Titanocene(III)-Mediated 5‑exo-trig Radical Cyclization: En Route to Spirooxindole-Based Tetrahydrofuran and Bicyclic Lactone

The isatin core system is of immense importance due to
the highly reactive prochiral C-3 position, which paves an easy way
to construct large arrays of spirooxindole heterocyclic motifs. Herein,
we depict an isatin-derived and 3,3′-disubstituted oxindole-appended
epoxy-acrylate undergoing Cp2Ti­(III)­Cl-mediated reductive
oxirane-ring opening with concomitant intramolecular 5-exo-trig radical
cyclization leading to tetrahydrofuran-based oxa-spirooxindole systems.
The fused spirooxindole structural feature is embedded in many natural
products and tends to exhibit a wide spectrum of biological activities.
The presence of more than one quaternary center and the availability
of multiple functional groups like hydroxyl, ester, or lactone in
the resultant products expand the scope of synthetic applications
of the newly acquired oxa-spirooxindole molecules.

靛红（isatin）核心体系具有极高的研究价值，因其存在高反应活性的前手性C-3位点，可为构建多样的螺吲哚酮（spirooxindole）杂环结构基元提供简便路径。本文报道了一种由靛红衍生、带有3,3'-二取代吲哚酮取代基的环氧丙烯酸酯，该底物在二茂钛(III)氯化物（Cp2Ti(III)Cl）介导下发生还原环氧开环反应，同时伴随分子内5-exo-trig自由基环化，最终生成基于四氢呋喃（tetrahydrofuran）的氧杂螺吲哚酮体系。稠合螺吲哚酮结构广泛存在于众多天然产物中，且通常展现出广谱的生物活性。所得产物中不仅包含多个季碳中心，还带有羟基、酯基或内酯等多种官能团，这进一步拓展了这类新型氧杂螺吲哚酮分子的合成应用空间。