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Article

Cobalt-Catalyzed C–Se Bond Activation: Cross-Coupling of Organoselenides with Grignard Reagents

by
Tais V. de Souza Pinto
1,
Kamilly D. V. P. Sobrinho
1,
Maria E. C. da Silva
2,
Sandynara A. de Oliveira
1,
Andreia P. V. de Jesus
1,
Tereza A. N. Ribeiro
1,
Leonardo G. de Vasconcelos
1,
Paulo T. de Sousa Júnior
1,
Sumbal Saba
3,
Jamal Rafique
2,3,* and
André L. Stein
1,*
1
Laboratório de Pesquisa de Produtos Naturais, Instituto de Química, Universidade Federal de Mato Grosso—UFMT, Cuiabá 78060-900, MT, Brazil
2
Instituto de Química (INQUI), Universidade Federal do Mato Grosso do Sul—UFMS, Campo Grande 79074-460, MS, Brazil
3
Laboratório de Síntese Sustentável e Organocalcogênio (LABSO), Instituto de Química (IQ), Universidade Federal de Goiás—UFG, Goiânia 74690-900, GO, Brazil
*
Authors to whom correspondence should be addressed.
Molecules 2025, 30(21), 4232; https://doi.org/10.3390/molecules30214232
Submission received: 14 August 2025 / Revised: 16 September 2025 / Accepted: 17 September 2025 / Published: 30 October 2025
(This article belongs to the Special Issue Cross-Coupling Strategies for the Synthesis of Functionalized Organic Compounds)
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Abstract

Herein, we report a cobalt-catalyzed cross-coupling of organoselenides with Grignard reagents using simple CoCl2 as the catalyst. This efficient method accommodates a broad scope of selenides, including vinyl, aryl, heteroaryl, and alkynyl derivatives, under mild and ligand-free conditions. Remarkably, the reaction proceeds efficiently without additives and afforded the desired products in moderate to good yields within just 3 h.

