Recent Advances in N-Heterocyclic Carbene Coinage Metal Complexes in A³-Coupling and Carboxylation Reaction

Abstract

Owing of their accessibility and wide range of reactivities, alkynes make for fascinating building blocks. Either a selective alkyne carbon-carbon triple bond reaction or activation of the terminal alkyne C-H bond may be employed to functionalize them. Monocationic coinage metal complexes with a d10 electronic configuration are effective catalysts for alkyne activation. Silver(I) and gold(I) N-heterocyclic (NHC) systems are emerging as promising catalysts in multicomponent alkyne activation reactions; this review paper focuses on A³ (aldehyde-amine-alkyne)-coupling reaction and carbon dioxide fixation, furnishing a systematic overview of the scientific advances achieved during the last two decades. This study will carefully compare the corresponding silver and gold complexes employed in the two processes. The differences in reaction routes brought about by the catalyst ligand structure will be investigated with an emphasis on evaluating the benefits provided by the easily tuneable NHC backbone, in terms of chemo- and stereo-selectivity.

1. Introduction

Alkynes provide for intriguing building blocks as they are easily accessible and display a variety of reactivities. Their functionalization can be carried out either with a selective alkyne carbon-carbon triple bond reaction or as activation of the terminal alkyne C-H bond. A single or multiple functional groups can be introduced by π-bond breaking; on the other hand, alkynyl C-H bonds (pKa = 25) are particularly responsive, since they are significantly more acidic than their equivalent alkenyl and alkyl C-H bonds (pKa = 43 and >50, respectively). Hence, under various basic circumstances, base-promoted additions of terminal alkynes to carbonyl compounds can occur [1]. Classical, stoichiometric alkyne addition have been taken over by more sustainable processes, which take into account atom economy and chemoselectivity. Innovative, effective procedures that take use of the substrate’s coexisting π-donor and π-acceptor features are transition metal-catalyzed insertion techniques across the triple bond of alkynes [1,2,3]. Monocationic coinage metal complexes with a d10 electronic configuration are effective catalysts for alkyne activation due to metal donation from p to s and metal to p* back-bonding. Although copper catalysis is the most investigated in the literature, silver(I) and gold(I) systems are emerging as efficient alternatives, thanks to their enhanced stability and ease management [3,4,5]. N-Heterocyclic Carbenes (NHCs) are ideal systems for suitably modifying ligands to fine-tune reactivity, chemo-, and stereo-selectivity; these two-electron donor ligands combine strong σ-donating properties with a steric profile that permits both stabilisation of the metal centre and improvement of its catalytic activity [6,7]. The synthesis of such complexes has been extensively investigated over the past couple of decades, as well as their catalytic applications, which are widespread [8,9,10]. The main focus of this review article is the application of NHC-silver(I) and gold(I) complexes in multicomponent (MC) reactions, with a specific attention to A³ (aldehyde-amine-alkyne)-coupling reaction and carbon dioxide fixation. Such processes have gained more and more attention over the past decade, as testified by the exponential growth in published papers. One-pot catalysis, performed in classical organic solvents, as well as neat conditions or even polar solvents such as water, renders for efficient, atom-economic processes. The main products, namely propargylamines and propiolic acids, constitute interesting, versatile building blocks towards more complex chemical architectures, some of which are mentioned in this paper. The variations in catalyst performance brought on by the various NHC backbones will be addressed, and a careful comparison of the analogous silver and gold complexes used in the two MC reactions will be conducted. With a focus on examining the reaction mechanism, the variations in reaction pathways brought about by the catalyst structure will be explored with the purpose of generating fresh ideas for the design and development of novel and ever more efficient catalytic complexes.

2. A³–Coupling Reaction

The A³-reaction is a three-component coupling involving an aldehyde, a terminal alkyne and an amine (Scheme 1). It represents the most efficient method to obtain propargylamines.

Scheme 1. A³–coupling reaction.

Propargylamines constitute an important family of chemicals employed as organic building blocks and for realizing medicinal drugs such as Selegenine [11] and Rasagiline [12], that are currently used in the early treatment of Parkinson’s and Alzheimer’s diseases. The classical route for the synthesis of propargylamines is the nucleophilic addition of a metal acetylide to an imine. The acetylide is obtained by reaction of terminal alkynes with a strong base, such as butyllithium. The need to use stoichiometric amounts of acetylide, anhydrous conditions, and low temperatures, makes this method inconvenient. An alternative synthetic strategy has been developed over the past decade; catalytic amounts of transition metal inorganic salts can be used in the coupling reaction of equimolar quantities of aldehydes, amines and alkynes (A³) [13,14]. Thanks to its atom economy and high chemical selectivity, this synthetic strategy has received more and more attention.

The first catalysts used in the A³-coupling reactions [15] displayed a few drawbacks: high catalyst loading percentages and high temperatures. Copper [16], silver and gold complexes with N-heterocyclic carbenes (NHCs) were synthesized and tested as valid catalytic alternatives meant to overcome these downsides [5].

A proposed plausible mechanism for this three-components reaction, catalyzed by a late-transition metal NHC complex, is reported in Scheme 2 [15,17]. After the formation of an intermediate complex by side-on coordination of the alkyne to the metal, the weakly basic amine deprotonates the alkyne (whose acidity is now increased) and thus generates the corresponding metal acetylide. Lastly, the addition of this intermediate to an in situ generated imine (or iminium ion), leads to the desired propargylamine [18,19,20,21,22].

Scheme 2. Proposed reaction mechanism for NHC-M-X catalyzed A³-coupling reactions.

In 2008, Wang and co-workers reported the synthesis of a series of NHC-Ag(I) (1a–d) and polystyrene supported PS-NHC-Ag(I) (2a–d) complexes (Figure 1) [23].

Figure 1. NHC-Ag(I) and PS-NHC-Ag(I) synthesized by Wang [23].

They were employed in the A³-coupling reaction of paraformaldehyde (1.0 mmol), phenylacetylene (1.1 mmol) and piperidine (1.1 mmol) at room temperature for 24 h, with a 2 mol% amount of the silver catalyst in CH₂Cl₂, under nitrogen atmosphere. The results are summarized in Table 1. The catalytic activity of NHC-Ag(I) and PS-NHC-Ag(I) complexes decreased in this order: 1b > 1c > 1d > 1a and 2b > 2c > 2d > 2a, and this was the result of the influence of the substituted groups of the imidazolium salts: CH₂Ph > Ph > t-Bu > Me.

Table 1. Effect of Silver catalysts on A³-coupling reaction.

Entry a	Catalyst	Yield (%) b
1	1a	61
2	1b	80
3	1c	74
4	1d	68
5	2a	69
6	2b	90
7	2c	80
8	2d	75
9	Ag2O	37
10	AgI	31

^a Reaction conditions: paraformaldehyde (1.0 mmol), piperidine (1.1 mmol), phenylacetylene (1.1 mmol), silver catalyst (2 mol%), CH₂Cl₂ (0.5 mL), nitrogen atmosphere, room temperature, 24 h. ^b Isolated yields.

Thus, 1b and 2b (Table 1, Entries 2 and 6) resulted as the best catalysts for the A³-coupling reaction. Low catalytic activities were observed with Ag₂O or AgI (Table 1, Entries 9 and 10); moreover, there was no propargylamine formation in the absence of the silver source.

The authors evaluated the effect of the solvent on the A³-coupling reaction as well, using catalyst 2b. Among the various solvents tested, acetone, acetonitrile, dimethyl sulfoxide, and dichloromethane proved to be the best, but the highest yield (97%) was obtained under neat conditions (Table 2, Entry 10).

Table 2. Effect of the solvent on A³-coupling reaction using 2b as catalyst.

Entry a	Solvent	Yield (%) b
1	Acetone	95
2	Acetonitrile	91
3	Dimethyl sulfoxide	90
4	Dichloromethane	90
5	Dimethylformamide	84
6	Toluene	69
7	Tetrahydrofuran	62
8	Ethanol	49
9	Water	42
10	Neat	97
11 c	Neat	71

^a Reaction conditions: paraformaldehyde (1.0 mmol); piperidine (1.1 mmol); phenylacetylene (1.1 mmol); 2b (2 mol%); solvent (0.5 mL); nitrogen atmosphere; room temperature; 24 h. ^b Isolated yields. ^c 2b (1 mol %) was used.

Furthermore, the recyclability of PS-NHC-Ag(I) catalyst 2b was also investigated. The catalyst recovered by filtration maintained its ability to give A³-coupling reaction for 12 consecutive cycles. The catalysis tests with these complexes were extended to different combinations of amines, aldehydes and alkynes obtaining the corresponding propargylamines in good to excellent yields (85–98%).

In 2010, Zou et al. [15] described the synthesis of some NHC-Ag-X complexes: 1-cyclohexyl-3-benzylimidazolylidene and 1-cyclohexyl-3-naphtylimidazolylidene chloride and bromide (3a–d) that are reported in Figure 2.

Figure 2. NHC-Ag-X complexes synthesized by Zou et al. [15].

These compounds were obtained by reaction of silver oxide with the corresponding imidazolium salts in dichloromethane, following a procedure reported previously in the literature [24].

One equivalent of sodium nitrate was added to the reaction mixture of silver oxide and 1-cyclohexyl-3-benzylimidazolylidene in tetrahydrofuran to give a weakly coordinating anion; in this way the desired biscarbene silver nitrate (4) was obtained (Figure 3).

Figure 3. (A) [(CyBn-NHC)AgCl]₂ complex 3a structure and relative (B) dimeric trans conformation crystal structure; (C) [(CyBn-NHC)₂Ag]⁺ NO₃⁻ complex 4 structure and relative (D) dimeric cis conformation crystal structure (anion omitted).

NMR and elemental analyses provided only a few information on the NHC silver complexes’ molecular structure, thus single crystal X-ray diffraction analysis was performed. The analysis revealed that the complexes 3a and 3b have a trans conformation dimeric structure with a non-polar Ag-Ag bond (Figure 3A,B) report the exemplificative structure for complex 3a); the complex 4 contains two NHC ligands with a cis orientation (Figure 3C,D), while the complexes 3c and 3d show the desired monomeric structure complexes 3a–d and 4 were tested as catalysts in the A³-coupling reaction of 3-phenylpropionaldehyde, phenylacetylene and piperidine; the same were used, at 100 °C in air, also with alkyl alkynes, such as octyne, and aromatic aldehydes, both electron rich and deficient ones, giving the desired propargylamine in good yields. The results are shown in Table 3.

Table 3. Complexes 3a–d and 4 catalytic activity in the A³-coupling reaction.

