Halides aryl, addition

As reported before, the reaction can be carried out in ethanol by adding quickly a stoichiometric quantity of NaCN after the catalyst and aryl halide additions. In methanol or in dimethylformamide the catalytic cyanation occurs only if the sodium cyanide is added slowly. In benzene, always in the presence of NaCN, the reaction does not occur and complexes 1 can be isolated. 

The prototypic substrate for intermolecular cascade reactions is norbomene or one of its analogs. Starting from an aryl halide, addition of the formed palladium species to the strained double bond of norbomene yields a norbomylpalladium derivative, which cannot undergo /3-hydride elimination but can accept hydride, for example, from piperidinium formate (Scheme 1) or potassium formate, the latter reaction occurring even at room temperature. 

A stable and reusable CuO/carbon nanotube catalyst (CuO/MWCNT) for N-arylation of imdazole was developed by Karvembu et al. TEM images of the nanocatalyst showed good adhesion of CuO nanoparticles to anchoring sites of acid-treated MWCNTs. Even a small amount of the catalyst (0.98 mol%) was sufficient for the coupling reactions of imidazole and aryl halides. Additionally, a variety of the desired V-arylimidazoles were smoothly generated (11 examples, at 120°C for 24 h, 44%-96% yields) (Gopiraman et al., 2013). However, the application scope of the method is limited because only electron-poor aryl halides have been investigated. 

Chami, Z., M. Gareil, J. Pinson, J.-M. Saveant, and A. Thiebault. Aryl radicals from electrochemical reduction of aryl halides. Addition on olefins. J. Org. Chem. 56, 1991 586-595. 

Galardon E, Ramdeehul S, Brown JM, Cowley A, Hii KK, Jutand A (2002) Profund steric control of reactivity in aryl halide addition to bisphosphane palladium(O) complexes. Angew Chem Int Ed 41 1760-1763... 

The reactions of the second class are carried out by the reaction of oxidized forms[l] of alkenes and aromatic compounds (typically their halides) with Pd(0) complexes, and the reactions proceed catalytically. The oxidative addition of alkenyl and aryl halides to Pd(0) generates Pd(II)—C a-hondi (27 and 28), which undergo several further transformations. 

In Grignard reactions, Mg(0) metal reacts with organic halides of. sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand. Pd(0) complexes react more easily with halides of carbons. In other words, alkenyl and aryl halides undergo facile oxidative additions to Pd(0) to form complexes 1 which have a Pd—C tr-bond as an initial step. Then mainly two transformations of these intermediate complexes are possible insertion and transmetallation. Unsaturated compounds such as alkenes. conjugated dienes, alkynes, and CO insert into the Pd—C bond. The final step of the reactions is reductive elimination or elimination of /J-hydro-gen. At the same time, the Pd(0) catalytic species is regenerated to start a new catalytic cycle. The transmetallation takes place with organometallic compounds of Li, Mg, Zn, B, Al, Sn, Si, Hg, etc., and the reaction terminates by reductive elimination. 

Success of the reactions depends considerably on the substrates and reaction Conditions. Rate enhancement in the coupling reaction was observed under high pressure (10 kbar)[l 1[. The oxidative addition of aryl halides to Pd(0) is a highly disfavored step when powerful electron donors such as OH and NHt reside on aromatic rings. Iodides react smoothly even in the absence of a... 

In the reaction of Q,/3-unsaturated ketones and esters, sometimes simple Michael-type addition (insertion and hydrogenolysis, or hydroarylation, and hydroalkenylation) of alkenes is observed[53,54]. For example, a simple addition product 56 to methyl vinyl ketone was obtained by the reaction of the heteroaromatic iodide 55[S5]. The corresponding bromide affords the usual insertion-elimination product. Saturated ketones are obtained cleanly by hydroarylation of o,/3l-unsaturated ketones with aryl halides in the presence of sodium formate, which hydrogenolyses the R—Pd—I intermediate to R— Pd—H[56]. Intramolecular hydroarylation is a useful reaction. The diiodide 57 reacts smoothly with sodium formate to give a model compound for the afla-toxin 58. (see Section 1.1.6)[57]. Use of triethylammonium formate and BU4NCI gives better results. 

The diazonium salts 145 are another source of arylpalladium com-plexes[114]. They are the most reactive source of arylpalladium species and the reaction can be carried out at room temperature. In addition, they can be used for alkene insertion in the absence of a phosphine ligand using Pd2(dba)3 as a catalyst. This reaction consists of the indirect substitution reaction of an aromatic nitro group with an alkene. The use of diazonium salts is more convenient and synthetically useful than the use of aryl halides, because many aryl halides are prepared from diazonium salts. Diazotization of the aniline derivative 146 in aqueous solution and subsequent insertion of acrylate catalyzed by Pd(OAc)2 by the addition of MeOH are carried out as a one-pot reaction, affording the cinnamate 147 in good yield[115]. The A-nitroso-jV-arylacetamide 148 is prepared from acetanilides and used as another precursor of arylpalladium intermediate. It is more reactive than aryl iodides and bromides and reacts with alkenes at 40 °C without addition of a phosphine ligandfl 16]. 

