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• Gold, unlike other transition metals such as Pd, Ni, and Cu, offers unique reactivity profiles and has emerged as an attractive area of research in organic chemistry over the last two decades. Initially, gold catalysts were widely used for the π-activation of unsaturated carbon−carbon bonds, particularly alkynes. Moreover, they exhibit favorable functional-group compatibility, good biocompatibility, and, generally, gold-catalyzed reactions are not sensitive to air or water. However, due to the high oxidation potential of the Au(Ⅰ)/Au(Ⅲ) couple (Au^Ⅲ/Au^Ⅰ 1.41 Ⅴ vs. Pd^Ⅱ/Pd⁰ 0.99 Ⅴ), achieving cross-coupling reactions with gold has proven to be a nontrivial task, often requiring strong external oxidants like PhI(OAc)₂ and Selectfluor [1].

  Gold-catalyzed cross-coupling of aryl (pseudo)halides represents a state-of-the-art technique in gold chemistry. Significant advancements were made by Glorius and Toste, who utilized reactive aryl diazonium salts to circumvent the need for stoichiometric oxidants by integrating gold catalysis with photoredox catalysis. This photoinduced electron transfer (PET) approach has led to the development of many dual photoredox-gold catalytic systems employing reactive aryl diazonium salts [2]. Recently, hemilabile ligand-promoted Au(Ⅰ)/Au(Ⅲ)-catalyzed cross-coupling reactions with less reactive aryl iodides have been explored for C—C, C—N, C—S/Se, and C—O bond formations by researchers such as Bourissou, Patil, Shi, Xie, Topczewski, Xia [3] and others. The use of bidentate ligands has enabled the oxidative addition of Au(Ⅰ) with aryl iodides, forming aryl Au(Ⅲ) complexes rapidly at low temperatures, as supported by stoichiometric studies and calculations.

  Compared with reactive aryl diazonium salts and less reactive aryl iodides, aryl bromides are considered particularly inactive partners in gold-catalyzed cross-coupling reactions (Scheme 1A-ⅰ). In fact, bromo groups in arenes are often regarded as well-tolerated groups in gold chemistry. It has been shown that the oxidative addition of Ar-Br with Au(Ⅰ) is extremely difficult, with phosphine-directed intramolecular oxidative addition of Ar-Br requiring heating at 130 ℃ to proceed (Scheme 1A-ⅱ). Density functional theory (DFT) calculations confirm that the energy barrier for the oxidative addition of bromobenzene with Au(Ⅰ) is much higher than that of iodobenzene (15.7 vs. 8.2 kcal/mol). Due to this high barrier, the cross-coupling of bromoarenes is limited to electron-rich substrates like trimethoxybenzene and requires elevated temperatures [4].

  Scheme 1

  

  Scheme 1.  Photosensitized gold-catalyzed cross-couplings of aryl bromides. Reaction conditions unless noted: carboxylic acid (0.2 mmol), aryl bromide (1.5 equiv.), MeDalphos-AuCl (5 mol%), AgSbF₆ (2.0 equiv.), [Mes-Acr-Me]⁺[ClO₄]^– ([Acr], 5 mol%), Na₂CO₃ (1.0 equiv.), DCE (0.1 mol/L), Kessil blue LED, 30 ℃, 18 h.

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  To address this limitation, Xia and coworkers propose an innovative energy transfer (EnT) strategy, using a (P, N)-gold(Ⅰ) catalyst and an acridinium photocatalyst under blue LED irradiation, to achieve cross-couplings of aryl bromides (Scheme 1A-ⅲ) [5]. Experimental and computational studies suggest that this photosensitized gold-catalyzed cross-coupling of aryl bromides involves two discrete photoinduced energy transfer (EnT) events (Scheme 1B): energy transfer (EnT) induces oxidative addition of aryl bromides with a gold(Ⅰ) complex and reductive elimination of the aryl-Au(Ⅲ) complex to regenerate Au(Ⅰ). In the presence of a (P, N)-gold(Ⅰ) catalyst and an acridinium photocatalyst under blue LED irradiation, C—O coupling of aryl bromides with carboxylic acids was achieved and soon it was found that this photoinduced gold-catalyzed cross-coupling of aryl bromides was appliable for other C—C, C—N, and C—S bond formation (Scheme 1C). Due to the biocompatibility of gold catalysts and the mild condition of photochemistry, this photo/gold-catalyzed protocol showed its potential to facilitate drug discovery. Therefore, the new synergistic catalytic method developed here highlights the tremendous potential of photochemical gold catalysis through excited-state organogold complexes and provides a powerful tool to potentially facilitate drug discovery.

  Declaration of competing interest

  The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

  CRediT authorship contribution statement

  Rong-Nan Yi: Writing – original draft. Zi-Jian Zhao: Writing – review & editing. Wei-Min He: Writing – review & editing.

  
  
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     B. Sahoo, M.N. Hopkinson, F. Glorius, J. Am. Chem. Soc. 135 (2013) 5505–5508. doi: 10.1021/ja400311h

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     J. Wu, W. Du, L. Zhang, et al., JACS Au 4 (2024) 3084–3093. doi: 10.1021/jacsau.4c00422

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     A. Zeineddine, L. Estévez, S. Mallet-Ladeira, et al., Nat. Commun. 8 (2017) 565.

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     J. Wu, F. Guo, C. Yi, et al., J. Am. Chem. Soc. 147 (2025) 5839–5850. doi: 10.1021/jacs.4c14501

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  Scheme 1  Photosensitized gold-catalyzed cross-couplings of aryl bromides. Reaction conditions unless noted: carboxylic acid (0.2 mmol), aryl bromide (1.5 equiv.), MeDalphos-AuCl (5 mol%), AgSbF₆ (2.0 equiv.), [Mes-Acr-Me]⁺[ClO₄]^– ([Acr], 5 mol%), Na₂CO₃ (1.0 equiv.), DCE (0.1 mol/L), Kessil blue LED, 30 ℃, 18 h.

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