Organicchemistryextra work copper catalyzed organic reactions

VIETNAM NATIONAL UNIVERSITY – HO CHI MINH CITY HO CHI MINH CITY UNIVERSITY OF TECHNOLOGY ORGANIC CHEMISTRY Extra Work Copper-catalyzed Organic Reactions Class: A01 Group: 08 Term: 212 Teacher: Professors PhD Phan Thanh Son Nam ►Ho Chi Minh City, February 2022◄ MEMBERS AND WORK ASSIGNMENT Student code Name Mission - Format báo cáo (hàng tuần) - Introduction - Ullman reaction: Classic Ullman reaction - Format báo cáo (hoàn chỉnh) - Ullman-type reactions: + Introduction + Mechanism + Synthesis of ether 2010777 Lê Trình Khánh Vân 2010587 Nguyễn Phú Sỹ 2010606 Lê Nguyễn Vân Thanh - Ullman-type reactions: Synthesis of amine 2010485 Nguyễn Trần Minh Nhật - Chuẩn bị slide thuyết trình PPT - Rosenmund-von Braun Reaction 2011784 Nguyễn Ngọc Kiều Oanh - Chan-Lam coupling: Introduction 2010683 Nguyễn Tấn Tâm Thy - Chan-Lam coupling: Recent Literature 2010005 Vũ Thế Anh - Chan-Lam coupling: Mechanism TABLE OF CONTENTS A Introduction: Copper, a naturally element is present in the earth's crust, in oceans, lakes, and rivers, can be found from minute trace element levels through to rich mine deposits It is essential to the life of even plants, animals and also humans, all need copper to function properly Before applying as a catalysis in organic synthesis, copper is widely known as a very versatile and environmentally metal that has been used for construction problem or appeared in many biological processes Moreover, copper has been extensively applied in catalyst in organic compounds, which is extremely inexpensive and plentiful Examine copper and its use in organic synthesis can be considered as a more costeffective and maintainable for researchers in academia and industry In point of fact, copper has been studied and applied as a chemical catalyst for organic synthesis since the late 20th century There has been a steady growth in publications on this topic since 1988 From the late 1980’s to early 1990’s, the topics focused on copper nitrene reactivity, copper carbene chemistry, conjugate additions and cross-coupling reactions Nowadays, while many new catalysts have found, copper still plays an important role in organic transformations A web of science TM topic search of “copper in organic synthesis” pointed out that over 500 papers had been published in 2014 There are numerous factors that lead to the growth in Cu-catalyzed methodologies First, copper is an earth-abundant metal, making its use more effective and more sustainable than transition metal catalysts Second, there is the diversity application of copper chemistry Depending on its oxidation state (copper can easily access Cu(0), Cu(I), Cu(II), and Cu(III) oxidation states), this metal can catalyze effectively reactions relating on both one and twoelectron (radical and polar) mechanisms, or both Additionally, dissimilar oxidation states of copper connect well with a large number of different functional groups via Lewis acid interactions or π-coordination and is wellknown to activate terminal alkynes These features confer a remarkably broad range of activities allowing copper to catalyze the oxidation and oxidative union of a wide range of substrates Its powerful catalytic ability can also be proven by the known named reactions based on copper catalysts For instance, asymmetric Ullmann and Goldberg couplings C–C and C–N cross-coupling reactions which were discovered over a century ago, has really developed brightly over the past twenty years thanks to its outstanding catalytic activity which are even better than that of noble metal catalysts such as palladium Using the copper catalysts, which opposed to the use of stoichiometric amounts of other typical promoters (like Bronsted acids, bases, radicals, ), has permitted the discovery of many new synthetic for organic chemistry Consequently, the beginning of using these copper-catalyzed organic reactions in different areas paved the way for the more convenient and successful synthesis of high value-added organic products (for instance agrochemical or pharmaceutical commodities) than before In this report, we will present kinds of organic reactions using copper catalyst which are well-known and commodious application Part I talks about Ullman reaction which contains Classic Ullman reaction, Ullman-type reaction and several typical synthesis of this reaction Part II talks about Rosenmund-von Braun reaction which contains its mechanism and recent research of this reaction Part III talks about Chan-Lam coupling reaction which contains its mechanism and recent research of this reaction B Copper catalysis in organic reactions I Ullman reaction: Classic Ullman reaction: Ullmann-type reactions: 2.1 Introduction: After the discovery of the classic Ullmann reaction, there have been many studies on other reactions that were applied the same methodology such as the synthesis of N-aryl amines, ethers, aryl amides, and other coupling reactions with various reactants and catalytic forms All of them are usually called “Ullmann-type” reactions, or Ullmann condensation Compared to other catalytic methodologies, copper-catalyzed reactions generally required harsh conditions (high temperature, strong bases, long reaction time,…), electron-poor aromatic