English

• Deuterated compounds have found wide applications in organic synthesis [1-4], fundamental biology [5-7], drug/agrochemical development process [8,9], and medical imaging [10-12]. In particular, the incorporation of deuterium into bioactive molecules have emerged as a powerful tool for medicinal chemists, as it can often dramatically improve the metabolic and pharmacokinetic properties [13,14]. In 2017, Austedo (deutetrabenazine) was approved by the US Food and Drug Administration as the first deuterated drug [15,16], which has been further stimulating the research on the direction of D-incorporation [2,17-38]. In this vein, a wide array of D-labelling techniques has been developed in recent years with particular success in hydrogen isotope exchange (HIE) reactions of aromatic substrates utilizing catalytic or stoichiometric amount of transition metal such as Ir [39-44], Pt [45-48], Pd [49-53], Rh [54-59], Ru [60-64], etc. [65-70]. Despite these progresses, the over-deuteration and installation and/or removal of DGs are often inevitable. Indeed, the precise control of both the labelled position and the degree of deuteration can greatly affect the physicochemical and biological properties of deuterated compounds [3,5-7]. As such, the selective incorporation of deuterium at aromatic ring remains to be a significant yet challenging task.

  Recently, sulfonium chemistry in particular aryl thianthrenium salt, has emerged as a powerful tool in modern organic synthesis [71-81]. In general, aryl thianthrenium salts can participate in both transition metal-catalyzed cross-coupling reactions as the aryl electrophiles [82-89] and photoredox/electrochemical radical reaction as the aryl radical reservoirs [78,90-96]. Moreover, the thianthrenation of aromatics could be achieved via direct C–H activation with corresponding sulfoxides that most of these reported protocols displayed excellent chemoselectivity by combining electronic effect and steric effect together. These progress indeed also empowered site-selective or even late-stage functionalization toward complex real-world targets, which should be beneficial toward medicinal chemistry efforts [71-81]. In addition, C–I bond cleavage (nucleophilic substitution) [97-99] or C–M bond activation (Chan-Lam coupling) [100] was also disclosed to install the thianthrenium group (Scheme 1).

  Scheme 1

  

  Scheme 1.  Background and working hypothesis.

  DownLoad: Full-Size Img PowerPoint

  In view of the rapid progress of aryne chemistry [101-131] and our interests in sulfonium zwitterion [77,132-140], we wonder if we could prepare ortho-deuterated aryl thianthrenium salts, and leverage them as a novel class of linchpin to access deuterated aromatic derivatives via versatile downstream derivatization. Indeed, our group and others have demonstrated the employment of aryne species to achieve the vicinal functionalization of arenes with neutral nucleophiles in a variety of transformations. As such, we sought to find the suitable “D⁺” source to drive the capture of sulfonium zwitterion that were in situ formed. This idea should allow us to control the deuteration selectivity, thereby addressing the aforementioned over-deuteration issues. However, there are two major concerns associated with our working hypothesis. On one hand, the sulfide addition step was kinetically unfavorable, and the solvent molecules or the counterion in D-source may directly couple with the highly reactive aryne species in a competitive pathway. On the other hand, ortho-sulfonium aryl anion intermediates should be thermodynamically unstable, which have been recently discovered as aryne precursors by Stuart and co-workers [141]. Despite these challenges, we herein would like to report the success execution of the abovementioned ideas, and present a linchpin-based platform strategy for facile preparation of ortho-deuterated aromatic derivative from corresponding easily available aryl sulfonium salts. Our user-friendly protocol substitution reactions, over 45 representative ortho-deuterated aryl employed cost effective heavy water as the deuterium source, and empower the precise selectivity control. With the downstream derivatization toolkit including transition metal catalysis, photo/electrochemical methods as well as nucleophilic derivatives could be readily accessed in good structural diversity and deuterium incorporations, part of which could be difficult to be obtained by existing methods. Additionally, an operationally simple phosphine arylation reaction was achieved via electron donor-acceptor complex photoactivation.

  We initiated the reaction condition optimization using thianthrene (1a), Kobayashi aryne precursor (2a) and “D⁺” source (3) as the model substrates (Table 1). At first, a series of fluoride source including potassium fluoride (KF), cesium fluoride (CsF), tetrabutylammonium fluoride (TBAF) and tetrabutylammonium difluorotriphenyl silicate (TBAT) were examined, among which CsF was surprisingly superior to give the desired product in 89% yield and 98% deuterium incorporation (entries 1–4). Reducing the amount of D₂O would lead to a decrease of deuterium incorporation whereas a high loading of D₂O also failed to increase either the yield or deuterium incorporation (entries 5 and 6). We discovered that further increasing the loading of D₂O resulted a heterogeneous reaction, which also failed to increase the yield of 4a as the competitive reaction took place to afford phenol byproduct from D₂O and aryne precursor (entry 7). Further screening of other D⁺ source indicated that chloroform-d (3b) methanol-d₄ (3c), and acetone-d₆ (3d) gave less satisfying reaction outcome (entries 8–10). Increasing the concentration has a negative effect on this transformation, leading to a slightly lower chemical yield of 78% (entry 11). Different reaction temperature also showed no improvement on the reaction outcome (entries 12 and 13).

  Table 1

  

  Table 1.  Reaction condition optimization of synthesis of ortho-deuterated arylthianthrenium salts.^a

  DownLoad: CSV

  Entry	“F-”/Solvent	3 (equiv.)	Yieldb (%) [D (%)]c
  1	KF/18-C-6/THF	D2O (10)	trace
  2	CsF/MeCN	D2O (10)	89 [98]
  3	TBAF/THF	D2O (10)	trace
  4	TBAT/THF	D2O (10)	trace
  5	CsF/MeCN	D2O (6)	75 [82]
  6	CsF/MeCN	D2O (25)	84 [98]
  7	CsF/MeCN	D2O (160)	trace
  8	CsF/MeCN	CDCl3 (10)	63 [87]
  9	CsF/MeCN	CD3OD (10)	trace
  10	CsF/MeCN	CD3COCD3 (10)	trace
  11d	CsF/MeCN	D2O (10)	78 [95]
  12e	CsF/MeCN	D2O (10)	55 [98]
  13f	CsF/MeCN	D2O (10)	90 [93]
  a Reaction conditions: 1a (0.1 mmol), 2a (0.25 mmol), “F-” (0.25 mmol), solvent (0.3 mL), “D+” source, N2, 60 ℃, 36 h. b Isolated yield. c Determined by 1H NMR. d CH3CN (0.15 mL). e 30 ℃. f 80 ℃.

