Enantioselective rapid assembly of bis-heterocycles by sequential palladium-catalyzed aza-Heck cyclization coupling reaction
Abstract
A highly efficient palladium-catalyzed enantioselective aza-Heck-catalyzed cyclization coupling reaction of alkyne-tethered oxygen- and nitrogen-centered nucleophiles is reported. This protocol enables versatile access to chiral isoindolinone-linked benzofuran and indole bis-heterocyclic derivatives bearing a quaternary stereogenic center in good yields with high enantioselectivities. A sterically demanding, electron-rich (S)-(+)-1,1'-Bi-2-naphthol (BINOL)-derived phosphoramidite ligand provides excellent control over both chemoselectivity and enantioselectivity. Density functional theory calculations were used to elucidate the reaction mechanism and the origin of enantioselectivity. Moreover, these bis-heterocycles exhibited promising antimicrobial activity.
Fields of Study & Subjects
Synthesis and pharmacology of benzodiazepine derivatives
Catalytic C–H Functionalization Methods
Catalytic Cross-Coupling Reactions
Publication details
- Journal / source
- Science Advances
- Publisher
- American Association for the Advancement of Science (AAAS)
- Volume
- 12
- Issue
- 2
- Pages
- eaec1048–eaec1048
- Publication date
- 9 January 2026
- Language
- EN