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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Modular Synthesis of Spiroisochromans with Spiro Quaternary Carbon Centers Via TBAT-Promoted Multicomponent Cascade
Wenbo Cai1, Chuanzhao Song2, Yangang Wu1
1College of Chemistry, Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001, China.
Abstract:
The construction of spiroisochroman frameworks featuring spiro quaternary carbon centers via multicomponent cascade reactions remains a formidable synthetic challenge. Herein, we report a tetrabutylammonium triphenyldifluorosilicate-initiated reaction system involving oxazolines, aryne precursors, and ketone derivatives. This protocol enables a facile one-pot synthetic approach to structurally challenging spiroisochroman scaffolds, including dispiro architectures and spiroisochromanone derivatives, which are otherwise difficult to synthesize. The transformation proceeds through aryne-triggered generation of reactive ortho-quinonoid intermediates, followed by selective [4 + 2] cycloaddition with carbonyl compounds. Notably, a substituent-controlled divergent pathway leading to phthalide derivatives was also discovered in this reaction system. The operational simplicity, broad applicability, and divergent reactivity highlight the synthetic utility of this cascade strategy.
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