Rapid Access to Amino-Substituted Quinoline, (Di)Benzofuran, and Carbazole Heterocycles through an Aminobenzannulation Reaction

Abstract

The use of a powerful aminobenzannulation reaction has been applied for the synthesis of amino-substituted quinolines, dibenzofurans, and carbazoles. The precursors are heterocycles bearing a methyl ketone group ortho to an internal alkyne. They are commercially available or can be obtained in three to four classical and efficient reactions: Vilsmeier-Haack, Sonogashira (diversity point), Grignard, and Ley's oxidation. Upon aminobenzannulation reaction-classical conditions being pyrrolidine neat or in a solvent and 4 A MS-an interesting range of disubstituted quinolines, dibenzofurans, and carbazoles are obtained along with enamine formation in some cases. The reaction is useful since meta-substituted heterocycles are produced and also differs from classical heterocyclic methods which go through closure at the heteroatom-containing ring instead of benzene ring formation.

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

“…The synthesis of precursor 2-bromo-1-methyl-1H-indole-3-carbaldehyde (1 a) was achieved from 2-oxindole following a literature procedure. [17] Initially, Cu-catalyzed Sonogashira coupling conditions [15] were applied to the mixture of 1 a, phenylacetylene (2 a) and aqueous ammonia. Precisely, in our first attempt, 1 a was reacted with 2 a (2 equiv.)…”

Tandem Silver‐Catalyzed Cyclization/Nucleophilic Functionalization of 2‐Alkynylindole‐3‐carbaldehyde Oximes to Afford New 2,4‐Disubstituted γ‐Carbolines

“…To perform the key silver‐catalyzed step, various 2‐alkynylindole‐3‐carbaldehyde oxime derivatives 3 were prepared. The rare (3 E )‐2‐alkynylindole‐3‐carbaldehyde oximes 3 were obtained in two‐step manner from N ‐Boc‐2‐bromo‐1 H ‐indole‐3‐carbaldehyde ( 1a , Table ) Sonogashira cross‐coupling at the brominated C2 position was first carried out with aliphatic or (het)aryl alkynes in the presence of Pd(PPh 3 ) 2 Cl 2 , CuI, and Et 3 N at room temperature. Whatever the electron‐donating or electron‐withdrawing nature of the substituents on the arylalkynes, the expected compounds 2a – i were isolated in good yields.…”

Regioselective alkynylation followed by Suzuki coupling of 2,4-dichloroquinoline: Synthesis of 2-alkynyl-4-arylquinolines

“…If the alkyne was at C-4, NOE enhancement at C-5 is expected in addition to C-3. It is note worthy that the use of the Sonogashira coupling or its modified form has been employed for the preparation of 2-alkynylquinolines or related derivatives earlier [7–17]. …”