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.

The Gänseliesel showcases the scientific magic in Göttingen! Scientific magic on the α‐anomer of d‐glucosamine helps the targeted cleavage of C−N bonds in d‐glucosamine (α‐2° amine) from biobased resources and the conjunction of nitrogen in the synthesis of imidazo[1,5‐a]pyridines. 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 through a seven‐membered‐ring transition state. More information can be found in the Research Article by K. Zhang and co‐workers (DOI: 10.1002/chem.202200648).

her thesis focusing on catalyst design and biomass conversion into high-value products.Her research now mainly focuses on chirality and physical chemistry in the self-assembly process of sugar-based compounds.

Carbohydrates have been known as chiral molecules and shown promises to the future applications based on their unique structures. By using carbohydrate as building blocks, versatile chiral superstructures can be fabricated and tuned via self-assembly processes. More details can be found in article number 2208286 by Kai Zhang and co-workers.

Imidazo[1,5-α]pyridines are one of the most important groups of N-heterocyclic compounds, with wide applications in pharmaceutics, chemical science and material science. Despite tremendous progress in their synthesis over the past decade, a number of important imidazo[1,5-α]pyridines as intermediate products remain inaccessible, such as 1-alkylimidazo[1,5-α]pyridines. Herein, we report a novel anomeric stereoauxiliary approach for the preparation of this important class of compounds. It strongly expands the scope of readily accessible imidazo[1,5-α]pyridines well beyond the existing state-of-the-art methods. More than 80 products with a substantial number of deemed unattainable ones were synthesized. With the first time accessibility to alkyl(pyridine-2-yl)methanone substrates, a group of important deuterated imidazo[1,5-α]pyridines derivatives were also efficiently achieved. The mechanism containing a key seven-membered ring transition state via α-anomeric stereoauxiliary for this new synthetic pathway is provided in great detail and supported by electronic structure calculations. In total, this novel synthetic approach for a broad range of imidazo[1,5-α]pyridines involving the native stereochemistry will open a new window for research endeavors in diverse fields, encompassing organic synthesis, biomass conversion via cleavage of C-N bonds and medicinal chemistry.