Wacker oxidation efficiency

For internal olefins, the Wacker oxidation is sometimes surprisingly regioselective. By using aqueous dioxane or THF, oxidation of P,y-unsaturated esters can be achieved selectively to generate y-keto-esters (Eq. 3.18).86 Under appropriate conditions, Wacker oxidation can be used very efficiently in transforming an olefin to a carbonyl compound. Thus, olefins become masked ketones. An example is its application in the synthesis of (+)-19-nortestosterone (3.11) carried out by Tsuji (Scheme 3.5).87... 

The most important reaction based on Pdn-catalysis is the Wacker oxidation [171], which is used industrially for the synthesis of acetaldehyde, starting from ethane. This process can be combined with a Heck reaction and has been used by Tietze and coworkers [172] for an efficient enantioselective synthesis of vitamin E (6/1-... 

Moreover, it was disclosed that PdCl2 in combination with N,N-dimethylaceta-mide (DMA) solvent could offer a simple and efficient catalyst system for acid-and Cu-free Wacker oxidation [102]. The reaction is illustrated in Fig. 4.37. A wide range of terminal olefins could be oxidized to form the corresponding methyl ketones in high yields, reaching a TOF up to 17 h-1. The Pd-DMA catalyst layer could be recycled. Furthermore this system is also capable of per-... 

Choi, K.-M., Mizugaki, T., Ebitani, K., Kaneda, K. Nanoscale palladium cluster immobilized on a Ti02 surface as an efficient catalyst for liquid-phase Wacker oxidation of higher terminal olefins. Chem. Lett. 2003, 32, 180-181. 

Paquette was one of the first to apply the Wacker oxidation in the total synthesis. In his synthesis of 18-oxo-3-virgene, a constituent of the waxy surface resins of tobacco, a Wacker oxidation was deployed to convert a terminal alkene to the corresponding methyl ketone.59 In an efficient total synthesis of ( )-laurene (77), alkene 75 was oxidized to keto-aldehyde 76 at ambient temperature.60 In Smith s total synthesis of calyculin, a modified Wacker oxidation with substoichiometric cupric acetate transformed terminal alkene 78 to methyl ketone 79 without concurrent acetonide hydrolysis.61,62... 

In a later work, both the CuCl/KCl molten salt Wacker oxidation system and a [Bu4N][SnCl3] system (melting point 60 °C) was applied to the electrocatalytic generation of acetaldehyde from ethanol by co-generation of electricity in a fuel cell [56]. In the cell set-up, porous carbon electrodes supported with an ionic liquid catalyst electrolyte were separated by a proton conducting membrane (Fig. 5.6-4), and current efficiency and product selectivity up to 87% and 83%, respectively, were reported at 90 °C. 

For the stereoselective synthesis of C-glycosides, deoxygenation of hemiketals, obtained from Wacker oxidation of sngar-derived olefin alcohols, was envisaged as an easy and efficient protocol. In our earlier study on the synthesis of 4-epiethisolide, attempted PdCV mediated conversion of the terminal olefin (1), obtained from sugar chiron into a methyl ketone (2) resulted in the exclnsive formation of an anti-Markovnikov product (3), which happened to be the first report in the literature (Scheme 22.1). 

Following the development of aerobic conditions, N-heterocychc carbenes (NHCs) were found to be equally efficient under conditions of homogeneous palladium catalysis [33]. Although initially their apphcation had focused on aerobic alcohol oxidation, later examples include Wacker oxidation of styrenes and 2-aUyl phenol cych2ation.[34]... 

FIGURE 2.9 Efficiency of the Wacker oxidation of n-alkenes with various MIP-CD. (Adapted fwmRef. [38].)... 

Earlier studies have also shown that a catalyst system consisting of palladium(II) and copper salts plus oxygen for the reoxidation did not work well,t in contrast to the result with the Wacker oxidation. However, if quinone or hydroquinone was added to a mixture of palladium acetate and copper acetate, oxygen could be used as an efficient oxidant for conversion of alkenes into allylic acetates. Thus, cyclohexene gave better than 85% cyclohexenyl acetate (Scheme 10). The combination of oxygen and cobalt or manganese acetate also works, but less well.t ... 

Electron-poor alkenes can also participate in the Wacker oxidation. Now, the role of the palladium is to enhance the natural electrophilicity of the alkene (Scheme 6.11)." In addition, the regioselectivity of the reaction is controlled by the electron-withdrawing group. Once again, alternative nucleophiles may be employed. The use of an alcohol, in place of water, leads to acetal formation. The scalability of the reaction is illustrated by formation of acetal 6.26 on a 200 g scale (Scheme 6.12)." In this case, a third catalyst, Fe(III), was included to improve the efficiency of the catalyst re-oxidation. 

One of the earliest uses of palladium(II) salts to activate alkenes towards additions with oxygen nucleophiles is the industrially important Wacker process, wherein ethylene is oxidized to acetaldehyde using a palladium(II) chloride catalyst system in aqueous solution under an oxygen atmosphere with cop-per(II) chloride as a co-oxidant.1,2 The key step in this process is nucleophilic addition of water to the palladium(II)-complexed ethylene. As expected from the regioselectivity of palladium(II)-assisted addition of nucleophiles to alkenes, simple terminal alkenes are efficiently converted to methyl ketones rather than aldehydes under Wacker conditions. 

Oxidation of allylic andhomallylic acetates (cf. 10,175-176).1 This system is an efficient catalyst for oxygenation of terminal alkenes to methyl ketones (Wacker process). Similar oxidation of internal olefins is not useful because it is not regioselective. However, this catalyst effects oxygenation of allylic ethers and acetates regioselectively to give the corresponding /i-alkoxy ketones in 40-75% yield. Under the same conditions, homoallylic acetates are oxidized to y-acetoxy ketones as the major products. 

Supported liquid-phase catalysts (SLPCs) combine the salient features of both homogeneous and heterogeneous catalysis for enhanced catalytic and/or process efficiency (337). SLPC catalysts, in which a liquid-phase (homogeneous) catalyst is dispersed within a porous support, have been used in Wacker-type ethylene oxidation for acetaldehyde and vinyl acetate production (337, 338). In the former case, a traditional homogeneous Wacker catalyst (vide supra) consisting of a chlorinated solution of Pd and Cu chlorides retained on a support with monomodal pore size distribution... 

The electrophilic activation of a C—C multiple bond as a result of coordination to an electron-deficient metal ion is fundamental to much of organometallic chemistry, both conceptually and in synthetic applications (11). The Wacker process, a classic example of an efficient catalytic oxidation, is an important industrial reaction, used for the conversion of ethylene into acetaldehyde. The catalytic reaction begins with the coordination of ethylene to a Pd(ll) center, leading to activation of the ethylene moiety. The key step is the reaction of the metal-olefin complex with a nucleophile to give substituted metal-alkyl species (12). The integration of this reaction into a productive catalytic cycle requires the eventual cleavage of the newly generated M—C bond. 

This development began to reduce steadily the capacities of acetaldehyde which previously had been made by oxidation of ethylene (Wacker-Hoechst process cf. Section 2.4.1) and converted to acetic acid (cf. Section 2.4.4). Moreover, the Monsanto process, the second-generation process for methanol carbonylation is now being followed by the third generation of highly efficient carbonylation processes, enabling acetic anhydride as well as acetic acid to be produced (cf Scheme 2 Tennessee-Eastman [36] and BP [37] processes). The most advanced process (Hoechst [40]) has so far not been implemented industrially because of neglects... 

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