  With optimal conditions described in Table 1, we then explored the substrate scope with various aryne precursors and sulfides (Scheme 2). To our delight, symmetric aryne precursors that incorporate a wide range of functional groups, were well-tolerated, leading to the corresponding deuterated arylthianthrenium salt products (4a-4f) in 55%−89% yields along with high level of deuterium incorporations (92%−98% D). In addition, the transformation with polycyclic arynes also proceeded smoothly, leading to naphthyl and phenanthryl-based products 4e (92% D) and 4f (98% D) in 55% and 78% yield, respectively. In accordance with the distortion/interaction model disclosed by Garg, Houk and colleagues [142], the utilization of 3-substituted benzyne delivered single regioisomer product of 4g-4i. To our surprise, when 4-substituted aryne were investigated for this three-component reaction, a unprecedently high regioselectivity was observed for 4k and 4l, whereas 4l + 4l’ was obtained as a 1:1 mixture. Further studies on extending the scope to 4m and 4n were also performed to afford the desired deuterated sulfonium salts in 96% and 65% yield (both 95% D-incorporation), respectively. Di-p-tolyl sulphide and phenoxathiin was also discovered to be amenable, leading to 4m with 4n with similar level of D-incorporation, both of which have been reported as synthetic handle for downstream transformations [143,144]. For 2,3-pyriydne, the direct two-component, nucleophilic addition of heavy water took place instead, leading to the 4o in 48% yield and 96% deuterium incorporation.

  Scheme 2

  

  Scheme 2.  Substrate scope of ortho-deuterated arylthianthrenium. ^a The crystal data please see Supporting information. ^b 4k (p): 4k’ (m) = 10.3:1. ^c 4l (p): 4l’ (m) = 1:1.

  DownLoad: Full-Size Img PowerPoint

  Next, we further demonstrated the application of downstream derivatization toolkit to access versatile ortho-deuterated aromatic derivatives (Scheme 3) [71-96]. At first, the model substrate 4a was evaluated as aryl pseudo-halides for classic transition-metal-catalyzed cross-coupling reactions, including Suzuki-Miyaura (a), Heck (b), Sonogashira (c), α-arylation of carbonyl compounds (d), carbonylation with phenyl formates (e), and arylations of 2H-indazole (f), all of which proceeded smoothly to give the desired products in moderate to good yields without compromising the D-level. Next, both palladium catalyzed arylsulfonamidation (g) and palladium-catalyzed C–H arylation of tryptophan (h) were also explored, leading to the medicinally relevant compound 12a and 13a in 80% and 83% yields, respectively. In addition to transition metal catalysis, the derivatization of ortho-deuterated arylthianthrenium salt could be accomplished via photochemical toolkits (photoredox catalysis or EDA complex). A series of representative transformations were explored including phosphorylation with triphenyl phosphite (i), hydroarylation of azine-substituted enamides (j), borylation with B₂Pin₂ (k), sulfonylation with sodium sulfinate salt (l), arylation of quinoxalinone (m) and di-aryl dithiocarbomates synthesis (n). These transformations provided straightforward access to versatile D-labelled building blocks with high efficiency, serving as a complementary tool to transition metal catalysis. The mildness and simplicity of photoredox catalysis also enabled a telescoped one-pot cascade reaction combining arylthianthrenium salt formation and photochemical sulfonylation, which successfully delivered 17a in 49% yield. In light of the resurgence of organic electrosynthesis [145-148], we next demonstrated the functionalization of deuterated arylthianthrenium salts using an electrochemically driven method. This exemplified approach provided a viable route to synthesize aryl sulfonyl fluoride (o) with deuterium positioned at the neighboring site, resulting in 20a with a 78% isolated yield. The α-amino alkyl radicals induced Minisci-type reactions of pyrazine using Na₂S₂O₈ and Bu₃N has also been demonstrated (p). Finally, we disclosed that the nucleophilic substitution of 4i selectively took place via thianthrene ring opening, allowing the incorporation of deuterated diphenyl thioether scaffold in a single step (q). More importantly, several active pharmaceutical ingredient or natural product derivatives could be successfully linked to the as-prepared ortho-deuterated aromatic modules (r-t), further showcasing the attractiveness that our protocol might have for deuterated lead discovery. Indeed, this indirect strategy expands far beyond the previously studied vicinal difunctionalization range of aryne chemistry, overcoming the functionality limitation brought by aryne initiation conditions. Note that, in all cases, we observed no erosion of the deuterium content, and strongly believed that our platform protocol offered a synthetic alternative toward ortho-deuterated aryl derivatives, allowing exclusive positional selectivity while avoiding over deuteration. At this stage, the overall results observed with respect to purpose-designed derivatization provided the first glimpse into the blueprint of our strategy, which clearly displayed its great promise and immense potential toward precise synthesis of deuterated aromatics.

  Scheme 3

  

  Scheme 3.  Substrate scope of ortho-deuterated aromatic derivative. Reaction conditions please see Supporting information. ^a 49% Yield for one-pot, two-steps method.

