Metathesis processes

Sulfonates for Lube Additives. Most petroleum sulfonates used as lube additives are based on calcium or magnesium salts. These salts can be produced by direct neutralization of the sulfonic acid with Ca(OH)2 or Mg(OH)2, or by use of a metathesis process involving the sodium salt ... 

The olefins that undergo metathesis include most simple and substituted olefins cycHc olefins give linear high molecular-weight polymers. The mechanism of the reaction is beheved to involve formation of carbene complexes that react via cycHc intermediates, ie, metaHacycles. Industrial olefin metathesis processes are carried out with soHd catalysts (30). 

The metathesis process can be illustrated by a catalytic cycle, as follows ... 

The synthetic utility of the alkene metathesis reaction may in some cases be limited because of the formation of a mixture of products. The steps of the catalytic cycle are equilibrium processes, with the yields being determined by the thermodynamic equilibrium. The metathesis process generally tends to give complex mixtures of products. For example, pent-2-ene 8 disproportionates to give, at equilibrium, a statistical mixture of but-2-enes, pent-2-enes and hex-3-enes ... 

Figure 9-3. A flow diagram showing the metathesis process for producing polymer grade propylene from ethylene and 2-butene.

Depending on the types of unsaturated functional units involved in the metathesis process, the reactions can be classified into three major categories diene, enyne, and diyne metathesis (Figs. 1-3). Another mode of classification... 

Diene 265, substituted by a bulky silyl ether to prevent cycloaddition before the metathesis process, produced in the presence of catalyst C the undesired furanophane 266 with a (Z) double bond as the sole reaction product in high yield. The same compound was obtained with Schrock s molybdenum catalyst B, while first-generation catalyst A led even under very high dilution only to an isomeric mixture of dimerized products. The (Z)-configured furanophane 266 after desilylation did not, in accordance with earlier observations, produce any TADA product. On the other hand, dienone 267 furnished the desired macrocycle (E)-268, though as minor component in a 2 1 isomeric mixture with (Z)-268. Alcohol 269 derived from E-268 then underwent the projected TADA reaction selectively to produce cycloadduct 270 (70% conversion) in a reversible process after 3 days. The final Lewis acid-mediated conversion to 272 however did not occur, delivering anhydrochatancin 271 instead. 

An illustrative example of an alternative strategy (cf Fig. 11c) involving the use of a novel traceless linker is found in the multistep synthesis of 6-epi-dysidiolide (363) and several dysidiolide-derived phosphatase inhibitors by Waldmann and coworkers [153], outlined in Scheme 70. During the synthesis, the growing skeleton of 363 remained attached to a robust dienic linker. After completion of intermediate 362, the terminal olefin in 363 was liberated from the solid support by the final metathesis process with concomitant formation of a polymer-bound cyclopentene 364. Notably, during the synthesis it turned out that polymer-bound intermediate 365a, in contrast to soluble benzoate 365b, produced diene 367 only in low yield. After introduction of an additional linker (cf intermediate 366), diene 367 was released in distinctly improved yield by RCM. 

More research efforts have focused on the ring-closing enyne metathesis, which usually [176] provides conjugated vinyl cycloalkenes (cf Fig. 2a, exo mode) useful for further manipulation, but also allows tandem metathesis processes for the formation of polycyclic compounds. 

The initially proposed mechanism [14], and one that continues to be considered as the likely pathway for most variants, involves the oxidative cyclization of a Ni(0) complex of an aldehyde and alkyne to a metallacycle (Scheme 18). Metallacycle formation could proceed independently of the reducing agent via metallacycle 19, or alternatively, metallacycle 20a or 20b could be formed via promotion of the oxidative cyclization transformation by the reducing agent. Cleavage of the nickel-oxygen bond in a o-bond metathesis process generates an alkenyl nickel intermediate 21. In the variants involv-... 

A domino metathesis process using the enyne 6/3-54 and ethylene as substrates was developed by Arjona, Plumet and coworkers (Scheme 6/3.15) [244]. Interestingly, by using catalyst 6/3-15 (Gmbbs II), the pyrrolidone 6/3-55 was obtained in 98% yield as the only product, whereas with catalyst 6/3-13 (Grubbs I), compounds 6/3-56 (60%) and 6/3-57 (25%) were formed. 

The skeletal rearrangements are cycloisomerization processes which involve carbon-carbon bond cleavage. These reactions have witnessed a tremendous development in the last decade, and this chemistry has been recently reviewed.283 This section will be devoted to 7T-Lewis acid-catalyzed processes and will not deal, for instance, with genuine enyne metathesis processes involving carbene complex-catalyzed processes pioneered by Katz284 and intensely used nowadays with Ru-based catalysts.285 By the catalysis of 7r-Lewis acids, all these reactions generally start with a metal-promoted electrophilic activation of the alkyne moiety, a process well known for organoplatinum... 

Selected examples of these and related applications are authoritatively discussed in the chapters by K.C. Nicolaou et al. (epothilone libraries) and S.E. Gibson and S.P. Keen (cross metathesis processes on solid phase) in this monograph. For some further advancements, the reader is referred to the recent literature [45]. 

This article will outline firstly the application of RCM technology to the preparation of the epothilones with particular emphasis on the generality and mild nature of the process. The second section will describe the use of cyclopentadi-enyl titanium reagents in metathesis processes and, in particular, their application to the preparation of polyether segments of marine neurotoxins. 