The generally accepted mechanism for nucleophilic aromatic substitution m nitro substituted aryl halides illustrated for the reaction of p fluoromtrobenzene with sodium methoxide is outlined m Figure 23 3 It is a two step addition-elimination mechanism, m which addition of the nucleophile to the aryl halide is followed by elimination of the halide leaving group Figure 23 4 shows the structure of the key intermediate The mech anism is consistent with the following experimental observations... 

Other aryl halides that give stabilized anions can undergo nucleophilic aromatic substitution by the addition-elimination mechanism Two exam pies are hexafluorobenzene and 2 chloropyridme... 

The reaction between an alkoxide ion and an aryl halide can be used to prepare alkyl aryl ethers only when the aryl halide is one that reacts rapidly by the addition-elim mation mechanism of nucleophilic aromatic substitution (Section 23 6)... 

Perfluoroalkyl or -aryl halides undergo oxidative addition with metal vapors to form nonsolvated fluonnated organometallic halides and this topic has been die subject of a review [289] Pentafluorophenyl halides react with Rieke nickel, cobalt, and iron to give bispentafluorophenylmetal compounds, which can be isolated in good yields as liquid complexes [290] Rieke nickel can also be used to promote the reaction of pentafluorophenyl halides with acid halides [297] (equation 193)... 

Elimination-addition mechanism (Section 23.8) Two-stage mechanism for nucleophilic aromatic substitution. In the first stage, an aryl halide undergoes elimination to form an aryne intermediate. In the second stage, nucleophilic addition to the aryne yields the product of the reaction. 

In the arylations of enamines with very reactive aryl halides (352,370) such as 2,4-dinitrochlorobenzene, the closely related mechanistic pathway of addition of the enamine to the aromatic system, followed by elimination of halide ion, can be assumed. The use of n-nitroarylhalides furnishes compounds which can be converted to indolic products by reductive cycliza-tion. Less reactive aryl halides, such as p-nitrochlorobenzene, lead only to N-arylation or oxidation products of the enamines under more vigorous conditions. 

Aryl halides undergo substitution, although not through an Sn2 mechanism, but rather via a two-step addition-elimination mechanism. (An elimination-addition mechanism is also possible see Chapter 13, Problem 12.)... 

This reaction is not a bona fide Heck reaction per se for two reasons (a) the starting material underwent a Hg Pd transmetallation first rather than the oxidative addition of an aryl halide or triflate to palladium(O) (b) instead of undergoing a elimination step to give an enone, transformation 134 136... 

The mechanism of action of the cyanation reaction is considered to progress as follows an oxidative addition reaction occurs between the aryl halide and a palladium(O) species to form an arylpalladium halide complex which then undergoes a ligand exchange reaction with CuCN thus transforming to an arylpalladium cyanide. Reductive elimination of the arylpalladium cyanide then gives the aryl cyanide. 

In addition to sodium, other metals have found application for the Wurtz coupling reaction, e.g. zinc, iron, copper, lithium, magnesium. The use of ultrasound can have positive effect on reactivity as well as rate and yield of this two-phase reaction aryl halides can then even undergo an aryl-aryl coupling reaction to yield biaryls. ... 

A co-solvent that is poorly miscible with ionic liquids but highly miscible with the products can be added in the separation step (after the reaction) to facilitate the product separation. The Pd-mediated FFeck coupling of aryl halides or benzoic anhydride with alkenes, for example, can be performed in [BMIM][PFg], the products being extracted with cyclohexane. In this case, water can also be used as an extraction solvent, to remove the salt by-products formed in the reaction [18]. From a practical point of view, the addition of a co-solvent can result in cross-contamination, and it has to be separated from the products in a supplementary step (distillation). More interestingly, unreacted organic reactants themselves (if they have nonpolar character) can be recycled to the separation step and can be used as the extractant co-solvent. 

The electrophilic character of the palladium atom in the complexes formed by oxidative addition of aryl halides and alkenyl halides to palladium(o) complexes can be exploited in useful ways. 

A number of approaches have been tried for modified halo-de-diazoniations using l-aryl-3,3-dialkyltriazenes, which form diazonium ions in an acid-catalyzed hydrolysis (see Sec. 13.4). Treatment of such triazenes with trimethylsilyl halides in acetonitrile at 60 °C resulted in the rapid evolution of nitrogen and in the formation of aryl halides (Ku and Barrio, 1981) without an electron transfer reagent or another catalyst. Yields with silyl bromide and with silyl iodide were 60-95%. The authors explain the reaction as shown in (Scheme 10-30). The formation of the intermediate is indicated by higher yields if electron-withdrawing substituents (X = CN, COCH3) are present. In the opinion of the present author, it is likely that the dissociation of this intermediate is not a concerted reaction, but that the dissociation of the A-aryl bond to form an aryl cation is followed by the addition of the halide. The reaction is therefore mechanistically not related to the homolytic halo-de-diazoniations. 

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