Copper catalysis aryl halide reactions

This reaction is similar to 13-1 and, like that one, generally requires activated substrates. With unactivated substrates, side reactions predominate, though aryl methyl ethers have been prepared from unactivated chlorides by treatment with MeO in HMPA. This reaction gives better yields than 13-1 and is used more often. A good solvent is liquid ammonia. The compound NaOMe reacted with o- and p-fluoronitrobenzenes 10 times faster in NH3 at — 70°C than in MeOH. Phase-transfer catalysis has also been used. The reaction of 4-iodotoluene and 3,4-dimethylphenol, in the presence of a copper catalyst and cesium carbonate, gave the diaryl ether (Ar—O—Ar ). Alcohols were coupled with aryl halides in the presence of palladium catalysts to give the Ar—O—R ether. Nickel catalysts have also been used. ... 

Although the preparation has been repeated, there have been no other reports of the type of reaction, (described in 1923) in which carbazole in the presence of excess potassium hydroxide and nitrobenzene at only 50°C gave a good yield of 9-(4-nitrophenyl)-carbazole, presumably via an adduct such as 43 subsequently oxidized by excess nitrobenzene and/or air. More recent examples of N-arylation of carbazoles have involved copper catalysis in reaction of aryl halides with carbazoles. Thus, copper bronze and potassium carbonate heated with the carbazole and the appropriate aromatic halide have produced 9-(4-methoxyphenyl)- and 9-(2-tolyl)carbazoles 9-(4-phenylphenyl)carbazole, l,4-di(carbazol-9-yl)benzene, 4,4 -di(carbazol-9-yl)biphenyl, and 9-(2-pyridyl)- and 9-(2-quinolyl)carbazoles 9-[2-(2-phenylphenyl)phenyl]- and 9-[2-(4-methylphenyl)phenyl] carbazoles 9-(3-bromo-6-nitrophenyl)-, 9-[3-(carbazol-9-yl]-, 9-(2-nitrophenyl)-, 9-(4-methyl-2-nitrophenyl)-, 9-(4-methoxycarbonyl)-l-nitro-, and l-nitro-9-(4-tolyl)carbazoles 9-(2-methoxycarbonylphenyl)carbazole 9-[2- 2-... 

In the last few years numerous reports have been published in the field of microwave-promoted aryl halide cyanation, utilizing nickel [71], palladium [72,73] and copper [74,75] catalysis. Even water [75] and ionic liquids [76] have proven useful as solvents in these processes. Srivastava and Collibee have exemplified a swift and dynamic procedure using polymer-supported triphenyl phosphine to enable easy subsequent removal through filtration [72]. As shown in Scheme 19, both bromides and iodides could be activated using palladium catalysis in DMF. Even without optimization of the individual reaction times, the overall process time involving simple filtration and extraction for compound isolation appears to be short. 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

It was suggested that the addition of 1,10-phenanthroline or dba as ligands to the copper salt creates a soluble, stable, and more active copper catalyst species in situ, which in turn improves the turnover rate of the reaction and lowers the activation barrier, in comparison to the classical Ullmann-type catalysis. Though only a catalytic amount of copper is needed, a stoichiometric amount of 1,10-phenanthroline (relative to aryl halide) is required to provide efficient catalysis. 

The arylation of nucleophiles by reaction with diaryliodonium salts can be greatly facilitated by copper catalysis. This effect was observed by Beringer et al in the thermal decomposition of diaryliodonium halides as well as by Caserio et al in the hydrolysis of diaryliodonium salts. 2 jhe thermal decomposition of diphenyliodonium chloride shows a reduced activation energy upon copper catalysis Ea = 19 kcal/mole in Methylene glycol in the presence of CuCl instead of 31 kcal/mole in the absence of catalyst.From the synthetic point of view, the copper-catalysed arylation with diaryliodonium salts has been particularly useful in the case of a number of reactions involving heteroatomic nucleophiles, in particular for 5-, 5e-, O- and N-arylation reactions. 

