DOCSLIB.ORG

University of California, San Diego

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
University of California, San Diego UNIVERSITY OF CALIFORNIA, SAN DIEGO SAN DIEGO STATE UNIVERSITY Part I: Copper(I) Iodide Dimethyl Sulfide Catalyzed 1,4-Addition of Alkenyl Groups From Alkenylzirconium and Alkenylzinc Reagents and Their Application Toward the Total Synthesis of Azaspirene Part II: Aqueous Wittig Chemistry Employing Stabilized Ylides and Aldehydes A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Chemistry by Amer Adnan El-Batta Committee in charge: University of California, San Diego Professor Joseph Adams Professor Simpson Joseph Professor Emmanuel A. Theodorakis San Diego State University Professor B. Mikael Bergdahl, Chair Professor Thomas Cole Professor Terrence Frey 2007 Copyright Amer Adnan El-Batta, 2007 All rights reserved. The dissertation of Amer Adnan El-Batta is approved, and is acceptable in quality and form for publication on microfilm: ____________________________________________________ ____________________________________________________ ____________________________________________________ ____________________________________________________ ____________________________________________________ ____________________________________________________ Chair University of California, San Diego San Diego State University 2007 iii TABLE OF CONTENTS Signature Page............................................................................................... iii Table of Contents........................................................................................... iv List of Figures................................................................................................ vii List of Schemes.............................................................................................. viii List of Tables................................................................................................. xi List of Abbreviations……………................................................................. xii Acknowledgements........................................................................................ xiv Vita……………………………………………………………………........xvi Abstract.........................................................................................................xvii Chapter 1: Introduction.................................................................................. 1 Part I: Copper(I) Iodide Dimethyl Sulfide Catalyzed 1,4-Addition of Alkenyl Groups From Alkenylzirconium and Alkenylzinc Reagents and Their Application Toward the Total Synthesis of Azaspirene……….... 6 Chapter 2: Copper(I) Iodide Dimethyl Sulfide Catalyzed 1,4-Addition of Alkenyl Groups From Alkenylzirconocene Reagents..........7 2.1 Introduction........................................................................................ 7 2.1.1 Background of Hydrozirconation………………………………….. 7 2.1.1.1 Preparation of Schwartz’s Reagent {Cp2Zr(H)Cl}…..…………….. 8 2.1.1.2 Applications of Hydrozirconation…………………………………. 10 2.1.2 Cu- and Ni-Promoted Conjugate Additions……………………….. 13 2.2 Results and Discussion…………………………………………….. 17 2.2.1 Additions to Enones and Enals…………………………………….. 17 2.2.2 Efficiency of the (CuI)4(SMe2)3 Complex…………………………. 20 2.3 Mechanistic Postulate…………………………………………….... 23 2.4 Conclusion…………………………………………………………. 24 iv Chapter 3: Copper(I) Iodide Dimethyl Sulfide Catalyzed 1,4-Addition of Alkenyl Groups From Alkenyl-Alkylzinc Reagents................................. 25 3.1 Introduction....................................................................................... 25 3.2 Results and Discussion…………………………………………….. 30 3.2.1 Additions to N-Enoyl Derived Oxazolidinones……………………. 30 3.2.2 Efficiency of the Zr→Zn Transmetalation Methodology in Cu(I)- Catalyzed 1,4-Additions of Alkenyl Groups to Enones and Enals.... 34 3.2.3 Efficiency of the (CuI)4(SMe2)3 Complex…………………………. 38 3.3 Mechanistic Postulate….…………………………………………... 39 3.4 Conclusion…………………………………………………………. 41 Chapter 4: Chemical Studies Toward the Total Synthesis of Azaspirene, a Novel Angiogenesis Inhibitor……………………...……….. 43 4.1 Introduction....................................................................................... 43 4.1.1 Biological Significance of Angiogenesis in Cancer……………….. 43 4.1.2 Mode of Action of Azaspirene…………………………………….. 45 4.2 Prior Total Syntheses of Azaspirene………………………………. 