Citation

Peng Jia, Luo Guo-Ping, Wu Chao, Wang Congyang. Visible light-induced deuteration of arenes via thianthrenation[J]. Chin. Chem. Lett., 2025, 36(8): 111255  

Jia Peng^a, Guo-Ping Luo^b, Chao Wu^a,*, Congyang Wang^c,*     

Deuterium (D), a stable and non-radioactive isotope of hydrogen, is naturally present in the environment and is distinguished from hydrogen by its greater mass. This mass difference results in a reduced stretching frequency of the carbon-deuterium (C-D) bond, leading to lower ground state energy and higher bond dissociation energy compared to the carbon-hydrogen (C–H) bond. Consequently, C-D bonds exhibit enhanced chemical stability relative to C–H bonds. In the realm of synthetic chemistry, deuterated compounds serve as invaluable tools for investigating kinetic isotope effects (KIEs) and as tracers in the exploration of reaction mechanisms. In medicinal chemistry, the strategic incorporation of deuterium atoms into drug molecules facilitates the tracking of the drug's in vivo dynamics without compromising its pharmacological efficacy. This capability allows for the comprehensive monitoring and quantification of the drug's absorption, distribution, metabolism, and excretion (ADME) [1]. Furthermore, due to the superior stability of C-D bonds, the introduction of deuterium into metabolic sites of drugs can significantly modify the drug's metabolic rate or pathway, thereby influencing its pharmacokinetic properties. Such modifications have the potential to extend the biological half-life of drugs, reduce required dosages, and alleviate adverse drug reactions [1].

Traditional organic synthesis methods for introducing deuterium predominantly rely on ionic reaction strategies, such as the reduction of unsaturated bonds with deuterated reagents like NaBD₄ or LiAlD₄, and hydrogen/deuterium exchange reactions between metal-organic compounds (R-MX) and deuterated reagents, including D₂O, DCl, D₂SO₄, or NaOD [1]. However, the application of reagents like LiAlD₄ and metal-organic compounds (e.g., Grignard and organolithium reagents) is fraught with inherent limitations, including their instability, the necessity of stringent reaction conditions, limited functional group compatibility, and challenges in achieving precise selectivity. These drawbacks significantly constrain their widespread use in modern synthetic chemistry. In contrast, photoredox catalysis has attracted growing interest due to its sustainability, environmental friendliness, and reliance on abundant, non-polluting energy sources [2]. Visible light, as a clean and renewable energy source, offers a promising alternative to traditional methods [3]. When applied to deuteration reactions, photoredox catalysis provides several advantages, including precise control over deuterium incorporation, milder reaction conditions, and the use of easily accessible, low-cost deuterium sources. These attributes position visible light-driven deuteration as an efficient, sustainable strategy for the synthesis of deuterated organic compounds, offering significant potential for advancing both fundamental research and applied synthetic chemistry.

In the field of photocatalysis, arylthianthrene salts have attracted widespread attention due to their importance in synthetic chemistry and materials science [4]. However, traditional catalytic methods typically rely on external electron donors to activate their reactions [5]. To address this limitation, Yu and coworkers propose an innovative energy transfer (EnT) strategy, combined with a metal-free photocatalyst, 2,3,4,5,6-penta-(9H-carbazole-9-yl)benzonitrile (5CzBN), to efficiently activate arylthianthrene salts [5]. Under visible light irradiation, this work cleverly utilized CDCl₃ as a deuterium source, successfully achieving the C–H deuteration of aromatic compounds and synthesizing various deuterated aromatic compounds (Scheme 1). Compared to the known photocatalytic deuteration methods using organic solvents, the present strategy uses water with high bond dissociation energy as the solvent, which not only obtains excellent reaction results but also effectively reduces the pollution to the environment. It is worth mentioning that the present strategy exhibits a very excellent level of deuteration. This process not only demonstrated the efficient and selective introduction of deuterium atoms but also provided a novel approach for the modification of natural products and pharmaceutical molecules. In addition, the study successfully achieved the late-stage modification of various complex drugs, including the lipid-lowering drug fenofibrate (Tricor) and the attention deficit hyperactivity disorder (ADHD) drug (R)-Tomoxetine, demonstrating the broad application potential of this method. This not only advances the development of medicinal chemistry but also provides crucial technical support for the development of new drugs.

Scheme 1

	Download: JPG larger image
Scheme 1. Visible light-induced deuteration of bioactive molecules via thianthrenation.

In summary, Yu and coworkers have recently developed a groundbreaking and highly efficient visible-light-driven 5CzBN-catalyzed energy transfer (EnT) strategy for the photoactivation of sulfonium salts, facilitating the selective deuteration of arenes through thianthrenation. By utilizing CDCl₃ as a deuterium source, this method significantly simplifies the reaction conditions and reduces the challenges typically encountered with traditional deuteration techniques. Moreover, the incorporation of sulfonium salts as substrates highlights the flexibility and broad applicability of this strategy, providing a new and effective route for the deuteration of various aromatic compounds. This approach not only opens up new avenues for isotopic labeling in synthetic organic chemistry but also offers a more sustainable and streamlined alternative to existing methods, with potential implications for both fundamental research and practical applications in areas like drug development and material science.

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.

Jia Peng: Writing – original draft. Guo-Ping Luo: Writing – original draft. Chao Wu: Writing – original draft. Congyang Wang: Writing – review & editing.

Financial support from Science and Technology Innovation Program of Hunan Province (No. 2022RC4044).