Transition metal-mediated reactions using [11C]cyanide in synthesis of11C-labelled aromatic compounds

Abstract

Aromatic and heteroaromatic nitriles, labelled with carbon-11 in the cyano group, have been synthesized by rapid palladium- and chromium-mediated reactions using hydrogen [11C]cyanide. The 11C-cyanation on aryl iodides, bromides, and triflate, or on heteroaromatic bromides, in the presence of tetrakis(triphenylphosphine)palladium, afforded 54–99% radiochemical yield in 5 min. The Pd0-promoted 11C-cyanation was performed with varying concentrations of substrate, down to the submicro molar scale ( > 0.1 µmol). The decay-corrected radiochemical yields of [cyano-11C]benzonitriles after purification by semi-preparative HPLC were 50–90%, based on hydrogen [11C]cyanide, with a total synthesis time of 20–25 min and a radiochemical purity >98%. Nucleophilic aromatic substitution with 11C-cyanide on tricarbonylchromium complexes of some fluoroarenes resulted in radiochemical yields of 46–74%. In a combined synthetic sequence, Pd0-assisted 11C-cyanation on chloroarene(tricarbonyl)chromium complexes, the radiochemical yields were 95%. By mono-11C-cyanation on 1,4-dibromobenzene, the difunctional precursor 4-bromo[cyano-11C]benzonitrile was obtained. Subsequent cross-coupling with phenyl(trimethyl)tin in the presence of tetrakis(triphenylphosphine)palladium afforded 4-[cyano-11C] biphenylcarbonitrile in 60% radiochemical yield. The synthesis time before purification was 15 min counted from end of bombardment.