DOCSLIB.ORG

Total Synthesis of Naturally Occurring Glycosylated Tetramic Acids

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Total Synthesis of Naturally Occurring Glycosylated Tetramic Acids Faculty of Biology, Chemistry and Geosciences University of Bayreuth Total synthesis of naturally occurring glycosylated tetramic acids Dissertation to obtain the degree Doctor of natural scienes (Dr. rer. nat.) Submitted by Sebastian Loscher Bayreuth 2015 The presented doctoral thesis was prepared at the Faculty of Chemistry, Biology and Geosciences in the Department of Organic Chemistry of the University of Bayreuth in Germany from September 2010 till April 2015. The work was supervised by Prof. Dr. Rainer Schobert. This is a full reprint of the dissertation submitted to obtain the academic degree of Doctor of Natural Sciences (Dr. rer. nat.) and approved by the Faculty of Biology, Chemistry and Geosciences of the University of Bayreuth. Date of submission: 20. May 2015 Date of approval by the commission: 27. May 2015 Date of scientific presentation: 31. July 2015 Prof. Dr. Rhett Kempe Acting Dean Doctoral Comittee Prof. Dr. Rainer Schobert 1st reviewer Prof. Dr. Karl-Heinz Seifert 2nd reviewer Prof. Dr. Andreas Kirschning 3rd reviewer Prof. Dr. Birgit Weber chairman Prof. Dr. Andreas Möglich member of the committee “The biggest problem on being successful is that it looks quite easy.” Prof. Dr. Jean-Jacques Dordain, General Director of the European Space Agency (ESA) in an interview 12.11.2014 concerning the Rosetta mission. TABLE OF CONTENT TABLE OF CONTENT I. ABSTRACT ........................................................................ 1 II. INTRODUCTION .............................................................. 3 II.1. Tetramic acid derivatives and their structural diversity ........ 3 II.1.1. 3-Acyl tetramic acids ................................................................................ 4 II.1.2. 3-Polyenoyl tetramic acids ....................................................................... 5 II.1.3. 3-Decanoyl tetramic acids ........................................................................ 7 II.1.4. Macrocyclic tetramic acids ...................................................................... 8 II.1.5. Additional tetramic acids ........................................................................ 9 II.2. Biological function of tetramic acids ......................................... 9 II.2.1. Cell wall interaction of tetramic acids and quorum sensing .............. 10 II.2.2. Tetramic acids as nucleotide or pyrophosphate mimics .................... 11 II.3. Chemical and structural properties of tetramic acids ........... 12 II.4. Biosynthesis of tetramic acids .................................................. 14 II.5. Chemical synthesis of tetramic acids ....................................... 17 II.5.1. Synthetic methods to form the core pyrrolidine-2,4-dione system .... 17 II.5.2. 3-Acylation of the tetramic acid core ................................................... 20 II.5.3. Aldol reaction for C-5 alkylation .......................................................... 21 II.5.4. Direct synthesis of 3-acyl tetramic acids .............................................. 22 i TABLE OF CONTENT II.6. Glycosylated tetramic acids ...................................................... 23 II.6.1. Ancorinosides .......................................................................................... 23 II.6.2. Epicoccamides......................................................................................... 24 II.6.3. Virgineone ............................................................................................... 25 II.6.4. Streptolydigin ......................................................................................... 27 II.6.5. Aurantosides ........................................................................................... 30 II.6.6. Rubrosides ............................................................................................... 30 III. PROJECT AIMS ............................................................. 32 IV. RESULTS ....................................................................... 33 IV.1. Total synthesis of epicoccamide D .......................................... 33 IV.1.2. Retrosynthesis of epicoccamide D ....................................................... 34 IV.1.3. Total Synthesis ...................................................................................... 