Synthesis of 8-Fluoro-3,4-dihydroisoquinoline and Its Transformation to 1,8-Disubstituted Tetrahydroisoquinolines

Molecules. 2018 May 26;23(6):1280. doi: 10.3390/molecules23061280.

Abstract

A simple procedure for the synthesis of 8-fluoro-3,4-dihydroisoquinoline is described below, based on a directed ortho-lithiation reaction. This key intermediate was then applied in various transformations. Fluorine⁻amine exchange afforded the corresponding 8-amino-3,4-dihydroisoquinolines, suitable starting compounds for the synthesis of 1-substituted 8-amino-tetrahydroisoquinolines. On the other hand, reduction and alkylation reactions of 8-fluoro-3,4-dihydroisoquinoline led to novel 1,2,3,4-tetrahydroisoquinoline derivatives that can be used as building blocks in the synthesis of potential central nervous system drug candidates.

Keywords: alkylation; cyclization; isoquinoline; lithiation; nucleophilic aromatic substitution; reduction.

MeSH terms

  • Alkylation
  • Cyclization
  • Isoquinolines / chemical synthesis*
  • Molecular Structure
  • Oxidation-Reduction
  • Tetrahydroisoquinolines / chemistry*

Substances

  • G 1616
  • Isoquinolines
  • Tetrahydroisoquinolines