Concise Cu-Catalyzed Synthesis of 3-Carboxyl-N-Aminoindoles

Significance

Reported is the amination of methyl 2-(2-bromoaryl)-3-hydroxyacrylates to form enehydrazines, and their subsequent Cu-catalyzed cyclization to form 3-carboxyl-N-aminoindoles. Only two of the eight examples of enehydrazines were formally purified, thus providing, in general, a one-pot synthesis of the aminoindoles from the parent acrylates. The reaction products obtained were highly dependent on the nature of the ene­hydrazine. Thus, hydrazines fully substituted at the terminal nitrogen gave N-aminoindole products in good yield, whereas secondary terminal N-benzyl enehydrazines gave N-benzylidene analogues in moderate yields. Enehydrazines bearing other secondary amines at the terminal nitrogen led only to decomposition. However, N-amino­indoles bearing a secondary amine could be obtained through reaction of a bis-Boc-substituted enehydrazine which gave the NHBoc aminoindole in good yield.