Ketal derivatives

Methods similar to those used to form and cleave dimethyl acetal and ketal derivatives can be used for other dialkyl acetals and ketals. 

Many functional groups are stable to alkaline hydrogen peroxide. Acetate esters are usually hydrolyzed under the reaction conditions although methods have been developed to prevent hydrolysis.For the preparation of the 4,5-oxiranes of desoxycorticosterone, hydrocortisone, and cortisone, the alkali-sensitive ketol side chains must be protected with a base-resistant group, e.g., the tetrahydropyranyl ether or the ethylene ketal derivative. Sodium carbonate has been used successfully as a base with unprotected ketol side chains, but it should be noted that some ketols are sensitive to sodium carbonate in the absence of hydrogen peroxide. The spiroketal side chain of the sapogenins is stable to the basic reaction conditions. 

Similar results were encountered by Bianchetti et al. (i52), who found that e ketal derivatives of //-alkyl methyl ketones with morpholine led to the enamines of the condensation products of these ketones. The authors have Suggested the following probable mechanism for the dienamine formation. 

Glycosides were originally defined as mixed acetals (ketals) derived from cyclic forms of monosaccharides. 

Just as certain pyranose sugars can give rise to bis-acetal or bis-ketal derivatives which constitute linearly fused 5 6 6 systems (cf. Section 12.17.2.1.7), another set of bis-acetals and bis-ketals - in many cases derived from the same sugars - correspond to angularly fused 5 6 6 systems. These, like their linearly fused analogues, serve to protect, selectively, four hydroxyl groups of the parent sugars, and cyclic carbonates (l,3-dioxolan-2-ones) may fulfill similar functions. 

Chiral acetals/ketals derived from either (R,R)- or (5,5 )-pentanediol have been shown to offer considerable advantages in the synthesis of secondary alcohols with high enantiomeric purity. The reaction of these acetals with a wide variety of carbon nucleophiles in the presence of a Lewis acid results in a highly diastereoselective cleavage of the acetal C-0 bond to give a /1-hydroxy ether, and the desired alcohols can then be obtained by subsequent degradation through simple oxidation elimination. Scheme 2-39 is an example in which H is used as a nucleophile.97... 

The elimination of the ketals derived from 4-alkylcyclohexanones and (R,/f)-2.3-butanedi-ol under these conditions failed no enol ether derivative was isolated. 

A wide variety of silyl ethers can be employed, leading to functionalized homo-allylic alcohols or ethers. This three-component coupling reaction, which generates in a single operation a range of homoallylic ethers, does not require the initial and independent synthesis of the acetal (or ketal) derived from 6. 

The spiro ketal derivatives studied by Giusti 105> are remarkably uniform in their behavior toward acid hydrolysis (Table 17). Ring opening usually occurs at the site of the less-substituted carbon and, in all cases, the ester is the sole product. The overwhelming preference shown by cyclopropanone ethylene ketals for path b) in Scheme 28 may be attributed to (a) the reversibility of path a) due to rapid intramolecular ketalization at the incipient Ci-carbonium ion 131 (R = CH2CH2OH) and (b) the stability of the intermediate dioxocarbonium ion 131 a generated in path 6).106>... 

In order to synthesize 17-a-hydroxyaldosterone 2a,12 a side chain protection was needed. Otherwise the 18-carbon radical tended to furnish a methylene group and open the 13-17 bond in ring D. A convenient protection for the corticoid side chain is the A/.v-ketal derived from formaldehyde. Thus Msmethyl-enedioxy-1-dehydrohydrocortisone 21 was converted to its nitrite and photolyzed in the usual way. The only product (60 % isolated yield) was the desired isomer 22. When this was treated with nitrous acid, an unusual sequence of reactions took place. The normal nitrosation intermediate underwent ring closure to 24 followed by oxonium ion formation 25 as indicated. The oxonium ion 25 then opened one of the adjacent methylenedioxy groups (25 -> 26) which on hydration with water afforded the isolated product 27. Acetylation of 27 with acetic anhydride and acid catalysis gave the triacetate 28 in 80 % overall yield from the oxime 22. Mild alkaline hydrolysis... 

Synthesis of fluorine-18 labelled progesterone ketal derivative 109... 

