DOCSLIB.ORG

Nickel-Catalyzed Hydrosilylation of Alkenes and Transition-Metal-Free

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read 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. I would like to thank my apprentice, Sébastien Keller, for helping me with synthesis of many complexes and substrates for Chapter 3 and also for our conversations in French. Many thanks to Dr. Gerald Bauer and Lucinda Batchelor for the proof reading of this manuscript and help with the SNSF application. It was a big pleasure to work in such a nice atmosphere created by LSCI group members. I am thankful to Pablo M. Perez Garcia for taking care about me upon my arrival to the lab and for teaching me some important laboratory techniques. I want to express my gratitude to Dr. Fang Song for helping me with microscopy methods. I enjoyed sharing the lab with two awesome co-workers: Dr. Tao Xu and Dr. Chi Wai Cheung. I thank them for fruitful scientific discussions and pleasant working environment. I will never forget many enjoyable moments spent with Jan, Jésus, Thomas, Yeonji and Gerald in and outside the lab. Special thanks to Gerald for our unforgettable trips and sharing various activities. Finally, I am very thankful to my family for the encouragements I received during these years. I give my deepest thanks to my wife for her love and support. I Abstract Transition-metal-catalyzed hydrosilylation of olefins is one of the most important methods for the preparation of organosilicon compounds, which have broad applications in both synthetic and material chemistry. For decades, precious metals, principally platinum-based complexes, have been utilized as catalysts for olefin hydrosilylation. However, due to the high and volatile cost and low abundance of Pt, the development of active and selective catalysts based on Earth-abundant metals is highly desirable. In the first chapter, a short overview of state-of-the-art Pt catalysts and recent advances in development of Fe, Co and Ni-catalysts for olefin hydrosilylation is given. The applications, mechanisms and remaining challenges of transition-metal-catalyzed hydrosilylation are discussed. In the chapter 2, chemoselective anti-Markovnikov hydrosilylation of functionalized alkenes using well-defined bis(amino)amide nickel pincer complexes is described. The catalysts exhibit both high turnover frequencies and turnover numbers. Alkenes containing amino, ester, amido, ketone, and formyl groups are selectively hydrosilylated with Ph2SiH2. Chemoselective hydrosilylation of carbon-carbon double bond in the presence of formyl group using a base metal catalyst is reported for the first time. A modification of reaction conditions allows tandem isomerization-hydrosilylation reactions of internal alkenes to give terminal alkyl silanes. Hydrosilylation of alkenes with tertiary silanes is more attractive from practical point of view. The screening of various nickel alkoxide complexes with reduced steric bulk led us to discovery of an efficient heterogeneous catalyst for alkene hydrosilylation with commercially relevant tertiary silanes (chapter 3). The catalyst exhibits high activity in anti-Markovnikov hydrosilylation of unactivated terminal alkenes and isomerizing hydrosilylation of internal alkenes. The catalyst can be applied to synthesize a single terminal alkyl silane from a mixture of internal and terminal alkene isomers. Furthermore, the same catalyst can be used to remotely functionalize an internal alkene derived from a fatty acid. Chapter 4 describes a catalytic system composed of a nickel amido(bisoxazoline) complex and NaOtBu for an unexpected synthetic transformation, leading to the synthesis of functionalized alkyl hydrosilanes from readily available alkenes and alkoxysilanes. This method provides a convenient and safe alternative to hydrosilylation using flammmable and II potentially dangerous Me2SiH2, MeSiH3 and SiH4. The reaction mechanism was also described. Efficient and atom-economical creation of C-N bond is one of the major tasks in synthetic organic chemistry. Direct C-H amination has emerged as an attractive method for the construction of new C-N bonds. In the chapter 5 a new transition-metal free method for the intermolecular amination of the α-C-H bonds of ethers is described. Using a hypervalent iodine reagent as oxidant the amination of cyclic and acyclic alkyl ethers with a wide range of amides, imides, and amines was achieved. The utility of this method was demonstrated in the synthesis of Tegafur and its analogues. This transition-metal-free method provides a rapid access to a large number of nitrogen-containing organic molecules that may serve as useful synthetic intermediates or biologically active agents. Key words: hydrosilylation, olefins, silanes, nickel, pincer ligands, chemoselectivity, isomerization, nanoparticles, C-H amination, hypervalent iodine III Résumé La reaction d’hydrosilylation d'oléfines catalysée par