Use of an Ionic Liquid as a Co-solvent for Recyclable Pd/C-mediated N-Debenzylation

摘要

Benzyl group is a widely used protecting group for amino, hydroxyl and sulfurhydryl groups in peptide and carbohydrate chemistry. Its popularity as a protecting group owes to its chemical stability under various reaction conditions including strongly acidic and basic environments. However, this robust character of the benzyl group sometimes turns out to be a liability when it comes to its deprotection. For the deprotection of the N-benzyl group, a variety of methods have been reported including hydrogenation with Pd/C at high or atmospheric pressure, catalytic transfer hydrogenation in acidic media or with ammonium formate, oxidation with molecular oxygen, use of Lewis acids, or employment of photosensitized single electron transfer reaction and use of other reagents. Except for the catalytic hydrogenation and transfer hydrogenation employing ammonium formate, most of the methods require rather harsh reaction conditions for satisfactory yields of the debenzylation. From our continued interest in peptidomimetic chemistry, we were in search of mild and possibly recyclable deprotection methods for various N-benzyl and N,N-dibenzyl protected amino groups. If the reagents or catalysts for the debenzylation can be recycled, the process would be amenable to large scale, practical applications.