Graphical Abstract

1. Introduction

Cross-coupling reactions represent one of the most powerful tools for constructing complex molecules, particularly for forming Csp2–Csp2 bonds [1]. The wide-ranging application of these reactions in the synthesis of bioactive molecules—particularly in the pharmaceutical and agrochemical industries—was recognized by the 2010 Nobel Prize in Chemistry [2,3]. These transformations typically involve a metal-catalyzed reaction between a nucleophilic organometallic reagent and an electrophilic substrate bearing a halide or pseudohalide leaving group. Prominent examples include the Suzuki–Miyaura [4], Kumada–Tamao–Corriu [5], Sonogashira [6], Stille [7], Negishi [8], and Hiyama [9] reactions.
In the past few years, significant efforts have been devoted to developing sustainable protocols that involve use of various solvents, catalysts, ligands, and additives to accommodate more readily available substrates (C–X) and less reactive organometallic reagents (e.g., Sn, Al, Zn, B, Si) [10]. However, Grignard reagents remain widely used due to their high reactivity and ease of preparation [5]. The application of Grignard reagents has evolved far beyond their classical role in nucleophilic addition, emerging as versatile bases for direct C–H metallation. Notably, their utility in this field is often enhanced by their surprisingly mild and selective basicity compared to stronger alternatives like alkyllithiums, which can lead to over-metallation or substrate decomposition. This strategic use of Grignard reagents as moderate bases has been powerfully demonstrated in recent years for the catalytic functionalization of a range of challenging substrates [11,12,13]. As a result, numerous cross-coupling protocols involving Grignard reagents and various substrates, catalyzed by nickel, palladium, or cobalt, have been reported in recent years [14,15,16].
Organoselenium compounds have attracted considerable attention, primarily due to their diverse biological activities [17,18,19]. These compounds can be selectively introduced into organic substrates through both nucleophilic and electrophilic pathways, often with high chemo-, regio-, and stereo-control [20,21]. Selenium compounds are generally stable in air and in common organic solvents, further enhancing their synthetic utility. Owing to the ability of selenium to exhibit oxidation states ranging from −2 to +6, these compounds display a wide range of structural diversity. Representative classes include diselenides, selenides, selenoxides, selenones, vinyl selenides, and selenoacetylenes [22].
A significant focus in chalcogen chemistry involves heterocyclic systems, where functionalization strategies range from simple reactions with elemental selenium or diselenides to sophisticated transition-metal-catalyzed transformations [23,24,25]. Among the most powerful methods, transition-metal-catalyzed cyclization of simple acyclic precursors stands out as a particularly attractive approach for the direct construction of chalcogen-containing heterocycles [26,27]. Although previous studies have demonstrated promising results, some of them have space of improvement considering the use of precious metals, costly catalysts, ligand, and high reagent loadings. To address these shortcomings, the development of a more sustainable and efficient alternative is urgently needed.
Although organohalides (C–X, where X = I, Br, Cl) and pseudohalides (X = OC(O)R, OTs, OTf, NC(O)R) are the most electrophiles in cross-coupling reactions [28,29]—mainly due to their low bond dissociation energies—organoselenium compounds have emerged as promising alternatives (Scheme 1). This potential is exemplified by the work reported by Zeni and co-authors in 2015, which describes the use of various classes of organoselenium compounds as substrates in palladium-catalyzed cross-coupling reactions, including Negishi, Suzuki, Kumada, and Sonogashira protocols [30]. Further advances include Silveira and co-workers’ iron-catalyzed (Fe(acac)3) cross-coupling of vinylic selenides (both E and Z isomers) and tellurides with Grignard reagents, which proceeds with complete retention of configuration and excellent yields [31]. Most recently, a nickel-catalyzed cross-coupling reaction was developed using an aryl alkyl selenide and an aryl bromide in the presence of 3 equivalents of magnesium [32]. This one-pot transformation proceeds via cleavage of the C–Se bond, affording the desired biaryls in moderate to good yields, while avoiding the pre-preparation of Grignard reagents.
As part of our ongoing interest in organoselenium chemistry and in the development of new synthetic methodologies [33,34,35,36,37,38,39,40], we herein report a cobalt-catalyzed cross-coupling of diverse organoselenides (vinyl, heteroaryl, aryl, and alkynyl) with Grignard reagents using CoCl2 as a simple, efficient catalyst.

