Benzene palladation

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. 

Malononitrile (133) undergoes Pd(0)-catalyzed dimerization to give 134[125,126]. The trimerization of malononitrile in boiling benzene catalyzed by potassium tetrakis(pentalluorophenyl)palladate gives 4.6-diamino-3,5-dicyano-2-cyanomethylpyridine (135)[127]. 

D. 2,3-Diamino pyridine (Note 12). In an apparatus for catalytic hydrogenation (Note 13) 56.4 g. (0.3 mole) of 2,3-diamino-5-bromopyridine suspended in 300 ml. of 4% sodium hydroxide solution is shaken with hydrogen in the presence of 1.0 g. of 5% palladized strontium carbonate (Note 14). When absorption of hydrogen is completed, the catalyst is removed by filtration, and, after saturation with potassium carbonate (about 330 g. is required), the resulting slushy mixture is extracted continuously with ether until all the precipitate completely disappears (usually about 18 hours, but this depends on the efficiency of the extraction apparatus). The ether is removed by distillation, and the residue of crude 2,3-diaminopyridine is recrystallized from benzene (about 600 ml. is required) using 3 g. of activated charcoal and filtering rapidly through a preheated Buchner funnel. The yield of 2,3-diaminopyridine, obtained as colorless needles, m.p. 115-116°, pKa 6.84, is 25.5-28.0 g. (78-86%) (Note 15). 

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. 

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 unstable phenylpalladium intermediate 164 is formed by palladation of benzene with Pd(OAc)2, and then the following three reactions occur. 

Oxidative cross-coupling with alkenes is possible with Pd(OAc)2 [109], The reaction proceeds by the palladation of benzene to form phenylpalladium acetate (164), followed by alkene insertion and elimination of /1-hydrogen. Heteroaromatics such as furan and thiophene react more easily than benzene [109]. Stilbene (177) is formed by the reaction of benzene and styrene. The complex skeleton of paraberquamide 179 was obtained in 80% yield by the Pd(II)-promoted coupling of the indole ring with the double bond in 178, followed by reduction of the intermediate with NaBELt [110]. 

Representative compounds having a pyrrolidine or piperidine nucleus have been dehydrogenated in benzene solution under pressure at 250-350° over a nickel catalyst, e.g., l-( -amyl)-pyrrolidine to l-( -aniyl)-pyrrole (88%), indoline to indole (75%), and 1,2,3,4-tetrahydrocarbazole to carbazole (95%). Indole is also prepared by the dehydrogenation of its 2,3-dihydro derivative over palladium in boiling xylene (62%)." Partially hydrogenated alkylpyridines are dehydrogenated over palladized asbestos." 2,4-Diphenylpyrrole is synthesized by the selenium dehydrogenation of its 2,3-dihydro compound (46%). ... 

Diamino-2-phenyltriazole and nitrosobenzene, stirred in an emulsion of benzene and 12 N sodium hydroxide, gave 4-amino-2-phenyl-5-phenylazotriazole (60°C, 10 min, 72%) (70BCJ3587). Potassium permanganate in dilute acetic acid oxidized 4-amino-3,5-diphenyltriazole to 3,3, 5,5 -tetraphenyl-4,4 -azotriazole (25 °C, 30%). This product, stirred with hydrazine hydrate and palladized carbon in chloroform, gave 4-amino-3,5-diphenyltriazole (25°C, 1 hr, 91%) (70JOC2215). 

Palladium-silica catalysts prepared from tetra-ammine palladous nitrate (to avoid chlorine introduction) showed a marked reduction effect , viz, the specific activity for benzene hydrogenation decreased with increased reduction temperature, i.e., 573 or 723Various explanations were considered, including a metal-support interaction. After reduction at 873 K, X-ray diffraction provided clear evidence of chemical reaction and at lower temperatures silicon insertion into palladium might still occur, which could either disrupt the palladium ensembles required for benzene adsorption or modify the properties of single palladium atoms, if these are the active sites. 

In the first step, it was proposed that the highly electrophilic Pdn(TFA)2 catalyst affected selective electrophilic C-H bond activation exclusively on the electron rich indole. This generated an indole-Pd(II) complex I, which was able to selectively activate the benzene via a transfer-palladation pathway, which is controlled by C-H acidity. Reductive elimination afforded biaryl C-C bond formation and released Pd(0) which required oxidation to regenerate the active Pd(II) catalyst. 

