Issue in Honor of Prof. Ferenc Fülöp ARKIVOC 2012 (v) 312-325
Recently, Spencer et al. have demonstrated a sequential deprotection strategy for sugars based upon the PMB, NAP and benzyl groups, applying CAN as a selective reagent to cleave PMB in the presence of the NAP-ether.4 This set of benzyl-type protecting groups would be more useful, if orthogonal deprotection of NAP would be carried out in the presence of PMB. Investigating the relative stability of benzyl, p-methoxybenzyl, 2-(naphthyl)methyl, 1( naphthyl)methyl,10,11 diphenylmethyl, 9-fluorenyl and p-chlorobenzyl ethers to catalytic hydrogenation in competitive reactions, we have found that splitting of the substituted benzyl ethers such as PMB did not start until the removal of the extended aromatic system became complete.12,13
To explore the utility of this observation, a series of mono-and disaccharides carrying NAP and PMB groups were prepared and subjected to catalytic hydrogenation.
Results and Discussion
Fully protected glucoside derivatives 2 and 5 carrying benzyl, p-methoxybenzyl and 2( naphthyl)methyl protecting groups were prepared by conventional alkylation, starting from 114
14
and 4, respectively. Tlc monitoring of the Pd/C-catalyzed hydrogenolysis of 2 showed formation of a single product until the conversion reached at 80-90%; prolongation of the reaction time led to the formation of some polar side products. Therefore, the reaction mixture was worked up at 90% completion, and compound 3, selectively deprotected at position 4, could be isolated with 68% yield. Similarly, the NAP group could be removed from primary hydroxyl group of 5 in the presence of PMB and benzyl ethers, to yield 6 (Scheme 1).
Scheme 1. Removal of the (2-naphthyl)methyl group in the presence of the p-methoxybenzyl PMB and benzyl groups by catalytic hydrogenation.
Compound 7 was alkylated with (2-naphthyl)methyl bromide in the presence of phase transfer catalyst (Bu4NHSO4) affording a mixture of 815 and 9, respectively, whose separation has been accomplished by column chromatography. Subsequently, their p-methyoxybenzylation gave the acetal-containing substrates 10 and 12. Catalytic hydrogenolysis of 10 was let to go to
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