Ruthenium-catalysed late-stage C–H alkynylation of carboxylic acids using sustainable deep eutectic solvents

Abstract

The demand for sustainable and environmentally friendly chemical processes has led to the development of innovative catalytic systems and solvent designs. Herein, we report a novel approach utilizing ruthenium catalysis in deep eutectic solvents (DESs) for the selective alkynylation of C–H bonds. Ruthenium, known for its low toxicity and cost-effectiveness, serves as an excellent alternative to other transition metals in eutectic liquids. Moreover, the utilization of supramolecular β-cyclodextrin-based deep eutectic liquids enhances the eco-friendliness and recoverability of the solvent system. The late-stage functionalization of drugs exemplifies the practical applicability and versatility of this method in organic synthesis, offering a sustainable pathway towards the synthesis of valuable compounds.

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Introduction

The synthesis of organic molecules plays a crucial role in drug discovery, materials science, and fine chemical manufacturing. However, traditional synthetic routes often rely on multiple steps, and harsh conditions, resulting in significant environmental impact and resource depletion.¹ In response to these challenges, the principles of green chemistry have been applied to develop more sustainable synthetic methodologies.² C–H activation reactions, which involve the selective cleavage of C–H bonds followed by functionalization, have garnered considerable interest due to their potential to streamline synthesis and reduce waste generation.³ By directly accessing C–H bonds, these reactions offer a more atom-efficient approach compared to traditional methods that rely on pre-functionalized starting materials.⁴ Moreover, C–H activation can enable the direct modification of complex molecules, facilitating late-stage functionalization and minimizing the number of synthetic steps required.⁵ Transition metal catalysis has revolutionized the field of organic synthesis, enabling the selective modification of complex molecules with unparalleled efficiency utilizing both first row and late transition metal catalysts.⁶ Recent advances in catalysis have broadened the scope of alternative transition metals, like iron, cobalt, and nickel. These first-row transition metals are gaining significant attention due to their natural abundance, lower cost, and reduced toxicity compared to noble metals.⁷ For instance, cobalt has been successfully employed in sustainable C–H activation strategies, demonstrating catalytic performance on par with noble metals in some cases.⁸ Among transition metals, ruthenium stands out for its remarkable catalytic properties, including high activity, selectivity, and cost-effectiveness. Ruthenium complexes have shown exceptional performance in hydrogenation, metathesis, and C–H functionalization reactions. Additionally, the development of water-compatible and ligand-modified ruthenium catalysts has significantly expanded its applicability in green chemistry. Moreover, its low toxicity makes it an attractive alternative to other transition metals, such as palladium or platinum, which are often associated with cost concerns.⁹

Transition metal-catalyzed C–H alkynylation is a powerful method for the direct functionalization of C–H bonds with alkynes under mild conditions.¹⁰ This transformation involves the use of catalysts, such as palladium, ruthenium, or copper, to activate C–H bonds adjacent to functional groups and insert alkynes to form new carbon–carbon bonds.¹¹ The process offers several advantages, including high efficiency, regioselectivity, and atom economy, making it a valuable tool in organic synthesis. By bypassing the need for pre-functionalized substrates, C–H alkynylation can potentially streamline the synthesis of complex molecules and natural products.¹² Bromoalkynes have become one of the most useful alkynylating reagents in these types of studies due to their versatile reactivity, and ease of preparation as well as subsequent modifications after the reactions.¹³ To this end Chatani et al. reported the first ruthenium catalyzed C–H alkynylation in 1,2-DCE.¹⁴ Later Echavarren and co-workers reported the ruthenium catalyzed peri and ortho alkynylation with bromoalkynes via insertion and elimination reactions in 1,2-DCE.¹⁵ However, the utilization of environmentally sustainable solvents for C–H activation under mild reaction conditions while abstaining from the incorporation of toxic additives are still scarce.

In recent years, there has been a concerted effort to develop green C–H activation reactions that minimize environmental impact while maintaining high efficiency and selectivity. This heightened attention stems from a collective drive to mitigate the environmental footprint associated with chemical processes. By embracing sustainable solvents, various research groups are striving to foster greener methodologies that minimize waste generation, energy consumption, and overall environmental impact.¹⁶ Such initiatives represent crucial steps towards achieving sustainable practices within the realm of chemical synthesis, aligning with broader global efforts to promote eco-friendly alternatives across diverse industrial sectors.