46 4.2.1 Hayashi’s Approach……………………………………………….. 47 4.2.2 Tadano’s Approach………………………………………………... 49 4.3 Retrosynthetic Strategy for Azaspirene……………………………. 51 4.4 Results and Discussion…………………………………………….. 53 4.4.1 Synthesis of the Amine Fragment………………………………….. 54 4.4.2 Synthesis of the Acid Fragment……………………………………. 55 4.4.3 Synthesis of Advanced Intermediate Toward Azaspirene…………. 58 4.5 Conclusion…………………………………………………………. 60 Part II: Aqueous Wittig Chemistry Employing Stabilized Ylides and Aldehydes……………………………………………… 61 Chapter 5: Aqueous Wittig Reactions………………………........................62 5.1 Introduction....................................................................................... 62 5.2 Results and Discussion…………………………………………….. 65 5.2.1 Aqueous Wittig Reactions Employing Various Aromatic Aldehydes………………………………………………………….. 65 5.2.2 Aqueous Wittig Reactions Employing Various Heterocylic Aromatic Aldehydes……………………………………………….. 68 5.2.3 Aqueous Wittig Reactions Employing Various Aliphatic Aldehydes………………………………………………………….. 70 v 5.2.4 Role of Water in the Aqueous Wittig Reactions…………………... 72 5.3 Mechanistic Studies of the Aqueous Wittig Reaction……………... 76 5.4 Conclusion.………………………………………………………… 78 Chapter 6: Future Work................................................................................. 81 6.1 Asymmetric Conjugate Additions of Alkenyl Groups Using Copper Catalysis…………………………………………………… 81 6.1.1 Enantioselective Additions of Alkenylzirconium Reagents……….. 82 6.1.2 Enantioselective Conjugate Additions of Mixed Alkenyl- Alkylzinc Reagents………………………………………………… 83 6.2 Expansion of the Methodology of Copper(I) Iodide Dimethyl Sulfide Catalyzed 1,4-Addition of Alkenyl Groups...…... 84 6.2.1 Employing β–Oxy-Substituted α,β-Unsaturated Carbonyl Substrates…………………………………………………………... 84 6.2.2 Allylic Additions (SN2’)…………………………………………… 85 6.2.3 Electrophilic Trapping of Zinc Enolates in α–Alkylation Type Reactions…………………………………………………….. 86 6.3 Mechanistic Studies of the Copper(I) Iodide Dimethyl Sulfide Catalyzed 1,4-Additions of Alkenyl Groups………………………. 86 6.4 Completion of the Total Synthesis of Azaspirene…………………. 90 Chapter 7: Experimental Section................................................................... 94 7.1 Chemicals and Instrumentals............................................................. 94 7.2 Experimental Procedures................................................................... 95 7.3 Compounds Characterized…............................................................114 Appendix.......................................................................................................147 References.....................................................................................................265 vi LIST OF FIGURES Figure 2.1: Applications of alkenylzirconocenes in organic synthesis..................12 Figure 4.1: Role of angiogenesis in cancer development, growth and Metastasis………………………………………………………..…..44 Figure 4.2: Structures of azaspirene, psuerotin A and synerazol……...................47 Figure 5.1: TS models to account for the E/Z-selectivity..............................…... .77 vii LIST OF SCHEMES Scheme 1.1: Cu(I)-catalyzed 1,4-addition of alkenylzirconocene to enones and enals……………………………………………………………...1 Scheme 1.2: TMSOTf-promoted Cu(I)-catalyzed conjugate addition of mixed alkenyl-alkylzincate reagents to α,β-unsaturated imides……………..3 Scheme 1.3: Synthetic strategy toward azaspirene………………………………....4 Scheme 1.4: Wittig reaction of aldehydes and stabilized ylides in water………….4 Scheme 2.1: Hydrozirconation of alkenes and alkynes using Schwartz’s reagent...8 Scheme 2.2: First reports by Schwartz using zirconocene hydrochloride………....8 Scheme 2.3: Buchwald’s protocol for the preparation of Schwartz’s reagent….....9 Scheme 2.4: Change of regioselectivity by the addition of copper(I)……………..14 Scheme 2.5: Copper(I)-promoted formation of diene by Schwartz.………............14 Scheme 2.6: First Cu(I)-promoted alkenylzirconocene addition to an enone……..15 Scheme 2.7: Using Me2CuLi(LiCN) in the 1,4-addition of alkenylzirconium reagents to α,β-unsaturated ketones…………………….……………15 Scheme 2.8: First Cu(I)-catalyzed alkylzirconocene addition to an enone……......16 Scheme 2.9: Conjugate addition of alkyl- and alkenylzirconocene to enone…......18 Scheme 2.10: Formation of diene product in presence of Cu(I) catalyst………….. 