Skip to main content
NCBI home page
ACS Organic & Inorganic Au logoLink to ACS Organic & Inorganic Au
. 2021 Jun 22;1(1):23–28. doi: 10.1021/acsorginorgau.1c00007

Visible-Light-Driven C–S Bond Formation Based on Electron Donor–Acceptor Excitation and Hydrogen Atom Transfer Combined System

Tatsuhiro Uchikura 1, Yurina Hara 1, Kazushi Tsubono 1, Takahiko Akiyama 1,*
PMCID: PMC9954416  PMID: 36855634

Abstract

graphic file with name gg1c00007_0010.jpg

Developed herein is a visible-light-driven synthesis of sulfides by an electron donor–acceptor/single electron transfer and hydrogen atom transfer combined system without transition metals and strong oxidants. This reaction proceeds through the excitation of an electron donor–acceptor complex between a thiolate and an aryl halide, followed by the hydrogen atom transfer from an alkane to the generated aryl radical.

Keywords: bond formation, donor−acceptor excitation, hydrogen atom transfer

Introduction

Organosulfur compounds are widely used in pharmaceuticals and functional materials.1,2 In this regard, C–S bond formation is a very important process in organic synthesis.3,4 In particular, C(sp3)–S bond formation has attracted much attention because many C(sp3)–S bonds exist in biologically active compounds (Figure 1).5−10 The C(sp3)–S bond is generally formed by the SN2 reaction of thiolate with haloalkane. The direct C–H sulfenylation of alkanes via radical processes utilizing thiyl radicals is an atom-economical reaction.11 A drawback of the formation of the thiyl radical is that strong oxidants or transition metals are required for the generation of the radical species (Figure 2a),12−15 and mild conditions for C–S bond formation reactions are desired.

Figure 1.

Figure 1

Open in a new tab

Pharmaceuticals bearing a C(sp3)–S bond.

Figure 2.

Figure 2

Open in a new tab

C–S bond-forming reactions mediated by thiyl radicals.

In the past decade, photocatalytic radical coupling reactions have been reported for the generation of radical species under mild conditions.16−19 For example, Fu et al. reported a photoinduced radical C–S bond formation reaction using a photocatalyst.20−24 More recently, an electron donor–acceptor (EDA) complex was developed for use in the visible-light-driven photoreaction instead of photocatalysts because EDA complexes often absorb visible light.25−39 Miyake et al. reported a visible-light-driven C(sp2)–S bond formation reaction via the EDA complexes of aryl thiols and aryl halides (Figure 2b),35 wherein reactive radical species are generated by single electron transfer (SET) from the EDA complexes. On the other hand, the reactive radical species can abstract a C(sp3)–H hydrogen atom (hydrogen atom transfer: HAT40−45) to give alkyl radical species. By utilizing these phenomena, novel photoreactions via EDA-SET and HAT combination are achieved.46−48

We wish to report herein transition-metal- and strong-oxidant-free visible-light-driven radical coupling reactions of thiols and alkanes to form C–S bonds based on the SET and HAT combination system (Figure 2c). Mechanistic studies revealed that the aryl radical species generated from the EDA excited state abstracted the hydrogen atom from alkanes to generate alkyl radicals.

Results and Discussion

At the outset, we examined the reaction of benzenethiol (1a) and THF in the presence of p-bromoacetophenone (3a) and cesium carbonate under blue LED irradiation. The desired C–S bond formation product 4a was obtained in 71% yield (Table 1, entry 1). Control experiments indicated that light irradiation and the addition of base and 3a were necessary for this reaction (entries 2–4). 4a was not obtained in air, and disulfide 5 was generated (entry 5). Therefore, the degassed condition was necessary for this reaction. Use of 4-bromobenzonitrile (3b) instead of 3a decreased the yield of 4a probably because the generation of an aryl radical was unfavorable due to the stability of the anion radical species and the instability of the radical (entry 6).49−51 Potassium carbonate was not suitable due to its low solubility (entry 7).52

Table 1. Standard Reaction Conditions and Control Experimentsa.

graphic file with name gg1c00007_0009.jpg

entry deviation from the standard conditions yieldb
1 none 71%c
2 without 3a <5%
3 without irradiation 0%
4 without Cs2CO3 0%
5 in air 0%
6 4-bromobenzonitrile (3b) instead of 3a 33%c
7 K2CO3 instead of Cs2CO3 0%
Open in a new tab
a

Performed with 1a (0.1 mmol), 2 (1.0 mL), 3a (0.15 mmol), and Cs2CO3 (0.2 mmol).

b

Determined by 1H NMR measurement.

c

Isolated yield.

