DOCSLIB.ORG

2 Metal-Catalyzed Borylation of Alkanes and Arenes Via C–H Activation for Synthesis of Boronic Esters

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
2 Metal-Catalyzed Borylation of Alkanes and Arenes Via C–H Activation for Synthesis of Boronic Esters 2 Metal-catalyzed Borylation of Alkanes and Arenes via C–H Activation for Synthesis of Boronic Esters Tatsuo Ishiyama and Norio Miyaura 2.1 Introduction Organoboron derivatives are an important class of compounds that have been uti- lized as synthetic intermediates [1–6], functional molecules [7–9], functional poly- mers [10], 10B carriers for neutron capture therapy [11], and biologically active agents [12]. A traditional method for their synthesis is the alkylation of trialkylborates or haloboranes with organomagnesium or -lithium reagents (transmetalation) [1, 13] or addition of hydroboranes to unsaturated hydrocarbons (hydroboration) [1, 14]. Al- though these methods are now common for large-scale preparations of organoboron compounds, catalyzed reactions are an interesting strategy for obtaining chemo-, re- gio-, and stereoselectivities that differ from those achieved by uncatalyzed reactions. For example, catalyzed hydroboration of alkenes and alkynes [15] with catecholborane (HBcat, cat = O2C6H4) or pinacolborane (HBpin, pin = Me4C2O2) has provided a method for asymmetric hydroboration of alkenes with chiral phosphine-rhodium cat- alysts [16], 1,4-hydroboration of 1,3-dienes [17], trans-hydroboration of terminal alkynes giving (Z)-1-alkenylboronates [18], or diastereoselective hydroboration of cyclic and acyclic allyl alcohol derivatives [19]. A protocol that involves oxidative addi- tion of an H–B bond to a low-valent transition metal has been successfully extended to analogous metal-catalyzed addition reactions of B–B [20], B–S [21], B–Si [22] or B–Sn [23] compounds [15c]. Conversely, cross-coupling reactions of B–B [15c, 20] or B–H [24] reagents with aryl, vinyl, allyl and benzyl halides or trif lates have provided a direct method for the bory- lation of organic electrophiles without using lithium or magnesium intermediates. Because of the availability of various electrophiles and mild reaction conditions, this method has allowed convenient access to organoboron compounds that have a vari- ety of functional groups. An extension of this methodology to aliphatic or aromatic C–H borylation is of significant value for direct preparation of organoboron com- pounds from various hydrocarbons [25]. Some key mechanistic steps in putative cat- alytic cycles have been established recently via stoichiometric C–H borylation of alka- Boronic Acids. Edited by Dennis G. Hall Copyright © 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN 3-527-30991-8 102 2Metal-catalyzed Borylation of Alkanes and Arenes via C–H Activation for Synthesis of Boronic Esters nes, arenes and alkenes with (boryl)metal complexes [26, 27]. Those discoveries were followed by the rapid development of catalytic processes for C–H borylation of hy- drocarbons with bis(pinacolato)diboron (B2pin2) or pinacolborane [20]. In most of these reactions, it is widely recognized that the catalytic cycle involves a (boryl)metal species originating by transmetalation or oxidative addition. The synthesis, charac- terization, bonding, and reactivity of these catalytically important species have been reviewed [28]. There have also been extensive theoretical studies on the M–B bond and its role in catalytic cycles [29]. 