Olefin metathesis dimerization

During the total synthesis of (-)-cylindrocyclophane F, A.B. Smith et al. used the Danheiser benzannuiation to construct the advanced aromatic intermediate for an olefin metathesis dimerization reaction. The starting material triisopropylsilyloxyalkyne was synthesized from the corresponding ethyl ester using the Kowalski two-step chain homologation. ... 

Olefin metathesis is the transition-metal-catalyzed inter- or intramolecular exchange of alkylidene units of alkenes. The metathesis of propene is the most simple example in the presence of a suitable catalyst, an equilibrium mixture of ethene, 2-butene, and unreacted propene is obtained (Eq. 1). This example illustrates one of the most important features of olefin metathesis its reversibility. The metathesis of propene was the first technical process exploiting the olefin metathesis reaction. It is known as the Phillips triolefin process and was run from 1966 till 1972 for the production of 2-butene (feedstock propene) and from 1985 for the production of propene (feedstock ethene and 2-butene, which is nowadays obtained by dimerization of ethene). Typical catalysts are oxides of tungsten, molybdenum or rhenium supported on silica or alumina [ 1 ]. 

Bent ansa-metallocenes of early transition metals (especially Ti, Zr, Hf) have attracted considerable interest due to their catalytic activity in the polymerization of a-olefins. Ruthenium-catalyzed olefin metathesis has been used to connect two Cp substituents coordinated to the same metal [120c, 121a] by RCM or to connect two bent metallocenes by cross metathesis [121b]. A remarkable influence of the catalyst on E/Z selectivity was described for the latter case while first-generation catalyst 9 yields a 1 1 mixture of E- and Z-dimer 127, -127 is the only product formed with 56d (Eq. 19). 

If the cycloaddition and cycloreversion steps occurred under the same conditions, an equilibrium would establish and a mixture of reactant and product olefins be obtained, which is a severe limitation to its synthetic use. In many cases, however, the two steps can very well be separated, with the cycloreversion under totally different conditions often showing pronounced regioselectivity, e.g. for thermodynamic reasons (product vs. reactant stability), and this type of olefin metathesis has been successfully applied to organic synthesis. In fact, this aspect of the synthetic application of four-membered ring compounds has recently aroused considerable attention, as it leads the way to their transformation into other useful intermediates. For example aza[18]annulene (371) could be synthesized utilizing a sequence of [2 + 2] cycloaddition and cycloreversion. (369), one of the dimers obtained from cyclooctatetraene upon heating to 100 °C, was transformed by carbethoxycarbene addition to two tetracyclic carboxylates, which subsequently lead to the isomeric azides (368) and (370). Upon direct photolysis of these, (371) was obtained in 25 and 28% yield, respectively 127). Aza[14]annulene could be synthesized in a similar fashion I28). 

More recently, the same principle was applied by the same authors to cyclic alkanes for catalytic ring expansion, contraction and metathesis-polymerization (Scheme 13.24) [44]. By using the tandem dehydrogenation-olefin metathesis system shown in Scheme 13.23, it was possible to achieve a metathesis-cyclooligomerization of COA and cyclodecane (CDA). This afforded cycloalkanes with different carbon numbers, predominantly multiples of the substrate carbon number the major products were dimers, with successively smaller proportions of higher cyclo-oligomers and polymers. 

Figure 1.12 Target-accelerated synthesis of vancomycin dimers via olefin metathesis (n = 2 or 4).

Generally, in conclusion, it is worth noting that the molecular and immobilized complexes show very similar catalytic activity in terms of the initial TOP in olefin metathesis. However, the supported catalyst has a longer lifetime under catalytic conditions, which indicates that the effect of active-site isolation prevents some deactivation pathways such as dimerization of reachve intermediates [30]. 

Such higher order prerequisites could be fulfilled by ensemble operation of several sites. For example, a dimeric cluster of cuprous ions on silica gel is very active for the oxidation of CO with NzO at room temperature, but isolated cuprous ions are entirely inactive for this reaction 60). More interesting selectivity may be found in the reaction of olefins with methylene complexes the reaction of olefins with mononuclear methylene undergoes an olefin metathesis reaction, but the reaction of ethylene with bridging methylene in /i-CH2Co2(CO)2(Cp)2 61), /<-CH2Fe2(CO)8 (62), and /<-CH2-/i-ClTi(Cp)2Al(Me)2 (65) (Cp = cyclopentadiene) leads to propene formation (homologation reaction). 

Scheme 5.11 Reaction products obtained by intramolecular olefin metathesis ofthe hydrogen bonded dimer 5-5, identified by nH NMR and ESI-MS spectra.

