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

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(sp2)−H and C(sp3)−H bonds were also efficiently achieved.