Arylations alkenes, palladium© acetate

Polystyrene-bound secondary aliphatic amines and /V-alkyl amino acids can be ally-lated by treatment with a diene and an aryl iodide or bromide in the presence of palla-dium(II) acetate (Entry 14, Table 10.3). As the diene, 1,3-, 1,4-, and 1,5-dienes can be used, and, besides aryl halides, heteroaryl bromides have also been successfully used [63], This remarkable reaction is likely to proceed via the formation of an aryl palladium complex, with subsequent insertion of an alkene into the C-Pd bond. The resulting organopalladium compound does not undergo ( -elimination (as in the Heck reaction), but isomerizes to an allyl palladium complex, which reacts with the amine to give the observed allyl amines. 

Aryl chlorides Aryl chlorides will substitute alkenes only under very special conditions, and then catalyst turnover numbers are generally not very high. Palladium on charcoal in the presence of triethylphos-phine catalyzes the reaction of chlorobenzene with styrene,58 but the catalyst becomes inactive after one use.59 Examples employing an activated aryl chloride and highly reactive alkenes, such as acrylonitrile, with a palladium acetate-triphenylphosphine catalyst in DMF solution at ISO C with sodium acetate as base react to the extent of only 51% or less.60 Similar results have been reported for the combination of chlorobenzene with styrene in DMF-water at 130 C, using sodium acetate as the base and palladium acetate-diphos as a catalyst.61 Most recently, a method for reacting chlorobenzene with activated alkenes has been claimed where, in addition to the usual palladium dibenzilideneacetone-tri-o-tolylphosphine catalyst, nickel bromide and sodium iodide are added. It is proposed that an equilibrium concentration of iodobenzene is formed from the chlorobenzene-sodium iodide-nickel bromide catalyst and the iodoben-zene then reacts in the palladium-catalyzed alkene substitution. Moderate to good yields were reported from reactions carried out in DMF solution at 140 C 62... 

The catalyst The amount of catalyst required in an aryl bromide or iodide alkene substitution varies widely with the reactants and the reaction conditions. Most examples reported have used 1-2 mol % of palladium salt relative to the aryl halide, but much lower amounts are sufficient in some instances. In an extreme case, where very reactive p-nitrobromobenzene was added to the very active alkene, ethyl acrylate and sodium acetate was the base in DMF solution at 130 C with a palladium acetate-tri-o-tolylphos-phine catalyst in 6 h the palladium turned over 134 000 times and ethyl p-nitrocinnamate was obtained in 67% yield.63... 

Essentially the same substituents as listed above may be present in the alkene being substituted, with the possible exception of chloro, alkoxy and acetoxy groups on vinyl or allyl carbons. These groups, especially chloro, may be lost or partially lost with palladium when the final elimination step occurs. For example, vinyl acetate, iodobenzene and triethylamine with a palladium acetate-triphenylphosphine catalyst at 100 C form mainly (E)-stilbene, presumably via phenylation of styrene formed in the first arylation step (equation 21 ).6 ... 

Palladium/silver-catalyzed Heck reactions have usually involved vinyl or aryl halides and alkenes, but these reaction conditions were also extended to allenes. Indeed, Zenner and Larock65 showed that simple alkyl allenes readily reacted with aryl and vinyl iodide derivatives in the presence of palladium acetate or chloride and silver phosphate. Moreover, the reaction could be rendered asymmetric using chiral ligands the best one was a bisoxazolidine derivative (Scheme 10.37). 

Commercially available palladium compounds in the presence of various ligands have often been used as catalysts (Table 3-1). The first choice is often the air-stable and relatively inexpensive palladium acetate however, several of the other published variants can be preferable in certain applications. It is commonly assumed that the palladium(II) species is reduced in situ by the solvent, the alkene [11], the amine [12] or the added ligand (frequently a phosphane, which is oxidized to a phosphane oxide) [13]. In some cases, highly dispersed elemental palladium on charcoal can be applied. In the case of alkenyl or aryl bromides, phosphanes are necessary to avoid precipitation of palladium black (c.f., however. Section 3.2.4.), whereas iodides have been reported to be less reactive in the presence of phosphanes. Triflates have been found to be more reactive in the presence of chloride ions, as the chloride ligand is more easily removed from palladium than the tiiflate ion [14], However, this also has become questionable, because successful coupling reactions of alkenyl triflates have been performed in the absence of chloride ions [15]. 

Since the pioneering work by Beletskaya and co-workers [8] the intra- and (more commonly) intermolecular arylation of alkenes has been shown to proceed very smoothly in aqueous medium in the presence of palladium acetate. At the beginning, the methodology seemed to be limited to aryl iodides under a strong influence of the base it was shown that the presence of potassium acetate instead of carbonate yielded lower reaction temperatures and higher rates (Eq. 4). 

Many examples of alkene and alkyne insertion into metal-carbon bonds can also be found in the section on homogeneous catalysis. Other recent examples include the insertion of conjugated dienes into palladium-allyl bonds, olefin arylation in the presence of palladium acetate, and the reaction of ethylene with arylmagnesium halides in the presence of nickel chloride. Reaction of isocyanates with nickel-ethynyl compounds... 

