Wacker Oxidation Research Articles

Synthesis of methyl ketones from terminal olefins using PdCl2/CrO3 system mimicking the Wacker process

An efficient synthesis of methyl ketones from terminal olefins using PdCl2/CrO3 system mimicking the Wacker process is developed. The method shows good functional groups compatibility, no aldehyde by-products and is operationally simple. CrO3 is the sole oxidant and replaces both Cu-salts and molecular oxygen, traditionally used in this process. The method holds potential for future applications in organic synthesis.

Domino Recombinant γ‐Isomerization and Reverse Wacker Oxidation of γ‐Vinyl‐γ‐butyrolactone: Synthesis of (+)‐trans‐, (–)‐ and (+)‐Disparlures

AbstractA domino palladium‐catalyzed recombinant γ‐isomerization and reverse Wacker oxidation of γ‐vinyl‐γ‐butyrolactone has been explored. The strategy has been used in the stereoselective synthesis of (+)‐trans‐, (–)‐ and (+)‐disparlures. The synthesis was achieved in seven to eight steps from D‐glucono‐δ‐lactone with overall yields of 19.3, 20.7 and 22.6 %, respectively.

Wacker-Type Oxidation and Dehydrogenation of Terminal Olefins Using Molecular Oxygen as the Sole Oxidant without Adding Ligand

An efficient and economical palladium-catalyzed oxidation system has been identified. The oxidation system, characterized by not adding ligand and using molecular oxygen as the sole oxidant, can realize the Tsuji-Wacker oxidation of terminal olefins and especially styrenes to methyl ketones; in addition, this system can achieve tandem Wacker oxidation-dehydrogenation of terminal olefins to α,β-unsaturated ketones.

Cover Picture: Synthesis of the Aglycone of the Argelosides: Antiproliferative 14,15-seco-Pregnane Glycosides (Asian J. Org. Chem. 3/2014)

Highly oxygenated steroidal derivatives are important targets in biology and chemistry. In their Communication on page 264 ff., Minoru Tamiya and co-workers accomplished the synthesis of the aglycon of the argelosides, a highly-oxygenated seco-pregnane with cage-like D, E, and F rings, through the three oxidative operations: 1) Sharpless asymmetric dihydroxylation, 2) Baeyer-Villiger oxidation, and 3) Wacker oxidation. Despite the rather simple strategy, the major challenge lay in handling the easy-to-aromatize structure in the intermediate and target molecules.

Wacker-Oxidation of Ethylene Over Pillared Layered Material Catalysts

This paper concerns the Wacker oxidation of ethylene by oxygen in the presence of water over supported Pd/VO x catalysts. High surface area porous supports were obtained from layer-structured materials, such as, montmorillonite (MT), laponite (smectites), and hydrotalcite (layered double hydroxide, LDH) by pillaring. Before introduction of Pd, supports MT and LDH were pillared by vanadia. The laponite was used in titania-pillared form (TiO2–LAP) as support of Pd/VO x active component. Acetaldehyde, acetic acid and CO2 were the products with yields and selectivities, depending on the reaction conditions and the properties of the applied catalyst. Under comparable conditions the pillared smectite catalysts gave higher AcH yield than the pillared LDH catalyst. UV–Vis spectroscopic examination suggested that the pillared smectites contained polymeric chains of VO4, whereas only isolated monomeric VO4 species were present in the pillared LDH. The higher catalytic activity in the Wacker oxidation was attributed to the more favorable redox property of the polymeric than of the monomeric vanadia. The V3+ ions in the polymeric species can reduce O2 to O2− ions, whereas the obtained V5+ ions are ready to pass over O to Pd0 to generate PdO whereon the oxidation of the ethylene proceeds.

ChemInform Abstract: Regioselective Wacker Oxidation of Internal Alkenes: Rapid Access to Functionalized Ketones Facilitated by Cross‐Metathesis.

AbstractThe key aspect of the title reaction is the identification of a wide range of directing groups for enabling a regioselective Wacker oxidation of internal alkenes.

Catalyst-Controlled Wacker-Type Oxidation: Facile Access to Functionalized Aldehydes

The aldehyde-selective oxidation of alkenes bearing diverse oxygen groups in the allylic and homoallylic position was accomplished with a nitrite-modified Wacker oxidation. Readily available oxygenated alkenes were oxidized in up to 88% aldehyde yield and as high as 97% aldehyde selectivity. The aldehyde-selective oxidation enabled the rapid, enantioselective synthesis of an important pharmaceutical agent, atomoxetine. Finally, the influence of proximal functional groups on this anti-Markovnikov reaction was explored, providing important preliminary mechanistic insight.

