Arenes acetoxylation

Early observations of benzylic acetoxylation were made in the study of arene acetoxylation and biaryl coupling when toluene was used as a substrate. In 1966, the reaction between stoichiometric Pd(OAc)2 and toluene to give benzyl acetate as the major product was disclosed [72]. Two years later, acetoxylation of toluene with catalytic Pd salts was reported by Union Carbide by using phosphines or a combination of Sn(OAc)2, charcoal, and air as oxidant to give 96TONs [73]. Additional metal acetates such as KOAc are beneficial for the reaction [74]. These acetoxylation methods were further applied to other arenes [75] (e.g., benzene, cyclohexene) and the synthesis of benzyl diacetate [76] (a precursor to benzalde-hyde). 

Nitrogen oxide (NO, ) cocatalysts [120] have received industrial interest in Pd-catalyzed aerobic oxidations such as oxidative carbonylation (see Section 8.2.2) [18], alkene oxidation [121], and arene acetoxylation [55]. Recent studies from academic literature have provided new insights into the roles of NO in these reactions. Pd-catalyzed aerobic alkene oxidation (Wacker reaction) typically affords methyl ketones arising from Markovnikov addition of water (or hydroxide) to an... 

SCHEME 24.47 Effect of pyridine equivalence on efficiency of arene acetoxylation. 

Prompted by the encouraging results for the modulation of site-selectivity for arene functionalization by the use of pyridine (Scheme 24.48), a more extensive exploration of ligand effects on the site-selectivity for arene acetoxylation was undertaken [44]. Several ligands lead to increased selectivities for the acetoxylation of 1,2-dichlorobenzene than those obtained in the absence of ligand, and the highest... 

SCHEME 24.50 Representative examples of arene acetoxylations using acridine as ligand. 

SCHEME 24.51 Ligand effects for arene acetoxylations using as the oxidant... 

Since these methoxylated and acetoxylated sulfides have an acetal structure, it is expected that Lewis acid catalyzed demethoxylation should generate a carbocation intermediate which is stabilized by the neighboring sulfur atom. In fact, nucleophilic substitution with arenes has been successfully achieved as shown in Scheme 6.7 [43], This procedure is useful for the preparation of trifluoroethyl aromatics. As already mentioned, generation of carbocations bearing an a-trifluoromethyl group is difficult due to the strong electron-withdrawing effect. Therefore, this carbon-carbon bond formation reaction is remarkable from both mechanistic and synthetic aspects. 

Nuclear597 or side-chain588,598 acetoxylation of arenes can be performed with good yields by persulfate and copper(II) salts in acetic acid (equations 268 and 269). As previously shown for cyclohexene (equation 263), persulfate oxidizes the aromatic ring to a radical cation which loses a proton to give a carbon radical, which is further oxidized by copper(II) acetate to the final acetoxylated product. 

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. 

Eberson and co-workers590-594 have made detailed studies of the Pd(II)-catalyzed nuclear acetoxylation of arenes. The conditions for optimum yields of nuclear acetate were established using p-xylene as a model compound. It was... 

The same workers590,591 also showed that, in the Pd(II)-catalyzed acetoxylation of substituted arenes, a complete reversal of the usual pattern of isomer distribution for electrophilic aromatic substitution or anodic oxidation of aromatics is observed. To explain these results it was suggested that acetoxylation by Pd(OAc)2 takes place via the following addition-elimination sequence ... 

Bis-(2,2-dipyridyl)-silver(II) peroxydisulfate, Ag(dipy)2S2 0g. Mol. wt. 684.44. The reagent is prepared in the same way as the corresponding pyridine complex. Oxidative acetoxylation of arenes. This Ag(II) salt oxidizes arenes in acetic acid containing sodium acetate to acetoxyarenes usually in high yield. The... 

In addition to the industrial apphcations, in Scheme 8.1, other reactions have been the focus of extensive research and development. For example. Chapter 12 surveys the research efforts directed toward Pd-catalyzed oxidative carbonylation of phenol affords the important monomer, diphenyl carbonate (Scheme 8.2a). Other reactions of potential industrial significance highlighted in this chapter include the oxidation of alcohols to aldehydes and ketones (Scheme 8.2b), oxidative coupling of arenes and carboxylic acids to afford aryl esters (Scheme 8.2c), benzylic acetoxylation (Scheme 8.2d), and oxidative Heck reactions (Scheme 8.2e). The chapter concludes by highlighting a number of newer research developments, including ligand-modulated catalytic oxidations, Pd/NO cocatalysis, and alkane oxidation. 

