Functionalisation of 11C-labelled olefinsvia a Heck coupling reaction

Abstract

A method for incorporation of ¹¹C (β⁺, t½ = 20.3 min) in internal alkenes has been developed. [β-¹¹C]Styrene and [1-¹¹C]pent-1-ene were synthesized from benzaldehyde and butyraldehyde respectively, using [¹¹C]methylenetri-o-tolylphosphorane in a Wittig reaction. The radiochemical yield based on analytical liquid chromatography was 85–90%. The ¹¹C-labelled olefins were further coupled with several aromatic halides in a palladium mediated cross-coupling reaction forming the compounds (E)-[β-¹¹C]stilbene, (E)-4′-amino[β-¹¹C]stilbene, (E)-[β-¹¹C]stilbene-2′-methanol, (E)-3′-ethoxycarbonyl[β-¹¹C]stilbene, (E)-4′-methyl[β-¹¹C]stilbene, (E)-1-phenyl[1-¹¹C]pent-1-ene and (E)-1-(4-aminophenyl)[1-¹¹C]pent-1-ene. The reaction sequence was performed without purification of the intermediate ¹¹C-labelled olefin. Radiochemical yields of the coupling products were 47–55% according to analytical liquid chromatography. The decay-corrected isolated radiochemical yield of (E)-[β-¹¹C]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 [¹¹C]methyl iodide, 450 MBq of (E)-[β-¹¹C]stilbene was obtained in a radiochemical purity higher than 95%. This method was also used for the synthesis of (E)-(β-¹³C)stilbene, which was used to verify the labelling position by ¹³C NMR.