Custom-Designed Robust MOF-Catalyst for Scalable 1,4-DHP Drugs With H-Bonding-Mediated Tandem Hantzsch Condensation and Shape-Reliant Friedel-Crafts Alkylation.

Flanked -NH2 functionality, polar carbonyl moiety and intrinsically unsaturated [Zn2(CO2)2(ATz)4] center-decked micropores in an ultra-robust metal-organic framework (MOF) are reported, assembled from bent dicarboxylate and triazole (ATz) ligand. The MOF serves as one-of-a-kind tandem Hantzsch condensation catalyst to yield a multitude of 1,4-dihydropyridines (1,4-DHPs) with low catalyst loading, short reaction duration at moderate temperature. Importantly, the MOF is used in the synthesis of six 1,4-DHP-based therapeutic molecules in >95% conversion, which are characterized in purest form via X-ray crystallography besides other spectroscopic analyses. Apart from gram-scale production of ethidine molecule at 40 °C in just 30 min, oxodipine drug is first-time synthesized by any framework-based catalyst. This mixed-ligand MOF further demonstrates highly recyclable Friedel-Crafts (FC) alkylation of indole and β-nitrostyrene and covers twenty electronically diverse substrates under relatively green conditions. Strikingly, larger-sized substrates can't diffuse inside the micropores and exemplifies rarest shape-reliant C‒C coupling reaction. Contrary to conventional Lewis-acid activation, the maximum contribution from hydrogen-bonding site promotes both tandem multi-component and FC reactions, as comprehensively supported from control experiments, analyte-induced emission articulation, inferior activity of task-specific site-truncated isoskeletal MOF, and density functional theory results. This work provides a major advancement on unconventional heterogeneous catalysis to produce valuable products.