Ruthenium carbene complex catalysts

Although numerous examples of successful RCM reactions have been demonstrated, a few limitations and/or side-reactions have been uncovered. Some cases where the RCM reaction proceeds with complications are depicted in Scheme 18. Sometimes RCM reactions are competitive with alkene isomerization. For example, the unexpected formation of 162 from precursor 160 was attributed to alkene isomerization (affording 161), followed by RCM to afford the ring-contracted compound 162. Later investigators went on to exploit this observation for the synthesis of cyclic enol ethers. Treatment of the allyl ether 164 with a ruthenium carbene complex catalyst affords the RCM... 

Acyclic diene molecules are capable of undergoing intramolecular and intermolec-ular reactions in the presence of certain transition metal catalysts molybdenum alkylidene and ruthenium carbene complexes, for example [50, 51]. The intramolecular reaction, called ring-closing olefin metathesis (RCM), affords cyclic compounds, while the intermolecular reaction, called acyclic diene metathesis (ADMET) polymerization, provides oligomers and polymers. Alteration of the dilution of the reaction mixture can to some extent control the intrinsic competition between RCM and ADMET. 

Ruthenium hydride complexes, e.g., the dimer 34, have been used by Hofmann et al. for the preparation of ruthenium carbene complexes [19]. Reaction of 34 with two equivalents of propargyl chloride 35 gives carbene complex 36 with a chelating diphosphane ligand (Eq. 3). Complex 36 is a remarkable example because its phosphine ligands are, in contrast to the other ruthenium carbene complexes described so far, arranged in a fixed cis stereochemistry. Although 36 was found to be less active than conventional metathesis catalysts, it catalyzes the ROMP of norbornene or cyclopentene. 

For the last 2 decades ruthenium carbene complexes (Grubbs catalyst first generation 109 or second generation 110, Fig. 5.1) have been largely employed and studied in metathesis type reactions (see Chapter 3) [31]. However, in recent years, the benefits of NHC-Ru complexes as catalysts (or pre-catalysts) have expanded to the area of non-metathetical transformations such as cycloisomerisation. 

Quite recently, ruthenium carbene complexes more typically known as olefin metathesis catalysts have been shown to act as alkyne hydrosilylation catalysts.78,79 7Vzz r-addition is the major product with trialkylsilanes, even in a single example with an internal alkyne.78 This result represents one of the very few examples of fra r-hydrosilylation of internal alkynes. 

The olefin binding site is presumed to be cis to the carbene and trans to one of the chlorides. Subsequent dissociation of a phosphine paves the way for the formation of a 14-electron metallacycle G which upon cycloreversion generates a pro ductive intermediate [ 11 ]. The metallacycle formation is the rate determining step. The observed reactivity pattern of the pre-catalyst outlined above and the kinetic data presently available support this mechanistic picture. The fact that the catalytic activity of ruthenium carbene complexes 1 maybe significantly enhanced on addition of CuCl to the reaction mixture is also very well in line with this dissociative mechanism [11] Cu(I) is known to trap phosphines and its presence may therefore lead to a higher concentration of the catalytically active monophosphine metal fragments F and G in solution. 

The ruthenium carbene complexes 1 discussed in the previous chapter have set the standards in the field of olefin metathesis and are widely appreciated tools for advanced organic synthesis [3]. A serious drawback, however, relates to the preparation of these compounds requiring either 3,3-diphenylcyclopropene or diazoalkanes, i.e. reagents which are rather difficult to make and/or fairly hazardous if used on a large scale [60]. Therefore, a need for metathesis catalysts persists that exhibit essentially the same activity and application profile as 1 but are significantly easier to make. 

Intermolecular enyne metathesis has recently been developed using ethylene gas as the alkene [20]. The plan is shown in Scheme 10. In this reaction,benzyli-dene carbene complex 52b, which is commercially available [16b], reacts with ethylene to give ruthenacyclobutane 73. This then converts into methylene ruthenium complex 57, which is the real catalyst in this reaction. It reacts with the alkyne intermolecularly to produce ruthenacyclobutene 74, which is converted into vinyl ruthenium carbene complex 75. It must react with ethylene, not with the alkyne, to produce ruthenacyclobutane 76 via [2+2] cycloaddition. Then it gives diene 72, and methylene ruthenium complex 57 would be regenerated. If the methylene ruthenium complex 57 reacts with ethylene, ruthenacyclobutane 77 would be formed. However, this process is a so-called non-productive process, and it returns to ethylene and 57. The reaction was carried out in CH2Cl2 un-... 

A Soluble Polymer-Bound Ruthenium Carbene Complex A Robust and Reusable Catalyst for Ring-Qosing Olefin Metathesis, Q. Yao, Angew. Chem. 2000,... 

In traditional synthetic organic chemistry, the Wittig reaction plays an important role in carbon-carbon bond extension from the carbonyl group. CM is an attractive alternative for carbon-carbon extension from a terminal alkene. In fact, a pyrroh-dine ring of anthramycin derivative 55 has been constructed by RCM of 52, and the sidechain has been extended by CM of terminal alkene of 54 with ethyl acrylate. " In the CM, ruthenium carbene complex Ij, reported by Blechert, gives a good result since the ligand of the catalyst easily dissociated from the ruthenium metal at room temperature ... 

