Cobalt(III) Halide Metal–Organic Frameworks Drive Catalytic Halogen Exchange

The selective halogenation of complex (hetero)­aromatic systems is a critical yet challenging transformation that is relevant to medicinal chemistry, agriculture, and biomedical imaging. However, current methods are limited by toxic reagents, expensive homogeneous second- and third-row transition me...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2024-04, Vol.146 (16), p.11164-11172
Main Authors: Azbell, Tyler J., Milner, Phillip J.
Format: Article
Language:English
Subjects:
catalytic activity
chlorine
cobalt
fluorine
Lewis bases
toxicity
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Summary:The selective halogenation of complex (hetero)­aromatic systems is a critical yet challenging transformation that is relevant to medicinal chemistry, agriculture, and biomedical imaging. However, current methods are limited by toxic reagents, expensive homogeneous second- and third-row transition metal catalysts, or poor substrate tolerance. Herein, we demonstrate that porous metal–organic frameworks (MOFs) containing terminal Co­(III) halide sites represent a rare and general class of heterogeneous catalysts for the controlled installation of chlorine and fluorine centers into electron-deficient (hetero)­aryl bromides using simple metal halide salts. Mechanistic studies support that these halogen exchange (halex) reactions proceed via redox-neutral nucleophilic aromatic substitution (SNAr) at the Co­(III) sites. The MOF-based halex catalysts are recyclable, enable green halogenation with minimal waste generation, and facilitate halex in a continuous flow. Our findings represent the first example of SNAr catalysis using MOFs, expanding the lexicon of synthetic transformations enabled by these materials.
ISSN:0002-7863
1520-5126
1520-5126
DOI:10.1021/jacs.3c13872