DOCSLIB.ORG

Room-Temperature Copper-Catalyzed Synthesis of Primary Arylamines from Aryl Halides and Aqueous Ammonia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Room-Temperature Copper-Catalyzed Synthesis of Primary Arylamines from Aryl Halides and Aqueous Ammonia LETTER 1355 Room-Temperature Copper-Catalyzed Synthesis of Primary Arylamines from Aryl Halides and Aqueous Ammonia SynthesisChuanzhou of Primary Arylamines Tao,*a Weiwei Liu,a Aifeng Lv,b Mingming Sun,a Ying Tian,a Qi Wang,a Jing Zhao*b a School of Chemical Engineering, Huaihai Institute of Technology, Lianyungang 222005, P. R. of China Fax +86(518)85895121; E-mail: [email protected] b State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, P. R. of China Fax +86(25)83592672; E-mail: [email protected] Received 11 February 2010 In the meantime, Fu et al. reported a mild copper-cata- Abstract: Primary arylamines can be prepared via a copper-cata- lyzed cross-coupling between aryl halides and aqueous ammonia lyzed coupling of aryl boronic acids and aqueous ammo- nia (Scheme 1).6 The reaction proceeds at room using K3PO4 as a base and DMF as a solvent at room temperature. temperature without ligands, bases, or other additives, and Key words: copper, catalysis, cross-coupling, room temperature, aqueous ammonia, primary arylamine many functional groups are tolerated under mild condi- tions. However, the cost and availability of the aryl boron- ic acids, particularly the highly functionalized ones, hampers their applications. Usually aryl halides are pre- Primary arylamines are important intermediates in the ferred substrates because these electrophiles tend to be manufacture of agrochemicals, pharmaceuticals, dyes, cheaper and easier to prepare. Thus, we set out to develop pigments, and rubber.1 Their preparation has attracted in- more economical, practical, and efficient protocols for the creasing attention. These compounds were traditionally synthesis of primary arylamines from aryl halides under synthesized through the amination of aryl halides using mild conditions. ammonia as the nucleophile,2 but high pressure and high temperature are necessary to achieve good yields. Several As part of our studies on the copper-catalyzed arylation of groups have recently studied the possibility of using tran- nucleophiles,3j,7 we now report that the synthesis of pri- sition metals to catalyze the synthesis of primary aryl- mary arylamines can be achieved by the copper-catalyzed amines from aryl halides. For instance, palladium- and cross-coupling between aryl halides and aqueous ammo- copper-catalyzed synthesis has been achieved with nia at room temperature (Scheme 1). ammonia surrogates. The nitrogen sources include allylamines,3a benzophenone imines,3b,c tert-butyl car- Fu's work bamates,3d,e Li[N(SiMe ) ],3f,g Zn[N(SiMe ) ] ,3h 3 2 3 2 2 Cu2O, MeOH 3i 3j B(OH) ⋅ amidines, 2,2,2-trifluoroacetamide. However, the use Ar 2 + NH3 H2O r.t. of masked ammonia suffers from low atom economy and NH Ar 2 needs an additional cleavage step to liberate the primary CuI, DMF, K3PO4 X ⋅ arylamine. Recently, Hartwig4a,b and Buchwald4c reported Ar + NH3 H2O this work palladium-catalyzed coupling reactions of aryl halides X = I, Br and free ammonia, in which bulky ferrocene or electron- rich phosphine ligands were used. These methods provide Scheme 1 Room-temperature