Electrochemical vicinal dichlorination and dibromination of unactivated alkenes using TMSX as the halogen source

Abstract

An environmentally friendly electrochemical method for vicinal dichlorination of unactivated alkenes has been developed using TMSCl as a chlorine source, facilitated by Et₄NI-mediated electrophilic addition under undivided electrolytic conditions. This sustainable and clean electrochemical system provides an efficient route to a series of dichloroalkanes. Replacing TMSCl with TMSBr enables the dibromination of unactivated alkenes. Mechanistic experiments indicate that this electrochemical strategy proceeds via an ionic process, where in situ generation of iodide ions and subsequent chlorination reactions drive the formation of dichloroalkanes.

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Organochlorides, particularly dichlorinated compounds, are highly valuable substances in both industrial and academic contexts. They not only represent key structural motifs in many pharmaceutical molecules and natural products (Scheme 1(a)), but also serve as versatile intermediates in organic transformations.^1,2 Alkenes, which can be sourced in bulk from renewable resources and petrochemical feedstocks, are considered one of the most cost-effective and widely used organic building blocks in synthetic chemistry. Consequently, the dichlorination of alkenes has long been recognized as an effective strategy and remains one of the most anticipated reactions in organic synthesis.³ Initially, Cl₂ was employed as a chlorine source for alkene dichlorination, but its strong corrosivity and toxicity pose significant safety concerns.⁴ To address these issues, milder and more practical chlorinating reagents have been developed, facilitating electrophilic addition reactions for alkene dichlorination (Scheme 1(b)).^5,6 Examples of such reagents include NCS-PPh₃, SO₂Cl₂, Oxone-NaCl, KMnO₄-Me₃SiCl-BnEt₃NCl, and Et₄NCl. However, the strong oxidative and electrophilic nature of these chlorinating agents limits their compatibility with certain functional groups, often resulting in trans-selectivity. By incorporating organocatalysis, Denmark and Gilmour achieved dichlorination of alkenes to access elusive vicinal syn-configured adducts via PhSeSePh catalysis and I^(I)/I^(III) catalysis, respectively.⁷ Nevertheless, these methods still require stoichiometric oxidants, reducing substrate compatibility and generating environmentally harmful waste.

Scheme 1 Representative natural products containing vicinal dihalogen unit and dihalogenation of alkenes.

Electrochemical methods have emerged as a promising alternative, offering a greener and more efficient pathway for traditional organic redox reactions.⁸ Through electrochemical redox, high-energy intermediates can be generated directly, enabling reactions that were previously challenging to achieve, such as Umpolung process. Furthermore, this approach significantly reduces the dependence on conventional chemical oxidants. In 2017, Lin pioneered the Mn-catalyzed electrochemical dichlorination of alkenes using MgCl₂ as the chlorine source via a Mn-mediated Cl atom transfer strategy (Scheme 1(c)).⁹ In 2021, Morandi reported the Mn-catalyzed electrochemically-assisted shuttle paradigm for the facile and scalable interconversion of alkenes and vicinal dihalides, enabling the synthesis of dihalogenated molecules.¹⁰ Despite these important advancements, the development of a metal-free, mild, selective, and sustainable approach to alkene dichlorination remains a significant and challenging frontier in organic synthesis.

Driven by our interest in electrochemical halogenation,¹¹ we herein report an Et₄NI-mediated electrochemical strategy that employs readily available TMSCl as a chlorine source for the regioselective synthesis of 1,2-dichloroalkanes (Scheme 1(d)). Under analogous conditions, substitution of TMSCl with TMSBr enables the corresponding dibromination of unactivated alkenes.