22 Scheme 2.11: Proposed mechanism for the Cu(I)-catalyzed conjugate addition of alkenylzirconocenes……………………………………. 23 Scheme 3.1: AgClO4-catalyzed addition of alkenylzirconocenes to aldehydes…. 26 Scheme 3.2: Alkenylzirconocenes addition to epoxides catalyzed by AgClO4…. 26 Scheme 3.3: Transmetalation of an alkenylzirconium to an alkenylzinc reagent....27 viii Scheme 3.4: Wipf’s report on the vinylation of aldehydes using mixed alkenyl-alkylzincate reagents………………………………………..28 Scheme 3.5: Catalytic asymmetric Zr→Zn transmetalation/ketone addition……..29 Scheme 3.6: The first attempt of a Cu(I)-catalyzed conjugate addition of alkenylzirconocenes to α,β-unsaturated imides……………………...31 Scheme 3.7: TMSOTf-promoted Cu(I)-catalyzed conjugate addition of mixed alkenyl-alkylzincate reagents to α,β-unsaturated imides……..32 Scheme
Load more

Recommended publications
  • Download (1MB)
    THE IN VITRO METABOLISM OF THREE ANTICANCER DRUGS by Yun Fan B.S., West China University of Medical Sciences, 1996 M.S., West China University of Medical Sciences, 2001 Submitted to the Graduate Faculty of School of Pharmacy in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Pittsburgh 2007 UNIVERSITY OF PITTSBURGH SCHOOL OF PHARMACY This dissertation was presented by Yun Fan It was defended on March 23, 2007 and approved by Samuel M. Poloyac, Assistant Professor, Pharmaceutical Sciences Raman Venkataramanan, Professor, Pharmaceutical Sciences Jack C. Yalowich, Associate Professor, Pharmacology Michael A. Zemaitis, Professor, Pharmaceutical Sciences Billy W. Day, Professor, Pharmaceutical Sciences ii Copyright © by Yun Fan 2007 iii THE IN VITRO METABOLISM OF THREE ANTICANCER DRUGS Yun Fan, Ph.D. University of Pittsburgh, 2007 Etoposide is a widely used topoisomerase II inhibitor particularly useful in the clinic for treatment of disseminated tumors, including childhood leukemia. However, its use is associated with the increased risk of development of secondary acute myelogenous leukemias. The mechanism behind this is still unclear. It was hypothesized that etoposide ortho-quinone, a reactive metabolite previously shown to be generated in vitro by myeloperoxidase, the major oxidative enzyme in the bone marrow cells from which the secondary leukemias arise, might be a contributor to the development of treatment-related secondary leukemias. Experiments showed that the glutathione adduct of etoposide ortho-quinone was formed in myeloperoxidase- expressing human myeloid leukemia HL60 cells treated with etoposide, that its formation was enhanced by addition of the myeloperoxidase substrate hydrogen peroxide, and that the glutathione adduct level was dependent on myeloperoxidase.
    [Show full text]
  • 1.1 10 Oxidation of Alcohols and Aldehydes
    1.1 10 Oxidation of alcohols and aldehydes By the end of this spread, you should be able to … 1Describe the oxidation of primary alcohols to form aldehydes and carboxylic acids. 1Describe the oxidation of secondary alcohols to form ketones. 1Describe the oxidation of aldehydes to form carboxylic acids. Key definition Oxidation of alcohols You will recall from your AS chemistry studies that primary and secondary alcohols can A redox reaction is one in which both reduction and oxidation take place. be oxidised using an oxidising agent. s !SUITABLEOXIDISINGAGENTISASOLUTIONCONTAININGACIDIlEDDICHROMATEIONS + 2− H /Cr2O7 . s 4HEOXIDISINGMIXTURECANBEMADEFROMPOTASSIUMDICHROMATE +2Cr2O7, and sulfuric acid, H2SO. During the reaction, the acidified potassium dichromate changes from orange to green. Remember that tertiary alcohols are not oxidised by acidified dichromate ions. Primary alcohols Primary alcohols can be oxidised to aldehydes and to carboxylic acids (see AS Chemistry spread 2.2.3). H H H O H O Oxidation Oxidation H CCOH H CC H CC H H H H H OH Primary alcohol Aldehyde Carboxylic acid Figure 1 Ethanol oxidised to ethanal, and finally to ethanoic acid The equation for the oxidation of ethanol to the aldehyde ethanal is shown below. Note that the oxidising agent is shown as [O] – this simplifies the equation. CH3CH2OH + [O] }m CH3CHO + H2O When preparing aldehydes in the laboratory, you will need to distil the aldehyde from the reaction mixture as it is formed. This prevents the aldehyde from being oxidised further to a carboxylic acid. Key definition When making the carboxylic acid, the reaction mixture is usually heated under reflux before distilling the product off.
