Ir(III)-Catalyzed Asymmetric C-H Activation/Annulation of Sulfoximines Assisted by the Hydrogen-Bonding Interaction

Transition-metal-catalyzed asymmetric C-H activation reactions generally rely on the design of ligands with sterically bulky groups to create a chiral environment for enantioinduction through steric repulsion. Here we describe an Ir(III)-catalyzed asymmetric C-H activation enabled by noncovalent interactions. A broad range of sulfur-stereogenic sulfoximines was prepared in high yields with excellent enantioselectivities via the asymmetric C-H activation/annulation of sulfoximines with diazo compounds. Desymmetrization, kinetic resolution, and parallel kinetic resolution are compatible with this protocol. Detailed DFT calculations suggested that the N-H center dot center dot center dot O hydrogen bonding interaction between sulfoximine and the chiral carboxylic acid ligand was crucial for the high enantiocontrol. Moreover, chiral iridacycle intermediates were isolated, characterized, and subjected to stoichiometric reactions. Computational and experimental studies suggested that the C-H cleavage step was the rate- and enantio-determining step.

Automated summary

The Ir(III)-catalyzed asymmetric C-H activation enabled by noncovalent interactions allows for the preparation of a broad range of sulfur-stereogenic sulfoximines with high yields and excellent enantioselectivities. Detailed DFT calculations and experimental studies have shown that the N-H···O hydrogen bonding interaction between sulfoximine and the chiral carboxylic acid ligand is crucial for the high enantiocontrol. Furthermore, chiral iridacycle intermediates have been isolated, characterized, and subjected to stoichiometric reactions, indicating that the C-H cleavage step is the rate- and enantio-determining step.