Metathese

Despite considerable localization of tt-electrons at the nitrogen atoms of pyrimidine, the ring system is still sufficiently aromatic to possess substantial stability. This is a great advantage in the primary synthesis of pyrimidines, in the synthesis of pyrimidines from the breakdown or modification of other heterocyclic systems and in the myriad of metatheses required to synthesize specifically substituted pyrimidines. 

Olefin metatheses are equilibrium reactions among the two-reactant and two-product olefin molecules. If chemists design the reaction so that one product is ethylene, for example, they can shift the equilibrium by removing it from the reaction medium. Because of the statistical nature of the metathesis reaction, the equilibrium is essentially a function of the ratio of the reactants and the temperature. For an equimolar mixture of ethylene and 2-butene at 350°C, the maximum conversion to propylene is 63%. Higher conversions require recycling unreacted butenes after fractionation. This reaction was first used to produce 2-butene and ethylene from propylene (Chapter 8). The reverse reaction is used to prepare polymer-grade propylene form 2-butene and ethylene ... 

In this process, which has been jointly developed by Institute Francais du Petrole and Chinese Petroleum Corp., the C4 feed is mainly composed of 2-butene (1-butene does not favor this reaction but reacts differently with olefins, producing metathetic by-products). The reaction between 1-butene and 2-butene, for example, produces 2-pentene and propylene. The amount of 2-pentene depends on the ratio of 1-butene in the feedstock. 3-Hexene is also a by-product from the reaction of two butene molecules (ethylene is also formed during this reaction). The properties of the feed to metathesis are shown in Table 9-1. Table 9-2 illustrates the results from the metatheses reaction at two different conversions. The main by-product was 2-pentene. Olefins in the range of Ce-Cg and higher were present, but to a much lower extent than C5. 

Both terminal and internal acyclic alkenes can be metathesized, corresponding to Eq. (4), where R is an alkyl group or a hydrogen atom. 

Cyclic dienes and polyenes, monocyclic as well as bicyclic, can be metathesized in the same way as cyclic monoenes. As expected, cyclobutene 27), 1,5-cyclooctadiene, and 1,5,9-cyclododecatriene 28) yield the same polyalkenamer, in this case polybutenamer (1,4-polybutadiene), since these reactants consist of the same base units, i.e.—(CH2)2CH==CH— ... 

Combination of lipase-catalyzed transesterification with unsaturated vinyl esters as acyl donors and ring-closing metatheses (RCMs) have also been reported [146-148]. Two groups applied this strategy for the synthesis of goniothalamin from cinnamaldehyde [147,148]. The key steps were a transesterification using vinyl acrylate as acyl donor, followed by an RCM, as depicted in Figure 6.55. 

The focus is on the primary formation of bonds, not on subsequent reactions of the products to form other bonds. These latter reactions are covered at the places where the formation of those bonds is described. Reactions in which atoms merely change their oxidation states are not included, nor are reactions in which the same pairs of elements come together again in the product (for example, in metatheses or redistributions). Physical and spectroscopic properties or structural details of the products are not covered by the reaction volumes which are concerned with synthetic utility based on yield, economy of ingredients, purity of product, specificity, etc. The preparation of short-lived transient species is not described. 

The use of tethered alcohols 50 for cyclizations in ring-closing metatheses (RCM) or as protection agents has already been briefly mentioned in Section 2.2. 

The reactivity of hydrido(ethoxo) complex 4 was examined (Scheme 6-15) [8]. Metatheses similar to those postulated for alcohol exchange (Eq. 6.5) occurred between HCl, LiCl, phenyl acetate or primary amines and yielded complexes 94. The reaction of 4 with cyclic anhydrides proceeded similarly to give iridium-assisted ring opening products 95. Heterocumulenes afforded the inserhon products 96 into the Ir-O bond. 

The monomer is the highest energy stage of the Durham synthesis of polyacetylene since the next stage, metathesized polymer, is known to be potentially explosive, the monomer is not likely to be absolutely safe. 

Heck reactions can also be combined with anion capture processes, animations, metatheses, aldol and Michael reactions, and isomerizations. The anion capture process has also been widely used with other Pd-catalyzed transformations. Outstanding examples of many different combinations have been developed by Grigg and coworkers, though not all of them match the requirements of a domino process. All of these reactions will be detailed here, despite the fact the nature of these intermediate transformations would also have permitted their discussion in Chapter 2. 

In contrast to the failure to metathesize terminal olefins, internal olefins such as cis-2-pentene can be metathesized to the extent of 50 turnovers. The chain terminating reaction in this case is rearrangement of intermediate ethylidene and propylidene complexes (equation 4). Both rearrangement of intermediate trisub-... 

Osborn s discovery (14) that aluminum halides bimTto oxo ligands in tungsten oxo neopentyl complexes, and that these complexes decompose to give systems which will efficiently metathesize olefins, raised more questions concerning the role of the Lewis acid. A subsequent communication (20) answered some of the questions the aluminum halide removes We oxo ligand and replaces it with two halides to yield neopentylidene complexes (equation 8). 

Additional aluminum halide coordinates to an axial halide to give a species which will metathesize olefins extremely efficiently. 

On the basis of the fact that tungsten(VI) alkylidene complexes will metathesize olefins one might predict that acetylenes should be metathesized by tungsten(VI) alkylidyne complexes (29). Acetylene metathesis is not unknown, but the catalysts are inefficient and poorly understood (30, 31). 

In view of the possibility of a-hydrogen transfer to metal, it remains possible that the metathesizing carbene complex has structure II rather than III [Eq. (13)] ... 

To summarize, experimental evidence has been advanced regarding hydride involvement in the initiation step of olefin metathesis with certain catalysts. One concept considers the source of the hydride to be external—that is, originating from a promoter or a cocatalyst. A second concept assumes a hydride being generated internally from the metathesizing olefin. It is quite possible that both concepts are operative. 

In a significant series of reports describing the formation of metathesislike products from cyclopropanes via a carbene retroaddition reaction, Gassman (68) also presented results that were interpreted to mean that carbenes which normally participate in conventional metatheses are negatively polarized (nucleophilic). 

The reactions reported by Casey (14) for a third carbene complex, (CO)5W=C(CH3)Ph, are not pertinent to the present topic because extremely rapid /8-H transfer to tungsten at -78°C initiates a sequence of reactions unique to this particular complex. This type of H transfer is atypical of conventional metatheses. 

In an attempt to further understand these observations, cis-directing catalysts for cyclopentene were examined in terms of their capability to metathesize acyclic olefins. 

The stereospecific catalysts capable of yielding high-cis polypentena-mers were found to be generally ineffective in metathesizing acyclic olefins. 

The first example of a heterogeneous catalyst able to metathesize olefinic esters was recently reported (92). The combination of Re207/ (CH3)4Sn at an olefin/Re/Sn molar ratio of 219/6/1 converted methyl 4-pentenoate at 50°C in 51% conversion to ethylene and the corresponding dimethyl ester of 4-octene-l,8-dioic acid. This reaction exhibited a high degree of selectivity (>99%), and in the absence of (CH3)4Sn the rhenium catalyst was inactive (90). 

Metatheses of 1,7-octadienes containing various functional groups are catalysed by ruthenium carbene complexes of the type 248. For instance, the alcohol 249 (R = CH2OH), the aldehyde 249 (R = CHO) and the carboxylic acid 249 (R = CO2H) are all converted into the corresponding cyclohexenes 250 in 82-88% yields (equation 127) and the heterocycles 252 (n = 0, 1 or 2) are efficiently produced from the amides 251 (equation 128)123. 

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