Nucleophilic Isocyanation

Abstract

Isonitriles are frequently employed as both substrates for organic transformations and ligands for organometallic chemistry. However, despite the wide application of the isonitriles, their synthesis generally depends on the traditional dehydration of N-formamide. "Nucleophilic isocyanation" using cyanide as an N-nucleophile is another straightforward strategy affording the corresponding isonitriles. This method has been available since the 19th century but is still an immature procedure and is therefore more rarely used. In this review, we summarize the concepts and recent progress in nucleophilic isocyanation, including the relatively rare examples of catalytic isocyanation.

Carbonyl and Isocyanide Complexes of Copper and Silver Supported by Fluorinated Poly(pyridyl)borates

“…The related molecules supported by the tris­(2-pyridyl)­borate 3 as well as a copper­(I) carbonyl complex of a fluorinated tris­(1-pyrazolyl)­borate are also presented. The carbonyl and isocyanide complexes were chosen for this study not only because of their importance ,− but also since their CO and CN stretch could serve as a gauge of ligand electronic effects on the metal sites . It is noteworthy that isolable silver carbonyl complexes are also quite rare. ,,− …”

Medicinal Chemistry of Isocyanides

“…Furthermore, despite the fact that many synthetic strategies for the preparation of isocyanides have been devised over the years, their preparation can still suffer from drawbacks and there is room for medicinal and organic chemists to improve or invent novel and mild procedures for their synthesis, especially for highly functionalized compounds. For example, tertiary isocyanides are not always easy to prepare, especially from alcohols, as the elimination reaction is a competitive path, and in several cases an excess of trimethylsilyl cyanide must be used. − The synthesis of molecules containing two or three isocyanide moieties, a prerequisite for metal binding coordination of free iron and copper ions, is always challenging and usually resulting in poor yields. Finally, the identification of a late-stage isocyanide functionalization of complex and densely functionalized molecules is yet to be discovered.…”

SNAr Isocyanide Diversification

“…[1] Hence isocyanides are used in natural product, [2] heterocycle, [3] peptide, [4] macrocycle, [5] or polymer synthesis [6] . The most common isocyanide syntheses are formylation of a primary amine followed by dehydration (Ugi method), [7] reductive amidation of aldehydes or ketones followed by dehydration (Leuckart‐Wallach), [8] and dichloro carbene addition onto primary amines (Hofmann method) [9] more specialized methods such as reduction of iso(thio)cyanates, [10] nucleophilic substitution reaction with a C‐blocked nitrile (Liecke method) [11] or ring‐opening reaction of epoxides using TMSCN and a suitable Lewis acid (Gassman method) [12] amongst many others [13] . In situ synthesis methods are popular as they avoid isolation of the often smelly and noxious isocyanides [14] .…”