substrates and high-boiling polar solvents Despite this, numerous industrial applications, such as the synthesis of intermediates in pharmaceutical, agrochemical, and polymer chemistry were found over the years However, recent reports have generated a renewed interest in Ullmanntype reactions by demonstrating the use of auxiliary ligands The addition of the ligands to the catalysts can improve the solubility of the copper complexes, leading to overcoming many drawbacks of the classical reaction As a result, a wide range of new procedures became available for applications in many areas 2.2 Mechanism: Generally, Cu(I) species are accepted as the active catalysts in Ullmanntype couplings Despite examples using either Cu(0) or Cu(II) species as the copper source are found, the in situ reduction or oxidation reactions occur to generate the active Cu(I) catalytic species Besides, in most of the published studies, the presence of a base causes the deprotonation of the heteroatom nucleophile (H-Nuc) to readily form Cu(I)-Nuc species, which are reputed as the real catalyst of reactions Among many mechanistic studies, the proposal involving the coordination of the nucleophile at the Cu(I) centre before the activation of the aryl halide is the most accepted one According to experimental studies, the nature and concentration of the auxiliary ligand used have a big impact on the equilibrium between different Cu(I) complexes present in solution as well as in the formation of the active catalysts Until the 1990s, the mechanisms proposed can be divided into four main classes: • Aromatic nucleophilic substitution, with Cu(I) π-coordinating to the aromatic ring of the aryl halide to render the aromatic position more electrophilic and susceptible to substitution • Mechanisms via Single Electron Transfer (SET) or Halogen Atom Transfer (HAT), involving the redox couple Cu(I)/Cu(II) and radical intermediates • Metathesis mechanisms, leading to the formation of four-membered cyclic transition states, through coordination of Cu to the halogen atom of the aryl halide, making it a better leaving group • Mechanisms involving an oxidative addition – reductive elimination cycle with Cu(III) intermediates, either via direct oxidation Cu(I)/Cu(III) or stepwise oxidation Cu(I)/Cu(II)/Cu(III) The most widely accepted mechanism is the two-electron redox process involving oxidative addition of the Cu(I)-Nuc complex to the aryl halide, leading to the formation of a Cu(III) intermediate There are two possible pathways for the relative order of the oxidative addition and the coordination of the nucleophile to the Cu(I) centre In one way, the first step is the oxidative addition and the coordination of the nucleophile to the Cu(I) centre, to form a copper(III) intermediate and the halide on copper is subsequently exchanged for the nucleophile and the obtained intermediate for this mechanism The final step is the reductive elimination step to form the Aryl-Nu coupling product and regenerate the Cu(I) species ready to reenter the catalytic cycle Although this proposed way cannot be dismissed, it is usually considered as a less probable mechanistic proposal Most recent reports favour another way in which the nucleophile reacts with the copper(I) halide catalyst before the oxidative addition Figure x Cu(I)/Cu(III) cycle catalyst proposed for most Ullman-type couplings 2.3 Recent research: 2.3.1 Synthesis of ethers – the most typical application of Ullmann-type reactions: Just a few years after the discovery of the classic Ullmann reaction, in 1905, the same methodology was applied by Ullmann to the reaction between an aryl iodide or bromide and a phenol for the formation of diaryl ether Since then, there are many reports about the use of auxiliary ligands in combination with bases such as K PO , Cs 2CO3 , and K 2CO3 to increase the activity and broaden the substrate scope of the synthesis reaction In 2003, Dawei Ma and his co-worker, Qian Cai, had a study about the Ullmann-type diaryl ether synthesis under the assistance of N,N- dimethylglycine They carried out reactions between either aryl iodides or aryl bromides and phenols with copper catalysis and the presence of the N,Ndimethylglycine or N,N-dimethylglycine hydrochloride salt These experiments showed that under the action of N,N-dimethylglycine, CuI-catalyzed coupling reaction of aryl halides and phenols could be carried out at 90o C to give the corresponding diaryl ethers in good to excellent yields 2.3.2 Synthesis of amine 2.3.2.1 Reaction of aryl halides with amino acids: Normal, aryl halides reaction occurs when the temperature is 150oC ad completed in 3-5h Effect of structure of R-amino acid in the Ullmann reaction and that the coupling of R-amino acids with aryl halides catalyzed by CuI makes temperature decrease more than tradditional Ullman but it takes longer time 48h to completed The basic mechanism of the Cu(I)- catalyzed coupling reaction of aryl halides with R-amino acid is : Firstly, ion Cu+ reacts with R-amino acid salt to produce chelate A, which coordinated with a suitable aryl halide to provide the π-complex B Then internal molecules nucleophilic substitution occurred at the aromatic ring to give intermediate C This step will increase distance