2.2 Borylation of Aromatic Halides and Trif lates 2.2.1 Cross-coupling Reaction of Diborons Metal-catalyzed cross-coupling reactions of disilanes [30] and distannanes [31] have been successfully used for the synthesis of organosilicon and -tin compounds from organic halides. The lack of suitable boron nucleophiles has limited this protocol for boron compounds, but tetra(alkoxo)diborons such as bis(pinacolato)diboron (B2pin2) acts as boron-nucleophiles for palladium-catalyzed cross-coupling reactions of or- ganic halides and trif lates (Scheme 2.1) [15c, 20]. Coupling reactions of diborons with aromatic halides [32, 33] and trif lates [34] directly provide arylboronic esters. The presence of a base such as KOAc is critical for coupling reactions of diborons, sug- gesting a transmetalation between B2pin2 and the Ar-Pd-OAc intermediate that is generated by displacement of X in Ar-Pd-X with an acetate anion [32]. Since strong bases such as K3PO4 and K2CO3 prompt the competitive formation of homocoupling biaryls (36–60% yields), KOAc is recognized to be a suitable base for a wide variety of aromatic substrates, including aryl iodides [32, 35], bromides [32, 36, 38], chlorides [33, 37] and trif lates [34]. Although PdCl2(dppf) works well as a catalyst for repre- sentative aromatic iodides and bromides (e.g., 1 and 2 in Scheme 2.1) [32], electron- donating PCy3 [33] and an N-heterocyclic carbene (NHC) [37] complex are advanta- geous for achieving high yields within a short reaction time for aryl chlorides and electron-rich aryl bromides or trif lates (e.g., 3, 4). These ligands are also effective for preventing the participation of phosphine-bound aryls, which will competitively oc- cur when PPh3 and dppf are used as a ligand. The reaction can be further accelerat- ed by irradiation with microwaves [37]. The reaction also offers a method for synthe- sizing boronic esters in the solid phase. For example, a polymer-bound boronate is quantitatively obtained by treating an iodobenzamide supported on polystyrene (5) with the diboron reagent at 80 °C for 20 h in the presence of PdCl2(dppf) and KOAc [39]. Subsequent coupling with haloarenes, followed by hydrolysis with trif luo- roacetic acid, furnishes various biaryls for parallel synthesis and combinatorial syn- thesis. In the synthesis of 1-alkenylboronic acids or esters from the corresponding mag- nesium or lithium reagents, it is often difficult to retain the stereochemistry of start- 2.2 Borylation of Aromatic Halides and Trif lates 103 ing 1-alkenyl halides and the required protection–deprotection of sensitive function- al groups is a tedious process. Borylation of 1-alkenyl halides or trif lates with di- borons proceeds with complete retention of alkene stereochemistry and is compati- ble with various functional groups [40, 41]. The reaction requires a stronger base than that for aryl halides in the presence of triphenylphosphine-palladium catalysts. Fine K2CO3 suspended in dioxane is recommended for trif lates conjugated to a carbonyl O O BB O O O R-X RB Pd catalyst, base O X=I, Br, Cl, OTf, N2BF4 OMe MeO2C I X Cl H N Br 2 X=Cl, Br, OTf 2 FG FG NHCbz O 2 (97%) 3 (70-98%) 4 (57-72%) OMe Pd(OAc) /NHC Pd(dba)2/2PCy3 2 PdCl2(dppf), KOAc KOAc, THF 1 (95%) DMSO, 80 °C KOAc, dioxane 80 °C microwave Ph I Ph P H Cl N N PS N Fe Pd Cl P O P 3 Ph 5 (95%) Ph PdCl2(dppf), KOAc dppf PCy3 NHC DMF, 80 °C OTf O O Me COMe Me X OTf Me OAc FG TBSO X=Cl, Br 6 (91%) 7 (86%) 8 (>71%) 9 (72-88%) PdCl2(PPh3)2/2PPh3 PdCl2(PPh3)2/2PPh3 Pd(dba)2/2AsPh3 Pd(dba)2 ° K2CO3, dioxane, 80 C PhOK, toluene, 50 °C toluene, 50 °C /2P(4-MeOPh)3 KOAc, toluene 50 °C Scheme 2.1 Organoboron compounds via cross-coupling reactions of diborons. 104 2Metal-catalyzed Borylation of Alkanes and Arenes via C–H Activation for Synthesis of Boronic Esters group (6) [41] and KOPh suspended in toluene for unactivated/unconjugated bro- mides or trif lates (7) [40]. Pinacol alkenylboronates thus obtained can be isolated by chromatography on silica gel without decomposition or they can be directly used for the cross-coupling reactions without isolation of the boron intermediates. Allylboron compounds are valuable reagents in organic synthesis since their di- astereoselective addition to a carbon–oxygen or the carbon–nitrogen double bond provides homoallylic alcohols or amines via a chair-like, six-membered cyclic transi- tion state [1]. Such allylborations of pinacol ester derivatives are very slow due to their steric hindrance, however, the reaction takes place at –78 °C in the presence of AlCl3 or Sc(OTf)3 (10 mol%) [42]. Palladium(0)-catalyzed