Copper nucleophilic aromatic

For a review of copper-assisted aromatic nucleophilic substitution, see Lindley, J. Tetrahedron, 1984, 40, 1433. 

In the copper catalyzed aromatic nucleophilic substitution of aryl halides bromoindole derivatives were converted to the appropriate cyanoindoles. Both 5-bromoindole and its 7V-tosyl derivative gave excellent yields, when a substoichiometric amount potassium iodide was added to the reaction mixture (6.80.), Pyrazole and benzothiophene showed a similar reactivity. The role of the added iodide is to activate the aromatic system through a bromine-iodine exchange.111... 

For a review of copper-assisted aromatic nucleophilic substitution, sec Lindley Tetrahedron 1984, 40. 1433-1456. "For a review of the Ullmann ether synthesis, see Moroz Shvartsbcrg Russ. Chem. Rev. 1974, 43. 679-689. Wcingarten J. Org. Chem. 1964, 29. 977. 3624. 

An extensive series of neutral macrocyclic complexes, mainly of nickel(II), copper(II), platinum(II) and palladium(II), has been developed by Dziomko and coworkers. The cyclization step in the template reaction is a nucleophilic aromatic substitution of an arylamine on to a haloaryl azo compound. A variety of aryl and heteroaryl rings can be incorporated in different combinations. For instance, a diaminoazo compound can be combined with a dihaloazo compound (Scheme 58).246 247 Another synthetic strategy involves the dimerization of an aminohaloazo compound and leads to more symmetrical macrocyclic complexes (Scheme 59).248 249 Most recently, dihalodiazo compounds have been synthesized from dihydrazines and pyrazolinediones and undergo template reactions with simple 1,2-diamines (Scheme 60).249 250... 

There are two different transformations referred as the Ullmann Reaction. The classic Ullmann Reaction is the synthesis of symmetric biaryls via copper-catalyzed coupling, the Ullmann-type Reactions include copper-catalyzed Nucleophilic Aromatic... 

Fig. 5.53. Mechanistic aspects I of nucleophilic aromatic substitution reactions of aryldiazonium salts via radicals introduction of Nu=Cl, Br, CN or N02 according to Figure 5.52. Following step 2 there are two alternatives either the copper(II) salt is bound to the aryl radical (step 3) and the compound Ar-Cu(III)NuX decomposes to Cu(I)X and the substitution product Ar-Nu (step 4), or the aryl radical reacts with the cop-per(II) salt in a one-step radical substitution reaction yielding Cu(I)X and the substitution product Ar-Nu.

Side Note 16.2. Figure 16.8 shows a nucleophilic aromatic substitution reaction conducted with copper Rosenmund-von-Braun cyanide. This Rosenmund-von-Braun reaction is not included among the numerous Ull-... 

Copper-mordenite catalyzed nucleophilic aromatic substitution reactions. 

Nucleophilic aromatic substitutions are a type of reactions frequently applied in the synthesis of chemical intermediates and fine chemicals. In general, these processes are performed in the liquid phase, batchwise, with dissolved copper salts as catalysts [1]. It is of interest to investigate the possibilities of heterogeneous catalysis, as a more convenient catalyst recycle can thus be achieved. 

Paine, A. J. Mechanisms and models for copper mediated nucleophilic aromatic substitution. 2. Single catalytic species from three different oxidation states of copper in an Ullmann synthesis of triarylamines. J. Am. Chem. Soc. 1987,109,1496-1502. 

Mechanistic interpretations of the copper-catalyzed aromatic nucleophilic substitution reactions remain unsettled even after half-a-century of debate [19, 20]. Possible pathways involve an S Ar reaction mediated by copper complexation to the pi-system (Scheme 4a), an electron transfer reaction followed by halide dissociation (Scheme 4b), four-centered c-bond metathesis reaction (Scheme 4c) and Cu(l) oxidative addition to the Ar-X bond, followed by the nucleophile exchange and reductive elimination in the resulting Cu(lll) system (Scheme 4d). There is presently a considerable body of experimental and theoretical data for and against each of the proposed mechanisms [21]. While the mechanistic studies were mostly related to the formation of C-C, C-O and C-N bonds, it is likely that the copper-catalyzed halogen exchange reactions follow a similar trend. 

The mechanism was postulated to involve a Cu(l)-carboxylate as the active species, which promotes oxidative addition of the thioimide. Subsequent transme-talation and C-S reductive elimination generates the thioether product. An excess of boronic acid is often required, as copper catalysts may competitively oxidize aryl substituted boronic acids to the corresponding phenol in the presence of adventitious water [21]. The rate of acceleration observed with amino acids and carboxylate-based ligands, such as 3-methylsalicylate, is attributed to stabilization of a 7i-Cu intermediate generated through a nucleophilic aromatic substitution type mechanism (Scheme 1) [72]. The amino acid or carboxylate ligand may also simply stabilize putative Cu(lll) intermediates. 

One group of nucleophilic aromatic substitution processes does not fit mechanistically into the previous categories. This group is a series of copper-catalyzed displacements of aromatic halogen compounds. 

Because the reactions of related in -cyclohexadienyl complexes are synthetically valuable, the reactions of this ligand have been studied extensively. An outline of how this chemistry can be conducted on the Fe(CO)j fragment is shown in Equation 11.51. A variety of cyclohexadienes are readily available from Birch reduction of substituted aromatics. Coordination and abstraction of a hydride, typically by trityl cation, leads to cationic cyclohexadienyl complexes. These cyclohexadienyl complexes are reactive toward organolithium, -copper, -cadmium, and -zinc reagents, ketone enolates, nitroal-kyl anions, amines, phthalimide, and even nucleophilic aromatic compounds such as indole and trimethoxybenzene. Attack occurs exclusively from the face opposite the metal, and exclusively at a terminal position of the dienyl system. This combination of hydride abstraction and nucleophilic addition has been repeated to generate cyclohexa-diene complexes containing two cis vicinal substituents. The free cyclohexadiene is ttien released from the metal by oxidation with amine oxides. ... 

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