Department of Chemistry , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
Department of Chemistry , University of Pittsburgh , Pittsburgh , Pennsylvania 15260 , United States.
J Am Chem Soc. 2018 Oct 24;140(42):13976-13984. doi: 10.1021/jacs.8b09565. Epub 2018 Oct 15.
Using a mechanically guided ligand design approach, a new ligand (SEGFAST) for the CuH-catalyzed hydroamination reaction of unactivated terminal olefins has been developed, providing a 62-fold rate increase over reactions compared to DTBM-SEGPHOS, the previous optimal ligand. Combining the respective strengths of computational chemistry and experimental kinetic measurements, we were able to quickly identify potential modifications that lead to more effective ligands, thus avoiding synthesizing and testing a large library of ligands. By optimizing the combination of attractive, noncovalent ligand-substrate interactions and the stability of the catalyst under the reaction conditions, we were able to identify a finely tuned hybrid ligand that greatly enables accelerated hydrocupration rates with unactivated alkenes. Moreover, a modular and robust synthetic sequence was devised, which allowed for the practical, gram-scale synthesis of these novel hybrid ligand structures.
采用机械引导配体设计方法，开发了一种用于 CuH 催化未活化末端烯烃的氢胺化反应的新型配体（SEGFAST），与之前最优配体 DTBM-SEGPHOS 相比，反应速率提高了 62 倍。结合计算化学和实验动力学测量的各自优势，我们能够快速识别出潜在的修饰方法，从而避免合成和测试大量配体文库。通过优化有吸引力的非共价配体-底物相互作用的组合以及催化剂在反应条件下的稳定性，我们能够确定一种精细调整的混合配体，极大地提高了对未活化烯烃的氢加成速率。此外，设计了一种模块化且稳健的合成序列，允许这些新型混合配体结构进行实际的、克级规模的合成。
