Azomethine ylids cycloaddition

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... 

Some cycloadditions to azirines have been reviewed by Anderson and Hassner.27 Schmid et al. 28 photolyzed the arylazirine 1 in benzene in the presence of 2 equivalents of DM AD and obtained 40% of the pyrrole 3, a compound prepared previously by Huisgen et al.29 30 from oxazolones and sydnones with DMAD. Padwa and his co-workers have investigated the scope of these photoinduced cycloadditions to arylazirines. Irradiation of 1 in pentane for 3 hours in the presence of DMAD gave 95% of (3)31 the azomethine ylid 2 was postulated as an intermediate. 

The azomethine ylid 53, generated thermally from the aziridine 52, underwent cycloaddition in near quantitative yield. With DMAD, only one product is possible with EP the sole product was 54, and EPP gave 54 and 55 in 80 20 ratio. This latter result indicates that steric effects are important with the phenylpropiolic ester.52 Nitrones (57) add to benzylideneacenaphthenone (56) forming the spiroisoxazolidines (58), which lose aldehyde fragments on heating or photolysis to give the... 

Fusion of an aziridine moiety in a structure which cannot open in a conrotatory fashion inhibits the formation of an azomethine ylid by the thermal process. An example of such a compound is 77 which failed to give cycloadditions up to 180°.50 Oida and Ohki80 irradiated a related compound (78) in dioxane at 15° for 2 hours in the presence of 2 equivalents of DMAD. They obtained 4% of compound 79 and 36% of the isomeric 80 mild alkaline hydrolysis of 79 gave the amorphous 82,... 

Methyl-(trimethylsilyl)methyhminoacetate, chosen as the azomethine ylid precursor, provides an elegant access to proline derivatives. However, the cycloaddition reaction has a low regiospecificity.386... 

Polymer-supported azomethine ylids generated from a-silylimines through a 1,2-silatropic shift, are shown to be versatile reagents suitable for the synthesis of libraries of pyrrolidine derivatives after 1,3-dipolar cycloaddition with a series of dipolarophiles. Effectively substituents R1, R2 and dipolarophiles A=B and A=B can be chosen to get the desired adduct.146... 

It has been demonstrated that TMS iodide (in combination with cesium fluoride) or TMS triflate in various solvents (THF, MeCN, HMPA) are excellent reagents to promote the generation of azomethine ylids from A-methoxymethyl-A-(trimethylsilylmethyl)aIkyl-amines and their cycloaddition to electron deficient alkenes with yields ranging from moderate to nearly quantitative. The geometry of the double bond in the alkene is preserved in the cycloadduct.410... 

The first study consisted of labelling one of the reactive carbon centers with deuterium. Thus, cycloaddition with a dissymmetric dipolarophile led to a 1 1 mixture of two deuterated pyrrolidines, indicative of the ambivalence.411 412 In the second study, 13C was used to label one of the carbons a- to nitrogen, and once again a 1 1 mixture of labeled pyrrolidines was obtained.413 These results demonstrate that free resonance of an unstabilized azomethine ylid occurs during the reaction. 

Lithium fluoride is able to promote the formation of azomethine ylids from /V-benzyl-/V-(met hox y met hy I)tri met h y I s i I y I met h y I am i ne. The reaction with methyl fumarate and maleate gives quantitative yields of trans and cis /V-benzyl-3,4-dicarbomethoxypyrro-lidines. Thus, the geometry of the alkenes is preserved during the cycloaddition reaction. These results are identical to those obtained using Achiwa s procedure (see Section VII.D.2). 

The benzotriazolyl group is a good leaving group. This feature was exploited in the use of benzotriazolylmethyl-aminomethyltrimethylsilane as a precursor of an azomethine ylid. At reflux in toluene, benzotriazolyltrimethylsilane was eliminated and formation of the ylid underwent quantitative [l,3]dipolar cycloaddition with diethyl fumarate, for example, giving a frans-3,4-dicarboethoxy pyrrolidine derivative exclusively. Other examples were reported as well.442... 

Silver fluoride also provides access to the azomethine ylid from /V-methoxymethyl-/V-(trimethylsilylmethyl)benzylamine, with the intermediate being trapped with classical dipolarophiles. No internal cycloaddition occurs when a non-activated ethylenic moiety... 

It was noted that using either the a- or a/-methylated precursor leads to the same mixture of the cycloaddition products. This demonstrates that the same azomethine ylid is generated as the common intermediate.64... 

