Metathesis Side Reactions

Isomerization can also be observed with the Grubbs ruthenium catalysts, both before and after metathesis. The isomerization reaction is believed to be catalysed by ruthenium hydride species, such as 8.460, generated by decomposition of the Grubbs catalyst.  

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Selectivity to primary metathesis products is usually less than 100%, as a consequence of side reactions, such as double-bond migration, dimerization, oligomerization, and polymerization. The selectivity can be improved by adding small amounts of alkali or alkaline earth metal ions, or, as has recently been shown, thallium 40), copper, or silver ions (41)-... 

Contradictory to a carbene mechanism is the high selectivity which is typical for the metathesis reaction. In the case of carbene complexes, side reactions must be expected, such as addition and insertion [Eqs. (38) and (39)] ... 

Because in metathesis reactions with most catalyst systems a selectivity of nearly 100% is found, a carbene mechanism seems less likely. Banks and Bailey ( ) reported the formation of small quantities of C3-C6-alkenes, cyclopropane, and methylcyclopropane when ethene was passed over Mo(CO)6-A1203, which suggests reactions involving carbene complexes. However, similar results have not been reported elsewhere most probably the products found by Banks and Bailey were formed by side reactions, typical for their particular catalyst system. 

These limitations were overcome with the introduction of the well-defined, single-component tungsten and molybdenum (14) alkylidenes in 1990. (Fig. 8.4).7 Schrock s discoveiy revolutionized the metathesis field and vastly increased die utility of this reaction. The Schrock alkylidenes are particularly reactive species, have no side reactions, and are quite effective as polymerization catalysts for both ROMP and ADMET. Due to the oxophilicity of molybdenum, these alkylidenes are moisture and air sensitive, so all reactions using these catalysts must be performed under anaerobic conditions, requiring Schlenk and/or glovebox techniques. 

The obviation of side reactions is essential to the success of ADMET, and this can be realized if the proper catalyst is chosen. Catalyst choice must avoid the possibility of cation formation,13 vinyl addition, and/or formation of multiple catalytic species, all of which are detrimental to clean metathesis chemistry. Over the past 10 years, our group has utilized a variety of different catalysts, several of which are illustrated in Fig. 8.4. 

The use of stoichiometric ruthenium-NHC complexes generated in situ from [Ruljd-COCKp-cymene)], an imidazohnm salt [4] or an imidizol(idin)ium-2-carboxylate [4] has been applied in the cyclopropanation of styrene 5 with ethyl diazoacetate (EDA) 6 (Scheme 5.2). No base was necessary when imidazolium-2 carboxylate were employed. The diastereoselectivity was low and the cis/trans ratio was around 50/50 (Table 5.1). Although the diastereoselectivity was moderate, the reaction was highly chemoselectivity as possible side reactions (homologation, dimerisation and metathesis) were totally or partially suppressed. 

With the renaissance in alkene chemistry engendered by the rising versatility of olefin metathesis in both fine chemical and commodity production, new methods for alkene isomerization are of increasing interest and importance. Alkene isomerization can be performed using Bronsted-Lowry acid or base catalysis (1). However, these reactions are limited to substrates which tolerate carbanionic or carbocation intermediates, and are susceptible to undesired side reactions. 

As opinions regarding the metathesis reaction pathway have shifted in recent years to favor a nonpairwise carbene-to-metallocyclobutane transformation, increasing attention has been given to the mechanistic significance of cyclopropane olefin interconversions. This interconversion process seems to occur primarily when certain relatively inefficient catalysts are employed, which in itself raises questions. Under ideal conditions, "good metathesis catalysts are remarkably efficient promoters of transalkylidenation, and consequently are well suited for olefin and polymer syntheses. Thus, most early studies focused primarily on applications. When side reactions did occur, they were usually ignored or presumed to be trivial cationic processes. 

Alkene isomerization/migration is a potential side-reaction in olefin metathesis processes that can significantly decrease the yield of a desired product, particularly in reactions that employ electron-rich allylic or homoallylic... 

If the metathesis polymerization is performed in solution, the preferred solvents are methylene chloride or chlorobenzene. Preferably, the solvent is aprotic in order to avoid ionic side reactions. The molecular weight is controlled by the addition of an acyclic olefin, such as 1-butene (13). 

Alkylation processes usually combine isobutane with an alkene or with mixed alkene streams (C3-C5 olefins from FCC units). The best octane ratings are attained when isobutane is alkylated with butylenes. Alkylation of higher-molecular-weight hydrocarbons (>C5) is less economic because of increased probability of side reactions. Phillips developed a technology that combines its triolefin process (metathesis of propylene to produce ethylene and 2-butenes) with alkylation since 2-butenes yield better alkylate than propylene.290 Since ethylene cannot be readily used in protic acid-catalyzed alkylations, a process employing AICI3 promoted by water was also developed.291... 

