Aziridine ring azomethines

Aziridines can also be synthesized from their unsaturated azirine counterparts or existing aziridine rings. The first examples of enantiopure 2-substituted 2Z/-azirine 3-carboxylates 46 were prepared via dehydrochlorination of methyl 2-chloroaziridine-2-carboxylates. Bicyclic and tricyclic aziridines such as 47 were then generated via an aza-Diels-Alder reaction with the corresponding dienes <070L1707>. A related azomethine cycloaddition in the presence of an aziridine has also been reported <07JOC8506>. 

When an aziridine ring is fused at the 2,3-bond to another ring system, the only ring opening structurally allowed is a disrotatory rotation, which must be photolytically performed as discussed above. Thus, the fused aziridine 8 on irradiation generates syn-azomethine ylide 9, which is captured by an acetylene to give a bicyclic cycloadduct (68CPB764). 

The thermal and photochemical reactions of aziridines and azirines primarily involve opening of the strained three-membered ring. Aziridines produce azomethine ylides, while 2//-azirines produce nitrile ylides or nitrenes. Typically, these intermediates react further in cycloaddition processes or other rearrangements. 

While the electrocyclic ring-opening of aziridines to azomethine ylides is well known, the reverse reaction has also been studied as a route to aziridines . This process is implicit in the cis-trans equilibration of substituted aziridines <67JA1753, 7UA1779), and may be involved in the reaction of diazoalkanes with imines <84T2569>. Convincing evidence for the electrocyclization of... 

Intramolecular 1,3-dipolar cycloaddition reactions normally proceed efficiently to give bicyclic products and these reactions do not require the presence of an electron-withdrawing group on the dipolarophile. Thus, in an approach to the alkaloid sarain A, the aziridine 221 was heated to generate the intermediate azomethine ylide 222, and hence, after intramolecular cycloaddition, the pyrrolidine 223 (3.143). " An alternative method for the formation of the required azomethine ylide, and which avoids the need for the prior synthesis of an aziridine ring, uses the simple condensation of an aldehyde and a primary or secondary amine. Thus, in another approach to sarain A, addition of formaldehyde to the amine 224 resulted in the formation of the cycloadduct 226 (3.144). Notice that in both cases the... 

Sodium hydride I dimethyl sulfoxide Ring closure with sulfonium ylids Aziridine ring from azomethines... 

Azomethine ylides are also frequently obtained by ring opening of aziridines, and the analogous carbonyl ylides from oxiranes. These aspects are dealt with in Section 3.03.5.1. A variety of five-membered heterocycles can also function as masked 1,3-dipoles and this aspect is considered in Section 3.03.5.2. 

Azomethine ylides (Section 4.03.6.1.1) have been generated from a wide variety of aziridines using both thermal and photochemical methods. With carbon-carbon unsaturated dipolarophiles, pyrrolines or pyrrolidines are obtained. With hetero double bonds, however, ring systems of interest to this discussion result. 

Aziridines, e.g. (91), undergo thermal ring opening in a conrotatory manner to generate azomethine ylides. These azomethine ylides are 47r-components and can participate in [4 + 2] cycloadditions with 1-azirines acting as the 27r-component 73HCA1351). 

Synthetic work commenced with evaluation of an azomethine ylide dipole for the proposed intramolecular dipolar cycloaddition. A number of methods exist for the preparation of azomethine ylides, including, inter alia, transformations based on fluoride-mediated desilylation of a-silyliminium species, electrocyclic ring opening of aziridines, and tautomerization of a-amino acid ester imines [37]. In particular, the fluoride-mediated desilylation of a-silyliminium species, first reported by Vedejs in 1979 [38], is among the most widely used methods for the generation of non-stabilized azomethine ylides (Scheme 1.6). 

Triazole derivatives also result from the cycloaddition of DEAZD to azomethine ylids derived from electrocyclic ring opening of aziridines.117 121 For example, the tetrahydro-1,2,4-triazole 73 was prepared by thermolysis of the cts-aziridine in the presence of DEAZD in 96% yield (Eq. 8), and... 

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). 

The intermolecular reaction of imines with acceptor-substituted carbene complexes generally leads to the formation of azomethine ylides. These can undergo several types of transformation, such as ring closure to aziridines [1242-1245], 1,3-dipolar cycloadditions [1133,1243,1246-1248], or different types of rearrangement (Figure 4.9). 

P8 Thermal conrotatory 4tt ring opening of aziridines and epoxides is a well-recognized method of generating azomethine and carbonyl ylidesd (From Johnson, 2003)... 

Pyrrolidine derivatives such as 206 have been synthesized by the addition of the corresponding azomethine ylide generated by the thermal ring opening of the aziridine 205 (or similar aziridines) as shown in Scheme 4.33 [204, 210-212],... 

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