Acid catalyzed ketalization

The effect of the catalyst-steroid ratio has been studied for the p-toluene-sulphonic acid-catalyzed ketalization of androst-4-ene-3,17-dione. Selective formation of the 3-monoketal is observed with the use of an equimolar amount of ethylene glycol and a low ratio of catalyst to steroid. ... 

Acid-catalyzed ketal exchange with piperidine glycol... 

Finally, the synthesis of both attenols was accomplished by employing both electrophiles 106 and 112 as shown in Scheme 1.2.24. The alkylation of dithiane 113 with 106 proceeded cleanly in 96% yield. The second alkylation using 112 had to be carried out in the presence of HMPA and yielded 115 in 84% yield. Copper-mediated hydrolysis of the dithiane and p-toluenesulfonic acid catalyzed ketal formation finally gave a mixture of the title compounds 100 (57%) and 101 (9%), each over two steps. This synthesis is so far the shortest and most efficient one [60]. 

This derivative is prepared from the diol by standard acid catalyzed ketal formation. It is cleaved by electrochemical reduction at a Hg electrode. ... 

These derivatives are prepared from the readily prepared hydroperoxide by the standard acid catalyzed ketal formation. Cleavage is achieved under basic conditions by treatment with Triton B in THF at rt, 62-87% yield. This group is stable to Grignard reagents, the Wadsworth-Emmons reaction, and reductive amination with NaBH(OAc)3. ... 

The procedure of Lowe (110) is outlined in Scheme 31. Reaction of ( )-mandelic acid (17) with phenyllithium yielded (S)-benzoin (18). Acid-catalyzed ketalization of 18 with ethylene glycol gave 19, which was converted back to [(S)-180]benzoin (20) by acidic hydrolysis in H2180. Reduction of 20 with LiAlH4 at 0°C (115) gave exclusively (l/ ,2S)-l,2-[l-180]dihydroxy-l,2-diphenylethane (21), according to Cram s (chelate) Rule. Treatment with... 

The electrolysis of ketosteroids in dichloromethane/methanol does not lead to the oxidation of unactivated CH bonds. With the 3-ketosteroids 5a-androstanone and 5a-cholestan-3-one as substrates besides the acid-catalyzed ketalization of the keto group only chlorination a to the carbonyl group occurs. The anodic oxidation of the 17-keto-steroids 5a-androstan-17-one, 3j -acetoxy-5a-androstan-17-one and 5a-androstan-3,17-dione (21) leads to the opening of the D-ring with the formation of 13,17-secosteroids, which form lactones under the weakly acidic conditions of the electrolysis and work-up (equation... 

The most commonly used protected derivatives of aldehydes and ketones are 1,3-dioxolanes and 1,3-oxathiolanes. They are obtained from the carbonyl compounds and 1,2-ethanediol or 2-mercaptoethanol, respectively, in aprotic solvents and in the presence of catalysts, e.g. BF, (L.F. Fieser, 1954 G.E. Wilson, Jr., 1968), and water scavengers, e.g. orthoesters (P. Doyle. 1965). Acid-catalyzed exchange dioxolanation with dioxolanes of low boiling ketones, e.g. acetone, which are distilled during the reaction, can also be applied (H. J. Dauben, Jr., 1954). Selective monoketalization of diketones is often used with good success (C. Mercier, 1973). Even from diketones with two keto groups of very similar reactivity monoketals may be obtained by repeated acid-catalyzed equilibration (W.S. Johnson, 1962 A.G. Hortmann, 1969). Most aldehydes are easily converted into acetals. The ketalization of ketones is more difficult for sterical reasons and often requires long reaction times at elevated temperatures. a, -Unsaturated ketones react more slowly than saturated ketones. 2-Mercaptoethanol is more reactive than 1,2-ethanediol (J. Romo, 1951 C. Djerassi, 1952 G.E. Wilson, Jr., 1968). 

As chemists proceeded to synthesize more complicated stmctures, they developed more satisfactory protective groups and more effective methods for the formation and cleavage of protected compounds. At first a tetrahydropyranyl acetal was prepared, by an acid-catalyzed reaction with dihydropyran, to protect a hydroxyl group. The acetal is readily cleaved by mild acid hydrolysis, but formation of this acetal introduces a new stereogenic center. Formation of the 4-methoxytetrahy-dropyranyl ketal eliminates this problem. 

The cleavage proceeds by initial reduction of the nitro groups followed by acid-catalyzed cleavage. The DNB group can be cleaved in the presence of allyl, benzyl, tetrahydropyranyl, methoxy ethoxy methyl, methoxymethyl, silyl, trityl, and ketal protective groups. 

Me3SiOCH2CH20SiMe3, Me3SiOTf, 15 kbar (1.5 GPa), 40°, 48 h. These conditions were used to prepare the ketal of fenchone, which cannot be done under normal acid-catalyzed conditions. 

