Oppenauer reaction

Oppenauer reaction is oxidation of secondary alcohols to ketones using aluminium t-butoxide... 

Catalytic reduction of codeine (2) affords the analgesic dihydrocodeine (7) Oxidation of the alcohol at 6 by means of the Oppenauer reaction gives hydrocodone (9)an agent once used extensively as an antitussive. It is of note that treatment of codeine under strongly acidic conditions similarly affords hydrocodone by a very unusual rearrangement of an allyl alcohol to the corresponding enol, followed by ketonization. 

The racemization mechanism of sec-alcohols has been widely studied [16,17]. Metal complexes of the main groups of the periodic table react through a direct transfer of hydrogen (concerted process), such as aluminum complexes in Meerwein-Ponn-dorf-Verley-Oppenauer reaction. However, racemization catalyzed by transition metal complexes occurs via hydrogen transfer processes through metal hydrides or metal dihydrides intermediates (Figure 4.5) [18]. 

Scheme 20.6 Mechanism of the Meerwein-Ponndorf-Verley-Oppenauer reaction.

There is obviously a relation with the classic activation of molecules by Lewis acids, but here we have confined ourselves to the activation of "soft" substrates by "soft" acids. Examples of "hard" acid activated reactions include Diels-Alder additions, nitrile solvolysis, ester solvolysis, ester formation, Oppenauer reactions etc (see Lewis acid catalysed reactions, 2.11). 

Nortricyclanone has been prepared by oxidation of nortri-cyclanol using chromic acid in acetic acid and using a modified Oppenauer reaction. The present procedure is based on the Jones modification of chromic acid oxidations. 

That specific hydride transfer from carbon to carbon does occur, was established by showing that use of labelled (Me2CDO)3Al led to the formation of RjCDOH. The reaction probably proceeds via a cyclic T.S. such as (47), though some cases have been observed in which two moles of alkoxide are involved—one to transfer hydride ion, while the other complexes with the carbonyl oxygen atom. The reaction has now been essentially superseded by MH reductions, but can sometimes be made to operate in the reverse direction (oxidation) by use of Al(OCMc3)3 catalyst, and with a large excess of propanone to drive the equilibrium over to the left. This reverse (oxidation) process is generally referred to as the Oppenauer reaction. 

Based on the catalytic activity of aluminum alkoxides in the Meerwein-Ponndorf-Verley-Oppenauer reaction, Berkessel et al. envisioned that aluminum complexes can act as alcohol racemization catalysts [32]. Aluminum alkoxide complexes generated from a 1 1 mixture of AlMes and a bidentate ligand such as binol or 2,2 -biphenol were effective catalysts for alcohol racemization. At room temperature, 10mol% of the aluminum catalyst racemized 1-phenylethanol completely within 3h in the presence of 0.5 equiv. of acetophenone. The aluminum catalysts were... 

In fact, the production of 5p-steroids from A5-3p-ols, readily available and cheap starting materials, requires preliminar oxidation through the Oppenauer reaction or, more recently, fermentation to the A4-3-keto derivative5. From this one 5p steroids are readily obtained through catalytic hydrogenation4. 

This alcohol is oxidized using an Oppenauer reaction under typical conditions with aluminium isopropoxide and cyclohexanone in boiling toluene. 

An Oppenauer reaction produces the selective oxidation of a secondary alcohol, leading to a (3-hydroxyketone that suffers a retro-aldol condensation under the basic reaction conditions, resulting in the evolution of formaldehyde. 

Iodo alkoxides, which were prepared according Eqs. (33) and (34), also revealed promising activity in MPV-Oppenauer reactions [243], but did not reach the activity of Sml2 [229], A cooperative effect of the basic alkoxide oxygen, the soft... 

Creyghton, E. J., Huskens, J., van der Waal, J. C. and van Bekkum, H. Meerwein-Ponndorf-Verley and Oppenauer reactions catalysed by heterogeneous catalyst. Stud. Surf. Sci. Catal., 1997, 108, 531. 

Typical for the Oppenauer reaction is high chemoselectivity, even in the presence of other oxidation-sensitive functional groups such as double bonds. Stable anchoring is not a problem with these Si02-based Zr catalysts, which is evident since the surface chemistry of Zr is reminiscent of that of Ti. 

In the second approach, 16-dehydropregnenolone was employed, the double bond of which at the 16,17- position was epoxidised, the epoxide cleaved with hydrogen bromide to the bromohydrin which was reduced and following formation of the 3-formoxy derivative, acetylation of the 17-hydroxy compound gave an intermediate which was oxidised by the Oppenauer reaction to give cortexolone (56) as the diacetate to which the microbiological oxidation could be applied. The process is outlined. 

Kow, R., Nygren, R., Rathke, M. W. Rate enhancement of the Meenwein-Ponndorf-Verley-Oppenauer reaction in the presence of proton acids. J. Org. Chem. 1977, 42, 826-827. 

Namy, J. L., Souppe, J., Collin, J., Kagan, H. B. New preparations of lanthanide aikoxides and their catalytical activity in Meerwein-Ponndorf-Verley-Oppenauer reactions. J. Org. Chem. 1984,49, 2045-2049. 

Otvos, L., Gruber, L., Meisei-Agoston, J. The Meerwein-Ponndorf-Veriey-Oppenauer reaction, i. investigation of the reaction mechanism with radiocarbon. Racemization of secondary aicohois. Acta Chim. Acad. Sci. Hung. 1965,43, 149-153. 

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