DOCSLIB.ORG

4.2. FG Strategies. Part II.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
4.2. FG Strategies. Part II.Pdf Master Course 2018-19 in Organic Chemistry methods and design in organic synthesis Pere Romea Rubik’s cube 4.2. Single & Double Bonds Non functional group R R disconnection Carbon-a Carbon-d R R ¿"? Alkyl%d Alkyl%a Li Potential precursors X Alkyl lithium Alkyl halide, X: Cl, Br, I MgBr RSO3 Alkyl magnesium halide Alkyl sulfonates M + Y M: Li, MgX M: halide, sulfonate The reaction is plagued by many side reactions due to high pKa of Alkyl-d (pKa 45–50) OH OMe O N O MeO H N O (–) Hennoxazole A ?antiviral Smith, T. E. JOC 2008, 73, 142 Polyfibrospongia OH OMe O N O MeO H N O ¿ FGA ? OPG OMe TBS O N O MeO H N O OPG OMe TBS O N O Li Br MeO H N O Oxazole alkylation studies O Ph N two potential reacting sites Oxazole alkylation studies Li Li O base O O –78 °C Ph N Ph N Ph N MeI MeI ratio 1:2 O Me Me O BuLi LDA LiNEt2 (14:86) (37:63) (99:1) Ph N Ph N 1 2 This reversal of regioselectivity is thought to arise from the ability of Et2NH to mediate the low-temperature equilibration of a kinetic mixture of otherwise noninterconverting lithiated intermediates However, such a situation was dramatically modified in a model close to the TGT structure TAKE-HOME MESSAGE: the model should be as similar as possible to the real system Oxazole alkylation studies single product Chelation could be the reason O Li O Li O MeO OMe MeO OMe MeO OMe N base N N H N N N –78 °C H H O O O three potential base: BuLi, LDA, LiNEt2 reacting sites These results suggest that deprotonation at the heterocycle is thermodynamically as well as kinetically favored SOLUTION: BLOCKING THAT POSITION? TBS TBS TBS O O Me O Me MeO OMe 1) base, –78 °C MeO OMe MeO OMe N N + N H N 2) 2 equiv MeI H N H N O O O ratio mono:di:SM Me BuLi LDA LiNEt2 (60:12:28) (43:8:48) (88:5:7) Alkylation of OTBS the real system OMe TBS N O O MeO H O N 1) LiNEt2, THF, –78 °C 2) Br 77% OTBS OMe TBS N O O MeO H O N TBAF, THF, rt 99% OH OMe TBS N O O MeO H (–) Hennoxazole A O N Alternative (I): Terminal Alkynes FGA Alkynyl&d Alkyl&a R H + n-BuLi R Li + n-BuH THF, –78 °C pKa ca 25 pKa 50 R H + EtMgBr R MgBr + EtH THF, 0 °C Larva of Mexican bean beetle O O NH Epilachnadiene defense agains ants Rao, B. V. TL 1995, 36, 147 ? O OH OH FGI O NH OH OH Br OH OH OPG Alkyl%a Br Alkyl%a Alkynyl%d OH O Alkynyl%d Alkyl%a Alkynyl%d Rao, B. V. TL 1995, 36, 147 Alternative (II): Organocuprates ORGANOCOPPER REAGENTS, easily prepared by transmetallation, are very