  DownLoad: Full-Size Img PowerPoint

  To further expand the elaboration toolkit and the utility of our linchpin-based methods, a photochemical method for phosphine arylation that leveraged the photoexcitation of electron donor–acceptor (EDA) complex was then developed. Upon extensive investigation, we discovered that in the presence of arylthianthrenium salt, triphenylphosphine could be easily arylated with arylthianthrenium salt (4a) under the blue LEDs (40 W, λ_max = 427 nm) irradiation to access ortho-deuterated aryl phosphonium salts (Table 2). Thianthrenium salts bearing both electron-rich and electron-poor substituents as well as various aryl phosphines all proved to be amenable, affording the corresponding ortho-deuterated phosphonium salt products (22a-22j) in good to excellent yields (69%−94% yields) along with 97%−98% D-incorporations (Scheme 4A) [149]. Next, non-deuterated sulfonium salts derived from either C–H thianthrenation with sulfoxides or Chan-Lam coupling of arylboronic acids were also investigated to further expand the scope of our protocol. To our delight, various functional groups (alkyl, phenyl, halogen, pseudo-halogen, methoxy and alkoxycarbonyl), and even complex drugs (flurbiprofen, bifonazole, pyriproxyfen and clofibrate), were well tolerated under mild, metal-, and photocatalyst-free conditions (Scheme 4B). The scale-up of 4a was also straightforward (Scheme 4D), leading to comparable reaction outcome. Overall, compared to classic strategy that rely on transition metal catalysis and high-temperature processes, this protocol can offer a sustainable alternative toward aryl phosphonium salts, which shall find potential applications in catalysis, ionic liquids, etc. [150-152]. A series of mechanistic experiments was performed to elucidate the reaction pathway. The redshift of the substrate mixture in the UV–vis spectrum compared to the independent substrates (Scheme 4C) and the ¹H NMR titration experiments results (for details, please see Supporting information) [95] indicated the formation of the EDA complex. The light ON—OFF experiments suggested the necessity of light during the reaction and excluded the possible radical chain mechanism (Scheme 4E). No desired product was observed in the presence of TEMPO under otherwise identical conditions, while the radical trapping intermediate was successfully identified by HRMS, suggesting the involvement of a radical process (Scheme 4F). On basis of the above experimental results and previous reports [153-155], a plausible mechanism is proposed (Scheme 4G).

  Table 2

  

  Table 2.  Reaction condition optimization of synthesis of ortho-deuterated tetraarylphosphonium salts.

  DownLoad: CSV

  Entry	Variations from the standard conditions	Yield (%) [D (%)]b
  1	Nonea	94 [98]
  2	456 nm, 40 W	45 [98]
  3	440 nm, 40 W	84 [98]
  4	427 nm, 20 W	53 [98]
  5	427 nm, 30 W	79 [98]
  6	Dark	N.D.
  a Reaction conditions: 4a (0.1 mmol), PPh3 (0.2 mmol, 2 equiv.), MeCN (0.5 mL). b Isolated yield [Deuterium incorporation].

  Scheme 4

  

  Scheme 4.  Research on the arylation of aryl phosphorus. (A) Substrate scope of ortho-deuterated tetraarylphosphonium salts. (B) Substrate scope of non-deuterated tetraarylphosphonium salts. (C) UV–vis studies, Black line: 4a (0.4 mmol) in 2 mL MeCN; Red line: PPh₃ (0.8 mmol) in MeCN (2 mL); Blue line: 4a (0.4 mmol) + PPh₃ (0.8 mmol) in MeCN (2 mL). (D) Gram scale synthesis. (E) Light ON—OFF experiment. (F) Control experiments. (G) Plausible mechanism.

  DownLoad: Full-Size Img PowerPoint

  In summary, we have established an ortho-deuterated arylthianthrenium based linchpin platform for the facile preparation of ortho-deuterated aromatic derivatives. Rapid assembly of such linchpin is achieved via a three-component coupling of arynes, thianthrene and heavy water. Both transition metal catalysis and organic photo-/electro-synthesis-based manifolds were explored for elaboration of sulfonium handles, enabling more modular, selective and expedient access to deuterated arene derivatives than previous methodologies. We also demonstrated that these methods can be applied to the modification of complex drug compounds via install D-labelling building blocks, further showcasing its applicability toward medicinal chemistry efforts. From an aryne chemistry perspective, this reported strategy significantly broadens the scope beyond the traditionally explored vicinal difunctionalization, addressing the limitations imposed by the conditions required for aryne generation. Overall, we envision that our platform strategy will allow for the precise synthesis of valuable deuterated aromatic analogues, and highly expedite the exploration of the deuterium isotope effect.

  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

  Yunhao Guan: Visualization, Validation, Investigation, Formal analysis, Data curation. Xia Peng: Writing – original draft, Visualization, Validation, Investigation, Formal analysis, Data curation. Rong Fan: Validation, Investigation, Data curation. Xiaoying Feng: Investigation, Data curation. Hongguang Du: Writing – review & editing, Validation, Supervision, Resources, Methodology, Funding acquisition, Data curation. Jiajing Tan: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Resources, Project administration, Methodology, Funding acquisition, Formal analysis, Data curation.

  Acknowledgments

  This work was supported by the National Natural Science Foundation of China (Nos. 22271010 and 21702013). We appreciate the assistance from Mr. Feiyang Liao during manuscript preparation.

  Supplementary materials

  Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.cclet.2025.111132.

  
  
• 1. [1]

     R. Zhou, L. Ma, X. Yang, J. Cao, Org. Chem. Front. 8 (2021) 426–444. doi: 10.1039/d0qo01299h

  2. [2]

     Y. Guo, Z. Zhuang, Y. Liu, et al., Coord. Chem. Rev. 463 (2022) 214525. doi: 10.1016/j.ccr.2022.214525

  3. [3]

     N. Li, Y. Li, X. Wu, C. Zhu, J. Xie, Chem. Soc. Rev. 51 (2022) 6291–6306. doi: 10.1039/d1cs00907a

  4. [4]

     G. Prakash, N. Paul, G.A. Oliver, D.B. Werz, D. Maiti, Chem. Soc. Rev. 51 (2022) 3123–3163. doi: 10.1039/d0cs01496f

  5. [5]

     H.M. Chandra Mouli, A. Vinod, S. Kumari, et al., Bioorg. Chem. 135 (2023) 106490. doi: 10.1016/j.bioorg.2023.106490

  6. [6]

     J. Atzrodt, V. Derdau, W.J. Kerr, M. Reid, Angew. Chem. Int. Ed. 57 (2018) 1758–1784. doi: 10.1002/anie.201704146

  7. [7]

     M.G. Horning, J.P. Thenot, O. Bouwsma, J. Nowlin, K. Lertratanangkoon, Adv. Pharmacol. Ther, Proc. Int. Congr. Pharmacol. 7 (1978) 245–256.

