Oppenauer-oxidation

Oppenauer, R. V. Rec. Trav. Chim. 1937, 56, 137. Rupert V. Oppenauer (1910-), bom in Burgstall, Italy, studied at ETH in Zurich under Ruzicka and Reichstei, both Nobel laureates. After a string of academic appointments around Europe and a stint at Hoffman—La Roche, Oppenauer worked for the Ministry of Public Health in Buenos Aires, Argentina. 

Lubin-Germain, N. Seghrouchni, L. Tetrahedron Lett. 2003, 44, 819. 

Oppenauer Oxidation. In oxidation reactions involving both Cr(VI) and DMSO reagents, the alcohol is converted to a complex in which the a-hydrogen of an alcohol can be removed as an acid. A classical and alternative method for the oxidation of alcohols focuses on the reversible reaction between ketones and metal alkoxides, which is especially effective when the metal is aluminuml34 xhe reversibility of the aluminum alkoxide reaction was first demonstrated by Verley 35 Ponndorf 36 for the reaction of a ketone with an aluminum alkoxide, which led to formation of a new aluminum alkoxide and a new ketone. In 

1937 Oppenauer applied this reaction to the oxidation of unsaturated steroidal alcohols using aluminum triiso-propoxide [Al(0/-Pr)3] in acetone. 37 The acetone acts as a hydrogen acceptor and the presence of excess acetone drives the reaction toward the oxidation product. Oppenauer used this method to oxidize the alcohol 

Nonsteroidal alcohols can, of course, be oxidized by this method. 42,143 jjj general, Oppenauer oxidation of primary alcohols gives low yields of aldehydes. Although oxidation of benzyl alcohol gave about 60% of 

There are two common side reactions that were mentioned previously. One is migration of a non-conjuga-ted double bond into conjugation, and the other is condensation of the aldehyde product with the carbonyl hydrogen acceptor (this is an acid catalyzed aldol condensation - sec. 9.4.A). 

Alkoxide-catalyzed oxidation of secondary alcohols. Reverse of the Meerwein-Ponndorf-Verley reduction. 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 185, Springer-Verlag Berlin Heidelberg 2009 

Lubin-Germain, N. Seghrouchni, L. Tetrahedron Lett. 2003, 44, 819-822. Hon, Y.-S. Chang, C.-P. Wong, Y.-C. Byrne, B. Karras, M. Tetrahedron Lett. 2004, 

Kloetzing, R. J. Krasovskiy, A. Knochel, P. Chem. Eur. J. 2006,13, 215—227. Fuchter, M. J. Oppenauer oxidation. In Name Reactions for Functional Group Transformations-, Li, J. J., Corey, E. J., Eds. John WUey Sons Hoboken, NJ, 2007, pp 265-373. (Review). 

Name Reactions A Collection ofDaailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 198, Springer International Publishing Switzerland 2014 

Example 5, Tandem nucleophilic addition-Oppenauer oxidation 

The oxidation of a hydroxyl group by an aluminum alkoxide-catalyzed hydrogen exchange with a receptor carbonyl compound is known as the Oppenauer oxidation. For oxidation of steroidal alcohols the reaction is generally 

The mechanism of the oxidation is considered to proceed via the cyclic complex as shown below. The reverse of this process is known as the Meerwein, Pondorff, Verley reduction. 

The Oppenauer oxidation has found considerable application in steroid chemistry since it is the most convenient method for converting the commonly 

Vicinal effects can also play a part in the course of the reaction utilizing Oppenauer conditions. 1,3-Diols or j5-amino alcohols may not react, presumably on account of format on of an aluminum complex. If oxida- 

Commercially available aluminum isopropoxide, aluminum butoxide and aluminum phenoxide are generally of sufficient purity for use in Oppenauer oxidations provided that these reagents are obtained from a freshly opened container and are freely soluble in the reaction solvent. The reagents may be conveniently stored as 20-40 per cent solutions in anhydrous benzene or toluene. 