copper-catalyzed synthesis of prima- a highly efficient route to anilines and can be carried out ry arylamines without the ammonia surrogates. More recently, progress has also been achieved in the copper-catalyzed coupling 1-Chloro-4-iodobenzene was selected as a model sub- Downloaded by: Lu YanBo, University Town of ShenZhen. Copyrighted material. ammonia with aryl halides5, such as CuI/L-proline,5b strate for optimization of the reaction conditions at room CuI/2,4-pentanedione,5c CuI/N,N-dimethylglycine/organ- temperature. As shown in Table 1, using CuI as a catalyst ic base,5d CuBr/2-pyridinyl b-ketone,5e and CuI/4- under ligand-free and base-free conditions, different sol- hydroxy-L-proline5f catalytic systems. Wolf and Xu also vents were screened for arylation of ammonia (entries 1– introduced a copper-catalyzed amination protocol in the 5). Low yields of the desired products were obtained in al- 5g solvent of H2O/NMP at 80 °C. The efficiency of all the cohol, acetone, toluene, and dioxane, while the use of above catalytic reactions using ammonia as the nucleo- DMF led to a fair yield (40%) of the cross-coupling prod- phile is highly dependent on the involvement of suitable uct (entry 5). Generally, in the copper-catalyzed carbon– ligands and elevated temperatures (80–110 °C).4,5 nitrogen bond formation of aryl halides, additional bases were essential.8 Although ammonia itself could play the role of a base in the catalyst system, we speculated that the basicity of reaction system was not strong enough. Then, SYNLETT 2010, No. 9, pp 1355–1358 xx.xx.2010 with DMF as solvent, several bases such as Na2CO3, Advanced online publication: 06.05.2010 K2CO3, K3PO4, Cs2CO3, and NaOH were introduced into DOI: 10.1055/s-0029-1219922; Art ID: W02410ST the reaction mixture. We were delighted to find that the © Georg Thieme Verlag Stuttgart · New York 1356 C. Tao et al. LETTER Table 1 Copper-Catalyzed Coupling of 1-Chloro-4-halobenzene of CuI as the catalyst and aqueous ammonia (6.5 equiv) as with Aqueous Ammonia: Optimization of the Reaction Conditionsa the amino source, relative to the aryl halide, DMF as the 9 X NH 2 solvent and K3PO4 as the base at room temperature. CuI, base + H O NH ⋅ 2 3 Having identified the catalytic system of CuI, K3PO4 and Cl Cl DMF, we next examined whether the same catalytic sys- Entry X Cat. Base Solvent Temp Yield (%)b tem could be applied to the coupling of aqueous ammonia with various aryl iodides and bromides with different 1ICuI– MeOHr.t.6 electronic and steric properties (Table 2). It was found that the coupling of aryl iodides containing electron- 2 I CuI – acetone r.t. 7 donating groups with ammonia afforded anilines in mod- 3ICuI– toluener.t.5 erate yields (entries 1–3). Aryl iodide carrying electron- withdrawing groups could be smoothly converted to the 4 I CuI – dioxane r.t. 10 desired products with good to excellent isolated yields 5ICuI– DMFr.t.40 (83–98%, entries 4–13). It is noteworthy that many func- tional groups including ether, cyano, nitro, keto, ester, and 6ICuINa2CO3 DMF r.t. 57 free carboxylic acid moiety were tolerated under these 7ICuIK2CO3 DMF r.t. 66 mild conditions. However, aryl iodide carrying an ortho substituent was not found to be a good substrate in the re- c 8ICuIK3PO4 DMF r.t. 80 (87 ) action (entry 14, 15). Only when a neighboring carboxylic