Pent-4-en-1-yl [1,1′-biphenyl]-4-carboxylate 1a was selected as the model substrate, with TMSCl (16 equiv.) as the chloride source and Et₄NI (1.0 equiv.) as the supporting electrolyte in MeCN/AcOH (4 : 1, 5.0 mL). Using a graphite anode and a Pt cathode under constant current electrolysis (50 mA) at 50 °C in air, the desired vicinal dichloride 2a was obtained in 77% yield (Table 1, entry 1). Evaluation of the electrode materials revealed that a C(+)/C(−) electrode pair was almost ineffective, whereas Pt(+)/Pt(−) and C(+)/Pb(−) gave the product 2a in 62% and 51% yield, respectively (Table 1, entries 2–4). Screening of chlorine sources showed that HCl and NaCl were inferior to TMSCl (Table 1, entries 5 and 6). The amount and nature of the supporting electrolyte were also crucial: when the loading of Et₄NI was significantly reduced, or when Et₄NI was replaced with nBu₄NBF₄ or nBu₄NPF₆, diminished yields were observed (Table 1, entries 7–9). Solvent effects were pronounced. Replacing AcOH with acetone or HFIP led to decreased yields (Table 1, entries 10 and 11). Using either MeCN or AcOH alone gave only 21% yield or no reaction, respectively, and DMF afforded only trace amounts of product (Table 1, entries 12–14). Performing the reaction under N₂ resulted in a lower yield, and no product formation was observed in the absence of an electric current (Table 1, entries 15 and 16).

Table 1 Optimization of reaction conditions^a

Entry	Variation from the standard conditions	Yield^b (%)
a Standard conditions: a platinum plate as cathode (1.0 cm × 1.0 cm × 0.1 mm) and a graphite plate as anode (1.0 cm × 1.0 cm × 2.0 mm), constant current = 50 mA, 1a (0.5 mmol), TMSCl (16 equiv.), Et4NI (0.5 mmol), MeCN/AcOH (4/1, 5.0 mL), undivided cell, open to air, 50 °C, ∼4 h, 7.46 F mol^−1.b Isolated yields.
1	None	77
2	C(+)/C(−) instead of C(+)/Pt(−)	N.R.
3	Pt(+)/Pt(−) instead of C(+)/Pt(−)	62
4	C(+)/Pb(−)instead of C(+)/Pt(−)	51
5	HCl instead of TMSCl	67
6	NaCl (4.0 equiv.) instead of TMSCl	13
7	Et4NI (0.1 equiv.), Et4NCl (0.9 equiv.) instead of Et4NI	34
8	nBu4NBF4 instead of Et4NI	26
9	nBu4NPF6 instead of Et4NI	31
10	MeCN : acetone = 4 : 1 as solvent	Trace
11	MeCN : HFIP = 4 : 1 as solvent	66
12	MeCN (5.0 mL) as solvent	21
13	AcOH (5.0 mL) as solvent	N.R.
14	DMF (5.0 mL) as solvent	13
15	Under N2	62
16	No electricity	N.R.

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Under the optimized conditions, the substrate scope of unactivated alkenes 1 was examined (Scheme 2). A broad range of substituents, including electron-withdrawing groups (F, Cl, Br, I, NO₂, CN, SO₂Me, CF₃) and electron-donating groups (Me, OMe), were well tolerated, providing the corresponding vicinal dichlorides (2a–2r) in generally good yields. Redox-sensitive functionalities such as aldehydes (2k) and carbonyl groups (2l, 2q), as well as acid/base-sensitive groups such as sulfonamides (2x), also remained intact under the electrolysis conditions. Both Z- and E-configured alkenes delivered the desired dichlorinated products 2v and 2w in relatively low yield probably due to steric hindrance. Other classes of unactivated alkenes furnished the corresponding products with moderate efficiency (2y–2z). Heterocyclic substrates, including glycine derivatives (2s), quinoline (2t), and thiophene (2u), were compatible with the protocol. Notably, derivatives of pharmaceutically relevant molecules such as ibuprofen could also be converted to the corresponding vicinal dichlorides (2aa–2ae) in moderate yields. Notably, under standard reaction conditions, substrate 1ae affords the target product 2ae in relatively low yield. This is mainly attributed to its facile oxidation under electrochemical conditions, leading to substantial byproduct formation.

Scheme 2 Electrochemical vicinal dichlorination of unactivated alkenes. Reaction conditions: the same as Table 1.

