Synthesis of enantiopure (S)-indolylglycine by organocatalyzed Friedel-Crafts alkylation of indole

Tritylsulfenyl- and 2-nitrophenylsulfenyl-substituted glyoxyl imines were used in chiral phosphoric acid catalyzed Friedel-Crafts (FC) reactions with indole. High yields and ee values ranging from 86% for Nps-protected (S)-indolylglycine to 88% for Trs-protected (R)-indolylglycine were obtained. On a preparative scale, a FC product with 99.5% ee and 71% yield was readily obtained by crystallization of the reaction mixture. Removal of the Nps protecting group under mild acidic conditions did not affect the stereochemical integrity of the alpha-carbon atom and (S)-indolylglycine was afforded in >= 98% ee.