cross-coupling reactions of di- boron with allyl acetates such as 8 provide variously functionalized allyboron com- pounds (Scheme 2.1) [43, 44]. The boron atom couples at the less-hindered terminal carbon to provide thermally stable (E)-allylboronates via a syn-π-allylpalladium inter- mediate [43]. Various 5-5, 6-5, and 7-5 cis-fused exomethylene cyclopentanols are di- rectly obtained from β-ketoesters or diketones via a cross-coupling/intramolecular al- lylboration sequence [44]. Benzyl chlorides and bromides such as 9 are borylated with B2pin2 in the presence of a palladium(0)-tris(p-methoxyphenyl)phosphine catalyst and KOAc [45]. 2.2.2 Cross-coupling Reaction of Pinacolborane Pinacolborane (HBpin) is a unique, economical boron nucleophile for borylation of aryl and 1-alkenyl halides or trif lates that is recommended for large-scale prepara- tions [24] (Scheme 2.2). Interestingly, various reducible functional groups in 10 re- main intact during the reaction at 80 °C; however, the reaction is generally accompa- nied by the formation of some undesirable dehalogenation products (ArH, 10–20%). Borylation of 2-bromoaniline (11) [46] or bromophenothiazine (12) [47] is directly fol- lowed by cross-coupling with haloarenes in high yields. The ester group of 13 remains intact at 120 °C in the synthesis of 2-pyrone-5-boronate [48]. The bisporphyrin-based synthetic receptor that has a molecular weight of 4198 is synthesized by a sequential double cross-coupling reaction. Borylation of bromoporphyrin (14) with pinacolbo- rane is followed directly by cross-coupling with 1,3-diiodobenzene to give a bis- porphyrin receptor [49]. The presence of Et3N plays a key role in not only preventing the production of ArH but also facilitating the B–C bond formation. The mechanism is unknown, but the displacement of Pd(II)–X with a weakly nucleophilic boryl anion + – σ (Et3NH Bpin ) or -bond metathesis between H-Pd-Bpin and ArX have been pro- posed for the process leading to the formation of an Ar-Pd-Bpin intermediate [24].
Load more

Recommended publications
  • 1 Structure, Properties, and Preparation of Boronic Acid Derivatives Overview of Their Reactions and Applications Dennis G
    j1 1 Structure, Properties, and Preparation of Boronic Acid Derivatives Overview of Their Reactions and Applications Dennis G. Hall 1.1 Introduction and Historical Background Structurally, boronic acids are trivalent boron-containing organic compounds that possess one carbon-based substituent (i.e., a CÀB bond) and two hydroxyl groups to fill the remaining valences on the boron atom (Figure 1.1). With only six valence electrons and a consequent deficiency of two electrons, the sp2-hybridized boron atom possesses a vacant p-orbital. This low-energy orbital is orthogonal to the three substituents, which are oriented in a trigonal planar geometry. Unlike carbox- ylic acids, their carbon analogues, boronic acids, are not found in nature. These abiotic compounds are derived synthetically from primary sources of boron such as boric acid, which is made by the acidification of borax with carbon dioxide. Borate esters, one of the key precursors of boronic acid derivatives, are made by simple dehydration of boric acid with alcohols. The first preparation and isolation of a boronic acid was reported by Frankland in 1860 [1]. By treating diethylzinc with triethylborate, the highly air-sensitive triethylborane was obtained, and its slow oxidation in ambient air eventually provided ethylboronic acid. Boronic acids are the products of a twofold oxidation of boranes. Their stability to atmospheric oxidation is considerably superior to that of borinic acids, which result from the first oxidation of boranes. The product of a third oxidation of boranes, boric acid, is a very stable and relatively benign compound to humans (Section 1.2.2.3). Their unique properties and reactivity as mild organic Lewis acids, coupled with their stability and ease of handling, are what make boronic acids a particularly attractive class of synthetic intermediates.