Under the optimized conditions, the generality of thiols was investigated (Figure 3). A range of para-substituted aryl thiols bearing tert-butyl, methoxy, hydroxy, chloro, and bromo moieties participated in the reaction successfully to give corresponding C–S coupling products (4a–4f) in good to moderate yields. The meta- and ortho-methoxythiophenols also gave corresponding products (4g and 4h) efficiently. 4-Aminothiophenol did not give 4i probably because of the lack of acidity for generating thiolate. In contrast, 2-aminothiophenol gave 4j in a moderate yield due to the stabilization of the thiolate anion by the ortho-amino group. In the case of methoxycarbonyl-substituted thiophenol, although para-substituted thiophenol did not furnish 4k, ortho-substituted thiophenol gave 4l in a moderate yield because the thiyl radical generated by the excitation of the EDA complex was stabilized by three-electron–two-center S–O bond formation with the carbonyl group at the ortho position.53−56 Interestingly, p-cyanobenzenethiol (1m) and 3,5-bis(trifluoromethyl)benzenethiol (1o) bearing electron-withdrawing groups, which are unfavorable compounds for EDA complex formation, were also suitable substrates. In contrast, p-nitrobenzenethiol (1n), which has a yellow color, was not suitable due to self-absorption of visible light to inhibit EDA absorption or its low electron density to donate the electron to 3a. Furthermore, 2-naphthalenethiol (1p) and heteroarenethiols (1q and 1r) afforded C–S coupling products in moderate yields. Interestingly, whereas phenylmethanethiol gave 4s in 45% yield, phenylethanethiol did not proceed to give 4t presumably because the aromatic moiety and sulfur anion are far apart. Alkanethiols without a phenyl group, such as cyclohexanethiol and decanethiol, did not give the coupling products (4u, 4v). The reaction of thiophenol with tetrahydrofuran proceeded smoothly on a 1 mmol scale to give the 4a in 83% yield (Scheme 1).

Figure 3.

Figure 3

Open in a new tab

Generality of thiols. ap-Bromobenzophenone (3c) was used as aryl halide instead of p-bromoacetophenone (3a). bAfter the irradiation, NaBH4 (1.0 equiv) and MeOH (1 mL) were added to the reaction mixture to reduce residual ketone.

Scheme 1. 1 mmol Scale Reaction.

Scheme 1

Open in a new tab

We investigated the generality of alkanes using 20 equiv of alkanes in ethyl acetate57 (Figure 4). Ethers, such as 1,4-dioxane, tetrahydropyran, 2,2-dimethyl-1,3-dioxolane, and o-xylylene oxide, gave corresponding thioacetals (4a, 6b–6e) in modest to good yields. However, isochroman and cyclopentyl methyl ether gave products (6f and 6g) in low yields due to steric hindrance, and acyclic primary ether was not suitable due to the low stability of the radical. Tetrahydrothiophene gave corresponding dithioacetal 6h in 51% yield. Cyclic amides, such as dimethyl imidazolidinone and N-methyl pyrrolidone, were also suitable substrates, furnishing products (6i and 6j) in moderate yields. Furthermore, cycloalkanes, such as cyclopentane, cyclohexane, and cycloheptane, were also applicable, generating desired sulfides (6k–6m) in modest yields.

Figure 4.

Figure 4

Open in a new tab

Generality of alkanes. aUsing 1.0 mL of hydrocarbons without AcOEt.

Several experiments were carried out to acquire mechanistic insight. First, the UV–vis spectra were measured in acetonitrile (Figure 5).58 The formation of the EDA complex was confirmed by the absorption in the 420–550 nm region in a mixture of sodium benzenethiolate (1a-Na) and 3a. This absorption was not observed in individual substrates (1a and 3a) or in a mixture of benzenethiol 1a and 3a. Thus, the generation of thiophenolate from 1a and base was necessary for the formation of the EDA complex.59

Figure 5.

Figure 5

Open in a new tab

UV–vis spectra of the EDA complex in CH3CN. Orange line: mixture of sodium benzenethiolate (1a-Na) and 3a. Light gray line: mixture of 1a and 3a. Dark gray line: 1a-Na.

