Multiple Absolute Stereocontrol in Cascade Lactone Formation via Dynamic Kinetic Resolution Driven by the Asymmetric Transfer Hydrogenation of Keto Acids with Oxo-Tethered Ruthenium Catalysts

A straightforward asymmetric construction of chiral fused γ- and δ-lactones containing multiple contiguous stereocenters was successfully developed by either (1) the dynamic kinetic resolution–asymmetric transfer hydrogenation (DKR-ATH) reaction using oxo-tethered Ru­(II) complexes followed by syn-selective lactonization or (2) the tandem DKR-ATH/lactonization in combination with asymmetric hydrogenation catalyzed by Ru–chiral diphosphine complexes. The expedient protocol is applicable to the enantioselective synthesis of natural wine lactone and a biologically active benzo-fused lactone with an unprecedented level of diastereo- and enantioselectivity.