  8. [8]

     A.C. Flick, H.X. Ding, C.A. Leverett, et al., J. Med. Chem. 60 (2017) 6480–6515. doi: 10.1021/acs.jmedchem.7b00010

  9. [9]

     T.G. Gant, J. Med. Chem. 57 (2014) 3595–3611. doi: 10.1021/jm4007998

  10. [10]

      T. Pirali, M. Serafini, S. Cargnin, A.A. Genazzani, J. Med. Chem. 62 (2019) 5276–5297. doi: 10.1021/acs.jmedchem.8b01808

  11. [11]

      J.C.M. Low, A.J. Wright, F. Hesse, J. Cao, K.M. Brindle, Prog. Nucl. Magn. Reson. Spectrosc. 134–135 (2023) 39–51. doi: 10.1093/oso/9780197543733.003.0003

  12. [12]

      S. Kopf, F. Bourriquen, W. Li, et al., Chem. Rev. 122 (2022) 6634–6718. doi: 10.1021/acs.chemrev.1c00795

  13. [13]

      A. Katsnelson, Nat. Med. 19 (2013) 656. doi: 10.1038/nm0613-656

  14. [14]

      R.M.C. Di Martino, B.D. Maxwell, T. Pirali, Nat. Rev. Drug. Discov. 22 (2023) 562–584. doi: 10.1038/s41573-023-00703-8

  15. [15]

      C. Schmidt, Nat. Biotechnol. 35 (2017) 493–494. doi: 10.1038/nbt0617-493

  16. [16]

      L. Liu, Z. Deng, K. Xu, et al., Org. Lett. 23 (2021) 5299–5304. doi: 10.1021/acs.orglett.1c01448

  17. [17]

      J. Atzrodt, V. Derdau, T. Fey, J. Zimmermann, Angew. Chem. Int. Ed. 46 (2007) 7744–7765. doi: 10.1002/anie.200700039

  18. [18]

      J. Atzrodt, V. Derdau, W.J. Kerr, M. Reid, Angew. Chem. Int. Ed. 57 (2018) 3022–3047. doi: 10.1002/anie.201708903

  19. [19]

      Q. Sun, J.F. Soulé, Chem. Soc. Rev. 50 (2021) 10806–10835. doi: 10.1039/d1cs00544h

  20. [20]

      P.L. Norcott, Chem. Commun. 58 (2022) 2944–2953. doi: 10.1039/d2cc00344a

  21. [21]

      M. Gómez-Gallego, M.A. Sierra, Inorg. Chem. Front. 8 (2021) 3934–3950. doi: 10.1039/d1qi00505g

  22. [22]

      H. Li, M. Peng, L. Wang, et al., Org. Lett. 26 (2024) 719–723. doi: 10.1021/acs.orglett.3c04155

  23. [23]

      Y. Ding, S. Luo, C. Weng, J. An, J. Org. Chem. 84 (2019) 15098–15105. doi: 10.1021/acs.joc.9b02056

  24. [24]

      X. Li, J. Zhou, W. Deng, et al., Chem. Sci. 15 (2024) 11418–11427. doi: 10.1039/d4sc03049d

  25. [25]

      S. Ning, C. Wu, L. Zheng, et al., Green Chem. 25 (2023) 9993–9997. doi: 10.1039/d3gc02345a

  26. [26]

      W. Li, R. Qu, W. Liu, et al., Chem. Sci. 12 (2021) 14033–14038. doi: 10.1039/d1sc04259a

  27. [27]

      A. Tortajada, E. Hevia, Catal. Sci. Technol. 13 (2023) 4919–4925. doi: 10.1039/d3cy00825h

  28. [28]

      W.J. Kerr, G.J. Knox, M. Reid, T. Tuttle, Chem. Sci. 12 (2021) 6747–6755. doi: 10.1039/d1sc01509e

  29. [29]

      N. Li, Y. Ning, X. Wu, et al., Chem. Sci. 12 (2021) 5505–5510. doi: 10.1039/d1sc00528f

  30. [30]

      L. Guo, C. Xu, D.C. Wu, et al., Chem. Commun. 55 (2019) 8567–8570. doi: 10.1039/c9cc03988k

  31. [31]

      H. Xu, M. Liu, L.J. Li, et al., Org. Lett. 21 (2019) 4887–4891. doi: 10.1021/acs.orglett.9b01784

  32. [32]

      Y. Fan, W. Ou, M. Chen, et al., Org. Lett. 25 (2023) 432–437. doi: 10.1021/acs.orglett.2c04154

  33. [33]

      B.Q. He, X. Wu, Org. Lett. 25 (2023) 6571–6576. doi: 10.1021/acs.orglett.3c02432

  34. [34]

      C.H. Hu, Y. Li, J. Org. Chem. 88 (2023) 6401–6406. doi: 10.1021/acs.joc.2c02299

  35. [35]

      J.L. Lu, J.T. Deng, M. Lang, J.B. Peng, Org. Chem. Front. 11 (2024) 5473–5478. doi: 10.1039/d4qo00956h

  36. [36]

      S. Liu, H. Liao, B. Chen, et al., Green Chem. 26 (2024) 10456–10462. doi: 10.1039/d4gc01134a

  37. [37]

      M. Lecomte, M. Lahboubi, P. Thilmany, A.E. Bouzakhi, G. Evano, Chem. Sci. 12 (2021) 11157–11165. doi: 10.1039/d1sc02622d

  38. [38]

      J. Dong, X. Wang, Z. Wang, et al., Chem. Sci. 11 (2020) 1026–1031. doi: 10.1039/c9sc05132e

  39. [39]

      E. Martinelli, M. Spiller, R. Weck, et al., Chem. Eur. J. 30 (2024) e202402038. doi: 10.1002/chem.202402038

  40. [40]

      M. Itoga, M. Yamanishi, T. Udagawa, et al., Chem. Sci. 13 (2022) 8744–8751. doi: 10.1039/d2sc01805e

  41. [41]

      M. Valero, T. Kruissink, J. Blass, et al., Angew. Chem. Int. Ed. 59 (2020) 5626–5631. doi: 10.1002/anie.201914220

  42. [42]

      W. Liu, L. Cao, Z. Zhang, et al., Org. Lett. 22 (2020) 2210–2214. doi: 10.1021/acs.orglett.0c00402

  43. [43]

