Three‐Component Synthesis of 3‐Aminoalkylindoles using Iron(III) Phosphate

Abstract

Catalytic synthesis of 3‐substituted indole derivatives by a one‐pot three‐component coupling reaction between aldehyde, N‐methyl aniline and indole in the presence of FePO4 is described. Aldehydes having both electron‐donating and electron‐withdrawing groups were used and resulted the desired products in high yields Simple procedure, easy work up and employing of reusable and green catalyst are advantages of this protocol.

Synthesis of Indole-Coupled KYNA Derivatives via C–N Bond Cleavage of Mannich Bases

“…To synthesize the Mannich base of indole (4), several literature methods have been explored. Reactions utilizing catalysts, such as ferric phosphate [47] and iodine [48], or protic solvents, such as ethanol, methanol [49], and ethylene glycol [50], resulted mainly in bisindole derivative 5 mentioned in the corresponding literature as a byproduct. However, Mannich base 4 could be synthesized under neat conditions applying only indole, benzaldehyde, and pyrrolidine (with or without L-proline as catalyst [51,52]).…”

Catalytic C3 aza-alkylation of indoles

“…Copper-catalysed C3-alkylation of indoles. 33 and Behbahani, 34 respectively. In the first case a multicomponent reaction between an aromatic aldehyde, an aniline and indole, under solvent-free conditions was considered.…”

“…The same multicomponent strategy, again under neat conditions, was published one year later by Behbahani et al, with similar outcomes, but using FePO 3 as catalyst of choice. 34 Another group of inexpensive catalysts is constituted by zincbased Lewis acids. In this field, Rawat et al developed a nanocomposite of reduced graphene oxide and zinc oxide (RGO/ZnO) as a heterogeneous catalyst, for the synthesis of various 3-substituted indoles in water.…”

Recent Advances of Three‐component Reactions of Simple Indoles

“…Reactions of secondary amines, aldehydes and indoles would afford novel condensation products via the C−N bond formation. Diverse secondary amines, such as N ‐methylhidine, [29a–e] hexapyrrole, [29b] morpholine [29b,c] and tetrahydroxopyrrole, [29b,c] have been studied during these years. For example, the use of elemental iodine (10 mol%) [29e] was able to achieve these reactions efficiently with good yields (80–96%) (Scheme 21).…”