selective RLi + CuX RCu + LiX Monoorganocopper 2 RLi + CuX R2CuLi + LiX Homocuprates or Gilman’s reagents RLi + CuCN RCu(CN)Li Heterocuprates I Me I Me2CuLi R Me R Et O, 0 °C to rt 90% 2 90% Br I 81% 75% Me Me Cecropia moth O A classical synthesis OMe O (±) Cecropia Juvenile Hormone Hormone involved in the development of larvae Corey, E. J. JACS 1968, 90, 5618 ? + I 1) TsCl, pyr 1) H3O OH OH 2) OTHP 2) LiAlH4, then i2 OTHP Li2CuEt2 TMS PBr3 Br OH TMS H 1) BuLi 2) CH2O Me 1) LiAlH4, I2 OH OH 2) Li2CuMe2 O O OMe OMe O Bacillus species O OH HO Iedomycin D Maulide, N. OL 2015, 17, 4486 ? Strained bicycle CO H 2 H O OH OH O HO O OH H 4π#Electrocyclic#transform CO H OTIPS Activated Zn 2 Then CuCN, LiCl OTIPS I H O 1) H2SO4, MeOH 2) LiOH, MeOH O 98% H CO H O OH 2 Δ OH HO 63% over three steps Alternative (III): Pd-Mediated Cross-Coupling Reactions cat Pd(0) R1 X + R2 M R1 R2 + M X GENERAL MECHANISM PdL2 R1 X R1: better no ß-H Pd(0) X: I, Br, (Cl), OTf Oxidative addition R1 R2 Reductive elimination R1 R1 Pd(II) L2 Pd L2 Pd Pd(II) R2 X M X R2 M R2: alkyl, alkenyl, alkynyl, aryl TRANSMETALATION Fürstner, A. ACIE 2005, 44, 674 Reactants Pd-Mediated Cross-Coupling Reactions TRANSMETALATION Transfer of an organic group from one metal center to another. The process involves no formal change in oxidation state for either metal. For palladium-mediated cross-coupling reactions R1 X + Pd R1 Pd X R1Li, R1MgY Kumada R1B(OR)2 SUZUKI R1CuLn SONOGASHIRA R1ZnY Negishi R1SnR3 STILLE Mignani, G. CR 2006, 106, 2651 Magano, J.; Dunetz, J. R. CR 2011, 111, 2177 Reactants Suzuki Cross-Coupling Reaction X 1 Csp2 X X: I > Br > OTf >> Cl R X + OH O O 2 2 2 2 Csp2 R B R B R B R : alkenyl, aryl OH O O R2 B 2 2 Csp3 R B R2 9-BBN R : alkyl Pd(0) Base Pd(0): Pd(PPh3)4 Ph Ph P PdCl Pd(II): Pd(OAc)2 / PR3 or AsR3 Fe 2 1 2 P R R Ph Ph for Csp3–Csp2 dppf Reactants Suzuki Cross-Coupling Reactions 0.2 mol% Pd(OAc)2 OH K2CO3 B + I NO2 NO2 OH Acetone / H2O, 65 °C 97% 2 mol% Pd(PPh ) OH I 3 4 B NaOEt + OH PhMe, 65 °C 98% O B O OTHP 85% OTHP 3 mol% Pd(PPh3)4, NaOEt Br PhMe, 85°C OTHP 73% O B O Reactants Suzuki Cross-Coupling Reactions H OMe B OMe OAc OMe OMe S Csp3–Csp2 Coupling OTBDPS OTBDPS N I THF, rt B OTBS OTBS PdCl2(dppf), AsPh3 71% Regioselective Hydroboration Cs2CO3 DMF, H2O OMe O OH O OAc OMe O S OTBDPS S OH N N OTBS O Epothilone A Danishefsky, S. ACIE 1996, 35, 2801 Csp2–Csp2 Coupling HO OMe B O HO O OMe OTBS EtO O I EtO O H H 5 mol % Pd(PPh3)4,Tl2CO3, THF/H2O, rt H H OTBS 91% O OMe (+) Herboxidiene O HO O GEX 1A H H OH Romea P.; Urpí, F. OL 2011, 13, 5350; OBC 2017, 15, 1842 Reactants Sonogashira Cross-Coupling Reaction X Csp2 X X: I > Br ≈ OTf >> Cl R1 X + pKa 25 pKa 12 CuX R3N 2 2 2 2 H R + CuX H R XCu R + R3NH XCu R The acidity of Csp–H is enhanced via π-complexation Pd(0) Pd(0): Pd(PPh3)4 Pd(II): PdCl 2(PPh3)2 R1 R2 Doucet, H.; Hierso, J.