Synthesis of the Aglycone of the Argelosides: Antiproliferative 14,15-seco-Pregnane Glycosides

The synthesis of the argeloside aglycon, the highly-oxygenated seco-pregnane with cage-like D, E, and F rings, is accomplished in 13 steps starting from a readily accessible vinyl cyclopentanone derivative. The key steps involve Sharpless asymmetric dihydroxylation to set the C16 stereocenter, Baeyer–Villiger oxidation to construct the seco-structure, and Wacker oxidation to introduce the C17 oxo groups.

Challenges in modelling homogeneous catalysis: new answers from ab initio molecular dynamics to the controversy over the Wacker process

We present here a review of the mechanistic studies of the Wacker process stressing the long controversy about the key reaction steps. We give an overview of the previous experimental and theoretical studies on the topic. Then we describe the importance of the most recent Ab Initio Molecular Dynamics (AIMD) calculations in modelling organometallic reactivity in water. As a prototypical example of homogeneous catalytic reactions, the Wacker process poses serious challenges to modelling. The adequate description of the multiple role of the water solvent is very difficult by using static quantum chemical approaches including cluster and continuum solvent models. In contrast, such reaction systems are suitable for AIMD, and by combining with rare event sampling techniques, the method provides reaction mechanisms and the corresponding free energy profiles. The review also highlights how AIMD has helped to obtain a novel understanding of the mechanism and kinetics of the Wacker process.

Highly efficient oxyfunctionalization of unsaturated fatty acid esters: an attractive route for the synthesis of polyamides from renewable resources

An efficient and environmentally benign strategy for the oxyfunctionalization of fatty acid methyl esters (FAMEs) employing molecular oxygen as an oxidizing agent is described. Keto-fatty acid esters were directly synthesized by co-catalyst-free Wacker oxidations employing oxygen as a sole re-oxidant. Amine functionalization of the thus obtained keto-fatty acid esters was achieved by reductive amination. The prepared renewable AB-type monomers were studied in homopolymerizations as well as in copolymerization reactions with hexamethylendimethylamine and dimethyl adipate to modify the properties of conventional Nylon 6,6. The obtained (co)-polymers were characterized by SEC, NMR and DSC analysis as well as water uptake tests.

Regioselective Wacker Oxidation of Internal Alkenes: Rapid Access to Functionalized Ketones Facilitated by Cross‐Metathesis

Wacker am anderen Ende: Die Titelreaktion nutzt eine Vielfalt von dirigierenden Gruppen (DG) für eine hoch regioselektive Alkenoxidation an der weiter entfernten Position, die E- und Z-Alkene in wertvolle funktionalisierte Ketone überführt. Die Synthese der Ausgangsmaterialien wird durch eine Kreuzmetathese erleichtert. BQ=Benzochinon.

Regioselective Wacker Oxidation of Internal Alkenes: Rapid Access to Functionalized Ketones Facilitated by Cross‐Metathesis

Wacka wacka: The title reaction makes use of a wide range of directing groups (DG) to enable the highly regioselective oxidation of alkenes, and occurs predictably at the distal position. Both E and Z alkenes afford valuable functionalized ketones and cross-metathesis was shown to facilitate the preparation of the starting materials. BQ=benzoquinone.

Desymmetrization of meso-2,5-diallylpyrrolidinyl ureas through asymmetric palladium-catalyzed carboamination: stereocontrolled synthesis of bicyclic ureas.

Desymmetrization of meso-2,5-diallylpyrrolidinyl ureas through asymmetric palladium-catalyzed carboamination: stereocontrolled synthesis of bicyclic ureas.

ChemInform Abstract: Wacker‐Type Oxidation of Internal Alkenes Using Pd(Quinox) and TBHP.

AbstractThe reaction is a useful complement to the traditional Tsuji—Wacker oxidation of internal alkenes.

A Continuous Flow Solution to Achieving Efficient Aerobic Anti‐Markovnikov Wacker Oxidation

AbstractAn aerobic anti‐Markovnikov Wacker oxidation for the flow‐synthesis of arylacetaldehydes is reported. In the process, flow chemistry techniques have provided a means to control and minimise the over‐oxidation of sensitive products. The reaction showed general applicability to various functionalised styrenes and provided a process capable of a multi‐gram scale.

A structure–activity relationship study on the Wacker oxidation of stilbenes at ambient condition

To evaluate which structural elements of the stilbenes are responsible for their activity on the Wacker oxidation, a series of stilbenes with various functional moieties and substitution patterns were considered. In this regard, it is found that the oxidation rate of stilbenes strongly depends on their structures to give the corresponding carbonyl compounds. Consequently, the ortho position of alkene and methoxy groups plays a key role in the complexation with PdCl2. The oxidation process is clean with high selectivity of product and low percentage of byproducts.

