Styrenes Wacker oxidation

Table 10.7 Copper-free Wacker oxidation of substituted styrenes [41]...

Wacker oxidation of styrene has also been performed in [bmim][BF4] and [bmim][PF6], at 60 °C with H2O2 and PdCF as a catalyst [19]. This system gave yields of acetophenone as high as 92 % after 3 h. Hydrogen peroxide may also be used under phase transfer conditions for alkene bond cleavage, to produce adipic acid (an intermediate in the synthesis of nylon-6) from cyclohexene (Scheme 9.9). 

It was observed that the substitution of a methyl group on the terminal carbon of styrene or adamantane [Eq. (9.185)] switches the regioselectivity from Markovnikov to anti-Markovnikov in the Wacker oxidation 1310... 

Alkenes can be transformed into ketones by Wacker oxidation (Entry 2, Table 12.3), but this reaction does not seem to proceed cleanly on polymeric supports. Janda and co-workers were able to oxidize styrenes bound to macroporous polystyrene to the corresponding acetophenones, but reported that the reaction did not proceed on PEG... 

It is well known that the properties of supercritical fluids are sensitive to pressure, and thus pressure may drastically influence the catalytic activity or the product selectivity when a reaction takes place in supercritical conditions. The favorable pressure for the Wacker oxidation of styrene is around 16 MPa of total pressure including 3 MPa 02, at which the selectivity toward acetophenone reaches 92 %, while under a total pressure of 9 MPa, the selectivity for acetophenone is lower (86 %). However, C02 with a higher pressure of over 20 MPa might retard the interaction between the substrate and the catalyst, and might cause a low concentration of substrate in the vicinity of the catalyst, thus resulting in a relatively low yield [38]. 

Figure 8.23 Catalytic Wacker oxidation of 8-nonen-l-ol (32) and styrene in the presence of cage 2.

Scheme 12 Proposed hydride-shift mechanism for the Wacker oxidation of styrene catalyzed by (I Pr)Pd(OTf)2...

To overcome the problems encountered in the homogeneous Wacker oxidation of higher alkenes several attempts have been undertaken to develop a gas-phase version of the process. The first heterogeneous catalysts were prepared by the deposition of palladium chloride and copper chloride on support materials, such as zeolite Y [2,3] or active carbon [4]. However, these catalysts all suffered from rapid deactivation. Other authors applied other redox components such as vanadium pentoxide [5,6] or p-benzoquinone [7]. The best results have been achieved with catalysts based on palladium salts deposited on a monolayer of vanadium oxide spread out over a high surface area support material, such as y-alumina [8]. Van der Heide showed that with catalysts consisting of H2PdCU deposited on a monolayer vanadium oxide supported on y-alumina, ethene as well as 1-butene and styrene... 

Feringa from The Netherlands was the first to report an abnormal Wacker oxidation in 1986.21 Dec-1 -ene was oxidized in the presence of a tertiary alcohol to a mixture of aldehyde 8 and methyl ketone 9. Surprisingly, aldehyde 8 was isolated as the major product (8/9 = 70/30). Even more strikingly, styrene was transformed exclusively to its corresponding phenylacetaldehyde under the same conditions. Feringa proposed that the aldehyde formation involved an oxygen transfer reaction via initial cycloaddition of the nitro-palladium complex, followed by p-hydrogen elimination. 

Under standard catalytic conditions (10% PdCh, 1 eq. CuCI, O2, in DMF/H2O), the Wacker oxidation of 4-methoxystyrene proceeded to give a mixture of the two possible products. As expected, the Markovnikov product, methylketone 31 was predominate and only a small amount of aldehyde 30 was isolated (31 30 = 8.4 1). However, Spencer and coworkers performed the reaction in the absence of the reoxidant CuCI and observed a reversal of the usual regioselectivity.26 Thus, reaction of 4-methoxystyrene with 2 equivalents of PdCb gave aldehyde 30 as the major product. The authors explained the regioselectivity by the involvement of a possible 4-palladium-styrene complex 29. 

Cuprous chloride tends to form water-soluble complexes with lower olefins and acts as an IPTC catalyst, e.g., in the two-phase hydrolysis of alkyl chlorides to alcohols with sodium carboxylate solution [10,151] and in the Prins reactions between 1-alkenes and aqueous formaldehyde in the presence of HCl to form 1,3-glycols [10]. Similarly, water-soluble rhodium-based catalysts (4-diphenylphosphinobenzoic acid and tri-Cs-io-alkylmethylam-monium chlorides) were used as IPTC catalysts for the hydroformylation of hexene, dodecene, and hexadecene to produce aldehydes for the fine chemicals market [152]. Palladium diphenyl(potassium sulfonatobenzyl)phosphine and its oxide complexes catalyzed the IPTC dehalogenation reactions of allyl and benzyl halides [153]. Allylic substrates such as cinnamyl ethyl carbonate and nucleophiles such as ethyl acetoactate and acetyl acetone catalyzed by a water-soluble bis(dibenzylideneacetone)palladium or palladium complex of sulfonated triphenylphosphine gave regio- and stereo-specific alkylation products in quantitative yields [154]. Ito et al. used a self-assembled nanocage as an IPTC catalyst for the Wacker oxidation of styrene catalyzed by (en)Pd(N03) [155]. 