-C. ACIE 2007, 46, 834 Reactants Sonogashira Cross-Coupling Reactions TBSO OH I 5 mol% PdCl2(PPh3)2 TBSO OH CO2Me CO Me CuI, Et3N 2 + N N CH3CN, –20 °C to rt MeO O MeO O 85% Meyers, A. I. JOC 2001, 66, 6037 TBSO TBSO O I O TBSO O O TBSO O O O O N N 5 mol% PdCl2(PPh3)2 S CuI, Et3N S CO2Et CO2Et CH3CN, –20 °C to rt 74% Kirschning, A. ACIE 2008, 47, 9134 Reactants Stille Cross-Coupling Reaction X 1 Csp2 X X: I > Br > OTf >> Cl R X + 2 2 R : alkynyl > alkenyl > aryl > benzyl ≈ allyl > alkyl R SnR3 Pd(0): Pd(PPh3)4, Pd2(dba)3 / PR 3 or AsR3 Pd(0) Pd(II): Pd(OAc)2 / PR3 or AsR3 R1 R2 Reactants Stille Cross-Coupling Reactions O O O SnBu3 O H OH H OH OMe O OMe O N Bu3Sn N I H 20 mol% PdCl2(MeCN)2, i-Pr2NEt H I O O DMF / THF, rt O O H H OMe OMe O OH 27% O OH O OH O OH OMe OMe Nicolaou, K. C. JACS 1993, 115, 4419 Extraordinary Functional Group Tolerance O O Bu3Sn OTIPS OH O 20 mol% Pd2(dba)3, AsPh3 CuTC O I OTIPS OH NMP, 35 °C OH OH 50% O O Williams, D. R. JACS 2001, 123, 765 Reactants Stille Cross-Coupling Reactions A total synthesis of Chivosazole F shows the tremendous potential of the Stille coupling Chivosazole F MeO OH O N O OH OH O OH Paterson, I. ACIE 2017, 56, 645 Reactants Stille Cross-Coupling Reactions A total synthesis of Chivosazole F 2 Stille coupling shows the tremendous potential of the Stille coupling MeO Br Stille coupling O OTBS Me Sn N 3 O O O O Si MeO I O t-Bu t-Bu P OH O (OCH2CF3)2 N O OH OH O OH 3 SG olefination 1 Stille coupling Stille coupling Bu Sn OH Bu3Sn H Stille coupling Still-Gennari olefination 3 OTES O The Stille coupling were carried out using Pd(PPh3)4 and CuTC [copper thiophene-2-carboxylate] Paterson, I. ACIE 2017, 56, 645 See Fürstner, A. Chem Commun. 2008, 2873 Reactants Heck Reaction cat Pd(0) R1 R1 X + R2 2 + HB X Base R HX R1 X R1: no ß-H PdL2 L X: I, Br, (Cl), OTf Reductive elimination Oxidative addition R1 H Pd L L Pd L X X Pd(0): Pd(PPh3)4, R1 Pd(dba)2+PR3 2 E olefin R Pd(II): Pd(OAc)2, R2 L PdCl 2(PR3)2, PdCl2(CH3CN)2 R1 H R1 Pd L Pd L R2 X R2 X Base: R3N, R2NH AcO–, CO32– β-Hydride elimination Olefin insertion R1 H H H H R1 R2 Pd L R2 Pd L H X H X Reactants Heck Reaction The regioselectivity of the Heck reaction is not completely defined.
