Alkenes Wacker reaction

The Wacker Reaction and Related Oxidations. An important industrial process based on Pd-alkene complexes is the Wacker reaction, a catalytic method for conversion of ethene to acetaldehyde. The first step is addition of water to the Pd(n)-activated alkene. The addition intermediate undergoes the characteristic elimination of Pd(0) and H+ to generate the enol of acetaldehyde. 

The Wacker reaction can also be applied to laboratory-scale syntheses.104 When the Wacker conditions are applied to terminal alkenes, methyl ketones are formed.105... 

This regiochemistry is consistent with the electrophilic character of Pd(II) in the addition step. Solvent and catalyst composition can affect the regiochemistry of the Wacker reaction. Use of /-butanol as the solvent was found to increase the amount of aldehyde formed from terminal alkenes, and is attributed to the greater steric requirement of /-butanol. Hydrolysis of the enol ether then leads to the aldehyde. 

The two reactions shown below are examples of the use of the Wacker reaction in multistep synthesis. In the first case, selectivity is achieved between two terminal alkene units on the basis of a difference in steric accessibility. Both reactions use a reduced amount of Cu(I) salt. In the second reaction this helps to minimize hydrolysis of the acid-sensitive dioxolane ring. 

Since nucleophilic addition to a metal-coordinated alkene generates a cr-metal species bonded to an -hybridized carbon, facile 3-H elimination may then ensue. An important example of pertinence to this mechanism is the Wacker reaction, in which alkenes are converted into carbonyl compounds by the oxidative addition of water (Equation (108)), typically in the presence of a Pd(n) catalyst and a stoichiometric reoxidant.399 When an alcohol is employed as the nucleophile instead, the reaction produces a vinyl or allylic ether as the product, thus accomplishing an etherification process. 

The metal-catalysed autoxidation of alkenes to produce ketones (Wacker reaction) is promoted by the presence of quaternary ammonium salts [14]. For example, using copper(II) chloride and palladium(II) chloride in benzene in the presence of cetyltrimethylammonium bromide, 1-decene is converted into 2-decanone (73%), 1,7-octadiene into 2,7-octadione (77%) and vinylcyclohexane into cyclo-hexylethanone (22%). Benzyltriethylammonium chloride and tetra-n-butylammo-nium hydrogen sulphate are ineffective catalysts. It has been suggested that the process is not micellar, although the catalysts have the characteristics of those which produce micelles. The Wacker reaction is also catalysed by rhodium and ruthenium salts in the presence of a quaternary ammonium salt. Generally, however, the yields are lower than those obtained using the palladium catalyst and, frequently, several oxidation products are obtained from each reaction [15]. 

At present the Wacker reaction should be regarded as a relatively slow process, with only a few hundred turnovers per hour at elevated temperatures and pressures. For internal alkenes the rate is one or two orders of magnitude lower and the reaction affords mixtures of products due to isomerisation. In the absence of isomerisation, the product of the Wacker oxidation of a 1-alkene is a... 

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. 

The palladium catalysed conversion of alkenes to enols, also known as the Wacker reaction, has also been used in the formation of oxygen heterocycles. In the example shown in 3.68. the subsequent formation of two carbon-oxygen bonds leads to the desired dioxabicyclo[3.2.1]octane derivative. The first Wacker reaction gives selectively a six membered ring formation (other possible routes would lead to even larger rings), while in the second Wacker reaction the selective formation of the five membered ring is observed.86... 

Takacs, J.M. and Jiang, X.-t. (2003) The Wacker reaction and related alkene oxidation reactions. Curr. Org. Chem., 7, 369. 

Textbook chemistry (297,298) teaches that palladium is the preferred catalyst for aerobic oxidation of olefins. When water is the solvent, nucleophilic water addition to coordinated olefins is the key step in the so-called Wacker cycle. Wacker oxidation occurs regiospecifically because a carbonyl group is formed at that carbon atom of the double bond where the nucleophile in a Markovnikov-like addition would enter. The Wacker reaction thus yields methylketones from primary alkenes ... 

