Asymmetric Dearomatization of Indoles through Cobalt‐Catalyzed Enantioselective C−H Functionalization Enabled by Photocatalysis

• Published in: Angewandte Chemie International Edition 2024-10, Vol.63 (40), p.e202407640-n/a
• Main Authors: Teng, Ming‐Ya, Liu, De‐Yang, Mao, Shi‐Yu, Wu, Xu, Chen, Jia‐Hao, Zhong, Ming‐Yu, Huang, Fan‐Rui, Yao, Qi‐Jun, Shi, Bing‐Feng
• Format: Article
• Language: English
• Subjects: Asymmetry; Catalysis; Catalytic Asymmetric Dearomatization (CADA); Chemical synthesis; Cobalt; C−H Activation; Enantiomers; Enantioselectivity; Indoles; Irradiation; Photocatalysis; Photoredox Catalysis
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202407640

Photocatalysis holds a pivotal position in modern organic synthesis, capable of inducing novel reactivities under mild and environmentally friendly reaction conditions. However, the merger of photocatalysis and transition‐metal‐catalyzed asymmetric C−H activation as an efficient and sustainable method for the construction of chiral molecules remains elusive and challenging. Herein, we develop a cobalt‐catalyzed enantioselective C−H activation reaction enabled by visible‐light photoredox catalysis, providing a synergistic catalytic strategy for the asymmetric dearomatization of indoles with high levels of enantioselectivity (96 % to >99 % ee). Mechanistic studies indicate that the excited photocatalyst was quenched by divalent cobalt species in the presence of Salox ligand, leading to the formation of catalytically active chiral Co(III) complex. Moreover, stoichiometric reactions of cobaltacycle intermediate with indole suggest that the irradiation of visible light also play a critical role in the dearomatization step. We report an efficient protocol for chiral dihydroisoquinolone‐fused indolines through a cobaltaphotoredox catalyzed enantioselective C−H activation/dearomatization of indoles. Mechanistic studies indicate the excited photocatalyst was quenched by cobalt(II) species in the presence of Salox ligand. The stoichiometric reactions of cobaltacycle intermediate suggest the irradiation of light also play a critical role in the dearomatization step.