les métaux de transition est l'une des méthodes en laboratoire et industrielle la plus importante pour la préparation de composés organosiliciés. Ces composés trouvent de vastes champs d'application en chimie synthétique et en chimie des matériaux. Pendant des décennies, les métaux précieux, principalement des complexes à base de platine, ont été utilisés comme catalyseurs pour l'hydrosilylation d'oléfines. Toutefois, en raison du coût élevé et fluctuant, et de la faible abondance en Pt, le développement de catalyseurs actifs et sélectifs à base de métaux abondant sur Terre est hautement souhaitable. Dans le premier chapitre, un bref aperçu de l'état de l’art des catalyseurs à base de Pt et les progrès récents dans le développement de catalyseurs à base de Fe, Co et Ni pour l'hydrosilylation d'oléfines est donné. Les applications, les mécanismes et les défis restants de hydrosilylation catalysée par les métaux de transition sont également discutés. Dans le chapitre 2, l'hydrosilylation chimiosélective anti-Markovnikov d'alcènes fonctionnalisés en utilisant des complexes pincer bis(amino)amide de nickel bien définis est décrite. Les catalyseurs montrent de hautes fréquences de rotation (TOF) et de hauts nombres de rotations (TON). Les alcènes contenant des groupes amino, ester, amido, cétone et formyle sont sélectivement hydrosilylés avec Ph2SiH2. L'hydrosilylation chimiosélective d'une double liaison carbone-carbone en présence d'un groupe formyle et en utilisant un catalyseur à base de métal non précieux est décrite pour la première fois. Une modification des conditions de réaction permet la réaction d'alcènes internes en tandem hydrosilylation-isomérisation pour donner les produits terminaux. L'hydrosilylation d'alcènes avec des silanes tertiaires ne contenant qu'une seule liaison Si- H est plus attrayante d'un point de vue pratique. La procédure de sélection de divers complexes d'alcoolate de nickel avec un encombrement stérique réduit nous a conduits à la découverte d'un catalyseur hétérogène efficace pour l'hydrosilylation d’alcène avec des silanes tertiaires commercialement utiles (chapitre 3). Le catalyseur montre une activité élevée pour l'hydrosilylation anti-Markovnikov des alcènes terminaux inactivés et l’isomérisation-hydrosilylation des alcènes internes. Le catalyseur peut être utilisé pour synthétiser un alkylsilane terminal à partir d'un mélange d'isomères d'alcènes internes et terminaux. En outre, le même catalyseur peut être utilisé pour fonctionnaliser à distance un alcène interne dérivé d'un acide gras. IV Le chapitre 4 décrit l'emploi d'un complexe amido(bisoxazoline) de nickel et d'une quantité catalytique de NaOtBu utilisés pour une transformation synthétique inhabituelle, ce qui conduit à la synthèse d'alkylhydrosilanes fonctionnalisés à partir d'alcènes et d'alcoxysilanes facilement disponibles. Cette méthode offre une alternative pratique et sans danger à l'hydrosilylation utilisant les composés inflammables et potentiellement dangereux Me2SiH2, MeSiH3 et SiH4. Le mécanisme réactionnel a été étudié. La création efficace et économique en atome d'une liaison C-N est l'une des principales tâches
Load more

Recommended publications
  • Studies Directed Towards the Stereoselective Total Synthesis of Miyakolide
    Studies Directed Towards the Stereoselective Total Synthesis of Miyakolide by Jinhua Song Submitted to the Department of Chemistry in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Organic Chemistry at the Massachusetts Institute of Technology February, 1999 @1999 Jinhua Song All rights Reserved The author hereby grants MIT permissions to reproduce and to distribute publicly paper and electronic copies of this thesis document in whole or in part. Signature of Author: Department of Chemistry September 25, 1998 Certified by: Professor Satoru Masamune A. C. Cope Professor of Chemistry Thesis Supervisor Accepted by:, ProfessotDietmar Seyferth, Chairman Departmental Committee on Graduate Students MASSACHUSETTS INSTITUTE OF TECHNOLOGY LrL J This doctoral thesis has been examined by a committee of the Department of Chemistry as follows: Professor Timothy M. Swager Chairman Professor Satoru Masamune Thesis Supervisor Professor Rick L. Danheiser , 2 Studies Directed Towards the Stereoselective Total Synthesis of Miyakolide by Jinhua Song Submitted to the Department of Chemistry on September 25, 1998, in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Organic Chemistry Abstract Presented are the stereoselective syntheses of the A (C18-C28), B (C14-C17), C (C6-C13), D (Cl-C5), C'D' (C1-C13) fragments and the efficient coupling of B and C'D' fragments of the marine natural product miyakolide, a 24-membered polyketide macrolide which exhibits anti-cancer activity. Fragment A was synthesized from the chiral aldehyde 4-4 through the successful application of the newly developed boron mediated anti-selective aldol methodology using the chiral ester 3-4.
