Copper with aryl halides

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 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. 

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... 

Under copper catalyzed conditions azoles (i.e. imidazoles) couple not only with aryl halides but also with arylboronic acids. The reaction, run in the presence of oxygen, follows a unique path (for details see Chapter 2.5.). From the synthetic point of view, the arylation of imidazole proceeds in good yield, although the regioselectivity in the arylation of 4-substituted imidazoles is only moderate (6.70.),102... 

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. 

Synthetic reactions involving activation of alkenyl- and arylsilanes by copper salts have also been reported. A copper-mediated system is effective in the cross-coupling reaction of aryl- and heteroarylsilanes with aryl halides under Pd-free conditions (Equation (13)).66 Alkenyl- and arylsilanes as well as alkynylsilanes undergo homocoupling in the presence of Cul and air.65,65a Functionalized alkenyl- and arylsilanes bearing a coordination site in the vicinity of silicon (e.g., 7) are easily activated by copper salts even at room temperature (Scheme 5).67,67l 67e 68 q-jle organocoppers such as 8 are useful for carbon-carbon bond-forming reaction with carbon electrophiles. 

Copper(I) derivatives of metal diynyl complexes have proven to be useful synthetic intermediates in Cadiot-Chodkiewicz coupling reactions,290 292 and similar species are implicated in coupling of metal diynyls with aryl halides under Pd/Cu catalyzed (Sonogashira) conditions241,242 and in the Cul-catalyzed coupling reactions of metal diynyl species with other metal halides.293... 

The synthesis of symmetrically and unsymmetrically substituted J ,J -diarylimidazolin-2-ones by copper-catalyzed arylamidation under microwave-assisted and conventional conditions was studied <07S1403>. Palladium-catalyzed direct functionalization of imidazolinone with aryl halides has been reported <07JA7768>. 

Arylphenoxazines have been obtained similarly with aryl halides in the presence of sodamide,67 or on heating phenoxazine and an aryl iodide or aryl bromide with anhydrous potassium carbonate and a small amount of copper bronze as catalyst.10... 

Since then, experiments have been reported which indicate that (1) organocopper compounds will couple with aryl halides (2) arylcopper compounds can be oxidatively and thermally dimerized (3) arylcopper compounds are intermediates in the Ullmann reaction (4) organocopper compounds are intermediates in copper-catalyzed decarboxylations and (5) copper-promoted coupling reactions are not restricted to aromatic halides. The copper(I) oxide-promoted coupling reactions, however, have still to yield firm evidence of a copper intermediate. 

The reactions between i-dinitrobenzene or 1,3,5-trinitrobenzene, aryl halides, and copper(I) oxide in quinoline 17-19, 21) provide a simple synthesis of nitrobiphenyls uncontaminated by symmetrical biphenyls. These couplings may be related to the Ullmann reaction, the decarboxylative coupling of benzoic acids with aryl halides, and the preparation of ethers from phenols 165). Although no intermediates... 

Fig. 8. Proposed scheme for the reaction of copper(I) oxide with aryl halides in pyridine.

The Castro-Stephens coupling also involves the reaction of copper(I) acetylide with aryl halides to form diarylacetylenes. 

Aryl selenides (ArSeAr and ArSeAr ) can be prepared by similar methodology. Symmetrical diaryl selenides were prepared by the reaction of iodobenzene with diphenyl diselenide (PhSeSePh), in the presence of Mg and a copper catalyst. Aryl halides react with tin selenides (ArSeSnR3), with a copper catalyst, to give the diaryl selenide. OS I, 220 III, 86, 239, 667 V, 107, 474 VI, 558, 824. Also see, OS V, 977. 

The use of transition-metal catalysts allows aryl halides to react with the nitrogen of amides or carbamates, as well as amines, to give the corresponding Al-aryl amide or Waryl carbamate. Amides react with aryl halides in the presence of a pal-ladium catalyst or a copper catalyst. WAryl lactams are prepared by the reaction of a lactam with an aryl halide in the presence of a palladium catalyst. 

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