Metathesis reactions benzylidene catalysts

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. 

A subsequent publication by Blechert and co-workers demonstrated that the molybdenum alkylidene 3 and the ruthenium benzylidene 17 were also active catalysts for ring-opening cross-metathesis reactions [50]. Norbornene and 7-oxanorbornene derivatives underwent selective ring-opening cross-metathesis with a variety of terminal acyclic alkenes including acrylonitrile, an allylsilane, an allyl stannane and allyl cyanide (for example Eq. 34). 

Ring-closing metathesis, which has proved to be a popular route to the marine toxins, has found a further application as the key step in the synthesis of the pheromone (-)- and ( )-frontalin <99TL1425>. The precursor in this reaction is a mixture of the syn- and anri-isomers 39. Ring closure in the presence of a ruthenium benzylidene catalyst occurs within minutes at room temperature when only the syn-isomer cyclises to 40. The unreacted anri-isomer can be re-equilibrated for a further cyclisation. 

Metathesis of conjugated enyne-enes has been carried out using bispyridine-substituted ruthenium benzylidene catalyst li. An intramolecular version with conjugated enynes affords novel butadienyl cycloalkenes (Equation (8)). The reaction does not proceed with Ic or Ig. 

Thanks to the development of the Grubbs benzylidene catalyst (2) and other related ruthenium complexes, olefin metathesis has experienced spectacular advances over the past 10 years. The various incarnations of the reaction (acyclic diene metathesis, ring-closing metathesis, ring-opening metathesis polymerization, etc.) have now acquired first rank importance in synthesis. Clearly, the emergence of a similar, generic, efficient catalytic system for con-... 

Recently, De Clercq and Verpoort reported the synthesis of a new class of homobimetallic mthenium-benzylidene complexes bearing a Schiff base ligand (12a-f). These complexes proved to be highly efficient catalyst precursors in various olefin metathesis reactions 14) and atom transfer radical... 

Barbasiewicz et al. [99] reported on the Hoveyda-Grubbs metathesis catalyst bearing a chelating benzylidene ligand assembled on / en -substituted naphthalene 8.68, as shown in Eq. (8.22). In contrast to usual naphthalene-based compounds 8.67, it exhibits a very fast initiation behavior for a ring-closing metathesis reaction (Eq. (8.22)), which is attributed to a distorted molecular structure and reduced i-electron delocalization within a weakly stabilized six-membered chelate ring. 

Cavallo and coworkers [56] have explored the decomposition of the second-generation ruthenium methylidene and benzylidene catalysts induced by the coordination of % acids. Carbon monoxide (CO) was used as a model it-acid ligand in these computations, although it is not normaUy added during metathesis. The DFT calculations indicated that the coordination of CO trans to the Ru-alkylidene bond was highly exothermic and promoted a cascade of reactions with very low energy barriers (Scheme 7.11) [57]. The coordination of the % acid reduced the electron density on the alkylidene and thus promoted the... 

As previously discussed, the unfavorable equilibria associated with ligand dissociation during the initiation step of an olefin metathesis reaction have traditionally hindered the direct observation of metathesis-active ruthenacyclobutane intermediates [24]. Thus far, we have seen that the use of phosphonium alkylidene complexes, such as 22, can enable facile access to metallacycle formation by providing an alternative route for catalyst initiation. However, despite the utility of these trialkylphosphonium alkylidene catalysts, their preparation requires a multi-step synthetic route that requires the use of costly reagents [28]. In addition, the vinyl trialkylphosphonium salt generated following the reaction of 22 presents a less relevant model in comparison to the styrene (34) formed from the commercially available benzylidene catalysts. 

The large majority of the reports of solvent effects on olefin metathesis reactions have appeared in the area of Ru-based catalysis. Since the mechanistic studies of Grubbs and coworkers [2], others have attempted to elucidate the effects of solvent on the initiation rates of popular Ru-based catalysts, such as 3 and 4 (Scheme 12.2) [4]. The initiation rates show that, for the Ru-based catalyst 3, chlorinated solvents tend to lead to better rates of initiation. However, for the benzylidene catalyst 4, there are a wide variety of solvents that lead to higher rates of initiation than the popular dichloromethane. Interestingly, methyl t-butyl ether and dimethyl carbonate, which are considered sustainable solvents [5], afforded faster rates of initiation than dichloromethane. The authors also demonstrated that there was not an evident link between the solvent dielectric constant and initiation rate... 

The first report of NHC-containing osmium compounds acting as catalysts came from Esteruelas and co-workers in 2005. Thus, cationic benzyli-dene complexes 44 were prepared by reaction of the corresponding 16-electron precursors [(NHC)OsCl(p-cymene)][OTf] (NHC = IMes or IPr) with phe-nyldiazomethane, and their potential as initiators for olefin metathesis was probed in the RCM of diethyl diallylmalonate, the ROMP of cyclooctene, and a variety of self- and cross-metathesis reactions (Equation (7.10)). Although they were not as efficient as standard ruthenium-benzylidene metathesis initiators, compounds 44 displayed, nevertheless, a fairly decent activity. More importantly, in addition to being the first NHC-Os catalytic application, this study constituted a rare example of osmium catalysed C-C bond formation. 

Olefin-metathesis is a useful tool for the formation of unsaturated C-C bonds in organic synthesis.186 The most widely used catalysts for olefin metathesis include alkoxyl imido molybdenum complex (Schrock catalyst)187 and benzylidene ruthenium complex (Grubbs catalyst).188 The former is air- and moisture-sensitive and has some other drawbacks such as intolerance to many functional groups and impurities the latter has increased tolerance to water and many reactions have been used in aqueous solution without any loss of catalytic efficiency. 

The cyclization of this key intermediate to the fully protected conduritol F derivative 19 showcases the different performance of the standard metathesis catalysts. Despite the excellent track record of the original Grubbs benzylidene carbene complex 2 (7) for the cyclization of 6-membered rings, compound 18 reacts poorly with this particular catalyst in refluxing CH2C12, leading to only 32% conversion after 60h reaction time. This reluctance is likely caused by the preference of diene 18 to adopt a zig-zag-conformation holding the olefin units far apart. 

A new acyclic diene metathesis polymerization method has been developed using 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene)benzylidene mthenium(II) dichloride as catalyst. This reaction catalyst was used for preparing oligomers and polymers containing amino acids or polypeptides. 

In a first model reaction, Danopoulos et al. [472] reacted a free pincer carbene ligand with [RuCPPhjljCl ] and obtained the corresponding octahedral pincer carbene adduct (see Figure 3.156). The complex lacks the yhdene functionality necessary for activity of the complex in olefin metathesis. Instead, the compound was successfully employed in the transfer hydrogenation of cyclohexanone, acetophenone and benzylidene anihne. Reaction temperatures were mostly low to moderate (25-55 °C) and catalyst loadings in the range of 0.015 to 0.1% with TONs of only 150 to 8800. 

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