Wacker oxidation, palladium-catalyzed

Palladium-catalyzed oxidation of hydrocarbons has been a matter of intense research for about four decades. The field was initiated by the development of the aerobic oxidation of ethylene to acetaldehyde catalyzed by palladium chloride and co-catalyzed by cupric chloride (the Wacker process, equation l)1. 

The electrochemical Wacker-type oxidation of terminal olefins (111) by using palladium chloride or palladium acetate in the presence of a suitable oxidant leading to 2-alkanones (112) has been intensively studied. As recyclable double-mediatory systems (Scheme 43), quinone, ferric chloride, copper acetate, and triphenylamine have been used as co-oxidizing agents for regeneration of the Pd(II) catalyst [151]. The palladium-catalyzed anodic oxidation of... 

The method involves a regioselective, trans-diastereoselective, and enantioselective three-component coupling, as shown in Scheme 7.26. In this case, the zinc enolate resulting from the 1,4-addition is trapped in a palladium-catalyzed allyla-tion [64] to afford trans-2,3-disubstituted cyclohexanone 96. Subsequent palladium-catalyzed Wacker oxidation [82] yields the methylketone 97, which in the presence of t-BuOK undergoes an aldol cyclization. This catalytic sequence provides the 5,6-(98) and 5,7- (99) annulated structures with ees of 96%. 

The Wacker process (Eq. 1) was developed nearly 50 years ago [1-3] and represents one of the most successful examples of homogeneous catalysis in industry [4-9]. This palladium-catalyzed method for the oxidation of ethylene to acetaldehyde in aqueous solution employs a copper cocatalyst to facilitate aerobic oxidation of Pd° (Scheme 1). Despite the success of this process, certain features of the reaction have Umited the development of related aerobic oxidation reactions. Many organic molecules are only sparingly sol-... 

Palladium-catalyzed, Wacker-type oxidative cycHzation of alkenes represents an attractive strategy for the synthesis of heterocycles [139]. Early examples of these reactions typically employed stoichiometric Pd and, later, cocat-alytic palladium/copper [140-142]. In the late 1970s, Hegedus and coworkers demonstrated that Pd-catalyzed methods could be used to prepare nitrogen heterocyles from unprotected 2-allylanilines and tosyl-protected amino olefins with BQ as the terminal oxidant (Eqs. 23-24) [143,144]. Concurrently, Hosokawa and Murahashi reported that the cyclization of allylphenol substrates can be accomplished by using a palladium catalyst with dioxygen as the sole stoichiometric reoxidant (Eq. 25) [145]. 

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. 

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). 

The synthetic applications of the palladium-catalyzed oxidation of alkenes to ketones have recently been reviewed.639 Improvements in the Wacker palladium-catalyzed ketonization of terminal alkenes have been obtained using phase-transfer catalysis,641 polyethylene glycol642 or phosphomolybdovanadic acids.643... 

The Wacker Oxidation is an industrial process, which allows the synthesis of ethanal from ethene by palladium-catalyzed oxidation with oxygen. Copper serves as redox cocatalyst. 

Another example is the palladium-catalyzed oxidation of ethylene to acetaldehyde in the presence of oxygen and cupric salts, the so-called Wacker reaction. This catalytic cycle combines two stoichiometric processes, which involve first the reduction of Pd11 to Pd°, followed by reoxidation with Cu11. The understanding of the first step of this process came from the earlier work of Kharasch et al., who showed that the stoichiometric dinuclear complex shown in Figure 2.14 decomposed in the presence of water to acetaldehyde (ethanal), Pd° and HC1 [38]. 

Wacker reactions, which is why we refer to them here [12, 15-17]. Finally, the general concept of a Wacker reaction could be regarded as the palladium-catalyzed oxidative coupling of heteronucleophiles and olefins, and this can obviously be extended to nitrogen nucleophiles and others [18] conversely, the principle of the Cu(I)/Cu(II)/02 reoxidation system for Pd(0) can be applied to other oxidation reactions (for example that of CO to C02), but the present overview is limited to sp2-C-H activation in olefins. 

