Recent Organic Transformations with Silver Carbonate as a Key External Base and Oxidant

Abstract

Silver carbonate (Ag₂CO₃), a common transition metal-based inorganic carbonate, is widely utilized in palladium-catalyzed C–H activations as an oxidant in the redox cycle. Silver carbonate can also act as an external base in the reaction medium, especially in organic solvents with acidic protons. Its superior alkynophilicity and basicity make silver carbonate an ideal catalyst for organic reactions with alkynes, carboxylic acids, and related compounds. This review describes recent reports of silver carbonate-catalyzed and silver carbonate-mediated organic transformations, including cyclizations, cross-couplings, and decarboxylations.

1. Introduction

Organic transformations using transition metal catalysts are essential synthetic techniques in total synthesis, medicinal chemistry, industrial chemistry, and chemical engineering [1]. A variety of transition metal catalysts have been developed and studied for various organic reactions, and they are generally used for selective bond formation and the interconversion of specific organic functional groups. Transition metal-catalyzed reactions can generally be classified into three types based on the role of the metal catalyst. The first class includes those in which the catalytic reaction is based on the oxidation/reduction cycle of the transition metal. As many transition metals can have more than two relatively stable oxidation states, the interconversion between oxidation states of a metal can be utilized to oxidize or reduce target molecules or functionalities. The second class of catalytic reactions are those in which the transition metal serves as a Lewis acid. The final group of organic transformations are those catalyzed by coinage metals [2]. As both Cu(I) and Cu(II) are generally stable states for copper, copper-catalyzed organic transformations have been widely studied. However, silver- and gold-promoted organic reactions are relatively rare.

Silver catalysts are generally less reactive than other transition metal catalysts; therefore, in organic reactions, silver compounds are generally used as cocatalysts or bond activators due to their Lewis acidity [3,4]. In addition, Ag(I) is one of the softest Lewis-acidic metal cations; thus, Ag(I) forms organometallic complexes with π-donor functionalities, such as alkenes, alkynes, allenes, and aromatic rings. Concurrently, Ag(I) generates relatively stable organometallic complexes with n-donor type molecules, for example, ethers, amines, and phosphines.

In the last decade, various silver-catalyzed organic transformations, such as carboxylations, halogenations, C–H bond functionalizations, cycloadditions, and oxidative couplings, have been reported [5,6,7,8]. The reported silver-catalyzed reactions were performed under relatively milder reaction conditions than the reactions by other methodologies, and silver complexes are less expensive than other rare transition metals, such as palladium, rhodium, ruthenium, and platinum.

Among the various silver species, silver carbonate (Ag₂CO₃) is not typically used as a catalyst or mediator of organic reactions, but it is known as a good oxidant (for example in the Fetizon oxidation) and inorganic base (for example in the Wittig reaction) [9,10]. Scheme 1 describes the general reactions involving Ag₂CO₃. Ag₂CO₃ enables the use of Lewis acids with internal alkynes, and readily activates alkynes to nucleophilic attack, providing the corresponding addition products. With terminal alkynes, Ag₂CO₃ generates silver acetylide intermediates through C–H functionalization, and then various reactions (for example, cross-couplings, and cycloadditions) can be used to convert these intermediates into useful organic frameworks, such as furans [11], pyrroles [12], and nitriles [13]. Additionally, Ag₂CO₃ is used as an oxidant for single-electron transfer (SET) processes to generate reactive radical species for various organic transformations, for example, the generation of acyl radicals from carboxylic acids. In addition, the basicity of the carbonate moiety can help prepare reactive partners from acidic organic molecules such as carboxylic acids, terminal alkynes, and 1,3-dicarbonyl compounds.

In this review, we summarize the recently reported Ag₂CO₃-catalyzed and Ag₂CO₃-mediated organic transformations and small molecule syntheses from 2005 to 2019 based on the reactivity of Ag(I) and the basicity of Ag₂CO₃. The focus will be on their synthesis and substrate scope as well as the principle reactivity of silver carbonate, and the substrates will also be discussed based on mechanistic clues.

2. Activation of Alkynes Using Silver Carbonate

2.1. Terminal Alkynes: Cross-Coupling Reactions

Oxidative double C–H functionalization/cross-coupling reactions are considered an attractive strategy for the synthesis of various heterocycles. The Ag₂CO₃-mediated activation of terminal alkynes is a good starting point for this heteroaromatic cyclization. In 2012, Lei and co-workers reported the direct C–H functionalization and oxidative coupling of two C–H bonds as an ideal synthetic strategy for accessing highly substituted furans (Scheme 2) [14]. Although synthetic methods for preparing substituted furans have been reported previously [15], new synthetic strategies are required to achieve selective cross coupling of two more hydrocarbons. The homocoupling of terminal alkynes occurs easily under most oxidative conditions [16]. This report shows that Ag₂CO₃ can be used as a mediator to induce C–H/C–H functionalization of terminal alkynes and 1,3-dicarbonyl compounds. This reaction affords furans with several functional groups in a facile, one-step manner. Terminal alkyne 1 can be converted to the corresponding silver acetylide intermediate by Ag₂CO₃, and furan 3 is synthesized by alkylation with 1,3-dicarbonyl compound 2 followed by oxidative radical cyclization.

