CPA-Catalyzed EnantioselectivePara-Addition of Anilinesto Cyclic Thioimidates: A Route to Chiral <i>N</i>,<i>S</i>‑Acetal-Containing Quaternary Carbon StereogenicCenters

Enantiopure <i>N</i>,<i>S</i>-acetals represent a vital class of sulfur-containing compounds commonly found in natural products and pharmaceutical agents. We herein report the first chiral phosphoric acid-catalyzed, highly -chemo, site-, and enantioselective para-addition of anilines to cyclic thioimidates. This protocol provides a new approach for the preparation of chiral <i>N</i>,<i>S</i>-acetal-containing quaternary carbon stereogenic centers, achieving high yields with excellent enantioselectivities (up to 96% yield and 99% ee). The practicality of the method was demonstrated by large-scale reaction and product transformation as well as the late-stage functionalization of complex biologically active molecules. Additionally, several control experiments were performed to highlight a plausible stereocontrol model.