Palladation of Aromatic Compounds

The asymmetric cyclopalladation of dimethylaminomethylferrocene takes place in the presence of an optically active carboxylic acid (e.g, A -acetylvaline), giving the cyclopalladation product 478 in 78% ee, from which optically active ferrocene derivatives were prepared[434]. 

The ij-arylpalladium bonds in these complexes are reactive and undergo insertion and substitution reactions, and the reactions offer useful methods for the regiospecific functionalization of the aromatic rings, although the reac- 

Two moles of diphenylacetylene insert into the benzyl methyl sulfide complex 481 to afford the eight-membered heterocycle 482[440j. The cinnolinium Salt 483 is prepared by the insertion of alkynes into the azobenzene com-plex[44l]. 

The facile insertion of CO takes place. The 2-aryl-3-indazolone 484 is obtained in high yields from the azobenzene complex 463 in alcohol or waterf442]. For unsymmetrically substituted 4-methyl, 4-chloro-, and 4-meth- 

Chlorination of the azobenzene complex 463 with chlorine produces mono-chloroazobenzene with regeneration of PdCN. Then complex formation takes place again with the chlorinated azobenzene. By this sequence, finally tetra-chloroazobenzene (503) is obtained using a catalytic amount of PdCT. The reaction, carried out by passing chlorine gas into an aqueous dioxane solution of azobenzene and PdCf for 16 h, gives a mixture of polychlorinated azoben-zenes[455]. 

The n-arylpalladium bonds in these complexes are reactive and undergo insertion and substitution reactions. The reactions offer useful methods for regiospecific functionalization of aromatic rings, although the reactions are difficult to make catalytic in most cases. Insertion of styrene to AA-dimcthylbcnzylaminc complex (180) to form the stilbene derivative 185 occurs smoothly at room temperature in AcOH [5]. The reaction has been extended to the functionalization of the dopamine analogue (A,A-dimethyl-2-arylethylamine) 187 via the six-membered o/Y/zo-palladated complex 186 [118]. 

The chromanone oxime 195 is carbonylated in the aromatic ring to give the ester 

197 via the oxime-stabilized palladated complex 196 [122], The acetanilide complex 

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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 preparation of organopalladium compounds by exchange reactions of palladium salts and organo-lead, -tin, or -mercury compounds is apparently not the only way that they can be obtained but it does seem to be the most useful way. Convincing evidence is now available to show that direct metalation of aromatic compounds with palladium salts (palladation) can occur. Since the initial report of Cope and Siekman 32> that palladium chloride reacted readily with azobenzene to form an isolable chelated, sigma-bonded arylpalladium compound, several additional chelated arylpalladium compounds have been prepared. 

The following compounds with H-C and H-M bonds vmdergo oxidative addition to form Pd hydrides. Reactions of terminal alkynes and aldehydes are known to start by the oxidative addition of their C-H bonds. The reaction, called "ortho-palladation , occurs on the aromatic C—H bond in 3 at an ortho position of such donor atoms as N, S, O and P to form a Pd—H bond and palladacycles. Formation of aromatic palladacycles is key in the C—H bond activation in a number of Pd-catalyzed reactions of aromatic compounds. Some reactions of carboxylic acids and active methylene compounds are desaibed as starting by oxidative addition of their acidic O—H and C—H bonds. 

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. 

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]. 

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). 

Aromatic compounds 413, bearing hetero atom-containing groups at positions suitable for forming mainly five-membered or sometimes six-membered chelating rings, undergo cyclopalladation at an ort/io-position to form a cr-arylpalladium bond as in 414 by virtue of the stabilization due to the chelation of these hetero atoms. The ort/io-palladation products 414 are stable and can be isolated [173]. After the first report on the preparation of the azobenzene and A, A-dimethylbenzy-lamine complexes 415 and 416 [174], numerous complexes have been prepared. 

Heteroleptic heterodinuclear m-Pd (C N)2 complexes such as 56 are obtained from the reaction of or/i o-mercurated 2-[(77 -phenyl)tricarbonylchromium]pyridine with /x-chloro cyclopalladated aromatic compounds in the presence of large amounts of [NMe4]Cl. The products are valuable precursors of planar chiral cyclopalladated Gr( 7 -arene)(GO)3 complexes, for example, 57. A series of or// o-palladated binuclear Gr(r7 -arene)(GO)3... 

A wide range of aromatic nitro and nitroso compounds are rapidly and smoothly reduced to the corresponding amines by sodium boron hydride in the presence of palladized charcoal . Selective and stereospecific reductions can be performed with di-imide, an unstable reagent prepared in situ from a number of precursors . Peroxyacetic acid is an excellent oxidizing agent for a variety of hydrazine derivatives... 

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. 

Hydraane-metal catalyst. Pietra found that in the presence of palladized charcoal hydrazine reduces aromatic nitro compounds to amines in high yield. Thus a suspension of 30 g, of 2-nitrofluorene in 250 ml. of 95% ethanol is warmed with stirring to 50°, 0.1 g. of 10% palladium on charcoal (moistened with alcohol) is added, and 15 ml. of 64% hydrazine is added by drops during 30 min. Another... 

Arenes, especially electron-rich ones, and five-membered-ring heteroaromatic compounds have been found to react with alkynes in the presence of Pd(II) or Pt(II) species in acidic solvents to give the corresponding hydroaryl-ation products (Eqs. 68 and 69) [155-158]. The mechanism proposed for the reaction involves aromatic palladation to form ArPd(II) species, as in the Fujiwara-Moritani reaction [10], insertion of an alkyne,and protonolysis of the... 

The Pd(II)-mediated reaction of benzene with alkenes affords styrene derivatives 164. The reaction can be vmderstood by palladation, insertion of olefin to give 163, and y3-H elimination [67,68]. In addition to benzene and naphthalene derivatives, electron-rich heteroaromatic compounds such as ferrocene, furan and thiophene react with alkenes to give vinyl heterocycles. The effect of substituents in this reaction is similar to that observed in the electrophilic aromatic substitution [69]. 

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