Carbamates, benzyl, cleavage hydrogenation

When it is time to remove the benzyloxycarbonyl protective group, the compound is reacted with hydrogen in the presence of a catalyst. The cleavage of the benzyl group by hydrogenolysis (see Section 23.3) is followed by spontaneous decarboxylation of the carbamic acid. An example is provided by the following equation ... 

The methyl ester is stable under these conditions as there is no nucleophilic hydroxyl function. The Cbz deprotection is initialized by protonation of the carbamate s carbonyl oxygen. Br is a good nucleophile it attacks the benzylic methylene carbon, and cleavage of the benzylic C-0 bond follows. The unsubstituted hydrogen carbamate is not stable carbon dioxide is lost, delivering the driving force of this reaction. 

The related o-bromobenzyl carbonates have been developed for use in solid-phase peptide synthesis. An aryl o-bromobenzyl carbonate is stable to acidic cleavage (CF3CO2H) of a f-butyl carbamate a benzyl carbonate is cleaved. The o-bromo derivative is quantitatively cleaved with hydrogen fluoride (0°C, 10 min). ... 

An important application of hydrogenating ester cleavage is involved in Bergmann s benzyloxycarbonyl method of synthesizing peptides.79 In this an amino acid is treated with benzyl chloroformate and then coupled with another amino acid molecule the benzyl group of the resulting benzyl carbamate residue produced is finally removed as toluene, the carbamic acid derivative that results decomposing immediately to carbon dioxide and the desired peptide ... 

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