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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Cis-Selective Double Spirocyclization via Dearomatization and Isomerization under Thermodynamic Control
Hiromasa Yokoe1, Akiko Kiriyama1, Miho Shimoda1
1School of Pharmacy and Pharmaceutical Sciences and Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Abstract:
Spiro compounds have been considered key scaffolds for pharmaceutical applications. Although many synthetic methods exist for monospirocycles, fewer approaches are known for dispirocycles. Here, we report a highly cis-selective method for constructing a 5/6/5-dispirocyclic structure containing pyrrolidine and γ-lactam rings with various substituents from a series of N-arylpropiolamides. The high cis-selectivity would result from isomerization under thermodynamic control. Cis- and trans-diastereomers can be in equilibrium, favoring cis-adducts.
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