In the same year, the Lei group reported a Ag-mediated, highly selective C–C/N–H oxidative cross-coupling/cyclization to construct imidazo[1,2-a]pyridines 5 from 2-aminopyridines 4 and terminal alkynes 1 (Scheme 3) [17]. This reaction is also initiated by the generation of a silver acetylide intermediate from the Ag salt and phenylacetylene; then, subsequent Ag-promoted nucleophilic attack and oxidative cyclization form imidazo[1,2-a]pyridine 5 as the product. After the reaction, the spent silver species can be recycled by filtration and treatment with nitric acid and Na₂CO₃.

As described above, oxidative C–H functionalization/cross-coupling reactions are considered an attractive strategy for the synthesis of various heterocycles. Pyrroles, as 5-membered heterocycles, are also a basic building block of numerous biologically and pharmaceutically important natural compounds [12], and the regiospecific synthesis of pyrroles is an attractive synthetic tool. The Lei group reported that pyrroles 7 containing various functional groups can be effectively synthesized by the C–H/C–H oxidative cross coupling/cyclization of terminal alkynes 1 and β-enamino esters 6 using Ag₂CO₃ as a mediator (Scheme 4) [18]. The proposed mechanism is shown in Scheme 5. Due to the effects of Ag₂CO₃, terminal alkyne 1 is primarily converted to silver acetylide 1-I; then, the nucleophilic addition of deprotonated β-enamino ester intermediate 6-I to silver acetylide 1-I delivers oxidative cross-coupling intermediate 6-II via two single-electron oxidations. The coordination of Ag(I) generated internal alkyne 6-III, which is cyclized by an intramolecular nucleophilic addition to provide cyclic intermediate 6-IV, and subsequent aromatization and protodemetallation give highly substituted pyrrole 7 as the product.

In 2014, Bi and co-workers reported an Ag₂CO₃-catalyzed cross-coupling reaction of propargylic alcohols 8 with isocyanides 9 to give 2,3-allenamides 10 (Scheme 6) [19]. Although the reaction mechanism is not clear, this reaction involves a unique β-C–C coupling and oxygen transposition of propargylic alcohols.

The Agrawal group reported the synthesis of indolizines 12 via a Ag-mediated oxidative C–H functionalization and cyclization of terminal alkynes 1 with pyridine derivatives 11 (Scheme 7) [20]. Indolizine is a basic organic building block for many alkaloids and bioactive molecules, so the development of regioselective synthetic pathways is an attractive topic in organic synthesis [21]. This reaction allows the highly selective synthesis of indolizines from readily available starting materials via a 5-endo-dig cyclization between the silver phenylacetylide generated from alkyne 1 and a chelated intermediate from the deprotonation of 2-pyridine derivative 11. After the reaction, Ag₂CO₃ can be recycled and reused.

In 2015, Lei and co-workers developed a Ag(I)-mediated selective oxidative cross coupling between C–H and P–H bonds to afford alkynyl (diaryl) phosphine oxides 14 (Scheme 8) [22]. To determine the mechanism of this reaction, the authors performed experiments with silver complexes as the starting materials. Phenylacetylide was mixed with Ph₂P(O)H and prepared silver; the reaction only provided only 17% of the desired product, but 60% of the desired product was obtained when an additional 1.0 equiv. of Ag₂CO₃ was added. When the reaction used Ph₂P(O)Ag instead of Ph₂P(O)H, only a trace amount of the product was obtained with phenylacetylene. In the presence of an additional 1.0 equiv. of Ag₂CO₃ in the same reaction, 37% of the product was obtained. With both silver phenylacetylide and Ph₂P(O)Ag, the reaction provided 30% of the desired product, and 71% of the product was produced when an additional 1.0 equiv. of Ag₂CO₃ was added.

Based on the experimental results, a mechanism was proposed as shown in Scheme 9. Silver acetylide 1-I and disubstituted phosphoryl silver species 13-I are formed from silver carbonate, and a cascade involving coordination and cross-coupling reactions via two single-electron oxidations provided alkynyl(diaryl)phosphine oxides 14.

