Ex situ generation of stoichiometric HCN and its application in the Pd-catalysed cyanation of aryl bromides: evidence for a transmetallation step between two oxidative addition Pd-complexes

A protocol for the Pd-catalysed cyanation of aryl bromides using near stoichiometric and gaseous hydrogen cyanide is reported for the first time. A two-chamber reactor was adopted for the safe liberation of ex situ generated HCN in a closed environment, which proved highly efficient in the Ni-catalysed hydrocyanation as the test reaction. Subsequently, this setup was exploited for converting a range of aryl and heteroaryl bromides (28 examples) directly into the corresponding benzonitriles in high yields, without the need for cyanide salts. Cyanation was achieved employing the Pd(0) precatalyst, P(tBu)(3)-Pd-G3 and a weak base, potassium acetate, in a dioxane-water solvent mixture. The methodology was also suitable for the synthesis of C-13-labelled benzonitriles with ex situ generated C-13-hydrogen cyanide. Stoichiometric studies with the metal complexes were undertaken to delineate the mechanism for this catalytic transformation. Treatment of Pd(P(tBu)(3))(2) with (HCN)-C-13 in THF provided two Pd-hydride complexes, (P(tBu)(3))(2)Pd(H)((CN)-C-13), and [(P(tBu)(3)) Pd(H)](2)Pd((CN)-C-13)(4), both of which were isolated and characterised by NMR spectroscopy and X-ray crystal structure analysis. When the same reaction was performed in a THF : water mixture in the presence of KOAc, only (P(tBu)(3))(2)Pd(H)((CN)-C-13) was formed. Subjection of this cyano hydride metal complex with the oxidative addition complex (P(tBu)(3)) Pd(Ph)(Br) in a 1 : 1 ratio in THF led to a transmetallation step with the formation of (P(tBu)(3))(2)Pd(H)(Br) and C-13-benzonitrile from a reductive elimination step. These experiments suggest the possibility of a catalytic cycle involving initially the formation of two Pd(II)-species from the oxidative addition of LnPd(0) into HCN and an aryl bromide followed by a transmetallation step to LnPd(Ar)(CN) and LnPd(H)(Br), which both reductively eliminate, the latter in the presence of KOAc, to generate the benzonitrile and LnPd(0).