Ruthenium carbene catalyst

The ruthenium carbene catalysts 1 developed by Grubbs are distinguished by an exceptional tolerance towards polar functional groups [3]. Although generalizations are difficult and further experimental data are necessary in order to obtain a fully comprehensive picture, some trends may be deduced from the literature reports. Thus, many examples indicate that ethers, silyl ethers, acetals, esters, amides, carbamates, sulfonamides, silanes and various heterocyclic entities do not disturb. Moreover, ketones and even aldehyde functions are compatible, in contrast to reactions catalyzed by the molybdenum alkylidene complex 24 which is known to react with these groups under certain conditions [26]. Even unprotected alcohols and free carboxylic acids seem to be tolerated by 1. It should also be emphasized that the sensitivity of 1 toward the substitution pattern of alkenes outlined above usually leaves pre-existing di-, tri- and tetrasubstituted double bonds in the substrates unaffected. A nice example that illustrates many of these features is the clean dimerization of FK-506 45 to compound 46 reported by Schreiber et al. (Scheme 12) [27]. 

With the development of an analogous ruthenium benzylidene catalyst 17 by Grubbs and co-workers in 1995, a ruthenium carbene catalyst suitable for the cross-metathesis reaction was in place [34]. Benzylidene 17 exhibited the same impressive tolerance of air and moisture, and the same stability towards functional groups as its predecessor 4, but benefited from easier preparation [35,36] and much improved initiation rates. 

Figure 16.16. The first isolated ruthenium carbene catalyst...

Another example is the ionic tagging of a ruthenium carbene catalyst for ringclosing alkene metathesis. A [-(CH2)4-MIM] PF6 moiety was built into the structure of the catalyst, which enabled the long-term retention of the catalyst in the [BMIM]PF6 ionic liquid for multiple recycles (188). 

A highly functionalized conjugated diene has been synthesized through sequential silicon-tethered ring-closing enyne metathesis by ruthenium-carbene catalyst Ic followed by Tamao oxidation (Equation (9)). ... 

The ruthenium carbene catalyst 19 is capable of effecting RCM of dienes bearing alcohol, aldehyde or carboxylic acid functions, with remarkably high yields (equation 33). 

Enyne intramolecular metathesis reactions, of the type shown in equation 61, can be very useful in organic synthesis. A number of such reactions, catalysed by tungsten or chromium carbene complexes, have been reported634,635,737 - 740. The ruthenium carbene catalysts 18-20 (Table 2) are likely to be increasingly used for this purpose because of their stability, ease of handling and good yields, as in the synthesis of various 5-, 6- and 7-membered heterocycles, e.g. equation 67741. 

With this experimental set-up, highly active, cationic ruthenium-carbene catalysts are used in ring-opening metathesis polymerization (ROMP). Four different structural features of the catalyst [ R2P(CH2) PR2-k2P XRu=CHR]+ (the halogen... 

Grubbs first well-defined ruthenium carbene catalyst ([Ru]) was introduced in the early 1990s as the first air stable metathesis catalyst allowing for manip-... 

The overall metathesis activity of this class of ruthenium-carbene catalysts is determined by the relative magnitudes of several rate constants (i) the rate constant of phosphine dissociation (fej), which dictates the rate at which the precatalyst complex enters the catalytic cycle (ii) the ratio of k i/k2. which dictates the rate of catalyst deactivation (by re-coordination of phosphine) versus catalytic turnover (by coordination of olefmic substrate and subsequent steps) and (iii) the rate constant of metallacyclobutane formation (k ), which dictates the rate of carbon-carbon bond formation. 

Case Study Developing a Ruthenium-Carbene Catalyst for Acrylonitrile Metathesis... 

The ruthenium carbene catalyst also effects the ring-closing metathesis of many acyclic dienynes to form fused bicyclic rings, containing five-, six-, and seven-... 

Recently, we found that Af-allyl-o-vinylaniline 44 gave 1,2-dihydroquinoline 45 by normal RCM and developed silyl enol ether-ene metathesis for the novel synthesis of 4-siloxy-l,2-dihydroquinoline and demonstrated a convenient entry to quinolines and 1,2,3,4-tetrahydroquinoline [13], We also have found a novel selective isomerization of terminal olefin to give the corresponding enamide 46 using ruthenium carbene catalyst [Ru] and silyl enol ether [14], which represented a new synthetic route to a series of substituted indoles 47 [12], We also succeeded an unambiguous characterization of ruthenium hydride complex [RuH] with A -heterocyclic carbene... 

The same authors later expanded the concept and additionaly provided an imidazolium-tagged Howeyda-Grubbs ruthenium carbene catalyst for the RCM reaction [260]. The resulting system proved to be highly active for the conversion of di-, tri- and tetrasubstituted diene and enyne substrates. In the catalyst solvent system [BMIM][PF6]-CH2Cl2 (volume ratios 1 1 to 1 9) the catalyst could be recycled 17 times with only very slight loss in activity. Also in this work it was demonstrated that the imidazolium tag is essential to obtain a stable and recycleable catalyst. 

The mechanism follows exactly the same sequence of events as before. First the ruthenium carbene catalyst undergoes [2 + 2] cycloaddition with the alkyne. The intermediate is now a metaUacyclobutene, and when the reverse [2 + 2] takes place the Ru carbene is still connected to the alkene product. 

The ruthenium carbene catalysts and 24 are two of the most widely used members of a large family of... 

It is supposed that similar to the ROMP of cycloolefins, initiated by bis-phosphine ruthenium carbenes (e.g. 4), one of the phosphines dissociates from the ruthenium center during RCM to free a coordination site where the olefin can bind and undergo a metathesis reaction. However, because of the dilute reaction medium to prevent the molecules to undergo a ROMP reaction, the active catalyst, which is now a four-coordinate species, is not stabilized enough to have an infinite lifetime. The lifetimes of 11 and 12 are much longer than of previous ruthenium carbene catalysts, because the pyridyl alkoxide ligands in 11 and 12 remain bonded to the metal, whereas the pyridyl ligands, e.g. in 9 and 10 are lost after the first metathesis reaction. 

Figure 3. RCM of BOC protected diallyl-amine (Scheme 8) with different ruthenium carbene catalysts.

Most alkene and enyne metathesis reactions are run in either chlorinated solvents or toluene. Chlorinated solvents, such as CH2CI2 or 1,2-dichloroethane (DCE), are excellent polar, aprotic solvents that dissolve most organic compounds, are easily purified, and have intermediate reflux temperatures. Because alkene metathesis commonly requires the loss of ethylene, reflux at moderate temperatures is desirable. Toluene is often the solvent of choice for the higher temperature conditions used for more sluggish applications. Most recently, Z-selective ruthenium carbene catalysts have been found to perform the best in tetrahydrofuran (THF). 

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... 

Figure 8.1 Ruthenium carbene catalysts used to generate biologically...

Scheme 5.8 Pathway for Z-selective olefin metathesis with ruthenium carbene catalysts.

With such an approach, the combination of diastereoselectivity and catalytic activity appears to be feasible. Catalyst stability, however, will remain a major challenge for ruthenium-carbene catalysts [20, 27]. 

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