2.2. Terminal Alkynes: Cycloaddition Reactions

The ideal method for the synthesis of substituted pyrroles is the cycloaddition of an alkyne and an isocyanide. Isocyanide-alkyne cycloaddition reactions are usually limited to use electron-deficient alkynes, and the yields are low. In 2013, two interesting papers were published on the synthesis of pyrroles via Ag₂CO₃-catalyzed cycloadditions of isocyanides and terminal alkynes. One is from the Bi group (Scheme 10, Conditions A) [23], and the other is from the Lei group (Scheme 10, Conditions B) [24]. The reaction mechanism is unclear, so these two groups explained the reaction mechanism in different ways. Based on the results of a deuterium-labeling experiment, Bi suggests that the reaction is initiated by the formation of a silver acetylide from terminal alkyne 1 and the Ag(I) catalyst, and this is followed by the 1,1-insertion of isocyanide 9 into the Ag–C bond. Protonolysis and intramolecular cyclization provide a pyrrolenine intermediate, and a 1,5-hydrogen shift gives the pyrrole. On the other hand, Lei suggests that the mechanism involves a click reaction like a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) [25], because they observed the coordination of the silver to the isocyano group by in situ IR spectroscopy of the stoichiometric reaction between ethyl 2-isocyanoacetate and Ag₂CO₃. Therefore, the Ag₂CO₃ catalyst generates both a silver acetylide and a silver isocyanide complex, and click cyclization provides substituted pyrroles 15.

In 2014, Bi and co-workers reported the synthesis of pyrroles and indolizines from the cyclization of 2-pyridyl alkynyl carbinols with isocyanides (Scheme 11) [26]. The divergent pathways are described in Scheme 12. 2,4-Disubstituted pyrroles 17a were synthesized from secondary 2-pyridyl alkynyl carbinols 16 by a regioselective [3+2] cycloaddition. Coordination of the pyridine moiety affords coordinated silver acetylide 16-I, and an additional coordination occurs with isocyanide 9 to form intermediate 16-II. [3+2] Cycloaddition affords 2,4-disubstituted pyrrole 16-III, and subsequent oxidation gives pyrrole 17a as the product. The indolizines are generated from tertiary propargyl alcohols 16. The Ag(I) catalyst reacts with terminal alkyne 16 to provide silver acetylide 16-IV, and then a 1,1-insertion of isocyanide 9 into the Ag–C bond affords acetylenic imido intermediate 16-V. Intramolecular rearrangement converts 16-V to 2,3-allenamide 16-VI, and subsequent intramolecular cycloisomerization gives indolizine 17b.

2.3. Terminal Alkynes: Reactions with Azide

In 2013, the Jiao group reported an Ag-catalyzed nitrogenation of alkynes, representing the first direct conversion of alkynes to nitriles via C≡C bond cleavage (Scheme 13) [27]. The reaction was performed with various alkynes as the starting material, including aryl-, heteroaryl-, alkyl- and alkenyl-substituted alkynes. In the proposed reaction mechanism (Scheme 14), Ag(I) simply coordinates to the alkyne, and no silver acetylide is generated. Then, the azide nucleophile adds to the activated alkyne (1-II) to form alkenyl metal complex 1-III. The protodemetallation of 1-III provides vinyl azide 1-IV, and unstable intermediate 1-V is formed by the click reaction of vinyl azide 1-IV. Upon the release of HN₃ and CH₂N₂, intermediate 1-V provides nitrile product 19.

In 2014, the Bi group reported a Ag(I)-catalyzed hydroazidation to provide 2-azidoallyl alcohols 21 from ethynyl carbinols 20 (Scheme 15) [28]. Hydroazidation is one of the most attractive routes for synthesizing vinyl azides [29]. In a study of the effects of residual water in DMSO as the solvent (Scheme 16), dry DMSO provided a mixture of product 23 and TMS-protected product 23-TMS in a 1:3 ratio. When 1.0 equivalents of H₂O was added, only the TMS-free product was obtained. When a large amount of water was added, a substantial amount of unreacted starting material 22 remained in the reaction. Based on the results of these reactions, water must play an important role in the reaction.

Based on a deuterium-labeling experiment, the Ag catalyst generates a silver acetylide from ethylnyl carbinol 20 and HN₃ by the Ag(I)-catalyzed hydrolysis of TMS-N₃ 18. HN₃ adds to the silver acetylide to give a vinyl silver intermediate, and subsequent protodemetallation gives 2-azidoallyl alcohol 21 as the product.

Unactivated terminal alkynes also provide vinyl azides via a Ag-catalyzed hydroazidation with TMS-N₃ (Scheme 17) [30]. Thus, various terminal alkynes with or without hydroxyl groups at the propargyl position can be successfully converted into vinyl azides in the presence of water.