Figure 23.14 Schematic setup for the synthesis of phenyiacetaidehydes from styrenes through an aerobic anti-Markovnikov Wacker oxidation.

The oxidation of alkenes (Wacker oxidation, mainly styrene to acetophenone. Scheme 5.3-13) has been reported to be catalyzed by PdQz in the presence of e.g. [BMIM][PF6] [143]. The need for only a small excess (1.15 equiv.) of aqueous H2O2 was demonstrated, which is a significant improvement in H2O2 utilization compared to previously reported methods. 

A palladium complex with cyclodextrin modified with propionitrile and benzoylnitrile groups 73-74 was active in Wacker oxidation of higher 1-alkenes (Experiment 11-4, Section 11.7), and its activity was much higher than the activity of a catalj ic system prepared as a mixture of cyclodextrin and the palladium complex owing to the cooperative substrate binding and to the increase in the stability constant of the catalyst-substrate complex. As in hydroformylation, the catalyst was more active in the reaction with an aromatic substrate, styrene, than with linear alkenes [59,210-211], The catalyst activity depended on the 1-alkene chain length and was maximum for 1-heptene. 

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 2.10 EfBdeiicy of the Wacker oxidation of styrene derivatives with various MIP-CD. (Adaptedfrom R. [38].)... 

The Wacker oxidation was also reahzed with styrene derivatives instead of linear alkene. This study also confirmed the importance of the template during the imprinting process. Styrene derivatives were submitted to the Wacker oxidation conditions in the presence of CD-based MIPs formed in the presence or in the absence of different templates (C16H32 or p-terf-butylstyrene) to evaluate the efficacy of the templating approach. The results are presented in Fig. 2.10. 

In [51], Wacker oxidation of olefins was studied in the presence of catalytic systems comprising water-soluble calixarenes (sulfonated and glycydylated derivatives), palladium salt, and copper salt. The presence of nonpolar cavities in these molecules enables binding nonpolar substrates and their transfer into the aqueous phase where the reaction takes place. The activity of these catalysts depends on the complementarity between the cavity size of the host molecule and the size of the guest molecule. Therefore, substrate selectivity was exhibited. For example, the addition of calixarene increased the reaction rate for linear 1-alkenes which size corresponded to the size of the calixarene cavity (1-hexene for calix[4]arene and 1-octene for calix[6]arene). The activity of catalytic system applied for the oxidation of substituted styrenes also depended on the ratio of the size of the substrate molecule and that of the calixarene cavity. 

Very recently, Reiser showed that a his(isonitrile) ligand forms robust Pd(II) complexes for the direct Wacker oxidation of alkenes without Cu co-catalysts under 1 atm of O2 at 70°C. The catal5dic system showed good activity towards terminal aliphatic alkenes, hut also styrene substrates, which are usually more challenging substrates for this kind of oxidation because of the competitive double-bond cleavage under oxidative conditions reacting readily, favoring the acetophenone products and concomitant formation of benzaldehydes as side products in 4-20% yield (Scheme 23.48). 

Cornell, C. and Sigman M. (2005). Discovery of and Mechanistic Insight into a Ligand-Modulated Palladium-Catalyzed Wacker Oxidation of Styrenes Using TBHP, J. Am. Chem. Soc., 127, pp. 2796-2797. 

Supercritical CO2 is a non-polar, aprotic solvent and promotes radical mechanisms in oxidation reactions, similar to liquid-phase oxidation. Thus, wall effects might occur as known, e.g. from olefin epoxidation with 02 or H202 which may decrease epoxide selectivities. The literature covers the synthesis of fine chemicals by oxidation either without catalysts (alkene epoxidation, cycloalkane oxidation, " Baeyer-Villiger oxidation of aldehydes and ketones to esters ), or with homogeneous metal complex catalysts (epoxidation with porphyrins, salenes or carbonyls ). Also, the homogeneously catalysed oxidation of typical bulk chemicals like cyclohexane (with acetaldehyde as the sacrificial agent ), toluene (with O2, Co +/NaBr ) or the Wacker oxidation of 1-octene or styrene has been demonstrated. 

Scheme 12.16 (a) Pd carbene-catalyzed Tsuji-Wacker oxidation of styrenes, (b)... 

Alteration of regioselectivity of the Wacker oxidation of styrenes (90) in favour of the corresponding aldehydes (92) rather than methylketones has been achieved simply using t-BuOH rather than water. The reaction presumably proceeds via the vinyl ether (91), resulting from the anti-Markovnikov attack of the bulky nucleophile at the sterically less hindered terminal carbon. A similar reversion was observed for other terminal olefins (styrenes, allyl ethers, and 1,5-dienes) when the oxidation was carried out in the presence of pinacol, another bulky nucleophile, which produced acetals of the corresponding aldehydes. Similar effects of bulky alcohols have been reported previously. ... 

PdCOTfj CIPr) generated in situ from [Pd(p,-Cl)(Cl)(IPr)]j and AgOTf was reported to catalyse the copper-free Wacker-type oxidation of styrene derivatives using ferf-butyl hydroperoxide (TBHP) as the oxidant (Table 10.7) [41]. Reaction conditions minimised oxidative cleavage of styrene, which is a common side-reaction in Wacker-type oxidations. However, when franx-stilbene was used as a substrate, a significant amount of oxidative cleavage occurred. 

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