Atroposelective synthesis of axially chiral imidazo[1,2- a ]pyridines via asymmetric multicomponent reaction
Year: 2024
Type: article
Abstract: Imidazo[1,2- a ]pyridines are privileged heterocycles with diverse applications in medicinal chemistry; however, the catalytic asymmetric synthesis of these heterocyclic structures remains underexplored. Herein, we present an efficient and modular approach for the atroposelective synthesis of axially chiral imidazo[1,2- a ]pyridines via an asymmetric multicomponent reaction. By utilizing a chiral phosphoric acid catalyst, the Groebke-Blackburn-Bienaymé reaction involving various 6-aryl-2-aminopyridines, aldehydes, and isocyanides gave access to a wide range of imidazo[1,2- a ]pyridine atropoisomers with high to excellent yields and enantioselectivities. Extensive control experiments underscored the pivotal role of the remote hydrogen bonding donor on the substrates in achieving high stereoselectivity for these reactions. The versatile derivatizations of these atropisomeric products, especially their role as an analog of NOBINs and their facile conversion into unique 6,6-spirocyclic products, further emphasize the merits of this methodology.
Source: Science Advances
Authors: Shibin Hong, Wei Liu, Chongyi Zhang, Xiaoyu Yang
Institution: ShanghaiTech University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $4,500
OpenAlex ID: W4405022870