    [Show full text]
  • Benzyl-L-Threitol
    A Publication of Reliable Methods for the Preparation of Organic Compounds Working with Hazardous Chemicals The procedures in Organic Syntheses are intended for use only by persons with proper training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011; the full text can be accessed free of charge at http://www.nap.edu/catalog.php?record_id=12654). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices. In some articles in Organic Syntheses, chemical-specific hazards are highlighted in red “Caution Notes” within a procedure. It is important to recognize that the absence of a caution note does not imply that no significant hazards are associated with the chemicals involved in that procedure. Prior to performing a reaction, a thorough risk assessment should be carried out that includes a review of the potential hazards associated with each chemical and experimental operation on the scale that is planned for the procedure. Guidelines for carrying out a risk assessment and for analyzing the hazards associated with chemicals can be found in Chapter 4 of Prudent Practices. The procedures described in Organic Syntheses are provided as published and are conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
    [Show full text]
  • Long Chain Alcohols (C6-22 Primary Aliphatic Alcohols)
    SIAM 22, 18-21 April 2006 UK/ICCA SIDS INITIAL ASSESSMENT PROFILE Chemical Category Name Long Chain Alcohols (C6-22 primary aliphatic alcohols) Chemical name CAS no. Chemical name CAS no. 1-Hexanol 111-27-3 Alcohols, C16-18 67762-27-0 1-Octanol 111-87-5 Alcohols, C14-18 67762-30-5 1-Decanol 112-30-1 Alcohols, C10-16 67762-41-8 1-Undecanol 112-42-5 Alcohols, C8-18 68551-07-5 1-Tridecanol 112-70-9 Alcohols, C14-16 68333-80-2 1-Tetradecanol 112-72-1 Alcohols, C6-12 68603-15-6 1-Pentadecanol 629-76-5 Alcohols, C12-16 68855-56-1 1-Hexadecanol 36653-82-4 Alcohols, C12-13 75782-86-4 CAS Nos 1-Eicosanol 629-96-9 Alcohols, C14-15 75782-87-5 1-Docosanol 661-19-8 Alcohols, C12-14 80206-82-2 Alcohols, C12-15 63393-82-8 Alcohols, C8-10 85566-12-7 Alcohols, C9-11 66455-17-2 Alcohols, C10-12 85665-26-5 Alcohols, C12-18 67762-25-8 Alcohols, C18-22 97552-91-5 9-Octadecen-1-ol 143-28-2 Alcohols, C14-18. 68155-00-0 (9Z)- & C16-18-unsatd Alcohols, C16-18 68002-94-8 Tridecanol, 90583-91-8 & C18 Unsaturated branched & linear Structural Formula CH3(CH2)nCH2OH Linear n = 4 to 20 CH3(CH2)nCHCH2OH 2-Alkyl branched n + m = 3 to 18, and m is predominantly (CH2)mCH3 = 0. Present in essentially-linear alcohols CH3(CH2)nCH(CH2)mOH Other-methyl branching n + m= 9 or 10 CH3 Present in essentially-linear Fischer- Tropsch derived alcohols CH3(CH2)7CH=CH(CH2)7CH2O Unsaturated H 9-Z unsaturated components are present in some commercial products.
