Applications in Synthesis

The Meerwein-Eschenmoser-Claisen rearrangement, in particular the Eschen-moser amide acetal version, has been extensively applied toward the synthesis of natural products and other complex target molecules. The literature is replete with cases where the reaction provided the only way to place a substituent in a sterically hindered environment. The following paragraphs provide selected examples of its use and also serve to highlight the further synthetic transformation of the unsaturated N,N-dimethylamides normally obtained. Perhaps the only drawback of the Eschenmoser-Claisen rearrangement is the stabiUty of these amides, whose hydrolysis and reduction requires relatively harsh conditions. However, electrophilic activation via the y,(5-double bond can be used to manipulate this functionality. 

Other alkaloids that have been synthesized using a Eschenmoser-Claisen rearrangement include dehydroquebrachamine [56], tabersonine [59], nominine [60, 61], and aspidophytine [62]. 

The Eschenmoser-Claisen rearrangement has found applications in the synthesis of polyketides as well. Eor instance, in Nicolaou s synthesis of rapamycin, a building block 90 corresponding to the functionalized cyclohexane ring of the nat- 

50 Mulzer, Bats,. W List, B. Opatz, T Trauner, D. Synlett 1997, 441-444. 

55 Lounasmaa. M. Jokela, R. Tirkkonen, B. Miettinen.). Halonen, M. Heterocydes 

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NMR data on the most common fluorinated aromatics are presented in three categories. Monofluorophenyls and pentafluorophenyls have found the greatest application in synthesis and spectroscopy. Data for polyfluorinated benzenes are also presented. 

The development of metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions is probably going to continue during the next decade. High level of control of the reactions of nitrones has been obtained, and for these reactions one of the next challenges is to explore new substrates that are designed for application in synthesis. The development of metal-catalyzed asymmetric reactions of the other... 

Although the Paterno-Buchi reaction is of high synthetic potential, its use in organic synthesis is still not far developed. In recent years some promising applications in the synthesis of natural products have been reported. The scarce application in synthesis may be due to the non-selective formation of isomeric products that can be difficult to separate—e.g. 6 and 7—as well as to the formation of products by competitive side-reactions such as Norrish type-I- and type-II fragmentations. 

The Peterson oleflnation presents a valuable alternative to the Wittig reaction. It has the advantage to allow for a simple control of the alkene geometry. Its applicability in synthesis depends on the availability of the required silanes.2... 

Aziridination remains less well developed than epoxidation. Nevertheless, high selectivity in inline aziridination has been achieved through the use of chiral sulfi-nimines as auxiliaries. Highly successful catalytic asymmetric aziridination reactions employing either sulfur ylides or diazo esters and chiral Lewis acids have been developed, although their scope and potential applications in synthesis have yet to be established. 

For a successful application in synthesis, several problems have to be solved regioselectivity, whether the C-C bond is formed with the 1- or 3-position in an unsymmetrical ambident anion, EjZ selectivity in the formation of the double bond, and simple diastereoselectivity, since two new stereogenic centers are created from prostereogenic compounds. Further, different types of induced stereoselectivity or enantioselectivity may be required. Allylmetals with a wide choice of substituents are accessible by various methods (Sections D. 1.3.3.3.1.-10.). 

Photolytic Dediazoniations and their Applications in Synthesis and in Image Technology 277... 

The aim of this volume is to convince the reader that metal carbene complexes have made their way from organometallic curiosities to valuable - and in part unique - reagents for application in synthesis and catalysis. But it is for sure that this development over 4 decades is not the end of the story there is both a need and considerable potential for functional organometallics such as metal carbon multiple bond species which further offer exciting perspectives in selective synthesis and catalysis as well as in reactions applied to natural products and complex molecules required for chemical architectures and material science. 

The /lomo-Diels-Alder reaction is a [2 + 2 + 2] cycloaddition of a 1,4-diene with a dienophile which produces two new bonds and a cyclopropane ring. This reaction is an example of a multi-ring-forming reaction that to date has found few applications in synthesis, since the use of 1,4-dienes has been limited mainly to bridged cyclohexa-1,4-dienes and almost exclusively to norbornadiene. Lewis-acid catalysts accelerate /lowo-Diels-Alder reactions and increase the selectivity for the [2 + 2 + 2] vs. [2 + 2] cycloaddition. 

The chemistry of cyclopentadienyltin compounds is reviewed in references (267) and (26S). The ready disproportionation of (CsH5)4Sn with SnCU (269), and the sensitivity of the cyclopentadienyl-tin bond to acidolysis and to photolysis (270) suggests that these compounds may find application in synthesis. 

Cyclophanes or 7r-spherands have played a central role in the development of supramolecular chemistry forming an important class of organic host molecules for the inclusion of metal ions or organic molecules via n-n interactions. Particular examples are provided by their applications in synthesis [80], in the development of molecular sensors [81], and the development of cavities adequate for molecular reactions with possible applications in catalysis [82]. The classical organic synthesis of cyclophanes can be quite complex [83], so that the preparation of structurally related molecules via coordination or organometallic chemistry might be an interesting alternative. 

Vinyl sulfides have found numerous applications in synthesis in the recent literature. Vinyl sulfides unsubstituted in the 1-position are metallated readily, and the resulting 1-phenythio- or 1-alkylthiovinyllithium reagents have been utilized for nucleophilic acylation and other applications. " The phenylthio-substituted... 

Chemistry of N-Methoxy N-Methyl Amides. Applications in Synthesis. A Review," Sibi. Org. Prep. Proceed. Int., 1993, 25, 5... 

Miscellaneous Reactions Reactions of Phosphonate Anions Selected Applications in Synthesis... 

The coupling of terminal alkynes with organic halides, known as the Castro-Stephens-Sonogashira reaction, has wide applications in synthesis. The most widely used method is the Sonogashira coupling, using a combination of palladium and copper as the catalyst.13 Recently,... 

Crich D, Brebion F, Suk D-H (2006) Generation of Alkene Radical Cations by Heterolysis of -Substituted Radicals Mechanism, Stereochemistry, and Applications in Synthesis. 263-. 1-38... 

However, more significant modifications in selectivity, which have useful applications in synthesis, have been reported in a number of other reactions performed under the action of MW irradiation [9, 44, 70]. Many of these reactions were performed under heterogeneous and/or solvent-free conditions, and only those performed under homogeneous conditions will be discussed here. 

To illustrate the multifaceted chemistry of nitrones and their application in synthesis, let us consider the synthetic scheme of bicyclic and tricyclic chiral ligands (Scheme 2.1) (7) as well as diastereo- and enantiostereoselective syntheses of alkaloids (Scheme 2.2) (8). 

Marek, I. Chechik-Lankin, H. In Handbook of Functionalized Organometallics. Applications in Synthesis Knochel, P., Ed. Wiley-VCH Weinheim 2005 Vol. 2, Chapter 12, pp 503-540. 

The cross-metathesis reaction has evolved extensively during the past few years, but there is still a considerable amount of work to be done before the full potential of this reaction is realised. The development of new metathesis catalysts, greater understanding and control of selectivity, and more extensive applications in synthesis that will surely follow in the near future, make this a particularly exciting time in the evolution of the alkene cross-metathesis reaction. 

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