Acetoxylation, with supported

More information has appeared concerning the nature of the side reactions, such as acetoxylation, which occur when certain methylated aromatic hydrocarbons are treated with mixtures prepared from nitric acid and acetic anhydride. Blackstock, Fischer, Richards, Vaughan and Wright have provided excellent evidence in support of a suggested ( 5.3.5) addition-elimination route towards 3,4-dimethylphenyl acetate in the reaction of o-xylene. Two intermediates were isolated, both of which gave rise to 3,4-dimethylphenyl acetate in aqueous acidic media and when subjected to vapour phase chromatography. One was positively identified, by ultraviolet, infra-red, n.m.r., and mass spectrometric studies, as the compound (l). The other was less stable and less well identified, but could be (ll). 

Support for the above view comes from NMR studies of the binding of phenyl and nitrophenyl acetates to a-CD (Komiyama and Hirai, 1980). These indicate that the nitro groups are located in the CD cavity and that the acetoxyl groups of the esters are held outside, more or less close to the secondary hydroxyls of the CD. It was calculated that the distance between the ester carbonyl carbon and the secondary hydroxyls decreases as p-nitro > phenyl > m-nitrophenyl, consistent with the observed order of rate acceleration (Komiyama and Bender, 1984). 

A number of reactions, principally of olefinic substrates, that can be catalyzed by supported complexes have been studied. These include hydrogenation, hydrosilylation, hydroformylation, polymerization, oxidative hydrolysis, acetoxylation, and carbonylation. Each of these will be considered in turn together with the possibility of carrying out several reactions consecutively using a catalyst containing more than one kind of metal complex. 

It should be noted that heterogeneous palladium acetoxylation catalysts do not contain copper cooxidants, presumably because the support stabilizes the resulting palladium(II) hydride such as (136) and prevents the formation of metallic palladium. The stabilized palladium hydride (136) may react with 02 to give the hydroperoxide (137), which is probably an important intermediate for the regeneration of the initial Pd11 catalyst. 

It can be seen that the cation radical of stilbene, but not stilbene itself, is subjected to acetoxylation. Stilbene in trans form yields the trans form of the cation radical, which undergoes further reaction directly. Stilbene in cis form gives the cation radical with the cis structure. Such a cis cation radical at first acquires the trans configuration and only after that adds the acetate ion. It is the isomerization that causes the observed retardation of the total reaction. It is the absence of adsorption at the electrode surface that allows the nonace-toxylated part of cis stilbene to isomerize and to turn into the more rich stereoisomeric set of final products. To support this point of view, one can mention the cation radical epoxi-dation and cylopropanation of stilbenes. In the aminiumyl ion-catalyzed reactions, cis stil-benes react about 2.5 times slower than trans stilbenes, whereas in electrophilic oxidations the cis isomers are more reactive (Kim et al. 1993 Bauld Yeuh 1994 Mirafzal et al. 1998 Adamo et al. 2000). 

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. 

The industrially important acetoxylation consists of the aerobic oxidation of ethylene into vinyl acetate in the presence of acetic acid and acetate. The catalytic cycle can be closed in the same way as with the homogeneous Wacker acetaldehyde catalyst, at least in the older liquid-phase processes (320). Current gas-phase processes invariably use promoted supported palladium particles. Related fundamental work describes the use of palladium with additional activators on a wide variety of supports, such as silica, alumina, aluminosilicates, or activated carbon (321-324). In the presence of promotors, the catalysts are stable for several years (320), but they deactivate when the palladium particles sinter and gradually lose their metal surface area. To compensate for the loss of acetate, it is continuously added to the feed. The commercially used catalysts are Pd/Cd on acid-treated bentonite (montmorillonite) and Pd/Au on silica (320). 

An earlier report [i8y] of the formation of 4a-acetoxy-cholest"5"en-3 One (4) from cholest-5-en-3-one (3) can now be interpreted as a preferential a-face attack upon the enolic 3,5-diene. The stereochemistry of acetoxylation suggests a connection with the sterically-controlled 4 -deprotonation of the A -3-ketone discussed in Chapter 4, section 6, but electrophilic attack at C<4) rather than at C 6> in the neutral enol is abnormal, and probably indicates that acetoxy transfer occurs via a cyclic transition state (3 with the reagent bonded to the C(3)-oxygen substituent. Corey [188] has proposed a mechanism of this type, and suggested that the enol triacetoxy-plumbate cf. 5) may arise by direct reaction between the ketone and the reagent. Supporting such an interpretation, the 3-acetoxy 3,5 diene(6) reacted normally (p. 184) with lead tetraacetate to give the 6j -acetoxy-A -3-ketone 7) [i8g] instead of a 4-acetoxy derivative. 

Concurrent with side-chain acetoxylation of alkylaromatic compounds in AcOH-NH4NO3, formation of benzyl nitrates, ArCH20N02, is observed in about the same yield as the ArCH20Ac [123,152,153]. It seems likely that N03 and AcOH compete as nucleophiles for an intermediate benzyl cation, although an indirect mechanism cannot be ruled out completely because of the complexity of the supporting electrolyte behavior [155]. 

When Pd compounds (PdfOAc) ", Pd2(OAc)i , or Pd3(OAc)e) are used as starting material, even small additions of water (1-3%) to the NaOAc/AcOH solvent give rise to a great deal of acetaldehyde instead of vinyl acetate [11-13]. In contrast to this, the Pd metal catalysts (e. g., supported Pd or Pd black, prepared by H2 reduction of Pd" complexes in combination with NaOAc) provide vinyl ester from alkene and AcOH with high selectivity, regardless of the water content up to 10% [11, 14, 15]. Further differences in the selectivity of reaction (1) with Pd" and Pd° catalysts were found for the oxidative acetoxylation of higher alkenes, viz., propylene, 1-hexene, and cyclohexene [7]. All these facts apparently implied that the alkene activation came from two different origins one from Pd" and another from Pd metal or, more exactly, low-valent Pd clusters formed upon Pd" reduction with H2. 

Two mechanisms have been suggested. A radical mechanism was first proposed and its involvement is supported by the presence of dimeric products. However, the ligand coupling mechanism is now generally accepted. An enol-lead (IV) triacetate intermediate (7) is first formed by reaction of lead tetraacetate with the enol form. Its formation is accelerated by catalysis by boron trifluoride. 14,33 Treatment of the preformed enolate with lead tetraacetate performs a-acetoxylation at lower temperature and more rapidly than in the reaction with the corresponding enol. 4 Ligand coupling then takes place on this intermediate to lead to the a-acetoxycarbonyl derivative. 

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... 

Addition Anodic oxidation of enolacetates, for example, 1-acetoxy-3,4-dihydronaphthaline and a-acetoxy- -alkylstyrene, afforded at —78°C in ace-tonitrile/TH F/ H O Ac containing tetraethy-lammonium (5)-camphorsulfonate as supporting electrolyte, enantioenriched acetoxylation products with 44 and 21% ee (enantiomeric excess) respectively [367]. 

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]. 

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