A novel synthesis of substituted quinolines using ring-closing metathesis (RCM): its application to the synthesis of key intermediates for anti-malarial agents

Abstract

A method for synthesizing substituted quinolines using ruthenium-catalyzed ring-closing metathesis as a key step has been developed. Substituted 1,2-dihydroquinolines, 4-silyloxy-1,2-dihydroquinoline and 4-methoxy-1,2-dihydroquinoline, were successfully synthesized in excellent yields via ene–ene metathesis and silyl or alkyl enol ether–ene metathesis, respectively. The synthetic intermediates of the antimalarial agents quinine, chloroquine, and PPMP–quinine hybrid were efficiently synthesized by this methodology.