Entry a	Catalyst	Aldehyde	Alkyne	Temp. (°C)	Time (h)	Yield (%) b
1	3a	3-phenylpropionaldehyde	phenylacetylene	100	2	79
2	3b	3-phenylpropionaldehyde	phenylacetylene	100	2	61
3	4	3-phenylpropionaldehyde	phenylacetylene	100	2	77
4	3c	3-phenylpropionaldehyde	phenylacetylene	100	2	99
5	3d	3-phenylpropionaldehyde	phenylacetylene	100	2	84
6	AgCl	3-phenylpropionaldehyde	phenylacetylene	100	2	80
7	AgBr	3-phenylpropionaldehyde	phenylacetylene	100	2	64
8	AgI	3-phenylpropionaldehyde	phenylacetylene	100	2	49
9	AgNO3	3-phenylpropionaldehyde	phenylacetylene	100	2	61
10	Ag2O	3-phenylpropionaldehyde	phenylacetylene	100	2	78
11	3c	3-phenylpropionaldehyde	phenylacetylene	50	12	81
12	3c	3-phenylpropionaldehyde	phenylacetylene	r.t.	72	69
13 c	3c	3-phenylpropionaldehyde	phenylacetylene	100	12	31
14	3c	3-phenylpropionaldehyde	octyne	100	6	64
15	3c	4-chlorobenzaldheyde	phenylacetylene	100	12	77
16	3c	Piperonaldheyde	phenylacetylene	100	12	49

^a Reaction conditions: aldehyde (1.0 mmol); piperidine (1.2 mmol); alkyne (1.5 mmol); NHC-Ag-X catalysts (3 mol%); dioxane (3 mL). ^b Isolated Yield. ^c Run in water. r.t. Room temperature.

The activities of NHC silver halides 3a and 3b were scarce when compared with simple inorganic silver halides AgCl and AgBr (Table 3, Entries 1–2 and 6–7). The yields increased with the complexes 3c and 3d thanks to the improved steric hindrance of 1-cyclohexyl-3-naphthalen-2-ylmethylimidazolylidene: in particular, the reaction with complex 3c completed in 2 h giving the product in a 99% yield (Table 3, Entries 4–5). Although cationic complexes are reported to exhibit high catalytic activity in the A³-coupling reaction, the cationic biscarbene silver nitrate complex 4 did not show better catalytic performance than the one observed with silver halides, due to the steric hindrance of the silver in the biscarbene cation [(NHC)₂Ag]⁺ (Table 3, Entry 3). Reaction times were longer at lower temperatures (Table 3, Entries 11–12).

In 2012 Navarro and co-workers [25] reported a study on A³-coupling reaction using analogous silver complexes with carbenes as ligands. They described the synthesis of NHC-Ag-X complexes starting from commercially available NHCs or their precursors, imidazolium salts [26,27,28,29]. These complexes, reported in Figure 4 (5a–d and 6a–b), were tested in the reaction of cyclohexanecarboxaldehyde (1.0 mmol), piperidine (1.1 mmol) and phenylacetylene (1.1 mmol) at 25 °C, with an amount of the catalyst of 1–2 mol% and with different solvents.

Figure 4. NHC-Ag(I) complexes synthesized by Navarro and co-workers [25].

The authors used 5a ((IPr)AgCl) complex to optimize the reaction conditions. As shown in Table 4 (Entry 11, the use of methanol as solvent led to the highest yields when 1 mol% of the complex was employed.

Table 4. Effect of the solvent on the A³-coupling reaction.

Entry a	Solvent	Time (h)	Yield (%) b
1	Neat	3	62
2	Acetone	3	63
3	Dichloromethane	3	69
4	Acetonitrile	3	96
5	Toluene	3	9
6	Dimethylformamide	3	57
7	Water	3	19
8	Isopropanol	1	88
9	Methanol	1	98
10	Isopropanol	0.25	68
11	Methanol	0.25	94

^a Reaction conditions: cyclohexanecarboxaldehyde (1.0 mmol); piperidine (1.1 mmol); phenylacetylene (1.1 mmol); catalyst 5a (1.2 mol%); solvent (0.5 mL); 25 °C. ^b GC yield (hexamethylbenzene as internal standard); average of 2 runs.

Subsequently, they carried out a study using methanol as solvent to evaluate the activity of the synthesized catalysts, i.e., 5a–d and 6a–b. The counterion has a notable effect, in fact the acetate ion gives the highest activity, while the halides follow the order Cl > Br >> I. Probably the polarizability of the counterion and its electronegativity are important factors. It should be noted that there are no important differences in the formation of the propargylamine, using a complex with saturated N-heterocyclic carbene based ligand (6a–b), compared to the complex with unsaturated ones (5a–d).

As shown in Table 5, the highest yield (96%, in 20 min) was obtained with 1 mol% of the complex 6b. The study was extended to different amines, aldehydes and alkynes. The complex 6b was able also to catalyze the coupling reaction of inactivated aryl aldehydes at room temperature, even if the reaction times resulted longer. Times could be shortened by increasing the temperature and/or the catalyst loading.

Table 5. Effect of the catalyst on the A³-coupling reaction after 20 min.

Entry a	Complex	Yield (%) b
1	5a	86
2	6a	88
3	5b	70
4	5c	9
5	5d	91
6	6b	96

^a Reaction conditions: cyclohexanecarboxaldehyde (1 mmol); piperidine (1 mmol), phenylacetylene (1.1 mmol); catalyst (1 mol%); methanol (0.5 mL); 25 °C; 20 min. ^b GC yield (hexamethylbenzene as internal standard); average of 2 runs.

The synthesis and the catalytic activity in A³-coupling reactions of a supported Ag(I)-NHC-MOF complex was reported in 2013 [30]. Metal-organic frameworks (MOFs) are efficient heterogeneous catalysts featuring a metallic core and malleable organic linkers (see Figure 5). They display large pores, high surface area, and can selectively adsorb small molecules. To combine the advantageous properties of MOFs and NHCs, the latter can be integrated into MOFs. In this way, systems with multiple, embedded catalytic sites in a single structure can be obtained. According to a previous work by Kitagawa et al., Mousavi, Verpoort and co-workers [31] reported the synthesis of the MOF A, consisting of the [Zn₈O] clusters with six metallomacrocycles and NHC moieties, as shown in Figure 5 [30].

Figure 5. MOF A consisting of the [Zn₈O] clusters with six metallomacrocycles and NHC moieties.

The NHC carbon of the MOF A was deprotonated and, then, different amounts of Ag(OAc) were added in order to obtain MOF-NHC-Ag(I) complexes (7–10), as shown in Table 6.

Table 6. MOF-NHC-Ag(I) synthesized complexes with different amounts of silver.

Entry a	Catalyst	Ag(OAc)	MOF A
1	7	25.0 mg, 0.15 mmol	60.0 mg, 0.1 mmol
2	8	20.0 mg, 0.12 mmol	60.0 mg, 0.1 mmol
3	9	12.5 mg, 0.075 mmol	60.0 mg, 0.1 mmol
4	10	7.5 mg, 0.045 mmol	60.0 mg, 0.1 mmol

^a Reaction conditions: Ag(OAc) (different amounts), MOF (60.0 mg, 0.1 mmol), CH₂Cl₂ (60 mL), nitrogen atmosphere, room temperature, 12 h; and then 39 °C, 24 h.

These complexes were tested in A³-coupling reaction of phenylacetylene (1.1 mmol), para-formaldehyde (1.0 mmol) and diisopropylamine (1.1 mmol) at room temperature in dichloromethane as solvent. In Table 7 and Table 8, the activities of MOF A and MOF-NHC-Ag(I) complexes in the A³-coupling reaction are reported.

Table 7. Effect of the catalyst on A³-coupling reaction.

Entry a	Catalyst	Time	Conversion (%) b	Yield (%) b
1	No catalyst	2 h	0	0
2	MOF A	24 h	>99	96
3	10	2 h	>99	97
4	9	1 h	>99	97
5	8	1 h	>99	97

^a Reaction conditions: paraformaldehyde (1.0 mmol); diisopropylamine (1.1 mmol); phenylacetylene (1.1 mmol); MOF or MOF-NHC-Ag(I) (5 mg); CH₂Cl₂ (2.0 mL); nitrogen atmosphere; room temperature. ^b Conversions and yields were determined by ¹H-NMR.

Table 8. Time-dependent conversion of catalysts MOF A and 9 in A³-coupling reaction.

Entry a	Catalyst	Time	Conversion (%) b
1	MOF A	2 h	30
2	MOF A	6 h	57
3	MOF A	15 h	86
4	MOF A	24 h	>99
5	MOF A	36 h	>99
6	9	15 min	22
7	9	30 min	67
8	9	45 min	83
9	9	1 h	>99

^a Reaction conditions: paraformaldehyde (1.0 mmol); diisopropylamine (1.1 mmol); phenylacetylene (1.1 mmol); MOF or MOF-NHC-Ag(I) (5 mg); CH₂Cl₂ (2.0 mL); nitrogen atmosphere; room temperature. ^b Conversions were determined by ¹H-NMR.

Complex 9 led to a full conversion of the reagents into the propargylamine after 1 h unlike the MOF A which led to the complete conversion in 24 h. This demonstrated that silver plays a crucial role in the catalysing the A³-coupling reaction. This is evident by observing Figure 6, which shows the conversions as a function of the amount of catalyst.

Figure 6. Effect of the amount of the catalyst on the A³-coupling reaction.

Using complex 9 as catalyst, the effect of the solvent on the A³-coupling reaction was also studied, and the results are summarized in Table 9. Reactions carried out in dichloromethane, acetone, acetonitrile gave the highest conversions. Toluene produced modest results and the reaction did not occur at all in solvents such as dimethyl sulfoxide and dimethylformamide. Reactions in tetrahydrofuran and in neat conditions generated the desired product.

Table 9. Effect of the solvent on A³_-coupling reaction using complex 7.

Entry a	Solvent	Conversion (%) b	Yield (%) b
1	Dichloromethane	>99	97
2	Acetone	78	75
3	Acetonitrile	92	89
4	Dimethyl sulfoxide	n.d. c	n.d.
5	Dimethylformamide	n.d.	n.d.
6	Tetrahydrofuran	62.5	59
7	Toluene	29	25
8	Neat	53	50

^a Reaction conditions: paraformaldehyde (1.0 mmol); diisopropylamine (1.1 mmol); phenylacetylene (1.1 mmol); complex 7 (5 mg); CH₂Cl₂ (2.0 mL); nitrogen atmosphere; room temperature. ^b Conversions and yields were determined by ¹H-NMR. ^c Not detectable.

In the years 2015–2017, Bantreil, Mètro, and co-workers [32,33,34] reported the solvent-free synthesis of NHC complexes bearing non-coordinating tetrafluoroborate or hexafluorophosphate counter-anions (11a–d, 12a–d, 13a–d, and 14a–b; Figure 7).

Figure 7. NHC–silver(I) complexes synthesized by Bantreil, Mètro et al. [32,33,34].

In 2017, they tested these complexes in the A³-coupling reaction of benzaldehyde (1.0 equiv.), piperidine (1.2 equiv.) and phenylacetylene (1.5 equiv.) in order to obtain the respective propargylamine [35]. The complexes were used at 3 mol% and the reactions were performed in methanol at 110 °C under microwave irradiation for 1 h. The results are shown in Table 10.