    [Show full text]
  • The Synthesis and Applications of N-Alkenyl Aziridines
    The Synthesis and Applications of N-Alkenyl Aziridines by Nicholas A. Afagh A thesis submitted in conformity with the requirements for the degree of Master of Science Department of Chemistry University of Toronto © Copyright by Nicholas A. Afagh 2010 The Synthesis and Applications of N-Alkenyl Aziridines Nicholas A. Afagh Master of Science Department of Chemistry University of Toronto 2010 Abstract N-alkenyl aziridines are a unique class of molecules that do not behave as typical enamines as a result of the inability of the nitrogen atom lone-pair of electrons to delocalize. The attenuated nucleophilicity of these enamines presents opportunities for the selective functionalization and reactivity not available to classical enamines. An operationally simple and mild copper-mediated coupling has been developed that facilitates the preparation of a broad range of N-alkenyl aziridines not available through existing methods. The preparation and reactivity of highly- functionalized N-alkenyl aziridines are reported. Also reported is the application of the chemoselective amine/aldehyde/alkyne (A 3) multicomponent coupling involving amphoteric aziridine aldehydes as the aldehyde component. This coupling allows access to propargyl amines with pendent aziridine functionality. ii Acknowledgments First and foremost, I would like to thank my supervisor, Professor Andrei K. Yudin for his continuous support and encouragement over the past two years. His wealth of knowledge and profound insight into all matters chemistry made for many interesting discussions. In addition, I would like to thank all the members of the Yudin group past and present with whom I have had the distinct pleasure of working alongside and shared many late evenings.
    [Show full text]
  • Radical Approaches to Alangium and Mitragyna Alkaloids
    Radical Approaches to Alangium and Mitragyna Alkaloids A Thesis Submitted for a PhD University of York Department of Chemistry 2010 Matthew James Palframan Abstract The work presented in this thesis has focused on the development of novel and concise syntheses of Alangium and Mitragyna alkaloids, and especial approaches towards (±)-protoemetinol (a), which is a key precursor of a range of Alangium alkaloids such as psychotrine (b) and deoxytubulosine (c). The approaches include the use of a key radical cyclisation to form the tri-cyclic core. O O O N N N O O O H H H H H H O N NH N Protoemetinol OH HO a Psychotrine Deoxytubulosine b c Chapter 1 gives a general overview of radical chemistry and it focuses on the application of radical intermolecular and intramolecular reactions in synthesis. Consideration is given to the mediator of radical reactions from the classic organotin reagents, to more recently developed alternative hydrides. An overview of previous synthetic approaches to a range of Alangium and Mitragyna alkaloids is then explored. Chapter 2 follows on from previous work within our group, involving the use of phosphorus hydride radical addition reactions, to alkenes or dienes, followed by a subsequent Horner-Wadsworth-Emmons reaction. It was expected that the tri-cyclic core of the Alangium alkaloids could be prepared by cyclisation of a 1,7-diene, using a phosphorus hydride to afford the phosphonate or phosphonothioate, however this approach was unsuccessful and it highlighted some limitations of the methodology. Chapter 3 explores the radical and ionic chemistry of a range of silanes.
    [Show full text]
  • 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]
  • Properties of Silicon Hafensteiner
    Baran Lab Properties of Silicon Hafensteiner Si vs. C Siliconium Ion - Si is less electronegative than C - Not believed to exist in any reaction in solution - More facile nucleophilic addition at Si center J. Y. Corey, J. Am. Chem. Soc. 1975, 97, 3237 - Pentacoordinate Si compounds have been observed Average BDE (kcal/mol) MeSiF4 NEt4 Ph3SiF2 NR4 C–C C–Si Si–Si C–F Si–F 83 76 53 116 135 - Lack of cation justified by high rate of bimolecular reactivity at Si C–O Si–O C–H Si–H Mechanism of TMS Deprotection 86 108 83 76 OTMS O Average Bond Lengths (Å) C–C C–Si C–O Si–O 1.54 1.87 1.43 1.66 Workup Si Si Silicon forms weak p-Bonds O O F F NBu4 p - C–C = 65 kcal/mol p - C–Si = 36 kcal/mol Pentavalent Silicon Baran Lab Properties of Silicon Hafensteiner Nucleophilic addition to Si b-Silicon effect and Solvolysis F RO–SiMe3 RO F–SiMe3 SiMe3 Me H H vs. Me3C H Me3C H OSiMe O Li 3 H OCOCF H OCOCF MeLi 3 3 A B Me-SiMe3 12 kA / kB = 2.4 x 10 Duhamel et al. J. Org. Chem. 1996, 61, 2232 H H SiMe Me b-Silicon Effect 3 vs. Me3C H Me3C H - Silicon stabalizes b-carbocations H OCOCF3 H OCOCF3 - Stabalization is a result of hyperconjugation 4 kA / kB = 4 x 10 SiR3 CR3 Evidence for Stepwise mechanism vs. Me3Si SiMe2Ph SiMe2Ph A B Me3Si SiMe2Ph *A is more stable than B by 38 kcal/mol * Me3Si SiMe2Ph Me3Si Jorgensen, JACS, 1986,107, 1496 Product ratios are equal from either starting material suggesting common intermediate cation Baran Lab Properties of Silicon Hafensteiner Evidence for Rapid Nucleophilic Attack Extraordinary Metallation Me SiMe3 SiMe3 Li Si t-BuLi Me SnCl4 Cl Me3Si Cl Me2Si Cl SiMe MeO OMe 3 OMe OMe Me2Si Cl vs.
