Ahmad Bayu I Z, Jerozal Ronald T, Meng Sijing, Oh Changwan, Cho Yeongsu, Kulik Heather J, Lambert Tristan H, Milner Phillip J
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14850, United States.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
J Am Chem Soc. 2024 Dec 18;146(50):34743-34752. doi: 10.1021/jacs.4c13196. Epub 2024 Dec 4.
The synthesis of amides from amines and carboxylic acids is the most widely carried out reaction in medicinal chemistry. Yet, most amide couplings are still conducted using stoichiometric reagents, leading to significant waste; few synthetic catalysts for this transformation have been adopted industrially due to their limited scope and/or poor recyclability. The majority of catalytic approaches focus on a single activation mode, such as enhancing the electrophilicity of the carboxylic acid partner using a Lewis acid. In contrast, nature effortlessly forges and breaks amide bonds using precise arrays of Lewis/Brønsted acidic and basic functional groups. Drawing inspiration from these systems, herein we report a simple defect engineering strategy to colocalize Lewis acidic Zr sites with other catalytically active species within porous metal-organic frameworks (MOFs). Specifically, the combination of pyridine -oxide and Zr open metal sites within the defective framework produces a heterogeneous catalyst that facilitates amide bond formation with broad functional group compatibility from amines and carboxylic acids, esters, or primary amides. Extensive density functional theory (DFT) calculations using cluster models support that the formation of a hydrogen-bonding network at the defect sites facilitates amide bond formation in this material. can be recycled at least five times without losing significant crystallinity, porosity, or catalytic activity and can be employed in continuous flow. This defect engineering strategy can be potentially generalized to produce libraries of catalytically active MOFs with different combinations of colocalized functional groups.
由胺和羧酸合成酰胺是药物化学中应用最广泛的反应。然而，大多数酰胺偶联反应仍使用化学计量的试剂进行，这导致大量浪费；由于适用范围有限和/或可回收性差，很少有用于这种转化的合成催化剂被工业采用。大多数催化方法都集中在单一的活化模式上，例如使用路易斯酸增强羧酸反应物的亲电性。相比之下，自然界利用精确排列的路易斯/布朗斯特酸性和碱性官能团轻松地形成和断裂酰胺键。受这些体系的启发，我们在此报告一种简单的缺陷工程策略，以在多孔金属有机框架（MOF）中将路易斯酸性Zr位点与其他催化活性物种共定位。具体而言，缺陷框架内吡啶氧化物和Zr开放金属位点的组合产生了一种多相催化剂，该催化剂有助于胺与羧酸、酯或伯酰胺形成具有广泛官能团兼容性的酰胺键。使用簇模型进行的广泛密度泛函理论（DFT）计算支持，缺陷位点处氢键网络的形成促进了该材料中酰胺键的形成。该催化剂可以循环使用至少五次而不会显著丧失结晶度、孔隙率或催化活性，并且可以用于连续流动。这种缺陷工程策略有可能被推广，以制备具有共定位官能团不同组合的催化活性MOF文库。
