Lewis Acid Mediated Aminobenzannulation Reactions of δ‐Ketoalkynes: Synthesis of 1‐Aminocarbazoles and 9‐Aminopyrido[1,2‐a]indoles

Abstract

Abstract2‐Acyl‐N‐propargylindoles 1 and 2‐acyl‐3‐propargylindoles 5 undergo aminobenzannulation reactions with pyrrolidine in the presence of an appropriate Lewis acid to give 9‐aminopyrido[1,2‐a]indoles 6 and 1‐aminocarbazoles 7, respectively. The selection of the appropriate Lewis acid, TiCl4 or GaCl3 for 1 and InCl3 for 5, allows the domino process involving the initial formation of an enamine intermediate, followed by a regioselective 6‐exo‐dig intramolecular nucleophilic attack of the nucleophilic terminus of the unsaturated system (the β‐carbon of the enamino moiety) to the carbon–carbon triple bond. Moreover, several features concerning the reaction mechanism and the role of both catalysts, in connection with the electronic properties of the reacting alkynes, are reported. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

InCl3-assisted one-pot synthesis of 1-aminocarbazoles

“…Several mechanistic aspects connected to steps 2 and 3 and to the dual role exerted by InCl 3 , for these and related reactions, have been discussed elsewhere. 23 As already stated, the deferred addition of the secondary amine to the reaction mixture is probably required to avoid catalyst Scheme 2. On the contrary, when 5b, InCl 3 , and pyrrolidine are added to CD 3 CN at the same time the benzylic hydrogen at 6.61 ppm remains unchanged.…”

“…21,18 All reported syntheses proceed under Lewis acid and/or transition metals catalysis and involve a nucleophilic attack of a hetero-or carbon-based nucleophile over a carbonecarbon triple bond. 22 Moreover, in a recent work 23 we reported an indium(III)-promoted domino aminobenzannulation reaction giving rise to 1-aminocarbazoles 1 starting from 2-acyl-3-propargyl-1H-indoles 2 and pyrrolidine 3a, Scheme 1, path A.…”

Synthesis of α-Aminonaphthalenes via Copper-Catalyzed Aminobenzannulation of (o-Alkynyl)arylketones with Amines

“…Recently, the benzannulations of α-acetylenic aryl ketone derivatives, such as their silyl enol ethers or β-ketoesters, via regioselective intramolecular electrophilic 6- endo -dig carbocyclizations have provided a series of efficient pathways for the synthesis of polysubstituted naphthalenes. − Thereafter, analogous aminobenzannulation reactions of α-acetylenic (hetero)­aryl ketones with secondary amines were also developed for the construction of amino-substituted aromatic compounds. , In 2001, Herndon reported the palladium-catalyzed Sonogashira coupling, followed by cyclization between o -bromoacetophenone and 1-hexyne in diethylamine or pyrrolidine as solvents (Scheme a) . Later, Belmont developed a metal-free pyrrolidine-triggered aminobenzannulation reaction of α-acetylenic heteroaryl ketones, which were used for the construction of amino-substituted acridines, quinolones, dibenzofurans, and carbazoles (Scheme b) .…”

Novel Domino Approach to Fluorescent Pyrimido[1,6-a]indolones

“…During the last years, we focused our attention on the catalyzed and uncatalyzed domino addition-annulation reactions of 2-acyl-N-propargylindoles and 2-acyl-3alkynyl(or propargyl)indoles for the synthesis of a-or bfused polycyclic indole systems, respectively. Thus, using this synthetic approach, b-carbolines, 3 6 1-aminocarbazoles, 7 and 9-amino-pyrido[1,2-a]indoles 7 have been obtained. Most of the reported reactions [3][4][5]7 involve in the second step, step b of the domino reaction, a nucleophilic attack onto a carbon-carbon triple bond that allows the annulation onto an existing ring (Figure 1, A).…”

“…Thus, using this synthetic approach, b-carbolines, 3 6 1-aminocarbazoles, 7 and 9-amino-pyrido[1,2-a]indoles 7 have been obtained. Most of the reported reactions [3][4][5]7 involve in the second step, step b of the domino reaction, a nucleophilic attack onto a carbon-carbon triple bond that allows the annulation onto an existing ring (Figure 1, A). Furthermore, we reversed the sequence by performing a domino reaction involving in the first step, step a, a TiCl 4 /t-BuNH 2 -catalyzed hydroamination of the carbon-carbon triple bond followed by nucleophilic attack of the enamine intermediate at the carbon-oxygen double bond (Figure 1, B).…”