Acetal, 4-methoxybenzylidene cleavage

Reductive cleavage, using the NaCNBHj-HCl-THF system to produce 2 -pro-penylidene acetals, produced the same regioselectivity as that found in benzylidene acetals [27] (Scheme 11), and also for the p-methoxybenzylidene acetals (Scheme 12) [27]. These observations open the way to further strategies for protecting group manipulations. 

Acid-catalysed hydrolysis offers a cheap and obvious method for the cleavage of arylmethylene acetals but oftentimes the conditions required (or pH 1) can be quite harsh, e.g. dilute sulfuric acid at elevated temperature. The lability of arylmethylene acetals can be enhanced both electronically or sterically. For example, p-methoxybenzylidene acetals hydrolyse about 10 times faster than benzylidene acetals79 owing to participation of the p-methoxy substituent in resonance stabilisation of the oxonium intermediate as illustrated by the hydrolysis shown in Scheme 3.48.80 p-Methoxybenzylidene acetals can be hydrolysed in 80% aqueous acetic acid at room temperature. 

The regiochemistry of reductive cleavage of p-methoxybenzylidene acetals depends on the substrate and the reaction conditions. By suitable choice of solvent and electrophile, the distribution of regioisomers can be controlled in some cases. For example, sodium cyanoborohydride cleaved glucose derivative 66.1 [Scheme 3.66] selectively to the 6-0-p-methoxybenzyl ether 663 using trifluoro-acetic add as electrophile and DMF as solvent whereas the 4-Op-methoxy-benzyl ether 663 predominated when chlorotrimethylsilane was used as electrophile in acetonitrile as solvent.115 Note, however, that application of the latter conditions to the p-methoxybenzylidene acetal 67,1 [Scheme 3.67] gave the p-methoxybenzyl ether of the less hindered primary hydroxyl as well as rearrangement of the isopropylidene acetal,116... 

AcOH, 25°C, 10h, 100% yield. Mesitylene acetals have been found to be stable during the acid (pH — l)-catalyzed cleavage of p-methoxybenzylidene acetals. ... 

In the presence of water, p-methoxybenzylidene acetals undergo oxidative cleavage with CAN or DDQ. In the latter case, the course of the reaction can be diverted if water is excluded and halide ions introduced [Scheme 3.77] but in the presence of water, the corresponding 6- and 4-0-p-methoxybenzoates were obtained in 85-98% yield. 

Reductive cleavage with lithium aluminium hydride-aluminium chloride, or with sodium cycloborohydride-hydrochloric acid, or with aluminium chloride-trimethylamine, of endo-3t4-0-(4-methoxybenzylidene) acetal rings of 1,6-anhydro- -D-galactopyranose derivatives gives predominantly the axial 3-0-(4-0-methoxybenzyl)ether derivatives. Oxidative cleavage with DDQ affords the axial 3-0-(4-inethoxybenzoyl)... 

Reductive cleavage of the p-methoxybenzylidene acetal (4) gave the two products (Scheme 2) in similar proportions, but the dimethyl ether (5) afforded... 

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