Organocatalytic synthesis of α-quaternary amino acid derivatives via aza-Friedel–Crafts alkylation of indoles with simple α-amidoacrylates

• DOI: 10.1016/j.tet.2011.08.039
• Publication Date: 2011-08-23T00:42:57Z
• Authors: Marika Righi; Francesca Bartoccini; Simone Lucarini; Giovanni Piersanti
• Keywords: Friedel–Crafts reaction; Pyrrole; Phosphoric acid

Abstract The first (organo)catalytic method for regio- and chemoselective aza-Friedel–Crafts (FC) alkylation of indoles and pyrroles with commercially available methyl α-acetamidoacrylates has been discovered. It minimizes/eliminates common competing reactions that occur due to the high and multiatom-nucleophilic character of indole and pyrrole. Diverse quaternary α-amino acids were successfully prepared in good yield and high selectivity using low catalyst loading. The enantioselective variant using BINOL-derived phosphoric acids was also explored with indole providing the desired F–C alkylation product with moderate enantioselectivities.