Dinuclear zinc catalyzed asymmetric Friedel–Crafts amidoalkylation of indoles with aryl aldimines

Abstract

The asymmetric Friedel-Crafts amidoalkylation of indoles with aryl aldimines could be efficiently catalyzed by Trost's bis-ProPhenol dinuclear zinc complexes to attain 3-indolyl methanamine derivatives in good to excellent yields (85-98%) with moderate to high enantiomeric ratios (from 70 : 30 up to 95 : 5 er). Remarkably, this approach provides efficient access to enantiomerically enriched 3-indolyl methanamines, which avoids the formation of the undesirable bis- and tris(indolyl)methanes (BIMs and TIMs) byproduct.

Dinuclear Metal‐ProPhenol Catalysts: Development and Synthetic Applications

“…Indoles 156 were also found to be effective pronucleophiles in ProPhenol‐catalyzed asymmetric Friedel–Crafts reactions with N ‐Ts aryl imines (Scheme a) . Using Zn‐ L‐1 a as the catalyst, a range of C3‐amidoaklylated indoles 157 were obtained in high yield and up to 95:5 er.…”

“…Indoles 156 were also found to be effective pronucleophiles in ProPhenol-catalyzed asymmetric Friedel-Crafts reactions with N-Ts aryl imines (Scheme 39 a). [74] Using Zn-L-1 a as the catalyst, a range of C3-amidoaklylated indoles 157 were obtained in high yield and up to 95:5 er. Moreover, the reaction occurred exclusively at the C3 position, and the free NÀH was required for reactivity, suggesting that deprotonation of indoles by Zn-ProPhenol is the key activation step.…”

Zweikernige Metall‐ProPhenol‐Katalysatoren: Entwicklung und Anwendungen in der Synthese

“…Indole 156 erwiesen sich in ProPhenol‐katalysierten asymmetrischen Friedel‐Crafts‐Reaktionen mit N ‐Ts‐Aryliminen ebenfalls als effektive Pronukleophile (Schema a) . Für Zn‐L‐1 a als Katalysator wurde eine Reihe C3‐amidoalkylierter Indole 157 mit hoher Ausbeute und bis zu 95:5 er erhalten.…”

Controlling Regioselectivity in the Enantioselective N‐Alkylation of Indole Analogues Catalyzed by Dinuclear Zinc‐ProPhenol

“…Due to the lack of methods available for the asymmetric synthesis of N,N‐acyclic aminals, these compounds have not been utilized to date. Indeed, the reported use of Zn‐ProPhenol led only to asymmetric C3‐alkylation when using the N‐Ts imine as the aminoalkylating agent (Scheme b) . One explanation for this regioselectivity could be that attack at the indole N occurs reversibly, whereas attack at C3 was irreversible.…”