Dynamic Kinetic Resolution of γ-Substituted Cyclic β-Ketoesters via Asymmetric Hydrogenation: Constructing Chiral Cyclic β-Hydroxyesters with Three Contiguous Stereocenters

An efficient asymmetric hydrogenation of racemic gamma-substituted cyclic beta-ketoesters via dynamic kinetic resolution to provide chiral cyclic beta-hydroxy esters with three contiguous stereocenters is reported. Using a chiral spiro iridium catalyst (R)-S (Ir-SpiroSAP), a series of racemic gamma-aryl/alkyl substituted cyclic P-ketoesters were hydrogenated to the corresponding chiral cyclic beta-hydroxy esters in high yields (84-97%) with good to excellent enantioselectivities (69->99% ee) and cis,cis-selectivities (up to >99:1).

Automated summary

An efficient asymmetric hydrogenation method using a chiral spiro iridium catalyst has been developed to convert racemic gamma-substituted cyclic beta-ketoesters into chiral cyclic beta-hydroxy esters with three stereocenters. The reaction provides high yields (84-97%) with good to excellent enantioselectivities (69->99% ee) and cis,cis-selectivities (up to >99:1).