Mo‐Catalyzed Synthesis of 3‐Substituted Quinolines From Nitroarenes and Aldehydes

This work reports a one‐pot Friedländer‐type protocol based on the dioxomolybdenum(VI)‐catalyzed reduction of readily available o ‐nitrobenzaldehydes with pinacol in the presence of external aliphatic aldehydes or acetals and p ‐toluenesulfonic acid as an additive. The tandem process proceeds through Mo‐catalyzed reduction to generate o ‐aminobenzaldehydes in situ, which subsequently undergo Friedländer annulation with the external carbonyl partner, thereby avoiding the isolation of unstable intermediates. The use of an excess of aldehyde suppresses competitive reactions involving acetone generated during the reduction. Under the optimized conditions, a broad range of functionalized o ‐nitrobenzaldehydes and aliphatic aldehydes afforded 3‐substituted quinolines with broad functional‐group tolerance. The use of acetals further expanded the scope, providing improved yields in several cases and enabling the synthesis of valuable 2,4‐unsubstituted quinoline‐3‐carboxylates, as well as 3‐acetyl‐, 3‐cyano‐, 3‐(2‐thienyl)‐, and nitrogen‐functionalized quinolines. The methodology is readily scalable and provides a convenient, chemoselective, and sustainable approach to structurally diverse quinoline scaffolds from inexpensive nitroarene precursors.