Gifu Pharmaceutical University, 1-25-4, Daigaku-Nishi, Gifu-shi, Gifu 501-1196, Japan.
J Org Chem. 2020 Aug 21;85(16):10709-10718. doi: 10.1021/acs.joc.0c01251. Epub 2020 Aug 7.
A novel three-component γ-iminolactonization reaction was developed, which relied on the C-C/C-O bond-forming bifunctionalization of olefins using molecular iodine and visible light. This strategy did not require any (heavy) metal reagents for double-bond activation because molecular iodine acted as a rare-metal-alternative reagent through visible light irradiation. In addition, the preactivation of amines and other substrates is not required. The mechanistic investigation revealed that the generated iodine radicals under visible light irradiation reacted with alkenes to form a highly reactive intermediate; then, the three-component reaction of diiodide, malonate, and amine furnished iminolactone. Of note, the developed reaction is simple and realized the diversity-oriented synthesis innovative methodology of γ-iminolactone derivatives in drug discovery chemistry.
发展了一种新型的三组分γ-亚氨基内酯化反应，该反应依赖于分子碘和可见光促进的烯烃的 C-C/C-O 键形成双官能化。该策略不需要任何（重）金属试剂进行双键活化，因为分子碘通过可见光照射充当了一种替代稀有金属试剂。此外，也不需要对胺和其他底物进行预活化。机理研究表明，可见光照射下生成的碘自由基与烯烃反应形成高活性中间体；然后，二碘化物、丙二酸酯和胺的三组分反应生成亚氨基内酯。值得注意的是，开发的反应具有简单性，并在药物发现化学中实现了γ-亚氨基内酯衍生物的多样性导向合成创新方法。