2. Results & Discussion

For the optimization, (Z)-butyl(styryl)selenide 1a and freshly prepared (4-methoxyphenyl) magnesium bromide 2a (1 M solution) were selected as model substrates (Table 1). Initially, 2a (2 equiv.) were added dropwise to a solution of 1a (0.25 mmol) in THF (1 mL) at 0 °C. After 2 h, product 3a was isolated in 50% yield (entry 1). We then evaluated common co-solvents for Grignard cross-coupling reactions, but THF/NMP (2:1) and THF/Et3N (2:1) mixtures did not improve the yield (entries 2–3). Similarly, conducted reaction at room temperature proved ineffective (entries 4–5), with incomplete consumption of 1a observed in all cases.
Notably, using 5 mol% of catalyst at 0 °C led to a significant increase in the yield of product 3a, whereas 2 mol% proved insufficient (entries 6–7). As expected, in the absence of the cobalt catalyst, only the starting material was recovered (Table 1, entry 8). Further optimization revealed that extending the reaction time to 3 h provided 3a in 73 and 83% yield for 2 mol% and 5 mol % catalytic loading, respectively (entry 9–10). Prolonging the reaction beyond 3 h did not further improve the yield. Temperature control was critical, as performing the reaction at room temperature substantially reduced the yield (entry 11). The use of an excess of Grignard reagent (2 equiv.) was necessary due to the competitive formation of a biaryl byproduct alongside product 3a. Although 1.5 equivalents of 2a appeared to be sufficient, we opted to maintain the use of 2 equivalents for consistency.
With the optimized conditions in hand (Table 1, entry 10), we next explored the scope and limitations of the method by applying it to a range of substrates (Table 2). First, we examined various aryl Grignard reagents (freshly prepared) with vinyl selenide 1a. Aryl Grignard reagents bearing electron-donating groups (2a and 2b) reacted efficiently, providing higher yields compared to phenylmagnesium bromide (2c) (Table 2, entries 1–3). In contrast, the presence of an electron-withdrawing substituent, such as fluorine, diminished reactivity, affording product 3b in only 63% yield (Table 2, entry 4). Notably, alkyl Grignard reagents generated multiple byproducts with similar polarity, preventing isolation of the desired products. Similarly, when substrate 1b was employed, product 3e and the corresponding biaryl byproduct co-formed an inseparable mixture, making purification and yield estimation challenging (Table 2, entry 5). However, when Grignard reagent 2b was used, product 3f was isolated in 87% yield (Table 2, entry 6).
Other vinyl selenides, such as 1c, 1d, and 1e, also reacted satisfactorily with reagent 2b (Table 2, entries 7–9). Interestingly, the reaction also proved efficient for the coupling between a divinylic selenide and Grignard reagents. In this case, the use of 4 equivalents of Grignard reagent 2a led to the formation of product 3a in 73% yield (Table 2, entry 10). The protocol tolerated functional groups such as alcohols, substrate 1g reacted successfully with 2a, albeit requiring 3 equivalents of the Grignard reagent (Table 2, entry 11).
Considering that heterocycle-based organoselenium compounds represent one of the most important classes of selenium-containing molecules, we investigated the reactivity of pyridine derivative 4a with various Grignard reagents under our optimized conditions. As shown in Scheme 2, both electron-rich and electron-deficient Grignard reagents successfully coupled with 4a, yielding products 5a–5c in good yields. Notably, Grignard reagents bearing electron-donating groups consistently provided superior yields compared to their electron-withdrawing counterparts.
To further explore the synthetic utility of and demonstrate the potential of alkynyl and aryl selenide derivatives as starting materials, we evaluated their reactivity in cobalt-catalyzed cross-coupling reactions. Under standard conditions, compound 6a coupled with Grignard reagent 2a to afford product 7a in 35% yield (Scheme 3A). More encouragingly, the reaction of aryl selenide 8a furnished the corresponding biaryl 9a in 61% yield (Scheme 3B), demonstrating the particular effectiveness of this substrate class.
Building upon the foundational work by Oshima and co-workers [41,42] on cobalt-catalyzed cross-coupling reactions involving Grignard reagents, and later advancements by Hayashi [43], we were encouraged to propose a detailed mechanism (Scheme 4). In these studies, a complex formed in situ from cobalt salts and at least 4 equivalents of PhMgBr drastically altered the reaction outcome, with the coupling product being preferentially obtained over biphenyl. In our proposal, CoCl2 is first reduced to a cobalt(0) complex by 4 equivalents of aryl Grignard reagent 2. This complex then undergoes oxidative addition to form a bis-aryl cobalt(III) intermediate B, which subsequently undergoes reductive elimination to give the product 3 and monoaryl-ate complex C. Finally, the reaction of C with 2 regenerates di-ate complex A.

3. Materials and Methods

The reagents used were purchased from Aldrich Chemical Co. (Cajamar, Brazil) and used without purification. All the solvents used were of PA grade and used without purification. Analytical thin-layer chromatography analysis was carried out using Merck DC Kieselgel 0 F254 (Merck, Darmstadt, Germany) (230–400 mesh) aluminum plates coated with treated silica. For visualization, TLC plates were either placed under ultraviolet light, or stained with iodine vapor, or acidic vanillin. Most reactions were monitored by TLC for disappearance of starting material. Chromatographic columns (LabGlass, Sao Paulo, Brazil) were filled with silica gel 60 (230–400 mesh ASTM). Nuclear magnetic resonance (NMR) spectra were recorded using a Bruker Ascend 500TM spectrometer or Bruker DPX 300 NMR spectrometer (Bruker, Rheinstetten, Germany), with the chemical shifts (δ) set in parts per million (ppm), referenced by the residual solvent peak. The multiplicity of each peak is designated by the following abbreviations: s (singlet), d (doublet), dd (doublet of doublet), t (triplet), quint (quintet), sext (sextet) and m (multiplet). The coupling constants (J) are reported in Hertz (Hz).

