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Anomeric Stereoauxiliary Cleavage of the C−N Bond of d ‐Glucosamine for the Preparation of Imidazo[1,5‐a]pyridines
Author(s) -
Zeng Kui,
Ye Jin,
Meng Xintong,
Dechert Sebastian,
Simon Martin,
Gong Shuaiyu,
Mata Ricardo A.,
Zhang Kai
Publication year - 2022
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202200648
Subject(s) - chemistry , pyridine , anomer , cleavage (geology) , bond cleavage , ketone , stereochemistry , medicinal chemistry , combinatorial chemistry , organic chemistry , catalysis , geotechnical engineering , fracture (geology) , engineering
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.