35 IV.1.4. Assignment and absolute configuration of synthetic products ........ 47 IV.1.5. Comparison of synthetic products with natural epicoccamide D .... 48 IV.2. Total synthesis of ancorinoside B diglycoside ....................... 49 IV.2.2. Retrosynthesis of ancorinoside B ........................................................ 49 IV.2.3. Disaccharide unit of ancorinoside B via glucuronic acid .................. 51 IV.2.4. Total synthesis of ancorinoside B diglycoside .................................... 54 IV.3. Contribution to virgineone total synthesis ............................ 61 IV.3.2. Retrosynthesis of the virgineone side chain ....................................... 62 IV.3.3. Synthesis of the virgineone side chain ................................................. 63 ii TABLE OF CONTENT IV.4. Contribution to aurantoside G and J total synthesis ............ 66 IV.4.2. Retrosynthesis of aurantoside G and J ............................................... 66 IV.4.3. Direct N-glycosylation trials with tetramic acids ............................... 69 IV.4.4. N-Glycosylated tetramic acids via Fukuyama-Mitsunobu reaction 70 IV.5. Stereoinduction by tetramic acid boron complexes .............. 72 V. CONCLUSION ................................................................ 74 V.1. Total synthesis of epicoccamide D ............................................ 74 V.2. Total synthesis of the ancorinoside B diglycoside .................. 75 V.3. Contribution to virgineone total synthesis .............................. 77 V.4. N-Glycosylation for aurantoside G and J synthesis ............... 79 V.5. Stereoinduction by tetramic acid boron complexes ............... 80 VI. EXPERIMENTAL SECTION ........................................ 82 VI.1. General remarks ....................................................................... 82 VI.2. Epicoccamide D ........................................................................ 83 VI.2.1. Glycosyl donor ....................................................................................... 83 VI.2.2. Synthesis of the C16 alkyl chain ........................................................... 87 VI.2.3. Phosphonate........................................................................................... 88 VI.2.4. Synthesis of alanine derivatives ........................................................... 90 VI.2.5. Synthesis of epicoccamide D and derivatives ..................................... 93 iii TABLE OF CONTENT VI.2.6. Synthesis of model compounds .......................................................... 116 VI.3. Ancorinoside B........................................................................ 122 VI.3.1. Glycosyl donor ..................................................................................... 122 VI.3.2. Synthesis of the C20 alkyl chain ......................................................... 123 VI.3.3. 6-O-PMB protected glycosyl acceptor .............................................. 125 VI.3.4. Total synthesis of ancorinoside B diglycoside .................................. 129 VI.4. Virgineone ............................................................................... 135 VI.4.1. Synthesis of the C20-alkene for Sharpless dihydroxylation ............. 135 VI.4.2. Dihydroxylation and selective protection ......................................... 138 VI.5. Aurantoside G and J .............................................................. 143 VI.5.1. O-Glycosylation ................................................................................... 143 VI.5.2. N-Glycosylation ................................................................................... 144 VI.6. Tetramic acid boron complexes ............................................ 147 VII. ABBREVIATIONS ..................................................... 149 VIII. LITERATURE ........................................................... 152 IX. ACKNOWLEDGEMENTS .......................................... 162 X. ABSTRACT (GERMAN VERSION) ............................ 163 iv TABLE OF SCHEMES TABLE OF SCHEMES II. INTRODUCTION .............................................................. 3 Scheme II.1. Tautomerism of 3-acyl tetramic acids ................................................................. 13 Scheme II.2. First biosynthetic steps to streptolydigin ............................................................. 