General Procedure for the Cobalt-Catalyzed Cross-Coupling Reaction of Organoselenides with Organomagnesium Reagents

A mixture of the organoselenide (0.20 mmol) and CoCl2 (0.05 equiv.) was dissolved in THF (1 mL). Subsequently, freshly prepared organomagnesium reagent (2 equiv., 1 M solution) was then added. The mixture was stirred for 3 h at 0 °C. Afterward, the reaction mixture was allowed to warm to room temperature, diluted with ethyl acetate (3 mL), and washed with a saturated solution of NH4Cl (20 mL). The organic layer was separated, dried over MgSO4, and concentrated under reduced pressure. The crude product was purified by flash chromatography, eluting with hexane. Spectra of all the synthesized compounds are available in the Supplementary Materials (Figures S1–S28).

Spectral Data of Synthesized Products (3a–3j, 5a–5c, 7a, 9a)

  • (Z)-1-methoxy-4-styrylbenzene 3a [44]. Yield: 83% (0.035 g), colorless liquid. RMN 1H (CDCl3, 500 MHz): δ = 7.27–7.17 (m, 7H); 6.75 (d, J = 8.7 Hz, 2H); 6.54–6.48 (m, 2H); 3.77 (s, 3H). RMN 13C (CDCl3, 125 MHz): δ = 158.60; 135.56; 137.57; 130.16; 129.78; 129.67; 128.83; 128.77; 128.25; 126.9; 55.20.
  • (Z)-1-methil-4-styrylbenzene 3b [45]. Yield: 87% (0.034 g), colorless liquid. RMN 1H (CDCl3, 500 MHz): δ = 7.46 (d, J = 7.9 Hz, 3H); 7.25–7.12 (m, 5H); 6.54 (s, 1H); 2.37 (s, 3H). RMN 13C (CDCl3, 125 MHz): δ = 138.49; 136.91; 130.41; 129.64; 129.11; 129.05; 128.99; 128.37; 128.39; 127.02; 21.25.
  • (Z)-1,2-diphenylethene 3c [44]. Yield: 72% (0.026 g), colorless liquid. RMN 1H (CDCl3, 500 MHz): δ = 7.65 (d, J = 7.2 Hz, 1H); 7.50 (t, J = 7,7 Hz, 1H) 7.43–7.39 (m, 1H); 7.31–7.23 (m, 7H); 6.66 (s, 2H). RMN 13C (CDCl3, 125 MHz): δ = 137.29, 130.29, 128.92, 128.25, 127.13.