Furthermore, the different reactivity of phenylmethanethiol and other alkanethiols (Figure 3) supports that π–π interaction between thiolate and aryl halide would be the driving force for formation of the EDA complex.

Next, radical inhibitors were added to the reaction mixture under the standard conditions (Scheme 2A). Because the addition of radical scavengers, such as 9,10-dihydroanthracene and TEMPO, inhibited the reaction, the radical process is plausible. Use of THF-d8 gave 4′-deuterated acetophenone 7 as the side product (Scheme 2B). This means that the hydrogen atom of alkanes was abstracted by an aryl radical generated from aryl halide via EDA-SET. Furthermore, when a 1:1 mixture of THF and THF-d8 was used, the kH/kD value was estimated to be 5.15 (Scheme 2C). Thus, C–H abstraction is expected to be the rate-determining step in this reaction.

Scheme 2. Mechanistic Studies.

Scheme 2

Open in a new tab

Based on these results, we propose the mechanism shown in Figure 6. First, an EDA complex of thiolate and 4′-bromoacetophenone is formed driven by π–π interaction (3a). This is followed by photoexcitation to generate a thiyl radical and an anion radical of aryl halide. Then, bromide is eliminated from the anion radical of aryl halide to generate aryl radical species, which in turn abstracts a hydrogen atom from an alkane10 to produce alkyl radical. Finally, a C–S bond is formed between the thiyl radical and the alkyl radical.

Figure 6.

Figure 6

Open in a new tab

Proposed mechanism.

Conclusion

In summary, a visible-light-driven C(sp3)–S bond formation reaction via the EDA excited state was developed. This reaction proceeds via the SET and HAT combination system. Mechanistic studies indicate that an aryl radical generated by EDA excitation abstracts a hydrogen atom from alkane, and the generated alkyl radical couples with the thiyl radical. To the best of our knowledge, this reaction is the first example of the EDA-SET and HAT combined photoreaction system that is expected to have several applications to other reactions.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsorginorgau.1c00007.

  • Experimental details including further optimization studies, and analytical and spectroscopic data for new compounds; copies of NMR spectra (PDF)

JSPS KAKENHI Grant Nos. JP20H00380 and JP20H04826 (Hybrid Catalysis) for T.A. JSPS KAKENHI Grant No. JP20K15287 for T.U.

The authors declare no competing financial interest.

Supplementary Material

gg1c00007_si_001.pdf (3.8MB, pdf)

