Catalysis

Intramolecular force

Enantioselective synthesis

Enantiomeric excess

Yield (engineering)

Enantiomer

Metallurgy

Materials science

Receptor

Biochemistry

Molecule

Stereochemistry

Combinatorial chemistry

Ligand (biochemistry)

Organic chemistry

Kinetic resolution

Asymmetric hydrogenation

Chemistry

Iridium

Chiral ligand

Journal of the American Chemical Society

We herein present a facile and column-free synthetic route toward a structurally unique oxa-spirocyclic diphenol, termed as O-SPINOL. Features of the synthesis include the construction of the all-carbon quaternary center at an early stage, a key double intramolecular SNAr step to introduce the spirocycles and the feasibility of operating on >100 g scale. Both enantiomers of O-SPINOL can be easily accessed through optical resolution with l-proline by control of the solvent. The chiral tridentate ligand O-SpiroPAP derived from O-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 H2.

Design and Synthesis of Chiral <i>oxa</i>-Spirocyclic Ligands for Ir-Catalyzed Direct Asymmetric Reduction of Bringmann’s Lactones with Molecular H<sub>2</sub>

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

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