Oppenauer-type alcohol oxidation

Metal-catalyzed oxidation of alcohols to aldehydes and ketones is a subject that has received significant recent attention [21,56,57]. One such method that utilizes NHC ligands is an Oppenauer-type oxidation with an Ir or Ru catalyst [58-62]. These alcohol oxidation reactions consist of an equilibrium process involving hydrogen transfer from the alcohol substrate to a ketone, such as acetone (Eq. 5), or an alkene. Because these reactions avoid the use of a strong oxidant, the potential oxidative instability of NHC ligands is less problematic. Consequently, these reactions represent an important target for future research into the utility of NHCs. 

These complexes were screened in the oxidation of sec-phene ihyl alcohol with acetone as the solvent and K2CO3 as a base [59]. It was found that the presence of smaller substituents on the nitrogen atoms of the NHC ligand promote catalytic activity, and the dicationic complex, 25a, is the most active catalyst. Accordingly, use of complex 25a enabled the catalyst loading to be lowered to 0.025 mol%, and 3200 turnovers were achieved. The utility of this catalyst was demonstrated for both primary and secondary benzylic alcohols and several aliphatic alcohols. 

Analogs of 25, wherein the NHC ligands are replaced with PPI13 or P Bu3, are almost completely inactive under comparable conditions [59]. Although a number of mechanistic details remain to be established, it is clear that including an NHC ligand in the Irm coordination sphere exerts a beneficial effect on the catalytic activity. 

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

Interestingly, when analogous phosphine adducts were tested, very poor catalytic activity was obtained (Table 10.4, entries 6 and 7). On the other hand, the NHC-cationic complex [IrCp (ITM)(NCMe)2][OTf]2 25 proved highly efficient for the Oppenauer-type oxidation of a large range of secondary as well as primary alcohols in acetone (e.g.. Table 10.4, entries 4, 5, 8-10). 

Zr compounds are also useful as Lewis acids for oxidation and reduction reactions. Cp2ZrH2 or Cp2Zr(0 Pr)2 catalyze the Meerwein-Ponndorf-Verley-type reduction and Oppenauer-type oxidation simultaneously in the presence of an allylic alcohol and benzaldehyde (Scheme 40).170 Zr(C)1 Bu)4 in the presence of excess l-(4-dimethylaminophenyl) ethanol is also an effective catalyst for the Meerwein-Ponndorf-Verley-type reduction.1 1 Similarly, Zr(0R)4 catalyze Oppenauer-type oxidation from benzylic alcohols to aldehydes or ketones in the presence of hydroperoxide.172,173... 

Selective oxidation of allylic alcohols.1 This zircononcene complex when used in catalytic amount can effect an Oppenauer-type oxidation of alcohols, including allylic ones, in the presence of a hydrogen acceptor, usually benzaldehyde or cyclohexanone. This system oxidizes primary alcohols selectively in the presence of secondary ones. Thus primary allylic alcohols are oxidized to the enals with retention of the configuration of the double bond in 75-95% yield. The method is not useful for oxidation of propargylic alcohols. 

Oppenauer-type oxidation of secondary alcohols can be a convenient procedure for obtaining the corresponding carbonyl compounds. It was found recently [19], that Ir(I)- and Rh(I)-complexes of 2,2 -biquinoline-4,4 -dicarboxylic acid dipotassium salt (BQC) efficiently catalyze the oxidation of secondary alcohols with acetone in water/acetone 2/1 mixtures (Scheme 8.5). The reaction proceeds in the presence of Na2C03 and affords medium to excellent yields of the isolated ketones. The process is much faster in largely aqueous solutions, such as above, than in wet organic solvents in acetone, containing only 0.5 % water, low yields were observed (15 % vs. 76 % in case of cyclohexanol). 

The catalytic activity of Cp Ir(III) complexes in the Oppenauer-type oxidation of alcohols was considerably enhanced by the introduction of N-heterocyclic carbene ligands. Here, high turnover numbers (TONs) of up to 950 were achieved in the oxidation of secondary alcohols [40]. 

Hydrogen Transfer Oxidation of Alcohols (Oppenauer-Type Oxidation)... 

Hydrogen transfer reactions from an alcohol to a ketone (typically acetone) to produce a carbonyl compound (the so-caUed Oppenauer-type oxidation ) can be performed under mild and low-toxicity conditions, and with high selectivity when compared to conventional methods for oxidation using chromium and manganese reagents. While the traditional Oppenauer oxidation using aluminum alkoxide is accompanied by various side reactions, several transition-metal-catalyzed Oppenauer-type oxidations have been reported recently [27-29]. However, most of these are limited to the oxidation of secondary alcohols to ketones. 

Hiroi et al. also reported the Cp lr complex-catalyzed Oppenauer-type oxidation of primary alcohols in acetone and butanone [31]. These authors prepared a novel Ir-ligand bifunctional catalyst 6 having an amido-alkoxo ligand, the... 

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. 

Recent advances in alcohol oxidations by rhodium and iridium complexes have mainly focused on Oppenauer-type oxidations or reactions in which this type of oxidation is an intermediate step. An independent result is the oxidation of allyhc (Eq. 9) and benzyUc alcohols with f-BuOOH to the corresponding a,/l-unsaturated ketones [38] with [Rh2(p.-OAc)4]. The reactions were carried out at room temperature in dichloromethane and yields of up to 92% (by GC) in 24-48 h have been described. 

