Regio- and stereoselective synthesis of functionalized and fused heterocycles from Morita-Baylis-Hillman adducts of dicyclopentadienone

An efficient protocol for the Morita-Baylis-Hillman (MBH) reaction of dicyclopentadienone using CTAB has been developed. The MBH adduct was subsequently transformed to its acetate and bromide derivatives. The 1,3-bielectrophilic character of the MBH acetate and bromide was further explored with various 1,3-binucleophiles to construct various oxa-, thia- and aza-heterocycles. These reactions proceed through a cascade double Michael addition of 1,3-binucleophiles to the MBH acetate/bromide under basic conditions. Amenability of these reactions to scale-up and applications of the products in the synthesis of cyclopentenone-fused chromenones and thiopyranoindoles have been demonstrated. Morita-Baylis-Hillman acetates and bromides undergo [3 + 3] annulation with binucleophiles and the products on retro-Diels-Alder reaction deliver cyclopentenone-fused heterocycles.