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Isocyanide-based multicomponent reactions (IMCR) are among the most important chemical reactions to efficiently generate molecular diversity and have found widespread use in industry and academia. Generally, isocyanides are synthesized in 1-2 steps starting from primary amines. Here, we provide experimental detail on an alternative approach toward formamides and, thus, isocyanides via the Leuckart-Wallach reaction in an improved variation. The resulting >50 synthesized and characterized formamides are useful starting materials for IMCR, as well as other chemistries. The advantage of using the Leuckart-Wallach pathway to formamides and isocyanides is the lower price, on average, of the starting materials, as well as their differential and complementary structural diversity, as compared to the primary amine pathway.

Original publication




Journal article


ACS combinatorial science

Publication Date





493 - 499


Department of Drug Design, University of Gröningen , A. Deusinglaan 1, Gröningen 9700AV, The Netherlands.


Cyanides, Formamides, Amines, Indicators and Reagents, Magnetic Resonance Spectroscopy, Costs and Cost Analysis