Furthermore, we evaluated the electrochemical chlorination of styrenes and aliphatic di- and trisubstituted alkenes 3 (Scheme 3). For these activated alkenes, the yields of vicinal dichlorides were generally lower than those observed for unactivated alkenes. para-Phenyl- and para-nitro-substituted styrenes furnished dichlorides 4a and 4b in 23% and 22% yield, respectively, whereas stilbene afforded 4c in 28% yield with a 3 : 1 dr. Aliphatic disubstituted alkene 5 and trisubstituted alkene 5′ gave mainly monochlorinated products under the standard electrolysis conditions. Importantly, replacement of TMSCl with TMSBr under otherwise identical conditions enabled an efficient vicinal dibromination, affording 7a–7d in 70–96% yields (Scheme 4).

Scheme 3 Electrochemical vicinal dichlorination of activated alkenes. Reaction conditions: the same as Table 1.

Scheme 4 Electrochemical vicinal dibromination of unactivated alkenes. Reaction conditions: a platinum plate as cathode (1.0 cm × 1.0 cm × 0.1 mm) and a graphite plate as anode (1.0 cm × 1.0 cm × 2.0 mm), constant current = 50 mA, 1a (0.5 mmol), TMSBr (16 equiv.), Et₄NI (0.5 mmol), MeCN/AcOH (4/1, 5.0 mL), undivided cell, open to air, 50 °C. Isolated yields.

To demonstrate the practicality of the method, a scale-up experiment was conducted using 1a (5.0 mmol) under the optimized dichlorination conditions, which furnished 1.3 g of 2a in 77% yield (Scheme 5(1)). To gain insight into the reaction mechanism, a series of control experiments was performed. The addition of radical scavengers such as TEMPO or BHT to the standard electrolysis conditions did not significantly affect the yield of 2a, suggesting that the process likely proceeds via an ionic rather than a radical pathway (Scheme 5(2)). In radical clock experiments, N-tosyl diallylamine and a vinylcyclopropane derivative gave only the corresponding vicinal dichlorides 9a and 10a, without formation of the ring-opened product 9b or the cyclized product 10b, further arguing against the involvement of Cl˙ species (Scheme 5(3) and (4)). Cyclic voltammetry (CV) measurements revealed an anodic oxidation peak at 0.85 V (vs. SCE) in the presence of Et₄NI alone. The CV trace of a mixture of the alkene and Et₄NI closely resembled that of Et₄NI alone, whereas no obvious oxidation peak was observed for the alkene when nBu₄NBF₄ was used as the electrolyte (see the SI for details). These results suggest that free I⁻ in solution is oxidized at the anode, while the alkene itself is not directly oxidized.

Scheme 5 Gram-scale reaction and mechanistic experiments.

On the basis of literature precedent and the above mechanistic studies, a plausible mechanism is proposed (Scheme 6). At the anode, I⁻ is oxidized to an electrophilic iodine species (I⁺), which reacts with the alkene 1 to form an iodonium ion intermediate I or I′. Concurrently, TMSCl reacts with AcOH to generate Cl⁻. Nucleophilic attack of Cl⁻ on the iodonium ion I yields a chloroiodinated intermediate II or II′. A second attack of Cl⁻ on this intermediate displaces I⁻, delivering the vicinal dichloride product 2. At the cathode, proton reduction occurs to evolve H₂. Reaction condition screening results (Table 1, entries 7–9) suggest this reaction may also proceed via a competitive mechanism. Specifically, chloride anions are oxidized to cations at the anode, react with alkenes to form chloronium intermediates, and subsequent nucleophilic addition gives the target product 2.

Scheme 6 Plausible mechanistic pathway.

Conclusions

In summary, we have developed an environmentally benign electrochemical method for the vicinal dichlorination and dibromination of unactivated alkenes, employing TMSCl and TMSBr as halogen sources, respectively, under undivided electrolytic conditions. The use of Et₄NI-mediated electrophilic addition facilitates efficient halogenation, providing a straightforward route to dichloroalkanes and dibromoalkanes. Mechanistic investigations reveal that the reaction proceeds via an ionic pathway, with in situ generation of iodide ions contributing to the halogenation process. Importantly, gram-scale reactions demonstrate the scalability and practical applicability of this approach.

