3,4-Dihydroquinoxalin-2-one privileged motif: A journey from classical chiral tools based synthesis to modern catalytic enantioselective strategies

Abstract

Optically pure 3,4-dihydroquinoxalin-2-ones, being members of the privileged quinoxaline family, received significant interest in organic synthesis, more particularly in medicinal chemistry, proving also to be useful building blocks for facile entry to a relevant bioactive pharmacophore, namely tetrahydroquinoxalines. The first asymmetric approaches to 3,4-dihydroquinoxalin-2-ones relied on classical use of chiral pool available reagents and auxiliares, such as α-amino acids and mandelates/tartaric acid derivatives, respectively. Over the years, more general and appealing enantioselective catalytic routes have been developed, mainly concerned with metal- and organocatalyzed reduction of quinoxalinones. Additionally, different organocatalytic cyclization strategies, including sustainable one-pot processes, have been added to the synthetic toolbox. This perspective aims to showcase the state of art of asymmetric approaches developed to prepare 3,4-dihydroquinoxalin-2-ones with a focus on catalytic routes, highlighting challenges and opportunities for future developments.

Keywords

• Nitrogen-based heterocycles
• Asymmetric catalysis
• Metal catalysis
• Organocatalysis
• Bioactive compounds