14 Scheme II.3. Second set of biosynthetic steps to streptolydigin .............................................. 15 Scheme II.4. Third set of biosynthetic steps to streptolydigin .................................................. 16 Scheme II.5. Terminal biosynthetic steps to streptolydigin ...................................................... 16 Scheme II.6. Tetramic acid synthesis via Meldrum’s acid ....................................................... 17 Scheme II.7. Tetramate synthesis with Bestmann’s ylide ........................................................ 18 Scheme II.8. Tetramate synthesis with SmI2 and CH2N2 ......................................................... 18 Scheme II.9. Tetramic acid synthesis via CO2 incorperation ................................................... 19 2+ Scheme
Load more

Recommended publications
  • Catalytic Asymmetric Di Hydroxylation
    Chem. Rev. 1994, 94, 2483-2547 2483 Catalytic Asymmetric Dihydroxylation Hartmuth C. Kolb,t Michael S. VanNieuwenhze,* and K. Barry Sharpless* Department of Chemistry, The Scripps Research Institute, 10666 North Torfey Pines Road, La Jolla, California 92037 Received Ju/y 28, 1994 (Revised Manuscript Received September 14, 1994) Contents 3.1.4. Differentiation of the Hydroxyl Groups by 2524 Selective, Intramolecular Trapping 1. Introduction and General Principles 2483 3.1.5. Miscellaneous Transformations 2525 2. Enantioselective Preparation of Chiral 1,2-Diols 2489 3.2. Preparation of Chiral Building Blocks 2527 from Olefins 3.2.1. Electrophilic Building Blocks 2527 2.1. Preparation of Ligands, Choice of Ligand, 2489 Scope, and Limitations 3.2.2. Chiral Diol and Polyol Building Blocks 2529 2.1.1. Preparation of the Ligands 2490 3.2.3. Chiral Monohydroxy Compounds Derived 2529 from Diols 2.1 -2. Ligand Choice and Enantioselectivity Data 2490 3.2.4. 5- and 6-Membered Heterocycles 2530 2.1.3. Limitations 2491 3.3. Preparation of Chiral Auxiliaries for Other 2530 2.2. Reaction Conditions 2493 Asymmetric Transformations 2.2.1. Asymmetric Dihydroxylation of the 2493 3.3.1. Preparation of 2530 “Standard Substrates” (1 R,2S)-trans-2-phenylcyclohexanol 2.2.2. Asymmetric Dihydroxylation of 2496 3.3.2. Optically Pure Hydrobenzoin (Stilbenediol) 2531 Tetrasubstituted Olefins, Including Enol and Derivatives Ethers 4. Recent Applications: A Case Study 2536 2.2.3. Asymmetric Dihydroxylation of 2496 Electron-Deficient Olefins 5. Conclusion 2538 2.2.4. Chemoselectivity in the AD of Olefins 2497 6. References and Footnotes 2542 Containing Sulfur 2.3.
    [Show full text]
  • Organic Seminar Abstracts
    Digitized by the Internet Archive in 2012 with funding from University of Illinois Urbana-Champaign http://archive.org/details/organicsemin1971752univ / a ORGANIC SEMINAR ABSTRACTS 1971-1972 Semester II School of Chemical Sciences Department of Chemistry- University of Illinois Urbana, Illinois 3 SEMINAR TOPICS II Semester 1971-72 Reactions of Alkyl Ethers Involving n- Complexes on a Reaction Pathway 125 Jerome T. Adams New Syntheses of Helicenes 127 Alan Morrice Recent Advances in Drug Detection and Analysis I36 Ronald J. Convers The Structure of Carbonium Ions with Multiple Neighboring Groups 138 William J. Work Recent Reactions of the DMSO-DCC Reagent ll+O James A. Franz Nucleophilic Acylation 1^2 Janet Ollinger The Chemistry of Camptothecin lU^ Dale Pigott Stereoselective Syntheses and Absolute Configuration of Cecropia Juvenile Horomone 1U6 John C. Greenfield Uleine and Related Aspidosperma Alkaloids 155 Glen Tolman Strategies in Oligonucleotide Synthesis 162 Graham Walker Stable Carbocations: C-13 Nuclear Magnetic Resonance Studies 16U Moses W. McMillan Organic Chlorosulfinates 166 Steven W. Moje Recent Advances in the Chemistry of Penicillins and Cephalosporins 168 Ronald Stroshane Cerium (iv) Oxidations 175 William C. Christopfel A New Total Synthesis of Vitamin D 18 William Graham Ketone Transpositions 190 Ann L. Crumrine - 125 - REACTIONS OF ALKYL ETHERS INVOLVING n-COMPLEXES ON A REACTION PATHWAY Reported by Jerome T. Adams February 2k 1972 The n-complex (l) has been described as an intermediate on the reaction pathway for electrophilic aromatic substitution and acid catalyzed rearrange- ment of alkyl aryl ethers along with sigma (2) and pi (3) type intermediates. 1 ' 2 +xR Physical evidence for the existence of n-complexes of alkyl aryl ethers was found in the observation of methyl phenyl ononium ions by nmr 3 and ir observation of n-complexes of anisole with phenol.
