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. 2023 Jul 11;35(13):4883-4896.
doi: 10.1021/acs.chemmater.3c00741. Epub 2023 Jun 21.

MOFganic Chemistry: Challenges and Opportunities for Metal-Organic Frameworks in Synthetic Organic Chemistry

Bayu I Z Ahmad  1 , Kaitlyn T Keasler  1 , Emily E Stacy  1 , Sijing Meng  1 , Thomas J Hicks  1 , Phillip J Milner  1
Affiliations

MOFganic Chemistry: Challenges and Opportunities for Metal-Organic Frameworks in Synthetic Organic Chemistry

Bayu I Z Ahmad et al. Chem Mater. .

Abstract

Metal-organic frameworks (MOFs) are porous, crystalline solids constructed from organic linkers and inorganic nodes that have been widely studied for applications in gas storage, chemical separations, and drug delivery. Owing to their highly modular structures and tunable pore environments, we propose that MOFs have significant untapped potential as catalysts and reagents relevant to the synthesis of next-generation therapeutics. Herein, we outline the properties of MOFs that make them promising for applications in synthetic organic chemistry, including new reactivity and selectivity, enhanced robustness, and user-friendly preparation. In addition, we outline the challenges facing the field and propose new directions to maximize the utility of MOFs for drug synthesis. This perspective aims to bring together the organic and MOF communities to develop new heterogeneous platforms capable of achieving synthetic transformations that cannot be replicated by homogeneous systems.

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Figures

Figure 1.
Figure 1.
Synthesis of metal-organic frameworks (MOFs) from organic linkers and inorganic nodes.
Figure 2.
Figure 2.
Favorable properties of MOFs relevant to synthetic organic and medicinal chemistry.
Figure 3.
Figure 3.
a) Structure of squaramide-containing MOF UiO-67-squar/bpdc. b) Catalytic activity for the Friedel-Crafts alkylation of indole with β-nitrostyrene. Tol = toluene.
Figure 4.
Figure 4.
a) Structure of ZrOTf-BTC and catalytically active Lewis acid sites. b) Catalytic activity of ZrOTf-BTC for alkene hydroalkoxylation. Adapted with permission from ref. Copyright 2019 American Chemical Society.
Figure 5.
Figure 5.
Mechanism of the dual photoredox/Lewis acid-catalyzed radical hydrofunctionalization of vinyl pyridines with N-hydroxyphthalimide esters using 1-OTf-Ir.
Figure 6.
Figure 6.
Reversal of phosphonium reactivity toward aldehydes in MixUMCM-1-NH2.
Figure 7.
Figure 7.
a) Pore engineering in MUF-77 enables discrimination between two different reaction pathways that proceed with a common substrate. b) Switching between Henry and aldol reactions. Adapted with permission from ref. Copyright 2019 American Chemical Society.
Figure 8.
Figure 8.
a) ʟ-proline-functionalized UiO-68. b) Reversal of diastereoselectivity for the asymmetric aldol reaction using ʟ-proline-functionalized UiO-68.
Figure 9.
Figure 9.
a) Structure of the azide-functionalized MOF Mn3(L)2(L′) (L, L′ = bis(4-(4-benzoate)-1H-3,5-dimethylpyrazolyl)methane). b) Selective mono-click reactions of diynes in Mn3(L)2(L′). Adapted with permission from ref. Copyright 2018 American Chemical Society.
Figure 10.
Figure 10.
Design rules for the synthesis of stable MOFs.
Figure 11.
Figure 11.
Acid modulation of MOF synthesis. Reproduced with permission under a Creative Commons Attribution 3.0 Unported License from ref. Copyright 2020 Royal Society of Chemistry.
Figure 12.
Figure 12.
PXRD patterns of UiO-68-Me2 prepared using different modulators (10 equiv.). 2-TP = 2-thiophenecarboxylic acid; 3-TP = 3-thiophenecarboxylic acid; AA = acetic acid; FA = formic acid; TFA = trifluoroacetic acid; BA = benzoic acid. Adapted with permission from ref. Copyright 2022 American Chemical Society.
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