Cu(I)-Catalyzed Atropselective Heterobiaryl Coupling Employing Umpoled Indoles

• DOI: 10.1021/acs.orglett.4c02482
• Publication Date: 2024-08-20T15:01:45Z
• Authors: Nguyen H. Nguyen; Sanghyup Seo; Jiwon Jang; Hyunwoo Kim; Seunghoon Shin
• Keywords: Chirality; Epimer; Axial Chirality; Stereoisomerism

An enantioselective Cu(I)-catalyzed coupling of N-carboxyindoles with various 2-naphthols and phenols for the synthesis axially chiral arylindoles has been developed. Our mechanistic studies, bolstered by experimental evidence DFT calculations, reveal a novel closed-shell mechanism involving outer-sphere attack on Cu-bound naphthols. This allows unprecedented diversity in C-H arylation. Enantiocontrol is achieved through center-to-axis chirality transfer via key dearomatized naphthol intermediate, which prevents undesired epimerization C-C axis.