1.3- Dipolar cycloaddition of azomethine ylides

Another example of a microwave-assisted 1,3-dipolar cycloaddition using azomethine ylides and a dipolarophile was the intramolecular reaction reported for the synthesis of hexahydrochromeno[4,3-fo]pyrrolidine 105 [70]. It was the first example of a solvent-free microwave-assisted intramoleciflar 1,3-dipolar cycloaddition of azomethine ylides, obtained from aromatic aldehyde 102 and IM-substituted glycinate 103 (Scheme 36). The dipole was generated in situ (independently from the presence of a base like TEA) and reacted directly with the dipolarophile present within the same molecifle. The intramolecu-... 

Scheme 10.10 1,3-Dipolar cycloadditions of azomethine ylides with maleimides in the...

Dipolar addition to nitroalkenes provides a useful strategy for synthesis of various heterocycles. The [3+2] reaction of azomethine ylides and alkenes is one of the most useful methods for the preparation of pyrolines. Stereocontrolled synthesis of highly substituted proline esters via [3+2] cycloaddition between IV-methylated azomethine ylides and nitroalkenes has been reported.147 The stereochemistry of 1,3-dipolar cycloaddition of azomethine ylides derived from aromatic aldehydes and L-proline alkyl esters with various nitroalkenes has been reported. Cyclic and acyclic nitroalkenes add to the anti form of the ylide in a highly regioselective manner to give pyrrolizidine derivatives.148... 

A general method for the functionalization of C60 (4) is the 1,3-dipolar cycloaddition of azomethine ylides. This process was first described by Prato [94] and leads to fulleropyrrolidines. Several fulleropyrrolidines (143a-c) have been prepared under microwave irradiation by Langa et al. [72]. These authors observed that microwave irradiation again competes favorably with thermal heating and, in this way, 143 a was... 

Other approaches including 1,3-dipolar cycloadditions of azomethine ylides or nitroxides to alkene or alkyne dipolarophiles have been applied to the synthesis of these ring systems. 

Da Ros T, Prato M, Novello F, Maggini M, Banfi E (1996) Easy access to water soluble fullerene derivatives via 1,3-dipolar cycloadditions of azomethine ylides to C60. J. Org. Chem. 61 9070-9072. 

Dipolar cycloaddition of azomethine ylides, generated by the condensation of an a-amino acid and an aldehyde, is an efficient method for covalent sidewall functionalisation and has been successfully used to solubilise CNTs in most organic solvents (Tasis et al., 2003 Holzinger et al., 2003). This particular technique has also been utilised to obtain the first example of a bioactive peptide covalently linked to CNTs by the prospect for the potential applications in immunology (Bianco and Prato, 2003 Pantarotto et al., 2003a, b Bianco et al., 2005b). 

Attaching a Ceo cluster to an [Ru(bpy)3] + core has been achieved by 1,3-dipolar cycloaddition of azomethine ylides to the fullerene. The electrochemistry of the complex is complicated a one-electron reversible oxidation of the Ru center, five one-electron reversible reductions associated with the Ceo cage, and five more reversible reductions centered on the bpy ligands. The photophysical properties of the complex have been discussed. ... 

The stereochemistry of 1,3-dipolar cycloadditions of azomethine ylides with alkenes is more complex. In this reaction, up to four new chiral centers can be formed and up to eight different diastereomers may be obtained (Scheme 12.4). There are three different types of diastereoselectivity to be considered, of which the two are connected. First, the relative geometry of the terminal substituents of the azomethine ylide determine whether the products have 2,5-cis or 2,5-trans conformation. Most frequently the azomethine ylide exists in one preferred configuration or it shifts between two different forms. The addition process can proceed in either an endo or an exo fashion, but the possible ( ,Z) interconversion of the azomethine ylide confuses these terms to some extent. The endo-isomers obtained from the ( , )-azomethine ylide are identical to the exo-isomers obtained from the (Z,Z)-isomer. Finally, the azomethine ylide can add to either face of the alkene, which is described as diastereofacial selectivity if one or both of the substrates are chiral or as enantioselectivity if the substrates are achiral. 

