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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Development of TfOH-Catalyzed Spirocyclization by Intramolecular Friedel-Crafts-type 1,4-Addition: Application to the
Keisuke Yoshida1, Arisa Hidaka1, Yuri Fukami1
1Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, 468-8503, Japan.
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.
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