    [Show full text]
  • Nicole Goodwin Macmillan Group Meeting April 21, 2004
    Discodermolide A Synthetic Challenge Me Me Me HO Me O O OH O NH2 Me Me OH O Me Me OH Nicole Goodwin MacMillan Group Meeting April 21, 2004 Me Me Me HO Discodermolide Me O O OH O NH2 Isolation and Biological Activity Me Me OH O Me Me OH ! Isolated in 1990 by the Harbor Branch Oceanographic Institution from the Caribbean deep-sea sponge Discodermia dissoluta ! Not practical to produce discodermolide from biological sources ! 0.002% (by mass) isolation from frozen sponge ! must be deep-sea harvested at a depth in excess of 33 m ! Causes cell-cycle arrest at the G2/M phase boundary and cell death by apoptosis ! Member of an elite group of natural products that act as microtubule-stabilizing agent and mitotic spindle poisons ! Taxol, epothilones A and B, sarcodictyin A, eleutherobin, laulimalide, FR182877, peloruside A, dictyostatin ! Effective in Taxol-resistant carcinoma cells ! presence of a small concentration of Taxol amplified discodermolide's toxicity by 20-fold ! potential synergies with the combination of discodermolide with Taxol and other anticancer drugs ! Licensed by Novartis from HBOI in 1998 as a new-generation anticancer drug 1 Cell Apoptosis M - Mitosis G0 Discodermolide disrupts the G2/M phases of the cell cycle. Resting Discodermolide, like Taxol, inhibits microtubule depolymerization by binding G1 - Gap 1 to tubulin. G2 - Gap 2 cells increase in size, cell growth control checkpoint no microtubules = no spindle fiber new proteins formation S - Synthesis DNA replication Me Me Me HO Discodermolide Me O O OH O NH2 Isolation
    [Show full text]
  • United States Patent (19) 11 Patent Number: 5,789,605 Smith, I Et Al
    IIIUSOO5789605A United States Patent (19) 11 Patent Number: 5,789,605 Smith, I et al. 45) Date of Patent: Aug. 4, 1998 54 SYNTHETICTECHNIQUES AND Jacquesy et al., "Metabromation Du Dimethyl-2, 6 Phenol INTERMEDIATES FOR POLYHYDROXY, Et De Son Ether Methylique En Milieu Superacide", Tetra DENYL LACTONES AND MIMCS hedron, 1981, 37, 747-751. THEREOF Kim et al., "Conversion of Acetals into Monothioacetals, O-Alkoxyazides and O-Alkoxyalkyl Thioacetates with 75) Inventors: Amos B. Smith, III. Merion; Yuping Magnesium Bromide". Tetra, lett, 1989, 30(48), Qiu; Michael Kaufman, both of 6697-6700. Philadelphia; Hirokaza Arimoto, Longley et al., "Discodermolide-A New, Marine-Derived Drexel Hill, all of Pa.; David R. Jones, Immunosuppressive Compound". Transplantation, 1991. Milford, Ohio; Kaoru Kobayashi, 52(4) 650-656. Osaka, Japan Longley et al., "Discodermolide-A New, Marine-Derived Immunosuppressive Compound". Transplantation, 1991. 73 Assignee: Trustees of the University of 52(4), 657-661. Pennsylvania, Philadelphia, Pa. Longley et al., "Immunosuppression by Discodermolide". Ann. N.Y. Acad. Sci., 1993. 696, 94-107. (21) Appl. No.:759,817 Nerenburg et al., "Total Synthesis of the Immunosuppres 22 Filed: Dec. 3, 1996 sive Agent (-)-Discodermolide". J. Am. Chem, Soc., 1993, 115, 12621-12622. (51) Int. Cl. ................. C07D407/06; C07D 319/06; Paterson, I. et al., "Studies Towards the Total Synthesis of CO7D 309/10 the Marine-derived Immunosuppressant Discodermolide; (52) U.S. Cl. .......................... 549/370; 549/374; 549/417 Asymmetric Synthesis of a C-Cö-Lactone Subunit". J. (58) Field of Search ..................................... 549/370,374, Chen. Soc. Chen, Commun., 1993, 1790-1792. 549/417 Paterson, I. et al., "Studies Towards the Total Synthesis of the Marine-derived Immunosuppresant Discodermolide; 56 References Cited Asymmetric Synthesis of a C-C Subunit".
