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

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 p...

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Published in:Chemistry : a European journal 2022-10, Vol.28 (60), p.e202202188-n/a
Main Authors: Yoshida, Keisuke, Hidaka, Arisa, Fukami, Yuri, Fujino, Yuta, Imaizumi, Yuri, Takao, Ken‐ichi, Kitagaki, Shinji
Format: Article
Language:English
Subjects:
acid catalysis
Alkaloids
Chemistry
cyclization
Demethylation
misrametine
spiro compounds
Substrates
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Summary: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. Effective method for TfOH‐catalyzed construction of spiroindanes and spirotetralines containing an all‐carbon quaternary stereocenter was developed, and the reaction was applied to the first total synthesis of (±)‐misrametine.
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.202202188