Although the molybdenum and ruthenium complexes 1-3 have gained widespread popularity as initiators of RCM, the cydopentadienyl titanium derivative 93 (Tebbe reagent) [28,29] can also be used to promote olefin metathesis processes (Scheme 13) [28]. In a stoichiometric sense, 93 can be also used to promote the conversion of carbonyls into olefins [28b, 29]. Both transformations are thought to proceed via the reactive titanocene methylidene 94, which is released from the Tebbe reagent 93 on treatment with base. Subsequent reaction of 94 with olefins produces metallacyclobutanes 95 and 97. Isolation of these adducts, and extensive kinetic and labeling studies, have aided in the eluddation of the mechanism of metathesis processes [28]. 

Another group of reactions that emerged as supporting companions to catalytic RCM reactions are transformations that provide specially outfitted and useful diene substrates for the metathesis process. Such compounds, in the presence of la, lb or 2, can be converted to otherwise difficult-to-make organic molecules. Research activity in this area has led to the design of synthesis methods that elevate the utility of 1 and 2 beyond ring closure. 

We later determined that with lower catalyst loadings (15 mol% 2), reaction efficiency suffers (<50% conversion). When Ru complex lb was used (20 mol%, benzene, 80°C), 5-10% dimer derived from reaction of the terminal olefins was formed as the only product. Continued investigation of the catalytic macrocycli-zation indicated that, with freshly prepared and recrystallized Mo catalyst, the metathesis process occurs smoothly at 22 °C to afford 2 in 90% isolated yield after only 4 h. With 40 mol% 2, the yield improved to 97%, and less than 20 mol% catalyst gave notably lower conversions and yields. 

Considering the facility with which dimerization products 81 and 84 are obtained, we reasoned that, in catalytic ring closure of 77, the derived dimer is perhaps initially formed as well. If the metathesis process is reversible [17b], such adducts may subsequently be converted to the desired macrocycle 76. To examine the validity of this paradigm, diene 77 was dimerized (— 85) by treatment with Ru catalyst lb. When 85 was treated with 22 mol% 2 (after pretreatment with ethylene to ensure formation of the active complex), 50-55% conversion to macrolactam 76 was detected within 7 h by 400 MHz H NMR analysis (Eq. 8). When 76 was subjected to the same reaction conditions, <2% of any of the acyclic products was detected. Although we do not as yet have a positive proof that 85 is formed in cyclization of 77, this observation suggests that if dimerization were to occur, the material can be readily converted to the desired macrolactam, which is kinetically immune to cleavage. 

Since the early disclosure by Negishi that zinc halide salts accelerate Pd(0) -catalyzed crosscouplings between vinyl zirconocenes and various halides [78], several methods have been developed that extend the utility of this metathesis process from a zirconium chloride to a zinc chloride (79 Scheme 4.47). Alternatively, routes to more reactive diorganozinc intermediates, e. g., using Me2Zn, convert readily available zinc derivatives to mixed species 80, which selectively couple with various electrophiles [14]. 

Another factor to be investigated in the metathesis process is the effect of bases in the reaction media. Bases such as triethylamine are added in the experimental conditions to stabilize the formic acid product because otherwise the product is thermodynamically less stable than the separate carbon dioxide and dihydrogen reactants. As discussed above, the o-bond methathesis involves the heterolytic H-H bond fission, which would be accelerated by the presence of the base. This effect was theoretically investigated in the four-center o-bond metathesis between RhOn1-... 

Instead of having the olefin insertion reactions, the calculations indicate that M2b and M2c can only proceed uphill with the reductive elimination of HB(OH)2, leading to the formation of M3, an olefin complex which could be in principle obtained directly from the addition of olefin to the catalyst Rh (PH3)2C1. The olefin complex M3 then could undergo a-bond metathesis processes with HB(OH)2, giving two isomeric products M4 and M5 depending on the orientation of the HB(OH)2 borane. The a-bond metathesis processes are however found to be unfavorable because of the very high reaction barriers (Figure 4). 

In this chapter, theoretical studies on various transition metal catalyzed boration reactions have been summarized. The hydroboration of olefins catalyzed by the Wilkinson catalyst was studied most. The oxidative addition of borane to the Rh metal center is commonly believed to be the first step followed by the coordination of olefin. The extensive calculations on the experimentally proposed associative and dissociative reaction pathways do not yield a definitive conclusion on which pathway is preferred. Clearly, the reaction mechanism is a complicated one. It is believed that the properties of the substrate and the nature of ligands in the catalyst together with temperature and solvent affect the reaction pathways significantly. Early transition metal catalyzed hydroboration is believed to involve a G-bond metathesis process because of the difficulty in having an oxidative addition reaction due to less available metal d electrons. 

In the chapter on olefms plants, in the section on propylene, a route to making propylene involved butene-2. In this process, called metathesis, ethylene and butene-1 are passed over a catalyst, and the atoms do a musical chair routine. When the music stops, the result is propylene. The conversion of ethylene to propylene is an attraction when the growth rate of ethylene demand is not keeping up with propylene. Then the olefins plants produce an unbalanced product slate, and producers wish they had an on-purpose propylene scheme instead of just a coproduct process. The ethylene/butene-2 metathesis process is attractive as long as the supply of butylenes holds out. Refineries are big consumers of these olefins in their alkylation plants, and so metathesis process has, in effect, to buy butylene stream away from the gasoline blending pool. 

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