With diynes, the generated vinyl azides can go on to react with the second alkyne moiety via an intramolecular pathway. The Bi group reported a Ag(I)-catalyzed tandem hydroazidation and alkyne-azide cycloaddition of diynes 26 to give 1,5-fused 1,2,3-triazole frameworks (Scheme 18) [31]. As discussed above, terminal alkynes readily provide vinyl azides via Ag-catalyzed hydroazidation. The remaining unreacted alkyne undergoes an intramolecular alkyne-azide 1,3-dipolar cycloaddition to give bicyclic 1,2,3-triazoles 27.

In 2015, Reddy and co-workers developed an efficient pathway for accessing 3-amino quinoline derivatives 30 from readily available 1-(2-aminophenyl) propargyl alcohols 28 (Scheme 19) [32]. The Ag(I) catalyst activates the terminal alkynes to promote the 5-exo-dig cyclization with the amine group. [2+3] Cycloaddition with azide 29 and a C–N bond migration with N₂ expulsion results in ring expansion and 6-endo cyclization. Subsequent tautomerization and dehydration afford 4-substituted 3-tosylaminoquinolines 30. This is a rare example of a 6-endo-dig reaction of a terminal alkyne, which tend to undergo 5-exo-dig cyclizations.

2.4. Internal Alkynes: Synthesis of Heterocyclic Compounds

Although internal alkynes cannot form reactive silver acetylides with Ag(I), where terminal alkynes easily can, internal alkynes can be activated by coordination. In 2005, the Ding group used internal alkynes, (Z)-2-alken-4-ynylphosphonic monoesters 31, as the starting material to access 2H-1,2-oxaphosphorin 2-oxides 32 by a Ag(I)-catalyzed cyclization (Scheme 20) [33]. Compared with using (Z)-2-en-4-ynoic acid to prepare the five- or six-membered ring products [34], this reaction provides high 6-endo-dig regioselectivity. The phosphonyl oxygen regioselectively attacks the Ag(I)-activated C≡C bond in an endo manner to give a vinyl silver intermediate, and subsequent proton transfer and protodemetallation provided 2-ethoxy-2H-1,2-oxaphosphorin 2-oxides under mild conditions. The cyclization of P–OH onto an internal alkyne is a unique reaction, and this platform provides an effective synthetic route for accessing potentially bioactive phosphorus-containing heterocycles.

In 2014, Pan and co-workers reported the construction of substituted indolizines via a Ag(I)-mediated C–H bond functionalization of 2-alkylazaarenes with alkynes (Scheme 21) [35]. We already discussed a Ag(I)-mediated synthesis of indolizines 12 from terminal alkynes 1 and pyridine derivatives 11 (Scheme 7), and the reaction was proposed to involve a 5-endo-dig cyclization between silver phenylacetylide and a chelated intermediate. Here, the authors suggested a reaction mechanism based on the results of a deuterium-labeling experiment. In the case of a terminal alkyne (Scheme 22a), silver acetylide 1-I was initially generated from alkyne 1 and Ag(I), and 2-alkylazaarene 11 was separately deprotonated by KOAc. The nucleophilic attack of anion 11-I by silver acetylide 1-I provides oxidative cross-coupled intermediate 11-II. Subsequent Ag(I)-assisted cycloisomerization and protodemetallation give indolizine product 12. In cases with internal alkynes (Scheme 22b), no silver acetylide intermediate is formed. 2-Alkylazaarene 11 undergoes single-electron oxidation to give radical intermediate 11-VI. Then, single-electron insertion into internal alkyne 33 provides intermediate 11-VII. Further oxidation of intermediate 11-VII by Ag(I) generates carbocation 11-VIII, and indolizine 34 is produced by intramolecular condensation.

A Ag(I)-mediated synthesis of alkynyl (diaryl) phosphine oxides from terminal alkyne with Ph₂P(O)H was previously described in Scheme 8. The reaction involves the generation of silver acetylide and an oxidative cross coupling. The Wu group developed a version of this reaction with an internal alkyne, namely, a Ag(I)-catalyzed synthesis of 3-phosphorated coumarins 36 via the radical cyclization of alkynoates 35 and dialkyl H-phosphonates 13 in a highly regioselective manner (Scheme 23) [36]. The reaction was completely suppressed by the presence of stoichiometric TEMPO ((2,2,6,6,-tetramethylpiperidin-1-yl)oxyl), which implies that the reaction proceeds through a radical pathway. With this experimental result in hand, a reaction mechanism was proposed, as shown in Scheme 24. Phosphorus radical 13-I is generated from diethyl H-phosphonate 13 by Ag(I), and subsequent selective addition of the P-radical to the α-position of the C=O bond in the alkynoate gives vinyl radical 35-I. Cyclization of intermediate 35-I generates intermediate 35-II, and subsequent SET from 35-II to Ag(I) releases 3-phosphorated coumarin 36.