    [Show full text]
  • Activation of Diboron Reagents: the Development of Mild Conditions for the Synthesis of Unique Organoboron Compounds
    Activation of diboron reagents: The development of mild conditions for the synthesis of unique organoboron compounds Steven Brandon Thorpe Dissertation submitted to the faculty of the Virginia Polytechnic Institute and State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy In Chemistry Webster L. Santos, Chairman Paul R. Carlier David G. I. Kingston James M. Tanko March 23, 2012 Blacksburg, Virginia Keywords: borylation, diboron reagent, boronic ester, conjugate addition, copper catalysis © 2012 by Steven B. Thorpe Activation of diboron reagents: The development of mild conditions for the synthesis of unique organoboron compounds Steven Brandon Thorpe ABSTRACT The first successful synthesis and isolation of a boronic acid was reported in 1860 by Frankland in the pursuit of novel organometallic compounds. For more than a century, further studies of boronic acids were sparsely published. Suzuki and Miyaura jumpstarted the field in 1979 with an innovative carbon-carbon bond forming reaction employing an organoboronic acid and a carbon halide under palladium catalysis. Indeed, the Nobel Prize in Chemistry was awarded to Professor Akira Suzuki, along with Professors Richard Heck and Ei-ichi Negishi, in 2010 for their important contributions in palladium-catalyzed cross-coupling chemistry. Over the last 30 years, reports on organoboron compounds have increased exponentially. This dissertation describes the author’s contributions to the development of preparative methods for organoboronic acid derivatives
    [Show full text]
  • Shungube Mbongeni M 2016.Pdf
    Hydroboration Studies of Olefins with Heterocyclic Hydroborating Reagents with Various Transition Metal Complexes: Attemped Diastereoselective Synthesis of Homoallylic Alcohols via Hydroboration. Thesis submitted in fulfilment of the requirements for the degree Master of Science By Mbongeni M. Shungube School of Chemistry and Physics College of Agriculture, Engineering and Science University of KwaZulu-Natal Pietermaritzburg December 2016 Declaration The experimental work described in this dissertation was carried out in the School of Chemistry, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, Pietermaritzburg, under the supervision of Professor Ross S. Robinson. I hereby declare that these studies represent original work by the author and have not otherwise been submitted in any form for any degree or diploma to any tertiary institution. Where the use of published information from other authors has been made and it is duly acknowledged in the text. Signed …………………………………………… Mbongeni M. Shungube (Candidate) I hereby certify that this statement is correct. Signed …………………………………. Professor Ross S. Robinson (Supervisor) i Abstract Hydroboration is one of the key routes to afford organoborane esters which are versatile intermediate in organic synthesis. Investigations of different hydroborating reagents and catalysts toward hydroboration present alternative to achieve organoborane ester with different stability, selectivity, and yield. Hence, a part of this study was focused on the preparation of heterocyclic hydroborating reagents with a single site available for hydroboration. Four reagents were prepared which included the well-known catecholborane (23) and pinacolborane (24) and the hardly studied 2,3-dihydro-1,3,2-benzodiazaborole (31) and 2,3-dihydro-1,3,2-benzoxazaborole (34). A study to utilize hydroboration to prepare allylic boronic esters using the four hydroborating reagent above was also undertaken.
    [Show full text]
  • Boronic Acids
    Boronic Acids Boronic Acids www.alfa.com INCLUDING: • Boronic Esters • Oxazaborolidine Reagents • Coupling and Hydroboration Catalysts • Phosphine Ligands • Borylation Reagents www.alfa.com Where Science Meets Service Quality Boronic Acids from Alfa Aesar Alfa Aesar is known worldwide for a variety of chemical compounds used in research and development. Recognized for purity and quality, our products and brands are backed by technical and sales teams dedicated to providing you the best service possible. In this catalog, you will find details on our line of boronic acids, esters and related compounds, which are manufactured to the same exacting standards as our full offering of over 33,000 products. Also included in this catalog is a 28-page introduction to boronic acids, their properties and applications. This catalog contains only a selection of our wide range of chemicals and materials. Also included is a selection of novel coupling catalysts and ligands. Many more products, including high purity metals, analytical products, and labware are available in our main catalog or online at www.alfa.com. Table of Contents About Us _____________________________________________________________________________ II How to Order/General Information ____________________________________________________ III Introduction __________________________________________________________________________ 1 Alkenylboronic acids and esters _____________________________________________________ 29 Alkylboronic acids and esters ________________________________________________________