Conflicts of interest

There are no conflicts to declare.

Data availability

The data supporting this article have been included as part of the supplementary information (SI). Supplementary information is available. See DOI: https://doi.org/10.1039/d6qo00047a.

Acknowledgements

This work was supported by National Natural Science Foundation of China (42376085), the Start-up Grant from Guangdong Pharmaceutical University (Grant No. 51304058046).

References

1. (a) W.-J. Chung and C. D. Vanderwal, Approaches to the Chemical Synthesis of the Chlorosulfolipids, Acc. Chem. Res., 2014, 47, 718–728; (b) S. Krautwald, C. Nilewski, M. Mori, K. Shiomi, S. Ōmura and E. M. Carreira, Bioisosteric Exchange of C_SP3-Chloro and Methyl Substituents: Synthesis and Initial Biological Studies of Atpenin A5 Analogues, Angew. Chem., Int. Ed., 2016, 55, 4049–4053; (c) G. W. Gribble, Naturally Occurring Organohalogen Compounds, Acc. Chem. Res., 1998, 31, 141–152; (d) D. A. Laskowski, Physical and Chemical Properties of Pyrethroids, Rev. Environ. Contam. Toxicol., 2002, 174, 49–170.
2. (a) I. Saikia, A. J. Borah and P. Phukan, Use of Bromine and Bromo-Organic Compounds in Organic Synthesis, Chem. Rev., 2016, 116, 6837–7042; (b) M.-Y. Liu, X.-B. Wu and P. J. Dyson, Tandem catalysis enables chlorine-containing waste as chlorination reagents, Nat. Chem., 2024, 16, 700–708; (c) H. Cui, Y. Shen, Y. Chen, R. Wang, H. Wei, P. Fu, X. Lei, H. Wang, R. Bi and Y. Zhang, Two-Stage Syntheses of Clionastatins A and B, J. Am. Chem. Soc., 2022, 144, 8938–8944.
3. (a) P. K. Sahoo, R. Maiti, P. Ren, J. J. Delgado Jaén, X. Dai, G. Barcaro, S. Monti, A. Skorynina, A. Rokicinska, A. Jaworski, A. Zakharov, T. Duchamp, A. C. Pearce, M. H. Agosta, S. L. Skerritt, D. W. Small, K. E. Metz, J. R. Gallagher, M. L. Gagliardi, A. M. Beiler and J. L. Dempsey, An Atomically Dispersed Mn Photocatalyst for Vicinal Dichlorination of Nonactivated Alkenes, J. Am. Chem. Soc., 2025, 147, 11829–11840; (b) P. Lian, W. Long, J. Li, Y. Zheng and X. Wan, Visible-Light-Induced Vicinal Dichlorination of Alkenes through LMCT Excitation of CuCl₂, Angew. Chem., Int. Ed., 2020, 59, 23603–23608; (c) K.-J. Bian, D. Nemoto, X.-W. Chen, S.-C. Kao, J. Hooson and J. G. West, Photocatalytic, modular difunctionalization of alkenes enabled by ligand-to-metal charge transfer and radical ligand transfer, Chem. Sci., 2024, 15, 124–133; (d) M. Zhang, J. Zhang and M. Oestreich, Photoinduced radical–ionic dihalogen transfer to carbon–carbon multiple bonds using oxime-based surrogates, Nat. Synth., 2023, 2, 439–447; (e) R. Giri, E. Zhilin, M. Kissling, S. Patra, A. J. Fernandes and D. Katayev, Visible-Light-Mediated Vicinal Dihalogenation of Unsaturated C–C Bonds Using Dual-Functional Group Transfer Reagents, J. Am. Chem. Soc., 2024, 146, 31547–31559; (f) Y. Li, Y. Gao, Z. Deng, Y. Cao, T. Wang, Y. Wang, C. Zhang, M. Yuan and W. Xie, Visible-light-driven reversible shuttle vicinal dihalogenation using lead halide perovskite quantum dot catalysts, Nat. Commun., 2023, 14, 4673–4684; (g) H.-C. Wang, M.-H. Qi, T.-M. Liu, P.-F. Zhao, C.-Y. Xu, D.-T. Xie, H.-L. Jiang, Y.-F. Li, X.-H. Wang and B. Han, Metal-Free Radical Vicinal Dihalogenation of Olefins Enabled by Synergetic Photocatalytic Energy Transfer and Halogen-Atom Transfer, ACS Catal., 2025, 15, 20584–20593.
