Carbon dioxide radical anion mediated regioselective carboxy-cyclization of alkenes

作者：Xinyue Ma, Yongxin Zhang, Xiao Cai, Hui Xu, Ligang Huang, Hengyu Huo, Chao Shu · 发表于：Green Synthesis and Catalysis · 年份：2025 · DOI：10.1016/j.gresc.2025.07.005 · 被引用次数：6 · 研究领域：Carbon dioxide utilization in catalysis、Cyclopropane Reaction Mechanisms、Catalytic Alkyne Reactions

Cyclopropyl fatty acid linkers and their derivatives serve as high-value pharmacophores in pharmaceutical and biotechnological research. Despite significant advancements in the hydrocarboxylation and carboxy-alkylation of alkenes, controlling regioselectivity in the carboxy-cyclization of alkenes using the CO 2 radical anion remains a problem. Herein, we present the first retrosynthetic analysis-driven carboxy-cyclization strategy for alkenes and introduce a highly cost-efficient radical-polar crossover cyclization protocol that leverages carbon dioxide radical anion (CO 2 • - ) to achieve distinctive regioselectivity. This method enables the economical synthesis of a diverse range of functionalized cyclopropyl fatty acid linkers and seven-membered lactones from readily available starting materials, demonstrating high functional group compatibility. The practicality and versatility of this approach are further validated through gram-scale synthesis, late-stage transformations, and the direct formal total synthesis of three drug molecules, highlighting its broad potential in pharmaceutical development.