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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Silver-Catalyzed Synthesis of Isoquinolones via Oxazole Ring Opening
Akiko Fujii1, Tomoki Hyodo1, Tsuyoshi Yamada2
1Laboratory of Advanced Chemistry and Next Generation Energy Chemistry Joint Research Laboratory, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
Abstract:
A novel method for synthesizing isoquinolones has been developed, involving the use of a silver(I)-catalyzed intramolecular cyclization and an oxazole ring-opening reaction. The 6-endo-dig cyclization from oxazole results in the formation of the isoquinolone core with a high degree of yield and selectivity. This method is executed under mild conditions, utilizing silver acetate as a cost-effective catalyst. A thorough examination of the reaction mechanism was undertaken, revealing that the addition of H2O is conducive to ring opening. The nitrogen atom of the oxazole ring attacks the silver acetate-activated alkyne. It was ascertained that a silver-vinyl intermediate is formed while retaining the oxazole ring during this process.
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