A transition metal-free three-component cascade reaction for the synthesis of pyrrolizine and indolizine derivatives

Pyrrolizine and indolizine related rings are present in natural products and bioactive molecules. Herein, we report a three-component cascade reaction of commercial aldehydes and cyclic secondary amino acids with the easily accessible phenyl vinyl selenone for the synthesis of tetrahydropyrrolizines or tetrahydroindolizines. The reactions proceed in refluxing 1,4-dioxane through a one-pot azomethine ylide formation, 1,3-dipolar cycloaddition, and elimination sequence. Replacement of L-proline with (D,L)-pipecolic acid as the amino acid, extended the cascade by introducing an additional dehydrogenative aromatization step, enabling the one-pot formation of five new bonds.