Reductive cyanation of organic chlorides using CO2 and NH3 via Triphos–Ni(I) species

Abstract

Cyano-containing compounds constitute important pharmaceuticals, agrochemicals and organic materials. Traditional cyanation methods often rely on the use of toxic metal cyanides which have serious disposal, storage and transportation issues. Therefore, there is an increasing need to develop general and efficient catalytic methods for cyanide-free production of nitriles. Here we report the reductive cyanation of organic chlorides using CO 2 /NH 3 as the electrophilic CN source. The use of tridentate phosphine ligand Triphos allows for the nickel-catalyzed cyanation of a broad array of aryl and aliphatic chlorides to produce the desired nitrile products in good yields, and with excellent functional group tolerance. Cheap and bench-stable urea was also shown as suitable CN source, suggesting promising application potential. Mechanistic studies imply that Triphos-Ni(I) species are responsible for the reductive CC coupling approach involving isocyanate intermediates. This method expands the application potential of reductive cyanation in the synthesis of functionalized nitrile compounds under cyanide-free conditions, which is valuable for safe synthesis of (isotopelabeled) drugs.

Catalytic Cyanation of C–N Bonds with CO2/NH3

“…Based on the experimental results and previous reports, we propose a plausible reaction mechanism for the benzyl nitriles (Figure ). ,,, First, the nickel­(II)-precursor formed in situ is reduced and the nickel(0)-species ( I ) is generated in the presence of silanes and Zn. Subsequently, the benzyl ammonium salt ( 1a ) can be reduced by nickel(0) to give a benzyl radical and a nickel­(I) species ( II ) followed by a radical addition reaction, which delivers the nickel­(II) intermediate ( III ).…”

“…Inspired by the biological 2e-reduction process for the formation of cyanide ligands in [NiFe]-hydrogenase from CO 2 and NH 3 , we have prepared aryl nitriles by cyanation of aryl halides using CO 2 . , The wide application of the Sandmeyer reaction of anilines led us to envision a Sandmeyer reaction-like system for cyanation of α-aryl amines, and to the best of our knowledge, a general procedure of C–N bond cyanation to afford α-aryl nitriles has not yet been reported. Moreover, the selective incorporation of cyano group has attracted tremendous attention. − Even by far, the most prominent production process for adiponitrile (>10 6 tons per year) is suffering from toxic cyanide and costly purification .…”

Nickel(I)–Phenolate Complexes: The Key to Well-Defined Ni(I) Species

“…14,16−18 In contrast, nickel(I) complexes stabilized by phosphine ligands are expected to play an active role in reductive carboxylation, 19−23 amidation, 24 and cyanation reactions (Figure 1A). 25 The key step in these reactions, e.g., the insertion of carbon dioxide into the nickel− carbon bond, was shown to proceed faster for nickel(I) compared to the analogous nickel(II) complexes due to the increased nucleophilicity. 19,26 Besides their important role in catalysis, monovalent nickel(I)−halide complexes have been shown to be valuable synthetic precursors to other well-defined nickel species (Figure 1B).…”

Chlorination of arenes via the degradation of toxic chlorophenols

“…With the extensive application of substitution reactions ( 21 , 22 ), transfunctionalizations ( 23 , 24 ), and cross-coupling reactions ( 25 , 26 ), aryl chlorides are regarded as one of the most important building blocks widely used in the manufacture of polymers, pharmaceuticals, and other types of chemicals and materials ( Fig. 1 B ) ( 27 – 31 ).…”