Catalytic aromatic halides

A new catalytic coupKng of aromatic halides (178) and alkenes (179) has been developed using a-arylnickel complexes (180) (Scheme 72) [292]. The coupling reaction can be realized in a THF/HMPA-LiCl04-(Au) system at 25 50 C. The a-arylnickel complexes (180) obtained are stable enough to be detected (reduction at — 1.3 V vs. SCE) however, they decompose... 

The most important point of this electrochemical study is the presence of a catalytic process depending on the aromatic halide concentration (increase of the reduction signal) and which occurs at the same potential at which the a-arylnickel complex is produced. This suggests a metal-exchange reaction between ArNiX and Zn(II) to give Ni(II) and an organozinc species, RZnX (equation 41). 

Controlled-potential (E = —1.40 V/SCE) preparative electrolyses of FG-CgFLtX carried out in the presence of a catalytic amount of C0X2 indicate competition between the disproportionation of Co1 and the oxidative addition. For instance, the latter is preponderant when X=Br and FG = The aromatic halide is thus reduced into a mixture of ArH and Ar-Ar. The origin of ArH can be explained by the process shown in Scheme 14. 

The nickel-catalyzed transformation of aromatic halides into the corresponding nitriles by reaction with cyanide ions is reported. Both tris(triarylphosphine)nickel(0) complexes and tY2ins-chloro( aryl )bis( triarylphosphine )nickel(II) complexes catalyze the reaction. The influence of solvents, organophos-phines, and substituents on the aromatic nucleus on catalytic cyanation is studied. A mechanism of the catalytic process is suggested based on the study of stoichiometric cyanation of ti3ins-chloro(aryl)bis(triphenylphosphine)nickel-(II) complexes with NaCN and the oxidative addition reaction of Ni[P(C6H5)3]s with substituted aryl halides. 

This process is an example of the ability of nickel complexes to catalyze substitution reactions of aromatic halides under very mild conditions. A further example of their catalytic activity is the carbonylation of aromatic halides at the atmospheric pressure of carbon monoxide (6). 

In general these reactions do not interefere with cyanation. Reaction 7 is a catalytic process (14) and is strongly favored by electron-releasing substituents on the aromatic halide. In fact in the case of p-aminochloro-benzene, formation of the phosphonium salt competes with the cyanation process. 

Aromatic halides react with nickel(O) phosphine complexes at room temperature to yield complexes 1 (8, 13) by oxidative addition. We observed that arylnickel complexes 1 react with sodium cyanide to produce aromatic nitriles and the phosphine nickel(O) complexes, thus closing the catalytic cycle. 

Therefore it seems reasonable to assume that cyanation of aryl halides involves two fundamental processes oxidative addition of the tris(triphenylphosphine)nickel complex on the aromatic halide (Reaction 2) and cyanation of the arylnickel(II) complex 1 (Reaction 8). A further proof of the validity of this scheme is that both Ni[P(C6H5)3]3 and arylnickel (II) complexes 1 have an equal catalytic activity, these latter being intermediates of the catalytic process. Recent studies (22) on the influence of substituents on the aromatic halide in the oxidative addition reaction with Ni[P(C6H5)3]3 have given the results shown in Figure 4. 

It is also known, that in addition to the catalytic reaction route the dehalogenation of aromatic halides can be carried out in stoichiometric reaction [ 1] in the presence of metal hydrides (e.g. LiAlH or NaBH ). Further characteristic feature of hydrodehalogenation reactions is the requirement for addition of free bases into the reaction mixture to fix the formed hydrochloric acid [2,4]. 

Catalytic formation of carbon-carbon bonds is a powerful tool for construction of complex molecular architectures, and has been developed extensively for applications in organic synthesis. Three main classes of carbon-carbon bond forming reactions have been studied in sc C02 carbonylation (with particular attention paid to the hydroformylation of a-olefins), palladium-catalyzed coupling reactions involving aromatic halides, and olefin metathesis. 

