[11C]Carbon monoxide in the palladium-mediated synthesis of 11C-labelled ketones

Abstract

[¹¹C]Carbon monoxide has been used in the palladium-mediated synthesis of [carbonyl-¹¹C]ketones. Methyl iodide, vinylic and arylic halides and trifluoromethanesulfonates (triflates) have been coupled with tin reagents with insertion of [¹¹C]carbon monoxide at very low concentrations (10–100 nmol [¹¹C]CO in a total volume of 10 ml). The labelled products are obtained in 36–62% isolated decay-corrected radiochemical yields within 30 min of the end of radionuclide production. In order to use [¹¹C]carbon monoxide efficiently, a gas handling system has been developed which allows the radioactive gas to recirculate through the reaction media. The reactions are performed using a one pot procedure. The best results are achieved with mixed tin reagents containing an unsaturated transferable substituent and Pd(AsPh₃)₄. In a typical experiment starting from 25 GBq of [¹¹C]carbon dioxide, 4.2 GBq (47%) of [carbonyl-¹¹C]acetophenone 1 is obtained 30 min after the end of radionuclide production. The specific radioactivity of 1 is 91 GBq µmol^-1. [carbonyl-¹³C]Benzophenone 6 has been synthesised using the same approach to verify the position of the label.