Double cobalt-catalyzed atroposelective C–H activation: One-step synthesis of atropisomeric indoles bearing vicinal C–C and C–N diaxes

Expanding the borders of asymmetric synthesis by designing original chiral molecules and sustainable strategies to synthesize them holds great promise not only for the pharmaceutical industry but also for material science and agrochemistry. In particular, straightforward, one-step synthesis of enantiopure scaffolds featuring two proximal stereogenic axes presents a great scientific challenge. Herein, a unique asymmetric C–H activation reaction has been used to achieve the first intermolecular direct arylation-type reaction, affording indoles bearing simultaneous C2-atropisomeric Ar–Ar’ axis and C–N axial chirality. Remarkably, the desired reactivity could be achieved using a chiral cobalt complex as a sustainable and cheap catalyst, thus delivering the expected multi-atropisomeric compounds in high yields and excellent diastereoselectivities and enantioselectivities. In addition, detailed mechanistic studies provide fundamental comprehension of this unique transformation. [Display omitted] •Unprecedented indoles bearing C–C and C–N atropisomeric axes are synthesized•Catalytic reaction allowing two chiral events within one C–H activation step is reported•High potential of low-valent Co-catalyst bearing an original NHC ligand is highlighted•Mechanism and stereoselectivity rationalization based on detailed mechanistic studies Chiral molecules are crucial structures not only for the pharmaceutical industry but also for agrochemistry and advanced organic materials. The design of original enantiopure molecules as well as the synthetic routes allowing their straightforward and efficient synthesis is therefore attracting expanding attention. In particular, the preparation of high-value-added scaffolds from simple, non-prefunctionalized substrates via asymmetric C–H activation is appealing and challenging. The state-of-the-art asymmetric C–H activation reactions are, however, mainly limited to the use of expensive and rare noble metals. This work not only describes the synthesis of unique enantiopure indoles bearing two chiral axes (C–C and C–N axes) but also demonstrates the potential of inexpensive low-valent chiral cobalt catalysts to control two chiral events with one C–H activation step. Overspreading the application of chiral molecules translates into an urgent need for sustainable synthetic routes providing enantiomerically pure compounds. This article reports not only a new type of chiral molecule, indoles bearing a perfectly controlled C–C atropisomeric ax