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

摘要

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 13C-labelled benzonitriles with ex situ generated 13C-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 H13CN in THF provided two Pd-hydride complexes, (P(tBu)₃)₂Pd(H)(13CN), and [(P(tBu)₃)Pd(H)]₂Pd(13CN)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)₂Pd(H)(13CN) 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)₂Pd(H)(Br) and 13C-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 L_nPd(0) into HCN and an aryl bromide followed by a transmetallation step to L_nPd(Ar)(CN) and L_nPd(H)(Br), which both reductively eliminate, the latter in the presence of KOAc, to generate the benzonitrile and L_nPd(0).