Functionalized benzenes preferentially induced ortho-para substitution with electron-donating groups and meta substitution with electron-withdrawing groups (see above). Additionally, the order of reactivity found with aromatics was similar to that of electrophilic aromatic substitution. These observations implicated an electrophihc metalation of the arene as the key step. Hence, Fujiwara et al. [4b] believed that a solvated arylpalladium species is formed from a homogeneous solution of an arene and a palladium(ll) salt in a polar solvent via an electrophilic aromatic substitution reaction (Figure 9.2). The alkene then coordinates to the unstable arylpalladium species, followed by an insertion into the aryl-palladium bond. The arylethyl-palladium intermediate then rapidly undergoes )8-hydride elimination to form the alkenylated arene and a palladium hydride species, which then presumably decomposes into an acid and free palladium metal. Later on, the formation of the arylpalladium species proposed in this mechanism was confirmed by the isolation of diphenyltripalladium(ll) complexes obtained by the C-H activation reaction of benzene with palladium acetate dialkylsulfide systems [19]. 

Indeed, Fujiwara and coworkers [4b, 20] discovered that when copper(II) acetate or silver(I) acetate is employed together with oxygen (or air), the palladium-acetate-assisted alkene arylation reaction proceeds catalytically with respect to both palladium and copper (or silver). For example, styrene (4a) reacted with benzene (2a) in the presence of 10 mol% Pd(OAc)2, 10mol% Cu(OAc)2 and 50atm oxygen, producing tra -stilbene (3a) in 45% yield (Equation (9.7)) [20]. 

The Heck reaction (the reaction among an aryl iodide [e.g., iodobenzene, QHsI], palladium acetate [Pd(02CCH3)], and an alkene [e.g., ethene, H2C=CH2] to yield an aryl-substituted alkene [e.g., ethenyl-benzene, styrene, QH5CH=CH2]) has already been described in Chapter 6 and Scheme 6.54. In contrast to what is discussed here, the organometallic (palladium) intermediate was not isolated. 

The exchange reactions of aryl or alkenyl bromides or iodides with alkenes (Scheme 26) is catalysed by a palladium acetate-triphenylphosphine catalyst in the presence... 

Solvent effects on, and products from, reaction of styrene with ethylene in the presence of di-)ti-chloro-dichlorobis(styrene)dipalladium(n), [Pd-(Ph CH—CH2)Cl2]2, indicate a mechanism similar to (i)->(iv) above, with the addition of a preliminary equilibrium between the dimer and solvated monomers. The mechanism of reaction of styrene with vinyl compounds, catalysed by the same chloride-bridged dipalladium complex, has been studied using isotopic tracer (H, D) experiments. Palladium-acetate-catalysed reaction of styrene with benzene, also investigated using deuterium tracer experiments, involves no hydride shift, in contrast to the rather closely related Wacker process. The importance of intermediates with palladium-carbon n-bonds in palladium(ii)-catalysed alkylation and arylation of alkenes has been demonstrated. 

Disubstituted alkenes are generally less reactive towards coupling than are monosubstituted alkenes. However, the use of the more reactive aryl iodides can result in reasonable yields of the coupled product, usually as a mixture of (E) and (Z) isomers. The reaction has been applied to a coupling of 2-iodoaniline derivatives with dimethyl maleate (eq 18), the product of which spontaneously cyclizes to form quinolone derivatives in 30-70% yield. If, instead, the 2-iodoaniline is coupled with isoprene or cyclohexadiene in the presence of palladium acetate, triphenylphosphine, and triethylamine, indole and carbazole derivatives are obtained by a coupling followed by intramolecular nucleophilic attack by the heteroatom. ... 

Palladium-catalyzed Direct Arylation of Indoles and Thiophenes. Five-membered ring heterocycles possessing only one heteroatom and no Af-oxide function can also be arylated using palladium(II) complexes, a phosphine ligand, and an inorganic base. In one example, a tandem palladium-catalyzed Heck coupling reaction and direct intramolecular C2 arylation reaction on a )V-(2-chlorobenzyl)-5-bromoindole was reported (eq 30). The procedure, which is catalyzed by palladium acetate, uses tn-tert-butylphosphonium tetrafluoroborate as a ligand and ferf-butyl acrylate as the alkene for the Heck reaction (eq 30). ... 

Oxidative addition of aryl halides to [Pd(dba)2] in the presence of tetramethylethylenediamine or 2,2 -bipyridine to produce cis- [Pd(N-N)(Ph)X] proceeds easily when iodides are used but with more difficulty with bromides. Methyllithium reacts with the iodo complexes to give the mixed dialkyls. Cross coupling of alkenylboronic and arylboronic acids with alkenes is catalysed by palladium acetate in acetic acid. The reaction is believed to occur by oxidative addition of the carbon-boron bond across an in situ Pd(0) centre. 35... 

The use of transition metal catalysts to effect alkylations, alkenylations, arylations, and acylations in pyridines has been reviewed, and there has been a computational study of the ortho-alkylation of pyridine by scandium-catalysed reactions with alkenes. DFT calculations indicate that the stability of the developing metal-aryl bonds may be important in determining regioselectivity in palladium-acetate-catalysed carbon-hydrogen substitution in heteroarenes. ... 

---