N-Sulfonyl Azalevoglucosan: A Versatile Platform for the Synthesis of Polysubstituted Piperidines

Substituted piperidines are key synthetic fragments for designing drugs and play a significant role in the pharmaceutical industry. The reported synthetic methods allow access to mono-, di-, and tri-substituted piperidines, but tetra- and penta-substituted piperidines are scarce in the literature. In this study, exploiting the inherent chirality of iminosugars, we report the synthesis of a levoglucosan mimic in which the endocyclic oxygen of the pyranose ring has been replaced by a N-sulfonyl group. The trans diaxial arrangement of its hydroxyl groups allows navigation on the piperidine ring to iteratively install functional groups at C1, C2, C3, C4, and C6 positions using simple experimental protocols with minimal protecting group manipulation. The broad functional group scope combined with the high regio- and stereo-selectivity make this approach an appealing process for diversity-oriented synthesis of polysubstituted piperidines, including modified iminosugars. We expect this platform will support drug discovery efforts to accelerate the discovery of therapeutically relevant molecules.