      W.J. Kerr, M. Reid, T. Tuttle, ACS Catal. 5 (2015) 402–410. doi: 10.1021/cs5015755

  44. [44]

      C.M. Stork, R. Weck, M. Valero, et al., Angew. Chem. Int. Ed. 135 (2023) e202301512. doi: 10.1002/ange.202301512

  45. [45]

      M.H. Emmert, J.B. Gary, J.M. Villalobos, M.S. Sanford, Angew. Chem. Int. Ed. 49 (2010) 5884–5886. doi: 10.1002/anie.201002351

  46. [46]

      M. Yamamoto, Y. Yokota, K. Oshima, S. Matsubara, Chem. Commun. (2004) 1714–1715.

  47. [47]

      A.J. Hickman, M.A. Cismesia, M.S. Sanford, Organometallics 31 (2012) 1761–1766. doi: 10.1021/om201105b

  48. [48]

      Y. Sawama, T. Yamada, Y. Yabe, et al., Adv. Synth. Catal. 355 (2013) 1529–1534. doi: 10.1002/adsc.201201102

  49. [49]

      C. Zheng, J. Xue, Z.J. Jiang, et al., Chem. Commun. 60 (2024) 10338–10341. doi: 10.1039/D4CC03089C

  50. [50]

      J. Li, Q. Lin, O. Dungan, et al., J. Am. Chem. Soc. 146 (2024) 31497–31506. doi: 10.1021/jacs.4c08176

  51. [51]

      C. Teja, S. Kolb, P. Colonna, et al., Angew. Chem. Int. Ed. 63 (2024) e202410162. doi: 10.1002/anie.202410162

  52. [52]

      J. Dey, S. Kaltenberger, M. van Gemmeren, Angew. Chem. Int. Ed. 63 (2024) e202404421. doi: 10.1002/anie.202404421

  53. [53]

      J. Kong, Z.J. Jiang, J. Xu, et al., J. Org. Chem. 86 (2021) 13350–13359. doi: 10.1021/acs.joc.1c01411

  54. [54]

      Q.K. Kang, Y. Li, K. Chen, et al., Angew. Chem. Int. Ed. 61 (2022) e202117381. doi: 10.1002/anie.202117381

  55. [55]

      C.P. Lenges, P.S. White, M. Brookhart, J. Am. Chem. Soc. 121 (1999) 4385–4396. doi: 10.1021/ja984409o

  56. [56]

      J.L. Rhinehart, K.A. Manbeck, S.K. Buzak, et al., Organometallics 31 (2012) 1943–1952. doi: 10.1021/om2012419

  57. [57]

      S.C. Schou, J. Labelled Compd. Radiopharm. 52 (2009) 376–381. doi: 10.1002/jlcr.1612

  58. [58]

      A.L. Garreau, H. Zhou, M.C. Young, Org. Lett. 21 (2019) 7044–7048. doi: 10.1021/acs.orglett.9b02618

  59. [59]

      W. Peng, Q. Liu, F. Yin, et al., RSC Adv. 11 (2021) 8356–8361. doi: 10.1039/d1ra00236h

  60. [60]

      M.H.G. Prechtl, M. Hölscher, Y. Ben-David, et al., Angew. Chem. Int. Ed. 46 (2007) 2269–2272. doi: 10.1002/anie.200603677

  61. [61]

      Q. Chen, Q. Liu, J. Xiao, X. Leng, L. Deng, J. Am. Chem. Soc. 143 (2021) 19956–19965. doi: 10.1021/jacs.1c10071

  62. [62]

      S. Kopf, F. Ye, H. Neumann, M. Beller, Chem. Eur. J. 27 (2021) 9768–9773. doi: 10.1002/chem.202100468

  63. [63]

      G. Pieters, C. Taglang, E. Bonnefille, et al., Angew. Chem. Int. Ed. 53 (2014) 230–234. doi: 10.1002/anie.201307930

  64. [64]

      E. Bresó-Femenia, C. Godard, C. Claver, B. Chaudret, S. Castillón, Chem. Commun. 51 (2015) 16342–16345. doi: 10.1039/C5CC06984J

  65. [65]

      Z.J. Jiang, S.H. Xu, Y. Su, et al., Chem. Commun. 60 (2024) 384–387. doi: 10.1039/d3cc05257e

  66. [66]

      C. Zarate, H. Yang, M.J. Bezdek, D. Hesk, P.J. Chirik, J. Am. Chem. Soc. 141 (2019) 5034–5044. doi: 10.1021/jacs.9b00939

  67. [67]

      S. Garhwal, A. Kaushansky, N. Fridman, L.J.W. Shimon, G. de Ruiter, J. Am. Chem. Soc. 142 (2020) 17131–17139. doi: 10.1021/jacs.0c07689

  68. [68]

      J. Corpas, P. Viereck, P.J. Chirik, ACS Catal. 10 (2020) 8640–8647. doi: 10.1021/acscatal.0c01714

  69. [69]

      H. Xu, Z.J. Jiang, Y. Jia, et al., J. Org. Chem. 89 (2024) 8468–8477. doi: 10.1021/acs.joc.4c00352

  70. [70]

      M. Yang, T. Chen, Z.F. Xu, M. Yu, C.Y. Li, Org. Biomol. Chem. 22 (2024) 7596–7600. doi: 10.1039/d4ob01251h

  71. [71]

      H. Meng, M.S. Liu, W. Shu, Chem. Sci. 13 (2022) 13690–13707. doi: 10.1039/d2sc04507a

  72. [72]

      L. Zhang, T. Ritter, J. Am. Chem. Soc. 144 (2022) 2399–2414. doi: 10.1021/jacs.1c10783

  73. [73]

      S.I. Kozhushkov, M. Alcarazo, Eur. J. Inorg. Chem. 2020 (2020) 2486–2500. doi: 10.1002/ejic.202000249

  74. [74]

      M.J. Kim, K. Targos, D.E. Holst, D.J. Wang, Z.K. Wickens, Angew. Chem. Int. Ed. 63 (2024) e202314904. doi: 10.1002/anie.202314904

  75. [75]

      R. Fan, C. Tan, Y. Liu, et al., Chin. Chem. Lett. 32 (2021) 299–312. doi: 10.1016/j.cclet.2020.06.003

  76. [76]