Table 10. Catalytic activity of synthesized complexes in A³-coupling reaction.

Entry a	Catalyst	Yield (%) b
1	13a	51
2	13b	36
3	13c	11
4	13d	30
5	14a	8
6	14b	12
7	11a	66
8	11b	53
9	11c	52
10	11d	55
11	12a	24
12	12b	81 c, 77 d
13	12c	14
14	12d	7

^a Reaction conditions: benzaldehyde (1.0 mmol); piperidine (1.2 equiv.); phenylacetylene (1.5 equiv.); catalyst (3 mol%); MeOH (2 mL); microwave irradiation; 110 °C; 1 h. ^b Determined by HPLC analysis by using mesitylene as an internal standard. ^c Yield of isolated product. ^d Yield of isolated product upon using 1.1 equiv. of both piperidine and phenylacetylene along with 4 mol% of the complex 12b.

The best yield was obtained with complex 12b which led to the desired propargylamine in 81% yield. (Table 10, Entry 12). Considering these good results, the catalytic activity of the complex 12b was evaluated for the synthesis of a wide range of propargylamines. This catalyst turned out to be versatile and compatible with aliphatic and aromatic aldehydes and alkynes. Propargylamines were obtained with good yield (73–95%) in fast reaction times (1–4 h) with reduced catalyst loads (4 mol%) and in a low-toxicity solvent, methanol (2 mL).

In 2017 Kılınçarslan and co-workers [36] reported the synthesis and catalytic activity in A³-coupling reaction of NHC-Ag(I) complexes based on 1-(methyl)-3-(alkyl)imidazole: 15a-c depicted in Figure 8.

Figure 8. NHC-Ag(I) complexes synthesized by Kılınçarslan et al. [36].

These complexes were tested using piperidine (1.2 mmol), several aldehydes (1.0 mmol) and phenylacetylene (1.5 mmol); the results are shown in Table 11. The complex 15a showed scarce catalytic activity in the presence of benzaldehyde, and high efficiency with paraformaldehyde. The reaction was carried out in different solvents and in neat conditions, at 80 °C, achieving yields ranging from 12% to 88%.

Table 11. Catalytic activity in A³-coupling reaction.

Entry a	Aldehyde	Solvent	Catalyst	Yield (%) b,c
1	Paraformaldehyde	Dioxane	15a	84
2	Cyclohexanecarboxaldehyde	Dioxane	15a	76
3	Cyclohexanecarboxaldehyde	Dioxane	15b	70
4	Cyclohexanecarboxaldehyde	Dioxane	15c	68
5	Benzaldehyde	Dioxane	15a	12
6	H	Dioxane	Ag2O	47
8 d	H	Acetone	15a	80
9	H	Dimethyl sulfoxide	15a	82
10 e	H	Water	15a	13
11 f	H	Ethanol	15a	14
12	H	Neat	15a	88
13	Cyclohexanecarboxaldehyde	Neat	15a	82
14	Benzaldehyde	Neat	15a	27

^a Reaction conditions: aldehyde (1.0 mmol); piperidine (1.2 mmol); phenylacetylene (1.5 mmol); NHC-Ag(I) catalyst (3 mol%); dioxane (2.0 mL); argon atmosphere; 80 °C; 8 h. ^b Isolated yields. ^c Average of two runs. ^d At 56 °C. ^e For 12 h. ^f At 78 °C.

In the same year Quayle et al. [37] reported a study concerning synthesis, characterization and evaluation of the catalytic activity of the gold complexes reported in Figure 9.

Figure 9. Gold complexes tested in A³-coupling reaction.

These complexes were tested as catalysts in the A³-coupling reaction of a variety of aldehydes, alkynes and amines. [AuCl₂(η^2-C,N-C₆H₄CH₂NMe₂)] 16a and (S)-[AuCl₂(η^2-C,N-C₆H₄CH(Me)NMe₂)] 16b, used at 1 mol%, in water at 40°C, led to quantitative conversion after 24 h. Instead, only 9 and 10% of aldehyde conversion was reported when the NHC-Au complexes 18a–b and 19 were tested, thus showing low activity in the A³-coupling reaction. In addition, a lack of enantioselectivity was also observed with the chiral complexes 16a, 17, and 18a–b and this was in line with what has been reported in the literature about obtaining enantiomers with gold complexes[38].

In 2019 A. Neshat et al. [22] presented a study on the synthesis of novel NHC-Ag(I) complexes 21 and 22 by substitution of chlorides in the previously reported complex 5a with homoscorpionate sulphur donor borate ligands (Figure 10). Complex 21 was tested in A³-coupling reactions, and its catalytic activity was compared with that of the complexes 5a and 20 already known. Since complexes 21 and 22 have close characteristics, the catalytic activity of complex 22 was not tested.

Figure 10. Ag-NHC and Au-NHC complexes tested by Neshat et al. [22].

Various amount of the complexes 5a, 20, 21 were tested in A³-coupling reaction of benzaldehyde (0.5 mmol), piperidine (0.75 mmol) and phenylacetylene (0.75 mmol) under different temperatures and reaction times. Employing a 1% mol amount of the 5a, 20, 21 catalysts, and running the reaction at 50°C and for 24 h, yields of 95%, >99% and >99%, were, respectively, obtained (Table 12, Entry 1).

Table 12. A³-coupling of benzaldehyde, piperidine and phenylacetylene with catalysts 5a, 20, 21 under different reaction conditions.

Entry a	Catalyst	Cat. (mol%)	Temp. (°C)	Time (h)	Yield (%) b
1	5a	1	50	24	95
	20				>99
	21				>99
2	5a	1	r.t.	24	87
	20				>99
	21				>99
3	5a	0.5	r.t.	24	30
	20				>99
	21				>99
4	5a	0.2	r.t.	24	<5
	20				>99
	21				>99
5	5a	0.2	r.t.	12	<5
	20				82
	21				45
6	5a	0.1	r.t.	24	0
	20				50
	21				39

^a Reaction conditions: benzaldehyde (0.5 mmol); piperidine (0.75 mmol); phenylacetylene (0.75 mmol); catalyst (indicated in the column); H₂O:THF (10:1, 2 mL). ^b Yield determined by ¹H-NMR. r.t. Room temperature.

Subsequent decrease of the temperature to ambient, with complex 5a, caused a drop in the yield from 95 to 87%, while it remained unchanged by employing complexes 20 and 21 (Table 12, Entry 2). A similar trend was observed by stitching the amount of catalyst from 1% to 0.5% and 0.2% (Table 12, Entries 3–4). They also tried reducing the reaction time from 24 to 12 h, employing the 0.2% catalysts, but, again, lower yields were obtained (Table 12, Entry 5) and the same occurred when they tried to lower the percentage of catalyst by going to 0.1% (Table 12, Entry 6).

As a conclusion, NHC-Ag(I) complexes with bidentate sulphur donor ligands (i.e., complex 21), showed great catalytic activity in A³-coupling reactions. The catalytic activity of the novel catalyst 21 was comparable with that of complex 20 and higher than that of the complex 5a.

In 2020 Mariconda and co-workers [19] synthetized two novel complexes of silver and gold bearing 4,5-dichloro-N-methyl-N’-(2-hydroxy-2-phenyl)ethyl-imidazole-2-ylidine ligand (23a, 24a) (Figure 11).

Figure 11. Silver(I) and gold(I) catalysts used in A³-coupling reactions.

According to the results of conductivity measurements, these complexes can be present in solution as ionic species [M(NHC)₂]⁺ [MX₂]^– or neutral species M(NHC)X, where the last were considered responsible of the catalytic activity in A³-coupling reaction (Figure 12).

Figure 12. Equilibrium between ionic and neutral species of NHC-M complexes.

They were tested as catalysts in A³-coupling reaction of aldehydes (i.e.,: formaldehyde or paraformaldehyde or cyclohexanecarboxaldehyde or benzaldehyde, 1.0 mmol) with piperidine (1.2 mmol) and phenylacetylene (1.5 mmol), in the absence of solvent or using dioxane (Table 13 and Table 14). The activity of complexes 23a and 24a were compared with two analogous complexes with hydrogens on the backbone (23b and 24b) synthesized by the same group [39,40]. The results, in neat conditions, are reported in Table 13.

Table 13. Solvent free synthesis of propargylamines via A³- coupling reactions catalyzed by NHC-Ag(I) (23a–b) and NHC-Au(I) (24a–b).

Entry a	Catalyst	Aldehyde	Conversion (%) b
1	23b	Formaldehyde solution (38%)	58
2		Paraformaldehyde	13
3		Cyclohexanecarboxaldehyde	99
4		Benzaldehyde	13
5	24b	Formaldehyde solution	96
6		Paraformaldehyde	99
7		Cyclohexanecarboxaldehyde	99
8		Benzaldehyde	83
9	23a	Formaldehyde solution	64
10		Paraformaldehyde	94
11		Cyclohexanecarboxaldehyde	99
12		Benzaldehyde	38
13	24a	Formaldehyde solution	81
14		Paraformaldehyde	99
15		Cyclohexanecarboxaldehyde	96
16		Benzaldehyde	86

^a Reaction conditions: aldehyde (1.0 mmol); piperidine (1.2 mmol); phenylacetylene (1.5 mmol); catalyst (3 mol%); nitrogen atmosphere; 80 °C; 6 h. ^b Conversions were determined by ¹H-NMR analysis using 2-bromo mesitylene as internal standard.

Table 14. Synthesis of propargylamines via A³-coupling reactions catalyzed by silver and gold NHC complexes in the presence of dioxane as solvent.

Entry a	Catalyst	Aldehyde	Conversion (%) b
1	23b	Formaldehyde solution (38%)	n.d.
2		Paraformaldehyde	n.d.
3		Cyclohexanecarboxaldehyde	71
4		Benzaldehyde	n.d.
5	24b	Formaldehyde solution	65
6		Paraformaldehyde	67
7		Cyclohexanecarboxaldehyde	68
8		Benzaldehyde	22
9	23a	Formaldehyde solution	62
10		Paraformaldehyde	30
11		Cyclohexanecarboxaldehyde	99
12		Benzaldehyde	14
13	24a	Formaldehyde solution	99
14		Paraformaldehyde	71
15		Cyclohexanecarboxaldehyde	99
16		Benzaldehyde	68

^a Reaction conditions: aldehyde (1.0 mmol); piperidine (1.2 mmol); phenylacetylene (1.5 mmol); catalyst (3 mol %); nitrogen atmosphere; 80 °C; 6 h. ^b Conversion determined by ¹H-NMR analysis using 2-bromo mesitylene as internal standard. n.d. Not detected.