  • (Z)-1-fluoro-4-styrylbenzene 3d [44]. Yield: 63% (0.024 g), colorless liquid. RMN 1H (CDCl3, 500 MHz): δ = 7.49–7.46 (m, 1H); 7.22–7.17 (m, 5H); 7.12–7,09 (m, 1H); 6,91–6.87 (m, 2H); 6,56 (q, J = 12.1 Hz, 2H). RMN 13C (CDCl3, 125 MHz): δ = 161,97 (d, J = 246.6 Hz); 137.24; 1336.37 (d, J = 3.4 HZ); 130.73 (d, 7.9 Hz); 130.46; 129.28, 129.03; 128.51; 127.40; 115.45 (d, J = 21.4 Hz).
  • (Z)-1-methoxy-4-(4-methylstyryl)benzene 3f [45]. Yield: 87% (0.0386 g), colorless liquid. RMN 1H (CDCl3, 500 MHz): δ = 7.21–7.14 (m, 4H); 7.03 (d, J = 8.0 Hz, 2H); 6.75 (d, J = 8.7 Hz, 2H); 6.47 (s, 2H); 2.31 (s, 3H); 3.79 (s, 3H); 2.33 (s, 3H). RMN 13C (CDCl3, 125 MHz): δ = 158.60; 136.65; 134.63; 130.28; 130.12; 129.12; 128.94; 128.76; 128.76; 113.58; 55.20; 21.25.
  • (Z)-1-methoxy-4-(4-methylstyryl)benzene 3g [44]. Yield: 69% (0.031 g), colorless liquid. RMN 1H (CDCl3, 500 MHz): δ = 7.22–7.17 (m, 4H); 7.05 (d, J = 8.0 Hz, 2H); 6.77 (d, J = 8.7 Hz, 2H); 6.49 (s, 2H); 2.31 (s, 3H); 3.79 (s, 3H); 2.33 (s, 3H). RMN 13C (CDCl3, 125 MHz): δ = 158.68; 136.81; 134.80; 130.29; 130.12; 129.28; 129.11; 128.93; 128.90; 113.75; 55.35; 21.42.
  • (Z)-1-choro-4-(4-methoxystyryl)benzene 3h [46]. Yield: 77% (0.038 g), colorless liquid. RMN 1H (CDCl3, 500 MHz): δ = 7.17 (d, J = 7.3 Hz, 4H); 7.15 (d, J = 8.6 Hz, 2H); 6.75 (d, J = 8.6 Hz, 2H); 6.49 (s, 2H); 6.53 (d, J = 12.1 Hz, 1H); 6.42 (d, J = 12.1 Hz, 1H); 3.79 (s, 3H). RMN 13C (CDCl3, 125 MHz): δ = 158.68; 136.81; 134.80; 130.29; 130.12; 129.28; 129.11; 128.93; 128.90; 113.75; 55.35.
  • (Z)-1-methoxy-4-(4-(trifluoromethyl)ystyryl)benzene 3i [47]. Yield: 69% (0.038 g), colorless liquid. RMN 1H (CDCl3, 500 MHz): 7.46 (d, J = 8.1 Hz, 2H); 7.35 (d, J = 8.1 Hz, 2H); 7.14 (d, J = 8.6 Hz, 2H); 6.76 (d, J = 8.6 Hz, 2H); 6.63 (d, J = 12.2 Hz, 1H); 6.48 (d, J = 12.2 Hz, 1H); 3.78 (s, 3H). RMN 13C (CDCl3, 125 MHz): δ = 159.25; 141.53; 132.02; 130.38; 129.28; 129.11; 127.41; 125.37 (q, J = 3.8 Hz); 123.34; 113.99; 54.42.
