Synthetic tools

Since the six carbons shown above have 10 additional bonds, the variety of substituents they carry or the structures they can be a part of is quite varied, making the Diels-Alder reaction a powerful synthetic tool in organic chemistry. A moment s reflection will convince us that a molecule like structure [XVI] is monofunctional from the point of view of the Diels-Alder condensation. If the Diels-Alder reaction is to be used for the preparation of polymers, the reactants must be bis-dienes and bis-dienophiles. If the diene, the dienophile, or both are part of a ring system to begin with, a polycyclic product results. One of the first high molecular weight polymers prepared by this synthetic route was the product resulting from the reaction of 2-vinyl butadiene [XIX] and benzoquinone [XX] ... 

The first syathesis of morphine, and therefore also codeiae, was completed ia 1956 (58). Although an additional twelve or so syntheses have been reported siace then, isolation of morphine remains more important than any synthetic process. However, synthetic endeavors continue to demonstrate new synthetic tools and capabiUties and to conduct the search for modified analogues that retain the analgesic properties of morphine but are nonaddicting. 

Reactions of quinones with radicals have been explored, and alkylation with diacyl peroxides constitutes an important synthetic tool (68). Although there are limitations, an impressive range of substituents can be introduced in good yield. Examples include alkyl chains ending with functional groups, eg, 50% yield of (70) [80632-67-3] (69,70). 

The photochemical reactions of organic compounds attracted great interest in the 1960s. As a result, many useful and fascinating reactions were uncovered, and photochemistry is now an important synthetic tool in organic chemistry. A firm basis for mechanistic description of many photochemical reactions has been developed. Some of the more general types of photochemical reactions will be discussed in this chapter. In Section 13.2, the relationship of photochemical reactions to the principles of orbital symmetry will be considered. In later sections, characteristic photochemical reactions of alkenes, dienes, carbonyl compounds, and aromatic rings will be introduced. 

Inverse Diels-Alder reaction as synthetic tool in the synthesis of annelated heterocycles 95F419. 

Abstract For many years after its discovery, olefin metathesis was hardly used as a synthetic tool. This situation changed when well-defined and stable carbene complexes of molybdenum and ruthenium were discovered as efficient precatalysts in the early 1990s. In particular, the high activity and selectivity in ring-closure reactions stimulated further research in this area and led to numerous applications in organic synthesis. Today, olefin metathesis is one of the... 

An obvious drawback in RCM-based synthesis of unsaturated macrocyclic natural compounds is the lack of control over the newly formed double bond. The products formed are usually obtained as mixture of ( /Z)-isomers with the (E)-isomer dominating in most cases. The best solution for this problem might be a sequence of RCAM followed by (E)- or (Z)-selective partial reduction. Until now, alkyne metathesis has remained in the shadow of alkene-based metathesis reactions. One of the reasons maybe the lack of commercially available catalysts for this type of reaction. When alkyne metathesis as a new synthetic tool was reviewed in early 1999 [184], there existed only a single report disclosed by Fiirstner s laboratory [185] on the RCAM-based conversion of functionalized diynes to triple-bonded 12- to 28-membered macrocycles with the concomitant expulsion of 2-butyne (cf Fig. 3a). These reactions were catalyzed by Schrock s tungsten-carbyne complex G. Since then, Furstner and coworkers have achieved a series of natural product syntheses, which seem to establish RCAM followed by partial reduction to (Z)- or (E)-cycloalkenes as a useful macrocyclization alternative to RCM. As work up to early 2000, including the development of alternative alkyne metathesis catalysts, is competently covered in Fiirstner s excellent review [2a], we will concentrate here only on the most recent natural product syntheses, which were all achieved by Fiirstner s team. 

The Diels-Alder cycloaddition is the best-known organic reaction that is widely used to construct, in a regio- and stereo-controlled way, a six-membered ring with up to four stereogenic centers. With the potential of forming carbon-carbon, carbon-heteroatom and heteroatom-heteroatom bonds, the reaction is a versatile synthetic tool for constructing simple and complex molecules [1], Scheme 1.1 illustrates two examples the synthesis of a small molecule such as the tricyclic compound 1 by intermolecular Diels-Alder reaction [2] and the construction of a complex compound, like 2, which is the key intermediate in the synthesis of (-)chlorothricolide 3, by a combination of an intermolecular and an intramolecular Diels-Alder cycloaddition [3]. 

Solid-phase chemistry is an efficient synthetic tool that, compared with solution-phase chemistry, simplifies the work-up of the reaction, allows the process to be driven to completion by using excess of reagents, and can be automatized [2a]. In recent years, many studies have been devoted to developing both surface-mediated and resin-supported synthesis. Today the solid-phase approach is not limited to peptides and oligonucleotides but is also used to synthesize molecules of lower molecular weight. 

