Modified Wacker oxidation

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. 

Paquette was one of the first to apply the Wacker oxidation in the total synthesis. In his synthesis of 18-oxo-3-virgene, a constituent of the waxy surface resins of tobacco, a Wacker oxidation was deployed to convert a terminal alkene to the corresponding methyl ketone.59 In an efficient total synthesis of ( )-laurene (77), alkene 75 was oxidized to keto-aldehyde 76 at ambient temperature.60 In Smith s total synthesis of calyculin, a modified Wacker oxidation with substoichiometric cupric acetate transformed terminal alkene 78 to methyl ketone 79 without concurrent acetonide hydrolysis.61,62... 

Total Synthesis of 6-Oxoalstophylline (279) Utilizing a Modified Wacker Oxidation... 

Similar results were obtained in the biphasic Wacker oxidation of 1-decene, catalyzed by PdS04, CUSO4 and a heteropolyacid H9PV6M06O40 in the presence of chemically modified p-cyclodextrins (methyl, methoxy, hydroxypropyl derivatives). The reactions yielded 2-decanone in rather high yield (up to 58 %) accompanied by extensive isomerization of 1-decene to internal decenes. Nevertheless, these latter apparently did not react, since the ratio of 2-decanone among the oxodecenes exceeded 99 % (Scheme 10.12). 

Cyclodextrines, modified with 2-cyanoethyl and with bis(2-cyanoethyl)amino groups were used as ligands in the [PdCy + [CuCU]-catalyzed Wacker-oxidation of 1-octene. Without the modified cyclodextrins the yield of 2-octanone was less than 1 %, which could be raised to 73 % by the addition of nitrile-modified P-cyclodextrin ligands (60 °C, 2 h). 

The well-known Wacker oxidation of terminal alkenes to methylketones has been used for many years on a large scale. It requires a catalytic amount of Pd(II) together with stoichiometric CuCl2 under aerobic conditions. But it is hmited by palladiiun decomposition and chlorinated byproducts. Therefore, a lot of research has been devoted to modifying the reaction, but most of the time copper cocatalysts were necessary. Another problem is the often observed cleavage of the double bond and the production of aldehydes. 

Francis, J. W., Henry, P. M. Oxidation of olefins by palladium(ll). Part XIV. Product distribution and kinetics of the oxidation of ethene by PdCl3(pyridine)- in aqueous solution in the presence and absence of CUCI2 a modified Wacker catalyst with altered reactivity. J. Mol. Catal. A Chemical 1995, 99, 77-86. 

Oxidations. Various primary and secondary alcohols are oxidized to give aldehydes and ketones by PdfOAcl -O -pyridine in the presence of 3A molecular sieves. Modified Wacker processes which obviate copper and chloride employ the Pd(OAcl -02 system and a water-soluble 1, 10-phenanthroline ligand or polypyrrole as redox-active ligand.- ... 

Oxidation. Terminally silylated homopropargylic alcohols give y-lactones. The Wacker oxidation can be carried out using substoichiometric Cu(OAc instead of the copper chloride. This modified procedure is operationally simpler and avoids hydrolysis of acetonide when it is present. 

Long-chain aliphatic olefins give only insufficient conversion to the acids due to low solubility and isomerization side reactions. In order to overcome these problems the effect of co-solvents and chemically modified /i-cyclodextrins as additives was investigated for the hydrocarboxylation of 1-decene [23], Without such a promoter, conversion and acid selectivity are low, 10% and 20% respectively. Addition of co-solvents significantly increases conversion, but does not reduce the isomerization. In contrast, the addition of dimethyl-/i-cyclodextrin increased conversion and induced 90% selectivity toward the acids. This effect is rationalized by a host/ guest complex of the cyclic carbohydrate and the olefin which prevents isomerization of the double bond. This pronounced chemoselectivity effect of cyclodextrins is also observed in the hydroformylation and the Wacker oxidation of water-insoluble olefins [24, 25]. More recent studies of the biphasic hydrocarboxylation include the reaction of vinyl aromatic compounds to the isomeric arylpropanoic acids [29, 30], and of small, sparingly water-soluble alkenes such as propene [31]. 