All complexes were found to be capable to catalyze the A³-coupling reaction. By comparing Entries 1–16 of Table 12, it was evident that the gold catalysts were much more efficient than silver ones. Cyclohexanecarboxaldehyde and paraformaldehyde were the most reactive in presence of all the catalysts (except 23b for the paraformaldehyde), whereas the benzaldehyde resulted the least reactive. As far as formaldehyde in aqueous solution is concerned, this was moderately reactive in the presence of silver complexes (Table 13, Entries 1 and 9), while good reactivity was observed with gold-based complexes (Table 13, Entries 5 and 13).The same reactions were performed using dioxane as solvent and the results are reported in Table 14. A trend of reactivity emerged from the results in Table 14: 24a > 24b > 23a > 23b. In conclusion, gold-based complexes were more performing than silver ones and the new complexes with chlorines on NHC backbone (23a and 24a) were more active than the previously synthesized complexes (23b and 24b).

Recently [21], a green approach for A³-coupling reactions using water as solvent or working in neat condition was proposed. In order to enhance the solubility of catalysts in water, four new complexes (25a–b, 26a–b) were designed by substitution of the alcohol group of the previously described 23b and 24b with sodium alcoholate or methoxyl group, as shown in Figure 13.

Figure 13. Silver and gold complexes with sodium alcoholate or methoxyl groups.

These complexes were tested as catalysts in A³-coupling reactions of an aldehyde (i.e.,: paraformaldehyde, butyraldehyde, cyclohexanecarboxaldehyde, and benzaldehyde) with piperidine and phenylacetylene in neat conditions or using water as solvent.

In Table 15 the catalytic activity of these new complexes, in the absence of solvents, are depicted. Gold complexes (25b and 26b) have shown better catalytic activity than silver analogues: 26b ≥ 25b > 26a ≥ 25a.

Table 15. NHC–Ag(I) and NHC–Au(I) catalyzed A³-coupling reaction.

Entry a	Aldehyde	Yield (%) b
		25a	25b	26a	26b
1	Formaldehyde	20	90	29	88
2	Butyraldehyde	43	74	46	87
3	Cyclohexanecarboxaldehyde	40	60	43	76
4	Benzaldehyde	10	47	11	43

^a Reaction conditions: aldehyde (1.0 mmol); piperidine (1.2 mmol); phenylacetylene (1.5 mmol); catalyst (3 mol%); nitrogen atmosphere; 80 °C; 6 h. ^b Conversions were determined by ¹ H-NMR analysis using 2-bromo mesitylene as internal standard.

In particular, paraformaldehyde was the most reactive substrate when gold complexes were used. Both gold and silver complexes with a methoxyl group performed better than the ones with sodium-alcoholate groups. The catalytic behaviour of the gold complexes 25b and 26b in the A³-coupling reaction of cyclohexanecarboxaldehyde and benzaldehyde with piperidine and phenylacetylene was investigated, in water. Comparing the activity of the complexes 25b and 26b with that of the previously reported 24b and 24a analogues (see Table 14), catalyst 24a, bearing chlorines on the NHC backbone, showed to be the most active (Table 16).

Table 16. NHC–Au(I) catalyzed A³-coupling reaction.

Entry a	Aldehyde	Yield (%) b
		24b	24a	25b	26b
1	Cyclohexanecarboxaldehyde	66	70	43	37
2	Benzaldehyde	19	25	20	11

^a Reaction conditions: aldehyde (1.0 mmol); piperidine (1.2 mmol); phenylacetylene (1.5 mmol); catalyst (3 mol%), water (3.0 mL), nitrogen atmosphere; 80 °C; 6 h. ^b Conversions were determined by ¹H-NMR analysis using 2-bromo mesitylene as internal standard.

Further improvement of the catalysts’ structure [41] resulted in four new complexes having an hydroxyl functional group on each of the nitrogen atoms of the imidazole ring (Figure 14). These complexes were even more soluble in green solvents and in physiological environments.

Figure 14. Water-soluble NHC-Ag(I) and NHC-Au(I) complexes.

As shown in Figure 14, silver and gold complexes 27a and 28a differ from complexes 27b and 28b for the presence of the chlorines on the backbone. These complexes were tested as catalysts in A³-coupling reactions of phenylacetylene, piperidine and three different aldehydes (paraformaldehyde, cyclohexanecarboxaldehyde, and benzaldehyde), at 80 °C in neat conditions. As shown in Table 17, all complexes were able to catalyze the coupling of aldehydes, piperidine, and phenylacetylene. By comparing Entries 1–12, it was evident that silver complexes (27a–b) having N-heterocyclic carbene with hydrogens on the backbone were less active than the gold complexes (28a–b) with chlorine atoms on the backbone.

Table 17. Catalytic activity of the water-soluble NHC-Ag(I) and NHC-Au(I) complexes in A³-coupling reactions.

Entry a	Catalyst	Aldehyde	Yield (%) b
1	27b	Paraformaldehyde	25
2	27b	Cyclohexanecarboxaldehyde	47
3	27b	Benzaldehyde	23
4	27a	Paraformaldehyde	65
5	27a	Cyclohexanecarboxaldehyde	52
6	27a	Benzaldehyde	36
7	28b	Paraformaldehyde	86
8	28b	Cyclohexanecarboxaldehyde	65
9	28b	Benzaldehyde	60
10	28a	Paraformaldehyde	99
11	28a	Cyclohexanecarboxaldehyde	99
12	28a	Benzaldehyde	60

^a Reaction conditions: aldehyde (1.0 mmol), piperidine (1.2 mmol), phenylacetylene (1.5 mmol), catalyst (3 mol%); nitrogen atmosphere; 80 °C; 6 h. ^b Conversions were determined by ¹H-NMR analysis using as internal standard 2-bromo mesitylene.

In 2022 Mateus et al. [42] reported the synthesis of a chelating bidentate NHC-based silver complex containing bisamides linkers (29) (Figure 15).

Figure 15. Chelating bidentate NHC-Ag(I) complex.

The catalytic activity of the complex 29 has been evaluated in the A³-coupling reaction of cyclohexanecarbaldehyde, pyrrolidine and phenylacetylene, as described in Table 18.

Table 18. Chelating bidentate NHC–Ag(I) complex catalyzed A³-coupling reaction.

Entry a	Catalyst (mol%)	Temperature (°C)	Time (h)	Yield (%) b
1	1	80	5	89
2	0.5	80	5	85
3	0.5	60	5	-
4	0.5	60	36	88
5	0.5	40	36	87
6	0.5	25	36	72
7	0.1	80	36	74
8	-	80	36	<5

^a Reaction conditions: cyclohexanecarbaldehyde (1.5 mmol), pyrrolidine (1.5 mmol), phenylacetylene (1.5 mmol). ^b Isolated yield.

The reaction conducted with 1 mol% of the catalyst 29 at 80 °C, led to a full conversion of the starting reagents and the desired propargylamine was isolated in 89% (Table 18, Entry 1). Given this interesting result, the catalyst load was lowered to 0.5 mol% and, even in this case, the full consumption of the reactants occurred leading to 85% of the desired product (Table 18, Entry 2). The scientists decided to proceed by lowering the reaction temperature and, then, by decreasing the catalyst load up to 0.1 mol%.

So, by extending the reaction times to 36 h and by using 0.5 mol% of the catalyst, the reaction gave high yields at temperatures lower than 80 °C (Table 18, Entries 3–6), even at room temperature (Table 18, Entry 6). It was also possible to obtain good yields when the catalyst load was decreased to 0.1 mol% in 36 h at 80 °C (Table 18, Entry 7).

3. Carboxylation Reaction

The greenhouse effect and relative change in climate have been causing concern in the scientific community, public opinion, and governments for the past few decades. The massive production of carbon dioxide (CO₂) is among the principal causes of climate change [43]. The increase in CO₂ levels is attributable to many factors such as intensive agriculture, transportation, industries, combustion of petroleum-based resources, and the rise of the population. In particular, India, China, the US, Russia, Canada, and Japan are the countries with the highest values of greenhouse emissions [43,44,45].

Reducing carbon dioxide levels has become a major global concern in the current scenario. Many research groups are involved in converting CO₂ into value-added molecules [46]. For example, photocatalysis and electrocatalysis can consent the conversion of carbon dioxide into methane, methanol, and carbon monoxide [47]. Furthermore, diverse toxic carbonylation agents, such as carbon monoxide and phosgene, can be replaced by carbon dioxide for the construction of C-C and C-X bonds (X=H, O, N) [48]. Therefore, developing an efficient, inexpensive, and eco-sustainable carbon dioxide utilization method is crucial.

Unfortunately, the transformations of CO₂ are particularly difficult due to its kinetic inertia and thermodynamic stability. The primary focus is the development of catalytic systems that can activate this inert molecule. Over recent years, N-heterocyclic carbenes and their relative complexes have earned significant attention in the activation of carbon dioxide, thanks to their steric and electronic properties [49]. Moreover, compared to other catalysts, NHCs are more facile and inexpensive to develop. It has been demonstrated that there are two approaches by that CO₂ can be activated by N-heterocyclic carbene metal complexes: interaction of the π electrons of the carbon dioxide molecule with the empty d-orbital of the transition metals. In such manner, it is possible to extend the carbonaceous chain of alkynes (carboxylation of terminal alkynes) [50]; by oxidative coupling of metal complexes, carbon dioxide, and olefins to produce cyclic intermediates (2-oxazolidinone and carbonates) (Figure 16) [51,52].

Figure 16. Carboxylation reaction catalyzed by Ag/Au(I) NHC complexes reported in this review.

This paragraph of the review summarizes and analyses the results in the functionalization/activation of carbon dioxide, obtained by silver(I) and gold(I) NHC complexes.

3.1. Carboxylation of Terminal Alkynes

Alkynyl carboxylic acids are a ubiquitous class of compounds due to their great utility in medicinal chemistry and in the production of synthetic fibres [53]. Different synthetic procedures have been developed for the preparation of this class of compounds including the oxidation of aldehydes or alcohols, or hydrolysis of bromide [54,55]. The carboxylation of terminal alkynes with carbon dioxide is the most powerful method for the synthesis of propiolic acids. Zhang’s [56] and Grooben’s [57] groups reported in 2010, for the first time, that the carboxylation of terminal alkynes, with carbon dioxide, can be catalyzed by copper or copper-NHC complexes (Figure 17A,B). Furthermore, Zhang and collaborators [50] have reported the direct carboxylation of alkynes with a transition metal-free catalytic system, at 120 °C and 2.5 atm (Figure 17C). Later, Zhang et al. [58] reported the development of a ligand-free Ag(I) catalyst, active in the carboxylation of the terminal alkynes under mild reaction conditions. (Figure 17D). The main limitations of these methods were that the yields obtained were generally moderate, and the reaction conditions (temperature and pressure) were quite harsh. In Figure 17 are reported all the early developed protocols to produce propiolic acids with alkynes and carbon dioxide.

Figure 17. Protocols developed for the synthesis of substituted propiolic acids from alkynes. (A,B) copper or copper-NHC complexes; (C) transition metal-free; (D) ligand-free Ag(I) catalyst; (E) poly-NHC-Ag nanoparticles, Poly-NHC-Ag-NPs.

