Subject metathesis

A different approach, taken by both Monsanto (58) and Gulf Research and Development Company (59), involved the oxidative coupling of two molecules of toluene to yield stilbene. The stilbene is then subjected to a metathesis reaction with ethylene to yield two molecules of styrene. 

The choice of the anion ultimately intended to be an element of the ionic liquid is of particular importance. Perhaps more than any other single factor, it appears that the anion of the ionic liquid exercises a significant degree of control over the molecular solvents (water, ether, etc.) with which the IL will form two-phase systems. Nitrate salts, for example, are typically water-miscible while those of hexaflu-orophosphate are not those of tetrafluoroborate may or may not be, depending on the nature of the cation. Certain anions such as hexafluorophosphate are subject to hydrolysis at higher temperatures, while those such as bis(trifluoromethane)sulfonamide are not, but are extremely expensive. Additionally, the cation of the salt used to perform any anion metathesis is important. While salts of potassium, sodium, and silver are routinely used for this purpose, the use of ammonium salts in acetone is frequently the most convenient and least expensive approach. 

Instead ef the name metathesis, the term disproportionation is frequently applied to the reaction, and sometimes the term dismutation. For historical reasons the name disproportionation is most commonly used for the heterogeneously catalyzed reaction, while the homogeneously catalyzed reaction is usually designated as metathesis. The name disproportionation is correct in the case of the conversion of acyclic alkenes according to Eq. (1) however, this name is inadequate in most other situations, such as the reaction between two different alkenes, and reactions involving cycloalkenes. Similar objections apply to the name dismutation. The name metathesis is not subject to these limitations and, therefore, is preferred. 

Chemistry on solid support has gained tremendous importance during the last few years, mainly driven by the needs of the pharmaceutical sciences. Due to the robust and tolerable nature of the available catalysts, metathesis was soon recognized as a useful technique in this context. Three conceptually different, RCM-based strategies are outlined in Fig. 11. In the approach delineated in Fig. 1 la, a polymer-bound diene 353 is subjected to RCM. The desired product 354 is formed with concomitant traceless release from the resin. This strategy is very favorable, since only compounds with the correct functionality will be liberated, while unwanted by-products remain attached to the polymer. However, as the catalyst is captured in this process by the matrix (355), a higher catalyst loading will be required, or ancillary alkenes have to be added to liberate the catalyst. 

Representatives of the bridged sulfone system 70 have been subjected to ruthenium catalysed ring-closing metathesis reactions (Grubbs catalyst) and shown to afford, in low yields, a few selected cyclic dimers and trimers, of all the possibilities available. The diastereoselectivities observed were rationalised in terms of kinetic control involved with internal ruthenium/sulfonyl oxygen coordination . 

It is important to note that the Ru-catalyzed RCM and the Zr-catalyzed resolution can be carried out in a single vessel, without recourse to intermediate isolation. The unsaturated medium-ring amides 5 and 8 can be subjected to 10 mol% of the chiral Zr catalyst and EtMgCl, in the same flask, to afford unsaturated 6 and 9 in 81% and 54% isolated yield, respectively. As depicted in Eq. 1, a similar tandem diene metathesis/ethylmagnesation can be carried out on ether 10, leading to the formation of unsaturated chiral alcohol 11 in 73% yield and >99% ee. 

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. 

Perhaps the most compelling research objective in this area will involve the development of a chiral metathesis catalyst that effects C-C bond formation efficiently and with excellent levels of enantioselectivity [41 ]. In such a case, all the reactions discussed herein, in addition to those expertly developed in other laboratories [40], will become subject to asymmetric catalysis. Such a development should prove to have an enormous impact on the field of inorganic, organome-tallic and synthetic organic chemistry. 

This review focuses on the cross-metathesis reactions of functionalised alkenes catalysed by well-defined metal carbene complexes. The cross- and self-metath-esis reactions of unfunctionalised alkenes are of limited use to the synthetic organic chemist and therefore outside the scope of this review. Similarly, ill-defined multicomponent catalyst systems, which generally have very limited functional group tolerance, will only be included as a brief introduction to the subject area. 

