Biomimetic Peptide-Iminophosphorane Superbases Enable Atroposelective Synthesis of C–O Axially Chiral Diaryl Ethers

The catalytic asymmetric construction of axial chiral diaryl ethers featuring conformationally flexible C–O axes remains a formidable challenge, significantly limiting their application as privileged chiral motifs. To address this gap, we here extend the recently disclosed bioinspired peptide-iminophosphoranes (PIMPs), a new class of programmable, multifunctional organosuperbase catalysts, to enable highly enantioselective catalysis for the Pudovik addition/ phospha -Brook rearrangement cascade. This strategy provides direct and efficient access to densely functionalized, axially chiral diaryl ethers in high yields with satisfactory enantioselectivity (up to >99% ee) and diastereoselectivity across a broad substrate scope, including aryl and alkoxy phosphine oxides spanning a wide p K a range─highlighting the good functional group tolerance and catalytic generality. Crucially, mechanistic investigations ruled out secondary kinetic resolution pathways, confirming the reaction proceeds via formal desymmetrization controlled by the PIMP catalyst. Experimental evidence highlights the versatility of the PIMP catalysts in this asymmetric event, wherein the peptide backbone orchestrates precise substrate preorganization via a network of noncovalent interactions, while the iminophosphorane superbase site drives efficient proton transfer.