Load more

Recommended publications
  • Synthesis of the Methyl Ester Of
    Master’s Thesis 2019 60 ECTS Faculty of Chemistry, Biotechnology and Food Science Synthesis of the Methyl Ester of MaR2n-3 DPA Jeanne Sønderskov Rasmussen Master’s degree in Chemistry and Biotechnology II Acknowledgements The master’s degree was performed as collaboration between the Faculty of Chemistry, Biotechnology and Food Science at the Norwegian University of Life Sciences and the Department of Pharmacy, University of Oslo. The practical work as part of this thesis was conducted in the LIPCHEM group at the Section of Pharmaceutical Chemistry. First, I would like to thank my two supervisors, Professor Trond Vidar Hansen and Professor Yngve Stenstrøm for excellent guidance, encouragement and especially, for sharing long-time experience. Also, thanks to Dr. Jørn Tungen and Associate professor Anders Vik for solid guidance and teaching, especially during the time in the laboratory. I would also like to thank the rest of the LIPCHEM group. It has been a great experience to be a part of a research group and witness the impressive work that is carried out. Also, I am very grateful for sharing this challenging period with the four master students in pharmaceutical chemistry, Amalie Føreid Reinertsen, Marie Hermansen Mørk, Aina Kristin Pham and Margrethe Kristiansen. It has been nice to get to know you and follow your progress as well. Finally, an enormous thank to my lovely boyfriend, family and friends. Thanks for fantastic support and cheering through my six years of education. Blindern, May 2019 Jeanne Sønderskov Rasmussen III Abstract This master thesis presents the first synthesis of the methyl ester of the specialized pro-resolving mediator named MaR2n-3 DPA.
    [Show full text]
  • Organoboranes in Organic Syntheses Including Suzuki Coupling Reaction
    HETEROCYCLES, Vol. 80, No. 1, 2010 15 HETEROCYCLES, Vol. 80, No. 1, 2010, pp. 15 - 43. © The Japan Institute of Heterocyclic Chemistry DOI: 10.3987/COM-09-S(S)Summary ORGANOBORANES IN ORGANIC SYNTHESES INCLUDING SUZUKI COUPLING REACTION Akira Suzuki In 1962 I had a lively interest in Wacker reaction [the oxidation of ethylene to acetaldehyde in the presence of palladium chloride and cupric chloride (Angew. Chem. 1959, 71, 176)] and began a literature survey. One Saturday afternoon during that time, I went a bookstore in Sapporo to look at new chemistry books and found a red and black two-tone colored book on the shelf that did not look like a chemistry book. The book was "Hydroboration" written by Professor Herbert C. Brown of Purdue University. It seemed to be an interesting book, so, I bought it. This book changed the course of my career, and my fascination with the chemistry of hydroboration reaction and organoboron compounds thus prepared by hydroboration began after reading the book. I immediately wrote to Professor Brown requesting to work as a postdoctoral research fellow. At that time Professor Brown was at Heidelberg in Germany as a visiting professor. He kindly wrote me a letter of acceptance, and I began a study of the stereochemistry of hydroboration reaction at Purdue (1963-65). Through this work I came to understand hydroboration and the interesting characteristics of organoboranes. My family (wife and two small girls) and I had a very good time there and made good friends. Of course I enjoyed chemistry. After a stay of about two years at Purdue, I returned to Japan with my family at the end of March 1965.
    [Show full text]
  • Syntheses and Eliminations of Cyclopentyl Derivatives David John Rausch Iowa State University
    Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1966 Syntheses and eliminations of cyclopentyl derivatives David John Rausch Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Organic Chemistry Commons Recommended Citation Rausch, David John, "Syntheses and eliminations of cyclopentyl derivatives " (1966). Retrospective Theses and Dissertations. 2875. https://lib.dr.iastate.edu/rtd/2875 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. This dissertation has been microfilmed exactly as received 66—6996 RAUSCH, David John, 1940- SYNTHESES AND ELIMINATIONS OF CYCLOPENTYL DERIVATIVES. Iowa State University of Science and Technology Ph.D., 1966 Chemistry, organic University Microfilms, Inc., Ann Arbor, Michigan SYNTHESES AND ELIMINATIONS OF CYCLOPENTYL DERIVATIVES by David John Rausch A Dissertation Submitted to the Graduate Faculty in Partial Fulfillment of The Requirements for the Degree of DOCTOR OF PHILOSOPHY Major Subject: Organic Chemistry Approved : Signature was redacted for privacy. Signature was redacted for privacy. Head of Major Department Signature was redacted for privacy. Iowa State University Of Science and Technology Ames, Iowa 1966 ii TABLE OF CONTENTS VITA INTRODUCTION HISTORICAL Conformation of Cyclopentanes Elimination Reactions RESULTS AND DISCUSSION Synthetic Elimination Reactions EXPERIMENTAL Preparation and Purification of Materials Procedures and Data for Beta Elimination Reactions SUMMARY LITERATURE CITED ACKNOWLEDGEMENTS iii VITA The author was born in Aurora, Illinois, on October 24, 1940, to Mr.
