南京师范大学杜炳南/南京大学王毅CCL:球磨促进镍催化酮和芳基卤代物的还原烯基化反应
图1. TOC (图片来源于Chin. Chem. Lett.)Aryl-substituted olefins are valuable structural motifs in pharmaceuticals and functional materials, yet the direct pathway for ketones olefination with aryl halides to achieve it remains challenging. Herein, we report an unprecedented mechanochemical-enabled ketone olefination with aryl halides via nickel catalysis. This protocol features mild reaction conditions, broad substrate scope, and excellent functional group compatibility, with its practical value demonstrated by the successful synthesis of diverse drug molecules. Mechanistic studies, including component analyses, control experiments, and density functional theory (DFT) calculations, give insight into the catalytic cycle and support the multiple roles of “zinc” in the catalytic cycle: (i) reductant, (ii) activator of the carbonyl group, (iii) promoter of C–O σ-bond cleavage. Furthermore, comparative experiments reveal that more effective ketone activation in mechano-condition is crucial for realizing this transformation.图2. 研究背景及本策略 (图片来源于Chin. Chem. Lett.)图3. 条件优化 (图片来源于Chin. Chem. Lett.)图4. 底物拓展 (图片来源于Chin. Chem. Lett.)图5. 合成应用 (图片来源于Chin. Chem. Lett.)图6. 机理研究 (图片来源于Chin. Chem. Lett.)图7. 对比实验 (图片来源于Chin. Chem. Lett.)图8. 可能的反应机理 (图片来源于Chin. Chem. Lett.)In conclusion, we have developed a novel mechanochemical-enabled ketone olefination with aryl halides via nickel catalysis. The reaction proceeds under mild conditions, shows broad substrate scope and excellent functional group tolerance, and has been applied to synthesize a series of drug molecules, thereby demonstrating the synthetic potential of this method. Mechanistic studies, which including component analyses, control experiments, DFT calculations, and comparative experiments, give insight into the catalytic path, and elucidate that the more effective ketone activation under ball milling conditions—particularly with aryl bromides as substrates—is a key factor in enabling this efficient transformation. We envision that these findings will not only serve as a tool for the synthesis of diverse aryl-substituted olefins but also offer insights about the potential of mechanochemistry in facilitating kinetically unfavourable reactions.
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