Asymmetric hydrolytic kinetic resolution with recyclable macrocyclic Co(III)-salen complexes: a practical strategy in the preparation of (R)-mexiletine and (S)-propranolol.

Arghya Sadhukhan, Noor-ul H Khan, Tamal Roy, Rukhsana I Kureshy, Sayed H R Abdi, Hari C Bajaj

Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute, Council of Scientific & Industrial Research, G. B. Marg, Bhavnagar-364 021, Gujarat, India.

Chemistry (Weinheim an der Bergstrasse, Germany) 2012 Apr 23

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A chiral cobalt(III) complex (1e) 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 1e 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 (1e) 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. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Citation

Arghya Sadhukhan, Noor-ul H Khan, Tamal Roy, Rukhsana I Kureshy, Sayed H R Abdi, Hari C Bajaj. Asymmetric hydrolytic kinetic resolution with recyclable macrocyclic Co(III)-salen complexes: a practical strategy in the preparation of (R)-mexiletine and (S)-propranolol. Chemistry (Weinheim an der Bergstrasse, Germany). 2012 Apr 23;18(17):5256-60