References

  1. Ruhee R. T.; Roberts L. A.; Ma S.; Suzuki K. Organosulfur Compounds: A Review of Their Anti-inflammatory Effects in human Health. Front. Nutr. 2020, 7, 64. 10.3389/fnut.2020.00064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Zhang X.; Chen K.; Sun Z.; Hu G.; Xiao R.; Cheng H.-M.; Li F. Structure-related Electrochemical Performance of Organosulfur Compounds for Lithium-Sulfur Batteries. Energy Environ. Sci. 2020, 13, 1076–1095. 10.1039/C9EE03848E. [DOI] [Google Scholar]
  3. Shen C.; Zhang P.; Sun Q.; Bai S.; Hor T. S. A.; Liu X. Recent Advances in C-S Bond Formation via C-H Bond Functionalization and Decarboxylation. Chem. Soc. Rev. 2015, 44, 291–314. 10.1039/C4CS00239C. [DOI] [PubMed] [Google Scholar]
  4. Choudhuri K.; Pramanik M.; Mal P. Noncovalent Interaction in C-S Bond Formation Reactions. J. Org. Chem. 2020, 85, 11997–12011. 10.1021/acs.joc.0c01534. [DOI] [PubMed] [Google Scholar]
  5. Le Grand B.; Pignier C.; Letienne R.; Cuisiat F.; Rolland F.; Mas A.; Vacher B. Sodium Late Current Blockers in Ischemia Reperfusion: Is the Bullet Magic?. J. Med. Chem. 2008, 51, 3856–3866. 10.1021/jm800100z. [DOI] [PubMed] [Google Scholar]
  6. Hartman I.; Gillies A. R.; Arora S.; Andaya C.; Royapet N.; Welsh W. J.; Wood D. W.; Zauhar R. J. Application of Screening Methods, Shape Signatures and Engineered Biosensors in Early Drug Discovery Process. Pharm. Res. 2009, 26, 2247–2258. 10.1007/s11095-009-9941-z. [DOI] [PubMed] [Google Scholar]
  7. Kostova M. B.; Myers C. J.; Beck T. N.; Plotkin B. J.; Green J. M.; Boshoff H. I. M.; Barry III C. E.; Deschamps J. R.; Konaklieva M. I. C4-Alkylthiols with Activity Against Moraxella Catarrhalis and Mycobacterium Tuberculosis. Bioorg. Med. Chem. 2011, 19, 6842–6852. 10.1016/j.bmc.2011.09.030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clayden J.; MacLellan P. Asymmetric Synthesis of Tertiary Thiols and Thioethers. Beilstein J. Org. Chem. 2011, 7, 582–595. 10.3762/bjoc.7.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ilardi E. A.; Vitaku E.; Njardarson J. T. Data-Mining for Sulfur and Fluorine: An Evaluation of Pharmaceuticals To Reveal Opportunities for Drug Design and Discovery. J. Med. Chem. 2014, 57, 2832–2842. 10.1021/jm401375q. [DOI] [PubMed] [Google Scholar]
  10. Beck T. N.; Lloyd D.; Kuskovsky R.; Minah J.; Arora K.; Plotkin B. J.; Green J. M.; Boshoff H. I.; Barry III C.; Deschamps J.; Konaklieva M. I. Non-transpeptidase Binding Arylthioether β-Lactams Active Against Mycobacterium Tuberculosis and Moraxella Catarrhalis. Bioorg. Med. Chem. 2015, 23, 632–647. 10.1016/j.bmc.2014.11.025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dénès F.; Pichowicz M.; Povie G.; Renaud P. Thiyl Radicals in Organic Synthesis. Chem. Rev. 2014, 114, 2587–2693. 10.1021/cr400441m. [DOI] [PubMed] [Google Scholar]
  12. Tang R.-Y.; Xie Y.-X.; Xie Y.-L.; Xiang J.-N.; Li J.-H. TBHP-mediated Oxidative Thiolation of an sp3 C-H Bond Adjacent to a Nitrogen Atom in an Amide. Chem. Commun. 2011, 47, 12867–12869. 10.1039/c1cc15397h. [DOI] [PubMed] [Google Scholar]
  13. Guo S.-R.; Yuan Y.-Q.; Xiang J.-N. Metal-Free Oxidative C(sp3)-H Bond Thiolation of Ethers with Disulfides. Org. Lett. 2013, 15, 4654–4657. 10.1021/ol402281f. [DOI] [PubMed] [Google Scholar]
  14. Zhao J.; Fang H.; Han J.; Pan Y.; Li G. Metal-Free Preparation of Cycloalkyl Aryl Sulfides via Di-tert-butyl Peroxide-Promoted Oxidative C(sp3)-H Bond Thiolation of Cycloalkaces. Adv. Synth. Catal. 2014, 356, 2719–2724. 10.1002/adsc.201400032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Zhao F.; Tan Q.; Wang D.; Chen J.; Deng G.-J. Efficient C-S Bond Formation by Direct Functionalization of C(sp3)-H Bond Adjacent to Heteroatoms under Metal-Free Conditions. Adv. Synth. Catal. 2019, 361, 4075–4081. 10.1002/adsc.201900666. [DOI] [Google Scholar]
