Selectivity in metathesis

Wallace DJ. Relay ring-closing metathesis—a strategy for achiev- 127. ing reactivity and selectivity in metathesis chemistry. Angew. 

Such olefins exist in cis and trans forms, and can undergo cis/trans isomerization by the metathesis reaction. Indeed when the olefin is symmetrical this is the only observable change, provided that there is no concomitant double-bond shift reaction. When the olefin is unsymmetrical there is an added point of interest, namely the extent to which a cis reactant gives rise to cis products, and a trans reactant to trans products. We have already touched on this important question of stereoselectivity in Section 3.3, and here we shall elaborate further in Section 6.7, after summarizing the cis/trans ratio observed for the products of metathesis of both alk-l-enes and alk-2-enes. The selectivities in metathesis of internal olefins are usually very high. 

Because in metathesis reactions with most catalyst systems a selectivity of nearly 100% is found, a carbene mechanism seems less likely. Banks and Bailey ( ) reported the formation of small quantities of C3-C6-alkenes, cyclopropane, and methylcyclopropane when ethene was passed over Mo(CO)6-A1203, which suggests reactions involving carbene complexes. However, similar results have not been reported elsewhere most probably the products found by Banks and Bailey were formed by side reactions, typical for their particular catalyst system. 

Abstract For many years after its discovery, olefin metathesis was hardly used as a synthetic tool. This situation changed when well-defined and stable carbene complexes of molybdenum and ruthenium were discovered as efficient precatalysts in the early 1990s. In particular, the high activity and selectivity in ring-closure reactions stimulated further research in this area and led to numerous applications in organic synthesis. Today, olefin metathesis is one of the... 

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]. 

Scheme 50 Epothilone synthesis via RCM between C9 and CIO dependence of chemo-selectivity on the size of the C12 substituent in metathesis substrates 244 [117]...

Fig. 3 Product selectivity in the metathesis of various acyclic alkanes...

In the case of olefin metathesis, the selectivity in initiation products can be understood in terms of minimization of the steric interactions in the metal-lacyclobutane intermediates (vide supra), which are governed by the relative position of the substituents the metallacyclobutane with substituents in pos-... 

The product selectivities in propane metathesis can also be explained by using the same model in which [1,3]- and [1,2]-interactions determine the ratio of products. For instance, the butane/pentane ratios are 6.2 and 4.8 for [(= SiO)Ta(= CHfBu)(CH2tBu)2] and [(= SiO)2Ta - H], respectively (Table 5). A similar trend is observed for the isobutane/isopentane ratio, which are 4.1 and 3.0, respectively. The higher selectivity in butanes (the transfer of one carbon via metallacyclobutanes involving [l,3]-interactions) than that of pentanes (the transfer of two carbons via metallacyclobutanes involving [1,2]-interactions) is consistent with this model (Scheme 28). 

While alkane metathesis is noteworthy, it affords lower homologues and especially methane, which cannot be used easily as a building block for basic chemicals. The reverse reaction, however, which would incorporate methane, would be much more valuable. Nonetheless, the free energy of this reaction is positive, and it is 8.2 kj/mol at 150 °C, which corresponds to an equihbrium conversion of 13%. On the other hand, thermodynamic calculation predicts that the conversion can be increased to 98% for a methane/propane ratio of 1250. The temperature and the contact time are also important parameters (kinetic), and optimal experimental conditions for a reaction carried in a continuous flow tubiflar reactor are as follows 300 mg of [(= SiO)2Ta - H], 1250/1 methane/propane mixture. Flow =1.5 mL/min, P = 50 bars and T = 250 °C [105]. After 1000 min, the steady state is reached, and 1.88 moles of ethane are produced per mole of propane consmned, which corresponds to a selectivity of 96% selectivity in the cross-metathesis reaction (Fig. 4). The overall reaction provides a route to the direct transformation of methane into more valuable hydrocarbon materials. 

At this early stage of comprehension of the interrelation between metathesis and cyclopropanation, many questions remain. Why is the formation of cyclopropanes such a rare occurrence with typical metathesis catalysts, yet favored with some zero-valent carbene complexes What is the role of prior complexation of the olefin with the metal in determining the reaction course for metal-carbene species How are typical metathesis carbenes polarized, and how does this polarization influence selectivity of metathesis reactions (e.g., regenerative metathesis of a-... 

