Alkenes Wacker process

A common property of coordinated alkenes is their susceptibility to attack by nucleophiles such as OH , OMe , MeC02, and Cl , and it has long been known that Zeise s salt is slowly attacked by non-acidic water to give MeCHO and Pt metal, while corresponding Pd complexes are even more reactive. This forms the basis of the Wacker process (developed by J. Smidt and his colleagues at Wacker Chemie, 1959-60) for converting ethene (ethylene) into ethanal (acetaldehyde) — see Panel overleaf. 

Early mechanistic studies have indicated that the oxypalladation step in the Wacker process proceeds through an <37z/z-pathway,399 although recent deuterium-labeling experiments have shown the viability of a yy/z-mechanism involving insertion of a metal-coordinated oxygen into the alkene.400,401 For example, with excess chloride ion present, the Wacker-type cyclization of a deuterated phenol system occurred in a primarily //-pathway, whereas the oxypalladation step favored a yy/z-mode in the absence of excess chloride ion (Scheme 16). Thus, either mechanism may be operative under a given set of experimental conditions. 

Anodic oxidation is used to promote the recycling of palladium(il) in the Wacker process for the conversion terminal alkenes to methyl ketones. Completion of the catalytic cycle requires the oxidation of palladium(O) back to the palla-dium(li) state and this step can be achieved using an organic mediator such as tri(4-bromophenyljamine. The mediator is oxidised at the anode to a radical-cation and... 

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. 

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. 

Although the oxidation of ethylene to acetaldehyde was known for a number of years,506 its utility depended on the catalytic regeneration of Pd(0) in situ with cop-per(II) chloride discovered by Smidt and coworkers.507 508 Air oxidation of Cu(I) to Cu(n) makes a complete catalytic cycle. This coupled three-step transformation is known as the Wacker process [Eqs. (9.97)-(9.99)]. The overall reaction [Eq. (9.100)] is the indirect oxidation with oxygen of alkenes to carbonyl compounds ... 

This process, developed in Germany, was one of the first to foretell the importance of alkenes following World War II. About 4 million pounds of aldehydes are produced yearly by this method. Acetaldehyde is easily oxidized to acetic acid and the overall conversion of ethylene to the acid represents a principal route to its synthesis, ft has been said that the invention of the Wacker process was a triumph of common sense. 82... 

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). 

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. 

Terminal alkenes can be selectively oxidized to aldehydes by reaction with oxygen, using a palladium-copper catalyst in tertiary butanol (equation 35)160. This reaction is contrary to the normal oxidation process which yields a ketone as the major product. The palladium(II) oxidation of terminal alkenes to give methyl ketones is known as the Wacker process. It is a very well established reaction in both laboratory and industrial synthesis161162. The Wacker oxidation of alkenes has been used in the key step in the synthesis of the male sex pheromone of Hylotrupes bajulus (equation 36)163. 

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. 

Various nucleophiles can attack coordinated alkenes. Typically the attack of OH anion on ethylene coordinated to Pd(II) as shown by 71 takes place in the Wacker process to afford acetaldehyde (72) [4], Also COD (73), coordinated to PdCl2, was shown to be attacked by carbon nucleophiles such as malonate to give 74. This reaction is the first example of carbopalladation of alkenes [5],... 

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. 

The Pd-catalyzed conversion of terminal alkenes to methyl ketones is a reaction that has found widespread use in organic chemistry [87,88]. These reactions, as well as the industrial Wacker process, typically employ CuCh as a co-catalyst or a stoichiometric oxidant. Recently Cu-free reaction conditions were identified for the Wacker-type oxidation of styrenes using fBuOOH as the oxidant. An NHC-coordinated Pd complex, in-situ-generated (I Pr)Pd(OTf)2, served as the catalyst (Table 5) [101]. These conditions min-... 

Nucleophilic attack by water on coordinated ethylene, as shown by Reaction 2.12, is the key step in the manufacture of acetaldehyde by the Wacker process (see Chapter 8). In Reaction 2.13 the high oxidation state of titanium makes the coordinated oxygen atom sufficiently electrophilic for it to be attacked by an alkene. As we will see in Chapter 8, this reaction is the basis for the homogeneous catalytic epoxidation of alkenes, using organic hydroperoxides as the oxygen atom donors. 

Ever since the initial discovery of the Wacker process [1], i.e. the Pd/Cu-catalyzed oxidation of ethylene to acetaldehyde (1) in water, methods for the palladium (II) - mediated oxidative functionalization of alkenes have found widespread application in the synthesis of complex molecules [2J. 

The Wacker process is carried out in an aqueous medium containing hydrochloric acid. In addition to ethylene, Smidt and coworkers carried out the oxidation of other alkenes in an acidic aqueous solution of PdCh to prepare carbonyl compoimds. After this report, a few studies on the oxidation of higher alkenes were carried out in organic media. In general, terminal alkenes are converted to methyl ketones rather than aldehydes (equation 1). 

The industrial Wacker process is carried out in aqueous hydrochloric acid using PdClj/CuCh as the catalyst under oxygen pressure. The oxidation of higher terminal alkenes under the same conditions is slow and sometimes accompanied by undesired by-products formed by the chlorination of carbonyl com-poimds by CuCh, and isomerization of double bonds. Earlier examples of oxidation of various alkenes, mainly in aqueous solutions, have been tabulated.The pseudo-first-order rate constants for oxidation of various alkenes, relative to the value for cycloheptene, with PdCb in the presence of benzoquinone in aqueous solution have been rqwrted. An accelerating effect of surfactants such as sodium lauryl sulfate on the stoichiometric oxidation of higher alkenes in an aqueous solution has been reported. 

Nucleophilic addition to metal-activated alkenes as a synthetic method can be traced to the Wacker Process, the oxidation of ethylene to acetaldehyde with Pd and... 

The activating effect of Pd and Fe° toward nucleophilic addition to alkenes is powerful and allows addition of stabilized anions to simple alkenes at low temperatures. However, the only efficient catalytic processes are based on the addition of oxygen nucleophiles to alkenes activated by spontaneous coordination with Pd extensions of the Wacker process. 

Several important nomadical catalytic oxidations go via organometalhc mechanisms. The commercially useful Wacker process converts ethylene to acetaldehyde with air as oxidant, using Pd(II) and Cu(II) catalysts. The Pd(II) binds to the ethylene to give an organometalhc intermediate, the alkene complex. This complex subsequently uses water as the O source to oxidize the ethylene to acetaldehyde, the Pd being reduced in the process. The resulting Pd(0) is reoxidized to Pd(II) with two equivalents of Cu(n) and the Cu(I) so formed is then reoxidized by air to close the cycle. 

---