Recent developments in isocyanide based multicomponent reactions in applied chemistry

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.

Multicomponent reactions (MCRs) are one-pot reactions employing more than two starting materials, e.g. 3, 4, … 7, where most of the atoms of the starting materials are incorporated in the final product.1 Several descriptive tags are regularly attached to MCRs (Fig. 1): they are atom economic, e.g. the majority if not all of the atoms of the starting materials are incorporated in the product; they are efficient, e.g. they efficiently yield the product since the product is formed in one-step instead of multiple sequential steps; they are convergent, e.g. several starting materials combine in one reaction to form the product; they exhibit a very high bond-forming-index (BFI), e.g. several non-hydrogen atom bonds are formed in one synthetic transformation.2 Therefore MCRs are often a useful alternative to sequential multistep synthesis.






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Figure 1


Above: multistep syntheses can be divergent (sequential) or convergent; below: in analogy MCR reactions are convergent and one or two component reactions are divergent or less convergent.

Chemistry and Biology Of Multicomponent Reactions

Recent Developments in the Isonitrile‐Based Multicomponent Synthesis of Heterocycles

2,5-Diketopiperazines: synthesis, reactions, medicinal chemistry, and bioactive natural products.

One-pot synthesis of quinolin-2-(1H)-ones via tandem Ugi-Knoevenagel condensations

A Facile Synthesis of β-Lactams Based on the Isocyanide Chemistry

A facile synthesis of 2,5-diketopiperazines based on isocyanide chemistry

Studies on isocyanides: synthesis of tetrazolyl-isoindolinones via tandem Ugi four-component condensation/intramolecular amidation

The Passerini reaction between arylglyoxals 1, isocyanides 2, and cyanoacetic acid affords N-substituted 3-aryl-2-cyanoacetoxy-3-oxopropionamides 3, which are cyclized in the presence of triethylamine to give N-substituted 3-aryl-4-cyano-2,5-dihydro-5-oxofuran-2-carboxamides 4

Roberto Pepino

Papers

One-pot synthesis of quinolin-2-(1H)-ones via tandem Ugi-Knoevenagel condensations

A Facile Synthesis of β-Lactams Based on the Isocyanide Chemistry

A facile synthesis of 2,5-diketopiperazines based on isocyanide chemistry

Studies on isocyanides: synthesis of tetrazolyl-isoindolinones via tandem Ugi four-component condensation/intramolecular amidation

Studies on Isocyanides and Related Compounds: A Novel Synthetic Route to Furan Derivatives