Atroposelective Ion-Pair Catalysis: Accessing C−C and C−N Axially Chiral Amino Acid Derivatives from Prochiral Electrophiles

Abstract

Axially chiral C−C and C−N amino acid derivatives constitute valuable structural motifs in organic synthesis. Here, we report a dynamic kinetic resolution strategy for the enantioselective construction via chiral cationic ion‑pair catalysis, in which prochiral electrophiles undergo stereocontrolled ring opening with alcohol nucleophiles. This protocol provides efficient access to a broad array of atroposelective biaryl derivatives, delivering more than 60 examples with yields up to 99% and enantiomeric excesses up to 99%. A bifunctional quinine‑derived ammonium catalyst bearing a hydroxyl group is essential for achieving high reactivity and stereocontrol. The synthetic utility of the method is demonstrated through gram‑scale reactions and downstream derivatizations of the products. Mechanistic control experiments support an ion‑pair catalytic pathway rather than a phase‑transfer process.