Substituting a benzyl group for the chiral a-cyanobenzyl group in the azomethine ylid provides insight into the diastereoselectivity of this cycloaddition. In fact, poor selection results, probably because the groups attached to the nitrogen atom of the ylid differ little in their size and electronic nature.65... 

In the presence of two equivalents of silver fluoride, N-protected bis[(trimethylsi-lyl)methyl]amines lead also to azomethine ylids which can be trapped by dipolarophiles. The mechanism of the cycloaddition reaction involves sequential electron-Me3Si+-electron transfer process from the amine to silver fluoride, which forms silver metal, ruling out a fluoride-induced desilylation process. Although silver is recovered at the end of the reaction, a cheaper oxidizing reagent is still lacking.448,449... 

Like imidates, thioimidates were shown to be the precursors of azomethine ylids which lead to the formation of pyrroline and pyrrole derivatives through cycloaddition with dipolarophiles.454... 

The covalent assembly of functional Jt-systems is a general synthetic principle and in some cases they can even be achieved in a multi-component fashion. One of the most impressive examples is the very elegant access to covalently linked donor-fullerene arrangements by 1,3-dipolar cycloadditions with in situ-generated azomethine ylids [59]. However, here only the multi-component de novo synthesis of the chromophore structures will be considered. The major developments have been achieved in condensation-based and cross-coupling strategies. 

A number of complex heterocycles have been assembled using dipolar cycloadditions (Fig. 6). The Affymax group [32] published an approach to the synthesis of tetrasubsti-tuted pyrrolidines by the reaction of azomethine ylids with electron-deficient olefins. A similar approach was described by researchers at Monsanto however, the aldehyde component was bound to the resin instead of the amino acid [33]. Kurth and co-workers [34] described a route to 2,5-disubstituted tetrahydrofurans using a nitrile oxide cycloaddition as the key reaction. Mjalli et al. [35] synthesized highly substituted pyrroles using the dipolar cycloaddition of intermediate 5 with mono- or disubstituted acetylenes. 

Finally, enantiomerically pure sulfinimines have also been used as precursors of chiral imidazolidines by 1,3-dipolar cycloaddition with azomethine ylids [181]. Reactions of different arylsulfinimines 245 with dipoles 246 are highly stereoselective, mainly affording diastereoisomer 247 (absolute configuration unequivocally established by X-ray studies), which was readily transformed into vicinal diamine 248 (Scheme 111). 

Cycloaddition to pyrrolidines. The reaction of diethyl aminomalonate with formaldehyde can generate an azomethine ylid (a - b) which cycloadds to 1,2-dipolarophiles to form pyrrolidines. 

The cyclodehydration of 2-substituted-A/-acylthiazolidine-4-carboxylic acids yields bicyclic munchnones. This mesoionic ring system acts as a cyclic azomethine ylid and can undergo 1,3-dipolar cycloaddition reactions with dipolarophiles. A range of chiral pyrrolo[l,2-c]thiazoles have been prepared by this method both intermolecularly and intramolecularly. 

An interesting spirocyclic thiazolidine ring system has been reported. Starting from the thiazolethione 67 and the aziridine 68, which when heated to 100 °C forms the azomethine ylid 69, undergoes a 1,3-dipolar cycloaddition reaction to afford the cycloadduct 70 as the sole regioisomer <02H393>. 

The products are azomethine ylids, and can be trapped by [3+21 cycloaddition reactions with dipolarophiles (look back at Chapter 35). 

The Stereoselectivity of 1,3-Dipolar Cycloadditions. There is no endo mle for 1,3-dipolar cycloadditions like that for Diels-Alder reactions. Stereoselectivity, more often than not, is low, as shown by the reactions of C,/V-diphenylnitrone—both regioisomers 6.238 and 6.239 (R=C02Et) from the reaction with ethyl acrylate are mixtures of exo and endo isomers, only a little in favour of the exo product. Similarly, the reactions of methyl crotonate with nitrones favour the exo product 6.242 over the endo 6.243. In contrast, other reactions are endo selective, as in the cycloaddition 6.244 of an azomethine ylid to dimethyl maleate giving largely the endo adduct 6.245. 

Aziridines, azomethine ylids from, cycloadditions, 60, 35 Aziridines, /3-hydroxy-, radical induced cleavage, 58, 41... 

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