      Á. Péter, G.J.P. Perry, D.J. Procter, Adv. Synth. Catal. 362 (2020) 2135–2142. doi: 10.1002/adsc.202000220

  77. [77]

      F. Berger, M.B. Plutschack, J. Riegger, et al., Nature 567 (2019) 223–228. doi: 10.1038/s41586-019-0982-0

  78. [78]

      J. Li, J. Chen, R. Sang, et al., Nat. Chem. 12 (2020) 56–62. doi: 10.1038/s41557-019-0353-3

  79. [79]

      M.J. Cabrera-Afonso, A. Granados, G.A. Molander, Angew. Chem. Int. Ed. 134 (2022) e202202706. doi: 10.1002/ange.202202706

  80. [80]

      D.M. Yan, S.H. Xu, H. Qian, et al., ACS Catal. 12 (2022) 3279–3285. doi: 10.1021/acscatal.2c00638

  81. [81]

      E.M. Alvarez, T. Karl, F. Berger, L. Torkowski, T. Ritter, Angew. Chem. Int. Ed. 60 (2021) 13609–13613. doi: 10.1002/anie.202103085

  82. [82]

      P.S. Engl, A.P. Häring, F. Berger, et al., J. Am. Chem. Soc. 141 (2019) 13346–13351. doi: 10.1021/jacs.9b07323

  83. [83]

      X.Y. Chen, X.X. Nie, Y. Wu, P. Wang, Chem. Commun. 56 (2020) 5058–5061. doi: 10.1039/d0cc00641f

  84. [84]

      Y. Wu, Y.H. Huang, X.Y. Chen, Org. Lett. 22 (2020) 6657–6661. doi: 10.1021/acs.orglett.0c02458

  85. [85]

      X.X. Nie, Y.H. Huang, P. Wang, Org. Lett. 22 (2020) 7716–7720. doi: 10.1021/acs.orglett.0c02913

  86. [86]

      T. Ueda, H. Konishi, K. Manabe, Org. Lett. 14 (2012) 3100–3103. doi: 10.1021/ol301192s

  87. [87]

      S.A. Ohnmacht, A.J. Culshaw, M.F. Greaney, Org. Lett. 12 (2010) 224–226. doi: 10.1021/ol902537d

  88. [88]

      E.M. Alvarez, M.B. Plutschack, F. Berger, T. Ritter, Org. Lett. 22 (2020) 4593–4596. doi: 10.1021/acs.orglett.0c00982

  89. [89]

      N. Kaplaneris, A. Puet, F. Kallert, J. Pöhlmann, L. Ackermann, Angew. Chem. Int. Ed. 62 (2023) e202216661. doi: 10.1002/anie.202216661

  90. [90]

      K. Sun, C. Ge, X. Chen, et al., Nat. Commun. 15 (2024) 9693. doi: 10.1038/s41467-024-54079-3

  91. [91]

      K. Cheng, E.W. Webb, G.D. Bowden, et al., Org. Lett. 26 (2024) 3419–3423. doi: 10.1021/acs.orglett.4c00929

  92. [92]

      X. Kong, Y. Chen, Q. Liu, et al., Org. Lett. 25 (2023) 581–586. doi: 10.1021/acs.orglett.2c03956

  93. [93]

      Y.L. Zhang, G.H. Wang, Y. Wu, C.Y. Zhu, P. Wang, Org. Lett. 23 (2021) 8522–8526. doi: 10.1021/acs.orglett.1c03229

  94. [94]

      J. Wu, Z. Wang, X.Y. Chen, et al., Sci. China Chem. 63 (2020) 336–340. doi: 10.1007/s11426-019-9652-x

  95. [95]

      K. Sun, A. Shi, Y. Liu, et al., Chem. Sci. 13 (2022) 5659–5666. doi: 10.1039/d2sc01241c

  96. [96]

      Y. Zhang, S. Xia, W. Shi, et al., Org. Lett. 24 (2022) 7961–7966. doi: 10.1021/acs.orglett.2c03077

  97. [97]

      L. Racicot, T. Kasahara, M.A. Ciufolini, Org. Lett. 16 (2014) 6382–6385. doi: 10.1021/ol503177q

  98. [98]

      D.Q. Qian, H.J. Shine, J.H. Thurston, K.H. Whitmire, J. Phys. Org. Chem. 16 (2003) 142–147. doi: 10.1002/poc.585

  99. [99]

      D.Q. Qian, B. Liu, H.J. Shine, I.Y. Guzman-Jimenez, K.H. Whitmire, J. Phys. Org. Chem. 15 (2002) 139–147. doi: 10.1002/poc.462

  100. [100]

       X.Y. Chen, Y.N. Li, Y. Wu, et al., J. Am. Chem. Soc. 145 (2023) 10431–10440. doi: 10.1021/jacs.3c03413

  101. [101]

       N. Kim, M. Choi, S.E. Suh, D.M. Chenoweth, Chem. Rev. 124 (2024) 11435–11522. doi: 10.1021/acs.chemrev.4c00296

  102. [102]

       J. Shi, L. Li, Y. Li, Chem. Rev. 121 (2021) 3892–4044. doi: 10.1021/acs.chemrev.0c01011

  103. [103]

       H. Takikawa, A. Nishii, T. Sakai, K. Suzuki, Chem. Soc. Rev. 47 (2018) 8030–8056. doi: 10.1039/c8cs00350e

  104. [104]

       K. Kamikawa, Nat. Rev. Chem. 7 (2023) 496–510. doi: 10.1038/s41570-023-00485-y

  105. [105]

       J. Shi, Y. Li, Y. Li, Chem. Soc. Rev. 46 (2017) 1707–1719. doi: 10.1039/C6CS00694A

  106. [106]

       J. Tan, X. Feng, R. Fan, Z. Zhuang, Y. Guo, Synlett 34 (2023) 2379–2387. doi: 10.1055/s-0042-1751476

  107. [107]

       D.B. Werz, A.T. Biju, Angew. Chem. Int. Ed. 59 (2020) 3385–3398. doi: 10.1002/anie.201909213

  108. [108]

       S. Yoshida, T. Yano, Y. Misawa, et al., J. Am. Chem. Soc. 137 (2015) 14071–14074. doi: 10.1021/jacs.5b10557

  109. [109]

