Diastereo- and atroposelective synthesis of N-arylpyrroles enabled by light-induced phosphoric acid catalysis

• Published in: Nature communications Vol. 14; no. 1; p. 4813
• Main Authors: Dai, Lei, Zhou, Xueting, Guo, Jiami, Dai, Xuan, Huang, Qingqin, Lu, Yixin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.08.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/933; 639/638/403/934; 639/638/77/883; Alkynes; Asymmetric synthesis; Asymmetry; Bioactive compounds; Biological activity; Catalysis; Catalysts; Chemical synthesis; Chirality; Humanities and Social Sciences; Ligands; Light effects; multidisciplinary; Natural products; Phosphates; Phosphoric acid; Scaffolds; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-40491-8

The C−N axially chiral N -arylpyrrole motifs are privileged scaffolds in numerous biologically active molecules and natural products, as well as in chiral ligands/catalysts. Asymmetric synthesis of N -arylpyrroles, however, is still challenging, and the simultaneous creation of contiguous C−N axial and central chirality remains unknown. Herein, a diastereo- and atroposelective synthesis of N -arylpyrroles enabled by light-induced phosphoric acid catalysis has been developed. The key transformation is a one-pot, three-component oxo-diarylation reaction, which simultaneously creates a C−N axial chirality and a central quaternary stereogenic center. A broad range of unactivated alkynes were readily employed as a reaction partner in this transformation, and the N -arylpyrrole products are obtained in good yields, with excellent enantioselectivities and very good diastereoselectivities. Notably, the N -arylpyrrole skeletons represent interesting structural motifs that could be used as chiral ligands and catalysts in asymmetric catalysis. Axially chiral N -arylpyrrole motifs are privileged scaffolds in numerous biologically active compounds but asymmetric synthesis of N- arylpyrroles is challenging. Here, the authors develop a diastereo- and atroposelective synthesis of N -arylpyrroles enabled by light-induced phosphoric acid catalysis.