Representative Synthetic Applications

Salicylihalamides/Oximidines Potent Antitumor Agents with Selective anti-V-ATPase Activity 

An excellent review was written by Yet in 2003 on the chemistry and biology of salicylihalamides, oximidines, and related compounds [48], Since that year, a few more studies on the synthesis of these compounds have appeared in the literature. In this section, we will try to examine the factors influencing the E/Z selectivity in 

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This section aims to highlight the most representative synthetic applications of enantioselective organocatalytic cascades involving the successive formation of one C-N bond and one C-C bond. As illustrated below, these methodologies are declined as either bi-component or multicomponent transformations. 

Rearrangements have been included in which sulfones participate not only as reactants but also as products. Reactions have been classified according to mechanism, but although the main emphasis has been on mechanism and stereochemistry, special attention to synthetic applications has also been given, wherever appropriate. Obviously, due to space limitations as well as the vast amount of work available, only selected and representative results of general importance, as judged by the concern of the reviewer, are presented below. Thus, the exclusion of a particular piece of work in no way passes judgement on its scientific value. 

Domino Michael/aldol addition processes unquestionably represent the largest group of domino transformations. Numerous synthetic applications - for example, in natural product synthesis as well as for the preparation of other bioactive compounds - have been reported. Thus, the procedure is rather flexible and allows the use of many different substrates [12]. In this process it is possible, in theory, to establish up to two new C-C-bonds and three new stereogenic centers in a single step. For example, Collin s group developed a three-component approach. 

A wide range of A-acylbenzotriazoles 915 have been prepared under mild conditions in reactions of carboxylic acids with thionyl chloride in the presence of fourfold excess of benzotriazole, including R = alkyl, a-haloalkyl, a-alkoxyalkyl, alkenyl, alkinyl, aryl, and heteroaryl <2003S2795, 2004RQM275>. They represent convenient acylating agents for variety of nucleophiles. Synthetic applications of such compounds have been reviewed <2005SL1656>. 

This review would give a brief survey of the literature concerning the synthetic application of cyclobutanes published mainly during 1975 to 1983. Due to the enormity of research efforts in this field, we do not intend to provide a thorough account of this subject, but would only try to present some representative research works which conclusively demonstrate the versatility of cyclobutane derivatives in synthetic organic chemistry. 

In contrast to the rich chemistry of alkoxy- and aryloxyallenes, synthetic applications of nitrogen-substituted allenes are much less developed. Lithiation at the C-l position followed by addition of electrophiles can also be applied to nitrogen-containing allenes [10]. Some representative examples with dimethyl sulfide and carbonyl compounds are depicted in Scheme 8.73 [147, 157]. a-Hydroxy-substituted (benzotriazo-le) allenes 272 are accessible in a one-pot procedure described by Katritzky and Verin, who generated allenyl anion 271 and trapped it with carbonyl compounds to furnish products 272 [147]. The subsequent cyclization of 272 leading to dihydro-furan derivative 273 was achieved under similar conditions to those already mentioned for oxygen-substituted allenes. 

We have recently reported ( ) several synthetic studies of weak nucleophile SnAr reactions. In the latter cases (26f-1), new synthetic methodology was reported for the direct introduction of fluoroalkoxy groups into a variety of aromatic systems. These reports represent synthetically useful procedures for obtaining some otherwise inaccessible fluoroalkoxy materials but, unfortunately, they require the use of a dipolar, aprotic solvent (usually hexamethylphosphoramide, HMPA) and, in some cases, elevated temperatures. However, because of their diverse and important applications ( ), the syntheses of these and other organofluoro compounds continue to be of interest. For example, two recent reports of useful fluoroalkoxy materials include the insecticide activity exhibited by fluoroalkoxy substituted 1,3,4-oxadiazoles... 

The chemistry and synthetic applications of oxazoles were first covered in 1986 in an comprehensive volume edited by I. J. Turchi (Volume 45 of The Chemistry of Heterocyclic Compounds series). In the meantime, the number of synthetic strategies directed toward oxazole assembly as well as the use of these versatile heterocycles as intermediates, catalytic ligands, and pharmaceutical building blocks has vastly increased. We felt that a supplement and update of oxazole chemistry would be welcomed by the international chemistry community, and we are delighted that Dr. Palmer and his colleagues have accomplished this onerous mission. This volume represents another outstanding service to the organic and... 

Synthetic applications of these photocycloadditions to aromatic compounds are sometimes hampered by low chemical yields and poor selectivity in the photoreactions. However, a number of elegant syntheses of tricyclic sesquiterpenes have been hased on intramolecular 1,3-phutocycloadditions ie.g. 3. SI), and these represent a completely new approach to the preparation of such systems. 

