The chemistry of Ru cyclopropylmethylidene complexes: Mechanistic studies and synthetic implications for the ring-closing metathesis reaction

被引：6

作者：

Farina, Vittorio ^{[1
]}

Zeng, Xingzhong ^{[1
]}

Wei, Xudong ^{[1
]}

Xu, Yibo ^{[1
]}

Zhang, Li ^{[1
]}

Haddad, Nizar ^{[1
]}

Yee, Nathan K. ^{[1
]}

Senanayake, Chris H. ^{[1
]}

机构：

[1] Boehringer Ingelheim Pharmaceut Inc, Dept Chem Dev, Ridgefield, CT 06877 USA

来源：

CATALYSIS TODAY | 2009年 / 140卷 / 1-2期

关键词：

Ru cyclopropylmethylidene complexes; Ring-closing metathesis; Macrocyclization; Epimerization; Mechanistic study; OLEFIN-METATHESIS; PROTEASE INHIBITOR; NS3; PROTEASE; RUTHENIUM; BILN-2061; ISOMERIZATION; CATALYSTS; SCALE; ACID;

D O I：

10.1016/j.cattod.2008.07.024

中图分类号：

O69 [应用化学];

学科分类号：

070301 [无机化学];

摘要：

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. (C) 2008 Elsevier B.V. All rights reserved.

引用

页码：74 / 83

页数：10

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