  16. Prier C. K.; Rankic D. A.; MacMillan D. W. C. Visible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic Synthesis. Chem. Rev. 2013, 113, 5322–5363. 10.1021/cr300503r. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Romero N. A.; Nicewicz D. A. Organic Photoredox Catalysis. Chem. Rev. 2016, 116, 10075–10166. 10.1021/acs.chemrev.6b00057. [DOI] [PubMed] [Google Scholar]
  18. Shaw M. H.; Twilton J.; MacMillan D. W. C. Photoredox Catalysis in Organic Chemistry. J. Org. Chem. 2016, 81, 6898–6926. 10.1021/acs.joc.6b01449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Michelin C.; Hoffmann N. Photosensitization and Photocatalysis-Perspectives in Organic Synthesis. ACS Catal. 2018, 8, 12046–12055. 10.1021/acscatal.8b03050. [DOI] [Google Scholar]
  20. Wimmer A.; König B. Photocatalytic Formation of Carbon-Sulfur Bonds. Beilstein J. Org. Chem. 2018, 14, 54–83. 10.3762/bjoc.14.4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Zhu X.; Xie X.; Li P.; Guo J.; Wang L. Visible-Light-Induced Direct Thiolation at α-C(sp3)-H of Ethers with Disulfides Using Acridine Red as Photocatalyst. Org. Lett. 2016, 18, 1546–1549. 10.1021/acs.orglett.6b00304. [DOI] [PubMed] [Google Scholar]
  22. Jiang M.; Li H.; Yang H.; Fu H. Room-Temperature Arylation of Thiols: Breakthrough with Aryl Chlorides. Angew. Chem., Int. Ed. 2017, 56, 874–879. 10.1002/anie.201610414. [DOI] [PubMed] [Google Scholar]
  23. Spinnato D.; Schweitzer-Chaput B.; Goti G.; Oseka M.; Melchiorre P. A Photochemical Organocatalytic Strategy for the α-Alkylation of Ketones by Using Radicals. Angew. Chem., Int. Ed. 2020, 59, 9485–9490. 10.1002/anie.201915814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Li J.; Yang X.-E.; Wang S.-L.; Zhang L.-L.; Zhou X.-Z.; Wang S.-Y.; Ji S.-J. Visible-Light-Promoted Cross-Coupling Reactions of 4-Alkyl-1,4-Dihydropyridines with Thiosulfonate or Selenium Sulfonate: A Unified Approach to Sulfides, Selenides, and Sulfoxides. Org. Lett. 2020, 22, 4908–4913. 10.1021/acs.orglett.0c01776. [DOI] [PubMed] [Google Scholar]
  25. Foster R. Electron Donor-Acceptor Complexes. J. Phys. Chem. 1980, 84, 2135–2141. 10.1021/j100454a006. [DOI] [Google Scholar]
  26. Rosokha S. V.; Kochi J. K. Flash Look at Electron-Transfer Mechanism via the Donor/Acceptor Bonding in the Critical Encounter Complex. Acc. Chem. Res. 2008, 41, 641–653. 10.1021/ar700256a. [DOI] [PubMed] [Google Scholar]
  27. Emmett L.; Prentice G. M.; Pantoş G. D. Donor-Acceptor Interactions in Chemistry. Annu. Rep. Prog. Chem., Sect. B: Org. Chem. 2013, 109, 217–234. 10.1039/c3oc90004e. [DOI] [Google Scholar]
  28. Lima C. G. S.; de M. Lima T.; Duarte M.; Jurberg I. D.; Paixao M. W. Organic Synthesis Enabled by Light-Irradiation of EDA Complexes: Theoretical Background and Synthetic Applications. ACS Catal. 2016, 6, 1389–1407. 10.1021/acscatal.5b02386. [DOI] [Google Scholar]
  29. Crisenza G. E. M.; Mazzarella D.; Melchiorre P. Synthetic Methods Driven by the Photoactivity of Electron Donor-Acceptor Complexes. J. Am. Chem. Soc. 2020, 142, 5461–5476. 10.1021/jacs.0c01416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yang Z.; Liu Y.; Cao K.; Zhang X.; Jiang H.; Li J. Synthetic Reactions Driven by Electron-Donor-Acceptor (EDA) Complexes. Beilstein J. Org. Chem. 2021, 17, 771–799. 10.3762/bjoc.17.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sumida Y.; Ohmiya H. Direct Excitation Strategy for Radical Generation in Organic Synthesis. Chem. Soc. Rev. 2021, 10.1039/D1CS00262G. [DOI] [PubMed] [Google Scholar]
