Ruthenium(II)/Imidazolidine Carboxylic Acid‐Catalyzed C−H Alkylation for Central and Axial Double Enantio‐Induction

Abstract

Abstract Enantioselective C−H activation has surfaced as a transformative toolbox for the efficient assembly of chiral molecules. However, despite of major advances in rhodium and palladium catalysis, ruthenium(II)‐catalyzed enantioselective C−H activation has thus far largely proven elusive. In contrast, we herein report on a ruthenium(II)‐catalyzed highly regio‐, diastereo‐ and enantioselective C−H alkylation. The key to success was represented by the identification of novel C2‐symmetric chiral imidazolidine carboxylic acids (CICAs), which are easily accessible in a one‐pot fashion, as highly effective chiral ligands. This ruthenium/CICA system enabled the efficient installation of central and axial chirality, and featured excellent branched to linear ratios with generally >20 : 1 dr and up to 98 : 2 er. Mechanistic studies by experiment and computation were carried out to understand the catalyst mode of action.

Ruthenium(II)‐catalyzed enantioselective C−H alkylations were realized with novel C2‐symmetric chiral imidazolidine carboxylic acids, with high chemo‐, regio‐, diastereo‐, and enantioselectivity. The C−H alkylation took place with simultaneous construction of central and axial chirality, reaching branched/linear ratios of >20 : 1 dr, and up to 98 : 2 er.

image