Modified Oppenauer oxidation

A modified Oppenauer oxidation, using activated neutral chromatographic alumina and chloral in CCI4 at room temperature, allows the oxidation of cyclobutanol in ... 

Aldol cyclization. Exposure of the hydroxy ketone 1 to excess potassium t-butoxide and benzophenone in refluxing benzene provides the o,/S-unsaturated ketone 2 directly/ This transformation involves a modified Oppenauer oxidation followed by aldol closure of the resulting keto aldehyde. The product serves as an intermediate in the synthesis of Elaeocarpus alkaloids. 

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. 

In a preliminary study of caranine, it was found that a modified Oppenauer oxidation of the base gave the phenanthridinium compound XXX which was identical with one of the oxidation products of lycorine (102). From this oxidation it was postulated that caranine possesses the lycorine ring system with a hydroxyl group in the 1-position. Subsequent... 

Administration of loganin-8- H (153) 35) to G. ledgeriana plants afforded inactive cinchonine (99) and radioactive quinine (10) (Table I) 36) which contained all the tritium at C-8. The site of radioactivity was secured by chemical means. A modified Oppenauer oxidation of the quinine and workup with DgO-DCl gave radioinactive quinidinone... 

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... 

Potassium tert-butoxide Modified Oppenauer oxidation... 

The lithium aluminum hydride reduction of deacetyldeformopicraline (picrinine, VI) affords deformopicralinol (XXI R = H), whose structural relationship with picralinol (XXI R = CH20H) was confirmed by comparison of their mass spectra. When subjected to a modified Oppenauer oxidation deformopicralinol yielded two products. One was the indole-... 

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. 

Chemically modified AI2O3,32 and an aluminium and magnesium carbonate33 have been studied in Oppenauer oxidations employing oxidants other than chloral. 

Maruoka has successfully developed a highly accelerated Oppenauer oxidation [31,32] system using a bidentate aluminum catalyst [29]. This modified, catalytic system effectively oxidizes a variety of secondary alcohols to the corresponding ketones as shown in Sch. 9. For example, reaction of (2,7-dimethyl-l,8-biphenylene-dioxy)bis(dimethylaluminum) (8, 5 moI%) with carveol (14) at room temperature in the presence of 4-A molecular sieves, and subsequent treatment with pivalaldehyde (3 equiv.) at room temperature for 5 h yielded carvone (15) in 91 % yield. Under these oxidation conditions, cholesterol (16) was converted to 4-cholesten-3-one (17) in 75 % yield (91 % yield with 5 equiv. t-BuCHO). 

The approach previously outlined in Scheme 8 was used to generate numerous TV, d-disubstituted isoquinuclidines. Red-Al reduction of the lactam (83) and subsequent oxidation of the hydroxyl groups to ketones 134 was achieved via a modified Oppenauer procedure [108] using benzophenone and potassium butoxide and was accomplished in 90 minutes and in fair yields. 

Horner and Kaps have used chlorinated y-Al203 in combination with a small amount of Al(Oz-Pr)3 as the catalyst for the reduction of benzaldehyde, cyclohexanone, and acetophenone by z-PrOH [4]. In the absence of Al(Oi-Pr)3, no reaction occurred. The addition of a small amount of strong base was found to enhance the reaction rate. Analogous phenomena have been observed in the Oppenauer oxidation of several secondary alcohols. Strong bases presumably assist the deprotonation of alumina-surface co-ordinated i-PrOH, thereby forming the required alkoxide surface species. The modified alumina, which contained ca 85 mmol chloride/ 100 g alumina, was obtained by heating dry alumina in thionyl chloride for 24 h. The chloride at the surface increases the Lewis acidity of the aluminum ions and the addition of the base facilitates the deprotonation of z-PrOH. 

Among the non-steroidal alcohols applied to the Oppenauer oxidation are the cis and trans a-decalols (14), which give excellent yields of the corresponding a-decalones (IS).22 Oxidation of phenolic compounds bearing pendent aliphatic secondary alcohols can be readily performed without prior protection of the phenolic alcohol functionality.23 Acid-sensitive acetal 16 is smoothly converted to the corresponding ketone 17, by exploiting a modified experimental procedure.3,24... 

Hydration of the double bond led to a mixture of alcohols, which were separated and heated with potassium hydroxide in diethylene glycol at 225°C in the presence of a trace of hydrazine (H2NNH2) to cause partial demethylation.That was followed by a modified Oppenauer (potassium t-butoxide-benzophenone) oxidation. Then, bromination of the arylketone produced a dibromide that formed a 2,4-dinitro-phenylhydrazone (DNPH) derivative identical to one obtained from 1-bromothe-... 

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). 

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-... 

Ooi, T., Otsuka, H., Miura, T., Ichikawa, H., Maruoka, K. Practical Oppenauer (OPP) oxidation of alcohols with a modified aluminum catalyst. Org. Lett. 2002, 4, 2669-2672. 

The cyclization depicted in equation (108) was a key step in a total synthesis of lycopodine. Oppen-auer oxidation of keto alcohol (47) gives keto aldehyde (48), which is cyclized under the reaction conditions to provide dehydrolycopodine (49). The transformation failed with keto diol (50). It was reasoned that, in this case, the tertiary hydroxy group acts as a general acid, protonating the nitrogen and allowing the intermediate p-amino aldehyde to undergo elimination. To remove this side reaction, compound (50) was deprotonated with KH prior to the Oppenauer reaction. Under these modified conditions, enone (51) is obtained in reasonable yield (equation 109). °... 

Catalytic hydrogenation of 17-methylated DHEA (13-1) provides the corresponding derivative 15-1, where hydrogen has been added from the backside (Scheme 5.15). Oxidation by any one of several methods, such as the Oppenauer reaction, restores the ketone at C3 This compound, 15-2, comprises starting material for several ring A-modified derivatives. 

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