarbene propiolic acids with alkenes led to a [4 + 2] annulation or enyne cross metathesis. The [4 + 2] annulation proceeds with net cis-addition with respect to alkenes and provides an expedient route to α,β-unsaturated δ-lactones, for which preliminary asymmetric reactions were also demonstrated. For 1,2-disubstituted alkenes, unprecedented enyne cross metathesis occurred to give 1,3-dienes in a completely stereospecific fashion. DFT calculations and experiments indicated that the cyclobutene derivatives are not viable We commenced our study using propiolic acid (4a) and intermediates and that the steric interactions during 10 concerted σ-bond rearrangements are responsible for the styrene derivatives as substrates. After extensive optimization, observed unique stereospecificity. we found that treating styrene 3a with 4a
    [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]
  • Application of Enzymes in Regioselective and Stereoselective Organic Reactions
    catalysts Review Application of Enzymes in Regioselective and Stereoselective Organic Reactions Ruipu Mu 1,*, Zhaoshuai Wang 2,3,* , Max C. Wamsley 1, Colbee N. Duke 1, Payton H. Lii 1, Sarah E. Epley 1, London C. Todd 1 and Patty J. Roberts 1 1 Department of Chemistry, Centenary College of Louisiana, Shreveport, LA 71104, USA; [email protected] (M.C.W.); [email protected] (C.N.D.); [email protected] (P.H.L.); [email protected] (S.E.E.); [email protected] (L.C.T.); [email protected] (P.J.R.) 2 Department of Pharmaceutical Science, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA 3 Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA * Correspondence: [email protected] (R.M.); [email protected] (Z.W.) Received: 22 June 2020; Accepted: 21 July 2020; Published: 24 July 2020 Abstract: Nowadays, biocatalysts have received much more attention in chemistry regarding their potential to enable high efficiency, high yield, and eco-friendly processes for a myriad of applications. Nature’s vast repository of catalysts has inspired synthetic chemists. Furthermore, the revolutionary technologies in bioengineering have provided the fast discovery and evolution of enzymes that empower chemical synthesis. This article attempts to deliver a comprehensive overview of the last two decades of investigation into enzymatic reactions and highlights the effective performance progress of bio-enzymes exploited in organic synthesis. Based on the types of enzymatic reactions and enzyme commission (E.C.) numbers, the enzymes discussed in the article are classified into oxidoreductases, transferases, hydrolases, and lyases.
    [Show full text]
  • Chapter 8: Alkenes: Structure and Preparation Via Elimination Reactions
    with cyanide anion affords a . N C: + H3C-H2C-H2C-H2C Br H3C-H2C-H2C-H2CC N + KBr K . with azide anion affords alkyl azides Br N3 + NaBr NN N + SN2 Na . with an thiols or thiolate ions affords a . – R–S + H3CH2C–Cl + H3CH2C– S–R + KCl S 2 + N Li 165 Chapter 8: Alkenes: Structure and Preparation via Elimination Reactions 8.1 Introduction to Elimination Reactions – Nucleophiles are Lewis bases. They can also promote elimination reactions of alkyl halides or sulfonates rather than substitution. SN2 – H3C-O Br OCH3 H H elimination + HOCH3 – H3C-O Br OH2 elimination + H O+ H 3 Br SN1 166 OH 83 8.2 Alkenes in Nature and in Industry (please read) 8.3 Nomenclature of Alkenes (please read and understand) Prefix-Parent-Suffix Suffix for alkenes: -ene Many of the same rules for alkanes apply to alkenes 1. Name the parent hydrocarbon by locating the longest carbon chain that contains the double bond and name it according to the number of carbons with the suffix -ene. H3C CH2 H C CH 3 2 C CH2 C CH 2 H C CH CH 3 2 2 H3C CH2 CH2 Parent = pentene not hexene (does not contain double bond) 2a. Number the carbons of the parent chain so the double bond carbons have the lowest possible numbers. Indicate the double bond by the number of the first alkene carbon. H3C CH2 CH2 CH CH CH3 123456 167 2-hexene 2b. If the double bond is equidistant from each end, number so the first substituent has the lowest number.
    [Show full text]
  • Development of the Interrupted Nazarov Cyclization of Allenyl Vinyl Ketones, with Application to the Total Synthesis of the Cyclooctane Natural Product Roseadione
    Development of the Interrupted Nazarov Cyclization of Allenyl Vinyl Ketones, with Application to the Total Synthesis of the Cyclooctane Natural Product Roseadione by Vanessa M. Marx Submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Dalhousie University Halifax, Nova Scotia May 2011 © Copyright by Vanessa M. Marx, 2011 DALHOUSIE UNIVERSITY DEPARTMENT OF CHEMISTRY The undersigned hereby certify that they have read and recommend to the Faculty of Graduate Studies for acceptance a thesis entitled “Development of the Interrupted Nazarov Cyclization of Allenyl Vinyl Ketones, with Application to the Total Synthesis of the Cyclooctane Natural Product Roseadione” by Vanessa M. Marx in partial fulfilment of the requirements for the degree of Doctor of Philosophy. Dated: May 19, 2011 Supervisor: _________________________________ Readers: _________________________________ _________________________________ _________________________________ Departmental Representative: _________________________________ ii DALHOUSIE UNIVERSITY DATE: May 19, 2011 AUTHOR: Vanessa M. Marx TITLE: Development of the Interrupted Nazarov Cyclization of Allenyl Vinyl Ketones, with Application to the Total Synthesis of the Cyclooctane Natural Product Roseadione DEPARTMENT OR SCHOOL: Department of Chemistry DEGREE: PhD CONVOCATION: October YEAR: 2011 Permission is herewith granted to Dalhousie University to circulate and to have copied for non-commercial purposes, at its discretion, the above title upon the request of individuals or institutions. I understand that my thesis will be electronically available to the public. The author reserves other publication rights, and neither the thesis nor extensive extracts from it may be printed or otherwise reproduced without the author’s written permission. The author attests that permission has been obtained for the use of any copyrighted material appearing in the thesis (other than the brief excerpts requiring only proper acknowledgement in scholarly writing), and that all such use is clearly acknowledged.
