Palladium in Quinoline Synthesis

Abstract

This chapter highlights the important preparative methods of the quinoline substrates, both as electrophiles and nucleophiles, and their synthetic utilities in palladium-mediated reactions. The unique characteristics of quinoline chemistry stem from the stereo-electronic effects that the nitrogen atom has exerted on the quinoline molecule. A popular method to prepare haloquinolines is the halogenation of quinolones using oxyphosphorus halides, most notably POCl3. Among the cross-coupling reactions with organometallic reagents that involve a quinoline fragment, the Suzuki and Stille coupling reactions are more prevalent, whereas there have been limited precedents for the Negishi and Hiyama reactions. Sonagashira reaction represents a palladium-catalyzed coupling between a nucleophile (e.g. aryl- and vinyl halides) and a terminal alkyne in the presence of an aliphatic amine and catalytic palladium and CuI or CuBr. Palladium-mediated reactions, especially cross-coupling reactions, have found many applications in quinoline synthesis. With the advent of the palladium chemistry and more commercially available organometallic substrates, more palladium-mediated quinoline syntheses are to be added to the repertoire of quinoline chemistry.