A Unified Approach to Decarboxylative Halogenation of (Hetero)aryl Carboxylic Acids

Chen, Tiffany Q.; Pedersen, P. Scott; Dow, Nathan W.; Fayad, Remi; Hauke, Cory E.; Rosko, Michael C.; Danilov, Evgeny O.; Blakemore, David C.; Dechert-Schmitt, Anne-Marie; Knauber, Thomas; Castellano, Felix N.; MacMillan, David W. C.

doi:10.1021/jacs.2c02392

A Unified Approach to Decarboxylative Halogenation of (Hetero)aryl Carboxylic Acids

Journal Article · Fri Apr 29 00:00:00 EDT 2022 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/jacs.2c02392· OSTI ID:1865855

Chen, Tiffany Q. ^[1]; Pedersen, P. Scott ^[2]; Dow, Nathan W. ^[2]; Fayad, Remi ^[3]; Hauke, Cory E. ^[3]; ^[3]; ^[3]; Blakemore, David C. ^[4]; Dechert-Schmitt, Anne-Marie ^[4]; ^[4]; ^[3]; ^[2]

Princeton Univ., NJ (United States); Princeton University
Princeton Univ., NJ (United States)
North Carolina State Univ., Raleigh, NC (United States)
Pfizer, Inc., Groton, CT (United States)

Aryl halides are a fundamental motif in synthetic chemistry, playing a critical role in metal-mediated cross-coupling reactions and serving as important scaffolds in drug discovery. Although thermal decarboxylative functionalization of aryl carboxylic acids has been extensively explored, the scope of existing halodecarboxylation methods remains limited, and there currently exists no unified strategy that provides access to any type of aryl halide from an aryl carboxylic acid precursor. Herein, we report a general catalytic method for direct decarboxylative halogenation of (hetero)aryl carboxylic acids via ligand-to-metal charge transfer. This strategy accommodates an exceptionally broad scope of substrates. Here, we leverage an aryl radical intermediate toward divergent functionalization pathways: (1) atom transfer to access bromo- or iodo(hetero)arenes or (2) radical capture by copper and subsequent reductive elimination to generate chloro- or fluoro(hetero)arenes. The proposed ligand-to-metal charge transfer mechanism is supported through an array of spectroscopic studies.

View Accepted Manuscript (DOE)

Research Organization:: North Carolina State Univ., Raleigh, NC (United States); Princeton Univ., NJ (United States)

Sponsoring Organization:: NIH; National Institute of General Medical Sciences (NIGMS); USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: SC0019370

OSTI ID:: 1865855

Journal Information:: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 18 Vol. 144; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Carboxylic acids
Chemical reactions
Copper
Halogenation
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A Unified Approach to Decarboxylative Halogenation of (Hetero)aryl Carboxylic Acids

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References (50)

Figures / Tables (8)

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