acid group was present, aryl iodide could be readily con- 9ICuICs2CO3 DMF r.t. 69 verted to aniline in 84% yield (entry 16). This finding was 10 I CuI NaOH DMF r.t. 62 consistent with the well-known accelerating effect of the carboxylate group on copper-catalyzed aryl halide ex- 11 I Free K3PO4 DMF r.t. 0 change reactions.10 Although nonactivated aryl bromide 12 I CuCl K3PO4 DMF r.t. 45 reacted sluggishly with ammonia (entry 17), satisfactory 13 I CuBr K PO DMF r.t. 33 yields (40–89%) of primary arylamines were obtained 3 4 when the electron-deficient aryl bromides (entries 18–23) 14 I Cu2OK3PO4 DMF r.t. 15 were utilized. 15 I CuO K PO DMF r.t. 0 3 4 Table 2 Copper(I) Iodide Catalyzed Cross-Coupling of Aryl Ha- lides 1 with Aqueous Ammonia at Room Temperaturea 16 I Cu2SO4 K3PO4 DMF r.t. 0 R R 17 Br CuI K PO DMF r.t. 29 (40c, 5d) CuI + X NH H O 3 4 ⋅ NH 3 2 2 K PO , DMF 4 a Reaction conditions: 1-chloro-4-halobenzene (1.0 mmol), 25% aq 3 12 NH3 (6.5 mmol, 0.5 mL), catalyst (10 mol%), base (2.0 mmol), sol- vent (1 mL), nitrogen atmosphere, 24 h. Entry Aryl halide Product Yield (%)b b Isolated yields. c Reaction time: 48 h. NH d I At 80 °C. 1 2 69 coupling yields can be increased to 60% (entries 6–10). 1a 2a I NH Gratifyingly, the use of K3PO4, an inexpensive base, re- 2 2 61 sulted in the coupled product in 80% yield. At this point we screened the copper sources including CuCl, CuBr, 1b 2b Downloaded by: Lu YanBo, University Town of ShenZhen. Copyrighted material. Cu2O, CuO, and CuSO4 (entries 11–16). The yields indi- MeO NH MeO I cated that CuI was the best catalyst. 3 2 50 When 1-chloro-4-iodobenzene was replaced by 1-bromo- 1c 2c 4-chlorobenzene, however, the reaction was less effective Cl NH Cl I providing 4-chloroaniline in 29% yield (entries 17). Sur- 4 2 87 prisingly, when the reaction temperature was raised to 80 1d 2d °C for the aryl bromide, only 5% yield was obtained. It is Br I Br NH noteworthy that in previous reports, an elevated tempera- 5 2 83 ture (up to 80 °C) was usually necessary for aryl bro- mides. However, in our catalytic system, elevating the 1e 2e MeOC NH MeOC reaction temperature results in a reduction of the product I 6 2 84 yield. We presumed that the low reactivity results from the decreased solubility of ammonia in the solvent. There- 1f 2f fore, our optimal reaction condition for room-temperature synthesis of primary arylamines was as follows: 10 mol% Synlett 2010, No. 9, 1355–1358 © Thieme Stuttgart · New York LETTER Synthesis of Primary Arylamines 1357 Table 2 Copper(I) Iodide Catalyzed Cross-Coupling of Aryl Ha- Table 2 Copper(I) Iodide Catalyzed Cross-Coupling of Aryl Ha- lides 1 with Aqueous Ammonia at Room Temperaturea (continued) lides 1 with Aqueous Ammonia at Room Temperaturea (continued) R R R R CuI CuI + + X X NH H O NH H O NH ⋅ NH ⋅ 3 2 3 2 2 2 K K PO , DMF PO , DMF 3 4 3 4 1212 Entry Aryl halide Product Yield (%)b Entry Aryl halide Product Yield (%)b EtOOC I NC Br NC NH EtOOC NH 2 7 2 90 20 76 1g 2g 1t 2h O N NH O N Br NC I NC NH 2 2 2 8 2 92 21 89 1h 2h 1u 2j NC NC HOOC I HOOC NH 9 2 88 22 50 Br NH 1i 2i 2 1v 2r O N I O N NH 2 2 2 O N O N 2 10 98 2 23 66 NH 1j 2j Br 2 Cl Cl 2m 11 85 1w I NH 2 a Reaction conditions: aryl halide (1.0 mmol), 25% aq NH3 (6.5 1k 2k mmol, 0.5 mL), CuI (10 mol%), K3PO4 (2.0 mmol), DMF (1 mL), r.t., nitrogen atmosphere, 36–48 h.
