Enantioselective Synthesis of Axially Chiral Biphenols via Oxygen-Triggered Kinetic Resolution by Peptide-Phosphonium Salt Catalysis

Axially chiral biphenolic compounds serve as versatile scaffolds for chiral catalysts and ligands, yet their asymmetric synthesis remains challenging in organic chemistry. Although diverse synthetic strategies have been developed, triplet oxygen (O2) (owing to its inherent low reactivity and difficulty in precise dosage control) has not been utilized for constructing axially chiral biphenols. Herein, we present an O2-triggered oxidative kinetic resolution catalyzed by bioinspired peptide-phosphonium salts (PPS), enabling the asymmetric synthesis of axially chiral biphenols with satisfactory enantioselectivities (up to >99% ee). The practicality of this method is demonstrated through scalable synthesis of diverse axially chiral biphenolic scaffolds, including privileged phosphoramidite ligands and Brønsted acid catalysts. Mechanistic studies reveal that stereoselectivity stems from chiral recognition and activation between the peptide-phosphonium catalyst and substrates via multiple noncovalent interactions (NCI). This work not only establishes a practical route to axially chiral biphenolic architectures but also offers a general strategy for substrate activation through weak-bonding interactions in asymmetric catalysis.