DOCSLIB.ORG

University of Groningen Alkaline Earth Organometallic Compounds In

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
University of Groningen Alkaline Earth Organometallic Compounds In University of Groningen Alkaline earth organometallic compounds in homogeneous catalysis Penafiel, Johanne IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2016 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Penafiel, J. (2016). Alkaline earth organometallic compounds in homogeneous catalysis: Synthesis, characterization and catalytic activity of calcium and magnesium complexes. Rijksuniversiteit Groningen. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license. More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne- amendment. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 10-10-2021 Alkaline earth organometallic compounds in homogeneous catalysis Synthesis, characterization and catalytic activity of calcium and magnesium complexes Proefschrift ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen op gezag van de rector magnificus prof. dr. E. Sterken en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op maandag 22 februari 2016 om 11.00 uur door Johanne Penafiel geboren op 16 september 1985 te San Isidro, Lima, Peru Promotor Prof. dr. S. Harder Beoordelingscommissie Prof. dr. A. J. Minnaard Prof. dr. J. G. de Vries Prof. dr. R. Dorta A ma famille, Catherine, Robert et Nicolas. The work described in this thesis was performed at the Stratingh Institute for Chemistry, University of Groningen, The Netherlands and at the Department of Chemistry and Pharmacy, Friedrich-Alexander University Erlangen-Nürnberg, Germany. The work was financially supported by the Dutch National Research School Combination Catalysis Controlled by Chemical Design (NRSC-Catalysis). Cover design : Catherine, Robert and Johanne Penafiel Printed by : Ipskamp Drukkers, Enschede, The Netherlands ISBN: 978-90-367-8499-3 (printed version) ISBN: 978-90-367-8498-6 (digital version) Contents The organometallic chemistry of alkaline earth metals ........................................................ 1 1.1 Alkaline earth metals ......................................................................................................................................... 2 1.1.1 The essentials ............................................................................................................................................... 2 1.1.2 Similarities between magnesium and zinc ..................................................................................................... 3 1.1.3 Grignard reagents ......................................................................................................................................... 4 1.1.4 The Schlenk equilibrium ................................................................................................................................ 5 1.2 Synthesis of alkaline earth metal organometallic compounds ........................................................................... 6 1.2.1 Post-Grignard reagents ................................................................................................................................. 6 1.2.2 Organoelimination ......................................................................................................................................... 6 1.2.3 Transamination.............................................................................................................................................. 7 1.2.4 Salt metathesis .............................................................................................................................................. 7 1.2.5 Direct metallation ........................................................................................................................................... 8 1.2.6 Redox transmetallation .................................................................................................................................. 8 1.2.7 Metal exchange ............................................................................................................................................. 9 1.3 Alkaline earth metal organometallic compounds in homogeneous catalysis ..................................................... 9 1.3.1 Hydroamination (C−N bond formation) ....................................................................................................... 10 1.3.2 Hydrophosphination (C−P bond formation) ................................................................................................. 11 1.3.3 Hydrosilylation (C−Si bond formation) ........................................................................................................ 12 1.3.4 Hydroboration (B−N and B−O bond formation) .......................................................................................... 12 1.3.5 Hydrogenation (C−H bond formation) ......................................................................................................... 12 1.3.6 Polymerization ............................................................................................................................................. 13 1.3.7 C−C bond formation and miscellaneous reactions ..................................................................................... 14 1.4 Outline of the thesis ......................................................................................................................................... 14 1.5 References ...................................................................................................................................................... 15 Alkaline earth metal complexes in asymmetric catalysis ..................................................21 2.1 Introduction ...................................................................................................................................................... 22 2.1.1 Chiral compounds ....................................................................................................................................... 22 2.1.2 Alkaline earth metals in asymmetric catalysis ............................................................................................. 24 2.1.3 Chiral ligands in asymmetric catalysis ......................................................................................................... 30 2.2 Aim of the project ............................................................................................................................................. 32 2.3 Results and discussion .................................................................................................................................... 33 2.3.1 Phosphoramidites ........................................................................................................................................ 33 2.3.2 Secondary Phosphine Oxides ..................................................................................................................... 40 2.4 Conclusions ..................................................................................................................................................... 44 2.5 Experimental section ....................................................................................................................................... 45 2.5.1 General ....................................................................................................................................................... 45 2.5.2 General procedure for complex synthesis ................................................................................................... 51 2.5.3 Intramolecular hydroamination of aminoalkenes ......................................................................................... 52 2.5.4 Single-crystal X-ray structure determination ................................................................................................ 52 2.6 References ...................................................................................................................................................... 53 Magnesium complexes in carbon dioxide activation .........................................................57 3.1 Introduction ...................................................................................................................................................... 58 3.1.1 Global warming and climate change ........................................................................................................... 58 3.1.2 Different strategies for CO2 transformation.................................................................................................
