Nickel-Catalyzed C–CN Bond Formation via Decarbonylative Cyanation of Esters, Amides, and Intramolecular Recombination Fragment Coupling of Acyl Cyanides

Abstract

An efficient nickel-catalyzed decarbonylative cyanation reaction which allows the direct functional-group interconversion of readily available esters into the corresponding nitriles was developed. This reaction successfully offers access to structurally diverse nitriles with high efficiency and excellent functional-group tolerance and provides a good alternative to classical synthetic pathways from diazonium salts or organic halide compounds.

Decarbonylative Cross-Couplings: Nickel Catalyzed Functional Group Interconversion Strategies for the Construction of Complex Organic Molecules

“…35,36 In contrast, a targeted C-CN bond formation allowing the use of abundant and readily available ester substrates could indeed be a good alternative. With the aim of developing the first ester to cyanide functional group interconversion, 37 we started our investigation and searched for an appropriate nitrile source. After careful evaluation, zinc cyanide as a cheap and harmless cyanating agent provided a successful decarbonylative introduction of the CN group in the presence of Ni(0)/dcype catalytic system.…”

Recent Advances in the Metal‐Catalyzed Activation of Amide Bonds

“…In 2017, Rueping and co-workers reported an on-preciousmetal (i.e.,n ickel)-catalyzed deamidative cyanation reactiono f amides through NÀCa ctivation (Scheme16). [51] This reaction was not only applicable to amides, ase sters could also be converted into cyanides. Av ariety of phosphine-based ligands were studied and KF (2 equiv) was found to be an accelerating factor that afforded improved results.…”

Decarbonylative Phosphorylation of Amides by Palladium and Nickel Catalysis: The Hirao Cross‐Coupling of Amide Derivatives

“…Ac areful control of the reaction stoichiometry is essential to harness reactivity of the acylmetal intermediate, in particular in the case of acylpalladium, which decarbonylates more slowly than acylnickel. [28,29] Theo bserved selectivity of the amide coupling in the presence of ArÀCl or ArÀ CN bonds is consistent with the facility of metal insertion into the resonance destabilized amides. [26][27][28][29][30][31][32][33] Notably,t his transformation is tolerant to functional groups that are prone to metal-catalyzed CÀOc leavage, such as aryl ester and aryl sulfonate (Scheme 2), highlighting the potential to achieve high selectivity using amide electrophiles under orthogonal cross-coupling conditions.…”

“…Amide bond cross-coupling has recently emerged as apowerful tool for the construction of organic molecules. [21][22][23][24] As amply demonstrated [25][26][27][28][29][30][31][32][33] aunique amide bond activation mode utilizing amide bond n N to p* C=O resonance destabilization [34] can be successfully deployed to accomplish direct metal insertion into the typically inert N À C(O) moiety. [21] To date,the ability to utilize amides as precursors to form C À O, CÀN, CÀC, CÀB, and CÀHbonds with high predictability and chemoselectivity via acyl and decarbonylative pathways has been demonstrated.…”

“…[35] Such bond forming reactions of readily accessible,b ench-stable amides [22] significantly expand the portfolio of electrophiles available for cross-coupling under synthetically attractive redox-neutral conditions,wherein the reactivity is controlled by geometry and N-substitution of the amide bond. [26,29] Moreover,the versatile amide electrophiles 1) are traditionally derived from different precursors than halides,p henols and anilines,2 )are easy to prepare,a nd 3) are inert to av ariety of conditions allowing for ring prefunctionalization. Despite the significant progress,t he intrinsic limitation is the reactivity of the N À C(O) amide bond for oxidative insertion and control of the relative reactivity of the acyl-metal intermediate towards decarbonylation.…”