In 2012, Zhang and collaborators [59] reported a heterogeneous catalytic system (poly-NHC-Ag nanoparticles, Poly-NHC-Ag-NPs) 30, active in the carboxylation of terminal alkynes with carbon dioxide (Figure 17E). The synthesis of poly-imidazolium salts and its relative AgNPs catalytic system are reported in Scheme 3 [60].

Scheme 3. Preparation of heterogeneous catalytic system (Poly–NHC–Ag–NPs 30).

The nano-composite catalytic system showed excellent yields with different aryl alkynes, under ambient reaction conditions. In an initial screening the desired propiolic acid was recovered up to 98% (0.3 mol% of the Ag catalyst). Based on this interesting result, the authors tested its reusability. Centrifugation and filtering of the reaction mixture allowed for the recovery of the catalytic system. The solid residue was washed with DMF and reused in the sequent runs. More than 93% of the yield was produced every five times the catalytic system was being used, evidencing its high activity. A fraction of the catalyst was lost throughout the recovery process, which was the cause of the activity’s decline. The reaction scope was implemented testing the carboxylation reaction of different aryl alkynes (Table 19).

Table 19. Carboxylation of terminal alkynes with poly-NHC-Ag-NPs.

Entry a	R	Yield (%) b
1	H	98
3	4-Ph	96
4	4-Cl	97
5	4-OCH3	95
2	4-CH3	97
6	3-OH	95
7	4-CHO	95
8	4-CH2OH	96
9	4-CN	96
10	4-NO2	95

^a Reaction conditions: alkyne (1.0 mmol), Poly-NHC-Ag NPs 30 (0.3 mol%), Cs₂CO₃ (1.2 mmol), CO₂ (1 atm), room temperature, DMF (5 mL), 20 h. ^b GC yields.

As shown in Table 19, excellent yields were obtained with both electron-donating groups (Entries 2, 3, 5, 6, 8), and electron-withdrawing groups (4, 7, 9, 10), demonstrating tolerance to diverse functional groups (OH, CHO, CN, NO₂, etc). The authors have not observed the formation of any by-products. They affirmed that the excellent catalytic activity is due to the synergistic action of the ligand (NHC) and Ag nanoparticles. Zhang et al. proposed a possible mechanism, shown in Scheme 4.

Scheme 4. Proposed mechanism for the carboxylation reaction of terminal alkynes catalyzed by poly-NHC–Ag-NPs catalyst.

They asserted that the first stage of the cycle is the formation of metal acetylide intermediate through the deprotonation of the alkyne by the base (I). Later, the carbene carbon atom reacts with CO_2, due to its nucleophilicity, to produce an NHC-carboxylate specie (II) [61,62]. Since Louie and colleagues [63] reported the activation of CO₂ with the generation of zwitterionic species in a reversible mechanism in 2004, the authors postulated the formation of carboxylate species (32, Scheme 5). Then, the coordination of the carboxylic group, near the silver centre, induces the nucleophilic attack by the acetylide species (III). Finally, the silver acetylide species is regenerated by the alkyne deprotonation by the base. The proposed mechanism highlights the synergic crucial role between the metal centre and the poly-NHC ligand.

Scheme 5. Activation of CO₂ by NHC, observed by Louie et al. [63].

In 2016, Fang et al. [64] reported the synthesis, structural characterization and catalytic activity in the carboxylation of terminal alkynes of four Ag-NHC complexes 33a–d. The synthesis of the complexes was reported in Scheme 6; they were obtained by the reaction of the corresponding imidazolium salt with 0.55 eq. of silver oxide (Ag₂O), with the exclusion of the light, at room temperature for 48 h.

Scheme 6. Synthesis of the complexes 33a–d.

Single crystals of 33a–d were obtained by slow evaporation of a diethyl ether/chloroform solution of the corresponding silver compounds at room temperature. Surprisingly, the authors found that whereas complexes 33b and 33d had a mononuclear structure, complexes 33a and 33c revealed a dinuclear structure. The reactivity of complexes was initially explored in the reaction of phenylacetylene with carbon dioxide. The results are reported in Table 20.

Table 20. Carboxylation reaction catalyzed by Ag(NHC) complexes.

Entry a	Catalyst (% mol)	Base (Equiv.)	Yield (%) b
1	-	Cs2CO3 (1.5)	n.d.
2	33a(1)	Cs2CO3 (1.5)	82
3	33a(3)	Cs2CO3 (1.5)	82
4	33a(5)	Cs2CO3 (1.5)	68
5	33b(1)	Cs2CO3 (1.5)	81
6	33c(1)	Cs2CO3 (1.5)	81
7	33d(1)	Cs2CO3 (1.5)	82
8 c	33a(1)	Cs2CO3 (1.5)	83
9 d	33a(1)	Cs2CO3 (1.5)	69
10	33a(1)	DBU(1.5)	38
11	33a(1)	K2CO3(1.5)	20
12	33a(1)	KOtBu(1.5)	5
13	33a(1)	NaOtBu(1.5)	Trace
14	33a(1)	NaOH(1.5)	Trace
15	33a(1)	-	n.d.
16	33a(1)	Cs2CO3 (1.0)	48
17	33a(1)	Cs2CO3 (1.2)	71
18	33a(1)	Cs2CO3 (2.0)	81
19 e	33a(1)	Cs2CO3 (1.5)	43
20 f	33a(1)	Cs2CO3 (1.5)	8
21 g	33a(1)	Cs2CO3 (1.5)	37
22 h	33a(1)	Cs2CO3 (1.5)	n.d.

^a Reaction conditions: 1-phenylacetylene (2.0 mmol), CO₂ (1 atm), DMF (10 mL), room temperature, 16 h. ^b Isolated yields. ^c 40 °C. ^d 60 °C. ^e In DMSO. ^f In DCM. ^g In acetonitrile. ^h In THF. n.d. Not detected.

The authors demonstrated that the reaction could not occur without the presence of the silver catalyst (Table 20, Entry 1). They also evaluated the suitable catalytic loading for the optimization of reaction conditions. The desired propiolic acid was isolated in good yield (82%), using 1–3 mol% of 33a, in DMF, and using 1.5 equiv. of Cs₂CO₃ (Table 20, Entries 2,3). When the reaction was loaded with 5% mol of catalyst, the yield dropped, probably, as suggested by the authors, due to the ability of the Ag-NHC complexes to also catalyze the decarboxylation process. (Table 20, Entry 4). It is worth note that in the literature a few examples of decarboxylation reactions of carboxylic acids catalyzed by Ag₂CO₃ are reported [65,66]. Other silver complexes were tested in the carboxylation reaction of phenylacetylene, using 1 mol% loading; they displayed comparable activity (Table 20, Entries 5–7). Although the complex 33a showed a dinuclear structure, and the complex 33b exhibited a mononuclear structure, their time-dependent experiments were comparable. For silver complex 33a any induction time during the initial period of the reaction was observed. The authors tried to explain this behaviour by asserting that the complexes 33a and 33c, in a polar medium, such as DMF, could display a monomeric structure, due to the weak Ag^…Cl interaction [9,67]. The increase in temperature did not positively influence the reaction: when the reaction was conducted at 40 °C, the yield was mostly unvarying (Table 20, Entry 8), while a further increase in temperature (60 °C) gave yield decrease (Table 20, Entry 9). The authors then deepened the influence of the base (Table 20, Entries 1 vs. 10–15). The best results were obtained with the inorganic base Cs₂CO₃. DBU (1,8-Diazabicyclo(5.4.0)undec-7-ene) and K₂CO₃ were less efficient (Table 20, Entries 10 and 11), while KO^tBu, NaO^tBu, and NaOH were ineffective (Table 20, Entries 12–14). Based on these data, the authors asserted that the carboxylation reaction is not correlated to the basicity. However, the presence of the base is fundamental for the course of the reaction (Table 20, Entry 15). The base loading was evaluated (Table 20, Entry 1 vs. Entries 15–18), e.g.,: when 1.2 or 1.0 equiv. of Cs₂CO₃ were employed_, the quantity of propiolic acid diminished. Finally, the author explored carefully diverse solvents (Table 20, Entry 19–22). Once the best reaction conditions were assessed (1 mol% of silver complex, 1.5 equiv. of Cs₂CO₃, 1 atm of CO₂, room temperature, in DMF, 16 h), a scope of the alkyne substrates was performed. The results are summarized in Table 21.

Table 21. Carboxylation reaction with different terminal alkynes, catalyzed by silver complex 33a.

Entry a	Alkyne	Yield (%) b
1	Phenylacetylene	82
2	4-Ethynyltoluene	85
3	1-Ethynyl-4-propylbenzene	83
4	4-Ethynyl-1,’1-biphenyl	78
5	1-Ethynyl-4-methoxybenzene	84
6	1-Ethynyl-4-fluorobenzene	80
7	1-Ethynyl-3-fluorobenzene	76
8	1-Ethynyl-4-chlorobenzene	71
9	4-Ethynylbenzaldehyde	61
10	1-Ethynyl-4-(trifluoromethyl)benzene	63
11	4-Ethynylbenzonitrile	54
12	1-Ethynyl-4-nitrobenzene	64
13	1,3-diethylnylbenzene	77
14	2-ethynylpyridine	n.d.
15	2-ethynylthiophene	70
16	(Prop-2-yn-yloxy)benzene	82
17	Ethynylcyclopropane	80
18	3,3-dimethylbut-1-yne	65
19	1-hexyne	79
20	1-heptyne	81
21	1-octyne	82

^a Reaction conditions: alkyne (2.0 mmol), 33a (1% mol), solvent (10 mL), Cs₂CO₃ (3.0 mmol), room temperature, 16 h. ^b Isolated yields. n.d. Not detected.

The Ag-NHC complex 33a demonstrated remarkable catalytic performances towards different substituents. Good yields were obtained with aromatic alkynes having electron-donating groups on the phenyl ring (e.g.,: CH₃, CH₃CH₂CH₂, Ph, OCH₃, Table 21, Entries 2–5). Analogous yields were achieved with aromatic alkynes having electron-withdrawing groups on the phenyl ring, i.e.,: fluoride and chloride. (Table 21, Entries 6–8) However, a lowering of the yields was observed with aromatic alkynes bearing strong withdrawing substituents (such as CHO, CF₃, CN, NO₂, Table 21, Entries 9–12) perhaps due to marked decrease in nucleophilicity of the α carbon. When the carboxylation reaction was conducted with 2-ethynyl pyridine (Table 21, Entry 14), the corresponding pyridyl propiolic acid was not isolated from the reaction mixture, as observed by Gooßet et al. [57]. Finally, good yields had been recorded with aliphatic terminal alkynes. (Table 21, Entries 16–21).

