A new route to privileged spirocyclic tetrahydroisoquinolines (spiroTHIQs) has been developed. The key step in which the spirocyclic system is formed in generally good yields and diastereoselectivity is the three-component Castagnoli-Cushman reaction of homophthalic anhydride, cyclic ketones and ammonium acetate. Decarboxylation of the initial adduct yields THIQ lactams which are reduced by lithium aluminum hydride. The route is shorter, more convergent and operationally simpler than the previously reported syntheses of similar spirocyclic building blocks.

Original languageEnglish
Article number152408
Number of pages3
JournalTetrahedron Letters
Volume61
Issue number42
Early online date31 Aug 2020
DOIs
StatePublished - 15 Oct 2020

    Research areas

  • Castagnoli-Cushman reaction, Decarboxylation, Lactam reduction, Privileged structures, Spirocycles, Tetrahydroisoquinolines, DESIGN, INHIBITORS

    Scopus subject areas

  • Drug Discovery
  • Biochemistry
  • Organic Chemistry

ID: 62463033