Benzylidene acetal, hydrogenolysis

A benzylidene acetal is a commonly used protective group for 1,2- and 1,3-diols. In the case of a 1,2,3-triol the 1,3-acetal is the preferred product. It has the advantage that it can be removed under neutral conditions by hydrogenolysis or by acid hydrolysis. Benzyl groups and isolated olefins have been hydrogenated in the presence of 1,3-benzylidene acetals. Benzylidene acetals of 1,2-diols are more susceptible to hydrogenolysis than are those of 1,3-diols. In fact, the former can be removed in the presence of the latter. A polymer-bound benzylidene acetal has also been prepared." ... 

We now tum our attention to the C21-C28 fragment 158. Our retrosynthetic analysis of 158 (see Scheme 42) identifies an expedient synthetic pathway that features the union of two chiral pool derived building blocks (161+162) through an Evans asymmetric aldol reaction. Aldehyde 162, the projected electrophile for the aldol reaction, can be crafted in enantiomerically pure form from commercially available 1,3,4,6-di-O-benzylidene-D-mannitol (183) (see Scheme 45). As anticipated, the two free hydroxyls in the latter substance are methylated smoothly upon exposure to several equivalents each of sodium hydride and methyl iodide. Tetraol 184 can then be revealed after hydrogenolysis of both benzylidene acetals. With four free hydroxyl groups, compound 184 could conceivably present differentiation problems nevertheless, it is possible to selectively protect the two primary hydroxyl groups in 184 in... 

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... 

Summarizing, it may be concluded that the ease of hydrogenolysis is (1) cyclic orthoester > isopropylidene acetal, cyclohexylidene acetal > benzylidene acetal > ethylidene acetal > methylene acetal, and (2) 5,6-O-linked and 3,5-O-linked > 1,2-0-linked acetals. 

Application of hydrogenolysis of benzylidene acetals to 2-amino-2-deoxy sugar derivatives was found to be possible.217 The reductive cleavage of benzyl 4,6-0-benzylidene-2-(benzyloxycarbonyl)amino-2-deoxy-a-D-glucopyranoside (209) gave, in a yield of 50%, a mixture of the 4-O-benzyl (210) and the 6-O-benzyl (211) derivatives. If the re-gioselectivity of this reaction, although notably inferior, was in ac-... 

A. Liptdk, J. Imre, J. Harangi, P. NSnisi, and A. Neszmilyi, Chemo-, stereo- and regioselective hydrogenolysis of carbohydrate benzylidene acetals. Synthesis of benzyl ethers of benzyl a-D-,... 

Benzylidene acetals can be removed by mild aqueous acid hydrolysis (80% AcOH or TFA/DCM/H2O) or by catalytic hydrogenolysis over Pd(OH)2 or Pd-C.30... 

Benzylidene acetals, very fragile in an acidic medium, are hydrolysed by aqueous acetic acid or cleaved by hydrogenolysis. Selectivity can be observed in the hydrolysis of isopropylidene acetals. With compound 5.10, only the ring spanning positions 5 and 6 is hydrolysed by aqueous acetic acid. Hydrolysis of the acetal function which involves the anomeric oxygen requires heating in mineral acid (0.1 M) for a few hours, comparable conditions to those of hydrolysis of a glycoside. 

Cleavage of the benzylidene acetal from 59 was next accomplished by heating it in an 8 2 mixture of acetie acid/water. Catalytic hydrogenolysis of the azido group in 60 was thereafter effected in ethanol, in the presence of 10% wet palladium on carbon. The newly liberated amine was subsequently A -acylated under standard biphasic conditions to give 42 in 62% yield. 

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