Although non-exhaustive, this review shows that a large variety of new difunc-tionalized mixed phosphorus and sulfur molecular structures have been described during the last ten years. It also demonstrates that such compounds are powerful synthetic tools or building blocks and, in some cases, molecules (or precursors of more complex molecules) with potential biological activities. 

The conversion of diarylthallium trifluoroacetates to aromatic iodides by treatment with molecular iodine is thus analogous to the well-known conversion of diarylmercury derivatives with iodine to a mixture of an aromatic iodide and an arylmercury iodide (134), but it is much more effective as a synthetic tool because of the spontaneous disproportionation to product of the intermediate arylthallium trifluoroacetate iodide. The present procedure thus provides a practical synthetic method for the ultimate conversion of aryl Grignard reagents to aromatic iodides. 

Transition metal catalysed cycloisomerisation of unsaturated systems is a powerful synthetic tool for the access of a wide range of heterocyclic and carbocyclic motifs [30], The use of NHCs as ligands for transition metal cycloisomerisation catalysts has been extensively studied [7],... 

There is much interest in the hydrosilylation of functionalized alkenes as a powerful synthetic tool [14]. Mesitylene-stabilized Pt nanoaggregates, obtained by reaction of Pt vapor and mesitylene, which have already been reported to be very active homogeneous catalysts in the hydrosilylation... 

The Barton-McCombie process is an important synthetic tool for the generation of radical species. Me3SiO-(SiHMeO)n-SiMe3 works as a stoichiometric reductant in the tin-catalyzed reaction since Bu3Sn(OPh) is reduced to Bu3SnH as shown in Scheme 31 [71]. 

As a synthetic tool, heterogeneous catalytic dehydrogenations offer selective conversions of functional groups. Most popular dehydrogenations involve... 

The Michael addition of nitroalkanes to election-deficient alkenes provides a powerful synthetic tool in which it is perceived that the nitro group can be transformed into various functionalities. Various kinds of bases have been used for this transformation in homogeneous solutions, or, alternatively, some heterogeneous catalysts have been employed. In general, bases used in the Henry reaction are also effective for these additions (Scheme 4.18).133... 

Dinitro-ll-oxatricyclo[6.2.1.01,6]undec-9-ene has been prepared by an intramolecular Diels-Alder reaction of the furan with a nitroalkene group as shown in Eq. 8.26. This tricyclic compound is a versatile synthetic tool for the preparation of ergot alkaloids.41... 

Alkyl and silyl nitronates are, in principle, /V-alkoxy and /V-silyloxynitrones, and they can react with alkenes in 1,3-dipolar cycloadditions to form /V-alkoxy- or /V-silyloxyisoxaz.olidine (see Scheme 8.25). The alkoxy and silyloxy groups can be eliminated from the adduct on heating or by acid treatment to form 2-isoxazolines. It should be noticed that isoxazolines are also obtained by the reaction of nitrile oxides with alkenes thus, nitronates can be considered as synthetic equivalents of nitrile oxides. Since the pioneering work by Torssell et al. on the development of silyl nitronates, this type of reaction has become a useful synthetic tool. Recent development for generation of cyclic nitronates by hetero Diels-Alder reactions of nitroalkenes is discussed in Section 8.3. 

The use of oxazolines in aromatic substitution is a valuable synthetic tool.2 The o-methoxy- or o-fluorophenyloxazoline reacts readily with a variety of organofithium or Grignard reagents to displace only the ortho substituent. In this fashion a number of ortho-substituted benzoic acids, benzaldehydes, and unsymmetrical biphenyls are accessible. The reaction takes place under very mild conditions, usually at or below room temperature, and thus allows a number of other sensitive groups to be present. 

The thiazolium-catalyzed addition of an aldehyde-derived acyl anion with a Michael acceptor (Stetter reaction) is a well-known synthetic tool leading to the synthesis of highly funtionalized products. Recent developments in this area include the direct nucleophilic addition of acyl anions to nitroalkenes using silyl-protected thiazolium carbinols <06JA4932>. In the presence of a fluoride anion, carbinol 186 is not cleaved to an aldehyde... 

Allying click chemistry with the use of environmentally benign catalysts, such as zeolites, may constitute a valuable synthetic tool, representing a true green and sustainable approach. 

The hetero-Diels-Alder reaction is one of the most important methods of synthesis of heterocycles, yet as a potentially powerful synthetic tool it has found relatively little general use. Microwave irradiation has been used to improve reactions involving heterodienophiles and heterodienes of low reactivity. 

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