Methods for the ¹¹C-labeling of carbonyl compounds applicable in the preparation of radiotracers for Positron Emission Tomography (PET) are described. To this end [¹¹C]carbon monoxide at low concentration was used in transition metal- mediated reactions.

Stille couplings were employed in the synthesis of [carbonyl-¹¹C]ketones from methyl and aryl halides with [¹¹C]carbon monoxide. The synthesized [carbonyl-¹¹C]ketones were obtained from the corresponding organostannanes with analytical radiochemical yields up to 98%.

A number of synthetic routes were designed using [¹¹C]carbon monoxide and rhodium complexes. Nitrene intermediates were generated from azides and reacted via a rhodium-mediated carbonylation reaction as a general synthetic route to [carbonyl-¹¹C]isocyanates, versatile precursors. [carbonyl-¹¹C]Isocyanate reacted via nucleophilic attack of an amine to form N,N’-diphenyl[¹¹C]urea in 82% analytical radiochemical yield, ethyl phenyl[¹¹C]carbamate was synthesized by the same route, using ethanol as the nucleophile, in 70% radiochemical yield. [¹¹C]Isocyanate was also able to react in a [2+3] cycloaddition with ethylene oxide to form 3-phenyl[carbonyl-¹¹C]oxazolidin-2-one in over 80% analytical radiochemical yield. This method was applied to the synthesis of a potential efflux system tracer [¹¹C]hydroxyurea in 38% isolated radiochemical yield and the derivative 1-hydroxy-3-phenyl[¹¹C]urea in 35% isolated radiochemical yield. Carbene intermediates, generated from diazo compounds, were reacted with [¹¹C]carbon monoxide in the rhodium-mediated synthesis of [carbonyl-¹¹C]ketenes. [carbonyl-¹¹C]Ketene intermediates were utilised in the synthesis of diethyl[carbonyl-¹¹C]malonate, from ethyl diazoacetate and ethanol. The product was obtained with a 20% isolated radiochemical yield. Alkylation of diethyl[carbonyl-¹¹C]malonate, with ethyliodide and tetrabutylammonium fluoride, was successfully accomplished and diethyl diethyl[carbonyl-¹¹C]malonate was synthesized in 50% analytical radiochemical yield. Several (carbonyl-¹³C)compounds were also synthesized using the described methods as a way of characterizing the position of the label using ¹³C-NMR.