Load more

Recommended publications
  • Part I: Carbonyl-Olefin Metathesis of Norbornene
    Part I: Carbonyl-Olefin Metathesis of Norbornene Part II: Cyclopropenimine-Catalyzed Asymmetric Michael Reactions Zara Maxine Seibel Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2016 1 © 2016 Zara Maxine Seibel All Rights Reserved 2 ABSTRACT Part I: Carbonyl-Olefin Metathesis of Norbornene Part II: Cyclopropenimine-Catalyzed Asymmetric Michael Reactions Zara Maxine Seibel This thesis details progress towards the development of an organocatalytic carbonyl- olefin metathesis of norbornene. This transformation has not previously been done catalytically and has not been done in practical manner with stepwise or stoichiometric processes. Building on the previous work of the Lambert lab on the metathesis of cyclopropene and an aldehyde using a hydrazine catalyst, this work discusses efforts to expand to the less stained norbornene. Computational and experimental studies on the catalytic cycle are discussed, including detailed experimental work on how various factors affect the difficult cycloreversion step. The second portion of this thesis details the use of chiral cyclopropenimine bases as catalysts for asymmetric Michael reactions. The Lambert lab has previously developed chiral cyclopropenimine bases for glycine imine nucleophiles. The scope of these catalysts was expanded to include glycine imine derivatives in which the nitrogen atom was replaced with a carbon atom, and to include imines derived from other amino acids. i Table of Contents List of Abbreviations…………………………………………………………………………..iv Part I: Carbonyl-Olefin Metathesis…………………………………………………………… 1 Chapter 1 – Metathesis Reactions of Double Bonds………………………………………….. 1 Introduction………………………………………………………………………………. 1 Olefin Metathesis………………………………………………………………………… 2 Wittig Reaction…………………………………………………………………………... 6 Tebbe Olefination………………………………………………………………………... 9 Carbonyl-Olefin Metathesis…………………………………………………………….
    [Show full text]
  • Chem 353: Grignard
    GRIG.1 ORGANIC SYNTHESIS: BENZOIC ACID VIA A GRIGNARD REACTION TECHNIQUES REQUIRED : Reflux with addition apparatus, rotary evaporation OTHER DOCUMENTS Experimental procedure, product spectra INTRODUCTION In this experiment you will synthesise benzoic acid using bromobenzene to prepare a Grignard reagent, which is then reacted with carbon dioxide, worked-up and purified to give the acid. This sequence serves to illustrate some important concepts of practical synthetic organic chemistry : preparing and working with air and moisture sensitive reagents, the "work-up", extractions, apparatus set-up, etc. The synthesis utilises one of the most important type of reagents discussed in introductory organic chemistry, organometallic reagents. In this reaction, the Grignard reagent (an organomagnesium compound), phenylmagnesium bromide is prepared by reaction of bromobenzene with magnesium metal in diethyl ether (the solvent). The Grignard reagent will then be converted to benzoic acid via the reaction of the Grignard reagent with excess dry ice (solid CO2) followed by a "work-up" using dilute aqueous acid : The aryl (or alkyl) group of the Grignard reagent behaves as if it has the characteristics of a carbanion so it is a source of nucleophilic carbon. It is reasonable to represent the structure of the - + Grignard reagent as a partly ionic compound, R ....MgX. This partially-bonded carbanion is a very strong base and will react with acids (HA) to give an alkane: RH + MgAX RMgX + HA Any compound with suitably acidic hydrogens will readily donate a proton to destroy the reagent. Water, alcohols, terminal acetylenes, phenols and carboxylic acids are just some of the functional groups that are sufficiently acidic to bring about this reaction which is usually an unwanted side reaction that destroys the Grignard reagent.