    [Show full text]
  • UC Santa Cruz Electronic Theses and Dissertations
    UC Santa Cruz UC Santa Cruz Electronic Theses and Dissertations Title OBSERVATIONS IN REACTIVITY BETWEEN BH CONTAINING COMPOUNDS AND ORGANOMETALLIC REAGENTS: SYNTHESIS OF BORONIC ACIDS, BORONIC ESTERS, AND MAGNESIUM HYDRIDES Permalink https://escholarship.org/uc/item/113107h0 Author Clary, Jacob William Publication Date 2012 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA SANTA CRUZ OBSERVATIONS IN REACTIVITY BETWEEN BH CONTAINING COMPOUNDS AND ORGANOMETALLIC REAGENTS: SYNTHESIS OF BORONIC ACIDS, BORONIC ESTERS, AND MAGNESIUM HYDRIDES A dissertation submitted in partial satisfaction of the requirements for the degree of DOCTOR OF PHILOSOPHY in CHEMISTRY AND BIOCHEMISTRY by Jacob William Clary March 2012 The Dissertation of Jacob W. Clary is approved: Professor Bakthan Singaram, Advisor Professor Rebecca Braslau, Chair Professor Claude Bernasconi Tyrus Miller Vice Provost and Dean of Graduate Studies Copyright © by Jacob W. Clary 2012 ii TABLE OF CONTENTS LIST OF FIGURES viii LIST OF SCHEMES x LIST OF TABLES xii ABSTRACT xviii DEDICATION AND ACKNOWLEDGEMENTS xv CHAPTER 1. Review of Boronic Acid Synthesis and Applications 1 1.1 Introduction 2 1.1.1 Nomenclature of Boronic Acids 3 1.1.2 Properties of Boronic Acids 5 1.1.3 Analysis of Boronic Acids 7 1.2 Boronic Acids in Organic Chemistry 9 1.2.1 Suzuki-Miyaura C-C Cross-Coupling 9 1.2.1.1 Applications of the Suzuki-Miyaura Cross-Coupling Reaction 11 1.2.1.2 Mechanism of the Suzuki-Miyaura Cross-Coupling 15 1.2.2 Stereoselective Suzuki Cross-Coupling 16 1.2.3 C-N and C-O Cross-Coupling Reactions with Boronic Acids 23 1.2.4 Biological and Medicinal Applications 26 1.3 Synthesis of Boronic Acids 31 1.3.1 Transmetallation of Grignard and Organolithium Reagent 32 iii 1.3.2 Cross-coupling Reaction of Bis(pinacolato)diboron and Pinacolborane 34 1.3.3 C-H Activation 40 1.4.
    [Show full text]
  • Cationic Rhodium-Catalyzed Hydroboration: Investigations Into Electronic and Ligand Effects; Lewis-Acid Reaction Acceleration and Regioselectivity Change
    Cationic Rhodium-Catalyzed Hydroboration: Investigations into Electronic and Ligand Effects; Lewis-Acid Reaction Acceleration and Regioselectivity Change by CHRISTOPHER JAMES LATA A thesis submitted to the Department of Chemistry in conformity with the requirements for the degree of Master of Science Queen’s University Kingston, Ontario, Canada September 2009 Copyright © Christopher James Lata, 2009 Abstract Mechanistic aspects of the asymmetric rhodium catalyzed hydroboration of vinyl arenes with catecholborane (HBCat) and pinacolborane (HBPin) have been probed. Competition studies conducted with catalysts bearing asymmetric ligands Josiphos or Quinap reveal substituent effects of varying sensitivity correlating to Hammett parameter sigma. In reactions involving the Quinap ligand, rho-values of +1.97 and +1.02 are observed for HBCat and HBPin, respectively. In Josiphos-ligated systems, rho-values of +1.38 and -3.17 are observed, indicating that the reaction proceeds through differing mechanisms depending on the borane employed. Labeling experiments reveal differences in the reversibility of the hydride insertion step of reaction depending on the ligand and borane implemented in hydroboration. A new methodology has been developed for regioselective rhodium-catalyzed hydroboration of internal olefins with pinacolborane. The addition of co-catalytic Lewis acids results in the activation of cationic rhodium catalysts in chlorinated solvents. Increased catalytic activity and regioselectivity are observed under these conditions. For internal alkyl olefins, selectivity for non-isomerized secondary boronate esters was found originate from the non-coordinating solvents employed in the reaction. For aromatic olefins, increased regioselectivity and reaction acceleration are both effects of the Lewis acid additive. Study of the reaction revealed that these properties are linked to Lewis acid-base mediated heterolytic B-H bond cleavage of pinacolborane, and suggests that the reagent is transferred to the rhodium catalyst as borenium ion and hydride moieties.
