Copper-Catalyzed Tandem Imine Formation, Sonogashira Coupling and Intramolecular Hydroamination: A Facile Synthesis of 3-Aryl-γ−carbolines

Abstract

A one‐pot, atom‐economical multicomponent reaction of 2‐bromoindole‐3‐carbaldehydes, alkynes and ammonia was developed in the presence of copper catalyst for the synthesis of a series of 3‐aryl‐γ−carboline derivatives in good to high yields. The developed reaction involved formation of imine followed by copper‐catalyzed directed Sonogashira coupling and intramolecular hydroamination sequence of reactions. This multicomponent approach features mild reaction conditions and good functional group tolerance to access variety of 3‐aryl γ‐carbolines.

Synthesis of 1,2-Fused Tricyclic Indoles via Cu-/Base-Mediated Hydroamination of Alkynes

“…24 Our lab has recently reported a Cu-catalyzed multicomponent reaction of 2-bromoindole-3carbaldehydes, alkynes, and ammonia for the synthesis of 3aryl-γ-carbolines. 25 The structural makeup of sulfide 4 bears a close resemblance with various components of our γ-carboline synthesis; hence, it was envisioned that 4 could potentially undergo similar intramolecular hydroamination in the presence of ammonia to produce 2,3-fused indoles containing seven/ eight-membered ring(s). To probe those avenues, unsubstituted sulfide 4a was chosen as a model reactant and subjected to Cu-catalysis in the presence of aqueous NH 4 OH in DMSO, conditions as per our 3-aryl-γ-carboline synthesis.…”

“…Copper­(I) has been shown to be highly effective in catalyzing intramolecular cyclization of terminal alkynes . Our lab has recently reported a Cu-catalyzed multicomponent reaction of 2-bromoindole-3-carbaldehydes, alkynes, and ammonia for the synthesis of 3-aryl-γ-carbolines . The structural makeup of sulfide 4 bears a close resemblance with various components of our γ-carboline synthesis; hence, it was envisioned that 4 could potentially undergo similar intramolecular hydroamination in the presence of ammonia to produce 2,3-fused indoles containing seven/eight-membered ring(s).…”

Synthesis Strategies for α‐, β‐, γ‐ and δ‐Carbolines

“…developed an atom‐economic multicomponent reaction to synthesize γ‐carboline derivatives by using 2‐bromoindole‐3‐formaldehyde ( 162 ) and alkyne in the presence of copper catalyst (Scheme 31). [60b] This reaction involved the formation of imine ( 163 ), followed by Cu‐catalyzed directed Sonogashira coupling reaction and intramolecular hydroamination [66] . Through this route, a series of 3‐aryl‐γ‐carboline ( 164 ) were obtained under mild conditions with good resistance to functional groups.…”

Copper-catalyzed Sonogashira reactions: advances and perspectives since 2014

“…Dhiman and co-workers formulated a copper catalyzed one-pot, atom-economical multicomponent reaction of 2-bromoindole-3-carbaldehydes, alkynes and ammonia to give a series of 3-aryl-γ-carboline derivatives in good to excellent yield. 43 This method involves the imine production followed by copper-catalyzed directed Sonogashira coupling and intramolecular hydroamination reactions. This multicomponent technique involves mild reaction conditions and exhibit good functional group compatibility.…”