In 2017, Verpoort et al. [68] reported the catalytic activity of a bis (N-heterocyclic carbene) Ag complex 34 (Figure 18) in the carboxylation of diverse terminal alkynes with CO₂. The results are listed in Table 22.

Figure 18. Strucuture of the bis (NHC)Ag complex 34 tested by Verpoort et al. [68].

Table 22. Carboxylation reaction with different terminal alkynes, catalyzed by silver complex 34.

Entry a	R	Yield (%) b
1	(4-MeO)-Ph	90
2	Ph-	85
3 c	HC≡C-Ph-	85
4 c	HC≡C-(CH2)3CH2-	77
5	(CH3)3Si-	72
6	(CH3)3C-	65
7	H-	40

^a Reaction conditions: alkyne (1.0 mmol), 34 (1% mol), solvent (1 mL), Cs₂CO₃ (1.2 mmol) room temperature, CO₂ (1 bar), 16 h. ^b Catalytic yield was obtained by ¹H-NMR integration, using 1,4-ethynylbenzene as the internal standard. ^c 2.4 equiv. of Cs₂CO₃.

As described in Table 22, best yields (upper 85%) were obtained with aromatic alkynes (Entries 1–3), while a sharp decrease was observed when aliphatic alkynes were tested (Entries 4–7). It should be noted that the carboxylation reaction of diynes required 2.4 equivalents of base for the formation of dicarboxylic acids (Entries 3,4).

Based on the results obtained by Zhang [59], on the synergistic effects between NHC and silver, seen above, Verpoort et al. tested a series of NHC/Ag systems (P-L1–P-L4, Figure 19) in the carboxylation reaction of terminal alkynes to give the corresponding carboxylic acids, using silver oxide as Ag source. The authors developed this series of catalytic systems, primarily to avoid the synthesis of the relevant photosensitive silver complexes, and to exploit the synergistic effects among Ag ions and the NHC-CO₂ adduct. Furthermore, in the catalytic system, different potassium salts were introduced, and the authors observed that the nature of the halogen played an important role in the catalysis. The authors have preliminary investigated the carboxylation reaction, using phenylacetylene as a standard substrate; the results are reported in Table 23.

Figure 19. Zwitterionic NHC pro-ligands P-L1–P-L4 tested in the carboxylation reaction.

Table 23. Investigation of the catalytic systems P-L1–P-L4/Ag.

Entry a	Catalytic System	Yield (%) b
1	P-L1 + Ag2O + KI	98
2	P-L2 + Ag2O + KI	94
3	P-L3 + Ag2O + KI	97
4	P-L4 + Ag2O + KI	93
5 c	AgI	83
6 d	P-L2 + Ag2O + KCl	79
7 d	P-L2 + Ag2O + KBr	96
8	Ag2O	18
9 e	-	10
10 f	-	10
11 g	-	25
12 h	P-L2 + Ag2O + KI	n.d.

^a Reaction conditions: alkyne (10 mmol), NHC/Ag system (0.0125 mmol of Ag₂O, 0.025 mmol of P-L1–P-L4, 0.025 mmol KI), DMF (40 mL), Cs₂CO₃ (15 mmol) 35 °C, CO₂ (1 bar), 24 h. ^b Isolated yield. ^c AgI (0.1 mmol). ^d 0.025 mmol of Ag₂O, 0.05 mmol of P-L1–P-L4, KX 0.05 mmol. ^e 0.025 mmol of KI, 15 mmol of Cs₂CO₃, DMF (40 mL), 35 °C, 1 bar, 24 h. ^f 15 mmol Cs₂CO₃, DMF (40 mL), 35 °C, 1 bar. ^g 15 mmol of Cs₂CO₃, DMF (40 mL), 35 °C, 1bar, 72 h. ^h Absence of CO₂. n.d. Not detected.

The activity of P-L1 and P-L3 were slightly better than their corresponding imidazolinium salts (P-L2, P-L4, Table 23, Entries 1, 3 vs. Entries 2, 4). There was no discernible pattern that could be attributed to the aliphatic chain’s length. High yields were attained utilising 0.5 mol% of the NHC salt (Table 23, Entries 6, 7); KBr could substitute KI as potassium salt efficiently. When Ag₂O was examined in the absence of NHC and KI, the carboxylic acid yield significantly decreased (Table 23, Entry 8). Only 10% of the phenyl-1-propionic acid was produced whether the base was used alone or in combination with KI (Table 23, Entries 10, 11). The authors optimized the reaction condition by evaluating the solvent effect, the time, and the loading of both base of the catalyst. The results are listed in Table 24.

Table 24. Optimization of the carboxylation reaction of phenylacetylene with P-L1/Ag system.

Entry a	Base	Solvent	Catalyst Loading (mol%)	Yield (%) b
1	Cs2CO3	DMF	0.25	98
2	Cs2CO3	DMSO	0.25	92
3	Cs2CO3	CH3CN	1.00	11
4	Cs2CO3	H2O	0.50	n.d.
5	Cs2CO3	CH3OH	0.50	n.d.
6	K2CO3 c	DMF	0.50	41
7	KOtBu	DMF	0.25	47
8 d	Cs2CO3	DMF	0.25	48
9 e	Cs2CO3	DMF	0.25	80
10	Cs2CO3	DMF	0.10	95
11	Cs2CO3	DMF	0.075	87

^a Reaction conditions: phenylacetylene (10 mmol), P-L1/Ag system (0.0125 mmol of Ag₂O, 0.025 mmol of P-L1, 0.025 mmol KI), solvent (40 mL), Cs₂CO₃ (15 mmol) 35 °C, CO₂ (1 bar), 24 h. ^b Isolated yield. ^c Cs₂CO₃ (30 mmol). ^d 12 h, ^e 18 h. n.d. Not detected.

As seen above, the solvent plays a crucial role in the carboxylation reaction (Table 24, Entries 1–5). DMF and DMSO showed to be the most suitable for this type of reaction thanks to their high polarity and aproticity. Verpoort et al. attributed the higher yields with DMF to its weak alkalinity, which has a beneficial effect in the of the alkyne deprotonation and promoting the formation of the acetylide species. Another polar and aprotic solvent was tested (CH₃CN, Table 24, Entry 3), but yields in the presence of this solvent were much lower than those obtained with DMF. H₂O and MeOH were found to be unsuitable for the carboxylation of the terminal alkynes (Table 24, Entries 4,5). The base also plays an essential role in the catalytic system as well: as seen by Fang et al. [64] Cs₂CO₃ showed superior efficiency than the other tested bases such as K₂CO₃ or KO^tBu (Table 24, Entries 6–7). Twenty four hours was the suitable time for the reaction (Entry 1 vs. Entries 8–9). The P-L1/Ag system showed interesting activity even when the catalytic loading was lowered (Table 24, Entries 10–11).

Thus, once the reaction was optimized, the authors tested the catalytic system in the carboxylation of different terminal alkynes (Table 25).

Table 25. Carboxylation reaction of terminal alkynes with P-L1/Ag.

Entry a	Alkyne	Yield (%) b
1	Phenylacetylene	95
2	4-Ethynyltoluene	99
3 c	1-Ethynyl-4-n-buthylbenzene	97
4	1-Ethynyl-4-t-buthylbenzene	99
5 c	1-Ethynyl-4-n-penthylbenzene	98
6	1-Ethynyl-4-methoxybenzene	98
7	1-Ethynyl-2-methoxybenzene	98
8	1-Ethynyl-4-penthoxybenzene	98
9	1-Ethynyl-2-fluorobenzene	72
10	1-Ethynyl-3-fluorobenzene	78
11	1-Ethynyl-4-fluorobenzene	96
12 c	1-Ethynyl-4-(trifluoromethyl)benzene	87
13	Ethynylcyclopropane	97
14	Ethynylcyclohexane	97
15	Prop-2-yn-1-ylcylohexane	97
16	3-methoxyprop-1-yne	94
17	1-hexyne	92
18	1-heptyne	98
19	1-octyne	99
20	2-ethynylthiophene	80
21 c	1-Ethynyl-4-nitrobenzene	72

^a Reaction conditions: alkyne (25 mmol), P-L1/Ag system (0.0125 mmol of Ag₂O, 0.025 mmol of NHC proligand, 0.025 mmol KI), DMF (40 mL), Cs₂CO₃ (37.5 mmol), 35 °C, CO₂ (1 bar), 24 h. ^b Isolated yield. ^c 36 h.

The results show high tolerance of the catalytic system with a wide range of terminal alkynes. Aliphatic alkynes were more active towards the carboxylation than aromatics (Table 25, Entries 13–19 vs. 1–12, 21), owing to their significant electron-donating properties. Aryl alkynes with strong electron-withdrawing substituents reacted less easily than the aryl alkynes with electron-releasing substituents (Entries 9–12, 21 vs. Entries 1–8).

To the best of our knowledge, only Gooßen et al. [69] dealt with gold-catalyzed carboxylation reaction of terminal alkynes. They tested the complex 20 (Figure 20, shown in Figure 10 as well) in the reaction of carboxylation of 1-octyne, obtaining a 9% conversion.

Figure 20. NHC-Au(I) complex 20 employed by Gooßen and co-workers.

Using DFT simulations, Maseras and Jover [70] identified the mechanism of the gold-catalyzed carboxylation process. The authors have used complex 20 as a model and propyne as olefin for the calculations (Scheme 7).

Scheme 7. Mechanism for the gold-catalyzed carboxylation, including the free energies in (kcal/mol). ‡ Transition state. Reprinted, with permission, from [70]. Copyright 2014, American Chemical Society.

By the analysis of the mechanism, reported in Scheme 7, the σ-acetylide gold complex results as the species with the lowest free energy (–62.8 Kcal/mol). The energy barrier required for the carboxylation of the alkyne is 22.9 kcal/mol. The low conversion could be attributed to the high stability of the gold acetylide complex and the middle-high energy to overcome.

3.2. Carboxylation Cyclization

The addition of carbon dioxide to alcohols and amines are two equilibrium transformations. The main limitation for these reactions is the difficulty to isolate the corresponding carbonate/carbamate, after the quenching the reaction. In fact, until few years ago, the synthesis of these compounds was conducted using phosgene, due to its higher reactivity than CO₂, avoiding the equilibrium condition [71].

Transformation of unstable scaffolds into stable products, and development of efficient catalysts have been the solution of the problems due to equilibrium condition and use of hazardous chemicals in harsh condition reaction.

In the 2007, the discovery of the catalytic activity of silver salts in the cascade carboxylation and cyclization of propargyl alcohols was an important breakthrough in the transition metal catalyzed conversion of carbon dioxide [72].

3.2.1. Reaction of Carboxylative Cyclization Catalyzed by AuNHC

In 2013, Ikariya and collaborators [73] reported the synthesis of (Z)-5-alkylidene-1,3-oxazolidin-2-ones, by carboxylative cyclization with 2 mol% of 20 in methanol, under 1 atm of carbon dioxide. Table 26 reports all the obtained results. The authors did not observe the formation of any other by-products or isomers. Furthermore, by ¹H-NMR spectroscopy and X-ray crystallographic analysis, the authors outlined the Z configuration of the C-C double bond.