Deep eutectic solvents (DES) have emerged as promising alternatives to conventional organic solvents due to their, in many cases, low cost, biodegradability, and minimal toxicity.¹⁷ These solvents, typically composed of a hydrogen bond acceptor and a hydrogen bond donor, offer unique properties that can be tailored for specific applications in catalysis and material synthesis.¹⁸ These solvents can be straightforward to prepare and often be utilized without the need for special precautions. Over recent years, the use of DES in cross-coupling reactions,¹⁹ heterocycle synthesis,²⁰ among other reactions,²¹ has been demonstrated. There are only a few and sporadic studies have demonstrated the utility of Ru catalysts in deep eutectic solvents (DES), highlighting their effectiveness in various transformations. For instance, Garcia-Alvarez et al. reported the use of a Ru(IV) complex for the redox isomerization of allylic alcohols, enabling the sustainable synthesis of saturated carbonyl compounds in DES.²² Similarly, the first example of a one-pot approach for the synthesis of tertiary alcohols, wherein Ru(IV)-catalyzed isomerization of allylic alcohols was followed by a chemoselective addition of polar organometallic reagents, achieving excellent conversions within DES was also reported.²³ Furthermore, the synergy between Ru catalysis and biocatalysis, achieving the highly enantioselective reduction of ketones with 99% yield and 99% ee in a DES medium has been achieved by Gonzalez-Sabin et al.^24a Moreover, the study by Baldino et al. provides a proof of concept for the use of deep eutectic solvents as H₂ sources in Ru(II)-catalyzed transfer hydrogenation of carbonyl compounds under mild reaction conditions.^24b These studies collectively underscore the versatility of Ru-based catalysis in DES, and reinforcing the significance of utilizing such solvent systems for sustainable catalytic transformations. However, the application of these solvents in C–H activation reactions is still in its infancy. Recently, Ramon et al. have reported a C–H activation protocol using a ruthenium catalyst for alkenylation and (4 + 2) cyclization reactions²⁵ and Faronola et al. reported a palladium-catalyzed thiophene-aryl coupling reaction via C–H bond activation in deep eutectic solvents.²⁶

Beta-cyclodextrin (β-CD) is a cyclic oligosaccharide composed of seven glucose units linked by α-1,4 glycosidic bonds, forming a toroidal structure with a hydrophobic cavity and a hydrophilic outer surface. Cyclodextrin-based eutectic liquids (CD-ELs) are created by combining, e.g. β-CD, with suitable hydrogen bond donors (HBDs) or hydrogen bond acceptors (HBAs), such as organic acids, alcohols, or amines.²⁷ These components interact with the hydroxyl groups on the outer surface of β-CD, resulting in a eutectic mixture with distinct physicochemical properties. Beta-cyclodextrin-based eutectic liquids offer several advantages over traditional eutectic liquids, including enhanced biocompatibility, superior solubilization and encapsulation abilities, and greater environmental friendliness.²⁸ These properties make CD-ELs particularly attractive for pharmaceutical, catalysis, biomedical, and environmentally conscious applications.²⁹ While other eutectic liquids may be more suitable for certain industrial processes due to their unique properties, the versatility and safety of CD-ELs position them as a promising alternative in areas where biocompatibility and sustainability are of paramount importance. Here, we report a silver-free ruthenium(II)-catalyzed C–H alkynylation reaction using a β-cyclodextrin (β-CD) and 1,3-dimethyl urea (DMU) based eutectic system with KOH as a base (Fig. 1).

Fig. 1 Synthetic method for the C–H alkynylation. (A) Previous work. (B) This work on the use of DES for C–H alkynylation.

