Palladium catalyzed oxidations aromatics

Chapter 11 focuses on aromatic substitution, including electrophilic aromatic substitution, reactions of diazonium ions, and palladium-catalyzed nucleophilic aromatic substitution. Chapter 12 discusses oxidation reactions and is organized on the basis of functional group transformations. Oxidants are subdivided as transition metals, oxygen and peroxides, and other oxidants. 

Palladium-catalyzed oxidative couplings of aromatic compounds with alkenes in air lead to cinnamate products with TONs attaining 280 (Equations (66) and (67)).67,67a,67b... 

Tsuji, J. Nagashima, H. Palladium-catalyzed oxidative coupling of aromatic compounds with olefins using tert-butyl perbenzoate as hydrogen acceptor. Tetrahedron 1984, 40, 2699-2702. 

Similarly, chelation-assisted palladium-catalyzed oxidative functionalizations of C—H bonds with, for example, hypervalent iodine(III) reagents turned out to be particularly valuable. These protocols allowed for, inter alia, regioselective acetoxyla-tion or etherification of aromatic and aliphatic C— H bonds [17-19], and also halogenations of arenes (Scheme 9.3) [20, 21]. 

Interestingly, this Heck-type palladium-catalyzed oxidative addition/insertion manifold can also be applied to the actual formation of the carbon-heteroatom bond. This was illustrated by Narasaka in the reaction of olefin-tethered oxime derivatives. This chemistry can be considered to arise from oxidative addition of the N—O bond to palladium (30) followed by the more classical olefin insertion and (3-hydride elimination, ultimately allowing the assembly of pyrroles (Scheme 6.58) [79]. The nature of the OR unit was found to be critical in pyrrole formation, with the pentafluorobenzoylimine leading to selective cyclization and rearrangement to the aromatic product. An analogous approach has also been applied to pyridines and imidazoles [80]. 

Besides six-membered heterocycles, the construction of five-membered analogs by C-H olefination of phenol derivatives has also been reported. In 2011, Wang and coworkers reported a palladium-catalyzed oxidative cyclization of 3-phenoxy acrylates to construct benzofurans via an intramolecular aromatic C-H olefination (Scheme 3.13) [31]. In the presence of 5 mol% Pd(OAc)2/PPh3 and 2.0 equiv. of CF3C02Ag, benzofurans were obtained in good yields in... 

Intramolecular arylation of G-H bonds gives cyclic aromatic compounds. In this intramolecular arylation, the carbon-palladium cr-bond is first formed by the oxidative addition of Pd(0) species and then the resulting electrophilic Pd(n) species undergoes the intramolecular G-H bond activation leading to the formation of the palladacycle, which finally affords the cyclic aromatic compounds via reductive elimination.87 For example, the fluoroanthene derivative is formed by the palladium-catalyzed reaction of the binaphthyl triflate, as shown in Scheme 8.88 This type of intramolecular arylation is applied to the construction of five- and six-membered carbocyclic and heterocyclic systems.89 89 89 ... 

In the palladium-catalyzed coupling reactions of arenes with alkenes, the cr-arylpalladium complexes react with CO to give aromatic acids in AcOH, as shown in Scheme u 97>97a 97c This carboxylation reaction of arenes with CO proceeds catalytically with respect to Pd at room temperature under atmospheric pressure of CO, when K2S2O8 is added as an oxidant and TFA is employed as a solvent. 

One of the rare examples, where the palladium catalyzed closure of a six membered ring leads to an aromatic heterocycle is presented in 4.18. Intramolecular transformation of the 2-bromoindole derivative in the presence of a palladium-BINAP catalyst led to the formation of the a-carboline (pyrido[2,3- ]indole) skeleton. The ring closure was accompanied by the oxidation of the intermediate dihydrocarboline derivative.21... 

Substituted imidazole 1-oxides 228 are predicted to be activated toward electrophilic aromatic substitution, nucleophilic aromatic substitution, and metallation as described in Section 1. Nevertheless little information about the reactivity of imidazole 1-oxides in these processes exists. The reason for this lack may be the high polarity of the imidazole 1-oxides, which makes it difficult to find suitable reaction solvents. Another obstacle is that no method for complete drying of imidazole 1-oxides exists and dry starting material is instrumental for successful metallation. Well documented and useful is the reaction of imidazole 1-oxide 228 with alkylation and acylation reagents, their function as 1,3-dipoles in cycloadditions, and their palladium-catalyzed direct arylation. 

While alcohol oxidations have been the most common metal promoted reactions involving molecular oxygen, a number of other metal catalyzed oxidations of potential synthetic interest have been reported. Supported palladium catalysts are comparable to many soluble palladium catalysts in promoting the selective oxidations of alkenes and aromatics. 2-Butene was oxidized primarily to crotonic acid over Pd/C in water but methyl vinyl ketone and crotonaldehyde were also formed in significant amounts. When this oxidation was run in acetic acid the allyl acetates were the major products, particularly when a Pd/Al203 catalyst... 

The palladium-catalyzed decarbonylation of aromatic acyl cyanides proceeds at 120 °C to give the corresponding nitriles in excellent yield. Since acyl cyanides are readily prepared by the ruthenium-catalyzed oxidation of cyanohydrins with BuKDOH this represents a good method for the conversion of aldehydes to nitriles under mild conditions (Scheme 29). 

Heterocycles - Aromatic substitution via N-oxides has been reviewed.51 Palladium catalyzed intramolecular addition of amines to olefins has resulted in new syntheses of indoles52-3 and isoquinuclidines.53... 

Few investigations have been devoted to the scope of palladium-catalyzed benzylic oxidation. Electron-donating substituents, e.g. MeO, in the aromatic ring have a promoting effect no reaction was observed with /7-nitrotoluene... 

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