Z-selective Ru metathesis catalysts

CM has, in most cases, a good to excellent ii-selectivity. This is primarily due to steric reasons in the metallacycle intermediate of the metathesis. The high ii-selectivity of the CM makes it an ideal method for the stereocontrolled synthesis of stilbenes [152], while there is still no highly Z-selective Ru-based catalyst known [153]. 

In order to give perspective on the kinetic versus thermodynamic balance, the cis-trans selectivity of some commonly utilized Ru metathesis catalysts is presented. A number of catalysts with modified ligands that result in a distinct stereochemical preference are then compared with these original catalysts and their reactivity discussed. Finally, the successful implementation of ligand-driven selectivity has led to three families of Ru-based metathesis catalysts that can perform Z-selective metathesis. For each of these catalyst families, a model for the origin of Z-selectivity, the role of ligands in influencing stereochemistry and trends in their reactivity are examined. 

Catalyst Structure and Cis-Trans Selectivity in Ruthenium-based Olefin Metathesis 33 2.4 Z-selective Ru-based metathesis catalysts 2.4.1 Thiophenolate-based Z-selective catalysts... 

A second design strategy based on choice of anionic ligand has proved successful in achieving Z-selective Ru-based metathesis catalysts by the Hoveyda group [37]. In contrast to the previous strategy, the selectivity of these catalysts relies on the formation... 

To date, three distinct strategies have been utilized to impose a preference for i yn-metal-lacycles in Ru-based olefin metathesis catalysts, resulting in three families of Z-selective catalysts. Promising initial reactivity has been observed with both thiophenolate- and dithiolate-based catalysts and both frameworks offer many opportunities for further tuning of activity and Z-selectivity. The cyclometallated catalysts have been further developed and have demonstrated high activity and Z-selectivity for a wide variety of substrates. However, in all cases, further improvements will be necessary to achieve Z-selective metathesis across the broad substrate scope demonstrated by previous generations of Ru-based catalysts. 

Scheme 7.16 (a) The first highly Z-selective Ru catalyst for cross-metathesis and olefin homodimerization reactions. Adapted from Ref [71]. 

Recent efforts have achieved Z-selective ruthenium carbene catalysts, providing a catalyst solution to a general problem in stereoselective alkene synthesis Diastereoselectivity in Olefin Metathesis Development of Z-Selective Ru Catalysts Vol 1, Chapter 3 Grubbs, Handbook of Metathesis, 2nd Edition, Volume 2, Chapter 7. As this is a relatively new field, mechanistic studies are... 

Accordingly, considerable effort has been dedicated to the development of olefin metathesis catalysts exhibiting kinetic selectivity. As a result, a number of Z-selective tungsten-, molybdenum-, and ruthenium-based olefin metathesis catalysts have been recently developed (For Mo- and W-based Z-selective catalysts [24-41], For Ru-based Z-selective catalysts [42-45], For cyclometalated Ru-based Z-selective catalysts [46-58]). Many of these systems exhibit consistently high levels of activity and selectivity across a broad range of substrates. Herein, we will focus specifically on the cyclometalated ruthenium-based catalysts developed in our laboratory [46-58]. This chapter is intended to provide a comprehensive summary of the evolution of these cyclometalated ruthenium catalysts, from their initial serendipitous discovery to their recent applications in Z-selective olefin metathesis transformations. Current mechanistic hypotheses and limitations, as well as future directions, will also be discussed. 

Earlier this year, the Grubbs group reported the preparation of the Ru-based catalyst with a chelating iV-heterocyclic carbene (NHC) ligand that catalyzes highly Z-selective olefin metathesis (Fig. 31) [69, 70]. This catalytic system provided similar levels of efficiency and selectivity to the W-alkylidene complexes for homocoupling reactions. The reason for the Z-selectivity is not clear at this point. Extension of the substrate scope of this catalytic system is expected. 

Fig. 31 New Ru-carbene catalyst for highly Z-selective olefin metathesis reactions...

Grubbs and coworkers studied a series of Ru-based catalysts and identified two lead catalysts for alkene cross metathesis that could provide the desired hetero-coupled product with high Z-selectivity for the resulting alkene moiety (Fig. 39) [91-93]. Comparably, Hoveyda and coworkers developed a number of Mo-based catalysts that enabled the selective synthesis of Z-alkenes [94, 95]. They successfully demonstrated that the novel molybdenum adamantylimido complexes (catalysts 154-156) could promote ring opening/cross metathesis (ROCM) of oxabicycle (157 or 158) in good yield and excellent Z-selectivity (Fig. 40) [96]. These elegant studies paved the way to develop further more effective catalysts for Z-selective alkene metathesis and utilize these methods for the synthesis of complex natural products. 

Only recently a selective crossed metathesis between terminal alkenes and terminal alkynes has been described using the same catalyst.6 Allyltrimethylsilane proved to be a suitable alkene component for this reaction. Therefore, the concept of immobilizing terminal olefins onto polymer-supported allylsilane was extended to the binding of terminal alkynes. A series of structurally diverse terminal alkynes was reacted with 1 in the presence of catalytic amounts of Ru.7 The resulting polymer-bound dienes 3 are subject to protodesilylation (1.5% TFA) via a conjugate mechanism resulting in the formation of products of type 6 (Table 13.3). Mixtures of E- and Z-isomers (E/Z = 8 1 -1 1) are formed. The identity of the dominating E-isomer was established by NOE analysis. 

The first reaction where Z selectivity was demonstrated with both MoAXi and Ru catalysts was the simple cross metathesis of one olefin substrate with itself to give the internal olefin dimer (e.g.. Figure 3.2). With Ru catalysts, high loadings (about 5 mol%) were initially required, but these have since been decreased to as low as 0.01 mol%. For the most part, only simple olefin substrates, such as... 

Catalysts continue to be developed for particular alkene metathesis applications, such as stereoselective cross metathesis. These precatalysts are tasked with selective metathesis and turnover, but must maintain Z-selectivity throughout the reaction. New ruthenium(II) species featuring a Ru-C bond have been recruited for this purpose. In a short time, reactivity gains and improved initiation rates have been achieved in this new area by manipulation of the X-type ligand. 

Liu P, XuX, DongX, et al. Z-Selectivity in Olefin Metathesis with Chelated Ru Catalysts Computational Studies of Mechanism and Selectivity. J dm Chem Soc. 2012 ... 

Khan RKM, Torker S, Hoveyda AH. Readily Accessible and Easily Modifiable Ru-Based Catalysts for Efficient and Z-Selective Ring-Opening Metathesis Polymerization and Ring-Opening/Cross-Metathesis. J Am Chem Soc. 2013 135(28) ... 

Thus, the treatment of metathesis precursor 142 with alkene 143 in the presence of catalyst [Ru]-ll (10mol%) furnished desired compound 144 in 61% yield with Z-selectivity Z/E = 5 1). Carbene 147 is proven to be a cata-lytically viable intermediate in the catalytic cycle. 

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