ASYMMETRIC-SYNTHESIS OF MK-0499

Described herein is an efficient asymmetric synthesis of the potent an tiarrhthymia agent MK-0499. The route is convergent and is highlighted by two stereoselective reactions. A ruthenium-catalyzed, enantioselec tive hydrogenation of an enamide was developed for the preparation of the key amine intermediate. Oxazaborolidine-mediated ketone reduction was utilized to establish the alcohol stereochemistry. Optimization of this chemistry led to an IPA modified reduction method which provides enhanced stereoselectivity.