Load more

Recommended publications
  • The Development and Application of Metal-Catalyzed Processes for Organic Synthesis
    The Development and Application of Metal-Catalyzed Processes for Organic Synthesis by Edward J. Hennessy B.A. Chemistry Northwestern University, 2000 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 June 2005 © 2005 Massachusetts Institute of Technology All Rights Reserved Signature of Author: " - - 1_"' .Da-uirnt of Chemistry May 19, 2005 Certified by: Stephen L. Buchwald Camille Dreyfus Professor of Chemistry Thesis Supervisor Accepted by: Robert W. Field Chairman, Departmental Committee on Graduate Students ARCHIVES: This doctoral thesis has been examined by a committee of the Department of Chemistry as follows: -/ Professor Gregory C. Fu: " Ch Chair Professor Stephen L. Buchwald Thesis Supervisor Professor Timothy M. Swager: , -L i \ O 2 The Development and Application of Metal-Catalyzed Processes for Organic Synthesis by Edward J. Hennessy Submitted to the Department of Chemistry on May 19, 2005 in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy at the Massachusetts Institute of Technology ABSTRACT Chapter 1. Copper-Catalyzed Arylation of Stabilized Carbanions A mild, general catalytic system for the synthesis of a-aryl malonates has been developed. Aryl iodides bearing a variety of functional groups can be effectively coupled to diethyl malonate in high yields using inexpensive and widely available reagents, making this a superior method to those previously described that employ copper reagents or catalysts. The functional group tolerance of the process developed makes it complementary to analogous palladium-catalyzed couplings. Importantly, a set of mild reaction conditions has been developed that minimize product decomposition, a problem that had not been addressed previously in the literature.
    [Show full text]
  • Nucleophilic Aromatic Substitution
    NUCLEOPHILIC AROMATIC SUBSTITUTION Ms. Prerana Sanas M.Pharm (Pharmceutical Chemistry) Asst.Professor, NCRD’s Sterling Institute of Pharmacy Nerul Navi Mumbai Nucleophilic aromatic substitution results in the substitution of a halogen X on a benzene ring by a nucleophile (:Nu– ). Aryl halides undergo a limited number of substitution reactions with strong nucleophiles. NAS occurs by two mechanisms i) Bimoleccular displacement (Addition –Elimination) ii) Benzyne Formation( Elimination –Addition) 7/5/2019 Ms.Prerana Sanas 2 Bimolecular displacement (Addition – Elimination) Aryl halides with strong electron-withdrawing groups (such as NO2) on the ortho or para positions react with nucleophiles to afford substitution products. For example, treatment of p-chloronitrobenzene with hydroxide (– OH) affords p-nitrophenol by replacement of Cl by OH. Nucleophilic aromatic substitution occurs with a variety of strong nucleophiles, including – OH, – OR, – NH2, – SR, and in some cases, neutral nucleophiles such as NH3 and RNH2 . 7/5/2019 Ms.Prerana Sanas 3 Mechanism…… The mechanism of these reactions has two steps: Step i) Addition of the nucleophile (:Nu– ) forms a resonance-stabilized carbanion with a new C – Nu bond—three resonance structures can be drawn. • Step [1] is rate-determining since the aromaticity of the benzene ring is lost. In Step ii) loss of the leaving group re-forms the aromatic ring. This step is fast because the aromaticity of the benzene ring is restored. 7/5/2019 Ms.Prerana Sanas 4 Factors affecting Bimolecular displacement Increasing the number of electron-withdrawing groups increases the reactivity of the aryl halide. Electron-withdrawing groups stabilize the intermediate carbanion, and by the Hammond postulate, lower the energy of the transition state that forms it.
