Functionalisation of 11C-labelled olefins via a Heck coupling reaction

A method for incorporation of C-11 (beta(+), t(1/2)=20.3 min) in internal alkenes has been developed. [beta-C-11]Styrene and [1-C-11]pent-1-ene were synthesized from benzaldehyde and butyraldehyde respectively, using [C-11]methylenetri-o-tolylphosphorane in a Wittig reaction. The radiochemical yield based on analytical liquid chromatography was 85-90%. The C-11-labelled olefins were further coupled with several aromatic halides in a palladium mediated cross-coupling reaction forming the compounds (E)-[beta-C-11]stilbene, (E)-4'-amino[beta-C-11]stilbene, (E)-[beta-C-11]stilbene-2'-methanol, (E)-3'-ethoxycarbonyl[beta-C-11]stilbene, (E)-4'-methyl[beta-C-11]stilbene, (E)-1-phenyl[1-C-11]pent-1-ene and (E)-1-(4-aminophenyl)[1-C-11]pent-1-ene. The reaction sequence was performed without purification of the intermediate C-11-labelled olefin. Radiochemical yields of the coupling products were 47-55% according to analytical liquid chromatography. The decay-corrected isolated radiochemical yield of (E)-[beta-C-11]stilbene was approximately 38% and the total synthesis time was 40 min, counted from the end of radionuclide production to the isolated product. In a typical experiment starting from 4.7 GBq [C-11]methyl iodide, 450 MBq of (E)-[beta-C-11]stilbene was obtained in a radiochemical purity higher than 95%. This method was also used for the synthesis of (E)-(beta-C-13)stilbene, which was used to verify the labelling position by C-13 NMR.