Chemo- and Diastereoselective Synthesis of Pyrrolidines from Aroylformates and δ-Tosylamino Enones via P(NMe₂)₃-Mediated Reductive Amination/Base-Catalyzed Michael Addition Cascade

Abstract

A novel P(NMe₂)₃-mediated tandem (1 + 4) annulation between aroylformates and δ-tosylamino enones has been developed that affords a facile synthesis of functionalized pyrrolidines in moderate to excellent yields with exclusive chemoselectivity and high diastereoselectivity. Mechanistic investigation reveals that the reaction proceeds through an unprecedented P(NMe₂)₃-mediated reductive amination/base-catalyzed Michael addition cascade. The reaction herein also represents the first study of the reactivity patterns of the Kukhtin-Ramirez adducts toward ambiphilic nucleophile-electrophiles.