Chapter 7 - Copper catalysis for the synthesis of quinolines and isoquinolines

Abstract

The quinoline scaffold is present in numerous alkaloids and bioactive compounds often associated with remarkable biological properties. Common approaches to assemble the quinoline ring system include the Skraup, Friedländer, Combes, Doebner-von Miller, and Conrad-Limpach reactions, but the utility of these synthesis methods is limited by their harsh acidic and extreme reaction conditions. Similarly, the isoquinoline moiety is a key structural feature of many natural products and pharmacologically relevant compounds. Owing to the significance of these scaffolds in drug discovery and medicinal chemistry, the development of new methodologies for the synthesis of quinoline and isoquinoline remains a very active field of research. Copper-catalyzed annulation reactions have emerged as powerful and promising approaches for the synthesis of diverse nitrogen heterocycles, including quinolines and isoquinolines. Moreover, copper salts, being economical and having low toxicity, have received significant attention as an inexpensive alternative to precious transition-metal catalysts. Consequently, this chapter summarizes the copper-catalyzed synthetic methodologies to access quinolines and isoquinolines.