       Y. Guo, Z. Zhuang, X. Feng, et al., Org. Lett. 25 (2023) 7192–7197. doi: 10.1021/acs.orglett.3c02785

  110. [110]

       O. Smith, M.J. Hindson, A. Sreenithya, et al., Nat. Synth. 3 (2024) 58–66.

  111. [111]

       C. Arakawa, K. Kanemoto, K. Nakai, et al., J. Am. Chem. Soc. 146 (2024) 3910–3919. doi: 10.1021/jacs.3c11524

  112. [112]

       J. Chen, S. Liu, S. Su, et al., Sci. Adv. 9 (2023) eadi1370. doi: 10.1126/sciadv.adi1370

  113. [113]

       A. Dasgupta, S. Bhattacharjee, Z. Tong, et al., J. Am. Chem. Soc. 146 (2024) 1196–1203. doi: 10.1021/jacs.3c13080

  114. [114]

       J. Yao, Z. Zhang, Z. Li, J. Am. Chem. Soc. 146 (2024) 8839–8846. doi: 10.1021/jacs.4c00426

  115. [115]

       Y. Li, D. Qiu, R. Gu, et al., J. Am. Chem. Soc. 138 (2016) 10814–10817. doi: 10.1021/jacs.6b06981

  116. [116]

       A. Saputra, R. Fan, T. Yao, J. Chen, J. Tan, Adv. Synth. Catal. 362 (2020) 2683–2688. doi: 10.1002/adsc.202000308

  117. [117]

       H. Tan, S. Yu, X. Yuan, et al., Nat. Commun. 15 (2024) 3665. doi: 10.1038/s41467-024-47952-8

  118. [118]

       G. Pan, M. Pu, H. Wang, et al., J. Am. Chem. Soc. 145 (2023) 26318–26327. doi: 10.1021/jacs.3c09594

  119. [119]

       T. Sephton, A. Charitou, C. Trujillo, et al., Angew. Chem. Int. Ed. 62 (2023) e202310583. doi: 10.1002/anie.202310583

  120. [120]

       J.K. Xu, S.J. Li, H.Y. Wang, W.C. Xu, S.K. Tian, Chem. Commun. 53 (2017) 1708–1711. doi: 10.1039/C6CC09311F

  121. [121]

       F. Luo, C.L. Li, P. Ji, et al., Chem 9 (2023) 2620–2636. doi: 10.1016/j.chempr.2023.05.032

  122. [122]

       T.R. Hoye, B. Baire, D. Niu, P.H. Willoughby, B.P. Woods, Nature 490 (2012) 208–212. doi: 10.1038/nature11518

  123. [123]

       D. Niu, P.H. Willoughby, B.P. Woods, B. Baire, T.R. Hoye, Nature 501 (2013) 531–534. doi: 10.1038/nature12492

  124. [124]

       S.K. Thompson, T.R. Hoye, J. Am. Chem. Soc. 141 (2019) 19575–19580. doi: 10.1021/jacs.9b11243

  125. [125]

       J. Liu, J. Li, B. Ren, et al., Adv. Synth. Catal. 363 (2021) 4734–4739. doi: 10.1002/adsc.202100697

  126. [126]

       K.A. Spence, J.V. Chari, M.D. Niro, et al., Chem. Sci. 13 (2022) 5884–5892. doi: 10.1039/d2sc01788a

  127. [127]

       J.V. Chari, K.A. Spence, R.B. Susick, N.K. Garg, Nat. Commun. 12 (2021) 3706. doi: 10.1038/s41467-021-23970-8

  128. [128]

       Y. Guo, J. Su, J. Xu, Q. Song, Org. Lett. 25 (2023) 6459–6463. doi: 10.1021/acs.orglett.3c01938

  129. [129]

       J. Shi, L. Li, C. Shan, et al., J. Am. Chem. Soc. 143 (2021) 2178–2184. doi: 10.1021/jacs.0c11119

  130. [130]

       Z. Liu, R.C. Larock, J. Am. Chem. Soc. 127 (2005) 13112–13113. doi: 10.1021/ja054079p

  131. [131]

       F.L. Liu, J.R. Chen, Y.Q. Zou, Q. Wei, W.J. Xiao, Org. Lett. 16 (2014) 3768–3771. doi: 10.1021/ol501638x

  132. [132]

       D. Kaiser, I. Klose, R. Oost, J. Neuhaus, N. Maulide, Chem. Rev. 119 (2019) 8701–8780. doi: 10.1021/acs.chemrev.9b00111

  133. [133]

       H. Yorimitsu, Chem. Rec. 21 (2021) 3356–3369. doi: 10.1002/tcr.202000172

  134. [134]

       T. Matsuzawa, T. Hosoya, S. Yoshida, Chem. Sci. 11 (2020) 9691–9696. doi: 10.1039/d0sc04450d

  135. [135]

       R. Fan, S. Liu, Q. Yan, et al., Chem. Sci. 14 (2023) 4278–4287. doi: 10.1039/d3sc00072a

  136. [136]

       L. Shang, Y. Chang, F. Luo, et al., J. Am. Chem. Soc. 139 (2017) 4211–4217. doi: 10.1021/jacs.7b00969

  137. [137]

       Z. Zhang, Z. Sheng, W. Yu, et al., Nature Chem. 9 (2017) 970–976. doi: 10.1038/nchem.2789

  138. [138]

       M.H. Aukland, M. Šiauciulis, A. West, G.J.P. Perry, D.J. Procter, Nat. Catal. 3 ˇ (2020) 163–169. doi: 10.1038/s41929-019-0415-3

  139. [139]

       D.E. Holst, D.J. Wang, M.J. Kim, I.A. Guzei, Z.K. Wickens, Nature 596 (2021) 74–79. doi: 10.1038/s41586-021-03717-7

  140. [140]

       X. Xiao, J. Zeng, J. Fang, et al., J. Am. Chem. Soc. 142 (2020) 5498–5503. doi: 10.1021/jacs.0c00447

  141. [141]

       R.A. Roberts, B.E. Metze, A. Nilova, D.R. Stuart, J. Am. Chem. Soc. 145 (2023) 3306–3311. doi: 10.1021/jacs.2c13007