    [Show full text]
  • Grignard Reaction: Synthesis of Triphenylmethanol
    *NOTE: Grignard reactions are very moisture sensitive, so all the glassware in the reaction (excluding the work-up) should be dried in an oven with a temperature of > 100oC overnight. The following items require oven drying. They should be placed in a 150mL beaker, all labeled with a permanent marker. 1. 5mL conical vial (AKA: Distillation receiver). 2. Magnetic spin vane. 3. Claisen head. 4. Three Pasteur pipettes. 5. Two 1-dram vials (Caps EXCLUDED). 6. One 2-dram vial (Caps EXCLUDED). 7. Glass stirring rod 8. Adaptor (19/22.14/20) Grignard Reaction: Synthesis of Triphenylmethanol Pre-Lab: In the “equations” section, besides the main equations, also: 1) draw the equation for the production of the byproduct, Biphenyl. 2) what other byproduct might occur in the reaction? Why? In the “observation” section, draw data tables in the corresponding places, each with 2 columns -- one for “prediction” (by answering the following questions) and one for actual drops or observation. 1) How many drops of bromobenzene should you add? 2) How many drops of ether will you add to flask 2? 3) 100 µL is approximately how many drops? 4) What are the four signs of a chemical reaction? (Think back to Chem. 110) 5) How do the signs of a chemical reaction apply to this lab? The Grignard reaction is a useful synthetic procedure for forming new carbon- carbon bonds. This organometallic chemical reaction involves alkyl- or aryl-magnesium halides, known as Grignard 1 reagents. Grignard reagents are formed via the action of an alkyl or aryl halide on magnesium metal.
    [Show full text]
  • Grignard Reagents and Silanes
    GRIGNARD REAGENTS AND SILANES By B. Arkles REPRINTED FROM HANDBOOK OF GRIGNARD REAGENTS by G. Silverman and P. Rakita Pages 667-675 Marcel Dekker, 1996 Gelest, Inc. 612 William Leigh Drive Tullytown, Pa. 19007-6308 Phone: [215] 547-1015 Fax: [215] 547-2484 Grignard Reagents and Silanes 32 Grignard Reagents and Silanes BARRY ARKLES Gelest Inc., Tullytown, Pennsylvania I. INTRODUCTION This review considers two aspects of the interaction of Grignards with silanes. First, focusing on technologies that are still viable within the context of current organosilane and silicone technology, guidelines are provided for silicon-carbon bond formation using Grignard chemistry. Second, the use of silane-blocking agents and their stability in the presence of Grignard reagents employed in organic synthesis is discussed. II. FORMATION OF THE SILICON-CARBON BOND A. Background The genesis of current silane and silicone technology traces back to the Grignard reaction. The first practical synthesis of organosilanes was accomplished by F. Stanley Kipping in 1904 by the Grignard reaction for the formation of the silicon-carbon bond [1]. In an effort totaling 57 papers, he created the basis of modern organosilane chemistry. The development of silicones by Frank Hyde at Corning was based on the hydrolysis of Grignard-derived organosilanes [2]. Dow Corning, the largest manufacturer of silanes and silicones, was formed as a joint venture between Corning Glass, which had silicone product technology, and Dow, which had magnesium and Grignard technology, during World War II. In excess of 10,000 silicon compounds have been synthesized by Grignard reactions. Ironically, despite the versatility of Grignard chemistry for the formation of silicon-carbon bonds, its use in current silane and silicone technology has been supplanted by more efficient and selective processes for the formation of the silicon-carbon bond, notably by the direct process and hydrosilylation reactions.
    [Show full text]
  • University of Oklahoma Graduate College
    UNIVERSITY OF OKLAHOMA GRADUATE COLLEGE SYNTHESIS OF NITROGEN HETEROCYCLES VIA TRANSITION METAL CATALYZED REDUCTIVE CYCLIZATIONS OF NITROAROMATICS A Dissertation SUBMITTED TO THE GRADUATE FACULTY in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY By David K. O Dell Norman, Oklahoma 2003 UMI Number: 3109054 INFORMATION TO USERS The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleed-through, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. UMI UMI Microform 3109054 Copyright 2004 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, Ml 48106-1346 Copyright DAVID K. O DELL 2003 Ail Rights Reserved SYNTHESIS OF NITROGEN HETEROCYCLES VIA TRANSITION METAL CATALYZED REDUCTIVE CYCLIZATIONS OF NITROAROMATICS A Dissertation APPROVED FOR THE DEPARTMENT OF CHEMISTRY AND BIOCHEMISTRY BY Kenneth M. Nicholas, chair Ronald L. Halterman I/- Vadim A. Soloshonok Richm-d W. Taylor I Michael H. Engel ACKNOWLEDGEMENTS I would like to thank my wife Sijy for her unwavering support and affection. I would also like to thank my parents John O'Dell and Marlene Steele, my deceased step­ parents Jim Steele and Laurie O'Dell, all for never discouraging my curiosity as a child.