Only recently a selective crossed metathesis between terminal alkenes and terminal alkynes has been described using the same catalyst.6 Allyltrimethylsilane proved to be a suitable alkene component for this reaction. Therefore, the concept of immobilizing terminal olefins onto polymer-supported allylsilane was extended to the binding of terminal alkynes. A series of structurally diverse terminal alkynes was reacted with 1 in the presence of catalytic amounts of Ru.7 The resulting polymer-bound dienes 3 are subject to protodesilylation (1.5% TFA) via a conjugate mechanism resulting in the formation of products of type 6 (Table 13.3). Mixtures of E- and Z-isomers (E/Z = 8 1 -1 1) are formed. The identity of the dominating E-isomer was established by NOE analysis. 

The synthesis of ionic liquids with BF4 and PF6 as cations has been the subject of much research since they are the most widely used in catalysis. However, it is difficult to make these ionic liquids in a pure form. The original route used to prepare ionic liquids with these anions consists of a metathesis (anion-cation exchange) reaction in which the imidazolium chloride is reacted with the sodium salt of the anion in a suitable solvent [8], The reaction is illustrated in Scheme 4.2 for the tetrafluoroborate salt. 

When dienes are subjected to olefin metathesis, either oligomerization (ADMET) [808,809,833-837] or cyclization (RCM) can occur [743,747,807] (Figure 3.50). 

The aryl radical cyclization has been successfully used for the preparation of substituted dihydrobenzo[Z)]indoline derivatives [59], An example is shown in Reaction (7.49). The diene 42 was preliminarly subjected to ring-closure metathesis using Grubbs catalyst and then treated with (TMS)3SiH and EtsB at -20 °C, in the presence of air, to provide the compound 43 with an excellent diastereoselectivity. 

Substituted malonates and (5-keto-esters have also been successfully used as pronucleophiles (Scheme 9.11) [25a, 36]. From P-ketoesters, approximately 1 1 mixtures of epimers are generally formed. Products derived from 2-alkenylmalo-nates have been subjected to Ru-catalyzed ring-closing metathesis to give cyclo-pentene derivatives in good yield [25a, 36]. With the ester-amide displayed in Scheme 9.11 as pronucleophile, 1 1 mixtures of epimers were also formed [44]. 

Direct metathesis reactions are characterized by tight transition states and involve the transfer of atoms or radicals as a consequence of the close proximity of the two reactants, and they are the only type of reactions that are not subject to becoming energy-transfer-limited at high temperatures and low pressures. A typical energy diagram for metathesis reactions is shown in Fig. 8c. Examples of such reactions include... 

The combination of allylic amination, ring-closing metathesis, and a free radical cyclization provides a convenient approach to the dihydrobenzo[b]indoline skeleton, as illustrated in Scheme 10.10. The rhodium-catalyzed aUylic amination of 43 with the lithium anion of 2-iodo-(N-4-methoxybenzenesulfonyl)arrihne furnished the corresponding N-(arylsulfonyl)aniline 44. The diene 44 was then subjected to ring-closing metathesis and subsequently treated with tris(trimethylsilyl)silane and triethylborane to afford the dihydrobenzojhjindole derivative 46a in 85% yield [14, 43]. 

The two most used reversible covalent reactions are disulfide exchange and palladium-catalyzed olefin metathesis. We first probed the incorporation of olefin units into the H bonded duplexes by subjecting the modified duplexes to a Pd (Gmbb s) catalyst. Based on a duplex template with the same unsymmetrical H bonding sequence used for directing the formation of the /3-sheet structures, we prepared two groups (strands 17 and 18) of five olefins covalently linked to the two template strands (Fig. 9.13). Mixing each one of components 17 with each one of components 18 in a 1 1 fashion results in a small library of 25 (5 x 5) members. 

The marine natural product ascidiatrienolide A 220 is a strong inhibitor of phospholipase A2. Compound 220 and the closely related didemnilactones 221-223 feature a common hydroxy-substituted anti to the ring oxygen) (Z)-nonenolide core. Lactone 219, which constituted the key intermediate in a previous total synthesis of 220 and can also be elaborated to lactones 221-223, has been the subject of an interesting study by Flirstner s group, that revealed once more the very subtle and cooperative influence of different parameters on the stereochemical course of metathesis reactions. Thus, it was shown that the ElZ ratio obtained in an RCM step is not only dependent on the relative configuration of the cyclization substrate, but also on the chosen catalyst (Scheme 41). When applied to the... 

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