Development of TfOH-Catalyzed Spirocyclization by Intramolecular Friedel-Crafts-type 1,4-Addition: Application to the Total Synthesis of the Unusual Proaporphine Alkaloid (±)-Misrametine

Keisuke Yoshida, Arisa Hidaka, Yuri Fukami, Yuta Fujino, Yuri Imaizumi, Ken ichi Takao, Shinji Kitagaki

Research output: Contribution to journalArticlepeer-review

Abstract

An effective method was developed for TfOH-catalyzed construction of spiroindanes and spirotetralines containing an all-carbon quaternary stereocenter. Intramolecular Friedel-Crafts-type 1,4-addition of the substrates which were di- or trimethoxybenzene and 2-cyclohexenone linked by an alkyl chain proceeded smoothly in the presence of 30 mol % of TfOH. A variety of spiroindanes and spirotetralines were obtained with moderate to excellent yield by this method. The reaction was successfully applied in the first total synthesis of the unusual proaporphine alkaloid (±)-misrametine, which included the gram-scale spirocyclization and selective O-demethylation used KCN in DMSO condition as key steps.

Original languageEnglish
JournalChemistry - A European Journal
DOIs
Publication statusAccepted/In press - 2022

Keywords

  • acid catalysis
  • alkaloids
  • cyclization
  • misrametine
  • spiro compounds

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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