Chiral Heterogeneous Scandium Lewis Acid Catalysts for Continuous-Flow Enantioselective Friedel-Crafts Carbon-Carbon Bond-Forming Reactions.

While continuous-flow reactions with chiral heterogeneous catalysts provide a highly efficient method to synthesize optically active compounds, chiral heterogeneous Lewis acid catalysis has been less extensively explored. We have developed the first example of chiral heterogeneous Sc catalysts, which demonstrated excellent activity and selectivity for continuous-flow enantioselective Friedel-Crafts reactions of isatins with indoles. Noncovalent interactions between chiral Sc complexes and heteropoly acid-anchored amine-functionalized SiO2 as support were utilized for the synthesis. The heteropoly acid was found to be crucial for the preparation, activity, and selectivity of the catalysts. The chiral ligand could be easily tuned without chemical modification and the continuous-flow synthesis of a biologically active compound was achieved.