The secondary alcohols are oxidized to ketones by refluxing with aluminium isopropoxide, A1[0CH(CH3)2]3 [or Al(0-iPr)3], or potassium t-butoxide, KOC(CH3)3 [or KO-t-Bu]. A ketone such as acetone used in the reaction as refluxing agent is reduced to alcohol, 2-propanol. The reaction is known as the Oppenauer oxidation. The reverse reaction known as the Meerwein-Ponndorf-Verly reduction is the reduction of ketones to alcohols in the presence of alcohol such as 2-propanol. Potassium fert-butoxide can be used for the oxidation of primary alcohols. Aluminium isopropoxide in acetone is particularly used for 

R = alkyl, aryl, alkenyl R = H, alkyl, aryl, alkenyl 

Both the oxidant carbonyl compound (acetone) and the substrate alcohol are bound to the metal ion (aluminum). The alcohol is bound as the alkoxide, whereas the acetone is coordinated to the aluminum which activates it for the hydride transfer from the alkoxide. The hydride transfer occurs via a six-membered chairlike transition state. The alkoxide product may leave the coordination sphere of the aluminum via alcoholysis, but if the product alkoxide has a strong affinity to the metal, it results in a slow ligand exchange, so a catalytic process is not possible. That is why often stoichiometric amounts of aluminum alkoxide is used in these oxidations. 

The modified Oppenauer oxidation was used in the synthesis of estrone by P. Kocovsiw et al. The tetracyclic did was exposed to aluminum isopropoxide and A/-methyl-piperidine-4-one (oxidizing agent) to obtain the corresponding enone in good yield. The formation of the enone involved the migration of the initial p,y-double bond. The treatment of this enone with TsOH overnight in ether led to the formation of estrone by aromatization. 

An intramolecular Diels-Alder reaction was the key step in D.D. Sternbach s total synthesis of the linearly fused triquinane (+)-hirsutene. The cycloaddition took place between a cyclopentadiene ring and an a,p-unsaturated ketone that was generated in situ by using the Oppenauer oxidation. 

The tricyclic ring system containing the fully functionalized CD ring of taxol was prepared from (S)-(+)-carvone by T.K.M. Shing et al. The bicyclic a-hydroxy ketone (4-hydroxy-5-one) was isomerized by an Intramolecular redox reaction in the presence of catalytic amounts of aluminum isopropoxide. This example was a special case where both reactants were in the same molecule the ketone was the oxidant for the Oppenauer oxidation, whereas the secondary alcohol was the hydride donor for the MVP reduction. The conversion to the thermodynamically more stable 5-hydroxy-4-one proceeded in good yield. 

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Secondary alcohols may be oxidised to the corresponding ketones with aluminium ferf.-butoxlde (or tsopropoxlde) In the presence of a large excess of acetone. This reaction Is known as the Oppenauer oxidation and Is the reverse of the Meerweln - Ponndorf - Verley reduction (previous Section) it may bo expressed ... 

Mccrwein-Pormdorf-Verley reduction Michael reaction Oppenauer oxidation... 

Meerwein-Ponndorf-Veriey Reduction opposite of Oppenauer oxidation Synthesis 1994, 1007 Organic Reactions 1944, 2, 178... 

The widely used Moifatt-Pfltzner oxidation works with in situ formed adducts of dimethyl sulfoxide with dehydrating agents, e.g. DCC, AcjO, SO], P4O10, CCXTl] (K.E, Pfitzner, 1965 A.H. Fenselau, 1966 K.T. Joseph, 1967 J.G. Moffatt, 1971 D. Martin, 1971) or oxalyl dichloride (Swem oxidation M. Nakatsuka, 1990). A classical procedure is the Oppenauer oxidation with ketones and aluminum alkoxide catalysts (C. Djerassi, 1951 H. Lehmann, 1975). All of these reagents also oxidize secondary alcohols to ketones but do not attack C = C double bonds or activated C —H bonds. 

Oppenauer oxidation Opposed jet mills Opposition searches Oprimol 01 PROCESS... 

Most terpene-based citral (5) produced is based on the catalytic oxidative dehydrogenation of nerol (47) and geraniol (48), or by the Oppenauer oxidation of nerol and geraniol (123—125). 