Results and discussion

Reaction optimization

The Ru(II) catalysed reaction of o-toluic acid (1a) and a bromo alkyne (2) was selected for use in this study,¹⁵ and used to screen for optimized conditions. We explored diverse reaction conditions for C–H alkynylation in DES (Table 1). Various DESs, including members of a range of non-ionic DESs³⁰ AA–NN′DMU, NMU–NMA, AA–urea, NMU–AA, and more traditional ChCl-based DESs with various hydrogen bond donors (HBDs) such as glycerol, ethylene glycol, acetamide, glucose, citric acid, malic acid, tartaric acid, and mannose, were evaluated for the C–H alkynylation reaction (Fig. 2). The choice of DES components significantly influenced the reaction yield, and to improve the reaction efficiency we have tested alternative reaction conditions (see ESI,† Table S1 for more detailed optimization studies). We synthesized various DESs containing β- or γ-cyclodextrin, with various hydrogen bond donors (Table 1, entries 1–9). The specific ratios of hydrogen bond acceptor (HBA) to hydrogen bond donor (HBD) in the β-CD–DMU eutectic system were selected to be 3 : 7, based on established methods from the literature,^29a which we adopted due to their proven efficacy in forming eutectic mixtures. When deviating from this 3 : 7 ratio, we found that higher temperatures were required to achieve a liquid eutectic phase. However, these conditions led to lower yields in our reactions, which we deemed unsuitable for the intended applications. Therefore, we maintained the 3 : 7 ratio, as it provided the most efficient and reproducible results for our desired outcomes. The combination of β-CD, acting as a nanoreactor by encapsulating reactants and improving solubility, and DMU, providing a compatible hydrophobic environment, was found to create an optimal microenvironment for the reaction. The inclusion of cyclodextrins in the DES systems led to diverse effects on the reaction yield. While β-CD, in particular, showed promising results in some cases, particularly when combined with organic acids, the performance varied depending on the molar ratio and type of CD used. This variability underscores the importance of optimizing the CD concentration and formulation to achieve the desired catalytic outcome. The use of β-cyclodextrin and dimethyl urea, a component used in some members of the recently described family of non-ionic DESs,³⁰ yielded the product in 40% in the presence of potassium carbonate as a base (Table 1, entry 10). Based on this result, we screened various bases and found that among those used, KOH afforded the product in 59% yield at 100 °C (Table 1, entries 11–22). The use of K₂CO₃-glycerol DES resulted in 6% product formation (Table 1, entry 23). When we employed pyrazole-glycerol DES in a 1 : 1 molar ratio, we observed no conversion (Table 1, entry 24). Finally, betaine-HFIP DES yielded the product in 32% yield (Table 1, entry 25).

Table 1 Optimisation of the reaction conditions

Entry	Deep eutectic solvent	Base	Temp (°C)	Yield (%) (molar ratio)
Reactions conditions: 1a (0.20 mmol), 1-bromo-2-(triisopropylsilyl)acetylene (2) (0.24 mmol, 1.2 equiv.), base (0.10 mmol), [RuCl2(p-cymene)]2 (5 mol%) and DES (1.5 mL). ChCl – choline chloride; DMU – 1,3-dimethyl urea; AA – acetamide; NN′DMU – 1,1-dimethylurea; NMU – 1-methyl urea; NMA – 1-methyl acetamide; β-CD – β-cyclodextrin; γ-CD – γ-cyclodextrin; HFIP – hexa fluoro isopropanol.
1	β-CD–citric acid (1 : 5)	K2CO3	80	22
2	β-CD–malic acid (1 : 5)	K2CO3	80	20
3	β-CD–tartaric acid (1 : 5)	K2CO3	80	17
4	β-CD–glycerol (1 : 10)	K2CO3	80	12
5	β-CD–citric acid–H2O (1 : 1 : 2)	K2CO3	80	33
6	β-CD–malic acid–H2O (1 : 10 : 20)	K2CO3	80	33
7	γ-CD–malic acid–H2O (1 : 10 : 20)	K2CO3	80	36
8	γ-CD–citric acid–H2O (1 : 10 : 20)	K2CO3	80	28
9	γ-CD–tartaric acid–H2O (1 : 10 : 20)	K2CO3	80	36
10	β-CD–DMU (3 : 7)	K2CO3	80	40
11^a	β-CD–DMU (3 : 7)	K2CO3	80	36
12^b	β-CD–DMU (3 : 7)	K2CO3	100	37
13	β-CD–DMU (3 : 7)	KHCO3	100	51
14	β-CD–DMU (3 : 7)	K2CO3	80	36
25	β-CD–DMU (3 : 7)	KHSO4	90	26
16	β-CD–DMU (3 : 7)	KOH	100	59
17	β-CD–DMU (3 : 7)	NaOH	100	49
18	β-CD–DMU (3 : 7)	Na2CO3	95	58
19	β-CD–DMU (3 : 7)	NaHCO3	95	51
20	β-CD–DMU (3 : 7)	KOAc	95	48
21	β-CD–DMU (3 : 7)	KNO3	95	31
22	β-CD–DMU (3 : 7)	No base	95	34
23	K2CO3–glycerol (1 : 5)	No base	90	6
24	Pyrazole–glycerol (1 : 1)	K2CO3	90	NR
25	Betaine–HFIP (1 : 2)	K2CO3	90	32

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Fig. 2 The library of hydrogen bond donor and acceptors for the synthesis of the DESs used in this study.

