Ruthenium-Catalyzed Chiral Sulfoximine Directed One-pot Asymmetric Multiple C-H Functionalizations

Unraveled herein is a Ru(II)-catalyzed two-fold C-H functionalization of arenes that combines an asymmetric intramolecular hydroarylation and a functionalization/annulation using alkynes, isocyanates, or alkenes. This process constructs complex heterocycles such as dihydrobenzofuran- or indoline-fused isoquinolinones or isoindolidinones having a tertiary or a qua-ternary stereocenter, with good yields and enantioselectivities (up to 97:3 er). The enantiopure rigid aryl-methyl-sulfoximine directing groups provides high asymmetric induction. In particular, the chiral sulfoxide (~99% ee) precursor used in the synthesis of the enantiopure sulfoximines is spontaneously eliminated during the reaction. It can be recovered without loss of enantiopurity and reused. Finally, density functional theory calculations show that the interaction between the p-cymene ligand attached to the Ru-species and the enantiopure sulfoximine moiety controls the facial selectivity in the migratory CH insertion of the olefin.