A DFT Evaluation on the Asymmetric Transfer Hydrogenation-Dynamic Kinetic Resolution of Isoflavanones Catalyzed by Noyori-Type Ru(II) Complex

This work evaluates stereocontrol in the Asymmetric Transfer Hydrogenation-Dynamic Kinetic Resolution of racemic isoflavanones catalyzed by a chiral Noyori-type Ru^II complex. Although the stereoselectivity of asymmetric transfer hydrogenation has been extensively studied for acetophenone derivatives, the factors governing flavonoid substrates remain poorly understood. Density functional theory calculations at the B97-D3(BJ)//M06-L/def2-SVP level, combined with CREST/GFN2-xTB conformational sampling, were employed to analyze the competing hydride-transfer transition states. The results reveal that the favored pathway involves hydride delivery to the less hindered face, while attack on the sterically congested face is disfavored by 5.2 kcal mol⁻¹, consistent with experimental enantioselectivity of >99% ee. Ongoing NCI and NBO analyses aim to identify the noncovalent and electronic factors responsible for substrate recognition and stereodiscrimination.