Arenes palladium® acetate

There are reports of an increasing number of palladium-assisted reactions, in some of which the palladium has a catalytic function. Thus furan and thiophene undergo facile palladium-assisted alkenylation giving 2-substituted products. Benzo[6 Jfuran and TV- acetyl-indole yield cyclization products, dibenzofurans and carbazoles respectively, in addition to alkenylated products (8UOC851). The arylation of pyrroles can be effected by treatment with palladium acetate and an arene (Scheme 86) (81CC254). 

The arylation of pyrroles can be effected by treatment with palladium acetate and an arene (Scheme 83) (81CC254). 

Pd-catalysed chelate-directed acetoxylation of meta -substituted arenes has been studied.61 Many substituted groups are tolerated by this process and the reaction shows a high degree of regioselectivity for the less sterically hindered ortfto-position. For example, 2-(3-nitrophenyl)pyridine forms 2-(2-acetoxy-3-nitrophenyl)pyridine. Finally, density functional calculations62 on the palladium acetate-promoted cyclomet-allation of dimethylbenzylamine suggest that reaction occurs via an agostic C-H complex rather than a Wheland intermediate. An intramolecular H-transfer to a coordinated acetate via a six-membered transition state follows. 

A few recent examples of related C-C bond-forming reactions, all involving a palladium-catalyzed C-H activation step at arenes, will be mentioned. Salts are produced in these reactions, or acetic acid, as in the first example. Allylation of indoles at the 3-position was achieved by using palladium acetate, and bipyridine and allylic acetates as the reactants (Scheme 5) [19]. 

An interesting application of the Fujiwara-Moritani/oxidative Heck reaction for the synthesis of benzo furans was recently reported by the Stoltz lab [31]. A variety of allyl phenyl ethers (all containing electron-rich aryl components) react with 10 mol% palladium acetate, 20 mol% ethyl nicotinate, 20 mol% sodium acetate, and one equivalent of benzoquinone at 100°C to provide benzofurans in 52-79% yield (e.g. 16—>17). The mechanism of this transformation begins with arene palladation of Pd(II) followed by olefin insertion, p-hydrogen elimination, and olefin isomerization to the thermodynamically favored benzofuran product. The resulting Pd(0) species is then oxidized to Pd(ll) thus regenerating the active catalyst. 

Several reports have appeared describing anilide arylation by arenes that do not involve coupling of a C-H bond with a C-Hal bond and thus will be discussed only briefly. Buchwald has shown that oxidative arylation of anilides takes place in presence of 5-10 mol% of palladium acetate and catalytic DMSO in trifluoroacetic acid solvent by using oxygen as the terminal oxidant [52], Pivalanilides afford the best results. Notably, only about four equivalents of the arene component are required for efficient arylation. However, regioisomer mixtures were obtained if monosubstituted arenes were used as the coupling components. 

Shi has reported a method for /V-alkylanilidc arylation by simple arenes [53], The reaction conditions include heating the anilide with excess arene in propionic acid in the presence of catalytic palladium acetate and copper triflate under oxygen atmosphere. Use of monosubstituted arenes leads to the formation of isomer mixtures however, from the point of atom economy C-H/C-H couplings are the most efficient way for formation of C-C bonds if oxygen is used as the terminal oxidant. Shi has also reported that anilides can be coupled with arylboronic acids and trialkoxyaryl-silanes [54, 55], Silver and copper salts are used as terminal oxidants. 

Palladium-catalyzed dimerization of 2-arylpyridines by employing oxone as the terminal oxidant has been reported [75], The reaction was shown to proceed via a Pd(II)-Pd(TV) pathway. A method for cross-coupling of simple arenes with 2-arylpyridine derivatives by using catalytic palladium acetate in the presence of two equivalents of silver carbonate requires use of a large excess of the less reactive arene [76],... 

In 1981, Itahara reported the palladium acetate-mediated direct arylation of pyrroles and indoles with arenes [59], With (sub)stoichiometric Pd(OAc)2 in benzene and acetic acid, arylation of 1-benzoylpyrrole and 1-acetylindole occurred with moderate to excellent conversions, but gave generally low yields of the desired cross-coupling products (Scheme 14). Direct arylation of isoxazole in the presence of stoichiometric amount of Pd(OAc)2 was also reported by Nakamura et al. [60]. 

Since then, a series of intramolecular oxidative coupling reactions between two arenes have been reported. This method was extensively used to synthesize many naturally occurring carbazoles (for reviews see [75, 76]), as shown in Table 2. However, most of these transformations are carried out in the presence of stoichiometric or substoichiometric amounts of palladium acetate. 