Substrate scope

Having established robust optimized conditions, we proceeded to investigate the substrate scope for the ruthenium-catalysed C–H alkynylation in the deep eutectic solvent (Schemes 1–3). Initially, we screened various ortho-substituted benzoic acids and the reactions exhibited promising yields, exemplified by o-toluic acid (1a) delivering a notable 59% yield (3a). Substrates bearing electron-donating and electron-withdrawing groups demonstrated moderate to good yields, with 2-methoxybenzoic acid (1b) yielding 38%, and 2-F, 2-Cl, and 2-Br substituted benzoic acids (1c–e) affording yields in the range of 39–42%. In the cases of carboxylic acids where low yields were observed, we found unreacted starting material in several instances after analysing the reaction mixtures, as evidenced by TLC analysis. This suggests that the conversion was partial for these substrates. Notably, electron-withdrawing groups such as CF₃ and nitro functionalities in 2-CF₃ and 2-nitrobenzoic acids (1f–g) yielded 51% and 27%, respectively, though only moderate yields, showcasing the versatility of the ruthenium catalyst in tolerating diverse electronic environments. The introduction of a phenyl group at the ortho-position (1h) resulted in 31% isolated yield, which reflects the impact of steric hindrance, and in accessing the reactive site for C–H activation. Interestingly, substrates containing fused aromatic rings, such as 1- and 2-naphthyl benzoic acids (1i–j), exhibited selective alkynylation, yielding products (3i–j) in 36% and 48% respectively. This selectivity suggests preferential activation of the benzoic acid moiety over the fused aromatic ring, offering opportunities for regioselective functionalization. Furthermore, the inclusion of heterocyclic substrates like 2-thiophene carboxylic acid (1k) resulted in a moderate yield of 33%, demonstrating the applicability of the reaction to diverse aromatic systems beyond simple benzene derivatives. Next, the utilization of meta-substituted benzoic acids (1l-p) revealed intriguing selectivity patterns, with varied outcomes depending on the nature of the substituents. For instance, meta-nitro substitution provided predominantly one selective product (3l) in 11%, highlighting the regioselective nature of the C–H activation process. Whereas the other meta-substituted benzoic acids like 3-Cl (1m), 3-OMe (1n) and 3-F (1o) substituted benzoic acids resulted in the formation of double alkynylated products (3m–3o) in 26–37% yield. Notably, the unsubstituted benzoic acid (1p) afforded a lower yield with 15% for the single alkynylation product (3p) and 21% for the bis-alkynylation product (4a), suggesting that electron-donating or electron-withdrawing groups are necessary for optimal reactivity. We also found that extending the reaction time to 36 hours led to exclusive formation of the dialkynylation product (4a) in 44% yield, suggesting that prolonged reaction times favour complete conversion to the dialkynylation product, albeit with moderate efficiency.

Scheme 1 Scope of benzoic acids.

Scheme 2 Scope of double alkynylation.

Scheme 3 Late-stage functionalization using DES.

Targeted Substrate scope for double alkynylation

When we increased the equivalents of the bromoalkynes (2) for the para-substituted benzoic acids, initial investigation with the unsubstituted benzoic acid (4a) revealed a modest yield of 44%, indicating the potential for further optimization to enhance reaction efficiency. Substrates bearing para-methyl (4b) and methoxy (4c) substituents exhibited yields of 35% and 20%, respectively, with the presence of unreacted starting material (21%) indicating lower reactivities. This observation suggests a potential limitation in accessing the reactive site for double alkynylation, possibly due to steric hindrance or electronic effects. Substrates containing halogen substituent 4-Br (4d) gave the dialkynylated product in 25% isolated yield. Electron-withdrawing group thio methyl (4e) functionality also yielded product (31%). Interestingly, substrates bearing phenyl (4f) and phenyloxy (4g) substituents demonstrated improved reactivity, affording products in 24% and 26% yield, respectively. This observation suggested a potential role of π-stacking interactions in facilitating substrate activation and subsequent alkynylation. The observed trends in substrate reactivity highlight the complexity of achieving efficient double alkynylation with para-substituted benzoic acids in DES. Challenges such as steric hindrance, electronic effects, and incomplete conversion necessitate further optimization of reaction conditions, including catalyst loading, temperature, and reaction time.