The palladium-catalyzed oxidation of ethylene to acetaldehyde (the Wacker process) was discovered by Smidt and co-workers514-518 in 1959. This process combines the stoichiometric reduction of Pd(II) with reoxidation of metal in situ by molecular oxygen in the presence of copper salts. The overall reaction constitutes a palladium-catalyzed oxidation of ethylene to acetaldehyde by molecular oxygen ... 

The field of homogeneous palladium catalysis traces its origin to the development of the Wacker process in the late 1950s (Eq. 7) [83]. Since this discovery, palladium-catalyzed reactions have evolved into some of the most versatile reactions for the synthesis of organic molecules [84,85]. Palladium-catalyzed Wacker-type oxidation of alkenes continues to be an active field of research [86-88], and several recent applications of NHC-coordinated Pd catalysts have been reported for such reactions. 

For Wacker oxidation, see The Organic Chemistry of Palladium, P. M. Maitlis, Academic Press, New York, 1971 Palladium Catalyzed Oxidation of Hydrocarbons, P. M. Henry, D. Reidel, Dordrecht, 1980. 

In my opinion (and I am convinced that Ernst Otto Fischer would have agreed), Walter Hafner was one of the best Ph.D. students, probably the best Fischer ever had. After he finished his doctoral research, he joined the Consortium filr Elektrochemische Industrie, a research subsidiary of Wacker-Chemie in Munich, where he laid the foundations for the palladium-catalyzed oxidation of ethene to acetaldehyde, the Wacker process. This process has been licenced to various chemical companies all over the world and initiated an evergrowing area of synthetic organic chemistry. Walter Hafner retired in 1992 and died in 2004. 

In this context it is also worth mentioning that Showa Denko has developed a new process for the direct oxidation of ethene to acetic acid using a combination of palladium(II) and a heteropoly acid [104]. However, the reaction probably involves heteropoly acid-catalyzed hydration followed by palladium-catalyzed aerobic oxidation of ethanol to acetic acid rather than a classical Wacker mechanism. 

Figure 28 shows that the chemistry involved in the Wacker process could in principle be extended to other nucleophiles. The modern catalytic manufacturing process making vinyl acetate from ethylene and acetic acid is based on the observation that palladium catalyzed oxidation of ethylene to acetaldehyde can be converted into an acetoxylation reaction if carried out in a solution of acetic acid and in the presence of sodium acetate (Equation 42). 

Suzuki reaction the palladium-catalyzed reaction of an aryl or vinyl halide with an aryl boronic acid to give an arylated or vinylated arene. In some cases, primary alkyl halides can react in place of the aryl or vinyl halides Wacker process the palladium-catalyzed oxidation of ethene to acetaldehyde by oxygen... 

The oxidation of ethene by palladium salts in water to give acetaldehyde has been known for 100 years see Oxidation Catalysis by Transition Metal Complexes). It is often called the Wacker Process, after Wacker Chemie GmbH, which first developed the process. The key steps in this oxidation are shown in Scheme 2. Palladium catalyzes the nucleophilic addition of water to ethene, leading to the reduction of Pd to Pd°. Then the palladium is reoxidized back to Pd with Cu salts, giving Cu which in turn is oxidized by oxygen. 

Among the several types of homogeneously catalyzed reactions, oxidation is perhaps the most relevant and applicable to chemical industry. The well-known Wacker oxidation of ethylene to ethylene oxide is the classic example, although this is not a true catalytic process since the palladium (II) ion becomes reduced to metallic palladium unless an oxygen carrier is present. Related to this is the commercial reaction of ethylene and acetic acid to form vinyl acetate, although the mechanism of this reaction does not seem to have yet been discussed publicly. Attempts to achieve selective oxidation of olefins or hydrocarbons heterogeneously do not seem very successful. 

Gaunt, M. J., Spencer, J. B. Derailing the Wacker Oxidation Development of a Palladium-Catalyzed Amidation Reaction. Org. Lett. 2001,... 

Trend, R. M., Ramtohul, Y. K., Ferreira, E. M., Stoltz, B. M. Palladium-catalyzed oxidative Wacker cyclizations in nonpolar organic solvents with molecular oxygen A stepping stone to asymmetric aerobic cyclizations. Angew. Chem., Int. Ed. Engl. 2003,42, 2892-2895. 

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