Cobalt-Catalyzed Enantioselective C-H Annulation with Alkenes

Herein, we disclose an efficient cobalt-catalyzed enantioselective C-H activation and annulation of benzamides with alkenes. This transformation is facilitated via the commercially available cobalt(II) catalyst in the presence of the easily prepared chiral salicyl-oxazoline (Salox) ligand, which provides facile access to (R) or (S) enantiomers of chiral dihydroisoquinolone derivatives. It is noticeable that the reaction proceeded efficiently within the extremely short reaction time from 10 to 30 min under mild conditions. A broad range of benzamides and alkenes that bear various functional substituents have been shown to have good compatibility to deliver targeted products with high yields and enantioselectivities (51 examples, up to 98% yield and 99% ee). The gram scale experiment and the removal of the directing group further demonstrate the practicability of this protocol to potential industrial applications. Density functional theory calculations elucidate the reaction mechanism, and the spin-state change in the olefin insertion step accelerates the subsequent C-N reductive elimination, which is identified as the stereo-determining step. The AIM analysis indicates that the pi pi and C-H pi interactions are vital for controlling and switching the stereoselectivity.