Indirect Friedländer Reaction: From Transfer Hydrogenation to Acceptorless Dehydrogenative Coupling and Metal‐Free Approaches

The Friedländer quinoline synthesis represents a fundamental method for the construction of quinoline derivatives, a versatile class of heterocyclic compounds widely prevalent in pharmaceuticals and materials science. This synthesis traditionally involves the condensation of 2-aminoaryl ketones with carbonyl compounds, typically ketones or aldehydes, in the presence of an acid or base under reflux conditions. However, recent advancements have highlighted indirect approaches (starting from 2-aminobenzyl alcohol) to achieve the same quinoline framework, offering distinct advantages in selectivity, substrate scope, and functional group tolerance. We have reviewed various indirect methods employed in the Friedländer quinoline synthesis, encompassing strategies such as oxidative processes, metal-catalyzed reactions, and innovative cascade reactions. All the reported reactions are discussed in detail by highlighting the advantages and the shortcomings. Moreover, the generality is discussed for each methodology, with examples and mechanisms that are discussed to elucidate the synthetic pathways and the strategic advantages of these indirect methodologies. The synthesis of quinoline derivatives through indirect approaches not only enhances the synthetic flexibility and efficiency but also opens avenues for the development of novel bioactive compounds and materials with tailored properties.