Cycloreversions, azomethine ylide generation

Intramolecular azomethine ylide cycloaddition to the C—O double bond of an aldehyde was reported in 197369 and cycloaddition to the C—C double bond was first reported in 1975.70 Competition between 1,1- and 1,3-cycloaddition is observed in intramolecular reactions, although intermolecular reactions give only 1,3-cycloaddition. Photolysis of 2//-azirines is one generation method of nitrile ylides applicable to intramolecular cycloaddition.70 Another method involves the base-catalyzed 1,3-elimination of hydrogen halide from alkenyl imidoyl halides. Still other procedures involve thermolytic and photolytic cycloreversions of oxazolinones and dihydrooxazaphospholes. 

Generation of azomethine ylides by starting from oxazoline heterocycles consists of the following steps (1) valence isomerization of 4-isoxazolines, (2) valence isomerization of 4-oxazolines, and (3) cycloreversion of 5-oxazo-lidinones or oxazolidines. These three generation methods as variations of the oxazoline route are reviewed in this section. 

The last variation of the oxazoline route is a cycloreversion of 5-oxazoli-dinones or oxazolidines. Thermal decarboxylation of 5-oxazolidinones is a convenient method of generating nonstabilized azomethine ylides, since the heterocyclic precursors are accessible, and sometimes isolable, by simply heating a-amino acids and carbonyl compounds. This has been discussed in Section II,E. 

From a synthetic viewpoint, iV-arylvinylamines are not appropriate as azomethine ylide precursors because the hydrogen shift from the intermediary ylides must be extremely accelerated by the rearomatization of the fused dihydro benzo moiety. Zaima and Mitsuhashi were the first to succeed with synthetic applications of the above photochemical generation method of cyclic azomethine ylides (83JHC1). The substrate employed in their work is bis(l-methoxycarbonylvinyl)amine. Irradiation of this divinylamine in carbon tetrachloride at 18°C in the presence of acetylenedicarboxylates produces excellent yields of 7-azabicyclo[2.2.1]hept-2-ene-l,2,3,4-tetracarboxylates 172, which correspond to the cycloadducts of the expected azomethine ylide intermediate 171. Heating the bicyclic cycloadducts 172 at 90-120°C induces a smooth cycloreversion eliminating a molecule of ethene to give pyrrole-2,3,4,5-tetracarboxylates in quantitative yields. The azomethine ylide 171 can be trapped also with olehnic dipolarophiles, such as maleates and fuma-rates, to furnish stereospecifically 7-azabicyclo [2.2.1] heptane-1,2,3,4-tetra-carboxylates 173 and 174, respectively (84JHC445). 

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