Five azomethine ylides generation

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). 

The generation and reactivity of conjugated azomethine ylides has been reviewed.148 1,3-Dipolar cycloaddition and 1,5- and 1,7-electrocyclizations have been described as powerful strategies for the synthesis of monocyclic and annulated five- and seven-membered nitrogen heterocyclic compounds. 

The generation of nonstabilized azomethine ylide 256 via PET-initiated sequential double desilylation and [3 + 2]-cycloaddition reaction with various dipolarophiles to generate five-membered heterocycles 257, has also been established by Pandey et al., as shown in Table 8.5 [110]. 

Rh(l)-catalyzed [2-I-2-I-2] cyclotrimerization of 1,6-diynes (e.g., 1391 and 1394) with monoynes (e.g., 1392) in combination with stereospecific Ag(i)-catalyzed aldimine (metallo)azomethine ylide — cycloaddition cascades affords rapid access to complex heterocyclic benzene derivatives 1393 and 1395 in one-pot processes with the generation of five new bonds, four stereocenters and three rings (Schemes 266 and 267) <2000T8967>. 

Oxazolidin-4-ones Difluorocarbene is generated by reaction of dibromodi-fluoromethane with lead powder. Trapping of the carbene by imines leads to azomethine ylides which, in the presence of aldehydes, provides five-raembered heterocycles. 

Cycloadditions 1,3-dipoles readily react with the (6,6)-double bond of C o that acts as a highly reactive dipolarophile. Five-membered rings are generated on the fullerene s surface this way, and these can bear a multitude of functional groups. Suitable 1,3-dipoles include, for instance, nitrile oxide, azomethine ylides, alkylazides, diazo compounds or trimethylenemethane (Figure 2.60). 

The intense interest in the formation of five-membered nitrogen heterocycles by a 1,3-dipolar cycloaddition of an azomethine ylide, or related species, and an alkene or alkyne has been maintained this year. The majority of synthetic effort continues to be directed towards the mild generation of non-stabilized azomethine... 

Five-membered heterocycles with one nitrogen atom can be prepared from azomethine ylide-type dipoles and alkynes or alkenes. Several solid-supported cycloadditions with maleimide as a dipolarophile have been reported. Trityl resin-bound maleimide captured azomethine ylides that were generated in situ from amino acid methyl esters and aldehydes, and substituted resin-bound pyrrolidines were obtained (Scheme 11.1). Traceless cleavage of the C—N bond between acid-sensitive trityl resin and the IV-unsubstimted cycloadduct was achieved with 50% trifluoroacetic acid. 

Targets with one Heteroatom Five-membered heterocycles with one heteroatom, such as pyrrolidine and tetrahydrofiiran skeletons, exist widely in numerous natural products and bioactive compounds. Therefore, intense efforts have been devoted to the synthesis of these five-membered ring systems. Among the various methods existing for the synthesis of chiral pyrrolidine and proline derivatives, few can match the synthetic potential of 1,3-DC reactions of azomethine ylides with alkenes [3]. Generally, azomethine yhdes are unstable species, so they are normally generated in situ and trapped by unsaturated bonds (Scheme 2.1) [2b]. 

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