Ketalization selective

Selective ketalization at C-3 in the presence of a 20-ketone is achieved by the selenium dioxide procedure, at room temperature with " or without an additional acid catalyst. 

The 12-ketone is generally less reactive than 3-, 6- and 7-ketones but more reactive than the 11-ketone. 12-Ethylene ketals are readily prepared by the usual procedures and the 12-ketone can be selectively ketalized in the presence of a 20-ketone bearing a 17a-hydrogen or 17a-hydroxyl substituent [(81)- (82)]. ° The procedure of choice for this reaction utihzes ethylene glycol and boron trifluoride-ether complex at room temperature. 

The following reaction provides an example of selective ketal formation. The product of the reaction is a single ketone-ketal with the formula CnHigOs. 

In order to predict the structure of the product, you must identify the factors that will tend to favor selective ketal formation. Consider selective carbonyl protonation first. Obtain energies and atomic charges, and display electrostatic potential maps of the alternative protonated ketones (protonated ketone A, protonated ketone B). Identify the more stable isomer. Compare geometries and draw whatever Lewis structures are needed to account for your data. Why is one isomer more stable than the other Is the more stable isomer also that in which the positive charge is better delocalized Will the more stable isomer undergo nucleophilic attack more or less easily than the other Explain. 

Can serve as catalyst for the selective ketalization of multicarbonyl-containing compounds. Sterically-hindered or conjugated carbonyl groups will react much more slowly to the reaction ... 

Fortunately, the reactivity levels of the two ketone carbonyls in 32 were sufficiently disparate to permit selective ketalization of that located on the pendant chain. The conversion to 33 was achieved in good yield by means of trimethyl orthoformate in excess methanol with p-toluenesulfonic acid as catalyst. Subsequent exposure of this... 

Selective enone ketalization. The reaction of ethylene glycol catalyzed by pyri-dinium p-toluenesulfonate (PPTS) does not discriminate between saturated and a, 3-unsaturated ketones. In contrast, this hindered pyridinium salt (1) permits selective ketalization of enones in the presence of saturated keto groups. 2,6-Lutidinium p-toluenesulfonate (2) is as effective. 

Selective ketallzation. Ketalization with lanthanoid catalysts can distinguish between aliphatic and aromatic ketones the latter remain unaffected. Also selective ketalization of aldehydes in the presence of ketones is usually possible. CeCI., and ErCU are more efficient than the heavier rare earth ions. 

The plant bufadienolide scillarenin (500) has been synthesized. The starting material was 15a-hydroxycortexone (501), which was converted into the diketone ketal (502) by cupric acetate oxidation at C(21), followed by selective ketalization and tosylate elimination. Protection at C(3) as the dienol ether, oxiran formation at C(20) with dimethylsulphonium methylide, and regeneration of the C(3)- and C(21)-oxo-groups by acid hydrolysis then provided (503). Selective reaction at C(21) with the sodium salt of diethyl methoxycarbonyl-methylphosphonate, and boron trifluoride rearrangement of the epoxide ring to the aldehydo-unsaturated ester (504), was followed by enol lactonization to the bufadienolide (505). This was converted, in turn, to scillarenin (500) via the 14,15-bromohydrin, by standard reactions. Unsubstituted bufadienolides have also been prepared by the same method. 

Both oxalic acid and the still weaker catalyst adipic acid are sometimes useful for the selective ketalization of steroid diketones." Progesterone, refluxed in benzene with ethylene glycol and oxalic acid, gave a mixture of the 3,20-bisethyleneketal (2) and... 

Engel and Rakhit found that selective ketalization of the 12-keto group of the 12,20-diketone (1) by reaction with ethylene glycol and boron trifluoride etherate proceeds best with methylene chloride present as co-solvent to provide a homogeneous medium. Without the cosolvent, the yield was 57%. 

Selective ketalization. Jones et al. have reported selective ketahzations of some diketosteroids with ethylene glycol with an acidic ion-exchange resin (AmberUte IR 120-H) as catalyst. This procedure was found more selective than the usual homogeneous conditions. 3,6-, 3,7-, and 3,17-Diketo-5o -androstanes were converted in this way into the 3-monoketals in very high yield. 

Birch reduction of the bisketal of 54 to the enone 55, followed by Eschenmoser cleavage of the derived epoxyketone with aminodiphenylaziridine, yielded the acetylide 56. Ring B was formed by aldol condensation, hydrolysis of the acetylene to the methyl ketone, and selective ketalization to give 57. The extensive manipulation of protecting groups resulted in a somewhat unsatisfactory overall yield of 14%. 

The inertness of the aldehyde group has been attributed to selective ketalization (in alcohol—water mixtures) catalyzed by the cerium cation, thus protecting the group from reduction. 

The selective ketalization of a typical Of-diketone, cyclohexane-1,2-dione, has been studied in some detail [259, 260]. It appeared that the monoketal, once formed, ketalizes more rapidly than the enolic starting material, thus accounting for the low yield of the mono-dioxolan (15-18%). The mono-oxathiolan and -dithiolan were formed in somewhat h her yield. Various nucleophilic reactions could be performed on the ee ketone function in these compounds. 

A variant in the production of an intermediate in the Robinson synthesis, the tricyclic ABC diketone (18), was developed by Banerjee and co-workers [635, 636] (Scheme 58). The triester (22) was obtained from a-ethoxycarbonylcyclohexanone (21) by the Michael reaction with methyl acrylate, alkaline cleavage, and esterification, and it was then cyclized by Dieckmann s method with subsequent bromination and dehydrogenation to give the unsaturated keto diester (23). The addition of cyanoacetic ester gave compound (26) from which the keto triester (25) was obtained by methylation, acid hydrolysis, and esterification. The latter, by Dieck-mann cyclization and hydrolysis, gave the BC fragment (24). Selective ketalization, reduction, and hydrolysis of the ketal led to the hydroxy-ketone (27). The trans-B/C linkage present in it required the protection... 

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