Alkene acetoxylation

Three oxidative reactions of benzene with Pd(OAc)2 via reactive rr-aryl-Pd complexes are known. The insertion of alkenes and elimination afford arylalk-enes. The oxidative functionalization of alkenes with aromatics is treated in Section 2.8. Two other reactions, oxidative homocoupling[324,325] and the acetoxylation[326], are treated in this section. The palladation of aromatic compounds is possible only with Pd(OAc)2. No reaction takes place with PdCl2. 

Allylic acetoxylation.2 Pd(OAc)2 in HOAc can effect allylic acetoxylation of alkenes, probably via a TT-allylpalladium complex, and only a catalytic amount is required in the presence of a cooxidant such as benzoquinone-Mn02. The reaction is not useful in the case of simple alkenes because of lack of discrimination between the two allylic positions, but this acetoxylation can be regioselective in the case of alicyclic alkenes. 

Acetoxylation proceeds mostly via the radical cation of the olefin. Aliphatic alkenes, however, undergo allylic substitution and rearrangement predominantly rather than addition [224, 225]. Aryl-substituted alkenes react by addition to vic-disubstituted acetates, in which the dia-stereoselectivity of the product formation indicates a cyclic acetoxonium ion as intermediate [226, 227]. In acenaphthenes, the cis portion of the diacetoxy product is significantly larger in the anodic process than in the chemical ones indicating that some steric shielding through the electrode is involved [228]. 

Allylic acetoxylation of alkenes is achieved using acetic acid with sodium acetate as solvent and nucleophile. Cyclohexene gives 1 -acetoxycyclohexene as the... 

The anodic oxidation of 4-methoxyphcnols in acetic acid effectively stabilises the phenoxonium ion, in an equlibrium with the acetoxylation product. Tbis allows an intermolecular [5 + 2] bx-cycloaddition processes with some alkenes [110], The cycloaddition process has been used very successfully in the synthesis of a number of natural products [III]. The rate of cycloaddition is sensitive to substituents on the alkene bond and in imfavourable cases other reactions of the phenoxonium ion predominate. 

In 1960, Moiseev and coworkers reported that benzoquinone (BQ) serves as an effective stoichiometric oxidant in the Pd-catalyzed acetoxylation of ethylene (Eq. 2) [19,20]. This result coincided with the independent development of the Wacker process (Eq. 1, Scheme 1) [Ij. Subsequently, BQ was found to be effective in a wide range of Pd-catalyzed oxidation reactions. Eor example, BQ was used to achieve Wacker-type oxidation of terminal alkenes to methyl ketones in aqueous DMF (Eq. 3 [21]), dehydrogenation of cyclohexanone (Eq. 4 [22]), and alcohol oxidation (Eq. 5 [23]). In the final example, 1,4-naphthoquinone (NQ) was used as the stoichiometric oxidant. 

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). 

Palladium-catalyzed addition of oxygen nucleophiles to alkenes dates back to the Wacker process and acetoxylation of ethylene (Sects. 1 and 2). In contrast, catalytic methods for intermolecular oxidative amination of alkenes (i.e., aza-Wacker reactions) have been identified only recently. Both O2 and BQ have been used as oxidants in these reactions. 

Scheme 14 Possible outcomes for the palladium-catalyzed oxidative acetoxylation of alkenes...

Two important extensions of this chemistry have been reported in recent years. White and coworkers demonstrated that terminal alkenes undergo regioselective acetoxylation at the C-1 or C-3 position, depending on the re-... 

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. 

Alkenes can be transformed to carbonyl compounds through the oxidation of the vinylic carbon atom. A special case of vinylic oxidation is acetoxylation of alkenes and dienes. 

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... 

The oxidation of 1-alkenes usually gives 2-acetoxy-l-alkenes.571,572 Oxidative acetoxylation of propylene with Pd(OAc)2 may yield allylic or vinylic acetates depending on reaction conditions573 (see Section 9.2.6). 

Pd(H) complexes with strongly electron-withdrawing ligands can insert into the allylic C—H bond (path c) to form directly the Jt-allyl complex via oxidative addi-tion.502,694,697 Pd(OOCCF3)2 in acetic acid, for example, ensures high yields of allylic acetoxylated products.698 The delicate balance between allylic and vinylic acetoxylation was observed to depend on substrate structure, too. For simple terminal alkenes the latter process seems to be the predominant pathway.571... 

