Chemoenzymatic Relay Synthesis of Quinolines: Laccase/TEMPO/ <scp>D</scp> -Glucose-Based Ionic Salt/atm O ₂ -Catalyzed Chemoselective Oxidation of 2-Aminobenzyl Alcohols

Laccases are widely applied as promising high-value enzymes for oxidation reactions. To provide more insight into this, we have developed a chemoenzymatic one-pot relay synthesis of quinolines incorporating a laccase/TEMPO system with a d-glucose-based ionic salt (GIS I–) run under air at room temperature. The developed relay strategy involves a two-step process where laccase/TEMPO performs the oxidation of o-aminobenzyl alcohols, forming an o-aminobenzaldehyde intermediate, which is further annulated by coupling with active methylene groups in the presence of GIS I–. This methodology allows a straightforward synthesis of 26 aldehydes up to 88% yield and 30 quinolines up to 81% yield. To provide more insight into the developed synergistic system, the stability of laccase vs GIS I– was studied, and the results indicated that the developed GIS I– did not degrade the protein structure and stabilized the enzyme. Environmental acceptability metrics were calculated for the developed process with a commendable E-factor of 2.02 and an atom economy of 89.41%. The developed catalytic system was successfully employed for the gram-scale synthesis of the antibacterial agent indenoquinolinone in good yield, which can help in developing active pharmaceutical ingredients (APIs).