    [Show full text]
  • Chemistry 301-301A - Hour Examination #3, December 11, 2003
    Chemistry 301-301A - Hour Examination #3, December 11, 2003 “.....as we know, there are known unknowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns - the ones we don't know we don't know.” Donald Rumsfeld (winner of a British award given to the worst mangler of the English language in 2003) “I know, a proof is a proof. What kind of a proof is a proof? A proof is a proof and when you have a good proof it's because it's proven." Jean Chrétien (hon. mention for the same award) 1[18 points] (a) Acid-catalyzed addition of water to 3-methyl-1-butene (1) results in formation of large amounts of a rearranged alcohol (2), in addition to the expected alcohol (3). Explain, with excellent arrow formalisms. H2O + H O+ 3 OH OH 1 3 2 (b) On the other hand hydroboration of 1, followed by oxidation, does not lead to any rearranged product. Only alcohol 4 is formed. Explain. Detailed mechanisms are not needed here, but a drawing of the transition state for the hydroboration step is. 1. BH3 OH 2. HOOH/HO – 1 4 (c) But there are some strange things that happen in hydroboration. For example when 2-methyl-2-butene (5) is hydroborated at high temperature, then treated with HOOH/HO–, alcohol 4 is still one of the products. Explain mechanistcally. Hint: at high temperature hydroboration is reversible.
    [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]
  • Stapled Peptides—A Useful Improvement for Peptide-Based Drugs
    molecules Review Stapled Peptides—A Useful Improvement for Peptide-Based Drugs Mattia Moiola, Misal G. Memeo and Paolo Quadrelli * Department of Chemistry, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy; [email protected] (M.M.); [email protected] (M.G.M.) * Correspondence: [email protected]; Tel.: +39-0382-987315 Received: 30 July 2019; Accepted: 1 October 2019; Published: 10 October 2019 Abstract: Peptide-based drugs, despite being relegated as niche pharmaceuticals for years, are now capturing more and more attention from the scientific community. The main problem for these kinds of pharmacological compounds was the low degree of cellular uptake, which relegates the application of peptide-drugs to extracellular targets. In recent years, many new techniques have been developed in order to bypass the intrinsic problem of this kind of pharmaceuticals. One of these features is the use of stapled peptides. Stapled peptides consist of peptide chains that bring an external brace that force the peptide structure into an a-helical one. The cross-link is obtained by the linkage of the side chains of opportune-modified amino acids posed at the right distance inside the peptide chain. In this account, we report the main stapling methodologies currently employed or under development and the synthetic pathways involved in the amino acid modifications. Moreover, we report the results of two comparative studies upon different kinds of stapled-peptides, evaluating the properties given from each typology of staple to the target peptide and discussing the best choices for the use of this feature in peptide-drug synthesis. Keywords: stapled peptide; structurally constrained peptide; cellular uptake; helicity; peptide drugs 1.
