Anomeric Stereoauxiliary Cleavage of the C−N Bond of d‐Glucosamine for the Preparation of Imidazo[1,5‐a]pyridines

Abstract The targeted cleavage of the C−N bonds of alkyl primary amines in sustainable compounds of biomass according to a metal‐free pathway and the conjunction of nitrogen in the synthesis of imidazo[1,5‐a]pyridines are still highly challenging. Despite tremendous progress in the synthesis of imidazo[1,5‐a]pyridines over the past decade, many of them can still not be efficiently prepared. Herein, we report an anomeric stereoauxiliary approach for the synthesis of a wide range of imidazo[1,5‐a]pyridines after cleaving the C−N bond of d ‐glucosamine (α‐2° amine) from biobased resources. This new approach expands the scope of readily accessible imidazo[1,5‐a]pyridines relative to existing state‐of‐the‐art methods. A key strategic advantage of this approach is that the α‐anomer of d ‐glucosamine enables C−N bond cleavage via a seven‐membered ring transition state. By using this novel method, a series of imidazo[1,5‐a]pyridine derivatives (>80 examples) was synthesized from pyridine ketones (including para ‐dipyridine ketone) and aldehydes (including para ‐dialdehyde). Imidazo[1,5‐a]pyridine derivatives containing diverse important deuterated C(sp 2 )−H and C(sp 3 )−H bonds were also efficiently achieved.