The quinoline ring system is one of the most ubiquitous heterocycles in the fields of medicinal and industrial chemistry, forming the scaffold for compounds of great significance. These include anti-inflammatory and antitumor agents, the antimalarial drugs quinine and chloroquine, and organic light-emitting diodes. Quinolines were first synthesized in 1879, and since then a multitude of synthetic routes have been developed. Many of these methods, such as the Skraup, Doebner–Von Miller, and Friedlander quinoline syntheses, are well-known but suffer from inefficiency, harsh reaction conditions, and toxic reagents. This review focuses on recent transition metal-free processes toward these important heterocycles, including both novel routes and modifications to established methods. For example, variations on the Skraup method include microwave irradiation, ionic liquid media, and novel annulation partners, all of which have shown increased reaction efficiency and improved yield of the heteroring-unsubstituted quinoline products. Similarly, modifications to other synthetic routes have been implemented, with the quinoline products displaying a wide variety of substitution patterns.

Recent Advances in Metal-Free Quinoline Synthesis.

This study reports a nickel-catalyzed sustainable synthesis of polysubstituted quinolines from α-2-aminoaryl alcohols by a sequential dehydrogenation and condensation process that offers the advantages of a low catalyst loading and wide substrate scope. In contrast to earlier reported methods, this strategy allows the use of both primary as well as secondary α-2-aminoaryl alcohols in combination with either ketones or secondary alcohols for desired product formation. Using this methodology, 30 substituted quinoline derivatives were synthesized with up to 93% isolated yields.

Synthesis of Polysubstituted Quinolines from α-2-Aminoaryl Alcohols Via Nickel-catalyzed Dehydrogenative Coupling

Over the past few years, the development of oxidative methodologies towards efficient and selective direct Csp3–H bond functionalization processes has attracted tremendous attention from synthetic chemists. However, only a little attention has been given to the key role of the nature of the oxidant. This review aims at providing a brief summary of the recent advances in mild and more benign oxidative Csp3–H bond functionalization reactions, which are classified according to the type of oxidation system employed.

Recent progress in mild Csp3–H bond dehydrogenative or (mono-) oxidative functionalization

A visible-light induced photocatalytic aerobic oxidative dehydrogenative coupling/aromatization tandem reaction of glycine esters with unactivated alkenes has been accomplished. This visible light-driven protocol has been successfully applied to a broad scope of glycine esters and simple alkenes, giving rise to diverse substituted quinoline derivatives in 18–84% yield under mild (at room temperature under air atmosphere) and operationally simple reaction conditions.

Visible-Light-Induced Photocatalytic Aerobic Oxidative Csp3-H Functionalization of Glycine Derivatives: Synthesis of Substituted Quinolines.

A highly efficient I2-catalyzed Povarov-type reaction of methyl ketones, arylamines, and α-ketoesters is developed. This reaction utilizes a catalytic amount of HI coproduct as a promoter for the synthesis of substituted quinolones. This simple procedure represents an interesting new form of reactivity for the Povarov reaction with good functional group compatibility.

Coproduct Promoted Povarov Reaction: Synthesis of Substituted Quinolines from Methyl Ketones, Arylamines, and α-Ketoesters.

Oxidative Povarov Reaction via sp3 C–H Oxidation of N-Benzylanilines Induced by Catalytic Radical Cation Salt: Synthesis of 2,4-Diarylquinoline Derivatives

An Unexpected Construction of 2‐Arylquinolines from N‐Cinnamylanilines through sp3 C ? H Aerobic Oxidation Induced by a Catalytic Radical Cation Salt

The reaction tolerates differently substituted N-benzylic aniline derivatives and styrene derivatives, but is not applicable to α-methylstyrene.

Oxidative Povarov Reaction via sp3 C—H Oxidation of N-Benzylanilines Induced by Catalytic Radical Cation Salt: Synthesis of 2,4-Diarylquinoline Derivatives.

Fang Liu

Papers

Oxidative Povarov Reaction via sp3 C–H Oxidation of N-Benzylanilines Induced by Catalytic Radical Cation Salt: Synthesis of 2,4-Diarylquinoline Derivatives

An Unexpected Construction of 2‐Arylquinolines from N‐Cinnamylanilines through sp3 C ? H Aerobic Oxidation Induced by a Catalytic Radical Cation Salt

Oxidative Povarov Reaction via sp3 C—H Oxidation of N-Benzylanilines Induced by Catalytic Radical Cation Salt: Synthesis of 2,4-Diarylquinoline Derivatives.

An Unexpected Construction of 2‐Arylquinolines from N‐Cinnamylanilines Through (sp3) C—H Aerobic Oxidation Induced by a Catalytic Radical Cation Salt.