Substrate scope for late-stage functionalization

The exploration of late-stage C–H functionalization presents a transformative strategy for streamlining synthetic routes and accessing structurally diverse compounds (Scheme 3).³¹ In this context, we investigated the substrate scope of ruthenium(II)-catalysed C–H alkynylation reactions in deep eutectic solvents (DES), focusing on the reactivity of various benzoic acid derivatives towards late-stage functionalization. Initially, Tranilast (5a), an antiallergic drug, was employed as a model substrate for the C–H alkynylation reaction, yielding the desired product in 23% yield.³² This modest outcome served as a baseline for evaluating the efficacy of subsequent benzoic acid derivatives in the reaction. Repaglinide (5b), an antidiabetic drug bearing a unique substituent pattern, provided the highest isolated yield of 63%, reinforcing the impact of substituent electronics and steric effects seen in the reaction scope studies.³³ This observation underscores the importance of structural diversity in tuning the reactivity of aromatic substrates towards C–H functionalization. Next, various non-steroidal anti-inflammatory drugs such as flufenamic acid (5c), tolfenamic acid (5d), and mefenamic acid (5e) were examined, yielding products in the range of 22–33% demonstrating moderate reactivity under the employed conditions.³⁴ The variations in yield among these substrates may be attributed to differences in substituent electronic properties and steric hindrance. In contrast, niflumic acid (5f) exhibited lower reactivity, affording the product in only 11% isolated yield. Notably, Probenecid (5g) a drug used to treat hyperuricemia displayed intriguing selectivity, yielding both mono- and dialkynylated products (6g & 6g′) in 31% and 32% isolated yield, respectively.³⁵

Solvent reusability studies

The recycling of solvents in organic synthesis represents a critical aspect of green chemistry, aiming to minimize waste generation and reduce environmental impact.³⁶ The C–H alkynylation reaction was carried out using o-toluic acid as the substrate in a DES system comprising 1,3-dimethylurea (DMU) and β-cyclodextrin (β-CD) (Table 2). o-Toluic acid (1a) (27.2 mg, 0.20 mmol), KOH (5.6 mg, 0.10 mmol, 0.5 equiv.), [RuCl₂(p-cymene)]₂ (6.2 mg, 0.05 mmol, 5 mol%) and 1,3-dimethylurea + β-cyclodextrin (70–30%, 1.5 mL) were placed in a 5 mL-vial. 1-Bromo-2-(triisopropylsylil)acetylene (2) (62.7 mg, 0.24 mmol, 1.2 equiv.) was then added and the reaction mixture was stirred at 95 °C for 24 hours. After the reaction, aqueous HCl (1% v/v, 1 mL) was added, and the mixture was extracted with CPME (3 × 3 mL). The combined organic layers dried over MgSO₄, filtered, and concentrated under reduced pressure. The residue was purified by preparative TLC using petroleum ether/EtOAc/AcOH (90/9/1) to yield the product (3a). Following the first reaction, the residual DES was reused after evaporating the aqueous phase and any residual CPME, followed by drying to regenerate the eutectic mixture. Fresh reagents were then added, and the second reaction was performed under identical conditions. Notably, the residual acidity did not compromise the reuse of the DES. After completion of the second reaction, the organic layer was separated and purified as described earlier. This process was repeated for subsequent reactions, with the third reaction being performed under the same conditions as the second reaction. We chose to evaluate three cycles based on literature precedent, where eutectic solvent systems have been assessed for recyclability within this range.

Table 2 Solvent reusability study

Entry	Reaction no.	Yield (%)
1	1st	61
2	2nd	66
3	3rd	84

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The efficiency of solvent recycling was evaluated based on the yields obtained in each successive reaction (Table 2). Remarkably, despite the reuse of the residual DES, the yields of the subsequent reactions remained consistently high. The second reaction yielded a product with a comparable yield of 66% (Table 2, entry 2), while the third reaction achieved an even higher yield of 84% (Table 2, entry 3). The increased activity observed in successive cycles suggests that part of the catalyst remains within the DES system, enhancing overall yield.

