Enantioselective cobaltaelectro-catalyzed C–H activations enabled by hydrogen evolution

Abstract

Despite the significant progress in enantioselective catalysis during the past decades, asymmetric redox transformations typically rely on costly transition metals as catalysts, along with the use of stoichiometric amounts of chemical redox agents. The exploitation of electrocatalysis in molecular synthesis represents a sustainable alternative towards value-added molecules through the hydrogen evolution reaction (HER). We herein, describe strategies for enantioselective cobaltaelectro-catalyzed C–H activations that avoid superstoichiometric chemical oxidants. Thus, highly enantioselective C–H/N–H annulations of carboxylic amides were achieved giving access to point and axially chiral compounds. Furthermore, the cobalta-electrocatalysis enabled the preparation of various P-stereogenic compounds by selective desymmetrization through dehydrogenative C–H activation reactions. These examples show how the valuable HER can be coupled to versatile enantioselective electrocatalytic organic transformations leading to relevant molecular scaffolds.

Recent Advances in Enantioselective Catalytic Electrochemical Organic Transformations

“…Ackermann and co-workers recently published a contribution where the enantioselective C-H activation was achieved by cobalt electrocatalysis [35]. They obtained enantioenriched spiro compound 17, N-annulation and phosphorous-containing molecules in galvanostatic conditions (Scheme 7).…”

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

“…Recently, stereocontrol strategies including transition metal catalysis, organocatalysis, and enzymatic catalysis have been gradually applied to this area . Although systems of enantioselective electrocatalysis are described, , its application to the synthesis of axially chiral compounds, especially with C–N axial chirality, is in its infancy. This might be attributed to the major challenges associated with atroposelective manifolds, including (a) the poor conformational stability and higher degree of rotational freedom of C–N atropoisomers, (b) electrochemical degradation of chiral ligands or of the resulting catalyst, and (c) unfavorable electrolyte interactions within the enantio-determining transition state.…”

“…Alternatively, the de novo construction of a new aromatic ring with the incorporation of the C or N atom can also generate C–N axially chiral skeletons. , Although this strategy exhibits highly convergent modular access to diverse chiral structures and a superior atom economy, it rarely involves the atroposelective construction of the C–N axially chiral units and is mainly focused on toxic and expensive rhodium catalysis . In contrast, the Earth-abundant 3d transition metal cobalt has been much less studied for atroposelective electrocatalyzed C–H activation . Very recently, our group developed the first enantioselective and regioselective cobaltaelectro-catalyzed C–H/N–H annulation with alkynes for C–N axially chiral scaffolds (Figure A) .…”

“…In contrast, the Earth-abundant 3d transition metal cobalt has been much less studied for atroposelective electrocatalyzed C–H activation . Very recently, our group developed the first enantioselective and regioselective cobaltaelectro-catalyzed C–H/N–H annulation with alkynes for C–N axially chiral scaffolds (Figure A) . This work provided a sustainable method for synthesis of C–N axially chiral compounds.…”