N-heterocyclic carbenes as ligands in palladium-mediated [11C]radiolabelling of [11C]amides for positron emission tomography

A model palladium-mediated carbonylation reaction synthesizing N-benzylbenzamide from iodobenzene and benzylamine was used to investigate the potential of four N-heterocyclic carbenes (N,N'-bis(diisopropylphenyl)-4,5-dihydroimidazolinium chloride (I), N,N'-bis(1-mesityl)-4,5-dihydroimidazolinium chloride (II), N,N'-bis(1-mesityl) imidazolium chloride (III) and N,N'-bis(1-adamantyl)imidazolium chloride (IV)) to act as supporting ligands in combination with Pd-2(dba)(3). Their activities were compared with other Pd-diphosphine complexes after reaction times of 10 and 120 min. Pd-2(dba)(3) and III were the best performing after 10 min reaction (20%) and was used to synthesize radiolabelled [C-11] N-benzylbenzamide in good radiochemical yield (55%) and excellent radiochemical purity (99%). A Cu(Tp*) complex was used to trap the typically unreactive and insoluble [C-11] CO which was then released and reacted via the Pd-mediated carbonylation process. Potentially useful side products [C-11] N,N'-dibenzylurea and [C-11] benzoic acid were also observed. Increased amounts of [C-11] N,N'-dibenzylurea were yielded when PdCl2 was the Pd precursor. Reduced yields of [C-11] benzoic acid and therefore improved RCP were seen for III/Pd-2(dba)(3) over commonly used dppp/Pd-2(dba)(3) making it more favourable in this case.