between the amino and carboxylate groups, so the ring size in the transition state C became larger and thereby C would be more unstable Finally, HX was removed from C with the assistance of potassium carbonate to deliver another π-complex, D, which could decompose to produce the N-aryl R-amino acid and regenerate the cuprous ion (1) (1) CuI-Catalyzed Coupling Reaction of β-Amino Acids or Esters with Aryl Halides at Temperature Lower Than That Employed in the Normal Ullmann Reaction Facile Synthesis of SB-214857 D Ma, C Xia, Org Lett., 2001, 3, 2583-2586 2.3.2 Copper-Catalyzed Coupling of Alkylamines and Aryl Iodides: The formation of carbon-nitrogen bonds is very popular to preparation of numerous products important in pharmaceutical and material sciences Efficient palladium-catalyzed aminations of aryl halides have been developed in recent years and have proven useful in both academic and industrial laboratories This method is being improved but they found out that limitations still exist Although using copper as catalysts still have a lot of limitations such as high temperature, poor substrate scope, , but Copper-mediated Ullmann and Goldberg couplings are attractive for large and/or industrial-scale applications Cu-catalyzed amination of functionalized aryl iodides using air-stable CuI as the catalyst, ethylene glycol as ligand and unpurified 2-propanol as the solvent; these reactions can be performed without protection from air or moisture 2.3.2.2 Copper-Catalyzed Amination of Bromobenzoic Acids Using Aliphatic and Aromatic Amines: Firstly, Ullman directs synthesis of N-aryl anthranilic acids from 2chlorobenzoic acid Then, various copper-catalyzed amination procedures suitable to ortho-chlorobenzoic acids Palladium-catalyzed amination of aryl halides exhibiting free carboxylic acid groups in the meta or para position N-Aryl anthranilic acids are usually prepared from 2-chlorobenzoic acids or via coupling of anthranilic acid and aryl halides, although a wide range of 2bromobenzoic acid derivatives are readily available Common drawbacks of cross-coupling procedures using bromobenzoic acids are limited tolerance of functional groups due to very high reaction temperatures and low yields with sterically hindered arylamines.We therefore wish to report a highly regioselective synthetic procedure providing convenient access to a range of Naryl and N-alkyl anthranilic acids exhibiting various functional groups through Cu-catalyzed amination of 2-bromobenzoic acids So, there is a highly regioselective synthetic procedure providing convenient access to a range of N- aryl and N-alkyl anthranilic acids exhibiting various functional groups through Cu-catalyzed amination of 2-bromobenzoic acids Initially, we employed CuI, Cu2O, or Cu and combinations thereof as catalysts in the reaction of 2-bromobenzoic acid, and aniline, using n-butanol, 2-ethoxyethanol, and ethylene glycol as solvent Further screening of bases (Na2CO3, Cs2CO3, K3PO4, NaOAc, tert-BuOK, and 2,2,6,6- tetramethylpiperidine) The best results for the synthesis of N-phenylanthranilic acid, are obtained in the presence of potassium carbonate and catalytic amounts of Cu powder and copper(I) oxide in 2-ethoxyethanol at 130 °C.(3) (3) Efficient Copper-Catalyzed Synthesis of 4-Aminoquinazoline and 2,4Diaminoquinazoline Derivatives X Yang, H Liu, R Qiao, Y Jiang, Y Zhao, Synlett, 2010, 101-106 II Rosenmund-von Braun Reaction Introduction Aryl nitriles play a significant role as important intermediates in organic chemistry synthiting Besides, it is a usual component of many herbicides, pharmaceuticals, agrochemicals, dyes,… Consequently, the synthesis way of aryl nitriles has a significant attention which explain why the development of methodologies is consider fast In recent year, numerous efforts have been devoted to transition metal-catalyzed cyanation reactions of aryl (pseudo)halides, organometallic reagents and aryl C–H bonds… But going back in time, the kick start of this chain of efforts, it must be Rosemund-von Braun synthesis Rosenmund–von Braun synthesis is an organic reaction, turning an aryl halide into an aryl nitrile with the presence of cuprous cyanide The name of the reaction is taken after Karl Wilhelm Rosenmund and Julius von Braun Karl Wilhelm Rosenmund together with his Ph.D student Erich Struck found that aryl halide reacts with alcohol water solution of potassium cyanide and catalytic amounts of cuprous cyanide at 200 °C Seperately, Alfred Pongratz and Julius von Braun changed the reaction by rasing the temperatures and removing solvent In the reaction, with an excess of copper(I) cyanide in a polar high-boiling solvent such as DMF, nitrobenzene, or pyridine at reflux temperature, aryl nitriles are produce from the cyanation of aryl halides Mechanism of the Rosenmund-von Braun Reaction 2.1 Mechamism The mechanism involves a middle step of forming a Cu(III) species form oxidative addition of the aryl halide, follow by a reductive elimination then leads to the aryl nitrile product Unfortunately, the excess amount of copper cyanide and the use of a highboiling point, polar solvent occurs to be an obstacle for the purifying process Futhermore, extreme teamperatures (up to 200°C) decrease the ability to tolerate of the functional group Instead, using alkali metal cyanides or cyanation reagents (eg Cyanohydrins), a catalytic amount of copper(I) iodide and kalium iodide, allows a mild, catalytic cyanation of various aryl bromides A simple mechanism which is similar to that of an Ulamann-type reaction can be prososed using aryl iodides, sodium cyanide and copper(I) iodide as catalyst: Adding alkali metal iodides to the reactions with aryl bromides could take part in an additional equilibria in which aryl bromides give the more reactive aryl iodides: For example, the formation of a copper(III) species and the use of cyanohydrins is discussed by H.