    [Show full text]
  • Chemfile Vol.7 No 7
    2007 VOLUME 7 NUMBER 7 Product Directory Boron Reagents for Suzuki Coupling BORYLATION REAGENTS BORONIC ACIDS BORONATE ESTERS TRIFLUOROBORATE SALTS Potassium cyclopropyltrifluoroborate: a simple reagent for the introduction of a cyclopropyl group via Suzuki cross–coupling. sigma-aldrich.com Table of Contents Sigma-Aldrich is committed to providing the most extensive portfolio of high-quality boronic acids, boronate esters, and trifluoroborate salts for use in Suzuki coupling, and we continually expand our product listing. Within each section of this directory, products are listed by increasing molecular formula. If you are unable to find a coupling reagent for your research, “Please Bother Us” at [email protected], or contact your local Sigma-Aldrich office (see back cover). If viewing the electronic version, simply select from the category below to jump to that section or activate your Adobe® Bookmarks. You may also search by name, product number, molecular formula, or CAS registry number by using the “find” feature in Adobe® (Ctrl+F in Windows® or Command+F in a Macintosh® environment). Borylation Reagents Boronate Esters Trifluoroborate Salts Introduction Boronic Acids Alkylboronate esters Alkyltrifluoroborates Alkylboronic acids Alkenylboronate esters Alkenyltrifluoroborates Alkenylboronic acids Allenyl- and Alkynylboronate esters Aryltrifluoroborates Arylboronic acids Arylboronate esters S-Heteroaryltrifluoroborates N-Heteroarylboronic acids N-Heteroarylboronate esters O-Heteroarylboronic acids O-Heteroarylboronate esters S-Heteroarylboronic acids S-Heteroarylboronate esters Foreword Akira Suzuki Professor Emeritus, Hokkaido University Sapporo, Japan Reactions in which new carbon–carbon bonds are formed are key steps in building the complex, bioactive molecules that become developed into drugs and agrochemicals. These reactions are also vital in developing the new generation of ingeniously designed organic materials with novel electronic, optical, or mechanical properties, that are likely to play a significant role in the burgeoning area of nanotechnology.
    [Show full text]
  • Division of Organic Chemistry
    ORGN DIVISION OF ORGANIC CHEMISTRY S. Silverman and E. McLaughlin, Program Chairs SUNDAY MORNING Section A Pennsylvania Convention Center 116 New Reactions & Methodology S. M. Silverman, Organizer 8:00 1. Copper catalyzed reductive carbonylation of alkyl iodides. S. Zhao, N.P. Mankad 8:20 2. Sulfenate-anion-catalyzed diastereoselective aziridination of imines. Z. Zheng, P.J. Walsh 8:40 3. Cyanoalkylcopper species in carbon-carbon bond forming reactions. D.L. Silverio 9:00 4. New reactivity enabled by cation-π interactions. P.J. Walsh 9:20 5. Dipolar alkynyl-prins (DAP) cyclization for the rapid construction of complex polycycles. S. Abdul-Rashed, G. Alachouzos, A. Frontier 9:40 6. Subphthalocyanines and perylene-diimide derivatives in organic photovoltaics. L. Chockalingam Kasi Viswanath 10:00 7. Silylated α-aminonitriles for late-stage functionalization. T. Mathew, T. Yamato, S.G. Prakash 10:20 8. Synthesis of differentially substituted diynes via tandem nucleophilic addition/fragmentation pathways. A. Tavakoli, G.B. Dudley 10:40 9. Analogues of Bestmann’s ylide, Ph3P=C=C=O: Syntheses, structures and Lewis acid catalyzed cyclizations with organic substrates. C. Krempner 11:00 10. Diastereoselective alkynylations of β-(Bromo)iminium ions via copper(I) catalysis. S.O. Santana, W. Guan, M.P. Watson 11:20 11. Modular three-component difunctionalization of aryl/cyclohexenyl triflates via arynes and cyclohexynes. S. Cho, Q. Wang 11:40 12. 1,2-aminocyanation of alkenes via distal migration. Y. Kwon, Q. Wang Section B Pennsylvania Convention Center 117 Heterocycles & Aromatics S. M. Silverman, Organizer 8:00 13. Formal [4+2] cycloaddition between alkynes and allene-ynes to generate functionalized toluenes.
