Oxidation, basic conditions Oppenauer

The Oppenauer oxidation presents two important limitations on one side it is unable to oxidize certain alcohols because of unfavourable thermodynamics, and on the other side, base-induced reactions between the oxidant and the product may become dominant. That is why, it is seldom employed for the obtention of aldehydes because these compounds react readily under basic conditions. On the other hand, although aluminium alkoxides promote aldol condensations, many base-sensitive functional groups such as most esters but not formates—25 resist its action. 

Although aluminium alkoxides are able to promote base-induced reactions, the basic conditions involved are not extremely strong and many base-sensitive functional groups remain unaffected during Oppenauer oxidations, including alkyl halides,51 epoxides52 and most esters.53 On the other hand, the very sensitive formate esters are hydrolyzed under Oppenauer conditions and the resulting alcohols are oxidized in situ.25... 

Cyclic acetal and ketal systems constitute useful protecting groups in that they are stable in most neutral and alkaline media [30, 126, 127]. Thus they are unaffected by the basic conditions required for alkylation and acylation they are also stable to oxidation by CrOa-pyridine, periodate, Pb(OAc)4, AgjO, alkaline permanganate and under Oppenauer conditions, and to reduction by NaBH4, LLA1H4, Na-Hg and, with the exception of benzylidene acetals, to catalytic hydrogenation. 

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... 

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 to ethynodrel (39), an orally active progestin. This is the progestational component of the first oral contraceptive to be offered for sale. Treatment of the ethynyl enol ether with strong acid leads to yet another oral progestin employed as a contraceptive, norethindrone (40). ° In practice these and all other so-called combination contraceptives are mixtures of 1-2% mestranol... 

Under the Oppenauer conditions, a formate is hydrolyzed resulting in an alcohol that is oxidized in situ to a ketone. Observe that an acetate and a ketone in the same molecule resist the basic reaction conditions. 

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. 

Although the traditional Oppenauer conditions utilized aluminum catalysts, alternative metal alkoxides, for example, chloromagnesium alkoxides, are competent in the transformation.3 In 1945, Woodward devised a new system, which involved the use of potassium r-butoxide, and benzophenone for the oxidation of quinine (29) to quinone (30).13 This was termed the modified Oppenauer oxidation. The traditional aluminum catalytic system failed in this case due to the complexation of the Lewis-basic nitrogen to the aluminum centre. The synthetic flexibility of this procedure was extended by the use of more potent hydride acceptors.46... 

The conversion of LIV to /3-cyanolycopodine LIX posed another problem. Treatment of LIV under conditions which smoothly converted XLIX to LIII gave only enol ether LV. When, however, the reduction was carried out at dry ice temperature in weakly basic medium LIX was obtained. Borohydride reduction of LIV in ethanol at 0° followed in turn by hydrogenolysis and Oppenauer oxidation provided an alternative route to LIX. It should be pointed out, however, that at room temperature treatment with borohydride gave exclusively LV. Modified Kuhn-Roth oxidation of the alcohol obtained on borohydride reduction of LIX yielded a mixture of acetic, propionic, and butyric acids, demonstrating the presence of a n-propyl group in LIX 41). 

---