The Ru-catalyzed enantioselective preparation of chiral halohydrins and their application in the synthesis of (R)-clorprenaline and (S)-sotalol

The asymmetric transfer hydrogenation of a series of halo-substituted aryl methyl ketones, including those substituted in both α-methyl and aryl rings, was studied for the preparation of chiral halohydrins. Up to 99.7% ee was obtained with 2-chloro-1-(2-chlorophenyl)ethanone as the substrate and Ru-CsDPEN as the catalyst in an HCOONa/H2O system. (R)-Clorprenaline, a drug used in the treatment of respiratory disorders, such as bronchitis and asthma, and (S)-sotalol, a class-III antiarrhythmic compound, were prepared with these chiral halohydrins.

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(R)-ClorprenalineC11H16ClNO[α]D25=-71.6 (c 1.5, EtOH)Source of Chirality: Asymmetric transfer hydrogenationAbsolute configuration: (R)

(S)-SotalolC12H21ClN2O3O[α]D25=+33.6 (c 1.0, H2O)Absolute configuration: (S)