Novel methods for the synthesis of heterocycles using highly reactive spirocyclopropanes

This review describes our recent efforts to develop efficient methods for the synthesis of heterocyclic compounds, such as indoles and benzofurans, employing ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes, which were prepared by the reaction of 1,3-cyclohexanediones with sulfonium salts. Ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes with primary amines proceeded at room temperature to provide 2-substituted tetrahydroindol-4(5H)-ones in good to excellent yield. The obtained product was readily converted into a 2-substituted 4-hydroxyindole derivative. Furthermore, acid-catalyzed ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes proceeded smoothly at room temperature to provide 2-substituted tetrahydrobenzofuran-4(2H)-ones in excellent yield. The obtained product was converted into a 2-substituted 4-hydroxybenzofuran derivative. The synthetic utility of this catalytic protocol was demonstrated by the total synthesis of cuspidan B.