Cobaltaelectro-Catalyzed C-H Activation for Central and Axial Double Enantio-Induction.

In recent years, enantioselective electrocatalysis has surfaced as an increasingly-effective platform for sustainable molecular synthesis. Despite indisputable progress, strategies that allow the control of two distinct stereogenic elements with high selectivity remain elusive. In contrast, we, herein, describe electrochemical cobalt-catalyzed C-H activations that enable the installation of chiral stereogenic centers along with a chiral axis with high levels of enantio- and diastereoselectivities. The developed electrocatalysis strategy allowed for C-H/N-H activations/annulations with cyclic and non-cyclic alkenes providing expedient access to various central as well as atropo-chiral dihydroisoquinolinones paired to the valuable hydrogen evolution reaction. Studies on the atropo-stability of the obtained compounds demonstrated that the exceedingly mild conditions ensured by the electrocatalytic process were key for the achieved high stereoselectivities.

Cobaltaelectro-Catalyzed C-H Annulation with Allenes for Atropochiral and P-Stereogenic Compounds: Late-Stage Diversification and Continuous Flow Scale-Up.

The 3d metallaelectro-catalyzed C-H activation has been identified as an increasingly viable strategy to access valuable organic molecules in a resource-economic fashion under exceedingly mild reaction conditions. However, the development of enantioselective 3d metallaelectro-catalyzed C-H activation is very challenging and in its infancy. Here, we disclose the merger of cobaltaelectro-catalyzed C-H activation with asymmetric catalysis for the highly enantioselective annulation of allenes. A broad range of C-N axially chiral and P-stereogenic compounds were thereby obtained in good yields of up to 98% with high enantioselectivities of up to >99% ee. The practicality of this approach was demonstrated by the diversification of complex bioactive compounds and drug molecules as well as decagram scale enantioselective electrocatalysis in continuous flow.

Enantioselective electrochemical cobalt-catalyzed aryl C-H activation reactions.

Enantioselective redox transformations typically rely on costly transition metals as catalysts and often stoichiometric amounts of chemical redox agents as well. Electrocatalysis represents a more sustainable alternative, in particular through the use of the hydrogen evolution reaction (HER) in place of a chemical oxidant. In this work, we describe strategies for HER-coupled enantioselective aryl carbon-hydrogen bond (C-H) activation reactions using cobalt in place of a precious metal catalyst for the asymmetric oxidation. Thus, highly enantioselective carbon-hydrogen and nitrogen-hydrogen (C-H and N-H) annulations of carboxylic amides were achieved, which gave access to point and axially chiral compounds. Furthermore, the cobalt-mediated electrocatalysis enabled the preparation of various phosphorus (P)-stereogenic compounds by selective desymmetrization through dehydrogenative C-H activation reactions.