Expedient Synthesis of N‐Fused Indoles: A CF Activation and CH Insertion Approach

Abstract

Easy does it: A wide range of N‐fused indole skeletons, which are core structures of many biologically potent molecules, are successfully furnished by a niobium‐catalyzed C(sp3)H insertion reaction (see picture). The precursors are readily prepared by a palladium‐catalyzed amination reaction of bromotrifluorotoluenes with cyclic amines.

Synthesis and Some Biological Properties of Pyrrolo[1,2‐a]indoles

“…The catalytic synthesis of pyrrolo[1,2-a]indoles from trifluoromethyl derivative 199 with niobium chloride was described [118]. The cyclization of diazoethers to 2,3-dihydropyrrolo[1,2-a]indoles using three different methods was studied [119][120][121].…”

“…The catalytic synthesis of pyrrolo[1,2‐ a ]indoles from trifluoromethyl derivative 199 with niobium chloride was described . The catalytic activation led to fluorocarbon niobium complex 200 , formation of a new bond with the carbon of the pyrrole cycle, and the closure of the pyrrole ring of the indole fragment with formation of fluoro‐indole 201 .…”

Indole synthesis through transition metal-catalyzed C–H activation

“…Niobium-catalyzed C(sp 3 )-H insertion to an in-situ generated fluorine-substituted carbenoid intermediate gave N-fused indoles (Scheme 34). 50 …”

Niob‐katalysierte Aktivierung von Aryltrifluormethylgruppen und Funktionalisierung von C‐H‐Bindungen: ein effizienter, konvergenter Ansatz zur N‐Heterocyclensynthese

“…Zusätzlich zur Hydrodefluorierung haben Akiyama und Mitarbeiter gezeigt, dass C-C-Bindungen durch Reduktion ortho-arylierter a,a,a-Trifluortoluolderivate gebildet werden können (Schema 5). [7,9,10] [11] Arylamine wie 20 werden von niedervalentem Niob reduziert, wobei Gemische des Indolins 21 und des Indols 22 erhalten werden [Gl. (1)].…”

“…[16] Der postulierte Mechanismus dieser Umwandlung verläuft über ein reaktives Carbenoid-Intermediat (Schema 7). [9,11]…”