α-Iminyl Cation-Involved Indole Construction via Brønsted Acid-Promoted Reaction of Isoxazol-5-ones

J Org Chem. 2022 Aug 19;87(16):11226-11230. doi: 10.1021/acs.joc.2c01086. Epub 2022 Jul 28.

Abstract

Herein, we report a strategically novel method for the efficient construction of indole skeletons using 2-phenylisoxazol-5-ones as the starting material. This reaction proceeds via Brønsted acid-promoted α-iminyl cation generation by N-O bond cleavage and a subsequent intramolecular cyclization to afford 1H-indole-3-carboxylic acid, which further undergoes decarboxylation to yield the final product. Control experiments show that N-O bond cleavage and intramolecular cyclization proceed so fast that the 1H-indole-3-carboxylic acid could be isolated in high yields even after 5-10 min. The substrate scope of this transformation is broad, and the desired products are obtained in moderate to good yields. The transition-metal-free reaction condition, CO2 as the sole byproduct, and good practicability add to the synthetic potential of this transformation in the pharmaceutical and flavor industries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acids / chemistry
  • Androstenols*
  • Cations
  • Cyclization
  • Indoles* / chemistry

Substances

  • Acids
  • Androstenols
  • Cations
  • Indoles
  • azastene