    [Show full text]
  • Syllabus CHEM 6352 2014
    CHEM 6352 Organic Reactions & Synthesis Fall 2014 Jeremy A. May Office: 5025 SERC Office hours: T/Th 10-11 am or by appointment (email me) Email: [email protected] Website: http://mynsm.uh.edu/groups/maygroup/wiki/b24dc/Classes.html Lectures: 154 Fleming Tuesdays and Thursdays 8:30–10:00. August 26–December 6, 2014. Homework Session Saturdays 3:00 pm to 5:30 pm in Fleming 154/160/162. No class November 27–29, 2014 (Thanksgiving recess); Oct. 31st is last day to withdraw Optional Texts (on reserve at MD Anderson Library) Zweifel, G.; Nantz, M. “Modern Organic Synthesis: An Introduction” March, J. “Advanced Organic Chemistry” Corey, E. J.; Cheng, X.-M. “The Logic of Chemical Synthesis” Warren, S. “Designing Organic Syntheses: A Programmed Introduction to the Synthon Approach” Kürti, L.; Czakó, B. “Strategic Applications of Named Reactions in Organic Synthesis” Grossman, R. “The Art of Writing Reasonable Organic Reaction Mechanisms” Model Sets: Students are strongly encouraged to purchase at least one set. HGS biochemistry molecular model sets are recommended and are available at Research Stores in the Old Science Building. Other relevant texts and references: Greene; Wuts. “Protective Groups in Organic Synthesis” Nicolaou, K.C.; Sorensen, E. “Classics in Total Synthesis” Nicolaou, K.C.; Snyder, S. “Classics in Total Synthesis II” Larock, R. C. "Comprehensive Organic Transformations" Hartwig, J. “Organotransition Metal Chemistry: From Bonding to Catalysis” Tsuji, J. “Palladium Reagents and Catalysts” Hegedus, L. “Transition Metals in the Synthesis of Complex Organic Molecules” Problem Sets: Problem Sets will be distributed on Tuesdays (or before) and are due by the next Saturday at the Homework Session.
    [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]
  • 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]
  • Organic & Biomolecular Chemistry
    Organic & Biomolecular Chemistry View Article Online PAPER View Journal | View Issue Diastereoselective synthesis of trisubstituted olefins using a silicon-tether ring-closing Cite this: Org. Biomol. Chem., 2020, 18, 2297 metathesis strategy† Stéphane Wittmann,‡ Alexander F. Tiniakos and Joëlle Prunet * The diastereoselective synthesis of trisubstituted olefins with concomitant C–C bond formation is still adifficult challenge, and olefin metathesis reactions for the formation of such alkenes are usually not high yielding or/and diastereoselective. Herein we report an efficient and diastereoselective synthesis of trisubstituted olefins flanked by an allylic alcohol, by a silicon-tether ring-closing metathesis strategy. Both E-andZ-trisubstituted alkenes were synthesised, depending on the method employed Received 30th November 2019, to cleave the silicon tether. Furthermore, this methodology features a novel Peterson olefination for Accepted 4th March 2020 the synthesis of allyldimethylsilanes. These versatile intermediates were also converted into the DOI: 10.1039/c9ob02563d corresponding allylchlorodimethylsilanes, which are not easily accessible in high yields by other Creative Commons Attribution 3.0 Unported Licence. rsc.li/obc methods. Introduction However, there are much fewer examples of RCM reactions with O–Si–C tethers. The reported formations of trisubstituted The trisubstituted E olefin motif with a methyl substituent is olefins from allyl silanes lead to bicyclic products,8 and the present in numerous polyketide natural products. Among others focus on vinyl silanes.9 We propose a strategy for an these, callipeltoside A1 and dolabelide C2 possess another efficient and diastereoselective synthesis of trisubstituted This article is licensed under a common feature: an allylic alkoxy group on the lone substitu- olefins flanked by an allylic alcohol, which involves a RCM ent of the trisusbstituted olefin (highlighted in red in reaction with a O–Si–C tether.
