Organocatalytic enantioselective Pictet-Spengler reactions for the syntheses of 1-substituted 1,2,3,4-tetrahydroisoquinolines

J Org Chem. 2014 Aug 15;79(16):7380-90. doi: 10.1021/jo501099h. Epub 2014 Jul 30.

Abstract

A series of 1-substituted 1,2,3,4-tetrahydroisoquinolines was prepared from N-(o-nitrophenylsulfenyl)phenylethylamines through BINOL-phosphoric acid [(R)-TRIP]-catalyzed asymmetric Pictet-Spengler reactions. The sulfenamide moiety is crucial for the rate and enantioselectivity of the iminium ion cyclization and the products are readily recrystallized to high enantiomeric purity. Using this methodology we synthesized the natural products (R)-crispine A, (R)-calycotomine and (R)-colchietine, the synthetic drug (R)-almorexant and the (S)-enantiomer of a biologically active (R)-AMPA-antagonist.

MeSH terms

  • Acetamides / chemical synthesis
  • Acetamides / chemistry
  • Biological Products / chemical synthesis*
  • Biological Products / chemistry
  • Catalysis
  • Cyclization
  • Ethylamines / chemistry*
  • Isoquinolines / chemical synthesis
  • Isoquinolines / chemistry
  • Molecular Structure
  • Naphthols / chemical synthesis
  • Naphthols / chemistry
  • Nitrobenzenes / chemistry*
  • Organophosphorus Compounds / chemical synthesis*
  • Organophosphorus Compounds / chemistry
  • Receptors, AMPA / antagonists & inhibitors*
  • Receptors, AMPA / chemistry*
  • Stereoisomerism
  • Tetrahydroisoquinolines / chemical synthesis*
  • Tetrahydroisoquinolines / chemistry

Substances

  • Acetamides
  • BINOL, naphthol
  • Biological Products
  • Ethylamines
  • Isoquinolines
  • Naphthols
  • Nitrobenzenes
  • Organophosphorus Compounds
  • Receptors, AMPA
  • Tetrahydroisoquinolines
  • crispine A
  • almorexant