Highly Enantioselective Hydroxylation of 1-Indanone-Derived β-Ketoesters Catalyzed by a Newly Designed C1-Symmetric Salan-Zr Complex

An efficient <b>L17</b>-Zr(IV)-catalyzed protocol for the enantioselective synthesis of chiral α-hydroxy-β-ketoesters derived from 1-indanone was presented. At loadings as low as 0.5-1.0 mol %, <i>C</i>₁-Symmetric chiral Salan ligand promotes the hydroxylation of small ester groups and sterically hindered esters with high yields (up to 99%) and excellent enantioselectivities (up to 99% ee). The method exhibits broad solvent compatibility and remarkable thermal robustness, allowing for gram-scale reactions under diverse conditions without compromising the efficiency. Combined experimental and density functional theory (DFT) studies identify key ligand features (an NH unit, a phenolic OH, a 3,5-dimethoxyphenyl moiety, and 3,5-bis(2-phenylpropan-2-yl) substituents) as responsible for enhanced steric shielding and a shallow catalytic pocket, which underpin its outstanding stereocontrol.