The reaction sequence in the vinylation of aromatic halides and vinyl halides, i.e. the Heck reaction, is oxidative addition of the alkyl halide to a zerovalent palladium complex, then insertion of an alkene and completed by /3-hydride elimination and HX elimination. Initially though, C-H activation of a C-H alkene bond had also been taken into consideration. Although the Heck reaction reduces the formation of salt by-products by half compared with cross-coupling reactions, salts are still formed in stoichiometric amounts. Further reduction of salt production by a proper choice of aryl precursors has been reported (Chapter III.2.1) [1]. In these examples aromatic carboxylic anhydrides were used instead of halides and the co-produced acid can be recycled and one molecule of carbon monoxide is sacrificed. Catalytic activation of aromatic C-H bonds and subsequent insertion of alkenes leads to new C-C bond formation without production of halide salt byproducts, as shown in Scheme 1. When the hydroarylation reaction is performed with alkynes one obtains arylalkenes, the products of the Heck reaction, which now are synthesized without the co-production of salts. No reoxidation of the metal is required, because palladium(II) is regenerated. 

The ortho-arylation of aromatic aldehydes in the presence of a combination of Pd(II)/saturated imidazolium salt has also been reported [174]. Remarkably, the formation of the mono- or bi-orf/zo-substituted product could be easily controlled depending on the nature of the aromatic halide employed (Scheme 23). Both electron-donating and electron-withdrawing substituents were well tolerated by the catalytic system and heteroaromatic aldehydes could also be coupled. 

Hydrogenolysis of aromatic halides using catalytic hydrogenation takes place easily with rates of replacement of halogen decreasing in the order I > Br > Cl > F. For example, replacement of chlorine in preference to fluorine takes place in chlorofluoropyridines (equation 21)."... 

Naskar, D., Roy, S. Catalytic Hunsdiecker reaction and one-pot catalytic Hunsdiecker-heck strategy synthesis of a,P-unsaturated aromatic halides, a-(dihalomethyl)benzenemethanols, 5-aryl-2,4-pentadienoic acids, dienoates and dienamides. Tetrahedron 2000, 56,1369-1377. 

The mechanism was discussed recently [15]. The zero-valent metal (produced at the interface by reduction of the metal cation) induces an oxidant addition, in principle followed by nucleophilic substitution and a reducing elimination. The scheme below exhibits a simplified catalytic mechanism with aromatic halides. Electrochemistry is involved in the activation phase (formation of zero-valent metal [16-18]). The nucleophile is obviously produced by the oxidant insertion, and in the catalytic cycle hereafter Ar—Nu has to be considered of course as the Ar—Ar dimer. 

The electroreduction of aromatic halides in the presence of catalytic amounts of [Ni-PPli3] [27] or [Ni-dppn] [28] mainly yields arylcarboxylates. Such a reduction process may also be catalyzed by palladium complexes. 

The turnover-limiting step in this catalytic cycle depends on the steric and electronic properties of both the organohalide and the organometallic reagent as well as the nature of the main-group metal, and can also be affected by the structure of the metal catalyst. The order of halide reactivity in oxidative addition processes is I > Br = OTf > Cl, and as noted above, the relative rate of oxidative addition of various aromatic halides is roughly... 

The catalytic cycle is initiated by oxidative addition of an aromatic halide Ar-X (2) to a stabilized Pd(0) species (1) attack of the acetylide follows. In many reactions, copper acetylides (29), which are generated from the alkyne and Cul in the presence of an amine base, give superior results (Scheme 4). 

The carbonylation of chloroarenes has been described by Alper and Grushin [27] and Jenner and Bentaleb [28], While the former showed that square-planar complexes of divalent palladium, [ L2PdCl2], where L = tertiary phosphine, are active catalysts for the biphasic carbonylation of aromatic halides, including chloroarenes (when L = tricyclohexylphosphine), to the corresponding carboxylic acids, the latter demonstrated that chloroarenes can be converted into aromatic acids via catalytic reaction with aqueous methyl formate under biphasic conditions. [ PdCl2(PCy3)2] was the most efficient catalyst. The addition of [ Ru3(CO)12] and ammonium formate improved yield and selectivity of the carbonylation reaction. The mechanism should involve oxidative addition of the C—Cl bond to a zero-valent Pd species followed by CO insertion. However, the palladium catalyst may also directly activate methyl formate. Compared to other carbonylations of aryl-Hal compounds the procedure is quite convenient (no solvent, no initial pressurization) [27]. 

Aromatic amines can be produced by reduction of the corresponding nitro compound, the ammonolysis of an aromatic halide or phenol, and by direct amination of the aromatic ring. At present, the catalytic reduction of nitrobenzene is the predominant process for manufacture of aniline. To a smaller extent aniline is also produced by ammonolysis of phenol. 

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