  142. [142]

       J.M. Medina, J.L. Mackey, N.K. Garg, K.N. Houk, J. Am. Chem. Soc. 136 (2014) 15798–15805. doi: 10.1021/ja5099935

  143. [143]

       Y.F. Yao, J.W. Song, C.P. Zhang, Org. Biomol. Chem. 22 (2024) 7866–7873. doi: 10.1039/d4ob01220h

  144. [144]

       J.W. Song, F. Xia, X.L. Zhang, C.P. Zhang, Org. Chem. Front. 11 (2024) 4219–4230. doi: 10.1039/d4qo00618f

  145. [145]

       Z. Tan, H. Zhang, K. Xu, C. Zeng, Sci. China Chem. 67 (2024) 450–470. doi: 10.1007/s11426-023-1735-x

  146. [146]

       J. Li, S. Zhang, K. Xu, Chin. Chem. Lett. 32 (2021) 2729–2735. doi: 10.1016/j.cclet.2021.03.027

  147. [147]

       S. Tang, Y. Liu, A. Lei, Chem 4 (2018) 27–45. doi: 10.1016/j.chempr.2017.10.001

  148. [148]

       M. Yan, Y. Kawamata, P.S. Baran, Chem. Rev. 117 (2017) 13230–13319. doi: 10.1021/acs.chemrev.7b00397

  149. [149]

       A. Bhunia, T. Kaicharla, D. Porwal, R.G. Gonnade, A.T. Biju, Chem. Commun. 50 (2014) 11389–11392. doi: 10.1039/C4CC05420B

  150. [150]

       M. Berchel, P.A. Jaffrès, Chapter 2 - recent developments in phosphonium chemistry, in: V. Iaroshenko (Ed.), Organophosphorus Chemistry: From Molecules to Applications, Wiley-VCH, Weinheim, 2019, pp. 59–111.

  151. [151]

       L.K. Hwang, Y. Na, J. Lee, Y. Do, S. Chang, Angew. Chem. Int. Ed. 44 (2005) 6166–6169. doi: 10.1002/anie.200501582

  152. [152]

       Y. Toda, S. Gomyou, S. Tanaka, et al., Org. Lett. 19 (2017) 5786–5789. doi: 10.1021/acs.orglett.7b02722

  153. [153]

       D.I. Bugaenko, A.A. Volkov, M.V. Livantsov, M.A. Yurovskaya, A.V. Karchava, Chem. Eur. J. 25 (2019) 12502–12506. doi: 10.1002/chem.201902955

  154. [154]

       W. Liu, H. Hou, H. Jing, et al., Org. Lett. 25 (2023) 8350–8355. doi: 10.1021/acs.orglett.3c03473

  155. [155]

       A.F. Fearnley, J. An, M. Jackson, P. Lindovska, R.M. Denton, Chem. Commun. 52 (2016) 4987–4990. doi: 10.1039/C6CC00556J

• 

  Scheme 1  Background and working hypothesis.

  下载: 全尺寸图片 幻灯片
  

  Scheme 2  Substrate scope of ortho-deuterated arylthianthrenium. ^a The crystal data please see Supporting information. ^b 4k (p): 4k’ (m) = 10.3:1. ^c 4l (p): 4l’ (m) = 1:1.

  下载: 全尺寸图片 幻灯片
  

  Scheme 3  Substrate scope of ortho-deuterated aromatic derivative. Reaction conditions please see Supporting information. ^a 49% Yield for one-pot, two-steps method.

  下载: 全尺寸图片 幻灯片
  

  Scheme 4  Research on the arylation of aryl phosphorus. (A) Substrate scope of ortho-deuterated tetraarylphosphonium salts. (B) Substrate scope of non-deuterated tetraarylphosphonium salts. (C) UV–vis studies, Black line: 4a (0.4 mmol) in 2 mL MeCN; Red line: PPh₃ (0.8 mmol) in MeCN (2 mL); Blue line: 4a (0.4 mmol) + PPh₃ (0.8 mmol) in MeCN (2 mL). (D) Gram scale synthesis. (E) Light ON—OFF experiment. (F) Control experiments. (G) Plausible mechanism.

  下载: 全尺寸图片 幻灯片

  Table 1.  Reaction condition optimization of synthesis of ortho-deuterated arylthianthrenium salts.^a

  Entry	“F-”/Solvent	3 (equiv.)	Yieldb (%) [D (%)]c
  1	KF/18-C-6/THF	D2O (10)	trace
  2	CsF/MeCN	D2O (10)	89 [98]
  3	TBAF/THF	D2O (10)	trace
  4	TBAT/THF	D2O (10)	trace
  5	CsF/MeCN	D2O (6)	75 [82]
  6	CsF/MeCN	D2O (25)	84 [98]
  7	CsF/MeCN	D2O (160)	trace
  8	CsF/MeCN	CDCl3 (10)	63 [87]
  9	CsF/MeCN	CD3OD (10)	trace
  10	CsF/MeCN	CD3COCD3 (10)	trace
  11d	CsF/MeCN	D2O (10)	78 [95]
  12e	CsF/MeCN	D2O (10)	55 [98]
  13f	CsF/MeCN	D2O (10)	90 [93]
  a Reaction conditions: 1a (0.1 mmol), 2a (0.25 mmol), “F-” (0.25 mmol), solvent (0.3 mL), “D+” source, N2, 60 ℃, 36 h. b Isolated yield. c Determined by 1H NMR. d CH3CN (0.15 mL). e 30 ℃. f 80 ℃.

  下载: 导出CSV

  Table 2.  Reaction condition optimization of synthesis of ortho-deuterated tetraarylphosphonium salts.

  Entry	Variations from the standard conditions	Yield (%) [D (%)]b
  1	Nonea	94 [98]
  2	456 nm, 40 W	45 [98]
  3	440 nm, 40 W	84 [98]
  4	427 nm, 20 W	53 [98]
  5	427 nm, 30 W	79 [98]
  6	Dark	N.D.
  a Reaction conditions: 4a (0.1 mmol), PPh3 (0.2 mmol, 2 equiv.), MeCN (0.5 mL). b Isolated yield [Deuterium incorporation].

  下载: 导出CSV
•