-J Christeau (Chem Eur J., 2005, 11, 2483 DOI) III Chan-lam coupling reaction Introduction Chan-Lam reactions are expected as the most efficient artificial methods to build a variety of carbon-heteroatom or carbon-carbon bonds A series of these were developed to boost organic synthesis In this part, we will discuss more in-depth the mechanism and the role of copper-related catalysts in these reactions The Chan-Lam coupling reaction is a cross-coupling reaction between an aryl boronic acid and an alcohol or an amine to form the corresponding secondary aryl ethers or aryl amines respectively The reaction is induced by a stoichiometric amount of copper(II) or a catalytic amount of copper catalyst which is reoxidized by atmospheric oxygen or another primary oxidant This reaction can be conducted at room temperature in air, which is more advantageous than others General scheme of Chan-Lam coupling Compared with the Ullmann-Goldberg reaction or Buchwald-Hartwig reaction, which were catalyzed by copper, Chan-Lam couplings proceed under milder conditions, often conducted at room temperature Also, this reaction is more attractive for complicated and sensitive substrates Some examples of this reaction: Chan-Lam coupling reactions for C-N bonds formation: In the beginning, the ligand switch took place between A and 2a to form the intermediate B followed by transmetallation of arylboronic acid producing the complex C Then reductive elimination of species C delivered the target products and copper(0) Meanwhile, the oxidation of complex C in the presence of ambient oxygen from air generated the copper(III) species D which provided the products and copper(I) via reductive elimination was also possible Eventually, the copper(0) or copper(I) could be oxidized to the active copper(II) species if the coupling proceeds in a catalytic manner Related research Many pieces of research have been conducted following the Chan-Lam coupling reaction’s mechanism Copper-related catalyst in different forms plays different roles in many reactions By changing the type of copper catalysts or the ratio of reactants and catalysts, the yield of reactions may change We mention some types of reactions, classified based on the functional groups of the product 3.1 Amine 3.1.1 Ligand and base–free copper (II) catalyzed C-N bond formation: Cross-Coupling reactions of organoboron compounds with aliphatic amines and anilines 3.1.1.1 Summary The reaction describes a C-N bond formation in a ligandless and base-free Arylboronic acids react with potassium aryltriflouroborate salts with primary and secondary aliphatic amines and anilines Catalytic copper (II) acetate monohydrade and Å molecular sieves in dichloromethane in slightly elevated temperatures under oxygen atmosphere 3.1.1.2 General reaction: 3.1.1.3 Reaction yields of different reactants with the highest yeilds There are many yields of reaction depending on BXn is BF3-K+ or B(OH)2 react with different amines The reaction between Isopropin amine with both types of BXn gives the highest yield 3.1.2 Spectroscopic studies of the Chan-Lam amination: A mechanism inspired solution to boronic ester reactivity 3.1.2.1 Summary After 14 years since the report in section 3.1.1 has been published, in 2017, there was a piece of research that shows a good way to synthesize amine based on the Chan-Lam mechanism has been reported The new report used almost the same copper-related catalysts to the old one but in different equivalent concentration and just a little bit changing There were some new methods which are used to improve the reaction such as: spectroscopy, computational modeling, crystallography However, Chan-Lam amination still has some problems such as: byproducts formation, elusive mechanism,…The report’s goal is to give us a better perspective about the Chan-Lam amination through the spectroscopic method in many aspects then provide us a simple solution to the catalytic Chan-Lam amination for more study in the future But in this section of extra work, we just get some basic knowledge in the report and know the general reaction to find out that when we change the amount of catalyst what will happen to the yields of the reaction 3.1.2.2 General reaction This reaction used eq of amine and 0.2 eq of Cu(Oac)2 in MeCN at a higher temperature than the one in section 3.1.1 One difference between the two reactions is that the one in section 3.1.1 used Aryl boronic acids but this reaction use aryl boronic acid pinacol ester 3.1.2.3 Reaction yields of some products Below here are some products with the highest yields of the above reaction Alkyl amines: Aryl amines: