Cycloaddition Reactions with Diazoalkanes in Organic Synthesis

5 Cycloaddition Reactions with Diazoalkanes in Organic Synthesis 

Some years ago, Huisgen et al. (1987 b) mentioned that diazoalkane cycloadditions to electron-deficient CC multiple bond compounds and other dipolarophiles represent the class of [3 + 2] cycloadditions that has been most intensively studied for synthetic purposes. This is also evident from the reviews that concentrate on preparative aspects of diazoalkane cycloadditions (Regitz and Heydt, 1984 Stanovnik, 1991). Yet, in contrast to these statements, not a single 1,3-dipolar cycloaddition with a diazoalkane is reported in Organic Syntheses 

The review of Stanovnik (1991) concentrates on diazoalkane additions to some nitrogen containing heteroaromatic systems, namely to monocyclic pyridazines, and to bicyclic and polycyclic azolo- and azinopyridazines with a bridgehead N atom. 

In this section, we will discuss some general aspects of synthetic applications and provide examples, including their use in synthesis of natural products. 

Buchner accomplished the first synthesis of pyrazole by a cycloaddition in 1889, but not by the direct reaction of diazomethane and ethyne, but with methyl diazoacetate and an electron-deficient dipolarophile, ethynedicarboxylate (see Sect. 6.2). Unsubstituted ethene and ethyne were considered for a very long time to be not sufficiently reactive for synthetic purposes, although von Pechmann (1898 b) had reported a 50 0 yield of pyrazole from diazomethane and ethyne shortly after the discovery of diazomethane. The knowledge of diazomethane being explosive is probably the reason that the obvious advantage of a reaction under pressure in order 

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The 1,3-dipolar cycloaddition reactions to unsaturated carbon-carbon bonds have been known for quite some time and have become an important part of strategies for organic synthesis of many compounds (Smith and March, 2007). The 1,3-dipolar compounds that participate in this reaction include many of those that can be drawn having charged resonance hybrid structures, such as azides, diazoalkanes, nitriles, azomethine ylides, and aziridines, among others. The heterocyclic ring structures formed as the result of this reaction typically are triazoline, triazole, or pyrrolidine derivatives. In all cases, the product is a 5-membered heterocycle that contains components of both reactants and occurs with a reduction in the total bond unsaturation. In addition, this type of cycloaddition reaction can be done using carbon-carbon double bonds or triple bonds (alkynes). 

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