Table 26. Fixation of CO₂ catalyzed by 20.

Entry a	Substrate	R1	R2	Time (h)	Yield (%) b
1	PAa	Me	Me	15	91
2	PAb	Et	Me	15	83
3	PAc	iPr	Me	15	87
4	PAd	tBu	Me	15	81
5	PAe	H	Me	15	16
6	PAf	Me	Et	48	85
7	PAg	Me	Prop	48	86
8	PAh	Me	Bn	15	83
9	PAi	Me	iPr	66	27
10	PAj	Ph	Me	48	76
11	Pak	Ph	H	48	47

^a Reaction condition: the reaction was carried out with 2.0 mmol of propargylamine substrates PAa-k and 20 (2 mol%) in MeOH (2.0 mL) under CO₂ (1 atm) at 40 °C. ^b The yields were determined by ¹H NMR.

The gold complex 20 converted various N-methylaminoalkynes into analogous urethanes with yields ranging from 81 to 91% (Table 26, Entries 1–4). The reaction between carbon dioxide and the terminal alkyne (N-methylpropargylamine) led to only 16% of the corresponding cyclic product (Entry 5). The authors associated the low yields with the formation of σ acetylide gold complex, less catalytically reactive. The conversion of the amine was reduced when the alkyl groups were replaced with aromatics, even with longer reaction times (Entries 10–11).

To gain mechanistic information, the authors evaluated the carboxylation reaction of the substrate 1-methylamin-2-butyne PAa (Table 26), using a stoichiometric amount of (IPr)AuOH 35 [74] in non-acid conditions, 1atm of CO₂, and in dehydrated THF at 40 °C. As shown in Scheme 8, they obtained the alkenylgold complex 36 in a 54% yield. The side product of the reaction is H₂O, which does not have sufficient acidity to damage the alkenylgold complex. The successive addition of an equimolar solution of acetic acid in CD₃OD to lead the urethane 37 with an 83% yield in 1 h.

Scheme 8. Synthesis of the alkenylgold complex.

Given these experimental observations, the authors proposed a mechanism of cyclization reaction promoted by the NHC gold complexes [75] (Scheme 9). In a polar medium (methanol), the gold precursor forms the catalytic species by dissociation of the chloride, whereas the carboxylation of the amine moiety (I) produces the formation of a propargylic carbamate. The triple bond of the propargylic carbamate is activated by the cationic gold(I) centre, which undergoes the nucleophilic attack by the carbamate ion on the triple bond to generate the neutral gold alkenyl compound. The subsequent addition of a proton (protodeuration) leads to the urethane II and regenerates the catalytic gold cation. This mechanism was also investigated by Lin and coworkers through DFT calculations [76]. It was found that polar protic solvents, such as CH₃OH, can stabilize the negative charge on the carboxylic moiety, promoting the catalytic reaction [76].

Scheme 9. Proposed mechanism of the carboxylation fixation of carbon dioxide by propargylamines, promoted by AuNHCX complexes. Adapted with permission from [75]. Copyright 2013, American Chemical Society.

Fujita et al. [77] conducted further studies, synthesizing a series of amphiphilic dendritic NHC gold complexes and evaluating the catalytic activity of carbon dioxide addition to propargylic amines in aqueous media. The main aim of this research was to introduce a hydrophilic group to a hydrophobic dendron in order to give the complexes amphiphilic. Tri(ethylene glycol) (TEG), penta(ethylene glycol) (PEG), and dodecyl(ethylene glycol) (DEG) were added to the dendron. The structures of such complexes are reported in Figure 21.

Figure 21. Structure of amphiphilic gold NHC complexes 38–40.

The authors of the paper examined the catalytic activity of the amphiphilic gold complexes in the reaction of carbon dioxide fixation to N-methyl-3-phenylprop-2-yn-1-amine (substrate PAj, Table 27), which lead in 15–24 h to the corresponding 2-oxazolidinone in aqueous solution at room temperature. As shown in Table 27, all the complexes are catalytically active. The NHC gold complex 39 showed the highest production of oxazolidinone (Entries 3–5). A good yield was obtained using 1% mol of the catalyst (Entries 4 and 5). A dramatical decrease in yield was recorded lowering the catalyst loading to 0.5% (Entry 6).

Table 27. Carboxylation of propargylamine in an aqueous solution catalyzed by dendritic NHC gold complexes 38–40.

Entry a	Complex	Au(%mol)	Time (h)	Yield (%) b
1	38	2	24	85
2	38	1	24	60
3	39	2	24	87
4	39	1	24	82
5	39	1	15	72
6	39	0.5	24	17
7	40	2	24	84
8	40	1	24	77
9	40	1	15	61

^a Reaction conditions: PAj (0.8 mmol), MeOH (1 M) under CO₂ (1 atm) at rt. ^b The yields were determined by ¹H NMR.

Furthermore, Fujita and collaborators [78] tested the catalytic activity of 39 in the carboxylation of various propargyl amines in aqueous media. The results are listed in Table 28. The reaction of carbon dioxide fixation was carried out for 48 h, except for the propargylamine PAj, using 1%mol of gold complex, to give the corresponding 2-oxazolidinone in acceptable to good yields. Despite the use of 2 mol% of gold complex, the reaction with terminal alkynes (Table 28, Entries 1 and 7) gave low chemical yields. However, terminal amines did not react with the carbon dioxide (Entry 8).

Table 28. Carboxylation of propargylamines catalyzed by complex 39.

Entry a	Substrate	R1	R2	Au (%mol)	Time (h)	Yield (%) b
1	PAe	H	Me	2	72	49
2	PAi	CH3	iPr	1	48	63
3	PAj	Me	Ph	1	48	82
4	PAl	4-Me C6H4	Me	1	48	87
5	PAm	Me	Bn	1	48	74
6	PAn	Et	Bn	1	48	72
7	PAo	H	Bn	2	48	20
8	Pap			2	72	n.d.

^a Reaction conditions: PA (0.8 mmol), MeOH (1 M) under CO₂ (1 atm) at rt. ^b The yields were determined by ¹H NMR. n.d. Not detected.

In 2020, Nolan and collaborators synthesized and characterized eight dinuclear gold(I) complexes (41–48, Figure 22), evaluating their catalytic activity in the fixation reaction of carbon dioxide to N-benzylbut-2-yn-1-amine (substrate PAh) [79]. All the eight complexes were active toward the cyclization of carbon dioxide at room temperature in MeOH. Table 29 reports the catalytic activity of these complexes. The complexes 41–44 (Table 29, Entries 1–4) bearing a 2,6-diisopropylphenyl group on the N-heterocyclic ligand, showed better catalytic activity than the mononuclear analogues (Table 29, Entry 9). A counter anion influence in terms of catalytic activity was not noticed. At the same time, a little drop in activity when the linker length on the NHC ligand is shortened was observed.

Figure 22. Structure of dinuclear complexes 41–48 tested by Nolan et al. [79].

Table 29. Carboxylative cyclization of PAh, catalyzed by dinuclear complexes 41–48.

Entry a	Catalyst	Yield (%) b
1	41	87
2	42	87
3	43	79
4	44	76
5	45	47
6	46	47
7	47	62
8	48	47
9	20	63

^a Reaction conditions: PAh (0.5 mmol) and dinuclear gold NHC complex (1% mol) in MeOH (0.4 mL) under CO₂ (1 atm) at room temperature for 15 h. ^b The yields were determined by ¹H NMR using 1,3,5-trimetoxybenzene as the internal standard.

3.2.2. Reaction of Carboxylative Cyclization Catalyzed by AgNHC

The carbon dioxide cycloaddition to propargylic alcohol, to achieve cyclic carbamates, mediated by silver salts, has gained more and more attention in the last years. In 2007, Yamada and collaborators reported for the first time silver catalyzed cycloaddition of carbon dioxide to propargyl alcohols (Scheme 10) [72]. They evaluated the catalytic activity of several inorganic silver salts (AgCN, AgOTf, Ag₂CO₃, AgOAc, AgBF₄, AgF, AgSbF₆, AgClO₄, AgOMs). AgOAc showed the best catalytic activity at room temperature in the incorporation of carbon dioxide, using a stochiometric amount of DBU as a base to reach cycloadduct yields ranging from good to quantitative. Other metal salts such as Rh(acac)₃, Hg(OTf)₂, PtCl₂, Pd(OAc)₂, CuCl, and AuCl were not effective in this transformation.

Scheme 10. Propargyl alchol cyclization catalyzed by AgOAc.

In 2015, Takao Ikariya et al. [80] reported, for the first time, the catalytic activity of NHC silver complexes in the carbon dioxide cycloaddition to the allenyl moiety. Initially, they tested a series of complexes of Group 11. Complex 5d (infra Figure 2) showed better catalytic activity (Table 30, Entry 1) than the gold and copper analogues (Table 30, Entries 2–3). Moreover, the silver NHC complex bearing the benzoate ion did not exhibit improved catalytic activity, and when the acetate ion moiety was replaced with the chloride ligand, it was found that conversion dramatically worsened (Entries 4 and 5). These findings imply that the carboxylation process depends critically on the production of active cationic species. Remarkably, the NHC ligand influences the selectivity of the reaction. In fact, the use of silver acetate has led to the formation of the carboxylated compound in 71% yield and the byproduct 49b in 26% yield (Entry 6). Other acetate silver complexes showed a reduced activity for carboxylation (Entries 8 and 9). As shown in Table 30 (Entries 10–16), the nature of the solvent plays an important role in the reaction rate and in the selectivity of cyclization. Aprotic solvents, such as toluene, THF, and CH₂Cl₂, compared to 2-propanol, produced low conversions of 1-benzylamino-2,3-butadiene (Entries 10–12). In MeOH and CF₃CH₂OH it was observed the formation of hydroamination product 49c (Entries 13 and 15). The authors asserted that the more acidity of these alcohol makes the allenyl moiety more susceptible to the amine group. Despite the low catalytic loading (0.1 mol%, Entry 16) the reaction of carboxylation continued in 2-propanol to give the urethane product a 77% yield with a long reaction time.

Table 30. Carboxylation of 1-(benzylamino)-2,3-butadiene.