Grigg and co-workers (383) found that chiral cobalt and manganese complexes are capable of inducing enantioselectivity in 1,3-dipolar cycloadditions of azomethine ylides derived from arylidene imines of glycine (Scheme 12.91). This work was published in 1991 and is the first example of a metal-catalyzed asymmetric 1,3-dipolar cycloaddition. The reaction of the azomethine yhde 284a with methyl acrylate 285 required a stoichiometric amount of cobalt and 2 equiv of the chiral ephedrine ligand. Up to 96% ee was obtained for the 1,3-dipolar cycloaddition product 286a. 

Supercritical carbon dioxide with a minute co-solvent addition is an effective medium for the 1,3-dipolar cycloaddition of azomethine ylides with DMAD to produce substituted pyrroles.67 The 1,3-dipolar cycloaddition of nitrile ylides [e.g. benzonitrile (4-nitrobenzylide) and 4-nitrobenzonitrile(benzylide)] with acrylamides provided a synthesis of 3,4-dihydro-2//-pyrroles with moderate to good yields.68 The Pt(II)-or Au(III)-catalysed 3 + 2-cycloaddition of the transition metal-containing azomethine ylide (63) with electron-rich alkenes provided a carbene complex (64), which yields tricyclic indoles (65) having a substituent at 3-position (Scheme 17).69 The 1,3-dipolar cycloadditions of azomethine ylides with aryl vinyl sulfones are catalysed by Cu(MeCN)4C104-Taniaphos with nearly complete exo- selectivity and enantioselec-tivities up to 85% ee.10 The 3 + 2-cycloaddition of benzol/>]thiophene 1,1-dioxide... 

Fluorous aminoesters have also been used in DOS of three unique triaza tricyclic and tetracyclic ring systems (Scheme 22) [44], Bicyclic pyrrolidines 12 generated from one-pot, three-component 1,3-dipolar cycloaddition of azomethine ylides were further converted to hydantoin-, piperazinedione-, and benzodiazepine-fused compounds 31-33, respectively. Each of these three heterocyclic scaffolds has four stereocenters on the central pyrrolidine ring and up to four points of diversity (R1 to R4). The structure of compound... 

Besides the 1,3-dipolar cycloaddition of azomethine ylides to C60, the Bingel cycloprop anation reaction is widely used for regioselective functionalization of fullerenes. In principle, this versatile modification involves the generation of carbon nucleophiles from a-halo esters and their subsequent addition to C60 [19]. The addition takes place exclusively on double bonds between two six-membered rings of the fullerene skeleton, yielding methanofullerenes. As shown in Scheme 2, addition of diethylbromomalonate to C60, in the presence of an auxiliary base... 

Azomethine ylides are very important 1,3-dipoles, and they are usually used to react with alkenes leading to the formation of the highly substituted pyrrolidine derivatives [17]. A novel and practical process for the 1,3-dipolar cycloaddition of azomethine ylides with alkenes had been reported by j0rgensen and coworkers [18]. They proposed that a dipol-chiral base ion pair would be generated between a-imino ester-metal complex and a cinchona alkaloid, and subsequent cycloaddition with dipolarophile would take place in a stereoselective manner (Scheme 10.13). 

Scheme 10.14 1,3-Dipolar cycloaddition of azomethine ylides and fert-butyl acrylate.

Azizian et al. [103] described a novel four-component reaction for the diastereo-selective synthesis of spiro-pyrrolizidines 170 using a 1,3-dipolar cycloaddition of azomethine ylides to N-aryl maleimides. Reaction of ninhydrin 166 with 1,2-phenylenediamine 167 in DMSO, and addition of L-proline 168 and N-aryl maleimides 169 in a one-pot four-component reaction (Scheme 11.41) usually required extended reaction times of up to 3 h at 100 °C to obtain the desired spiro-pyrrolizidines 170 in 76-86% yield as single diastereoisomers. This process can be accelerated substantially (3-5 min) with good yields (87-95%) by performing the reaction under microwave irradiation conditions. 

Novikov, M.S. Khlebnikov, A.F. Sidorina, E.S. Kostikov, R.R. 1,3-Dipolar cycloaddition of azomethine ylides derived from imines and difluorocarbene to alkynes a new active Pb-mediated approach to 2-fluoropyrrole derivatives. J. Chem. Soc., Perkin Trans. 1 2000, 231-237. 

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