Enantioselective Synthesis of Axially Chiral Diaryl Ethers via Rhodium‐Catalyzed [2 + 2 + 2] Cycloaddition

Abstract

ABSTRACT Axially chiral diaryl ethers are important structural motifs in biologically active molecules, functional materials, and chiral catalysts. However, their enantioselective synthesis remains challenging because rotation around the Ar–O bond often occurs with relatively low rotational barriers, and most existing methods rely on desymmetrization strategies that inherently limit the accessible substitution patterns. Here we report a rhodium‐catalyzed enantioselective [2 + 2 + 2] cycloaddition of triynes bearing alkynyl ether units that provides axially chiral diaryl ethers with high enantioselectivity. In this transformation, benzannulation simultaneously constructs the aromatic ring and restricts rotation about the Ar–O bond while introducing diverse substituents, thereby enabling efficient atroposelective synthesis. The reaction exhibits a broad substrate scope and affords the desired products in good yields and enantioselectivities. In suitably designed substrates, the benzannulation process generates multiple atropisomeric axes in a single step, providing complex stereochemical architectures with up to four stereogenic axes. DFT calculations indicate that steric and dispersion interactions during oxidative cyclization govern the stereochemical outcome, and a stepwise alkyne insertion, featuring shortened Rh–C bonds in the transition state, likely enables efficient stereoinduction within the chiral environment, accounting for the observed high enantioselectivity.