Since 1995 the new chemistry of multicomponent reactions and their libraries, including their heterocyclic chemistry

Abstract

A growing number of products, including many heterocycles, can be prepared by the one‐pot MultiComponent Reactions (MCRs) just by mixing three or more educts, and in many cases practically quantitative yields of pure products can be obtained. The 3CR by α‐aminoalkylations of nucleophiles began in the middle of the last century, and the syntheses of heterocycles by MCRs of three and four components were introduced by Hantzsch in the 1880s. The MCRs of the isocyanides with four and more educts began in 1959, and their compound libraries were mentioned since 1961. However, only since 1995 the often automated one‐pot chemistry of the MCR of the isocyanides is used extensively. If a chemical compound can be prepared by a sequence of two component reactions or a suitable MCR, the latter is always a superior procedure. The U‐4CR can be combined with other chemical reactions and MCRs as one‐pot reactions of n > 4 components, and such unions even have a much greater variety of structurally and stereochemically different products. The educts and products of Ugi‐type MCRs are more variable than those of all previous chemical reactions and other MCRs. Due to the progress in screening and automation processes in the last few years, many new compounds have been formed and investigated more rapidly than ever before. The search for new desirable products can be accomplished more than 10,000 times faster than by the older conventional methods. The now popular chemistry of the MCRs of the isocyanides fills the since long empty part of organic chemistry.

Sulfamic Acid Catalyzed Five Component Reaction for Efficient and One-Pot Synthesis of Densely Functionalized Tetrahydropyridine Scaffold

“…In the midst of prominent efforts to develop new MCRs, 3 Bonfield et al 4 recently reported a resourceful method for the preparation of the isoindoline framework via a six component, tandem double A3-coupling and [2+2+2] cycloaddition reaction. In addition, one-pot, multi-component reactions continue to be of attention in the synthesis of a range of composites containing particularly nitrogen atom 5,6 due to the quick assembly of substituted systems lacking isolation of unstable intermediates. The significance of these one-pot reactions in such syntheses has been well established in the Mannich, Ugi,5 Biginelli, 6 aza-Baylise Hillman 7 reactions, and in Hantzsch dihydropyridine synthesis.…”

“…In addition, one-pot, multi-component reactions continue to be of attention in the synthesis of a range of composites containing particularly nitrogen atom 5,6 due to the quick assembly of substituted systems lacking isolation of unstable intermediates. The significance of these one-pot reactions in such syntheses has been well established in the Mannich, Ugi,5 Biginelli, 6 aza-Baylise Hillman 7 reactions, and in Hantzsch dihydropyridine synthesis. 8 Furthermore, the Orru group 9 developed a one-pot reaction of up to eight components that involves nine new bond formations and eleven faces of multiplicity.…”

Nano-TiO₂ as a novel and efficient catalyst for the synthesis of pyridine dicarbonitriles

“…In recent years, multicomponent reactions (MCRs) have become important tools in modern preparative synthetic chemistry because these reactions increase the efficiency by combining several operational steps without any isolation of intermediates or change of the conditions [1,2] and MCRs have recently emerged as valuable tools in the preparation of structurally diverse chemical libraries of drug-like heterocyclic compounds [3][4][5].…”

A novel one-pot synthesis of spirooxindole derivatives catalyzed by nano ZnO

“…There has been tremendous development in three or four component reaction specially the Bignelli [14], Passerini [15], Ugi [16] and Mannich [17] reactions, which have further led to renaissance of MCRs. MCRs have emerged as valuable tools for the preparation of structurally diverse chemical libraries of drug-like heterocyclic compounds [18][19][20]. Nevertheless, great efforts have been and still are being made to find and develop new MCRs.…”