A carbonyl group cannot be protected as its ethylene ketal during the Birch reduction of an aromatic phenolic ether if one desires to regenerate the ketone and to retain the 1,4-dihydroaromatic system, since an enol ether is hydrolyzed by acid more rapidly than is an ethylene ketal. 1,4-Dihydro-estrone 3-methyl ether is usually prepared by the Birch reduction of estradiol 3-methyl ether followed by Oppenauer oxidation to reform the C-17 carbonyl function. However, the C-17 carbonyl group may be protected as its diethyl ketal and, following a Birch reduction of the A-ring, this ketal function may be hydrolyzed in preference to the 3-enol ether, provided carefully controlled conditions are employed. Conditions for such a selective hydrolysis are illustrated in Procedure 4. 

Oppenauer oxidation, 236 Oxidation of allylic alcohols with dichloro-dicyanobenzoquinone, 248 Oxidation of allylic alcohols with manganese dioxide, 247... 

In the androstane and pregnane series the 7-methyl-A -3-ketones (36) are produced from 3j -acetoxy-A -7-ketones (34) with methyllithium, and subsequent Oppenauer oxidation of (35). ° ... 

The orally active progestational agent 17a-ethynyltestosterone (56) was subsequently obtained by Oppenauer Oxidation. Similarly ethynyla-tion of 3-ethoxyandrosta-3,5-dien-17-one followed by acid hydrolysis afforded the 17a-ethynyl compound (56). ... 

Hydrolysis of the acetate (71) followed by Oppenauer oxidation gives B-norcholest-4-en-3-one in high yield. An analogous reaction sequence can be used to prepare B-norprogesterone and derivatives of B-nortestosterone from pregnenolone acetate and dehydroepiandrosterone acetate, respectively."" ... 

Oppenauer oxidation and spontaneous cychzation to give 73. This represents an interesting chemical route from the cinchona to the indole alkaloids. 

Hydroxysanguinarinebetaine (367) is formed on Oppenauer oxidation of Chelidonine (366) as a red compound (65MI2) (Scheme 109). Deprotonation of the benzo[c]phenanthridine alkaloid Fagaronine (93T10305), which is known to inhibit various reverse transcriptases (77MI1), resulted in the... 

The reduction of ketones to secondary alcohols and of aldehydes to primary alcohols using aluminum alkoxides is called the Meerw>ein-Ponndorf-Verley reduction. The reverse reaction also is of synthetic value, and is called the Oppenauer oxidation. ... 

The reverse reaction, the so-called Oppenauer oxidation, is carried out by treating a substrate alcohol with aluminum tri-r-butoxide in the presence of acetone. By using an excess of acetone, the equilibrium can be shifted to the right, yielding the ketone 1 and isopropanol ... 

As a synthetic method however the Oppenauer oxidation is of limited importance. 

Oppenauer oxidation of the enol ether (34) affords the corresponding 17 ketone (37) (the enol ether is stable to the basic oxidation conditions). This ketone affords the corresponding 17a-ethynyl compound on reaction with metal acetylides. Hydrolysis of the enol ether under mild conditions leads directly... 

In a modification of this scheme, hydroxypregnenolone is first acetylated under mild conditions to the 3-acetate and then under forcing conditions with caproic anhydride to give the acetate-caproate (122). Ester interchange with methanol removes the acetate at 3 Oppenauer oxidation affords hydroxyprogesterone caproate (124). ... 

The much simpler steroid, 253, was fortuitously found to fulfill this role when injected into animals. Its lack of oral activity was overcome by incorporation of the 7a-thioacetate group. Reaction of the ethisterone intermediate, 77b, with a large excess of an organomagnesium halide leads to the corresponding acetylide salt carbonation with CO2 affords the carboxyllic acid, 251. This is then hydrogenated and the hydroxy acid cy-clized to the spirolactone. Oppenauer oxidation followed by treatment with chloranil affords the 4,6-dehydro-3-ketone (254). Conjugate addition of thiolacetic acid completes the synthesis of spironolactone (255), an orally active aldosterone antagonist. ... 

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