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

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.