With some catalyst systems, selectivity to primary metathesis products is near 100%, but side reactions (double-bond migration, dimerization, cyclopropanation, polymerization) often reduce selectivity. Such side reactions, such as oligomerization and double-bond shift over oxide catalysts, may be eliminated by treatment with alkali and alkaline-earth metal ions.26... 

For the cleavage of alkenes from a support by metathesis, several strategies can be envisaged. In most of the examples reported to date, ring-closing metathesis of resin-bound dienes has been used to release either a cycloalkene or an acyclic alkene into solution (Figure 3.38, Table 3.44). Further metathesis of the products in solution occurs only to a small extent when the initially released products are internal alkenes, because these normally react more slowly with the catalytically active carbene complex than terminal alkenes. If, however, terminal alkenes are to be prepared, selfmetathesis of the product (to yield ethene and a symmetrically disubstituted ethene) is likely to become a serious side reaction. This side reaction can be suppressed by conducting the metathesis reaction in the presence of ethene [782,783]. 

The 10-undecenoic acid motif has also been attached to isosorbide in the preparation of a fatty acid-/carbohydrate-based monomer [131]. ADMET polymerization in the presence of C3 and C4 produced fully renewable unsaturated polyesters (Scheme 18). Most importantly, the transesterification of these polyesters with MeOH, and subsequent analysis by GC-MS of the products, allowed for the quantification of double-bond isomerization during ADMET in a very simple manner. This strategy was then extended to fatty acid-based ADMET polyesters synthesized in the presence of indenylidene metathesis catalysts [132]. With these studies, the knowledge on the olefin isomerization in ADMET reactions was widened, and it is now possible to almost completely suppress this undesired side reaction. 

Metathetical polycondensation of acyclic dienes has not been successful with conventional catalysts used for the ring-opening metathesis polymerisation of cycloolefins, which is due to the fact that Lewis acids are usually present, and produce deleterious side reactions [13,16,17]. Only Lewis acid-free, well-defined catalysts have been successfully applied for acyclic diene metathesis polycondensation the key success has been to choose catalysts that obviate other pathways not involving the metathesis mechanism [18-20]. It was Wagener et al. [16,21] who first were able to convert an acyclic a, co-diene (1,9-decadiene), by using an acid-free metal alkylidene catalyst, to a high molecular weight... 

Catalyst decomposition is, overall, receiving little attention in academic work on homogeneous catalysis, and only in recent years has research on decomposition and stabilization of organometallic catalysts started to expand (116), with emphasis on reactions of significant commercial interest such as hydroformylation (117), metathesis 118), crosscoupling, and polymerization 119). Ligand decomposition seems to be a key issue for industrial application, because it affects the total number of turnovers, TON. Phosphine decomposition is an unavoidable side reaction in metal-phosphine complex-catalyzed reactions and the main barrier for commercial application of homogeneous catalysts. There are a few exceptions to this statement for example, the rhodium tppts-catalyzed hydroformylation of propene, a process developed by Ruhrchemie-Rhone Poulenc (now Celanese). 

Near-quantitative conversion of monomer to polymer is standard in these polymerizations, as few side reactions occur other than a small amount of cychc formation common in all polycondensation chemistry [41]. ADMET depolymerization also occurs when unsaturated olefins are exposed to pressures of ethylene gas [42,43]. In this case, the equilibriiun nature of metathesis is shifted towards low molecular weight products under saturation with ethylene. Due to the high catalytic activity of [Ru] and the abihty of [Mo] and [Ru] to create exact structures, ADMET has proven a valuable tool for production of novel polymer structures for material applications as well as model copolymer systems to help elucidate fundamental structure property relationships [5]. 

Many reactions afford, in addition to the naphthalene derivatives, mixtures of products. One of the major side reactions is the formation of indene derivatives directly from the metathesis intermediate without insertion of carbon monoxide. Other products frequently isolated as minor components are furans, cyclobutanones, and cyclopentenediones. The product distribution is dependent on numerous factors, including solvent, reaction temperature, concentration of the alkyne, and the nature of the aryl substituent. Molybdenum carbenes give, depending on the alkyne, either naphthols or indenes exclusively. The molybdenum Fischer carbenes can be tuned to give naphthoquinones by replacing one of the carbon monoxide ligands with a phosphine (Scheme 45). 

Grubbs reported tandem olefin metathesis/hydrogenation as a means to make satnrated cyclic prodncts and a one-pot RCM/transfer dehydrogenation/hydrogenation ronte to (R)-(-)-Mnscone utilizing (4a) (Scheme 19). Snapper and coworkers took advantage of the isomerization side reaction... 

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