One-Pot Phosphine-Catalyzed Syntheses of Quinolines

Abstract

In this study we developed an efficient one-pot procedure for the preparation of 3-substituted and 3,4-disubstituted quinolines from stable starting materials (activated acetylenes reacting with <i>o</i>-tosylamidobenzaldehydes and <i>o</i>-tosylamidophenones, respectively) under mild conditions. The reaction appears to operate under a general base catalysis mechanism, instigated by the β-phosphonium enoate α-vinyl anion generated in situ through nucleophilic addition of PPh₃ to the activated alkyne. Michael addition of the deprotonated tosylamides to the activated alkynes and subsequent rapid aldol cyclization led to the formation of labile <i>N</i>-tosyldihydroquinoline intermediates. Driven by aromatization, detosylation of the dihydroquinoline intermediates occurred readily in the presence of dilute aqueous HCl to give the final quinoline products