Multicomponent reactions (MCRs) are fundamentally different from two-component reactions in several aspects. Among the MCRs, those with isocyanides have developed into popular organic-chemical reactions in the pharmaceutical industry for the preparation of compound libraries of low-molecular druglike compounds. With a small set of starting materials, very large libraries can be built up within a short time, which can then be used for research on medicinal substances. Due to the intensive research of the last few years, many new backbone types have become accessible. MCRs are also increasingly being employed in the total synthesis of natural products. MCRs and especially MCRs with isocyanides offer many opportunities to attain new reactions and basic structures. However, this requires that the chemist learns the “language” of MCRs, something that this review wishes to stimulate.

Multicomponent Reactions with Isocyanides.

Synthesis and biological activity of pyrrole, pyrroline and pyrrolidine derivatives with two aryl groups on adjacent positions

The sphingolipid bases, D-erythro- and D-threo-sphingosines, are the target molecules that have been synthesized to demonstrate the efficiency of a new methodology to control both absolute and relative configurations in acyclic systems. Tubulysins are compounds of extraordinary potency, rapidly degrading the tubulin cytoskeleton, with tubulysin D being the most active tubulin-modifier known so far. Among other isonitriles, isocyanoacetate derivatives occupy an important place in the field of synthetic application and reaction diversity, which makes them strongly attractive objects for investigation. The unique multifunctional nature of isocyanoacetic acid derivatives opens up a range of exciting reactions, especially tandem/cascade processes for the synthesis of complex cyclic and macrocyclic systems. Multicomponent chemistry of isocyanoacetates is also a powerful instrument to access different classes of biochemically relevant compounds such as peptides, peptide molecules, and nitrogen heterocycles.

Isocyanoacetate derivatives: synthesis, reactivity, and application.

Multikomponentenreaktionen (MCRs) unterscheiden sich in mehreren Aspekten grundlegend von Zweikomponentenreaktionen. Unter den MCRs haben sich solche mit Isocyaniden in der pharmazeutischen Industrie zu popularen organisch-chemischen Reaktionen zur Herstellung von Substanzbibliotheken aus niedermolekularen wirkstoffartigen Verbindungen entwickelt. Mit einem kleinen Set von Ausgangsverbindungen konnen in kurzer Zeit sehr grose Bibliotheken aufgebaut und fur Fragestellungen in der Wirkstoff-Forschung verwendet werden. Aufgrund der intensiven Forschung der letzten Jahre sind viele neue Strukturtypen zuganglich geworden. Vermehrt werden MCRs auch in der Totalsynthese von Naturstoffen eingesetzt. MCRs und insbesondere MCRs mit Isocyaniden bieten viele Moglichkeiten, zu neuen Reaktionen und Grundgerusten zu gelangen. Dies setzt jedoch voraus, dass der Chemiker die „Sprache“ der MCRs lernt, wozu dieser Ubersichtsartikel anregen soll.

Multikomponentenreaktionen mit Isocyaniden

Isocyanides have long proved themselves to be irreplaceable building blocks in modern organic chemistry. The unique features of the isocyano group make isocyanides particularly useful for the synthesis of a number of important classes of nitrogen heterocycles, such as pyrroles, indoles, and quinolines. Several cocyclizations of isocyanides via zwitterions and radical intermediates as well as transition-metal-catalyzed syntheses of different types of heterocycles have recently been developed. Methods starting from isocyanides often have distinct advantages over alternative approaches to the same heterocycles because of their enhanced convergence, the great simplicity of most of the operations with them, and the great variety of isocyanides readily available for use. Isocyanides have also been used in some enantioselective syntheses of chiral heterocyclic compounds, including natural products as well as precursors thereof.

Isocyanides in the Synthesis of Nitrogen Heterocycles

A new and simple synthesis of the pyrrole ring system from Michael acceptors and tosylmethylisocyanides

A novel and efficient synthesis of oxazoles from tosylmethylisocyanide and carbonyl compounds

Chemistry of sulfonylmethyl isocyanides. 11. Synthesis of 1,2,4-triazoles from tosylmethyl isocyanide and aryldiazonium compounds

p-Tolylsulfonylmethyl isocyanide



intermediate: N-(p-tolylsulfonylmethyl)formamide




solvent: One liter of petroleum ether




product: p-tolylsulfonylmethyl isocyanide





Keywords:

elimination, dehydration;
diethyl ether

B. E. Hoogenboom

Papers

A new and simple synthesis of the pyrrole ring system from Michael acceptors and tosylmethylisocyanides

A novel and efficient synthesis of oxazoles from tosylmethylisocyanide and carbonyl compounds

Chemistry of sulfonylmethyl isocyanides. 11. Synthesis of 1,2,4-triazoles from tosylmethyl isocyanide and aryldiazonium compounds

Para-tolylsulfonylmethyl isocyanide

Neue und einfache synth. des pyrrolringsyst. aus michaelakzeptoren und tosylmethylisocyaniden