Reuse of Catalysts in Ring-Closure Metathesis with an Ionic Tagged Ruthenium Carbene Complex (188)... 

It has been shown that ruthenium carbene complex lb developed for olefin metathesis can catalyze RCM of enynes. Using this catalyst lb, five- to nine-membered ring compounds 3 are synthesized from enyne 2 (Scheme j) i Sa-iSc The reaction procedure for RCM of an enyne is very simple. A benzene solution of enyne 2b is stirred in the presence of 1 mol% of ruthenium carbene complex lb at room temperature (RT) under argon gas to give cyclic compound 3b having a diene moiety. 

Subsequently, alternative syntheses of sulfoximine-containing heterocycles were studied, and one such approach was based on Grubbs olefin metathesis reaction. Using the ruthenium carbene complex 39 as catalyst, a wide range of... 

Metallocene complexes of early transition metals [Cp2MR R2] (R1, R2 = H, alkyl, M = Zr, Ti, Hf) are active and selective catalysts in semi hydrogenation of dienes.431 Two ruthenium-carbene complexes display high activity in alkene hydrogenation, which may be further enhanced by the addition of HBF4-OEt2.432 A turnover number of 12,000 h 1 was obtained. 

With the discovery of ruthenium carbene complexes as highly effective catalysts for olefin metathesis under mild reaction conditions [233,234], the scope of ring-opening metathesis polymerization could be extended to include functionalized and sensitive monomers. The resulting (soluble) polymers have been used as supports for simple synthetic transformations [235-237]. Insoluble polymers have been prepared by ringopening metathesis copolymerization of norbornene with l,4,4a,5,8,8a-hexahydro-1,4,5,8-exo-endo-dimethanonaphthalene. These polymers have been used as supports for ruthenium carbene complexes [238]. 

Dihydropyrroles have recently become readily available by ring-closing metathesis. For this purpose, N-acylated or N-sulfonylated bis(allyl)amines are treated with catalytic amounts of a ruthenium carbene complex, whereupon cyclization to the dihydropyrrole occurs (Entries 6 and 7, Table 15.3 [30,31]). Catalysis by carbene complexes is most efficient in aprotic, non-nucleophilic solvents, and can also be conducted on hydrophobic supports such as cross-linked polystyrene. Free amines or other soft nucleophiles might, however, compete with the alkene for electrophilic attack by the catalyst, and should therefore be avoided. 

Organosubstituted octasilsesquioxanes (Fig. lb) have also been prepared by cross-metathesis (CM) and silylative coupling of vinylsilsesquioxane with olefins in the presence of the ruthenium carbene complex Cl2(PCy3)2Ru(=CHPh) (Grubbs catalyst) and Ru-H (Ru-Si) complexes, for example, RuHCl(CO)(PCy3)2, respectively [57]. 

The ruthenium carbene complex (Grubbs catalyst) which has shown high efficiency in alkene methathesis and related processes, since it displays tolerance toward a wide variety of common functional groups, has also appeared of synthetic utility in the hydrosilylation of ketones to yield silyl ethers-one of the most widely used classes of protecting groups in synthetic chemistry (Eq. 97) [ 151 ]. The reaction requires temperatures above 50 °C, which generate a slightly increased amount of silylated by-products. 

In a related observation, Furstner and co-workers reported that while both the FMC and the MC2 lead to the same E Z alkene ratio in the case of 18-RCM, the use of the same conditions with 19 leads to product enriched selectively in either of the two isomers <02MI657> depending on catalyst selection (Scheme 9). Furstner notes that this "illustrates the subtle influence of remote substituents on the stereochemical outcome of RCM in the macrocyclic series." Studies concerning the effects of chelation of the reactivity of ruthenium carbene complexes were reported by Furstner and co-workers <02OM331>. Paquette and co-workers observed that the use of either the GMC or the MC2 led to different outcomes in the macrocyclization RCM of 1,2-amino-alcohol-templated ene-dienes <02HCA3033, 02MI615> hinting that catalyst selection is also an important consideration in those processes. 

Several catalysts for ring-closing metathesis are now known. Prominent examples are shown in Scheme 1 the molybdenum carbene complex 8, introduced by Schrock et al. [4], methyltri-oxorhenium 9, discovered by Herrmann et al. [5] and the ruthenium carbene complex 10, developed by Grubbs et al. [6]... 

This chapter is concerned specifically with olefin metathesis reactions catalyzed by ruthenium-carbene complexes, mainly because of their great success during recent years. We begin with an overview of these catalysts, and then focus on mechanistic considerations that are important for understanding the reactivity profiles of various catalyst derivatives. The second part of the chapter deals with applications of ruthenium-catalyzed olefin metathesis, especially RCM, CM, and combination processes in organic synthesis. 

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