Oxidative esterification of arenes with carboxylic acids produces aryl esters, which can be used as precursors to valuable phenol derivatives (Scheme 8.6). Commercial production of phenol involves the aerobic oxidation of cumene to cumene hydroperoxide, followed by conversion to acetone and phenol under acidic conditions (Hock process) [49]. Aerobic acetoxylation of benzene to phenyl acetate provides a potential alternative route to phenol, and Pd-catalyzed methods for this transformation have been the focus of considerable effort. None ofthese methods are yet commercially viable, however. 

Benzyl acetates are important precursors to fragrances, and their hydrolyzed alcohol products are valuable synthons. Benzylic acetoxylation of toluene to benzyl acetate is seen as a potential route for commercial production. The major existing route to benzyl acetate proceeds via benzyl chlorides [71]. Pd-catalyzed aerobic acetoxylation toluene and other methyl arenes would offer an appealing alternate route to these products (Scheme 8.7). 

Acetoxylation of arenes. Arenes are acetoxylated by acetic acid (sodium acetate can be added) with potassium persulfate as oxidant and palladium(II) acetate as catalyst. The reaction is unusual in that wie/a-acetoxylation predominates this selectivity can be enhanced by addition of a complexing amine such as 2,2 -bipyridine. Side-chain acetoxylation can be effected with some arenes. Thus mesitylene and durene arc acetoxylated mainly in the a-position of the substituents. ... 

Charette and coworkers have developed tetraarylphosphonium (TAP)-supported (diacetoxyiodo)benzene 109 (Figure 5.5), which can be used as a recyclable reagent or a catalyst for the a-acetoxylation of ketones [101]. Similarly to the imidazolium-supported [bis(acyloxy)iodo]arene 99, the reduced form of the TAP-supported reagent 109 can be recovered from the reaction mixture by simple filtration after treatment with ether. 

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... 

The acylation of arenes with alcohols has been shown to be possible using a palladium chloride catalyst in the presence of f-butylhydroperoxide. In 2-arylpyridines, substitution is directed to the ortho-position and, after initial paUadation, the formation of intermediate (59) is likely before reductive elimination yields the acylated product. The regioselective acetoxylation of indoles, at the 3-position, has been achieved using the palladium-catalysed reaction with phenyliodonium acetate. 3-Acyl indoles may also be prepared using acetyl chlorides with zirconium tetrachloride as a Lewis acid catalyst. 

Carbon-heteroatom bond-forming reductive elimination from transient intermediates has been proposed as the product release step of a variety of important Pd-catalyzed transformations, including arene and alkane C-H bond functionahza-tion [1,2], ally lie acetoxylation [3], alkene borylation [4], and olefin difunctionalization [5]. Over the past 25 years, a variety of Pd " model complexes have been synthesized to study reductive elimination reactions at Pd centers. For instance, in 1986, Canty reported the first example of a crystallographically characterized organometallic Pd complex, /ac-[(bpy)Pd (CH3)3(l)] (bpy = 2,2 -bipyridine) (1). In addition, his group has demonstrated that this species undergoes facile C-C bond-forming reductive elimination to release ethane (Eq. 1) [6],... 

Table 1 Nuclear HOAc/0.5 M KOAc acetoxylation of arenes using Ag (bipy)2S20s in ...

Reactions involving electrophilic substitution of hydrogen in arenes are known for both nontransition [Hg(II), Tl(III), Pb(IV)] and transition metals [Au(III), Pd(II), Pt(IV)] [49]. Pd(II)-catalyzed acetoxylation involves arene activation via formation of an organometallic aryl-Pd c-complex followed by oxidative addition of oxidant and reductive elimination to restore Pd(II) and release the product [11, 50]. Without oxidant, coupling reactions predominate, suggesting arylpalladium(IV) and arylpalladium(II) intermediates in the routes leading to aryl acetates and biaryls, respectively (Scheme 14.10). 

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