In 2014, the Fillion group reported a Ag(I)-catalyzed 5-exo-dig cyclization of propargylic Meldrum’s acid derivatives 37 to give γ-alkylidene butyrolactones 38 (Scheme 25) [37]. The formation of the E/Z-isomers of the product is controlled by the coordination of Ag(I). The alkyne-Ag(I) complex determines the form of an E- or Z-isomer based on the 5-exo-dig cyclization through the attack of the carbonyl-O. Syn-attack of the carbonyl-O and Ag(I)-activated alkyne provides the E-intermediate; on the other hand, anti-attack of the carbonyl-O onto the Ag(I)-coordinated alkyne gives the Z-intermediate. Both intermediates undergo thermally induced cycloreversion to provide the corresponding acylketene intermediates; then, γ-alkylidene butyrolactones 38 are obtained by nucleophilic attack of the solvent.

Indoloquinolines are among the most important skeletons in the design, development, and synthesis of drugs currently on the market [38]. Most synthetic approaches rely on the use of indole or its derivatives as a coupling partner, and a new synthetic pathway for indolo[2,3-b]quinolone has been developed via a cascade radical annulation of o-alkynylthiourea [39]. In 2017, the Patel group reported a microwave-assisted Ag(I)-catalyzed cascade reaction toward indolo[2,3-b]quinolines 41 via the in situ generation of o-alkynylthioureas from 2-(phenylethynyl)anilines 39 with phenyl isothiocyanate 40 (Scheme 26) [40]. The reaction of 2-(phenylethynyl)anilines 39 and phenyl isothiocyanate 40 provides thiourea, followed by desulfurization in the presence of Ag₂CO₃, to give a carbodiimide intermediate. An intramolecular thermal cyclization drives the carbodiimide intermediate to a carbene-type intermediate; then, indoloquinoline 41 is produced by carbene C−H insertion followed by aromatization.

3. Functionalization of Carboxylic Acid Using Ag₂CO₃

3.1. Decarboxylation of Carboxylic Acids

In 2009, the Larrosa group reported a Ag(I)-catalyzed protodecarboxylation of ortho-substituted benzoic acids 42 (Scheme 27) [41]. This reaction only proceeds with ortho-substituted benzoic acids although they can have a range of functionalities, such as halogens, NO₂, alkoxides, and even unprotected phenols and amines, regardless of the presence of any functional group at positions other than the ortho-position of the benzoic acid. A proposed mechanism for the reaction involves conversion of the Ag(I) species to the silver carboxylate with benzoic acid 42. After decarboxylation of the silver carboxylate, the silver arene intermediate gives corresponding arene 43 by protodemetallation with concomitant generation of a new silver carboxylate to turn over the catalytic cycle (Scheme 28).

In the same year, the Larrosa group reported another Ag(I)-catalyzed protodecarboxylation of various heteroaromatic carboxylic acids 44 (Scheme 29) [42]. This reaction uses acetic acid as an additive. Not only α-heteroaromatic carboxylic acids but also ortho-substituted benzoic acids are converted to silver carboxylates by Ag(I), and the silver carboxylates then undergo decarboxylation. The details of the role of the heteroatoms in the decarboxylation are difficult to predict, but heteroatoms are expected to serve as activators in this reaction. Diacids were also subjected to these conditions, and they provided the corresponding monoacids with complete regioselectivity. In the case of heteroaromatic compounds, the reactivity of the carboxylic acid at the α-position is still controlled by the heteroatoms. In addition to the effect of the α-heteroatom, the conversion to the monoacid proceeds well even if an electron-withdrawing group is located at the ortho-position. Since both acids, 1,2-diacid and 1,4-diacid, underwent decarboxylation with high yields, the number of adjacent carboxylic acids seems to have no effect on the decarboxylation.

The Jafapour group reported a Ag(I)-catalyzed decarboxylation of heteroaromatic compounds (Scheme 30) [43]. In the case of coumarins, the decarboxylation is restricted to carboxylic acids containing α-heteroatoms. After tuning the solvent, even unactivated coumarin-3-carboxylic acids 46 produced corresponding decarboxylated products 47 under mild conditions with wide substrate compatibility.

3.2. Decarboxylative Functionalization and Carboxylations

Aryl halides are useful synthetic intermediates and can be used for a variety of reactions [44]. In general, boron–halogen exchange reactions have attracted attention as a synthetic pathway for accessing aryl halides. Previous common decarboxylative halogenation reactions use very insoluble NaCl and LiCl as chloride sources. In 2010, the Wu group reported a Ag(I)-catalyzed decarboxylative halogenation of benzoic acids in the presence of Cu(II) halides to provide the corresponding aryl halides (Scheme 31) [45]. Cu(II) halides are inexpensive organometallic reagents and readily available halide sources with superior solubility in organic solvents.

