A three-component domino protocol for the facile synthesis of highly functionalized tetrahydroisoquinolines by creation of their benzene ring

A simple and efficient one-pot synthesis of novel 6-amino-8-aryl-2-methyl/benzyl-7-nitro-1,2,3,4-tetrahydroisoquinoline-5-carbonitriles from the reaction of 1-methyl/benzylpiperidin-4-one with β-nitrostyrenes and malononitrile in the presence of morpholine is described. This transformation proceeds through the creation of three CC bonds, leading to a new benzene ring, and presumably occurs via a domino sequence involving Knoevenagel, Michael, Thorpe–Ziegler, and dehydrogenation reactions.

The three-component reaction between 4-piperidones, nitrostyrenes, and malononitrile in the presence of morpholine afforded good yields of pentasubstituted tetrahydroisoquinolines in a single synthetic operation.Figure optionsDownload as PowerPoint slide