Transition‐Metal‐Catalyzed Cyanation by Using an Electrophilic Cyanating Agent, N‐Cyano‐N‐phenyl‐p‐toluenesulfonamide (NCTS)

Abstract

The ability to introduce a nitrile group into a biologically active compound is very useful in organic synthesis, owing to the importance of nitrile groups in transformations and tuning molecular properties. To date, nucleophilic cyanation has been the most used strategy for this purpose, whilst electrophilic cyanation reactions are less developed. Recently, the electrophilic cyanation reagent N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) has received increasing attention, owing to its superior properties in terms of safety and practicality. This Focus Review summarizes recent progress in transition-metal-catalyzed cyanation reactions that use NCTS.

Cobalt-catalyzed C–H cyanations: Insights into the reaction mechanism and the role of London dispersion

“…Currently, the strategic application of London dispersion in catalysis is still very difficult to achieve and, as a consequence, detailed insights in how dispersion influences organic reactions continue to be in high demand. Therefore, we have computationally analyzed the recently developed cobalt-catalyzed C–H cyanation of arenes ( Scheme 2 ) [ 30 – 34 ]. Dispersion effects can be envisioned to be highly important in this system, as the relatively C–H-rich ligand Cp* can interact with both substrates within the cobalt complexes.…”

Recent advances in the rhodium‐catalyzed cyanation reactions

“…Jie Cui et al discussed the recent developments in the cyanation reactions by using NCTS as the cyanating agent. [ 30 ] From this in‐depth study, they concluded that transition metal‐catalyzed cyanation reactions using NCTS are reasonably good and environmentally friendly.…”

Metal-free three-component cyanoalkylation of quinoxalin-2(1H)-ones with vinylarenes and azobis(alkylcarbonitrile)s

“…3 However, these methods use expensive and complex catalysts of metals such as ruthenium, 4 rhodium, 5 or palladium 6 and also toxic cyanide sources, 7 namely KCN, NaCN, TMSCN, CuCN, and Zn(CN) 2 . Although a few mild cyanating agents such as diaminomaleonitrile, 8 aryl cyanates, 9 tosyl cyanide, 10 cyanobenziodoxole, 11 aryl(cyano)iodonium triflates, 12 N -cyano- N -phenyl- p -toluene sulfonamide, 13 cyanocarbonyls 14 and Zhdankin's reagent 15 efficiently drive C–H cyanation reactions, these cyanide sources are generally prepared from highly toxic precursors. Hence, a more affordable and commercially available nitrile source is in high demand.…”