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. 2019 Apr;2(4):266-373.
doi: 10.1038/s41929-019-0231-9. Epub 2019 Feb 18.

Photoelectrocatalytic Arene C-H Amination

Lei Zhang  1 , Laurent Liardet  1 , Jingshan Luo  2   3 , Dan Ren  2 , Michael Grätzel  2 , Xile Hu  1
Affiliations

Photoelectrocatalytic Arene C-H Amination

Lei Zhang et al. Nat Catal. 2019 Apr.

Abstract

Photoelectrochemical cells are widely studied for solar energy conversion. However, they have rarely been used for the synthesis of high added-value organic molecules. Here we describe a strategy to use hematite, an abundant and robust photoanode, for non-directed arene C-H amination. Under illumination the photo generated holes in hematite oxidizes electron-rich arenes to radical cations which further react with azoles to give nitrogen heterocycles of medicinal interest. Unusual ortho-selectivity has been achieved probably due to a hydrogen bonding interaction between the substrates and the hexafluoroisopropanol co-solvent. The method exhibits broad scope and is successfully applied for the late-stage functionalization of several pharmaceutical molecules.

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Conflict of interest statement

Competing Interests The authors declare no competing interests.

Figures

Figure 1
Figure 1. Photoelectrochemical cells.
a. Cell for water oxidation; b. Cell for oxidative transformations of organic substrates.
Figure 2
Figure 2. Arene C-H amination.
a. Via organic photoredox catalysis; b. Via direct electrochemical oxidation; c. Via photoelectrocatalysis.
Figure 3
Figure 3. Late-stage Functionalization of Pharmaceuticals.
a. C-H Amination of clofibrate; b. C-H Amination of metaxalone; c. C-H Amination of benzethonium chloride.
Figure 4
Figure 4. (Photo)electrochemical measurements.
a. LSV curves of a hematite photoelectrode under LED illumination (red line) and in the dark (black line) in HFIP/MeOH (4:1, 3 mL) containing LiClO4 (0.1 M), anisole (0.2 mmol) and pyrazole (0.4 mmol). Scan rate: 30 mV/s; b. Mott-Schottky plot measured in HFIP/MeOH (4:1); c. IPCE of hematite measured under catalytic conditions at E = 0.73 V vs Fc/Fc+.
Figure 5
Figure 5. Mechanistic hypothesis.
a. Proposed Mechanism of C-N bond formation; b. Proposed hydrogen bonding among anisole, HFIP and pyrazole.
See this image and copyright information in PMC

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