    [Show full text]
  • Hydroboration-Oxidation Of
    molecules Article Hydroboration-Oxidation of (±)-(1α,3α,3aβ,6aβ) -1,2,3,3a,4,6a-Hexahydro-1,3-pentalenedimethanol and Its O-Protected Derivatives: Synthesis of New Compounds Useful for Obtaining (iso)Carbacyclin Analogues and X-ray Analysis of the Products Constantin I. Tănase 1,* ID , Florea G. Cocu 1, Miron Teodor Căproiu 2, Constantin Drăghici 2 and Sergiu Shova 3 1 National Institute for Chemical-Pharmaceutical Research and Development, Department of bioactive substances and pharmaceutical technologies, 112 Vitan Av., 031299, Bucharest-3, Romania; [email protected] 2 Organic Chemistry Center “C.D.Nenitescu”, Spectroscopy Laboratory, 202 B Splaiul Independentei, 060023 Bucharest, Romania; [email protected] (M.T.C.); [email protected] (C.D.) 3 Institute of Macromolecular Chemistry “Petru Poni”, Crystallography Department, 700478 Iasi, Romania; [email protected] * Correspondence: [email protected]; Tel.: +40-21-321-2117; Fax: +40-21-322-2917 Received: 22 October 2017; Accepted: 16 November 2017; Published: 24 November 2017 Abstract: Hydroboration-oxidation of 2α,4α-dimethanol-1β,5β-bicyclo[3.3.0]oct-6-en dibenzoate (1) gave alcohols 2 (symmetric) and 3 (unsymmetric) in ~60% yield, together with the monobenzoate diol 4a (37%), resulting from the reduction of the closer benzoate by the intermediate alkylborane. The corresponding alkene and dialdehyde gave only the triols 8 and 9 in ~1:1 ratio. By increasing the reaction time and the temperature, the isomerization of alkylboranes favours the un-symmetrical triol 9. The PDC oxidation of the alcohols gave cleanly the corresponding ketones 5 and 6 and the deprotection of the benzoate groups gave the symmetrical ketone 14, and the cyclic hemiketal 15, all in high yields.
    [Show full text]
  • Appendix I: Named Reactions Single-Bond Forming Reactions Co
    Appendix I: Named Reactions 235 / 335 432 / 533 synthesis / / synthesis Covered in Covered Featured in problem set problem Single-bond forming reactions Grignard reaction various Radical couplings hirstutene Conjugate addition / Michael reaction strychnine Stork enamine additions Aldol-type reactions (incl. Mukaiyama aldol) various (aldol / Claisen / Knoevenagel / Mannich / Henry etc.) Asymmetric aldol reactions: Evans / Carreira etc. saframycin A Organocatalytic asymmetric aldol saframycin A Pseudoephedrine glycinamide alkylation saframycin A Prins reaction Prins-pinacol reaction problem set # 2 Morita-Baylis-Hillman reaction McMurry condensation Gabriel synthesis problem set #3 Double-bond forming reactions Wittig reaction prostaglandin Horner-Wadsworth-Emmons reaction prostaglandin Still-Gennari olefination general discussion Julia olefination and heteroaryl variants within the Corey-Winter olefination prostaglandin Peterson olefination synthesis Barton extrusion reaction Tebbe olefination / other methylene-forming reactions tetrodotoxin hirstutene / Selenoxide elimination tetrodotoxin Burgess dehydration problem set # 3 Electrocyclic reactions and related transformations Diels-Alder reaction problem set # 1 Asymmetric Diels-Alder reaction prostaglandin Ene reaction problem set # 3 1,3-dipolar cycloadditions various [2,3] sigmatropic rearrangement various Cope rearrangement periplanone Claisen rearrangement hirstutene Oxidations – Also See Handout # 1 Swern-type oxidations (Swern / Moffatt / Parikh-Doering etc. N1999A2 Jones oxidation
    [Show full text]
  • Manipulating Selectivity and Reactivity in Palladium-Catalyzed Oxidation Reactions