    [Show full text]
  • The Total Synthesis of Securinine and Other Methodology Studies
    University of Windsor Scholarship at UWindsor Electronic Theses and Dissertations Theses, Dissertations, and Major Papers 2010 The total synthesis of securinine and other methodology studies Bhartesh Dhudshia University of Windsor Follow this and additional works at: https://scholar.uwindsor.ca/etd Recommended Citation Dhudshia, Bhartesh, "The total synthesis of securinine and other methodology studies" (2010). Electronic Theses and Dissertations. 8275. https://scholar.uwindsor.ca/etd/8275 This online database contains the full-text of PhD dissertations and Masters’ theses of University of Windsor students from 1954 forward. These documents are made available for personal study and research purposes only, in accordance with the Canadian Copyright Act and the Creative Commons license—CC BY-NC-ND (Attribution, Non-Commercial, No Derivative Works). Under this license, works must always be attributed to the copyright holder (original author), cannot be used for any commercial purposes, and may not be altered. Any other use would require the permission of the copyright holder. Students may inquire about withdrawing their dissertation and/or thesis from this database. For additional inquiries, please contact the repository administrator via email ([email protected]) or by telephone at 519-253-3000ext. 3208. The Total Synthesis of Securinine and Other Methodology Studies by Bhartesh Dhudshia A Dissertation Submitted to the Faculty of Graduate Studies through the Department of Chemistry and Biochemistry in Partial Fulfillment of the Requirements
    [Show full text]
  • Organic Synthesis: New Vistas in the Brazilian Landscape
    Anais da Academia Brasileira de Ciências (2018) 90(1 Suppl. 1): 895-941 (Annals of the Brazilian Academy of Sciences) Printed version ISSN 0001-3765 / Online version ISSN 1678-2690 http://dx.doi.org/10.1590/0001-3765201820170564 www.scielo.br/aabc | www.fb.com/aabcjournal Organic Synthesis: New Vistas in the Brazilian Landscape RONALDO A. PILLI and FRANCISCO F. DE ASSIS Instituto de Química, UNICAMP, Rua José de Castro, s/n, 13083-970 Campinas, SP, Brazil Manuscript received on September 11, 2017; accepted for publication on December 29, 2017 ABSTRACT In this overview, we present our analysis of the future of organic synthesis in Brazil, a highly innovative and strategic area of research which underpins our social and economical progress. Several different topics (automation, catalysis, green chemistry, scalability, methodological studies and total syntheses) were considered to hold promise for the future advance of chemical sciences in Brazil. In order to put it in perspective, contributions from Brazilian laboratories were selected by the citations received and importance for the field and were benchmarked against some of the most important results disclosed by authors worldwide. The picture that emerged reveals a thriving area of research, with new generations of well-trained and productive chemists engaged particularly in the areas of green chemistry and catalysis. In order to fulfill the promise of delivering more efficient and sustainable processes, an integration of the academic and industrial research agendas is to be expected. On the other hand, academic research in automation of chemical processes, a well established topic of investigation in industrial settings, has just recently began in Brazil and more academic laboratories are lining up to contribute.
    [Show full text]
  • Reactions of Aromatic Compounds Just Like an Alkene, Benzene Has Clouds of  Electrons Above and Below Its Sigma Bond Framework
    Reactions of Aromatic Compounds Just like an alkene, benzene has clouds of electrons above and below its sigma bond framework. Although the electrons are in a stable aromatic system, they are still available for reaction with strong electrophiles. This generates a carbocation which is resonance stabilized (but not aromatic). This cation is called a sigma complex because the electrophile is joined to the benzene ring through a new sigma bond. The sigma complex (also called an arenium ion) is not aromatic since it contains an sp3 carbon (which disrupts the required loop of p orbitals). Ch17 Reactions of Aromatic Compounds (landscape).docx Page1 The loss of aromaticity required to form the sigma complex explains the highly endothermic nature of the first step. (That is why we require strong electrophiles for reaction). The sigma complex wishes to regain its aromaticity, and it may do so by either a reversal of the first step (i.e. regenerate the starting material) or by loss of the proton on the sp3 carbon (leading to a substitution product). When a reaction proceeds this way, it is electrophilic aromatic substitution. There are a wide variety of electrophiles that can be introduced into a benzene ring in this way, and so electrophilic aromatic substitution is a very important method for the synthesis of substituted aromatic compounds. Ch17 Reactions of Aromatic Compounds (landscape).docx Page2 Bromination of Benzene Bromination follows the same general mechanism for the electrophilic aromatic substitution (EAS). Bromine itself is not electrophilic enough to react with benzene. But the addition of a strong Lewis acid (electron pair acceptor), such as FeBr3, catalyses the reaction, and leads to the substitution product.
