Atroposelective synthesis of axially chiral imidazo[1,2- a ]pyridines via asymmetric multicomponent reaction DOI Creative Commons

Shibin Hong,

Wei Liu, Chengmin Zhang

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(49)

Published: Dec. 4, 2024

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 atroposelective axially chiral imidazo[1,2- via multicomponent reaction. By utilizing phosphoric acid catalyst, Groebke-Blackburn-Bienaymé reaction involving various 6-aryl-2-aminopyridines, aldehydes, isocyanides gave access to wide range ]pyridine atropoisomers high excellent yields enantioselectivities. Extensive control experiments underscored pivotal role remote hydrogen bonding donor on substrates achieving stereoselectivity reactions. The versatile derivatizations atropisomeric products, especially their as analog NOBINs facile conversion into unique 6,6-spirocyclic further emphasize merits this methodology.

Language: Английский

Catalytic Enantioselective Synthesis of Axially Chiral Diaryl Ethers Via Asymmetric Povarov Reaction Enabled Desymmetrization DOI Creative Commons

Zidan Ye,

Wansen Xie,

Wei Liu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Axially chiral diaryl ethers represent a distinct class of atropisomers, characterized by unique dual C─O axes system, which have been found in variety natural products, pharmaceuticals, and ligands. However, the catalytic enantioselective synthesis these atropoisomers poses significant challenges, due to difficulty controlling both axes, their more flexible conformations. Herein, an efficient protocol for axially is presented using organocatalyzed asymmetric Povarov reaction-enabled desymmetrization, followed aromatizations. This method yields wide range novel quinoline-based ether good high enantioselectivities. Notably, various aromatization protocols are developed, resulting diverse set polysubstituted quinoline-containing atropisomers. Thermal racemization studies suggested excellent configurational stabilities atropisomers (with barriers up 38.1 kcal mol

Language: Английский

Citations

2
Atroposelective synthesis of axially chiral imidazo[1,2- a ]pyridines via asymmetric multicomponent reaction DOI Creative Commons

Shibin Hong,

Wei Liu, Chengmin Zhang

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(49)

Published: Dec. 4, 2024

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 atroposelective axially chiral imidazo[1,2- via multicomponent reaction. By utilizing phosphoric acid catalyst, Groebke-Blackburn-Bienaymé reaction involving various 6-aryl-2-aminopyridines, aldehydes, isocyanides gave access to wide range ]pyridine atropoisomers high excellent yields enantioselectivities. Extensive control experiments underscored pivotal role remote hydrogen bonding donor on substrates achieving stereoselectivity reactions. The versatile derivatizations atropisomeric products, especially their as analog NOBINs facile conversion into unique 6,6-spirocyclic further emphasize merits this methodology.

Language: Английский

Citations

0