Oppenauer oxidation transforming

Aluminum methoxide Al(OMe)3 is a solid which sublimes at 240 °C in vacuum. Aluminum isopropoxide melts in the range 120-140 °C to a viscous liquid which readily supercools. When first prepared, spectroscopic and X-ray evidence indicates a trimeric structure which slowly transforms to a tetramer in which the central Al is octahedrally coordinated and the three peripheral units are tetrahedral.162,153 Intramolecular exchange of terminal and bridging groups, which is rapid in the trimeric form, becomes very slow in the tetramer. There is MS and other evidence that the tetramer maintains its identity in the vapour phase.164 Al[OCH(CF3)2]3 is more volatile than Al[OCH(Me)2]3 and the vapour consists of monomers.165 Aluminum alkoxides, particularly Al(OPr )3, have useful catalytic applications in the synthetic chemistry of aldehydes, ketones and acetals, e.g. in the Tishchenko reaction of aldehydes, in Meerwein-Pondorf-Verley reduction and in Oppenauer oxidation. The mechanism is believed to involve hydride transfer between RjHCO ligands and coordinated R2C=0— A1 groups on the same Al atom.1... 

Regardless of the veracity of the proposed assembling depicted in Figure 6.1, the fact remains that the catalyst 67 is highly efficient in the promotion of Oppenauer oxidations under mild conditions and have been employed in a very elegant way in oxidation-reduction transformations, in which in the same molecule a secondary alcohol is oxidized while an aldehyde is reduced with no addition of external redox reagents. 

Sometimes, diols are transformed into lactones under the action of the Oppenauer oxidation.54... 

A selective oxidation of a secondary alcohol is achieved by the Oppenauer oxidation of a sterol. A primary alcohol is partially transformed in an aldehyde that condenses in situ with cylohexanone employed as oxidant. 

Dehydrorotenone 1 can be readily transformed into rotenone 2 by reduction of the chromone to the chromanol followed by Oppenauer oxidation. Two elegant syntheses of dehydrorotenone 1 used DCC as a key reagent as follows (i) treatment of derrisic acid 3 with DCC/EtjN followed by reaction of the intermediate thus obtained with sodium propanoate in ethanol gave 1. (ii) Condensation of tubaic acid 4 with the pyrrolidine enamine derived from 5 in the presence of DCC also gave 1. 

The close relation of alloyohimbine (LXIII) to a-yohimbine is proved by the observation that Oppenauer oxidation of either gives alloyohim-bone (LXIV). Their difference is due to the orientation of the hydroxyl at C-18, axial /3 in alloyohimbine and equatorial a in a-yohimbine (Volume VII, p. 56). The latter configuration is the more stable since potassium f-butoxide in benzene transforms alloyohimbine into a-yohimbine (13,25). 

Cinchonine (CVI) can be transformed into dihydrocorynantheane (XV) by a series of reactions which first changes it into 9-benzoy]-2-oxyhexahydrocinchonine (CVII). The latter reacts with cyanogen bromide to give CVIII and this in turn under alkaline conditions suffers reduction and rearrangement to CIX, which on further reduction with lithium aluminum hydride followed finally by Oppenauer oxidation generates 3-epidihydrocorynantheane (CX). This can be isomerized by known means to dihydrocorynantheane (XV) (71). 

Bicyclo[2.2.0]hexan-2-ols oxidize with rearrangement to the isomeric bicyclo[2.1.1]hexan-2-ones. This takes place under Oppenauer oxidation conditions, as well as with chromic acid, and is illustrated for photolevopimarate and chromic acid in equation (51). The yield for this transformation is excellent, although the scope and synthetic potential are probably quite limited. The reaction is highly dependent on the nature of the oxidant, as the chromate yridine reagent gave only 15% of the product afitn several days, and most of the starting alcohol was recovered. 

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. 

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... 

Thus it has been used as the first stage to obtain the starting material for the microbiological method with CSD-10 and simplified in more recent work leading to a synthesis of estrone in four steps from 3p-acetoxy-19-hydroxyandrost-5-en-17-one (ref. 116). Cholesteryl acetate was transformed by standard methods to the required androstane compound shown in the following scheme, which with hypobromous acid followed by lead tetraacetate and zinc reduction (cf. ref. 115) afforded the 19-hydroxy derivative. This with thallium nitrate in dioxan underwent loss of formaldehyde and hydration with water to afford the 19-nor-10p-alcohol in 70% yield. The diol obtained by saponification was converted by Oppenauer oxidation with N-methylpiperid-4-one as hydride aceptor (ref. 117) and afforded a 78% yield of the enone which was transformed almost quantitatively into... 

Fuchter, M. J. Oppenauer oxidation. In Name Reactions for Functional Group Transformations-, Li, J. J., Corey, E. J., Eds. John Wiley Sons Hoboken, NJ, 2007, pp 265-373. (Review). 

At an early date it was already recognized that the ketone (IX) derived from an oxidation of the C-18 carbinol function of methyl reserpate could be of considerable utility for further transformation of the reserpine pentacyclic ring system, but early attempts at the preparation of the desired compound by conventional oxidation, e.g., by Oppenauer s method, AAchlorosuceinimide, sodium dichromate, or chromic oxide in pyridine, were unsuccessful with both methyl reserpate and methyl 18-epireserpate. The ketone was finally obtained by heating methyl reserpate p-bromobenzene sulfonate with dimethyl sulfoxide in the presence of triethylamine (162), a method successfully used for simpler compounds (163). Subsequently, it was found that this oxidation could also be realized with other benzene sulfonate esters of methyl reserpate and 18-epireserpate. That the stereochemistry of the molecule was unaffected was proved by sodium borohydride reduction of the ketone, which gave equal amounts of methyl reserpate and its 18-epimer. This and other simple reactions of the ketone are sketched in Chart III, and additional observations will be given. 

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). °... 

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