Halides, aryl reaction with copper

The Ullmann biaryl synthesis(lQl,102) invokes the reaction of copper powder with aryl halides at relatively high temperatures, typically 100-300 °C, to give biaryl products. The intermediacy of arylcopper species is presumed but not specifically proven due to the instability of the arylcopper at the temperatures required for reaction. The Ullmann reaction has seen appreciable usage as it allows considerable functionality to be incorporated in the products. 

Terminal alkynes can be alkenylated by alkenyl triflates (bromides, iodides) and aryl-ated by aryl triflates (bromides, iodides). These reactions are called Cacchi coupling reactions if the reaction is catalyzed by Cu(I) and Pd(0) and if triflate reagents are employed, Sonogashira-Hagihara coupling reactions if the reaction is catalyzed by Cu(I) and Pd(0) and halides are employed as substrates, and Stephens-Castro coupling reactions for the more specialized case of the noncatalyzed coupling of copper acetylides with aryl halides. 

Sodium benzenetellurolate is arylated in liquid ammonia via photoinduced reactions with aryl halides Aryl iodides reacted with sodium benzenetellurolate in the presence of copper(I) iodide in hexamethylphosphoric triamide (but not in DMF or DMSO) to produce aryl phenyl tellurium compounds. However, lithium benzenetellurate reacted with 1,2-bromoiodobenzene and lithium methane tellurolate with 1,2-dibromobenzene in tetrahydrofuran at 20° to yield l,2-bis[organotelluro]benzenes . 

The last example discussed concerns secondary acyclic amides, known to be poor nucleophilic partners rarely involved in coupling reactions with aryl halides. Recently a procedure (TaUlefer, Monnier et al.) has described a versatile catalytic system allowing their intermolecular N-arylation (Scheme 12) [165]. Overcoming this challenge using a simple copper/diketone (L27) system offers a general method for the preparation of acyclic tertiary amides. The structure-activity relationship studies of these important targets are thus facilitated by this method, which complements the known systems based on palladium. 

The copper species formed depends on the solvent, and three different species were detected by F NMR, although the structure of each species was not elucidated [245 This copper reagent undergoes a variety of coupling reactions with aryl, alkenyl, allyl, and acetylenic halides [244, 245 (equation 162)... 

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. ... 

The reaction between aryl halides and cuprous cyanide is called the Rosenmund-von Braun reactionP Reactivity is in the order I > Br > Cl > F, indicating that the SnAt mechanism does not apply.Other cyanides (e.g., KCN and NaCN), do not react with aryl halides, even activated ones. However, alkali cyanides do convert aryl halides to nitrilesin dipolar aprotic solvents in the presence of Pd(II) salts or copper or nickel complexes. A nickel complex also catalyzes the reaction between aryl triflates and KCN to give aryl nitriles. Aromatic ethers ArOR have been photochemically converted to ArCN. 

There are many other transition-metal catalyzed coupling reactions that are based on organic halides in aqueous media. One example is the coupling of terminal alkyne with aryl halides, the Sonogashira coupling, which has been discussed in detail in the chapter on alkynes (Chapter 4). An example is the condensation of 2-propynyl or allyl halides with simple acetylenes in the presence of copper salts. 

The reaction of benzotriazoles with aryl halides catalyzed by a mixture of Pd(dppe)Cl2 (DPPE = bis-(diphenylphosphino)ethane) or Pd(dppf)Cl2, copper(I)iodide or copper(II)carboxylates, and a phase-transfer catalyst has been shown to proceed in good yield in DMF solvent.104 Both copper and palladium were required for these reactions to occur at the N-l position in high yields. Similar results for the coupling of amines with aryliodonium salts in aqueous solvent were observed.105... 

Similarly, copper salts (cupric and cuprous) facilitate the reaction of aryl halides with trialkyl phosphites in the formation of dialkyl arylphosphonates under conditions like those found in nickel systems.37-39 Again, the copper salts appear to undergo an initial reaction with the phosphites to form a complex that subsequently undergoes reaction with the aryl halide. The requirement for copper is also similar to that for nickel saltstonly a catalytic amount is needed. Further, a preference among halides on the aromatic ring is noted iodide is replaced preferentially to other halides (Figure 6.10).40... 

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-... 

---