Selectivity acetoxylations

An unactivated methyl group can be functionalized by the cyclopalladation of oximes. The equatorial methyl of geminal methyls in steroids or hexapyr-anosides is selectively acetoxylated by the reaction of the palladation complex 523 of the 3-oxime with lead tetraacetate[467,468]. 

No reaction was observed with stoichiometric amounts of Pd(OAc)j under argon, suggesting that Oj is likely involved in the product formation step rather than reoxidation of Pd(0). Labeling studies using and supported a direct oxygenation of the arylpalladium intermediates with Oj instead of an acetoxylation/hydrolysis sequence. Pyridyl group also enabled direct Cu-catalyzed orf/io-selective acetoxylation of aryl C—H bonds with in AcOH/ACjO [39]. 

If acetoxylation were a conventional electrophilic substitution it is hard to understand why it is not more generally observed in nitration in acetic anhydride. The acetoxylating species is supposed to be very much more selective than the nitrating species, and therefore compared with the situation in (say) toluene in which the ratio of acetoxylation to nitration is small, the introduction of activating substituents into the aromatic nucleus should lead to an increase in the importance of acetoxylation relative to nitration. This is, in fact, observed in the limited range of the alkylbenzenes, although the apparently severe steric requirement of the acetoxylation species is a complicating feature. The failure to observe acetoxylation in the reactions of compounds more reactive than 2-xylene has been attributed to the incursion of another mechan-104... 

In MeOH, l,4-dimethoxy-2-cyclohexene (379) is obtainejl from 1,3-cydo-hexadiene[315]. Acetoxylation and the intramolecular alkoxylation took place in the synthesis of the naturally occurring tetrahydrofuran derivative 380 and is another example of the selective introduction of different nucleo-philes[316]. In intramolecular 1,4-oxyacetoxylation to form the fused tetrahy-drofurans and tetrahydropyrans 381, cis addition takes place in the presence of a catalytic amount of LiCI, whereas the trans product is obtained in its absence[317]. The stereocontrolled oxaspirocyclization proceeds to afford the Irons product 382 in the presence of Li2C03 and the cis product in the presence of LiCl[ 318,319]. 

In the first step of the reaction, the acetoxylation of propylene is carried out in the gas phase, using soHd catalyst containing pahadium as the main catalyst at 160—180°C and 0.49—0.98 MPa (70—140 psi). Components from the reactor are separated into Hquid components and gas components. The Hquid components containing the product, ahyl acetate, are sent to the hydrolysis process. The gas components contain unreacted gases and CO2. After removal of CO2, the unreacted gases, are recycled to the reactor. In the second step, the hydrolysis, which is an equhibrium reaction of ahyl acetate, an acid catalyst is used. To simplify the process, a sohd acid catalyst such as ion-exchange resin is used, and the reaction is carried out at the fixed-bed Hquid phase. The reaction takes place under the mild condition of 60—80°C and ahyl alcohol is selectively produced in almost 100% yield. Acetic acid recovered from the... 

Table 4.1 weighs the positional selectivity of the side-chain cation-radical acetoxylation against the side-chain pure radical bromination. 

Synthesis of northern half building block 53 (Scheme 9) commenced with the acetoxylation of commercially available tert-hutyl acetoacetate to 54 by bromination and in situ displacement of the bromide by acetate. Deprotonation with NaH and alkylation with neryl bromide (55) afforded 58 in excellent yield. Catalytic Se02 oxidation led to selective oxidation of the terminal E-methyl group and gave 59 in 45% yield. Since the remainder is mainly unreacted starting material, this can be re-used. Reduction of the C8-C9 double... 

Allylic acetoxylation with palladium(II) salts is well known however, no selective and catalytic conditions have been described for the transformation of an unsubstituted olefin. In the present system use is made of the ability of palladium acetate to give allylic functionalization (most probably via a palladium-x-allyl complex) and to be easily regenerated by a co-oxidant (the combination of benzoquinone-manganese dioxide). In contrast... 

These multicomponent catalyst systems have been employed in a variety of aerobic oxidation reactions [27]. For example, use of the Co(salophen) cocatalyst, 1, enables selective allylic acetoxylation of cyclic alkenes (Eq. 6). Cyclo-hexadiene undergoes diacetoxylation under mild conditions with Co(TPP), 2 (Eq. 7), and terminal alkenes are oxidized to the corresponding methyl ketones with Fe(Pc), 3, as the cocatalyst (Eq. 8). 

The mechanistic role of BQ in the allylic acetoxylation of alkenes suggests that it may not be possible to achieve direct dioxygen-coupled turnover. Recently, however, Kaneda and coworkers reported BQ-free conditions for aerobic allylic acetoxylation that feature a solvent mixture of acetic acid and M,M-dimethylacetamide (DMA) and O2 as the sole oxidant for the Pd catalyst (Eq. 55) [209]. The reactions are highly selective for C-1 acetoxylation (C-1 C-3 = 7-45 1). High pressures of O2 (6 atm) are required to achieve these results. 

Side-chain acetoxylations of alkyl aromatic compounds can be performed selectively by use of internally electrogenerated cobalt(ni) acetate (Eq. (17))... 

Oxidation with lead tetraacetate is a far less selective process.490,491 Studied mainly in the oxidation of cycloalkenes, it gives stereoisomeric 1,2-diol diacetates, but side reactions (allylic acetoxylation, skeletal rearrangement) often occur. A change in reaction conditions in the oxidation of cyclopentadiene allows the synthesis of different isomeric mono- and diesters.492... 

