Chiral Osmium(II)/Salox Species Enabled Enantioselective Γ‐c(sp3)−h Amidation: Integrated Experimental and Computational Validation for the Ligand Design and Reaction Development

Herein, multiple types of chiral Os(II) complexes have been designed to address the appealing yet challenging asymmetric C(sp3)-H functionalization, among which the Os(II)/Salox species is found to be the most efficient for precise stereocontrol in realizing the asymmetric C(sp(3))-H amidation. As exemplified by the enantioenriched pyrrolidinone synthesis, such tailored Os(II)/Salox catalyst efficiently enables an intramolecular site-/enantioselective C(sp(3))-H amidation in the gamma-position of dioxazolone substrates, in which benzyl, propargyl and allyl groups bearing various substituted forms are well compatible, affording the corresponding chiral gamma-lactam products with good er values (up to 99 : 1) and diverse functionality (>35 examples). The unique performance advantage of the developed chiral Os(II)/Salox system in terms of the catalytic energy profile and the chiral induction has been further clarified by integrated experimental and computational studies.