清华大学李隽研究团队报道了双取代原子催化交叉偶联。相关研究成果发表在2023年9月20日出版的《自然》。

单原子催化剂（SACs）具有明确的活性位点，使其对有机合成具有潜在的兴趣。然而，由于空间环境和电子量子态的限制，这些稳定在固体载体上的单核金属物种的结构可能不是催化复杂分子转化的最佳结构。

该文中，研究人员报道了一类非均相双子原子催化剂（GACs），它以特定的配位和空间接近度对单原子位点进行配对。聚合物氮化碳（PCN）主体中具有离域π键性质规则分离的氮锚定基团使Cu双子位点的配位，在高金属密度下基态分离约为4。GACs中单个Cu位点的适应性配位通过动态Cu–Cu键合实现了具有低激活势垒的不同C–X（X=C，N，O，S）交叉耦合的协同桥耦合途径。

原位表征和量子理论研究表明，这种交叉耦合的动力学过程是由两种不同反应物在双子金属位点的吸附引发的，这使得均耦合不可行。GACs的这些内在优势使得能够组装具有几个配位位点的杂环、空间拥挤的支架和具有高度特异性和稳定活性的药物。放大实验和转化为连续流动表明，精细化学品的制造具有广泛的适用性。

附：英文原文

Title: Geminal-atom catalysis for cross-coupling

Author: Hai, Xiao, Zheng, Yang, Yu, Qi, Guo, Na, Xi, Shibo, Zhao, Xiaoxu, Mitchell, Sharon, Luo, Xiaohua, Tulus, Victor, Wang, Mu, Sheng, Xiaoyu, Ren, Longbin, Long, Xiangdong, Li, Jing, He, Peng, Lin, Huihui, Cui, Yige, Peng, Xinnan, Shi, Jiwei, Wu, Jie, Zhang, Chun, Zou, Ruqiang, Guilln-Goslbez, Gonzalo, Prez-Ramrez, Javier, Koh, Ming Joo, Zhu, Ye, Li, Jun, Lu, Jiong

Issue&Volume: 2023-09-20

Abstract: Single-atom catalysts (SACs) have well-defined active sites, making them of potential interest for organic synthesis1,2,3,4. However, the architecture of these mononuclear metal species stabilized on solid supports may not be optimal for catalysing complex molecular transformations owing to restricted spatial environment and electronic quantum states5,6. Here we report a class of heterogeneous geminal-atom catalysts (GACs), which pair single-atom sites in specific coordination and spatial proximity. Regularly separated nitrogen anchoring groups with delocalized π-bonding nature in a polymeric carbon nitride (PCN) host7 permit the coordination of Cu geminal sites with a ground-state separation of about 4 at high metal density8. The adaptable coordination of individual Cu sites in GACs enables a cooperative bridge-coupling pathway through dynamic Cu–Cu bonding for diverse C–X (X=C, N, O, S) cross-couplings with a low activation barrier. In situ characterization and quantum-theoretical studies show that such a dynamic process for cross-coupling is triggered by the adsorption of two different reactants at geminal metal sites, rendering homo-coupling unfeasible. These intrinsic advantages of GACs enable the assembly of heterocycles with several coordination sites, sterically congested scaffolds and pharmaceuticals with highly specific and stable activity. Scale-up experiments and translation to continuous flow suggest broad applicability for the manufacturing of fine chemicals.

DOI: 10.1038/s41586-023-06529-z

Source: https://www.nature.com/articles/s41586-023-06529-z