Silver tungstate: a single-component bifunctional catalyst for carboxylation of terminal alkynes with CO₂ in ambient conditions

Abstract

Silver tungstate was successfully developed as a bifunctional catalyst for the ligand-free carboxylation of various terminal alkynes with electron-withdrawing or electron-donating groups under atmospheric pressure of carbon dioxide (CO₂) at room temperature. In this protocol, dual activation – i.e., the terminal alkyne activated by silver, and CO₂ activation by the tungstate anion – was verified using nuclear magnetic resonance spectroscopy, and means that this reaction can be run under ambient conditions. Notably, this protocol can be applied to the preparation of a phenylacrylate derivative by a cascade reaction using phenylacetylene, CO₂ and benzylamine as starting materials.

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1. Introduction

The design of efficient methods to conveniently form carbon–carbon bonds is exciting and challenging.¹ Recently, because of the advantages of being nontoxic, renewable, abundant and economical, carbon dioxide (CO₂) is considered more and more to be an ideal C₁ synthon for production of value-added chemicals in both academic and pharmaceutical laboratories.² However, compared with traditional C₁ sources, (e.g., carbon monoxide and phosgene), CO₂ is in its highest oxidation state and the molecule is thermodynamically stable and kinetically inert. In this respect, high-energy active reagents, low-energy targets, powerful catalysts, extra energy or high CO₂ pressure are usually required for successful CO₂ incorporation.³ In particular, utilization of CO₂ under mild conditions will inevitably rely on its activation. For example, transition metal mediated CO₂ fixation and conversion has been successfully applied to the synthesis of natural products and biologically active molecules. Although significant achievements have been accomplished, chemical conversion of CO₂ at atmospheric pressure and room temperature remains a great challenge.⁴ In this context, bifunctional catalysts able to simultaneously activate both CO₂ and the substrate are promising candidates for highly efficient CO₂ chemical conversion under milder conditions.⁵

Carboxylic acids, especially unsaturated ones such as acrylic acid, are important starting materials/intermediates in organic synthesis and are popular skeletons in a wide number of natural products, agrochemicals, or pharmaceutically relevant compounds such as Lipitor®, Blopress, Prandin®, Vancomycin, and so on.⁶ Traditional synthesis of carboxylic acids commonly employs strong oxidants or toxic cyanides via cumbersome operations. In this context, convenient approaches to preparing carboxylic acid derivatives with CO₂ as a carboxylative reagent under mild conditions have attracted more and more attention. Indeed, a renaissance has recently been witnessed in the carboxylation of organotin,⁷ organozinc,⁸ and organoboron⁹ reagents with CO₂. However, the benefits associated with CO₂ are more than offset by unavoidably using such expensive organometallic reagents. Therefore, using the insertion of CO₂ into active C–H bonds to give the corresponding carboxylic acids has been used.

Since Inoue et al. reported the first carboxylation of terminal alkynes and CO₂,¹⁰ remarkable progress has been made in the field of the Ag(I)/Cu(I)-catalyzed carboxylation of terminal alkynes and CO₂.^2e,11 Silver salts have been widely employed as C≡C triple-bond activators in organic synthesis,¹² and several important studies about the silver-catalyzed carboxylation of terminal alkynes with CO₂ have been reported. The AgI catalytic system was developed by Lu et al. with a relatively high CO₂ pressure and the catalytically active species was investigated by density functional theory (DFT) studies.¹³ Gooßen et al. found that the AgBF₄-catalyzed carboxylation reactions could be conducted under atmospheric pressure of CO₂ in dimethyl sulfoxide (DMSO) at 50 °C.¹⁴ With the poly-NHC-Ag (NHC, N-heterocyclic carbene) catalytic system developed by Zhang et al., the carboxylation of terminal alkynes under ambient CO₂ pressure and room temperature was achieved.¹⁵ Unfortunately, rigorous reaction conditions, such as the extra addition of ligands or high CO₂ pressure, are commonly indispensable to the previously mentioned catalytic reactions.

In this paper, we would like to report on the use of a simple bifunctional silver tungstate (Ag₂WO₄) catalyst for the direct carboxylation of terminal alkynes without utilization of any ligand or additive. The synergistic effect of the silver cation being able to activate the C–C triple bond and the tungstate anion able to activate the CO₂ molecule allows the reaction to perform smoothly at room temperature and under the atmospheric pressure of CO₂ without the extra addition of ligand, as shown in Scheme 1.

Scheme 1 Metal-catalyzed carboxylation of terminal alkynes with CO₂.

