Wacker oxidation olefins

The palladium chloride process for oxidizing olefins to aldehydes in aqueous solution (Wacker process) apparendy involves an intermediate anionic complex such as dichloro(ethylene)hydroxopalladate(II) or else a neutral aqua complex PdCl2 (CH2=CH2)(H2 0). The coordinated PdCl2 is reduced to Pd during the olefin oxidation and is reoxidized by the cupric—cuprous chloride couple, which in turn is reoxidized by oxygen, and the net reaction for any olefin (RCH=CH2) is then... 

In 1974, Hegedus and coworkers reported the pa]ladium(II)-promoted addition of secondary amines to a-olefins by analogy to the Wacker oxidation of terminal olefins and the platinum(II) promoted variant described earlier. This transformation provided an early example of (formally) alkene hydroamination and a remarkably direct route to tertiary amines without the usual problems associated with the use of alkyl halide electrophiles. 

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... 

One of the earliest use of cyclodextrins as inverse phase transfer agents was in the Wacker oxidation of higher olefins to methyl ketones [22] with [PdCU] + [CuCU] catalyst (Scheme 10.12). Already at that time it was discovered, that cyclodextrins not only transported the olefins into the aqueous phase but imposed a substrate-selectivity, too with Ckh olefins the yields decreased dramatically and 1-tetradecene was only slightly oxidized. 

Scheme 1. Reaction scheme for Wacker type olefin oxidation on Pd +Cu +Y.

In the course of examining the CAI effect of conformational restriction of the C3-side-chain, intermediate 24 was prepared. Shankar and co-workers (Shankar et al., 1996) demonstrated that 10, a key intermediate in the research synthesis could be accessed by Wacker oxidation of olefin 24 (Scheme 13.7). Additionally, an alternative chiral variant of the well-precedented addition of zinc enolates to imines was demonstrated. Treatment of the bromoacetate 25, derived from 8-phenylmenthol with zinc and sonication followed by imine addition afforded 26 in 55% yield with greater than 99% de. Ethyl magnesium promoted ring-closure followed by C3 alkylation with 28, intercepts the previously demonstrated route through formation of olefin 24 (Shankar et al., 1996). 

SAP catalysts have also been applied in the Wacker oxidation584 of higher olefins where the separation of products from the catalyst is cumbersome. Palladium(II) and copper(II) salts immobilized on controlled pore glass CPG-240 in the presence of water catalysed the oxidation of 1-heptene to 2-heptanone in conversions up to 24%.585 Significant isomerization to 2-heptene and 3-heptene (isomerization/oxidation=2/3) was also observed. However, an advantage of SAP-Wacker oxidation catalysts over classical systems is that the Cu(II) is confined to the support and therefore not corrosive whereas aqueous Cu2+ is very corrosive to steel. 

Four common aromatic olefins as well as two aliphatic counterparts could be converted to the desired methyl ketones in good to excellent yields and selectivity through Wacker oxidation reaction as shown in Scheme 3.4. 

Ansari IA, Joyasawal S, Gupta MK et al (2005) Wacker oxidation of terminal olefins in a mixture of [bmim][BF4] and water. Tetrahedron Lett 46(44) 7507-7510... 

Scheme 2. The Cu(l)/Cu(ll)-reoxidation system in the Wacker-Hoechst olefin oxidation reaction.

Intramolecular coordination is apparently responsible for most examples of regioselective Wacker oxidations of internal olefins, but electronic effects are also operating [28], specifically in acceptor-substituted olefins. Steric effects are currently not well explored [8], Recent theoretical studies on the mechanism of the Wacker and related reactions are available elsewhere [29, 30],... 

Acetals result from oxidative coupling of alcohols with electron-poor terminal olefins followed by a second, redox-neutral addition of alcohol [11-13]. Acrylonitrile (41) is converted to 3,3-dimethoxypropionitrile (42), an intermediate in the industrial synthesis of thiamin (vitamin Bl), by use of an alkyl nitrite oxidant [57]. A stereoselective acetalization was performed with methacrylates 43 to yield 44 with variable de [58]. Rare examples of intermolecular acetalization with nonactivated olefins are observed with chelating allyl and homoallyl amines and thioethers (45, give acetals 46) [46]. As opposed to intermolecular acetalizations, the intramolecular variety do not require activated olefins, but a suitable spatial relationship of hydroxy groups and the alkene[13]. Thus, Wacker oxidation of enediol 47 gave bicyclic acetal 48 as a precursor of a fluorinated analogue of the pheromone fron-talin[59]. 

