Synthesis of 4-Cyano Pyrroles via Mild Knorr Reactions with β-Ketonitriles

Mild methods for conducting Knorr chemistry with β-ketonitriles were developed. This enabled the preparation of 4-cyano-penta-substituted pyrroles and gave access to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor potentiators for biological evaluation. In addition, a series of alkyl and aryl β-ketonitriles were employed in Knorr cyclizations to probe steric tolerance and the possibility of direct introduction of aromatic moieties via Knorr chemistry.