As discussed before, the strategy to synthesize catenanes is not necessarily restricted to olefin metathesis as the ring closing reaction. Any reaction which can be carried out under conditions where the hydrogen-bonded dimers exist should be appropriate. A first example was realized by the formation of anhydride linkages with dicyclohexylcarbodiimide as the reagent in benzene as the solvent [57], as schematically illustrated in Scheme 5.19. 

Only one example of an NHC-containing olefin metathesis catalyst containing a transition metal other than ruthenium has been reported in the literature. The NHC-osmium complexes 53a and 53b (Scheme 2) are synthesized from the dichloro(i]6-p-cymene)osmium dimer by addition of the NHC prepared in situ and abstraction of the chloride, followed by introduction of the ben-zylidene moiety with phenyl diazomethane. 

Schreiber utilized intra-site olefin metathesis as a key step in synthesizing C2-symmetric fhnctionalized dimeric molecules for the close association of proteins. Both (2a) and (4a) were effective at 5 mol% giving very high conversions to the dimerized product (equation 66). The E. Z ratios of the linked bead dimerized molecules were similar to what was found in analogous solution reactions. 

Rhodium-based catalysis suffers from the high cost of the metal and quite often from a lack of stereoselectivity. This justifies the search for alternative catalysts. In this context, ruthenium-based catalysts look rather attractive nowadays, although still poorly documented. Recently, diruthenium(II,II) tetracarboxylates [42], polymeric and dimeric diruthenium(I,I) dicarboxylates [43], ruthenacarbor-ane clusters [44], and hydride and silyl ruthenium complexes [45 a] and Ru porphyrins [45 b] have been introduced as efficient cyclopropanation catalysts, superior to the Ru(II,III) complex Ru2(OAc)4Cl investigated earlier [7]. In terms of efficiency, electrophilicity, regio- and (partly) stereoselectivity, the most efficient ruthenium-based catalysts compare rather well with the rhodium(II) carboxylates. The ruthenium systems tested so far seem to display a slightly lower level of activity but are somewhat more discriminating in competitive reactions, which apparently could be due to the formation of less electrophilic carbenoid species. This point is probably related to the observation that some ruthenium complexes competitively catalyze both olefin cyclopropanation and olefin metathesis [46], which is at variance with what is observed with the rhodium catalysts. 

A.B. Smith and co-workers have devised an efficient strategy for the synthesis of the cylindrocyclophane family of natural products. Olefin ring-closing metathesis was used for the assembly of the [7,7]-paracyclophane skeleton. During their investigations they discovered a remarkably efficient CM dimerization process, that culminated in the total synthesis of both (-)-cylindrocyclophane A and (-)-cylindrocyclophane F. They established that the cross metathesis dimerization process selectively led to the thermodynamically most stable member of a set of structurally related isomers. Out of three commonly used ROM catalysts, Schrock s catalyst proved to be the most efficient for this transformation. 

Olefin additions to bridging alkylidenes yield dimetallacyclopentanes . These reactions also provide a mechanism for olefin metathesis, a topic not discussed here. Although addition of an olefin to a metal carbone, a 2n + In addition, would be symmetry forbidden in organic chemistry, ab initio calculations " of the conversion of a metal carbene-alkene to a metallocyclobutane show it to be a barrierless reaction. Metal d orbitals relax the symmetry restrictions for the In + 2n addition. The mechanism of reaction (p) has not been widely considered for the olefin polymerization, but it may be relevant to olefin dimerization and oligomerization—reaction (s), for example ... 

The polymerization of ether and thioether monomers was also studied, and it was found that the rate of polymerization was a great deal slower with the functionalized monomers. The number of methylene units between the olefin and the heteroatom greatly affected the rates observed, giving credence to the chelation effect shown in Fig. 6.1. In addition, catalyst 2 polymerizes 1,5-hexadiene, whereas catalyst 6 mainly cyclizes the metathesis dimer to cyclo-l,5-octadiene. At this point there is no clear explanation for this result, and, furthermore, the reason that the COD generated did not undergo ROMP in these reactions is unclear. The data from these experiments clearly shows that Lewis basic functionality retards the rate of metathesis with complex 6 more than with complex 2, although 6 is clearly the more functional group-tolerant complex overall [35]. 

The synthesis of vinylphosphonate-linked nucleotide dimer (93) has been achieved using an olefin-metathesis reaction step between the vinylphosphonate (91) and the 5 -alkene derivative of thymidine (92). The second-generation Grubb s catalyst was reported to be the superior catalyst for this conversion in which no vinyl phosphonate homo-coupling was detected. ... 

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