The L -iodane PhI(OAc)2 has been used extensively, most notably by Sanford, to oxygenate the C-H bonds of arenes and even alkanes in the presence of palladium catalysts." Interestingly, this reaction was likely mediated by a binuclear complex featuring two Pd(III) atoms joined by a palladium-palladium (Pd-Pd) bond however, this complex can disproportionate into a Pd(IV)-Pd(II) complex without a formal Pd-Pd bond, and this intricate interplay is often controlled by the presence and nature of hypervalent iodine oxidants." We discovered that this reaction manifold could be extended to include the amination of arene substrates heating 2-phenylindole 51 in the presence of the -iodane 49 and palladium acetate provided the ortho-aminated product 52 in a 19% yield however, switching the metal from palladium acetate... 

Sanford and coworkers have reported the use of Oxone in combination with palladium acetate for the oxime-ether directed C-H oxygenation of arenes (eq 111). A range of substituted arenes are tolerated under the reaction conditions and the use of Oxone rather than periodate-based oxidants afforded A -oxidized products in some cases. 

The palladation of arenes can be used for direct thermal functionalization. A palladium acetate/phenanthroline catalyst in the presence of acetic acid and under a CO atmosphere converts naphthalene into naphthoic acid with up to 91% selectivity for the )8-isomer. The reaction proceeds at 115 °C over 24-72 h. Ligands other than phenanthroline are less effective. Even saturated hydrocarbons are not inert to activation by palladium. In stoichiometric reactions, Pd(OAc)2 in CF3COOH as solvent at 80 °C reacts with methane to give CF3COOMe and Pd(0) as in equation (32), and adamantane gives 1-adamantyltrifluoroacetate. Since the esters can be hydrolyzed, the overall reaction corresponds to the reaction of the hydrocarbon with water to give alcohols shown in equation (33). Arenes are... 

An early example of this arene coupling was reported by Ames and BuU,t who noted the formation of benzofuro[3,2-c]cinnoline in the reaction of 3-bromo -phenoxycinnohne with ethyl acrylate in the presence of a catalytic amount of paUadium(n) acetate (Scheme 2, Eq. 1). Subsequent studies showed that ethyl acrylate is not necessary, and the arylation reaction was achieved by using 0.1 equiv of palladium acetate, 0.2 equiv of triphenylphosphine, and 3 equiv of sodium acetate in DMA at 170 °C (Scheme 2, Eq. 

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]. 

In parallel with progress on the oxidation of alkanes to alcohols and alkyl halides have been reports on the oxidative carbonylations of alkanes and arenes to form carboxylic acids. Fujiwara showed that stoichiometric amounts of arylpalladium acetates formed from the reaction of Pd(OAc)j with arenes and that the resulting arylpalladium complex reacts with CO in acetic acid to form aromatic acids (Equation 18.22). When O, BuOOH, alkyl halides, or K SPj were added as oxidant, the reaction became catalytic in palladium, and benzoic acids were generated from benzene, CO, and the oxidant in the presence of palladium acetate (Equation 18.23). Tl-ie highest yields were obtained with KjSPg as oxidant. Sen has reported related oxidation reactions in acidic media. - ... 

ItaharaT (1981) Arylatirai of A-acyl-pyrroles and-indoles with arenes and palladium acetate. J Chem Soc Chem Commun 254-255... 

Oxidation of benzoquinones and naphthoquinones by palladium diacetate in arene-containing acetic acid gave the corresponding aryl-substituted quinones (eq 70). Treatment of 1,4-naphthoquinone with aromatic heterocycles, for example furfural, 2-acetylfuran, 2-acetylthiophene, and 4-pyrone, yielded the corresponding 2-heteroaryl-substituted 1,4-naphthoquinones. 

Arene Amination. Alternative methods for the A-arylation of N-H-containing heterocycles that proceed directly with arenes (i.e., where aryl halides are not required) have emerged in the literature. In a recently reported procedure, a succinimide derivative was iV-arylated using palladium acetate as the catalyst, tri-ferf-butylphosphine as the ligand, and (diacetoxyiodo)benzene as a stoichiometric oxidant. This reaction allows the formation of ster-ically controlled products with monosubstituted arenes, yielding mainly meta- and / ara-arylated products and di- and trisubsti-tuted arenes, mostly providing the products of arylation at the meta-position (eq 15). ... 

The palladium-catalyzed cross-coupling of arenediazonium tetrafluoroborates and secondary phosphine oxides generates arylphosphine oxides in moderate to excellent yields (Scheme 4.196) [292]. Palladium acetate was the most effective palladium precursor, and no additional ligand was needed for solubilization and stabilization of the palladium center. The chemistry was successful with arenes bearing esters, ethers, and halogens. 

The acetoxylation of arenes tethered to 3,4-dihydroisoquinoline has been achieved using phenyliodonium acetate and acetic anhydride with a palladium acetate catalyst. 

Other metals capable of electrophilic substitution of C-H bonds are salts of palladium and, environmentally unattractive, mercury. Methane conversion to methanol esters have been reported for both of them [29], Electrophilic attack at arenes followed by C-H activation is more facile, for all three metals. The method for making mercury-aryl involves reaction of mercury diacetate and arenes at high temperatures and long reaction times to give aryl-mercury(II) acetate as the product it was described as an electrophilic aromatic substitution rather than a C-H activation [30],... 

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