Efficient and General Synthesis of 3‐Aminoindolines and 3‐Aminoindoles via Copper‐Catalyzed Three‐Component Coupling Reaction

Abstract

An efficient three component coupling (TCC) reaction toward a variety of 3-aminoindoline and 3-aminoindole derivatives has been developed. This cascade transformation proceeds via the copper-catalyzed coupling reaction between 2-aminobenzaldehyde, secondary amine, and alkyne leading to propargylamine intermediate, which, under the reaction conditions, undergoes cyclization into the indoline core. The latter, upon treatment with a base, smoothly isomerizes into indole. Alternatively, indole can directly be synthesized in a one-pot sequential reaction.

Aminoindolines versus Quinolines: Mechanistic Insights into the Reaction between 2-Aminobenzaldehydes and Terminal Alkynes in the Presence of Metals and Secondary Amines

“…11 Similarly, there exists a conceptually analogous report from Sakai's laboratory which involves the process for the synthesis of benzofurans in good yields (Scheme 1, path b, Z = O). 12 The main mechanistic feature distinguishing our report 9 from Gevorgyan's 11 and Sakai's 12 reports is the fate of cyclization of in situ generated propargyl amines with tethered nucleophiles.…”

One-Pot Phosphine-Catalyzed Syntheses of Quinolines

“…12 The N -tosyl- o -aminophenones 1t and 1u were prepared directly from the corresponding o -aminophenones through a single tosylation step. 13 The N -tosyl- o -aminophenones 1v and 1w were prepared from the corresponding 2-aminobenzonitriles in two steps, without purification of any intermediates.…”

Copper‐Catalyzed Indole Synthesis

“…The method was extended to a synthesis of homofascaplysin C. Duan and colleagues found that aqueous ammonia and 2-bromo arylacetylenes provides a simple and direct copper(II)catalyzed indole synthesis (equation 2) [97]. A new synthesis of 3-aminoindoles (and indolines) was developed by Gevorgyan from 2-aminobenzaldehyde, a secondary [98]. The initially formed (isolable) 3-aminoindolines were easily isomerized to the 3-aminoindoles (Cs 2 CO 3 , THF, MeOH, 65%-87%).…”