    [Show full text]
  • Diboron(4) Compounds: from Structural Curiosity to Synthetic Workhorse Emily C
    This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. Review pubs.acs.org/CR Diboron(4) Compounds: From Structural Curiosity to Synthetic Workhorse Emily C. Neeve,† Stephen J. Geier,§ Ibraheem A. I. Mkhalid,‡ Stephen A. Westcott,*,§ and Todd B. Marder*,† † Institut für Anorganische Chemie, Julius-Maximilians-UniversitatWü ̈rzburg, Würzburg 97074, Germany § Mount Allison University, Department of Biochemistry and Chemistry, Sackville, New Brunswick E4L 1G8, Canada ‡ Department of Chemistry, King Abdulaziz University, Jeddah 21413, Saudi Arabia ABSTRACT: Although known for over 90 years, only in the past two decades has the chemistry of diboron(4) compounds been extensively explored. Many interesting structural features and reaction patterns have emerged, and more importantly, these compounds now feature prominently in both metal-catalyzed and metal-free methodologies for the formation of B−C bonds and other processes. CONTENTS 4. Boryl Addition (Hydroboration) Reactions 9115 4.1. α,β-Unsaturated Carbonyls, Imines, and 1. Introduction 9092 Related Compounds 9115 2. Synthesis, Structure, and Bonding of Diboron(4) 4.2. Alkynes 9119 Compounds 9093 4.3. Alkenes 9121 2.1. B2X4 Compounds 9093 4.4. Dienes, Enynes, and Allenes 9122 2.2. B2H4 Chemistry 9094 4.5. Aldehydes and Imines 9123 2.3. B2(NR2)4 Compounds 9094 4.6. Ring-Opening Reactions 9123 2.4. B2(alkyl)n Compounds 9095 4.7. Borylative Cyclizations and Related Intermo- 2.5. B2(OR)4 Compounds 9095 lecular Reactions 9124 2.5.1. Synthesis of B2(OR)4 9095 4.8.
    [Show full text]
  • Nonane-Catalyzed Hydroboration of Terminal Aromatic Alkynes with Pinacolborane
    American Journal of Undergraduate Research ZZZDMXURQOLQHRUJ 9-Borobicyclo[3.3.1]nonane-Catalyzed Hydroboration of Terminal Aromatic Alkynes with Pinacolborane Garett L. Ruesch, Sydney L. Rowley, Marcus C. Mifflin, & Nathan S. Werner* Department of Physical Science, Southern Utah University, Cedar City, UT https://doi.org/10.33697/ajur.2020.011 Students: [email protected], [email protected], [email protected] Mentor: [email protected]* ABSTRACT Organoboron compounds are extensively used in organic synthesis. The alkenylboronic acid pinacol esters formed from the hydroboration reaction of alkynes with pinacolborane are stable, easy to handle, and useful in many synthetic transformations. However, pinacolborane lacks the reactivity necessary to undergo facile hydroboration reaction with terminal aromatic alkynes. 9- Borobicyclo[3.3.1]nonane (9-BBN) can be used to catalyze the hydroboration reaction of phenylacetylene with pinacolborane. The hydroboration reaction parameters and product purification conditions were evaluated to maximize the yield of (E)-2- phenylethenylboronic acid pinacol ester. It was found that the optimal reaction conditions for the 9-BBN-catalyzed hydroboration of phenylacetylene with pinacolborane were: phenylacetylene (1.0 equiv), pinacolborane (1.2 equiv), 9-BBN (20 mol%), and THF [0.2] at 65 °C. The compatibility of these reaction conditions with p-substituted terminal aromatic alkynes bearing electronically diverse groups was studied. Moderate to good yield (49–76%) of the hydroboration products were isolated after purification by liquid-liquid extraction and flash chromatography. KEYWORDS Organic Synthesis; Catalysis; Methods Development; Hydroboration; Reaction Optimization; Alkenylboronic Ester; Alkyne; Pinacolborane; 9-Borobicyclo[3.3.1]nonane INTRODUCTION Boron containing organic compounds are useful reagents in the synthesis of important carbon-containing medicines, materials, and fine chemicals.
