Ketals ethylene

The phenylenedioxy ketal is prepared from catechol (TsOH, 90°, 30 h, 85% yield) and is cleaved with 5 N HCl (dioxane, reflux, 6 h). It is more stable to acid than the ethylene ketal. 

HS(CH2) SH, BF3-Et20, CH2CI2, 25°, 12 h, high yield, n = 2, n = 3. In a,/3-unsaturated ketones the olefin does not isomerize to the /3,7-position as occurs when an ethylene ketal is prepared. Aldehydes are selectively protected in the presence of ketones except when steric factors force the ketone to be protected as in the example below." A TBDMS group is not stable to these conditions. ... 

Reduction of the sodium salt of equilenin 17-ethylene ketal with lithium, sodium or potassium in ammonia at —70° occurs predominantly in the B-ring, affording, after acid hydrolysis, equilin (29) in up to 76% yield (55% isolated). The preferential reduction of the B-ring reflects the relative, but not absolute, resistance to reduction conferred on the A-ring by the naphthoxide ion. Some A-ring reduction does compete kinetically with B-ring reduction, since the epimeric 3-hydroxyestra-5,7,9-trien-17-ones are the major reaction by-products. Simple phenoxide ions usually reduce slowly... 

A carbonyl group cannot be protected as its ethylene ketal during the Birch reduction of an aromatic phenolic ether if one desires to regenerate the ketone and to retain the 1,4-dihydroaromatic system, since an enol ether is hydrolyzed by acid more rapidly than is an ethylene ketal. 1,4-Dihydro-estrone 3-methyl ether is usually prepared by the Birch reduction of estradiol 3-methyl ether followed by Oppenauer oxidation to reform the C-17 carbonyl function. However, the C-17 carbonyl group may be protected as its diethyl ketal and, following a Birch reduction of the A-ring, this ketal function may be hydrolyzed in preference to the 3-enol ether, provided carefully controlled conditions are employed. Conditions for such a selective hydrolysis are illustrated in Procedure 4. 

A variety of conjugated dienones are reduced by lithium-ammonia, presumably via dienyl carbanions analogous to the allyl carbanions encountered in enone reductions. Cross-conjugated l,4-dien-3-ones afford 4-en-3-ones as the major reduction products, indicating that the cyclohexadienyl carbanion (55) protonates largely at C-1. Some protonation at C-5 does occur as shown by examination of the NMR spectrum of the crude reduction product derived from the 17-ethylene ketal of androsta-l,4-diene-3,17-dione. The 17-ethylene ketal of androst-4-ene-3,17-dione is formed in 75%... 

The 17-ethylene ketal of androsta-l,4-diene-3,17-dione is reduced to the 17-ethylene ketal of androst-4-en-3,17-dione in about 75% yield (66% if the product is recrystallized) under the conditions of Procedure 8a (section V). However, metal-ammonia reduction probably is no longer the method of choice for converting 1,4-dien-3-ones to 4-en-3-ones or for preparing 5-en-3-ones (from 4,6-dien-3-ones). The reduction of 1,4-dien-3-ones to 4-en-3-ones appears to be effected most conveniently by hydrogenation in the presence of triphenylphosphine rhodium halide catalysts. Steroidal 5-en-3-ones are best prepared by base catalyzed deconjugation of 4-en-3-ones. ... 

Weiss and his associates have studied the reductive alkylation of the 3-ethylene ketal of pregna-5,16-diene-3,20-dione (81) as a route to the 3-ethylene ketals of 17a-alkylpregn-5-ene-3,20-diones. The unsaturated ketone is reduced in ammonia-tetrahydrofuran using the theoretical quantity of lithium... 

Reductive Methylation of the 3-Ethylene Ketal of Pregna-5,16-diene-3,20-dione ... 

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 double bond migration which normally occurs on forming ethylene ketals from A -3-ketones has frequently been utilized to form derivatives of the A -system. The related transformation of A -3-ketones into A -3-alcohols is usually accomplished by treatment of the enol acetate (171) (X = OAc) with borohydride. This sequence apparently depends on reduction of the intermediate (172) taking place faster than conjugation ... 

The saturated 3-ketone can also be protected as the ethylene ketal, which is prepared directly by reaction with ethylene glycol or by exchange dioxo-lanation. Selective formation of 3-ethylenedioxy compounds is also possible, but the former method is not particularly effective in the presence of 6-, 17- or 20-ketones. However, the exchange dioxolanation technique is more sensitive to steric effects and good selectivity at C-3 can be achieved in the presence of a 17-ketone, provided the reagent does not contain glycol. ... 

Ethylene ketals can be readily prepared by the ethylene glycol technique. 6-Ethylene ketals can also be prepared by exchange dioxolanation and suitable conditions have been described for the preparation of either the 3-mono-ketal (78), the 3,6-diketal (79) or 3,6,17-triketal (80) from the triketone... 

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. 

Ketals other than ethylene ketals are prepared by the orthoformate procedure with heating. Thioketals are obtained from dithiols, monothiols and hemithioketals by the boron trifluoride-catalysis method. Hemi-thioketals have also been prepared in high yield by the exchange proce-dure.""""... 

Nevertheless, derivatives of the 11-ketone have been prepared in special cases. Thus the ethylene ketal of 3a,20) -dihydroxypregnan-l l-one is obtained in 50% yield by prolonged reaction according to the direct procedure. Ketals of A/B aromatic-11-ketones are formed by exchange dioxolanation. 11 -Semicarbazones have not been prepared, but hydrazones... 

The influence of the conformational factors, which play a decisive role in directing oxide fission in the above cases is no longer operative in the case of 3-keto-5a,6a-epoxides and their 3-ethylene ketals. With these substrates the —I effect of the BFs-complexed 3-keto or 3-ketal grouping predominates leading to the fluorohydrins. Thus, treatment of both 5a,6a-oxidopregnane-3,20-dione (35) and its 3,20-bisethylene ketal with BFg-etherate in benzene-ether affords in 45% yield the 6jff-fluoro-5a-hydroxy-derivative (36) and its 3-ethylene ketal, respectively. which are converted into the 6a-fluoro-A -CH3... 

Deuteration at C-3 by lithium aluminum deuteride reduction of 5a-pregnane-3, 20-dione 3-tosylhydrazone 20-ethylene ketal, 177... 

Reduction with sodium borohydride without protecting groups, 92 Reductive deacetoxylation of ll-keto-12/3-hydroxytigogenin diacetate, 53 Reductive methylation of the 3-ethylene ketal of pregna-5, 16-diene-3, 20-dione, 54... 

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