    [Show full text]
  • Bridging Mcmurry and Wittig in One-Pot
    Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 1755 Bridging McMurry and Wittig in One-Pot Olefins from Stereoselective, Reductive Couplings of Two Aldehydes via Phosphaalkenes JURI MAI ACTA UNIVERSITATIS UPSALIENSIS ISSN 1651-6214 ISBN 978-91-513-0536-3 UPPSALA urn:nbn:se:uu:diva-368873 2019 Dissertation presented at Uppsala University to be publicly examined in Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, Friday, 15 February 2019 at 10:15 for the degree of Doctor of Philosophy. The examination will be conducted in English. Faculty examiner: Professor Dr. Christian Müller (Freie Universität Berlin, Institute of Chemistry and Biochemistry). Abstract Mai, J. 2019. Bridging McMurry and Wittig in One-Pot. Olefins from Stereoselective, Reductive Couplings of Two Aldehydes via Phosphaalkenes. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 1755. 112 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-513-0536-3. The formation of C=C bonds is of great importance for fundamental and industrial synthetic organic chemistry. There are many different methodologies for the construction of C=C bonds in the literature, but currently only the McMurry reaction allows the reductive coupling of two carbonyl compounds to form alkenes. This thesis contributes to the field of carbonyl olefinations and presents the development of a new synthetic protocol for a one-pot reductive coupling of two aldehydes to alkenes based on organophosphorus chemistry. The coupling reagent, a phosphanylphosphonate, reacts with an aldehyde to yield a phosphaalkene intermediate which upon activation with a base undergoes an olefination with a second aldehyde. A general overview of synthetic methods for carbonyl olefinations and the chemistry of phosphaalkenes is given in the background chapter.
    [Show full text]
  • PDF (Chapter 1)
    Chapter 1–Evolving Strategies Toward the Synthesis of Curcusone C 1 CHAPTER 1 Evolving Strategies Toward the Synthesis of Curcusone Ci 1.1 INTRODUCTION AND ALTERNATE SYNTHETIC STRATEGIES 1.1.1 INTRODUCTION Indigenous to Central America, the flowering plant Jatropha curcas has traditionally been used in the manufacturing of soaps and lamp oil but has also drawn attention due to its potential applications in the biodiesel industry.1 J. curcas has also received notice by organic chemists owing to its structurally diverse array of diterpenoid secondary metabolites, which includes the curcusone (i) This research was a collaborative effort between A. C. Wright and C. W. Lee, see: reference 6, reference 19, and reference 20. Chapter 1–Evolving Strategies Toward the Synthesis of Curcusone C 2 family of natural products. This family comprises various synthetically challenging and biologically active rhamnofolane diterpenoid natural products. In 1986, Naengchomnong and coworkers first isolated curcusones A–D (1–4, Figure 1.1.1) and elucidated the structures of 2 and 3 via X-ray diffraction.2 Over the ensuing three decades, several more members of this family were structurally identified and were further discovered to possess anticancer activity.3 Among them, curcusone C (3) demonstrates the most potent and varied anticancer properties, including anti- proliferative activity against human hepatoma (IC50 in 2.17 uM), ovarian carcinoma (IC50 in 0.160 2 uM), and promyeolycytic leukemia (IC50 in 1.36 uM). Figure 1.1.1. Reported Structures of Curcusones A–J O O H O H H H H H R2 H Me Me R1 HO MeO O O O R1, R2 = Me, H : Curcusone A (1) Curcusone E Curcusone F R1, R2 = H, Me : Curcusone B (2) R1, R2 = Me, OH : Curcusone C (3) R1, R2 = OH, Me : Curcusone D (4) O O O H H H H H H H R2 O OH R1 O OH MeO O O O Curcusone G Curcusone H R1, R2 = Me, H : Curcusone I (5) R1, R2 = H, Me : Curcusone J (6) Despite these enticing biological features, 3 and all of its structural relatives have yet to surrender to any total synthesis campaigns.