    [Show full text]
  • AROMATIC NUCLEOPHILIC SUBSTITUTION-PART -2 Electrophilic Substitution
    Dr. Tripti Gangwar AROMATIC NUCLEOPHILIC SUBSTITUTION-PART -2 Electrophilic substitution ◦ The aromatic ring acts as a nucleophile, and attacks an added electrophile E+ ◦ An electron-deficient carbocation intermediate is formed (the rate- determining step) which is then deprotonated to restore aromaticity ◦ electron-donating groups on the aromatic ring (such as -OH, -OCH3, and alkyl) make the reaction faster, since they help to stabilize the electron-poor carbocation intermediate ◦ Lewis acids can make electrophiles even more electron-poor (reactive), increasing the reaction rate. For example FeBr3 / Br2 allows bromination to occur at a useful rate on benzene, whereas Br2 by itself is slow). In fact, a substitution reaction does occur! (But, as you may suspect, this isn’t an electrophilic aromatic substitution reaction.) In this substitution reaction the C-Cl bond breaks, and a C-O bond forms on the same carbon. The species that attacks the ring is a nucleophile, not an electrophile The aromatic ring is electron-poor (electrophilic), not electron rich (nucleophilic) The “leaving group” is chlorine, not H+ The position where the nucleophile attacks is determined by where the leaving group is, not by electronic and steric factors (i.e. no mix of ortho– and para- products as with electrophilic aromatic substitution). In short, the roles of the aromatic ring and attacking species are reversed! The attacking species (CH3O–) is the nucleophile, and the ring is the electrophile. Since the nucleophile is the attacking species, this type of reaction has come to be known as nucleophilic aromatic substitution. n nucleophilic aromatic substitution (NAS), all the trends you learned in electrophilic aromatic substitution operate, but in reverse.
    [Show full text]
  • Aryl Halides
    Block 3 Aromatic Hydrocarbons and Halogen Derivatives UNIT14 ARYL HALIDES Structure 14.1 Introduction Electophilic Substitution Reactions Expected Learning Outcomes 14.2 Structure and Reactivity Reactions due to C−X bond 14.5 Reactivity and Relative 14.3 Preparation of Aryl Halides Strength of C−X Bonds in 14.4 Reaction of Aryl Halides Halogen Derivatives Nucleophilic Substitution by 14.6 Summary Addition-Elimination 14.7 Terminal Questions Nucleophilic Substitution via 14.8 Answers Benzene Intermediate 14.1 INTRODUCTION In Unit 13, we have pointed out that there is a difference in the nature of C−X bond of aryl halides and aryl halides. Because of this aryl halides differ from the alkyl halides in their preparation and properties. In this Unit, we will study the unique chemistry of aryl halides. First, we shall take up the structure and reactivity of aryl halides, which is followed by their preparations and properties. At the end of the unit we shall compare the reactivity and relative strength of C−X bond in different type of halogen derivatives. Expected Learning Outcomes After studying this unit, you should be able to: explain why aryl halides are less reactive than alkyl halides, outline the methods of preparation of aryl halides, describe the reactions of aryl halides, and explain the difference in structure and reactivity of alkyl, alkenyl and aryl halides towards nucleophilic substitution reactions. 94 Unit 14 Aryl Halides 14.2 STRUCTURE AND REACTIVITY Before going into the details of the preparations and properties of aryl halides let us take a look at the structure and reactivity of these compounds so that we can understand why their reactions are different from alkyl halides.
