Styrene-Based Axial Chiral Catalyst-Catalyzed Asymmetric Synthesis of Spirobarbiturates through Chiral Proton Shuttle

Chiral spirobarbiturates have become recognized as crucial structural motifs in biologically active compounds owing to their rigid frameworks. However, current approaches for constructing chiral spirobarbiturates that utilize barbiturates as Michael donors remain underdeveloped. Herein, we present a synthetic strategy for the construction of chiral spirobarbiturates through a chiral proton shuttle approach designed to suppress background and side reactions. Barbituric isothiocyanates are employed as effective Michael donors, enabling asymmetric cyclization with enynamides to proceed in good yields and with high enantioselectivity under mild reaction conditions. Mechanistic investigations, encompassing control experiments, kinetic analyses, and density functional theory (DFT) calculations, are conducted to clarify the reaction pathway and to elucidate the roles of the chiral proton shuttle and the styrene-based axial chiral catalyst in achieving asymmetric induction.