Palladium(II)-promoted oxidative cyclization of alkenes bearing tethered nucleophiles represents an intramolecular variant of the Wacker reaction. These reactions, which typically generate five- and six-membered heterocycles, have been the subject of considerable interest in organic chemistry [89-96]. Contemporary interest centers on the development of enantioselective examples [95,97] and reactions that employ dioxygen as the sole oxidant for the Pd catalyst [92-96]. 

Based on the results of mechanistic studies on the stereochemical course of the Wacker reaction and related processes [7], one would expect the alkoxypalladation of alkenes to proceed stereo-specifically as a traw-addition. Indeed, this was confirmed in the highly diastereoselective formation of compound rac-18 from 20 and of rac-19 from 21. 

The oxidation of terminal alkenes to the corresponding 2-alkanones (Wacker reaction cf. Section 2.4.1) has also been carried out under PTC conditions. This process is catalyzed by a PT agent and PdCl2 in the presence of CUCI2 (reoxidant eq. (6)) [84]. The reaction is very sensitive to the nature of the PT catalyst only quaternary salts of type Me3N" (Ci2-Ci4-alkyl) Br are effective. 

For the oxidation of terminal alkenes to methyl alkyl ketones, RhCl3 and RuCls as well as their complexes may be used instead of PdCl2. In these cases, symmetrical quaternary ammonium salts are also effective. However, under these conditions, the isomerization of alkenes occurs simultaneously with the oxidation [85]. The biphasic Wacker reaction can also be carried out under IPTC conditions using a- or /i-CD as the PT agent [86, 87]. 

The Wacker reaction has also been applied to numerous simple alkenes such a-alkenes or cycloalkenes, or to functionalized alkenes such nitroethylene, acrylonitrile, styrene, allyl alcohol, or maleic acid [3]. The carbonyl group is formed at the carbon atom of the double bond where the nucleophile would add in a Markovni-kov addition (Eq. 5). Among these different alkenes, the oxidation of propene to acetone is the only oxidation which has been developed to an industrial scale. 

Nitrogen oxide (NO, ) cocatalysts [120] have received industrial interest in Pd-catalyzed aerobic oxidations such as oxidative carbonylation (see Section 8.2.2) [18], alkene oxidation [121], and arene acetoxylation [55]. Recent studies from academic literature have provided new insights into the roles of NO in these reactions. Pd-catalyzed aerobic alkene oxidation (Wacker reaction) typically affords methyl ketones arising from Markovnikov addition of water (or hydroxide) to an... 

The Wacker reaction has found most use for the oxidation of terminal alkenes to give methyl ketones. It is believed to take place by an initial trans hydroxypallada-tion of the alkene to form an unstable complex that undergoes rapid p-elimination to the enol 112 (5.112). Hydropalladation then reductive elimination completes the overall process that involves transfer of hydride ion from one carbon to the other, via the palladium atom. The hydride migration is required to explain the observation that when the reaction is conducted in deuterium oxide, no deuterium is incorporated in the aldehyde produced. 

The Wacker reaction provides a method for the preparation of 1,4-dicarbonyl compounds, by formation of an enolate, allylation with an allyl halide, followed by palladium-catalysed oxidation of the terminal alkene. The product 1,4-dicarbonyl compounds can be treated with base to promote intramolecular aldol reaction (Robinson annulation - see Section 1.1.2) to give cyclopentenones. Thus, in a synthesis of pentalenene, Wacker oxidation of the 2-aUyl ketone 115 gave the 1,4-diketone 116, which was converted to the cyclopentenone 117 (5.115). ... 

The Wacker reaction was chosen as a representative reaction since in this case the conversion of an alkene to a ketone or an aldehyde can be achieved in one step, which is of industrial relevance. The reaction was carried out in a biphasic water/ acetonitrile system at 50-60 °C in an oxygen atmosphere, using the copper/ polyaniline nanocomposite, as well as a bare copper nanocluster. In the system, copper is present in the zero-valent state supported by polyaniline. Although 2-decanone is the only product formed, the yield obtained is still relatively low. It has to be mentioned in this context that the reaction carried out in the presence of bare copper nanoclusters showed no evidence for the presence of 2-decanone, indicating that those copper nanoclusters alone do not bring about the oxidation of 1-decene. 