  32. Arceo E.; Jurberg I. D.; Álvarez-Fernández A.; Melchiorre P. Photochemical Activity of a Key Donor-Acceptor Complex Can Drive Stereoselective Catalytic α-Alkylation of Aldehydes. Nat. Chem. 2013, 5, 750–756. 10.1038/nchem.1727. [DOI] [PubMed] [Google Scholar]
  33. Marzo L.; Wang S.; König B. Visible-Light-Mediated Radical Arylation of Anilines with Acceptor-Substituted (Hetero)aryl Halides. Org. Lett. 2017, 19, 5976–5979. 10.1021/acs.orglett.7b03001. [DOI] [PubMed] [Google Scholar]
  34. Zhang J.; Li Y.; Xu R.; Chen Y. Donor-Acceptor Complex Enables Alkoxy Radical Generation for Metal-Free C(sp3)-C(sp3) Cleavage and Allylation/Alkenylation. Angew. Chem., Int. Ed. 2017, 56, 12619–12623. 10.1002/anie.201707171. [DOI] [PubMed] [Google Scholar]
  35. Liu B.; Lim C.-H.; Miyake G. M. Visible-Light-Promoted C-S Cross-Coupling via Intermolecular Charge Transfer. J. Am. Chem. Soc. 2017, 139, 13616–13619. 10.1021/jacs.7b07390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Liu B.; Lim C.-H.; Miyake G. M. Light-Driven Intermolecular Charge Transfer Induced Reactivity of Ethynylbenziodoxol(on)e and Phenols. J. Am. Chem. Soc. 2018, 140, 12829–12835. 10.1021/jacs.8b05870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zhang H.-H.; Yu S. Visible-Light-Induced Radical Acylation of Imines with α-Ketoacids Enabled by Electron-Donor-Acceptor Complexes. Org. Lett. 2019, 21, 3711–3715. 10.1021/acs.orglett.9b01169. [DOI] [PubMed] [Google Scholar]
  38. Liang K.; Li N.; Zhang Y.; Li T.; Xia C. Transition-Metal-Free α-Arylation of Oxindoles via Visible-Light-Promoted Electron Transfer. Chem. Sci. 2019, 10, 3049–3053. 10.1039/C8SC05170D. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Uchikura T.; Oshima M.; Kawasaki M.; Takahashi K.; Iwasawa N. Supramolecular Photocatalysis by Utilizing the Host-Guest Charge-Transfer Interaction: Visible-Light-Induced Generation of Triplet Anthracenes for [4 + 2] Cycloaddition Reactions. Angew. Chem., Int. Ed. 2020, 59, 7403–7408. 10.1002/anie.201916732. [DOI] [PubMed] [Google Scholar]
  40. Jing L.; Nash J. J.; Kenttämaa H. I. Correlation of Hydroge-Atom Abstraction Reaction Efficiencies for Aryl Radicals with their Vertical Electron Affinities and the Vertical Ionization Energies of the Hydrogen-Atom Donors. J. Am. Chem. Soc. 2008, 130, 17697–17709. 10.1021/ja801707p. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Parasram M.; Chuentragool P.; Sarkar D.; Gevorgyan V. Photoinduced Formation of Hybrid Aryl Pd-Radical Species Capable of 1,5-HAT: Selective Catalytic Oxidation of Silyl Esters into Silyl Enol Ethers. J. Am. Chem. Soc. 2016, 138, 6340–6343. 10.1021/jacs.6b01628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Chen J.-Q.; Wei Y.-L.; Xu G.-Q.; Liang Y.-M.; Xu P.-F. Intramolecular 1,5-H Transfer Reaction of Aryl Iodides Through Visible-Light Photoredox Catalysis: A Concise Method for the Synthesis of Natural Product Scaffolds. Chem. Commun. 2016, 52, 6455–6458. 10.1039/C6CC02007K. [DOI] [PubMed] [Google Scholar]
  43. Hokamp T.; Dewanji A.; Lübbesmeyer M.; Mück-Lichtenfeld C.; Würthwein E.-U.; Studer A. Radical Hydrodehalogenation of Aryl Bromides and Chlorides with Sodium Hydride and 1,4-Dioxane. Angew. Chem., Int. Ed. 2017, 56, 13275–13278. 10.1002/anie.201706534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Si X.; Zhang L.; Wu Z.; Rudolph M.; Asiri A. M.; Hashmi A. S. K. Visible light-Induced α-C(sp3)-H Acetalization of Saturated Heterocycles Catalyzed by a Dimeric Gold Complex. Org. Lett. 2020, 22, 5844–5849. 10.1021/acs.orglett.0c01924. [DOI] [PubMed] [Google Scholar]