Enantioselective Total Synthesis of (−)‐Blennolide A

Blennolide A can be synthesized through an enantioselective domino-Wacker/carbonylation/methoxylation reaction of 7a with 96 % ee and an enantioselective Wacker oxidation of 7b with 89 % ee. Further transformations led to the α,β-unsaturated ester (E)-17, which was subjected to a highly selective Michael addition, introducing a methyl group to give 18a. After a threefold oxidation and an intramolecular acylation, the tetrahydroxanthenone 4 was obtained, which could be transformed into (-)-blennolide A (ent-1) in a few steps.

Palladium‐Catalyzed Selective Anti‐Markovnikov Oxidation of Allylic Esters

The palladium(II)-catalyzed oxidation of alkenes to carbonyl compounds, usually referred to as the Wacker or Wacker– Tsuji reaction, is arguably one of the best-known reactions catalyzed by palladium. It is an important catalytic process industrially, for the production of ethanal, and synthetically, for the conversion of olefins to ketones. The oxidation of terminal alkenes typically proceeds with selective formation of methylketones. The anti-Markovnikov (AM) Wacker oxidation of terminal olefins to aldehydes remains, however, a major challenge. Under certain conditions, AM selectivity is obtained with styrenes, Michael-type acceptor alkenes and certain olefins, such as 2-vinyl-furanosides, bearing a directing functional group. Indeed, high aldehyde selectivity in the catalytic oxidation of phthalimide-protected allylic amines was reported by our group to yield a key intermediate in the preparation of b-amino acids. On the other hand, Sigman and co-workers have reported the regioselective oxidation of protected allylic amines controlled by various palladium catalysts to yield the corresponding methyl ketones. In 1986, Pd-catalyzed aldehyde selective oxidation of styrene with O2 and CuCl in tBuOH at 30 8C was reported by Feringa. Later, Wenzel reported good selectivity (6:1) for aldehyde formation from allyl acetate (56% combined yield of aldehyde and ketone), in tBuOHwith PdCl2/CH3CN/CuCl/ NaCl at 50 8C. More recently, the aldehyde-selective oxidation of styrenes was reported by Grubbs and co-workers using the catalyst [PdCl2(CH3CN)2], p-benzoquinone as oxidant, and tBuOH as solvent at 85 8C. However, a more general anti-Markovnikov alkene oxidation of non-aryl alkenes under mild conditions remains a challenge, despite the tremendous value in extending this reaction to other substrate classes, in particular allylic alcohols and esters. b-Hydroxy aldehydes are usually prepared by the crossaldol reaction between aldehydes or an aldehyde and a ketone. The direct catalytic formation of an aldehyde by selective attack at the terminal carbon of an a-olefin would be a highly valuable alternative. However, the selective antiMarkovnikov oxidation of allylic alcohols into b-hydroxy aldehydes has proven to be very difficult owing to formation of the ketone products and competing olefin isomerization. Herein, we demonstrate the aldehyde-selective catalytic oxidation of ester-protected allylic alcohols with as low as 0.5 mol% of [PdCl2(PhCN)2] and p-benzoquinone (BQ) as oxidant in tBuOH under ambient conditions. Importantly, the same anti-Markovnikov oxidation products were obtained selectively from both branched and linear allylic esters (Scheme 1), owing to rapid isomerization between allylic esters under the reaction conditions (see below).

Hydroxypalladation Precedes the Rate‐Determining Step in the Wacker Oxidation of Ethene

The complete reaction mechanism and kinetics of the Wacker oxidation of ethene in water under low [Cl(-)], [Pd(II)], and [Cu(II)] conditions are investigated in this work by using ab initio molecular dynamics. These extensive simulations shed light on the molecular details of the associated individual steps, along two different reaction routes, starting from a series of ligand-exchange processes in the catalyst precursor PdCl4(2-) to the final aldehyde-formation step and the reduction of Pd(II). Herein, we report that hydroxylpalladation is not the rate-determining step and is, in fact, in equilibrium. The newly proposed rate-determining step involves isomerization and follows the hydroxypalladation step. The mechanism proposed herein is shown to be in excellent agreement with the experimentally observed rate law and rate. Moreover, this mechanism is in consensus with the observed kinetic isotope effects. This report further confirms the outer-sphere (anti) hydroxypalladation mechanism. Our calculations also ratify that the final product formation proceeds through a reductive elimination, assisted by solvent molecules, rather than through β-hydride elimination.

Syntheses of the C1–C14 and C15–C25 Fragments of Amphidinolide C

Divergent syntheses of the C1-C14 and C15-C25 fragments of amphidinolide C have been achieved. The synthesis of the C15-C25 fragment featured cobalt-catalyzed modified Mukaiyama aerobic alkenol cyclization and sulfur-directed regiocontrolled Wacker oxidation of an internal alkene. The C1-C14 fragment was established by alkenyllithium addition to an aldehyde followed by a challenging olefination of a highly inert C9 ketone.