Chiral Osmium(II)/Salox Species Enabled Enantioselective γ‐C(sp3)−H Amidation: Integrated Experimental and Computational Validation For the Ligand Design and Reaction Development

Based on a computer-aided ligand design, the first chiral Os(II)/Salox catalytic system is realized to address the appealing yet challenging asymmetric γ-C(sp³)−H amidation of dioxazolones with precise site-/enantioselectivity control and diverse functionality. The catalytic energy profile and the chiral induction mode of the developed chiral Os(II)/Salox system are also further clarified by integrated experimental and computational studies.

Abstract

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(sp³)−H amidation. As exemplified by the enantioenriched pyrrolidinone synthesis, such tailored Os(II)/Salox catalyst efficiently enables an intramolecular site-/enantioselective C(sp³)−H amidation in the γ-position of dioxazolone substrates, in which benzyl, propargyl and allyl groups bearing various substituted forms are well compatible, affording the corresponding chiral γ-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.

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