Organic synthesis drawbacks

All three coupling procedures are suitable to give high yields under mild reaction conditions. Many functional groups do not interfere. For the application in organic synthesis the Eglinton variant may be more convenient than the Glaser method a drawback however is the need for stoichiometric amounts of copper salt. 

Metal-catalyzed hydrophosphination has been explored with only a few metals and with a limited array of substrates. Although these reactions usually proceed more quickly and with improved selectivity than their uncatalyzed counterparts, their potential for organic synthesis has not yet been exploited fully because of some drawbacks to the known reactions. The selectivity of Pt-catalyzed reactions is not sufficiently high in many cases, and only activated substrates can be used. Lanthanide-catalyzed reactions have been reported only for intramolecular cases and also sulfer from the formation of by-products. Recent studies of the mechanisms of these reactions may lead to improved selectivity and rate profiles. Further work on asymmetric hydrophosphination can be expected, since it is unlikely that good stereocontrol can be obtained in radical or acid/base-catalyzed processes. 

Olefin-metathesis is a useful tool for the formation of unsaturated C-C bonds in organic synthesis.186 The most widely used catalysts for olefin metathesis include alkoxyl imido molybdenum complex (Schrock catalyst)187 and benzylidene ruthenium complex (Grubbs catalyst).188 The former is air- and moisture-sensitive and has some other drawbacks such as intolerance to many functional groups and impurities the latter has increased tolerance to water and many reactions have been used in aqueous solution without any loss of catalytic efficiency. 

The utility of such reagents in the oxidation processes is compromised due to their inherent toxicity, cumbersome preparation, potential danger in handling of metal complexes, difficulties encountered in product isolation and waste disposal problems. Immobilization of metallic reagents on solid supports has circumvented some of these drawbacks and provided an attractive alternative in organic synthesis because of the selectivity and associated ease of manipulation. Further, the localization of metals on the mineral oxide surfaces reduces the possibility of their leaching into the environment. 

The ruthenium carbene complexes 1 discussed in the previous chapter have set the standards in the field of olefin metathesis and are widely appreciated tools for advanced organic synthesis [3]. A serious drawback, however, relates to the preparation of these compounds requiring either 3,3-diphenylcyclopropene or diazoalkanes, i.e. reagents which are rather difficult to make and/or fairly hazardous if used on a large scale [60]. Therefore, a need for metathesis catalysts persists that exhibit essentially the same activity and application profile as 1 but are significantly easier to make. 

The formation of carbon-carbon bonds using olefin metathesis methodology is a powerful technique in fine organic synthesis and polymer chemistry. The increasing importance of these reactions is reflected by the numerous publications over the last few years. Many of these pubhcations deal with the design and apphca-tion of polymer-supported olefin metathesis catalysts with the aim to overcome the common drawbacks of the homogeneous catalysts low thermal stability and difficulties associated with their recovery from the reaction mixtures. The modem state of art in this important field is described in chapter 11 of this volume. 

First developments in the Friedel-Crafts alkylation were concentrated on the use of stoichiometric amounts of Lewis acids, such as A1C13, BF3 or TiCl4, to produce stoichiometric amounts of salt by-products [5-9]. However, in recent years more and more catalytic methods have been developed. In particular, rare earth metal triflates, including Sc(OTf)3, La(OTf)3 and Yb(OTf)3, have been extensively used as Lewis acid catalysts in various C-C and C-X bond forming reactions [10-13], Despite the benefit of their versatility for organic synthesis, these Lewis acids possess major drawbacks. They are expensive, rather toxic [14], and air- and moisture-sensitive. 

Few organic transformations add as much molecular complexity in one step as the Pauson-Khand reaction. This reaction is one of the best examples of how organometallic chemistry is useful in modern organic synthesis, and can serve as a key tool for the synthesis of natural products, in this case those possessing cyclopentane units. The limited scope, low yields and lack of efficient catalytic procedures were serious drawbacks in the past that have been... 

The first drawback in the use of water (the solubility problem) may be overcome by using surfactants, which solubilize organic materials or form emulsions with them in water. Indeed, surfactants have been occasionally used in organic synthesis [3-6]. A successful example is emulsion polymerization [7]. Some late transition metal-catalysed reactions in water have also been conducted in the presence of surfactants or surfactantlike ligands [8-15]. In many other cases, however, large quantities of surfactant molecules compared with the reaction substrates are needed for the desired reactions to proceed efficiently, and thus, the systems are impractical even if water can be used as a solvent. From the viewpoints of practicability and applicability, the surfactant-aided organic synthesis is still at the preliminary stage. 

In the course of our investigations to circumvent the second drawback in the use of water (the decomposition problem), we have found that some metal salts such as rare earth metal triflates (triflate = trifluoromethanesulfonate) can be used as water-compatible Lewis acids [16,17]. Lewis acid catalysis has attracted much attention in organic synthesis [18]. Although various kinds of Lewis acids have been developed and many have been applied in industry, these Lewis acids must be generally used under strictly anhydrous conditions. The presence of even a small amount of water stops the reactions, because most Lewis acids immediately react with water rather than substrates. In addition, recovery and reuse of the conventional Lewis acids are formidable tasks. These disadvantages have restricted the use of Lewis acids in organic synthesis. 

One drawback of the Stille coupling is that the tin by-products are toxic and are not easily removed from the product. A solution to this problem developed by Suzuki uses a boronic acid in place of the organ-otin compound. The boron-containing by-products are innocuous and are easily removed because of their solubility in water. The Suzuki coupling has found widespread use in organic synthesis (Scheme 10.20). These reactions are extremely important and the methodology is extensively used, particularly in the search for new pharmaceutical products. 

These deselenations do not tolerate halides, which are generally reduced. Among the drawbacks in addition to side reactions inevitable with radical intermediates, the use of an excess of an expensive reagent and a high reaction temperature may make the procedure less useful, especially with sensitive substrates. Note that the generation of radicals using deselenation by tin hydrides is also very useful in organic synthesis. ... 

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