Phosphoric acid-catalyzed atroposelective construction of axially chiral arylpyrroles

• Published in: Nature communications Vol. 10; no. 1; p. 566
• Main Authors: Zhang, Lei, Xiang, Shao-Hua, Wang, Jun (Joelle), Xiao, Jian, Wang, Jun-Qi, Tan, Bin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-02-2019; Nature Publishing Group; Nature Portfolio
• Subjects: 140/131; 639/638/403/933; 639/638/77/883; 639/638/77/888; Biological activity; Catalysis; Catalysts; Construction; Enantiomers; Functional groups; Humanities and Social Sciences; Ligands; Materials selection; multidisciplinary; Natural products; Optical activity; Phosphoric acid; Pyrroles; Remote control; Science; Science (multidisciplinary); Transformations
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-08447-z

Axially chiral arylpyrroles are key components of pharmaceuticals and natural products as well as chiral catalysts and ligands for asymmetric transformations. However, the catalytic enantioselective construction of optically active arylpyrroles remains a formidable challenge. Here we disclose a highly efficient strategy to access enantioenriched axially chiral arylpyrroles by means of organocatalytic atroposelective desymmetrization and kinetic resolution. Depending on the remote control of chiral catalyst, the arylpyrroles were obtained in high yields and excellent enantioselectivities under mild reaction conditions. This strategy tolerates a wide range of functional groups, providing a facile avenue to approach axially chiral arylpyrroles from simple and readily available starting materials. Selected arylpyrrole products proved to be efficient chiral ligands in asymmetric catalysis and also important precursors for further synthetic transformations into highly functionalized pyrroles with potential bioactivity, especially the axially chiral fully substituted arylpyrroles.
Axially chiral arylpyrroles are structural motifs often found in natural and medicinal products. Here, the authors report the atroposelective synthesis of axially chiral arylpyrrole derivatives, which proved to be efficient chiral ligands for asymmetric catalysis, through desymmetrization and kinetic resolution.