    [Show full text]
  • Aromatic Substitution Reactions: an Overview
    Review Article Published: 03 Feb, 2020 SF Journal of Pharmaceutical and Analytical Chemistry Aromatic Substitution Reactions: An Overview Kapoor Y1 and Kumar K1,2* 1School of Pharmaceutical Sciences, Apeejay Stya University, Sohna-Palwal Road, Sohna, Gurgaon, Haryana, India 2School of Pharmacy and Technology Management, SVKM’s NMIMS University, Hyderabad, Telangana, India Abstract The introduction or replacement of substituent’s on aromatic rings by substitution reactions is one of the most fundamental transformations in organic chemistry. On the basis of the reaction mechanism, these substitution reactions can be divided into electrophilic, nucleophilic, radical, and transition metal catalyzed. This article also focuses on electrophilic and nucleophilic substitution mechanisms. Introduction The replacement of an atom, generally hydrogen, or a group attached to the carbon from the benzene ring by another group is known as aromatic substitution. The regioselectivity of these reactions depends upon the nature of the existing substituent and can be ortho, Meta or Para selective. Electrophilic Aromatic Substitution (EAS) reactions are important for synthetic purposes and are also among the most thoroughly studied classes of organic reactions from a mechanistic point of view. A wide variety of electrophiles can effect aromatic substitution. Usually, it is a substitution of some other group for hydrogen that is of interest, but this is not always the case. For example, both silicon and mercury substituent’s can be replaced by electrophiles. The reactivity of a particular electrophile determines which aromatic compounds can be successfully substituted. Despite the wide range of electrophilic species and aromatic ring systems that can undergo substitution, a single broad mechanistic picture encompasses most EAS reactions.
    [Show full text]
  • Simple, Efficient Catalyst System for the Palladium-Catalyzed Amination of Aryl Chlorides, Bromides, and Triflates
    1158 J. Org. Chem. 2000, 65, 1158-1174 Simple, Efficient Catalyst System for the Palladium-Catalyzed Amination of Aryl Chlorides, Bromides, and Triflates John P. Wolfe,† Hiroshi Tomori, Joseph P. Sadighi,‡ Jingjun Yin, and Stephen L. Buchwald* Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Received October 29, 1999 Palladium complexes supported by (o-biphenyl)P(t-Bu)2 (3)or(o-biphenyl)PCy2 (4) are efficient catalysts for the catalytic amination of a wide variety of aryl halides and triflates. Use of ligand 3 allows for the room-temperature catalytic amination of many aryl chloride, bromide, and triflate substrates, while ligand 4 is effective for the amination of functionalized substrates or reactions of acyclic secondary amines. The catalysts perform well for a large number of different substrate combinations at 80-110 °C, including chloropyridines and functionalized aryl halides and triflates using 0.5-1.0 mol % Pd; some reactions proceed efficiently at low catalyst levels (0.05 mol % Pd). These ligands are effective for almost all substrate combinations that have been previously reported with various other ligands, and they represent the most generally effective catalyst system reported to date. Ligands 3 and 4 are air-stable, crystalline solids that are commercially available. Their effectiveness is believed to be due to a combination of steric and electronic properties that promote oxidative addition, Pd-N bond formation, and reductive elimination. Owing to the many important applications of aniline derivatives, and the limitations of most methods for their synthesis, a considerable amount of effort has been recently devoted to the development of catalysts that are capable of effecting the cross-coupling of amines with aryl halides and sulfonates.1 However, the proper choice of catalyst (Pd source, ligand choice) is crucial for the success of these reactions.
    [Show full text]
  • Electrochemical Radical Borylation of Aryl Iodides.Pdf
    borylation, electrochemistry, aryl iodides, arylboronic esters, radical 中 国 化 学 Electrochemical Radical Borylation of Aryl Iodides† Junting Hong,‡,a Qianyi Liu,‡,a Feng Li,b Guangcan Bai,b Guoquan Liu,b Man Li,a Onkar S. Nayal,a Xuefeng Fu,c and Fanyang Mo*,a,d a Department of Energy and Resources Engineering, College of Engineering, Peking University, Beijing 100871, China b State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China c Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China d Jiangsu Donghai Silicon Industry S&T Innovation Center, Jiangsu Weiming Environmental Protection S&T Co., Ltd., No. 38, Guangming Rd, Donghai County, Jiangsu 222300, China Cite this paper: Chin. J. Chem. 2019, 37, 347—351. DOI: 10.1002/cjoc.201900001 Summary of main observation and conclusion Herein, we report the first electrochemical strategy for the borylation of aryl iodides via a radical path- way using current as a driving force. A mild reaction condition allows an assorted range of readily available aryl iodides to be proficiently converted into synthetically valuable arylboronic esters under transition metal catalyst-free conditions. Moreover, this method also shows good functional group toler- ance. Initial control mechanistic experiments reveal the formation of aryl radical as a key intermediate and the current plays an important role in the generation of radical intermediate. Background and Originality Content Scheme 1 Electrochemical borylation of aryl halides Arylboronic acids and their derivatives possess widespread applications in organic synthesis.[1] Consequently, the methods of their preparation have been intensively developed in the past decades.
