Palladation, aromatic

The presence of chelating groups in those complexes is necessary to stabilize the intermediate aryl-palladium complex for isolation but it does not seem necessary to cause palladation. The chelating group does, however, tremendously accelerate the palladation. Aromatic compounds reactive to electrophilic substitution apparently undergo palladation with palladium acetate in acetic acid solution fairly readily at 100 °C or above. Of course, the arylpalladium acetates presumably formed, are not stable under these conditions, and they decompose very rapidly into biaryls and palladium metal 34,35,36) ag do aryl palladium salts prepared by the exchange route 24>. If the direct palladation is carried out in the presence of suitable olefins, arylation can be achieved, so far, however, only in poor yields, arid with concurrent loss of stereospecificity and formation of isomers and other side products 37.38). 

The Pd—C cr-bond can be prepared from simple, unoxidized alkenes and aromatic compounds by the reaction of Pd(II) compounds. The following are typical examples. The first step of the reaction of a simple alkene with Pd(ll) and a nucleophile X or Y to form 19 is called palladation. Depending on the nucleophile, it is called oxypalladation, aminopalladation, carbopalladation, etc. The subsequent elimination of b-hydrogen produces the nucleophilic substitution product 20. The displacement of Pd with another nucleophile (X) affords the nucleophilic addition product 21 (see Chapter 3, Section 2). As an example, the oxypalladation of 4-pentenol with PdXi to afford furan 22 or 23 is shown. 

Palladation of aromatic compounds with Pd(OAc)2 gives the arylpalladium acetate 25 as an unstable intermediate (see Chapter 3, Section 5). A similar complex 26 is formed by the transmetallation of PdX2 with arylmetal compounds of main group metals such as Hg Those intermediates which have the Pd—C cr-bonds react with nucleophiles or undergo alkene insertion to give oxidized products and Pd(0) as shown below. Hence, these reactions proceed by consuming stoichiometric amounts of Pd(II) compounds, which are reduced to the Pd(0) state. Sometimes, but not always, the reduced Pd(0) is reoxidized in situ to the Pd(II) state. In such a case, the whole oxidation process becomes a catalytic cycle with regard to the Pd(II) compounds. This catalytic reaction is different mechanistically, however, from the Pd(0)-catalyzed reactions described in the next section. These stoichiometric and catalytic reactions are treated in Chapter 3. 

Similarly to mercuration reactions, Pd(OAc)2 undergoes facile palladation of aromatic compounds. On the other hand, no reaction of aromatic compounds takes place with PdClj. PdCl2 reacts only in the presence of bases. The aro-... 

Mechanistic studies show that the arylation of alkenes proceeds via the palladation of aromatic compounds to form a rr-aryl-Pd bond (261), into which insertion of alkene takes place to form 262. The final step is i3-elimina-tion to form the arylated alkenes 259 and Pd(0). 

Three oxidative reactions of benzene with Pd(OAc)2 via reactive rr-aryl-Pd complexes are known. The insertion of alkenes and elimination afford arylalk-enes. The oxidative functionalization of alkenes with aromatics is treated in Section 2.8. Two other reactions, oxidative homocoupling[324,325] and the acetoxylation[326], are treated in this section. The palladation of aromatic compounds is possible only with Pd(OAc)2. No reaction takes place with PdCl2. 

The transmetallation of various organometallic compounds (Hg, Tl, Sn, B, Si, etc.) with Pd(II) generates the reactive cr-aryl, alkenyl, and alkyl Pd compounds. These carbopalladation products can be used without isolation for further reactions. Pd(II) and Hg(II) salts have similar reactivity toward alkenes and aromatic compounds, but Hg(II) salts form stable mercuration products with alkenes and aromatic rings. The mercuration products are isolated and handled easily. On the other hand, the corresponding palladation products are too reactive to be isolated. The stable mercuration products can be used for various reactions based on facile transmetallation with Pd(II) salts to generate the very reactive palladation products 399 and 400 in rim[364,365]. 

