Manganese-Catalyzed Asymmetric Hydrogenation for Atroposelective Dynamic Kinetic Resolution of Heterobiaryl Ketone N-Oxides

An atroposelective dynamic kinetic resolution of configurationally labile heterobiaryl ketone N-oxides via Mn-catalyzed asymmetric hydrogenation has been disclosed. By use of a structurally finely tuned chiral ferrocenyl P,N,N-ligand, the hydrogenation proceeds smoothly under mild conditions with simultaneous installation of central and axial chirality, giving a wide range of atropisomeric 1-arylisoquinoline and 2-arylpyridine N-oxides bearing a chiral alcohol structure with high diastereo- and enantioselectivities. The diastereomer of the hydrogenation product could be readily prepared in a stereospecific way with the complete inversion of the central chirality via Mitsunobu reaction. The value of this central- and axial-chiral heterobiaryl N-oxide scaffold is preliminarily demonstrated by its successful utility as a chiral catalyst in asymmetric allylation of benzaldehyde with allyltrichlorosilane.