The conditions for allylic acyloxylation of internal olefins are, for reasons which are not clear, unsuitable for terminal olefins. They undergo Wacker oxidation (Markovnikov oxypalladation//) - h yd ride elimination) to yield mixtures of vinyl acetates and methyl ketones [37a]. A combination of Pd(OAc)2/BQ with air as cooxidant in a mixture of DMSO/AcOH (1 1) enables conversion of a broad range of functionalized terminal olefins to the corresponding linear allylic acetates in acceptable yields (Scheme 5) [41]. 

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 ... 

However, all these systems suffer from high concentrations of chloride ion, so that substantial amounts of chlorinated by-products are formed. For these reasons there is a definite need for chloride- and copper-free systems for Wacker oxidations. One such system has been recently described, viz., the aerobic oxidation of terminal olefins in an aqueous biphasic system (no additional solvent)... 

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-... 

Fig. 4.37 PdCI2// /,/ /-dimethylacetamide system for Wacker oxidation of olefins.

Interesting properties may also be obtained when using a mixed addenda system in the presence of a co-catalyst The best known system [34d] is the V-substituted phosphomolybdate in conjunction with Pd for the oxidation of olefins to carbonyl compounds. This is analogous to the Wacker oxidation process based on CUCI2 and Pd. Unlike the Wacker process, the HPA system works at very low chloride concentration, or even in its absence. In addition the HPA is more active and selective and less corrosive. Other examples of such two-component catalytic systems include TF /TP, PT /Pt ", Ru"7Ru ", Br 7Br" and l /h-... 

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. 

The reaction according to eq. (4) seems to proceed via a mechanism which is common for the homogeneous Pd-catalyzed reactions that are often referred to as Wacker oxidations (cf. Section 2.4.1, [4, 8, 9]). In fact, there are several liquid-phase olefin oxidations that are catalyzed by Pd complexes, and the nature of the reaction products depends on the solvent used (Scheme 3). 

Non-oxidative isomerizations often occur when olefinic compounds react with noble metal compounds, e. g., in Wacker oxidation of higher olefins. An example is found in the oxidation of 1-octene where octane-2-, 3-, and 4-ones are formed, in this example with an immobilized Pd" catalyst [130]. A plausible mechanism with a hydridorhodium species as catalytically active moiety has been described by Cramer [131]. 

For a long time, electrocatalysis (cf. Section 3.2.8) has not been considered important in organometallie chemistry although numerous known processes depend on redox reactions (e. g., Wacker-type catalysis, oxidative olefin carbonylation. 

The antiviral marine natural product, (-)-hennoxazole A, was synthesized in the laboratory of F. Yokokawa." The highly functionalized tetrahydropyranyl ring moiety was prepared by the sequence of a Mukaiyama aldol reaction, cheiation-controiied 1,3-syn reduction, Wacker oxidation, and an acid catalyzed intramolecular ketalization. The terminal olefin functionality was oxidized by the modified Wacker oxidation, which utilized Cu(OAc)2 as a co-oxidant. Interestingly, a similar terminal alkene substrate, which had an oxazole moiety, failed to undergo oxidation to the corresponding methyl ketone under a variety of conditions. 

Wacker oxidation One-pot oxidation of olefins to the corresponding ketones in the presence of catalytic amounts of Pd(ll)-salts 474... 

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. 

Monflier, E., Tilloy, S., Blouet, E., Barbaux, Y., Mortreux, A. Wacker oxidation of various olefins in the presence of per(2,6-di-0-methyl)-P-cyclodextrin mechanistic investigations of a multistep catalysis in a solvent-free two-phase system. J. Mol. Catal. A Chemical 1996,109, 27-35. 

The Wacker oxidation oxidizes a terminal olefin to a methyl ketone. 

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