0-benzylidene acetals benzyl ethers, from

Cyclic Acetals Benzyl ethers are obtained from benzylidene acetals on Ni but the product ethers are cleaved about as readily as the acetals.166 The hydrogenolysis of a p-bromobenzylidene derivative was achieved on 10% Pd/C in AcOEt and NaHC03.154... 

With ring G in place, the construction of key intermediate 105 requires only a few functional group manipulations. To this end, benzylation of the free secondary hydroxyl group in 136, followed sequentially by hydroboration/oxidation and benzylation reactions, affords compound 137 in 75% overall yield. Acid-induced solvolysis of the benzylidene acetal in 137 in methanol furnishes a diol (138) the hydroxy groups of which can be easily differentiated. Although the action of 2.5 equivalents of tert-butyldimethylsilyl chloride on compound 138 produces a bis(silyl ether), it was found that the primary TBS ether can be cleaved selectively on treatment with a catalytic amount of CSA in MeOH at 0 °C. Finally, oxidation of the resulting primary alcohol using the Swem procedure furnishes key intermediate 105 (81 % yield from 138). 

Methyl ethers have been employed, but alkyl glycosides may be unstable following hydrogen abstraction from the anomeric center (see Section 11,9). Benzyl ethers and benzylidene (and other aldehyde-based) acetals, which themselves undergo ready radical bromination,27 can be expected to be entirely unsuitable protecting groups. Ketone-derived acetals, on the other hand, should be stable, at least in the absence of acid, and a few examples of successful brominations in their presence are reported in Section 11,4. 

Phase-transfer catalysts e.g. benzyltriethylammonium chloride and tetrabutyl-ammonium bromide) have been used in the preparation of O-methyl and 0-benzyl ethers and acetals of formaldehyde e.g. methyl 4,6-O-benzylidene-2,3-0-methylene-a-D-mannopyranoside). A new cyclic ether, methyl 4,6-0-benzylidene-2,3-0-ethylene-a-D-glucopyranoside, resulted when methyl 4,6-0-benzylidene-a-D-glucopyranoside reacted with 1,2-dichloroethane under basic aqueous conditions in the presence of a phase-transfer catalyst. Partially protected sugars e.g. l,2 5,6-di-0-isopropylidene-a-D-gIucofuranose) have also been methylated and benzylated by reaction with methyl and benzyl trifluoro-methanesulphonate (triflate), respectively, using 2,6-di-t-butylpyridine as base. The reactions with benzyl triflate, prepared in situ from benzyl alcohol and trifluoromethanesulphonic anhydride, occurred readily at ca. — 70 °C, whereas those with methyl triflate were performed in refluxing dichloromethane. 

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