Enantioselective rapid assembly of bis-heterocycles by sequential palladium-catalyzed aza-Heck cyclization coupling reaction.
basic_science · Level V
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- Record sourced from PubMed, PMID 41512067.
- Also identified by DOI 10.1126/sciadv.aec1048 and PMC identifier 12787585.
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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.