    [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]
  • Convergent Total Synthesis and Preliminary Biological Investigations
    Norrislide: Convergent Total Synthesis and Preliminary Biological Investigations Author: Krista Elizabeth Granger Persistent link: http://hdl.handle.net/2345/731 This work is posted on eScholarship@BC, Boston College University Libraries. Boston College Electronic Thesis or Dissertation, 2009 Copyright is held by the author, with all rights reserved, unless otherwise noted. Boston College The Graduate School of Arts and Sciences Department of Chemistry NORRISOLIDE: CONVERGENT TOTAL SYNTHESIS AND PRELIMINARY BIOLOGICAL INVESTIGATIONS a dissertation by KRISTA ELIZABETH GRANGER submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy August 2009 © copyright by KRISTA ELIZABETH GRANGER 2009 Norrisolide: Convergent Total Synthesis and Preliminary Biological Investigations Krista Elizabeth Granger Thesis Advisor: Professor Marc L. Snapper Abstract • Chapter 1: A review of Shapiro reactions as a coupling strategy in natural product total synthesis. The syntheses of lycoramine, galanthamine, yuehchukene analogues, ovalicin, studies toward the ingenol core, haemanthidine, pretazettine, tazettine, crinamine, Taxol, colombiasin A, elisapterosin B, the AB ring fragment of spongistatin 1 and 8-epipuupewhedione are discussed. Ar O S O nBuLi Li E+ E NH R' R' N R R R' R • Chapter 2: The convergent total synthesis of the marine natural product norrisolide is described. Both subunits, the hydrindane core and the norrisane side chain, are prepared in an asymmetric fashion through kinetic resolution and enantioselective cyclopropanation, respectively. A Shapiro reaction couples the two fragments and a Peterson olefination installs the 1,1-disubstituted olefin. O O MeO OTBS AcO MeO O O O O N Me Me Me MeO O O Me Li O OP H H Me Me Me Me norrisolide H Me Me • Chapter 3: Preliminary experiments to isolate the biological target of norrisolide through reductive alkylation and tritium labeling are investigated.
    [Show full text]
  • Science Fair Project
    OrganicOrganic ChemistryChemistry ofof LowLow--CoordinateCoordinate PhosphorusPhosphorus CompoundsCompounds Tom Hsieh University of Toronto Organic and Biological Seminar November 12, 2007 I.I. Background:Background: MakingMaking BondsBonds AnalogousAnalogous toto CC--CC DoubleDouble BondsBonds 2 BreakingBreaking thethe ““DoubleDouble BondBond RuleRule”” Generally held belief: elements outside the first row do not form multiple bonds Phosphaalkene chemistry deals with 3p-2p (P=C) π-bonds!! 3 CarbonCarbon--SiliconSilicon MultipleMultiple BondsBonds 1981: West discovered Si=Si double bond C N Si P 1981: Brook discovered Si=C double bond West, Fink, Michl. Science. 1981, 214, 4527. Brook, Abdesaken, Gutekunst, Gutekunst, Kallury. J. Chem. Soc., Chem. Commun. 1981, 191. 4 CarbonCarbon--NitrogenNitrogen MultipleMultiple BondsBonds C-N bonds are ubiquitous C N Si P C=N and C=C double bonds are stable Reactivity requires either: high-lying HOMOs accessible, low-lying LUMOs π-bonds, strained rings, electron deficient species, etc. 5 UltravioletUltraviolet PhotoelectronPhotoelectron SpectroscopySpectroscopy (UPS)(UPS) UPS determines molecular energy levels in the valence region Helium discharge lamp is used as the photon source Measures the kinetic energy spectra of electrons emitted by UV photons 6 UltravioletUltraviolet PhotoelectronPhotoelectron SpectroscopySpectroscopy (UPS)(UPS) Each of the peaks in the spectrum corresponds to the - 10.30 MO energy level - 10.70 (in eV) of one valence-region He (eV) 7 MethanimineMethanimine vs.vs. EthyleneEthylene UV photoelectron spectroscopic measurements C N Si P HOMO of methanimine is the lone pair π-bond lies much lower in energy Consequently, methanimine usually reacts through its lone pair before through its π-bond Lacombe, Gonbeau, Cabioch, Pellerin, Denis, Pfister-Guillouzo. J. Am. Chem. Soc.
    [Show full text]