    [Show full text]
  • Dissertation.Pdf (1.198Mb)
    Syntheses and Bioactivities of Targeted and Conformationally Restrained Paclitaxel and Discodermolide Analogs Chao Yang Dissertation submitted to the faculty of the Virginia Polytechnic Institute and State University In the partial fulfillment of the requirement for the degree of Doctor of Philosophy In Chemistry Dr. David G. I. Kingston, Chairman Dr. Karen Brewer Dr. Paul R. Carlier Dr. Felicia. Etzkorn Dr. Harry W. Gibson August 26 2008 Blacksburg, Virginia Keywords: Taxol, drug targeting, , thio-taxol, tubulin-binding conformation, , T-taxol conformation, macrocyclic taxoids, discodermolide Copyright 2008, Chao Yang Syntheses and Bioactivities of Targeted and Conformationally Restrained Paclitaxel and Discodermolide Analogs Chao Yang Abstract Paclitaxel was isolated from the bark of Taxus brevifolia in the late 1960s. It exerts its biological effect by promoting tubulin polymerization and stabilizing the resulting microtubules. Paclitaxel has become one of the most important current drugs for the treatment of breast and ovarian cancers. Studies aimed at understanding the biologically active conformation of paclitaxel bound on β–tubulin are described. In this work, the synthesis of isotopically labeled taxol analogs is described and the REDOR studies of this compound complexed to tubulin agrees with the hypothesis that palictaxel adopts T-taxol conformation. Based on T-taxol conformation, macrocyclic analogs of taxol have been prepared and their biological activities were evaluated. The results show a direct evidence to support T-taxol conformation. (+) Discodermolide is a polyketide isolated from the Caribbean deep sea sponge Discodermia dissoluta in 1990. Similar to paclitaxel, discodermolide interacts with tubulin and stabilizes the microtubule in vivo. Studies aimed at understanding the biologically active conformation of discodermolide bound on β–tubulin are described.
    [Show full text]
  • Total Synthesis of the Marine Natural Product (+)-Discodermolide in Multigram Quantities*
    Pure Appl. Chem., Vol. 79, No. 4, pp. 685–700, 2007. doi:10.1351/pac200779040685 © 2007 IUPAC Total synthesis of the marine natural product (+)-discodermolide in multigram quantities* Stuart J. Mickel Novartis Pharma AG, CHAD, WKL-684.2.31 Klybeckstrasse, 4052 Basel, Switzerland Abstract: The novel polyketide (+)-discodermolide was isolated in very small quantities from sponge extracts. This compound is one of several microtubule stabilizers showing promise as novel chemotherapeutic agents for the treatment of cancer. The clinical evaluation of this and similar compounds is hampered by lack of material, and at present, the only way to obtain the necessary quantities is total chemical synthesis. Keywords: discodermolide; boron aldol reaction; isolation; side products; olefination. INTRODUCTION The marine natural product (+)-discodermolide 1 was isolated by workers at the Harbor Branch Oceanographic Institute from the deep-sea sponge Discodermia dissoluta in 1990 [1]. It is obtained from the sponge in extremely small quantities, 0.002 % in the frozen material. This compound is one of several natural products exhibiting inhibition of microtubule depolymerization and as such shows considerable promise as a novel chemotherapeutic agent for the treatment of cancer [2]. In contrast to Taxol®, another microtubule stabilizer, (+)-1 shows activity in the Taxol-resistant cell lines which over- express P-glycoprotein, the multidrug-resistant transporter. The similarities and differences between (+)-1 and Taxol have recently been discussed in detail [3]. The structure of (+)-1 consists of a linear polypropionate chain interrupted by 3 cis-olefins. It con- tains 13 chiral centers, 6 of which are hydroxyl groups, one esterified as a lactone, another as a car- bamic acid ester.
    [Show full text]
  • Transcription 12.01.12
    Lecture 2B • 01/12/12 We covered three different reactions for converting alcohols into leaving groups. One was to turn an alcohol into an alkyl chloride, that was using thionyl chloride. Second reaction was using tosyl chloride; the primary difference between those two reactions is one of stereochemistry. An inversion of stereochemistry does occur if you use thionyl chloride, because it does affect the carbon-oxygen bond, but because forming a tosylate does not touch the carbon-oxygen bond, only the oxygen- hydrogen bond, there’s no change in stereochemistry there. We then saw phosphorus tribromide that reacts very similarly to the thionyl chloride; you get an alkyl bromide instead, but it also has inversion of configuration. The last reaction is not a new mechanism, it is just an Sn2 reaction, it’s called the Finkelstein reaction. Really this works, in a sense, off of Le Châtelier’s principle. In solution, in theory, sodium iodide can displace bromide, but sodium bromide can displace iodide, so you can have an Sn2 reaction that goes back and forth and back and forth and back and forth. Except, sodium iodide is somewhat soluble in acetone, while sodium chloride and sodium bromide are not. So, in fact, one of the things that we get out of this as a by-product is sodium bromide, which, again, is not soluble in acetone and therefore precipitates out and is no longer part of the reaction mixture, so there’s no reverse reaction possible. Because of this solubility trick, it allows this reaction to be pulled forward, which means you can get the alkyl iodide.