4. (a) W. Manchot, J. C. Withers and H. Oltrogge, Zur Kenntnis der Körper mit dreifacher Bindung, Liebigs Ann. Chem., 1912, 387, 257–293; (b) A. Atterberg and O. Widman, Neue Chlornaphtaline, Chem. Ges., 1877, 10, 1841–1844.
5. (a) T. Schlama, K. Gabriel, V. Gouverneur and C. Mioskowski, Tetraethylammonium Trichloride: A Versatile Reagent for Chlorinations and Oxidations, Angew. Chem., Int. Ed. Engl., 1997, 36, 2342–2344; (b) M. Kleoff, P. Voßnacker and S. Riedel, The Rise of Trichlorides Enabling an Improved Chlorine Technology, Angew. Chem., Int. Ed., 2023, 62, e202216586; (c) Y. Kamada, Y. Kitamura, T. Tanaka and T. Yoshimitsu, Dichlorination of olefins with NCS/Ph₃P, Org. Biomol. Chem., 2013, 11, 1598–1601; (d) S. Yakabe, M. Hirano and T. Morimoto, vic-Dichlorination of Olefins with Sodium Chlorite, Mn(acac)₃, and Moist Alumina in Dichloromethane, Synth. Commun., 1998, 28, 1871–1878; (e) J. Ren and R. Tong, Convenient in situ generation of various dichlorinating agents from oxone and chloride: diastereoselective dichlorination of allylic and homoallylic alcohol derivatives, Org. Biomol. Chem., 2013, 11, 4312–4315.
6. (a) Z. Dagalan, R. Koçak, A. Dastan and B. Nişancı, Selectfluor and TBAX (Cl, Br) Mediated Oxidative Chlorination and Bromination of Olefins, Org. Lett., 2022, 24, 8261–8264; (b) S. Gaspa, A. Porcheddu and L. De Luca, Metal-Free Oxidative Cross Esterification of Alcohols via Acyl Chloride Formation, Adv. Synth. Catal., 2016, 358, 154–158.
7. (a) A. J. Cresswell, S. T.-C. Eey and S. E. Denmark, Catalytic, stereospecific syn-dichlorination of alkenes, Nat. Chem., 2015, 7, 146–152; (b) J. C. Sarie, J. Neufeld, C. G. Daniliuc and R. Gilmour, Catalytic Vicinal Dichlorination of Unactivated Alkenes, ACS Catal., 2019, 9, 7232–7237.
8. (a) Y. Yuan and A. Lei, Is electrosynthesis always green and advantageous compared to traditional methods?, Nat. Commun., 2020, 11, 802–804; (b) J. C. Siu, N. Fu and S. Lin, Catalyzing Electrosynthesis: A Homogeneous Electrocatalytic Approach to Reaction Discovery, Acc. Chem. Res., 2020, 53, 547–560; (c) M. Yan, Y. Kawamata and P. S. Baran, Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance, Chem. Rev., 2017, 117, 13230–13319; (d) R. Francke and R. D. Little, Redox catalysis in organic electrosynthesis: basic principles and recent developments, Chem. Soc. Rev., 2014, 43, 2492–2521; (e) J. Yoshida, K. Kataoka, R. Horcajada and A. Nagaki, Modern Strategies in Electroorganic Synthesis, Chem. Rev., 2008, 108, 2265–2299; (f) S. R. Waldvogel and B. Janza, Renaissance of Electrosynthetic Methods for the Construction of Complex Molecules, Angew. Chem., Int. Ed., 2014, 53, 7122–7123; (g) W. Zeng, Y. Wang, C. Peng and Y. Qiu, Organo-mediator enabled electrochemical transformations, Chem. Soc. Rev., 2025, 54, 4468–4501; (h) P. Li, Y. Wang, H. Zhao and Y. Qiu, Electroreductive Cross-Coupling Reactions: Carboxylation, Deuteration, and Alkylation, Acc. Chem. Res., 2025, 58, 113–129; (i) C. Ma, J.