Enhanced Efficiency of Thiourea Catalysts by External Bronsted Acids in the Friedel-Crafts Alkylation of Indoles

A novel study on the influence of external Bronsted acids on thiourea catalysts in the asymmetric Friedel-Crafts alkylation of indoles with nitroalkenes is reported. The final 3-substituted indole derivatives were synthesized with better results because of cooperative effects between the chiral thiourea and a Bronsted acid additive (1a center dot HA). The effects of diverse catalysts, different acid additives, solvents, and temperatures in the reaction were also explored. The high reactivity and selectivity of the reaction is presumptively attributed to an appropriate assembly between the Bronsted acid and the thiourea structure, affording a more acidic and rigid catalytic complex.