    [Show full text]
  • Marine Natural Products: a Source of Novel Anticancer Drugs
    marine drugs Review Marine Natural Products: A Source of Novel Anticancer Drugs Shaden A. M. Khalifa 1,2, Nizar Elias 3, Mohamed A. Farag 4,5, Lei Chen 6, Aamer Saeed 7 , Mohamed-Elamir F. Hegazy 8,9, Moustafa S. Moustafa 10, Aida Abd El-Wahed 10, Saleh M. Al-Mousawi 10, Syed G. Musharraf 11, Fang-Rong Chang 12 , Arihiro Iwasaki 13 , Kiyotake Suenaga 13 , Muaaz Alajlani 14,15, Ulf Göransson 15 and Hesham R. El-Seedi 15,16,17,18,* 1 Clinical Research Centre, Karolinska University Hospital, Novum, 14157 Huddinge, Stockholm, Sweden 2 Department of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, SE 106 91 Stockholm, Sweden 3 Department of Laboratory Medicine, Faculty of Medicine, University of Kalamoon, P.O. Box 222 Dayr Atiyah, Syria 4 Pharmacognosy Department, College of Pharmacy, Cairo University, Kasr el Aini St., P.B. 11562 Cairo, Egypt 5 Department of Chemistry, School of Sciences & Engineering, The American University in Cairo, 11835 New Cairo, Egypt 6 College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China 7 Department of Chemitry, Quaid-i-Azam University, Islamabad 45320, Pakistan 8 Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudingerweg 5, 55128 Mainz, Germany 9 Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, 12622 Giza, Egypt 10 Department of Chemistry, Faculty of Science, University of Kuwait, 13060 Safat, Kuwait 11 H.E.J. Research Institute of Chemistry,
    [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]
  • Reactions of Alcohols & Ethers 1
    REACTIONS OF ALCOHOLS & ETHERS 1. Combustion (Extreme Oxidation) alcohol + oxygen carbon dioxide + water 2 CH3CH2OH + 6 O2 4 CO2 + 6 H2O 2. Elimination (Dehydration) ° alcohol H 2 S O 4/ 1 0 0 C alkene + water H2SO4/100 ° C CH3CH2CH2OH CH3CH=CH2 + H2O 3. Condensation ° excess alcohol H 2 S O 4 / 1 4 0 C ether + water H2SO4/140 ° C 2 CH3CH2OH CH3CH2OCH2CH3 + H2O 4. Substitution Lucas Reagent alcohol + hydrogen halide Z n C l2 alkyl halide + water ZnCl2 CH3CH2OH + HCl CH3CH2Cl + H2O • This reaction with the Lucas Reagent (ZnCl2) is a qualitative test for the different types of alcohols because the rate of the reaction differs greatly for a primary, secondary and tertiary alcohol. • The difference in rates is due to the solubility of the resulting alkyl halides • Tertiary Alcohol→ turns cloudy immediately (the alkyl halide is not soluble in water and precipitates out) • Secondary Alcohol → turns cloudy after 5 minutes • Primary Alcohol → takes much longer than 5 minutes to turn cloudy 5. Oxidation • Uses an oxidizing agent such as potassium permanganate (KMnO4) or potassium dichromate (K2Cr2O7). • This reaction can also be used as a qualitative test for the different types of alcohols because there is a distinct colour change. dichromate → chromium 3+ (orange) → (green) permanganate → manganese (IV) oxide (purple) → (brown) Tertiary Alcohol not oxidized under normal conditions CH3 KMnO4 H3C C OH NO REACTION K2Cr2O7 CH3 tertbutyl alcohol Secondary Alcohol ketone + hydrogen ions H O KMnO4 H3C C CH3 + K2Cr2O7 C + 2 H H3C CH3 OH propanone 2-propanol Primary Alcohol aldehyde + water carboxylic acid + hydrogen ions O KMnO4 O H H KMnO H H 4 + CH3CH2CH2OH C C C H C C C H + 2 H K2Cr2O7 + H2O K Cr O H H H 2 2 7 HO H H 1-propanol propanal propanoic acid 6.
    [Show full text]