Non-stabilized azomethine ylides

Pandey, G., Bagul, T.D., Sahoo, A.K. (1998) [3 -E 2] Cycloaddition of Non stabilized Azomethine Ylides. 7. Stereoselective Synthesis of Epibatidine and Analognes. Journal of Organic Chemistry, 63, 760-768. 

Synthetic work commenced with evaluation of an azomethine ylide dipole for the proposed intramolecular dipolar cycloaddition. A number of methods exist for the preparation of azomethine ylides, including, inter alia, transformations based on fluoride-mediated desilylation of a-silyliminium species, electrocyclic ring opening of aziridines, and tautomerization of a-amino acid ester imines [37]. In particular, the fluoride-mediated desilylation of a-silyliminium species, first reported by Vedejs in 1979 [38], is among the most widely used methods for the generation of non-stabilized azomethine ylides (Scheme 1.6). 

Alkynyl azomethine ylides containing an aryl bridge have been shown to undergo cyclization. Thus, tautomerization of imine (137) afforded an azomethine ylide which cyclized to give two diastereomeric dihydropyrroles and traces of aromatized product (Scheme 42).56 The activated cyclic ylide (138), generated via the desilylation route, underwent cyclization to afford dihydropyrrole (139) in 42% yield.67b The structure of (139) is closely related to erythramine. The structurally related non-stabilized azomethine ylide (140) did not cyclize, tautomerizing to the corresponding enamine instead. 

The 1,3-dipolar cycloadditions of azomethine ylides with aldehydes readily produced high yields of oxazolidines, which hydrolysed to anti a-amino-y -hydroxy esters." Non-stabilized azomethine ylides with isotonic anhydrides produced oxa-zolidine intermediates, which were converted into l,3-benzodiazepin-5-ones via ringopening-decarboxylation-ring-closing reaction cascades." ... 

The [Ni(cod)2]-catalysed 3 + 2-cycloaddition of methyleneaziridines (32) with diynes (33) yielded substituted pyrroles (34), via azomethine ylides, with excellent regios-electivity (Scheme 10)." ° Aromatic heterocycles and carbocycles, including benzene and pyridine derivatives, have been shown to behave as 2a -electron components in the 3 + 2-cycloaddition reactions of non-stabilized azomethine ylides. Highly functionalized polyheterocyclic adducts are produced by this cycloaddition process." ... 

The 1,3-dipolar cycloaddition reaction of non-stabilized azomethine ylides, derived from A-alkyl-cf-amino acids, with 3-nitro-2-trifluoro(trichloro)methyl-2//-chromenes produced l-benzopyrano[3,4-c]pyrrolidines in good yields." AgOAc-catalysed asymmetric 3 + 2-cycloaddition reactions of azomethine ylides with e-deficient alkenes yielded enr/o-adducts with up to 99% ee. New chiral ferrocenyl P,N-ligands possessing a benzoxazole ring as the Af-donor (35) are effective asymmetric catalysts... 

The 3 + 2-cycloaddition reaction of azomethine ylides with c-deficient alkenes produced polysubstituted l- and D-unnatural prolines. Also, phosphoramidite-(7u(OTf)2 complexes catalyse the 1,3-dipolar cycloaddition reactions of azomethine ylides with nitroalkenes to yield exo-tetrasubstituted proline esters." The 1,3-dipolar cycloaddition of non-stabilized azomethine ylides, from iV-alkyl-a-amino acids and aldehydes, with 3-substituted coumarins provides l-benzopyrano[3,4-c]pyrrolidines in good yields and high regio- and stereo-selectivity." The organocatalytic 1,3-dipolar cycloaddition of azomethine ylides, derived from azlactones, with methyleneindolinones produced spirooxindoles with high yields (up to 95%) and high diastereo- (93 7 dr) and enantioselectivity (98% ee). ... 

The azomethine ylides described above all bear an ester or other electron-withdrawing group in order to promote yhde formation. Non-stabihzed azomethine ylides are less common, but can be produced, for example by decarboxylation or desilylation. The parent azomethine yhde 233 can be conveniently prepared by desilylation of an a-amino-silane, in which a leaving group (alkoxide, cyanide, benzotriazole, etc.) is present at an a position (3.147). Formation of the non-stabilized ylide 233 in the presence of an alkene or alkyne dipolarophile leads to the 2,5-unsubstituted pyrrolidine or dihydropyrrole product. 

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... 

Non-stabilized a, p y, 5-unsaturated azomethine ylides (158), generated by the decarboxylation method from 3,3-diarylpropenals (156) and secondary amino acids (157), have been found to undergo [1,7]-electrocyclization followed by a [1,5]-hydrogen shift, to yield 2,3-dihydro-17/-2-benzazepines (159). 

Pandey, G., Laha, J.K., and Lakshmaiah, G. 2002. Stereoselective construction of X-azabicyclo[ i.2.1]alkanes by [3+2]-cycloaddition of non-stabilized cyclic azomethine ylides synthesis of enantiopure constrained amino acids and formal total synthesis of optically active epibatidine. Tetrahedron 58, 3525-3534. 

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