Since these are chemical equilibriiun reactions, by modifying the reaction conditions, i.e., using acetone as solvent instead of isopropanol, the reaction can be reversed, and therefore used for the oxidation (dehydrogenation) of alcohols (Oppenauer-type oxidation) [43]. Moreover, since acetone is the hy-... 

Water-soluble catalysts for Oppenauer-type oxidation of alcohols can be achieved by adding functionalized salts of classical ligands such as dipotassium 2,2 -biquinoline-4,4 -dicarboxylate (BQC) to acetone-water mixtures. In this way, the catalyst system [ Ir(ix-Cl)(cod) 2]/BQC is highly efficient for the selective oxidation of a wide range of alcohols such as benzylic. 

Perillyl aldehyde (entry 11 in Table 13.3) is typically obtained from the corresponding alcohol via Oppenauer-type oxidation by using alkylboron compounds... 

Dehydroamination is performed in the presence of a hydrogenation-dehydrogenation catalyst and an alcohol. It has been proven that an aldehyde is formed as an intermediate. Formally, this transformation is obtained by three successive reac-tions-dehydrogenation of the alcohol (Oppenauer type oxidation), formation of an imine by nucleophilic attack then dehydration, and, finally, reduction of the imine (MPV-type reduction). In the last reaction step, it can be assumed that the dehydroamination pathway is similar to that of reductive amination. 

The zirconocene complex [2ZrH2] catalyses an Oppenauer-type oxidation of alcohols in the presence of an appropriate hydrogen acceptor. On oxidation of diols containing two primary alcohols, and of diols containing two secondary alcohol groups, one of the alcohol groups is selectively oxidized to form hydroxy-aldehydes and hydroxy-ketones respectively. This system... 

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. 

When used in combination with TBHP, DIBAL can promote the oxidation of alcohols into the corresponding ketones via an Oppenauer type reaction with the TBHP being reduced by the aluminum alkoxide (eq 39). In the case of allylic alcohols, this combination affords the epoxidation products (eq 40). ... 

The lanthanide (especially samarium) alkoxides serve as highly effective cata-lysts ° ° for Oppenauer-type oxidation of alcohols to aldehydes and ketones (Eq. 2.349) ... 

The use of NHCs as ancillary ligands in iridium-catalyzed Oppenauer-type oxidation of alcohols to carbonyls has led to some of the most active catalysts for this class of transformation. In 2005, Yamaguchi and co-workers reported the synthesis of a number of [(Cp )Ir] complexes featuring NHCs as the ancillary ligands.In addition to neutral complexes of the formula... 

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... 

Shvo s catalyst 1 is a cyclopentadienone-ligated dimthenium complex, [Ru2(CO)4 (/t-H)(C4Ph4COHOCC4Ph4)]. It was first synthesized in 1984 by Shvo et al. [1, 2], Since then it has been widely applied in various hydrogen transfer reactions, including hydrogenation of carbonyl compounds [2, 3], transfer hydrogenation of ketones and imines [4,5], disproportion of aldehydes to esters [6], and Oppenauer-type oxidations of alcohols [7-9] and amines [10-12]. Shvo s complex 1 has also been found to be effective as a racemization catalyst for secondary alcohols and amines, and complex 1 has therefore been used together with enzymes in several dynamic kinetic resolution (DKR) protocols [13-18]. 

Although these systems will not be discussed further here, it should be noted that NHC-Ir complexes were also used to catalyze the Oppenauer-type oxidation of alcohols. ... 

Indium trichloride promotes catalytically the addition of alkynylstannanes to aldehydes (Table 25).42 Metallic indium also mediates the same Barbier-type coupling between alkynyl halides and aldehydes or ketones to give secondary or tertiary propargyl alcohols (Table 26). Secondary alcohols can be oxidized in situ according an Oppenauer process.395 Thus, alkynyl ketones have been prepared from aldehydes via an indium-mediated alkynylation reaction followed by an indium-mediated Oppenauer oxidation. They are also obtained via an indium-mediated alkynylation of the relevant acyl chlorides (Table 27).396... 

Peroxide intermediates are not fhe only species that enable oxidation of secondary alcohols. Oppenauer oxidation of secondary alcohols is of practical value, because only catalytic amounts of aluminum species are required and without aid from transition metals, which are usually more toxic. A new type of Oppenauer oxidation was recently discovered by Ooi and Maruoka [167]. This mefhod includes the use of bidentate aluminum catalyst which is also effective for MPV reduction (Scheme 6.144). The Oppenauer oxidation is the reverse of MPV reduction when pivalaldehyde is used as hydride-capturing agent, however, fhe reaction is virtually irreversible, giving the ketone in high yield. 

Aluminum alkoxides, particularly those formed from secondary alcohols, have been of interest to synthetic chemists since the mid-1920s due to their catalytic activity. Examples of these trialkoxides include aluminum isopropoxide (AIP) and aluminum sec-butoxide (ASB). They are easily prepared at lab or plant scale and provide highly selective reductions and oxidations under mild conditions. These reductions are termed Meerwein-Ponndorf-Verley (MPV) reactions after the chemists (1-3) who first investigated their utility. Because a MPV reaction are accuratelybe described as an equilibrium process, the reverse reaction (oxidation) can also be exploited. These associated reactions are termed Oppenauer oxidations (4). Meerwein-Ponndorf-Verley reductions and Oppenauer oxidations as well as other reaction types and applications will be discussed, but first some background is provided concerning structure, preparation, and characterization of aluminum isopropoxide and related compounds. 

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