Entry a	Catalyst	Solvent	Yield (%) b
			49a	49b	49c
1	5d	2-propanol	86	6	7
2	(IPr)Au(OAc)	2-propanol	n.d.	n.d.	n.d.
3	(IPr)Cu(OAc)	2-propanol	3	n.d.	n.d.
4	(IPr)AgOBz	2-propanol	85	6	7
5	5a	2-propanol	7	n.d.	n.d.
6	AgOAc	2-propanol	71	1	26
7 c	(ItBu)Ag(OAc)	2-propanol	69	2	26
8	(PPh3)Ag(OAc)	2-propanol	3	n.d.	3
9 d	[(S)-BINAP]Ag(OAc)	2-propanol	3	n.d.	3
10	5d	toluene	2	n.d.	2
11	5d	THF	5	n.d.	4
12	5d	CH2Cl2	50	3	4
13	5d	CH3OH	61	4	31
14	5d	t-BuOH	71	6	4
15	5d	CF3CH2OH	31	2	36
16 e	5d	2-propanol	77	5	7

^a The reaction was carried out with 1-(benzylamino)-2,3-butadiene (1.0 mmol) and the catalyst (2% mol) in solvent (1.0 mL) under CO₂ (1 MPa) at 30°C for 6 h. ^b The yields were determined by ¹H NMR using durene as internal standard. ^c 40 °C, 7.0 MPa, 15 h. ^d 5 MPa. ^e 0.1 mol% of the catalyst for 96 h. BINAP: 2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene. n.d. Not detected.

Verpoort et al. [81] tested the catalytic precursors represented in Figure 19 (infra Page 30) in the cycloaddition of carbon dioxide to propargyl alcohols, gaining the corresponding α-alkylidene cyclic carbamates, under atmospheric CO₂ pressure; the results are listed in Table 31. The authors tested Ag₂O, KI and NHC precursor as catalyst individually, observing no formation of the desirable product (Entries 1–3, Table 31). The addition of AgI to Ag₂O or the use of the only AgI ware found to be ineffective to catalyze the cycloaddition to propargyl alcohol (Entries 4–5, Table 31). Yet, the Ag₂O/KI system was able to catalyze that reaction when NHC precursor was added (Entries 6–9). The imidazolium salt with the greatest catalytic activity was P-L3. The authors have looked at the impacts of the silver salt and halide, in order to determine the ideal reaction conditions. The best catalytic system, as demonstrated in Entries 8 through 13 was composed of Ag₂O, KI, and P-L3. The catalytic system was also examined in several solvents (DMF, DMSO, CH₃CN, CH₂Cl₂, CH₃OH). The system AgI/P-L3/KI has showed excellent activity in both polar and aprotic solvents. The solvent basicity, which is likely capable of activating the hydroxyl group of substrates, is the cause of the somewhat greater activity in DMF.

Table 31. Optimization of reaction conditions.

Entry a	Catalyst	Solvent	Yield (%) b
1	Ag2O	DMF	n.d.
2	KI	DMF	n.d.
3	P-L1	DMF	n.d.
4	AgI	DMF	n.d.
5	Ag2O + KI	DMF	n.d.
6	Ag2O + KI + P-L1	DMF	59
7	Ag2O + KI + P-L2	DMF	60
8	Ag2O + KI + P-L3	DMF	65
9	Ag2O + KI + P-L4	DMF	62
10	Ag2CO3 + KI + P-L1	DMF	10
11	Ag2WO4 + KI + P-L1	DMF	n.d.
12	Ag2O + KBr + P-L1	DMF	40
13	Ag2O + KCl + P-L1	DMF	38
14	Ag2O + KI + P-L1	DMSO	41
15	Ag2O + KI + P-L1	CH3CN	n.d.
16	Ag2O + KI + P-L1	CH2Cl2	n.d.
17	Ag2O + KI + P-L1	CH3OH	n.d.
18 c	Ag2O + KI + P-L1	DMF	94

^a The reaction was carried out with Ag salts (1 mol%), KX (2% mol), NHC (2% mol), in 10 mL of solvent, at 65 °C for 3 h. 2-methylbut-3-yn-2-ol (5 mmol) was then added and reacted for 12 h at 1 bar of CO₂. ^b Yield determined by NMR, using 1,1,2,2-tetrachloroethane as internal standard. ^c Ag₂O (2 mol%), KI (4% mol), NHC (4% mol), in 10 mL DMF, at 65 °C, for 24 h. 2-methylbut-3-yn-2-ol (2.5 mmol) was then added and reacted for 24 h at 1 bar of CO₂. n.d. Not detected.

The catalytic system was tested in the reaction of carboxylation with other substrates under 1 bar of CO₂, to lead the α-alkylidene cyclic carbamates. It was observed that the steric hindrance of the substituted group has influenced the catalytic activity. Less sterically hindered propargyl alcohols exhibited better tendency to undergo the reaction of cyclization (Table 32).

Table 32. Cyclization of propargyl alcohols catalyzed by NHC proligands/Ag system P-L3.

Entry a	R1	R2	R3	Yield (%) b
1	Me	Me	H	94 (90)
2	Me	Et	H	90 (87)
3	Et	Et	H	93 (90)
4	Me	i-Pr	H	87 (85)
5 c				99 (95)
6 d				80 (77)
7 c	Ph	Me	H	25 (20)
8 c	Me	Me	Ph	25 (21)

^a The reaction was carried out with Ag₂O (2 mol%), KI (4mol%), P-L3 (4 mol%), in DMF 10 mL of solvent at 65 °C, substrate (2.5 mmol), 1 bar of CO₂. ^b Yields determined by ¹H NMR using 1,1,2,2-tetrachloroethane as internal standard. The isolated yields were shown in parenthesis. ^c 48 h. ^d 36 h.

In 2018, an interesting paper by Chen [82] and collaborators was published, in which they synthesized carbon nanotube (CNT) and graphene (GN) grafted NHC-Ag complexes as heterogenous catalysts for the cycloaddition of CO₂ to propargyl alcohol.

In Scheme 11, the synthesis of these heterogenous catalysts is represented. The composite materials were synthesized by reaction of polymerization of 3-allyl-1-vinylimidazolium chloride in presence of CNT or GN suspension. The heterogenous catalysts (Scheme 11, catalysts 50 and 51) were synthesized by reaction of corresponding materials with Ag₂O. These heterogenous complexes were tested in the cycloaddition of carbon dioxide to terminal propargyl alcohols showing an interesting activity in the formation of carbonate. As shown in Table 33, the reaction doesn’t occur in absence of the catalyst. Silver salts, like Ag₂O, Ag₂CO₃, AgOTf, AgOAc were inactive toward the transformation (Entries 1–6).

Scheme 11. Synthesis of the heterogenous catalysts 50–51.

Table 33. Formation of carbonate by cycloaddition of CO₂ to terminal propargyl alcohols using heterogenous catalysts.

Entry a	R1	R2	R3	Catalyst	Yield (%) b
1	H	Me	Me	CNT-IL	n.d.
2c	H	Me	Me	Ag2O	2
3c	H	Me	Me	Ag2CO3	2
4 c	H	Me	Me	AgOTf	1
5 c	H	Me	Me	AgOAc	n.d.
6 c	H	Me	Me	50	99
7 c	H	Me	Me	51	99
8 c	H	Me	Et	50	99
9	H	Me	Et	51	99
10	H	Me	i-Pr	50	97
11	H	Me	i-Pr	51	95

^a The reaction was carried out with propargylic alcohol (0.53 mmol); catalyst (80 mg); PCO₂ (3.0 MPa); T 80 °C; t 24 h. ^b Isolated yields based on propargylic alcohols. ^c Ag species (0.073 mmol) in the Ag catalysts are used on equimolar amount of Ag sites in the CNT-NHC-Ag. n.d. Not detected.

Very recently Hashimi and co-workers [83] reported the synthesis, the characterization, and the catalytic application of new silver carboxylate carbene complexes, in the carbon dioxide cycloaddition to propargyl alcohols and propargylic amines. The synthesis of the silver carboxylate complexes is reported in Scheme 12. As shown, the carboxylate complexes were synthesized by the preparation in the first instance, of the silver bromide complexes, followed by ion exchange to gain the silver carboxylate salts (acetate, benzoate).

Scheme 12. Synthesis of carboxylate silver carbene complexes.

Complex 52 showed the best catalytic activity. Under the optimized reaction conditions, a variety of propargylic alcohols were converted to the corresponding carbamates. In Table 34 the yields obtained using the complex 52 are reported. By the analysis of the yields, the authors observed that the presence of alkyl or aryl group on the Ph ring contributed to a slightly better yield than the ones bearing electron withdrawing group (Entries 1–8 vs. 13).

Table 34. Cyclization of various alcohols catalyzed by complex 52.

Entry a	R	Yield (%) b
1		87
2		89
3		90
4		83
5		85
6		84
7		82
8		90
9		91
10		93
11		84
12		81
13		72

^a The reaction was carried out with propargylic alcohol (0.5 mmol); CH₃CN (0.5 mL); P CO₂ (2.0 bar); 52 (1.5%mol); r.t.. ^b Isolated compounds.

Instead, the silver NHC acetate complex 53 showed better catalytic activity in the synthesis of 2-oxazolidinones by cyclization of propargylic amines than complex 52. As listed in Table 35, all the examined reactions give good yields. The reaction times vary from 1.5 to 16 h.

Table 35. Cyclization of various amines catalyzed by 53.

Entry a	R1	Yield (%)
1	Me	94
2 b	nBu	92
3 b	Cy	90
4 b		95
5 c		86
6 c		92
7 c		89
8 c		93
9 d		85
10 c		91
11 c		95

^a The reaction was carried out with propargylic alcohol (1 mmol); CH₂Cl₂ (0.5 mL); P CO₂ (balloon); 53 (0.01 mol%); r.t, 6 h. ^b 8 h. ^c 12 h. ^d 16 h.

Another important aspect, evaluated by the authors, was the recyclability of the catalysts. The complexes synthesized were insoluble in organic polar solvent, whereas the cyclic carbonate was soluble in solvent such as CH₃CN and AcOEt. This immiscibility has allowed for the easy recyclability of the complexes by filtration. In fact, decomposition of the silver complexes was not recorded, and the catalytic activity was up 96% yield after the 7th cycle.

4. Conclusions

The plethora of efficient one-pot reactions catalyzed by NHC metal complexes has expanded greatly in the past couple of decades, since the first isolation of an N-heterocyclic carbene by Arduengo. NHC complexes of silver(I) and gold(I) have received a great deal of attention thanks to their easy handling, compared to the parent coinage metal copper. This advantage, together with the wide applicability, has made possible an exponential growth of published papers. This review article focused on two particularly interesting multicomponent reactions involving alkynes, i.e.,: A³-coupling and CO₂ fixation, having as main aim to furnish an up-to-date comprehensive overview of the application of such complexes in these processes. Multicomponent reactions outcome can be strictly controlled employing a late-transition metal catalyst. Particularly, in the presence of a NHC metal complex, for the A³ coupling, reaction conditions can be easily adjusted towards a greener process, while maintaining good yields, when compared to the metallic inorganic salt. As far as carboxylation is concerned, the presence of such catalysts allows the reduction of the reaction temperatures and CO₂ pressure, making for a straightforward synthetic procedure. The undiscussed versatility of the heterocyclic ring, both from the electronic and steric point of view, together with the multitude of the counteranions available, produces a platform of tunable catalytic systems whose metal complexes’ characteristics may be tailored to the chemist’s imagination and have yet to be fully explored.