Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
57255 | Catalysis Today | 2009 | 10 Pages |
Abstract
We describe the Ru-catalyzed ring-closing metathesis (RCM) reaction of a densely functionalized diene leading to the 15-membered ring of HCV protease inhibitor BILN 2061. The evaluation of several catalysts led us to the discovery of a new epimerization reaction which plagued our initial attempts to scale-up the reaction. A mechanistic study of this side reaction is described. Factors that may contribute to render our RCM sub-optimal were identified in the low initiation rate of the best catalyst (first-generation Hoveyda), to yield what seems to be a highly stabilized and perhaps catalytically inactive intermediate. Preliminary efforts to affect the initiation site by substrate modification are also discussed.
Related Topics
Physical Sciences and Engineering
Chemical Engineering
Catalysis
Authors
Vittorio Farina, Xingzhong Zeng, Xudong Wei, Yibo Xu, Li Zhang, Nizar Haddad, Nathan K. Yee, Chris H. Senanayake,