Vinylic Acetoxylation. When alkenes are treated with Pd(II) compounds in the presence of acetic acid in a nonaqueous medium, acetoxylation takes place.495 498,499,501 503 567"569 Ethylene is converted to vinyl acetate in high yields and with high selectivity with PdCl2568,569 in the presence of added bases (NaOAc,568 Na2HP04569) or with Pd(OAc)2 570... 

Highly selective formation of phenyl acetate was observed in the oxidation of benzene with palladium promoted by heteropoly acids.694 Lead tatraacetate, in contrast, usually produces acetoxylated aromatics in low yields due to side reac-tions. Electrochemical acetoxylation of benzene and its derivatives and alkoxylation of polycyclic aromatics789 790 are also possible. Thermal or photochemical decomposition of diacyl peroxides, when carried out in the presence of polycyclic aromatic compounds, results in ring acyloxylation.688 The less reactive... 

The homogeneous palladium-catalyzed process for acetoxylation was never commercialized because of low selectivity and the difficulty in separating the catalyst from the reaction mixture. Heterogeneous palladium catalysts applied in the gas phase, in turn, quickly lose activity caused by buildup of polybutadiene. The Mitsubishi process uses a Pd-Te-on-active-carbon catalyst in the liquid phase. Tellurium apparently prevents palladium elution to acetic acid. 

The acetoxylation reaction is carried out at 70°C under 70 atm pressure by reacting 1,3-butadiene and acetic acid in the presence of air and a small amount of polymerization inhibitor. A special three-step activation (reduction-oxidation-reduction), also used in regeneration of the used catalyst, ensures high activity and selectivity. Regeneration of the catalyst is necessary after about one year of operation. 

Such a stabilization of the palladium catalyst can also be achieved in homogeneous liquid phase by the use of appropriate ligands. Thus, it has recently been shown that palladium(II) hydroxamates are effective catalysts for the acetoxylation of ethylene with high selectivity and a high turnover (>200) (equation (162), whereas Pd(OAc)2 rapidly becomes deactivated and precipitates in the form of metallic palladium.419 It is probable that the bidentate hydroxamate ligand stabilizes the hydride Pd—H species and prevents palladium from precipitating. 

Acetoxylation of propene to allyl acetate can be performed in the liquid phase with high selectivity (98%) in acetic acid in the presence of catalytic amounts of palladium trifluoroacetate. The stability and activity of this catalyst can be considerably increased by adding copper (II) trifluoroacetate and sodium acetate as cocatalysts (100 °C, 15 bar, reaction time = 4 h, conversion = 70%, selectivity = 97%). Gas-phase procedures for the manufacture of allyl acetate are described in several patents and use conventional palladium catalysts deposited on alumina or silica, together with cocatalysts (Au, Fe, Bi, etc.) and sodium acetate. The activity and selectivity reported for these catalysts are very high (100-1000 g l-1 h-1, selectivity = 90-95% ).427 A similar procedure has been used for the synthesis of methallyl acetate from 2-methylpropene.428... 

Acetoxylation of toluene using a Pd(OAc)2-Sn(OAc)2-charcoal catalyst selectively produces benzyl acetate with high turnover numbers ( 100).373,434 The active catalyst presumably contains Pd—Sn bonds. Tin ligands are known to increase the 7r-acceptor ability of palladium, and may favor the coordination of the toluene in the form of a benzylic 7r-allyl complex (141) which is nucleophilically attacked by the acetate anion.435... 

Allylic acetoxylation of cyclohexene can be selectively effected by palladium acetate in the presence of Mn02 and p-benzoquinone (bq) (equation 298).640... 

Very little work has been done on selectivity in anodic reactions of pyridines. Selective methoxylation and acetoxylation are known for al-kylbenzenes, but such reactions have not been reported for alkylpyridines. Also, reports on the oxidation of pyridines having aldehyde, ketone, halogen, hydroxyalkyl, or aminoalkyl functionalities are sparse. 

The in situ regeneration of Pd(II) from Pd(0) should not be counted as being an easy process, and the appropriate solvents, reaction conditions, and oxidants should be selected to carry out smooth catalytic reactions. In many cases, an efficient catalytic cycle is not easy to achieve, and stoichiometric reactions are tolerable only for the synthesis of rather expensive organic compounds in limited quantities. This is a serious limitation of synthetic applications of oxidation reactions involving Pd(II). However it should be pointed out that some Pd(II)-promoted reactions have been developed as commercial processes, in which supported Pd catalysts are used. For example, vinyl acetate, allyl acetate and 1,4-diacetoxy-2-butene are commercially produced by oxidative acetoxylation of ethylene, propylene and butadiene in gas or liquid phases using Pd supported on silica. It is likely that Pd(OAc)2 is generated on the surface of the catalyst by the oxidation of Pd with AcOH and 02, and reacts with alkenes. 

If defined amounts of water are added to the electrolyte, the anodic acetoxylation yields the corresponding aldehydes with very good selectivities. The reaction passes smoothly through the benzyl acetate stage. On the basis of this method, BASF has developed industrial processes for the production of aromatic aldehydes 174-,75>. 

Fuchigami, Marken and coworkers also reported self-supported anodic methoxy-lation and acetoxylation of several aromatic compounds using a simple thin-layer flow cell reactor (interelectrode gap of 80 pm) (Scheme 4.41) [56]. The current efficiency (CE) of this process was 10% at best because of oxidation of methanol at flow rates lower than 0.03 ml/min. Even though CE increased at a faster flow rate (0.5 ml/min), the yield decreased sharply. The importance of selecting an appropriate choice of electrode material also was noted. 

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