TiCl4-Promoted Baylis−Hillman Reactions of Substituted 5-Isoxazolecarboxaldehydes with Cycloalkenones1

TLDR: The Baylis−Hillman (BH) reaction of substituted 5-isoxazolecarboxaldehydes with cyclohexenone in the presence of TiCl4 invariably lead to the formation of hemiacetals beside the BH adducts as discussed by the authors.

Abstract: The Baylis−Hillman (BH) reaction of substituted 5-isoxazolecarboxaldehydes with cyclohexenone in the presence of TiCl4 invariably lead to the formation of hemiacetals beside the BH adducts. A similar reaction in the presence of DABCO, DBU, or 3-HQN yielded minor quantities of phenols in addition to the usual BH adducts. Similar to 5-isoxazolecarboxaldehydes, the TiCl4-mediated BH reaction of cyclohexenone with various benzaldehydes also furnishes hemiacetals in considerable yields. The reaction mechanism involving the formation of α-chloromethyl enone as an intermediate has been proposed. The synthesis of hemiacetals 5 and 14 from compound 4 in the presence of cyclohexenone and cyclopentenone, respectively, under acidic conditions indicates that enolization and aromatization of the cyclohexene ring are the key steps in the reaction mechanism.