Synthesis and [*C]CO-labelling of (C,N) gem-dimethylbenzylamine–palladium complexes for potential applications in positron emission tomography

Abstract

Various aryl–palladium complexes were synthesised from gem-dimethylbenzylamine derivatives by C–H activation under extremely mild conditions. Interestingly, these highly stable structures reacted with [¹³C]carbon monoxide to produce the desired labelled lactams in 29% to 51% yields over the C–H activation/carbonylation steps. As representative examples, a non-natural amino acid and an estradiol-based conjugate were prepared and labelled in model experiments with [¹³C]CO in homogeneous or heterogeneous conditions. Especially, the latter was radiolabelled with [¹¹C]CO using a convenient procedure from the resin-supported palladium complex precursor. Thus, these results strongly suggest that cyclometallated palladium complexes obtained from gem-dimethylbenzylamine moieties are promising precursors for the practical synthesis of new [¹¹C]tracers for Positron Emission Tomography.