Kinetic resolution of sulfur-stereogenic sulfoximines by Pd(ii)-MPAA catalyzed C-H arylation and olefination

A direct Pd(ii)-catalyzed kinetic resolution of heteroaryl-enabled sulfoximines through an ortho-C-H alkenylation/arylation of arenes has been developed. The coordination of the sulfoximine pyridyl-motif and the chiral amino acid MPAA ligand to the Pd(ii)-catalyst controls the enantio-discriminating C(aryl)-H activation. This method provides access to a wide range of enantiomerically enriched unreacted aryl-pyridyl-sulfoximine precursors and C(aryl)-H alkenylation/arylation products in good yields with high enantioselectivity (up to >99% ee), and selectivity factor up to >200. The coordination preference of the directing group, ligand effect, geometry constraints, and the transient six-membered concerted-metalation-deprotonation species dictate the stereoselectivity; DFT studies validate this hypothesis.

Automated summary

A direct Pd(ii)-catalyzed kinetic resolution of heteroaryl-enabled sulfoximines through an ortho-C-H alkenylation/arylation of arenes has been developed, providing access to a wide range of enantiomerically enriched unreacted aryl-pyridyl-sulfoximine precursors and C(aryl)-H alkenylation/arylation products in good yields with high enantioselectivity. The coordination of the directing group, ligand effect, geometry constraints, and the transient six-membered concerted-metalation-deprotonation species dictate the stereoselectivity, which is validated by DFT studies.