    [Show full text]
  • 1 the Nazarov Cyclization
    THE NAZAROV CYCLIZATION: DEVELOPMENT AND APPLICATIONS Reported by Jenna Klubnick September 24, 2009 INTRODUCTION The classic Nazarov cyclization is a Lewis or Brønsted acid catalyzed 4-π electrocyclic ring closure of a divinyl ketone to a 2-cyclopentenone. Cyclopentenones and five-membered carbocycles are common structural motifs in biologically active compounds. Consequently, a number of methods have been developed to access these moieties.1 Recent modifications to the Nazarov cyclization have made this reaction a powerful tool for the construction of these important structural themes. For example, the Nazarov cyclization was essential to the syntheses of the three biologically active natural products shown in Scheme 1.2a-c Scheme 1. Natural Products Synthesized via the Nazarov Cyclization MeO O OH O HO O Cl Cl HO O Me O Me MeO NMe2 H Me Me O O O OH O H Me H Me HO O Br OMe H (-) -Scabronine G Nakiterpiosin (±)-Rocaglamide DISCOVERY AND ELUCIDATION OF MECHANISM The history of the Nazarov cyclization dates back more than a century. In 1903, David Vorlander reported a cyclization of dibenzylideneacetone upon treatment with acetic anhydride and sulfuric acid.3 He was unable to determine the structure the product, but it was later identified as the Scheme 2. Cyclization Observed by D. Vorlander 1 Copyright © 2009 by Jenna A. Klubnick cyclic ketol by Shoppee and coworkers (Scheme 2).4 In the context of his work on the hydration of dieneynes, C. S. Marvel also noted a cyclization but was unable to correctly identify the structure of the product.5 Similar hydration studies were what led Igor Nazarov to the discovery of the Nazarov cyclization in 1942.6 During his work on mercuric salt and acid-catalyzed formation of allyl vinyl ketones from divinyl acetylenes, Nazarov observed the spontaneous cyclization of the intermediate allyl vinyl ketones under the acidic conditions to yield 2-cyclopentenones.
    [Show full text]
  • Stereoselective Acetate Aldol Reactions from Metal Enolates
    REVIEW 2175 Stereoselective Acetate Aldol Reactions from Metal Enolates StereoselectiveXavier Acetate Aldol Reactions from Metal Enolates Ariza, Jordi Garcia, Pedro Romea,* Fèlix Urpí* Departament de Química Orgànica, Universitat de Barcelona, Martí i Franqués 1-11, 08028 Barcelona, Catalonia, Spain Fax +34(93)3397878; E-mail: [email protected]; E-mail: [email protected] Received 27 January 2011; revised 24 February 2011 Dedicated to the memory of recently deceased Professor Rafael Suau often contests their capacity to install the required stereo- Abstract: This review deals with stereoselective acetate aldol reac- tions mediated by metal enolates. It summarizes recent advances in centers efficiently. Hence, it has always been seen as aldol additions of unsubstituted metal enolates that either incorpo- highly desirable to achieve parallel transformations from 8 rate chiral auxiliaries, stoichiometric Lewis acids, or catalytic metal enolates. Unfortunately, acetate aldol reactions Lewis acids or bases, or act in substrate-controlled reactions. These mediated by such intermediates can proceed through dif- approaches provide stereocontrolled aldol transformations that al- ferent six-membered cyclic transition states, represented low the efficient synthesis of structurally complex natural products. in Scheme 2, which hampers the proper differentiation of the two faces of the carbon–oxygen double bond by the 1 Introduction 3,9,10 2 Chiral Auxiliaries unsubstituted enolate. Therefore, stereocontrol in 3 Stoichiometric Lewis Acids these reactions relies on the appropriate choice of the met- 4 Catalytic Lewis Acids and Bases al and the chiral elements on the substrate, the aldehyde or 5 Substrate-Controlled Aldol Reactions the ligands (R1, R2, and L, respectively) to provide a single 5.1 a-Methyl Ketones highly organized transition state.
    [Show full text]
  • 1,3-Dipolar Cycloadditions of Nitrones and Nitrile Oxides. Yau-Min Chang Louisiana State University and Agricultural & Mechanical College
    Louisiana State University LSU Digital Commons LSU Historical Dissertations and Theses Graduate School 1975 1,3-Dipolar Cycloadditions of Nitrones and Nitrile Oxides. Yau-min Chang Louisiana State University and Agricultural & Mechanical College Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_disstheses Recommended Citation Chang, Yau-min, "1,3-Dipolar Cycloadditions of Nitrones and Nitrile Oxides." (1975). LSU Historical Dissertations and Theses. 2865. https://digitalcommons.lsu.edu/gradschool_disstheses/2865 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Historical Dissertations and Theses by an authorized administrator of LSU Digital Commons. For more information, please contact [email protected]. INFORMATION 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]