Zirconium-Salan Catalyzed Enantioselective α-Hydroxylation of β-Keto Esters

We report herein the development of enantioselective and scalable alpha-hydroxylation of 1-indanone-derived beta-keto esters by Zr(IV) complexes bearing readily availableC(2)-symmetric salan ligands and cumene hydroperoxide as an oxidant, affording synthetically valuable hydroxylation products in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee) under mild reaction conditions. In mechanistic studies, we have shown that (1) a Zr(IV)-salan complex was generated in situ as the active catalyst responsible for the chiral induction, (2) the transfer of the electrophilic fragment from cumene hydroperoxide to the Zr(IV)-bound enolate was accompanied by a heterolytic O-O bond cleavage, and (3) the formation of hydrogen bond between the amine hydrogen atom(s) of the salan ligand and the hydroxy group of cumene hydroperoxide was significant for stabilizing the stereocontrolled transition state and improving the enantioselectivity.