Effect of the Counter Anion on the NHC-Catalyzed Aroylation Reaction

The influence of the counter anion and solvent on the N-heterocyclic carbene (NHC)-catalyzed nucleophilic aroylation of electron-deficient aromatic compounds was investigated using iodide, bis(trifluoromethanesulfonyl)imide (TFSA), and tetrafluoroborate (BF4−) precatalysts. For quinazoline substrates, the relative efficiency of the precatalysts depended strongly on the solvent. The iodide precatalyst showed higher reactivity in MeCN, whereas the TFSA and BF4− precatalysts were more effective under some conditions in THF/DMF. Additive experiments using NaI, NaNTf2, and AgOTs suggested that free iodide plays an active role in promoting the reaction in MeCN. Halogen-exchange experiments and time-course 1H NMR analysis supported a pathway involving iodide-mediated substitution of the quinazoline substrate followed by aroylation of the resulting iodo intermediate. The magnitude of the counter-anion effect varied with the structure of the aromatic substrate, whereas nitrobenzene derivatives showed little dependence on the counter anion. The iodide/MeCN conditions were also successfully applied to the synthesis of a precursor of termicalcicolanone A.