    Manipulating Selectivity and Reactivity in Palladium-Catalyzed Oxidation Reactions Thesis by Zachary Kimble Wickens In Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy CALIFORNIA INSTITUTE OF TECHNOLOGY Pasadena, California 2015 (Defended June 2nd, 2015) © 2015 Zachary Kimble Wickens All Rights Reserved 1 Dedicated to my parents for never pushing me to become a scientist 2 Acknowledgments The work I have the pleasure of sharing with you in this thesis would have been completely impossible without the help (both emotional and intellectual) of a tremendously large number of people. First, I want to thank my advisor, Bob Grubbs. I truly could not have asked for a more incredible thesis advisor. Since the beginning of my time at Caltech, you have subtly guided me towards the water but never forced me to drink. You have given me independence in choosing which projects to pursue and the directions these projects go, but always provided suggestions and hints along the way that have kept me on track. I know you will continue to provide great advice and strong support even long after I've left Caltech. Thanks for being my invisible safety net over the last five years. I would have never even considered pursuing a Ph.D in chemistry in the first place if it weren't for the fantastic chemistry faculty at Macalester College. Rebecca Hoye, Ronald Brisbois, Paul Fischer, Keith Kuwata, Thomas Varberg and Katherine Splan, you were all tremendously influential in my life. You taught me how to see the exciting puzzles that are scattered throughout the field of chemistry.
    [Show full text]
  • Studies in Directed Catalytic Asymmetric Hydroboration of 1,2-Disubstituted Unsaturated Amide
    University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Student Research Projects, Dissertations, and Chemistry, Department of Theses - Chemistry Department Summer 7-2017 STUDIES IN DIRECTED CATALYTIC ASYMMETRIC HYDROBORATION OF 1,2-DISUBSTITUTED UNSATURATED AMIDE Shuyang Zhang University of Nebraska - Lincoln, [email protected] Follow this and additional works at: http://digitalcommons.unl.edu/chemistrydiss Part of the Organic Chemistry Commons Zhang, Shuyang, "STUDIES IN DIRECTED CATALYTIC ASYMMETRIC HYDROBORATION OF 1,2-DISUBSTITUTED UNSATURATED AMIDE" (2017). Student Research Projects, Dissertations, and Theses - Chemistry Department. 85. http://digitalcommons.unl.edu/chemistrydiss/85 This Article is brought to you for free and open access by the Chemistry, Department of at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Student Research Projects, Dissertations, and Theses - Chemistry Department by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. STUDIES IN DIRECTED CATALYTIC ASYMMETRIC HYDROBORATION OF 1,2- DISUBSTITUTED UNSATURATED AMIDE by Shuyang Zhang A THESIS Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillment of Requirements For the Degree of Master of Science Major: Chemistry Under the Supervision of Professor James M. Takacs Lincoln, Nebraska July 2017 DIRECTED CATALYTIC ASYMMETRIC HYDROBORATION OF 1,2- DISUBSTITUTED ALKENES Shuyang Zhang, M.S. University of Nebraska 2017 Advisor: Professor James M. Takacs The Rh-catalyzed, substrate directed catalytic asymmetric hydroboration of γ,δ-unsaturated amides provides a direct route to enantioenriched acyclic secondary γ- borylated carbonyl derivatives with high regio- and enantioselectivity. The catalytic condition optimization and substrate scope study is discussed, including the effects in catalytical asymmetric hydroboration on pre-installed chiral γ,δ-unsaturated amides.