The Gas-Liquid Partition Chromatography of Carbohydrate Derivatives. Part III. The Separation of Amino Glycose Derivatives and of Carbohydrate Acetal and Ketal Derivatives, H. G. Jones, J. K. N. Jones, and M. B. Perry, Can.]. Chem., 40 (1962) 1559 -1563. 

An even closer parallel is found in the work of Kreilick (33, 34), who prepared the ketal derived from 2,6-di-tert-butyl-4-acetoxyphenol. From a study of the effect of temperature on line broadening in the NMR spectrum of this compound he concluded that rearrangement occurs both by dissociation to radicals and recombination and by a direct intramolecular process. The former corresponds to the key reaction of the redistribution mechanism, while the latter is entirely analogous to the ketal rearrangement mechanism (Reaction 15). 

Glycal-substituted quinols and quinol ketals, derived from the 1,2-addition of lithiated glycals to quinones or quinone monoketals, are versatile intermediates for the synthesis of aryl C-glycosides, providing access to all four substitution patterns found in the natural products. For example, reduction of a quinol provides a p-hydroxyaryl glycal (8 9,11 -> 12). On... 

Acyclic and cyclic ketals derived from aromatic aldehydes have been deprotonated with n-BuLi (4 h) at —45 °C or LDA (24 h) at —45 °C to room temperature, and the corresponding organolithiums 445 and 446 deuteriated with MeOD655,656. 2-Aryl acetal anions show a great tendency to rearrange and/or fragment657 when they bear the electron-withdrawing oxazoline moiety at the para-position. 

A word about nomenclature. Once upon a time, chemists made a useful distinction between acetals (derived from aldehydes) and ketals (derived from ketones) which has since perished. The International Union of Pure and Applied Chemistry (IUPAC) decided (Rule C-331.1) that the term ketal is redundant and that the term acetal should now apply to all 1,1-to-ethers whether derived from aldehydes or ketones. Nevertheless, in A Guide to IUPAC Nomenclature of Organic Compounds, Recommendations 1993 (R. Panico, W.H. Powel, I-C Richter, Eds. Blackwell Science Oxford, 1993) the IUPAC graciously reinstated the term ketal , by popular demand, as a subclass of the generic term acetals (Rule R-5.6,4),... 

Oxidation of Ethers, Acetal and Ketal Derivatives. Haines, A. H.T Methods for the Oxidation of Organic Compounds Academic Press London, 1988 p 183. 

Nesvadba [2] used both aromatic and cyclohexene spiro-ketal derivatives, (I) and (II), respectively, as free radical polymerization reaction regulators. 

Reaction with chiral acetals. The chiral ketals derived from (2R,4R)-(-)-2,4-pentanediol (1) can be cleaved with high diastercoselectivity by aluminum hydride reagents, in particular DIBAH, CI2AIH, and Br,AlH. Oxidative removal of the chiral auxiliary affords optically active alcohols. This process provides a useful method for highly asymmetric reduction of dialkyl ketones. ... 

Chiral -substituted ketones Conjugate addition of (CH,)iAI to the kctal (2) of cyclohexenone derived from (S,S)-1 followed by acetylation results in the adduct 3, which is hydrolyzed by acid to (S)-3-mcthylcyclohcxanonc (4) in 77% ee. The ketal derived from (2R,3R)-2,3-butanediol undergoes a similai conjugate addition with low a.symmetric... 

Interestingly, instead of the usual aliphatic ketone, the substrate undergoing ami-noalkylation is in this case the corresponding ketal derivative. ... 

As an alternative route to the sesquicarane-type sesquiterpenoids, Hortmann and Ong have examined the carbanionic opening of the epoxy-ester (70) derived from perillaldehyde (71). The two products of this reaction are (72) and (73) in the ratio 3 1. Further elaborations of these two compounds have still to be carried out. Plattner and Rapoport have now reported the preparation of both (+)- and (— )-sirenin. This was accomplished by preparative g.l.c. separation of the two diastereoisomeric pairs of ketals derived from the synthetic ketone (74) and D-( —)- and L-( -1- )-butane-2,3-diols. Synthetic procedures for the conversion of racemic (74) into both racemic sirenin and racemic sesquicarene had already been developed. Furthermore, these authors have firmly established by chemical correlation and c.d. studies that naturally-occurring sirenin and sesquicarene have the same absolute stereochemistry, i.e. (75) and (76) respectively. 

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