Acetoxyandrost-5-en-17-one (59) is converted into the ethylene ketal (60) by treatment with ethylene glycol, triethylorthoformate and p-toluenesulfonic acid. The ketal is brominated with pyridinium bromide perbromide in THF and then treated with sodium iodide to remove bromine from the 5 and 6 positions. This gives the 16a-bromo compound (61) which is hydrolyzed in methanol to the free alcohol (62). Dehydrobromination is effected with potassium Fbutoxide in DMSO to give the -compound (63). Acid catalyzed hydrolysis of the ketal in aqueous acetone gives the title compound (64). ... 

The conjugated enone (177) is treated withp-toluenesulfonic acid in refluxing toluene to form the more stable product (178). The A -17-keto-system is formed by acid catalyzed cleavage of the A -17-ketal (see page 304), but the conditions are not drastic enough to cause equihbration to the more stable A " -compound. (The latter may be ketalized to form the A -17-ketal.) ... 

Thioketals are readily formed by acid-catalyzed reaction with ethane-dithiol. Selective thioketal formation is achieved at C-3 in the presence of a 6-ketone by carrying out the boron trifluoride catalyzed reaction in diluted medium. Selective protection of the 3-carbonyl group as a thioketal has been effected in high yield with A" -3,17-diketones, A" -3,20-diketones and A" -3,l 1,17-triones in acetic acid at room temperature in the presence of p-toluenesulfonic acid. In the case of thioketals the double bond remains in the 4,5-position. This result is attributed to the greater nucleophilicity of sulfur as compared to oxygen, which promotes closure of intermediate (66) to the protonated cyclic mercaptal (67) rather than elimination to the 3,5-diene [cf. ketal (70) via intermediates (68) and (69)]." " ... 

Unsubstituted 20-ketones undergo exchange dioxolanation nearly with the same ease as saturated 3-ketones although preferential ketalization at C-3 can be achieved under these conditions. " 20,20-Cycloethylenedioxy derivatives are readily prepared by acid-catalyzed reaction with ethylene glycol. The presence of a 12-ketone inhibits formation of 20-ketals. Selective removal of 20-ketals in the presence of a 3-ketal is effected with boron trifluoride at room temperature. Hemithioketals and thioketals " are obtained by conventional procedures. However, the 20-thioketal does not form under mild conditions (dilution technique). ... 

Selective hydroxylation with osmium tetroxide (one equivalent in ether-pyridine at 0 ) converts (27) to a solid mixture of stereoisomeric diols (28a) which can be converted to the corresponding secondary monotoluene-sulfonate (28b) by treatment with /7-toluenesulfonyl chloride in methylene dichloride-pyridine and then by pinacol rearrangement in tetrahydrofuran-lithium perchlorate -calcium carbonate into the unconjugated cyclohepte-none (29) in 41-48 % over-all yield from (27). Mild acid-catalyzed hydrolysis of the ketal-ketone (29) removes the ketal more drastic conditions by heating at 100° in 2 hydrochloric acid for 24 hr gives the conjugated diketone (30). 

Butylethylidene and 1-phenylethylidene ketals were prepared selectively from the C4-C6, 1,3-diol in glucose by an acid-catalyzed transketalization reaction [e.g., Me3CC(OMe)2CH3, TsOH/DMF, 24 h, 79% yield PhC(OMe)2Me, TsOH, DMF, 24 h, 90% yield, respectively]. They are cleaved by acidic hydrolysis AcOH, 20°, 90 min, 100% yield, and AcOH, 20°, 3 days, 100% yield, respectively. Ozonolysis of the /-butylmethylidene ketal affords hydroxy ester, albeit with poor regiocontrol, but a more sterically differentiated derivative may give better selectivity, as was observed with the ethylidene ketal. ... 

Compounds i, ii, and iii can be prepared by an acid-catalyzed reaction of a diol and the cycloalkanone in the presence of ethyl orthoformate and mesitylene-sulfonic acid. The relative ease of acid-catalyzed hydrolysis [0.53 M H2SO4, H2O, PrOH (65 35), 20°] for compounds i, iii, acetonide, and ii is C5 C7 > acetonide C (e.g., t.//s for 1,2-O-alkylidene-a-D-glucopyranoses of C5, C7, acetonide, and C derivatives are 8, 10, 20, and 124 h, respectively). The efficiency of cleavage seems to be dependent upon the electronic environment about the ketal. ... 

The p-methoxybenzylidene ketal can be prepared by DDQ oxidation of a p-methoxybenzyl group that has a neighboring hydroxyl. This methodology has been used to advantage in a number of syntheses. " In one case, to prevent an unwanted acid-catalyzed acetal isomerization, it was necessary to recrystallize the DDQ and use molecular sieves. The following examples serve to illustrate the reaction " ... 

The acid-catalyzed cleavage of acetals and ketals is greatly influenced by the substitution on the acetal or ketal carbon atom. The following values for k illustrate the magnitude of the effect ... 

The aromatization of the oxepin structure can be accompanied by other acid-catalyzed reactions such as the hydrolysis of ketals. Dimethyl 11 -oxo-6-oxabicyclo[5.4.0]undeca-l (7),2,4-triene-2,3-dicarboxylate ethylene ketal reacts in the presence of trifluoroacetic acid to give the tetralone system 3.133... 

Mukaiyama reaction (Lewis acid-catalyzed Michael reaction) with electron-poor olefins, ketals and acetals, and enones 32... 

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