In fact, the role of copper and oxygen in the Wacker Process is certainly more complicated than indicated in equations (151) and (152) and in Scheme 10, and could be similar to that previously discussed for the rhodium/copper-catalyzed ketonization of terminal alkenes. Hosokawa and coworkers have recently studied the Wacker-type asymmetric intramolecular oxidative cyclization of irons-2-(2-butenyl)phenol (132) by 02 in the presence of (+)-(3,2,10-i -pinene)palladium(II) acetate (133) and Cu(OAc)2 (equation 156).413 It has been shown that the chiral pinanyl ligand is retained by palladium throughout the reaction, and therefore it is suggested that the active catalyst consists of copper and palladium linked by an acetate bridge. The role of copper would be to act as an oxygen carrier capable of rapidly reoxidizing palladium hydride into a hydroperoxide species (equation 157).413 Such a process is also likely to occur in the palladium-catalyzed acetoxylation of alkenes (see Section 61.3.4.3). 

Acetoxylation of Alkenes, Dienes and Aromatic Hydrocarbons 61.3.4.3.1 Vinyl acetate from ethytene... 

In contrast to ethylene, which gives only vinylic or oxidative addition products, the acetoxylation of higher alkenes results in the formation of a mixture of allylic and vinylic acetates.367 The... 

A somewhat similar catalytic acetoxylation of ethylene to vinyl acetate by 02 has been carried out in acetic acid in the presence of a Pd(OAc)2-pyCo(TPP)N02 system.472 A stoichiometric epoxidation of alkenes such as 1-octene or propene by cobalt-nitro complexes has been shown to occur in the presence of thallium(III) benzoate. Oxygen labeling studies showed that the epoxide oxygen atom comes only from the nitro ligand (equation 197).473... 

Finally, Thiele acetoxylation of quinones, by treatment with acetic anhydride and sulfuric acid, is another excellent method of introducing functionality at an alkene carbon atom, for further synthetic elaboration (equation 50)196. This reaction was recently used as a key synthetic step in the total synthesis of metachromin-A, a useful sesquiterpene quinone moiety197. 

Allylic acetoxylation.1 The combination of r-butyl hydroperoxide and Se02 has been used for allylic hydroxylation of alkenes (8, 64-65), but this system is not useful for oxidation of cycloalkenes. Allylic acetoxylation of cycloalkcnes is possible, but in modest yield, with PdCl2 and AgOAc, which probably form a reactive species such as [PdCl(OAc)] . This system can be used in catalytic amounts in the presence of t-butyl hydroperoxide for a reoxidation step. The yield is improved by addition of TcO, which seems to accelerate the oxidation. The most satisfactory ratios of... 

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. 

A variety of alkylbenzenes undergo anodic acetoxylation, in which the loss of an a proton and solvation of the radical cation intermediate form the basis of side-chain and nuclear acetoxylation, respectively.30Sa b The nucleophilicity of the solvent can be diminished by replacing acetic acid with TFA. The attendant increase in the lifetimes of aromatic radical cations has been illustrated in anodic oxidations.308 Radical cations also appear to be intermediates in the electrochemical oxidation of alkanes and alkenes.309a-c... 

Other transition metal salts mediate in similar oxidations. For example, mercury(II) acetate, a milder reagent than LTA, effects a-acetoxylation through a comparable mechanism. However the corresponding yields for these processes are poor. 3,3-Dimethylcyclohexanone, for example, is oxidized to the a-acetoxy derivative in only 14% yield.The, 7-unsaturated ketone, isopugelone, exhibits no oxidation at the a- or a -positions, but affords a product derived from isomerization of the alkene and allylic oxidation. Not surprisingly therefore the reagent has found little synthetic application for this transformation. 

Some other reactions involving oxidation of the C—Hg bond have been known for some time, but these are either of limited synthetic appeal or have experienced no significant development in recent years. Thus ozonolysis of the C—Hg bond to form carboxylic acids or ketones falls into the first category, whereas allylic acetoxylation of alkenes by Hg(OAc>2 falls into the second category. Nevertheless, this allylic oxidation (Treibe s reaction) has considerable synthetic utility, and has been reviewed quite recently.5 ... 

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