The Chemistry of Isocyanides, their MultiComponent Reactions and their Libraries

Abstract

The first century of isocyanide chemistry, which was then still a rather empty part of Organic Chemistry, began in 1859. In 1958 isocyanides became generally available by dehydration the formylamines. One year later the four component reaction of isocyanides (U-4CR) was introduced. This one-pot reaction is accomplished just by mixing amines, carbonyl compounds, suitable acids and isocyanides. Most chemical reactions have their own ”scope and limitation”, whereas the U-4CR can convert almost all combinations of educts into their products. Until 1995 this chemistry was moderately used, but since then a new era of the U-4CR and its unions with further reactions have become increasingly popular, particularly as libraries. In industry this chemistry became one of its most often used methods of finding new desirable products. In contrast to most other areas of chemistry, isocyanide chemistry is not yet exhausted and still much progress can be expected there.

Synthesis of cyclic analogues of hexamethylenebis(3-pyridine)amide (HMBPA) in a one-pot process

“…15a, 15c Efficiency and atom economy are the potential characteristics of the MCR's, especially the Ugi three-and four-component reaction (U−3R, and U−4CR). 18 In this context, the isocyanidebased multicomponent reactions (I−MCR) become a very powerful synthetic tool, to prepare molecular frameworks suitable for further elaborations, 17,19 especially when is sequentially combined with a post-condensation processes to increase the molecular complexity. 20,21 As part of our research program directed to synthesizing drug-like heterocycles, we are interested in the development of a novel multicomponent synthesis of polysubstituted heterocycles which contain the pirrolopyridine skeleton.…”

Four-Component Preparation of Disubstituted 1,3,4-Oxadiazoles from (N-isocyanimino)triphenylphosphorane, Phenylacetylenecarboxylic Acid, Biacetyl and Primary Amines

“…The isocyanide-based MCR are very important in this area. [2][3][4] Among the known multicomponent reactions to date, the most valuable reactions are those based on isocyanides. Isocyanide-based multicomponent reactions (abbreviated to IMCRs by Ugi and Dömling) by virtue of their synthetic potential, their inherent atom efficiency, convergent nature, ease of implementation, and the generation of molecular diversity, have attracted considerable attention because of the advantages that they offer to the field of combinatorial chemistry.…”

Preparation of Fully Substituted 1,3,4-Oxadiazole Derivatives from N-Isocyaniminotriphenylphosphorane, (E)-Cinnamic Acids, Chloroacetone and Primary Amines

“…Isocyanide-based multicomponent reactions (abbreviated to IMCRs by Ugi and Dömling) by virtue of their synthetic potential, their inherent atom efficiency, convergent nature, ease of implementation, and the generation of molecular diversity, have attracted much attention because of the advantages that they offer to the field of combinatorial chemistry. 6 The intramolecular version of the aza-Wittig-type reaction has attracted considerable attention recently because of its high potential for the synthesis of a wide variety of nitrogen heterocycles, which can be attributed, in good measure, to the rapid progress in the preparation of functionalized iminophosphoranes. Several interesting hetero-cyclization reactions involving iminophosphoranes have been reviewed.…”