    [Show full text]
  • Synthetic Applications of Organoboranes
    ú 7lt) f SYNTHETIC APPLICATIONS OF ORGANOBORANES A Thesis Presented for the Degree of Doctor of Philosophy in The Uníversity of Adelaide by Roger Murphy, B.Sc. (Hons.) Department of Organíc Chemistry L976. CONTENTS Page SUMMARY (f) STATEMENT (fií) PUBL ICATIONS (iv) ACKNOI^JLEDGEMENTS (v) CHAPTER 1. Synthesis of Products Isolated from the Hydroboration-Cyanidation of Unsaturated Terpenes. / 1.1 Introduction. 1 L.2 Synthesis of Products Derived from L2 Geraniol. 1.3 Synthesis of Products Derived from L7 LÍnalyl AceËate. L.4 SynthesÍs of Products Derived from 22 Myrcene. CHAPTER 2. Cyanidation of Dialkyìboranes and Borinic Acids and Esters. 2.L Introduction. 43 2.2 Cyanidation of Dialkylboranes. 50 2.3 Cyanidation of BorÍnic Acíds and EsËers. 65 CHAPTER 3. Silver(I) 0xidation of Organoboranes. 3.1 Introduction. 70 3.2 Cycl-izatlon of Díenes vía Intramolecular 76 Alkyl Coupling. 3.3 AÈtenpted Reduction of Intemedl-ates 84 Obtaíned by Reaction of Organoboranes with Alkalíne SÍ1ver nltrate. CHAPTER 4. Asymmetric Induction by Hydroboration with Optical ly Active Dial llyl boranes. 4.L Introductlon. 88 4.2 AËterpted Resolution of (t)-414,6- 96 Trfnethylcaprolactam and (t)-4 16 16- Tr lmethylcapro lactam. 4.3 Attempted Resolutíon of (1)-31515- 100 Trinethylcyclohexanone . 4.4 Asynrmetric Hydroboratfon of 6r7-Dihydro- 110 416 r6-trTmethyl-5H-azepínone and 3r5,5- TrirneËhylcyclohex-2-enone (Isophorone) . CHAPTER 5. Experimental. 5.1 General. 118 5.2 I^Iork described in chapter 1. L2T 5.3 Ilork described in chapter 2. 163 5.4 Work descríbed ín chapËer 3. 178 5.5 lJork described Ín chapter 4.
    [Show full text]
  • 10: Alkenes and Alkynes. Electrophilic and Concerted Addition Reactions
    (2/94)(8,9/96)(12/03)(1,2/04) Neuman Chapter 10 10: Alkenes and Alkynes. Electrophilic and Concerted Addition Reactions Preview 10-3 10.1 Addition Reactions 10-3 General Considerations (10.1A) 10-3 Ionic Addition Reactions (10.1B) 10-4 Electrophilic Addition Electrophiles and Nucleophiles Nucleophilic Additions Non-Ionic Addition Reactions (10.1C) 10-5 Radical Addition Concerted Addition Summary 10.2 Electrophilic Addition of H-X or X2 to Alkenes 10-6 Addition of H-X (10.2A) 10-6 Intermediate Carbocations Markovnikov's Rule Carbocation Rearrangements Stereochemistry Electrophilic Addition of Br2 (10.2B) 10-11 Mechanism Stereochemistry Electrophilic Addition of Other Molecular Halogens (10.2C) 10-12 Cl2 Addition F2 or I2 Addition Iodonium Ions are Possible Formation of Halohydrins (10.2D) 10-14 Mechanism Orientation 10.3 Addition of H-X and X2 to Alkynes 10-15 Addition of H-X (10.3A) 10-15 Addition of X2 (10.3B) 10-16 (continued) 1 (2/94)(8,9/96)(12/03)(1,2/04) Neuman Chapter 10 10.4 Alkenes to Alcohols by Electrophilic Addition 10-16 Acid Catalyzed Hydration of Alkenes (10.4A) 10-17 Mechanism Orientation of Addition Rearranged Products Oxymercuration-Demercuration (10.4B) 10-17 Overall Transformation Mechanism Hydration of Alkynes (10.4C) 10-19 10.5 Alkenes to Alcohols by Hydroboration 10-21 Hydroboration of Alkenes with BH3 (10.5A) 10-22 Overall Reaction Sequence Formation of the Organoborane Intermediate Concerted Addition Mechanism The BH3 Reagent Conversion of R3B to the Alcohol (R-OH) Hydroboration with RBH2 and R2BH Reagents (10.5B)
    [Show full text]