Ketals cleavage, selective

A number of highly selective acetal and ketal cleavages of derivatives of carbohydrates and related compounds have been reported recently [ 1451. One of these is illustrated in eq. (2.39) (I46. The configuration of the new stereogenic center implies retention in tile displacement. 

The approach was carried out on a ketohexo backbone bearing acid-sensitive ketal groups (Scheme 29). l,2 4,5-Di-0-isopropylidene-/ -D-fructo-pyranose readily underwent PDC oxidation of the 3-OH, followed by selective acid-catalyzed hydrolysis of the 4,5-ketal to afford a partially protected ketone in 94% overall yield. For the subsequent HSCN condensation, adapted acidic conditions had to be established to avoid 1,2-isopropylidene cleavage under thermal conditions and the target OZT (R = H) could be isolated in 60% yield. When performed in ethanol, the condensation afforded the acetalic counterpart (R = Et) albeit in lower yield. 

Kim KS, Song YH, Lee BH, Hahn CS (1986) Efficient and selective cleavage of acetals and ketals using ferric chloride adsorbed on silica gel. J Org Chem 51 404 -06... 

Johnstone C, Kerr W J, Scott J S (1996) Selective cleavage of ketals and acetals under neutral, anhydrous conditions using triphenylphosphine and carbon tetrabromide. Chem Commun 1996 341-342... 

Reduction of bicyclic ketals. Reductive cleavage of the bicyclic ketal 1 in the presence of a Lewis acid favors ds-products, regardless of the reductant. The highest dr-selectivity is obtained with (C2H5)3SiH and TiCl4. DIBAL shows high... 

Asymmetric reduction of ketones. Chiral ketals 2, obtained by reaction of 1 with prochiral ketones, are reduced diastereoselectively to 3 by several aluminum hydride reagents, the most selective of which is dibromoalane (LiAIHj-AIBr, 1 3). Oxidation and cleavage of the chiral auxiliary furnishes optically active alcohols (4) in optical yields of 78-96% ee (equation 1). 

Diisobutylaluminum hydride (DIBAL-H) hydrogenolyzes simple ortho esters to acetals at room temperature and reduces acetals and ketals to ethers at 70-80 °C (equation 6) benzyl ethers are cleaved at still higher temperatures. This reagent shows good selectivity and considerable versatility. It has been used to reduce acetals of formaldehyde (equation 7), ° which few other reagents can accomplish. With catechol ketals a single reductive cleavage occurs at room temperature (equation 8). ... 

Methyl acetals and ketals are rapidly reduced to methyl ethers by sodium cyanoborohydride in methanol with dry HCI at ice temperatures. A dioxolane is completely cleaved to a methyl ether, showing intervention by the solvent at some stage (equation 14), but when an inert solvent such as THF is used only single cleavage occurs this reagent shows interesting selectivity in the reduction of benzylidene acetals in the carbohydrate series (see Section 1.9.3.4). 

An alternate strategy involved anodic oxidation of /> 7ra-methoxyphenol TBDPS ether derivatives (LXXVIII). The resulting mixed 0-silyl 0-methyl bisketals (LXXIX) underwent selective monohydrolysis of the dimethyl ketal moiety [87]. Alternatively, desi-lylation of LXXIX with B114NF gave dimethyl monoketals of the opposite regiochemistry [Eq. (37)]. This work was in contrast to earlier studies on similar silyl ethers systems, wherein O-Si bond cleavage predominated during electrolysis [88]. 

TESOTf, 2,6-lutidine, CH2CI2, 0"C, 5 min, 50-93% yield. This is an unusual method in that deprotection occurs under basic conditions. The reaction is selective for the cleavage of acetals over ketals with excellent chemoselectiv-ity. Similar selectivity is achieved with dioxolanes. ... 

To test the proposed route we capitalized upon our ability to use the intramolecular diyl trapping reaction to synthesize 95, the mono-ketal analog of 143. Ozonolytic cleavage of the C-C n bond of 95 followed by reduction with NaBIfy afforded diol 145 in an 85% yield. The primary alcohol was selectively protected as a silyl ether, and the secondary alcohol oxidized with PCC to provide ketone 146 as a 1 1 mixture of diastereomers. 

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