    [Show full text]
  • 9 Mechs-115.Cdx
    from "Master Organic Chemistry" masterorganicchemistry.wordpress.com Nine Key Mechanisms In Carbonyl Chemistry Version 1.1 Sept 2012 copyright 2012 James A. Ashenhurst [email protected] Mechanism Description Promoted by Hindered by Examples Addition Anything that makes the carbonyl carbon a better electrophile 1) Anything that makes the carbonyl carbon Grignard reaction Attack of a nucleophile at the (more electron-poor) a poorer electrophile (more electron-rich) [sometimes "[1,2] addition"] Imine formation carbonyl carbon, breaking the 2) Sterically bulky substituents next to the carbonyl Fischer esterification Electron withdrawing groups on carbon C–O π bond. α X-groups that are strong -donors (e.g. amino, hydroxy, Aldol reaction O Electron-withdrawing X groups that are poor -donors (e.g. Cl, Br, π O Nu π alkoxy) Acetal formation I, etc.) Claisen condensation Cα X Cα X Addition of acid (protonates carbonyl oxygen, making carbonyl Sterics: X=H (fastest) > 1° alkyl > 2° alkyl > 3° alkyl (most hindered, slowest) Nu carbon more electrophilic. Note: acid must be compatible with nucleophile;alcohols are OK, X=Cl (poorest π-donor, fastest addition) > OAc > OR > NH2/NHR/NR2 strongly basic nucleophiles (e.g. Grignards) are not. (best π donor, slowest rate) Elimination The better the leaving group X, the faster the reaction will be. The [sometimes "[1,2] elimination"] Lone pair on carbonyl oxygen comes down to carbonyl carbon, rate follows pKa very well. Acid can turn poor leaving groups Fischer esterification X groups that are strong bases are poor leaving groups. forming new π-bond and displacing (NR2, OH) into good leaving groups (HNR2, H2O) Formation of amides by Alkyl groups and hydrogens never leave.
    [Show full text]
  • Modeling of Transition State in Grignard Reaction of Rigid N- (Aryl)Imino-Acenapthenone (Ar-BIAO): an Experimental and Computational Approach
    Modeling of Transition State in Grignard Reaction of Rigid N- (Aryl)imino-Acenapthenone (Ar-BIAO): An Experimental and Computational Approach A Project Report Submitted to the Department of Chemistry Indian Institute of Technology, Hyderabad As part of the requirements for the degree of Master of Science By Sayak Das Gupta Roll No: CY12M1017 Under the supervision of Dr. Tarun K. Panda DEPARTMENT OF CHEMISTRY INDIAN INSTITUTE OF TECHNOLOGY, HYDERABAD April, 2014 Approval Sheet This thesis entitled “Modeling of Transition State in Grignard Reaction of Rigid N- (Aryl)imino-Acenapthenone (Ar-BIAO): An Experimental and Computational Approach” by Sayak Das Gupta is approved for the degree of Master of Science from IIT Hyderabad. Name and affiliation- Examiner Name and affiliation- Examiner Name and affiliation- Adviser Name and affiliation- Co-Adviser Name and affiliation- Chairman 3 Acknowledgements The completion of my M.Sc. project would not have been possible without the kind support and help of many individuals. I would like to extend my sincere thanks to all of them. I express my deep sense of gratitude to my thesis supervisor Dr. Tarun K. Panda who guided me in my every possible aspect of my project from the very beginning and played a pivotal role in suggesting and helping me to develop ideas for this project. He has been a constant source of moral support and encouragement, especially during the difficult times. I would like to thank him once again for being patient with me while clearing all my doubts. Thank you Sir. I would like express my sincere thanks to Dr.
