Aluminum Cation-Catalyzed C2–H Activation and Enantioselective Michael Addition of Indoles

In this work, we demonstrate that prolinol-supported tetracoordinate aluminum cations can activate the C2–H bond of 3-substituted indoles and facilitate an enantioselective Michael addition to enones, furnishing alkylated indoles with good to excellent enantioselectivity.

In contrast to transition-metal-catalyzed systems, the use of specially designed chelating enone substrates is no longer essential for the aluminum cation catalyst to induce stereoselectivity. Mechanistic studies suggest that the ligand-assisted concerted metalation-deprotonation of the C2–H bond is the rate-determining step (RDS). Stoichiometric NMR experiments provide direct evidence for an on-cycle aluminum complex, further supporting the proposed C2–H activation pathway.