Nitrogen-containing aziridines

The preparation and chemistry of organic azides have been intensively investigated since about 1960 because of their importance in preparative heterocyclic chemistry and as a source of nitrenes [1]. Many nitrogen-containing heterocycles such as carbazoles, furoxans, azepines, A2-triazolines, triazoles [2], tetrazoles [3], aziridines [4, 5], and azirines have been obtained by either the addition or the decomposition of azides. 

Although there is no direct evidence for the postulated intermediate 3 in this example, there is evidence for the existence of analogous ylids in the aziridine series (see Section II, B), and in some reactions of pyridine-type heterocycles with DMAD intermediates corresponding to 3 have been trapped. The formation of intermediates similar to 3 is the commonest first stage in reactions of nitrogen-containing heterocycles with activated acetylenes. 

One of the features of a,/3-unsaturated ketones is the presence of two electrophilic centers. Because of this feature, reactions with binucleophiles can proceed as a 1,2-addition or as a 1,4-addition. Regarding three-membered nitrogen-containing heterocycles formed from a,/3-unsaturated ketones and their derivatives, the unsaturated ketone acts either as a 1,2-bielectrophile (substituted ethylene), which leads to the formation of ethyleneimines, or as a 1,4-bielectrophile, giving rise to either bi- or tricyclic aziridines. Hence, the present chapter is divided into two parts, one which is entirely dedicated to aziridinyl ketones and the other to bi- and tricyclic aziridines. 

Schemer s observations (1964) on spin inversion and bond rotation in nitrogen-containing diradicals lends support to Skell s view. Direct photolysis of the triazolines 42 and 43 gives the related aziridines, 44 and 45 with predominant retention of the geometric arrangement of the methyl and adjacent phenyl substituents. Photolysis in the presence of a triplet sensitizer, benzophenone, results in a product distribution showing much lower stereoselectivity. The inference is that...

The vast majority of organocatalytic reactions proceeds via covalent formation of the catalyst-substrate adduct to form an activated complex. Amine-based reactions are typical examples, in which amino acids, peptides, alkaloids and synthetic nitrogen-containing molecules are used as chiral catalysts. The main body of reactions includes reactions of the so-called generalized enamine cycle and charge accelerated reactions via the formation of iminium intermediates (see Chapters 2 and 3). Also, Morita-Baylis-Hillman reactions (see Chapter 5), carbene-mediated reactions (see Chapter 9), as well as asymmetric ylide reactions including epoxidation, cyclopropanation, and aziridination (see Chapter 10), and oxidation with the in situ generation of chiral dioxirane or oxaziridine catalysts (see Chapter 12), are typical examples. 

Expansion of aziridines to -lactams. This rhodium complex catalyzes a regio-specific carbonylation of N-f-butyl-2-arylaziridines (1) to form lactams (2). The reaction fails if the alkyl group on nitrogen contains acidic hydrogens adjacent to nitrogen. 

Monocyclic aziridines and 2//-azirines have found broad application in the synthesis of complex natural products. The facility with which these small ring nitrogen-containing compounds can be converted to important pharmaceutical products under mild conditions with wide functional group compatibility makes these molecules quite useful for heterocyclic chemistry. 

The synthesis of aziridine derivatives has received much attention in recent years, because these are versatile building blocks for synthesis for a wide range of nitrogen-containing substrates. Oxidation of N-aminophthalimide with lead tetraacetate in the presence of a variety of electrophilic and nucleophihc olefins is a useful, stereospecific route to aziridines (Scheme 13.46) [67]. 

Synthesis of l-azabicyclo[1.1.0]butane, which contains both a four-membered and two three-membered nitrogen-containing rings ( ), follows the general route described above. As one would anticipate, ringopening reactions, one of which is illustrated, lead to products with an azetidine unit, rather than an aziridine unit. 

Aziridine derivatives where the aziridine groups are linked to nitrogen-containing heterocyclic carrier groups are 2,6-bis(l-aziridinyl)pyrazine (ENT-50457, 17), 4,8-bis(l-aziridinyl)pyrimidino-[5,4d]-pyrimidine (ENT-50792,18) and 2,4,6-tris(l-aziridinyl)-j-triazine (triethylene-melamine, tretamine, 19). 

Aziridines (three-membered saturated nitrogen-containing rings) are also found in anti-tumour agents, such as the mitomycins. Thiiranes also occur naturally, as plant products such as thiirane-2-carboxylic acid, isolated from asparagus. 

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