Sun Hui, Yang Li-Heng, Fu Meng-Yun, Cui Bin
Manganese Catalysis and Asymmetric Synthesis Laboratory, Hebei University of Science and Technology, Shijiazhuang 050018, China.
Molecules. 2025 Feb 28;30(5):1114. doi: 10.3390/molecules30051114.
A facile strategy to increase the chemoselectivity of domino reactions was proposed and successfully applied in the α-functionalization of ketones. The strategy involved widening the activation energy of the main reaction and side reaction through intermolecular interactions, thereby increasing the chemoselectivity of the domino reaction. In the proposed α-functionalization reaction, TMSCF acted as an excellent reagent which increased the nucleophilicity of DMF through the Van der Waals force and reduced the nucleophilicity of HO through a hydrogen bond. We found that TMSCF can increase the activation energy difference between the main reaction and side reaction using DFT calculations, which greatly increased chemoselectivity and avoided the formation of by-products. TMSCF was recycled by rectification, and the average recovery rate was 87.2%. DFT calculations, XRD experiments, and control experiments were performed to support this mechanism. We are confident that this strategy has the potential to deliver significant practical advancements while simultaneously fostering broader innovation in the field of domino synthesis.
提出了一种提高多米诺反应化学选择性的简便策略，并成功应用于酮的α-官能化反应。该策略通过分子间相互作用扩大主反应和副反应的活化能，从而提高多米诺反应的化学选择性。在所提出的α-官能化反应中，TMSCF作为一种优良试剂，通过范德华力增加DMF的亲核性，并通过氢键降低HO的亲核性。我们发现，通过密度泛函理论（DFT）计算，TMSCF可以增加主反应和副反应之间的活化能差，这大大提高了化学选择性并避免了副产物的形成。通过精馏回收TMSCF，平均回收率为87.2%。进行了DFT计算、X射线衍射（XRD）实验和对照实验来支持这一机理。我们相信，这一策略有潜力带来重大的实际进展，同时促进多米诺合成领域更广泛的创新。
