Enantioselective Continuous-Flow Production of 3-Indolylmethanamines Mediated by an Immobilized Phosphoric Acid Catalyst

• Published in: Chemistry : a European journal Vol. 20; no. 8; pp. 2367 - 2372
• Main Authors: Osorio-Planes, Laura, Rodriguez-Escrich, Carles, Pericas, Miquel A
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 17.02.2014; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: asymmetric catalysis; Catalysts; Chemistry; Chemistry, Multidisciplinary; chiral phosphoric acids; flow processes; Friedel-Crafts reaction; Friedel-Crafts reactions; immobilization; Indoles; Libraries; Phosphoric acid; Physical Sciences; Productivity; Pumping; Recycling; Science & Technology; Friedel-Crafts reactions; ORGANIC-SYNTHESIS; flow processes; immobilization; asymmetric catalysis; SILYL ETHERS; MICHAEL ADDITION; BOND DONORS; SOLID-SUPPORTED ORGANOCATALYST; chiral phosphoric acids; CHIRAL BRONSTED ACID; N-SULFONYL ALDIMINES; ASYMMETRIC ORGANOCATALYSIS; FRIEDEL-CRAFTS REACTION; MULTISTEP SYNTHESIS
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201303860

A polystyrene‐supported 1,1’‐bi‐2‐naphthol derived phosphoric acid has been synthesized and applied in the enantioselective Friedel–Crafts reaction of indoles and sulfonylimines. The immobilized catalyst was highly active and selective, and gave rise to a broad range of 3‐indolylmethanamines (19 examples) in high yields and excellent enantioselectivities (up to 98 % enantiomeric excess) after short reaction times under very convenient reaction conditions (RT in dichloromethane). Moreover, repeated recycling (14 cycles) was possible with no substantial loss in catalytic performance and the system could be adapted to a continuous‐flow operation (6 h). Finally, the applicability of the system was further confirmed by rapid access to a library of compounds with three points of diversity in a single continuous‐flow experiment that involved sequential pumping of different substrate combinations. A solid‐supported phosphoric acid has been prepared that shows excellent catalytic activity in the Friedel–Crafts reaction between indoles and sulfonylimines (see figure). Diverse libraries of indoles can be sequentially prepared by a continuous‐flow process with high productivities.