2. Results and discussion

In a prototype experiment designed to test the validity of the concept outlined previously (Scheme 1), 5 mol% of Ag₂WO₄ was used as a catalyst for the carboxylation of phenylacetylene 1a in the presence of n-butyl iodide and caesium carbonate (Cs₂CO₃), with atmospheric pressure of CO₂ in dimethylformamide (DMF) at room temperature. The desired product, butyl 3-phenylpropiolate 2a was obtained at a 71% yield as a colorless oil (entry 1, Table 1). As shown in Table S1 (see ESI†), it was found that CO₂, Cs₂CO₃ and silver(I) catalyst are prerequisites for performing the carboxylation. In addition, 2.5 mol% Ag₂WO₄ was found to be enough for the reaction to run smoothly (entries 1–3). Furthermore, the presence of the ligand had a negative effect on the catalyst activity. For example, the yield decreased to 46% and 66% in the presence of triphenyl phosphine (Ph₃P) and 1,4-diazabicyclo[2.2.2]octane (DABCO), respectively (entries 4 and 5). A high catalyst loading and the addition of extra ligand resulted in a lower yield, which might be tentatively be ascribed to the decarboxylative activity of the Ag(I) salt.¹⁶

Table 1 Ag(I)-promoted carboxylation of 1a with CO₂^a

Entry	Catalyst (mol%)	Additive (mol%)	Yield^b (%)
a Reaction conditions: phenylacetylene (0.0511 g, 0.5 mmol), catalyst (molar percentage to 1a), Cs2CO3 (0.1955 g, 0.6 mmol), ^nBuI (0.1104 g, 0.6 mmol), DMF (3 mL), CO2 (99.999%, balloon), room temperature, 12 h. b Determined by gas chromatography (GC) with biphenyl as the internal standard.
1	Ag2WO4 (5)	—	71
2	Ag2WO4 (2.5)	—	76
3	Ag2WO4 (1)	—	46
4	Ag2WO4 (2.5)	Ph3P (3)	46
5	Ag2WO4 (2.5)	DABCO (3)	66
6	AgCl (5)	—	45
7	AgBr (5)	—	43
8	AgI (5)	—	52
9	AgOAc (5)	—	26
10	Ag2CO3 (2.5)	—	27
11	AgOTf (5)	—	42
12	AgBF4 (5)	—	22
13	AgO2CCF3 (5)	—	26
14	Ag2O (2.5)	—	4
15	AgNO3 (5)	—	54
16	Na2WO4 (2.5)	—	<1
17	AgNO3 (5)	Na2WO4 (2.5)	72

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Subsequently, several silver salts were investigated. Most of the tested silver compounds exhibited poor to moderate activity without any additive at room temperature (entries 6–14). Interestingly, when Na₂WO₄ was added to the AgNO₃-catalyzed system, the yield of 2a dramatically improved from 54% to 72%. However, Na₂WO₄ itself showed no catalytic activity under the reaction conditions (entries 15–17). This implied that the tungstate anion could efficiently activate CO₂. As a result, Ag₂WO₄ was determined to be the most active silver catalyst for the carboxylation of terminal alkynes with CO₂.

Furthermore, the presence of a base could strongly affect the carboxylation (entries 1–4, Table 2). Similarly to previous research,¹⁷ Cs₂CO₃ could play an essential role in the carboxylation reaction. Other inorganic bases, such as K₂CO₃, KOH, CsF, t-BuOLi, CsOAc, and NaNH₂ (Table S1†), gave unsatisfactory yields under identical conditions. In addition, several organic bases were also examined. Among them (Table S1†), only 1,5,7-triazabicyclo[4.4.0]dec-1-ene (TBD) was effective (entry 4), suggesting that the reaction goes through the TBD-CO₂ intermediate pathway.¹⁸

Table 2 Optimization of the reaction conditions^a

Entry	Base (eq.)	^nBuI (eq.)	Solvent	Time (h)	Yield^b (%)
a Unless otherwise stated, the reactions were carried out with 0.5 mmol 1a in 3 mL solvent in the presence of base and ^nBuI, at room temperature. b GC yield with biphenyl as the internal standard.
1	Cs2CO3 (1.2)	1.2	DMF	12	76
2	K2CO3 (1.2)	1.2	DMF	12	5
3	^tBuOLi (1.2)	1.2	DMF	12	2
4	TBD (1.2)	1.2	DMF	12	21
5	Cs2CO3 (1.2)	1.2	PC	12	<1
6	Cs2CO3 (1.2)	1.2	DMC	12	<1
7	Cs2CO3 (1.2)	1.2	DEC	12	<1
8	Cs2CO3 (1.2)	1.2	THF	12	<1
9	Cs2CO3 (1.2)	1.2	1,4-Dioxane	12	<1
10	Cs2CO3 (1.2)	1.2	DMSO	12	<1
11	Cs2CO3 (1.2)	1.2	MeCN	12	25
12	Cs2CO3 (1.2)	1.2	DMF	12	81
13	Cs2CO3 (1.2)	1.2	DMF	12	82
14	Cs2CO3 (1.2)	1.5	DMF	12	76
15	Cs2CO3 (1.2)	2.0	DMF	12	78
16	Cs2CO3 (1.2)	1.2	DMF	18	91
17	Cs2CO3 (1.2)	1.2	DMF	24	>99