-F. Guo, S.-S. Xu and T.-S. Mei, Recent Advances in Asymmetric Organometallic Electrochemical Synthesis (AOES), Acc. Chem. Res., 2025, 58, 399–414; (j) P. Xiong and H.-C. Xu, Molecular Photoelectrocatalysis for Radical Reactions, Acc. Chem. Res., 2025, 58, 299–311; (k) Q. Wan, R.-X. Liu, Z. Zhang, X.-D. Wu, Z.-W. Hou and L. Wang, Recent Advances in the Electrochemical Defluorinative Transformations of C-F Bonds, Chin. J. Chem., 2024, 42, 1913–1928; (l) Z. Wang, W.-F. Liang, C.-X. Gong, X. He, J.-H. Li, Y. Lin and K.-Y. Ye, Chemo-, Regio-, and Stereoselective Electrochemical Dearomative Multi-functionalization of Pyridines, CCS Chem., 2026 DOI:10.31635/ccschem.025.202507069.
9. (a) N.-K. Fu, G. S. Sauer and S. Lin, Electrocatalytic Radical Dichlorination of Alkenes with Nucleophilic Chlorine Sources, J. Am. Chem. Soc., 2017, 139, 15548–15553; (b) A. Saju, J. R. Griffiths, S. N. MacMillan and D. C. Lacy, Synthesis of a Bench-Stable Manganese(III) Chloride Compound: Coordination Chemistry and Alkene Dichlorination, J. Am. Chem. Soc., 2022, 144, 16761–16766.
10. X.-C. Dong, J. L. Roeckl, S. R. Waldvogel and B. Morandi, Merging shuttle reactions and paired electrolysis for reversible vicinal dihalogenations, Science, 2021, 371, 507–514.
11. (a) L. Wen, Z. Zou, N. Zhou, C. Sun, P. Xie and P. Feng, Electrochemical Fluorination Functionalization of gem-Difluoroalkenes with CsF as a Fluorine Source: Access to Fluoroalkyl Building Blocks, Org. Lett., 2024, 26, 241–246; (b) L. Wen, N. Zhou, Z. Zhang, C. Liu, S. Xu, P. Feng and H. Li, Electrochemical Difunctionalization of gem-Difluoroalkenes: A Metal-Free Synthesis of α-Difluoro(alkoxyl/azolated) Methylated Ethers, Org. Lett., 2023, 25, 3308–3313; (c) L. Wen, B. Li, Z. Zou, N. Zhou, C. Sun, P. Feng and H. Li, Direct electrochemical difluorination and azo-fluorination of gem-difluorostyrenes, Org. Chem. Front., 2024, 11, 142–148; (d) W. Jiang, X. Liu, C. Zhu, M. Chen, W. Li and H. Cao, Regioselective electrochemical cascade C-H sulfonylation–bromination of indolizines to access difunctionalized indolizines, Org. Chem. Front., 2024, 11, 2306–2312; (e) B. Li, X. Liao, L. Wen, M. Mi, X. Xing, P. Feng and S. Xu, Electrochemically Direct Fluorination Functionalization of Styrenes with Different Fluorine Source: Access to Fluoroalkyl Derivatives, J. Org. Chem., 2024, 89, 9440–9449; (f) X. Liu, Y. Zhang, Y. Zheng, C. Huang and H. Cao, Controllable Construction of Vinyl Sulfones and β-Keto Selenosulfones via Selective Oxidative Sulfonylation of Alkenes, Chin. J. Chem., 2024, 42, 1367–1372.

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Footnote

† These authors contributed equally.

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