The oxidation of alkenes by palladium complexes (Wacker reaction) has also been successfully performed in ILs such as the hydrogen peroxide oxidation of styrene to acetophenone by PdGl2 in [G4GiIm]PF6 or [G4GiIm]BF4 (Scheme 25). ... 

Finally, the C—C bond formation by the reaction of 7r-complexes of Pd derived from alkenes, dienes, and other 7r-compounds with enolates and related carbon nucleophiles a la Wacker reaction (Method VI in Scheme 1) provides yet another alternative, as exemplified by the results shown in Scheme For a more general discussion of the C—C bond formation via Wacker-type reaction of Pd rr-complexes with carbanions, the reader is referred to Sect. V.3.4. 

The last catalytic reaction we examine in this overview is the Wacker oxidation of ethylene to acetaldehyde with O2, now used to make about 4 million tons a year of aldehydes from alkenes. This reaction shows several new features of great interest. Although the work started with a commonplace observation— the stoichiometric oxidation of alkenes by Pd(II) salts with formation of Pd(0)— the authors were able to make the system catalytic by finding a clean way to reoxidize the Pd(0) to Pd(II) with air. The mechanism was obscure for years because the kinetics gave an incomplete picture and it was only with sophisticated labeling studies that the currently accepted mechanism was discovered. 

However, the seminal impact of the Wacker process consists in the important insight that the reaction can be conducted with a catalytic amount of precious palladium metal due to efficient reoxidation of palladium using a copper salt as cocatalyst. While the Wacker reaction uses water as the nucleophile in its initial step of nucleopalladation, the underlying principle of addition of a heteroatom to an alkene has resulted in general synthetic utility. The mechanistic question on the exact course of water addition to ethylene has remained an issue of debate, which has been covered from such a perspective recently [5]. 

Ligand fine-tuning continues to provide an important possibility to alter the individual product formation in the aerobic aza-Wacker reaction. For example, Zhang could show that phenanthroHne also constitutes a suitable ligand for this type of reaction, surpassing the more common pyridine in the transformations of alkene 37 to allylamine 38 (Scheme 16.9). 

The stereochemistry of aminopalladation, as is involved in the initial step of the aza-Wacker reaction, is still a subject of ongoing research. A particularly extensive mechanistic study by Stahl and Liu uncovered the stereochemical aspects of intramolecular aminopalladation under Wacker-type conditions. Here, the selectively deuterated compound 46 was used to probe the overall mechanism through product evaluation. It turned out that, for almost all common catalyst combinations, the reaction led to two deuterated alkenes, which were identified as product 47 and its regioisomer. As the final step of 3-hydride elimination must be a syn-selective... 

The Wacker reaction of ethylene or terminal aUcenes proceeds via nncleophilic attack of water to coordinated alkenes to give oxypalladation intermediates from which /3-Pd-H elimination takes place. This process produces vinyl alcohols, which, nnder the influence of palladium, lead to acetaldehyde or methyl ketones as the final prodnct (Scheme 1). 

Unlike the cases of alkenes, Wacker-type intermolecular oxypalladation reactions of alkynes have not been extensively investigated, although their intramolecular cyclization reactions have been developed into synthetically useful procedures (Sects. V3.2). In principle, they can proceed by a few alternative paths shown for the cases of terminal alkynes in Scheme 14. In reality, however, alkynyl C—H activation by Pd to give alkynylpalladium derivatives shown in Scheme 3 may well be the dominant path, as suggested by the carbonylative oxidation of terminal alkynes to give alkynoic acid esters shown in Scheme 15. Oxidative dimerization of alkynes is a potentially serious side reaction. Further systematic investigation of this fundamentally important process appears to be highly desirable. 

The chemistry of the Wacker reaction is not limited to ethylene, but may be extended to a wide range of alkenes, and is useful throughout organic synthesis." For the synthesis of complex molecules, the Wacker... 

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