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To prove the origin of the carboxylate, an isotope labeling experiment was performed. The carboxylation of 1a was conducted using labeled ¹³CO₂, and the ¹³C-labeled product 2ac was obtained as shown in Fig. 1. This result clearly demonstrated that CO₂ was the carboxyl source of this transformation.

Fig. 1 Proton-nuclear magnetic resonance (¹³C-NMR) spectrum of ¹³C_carbonyl-labeled product 2ac.

Type of solvent is another important influencing factor for this transformation. Organic carbonates – e.g., propylene carbonate (PC), dimethyl carbonate (DMC), or diethyl carbonate (DEC) – were found to be inefficient (entries 5–7, Table 2).¹⁷ Other conventional solvents did not work at all (entries 8–10) or gave poor yield (entry 11) compared with DMF (entry 1). Therefore, DMF was chosen as the reaction medium for further investigations. On the other hand, an excess amount of Cs₂CO₃ and n-BuI hardly affected the reaction (entries 12–15). Further prolonging the reaction time to 24 h gave 2a in quantitative yield (entries 1, 16, 17).

With the optimized reaction conditions to hand, we evaluated the scope of the substrate in this reaction. All the products were characterized by conventional spectroscopic methods and by comparison with the data available in the literature.^17,19 The reaction conditions were broadly adapted to a series of terminal alkynes 1a–1n and the corresponding alkyl 2-alkynoates 2a–2n were obtained in good to excellent yields, as summarized in Table 3. Both electron-donating and electron-withdrawing group substituted phenylacetylenes were successfully carboxylated with this method (entries 2–9). For 1,4-diethynylbenzene, biscarboxylative product 2ja was formed as the major product with 64% yield and 24% yield of the monocarboxylative product 2jb, which was also detected (entry 10). Aliphatic alkynes (entry 11) and heteroaromatic acetylenes (entries 12–15) were also found to be suitable substrates. In agreement with the DFT calculation, 3-ethynylpyridine showed lower activity when compared with 2-ethynylpyridine (entry 12 vs. 13), indicating that the acidity of the alkyne proton strongly impacts on the activity.²⁰

Table 3 Ag₂WO₄-catalyzed carboxylation of various terminal alkynes^a

Entry	RC≡CH	R^1X	Product	Yield^b (%)
a Reaction conditions: Substrate (1.0 mmol), Ag2WO4 (0.0116 g, 0.025 mmol), Cs2CO3 (0.3910 g, 1.2 mmol; 2.4 mmol for entry 10), alkyl halide (1.2 mmol; 2.4 mmol for entry 10), DMF (3 mL; 5 mL for entry 10), CO2 (99.999%, balloon), 25 °C, 24 h. b Isolated yield.
1		^nBuI		96
2		^nBuI		80
3		^nBuI		82
4		^nBuI		81
5		^nBuI		84
6		^nBuI		80
7		^nBuI		75
8		^nBuI		68
9		^nBuI		91
10		^nBuI		64
				24
11		^nBuI		60
12		^nBuI		84
13		^nBuI		70
14		^nBuI		90
15		^nBuBr		92
16		EtBr		92
17		^nBuCl		59

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The reactivity of the alkylating reagent was also examined. Bromoalkanes such as n-BuBr and EtBr gave 2a in excellent yields (entries 15 and 16). Even n-BuCl with poor activity²¹ also worked well in this protocol to give 2a with a 59% yield (entry 17).

To explore the reaction mechanism, the interactions of WO₄²⁻ with CO₂ were examined by NMR spectroscopy. In the ¹³C-NMR spectrum, a new signal appeared at δ = 157.8 ppm when CO₂ was absorbed by a suspension of deuterated DMSO (DMSO-d₆) and Ag₂WO₄ (Fig. 2), indicating that the interaction of the tungstate anion with CO₂ {Ag⁺₂[WO₄]²⁻-CO₂} leads to the activation of the CO₂ molecule.

Fig. 2 ¹³C-NMR study: (a) DMSO-d₆ under atmospheric CO₂ (1 atm, 25 °C); (b) Ag₂WO₄ in DMSO-d₆ under atmospheric CO₂ (1 atm, 25 °C).