    [Show full text]
  • UC Santa Cruz Electronic Theses and Dissertations
    UC Santa Cruz UC Santa Cruz Electronic Theses and Dissertations Title Synthesis of Boronic Acids and Esters from Pinacolborane and Aminoborane Under Ambient Magnesium-, Iodine-, and Zinc-Mediated Conditions Permalink https://escholarship.org/uc/item/8dw380vb Author Murphy, Christopher Lee William Publication Date 2016 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA SANTA CRUZ SYNTHESIS OF BORONIC ACIDS AND ESTERS FROM PINACOLBORANE AND AMINOBORANE UNDER AMBIENT MAGNESIUM-, IODINE-, AND ZINC-MEDIATED CONDITIONS A dissertation submitted in partial satisfaction of the requirements for the degree of DOCTOR OF PHILOSOPHY in CHEMISTRY AND BIOCHEMISTRY by Christopher Lee William Murphy December 2016 The Dissertation of Christopher L. W. Murphy is approved: ______________________________ Professor Bakthan Singaram, Advisor ______________________________ Professor Rebecca Braslau, Chair ______________________________ Professor Scott Lokey ______________________________ Tyrus Miller Vice Provost and Dean of Graduate Studies Copyright © by Christopher L. W. Murphy 2016 TABLE OF CONTENTS LIST OF FIGURES vii LIST OF SCHEMES x LIST OF TABLE xix ABSTRACT xxi CHAPTER 1. Review of Boronic Acid and Ester Synthesis and their Applications in Organic Chemistry 1 1.1 Introduction 2 1.1.1 Boron and Boranes 2 1.1.2 Boronic Acids and Esters 3 1.1.3 Structural, Electronic, and Acidic Properties 4 1.1.4 Analysis of Boronic Acids and Esters 11 1.2 Synthesis of Boronic Acids and Esters 12 1.2.1 Early Synthetic Methods of Boronic Acids and Esters 13 1.2.2 Miyaura Borylation 16 1.2.3 Synthesis of Boronic acids via Aminoboranes 18 1.2.4 C-H Activation 19 1.2.5 Synthesis of Boronic Acids and Esters through Transition Metals 21 1.3 Applications of Boronic Acids and Esters 23 iii 1.3.1 Suzuki Coupling 23 1.3.2 Chan-Lam Coupling 35 1.3.3 Boronic Acids as Saccharide Sensors 41 1.4 Conclusion 46 1.5 Thesis Outline 47 1.6 References 48 CHAPTER 2.
    [Show full text]
  • Palladium-Catalyzed Borylation and Cross-Coupling of Aryl and Heteroaryl Halides Utilizing Dibora Derivatives
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2012 Palladium-Catalyzed Borylation And Cross-Coupling Of Aryl And Heteroaryl Halides Utilizing Dibora Derivatives Sarah Little Jane Trice University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Organic Chemistry Commons Recommended Citation Trice, Sarah Little Jane, "Palladium-Catalyzed Borylation And Cross-Coupling Of Aryl And Heteroaryl Halides Utilizing Dibora Derivatives" (2012). Publicly Accessible Penn Dissertations. 712. https://repository.upenn.edu/edissertations/712 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/712 For more information, please contact [email protected]. Palladium-Catalyzed Borylation And Cross-Coupling Of Aryl And Heteroaryl Halides Utilizing Dibora Derivatives Abstract ABSTRACT PALLADIUM-CATALYZED BORYLATION AND CROSS-COUPLING OF ARYL AND HETEROARYL HALIDES UTILIZING DIBORA DERIVATIVES Sarah Little Jane Trice Professor Gary A. Molander Although much current research focuses on developing new boron reagents and identifying robust catalytic systems for the cross-coupling of these reagents, the fundamental preparations of the nucleophilic partners (i.e., boronic acids and derivatives) has been studied to a lesser extent. Most current methods to access boronic acids are indirect and require harsh conditions or expensive reagents. Therefore, we sought to provide a simple, efficient, and direct synthesis of arylboronic acids. Utilizing aryl halides and an underutilized reagent, tetrahydroxydiboron B2(OH)4, we developed a palladium-catalyzed method that now provides access to boronic acids in high yield. The method eliminates the necessity to employ the extremely wasteful and most commonly used source of boron, bis(pinacolato)diboron.
    [Show full text]