Desymmetric Hydroacyloxylation of Paracyclophyne by Catalytic Coordination‐Induced Asymmetric Addition

Strained arynes are highly reactive, transient, and neutral intermediates. Stereoselective manipulation of these species in asymmetric catalysis remains a significant challenge. In this study, we reported a new catalytic copper(I) complexation induced asymmetric addition mode on paracyclophyne intermediate. The direct addition of carboxylates to paracyclophynes is a fast, strain-releasing reaction that typically leads to racemic products. Upon the introduction of a catalytic amount of a chiral copper(I) complex, an unprecedented stereoconvergent hydroacyloxylation reaction was developed, affording planar chiral [2.2]paracyclophane esters in high yields with excellent enantioselectivity. The resulting addition products can be readily transformed into a variety of functionalized hydroxyl-[2.2]paracyclophanes via Fries rearrangement or Friedel-Crafts reactions. These are valuable synthetic building blocks for the construction of functionalized planar chiral [2.2]paracyclophane (PCP) derivatives, which currently rely heavily on preparative HPLC or classical chemical/kinetic resolution methods. Control experiments and DFT calculations reveal that copper(I) complexation stabilizes the reactive aryne intermediate and promotes the subsequent asymmetric nucleophilic addition via a six-membered ring transition state.