Catalyst-free reactions developed during the last decade and the latest developments in this emerging field are summarized with a focus on catalyst-free reactions in-water and on-water. Various named reactions, multi-component reactions and the synthesis of heterocyclic compounds are discussed including the use of various energy input systems such as microwave- and ultrasound irradiation, among others. Organic chemists and the practitioners of this art both in academia and industry hopefully will continue to design benign methodologies for organic synthesis in aqueous media under catalyst-free conditions by using alternative energy inputs based on fundamental principles.

Benign by design: catalyst-free in-water, on-water green chemical methodologies in organic synthesis

Direct and rapid heating by microwave irradiation in combination with sealed vessel processing in many cases enables reactions to be carried out in a fraction of the time generally required using conventional conditions. This makes microwave chemistry an ideal tool for rapid reaction scouting and optimization of conditions, allowing very rapid progress through hypotheses–experiment–results iterations. The speed at which multiple variations of reaction conditions can be performed allows a morning discussion of “What should we try?” to become an after-lunch discussion of “What were the results” Not surprisingly, therefore, many scientists both in academia and industry have turned to microwave synthesis as a front-line methodology for their projects. In this review, more than 220 published examples of microwave-assisted synthetic organic transformations from the 2004 to 2008 literature are discussed. An additional ca. 500 reaction schemes are presented in the Electronic Supplementary Material, providing the reader with an overall number of ca. 930 references in this fast-moving and exciting field.

Controlled microwave heating in modern organic synthesis: highlights from the 2004–2008 literature

Metal-Free Multicomponent Syntheses of Pyridines

Multicomponent domino reactions (MDRs) serve as a rapid and efficient tool for the synthesis of versatile heterocycles, particularly those containing structural diversity and complexity, by a one-pot operation. These reactions can dramatically reduce the generation of chemical wastes, costs of starting materials, and the use of energy and manpower. Moreover, the reaction period can be substantially shortened. This Review covers recent advances on multicomponent domino reactions for the construction of five-, six-, and seven-membered heterocyclic skeletons and their multicyclic derivatives.

Multicomponent Reactions for the Synthesis of Heterocycles

Deep eutectic solvents (DESs) as eco-friendly and sustainable solvent/catalyst systems in organic transformations

A series of unusual fused heterocyclic compound derivatives, consisting of a pyridine and a imidazole or pyrimidine core, with a bridgehead nitrogen, were successfully synthesized by a microwave-assisted, three-component domino reaction of aldehydes, enaminones, and malononnitrile. In this one-pot reaction, up to five new bonds were formed accompanied by generating the lactam group. This method has the advantages of short synthetic route, operational simplicity, increased safety for small-scale high-speed synthesis, and minimal environment impact.

Microwave-assisted combinatorial synthesis of polysubstituent imidazo[1,2-a]quinoline, pyrimido[1,2-a]quinoline and quinolino[1,2-a]quinazoline derivatives.

Microwave‐assisted efficient synthesis of benzo[4,5]imidazo[1,2‐a]‐pyrimidine derivatives in water under catalyst‐free conditions

A novel three-component reaction for the synthesis of new 4-azafluorenone derivatives

A facile and selective synthesis of poly-substituted pyrido[2,3- D]pyrimidines is accomplished via microwave-assisted multicomponent reactions controlled by the nature of solvent. In addition, a possible mechanism accounting for the reaction is proposed.

Qingqing Shao

Papers

Microwave-assisted combinatorial synthesis of polysubstituent imidazo[1,2-a]quinoline, pyrimido[1,2-a]quinoline and quinolino[1,2-a]quinazoline derivatives.

Microwave‐assisted efficient synthesis of benzo[4,5]imidazo[1,2‐a]‐pyrimidine derivatives in water under catalyst‐free conditions

A novel three-component reaction for the synthesis of new 4-azafluorenone derivatives

An Efficient Chemoselective Synthesis of Pyrido[2,3-d]pyrimidine Derivatives under Microwave Irradiation

An efficient synthesis of pyrido[2,3-d]pyrimidine derivatives and related compounds under ultrasound irradiation without catalyst.