Nevertheless, it must be pointed out that the formation of such transient species has never been spectroscopically observed. Native CDs are effective inverse phase-transfer catalysts for the deoxygenation of allylic alcohols, epoxydation,or oxidation " of olefins, reduction of a,/ -unsaturated acids,a-keto ester,conjugated dienes,or aryl alkyl ketones.Interestingly, chemically modified CDs like the partially 0-methylated CDs show a better catalytic activity than native CDs in numerous reactions such as the Wacker oxidation,hydrogenation of aldehydes,Suzuki cross-coupling reaction, hydroformylation, " or hydrocarboxylation of olefins. Methylated /3-CDs were also used successfully to perform substrate-selective reactions in a two-phase system. 

Palladium complexes with poly(ethylene oxide)s and ethylene oxide-propylene oxide block copolymers modified with iminodipropionitrile groups are catalysts for Wacker oxidation of unsaturated compounds in aqueous and water-alcohol media [64,65]. The yields of the product, methyl ketone, was above 90%, and the catalyst activity considerably exceeded the activity of similar low molecular weight catalytic systems. 

Complexes with modified cyclodextrins were initially used as models of hydrolytic enzymes [20,181,197,198]. Then, Breslow and Kato studied such complexes in biomimetic oxidation and epoxidation. Reetz and some other researchers investigated them in hydroformylation. We examined cyclodextrin-based catalysts in hydroxylation and Wacker oxidation. Note that some of these studies demonstrated a substantial increase in the activity of the catalysts in comparison with their analogues prepared as ordinary mixtures, which was due to the cooperative substrate binding. 

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. 

In Wacker oxidation, palladium complexes with sulfocalixarenes modified with nitrile-containing groups were more active than unmodified sulfocalixarenes. It has been shown that the activity of the catalysts in alkene oxidation from hexene to decene depends on the calixarene cavity size calix[4]arene is most active in the reaction with 1-hexene and calix[6]arene is most active in 1-octene oxidation [215]. 

Monflier, E. Blouet, E. Barbaux. Y. Mortreux. A. Wacker oxidation of I-decene to 2-decanone in the presence of a chemically modified cyclodextrin system A happy union of host-guest chemistry and homogeneous catalysis. Angew. Chem.. Int. Ed. 1994. 33. 2100-2102. 

There are two directions in the development of supramolecular catalytic compositions, that is, (1) creation of systans based on macrocyclic compounds as host molecules that bind substrates with their hydrophobic cavity and (2) development of the systems that bind substrates using aggregates formed by am-phiphihc compounds. Compounds that form host-guest complexes like modified cahxarenes are able to aid transport of substrates into the aqueous phase. This approach has been implemented in the Wacker oxidation [40,41], oxidation of alkylaromatic compounds [42], hydroxylation of aromatic compounds [43], hydrogenation [44,45], hydroformylation [45-48], and carbonylation [49]. In this case, the substrate is transported into the aqueous phase in the form of the corresponding inclusion complex. This not only affects the activity of the catalyst, but also provides selectivity of the process. Thus, in the Wacker oxidation of 1-alkenes the maximum yield of methyl ketone was achieved when 1-hexene is used, and for systems based on calix[6]arene with 1-octene among catalytic systems with modified calix[4]arenes [50]. 

PdS04/H9PV6Mo604o/CuS04 in the presence of chemically modified P-cyclodextrins were also used as CPTC systems in the Wacker-type oxidation of higher a-olefins (Cg-Cje) to the corresponding 2-ketones (Equation 18) with high yields (90-98%) in an aqueous/organic two phase system.545,571... 

Even with our modified definition of indifferent , we still require that the catalytic material should act indefinitely once introduced. This requirement is also fulfilled by a number of essential materials added to some catalytic processes, and often referred to as co-catalysts or promoters. For example, the copper (I)-copper (II) chloride redox system used in Wacker s palladium-catalysed oxidation of ethylene to acetaldehyde (section 11.7.7.3) behaves in a true catalytic manner in the single-reactor variant of the process (ethylene and O2 introduced into the same reaction vessel). 

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