There are however a few important synthetic applications of photochemistry, and we shall consider here three representative examples. 

Representatives of all kinds have been explored for synthetic applications while mechanistic investigations were mainly focussed on the distinct FruA enzymes isolated from rabbit muscle [196] and yeast [197,198]. For mechanistic reasons, all DHAP aldolases appear to be highly specific for the donor component DHAP [199], and only a few isosteric replacements of the ester oxygen for sulfur (46), nitrogen (47), or methylene carbon (48) were found to be tolerable in preparative experiments (Fig. 7) [200,201], Earlier assay results [202] that had indicated activity also for a racemic methyl-branched DHAP analog 53 are now considered to be artefactual [203]. Dihydroxyacetone sulfate 50 has been shown to be covalently bound via Schiff base formation, but apparently no a-deprotonation occurred as neither H/D-exchange nor C-C... 

The major focus in this chapter will be on synthesis, with emphasis placed on more recent applications, particularly those where regiochemistry and stereochemistry are precisely controlled. The reader is referred to the earlier reviews for full mechanistic information and details of historic interest. Electrophilic addition of X—Y to an alkene, where X is the electrophile, gives products with functionality Y (3 to the heteroatom X. Further transformations of X and/or Y provide the basis for diverse synthetic applications. These transformations include replacement of Y by hydrogen, elimination to form a ir-bond (either including the carbon bonded to X or (3 to that carbon so that X is now in an allylic position), and nucleophilic or radical substitution. Representative examples of these synthetic methods will be given below. This chapter will include examples of heterocycles formed in one-pot reactions where the the initial alkene-electrophile adduct contains an electrophilic group that can react further. Examples of heterocycles formed in several steps from alkene-electrophile adducts will also be considered. Cases in which activation by an external electrophile directly results in addition of an internal heteroatom nucleophile are treated in Chapter 1.9 of this volume. 

The trichothecenes, a group of sesquiterpenes having a reasonably complex tricyclic structure, represent useful targets for the synthetic application of cyclohexadienyliron complexes. Several members of... 

While the optical yields are rather low for useful synthetic application, this represents a promising lead for future work in the area of asymmetric complexation reactions. 

When applicable, issues relating to ecology and biology are addressed. The inorganic participants in the ion radical organic reactions are also considered. One of the chapters gives representative synthetic procedures and considers the background of related synthetic approaches. 

For the synthesis of optically pure building blocks we mainly focused on the synthesis of protected noncoded (R)- and (S)-amino acids, as they can be synthesized reliably in enantiomerically pure form with a large variety of side chains using asymmetric hydrogenation of a-amino-a, 3-didehydroamino acids using cationic diphosphine rhodium catalysts.216,217 As a typical example of a reactophore we present a-alkynyl ketones, which is a representative bis-acceptor molecule. In Scheme 5 are depicted some of the many synthetic applications of acetylenic ketones in heterocyclic synthesis, which have great potential for combinatorial and parallel organic synthesis. 

The use of ac electrolysis in all its variations is certainly an interesting and valuable technique for study of the mechanism of electron transfer reactions. The generation of a short-lived redox pair as chemical intermediates is an important feature of the ac electrolysis. In the future it may even be developed to synthetic applications irrespective of the mechanistic details. In some cases it could be a convenient alternative to photochemical reactions. In other cases it represents a new reaction type which has no precedent. 

A noteworthy synthetic application for the reaction of J with a,g-unsaturated phosphoryl compounds is represented by the addition involving hitherto unknown (-)-(Sp)-methylphenylvinylphosphine oxide J 2. The resulting tertiary phosphine oxides 13 with saturated carbon chains and known stereochemistry at phosphorus constitute attractive starting materials for the preparation of optically pure phosphines. The organophosphorus substrate 12 was obtained by decarbomenthoxylation of the enantiomeric ester... 

The discussion of this reaction can be limited to a short summary (see Table 11 for some representative examples) since there are exhaustive and critical reviews on both the mechanism 14>21>324) and the synthetic applications 14>32S> 3 2 6 of the Kolbe electrolysis available. 

From the huge number of model studies and synthetic applications realized during the last ten years, it is possible nowadays to delineate the main factors that affect the course of M-RCM. The following section, through convenient examples, illustrates some of the most representative studies that have helped to establish the scope and limitations of the application of RCM to the synthesis of macrocydes. These contributions have made the use of RCM a predictive tool particularly well suited for the closing key step. However, as will be seen later, some complex situations can still occur where the course of the RCM reaction remains unpredictable and continues to require further studies. 

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