Terminal olefins, Wacker oxidations

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. 

The electrochemical Wacker-type oxidation of terminal olefins (111) by using palladium chloride or palladium acetate in the presence of a suitable oxidant leading to 2-alkanones (112) has been intensively studied. As recyclable double-mediatory systems (Scheme 43), quinone, ferric chloride, copper acetate, and triphenylamine have been used as co-oxidizing agents for regeneration of the Pd(II) catalyst [151]. The palladium-catalyzed anodic oxidation of... 

Terminal olefins may be oxidatively cleaved by hydrogen peroxide, catalyzed by a palladium ) complex, to give methyl ketones in almost quantitative yields (equation 38)167. This methodology is an alternative to the well established Wacker protocol using palladium ) complexes. 

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... 

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]. 

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-... 

The Wacker chemistry can also be used to oxidize higher olefins. Terminal olefins are converted to methylketones. In general rates and yields of ketone formation decrease with increasing alkyl chain length. Hence only propylene to acetone has found commercial application. 

It is surprising that the Wacker-type oxidation of 1-octene to 2-octanone is faster with the Co-salophen/zeolite catalyst than with the free complex. However, it is known that the Pd(II)-catalyzed oxidation of terminal olefins to ketones is accelerated by the presence of a catalytic amount of strong acid [1,2]. An explanation of the fester rate of the zeolite-encapsulated Co-salophen in this case is therefore that the acidic sites in the zeolite accelerate the reaction. 

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. 

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. 

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

Tsuji has completed three syntheses of zearalenone (119), all by quite similar routes. The first, shown in Scheme 1.28, began with acetate 59b, the minor product from the telomerization of butadiene in acetic acid. Cleavage to the alcohol and gas-phase dehydrogenation led to enone 141. Chain extension to 142 was accomplished in 70% yield by way of Michael addition of diethyl malonate to enone 141. Decarboalkoxylation and protection of the ketone then gave 143 (63%). Conversion of the ester to the primary tosylate 144 was achieved by conventional methods in 62% yield. A Wacker oxidation of the terminal olefin followed by reduction and exchange of the tosylate for an iodide then provided the aliphatic segment 145 in 64% yield. 

The Wacker oxidation oxidizes a terminal olefin to a methyl ketone. Review Takars, J. M. Jiang, X.-t. Curt. Org. Chem. 2003, 7, 369-396. 

In the well-known Wacker process ethylene is converted to acetaldehyde by aerobic oxidation in an aqueous medium in the presence of PdCl2 as catalyst and CuCl2 as cocatalyst [7], Terminal olefins afford the corresponding methyl ketones. Oxidative acetoxylation of olefins with Pd(II) salts as catalysts in acetic acid was first reported by Moiseev and coworkers [8], The addition of an alkali metal acetate, e. g. NaOAc, was necessary for the reaction to proceed. Palladium black was also found to be an active catalyst under mild conditions (40-70 °C, 1 bar) in the liquid phase, if NaOAc was added to the solution before reducing Pd(II) to Pd black, but not afterwards [9,10]. These results suggested that catalytic activity... 

Jiro Tsuji carried out many mechanistic and synthetic studies on the initial Wacker oxidation process.7-" It is now known as the Wacker-Tsuji oxidation for the oxidation of terminal olefin 1 to the corresponding methyl ketone 2 with oxygen in the presence of a catalytic amount of palladium and one equivalent of copper salt.12-" Nowadays, the Wacker-Tsuji oxidation is a standard methodology for transforming the terminal olefin to the corresponding methyl ketone.17 The reaction is so widely used that Tsuji declared that a terminal olefin could be viewed as a masked methyl ketone."... 

Pellissier and colleagues reported that terminal olefin 18 underwent a Wacker oxidation to give methylketone 19 as the major product in 85% yield and aldehyde 20 as the minor product in 7% yield.23,24 However, when the configuration of the neighboring lactone was switched like in substrate 21, the yield for the anti-Markovnikov addition product 23 was 35%. The authors proposed the assistance of the neighboring oxygen contributed to the regiochemistry. 

In Leighton s total synthesis of dolabelide D, the Wacker-Tsuji oxidation diene 70 was achieved chemoselectively to produce methyl ketone 71.54 55 Furthermore, addition of (-)-sparteine as a ligand prevented olefin isomerization and led to selective formation of methyl ketone 71 from the terminal olefin in good yield.56... 

A new approach to construction of 3-aminosugar moieties by stereospecific intramolecular addition of a carbon-free radical to hydrazone 125 derived from crotonaldehyde was recently demonstrated by Friestad. This synthesis, comprising asymmetric dihydroxylation, PhS radical-induced C = N bond alkylation (C-vinylation) and subsequent Wacker oxidation [88] of terminal olefin 128, which afforded L-daunosaminide derivative 129, in overall 32% yield, is outlined in Scheme 23 [89]. 

For the stereoselective synthesis of C-glycosides, deoxygenation of hemiketals, obtained from Wacker oxidation of sngar-derived olefin alcohols, was envisaged as an easy and efficient protocol. In our earlier study on the synthesis of 4-epiethisolide, attempted PdCV mediated conversion of the terminal olefin (1), obtained from sugar chiron into a methyl ketone (2) resulted in the exclnsive formation of an anti-Markovnikov product (3), which happened to be the first report in the literature (Scheme 22.1). 

The redox interaction between transition metals and redox-active ligands is likely to permit a smooth reversible redox cycle in the transition metal-catalyzed oxidation reactions. Actually, the Wacker oxidation reaction of a terminal olefin proceeds catalytically only in the presence of a catalytic amount of polyaniline or polypyrrole derivative as a cocatalyst in acetonitrile-water under oxygen atmosphere to give 2-alkanone (Scheme Copper-free catalytic systems are... 

To explain the observed behavior, it has been suggested [163,164,169,171] that the oxidation of terminal olefins to methyl ketones takes place via two complementary reactions occurring in a coupled mode (Scheme 12). These reactions are the activation of dioxygen (path A) and a Wacker type oxidation (path B). In path A, the cationic rhodium(II) complex 17, formed from RhCl, olefin, EtOH and... 

In 1979, Tsuji s group [51] reported an alternative approach to macrolactonization. Inspired by their previous success in the preparation of recifeiolide and 9-decanolide, the authors envisioned that the dimethyl ether of zearalenone (6) could be obtained via olefination using the co-iodoalkyl phenylthioacetate 7 (Scheme 7.2). The Michael addition of diethyl malonate (11) to 10 followed by decarboxylation afforded an ethyl ester, which was reduced to alcohol and converted into the tosylate 12. Wacker-Tsuji oxidation of the terminal olefin was then followed by reduction of the ketone and conversion of the tosylate into iodide to provide 9. This was... 

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