    [Show full text]
  • Grignard Synthesis of Triphenylmethanol Reactions That Form Carbon-Carbon Bonds Are Among the Most Useful to the Synthetic Organic Chemist
    1 Experiment 12: Grignard Synthesis of Triphenylmethanol Reactions that form carbon-carbon bonds are among the most useful to the synthetic organic chemist. In 1912, Victor Grignard received the Nobel prize in chemistry for his discovery of a new series of reactions that result in the formation of a carbon-carbon bond. A Grignard synthesis first involves the preparation of an organomagnesium reagent via the reaction of an alkyl bromide with magnesium metal: δ– δ+ R Br + Mg R MgBr The resulting “Grignard reagent” acts as both a good nucleophile and a strong base. Its nucleophilic character allows it to react with the electrophilic carbon in a carbonyl group, thus forming the carbon-carbon bond. Its basic property means that it will react with acidic compounds, such as carboxylic acids, phenols, thiols and even alcohols and water; therefore, reaction conditions must be free from acids and strictly anhydrous. Grignard reagents will also react with oxygen to form hydroperoxides, thus they are highly unstable when exposed to the atmosphere and are generally not isolated from solution. For a variety of reasons, anhydrous diethyl ether is the solvent of choice for carrying out a Grignard synthesis. Vapors from the highly volatile solvent help to prevent oxygen from reaching the reaction solution. In addition, evidence suggests that the ether molecules actually coordinate with and help stabilize the Grignard reagent: Et Et O R Mg Br O Et Et The magnesium metal used in the synthesis contains a layer of oxide on the surface that prevents it from reacting with the alkyl bromide. The pieces of metal must be gently scratched while in the ether solution to expose fresh surface area so that the reaction can commence.
    [Show full text]
  • The Effects of Stoichiometry and Starting Material on the Product Identity and Yield in Grignard Addition Reactions
    Supplementary information for Comprehensive Organic Chemistry Experiments for the Laboratory Classroom © The Royal Society of Chemistry 2017 The effects of stoichiometry and starting material on the product identity and yield in Grignard addition reactions Supplementary Material This experiment has been performed both in the 150 person standard introductory organic chemistry laboratory (taught primarily by undergraduate teaching assistants in five sections of 30-40 students) and in a special introductory organic chemistry laboratory for freshman, taught to 23 students in sections of 7 and 16. This course is the first organic laboratory for these students but has been taught in the spring semester along with the second semester of organic lecture. The lab periods for this course are five hours long, and this experiment is typically performed in the latter half of the semester. This experiment is used to illustrate to students the importance of planning their time in lab; they must be out of the lab in the 5 hours allotted. While many students finish the experiment in this time, others plan to finish the following week along with a shorter experiment. Those who were running behind were encouraged to finish through the drying of their organic layer with MgSO4 and set up the distillation the following week. When doing this they should make sure that their organic layer is in a closed container to prevent evaporation of their product. Moisture Sensitive Conditions There are many diverse protocols for maintaining the anhydrous conditions required to successfully prepare and utilize Grignard reagents. We typically open a fresh can of anhydrous ether and dispense it directly, without additional drying in a still or air sensitive techniques for solvent transfers.