Another important class of reactions involves the introduction of a cyano group by substitution in an Ar-Z precursor. In fact, novel pathways leading to aromatic nitriles-for example, photosubstitution reactions-are desirable in view of the many applications of aryl cyanides as agrochemicals and pharmaceuticals. Today, the classical copper(l)-mediated Rosenmund-von Braun and Sandmeyer reactions, from aryl halides and aryldiazonium salts respectively, have been supplanted by reactions which employ palladium- or copper-catalysis [57]. The rather common use of excess cyanide anion may lead to a deactivation of the catalyst, and affect to a remarkable extent each of the key steps of the catalytic cycle [58aj. Although the use of complex iron cyanide has been shown to offer an effective solution to this limitation [58b,c], photocyanation provides an equally useful alternative [10],... 

There has been a review of the use of transition-metal catalysts in the formation of C—S, C—Se, and C—Te bonds." Copper catalysis enables the formation of unsymmetrical diaryl thioethers from two differently substituted aryl iodides using ethylxanthogenate as the source of sulfur. Initial formation of an aryl xanthate, such as (17), is followed by hydrolysis to the arenethiolate, which couples with the second aryl iodide." Copper catalysis has also been used in the methylthiolation of aryl halides by DMSO. The method requires the presence of a source of fluoride ions, such as zinc fluoride." In the presence of a palladium catalyst, the reaction of aryl and heteroaryl bromides with AgSCp3 gives the corresponding trifluoromethylsulfldes." ... 

The possibilities for the formation of carbon-carbon bonds involving arenes have been dramatically increased in recent years by the use of transition metal catalysis. Copper-mediated reactions to couple aryl halides in Ulknann-type reactions [12, 13] have been known for many years, and copper still remains an important catalyst [14, 15]. However, the use of metals such as palladium [16,17] to effect substitution has led to such an explosion of research that in 2011 transition metal-catalyzed processes comprised more than half of the reactions classified as aromatic substitutions in Organic Reaction Mechanisms [18]. The reactions often involve a sequence outlined in Scheme 6.6 where Ln represents ligand(s) for the palladium. Oxidative addition of the aryl halide to the paiiadium catalyst is followed by transmetalation with an aryl or alkyl derivative and by reductive elimination to give the coupled product and legeuCTate the catalyst. Part 6 of this book elaborates these and related processes. 

Over a century ago, Ullmann reported coupling reactions catalysed by metallic copper. ° ° The harsh conditions typically involved limited its applicability, but Ullmann s work ultimately stimulated the search for milder conditions using copper catalysis. Both copper(I) and copper(II) salts can catalyse the coupling of aryl halides with a range of heteroatom nucleophiles, including phenols (Scheme 2.168, 2.169), ° alcohols (Scheme 2.170),thiols (Scheme 2.171, 2.172), amines (Scheme 2.173), anilines (Scheme 2.174)2" and A/ -heterocycles (Scheme 2.175,2.176).2i2.2i3... 

For example the coupling reactions of aryl halides, classically based on copper metal catalysis (Ullmann coupling), can now be advantageously realized when using Ni(0) or Pd(0) reagents, transient aryl metal derivatives being formed as reactive intermediates. 

Organoindium reagents can also be used in the crosscoupling reaction with imines via copper(I) chloride catalysis. Copper-catalyzed direct amination of nitrobenzenes with O-alkylhydroxylamines is known however, more general ami-nation and amidation reactions involve activation of aryl halides with CuCl and l,10-phenanthroline(phen) or other sterically well-defined ligands. ... 

Sodium mercaptides are prepared from the mercaptans and aqueous or alcoholic solutions of sodium hydroxide or alcoholic sodium eth-oxide. The sodium mercaptide reacts with halides, chlorohydrins, esters of sulfonic acid, or alkyl sulfonates [6] to give sulfides in yields of 70% or more. A recent report describes a general procedure for synthesizing aryl thioesters by a nucleophilic displacement of aryl halide with thiolate ion in amide solvents. No copper catalysis is necessary as in an Ullmann-type reaction. 

Recently, hydrosilanes are also employed for the silylation of aryl halides in the presence of a palladium,platinum, or rhodium catalyst. In view of atom efficiency, this procedure has an advantage. Palladium-catalyzed reactions are suitable for the silylation of electron-rich aryl halides, whereas rhodium-catalysis works well with a wide range of aryl halides (Scheme 3-17). Silylation of allyl halides with trichlorosilane proceeds in the presence of a copper catalyst. ... 

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