    [Show full text]
  • Title Synthetic Studies on the Chemistry of Gem-Dimetalation with Inter-Element Compounds( Dissertation 全文 )
    Synthetic Studies on the Chemistry of gem-Dimetalation with Title Inter-element Compounds( Dissertation_全文 ) Author(s) Kurahashi, Takuya Citation Kyoto University (京都大学) Issue Date 2003-03-24 URL http://dx.doi.org/10.14989/doctor.k10168 Right Type Thesis or Dissertation Textversion author Kyoto University Synthetic Studies on the Chemistry ofgem-Dimetalation with Inter-element Compounds Takuya Kurahashi 2003 Synthetic Studies on the Chemistry ofgem-Dimetalation with Inter-element Compounds Takuya Kurahashi 2003 Contents Chapter 1 Introduction and General Summary 1 Chapter 2 Silylborylation and Diborylation of Alkylidene-type Carbenoids. Synthesis of 1-Boryl-1-silyl-1-alkenes and 1,1-Diboryl-1-alkenes 21 Chapter 3 Stereospecific Silylborylation of a-Chloroallyllithiums. Synthesis and Reactions of Allylic gem-Silylborylated Reagents 53 Chapter 4 Synthesis and Reactions of 1-Silyl-1-borylallenes 81 Chapter 5 Efficient Synthesis of 2,3-Diboryl-1,3-butadiene and Synthetic Applications 95 List ofPublications - 115 Acknowledgments - 117 Abbreviations Ac acetyl J coupling constant in Hz Anal. element analysis LDA lithium diisopropylamide aq. aqueous m multiplet (spectral) Bn benzyl M mol per liter Bpin 4,4,5,5-tetramethyl-I,3,2-dioxabolan-2-yl Me methyl brs broad singlet (spectral) MEM 2-methoxyethoxymethyI Bu butyl min minute(s) calcd calculated mL mililiter cat. catalytic mp melting point Cy cyclohexyl Ms mesyl d doublet (spectral) NMR nuclear magnetic resonance dba dibenzylideneacetone Pent pentyl DME 1,2,-dimethoxyethane Ph phenyl DMF N,N-dimethylformamide
    [Show full text]
  • Nickel-Catalyzed Hydrosilylation of Alkenes and Transition-Metal-Free
    Nickel-catalyzed Hydrosilylation of Alkenes and Transition- Metal-Free Intermolecular α-C-H Amination of Ethers THÈSE NO 7129 (2016) PRÉSENTÉE LE 28 JUILLET 2016 À LA FACULTÉ DES SCIENCES DE BASE LABORATOIRE DE SYNTHÈSE ET DE CATALYSE INORGANIQUE PROGRAMME DOCTORAL EN CHIMIE ET GÉNIE CHIMIQUE ÉCOLE POLYTECHNIQUE FÉDÉRALE DE LAUSANNE POUR L'OBTENTION DU GRADE DE DOCTEUR ÈS SCIENCES PAR Ivan BUSLOV acceptée sur proposition du jury: Prof. K. Severin, président du jury Prof. X. Hu, directeur de thèse Prof. E. P. Kündig, rapporteur Prof. M. Driess, rapporteur Prof. H.-A. Klok, rapporteur Suisse 2016 Acknowledgements First, I would like to thank my scientific advisor, Prof. Xile Hu, for giving me the opportunity to carry out my doctoral studies in his group. I am deeply grateful for his support, encouragement and guidance during my time as a Ph.D. student at EPFL. His optimistic energy and confidence in my research always inspired me and helped me to move forward. I would like to thank my thesis jury: Prof. Kay Severin, Prof. Ernst Peter Kündig, Prof. Matthias Driess and Prof. Harm-Anton Klok for accepting to examine this manuscript. Many thanks to the people working at EPFL: Annelise Carrupt, Gladys Pache and Benjamin Kronenberg - the team of BCH chemical store - for their excellent work; Dr. Pascal Miéville for his help with NMR machines and methods; Dr. Rosario Scopelliti and Dr. Euro Solari for performing the X-ray and elemental analyses; Dr. Laure Menin, Daniel Baumann and Francisco Sepulveda for the mass spectrometry analyses; Christina Zamanos-Epremian and Anne Lene Odegaard for their kind support and for the administrative work.