A second observation was the fact that isomerization of the starting asymmetric olefin was much faster than the formation of new symmetric olefins. In fact, 40% of the initial cis olefin (Fig. 1) had isomerized to trans after only 4% conversion to new olefins. This result formally parallels the highly selective regenerative metathesis of a-olefins (60, 61), except that steric factors now prevail, because electronic effects should be minimal. Finally, the composition of the initially formed butene from r/j-4-methyl-2-pentene was essentially identical to that obtained when cA-2-pentene was used (18). When tra .v-4-methyl-2-pentene was metath-esized (Fig. 2), the composition of the initially formed butenes indicated a rather high trans specificity. 

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. 

McNaughton, B. R. Bucholtz, K. M. Camaano-Moure, A. Miller, B. L. Self-selection in olefin cross metathesis The effect of remote functionality. Org. Lett. 2005, 7, 733-736. 

Table 11.4 Activity and selectivity in propane metathesis by metal-hydrocarbyl and related metal-hydride surface species .

Group-selective enyne metathesis of dienyne 127f having a large substituent on the alkyne proceeds in the presence of aUcene 130 to give small ring compound 131... 

A series of zeolite-Y hosts containing different proton concentrations has been used for MTO encapsulation [80], and the resulting materials were studied for 1-hexene metathesis. The MTO molecule was activated by intra-zeolite protons, and simultaneously blocks their isomerisation activity. The ability to tune intra-zeolite acidity and the doping levels of the intact MTO precatalyst permits control over selectivity in the metathesis reaction. 

The CM of olefins bearing electron-withdrawing functionalities, such as a,/ -unsaturated aldehydes, ketones, amides, and esters, allows for the direct installment of olefin functionality, which can either be retained or utilized as a synthetic handle for further elaboration. The poor nucleophilicity of electron-deficient olefins makes them challenging substrates for olefin CM. As a result, these substrates must generally be paired with more electron-rich crosspartners to proceed. In one of the initial reports in this area, Crowe and Goldberg found that acrylonitrile could participate in CM reactions with various terminal olefins using catalyst 1 (Equation (2))." Acrylonitrile was found not to be active in secondary metathesis isomerization, and no homodimer formation was observed, making it a type III olefin. In addition, as mentioned in Section 11.06.3.2, this reaction represents one of the few examples of Z-selectivity in CM. Subsequent to this report, ruthenium complexes 6 and 7a were also observed to function as competent catalysts for acrylonitrile... 

A very common point for most of these processes is the presence of triarylpho-sphine bonded to gold in the catalytic system employed. This seems to be a crucial factor for achieving high selectivity in enyne metathesis. Thus, gold is the most active metal for catalyzing these processes using the mildest reaction conditions [147]. 

Ru catalysts were prepared and screened before 83 was identified as the most suitable. In addition, reactions were shown to be more selective in the presence of Nal. This important initial investigation is likely the harbinger of upcoming highly effective and practical chiral Ru-based metathesis catalysts. 

The maximal Y value for Cu-PPX catalyst is 1150 [116], It is much more than the activity of all known catalysts of this reaction. For comparison, the same reaction of C-Cl bond metathesis was investigated on the special prepared catalyst containing 1 mass% of high-dispersed metallic Cu deposited on silica. In conditions analogous to those of the reaction with the nanocomposite Cu-PPX film, Y for this catalyst was 4. Moreover, it has low selectivity in this case the formation of by-products from condensation processes takes place along with the main reaction, whereas Cu-PPX catalyst gives monochlorosubstituted decanes only [116]. 

The most recent method developed for the nA —> An approach relies on dynamic covalent bond formation using a metathesis reaction. In this case, reactions are typically under thermodynamic control, providing the potential for increased selectivity in product formation. The initial examples using alkyne metathesis toward the formation of SPMs were reported by Adams, Bunz, and coworkers using the precatalyst [Mo(CO)6] [27,28], but rather low yields of the desired products (4) limited general applicability (Scheme 6.2). Recent efforts by Moore and coworkers using a Mo(VI)-alkylidyne catalyst, however, have refined this process such that precipitation-driven reactions now provide moderate to excellent results (see Scheme 6.24) [29]. 

To achieve selectivity in these reactions, a steric or electronic bias is required to favour one particular product or (more importantly given the reversible nature of CM) one metal-alkylidene precursor in the catalytic cycle.1 In particular, it has been known for some time that metathesis reactions involving one highly electron deficient olefin partner can be selective (for the first example using acrylonitrile or styrene and 1 see Ref. [40]) however,readily available potential substrates such as enones, acrylates and acrylamides are generally incompatible with either 1 or 2 (for two reported exceptions see Ref. [41]). This was partially overcome by the use of acrolein acetals as a,/i-unsaturated car-... 

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