Tuning of Regioselectivity in Inorganic Iodide-Catalyzed Alkylation of 2-Methoxyfurans via Electronic and Steric Effects

In the presence of inorganic iodide, the methoxy C?O bond in 2-methoxyfurans may be cleaved to afford the corresponding lactonic anion. Due to the presence of an electron-withdrawing group at the 3-position, the alkylation with normal organic iodides occurred at the 3-position highly regioselectively. However, when electron-deficient allylic iodides with an electron-withdrawing group at the 2-position were used the 5-alkylation products were formed as the major products with sodium iodide as the catalyst. With magnesium iodide as the catalyst, the 5-allylation occurred highly regioselectively. As a whole, the 3- vs. 5-alkylation selectivity may be determined by the relative steric hindrance at the 3- and 5-positions and the electronic effect of the allylic iodides. A rationale was proposed.