Organocatalytic Cascade Aza-Mannich/Michael Addition Sequence for the Synthesis of Chiral ε-Sultam Derivatives

Abstract

Herein, we present a bifunctional hydrogen-bonding catalytic system for the synthesis of ε-sultam derivatives via C–N bond formation. Through the [3 + 2] and [4 + 2] annulation reactions between aminoenones and seven-membered cyclic N-sulfonylimines, an array of ε-sultam derivatives has been efficiently obtained in good yields with excellent diastereoselectivities (up to >20:1 dr) and high enantioselectivities (up to 99:1 er). The practical value of this methodology was further demonstrated by the gram-scale reaction and versatile synthetic transformations of the resulting sultams.