    [Show full text]
  • WO 2014/183211 Al 20 November 2014 (20.11.2014) WIPOIPCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2014/183211 Al 20 November 2014 (20.11.2014) WIPOIPCT (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07D 307/32 (2006.01) C07D 493/22 (2006.01) kind of national protection available)·. AE, AG, AL, AM, C07D 307/28 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) International Application Number: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/CA2014/050438 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, 9 May 2014 (09.05.2014) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (25) Filing Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (26) Publication Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/823,579 15 May 2013 (15.05.2013) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available)·. ARIPO (BW, GH, (71) Applicant: ALPHORA RESEARCH INC. [CA/CA]; GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, 2395 Speakman Drive, Suite 2001, Mississauga, Ontario UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, L5K 1B3 (CA).
    [Show full text]
  • Synthesis and Characterization of Ruthenium (II) Complexes and Their Applications to Atom Transfer Radical Addition Reactions
    University of Nevada, Reno Synthesis and Characterization of Ruthenium (II) Complexes and their Applications to Atom Transfer Radical Addition Reactions A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry By Radhika P. Nair Dr. Brian J. Frost/Dissertation Advisor December, 2009 THE GRADUATE SCHOOL We recommend that the dissertation prepared under our supervision by R A D H I K A P. N A IR entitled Synthesis And Characterization Of Ruthenium (II) Complexes And Their Applications To Atom T ransfer Radical Addition Reactions be accepted in partial fulfillment of the requirements for the degree of D O C T O R O F PH I L OSOPH Y Dr. Brian J. Frost, Advisor Dr. Vincent J. Catalano, Committee Member Dr. Sean M. Casey, Committee Member Dr. Robert C. Mancini, Committee Member Dr. Dhanesh Chandra, Graduate School Representative Marsha H. Read, Ph. D., Associate Dean, Graduate School December, 2009 i Abstract A series of mixed-phosphine ruthenium complexes of the type CpRu(PR3)(PPh3)Cl, here Cp 0 Cp*, Dp, Ind, Cp, Tp; PR3 = PTA or PMe3 have been synthesized by liand e>chane reactions ith CpRu(PPh3)2Cl, and characterized by multinuclear NMR spectroscopy and X-ray crystallography. We have explored the efficiency of these complexes as catalysts for the atom transfer radical addition (ATRA) of various chloro-substrates (CCl4, CHCl3, p-TsCl, CCl3CO2Et, and CH2ClCO2Et) to styrene in the presence of AIBN as a radical source. For comparison purposes, we also investi<ated the activity of CpRu(PPh3)2Cl and CpRu(PTA)2Cl complexes towards ATRA.
    [Show full text]
  • Wittig Reaction
    Wittig reaction The Wittig reaction or Wittig olefination is a chemical reaction of an aldehyde or Wittig reaction ketone with a triphenyl phosphonium ylide (often called a Wittig reagent) to give an Named after Georg Wittig alkene and triphenylphosphine oxide. Reaction Coupling reaction type Reaction aldehyde or ketone + [1][2][3] It is widely used in organic synthesis for the preparation of alkenes. It should triphenyl phosphonium ylide not be confused with the Wittig rearrangement. ↓ Wittig reactions are most commonly used to couple aldehydes and ketones to singly- alkene substituted triphenylphosphonium ylides. For the reaction with aldehydes, the double bond geometry is readily predicted based on the nature of the ylide. With unstabilised + ylides (R3 = alkyl) this results in (Z)-alkene product with moderate to high selectivity. triphenylphosphine oxide 3 With stabilized ylides (R = ester or ketone), the (E)-alkene is formed with high Conditions selectivity. The (E)/(Z) selectivity is often poor with semistabilized ylides (R3 = Typical typically THF or aryl).[4] solvents diethyl ether To obtain the (E)-alkene for unstabilized ylides, the Schlosser modification of the Identifiers Wittig reaction can be used. Alternatively, the Julia olefination and its variants also March's 16–44 (6th ed.) provide the (E)-alkene selectively. Ordinarily, the Horner–Wadsworth–Emmons Advanced reaction provides the (E)-enoate (α,β-unsaturated ester), just as the Wittig reaction does. To obtain the (Z)-enoate, the Still-Gennari modification of the Horner-
    [Show full text]
  • WO 2014/183211 Al 20 November 2014 (20.11.2014) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2014/183211 Al 20 November 2014 (20.11.2014) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07D 307/32 (2006.01) C07D 493/22 (2006.01) kind of national protection available): AE, AG, AL, AM, C07D 307/28 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) Number: International Application DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/CA2014/050438 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, 9 May 2014 (09.05.2014) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (25) Filing Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (26) Publication Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/823,579 15 May 2013 (15.05.2013) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant: ALPHORA RESEARCH INC. [CA/CA]; GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, 2395 Speakman Drive, Suite 2001, Mississauga, Ontario UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, L5K 1B3 (CA).
