Oppenauer oxidation mechanisms

The Oppenauer Oxidation. When a ketone in the presence of base is used as the oxidizing agent (it is reduced to a secondary alcohol), the reaction is known as the Oppenauer oxidation. This is the reverse of the Meerwein-Ponndorf-Verley reaction (16-23), and the mechanism is also the reverse. The ketones most commonly used are acetone, butanone, and cyclohexanone. The most common base is aluminum r r/-butoxide. The chief advantage of the method is its high selectivity. Although the method is most often used for the... 

Some conversion into the anhydrovitamin (112) occurs during silica gel t.l.c. of retinyl palmitate in non-polar solvents. Some new colour reactions of vitamin A are reported to be better than the Carr-Price reaction. The kinetics and mechanism of acid-catalysed isomerization of retinyl acetate into the trans-retro-derivative (113) have been studied. Oppenauer oxidation of kitol (39) results in specific cyclopentanol-cyclopentanone oxidation. ... 

Aluminum methoxide Al(OMe)3 is a solid which sublimes at 240 °C in vacuum. Aluminum isopropoxide melts in the range 120-140 °C to a viscous liquid which readily supercools. When first prepared, spectroscopic and X-ray evidence indicates a trimeric structure which slowly transforms to a tetramer in which the central Al is octahedrally coordinated and the three peripheral units are tetrahedral.162,153 Intramolecular exchange of terminal and bridging groups, which is rapid in the trimeric form, becomes very slow in the tetramer. There is MS and other evidence that the tetramer maintains its identity in the vapour phase.164 Al[OCH(CF3)2]3 is more volatile than Al[OCH(Me)2]3 and the vapour consists of monomers.165 Aluminum alkoxides, particularly Al(OPr )3, have useful catalytic applications in the synthetic chemistry of aldehydes, ketones and acetals, e.g. in the Tishchenko reaction of aldehydes, in Meerwein-Pondorf-Verley reduction and in Oppenauer oxidation. The mechanism is believed to involve hydride transfer between RjHCO ligands and coordinated R2C=0— A1 groups on the same Al atom.1... 

The available experimental data supports a mechanism for the Oppenauer oxidation, involving an initial complexation of a carbonyl group with the aluminium from an aluminium alkoxide, followed by a rate-determining hydride transfer via a six-membered transition state.22... 

Oppenauer oxidation, using alkoxides other than aluminium, operates via a hydride transfer mechanism similar to the one depicted in the above Equation, although a complexation of the metal with the carbonyl group may not be present.22d Evidence for a radical mechanism was put forward in the case of the interaction between lithium isopropoxide and benzophenone.24... 

Oxidations under Oppenauer conditions are highly selective for alcohols, normally resulting other functionalities sensitive to oxidation unchanged. This happens because the Oppenauer oxidation operates via a mechanism involving a hydride transfer from a metallic alkoxide, which is very specific for alcohols. Over-oxidations have been described only for situations in which very reactive oxidants, such as p-quinone, are employed.14... 

In this paper, the published yields were modest and the full versatility of the procedure was not checked. However, this paper established the conceptual principle that magnesium alkoxides could be efficiently oxidized in the presence of good hydride abstractors, such as l,l -(azodicarbonyl)di-piperidine (ADD), via a hydride transfer resembling the mechanism of the Oppenauer oxidation. 

Although the Mukaiyama oxidation is not in the top list of the most frequently used alcohol oxidants, the authors of this book have decided to pay full attention to this procedure because it succeeds in very sensitive organometallic compounds, where most other oxidants fail. The Mukaiyama oxidation operates via a somehow unique mechanism involving a hydride transfer from a metal alkoxide to a very good hydride acceptor, which resembles the Oppenauer oxidation. In variance with the Oppenauer oxidation, the Mukaiyama protocol involves much milder conditions and it does not promote as easily base-induced side reactions. 

Secondary alcohols may be oxidised to the corresponding ketones by the use of an aluminium alkoxide, frequently the t-butoxide, in the presence of a large excess of acetone (the Oppenauer oxidation). The reaction involves an initial alkoxy-exchange process followed by a hydride ion transfer from the so-formed aluminium alkoxide of the secondary alcohol by a mechanism analogous to that of the Meerwein-Ponndorf-Verley reduction (see Section 5.4.1, p. 520). 

The mechanism of the Oppenauer oxidation with potassium fert-butoxide is given in Scheme 7.13. 

Wettstein described the oxidation of pregnenolone to 6-dehydroprogesterone in detail but did not record the yield. In discussing the mechanism of the Wettstein-Oppenauer oxidation, Mandell surveyed the literature and stated that yields are as high as 50%. ... 

