Diastereoselectivity in 1,3-Dipolar Cycloaddition Reactions between Indolic Nitrones and Electron-Deficient Alkenes

Abstract

2-Phenyl-3H-indol-3-one N-oxide (2-phenylisatogen), 2-phenyl-3-phenylimino-3H-indole N-oxide and 2-phenyl-3H-indole N-oxide (the tautomeric form of 1-hydroxy-2-phenylindole) reacted in refluxing toluene with maleimides with different substituents at the nitrogen, yielding 1,3-cycloaddition products. The cycloaddition was diastereoselective for the first two nitrones, whereas in the case of 2-phenyl-3H-indole N-oxide only the formation of the endo cycloadduct was observed. This different behaviour is attributed to the substituent at C-3 of the five-membered ring in the indole nucleus. In 95% ethanol at room temperature, metal cations such as CoII, CuII, CaII, MnII, ZnII, and NiII catalyse the reaction between 2-phenylisatogen and N-phenylmaleimide without substantially affecting the diastereoselectivity. The crystal structures of endo-3a,10,10a,10b-tetrahydro-10aphenyl-1H-pyrrolo[3′,4′:4,5]isoxazolo[2,3-a]indole-1,3,10trione (5a), endo-2-methyl-10a-phenyl-3a,10,10a,10b-tetrahydropyrrolo[3′,4′:4,5]isoxazolo[2,3-a]indole-1,3-dione (8a), and endo-2,10a-diphenyl-3a,10,10a,10b-tetrahydropyrrolo[3′,4′:4,5]isoxazolo[2,3-a]indole-1,3-dione (8b) are reported.