Decarboxylation can lead to changes in the functional groups on the starting material as well as the formation of new C−C bonds. Muthusubramanian and co-workers reported a Ag-catalyzed acylation of pyridine N-oxides 49 by α-oxocarboxylic acids 50 in 2014 (Scheme 32) [46]. Through this reaction, various aryl ketones can be synthesized by effectively promoting the acylation at the C-2 position of the pyridine. When this reaction was conducted in the presence of TEMPO, the acylated TEMPO adduct was formed, indicating that the reaction proceeds through an acyl radical intermediate. Based on this result, the reaction may start by generating a silver dicarboxylate intermediate, and then the acyl radical intermediate is generated by the release of CO₂ and a Ag(I) carboxylate. A new C−C bond between the acyl radical and pyridine N-oxide 49 was generated by a radical addition reaction, affording acylated pyridine N-oxide 51 as the product.

In 2014, Qi and co-workers reported Ag-catalyzed decarboxylative acylation of arylglyoxylic acids 50 with arylboronic acids 52 (Scheme 33) [47]. This Ag₂CO₃-catlayzed decarboxylation enables the synthesis of ketones 53 with aromatic rings bearing various functional groups. The most useful feature of this reaction is not only the fact that the arylglyoxylic acid bears a carboxylic acid but also the decarboxylative acylation that occurs when a phenylboronic acid has a carboxylic acid. The reaction pathway may be initiated by a free radical because no product was generated in the presence of TEMPO. Acyl radicals can be prepared by decarboxylation of silver carboxylate, and subsequent radical transformation can provide cross-coupled diaryl ketone 53.

Among the various C1 insertion reactions, CO is the most common acceptor for generating new acyl radicals through carbonylation. Isocyanide is also a radical acceptor for imidoyl radical formation. In recent years, decarboxylations of carboxylic acids using transition metals have contributed significantly to the formation of various C–C bonds and C–heteroatom bonds [48]. The Lei group reported an Ag-mediated oxidative radical decarboxylation-cyclization of α-oxocarboxylates 55 and isocyanides 54 to give 6-acyl phenanthridines 56 (Scheme 34) [49]. In the proposed mechanism (Scheme 35), acyl radical 55-I is formed by oxidative radical decarboxylation in the presence of Ag₂CO₃ as a catalyst. Then, radical addition to isocyanide 54 provided imidoyl radical 55-II. The intramolecular cyclization of imidoyl radical 55-II then gave cyclohexadienyl radical 55-III, and SET from Ag(I) provides 6-acyl phenanthridine 56 as the product.

In 2016, the Kim group developed an Ag-mediated temperature-controlled acyloxylations and subsequent hydrolysis for hydroxylation (Scheme 36) [50]. At lower temperature (100 °C), various esters 59 were synthesized from 10-bromobenzo[h]quinoline 57. Interestingly, at higher temperature (150 °C), ester products 59 were hydrolyzed to 10-hydroxybenzo[h]quinoline 60. 2-Methylbenzoic acid showed the best conversion in this hydroxylation. The silver species activated the carboxylic acid through silver benzoate formation, and the two-step acyloxylation and hydrolysis were confirmed by NMR spectroscopy.

4. Miscellaneous

Leblanc’s deamination of hydrazides is a useful reaction using Zn and acetic acid [51]. In general, hydrazides are converted into hydrazines instead of generating the corresponding amines from transition metal-catalyzed hydrogenolytic N–N bond cleavage [52]. In 2002, the Cho group reported a Ag(I)-mediated deamination of N-Boc aryl hydrazines 61 to afford N-Boc aryl amines 62 (Scheme 37) [53]. When an electron-donating group was present on the substrate, the corresponding products were obtained in high yields within relatively short reaction time (2 h). When an electron-withdrawing group was present on the substrate, the required reaction time increased to over 48 h (NO₂) or 72 h (CO₂Me) and the yields were relatively low.

The construction of C−N bonds in heteroaromatic compounds is important in the fields of biological, pharmaceutical, and materials science [54]. Although hydroamination [55] and oxidative amination [56], for the formation of C−N bonds, have been studied in great detail in recent decades, the direct installation of amino groups or their surrogates into aryl or alkyl C–H bonds is still challenging. In 2009, the Chang group reported a Ag-mediated amination of benzoxazoles 63 using formamides 64 or their parent amines (Scheme 38) [57]. The reaction gives 2-aminobenzoxazoles 65 with various functional groups by the regioselective formation of C–N bonds through the direct C(sp²)–H functionalization of heteroarenes.

A possible reaction mechanism is shown in Scheme 39. First, the acid promotes the decarbonylation of formamide 64 to give corresponding secondary amine 64-I. Secondary amine 64-I reacts with protonated benzoxazole 63-I to form 2-amino benzoxazoline intermediate 63-II. Finally, Ag₂CO₃ facilitates rearomatization to provide 2-aminated benzoxazole 65.