Oxidations of pyridopyrimidines are rare, but the covalent hydrates of the parent compounds undergo oxidation with hydrogen peroxide to yield the corresponding pyridopyrimidin-4(3 T)-ones. Dehydrogenation of dihydropyrido[2,3-(i]pyrimidines by means of palladized charcoal, rhodium on alumina, or 2,3-diehloro-5,6-dicyano-p-benzo-quinone (DDQ) to yield the aromatic derivatives have been reported. Thus, 7-amino-5,6-dihydro-1,3-diethylpyrido[2,3-d]-pyri-midine-2,4(lif,3f/)-dione (177) is aromatized (178) when treated with palladized charcoal in refluxing toluene for 24 hours. 

The role of acetic acid in such oxidative cyclization processes is to protonate the acetate ligand, making Pd(II) more electrophilic, thereby promoting the initial electrophilic palladation of the aromatic ring. 

Presumably, the oxidative cyclization of 3 commences with direct palladation at the a position, forming o-arylpalladium(II) complex 5 in a fashion analogous to a typical electrophilic aromatic substitution (this statement will be useful in predicting the regiochemistry of oxidative additions). Subsequently, in a manner akin to an intramolecular Heck reaction, intermediate 5 undergoes an intramolecular insertion onto the other benzene ring, furnishing 6. (i-Hydride elimination of 6 then results in carbazole 4. 

In contrast, Tsuji s group coupled 2-methylfuran with ethyl acrylate to afford adduct 6 via a Pd-catalyzed reaction using tm-butyl peroxybenzoate to reoxidize Pd(0) to Pd(II) [16]. The palladation of 2-methylfuran took place at the electron-rich C(5) in a fashion akin to electrophilic aromatic substitution. The perbenzoate acted as a hydrogen acceptor. 

In a similar way, carboxylic esters have been obtained stoichiometrically by ortho palladation of aromatic amides (Scheme 25) [147] and of phenyl-substituted isoxazoles or oxazoles [148] followed by alkoxycarbonylation. 

This complex is soluble in dichloromethane, chloroform, benzene, and acetone, and sparingly soluble in hexane and diethyl ether. The H NMR spectra of this complex indicate that the six-membered palladated 2-(2-pyridinylmethylJphenyl-C1, N moiety shows a fluxional motion above — 30 °C. In the low-temperature limiting spectrum measured in chloroform- at — 35 °C, the methylene protons are observed at S 4.45 as an AB quartet [Ad = 0.93, 2J(hh) = 14 Hz], which changes to a sharp singlet at S 4.51 in the high-temperature limiting spectrum at 55 °C. The cyclopalladated structure of the 2-(2-pyridinylmethyl)phenyl-C1, N moiety is confirmed by the fact that the aromatic protons appear as two sets of ABCD patterns at — 35 °C.7... 

The aromatization of 3,5-dibenzylidenetetrahydropyran-4-ones is achieved in boiling diethylene glycol solution in the presence of palladized charcoal (57JA156). 

Other products from pyridine and its 3- and 4-methyl and 3,5-dimethyl derivatives and MP are cyclazines (e.g., 100),291 which are probably formed from indolizines of type 97 by further reaction with MP and subsequent aromatization. This type of reaction has been achieved by heating appropriate indolizines with DMAD293 or MP in the presence of palladized charcoal, and the direction of the addition, as shown below, has been established in several instances.294 Heating MP with diethyl-2-pyridylmethylene malonate gave the pyrrolo[2,l,5- /]indolizine corresponding to 100, no trace of the expected indolizine intermediate (cf. 97) being observed.292... 

The direct palladation procedure is limited to substitution with aryl and heterocyclic groups. The met-allation is an electrophilic process and therefore does not work well with deactivated aromatics. When possible, mixtures of isomers may be obtained. Since the palladium salts employed for the metallation are moderately strong oxidizing agents, the reaction cannot be used with easily oxidizable alkenes or aromatics. The only effective method for making this procedure catalytic is to reoxidize the palladium in situ with oxygen under pressure an inconvenient and potentially dangerous procedure. 

The mechanism shown in Scheme 1 seems to be die one operating in most of the known examples of the reaction. The initial aromatic palladation is an electrophilic substitution, but unfortunately it is not a very selective one.4 Therefore, isomeric mixtures of products may be expected in cases where palladation can occur at different aromatic positions. 

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