  • (Z)-3-(4-mehoxyphenyl)prop-2-en-1-ol 3j [44]. Yield: 43% (0.013 g), colorless liquid. RMN 1H (CDCl3, 500 MHz): 7.14 (d, J = 8.6 Hz, 2H); 6.85 (d, J = 8.6 Hz, 2H); 6.49 (d, J = 11.6 Hz, 1H); 5.78–5.73 (m, 1H); 4.41 (d, J = 6.4 Hz, 1H); 3.80 (s, 3H). RMN 13C (CDCl3, 125 MHz): δ = 158.75; 130.67; 130.11; 129.41; 127.15; 113.71; 59.78; 55.29.
  • 2-(4-methoxyphenyl)pyridine5a [30]. Yield: 83% (0.031 g), colorless solid. RMN 1H (CDCl3, 500 MHz): δ = 8.63 (ddd, J = 4.8, 1.6, 1.0 Hz, 1H); 7.95–7.91 (m, 2H); 7.71–7.63 (m, 2H); 7.15 (ddd, J = 7.2, 4.8, 1.3 Hz, 1H); 7.71–7.63 (m, 2H); 3.84 (s, 3H). RMN 13C (CDCl3, 125 MHz): δ = 160.65; 157.29; 149.93; 136.85; 132.24; 128.19; 121.67; 120.00; 114.41; 55.44.
  • 2-(p-tolyl)pyridine5b [48]. Yield: 73% (0.025 g), colorless solid. RMN 1H (CDCl3, 500 MHz): δ = 8.66 (ddd, J = 4.8, 1.6, 1.0 Hz, 1H); 7.87 (d, J = 8.2 Hz, 1H); 7.73–7.67 (m, 2H); 7.26 (d, J = 8.2 Hz, 1H); 7.18 (ddd, J = 6.7, 4.8, 1.6, Hz, 1H); 3.84 (s, 3H). RMN 13C (CDCl3, 125 MHz): δ = 157.70; 149.68; 139.19; 136.91; 129.69; 126.88; 122.01; 120.37; 115.36; 21.47.
  • 2-(4-chorophenyl)pyridine5c [48]. Yield: 61% (0.023 g), colorless solid. RMN 1H (CDCl3, 500 MHz): δ = 8.71 (ddd, J = 4.8, 1.6, 1.0 Hz, 1H); 7.96 (d, J = 7.9 Hz, 2H); 7.77 (td, J = 7.7, 1.7 Hz, 2H); 7.72 (d, J = 8.0 Hz, 2H); 7.47 (d, J = 7.9 Hz, 2H); 7.28–7.25 (m, 1H). RMN 13C (CDCl3, 125 MHz): δ = 156.42; 150.00; 138.01; 137.13; 129.16; 128.37; 122.56; 120.40.
  • 1-methoxy-4-(phenylethynyl)benzene7a [30]. Yield: 35% (0.015 g), colorless solid. RMN 1H (CDCl3, 500 MHz): δ = 7.51–7.49 (m, 2H); 7.45 (d, J = 8.6 Hz, 2H); 7.34–7.29 (m, 3H); 6.86. (d, J = 8.6 Hz, 2H); 3.81 (s, 3H). RMN 13C (CDCl3, 125 MHz): δ = 159.23; 133.20; 131.66; 128.61; 128.09; 123.66; 115.49; 114.13; 89.57; 88.23; 55.51.
  • 4-methoxy-1,1′-biphenyl9a [30]. Yield: 61% (0.022 g), white solid. RMN 1H (CDCl3, 500 MHz): δ = 7.55–7.51 (m, 4H); 7.42–7.39 (m, 2H); 7.31–7.28 (m, 1H); 6.97 (d, J = 8.6 Hz, 2H); 3.84 (s, 3H). RMN 13C (CDCl3, 125 MHz): δ = 159.34; 141.03; 135.44; 133.92; 128.92; 128.36; 126.94; 114.29; 55.55.

