Design and Synthesis of Chiral <i>oxa</i>-Spirocyclic Ligands for Ir-Catalyzed Direct Asymmetric Reduction of Bringmann’s Lactones with Molecular H₂

We herein present a facile and column-free synthetic route toward a structurally unique oxa-spirocyclic diphenol, termed as <i>O</i>-SPINOL. Features of the synthesis include the construction of the all-carbon quaternary center at an early stage, a key double intramolecular <i>S</i>_NAr step to introduce the spirocycles and the feasibility of operating on >100 g scale. Both enantiomers of <i>O</i>-SPINOL can be easily accessed through optical resolution with l-proline by control of the solvent. The chiral tridentate ligand <i>O</i>-SpiroPAP derived from <i>O</i>-SPINOL has been successfully synthesized and applied in the iridium-catalyzed asymmetric hydrogenation of bridged biaryl lactones under mild reaction conditions, providing valuable and enantioenriched axially chiral molecules in excellent yields and enantioselectivities (up to 99% yield and >99% ee). This method represents a rare example of constructing axially chiral molecules by direct reduction of esters with H<sub>2