Asymmetric Synthesis of MK-0499

Described herein is an efficient asymmetric synthesis of the potent antiarrhthymia agent MK-0499. The route is convergent and is highlighted by two stereoselective reactions. A ruthenium-catalyzed, enantioselective hydrogenation of an enamide was developed for the preparation of the key amine interm...

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Bibliographic Details
Published inJournal of organic chemistry Vol. 60; no. 14; pp. 4324 - 4330
Main Authors Tschaen, David M, Abramson, Lee, Cai, Dongwei, Desmond, Richard, Dolling, Ulf-H, Frey, Lisa, Karady, Sandor, Shi, Yao-Jun, Verhoeven, Thomas R
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 01.07.1995
Amer Chemical Soc
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
KETONES
AZIDES
REDUCTION
BORANE
AMINES
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Summary:Described herein is an efficient asymmetric synthesis of the potent antiarrhthymia agent MK-0499. The route is convergent and is highlighted by two stereoselective reactions. A ruthenium-catalyzed, enantioselective 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.
Bibliography:istex:F2ECAC1563757F4B78811DE431F5B7C5B5122B6C
ark:/67375/TPS-S9LWH8XF-S
ISSN:0022-3263
1520-6904
DOI:10.1021/jo00119a008