Alkene metathesis precatalyst

A relatively new class of alkene metathesis precatalysts has emerged that contains the highly conjugated indenylidene fragment (Chapter 14). The ruthenium carbene is geminally disubstituted and easily prepared. Representative examples of these complexes (32-36) are shown in Figure 9.1. 

Figure 2.2 Selected examples of A/-heterocyclic carbene (NHQ ligands used for ruthenium-based alkene metathesis precatalysts.

Typical alkene metathesis precatalysts take the form displayed in Figure 2.3, consisting of a ruthenium(II) center, a carbene with substituent R, two anionic ligands X (typically chloride), a nondissociating l and L (typically a trialkylphosphine or NHC), and a dissociating ligand, which is most often either a phosphine or a chelating alkoxyarene. While the nature of X, L,, and R all influence the initiation rate and mechanism, it is the nature of L and X that detemiine the catalytic activity of the active species itself complexes G2, M2, and GH2 all produce the same active species, albeit via different mechanisms and at different rates. 

We will focus on the development of ruthenium-based metathesis precatalysts with enhanced activity and applications to the metathesis of alkenes with nonstandard electronic properties. In the class of molybdenum complexes [7a,g,h] recent research was mainly directed to the development of homochi-ral precatalysts for enantioselective olefin metathesis. This aspect has recently been covered by Schrock and Hoveyda in a short review and will not be discussed here [8h]. In addition, several important special topics have recently been addressed by excellent reviews, e.g., the synthesis of medium-sized rings by RCM [8a], applications of olefin metathesis to carbohydrate chemistry [8b], cross metathesis [8c,d],enyne metathesis [8e,f], ring-rearrangement metathesis [8g], enantioselective metathesis [8h], and applications of metathesis in polymer chemistry (ADMET,ROMP) [8i,j]. Application of olefin metathesis to the total synthesis of complex natural products is covered in the contribution by Mulzer et al. in this volume. 

Among the R2C(=C) =Ru homologs promoting alkene metathesis the most recent discoveries deal vhth the allenylidene-ruthenium and related pre-catalysts. This chapter is devoted to the class of ruthenium-allenylidene metathesis precatalysts, their intramolecularly rearranged indenylidene catalysts, and their use in... 

Castarlenas, R., Fischmeister, C., Bruneau, C., Dixneuf, P. H. Allenylidene-ruthenium complexes as versatile precatalysts for alkene metathesis reactions. J. Mol. Catal. A Chemical 2004, 213, 31-37. 

The next critical step was to measure the alkene binding step. To investigate this, the partitioning of the 14-electron reactive intermediate between productive alkene metathesis (Step 2) reversion back to precatalyst (A .i) was probed. Unfortunately, the rate of alkene binding could not be directly determined instead, the metathesis efficiency ratio k /t2 was kinetically determined from a plot of 1//Toi,s versus [CygP]/[alkene]. 

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. 

The development of new precatalysts for alkene metathesis has been a highly active and creative area of research. The number of new precatalysts being produced continues at a dizzying pace. However, few meet the needs of stability, efficiency, and activity required for a useful catalyst. That said, there are still many useful precatalysts available to choose from. Precatalyst selection depends on many considerations, but one must take into account the initiation rate, either as a pure measure of the efficiency of conversion to an active form of the catalyst or to help determine initial precatalyst loading. It is important to note, however, that a fast initiator does not always finish the race. This is because initiation alone does not determine how well the catalyst is matched to the reactivity of the reactants in a given application. However, initiation rates can help guide catalyst selection and will narrow the field to a few select precatalysts to screen for a desired application. 

Alkene metathesis has grown from a niche technique to a common component of the synthetic organic chemistry toolbox, driven in part by the development of more active catalyst systems, or those optimized for particular purposes. While the range of synthetic chemistry achieved has been exciting, the effects of structure on reactivity have not always been particularly clear, and rarely quantified. Understanding these relationships is important when designing new catalysts, reactions, and syntheses. Here, we examine what is known about the effect of structure on reactivity from two perspectives the catalyst, and the substrate. The initiation of the precatalyst determines the rate at which active catalyst enters the catalytic cycle the rate and selectivity of the alkene metathesis reaction is dependent on how the substrate and active catalyst Interact. The tools deployed in modern studies of mechanism and structure/activity relationships in alkene metathesis are discussed. 

During the past two decades, the alkene metathesis reaction has developed from its early appUcations in large-scale processes with heterogeneous and ill-defined catalyst systems to a standard technique in synthetic chemistry and polymer laboratories. The development of well-defined and often bench-stable precatalysts " has been key to the widespread use of alkene metathesis in modem target synthesis projects. The impact of this useful reaction was recognized in 2005 by the award of the Nobel Prize in Chemistry to Yves Chauvin, Robert Gmbbs, and Richard Schrock. Astmc has published an excellent article on the early history of the alkene metathesis reaction, which covers the determination of the mechanism and the rejection of alternative hypotheses, so this early history will not be discussed here. 

