Asymmetric Hydrolytic Kinetic Resolution with Recyclable Macrocyclic CoIII–Salen Complexes: A Practical Strategy in the Preparation of (R)‐Mexiletine and (S)‐Propranolol

A chiral cobalt(III) complex ( 1 e ) was synthesized by the interaction of cobalt(II) acetate and ferrocenium hexafluorophosphate with a chiral dinuclear macrocyclic salen ligand that was derived from 1R,2R‐(?)‐1,2‐diaminocyclohexane with trigol bis‐aldehyde. A variety of epoxides and glycidyl ethers were suitable substrates for the reaction with water in the presence of chiral macrocyclic salen complex 1 e at room temperature to afford chiral epoxides and diols by hydrolytic kinetic resolution (HKR). Excellent yields (47 % with respect to the epoxides, 53 % with respect to the diols) and high enantioselectivity (ee>99 % for the epoxides, up to 96 % for the diols) were achieved in 2.5–16 h. The Co^III macrocyclic salen complex ( 1 e ) maintained its performance on a multigram scale and was expediently recycled a number of times. We further extended our study of chiral epoxides that were synthesized by using HKR to the synthesis of chiral drug molecules (R)‐mexiletine and (S)‐propranolol.