    [Show full text]
  • Chem 232 Lecture 28.Pdf
    CHEM 232 University of Illinois Organic Chemistry I at Chicago UIC Lecture 28 Organic Chemistry 1 Professor Duncan Wardrop April 22, 2010 1 Today’s Lecture Topics Covered: 1. Aryl Halides - Bonding, Physical Properties and Reactions 2. Nucleophilic Aromatic Substitution of Chlorobenzene 3. Nucleophilic Aromatic Substitution: Addition-Elimination 4. Floxcin - Application of Nucleophilic Aromatic Substitution 5. Nucleophilic Aromatic Substitution: Elimination-Addition 2 What’s the Difference Between Ar- and Ph-? Phenyl refers specifically to this: Aryl is a general term for all aromatic ring systems: C N N O 3 Chapter 23 Aryl Halides 4 23.1 Bonding in Aryl Halides 5 Aryl Halides X Aryl halides are halides in which the halogen is attached directly to an aromatic ring. Carbon-halogen bonds in aryl halides are shorter and stronger than carbon- halogen bonds in alkyl halides. 6 Dissociation Energies of Selected Compounds Bond Energy: kJ/mol (kcal/mol) X = H X = Cl CH3CH2X sp3 410 (98) 339 (81) 2 H2C CHX sp 452 (108) 368 (88) X sp2 469 (112) 406 (97) 7 Resonance Picture X X X H H C-X bonds in aryl halides have more double bond character than C-X bonds in alkyl halides 8 23.2 Sources of Aryl Halides 9 Preparation of Aryl Halides Halogenation of arenes (Section 12.5) H Br FeBr3 Br2 HBr electrophilic aromatic substitution 10 Preparation of Aryl Halides The Sandmeyer reaction (Section 22.17) N H H N N Cl Cl NaNO2 CuCl O HCl, H2O O heat O N+ N+ N+ O– O– O– Primary Aryl Diazonium Aryl Chloride Arylamine Salt diazotization-nucleophilic aromatic substitution 11 Preparation of Aryl Halides The Schiemann reaction (Section 22.17) N H H N BF4 N F 1.
    [Show full text]
  • Metal-Catalysed Halogen Exchange Reactions of Aryl Halides
    EMERGING AREA www.rsc.org/obc | Organic & Biomolecular Chemistry Metal-catalysed halogen exchange reactions of aryl halides Tom D. Sheppard* Received 15th October 2008, Accepted 11th December 2008 First published as an Advance Article on the web 30th January 2009 DOI: 10.1039/b818155a Aryl halides are common synthetic targets themselves, and also highly versatile synthetic intermediates. Aryl chlorides are much more widely available and easier to synthesise than the other halide derivatives, so the development of effective methods for interconverting aryl halide derivatives would therefore be extremely useful. This article outlines which transformations are particularly desirable, and describes the progress that has been made on developing methods for carrying out those transformations using copper, nickel or palladium catalysts. The possible mechanisms of these reactions are discussed, with a view to identifying areas for future investigation. Introduction Aryl halides are highly useful synthetic intermediates which have many applications in organic chemistry. The aryl halide functional group can readily be exploited in a wide range of cross-coupling reactions, be used for the formation of organometallic reagents or act as a precursor for the generation of free-radical intermediates (Scheme 1). Aryl halides are often important synthetic targets in their own right, as illustrated by the pharmaceuticals and agrochemicals shown in Fig. 1. The regioselective synthesis of aryl halide derivatives containing radioactive halogen isotopes is also of great importance for medical applications (e.g. introduction of 18Flabels for PET).1,2 Scheme 1 Useful reactions of aromatic halides. The properties of aryl halides are highly dependent on the nature of the halogen atom.
    [Show full text]