Azomethine ylide forming

The azomethine ylide formed in situ from benzaldehyde and an A -alkyl AA reacts with an alkene to give a mixture of diastereomeric pyrrolidines (85TL2775). 

Dodd and co-workers (5) reported the first known synthesis of 11//-indolizino[8,7-h]indoles by the cycloaddition reaction of a nonstabilized ylide 21 and diethylacetylene dicarboxylate (DEAD). The azomethine ylide, formed by the alkylation of the 3,4-dihydro-p-carboline (22) with trimethylsilyl methyl triflate to the triflate salt, followed by in situ desilyation with cesium fluoride, underwent cycloaddition with DEAD at low temperature. The expected major cycloadduct 23 was isolated, along with quantities of a minor product 24, presumed to have been formed by initial reaction of the ylide with 1 equiv of DEAD and the intermediate undergoing reaction with a further equivalent of DEAD before cyclization. Dodd offers no explanation for the unexpected position of the double bond in the newly generated five-membered ring, although it is most likely due to post-reaction isomerization to the thermodynamically more stable p-amino acrylate system (Scheme 3.5). 

Another approach employing chiral acyclic azomethine ylides was published in two recent papers by Alcaide et al. (85,86). The azomethine ylide-silver complex (51) was formed in situ by reaction of the formyl-substituted chiral azetidinone (50) with glycine (or alanine) in the presence of AgOTf and a base (Scheme 12.18). Azomethine ylides formed in this manner were subjected to reaction with various electron-deficient alkenes. One example of this is the reaction with nitrostyrene, as illustrated in Scheme 12.18 (86). The reaction is proposed to proceed via a two step tandem Michael-Henry process in which the products 52a and 52b are isolated in a... 

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). 

A red coloration forms and slowly disappears in the course of the reaction owing to irradiation. To ascertain the structure of the colored intermediate DoMinh and Trozzolo [90] attempted to catch it chemically. When the dipolar -ophile 135 was added to the reaction mixture, the coloration immediately disappeared and the corresponding cycloadduct 142 was formed. Irradiation of 72 with tetracyanoethylene 143 gave the adduct 144 in high yield. On the basis of these data, a structure of azomethine ylide formed by aziridine carbon-carbon bond cleavage is assigned to the colored intermediate. 

M. J. Mariano, P. S. Investigations of novel azomethine ylide-forming photoreactions of N-silylmethylimides. J. Org. Chem. 1995, 60, 2353-2360. 

The formation and intramolecular dipolar cycloaddition of azomethine ylides formed by carbenoid reaction with C=N bonds has recently been studied by the authors group.84 Treatment of 2-(diazoace-tyl)benzaldehyde O-methyl oxime (176) with rhodium(II) octanoate in the presence of dimethyl acetylenedicarboxylate or N-phenylmaleimide produced cycloadducts 178 and 179, respectively. The cycloaddition was also carried out using p-quinone as the dipolarophile. The major product isolated corresponded to cycloadduct 180. The subsequent reaction of this material with excess acetic anhydride in pyridine afforded diacetate 181 in 67% overall yield from 176. The latter compound incorporates the basic dibenzofa, d -cyclohepten-5,10-imine skeleton found in MK-801,85 which is a selective ligand for brain cyclidine (PCP) receptors that has attracted considerable attention as a potent anticonvulsive and neuro-protective agent.86,87... 

Pc with osmium tetroxide and sodium periodate, and subsequent 1,3-dipolar cycloaddition of the azomethine ylide, formed in the presence of an excess of sarco-sine, and Cgo to give the fulleropyrrolidine-Pc conjugate 17. The second protocol relies on the fulleropyrrolidine formation prior to the statistical cyclotetrameriza-tion with 4-tert-bu tv I p It lit a lonitrile. The low yields obtained via the latter strategy are presumably a result of the steric congestion of the benzodinitrile-functionalized fullerene precursor in the statistical crossover condensation. 

The formation and intramolecular dipolar cycloaddition of azomethine ylides formed by carbenoid reaction with C-N double bonds has recently been studied by the author s group [66]. Treatment of 2-(diazoacetyl)benzaldehyde O-methyl oxime (118) with rhodium (II) octanoate in the presence of dimethyl acetylenedicarboxylate or iV-phenylmaleimide produced cycloadducts 120 and... 

Surprisingly, the indolizidine aziridine 39 was synthesized in 88% yield, but was found to be an uncatalyzed reaction, providing the product upon diazo-transfer at 0°C to oxime 37. Two plausible mechanisms are invoked for this carbene reaction sequence (1) a carbenoid insertion process or (2) collapse of the azomethine ylide formed upon addition of the diazoamide. The uncatalyzed process is likely due to a dipolar cycloaddition of the diazo and pendent oxime. 

Cycloaddition reactions of aziridines have also been of considerable interest since the early 1980s, and the synthetic applications of these reactions have attracted a great deal of attention. Conclusive evidence has been presented that the reactions proceed via intermediate azomethine ylides, formed... 

A chiral selenophosphoramide catalyst was employed for the intramolecular cyclization of an alkenyl sulfonamide to achieve the enantioselective formation of N-heterocycles including an azepane derivative via a mechanism proposed to include formation of a three-membered sulfur-containing ring (14JA8915). A [4 + 3]-cycloaddition reaction of methyl coumalate 12 with an azomethine ylide, formed from imine esters 13 yielded functionalized azepine derivatives 14 (14OL4508). 

Pyrrolidinofullerenes are probably the most widely used fullerene derivatives because of their stability, versatility, and the availability of reactants. Their synthesis is based on the 1,3-dipolar cycloaddition of azomethine ylides formed by thermal treatment from aldehydes and amino acids [54, 55] or from iminoesters [56, 57], The latter lacks selectivity since it affords a diastereomeric mixture (cis and trans) of 2,5-disubstituted pyrrolidinofullerenes. 

The reaction of azomethine ylide formed from the aziridine 77a with trifluoro-methylaryl acetylenes gave a mixture of dihydropyrroles 109 and 110, which formed a 1 3 mixture of pyrroles 111 and 112 by oxidation with DDQ [49]. 

Scheme 42.44 Synthesis of chiral pyrrolidines 193 by enantioselective domino 1,3-dipolar cycloaddition of azomethine ylides formed in situ and dialkyl fumarates 192 catalyzed by phosphoric acid catalyst 106.

Azomethine Ylide Forming Photoreactions of N-Trimethylsilylphthalimides and Related Conjugated Imides... 

---