Regio- and Enantioselective Synthesis of Diarylindolylmethanes via Lewis Acid Catalyzed Friedel–Crafts Alkylation of Indoles with In Situ Generated o-Quinone Methides

We report an efficient Lewis acid catalyzed enantioselective synthesis of diarylindolylmethanes via in situ generated ortho -quinone methides. The protocol enables selective Friedel–Crafts alkylation at indole C3, and by blocking this site, extends selectively to C2 position. Mechanistic studies, including quantum calculations and Hammett analysis, reveal selectivity arising from β-methide steric hindrance and catalyst–substrate π–π interactions. This method provides broad substrate scope, high yields, excellent functional group tolerance, and access to complex indole derivatives.