Expedient Modular Assembling of Chiral η 6 -Benzene Ligands: Empowering Ruthenium-Catalyzed Asymmetric C–H Activation

Transition metal-catalyzed asymmetric C–H activation is an atom- and step-economical route to chiral molecules, yet the development of cost-effective ruthenium catalysts lags far behind that of palladium and rhodium. Notably, chiral η 6 -benzene ruthenium catalysts (BenRu) provide an effective tool to tackle the ruthenium-catalyzed asymmetric C–H activation. However, the existing catalysts suffer from tedious synthesis and limited tunability. To address this problem, we report herein a modular assembly strategy that enables a concise two-step synthesis of highly tunable chiral Ben ligands from readily available chemicals. The key feature is to use 1,2-dibromo-4,5-difluorobenzene as the versatile linchpin, allowing for flexible bidirectional functionalization of the benzene core for metal complexation. Gladly, the resulting BenRu catalysts exhibit superior performance in two asymmetric C–H activation reactions, including the reaction of N -methoxybenzamides with alkenes to give various chiral dihydroisoquinolones (38 examples, up to 99% yield, up to 97% ee), and the reaction of indoles with alkenes to afford a range of chiral indoles bearing both central and axial chirality (37 examples, up to 99% yield, up to >99% ee).