The transition states leading to the cis and trans alcohols differ substantially in size and the way in which they can be accommodated in the pores of zeolite Beta. That for the cis isomer is more or less linearly aligned with the pore axis and can easily be accommodated within the straight channels of the zeolite. The transition state for the formation of the trans isomer is more or less perpendicular to the channel wall and cannot be well accommodated within the micropores (Scheme 5). As required by this mechanism, the cis alcohol was found to undergo Oppenauer oxidation over zeolite Beta whereas activity for the trans isomer being negligible. 

The generally accepted mechanism for the Oppenauer oxidation involves a cyclic transition state 1,12 as originally proposed by both Woodward13 and Oppenauer.14... 

Having developed an efficient artificial transfer hydrogenase, we attempted to apply the same methodology to the reverse reaction the kinetic resolution of racemic alcohols. To our disappointment, we were forced to use strong oxidizing agents (eg. f-BuOOH rather than acetone, in the spirit of an Oppenauer-type mechanism) to drive the reaction to completion. We speculate that, in the presence of water, the ruthenium is unable to abstract the j8-hydrogen on the prochiral alcohol. 

The Oppenauer oxidation of alcohols using fluorenone (27) as a hydride acceptor may not proceed by the mechanism in which is delivered to the carbon of the carbonyl group. The following description remains a distinct possibility. 

One of the chemoselective and mild reactions for the reduction of aldehydes and ketones to primary and secondary alcohols, respectively, is the Meerwein-Ponndorf-Verley (MPV) reduction. The lifeblood reagent in this reaction is aluminum isopropoxide in isopropyl alcohol. In MPV reaction mechanism, after coordination of carbonyl oxygen to the aluminum center, the critical step is the hydride transfer from the a-position of the isopropoxide ligand to the carbonyl carbon atom through a six-mem-bered ring transition state, 37. Then in the next step, an aluminum adduct is formed by the coordination of reduced carbonyl and oxidized alcohol (supplied from the reaction solvent) to aluminum atom. The last step is the exchange of produced alcohol with solvent and detachment of oxidized alcohol which is drastically slow. This requires nearly stoichiometric quantities of aluminum alkoxide as catalyst to prevent reverse Oppenauer oxidation reaction and also to increase the time of reaction to reach complete conversion. Therefore, accelerating this reaction with the use of similar catalysts is always the subject of interest for some researchers. 

Gabrielsson et al. reported the aerobic oxidation of alcohols catalyzed by a cationic Cp Ir complexes bearing diamine ligands such as bipyrimidine 10 (Scheme 5.8) [35], the mechanism of which is closely related to the Oppenauer-type oxidation mentioned above. In this reaction, the deprotonation of Ir hydrido species to afford Ir species, and the reoxidation of Ir to Ir by O2, are crucial. 

Scheme 8 Proposed mechanism for Oppenauer-type alcohol oxidation...

Meerwein-Ponndorf-Verley-Oppenauer (MPVO) reactions are usually mediated by metal alkoxides such as Al(0/-Pr)3. The activity of these catalysts is related to their Lewis-acidic character in combination with ligand exchangeability. The mechanism of these homogeneous MPVO reactions proceeds via a cyclic six-membered transition state in which both the reductant and the oxidant are co-ordinated to the metal center of the metal alkoxide catalyst (Scheme 1). The alcohol reactant is co-ordinated as alkoxide. Activation of the carbonyl by co-ordination to Al(III)-alkoxide initiates the hydride-transfer reaction from the alcoho-late to the carbonyl. The alkoxide formed leaves the catalyst via an alcoholysis reaction with another alcohol molecule, usually present in excess [Ij. 

A review describes the asymmetric epoxidation of allylic alcohols,369 another the role of metal oporphyrins in oxidation reactions.370 jhe TiiOPrMi, catalysed self-epoxidation of allylic peroxides proceeds via an intermolecular mechanism.371 Racemic allyl alcohols can be resolved by asymmetric epoxidation (eq.35).372 a Pd(II)/Mn02/benzoquinone system catalyses the oxidative ring-closure of 1,5-hexadienes (eq.36).373 propenyl phenols are oxidatively degraded to aryl aldehydes and MeCHO in the presence of Co Schiff-base catalysts.374 An Oppenauer-type oxidation with Cp2ZrH2/cyclohexanone converts primary alcohols selectively into aldehydes.375 co macrocycles catalyse the oxidation of aryl liydrazones to diazo compounds in high yields.376 similar Co complexes under CO oxidise primary amines to azo compounds.377 Arene Os complexes in the presence of base convert aldehydes and water slowly into carboxylic acids and H2.378... 

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