Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines - a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

Melzer, Benedikt C.; Felber, Jan G. und Bracher, Franz (2018): Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines - a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline. In: Beilstein Journal of Organic Chemistry, Bd. 14: S. 130-134

Abstract

Highly-substituted isoquinolines are important scaffolds in syntheses of natural products and in drug development and hence, effective synthetic approaches are required. Here we present a novel method for the introduction of a methyl group at C1 of isoquinolines. This is exemplified by a new total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline. Direct metalation of 7-benzyloxy-6-methoxyisoquinoline with Knochel-Hauser base, followed by cuprate-mediated methylation gives the target alkaloid directly, but separation from the educt is cumbersome. Quenching the metalated intermediate with Eschenmoser's reagent gives an easy to clean tertiary benzylamine, which, after quaternization with iodomethane, is easily converted into the desired 1-methylisoquinoline by hydrogenolysis of both the benzylamine and benzyl ether groups.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 1860-5397
• Sprache: Englisch