    [Show full text]
  • "Front Matter and Index". In: Titanium and Zirconium in Organic Synthesis
    Titanium and Zirconium in Organic Synthesis. Edited by Ilan Marek Copyright c 2002 Wiley-VCH Verlag GmbH & Co. KGaA ISBNs: 3-527-30428-2 (Hardback); 3-527-60067-1 (Electronic) Titanium and Zirconium in Organic Synthesis Edited by Ilan Marek Titanium and Zirconium in Organic Synthesis. Edited by Ilan Marek Copyright c 2002 Wiley-VCH Verlag GmbH & Co. KGaA ISBNs: 3-527-30428-2 (Hardback); 3-527-60067-1 (Electronic) Further Reading from Wiley-VCH Ricci, A. (Ed.) Modern Amination Methods 2000. ISBN 3-527-29976-9 Krause, N. (Ed.) Modern Organocopper Chemistry 2001. ISBN 3-527-29773-1 Yamamoto, H. (Ed.) Lewis Acids in Organic Synthesis AComprehensive Handbook in Two Volumes 2000. ISBN 3-527-29579-8 Beller, M., Bolm, C. (Eds.) Transition Metals for Organic Synthesis Building Blocks and Fine Chemicals 1998. ISBN 3-527-29501-1 Titanium and Zirconium in Organic Synthesis. Edited by Ilan Marek Copyright c 2002 Wiley-VCH Verlag GmbH & Co. KGaA ISBNs: 3-527-30428-2 (Hardback); 3-527-60067-1 (Electronic) Titanium and Zirconium in Organic Synthesis Edited by Ilan Marek Titanium and Zirconium in Organic Synthesis. Edited by Ilan Marek Copyright c 2002 Wiley-VCH Verlag GmbH & Co. KGaA ISBNs: 3-527-30428-2 (Hardback); 3-527-60067-1 (Electronic) Editor: This book was carefully produced. Never- theless, editor, authors and publisher Prof. Ilan Marek do not warrant the information contained Department of Chemistry therein to be free of errors. Readers are Technion ± Israel Institute of Technology advised to keep in mind that statements, Haifa 32000 data, illustrations, procedural details or Israel other items may inadvertently be inaccurate.
    [Show full text]
  • Some Examples of Benzotriazole-Mediated Sythesis
    SOME EXAMPLES OF BENZOTRIAZOLE-MEDIATED SYNTHESIS BY DAI CHENG A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 1997 Dedicated to all the scientists, who made this world better by the power of understanding. ACKNOWLEDGEMENTS I would like to thank all those who have helped to make this dissertation a reality. First, I want to express my deep gratitude to and appreciation for Professor Alan R. Katritzky, my advisory committee chair. His support has been essential for my success in finishing the doctoral training. His guidance developed me as a chemist and developed my interest in organic synthesis. His industrious spirit inspired my diligence. His achievements have been and will be an invaluable inspiration to me in pursuing my career. I also feel indebted to other members of my advisory committee. Professors Merle A. Battiste who not only taught me in my organic synthesis course but also inspired me to pursue excellence in chemistry. Professor Lisa McElwee-White from whom I have benefited a lot because of her perfect performance as a teacher. Professor William M. Jones, Professor Gus J. Palenik and Professor Nicholas S. Bodor, for their generous time and helpful suggestions. Professors James A. Deyrup, to whom I have been so grateful for admitting me into the graduate program, and Robert T. Kennedy are sincerely appreciated for their helpful participation. I thank members of the Katritzky Group for their daily help and cooperation, especially my group leaders: Dr. Sergei A.
    [Show full text]