4. Conclusions

In summary, we have developed a practical and efficient cobalt-catalyzed cross-coupling of organoselenides with Grignard reagents under mild conditions. Under the optimized conditions, the reaction operates without any ligands or co-solvents, and good yields were achieved in just 3 h using only 5 mol% of the cobalt catalyst. This method significantly expands the scope of metal-catalyzed cross-coupling reactions involving freshly prepared Grignard reagent, accommodating not only vinyl selenides but also aryl, heteroaryl, and alkynyl derivatives. Given the facile preparation of organoselenium compounds and their inherent chemo-, regio-, and stereoselective reactivity, this transformation offers a versatile and powerful strategy for C–C bond formation.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules30214232/s1, NMR Spectra (Figures S1–S28).

Author Contributions

Conceptualization: J.R. and A.L.S.; Methodology: T.V.d.S.P., K.D.V.P.S., M.E.C.d.S., S.A.d.O., A.P.V.d.J. and T.A.N.R.; Validation: T.V.d.S.P., K.D.V.P.S., M.E.C.d.S., S.A.d.O., A.P.V.d.J. and T.A.N.R.; Formal analysis: T.V.d.S.P., K.D.V.P.S., M.E.C.d.S., S.A.d.O., A.P.V.d.J., T.A.N.R., L.G.d.V., P.T.d.S.J. and S.S.; Investigation: T.V.d.S.P., K.D.V.P.S., M.E.C.d.S., S.A.d.O., A.P.V.d.J. and T.A.N.R.; Resources: J.R. and A.L.S.; Data curation: T.V.d.S.P., K.D.V.P.S., M.E.C.d.S., S.A.d.O., A.P.V.d.J. and T.A.N.R.; Writing—Original draft: A.L.S.; Writing—Review & Editing: S.S., J.R. and A.L.S.; Visualization: S.S., J.R. and A.L.S.; Supervision: J.R. and A.L.S.; Project administration: J.R. and A.L.S.; Funding acquisition: S.S., J.R. and A.L.S. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Finance Code 001), UFMS, FUDECT, UFMT, UFG, and FAPEMAT for financial support and fellowships. This study was financed in part by the Universidade Federal de Mato Grosso do Sul- Brasil (UFMS)—Finance Code 001. A.L.S. acknowledge CNPq for Universal 420048/2023-5. S.S., and J.R. would like to acknowledge CNPq (401355/2025-0, 316687/2023-5, 309975/2022-0, 404172/2023-7, and 405655/2023-1). S.S. also acknowledges the following FAPEG public calls: Chamada Pública FAPEG/SES No. 18/2025 (ARB2025191000003), and Chamada Pública FAPEG No. 05/2025 (PVE2025041000055).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The original contributions presented in this study are included in the article and Supplementary Materials. Further inquiries can be directed to the cor-responding authors.

Acknowledgments

The authors thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação Universidade Federal de Mato Grosso do Sul (UFMS), Universidade Federal de Mato Grosso (UFMT), and Universidade Federal de Goiás (UFG) for the support offered in this research. S.S. would like to acknowledge Programa futuras Cientistas (Edital CETENE No. 04/2025).

Conflicts of Interest

The authors declare no conflicts of interest.