In line with this observation, we performed ICP-MS analysis to investigate the stability of the metal catalyst, specifically ruthenium, in the DES over successive cycles (Fig. 3). The results from the ICP-MS analysis show an increasing concentration of ruthenium across the cycles, further supporting the hypothesis of catalyst retention within the DES.

Fig. 3 ICP-MS analysis of solvent recyclability.

These results indicate that a portion of the ruthenium catalyst remains in the DES after each cycle, with the concentration of ruthenium increasing over successive cycles. This is consistent with the observed increase in yields and suggests that the retained catalyst continues to contribute to the reaction's efficiency. The consistent presence of ruthenium in the DES over multiple cycles provides evidence for its reusability and stability, ensuring that the catalyst is not leached out or deactivated in the process.

Moreover, the continued increase in yields suggests that the retained ruthenium does not lose its catalytic activity over time. Instead, it seems to be effectively reused in each cycle, supporting the sustainability and efficiency of the DES as both a solvent and catalyst support medium. Given these findings, it is evident that the DES system exhibits excellent recyclability, with ruthenium retention playing a key role in sustaining the catalyst's activity and enhancing the reaction efficiency. The results also align with the findings from the literature on metal catalyst-based DES systems, where the presence of metal catalysts in the solvent contributed to enhanced catalyst stability and solvent reusability. However, while our results support these findings, we also note that further studies, including more cycles, would be beneficial to fully assess the long-term stability and performance of the DES in catalysis.

These results highlight the robustness and effectiveness of solvent recycling in the described C–H alkynylation reactions. Reuse of the DES system not only reduces waste generation but also contributes to the sustainability of the synthetic process. The successful recycling of solvents in ruthenium-catalysed C–H alkynylation reactions using DES underscores the potential of solvent recycling as a viable strategy for promoting sustainability in organic synthesis. By minimizing solvent consumption and waste generation, solvent recycling aligns with the principles of green chemistry and contributes to the development of more sustainable synthetic methodologies.

Conclusions

In summary, we demonstrated the potential of ruthenium-catalysed C–H alkynylation reactions in a deep eutectic solvent (DES) as a sustainable synthetic strategy for the late-stage functionalization of aromatic carboxylic acids. Through systematic substrate scope investigations and solvent recycling strategies, valuable insights into the feasibility and effectiveness of DES-mediated C–H alkynylation have been gained, contributing to the advancement of green chemistry principles in organic synthesis. The ruthenium-DES system exhibits excellent recyclability, with ruthenium retention playing a key role in sustaining the catalyst's activity and enhancing the reaction efficiency. Furthermore, the ability to use the drugs, offers opportunities for divergent synthesis and structural elaboration of complex molecules in a sustainable manner. Further studies are currently underway in our laboratory to enhance the utility of DES in various C–H activation reactions.

General experimental procedure

Carboxylic acids (0.20 mmol), KOH (5.6 mg, 0.10 mmol, 0.5 equiv.), [RuCl₂(p-cymene)]₂ (6.2 mg, 0.05 mmol, 5 mol%) and 1,3-dimethylurea + β-cyclodextrin (70 : 30, 1.5 mL) were placed in a 5 mL-vial. 1-Bromo-2-(triisopropylsylil)acetylene (62.7 mg, 0.24 mmol, 1.2 equiv.) was then added and the reaction mixture was stirred at the appointed temperature for 14 h in 100 °C. After that aqueous HCl (1% v/v, 1 mL) was added, the mixture was extracted with CPME (3 × 3 mL), and the combined organic layers dried over MgSO₄, filtered and concentrated under reduced pressure. The residue was purified by preparative TLC with Petroleum ether/EtOAc/AcOH (90/9/1 v/v) to yield the corresponding products.

Author contributions

SK designed the project. JW performed experiments and analysis. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

Data availability

The data supporting this article have been included as part of the ESI.† Data are available upon request from the authors.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

We thank Linnaeus University, the Swedish Research Council (2014-4573 and 2023-03406), the Crafoord Foundation (2019-0925 and 2020-0775) and the Helge Ax:son Johnsons Foundation (2019-0318 and 2022-0317) for generous financial support. We are also grateful to Dr Subramanian Suriyanarayanan and Dr Charlotte Parsland (LNU) for helpful discussions on ICP-MS analysis.

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Footnote

† Electronic supplementary information (ESI) available: Experimental procedure, copies of NMR spectra, pictures of solvents and reactions. See DOI: https://doi.org/10.1039/d5nj00359h

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