Asymmetric Hydrogenation: Design of Chiral Ligands and Transition Metal Complexes. Synthetic and Industrial Applications.

Abstract

This personal account focuses on the development of atropisomeric ligands and chiral transition metal complexes and their applications to the asymmetric hydrogenation of alkenes, ketones and heteroaromatics using Ru(II) and Ir(III) catalysts in‐house developed. Particularly, effective scaled‐up development syntheses of SYNPHOS and DIFLUORPHOS have been successfully achieved and their steric and electronic profiling established. Going further, we demonstrated the utility of such homogeneous catalytic process highlighted with examples of industrial applications and total syntheses of biorelevant targets. Asymmetric hydrogenation provides a powerful tool for performing precise stereocontrolled transformations on valuable complex molecules.

Asymmetric hydrogenation of all-carbon tetrasubstituted α-acylpyrazole-β-alkyl cycloalkenes

“…One of the most straightforward approaches to access such frameworks would be asymmetric hydrogenation of the corresponding tetrasubstituted cycloalkenes. [7][8][9][10][11][12][13][14][15] However, achieving efficient enantioselective hydrogenation remains challenging, particularly when all substitutions involve carbon, because steric congestion in the substrate inhibits its reaction with the ligand-metal complex. Chelating or directing groups might mitigate this problem, yet they may also inactivate the catalyst by binding too strongly to it.…”