    [Show full text]
  • Grignard-Type Arylation of Aldehydes Using Unactivated Aryl Iodides in Water
    ARTICLE Received 27 Jan 2014 | Accepted 27 May 2014 | Published 26 Jun 2014 DOI: 10.1038/ncomms5254 The Barbier–Grignard-type arylation of aldehydes using unactivated aryl iodides in water Feng Zhou1 & Chao-Jun Li1 Carbon–carbon bond formation is the essence of organic synthesis. One of the most important methods for forming carbon–carbon bonds is the Barbier–Grignard-type reaction, which was discovered over a century ago. However, it is still highly desirable to further improve this process. In this article, we describe a Barbier–Grignard-type direct arylation of aldehydes by using unactivated iodides mediated by zinc and catalysed by rhodium in water. This method bypasses a number of challenges encountered by the conventional Barbier– Grignard reaction, such as strict exclusion of moisture and air, protection–deprotection of various acidic hydrogens in the substrates, and so forth. It thereby creates a safer, more convenient and more environmentally benign strategy to access the diarylmethanols and aryl alkyl alcohols, ubiquitous skeletons found in fine chemicals, biologically active molecules and pharmaceuticals. Importantly, the same reaction performed in an organic solvent proceeded sluggishly to give much inferior yields. 1 Department of Chemistry and FQRNT Center for Green Chemistry and Catalysis, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 0B8. Correspondence and requests for materials should be addressed to C.-J.L. (email: [email protected]). NATURE COMMUNICATIONS | 5:4254 | DOI: 10.1038/ncomms5254
    [Show full text]
  • Gram-Scale Preparation of Negative-Type Liquid Crystals with a CF2CF2-Carbocycle Unit Via an Improved Short-Step Synthetic Protocol
    Gram-scale preparation of negative-type liquid crystals with a CF2CF2-carbocycle unit via an improved short-step synthetic protocol Tatsuya Kumon, Shohei Hashishita, Takumi Kida, Shigeyuki Yamada, Takashi Ishihara and Tsutomu Konno* Full Research Paper Open Access Address: Beilstein J. Org. Chem. 2018, 14, 148–154. Faculty of Molecular Chemistry and Engineering, Kyoto Institute of doi:10.3762/bjoc.14.10 Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan Received: 26 October 2017 Email: Accepted: 05 December 2017 Tsutomu Konno* - [email protected] Published: 15 January 2018 * Corresponding author This article is part of the Thematic Series "Organo-fluorine chemistry IV". Keywords: Guest Editor: D. O'Hagan gram-scale preparation; liquid crystals; short-step preparation; tetrafluorinated cyclohexadiene; tetrafluorinated cyclohexane © 2018 Kumon et al.; licensee Beilstein-Institut. License and terms: see end of document. Abstract Herein, we demonstrate an improved short-step protocol for the synthesis of multicyclic molecules having a CF2CF2-containing cyclohexadiene or cyclohexane framework in a mesogenic structure. These molecules are promising candidates for vertical align- ment (VA)-mode liquid crystal (LC) display devices owing to their large negative dielectric constant. The tetrafluorinated multi- cyclic molecules were successfully obtained in only five or six reaction steps without the need for special handling techniques, as is generally required for thermally unstable organometallic species, representing a reduction of three reaction steps. The improved short-step synthetic protocol was also amenable to the multigram preparation of these promising molecules, which may contribute significantly to the development of novel negative-type LC molecules containing CF2CF2 carbocycles. Introduction Fluorine-containing organic compounds have attracted much efficient synthetic protocols for fluorine-containing organic attention in various areas, such as the medicinal, agrochemical, compounds.
    [Show full text]
  • Y Isoph Nicole S
    USOO8664386B2 (12) United States Patent (10) Patent No.: US 8,664,386 B2 Colby et al. (45) Date of Patent: Mar. 4, 2014 (54) METHODS FOR PREPARING ANTI-VIRAL (57) ABSTRACT NUCLEOTIDE ANALOGS Methods for isolating 9-((R)-2-((S)-(S)-1-(isopropoxy carbonyl)ethylamino)phenoxyphosphinyl)methoxy (71) Applicant: Gilead Sciences, Inc., Foster City, CA propyladenine (compound 16): (US) 16 (72) Inventors: Denise A. Colby, San Francisco, CA (US); Andrew Anthony Martins, NH2 Edmonton (CA); Benjamin James Roberts, San Mateo, CA (US); Robert N N William Scott, San Mateo, CA (US); y isoph Nicole S. White, San Mateo, CA (US) N1, SS f (73) Assignee: Gilead Sciences, Inc., Foster City, CA (US) 2. s (*) Notice: Subject to any disclaimer, the term of this a method for preparing, in high diastereomeric purity, inter patent is extended or adjusted under 35 mediate compounds 13 and 15: U.S.C. 154(b) by 0 days. 13 (21) Appl. No.: 13/573,666 NH (22) Filed: Oct. 3, 2012 N1S-N (65) Prior Publication Data se y \ US 2013/0090473 A1 Apr. 11, 2013 Related U.S. Application Data 15 (60) Provisional application No. 61/544.950, filed on Oct. 7, 2011. (51) Int. Cl. C07F 9/06 (2006.01) (52) U.S. Cl. USPC ........................................... 544/244; 544/242 (58) Field of Classification Search USPC .......................................... 544/242, 243, 244 and a method for preparing intermediate compound 12: See application file for complete search history. 12 (56) References Cited NH2 U.S. PATENT DOCUMENTS N1S-N 7,390,791 B2 6, 2008 Becker et al.
    [Show full text]