Enantioselective synthesis of ( S)-timolol via kinetic resolution of terminal epoxides and dihydroxylation of allylamines

Abstract

An efficient enantioselective synthesis of ( S)-timolol has been described using chiral Co–salen-catalyzed kinetic resolution of less expensive (±)-epichlorohydrin with 3-hydroxy-4-( N-morpholino)-1,2,5-thiadiazole in good overall yield (55%) and excellent enantioselectivity (98%). Synthesis of ( S)-timolol has also been achieved using hydrolytic kinetic resolution as well as asymmetric dihydroxylation routes in 90% ee and 56% ee, respectively.