This chapter will focus almost exclusively on alkene metathesis catalyzed by well-defined homogeneous ruthenium-catalyst systems and is divided into three sections (1) a discussion of how precatalyst structure affects the rate and mechanism of initiation in two key series of metathesis precatalysts (2) a discussion of how substrate structure, both close to and remote from the alkene termini, affects the rate and selectivity of alkene metathesis in synthetic chemistry and (3) the tools that have been used by experimental and theoretical chemists to study alkene metathesis reactions. In each case, the discussion will be focused on the specific topics interested readers are referred to a recent article which covers a wider range of the mechanistic aspects of alkene metathesis with ruthenium complexes, albeit in less depth. 

Mass spectrometry (MS) studies have played a key role in the study of metathesis reactions, particularly in the hands of Chen and coworkers, who have identified intermediates in the catalytic cycle,and probed the energetics of their reactions, using electrospray MS techniques. Species such as 14e ruthenium carbene complexes can be detected by MS in the presence of different alkene substrates, the different carbene products (from CM or ROMP, for example) can be detected. Further, the fragments into which any proposed species can be broken by successively higher lens potentials can be used to check the species structure. In successive and more advanced studies, interpretation of data from the energy-resolved, coUision-induced dissociation cross-section measurements allowed the construction of potential energy surfaces for some steps of the metathesis reaction.Metathesis precatalysts were typically custom-made species, modified with ionic tags, to facilitate detection by MS. 

In summary, we have presented and discussed selected examples of (predominantly experimental) studies of how stmcture can affect reactivity, broadly divided into how precatalyst stmcture affects the rate of dehvery of the active catalyst into solution, and how the stmcture of the substrate affects its reactivity in alkene metathesis reactions. 

Heppekausen J, Piirstner A. Rendering schrock-type molybdenum alkylidene complexes air stable user-friendly precatalysts for alkene metathesis. Angew Chem Int Ed. 2011 50(34) 7829-7832. 

In the presence of diazo compounds 9, enynes 10 containing a fluorinated amino acid moiety could be transformed into fluorinated alkenyl bicyclo[4.1.0]heptane amino acid derivatives 11 using Cp (Cl)Ru(COD) as the precatalyst (Scheme 5.5) [12], In this process, the in situ-generated catalyst from ruthenium complex and diazo compound completely inhibits RCM of enyne to the profit of cascade alkenyl-ation/cyclopropanation. The Cp (Cl)Ru moiety in ruthenacyclobutane is believed to favor reductive elimination versus expected alkene metathesis. 

The overall conversion, formally described as alkane metathesis, consists of three steps alkane dehydrogenation, alkene metathesis, and hydrogenation. As shown by reaction 7.3.3.3, an iridium pincer complex (see Section 2.3.5) is used in the first step as the precatalyst. Here the thermodynamically unfavorable dehydrogenation of the alkane to alkene is achieved. Notice that in this reaction other isomers of the alkene may also be produced. 

Density Functional Theory Computational Study of Phosphine Ligand Dissociation versus Hemilability in a Grubbs-Type Precatalyst Containing a Bidentate Ligand during Alkene Metathesis... 

M. Jordaan and H. C. M. Vosloo. A DPT computational study of phosphine ligand dissociation versus hemilability in a Grubbs-type precatalyst containing a bidentate ligand during alkene metathesis. Mol. Simul. 34, 2008, 10-15. 

A first evaluation of complex 71a by Blechert et al. revealed that its catalytic activity differs significantly from that of the monophosphine complex 56d [49b]. In particular, 71a appears to have a much stronger tendency to promote cross metathesis rather than RCM. Follow-up studies by the same group demonstrate that 71a allows the cross metathesis of electron-deficient alkenes with excellent yields and chemoselectivities [50]. For instance, alkene 72 undergoes selective cross metathesis with 3,3,3-trifluoropropene to give 73 in excellent yield and selectivity. Precatalyst 56d, under identical conditions, furnishes a mixture of 73 and the homodimer of 72 (Scheme 17) [50a]. While 56d was found to be active in the cross metathesis involving acrylates, it failed with acrylonitrile [51]. With 71a, this problem can be overcome, as illustrated for the conversion of 72—>74 (Scheme 17) [50b]. 

The cross metathesis of acrylic amides [71] and the self metathesis of two-electron-deficient alkenes [72] is possible using the precatalyst 56d. The performance of the three second-generation catalysts 56c,d (Table 3) and 71a (Scheme 16) in a domino RCM/CM of enynes and acrylates was recently compared by Grimaud et al. [73]. Enyne metathesis of 81 in the presence of methyl acrylate gives the desired product 82 only with phosphine-free 71a as a pre-... 

The catalytic cycle proposed for the rhodium-porphyrin-based catalyst is shown in Fig. 7.18. In the presence of alkene the rhodium-porphyrin precatalyst is converted to 7.69. Formations of 7.70 and 7.71 are inferred on the basis of NMR and other spectroscopic data. Reaction of alkene with 7.71 gives the cyclopropanated product and regenerates 7.69. As in metathesis reactions, the last step probably involves a metallocyclobutane intermediate that collapses to give the cyclopropane ring and free rhodium-porphyrin complex. This is assumed to be the case for all metal-catalyzed diazo compound-based cyclo-propanation reactions. 

These classifications demonstrate the superior reactivity of the second-generation precatalysts substrates that react slowly with Gl, such as 1,1-disubstituted alkenes, wiU often undergo metathesis mediated by G2, for example. 

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