Domino Synthesis of 1,2,5-Trisubstituted 1<i>H</i>-Indole-3-carboxylic Esters Using a [3+2] Strategy.

ABSTRACT: A new approach to 1,2,5-trisubstituted 1H-indole-3-carboxylic esters has been developed and studied. The method begins with the preparation of imines from aldehyde and primary amine derivatives. Treatment of these imines with the K₂CO₃-derived anion from methyl 2-(2-fluoro-5-nitrophenyl)acetate or methyl 2-(5-cyano-2-fluorophenyl)acetate in DMF initiates a [3+2] cyclization by addition of the anion to the imine followed by ring closure of the adduct nitrogen to the activated aromatic moiety via an S_NAr process. Twenty-one examples are reported. Temperatures required for the conversion range from 90 to 95 °C for the nitro-activated substrates to 125 to 130 °C for the cyano-activated precursors. Though efficient and atom economical, limitations arise f

SUBMITTER: Maji S 

PROVIDER: S-EPMC11820459 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature