Azomethine ylide generation

The regio- and stereochemical outcome of the intermolecular 1,3-dipolar cycloaddition of an azomethine ylide generated by the decarboxylative condensation of an isatin with an a-amino acid was unambiguously determined by a single-crystal X-ray study of the spirocyclic heterocycle 49 (R1 =4-Br, R2 = H, X = CH2) <1998TL2235>. 

The feasibility of azomethine ylide generation from 7 and intramolecular dipolar cycloaddition was examined under a variety of conditions. For example, activation of vinylogous amide 71 with BzOTf [41] followed by desilylation with TBAT led to complex mixtures of products. Likewise, using MeOTf as the activating agent yielded similar results. Significantly, none of these protocols furnished the desired pyrrolidine 73. Only decomposition of the silylpyridinone to form unidentified products was observed, despite the fact that quantitative O-methylation of the... 

Our first entry to the use of porphyrins as dipolarophiles in 1,3-DC reactions involved the reaction of porphyrins with azomethinic ylides, generated in situ from a-amino acids and aldehydes, to yield chlorins and isobacteriochlorins (bisadducts) <99CC1767, 05JOC2306>. 

In the particular scenario of the reaction of ie.vo-tctrakis(pcntafluorophenyl)porphyrin Id with the azomethine ylide, generated in situ from /V-mcthylglycine and paraformaldehyde, in refluxing toluene during 15 hours, the pyrrolidinochlorin derivative 62 was obtained as the main product (Scheme 19), together with a small amount of isobacteriochlorin 63 (bis-adduct, Figure 5). 

Another example illustrating the versatility of 1,3-DC reactions is concerned with the reaction of [36]octaphyrin 71 with azomethine ylide generated in the usual way from N-methylglycine and paraformaldehyde, to give mono- and bis-pyrrolidine-fused adducts 72 and 73 (Scheme 25) <06OLl 169>... 

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). 

The scope of these reactions has not yet been thoroughly investigated. The examples listed in Table 4.17 suggest that azomethine ylides generated by intramolecular, carbene-mediated N-alkylation of imines enable convergent and fast... 

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],... 

Azomethine ylide generation from oxazolidines has also been achieved by flash vacuum thermolysis (20,21). During synthetic efforts toward alkaloid central skeletal cores, Joucla and co-workers (22) revealed that flash vacuum thermolysis of oxazolidine (84) led to an intramolecular [3 + 2] cycloaddition furnishing pyrrolidine 85 in 82% as a single regio- and stereoisomer. Subsequent Dieckmann... 

Although Padwa et al. (25) extensively studied and developed sihcon mediated technologies in azomethine ylide generation, he also developed other entries into azomethine ylides. In particular, the development of rhodium mediated transmuta-... 

N-Metalated azomethine ylides generated from a-(alkylideneamino) esters can exist as tautomeric forms of the chelated ester enolate (Scheme 11.8). On the basis of the reliable stereochemical and regiochemical selectivities described below, it is clear that the N-metalated tautomeric contributor of these azomethine ylides is important. Simple extension of the above irreversible lithiation method to a-(alkylideneamino) esters is not very effective, and cycloadditions of the resulting lithiated ylides to a,(3-unsaturated carbonyl compounds are not always clean reactions. When the a-(alkylideneamino) esters bear a less bulky methyl ester moiety, or when a,(3-unsaturated carbonyl compounds are sterically less hindered, these species suffer from nucleophihc attack by the organometalhcs, or the metalated cycloadducts undergo further condensation reactions (81-85). 

Garner et al. (90,320) used aziridines substituted with Oppolzer s sultam as azomethine ylide precursors. The azomethine ylide generated from 206 added to various electron-dehcient alkenes, such as dimethyl maleate, A-phenylmalei-mide, and methyl acrylate, giving the 1,3-dipolar cycloaddition product in good yields and up to 82% de (for A-phenylmaleimide). They also used familiar azomethine ylides formed by imine tautomerization (320). Aziridines such as 207 have also been used as precursors for the chiral azomethine ylides, but in reactions with vinylene carbonates, relatively low de values were obtained (Scheme 12.59) (92). 

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