A catalytic cycle for the single-component bifunctional carboxylation catalytic system is proposed, as delineated in Scheme 2. On the basis of the coordination of silver with a C–C triple bond, phenylacetylene 1a is converted to silver acetylide II with the aid of a base, and CO₂ is simultaneously activated by tungstate to form WO₄²⁻-CO₂ adduct III. Subsequently, insertion of III into the sp-hybridized Ag–carbon bond forms the silver phenylpropiolate IV with release of WO₄²⁻. Finally, IV is esterified in situ by using n-BuI to produce the ester 2a.

Scheme 2 The dual activation pathway for the present Ag₂WO₄-catalyzed carboxylation of terminal alkynes with CO₂.

The effectiveness of the Ag₂WO₄-catalyzed carboxylation of terminal alkynes and CO₂ provides a convenient approach for the synthesis of carboxylic acid derivatives and various useful chemicals under the very mild reaction conditions. For example, β-enaminoesters, widely used in organic syntheses, were traditionally prepared from β-ketoesters.²² Here, we have successfully prepared such a β-enaminoester through the carboxylation and hydroamination sequence from a terminal alkyne in one pot as demonstrated in Scheme 3. The Ag(I)-catalyzed carboxylation of 1a with CO₂ gave 2-alkynoate 2ab, which further reacted with benzylamine, resulting in the formation of ethyl (Z)-3-(benzylamino)-3-phenylacrylate 3a in 80% isolated yield. The configuration of the enamino double bond was identified by NMR spectroscopy and compared with those previously reported.²³

Scheme 3 One-pot synthesis of ethyl (Z)-3-(benzylamino)-3-phenylacrylate from phenylacetylene, benzylamine and CO₂.

3. Conclusions

In summary, we have developed a convenient ligand-free Ag(I)-based bifunctional catalytic system, i.e., silver tungstate, which can simultaneously activate both CO₂ and a C–C triple bond for the direct carboxylation of terminal alkynes with atmospheric CO₂ at room temperature, as confirmed using ¹³CO₂. This protocol also features a halogen-free catalyst and a simple process with low energy consumption and avoidance of complicated preparation of the catalyst. The origin of the carboxylate was corroborated by the isotope labeling experiment. Dual activation of the alkyne substrate by silver(I) and CO₂ by tungstate could account for such carboxylation working under extremely mild conditions. Furthermore, the utility of this catalytic system was demonstrated by the convenient synthesis of β-enaminoester in a one-pot process.

Such findings in this study encourage us to further develop cost-effective, green and efficient bifunctional catalysts for the chemical fixation of atmospheric CO₂ under mild reaction conditions.

4. Experimental details

The general procedure for the carboxylation of terminal alkynes is described here.

The terminal alkyne (1.0 mmol), Ag₂WO₄ (0.0116 g, 0.025 mmol), Cs₂CO₃ (0.3910 g, 1.2 mmol), ⁿBuI (0.2208 g, 1.2 mmol) and DMF (3 mL) were added in a 10 mL Schlenk flask. The flask was capped and sealed. Then a gas-exchanging process was conducted using the “freeze–pump–thaw” method. The reaction mixture was stirred at 25 °C for 24 h under an atmosphere of CO₂ (99.999%, balloon). After the reaction, water was added to the mixture, which was extracted with acetic ether five times. The combined organic layer was washed with saturated aqueous NaCl and then dried over MgSO₄. Then the solvent was removed under reduced pressure to get a crude product and the residue was purified by column chromatography (silica gel, petroleum ether–EtOAc) to give the desired product. The products were further identified by NMR and mass spectroscopy (see the ESI†), which are consistent with those reported in the literature and were in good agreement with the assigned structures. 2a. Colorless oil; ¹H-NMR (400 MHz, deuterated chloroform (CDCl₃)) δ (ppm): 7.58–7.57 (d, J = 4.0 Hz, 2H), 7.45–7.34 (m, 3H), 4.23 (t, J = 6.7 Hz, 2H), 1.73–1.66 (m, 2H), 1.48–1.38 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H); ¹³C-NMR (100 MHz, CDCl₃) δ (ppm): 154.1, 132.9, 130.5, 128.5, 119.6, 86.0, 80.7, 65.9, 30.4, 19.0, 13.6; EI-MS, m/z (%): 129.15 (100), 201.20 (11.72) [M⁺].

Acknowledgements

We are grateful to the National Natural Sciences Foundation of China (no. 21172125, 21121002, 21472103), Specialized Research Fund for the Doctoral Program of Higher Education (20130031110013), MOE Innovation Team (IRT13022) of China for financial support.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Characterization products and copies of the NMR spectra. See DOI: 10.1039/c4gc01638f

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