Mukhopadhyay reported a Ag(I)-mediated synthesis of diverse 1,2,4,5-tetrasubstituted imidazoles 68 via the tandem C_α(sp³)–H bond functionalization of primary amines 67 and oxidative C–N cross-coupling reaction (Scheme 40) [58]. Although the reaction required stoichiometric Ag₂CO₃, the recycled silver reagent provided the product in good yield without any loss of activity.

According to the proposed mechanism (Scheme 41), the reaction is initiated by the generation of imino ketone 66-I from diketone 66 and primary amine 67. Ag(I)-mediated C–H functionalization then gives intermediate 66-II, and the subsequent addition of another equivalent of amine 67 provides diamine intermediate 66-III. Finally, the silver-mediated oxidative cyclization of 66-III gives imidazole product 68.

In 2015, the Youn group reported the silver(I)-mediated synthesis of diverse substituted indoles via the C–H amination of 2-alkenylanilines 69 (Scheme 42) [59]. Interestingly, the products are dependent on the reaction solvents. In DMF, indoles 70 with R¹ at the 2-position are selectively obtained; however, mixtures of 2- and 3-substituted indoles are observed when heptane is used as the solvent. To elucidate the reaction mechanism, the reaction was performed in the presence of TEMPO and BHT (butylated hydroxytoluene). In the absence of radical scavengers, the reaction was completed in 30 min, but it took 3 h for the reaction to reach completion with 1.0 equiv. of TEMPO. With 1.0 equivalent of BHT, 80% of the starting material remained unreacted after 24 h. Based on the results of the reactions with radical scavengers, the reaction should proceed through a radical pathway. According to the proposed mechanism, a nitrogen radical cation is generated from substrate 69 with Ag(I) salt by a SET; then, the nitrogen radical undergoes an intramolecular electrophilic addition to the alkene to provide a benzylic radical with the loss of a proton. A benzylic carbocation is generated by a SET from the benzylic radical to Ag(I), and subsequent deprotonation affords desired indole product 70.

The isocyanide group has the similar reactivity as carbenes, making them useful reagents for generating new C–C bonds, and they are used as building blocks in organic synthesis [60]. In addition, isocyanides have reactivities similar to multicomponent reactions, and they are often used for C–H functionalization reactions. In 2015, the Bi group reported a silver-catalyzed cross coupling of isocyanides 72 and active methylene compounds 73 to access various β-aminoenones 74 and tricarbonylmethanes 75 by a radical process (Scheme 43) [61].

To determine the reaction mechanism, both isotope-labeling studies and control experiments with radical scavengers were performed, and the reaction did not proceed in the presence of radical scavengers. Based on the deuterium-labeling experiments, hydrogen atom transfer occurred from the α-hydrogen of methylene compound 72 to the hydrogen on the olefin of product 74. In the ¹⁸O-labeling experiments, ¹⁸O₂ provided a high degree of ¹⁸O-incorporated product 75, but H₂¹⁸O did not produce any ¹⁸O-incorporated 75. Based on these experimental results, a plausible mechanism was proposed as described in Scheme 44. Ag₂CO₃ abstracts a proton from 73 due to its basicity, and subsequent oxidation by Ag(I) generates radical intermediate 73-I. Ag₂CO₃ has a dual role as a base and a one-electron oxidant. At the same time, Ag₂CO₃ coordinates to isocyanide 72 to form 72-I. The coupling reaction between radical 73-I and silver complex 72-I produces imidoyl radical 72-II. With an aromatic isocyanide, imidoyl radical 72-II can provide imine intermediate 72-IV by abstracting a H atom from the generated AgHCO₃ during the one-electron oxidation or by a 1,2-H migration to form stable tricarbonylmethenyl radical 72-III followed by abstraction of an H atom from AgHCO₃. Imine 72-IV gives β-aminoenone 74 by tautomerization. With tert-butyl isocyanide, radical 72-II is converted to hydroperoxide 72-V by oxygenation. Hydroperoxide 72-V is reduced by Ag(s) to form oxyanion intermediate 72-VI, and the protonation gives tricarbonylmethane 75 as the product.

Zou and co-workers reported a silver-catalyzed direct C(sp²)–H phosphorylation of indoles in the presence of Mg(NO₃)₂ leading to phosphoindoles (Scheme 45) [62]. Ag₂CO₃ is used as an oxidant and Mg(NO₃)₂ is used as an additive to form a new C–P bond. The reaction occurs by the addition of the electrophilic phosphorous radical to the available C(sp²)–H position of the indole, followed by a SET by Ag(I) and aromatization by deprotonation to give the phosphoindole product.

