Transition metal-mediated reactions using [11C]cyanide in synthesis of 11C-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.