Azomethine ylides formation

Dehydrogenation has been used as a method for azomethine ylide formation. Treatment of compound 206 with iV-methylmaleimide in the presence of palladium black gives a 1 1 mixture of the endo- and f .tf-diastereomcrs 207 and 208, in 65% combined yield <1989J(P1)198> (Equation 24). 

Another important method for preparation for exohedrally functionalized fullerenes is the 1,3-dipolar cycloaddition of in s/Yw-generated azomethine ylides to C60 yielding fulleropyrrolidines (Maggini et al., 1993). Further functionalization is facilitated either by the use of adequate aldehydes for the azomethine ylide formation or quatemization of the pyrrolidine nitrogen atom. Both bisaddition (Kordatos et al.,... 

The success achieved with the Rh(II)-catalyzed transformations of -oximino diazo carbonyl compounds prompted our group to study some additional systems where the C-N 7i-bond was configurationally locked so that azomethine ylide formation would readily occur. Toward this end, we investigated the Rh(II)-catalyzed behavior of isoxazoline 186 in the presence of DMAD. This reaction afforded the azomethine-derived cycloadduct 187 as a 4 1 mixture of diastereomers in 65% yield. A similar transformation occurred using the a-diazoacetophenone derivative 188 which produced isoxazolo[3,2-a]isoquinoline 189 as a 2 1 mixture of diastereomers in 82% yield.84... 

Reaction with Azomethine Ylides Formation of Pyrrolidines... 

Chiral induction in cycloaddition reactions of azomethine ylide has been achieved when the a-amino acid (233) reacts with isatin or benzthiophen derivatives (234 X = NH, NBu, S) and menthyl acrylate. The course of the reactions involves decarboxylative azomethine ylide formation followed by cycloaddition through an endo transition state ultimately affording the cycloadduct (61) (Table 9) in 67-82% diastereomeric excess <91TL5417>. 

Various 3-methyleneoxindoles have been converted to spirooxindoles in enan-tioselective fashion by Gong and coworkers who made use of a chiral organic catalyst to direct 1,3-dipolar cycloadditions across the exocyclic Jt-system [76]. As illustrated in Scheme 34, azomethine ylide formation arising from condensation of... 

Ruthenium (II) polypyridyl complexes promote the photoredox reactions such as Diels-Alder reaction (see formulae 29 31) and azomethine ylide formation followed by [3 + 2] cycloaddition (32-34) by use of visible light. Yoon found 2,2 -bipyrazine ligand is better than 2,2 -bipyridine. Bach reported enantioselective intramolecular [2 + 2] and intermolecular [3 + 2] photocycloaddition by use of chiral hydrogen bond templates (37) and (41). ... 

For the reactions of other 1,3-dipoles, the catalyst-induced control of the enantio-selectivity is achieved by other principles. Both for the metal-catalyzed reactions of azomethine ylides, carbonyl ylides and nitrile oxides the catalyst is crucial for the in situ formation of the 1,3-dipole from a precursor. After formation the 1,3-di-pole is coordinated to the catalyst because of a favored chelation and/or stabiliza-... 

For azomethine ylides and carbonyl ylides, the diastereoselectivity is more complex as the presence of an additional chiral center in the product allows for the formation of four diastereomers. Since the few reactions that are described in this chapter of these dipoles give rise to only one diastereomer, this topic will not be mentioned further here [10]. 

In addition to nitrones, azomethine ylides are also valuable 1,3-dipoles for five-membered heterocycles [415], which have found useful applications in the synthesis of for example, alkaloids [416]. Again, the groups of both Grigg [417] and Risch [418] have contributed to this field. As reported by the latter group, the treatment of secondary amines 2-824 with benzaldehyde and an appropriate dipolarophile leads to the formation of either substituted pyrrolidines 2-823, 2-825 and 2-826 or oxa-zolidines 2-828 with the 1,3-dipole 2-827 as intermediate (Scheme 2.184). However, the yields and the diastereoselectivities are not always satisfactory. 

Tominaga and coworkers have reported the formation of indolizine by the reaction of azomethine ylide with l-nitro-2-phenylthioethylene (Eq. 10.86).146... 

The three-component reaction between isatin 432a, a-aminoacids 433 (proline and thioproline) and dipolarophiles in methanol/water medium was carried out by heating at 90 °C to afford the pyrrolidine-2-spiro-3 -(2-oxindoles) 51. The first step of the reaction is the formation of oxazlidinones 448. Loss of carbon dioxide from oxazolidinone proceeds via a stereospecific 1,3-cycloreversion to produce the formation of oxazolidinones almost exclusively with /razw-stereoselectivity. This /f-azomethine ylide undergo 1,3-dipolar cycloaddition with dipolarophiles to yield the pyrrohdinc-2-r/ V -3-(2-oxindolcs) 51. (Scheme 101) <2004EJ0413>. 

Hynninen and coworkers <99JCS(PT1)2403> used a similar approach to prepare phytochlorin-C6o diad 38 (Scheme 11). The protocol employed the pyrolysis of the natural chlorophyll a molecule 35, followed by transesterification and demetallation to furnish derivative 36. Subsequent oxidation of 36 with OsCU and NaI04 has allowed the synthesis of the formyl derivative 37, which was further used as precursor of the azomethinic ylide intermediate in the 1,3-DC reaction with Cm leading to the formation of diad 38. Photochemical studies revealed that this diad underwent a fast intramolecular photoinduced electron transfer in polar solvents such a benzonitrile <99JACS9378>. 

Besides the use of porphyrins as azomethinic ylide derivatives, the porphyrin macrocycle can also be used to generate porphyrinic nitrile oxides 55 (Scheme 17) <04RCB(E)2192>. Thus, the treatment of oxime 54 with /V-bromosuccinimide in the presence of triethylamine, led to the formation of nitrile oxide 55, which was trapped in 1,3-DC reactions with dimethyl maleate and 2,5-norbomadiene to afford 56 and 57, respectively. In the reaction with 2,5-norbomadiene, if an excess of 55 was used, then the corresponding bis-adduct was obtained in good yield. 

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). 

Fig. 4.9. Formation and transformations of azomethine ylides from imines and electrophilic carbene complexes.

The formation of the A-vinylaziridine 70 in the photoreaction of 68 deserves additional comment. Depending on the multiplicity, the intermediate 72 formed by path b could be a triplet 1,3-biradical. However, if intersystem crossing occurs along the reaction coordinate, the singlet biradical must be considered as a dipolar azomethine ylide. According to literature precedents, both intermediates, the 1,3-biradical and the ylide, will cyclize to form the observed aziridine. This is the first case in a DPM process where a zwitterion can be postulated as a possible intermediate. 

Dipoles can also be generated from rearrangements that take place after the formation of an initial rhodium carbenoid product ]40, 70, 71]. One example of this type of transmutation, also known as a dipole cascade process, involves the formation of an azomethine ylide via the initial formation of a carbonyl ylide [72]. This process was... 

Dipolar cycloaddition is another route to benzopyrrolo[l,2-a]azepines by pyrrole ring formation. The azomethine ylide derived from imine 88 and difluorocarbene adds to DMAD to produce dimethyl 3-fluoro-9H-dibenzo[c,/]-pyrrolo[l,2-fl]azepine-l,2-dicarboxylate 89 in 20% yield (Equation (12)... 

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