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Molecules 30 04232 sch001
Scheme 1. Metal-catalyzed cross-coupling of organoselenides and Grignard Reagents [26,27,28].
Scheme 1. Metal-catalyzed cross-coupling of organoselenides and Grignard Reagents [26,27,28].
Molecules 30 04232 sch001
Molecules 30 04232 sch002
Scheme 2. Cross-Coupling of 2-(buthylselanyl)pyridine with Grignard Reagents.
Scheme 2. Cross-Coupling of 2-(buthylselanyl)pyridine with Grignard Reagents.
Molecules 30 04232 sch002
Molecules 30 04232 sch003
Scheme 3. Reactivity of Grignard Reagent 2a. (A) with 6a; (B) with 8a.
Scheme 3. Reactivity of Grignard Reagent 2a. (A) with 6a; (B) with 8a.
Molecules 30 04232 sch003
Molecules 30 04232 sch004
Scheme 4. A possible mechanism.
Scheme 4. A possible mechanism.
Molecules 30 04232 sch004
Table 1. Optimization of the cross-coupling conditions [a].
Table 1. Optimization of the cross-coupling conditions [a].
Molecules 30 04232 i001
EntryCoCl2 (mol%)SolventTemp. (°C)Yield 3a (%) [b]
110THF050
210THF/NMP (2:1)028
310THF/Et3N (2:1)040
410THF2544
55THF2546
65THF065
72THF062
8-THF00
92THF073 [c]
105THF083 [c]
115THF2558 [c]
125THF081 [c,d]
[a] Reaction conditions: 0.25 mmol 1a, 0.50 mmol (2 equiv.) freshly prepared Grignard reagent 2a, 5 mol% CoCl2, in 1 mL THF, 2 h. [b] Yield of isolated product. [c] 3 h. [d] 1.5 equiv. of 2a.
Table 2. Scope of the Reaction Between Vinyl Selenides and Grignard Reagents [a].
Table 2. Scope of the Reaction Between Vinyl Selenides and Grignard Reagents [a].
Molecules 30 04232 i002
Entry1RSeBu
1		R2MgBr
2		Yield 3 (%) [b]
1Molecules 30 04232 i003Molecules 30 04232 i004Molecules 30 04232 i005
2Molecules 30 04232 i006Molecules 30 04232 i007Molecules 30 04232 i008
3Molecules 30 04232 i009Molecules 30 04232 i010Molecules 30 04232 i011
4Molecules 30 04232 i012Molecules 30 04232 i013Molecules 30 04232 i014
5 [c]Molecules 30 04232 i015Molecules 30 04232 i016Molecules 30 04232 i017
6Molecules 30 04232 i018Molecules 30 04232 i019Molecules 30 04232 i020
7Molecules 30 04232 i021Molecules 30 04232 i022Molecules 30 04232 i023
8Molecules 30 04232 i024Molecules 30 04232 i025Molecules 30 04232 i026
9Molecules 30 04232 i027Molecules 30 04232 i028Molecules 30 04232 i029
10 [d]Molecules 30 04232 i030Molecules 30 04232 i031Molecules 30 04232 i032
11Molecules 30 04232 i033Molecules 30 04232 i034Molecules 30 04232 i035
[a] Reaction conditions: 0.25 mmol 1, 0.50 mmol (2 equiv.) freshly prepared Grignard reagent 2, 5 mol% CoCl2 in 1 mLTHF, 0 °C, 3 h. [b] Yield of isolated product. [c] Inseparable mixture of the product with the formed biaryl, derived from the Grignard reagent. [d] 4 equivalents of the Grignard reagent were used.
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de Souza Pinto, T.V.; Sobrinho, K.D.V.P.; da Silva, M.E.C.; de Oliveira, S.A.; de Jesus, A.P.V.; Ribeiro, T.A.N.; de Vasconcelos, L.G.; de Sousa Júnior, P.T.; Saba, S.; Rafique, J.; et al. Cobalt-Catalyzed C–Se Bond Activation: Cross-Coupling of Organoselenides with Grignard Reagents. Molecules 2025, 30, 4232. https://doi.org/10.3390/molecules30214232

AMA Style

de Souza Pinto TV, Sobrinho KDVP, da Silva MEC, de Oliveira SA, de Jesus APV, Ribeiro TAN, de Vasconcelos LG, de Sousa Júnior PT, Saba S, Rafique J, et al. Cobalt-Catalyzed C–Se Bond Activation: Cross-Coupling of Organoselenides with Grignard Reagents. Molecules. 2025; 30(21):4232. https://doi.org/10.3390/molecules30214232

Chicago/Turabian Style

de Souza Pinto, Tais V., Kamilly D. V. P. Sobrinho, Maria E. C. da Silva, Sandynara A. de Oliveira, Andreia P. V. de Jesus, Tereza A. N. Ribeiro, Leonardo G. de Vasconcelos, Paulo T. de Sousa Júnior, Sumbal Saba, Jamal Rafique, and et al. 2025. "Cobalt-Catalyzed C–Se Bond Activation: Cross-Coupling of Organoselenides with Grignard Reagents" Molecules 30, no. 21: 4232. https://doi.org/10.3390/molecules30214232

APA Style

de Souza Pinto, T. V., Sobrinho, K. D. V. P., da Silva, M. E. C., de Oliveira, S. A., de Jesus, A. P. V., Ribeiro, T. A. N., de Vasconcelos, L. G., de Sousa Júnior, P. T., Saba, S., Rafique, J., & Stein, A. L. (2025). Cobalt-Catalyzed C–Se Bond Activation: Cross-Coupling of Organoselenides with Grignard Reagents. Molecules, 30(21), 4232. https://doi.org/10.3390/molecules30214232

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