Recently, the Bi group reported the Ag(I)-catalyzed synthesis of 1,2,4,5-tetrasubstituted pyrroles 80 via the cascade reaction of β-enaminones 78 and isocyanoacetates 79 (Scheme 46) [63]. β-Enaminones are used as building blocks in a variety of reactions and are easily obtained. One of the key features of β-enaminones is their tautomeric equilibrium with β-ketoimines. As β-ketoimines are a minor product, imines are present in this equilibrium system.

To investigate the reaction pathway, a deuterium-labeling experiment was performed using 2.0 equiv. of D₂O. As shown in Scheme 47, deuterium-labeled pyrrole 80-D was obtained, and the reaction should involve a proton transfer between the imine-metal complex and D₂O. Based on this experimental result, the reaction may be initiated by the deprotonation of isocyanoacetate 79 by basic Ag₂CO₃ to form an α-metalated isocyanoacetate. Then, [3+2] dipolar cycloaddition with β-ketoimine follows, and the β-ketoimine was derived from β-enaminone 78. The retro-hetero-Michael addition ring-opens the 2-imidazoline (78-I) to give the imidamide intermediate, and then a cascade involving nucleophilic addition, proton transfer, and dehydration provides highly substituted pyrrole 80 as the product.

In 2017, Xu and co-workers developed a silver-catalyzed chemoselective [4+2] annulation of aryl and heteroaryl isocyanides 72 with α-substituted isocyanoacetamides 81 to afford pyridone-fused carbo- and heterocycles 82 (Scheme 48) [64]. To determine the reaction mechanism, the reaction was performed with a ¹³C labeled isocyanide group in 72, and the NMR spectrum showed the benzo[h]quinolone product 82 with ¹³C at the 2-position. This result indicated that an α-amidoketenimine is a likely reaction intermediate.

Based on the ¹³C-labeling experiments, a mechanism was proposed as described in Scheme 49. Ag₂CO₃ abstracts a proton from isocyanoactamide 81 and coordinates to the isocyanide moiety. Another equivalent of Ag₂CO₃ coordinates to isocyanide 72, and the subsequent C–C coupling occurs via a nucleophilic attack and elimination to generate amidoketenimine 72-VII. The rearrangement of α-amidoketenimine 72-VII to α-imidoylketene 72-VIII occurs via a 1,3-amino migration. Subsequent 6π electrocyclization and 1,3-proton shift convert 72-VIII to quinolone 82. In this reaction, a catalytic amount of Li₂CO₃ was used as an additive to promote the regeneration of the Ag₂CO₃ catalyst.

In 2017, the Xu group developed a formal [3+2] cycloaddition of α-trifluoromethylated methyl isocyanides 84 and aldehydes 83 for the silver-catalyzed divergent synthesis of trifluoromethylated heterocycles (Scheme 50) [65]. With imines or acrylonitriles instead of aldehyde 83, the reaction produces the corresponding imidazoles or pyrrolines as the major products. Ag(I) coordinates to isocyanide 84, then DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) abstracts a proton to form the carbanion nucleophile. A formal [3+2] cycloaddition, which consists of the nucleophilic addition of the carbanion from the isocyanide to aldehyde 83 and cyclization, affords an oxazoline silver complex; then, protodemetallation gives oxazoline 85.

In 2017, Wang and co-workers reported the synthesis of pyrroles via a tandem Ag-catalyzed 1,3-dipolar cycloaddition and BPO (benzoyl peroxide)-mediated oxidative dehydrogenative aromatization (Scheme 51) [66]. Ag₂CO₃ facilitates the [3+2] cycloaddition of the 1,3-dipolar intermediate generated from compound 86 by deprotonation of the α-position with alkene 87 to form a tetrasubstituted pyrrolidine. Peroxide abstracts a H atom from the α-position of the pyrrolidine, then two oxidations, which each consists of a SET and tautomerization, provide highly substituted pyrrole 88.

5. Conclusions

In this review, we summarized the recent studies and developments in Ag₂CO₃-catalyzed/mediated organic transformations. Silver carbonates were employed as either external bases for activating acidic molecules or an external oxidant for turning over catalytic cycles. Notably, heteroaromatic compounds can be elegantly synthesized using silver carbonate to combine heteroatom-containing fragments and more than two carbon skeletons through alkyne activation. At the same time, silver carboxylate can be generated from the simple reaction between silver carbonates and various carboxylic acids. The following cross-couplings and decarboxylative reactions were investigated.

Despite the substantial progress and important advances described in these reports, there is still significant room for improvement at the present level. For example, alkene-related substrates cannot be efficiently activated by silver carbonate. The utilization of an alkene could expand the possible synthetic targets of these silver carbonate-catalyzed reactions. Further detailed studies on the transmetallation from silver to other transition/main group metals should be conducted. In addition, detailed mechanism studies, including the structural determination of various intermediates should be performed. We hope that this review will inspire the development of various silver carbonate-catalyzed organic reactions and other related methodologies.