  45. Kang J.; Hwang H. S.; Soni V. K.; Cho E. J. Direct C(sp3)-N Radical Coupling: Photocatalytic C-H Functionalization by Unconventional Intermolecular Hydrogen Atom Transfer to Aryl Radical. Org. Lett. 2020, 22, 6112–6116. 10.1021/acs.orglett.0c02179. [DOI] [PubMed] [Google Scholar]
  46. Panferova L. I.; Zubkov M. O.; Kokorekin V. A.; Levin V. V.; Dilman A. D. Using the Thiyl Radical for Aliphatic Hydrogen-Atom Transfer: Thiolation of Unactivated C-H Bonds. Angew. Chem., Int. Ed. 2021, 60, 2849–2854. 10.1002/anie.202011400. [DOI] [PubMed] [Google Scholar]
  47. Kobayashi F.; Fujita M.; Ide T.; Ito Y.; Yamashita K.; Egami H.; Hamashima Y. Dual-Role Catalysis by Thiobenzoic Acid in Cα-H Arylation under Photoirradiation. ACS Catal. 2021, 11, 82–87. 10.1021/acscatal.0c04722. [DOI] [Google Scholar]
  48. Zhang L.; Liu Z.; Tian X.; Zi Y.; Duan S.; Fang Y.; Chen W.; Jing H.; Yang L.; Yang X. Transition-Metal-Free C(sp3)-H Coupling of Cycloalkenes Enabled by Single-Electron Transfer and Hydrogen Atom Transfer. Org. Lett. 2021, 23, 1714–1719. 10.1021/acs.orglett.1c00135. [DOI] [PubMed] [Google Scholar]
  49. According to the screening of aryl halide, p-bromoacetophenone and 4′’-bromobenzophenone gave the best results (Table S1; see Supporting Information).
  50. Pryor W. A.; Echols J. T. Jr.; Smith K. Rates of the Reactions of Substituted Phenyl Radicals with Hydrogen Donors. J. Am. Chem. Soc. 1966, 88, 1189–1199. 10.1021/ja00958a021. [DOI] [Google Scholar]
  51. Takayama K.; Kosugi M.; Migita T. Reactivities of Substituted Phenyl Radicals. Chem. Lett. 1973, 2, 215–218. 10.1246/cl.1973.215. [DOI] [Google Scholar]
  52. According to the screening of the base, cesium carbonate was identified to be the most suitable (Table S2; see Supporting Information).
  53. Schöneich C.; Pogocki D.; Hug G. L.; Bobrowski K. Free Radical Reactions of Methionine in Peptides: Mechanisms Relevant to β-Amyloid Oxidation and Alzheimer’s Disease. J. Am. Chem. Soc. 2003, 125, 13700–13713. 10.1021/ja036733b. [DOI] [PubMed] [Google Scholar]
  54. Glass R. S.; Schöneich C.; Wilson G. S.; Nauser T.; Yamamoto T.; Lorance E.; Nichol G. S.; Ammam M. Neighboring Pyrrolidine Amide Participation in Thioether Oxidation. Methionine as a “Hopping” Site. Org. Lett. 2011, 13, 2837–2839. 10.1021/ol200793z. [DOI] [PubMed] [Google Scholar]
  55. Yamamoto T.; Dai J.; Jacobsen N. E.; Ammam M.; Hall G. B.; Mozziconacci O.; Schöneich C.; Wilson G. S.; Glass R. S. Neighboring π-Amide Participation in Thioether Oxidation: Conformational Control. Org. Lett. 2016, 18, 3522–3525. 10.1021/acs.orglett.6b01309. [DOI] [PubMed] [Google Scholar]
  56. Wang M.; Zhang L.; Si W.; Song R.; Li M.; Lv J. Neighboring Thioether Participation in Bioinspired Radical Oxidative C(sp3)-H α-Oxyamination of Pyruvate Derivatives. Org. Lett. 2020, 22, 8941–8946. 10.1021/acs.orglett.0c03320. [DOI] [PubMed] [Google Scholar]
  57. Ethyl acetate was the most suitable solvent for the SET–HAT combined reactions. Use of more polar solvents such as DMF or acetonitrile led to the formation of C(sp2)–S coupling product (Miyake’s reaction; see ref (35)) as a major product (Table S3; see Supporting Information).
  58. In THF, the EDA absorption band was not observed due to the insolubility of cesium carbonate. The reaction probably proceeded by the small amount of dissolving thiolate. In acetonitrile, the desired coupling product was obtained in a low yield (Table S3; see Supporting Information).
  59. The EDA complex was supported to be 1:1 complex by a Job plot by the method of continuous variation (Figure S2; see Supporting Information).

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

gg1c00007_si_001.pdf (3.8MB, pdf)

Articles from ACS Organic & Inorganic Au are provided here courtesy of American Chemical Society

RESOURCES