Electrochemical reduction of sulfoxides to thioethers with hydrosilanes catalyzed by a recyclable ionic liquid

Abstract

The first electrochemical reduction of sulfoxides to thioethers has been achieved using a recyclable ionic liquid as both catalyst and electrolyte, without metal catalysts, stoichiometric redox reagents, or external electrolytes. The ionic liquid showed no significant loss of catalytic activity over six cycles. Various sulfoxides (32 examples) were efficiently reduced to the corresponding thioethers in up to 98% yield using hydrosilanes as the activating agent. Notably, the protocol exhibits robust scalability under optimized conditions.

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Green foundation

1. We present a paired electrolysis strategy that efficiently reduces sulfoxides to thioethers at room temperature. This approach employs a recyclable ionic liquid as both catalyst and electrolyte, in combination with hydrosilanes as the activating agents.

2. This protocol requires no additional metal catalysts, stoichiometric redox reagents, or external supporting electrolytes, fundamentally minimizing waste generation and the use of hazardous substances. Moreover, the method operates without an inert atmosphere, is simple to perform, and employs an ionic liquid catalyst that can be reused for six cycles without significant loss of activity, thereby reducing material consumption.

3. For a greener future, this electrochemical process could be adapted to a simpler and more sustainable continuous-flow regime to enhance reaction efficiency and pave the way for industrial production.

Introduction

The thioether moiety is not only widely distributed in pharmaceuticals¹ and natural products,² but also plays vital roles in medicinal chemistry³ and materials science.⁴ 29% of FDA-approved sulfur-bearing small-molecule drugs contain thioether functionalities⁵ (Fig. 1). Given the broad applications of thioethers, their synthesis has become a central topic in synthetic chemistry.⁶

Fig. 1 Representative sulfur-containing drugs.

The catalytic reduction of sulfoxides to sulfides constitutes a cornerstone transformation in modern synthetic organic chemistry. However, the existing methods⁷ face significant limitations, including (1) energy-intensive conditions (e.g., high temperature or pressure), (2) residual metal contamination from transition-metal catalysts, which precludes pharmaceutical applications, (3) cumbersome workup procedurs, and (4) inefficient reaction outcomes (e.g., low yields or selectivity). Thus, developing a sustainable, metal-free, simple operation and efficient protocol for sulfide synthesis remains a critical challenge.

As a green chemistry paradigm, electrochemical synthesis has gained widespread application in organic transformations owing to its mild conditions and superior atom economy.⁸ Nevertheless, electrochemical approaches for sulfoxide reduction remain underdeveloped. To date, only two effective electrochemical deoxygenation strategies have been documented (Scheme 1a). In 2014, Waldvogel's group⁹ first achieved efficient electrochemical sulfoxide reduction under ambient conditions. However, this method suffered from non-green characteristics, notably requiring strongly acidic electrolytes and toxic lead electrodes. In 2021, Guo's group¹⁰ tackled the toxicity issue by employing an aluminum anode system in place of lead, achieving broad substrate compatibility. Nevertheless, this system introduced new challenges: (1) gradual degradation of the sacrificial anode, (2) the necessity for strictly anaerobic conditions, and (3) a reliance on Lewis acids and supporting electrolytes—all of which impede practical scalability.

Scheme 1 Strategies for the reduction of sulfoxides to thioethers.

Hydrosilanes have gained considerable attention as environmentally benign reducing agents in green organic synthesis.¹¹ Nonetheless, their application in sulfoxide reduction still faces significant challenges: current catalytic systems typically require transition metals (e.g., Pt, Ru) or strong Lewis acids (e.g., boron compounds) as catalysts¹² (Scheme 1b). These methodologies not only increase the synthetic expense but also introduce issues of metal residue.

To address these limitations, building upon our group's expertise in ionic liquid catalysis,¹³ we herein present an efficient and sustainable electrochemical protocol for the metal-free reduction of sulfoxides to thioethers under ambient conditions. This strategy employs a recyclable ionic liquid that serves dual functions as both electrolyte and catalyst, coupled with cost-effective graphite electrodes, and proceeds efficiently at room temperature in air. As a result of these features, our approach represents an environmentally benign and practically attractive alternative for thioether synthesis.

