Expedient Modular Assembling of Chiral η⁶-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 η⁶-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).