2024/12/04 by Bayu I. Z. Ahmad, R.T. Jerozal, Sijing Meng +5 · 1 voice · 1 citation
Chemistry · Biochemistry, Genetics and Molecular Biology · #Metal-Organic Frameworks: Synthesis and Applications #Chemical Synthesis and Reactions #Chemical Synthesis and Analysis
paper · doi:10.1021/jacs.4c13196
openalex publication_date 2024/12/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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 N -oxide and Zr open metal sites within the defective framework MOF-808-py-Nox 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. MOF-808-py-Nox 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.