C-H activation on benzene via proton transfer-palladation controlled by C-H acidity... 

Alkenylation and arylation. Alkenyl triflates are highly active in intramolecular alkenylation of both electron-rich and electron-poor arenes. 2-Alkynylbiaryls give 9-aIkylidenefluorenes via palladation of the o -position [the benzene ring bearing electron-withdrawing group(s)]. ... 

Palladous acetate has been widely studied in connection with vinyl acetate synthesis (page 798). It acts to some extent like Hg11 and Pblv acetates in attacking benzene and other aromatic hydrocarbons in acid media.11 Thus, in acetic acid, it specifically attacks the side chain of toluene. 

Mattox and Grosse262 report the formation of biphenyl, anthracene, and naphthalene from benzene, toluene, or butylbenzene in presence of a chromium-aluminum dehydrogenation catalyst and if 1 -phenyl-frws-l,cis-3, f/my-5-heptatriene is heated for 15 min with palladized charcoal in an evacuated tube at 180°, a very good yield of 2-methylbiphenyl is obtained 263... 

In place of the dihydrophellandrene recommended by Kindler and Peschke, decahydronaphthalene (decalin) is the solvent of choice in the dehydrogenation. A 5 % palladized carbon catalyst is preferable to other catalysts but necessitates reagents containing less than 0.005 % sulfur. The benzene is removed from the dihydropapaverine and displaced by decalin until the temperature reaches 165°. The catalyst is slurried in, and the mixture is refluxed for five hours. Filtration of the catalyst from the hot solution, crystallization of papaverine from the filtrate, slurrying of the product with ether, and recrystallization from hot aqueous alcohol complete the procedure. 

Palladium-mediated oxidative arylation of thiophene has also been reported <8SJ0CS272>. Thus, treatment of 2-formylthiophene with palladium acetate in a mixture of acetic add and benzene gave 2-formyl-4-phenylthiophene (30%), 2-formyl-5-phenylthiophene (5%) and 5,5 -diformyl-2,2 -bithienyl (16%). It has been suggested that preliminary palladation of benzene would lead to 4-phenylation of the thiophene, while palladation of the thiophene would produce the 5-phenylated product. 

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]. 

There is support for the occurrence of Pd(IV) species in the acetoxylation of arenes,t with the most recent proposal shown in Scheme 17, consistent with demonstrated palladation of benzene, for example, by Pd(02CMe)2/SEt2 to form... 

Oxidative couplings of simple arenes, whose reactivity is comparable with benzene itself, to biaryls have been performed with stoichiometric palladium salts [2-5], Biphenyl (8) is obtained in high yield from two molecules of benzene by the influence of palladium(II) acetate or mixture of palladium(II) chloride (1 eq.) and sodium acetate (2 eq.). The reaction apparently involves the electrophilic palladation of benzene to give phenylpalladium(ll) acetate (370) which further reacts with the... 

Mechanistic studies revealed a significant kinetic isotope effect (kn/ko = 4.2) which excluded an electrophUic palladation pathway (unless the deprotonation is rate-limiting). A CMD process was proposed as a plausible C—H activation route as illustrated in Scheme 36. The superior activity of pyridine over benzene is attributed to the initial coordination of the Pd metal via the N(sp ) of the pyridine ring. The authors assumed that subsequent reorientation of the pyridine to bind with its Tt-system promotes the C3-H activation via CMD (after all, the C3-position of pyridine is expected to be the most electron-rich and therefore less favorable for CMD) (2013JOC8927). An aryl-Pd species (C) is formed which undergoes oxidative addition with an aryl halide to form Pd -intermediate D. Selective C3-arylated pyridine is formed upon reductive elimination from intermediate D. 

Acetoxyindole derivatives have been prepared by the reaction of Af-benzylindole with (diacetoxyiodo)benzene catalysed by palladium acetate. Kinetic experiments suggest that palladation to produce intermediates, such as (60), is rate limiting. " Palladium catalysis, using a Josiphos ligand, has also been used to prepare (V-alkyltacrines, such as (61), by amination of 9-chlorotetrahydro-acridines. " ... 

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