With the assistance of a six-position parallel current/voltage/electrode-regulated electrochemical reactor, optimization experiments were conducted with 4,4′-dimethylphenyl sulfoxide (1) as the model substrate. Optimal conditions were identified as follows: graphite as anode and cathode, [C₄MPd]Br as both a catalyst and an electrolyte, phenylsilane as the activating agent, and DCE as solvent, under constant current (10 mA, 3 h) with a yield of 98% (Table 1, entry 1). Bromide-based ionic liquids with piperidinium or pyrrolidinium cations demonstrated higher activity than those with imidazolium cations (entries 2–6). No reaction occurred when [Bmpyrr]BF₄ was used instead of [C₄MPd]Br (entry 7). Silanes screening revealed an inverse relationship between phenyl substitution degree and yield (entries 8–9). Suboptimal results were obtained with alternative cathodes (Ni, stainless steel, etc., entries 10 and 11, Table S2-1, entries 15–21) or solvents (DCM, MeCN, entries 12 and 13). Neither current intensity nor reaction time variations improved yields (Table S2-1, entries 28–37). Control experiments confirmed the necessity of both constant current and ionic liquid (entries 14 and 15).

Table 1 Optimization of the reaction conditions^a

Entry	Variation from the standard conditions	Yield^b (%)
a Reaction conditions: graphite plate as anode and cathode, constant current = 10 mA, 1 (0.3 mmol), [C4MPd]Br (0.6 eq.), PhSiH3 (2.0 eq.), DCE (5.0 mL), room temperature, 3 h, undivided cell, under air. b Yield of isolated product. n.d. = not detected. SS = stainless steel.
1	None	98
2	[Bmpyrr]Br instead of [C4MPd]Br	90
3	PmimBr instead of [C4MPd]Br	30
4	BzmimBr instead of [C4MPd]Br	35
5	AmimBr instead of [C4MPd]Br	50
6	HmmimBr instead of [C4MPd]Br	47
7	[Bmpyrr]BF4 instead of [C4MPd]Br	n.d.
8	Ph2SiH2 instead of PhSiH3	42
9	Ph3SiH instead of PhSiH3	Trace
10	C/Ni instead of C/C	70
11	C/SS instead of C/C	62
12	DCM instead of DCE	70
13	MeCN instead of DCE	52
14	without constant current	n.d.
15	without [C4MPd]Br	n.d.

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With the optimized conditions in hand, we evaluated the reaction scope using various sulfoxide substrates (Table 2). Unsubstituted diphenyl sulfoxide exhibited excellent reactivity, affording the desired product 3 in 92% yield. The electronic effects of substituents on the phenyl rings were then investigated. Both electron-donating groups (methyl, methoxy) and electron-withdrawing groups (Cl, Br) were well tolerated, delivering products 2–6 in high yields (77–98%). However, 4,4′-diiodophenyl sulfoxide showed low reactivity, yielding 7 with only 35%. Notably, the system demonstrated excellent compatibility with benzyl-substituted sulfoxides (benzyl phenyl sulfoxide and dibenzyl sulfoxide), providing products 8 and 9 in 87% and 85% yields, respectively. Fused-ring sulfoxides exhibited exceptional reactivity, furnishing products 10–12 with 88–98% yields.

Table 2 Substrate scope of sulfoxides^a

a Reaction conditions: graphite plate as anode and cathode, constant current = 10 mA, sulfoxides (0.3 mmol), [C₄MPd]Br (0.6 eq.), PhSiH₃ (2.0 eq.), DCE (5.0 mL), room temperature, 3 h, undivided cell, under air, yield of isolated product.

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We next explored the applicability of methyl aryl sulfoxides. The electronic nature of the para-substituents significantly influenced reactivity: substrates bearing I or (ethoxycarbonyl)methyl group gave lower yields (18, 51%; 22, 50%), while those with electron-donating (methyl, methoxy) or moderately electron-withdrawing halides (F, Cl, Br) performed well (50–95% yields, 13–23). Remarkably, 2-(methylsulfinyl)naphthalene was exceptionally reactive, yielding 24 in 96%.

Finally, we examined aliphatic and heterocyclic sulfoxides. Dialkyl sulfoxides demonstrated outstanding reactivity, with di-n-butyl, di-n-hexyl, and dodecyl methyl sulfoxide being reduced to the corresponding thioethers (25–27) with 93–96% yields. Heterocycle-containing sulfoxides (pyridyl, furyl) also proved viable, affording products 28–32 in moderate to good yields.

To evaluate the scalability of this method, a gram-scale constant-current electrolysis (30 mA, 9 h, rt) of 4,4′-dimethylphenyl sulfoxide 1 (8 mmol) was conducted, affording the desired product 2 in 96% yield (1.65 g), which demonstrates its potential for practical synthesis (Scheme 2a). It is noteworthy that the ionic liquid [C₄MPy]Br could be conveniently recovered and reused. Upon completion of the reaction, the mixture was partitioned between water and ethyl acetate, allowing [C₄MPy]Br to be isolated from the aqueous phase. The ionic liquid was subsequently dried under vacuum and successfully employed in six consecutive reaction cycles with no significant decrease in activity (Scheme 2b).

