Benzylidene camphorsulfonic acid

The synthesis of the right-wing sector, compound 4, commences with the prochiral diol 26 (see Scheme 4). The latter substance is known and can be conveniently prepared in two steps from diethyl malonate via C-allylation, followed by reduction of the two ethoxy-carbonyl functions. Exposure of 26 to benzaldehyde and a catalytic amount of camphorsulfonic acid (CSA) under dehydrating conditions accomplishes the simultaneous protection of both hydroxyl groups in the form of a benzylidene acetal (see intermediate 32, Scheme 4). Interestingly, when benzylidene acetal 32 is treated with lithium aluminum hydride and aluminum trichloride (1 4) in ether at 25 °C, a Lewis acid induced reduction takes place to give... 

Trost first introduced the di-fe/7-butylsilylene derivative as a means for protecting 1,2- and 1,3-diols during a synthesis of PiUaromycinone derivatives.213 Di-ferf-butylsilylene derivatives are not as robust as isopropylidene or benzylidene acetals and their use is best reserved for systems requiring deprotection under very mild conditions. Di-isopropylsiiylene derivatives are occasionally used but they usually only survive in highly crowded environments.214 Di-feri-butylsily-lene derivatives survive hydroboration with 9-BBN, mild oxidation (e g the Dess-Martin, ozone), Lewis acids such as trifluoroborane e the rate and titanium tetrachloride, mild acids (pyridinium p-toluenesulfonate). camphorsulfonic acid, strong bases such as feri-butyllithium (THF, -50 °C), DDQ, and sodium meth-oxide in methanol at 0 C — conditions used to cleave acetate esters. 

Treatment of methyl a-D-glucopyranoside with benzaldehyde dimethyl acetal in the presence of camphorsulfonic acid (CSA) gives methyl 4,6-0-benzylidene-a-D-glucopyranoside. ... 

The most common methods generally used to prepare benzylidene acetals involve (a) reaction of a diol with benzaldehyde in the presence of p-toluenesul-fonic acid or a Lewis acid (usually zinc chloride) - — a reaction that is accelerated by ultrasonication — or (b) reaction of the diol with benzaldehyde dimethyl acetal (a,a-dimethoxytoluene) in the presence of camphorsulfonic acid or p-toluenesulfonic acid as shown in Scheme 3.79. Both 1.3-dioxolanes or 1,3-dioxanes can be formed under these conditions. Yields may be improved by running the reactions under reduced pressure to remove the methanol as it is formed. ... 

A detailed comparative study on the benzylidenation of D-arabinose diethyl-dithioacetal with benzaldehyde dimethylacetal and catalytic TsOH or with benzaldehyde in the presence of HCl or ZnCb has been published, and the benzylidenation of methyl a-D-mannopyranoside with benzaldehyde and TsOH has been improved, with yields of acetal 9 >72%." Transacetalation of fully 6-0-pivaloylated a-, P-, and y-cyclodextrins with benzaldehyde dimethylacetal and catalytic camphorsulfonic acid gave mono-benzylidene products 10. Reductive ring-opening (LAH/AIQ3) of compounds 10 afforded predominantly the 2 -0-unprotected derivatives 11. ... 

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