Scheme 2 (a) Gram-scale electrochemistry synthesis of di-p-tolylsulfane (b) lonic liquid recyclability tests.

To verify the potential involvement of radical intermediates during the reaction process, radical trapping experiments were conducted (Table 3). The results demonstrated a significant decrease in reaction yields with increasing amounts of the radical scavenger TEMPO. Furthermore, silicon-centered radical intermediate was successfully detected by high-resolution mass spectrometry (HRMS).

Table 3 Radical trapping experiments

Entry	Radical scavenger	Yield (%)
1	None	98
2	TEMPO (2 equiv.)	47
3	TEMPO (4 equiv.)	32

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To elucidate the reaction mechanism, cyclic voltammetry (CV) experiments were first conducted (Fig. 2). The black curve represents the system containing only compound 1. Under standard conditions, the green curve exhibits an oxidation peak at 0.64 V with a current of 76.7 μA. When [C₄MPd]Br was replaced by TBAClO₄, the cyclic voltammogram (red curve) exhibited no discernible oxidation peak, implying that [C₄MPd]Br played a catalytic role in the reaction. The blue curve, recorded in the absence of phenylsilane, exhibited no oxidation peak, further supporting the essential roles of both [C₄MPd]Br and phenylsilane in the reaction. Moreover, the green curve exhibited a well-defined reduction peak at −0.39 V (current: −31.8 μA), which is indicative of electron transfer at the cathode.

Fig. 2 CV experiments. The glassy carbon-disk (R = 5.5 mm, h = 10 mm) was used as the working electrode. The Pt disk (R = 5.5 mm, h = 10 mm) and Ag/AgCl (R = 5.0 mm, h = 10 mm) was used as counter and reference electrode, respectively. The scan rate was 100 mV s⁻¹.

High-resolution mass spectrometry (HRMS) analysis unambiguously confirmed the formation of silanol compounds under standard reaction conditions (Scheme 3a). To gain deeper mechanistic insights, in situ FTIR spectroscopy was employed to monitor the reaction in real time (Scheme 3b). The IR spectral data revealed two key observations: (1) the characteristic S=O stretching absorption at 920 cm⁻¹ exhibited a progressive decrease in intensity with reaction time; (2) a new absorption band emerged at 1130 cm⁻¹, which was unequivocally assigned to the Si–O stretching vibration and showed gradual intensification as the reaction proceeded. These experimental results provide definitive evidence that the oxygen atom from sulfoxides is eliminated in the form of silanol, offering crucial support for the proposed reaction mechanism.

Scheme 3 (a) HRMS analysis of silanol (b) in situ infrared experiments.

Based on mechanistic studies and literature precedent, a plausible pathway for the electrocatalytic deoxygenative reduction of sulfoxides to sulfides is proposed (Scheme 4). The mechanism initiates with single-electron oxidation of bromide anions at the anode to generate bromine radical.¹⁴ The radical subsequently abstract a hydrogen atom from the hydrosilane via hydrogen atom transfer (HAT), affording silyl radical¹⁵ along with regeneration of bromide ion and proton. The silyl radical is then oxidized at the anode to form silyl cation,¹⁶ which engage in nucleophilic attack with the sulfoxide to form intermediate A. Cathodic reduction of A yields the sulfide product and releases a siloxide anion. This anion is subsequently protonated to form silanol.

Scheme 4 Plausible mechanism.

Conclusions

In summary, we developed a green and efficient protocol for S=O bond cleavage, achieving the first electrochemical transformation of sulfoxides to thioethers using recyclable ionic liquids as electrolyte and catalyst, phenylsilane as the activating reagent. This metal-free, redox-reagent-free strategy requires no additional supporting electrolyte and demonstrates remarkable advantages: (1) operational simplicity (no inert atmosphere protection required), (2) excellent substrate scope (32 examples, up to 98% yield) and (3) outstanding scalability (successful gram-scale synthesis).

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/d5gc05274b.

Acknowledgements

The authors acknowledge the financial support from the Tianshan Talents Program for Leading Talents in Science and Technology Innovation (no. 2022TSYCLJ0016), the National Natural Science Foundation of China (no. 22361044 and 22201241), the Key Program of the Natural Science Foundation of Xinjiang Uygur Autonomous Region (no. 2022D01D06), and the Tianchi Talents Introduction Program (no. 5105240151a).

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