The formation of carbon–carbon and carbon–heteroatom bonds using silver tetrafluoroborate as a promoter

1 Introduction

Transition metal promoters, widely used for carbon–carbon, carbon–heteroatom and heteroatom–heteroatom bond formation, are active areas of research in organic chemistry. Silver salts, particularly AgBF₄ (a Lewis acid, a white deliquescent crystal inorganic salt), have been used to form carbon–carbon and carbon–heteroatom bonds under mild and environmentally friendly conditions and in good yields (Chen et al., 2010; Steynberg et al., 1998; Barrett et al., 1989). The importance of AgBF₄ promoted rearrangements in organic synthetic chemistry has grown significantly over the last four decades (Paquette and Stowell, 1971). A comprehensive search revealed reviewed papers (Álvarez-Corral et al., 2008; Weibel et al., 2008, 2010a,b; Grant and West, 2010; Belmont, 2010; Kawasaki and Yamamoto, 2010; Driver, 2010; Lovely, 2010; Li and He, 2006; Kantorowski and Kurth, 2000) in which varieties of silver-mediated syntheses, including AgBF₄-promoted reactions, were summarised. Weibel et al. (2008) comprehensively reviewed a number of articles (Kinsman et al., 1987; Mitasev and Brummond, 2006; Gallagher et al., 1991; Lathbury and Gallagher, 1985, 1986; Davies et al., 1992; Lathbury et al., 1989) that demonstrate interesting AgBF₄-promoted hetero-cyclisations through C–N bond formations to provide optically active compounds. Kantorowski and Kurth (2000) reviewed two articles that described the ability of AgBF₄ to promote reactions that afford ring expansion to seven-membered rings via BF₄⁻ anion stabilised intermediates.

Silver tetra-fluoroborate (AgBF₄) has interesting properties that are attributed to the anion (BF₄⁻), but this non-basic, non-nucleophilic, anionic BF₄⁻ ion has been assumed not to take part in identified reactions (Honeychuck and Hersh, 1989; Rosenthal, 1973) and it is speculated that it stabilises positively charged intermediates (Achilonu et al., 2008). Nevertheless, the participation of BF₄⁻ in fluorination of compounds has been recorded (Chen et al., 2010, 2012; Cochrane et al., 2013; Wang et al., 2013a,b, 2010; Tang and Ritter, 2011; Shibata et al., 2010; Kirk and Othmer, 1966). Another noteworthy property of AgBF₄ is its ability to act as a moderately strong oxidant (one-electron abstraction) (Achilonu et al., 2008). AgBF₄ is soluble in H₂O, diethyl ether, tetrahydrofuran (THF), toluene and nitromethane, moderately soluble in benzene and cyclohexene, and insoluble in cyclohexane (Sharpe, 1952). However, when a polar solvent such as acetonitrile or water is used in a reaction system involving AgBF₄, the solvent binds and deactivates the Ag+ ion that is supposed to be the driving force of the reaction.

The salt is commonly used to replace halogens. The abstraction of the halide is driven by characteristic precipitation of the appropriate silver halide while activating the actual catalytic species (Broka and Gerlits, 1988). Its importance in cyclisation reactions has also been widely demonstrated (Luo et al., 2005; Liu et al., 2010). In the present review, we summarise the role of AgBF₄ in activating oxygen and sulphur leaving groups, in oxidative coupling reactions via hydride abstraction, as a reaction promoter through halide abstraction and Ag(I) halide formation, and activity in stereo-selective and regiospecific halogenation reactions. We also considered AgBF₄ mediation in heterocyclisation reactions and ring-opening and subsequent cyclisation reactions. Furthermore, we recapitulated complexation with strained σ-bonds with enhanced p character, and the activities of the BF₄⁻ anion in organic synthesis. The use of AgBF₄ in heteroatom–heteroatom bond-forming reactions (Álvarez-Corral et al., 2008; Weibel et al., 2008; Grimaldi and Cormons, 1989) and in formation of complexes falls outside the scope of this review and will therefore not be considered.

2 AgBF₄-promoted activation of oxygen and sulphur containing leaving groups

The affinity of dimethyl(methylthio)-sulphonium tetrafluoroborate (DMTSF) and AgBF₄ towards oxygen and sulphur has been exploited to activate the benzylic C–S and C–O ether leaving groups of flavan-3-ol analogues for carbon nucleophiles. This property has been explored to create good routes to obtain procyanidins 1 under neutral reaction conditions. Trost et al. (1981, 1985) and Barrett 1989 demonstrated the effectiveness of DMTSF and AgBF₄ in activating benzylic thioether bond of flavan-3-ol for C–C interflavanyl bond formation. The studies of Thompson and coworkers (1972) revealed that reactions of thiophilic Lewis acids with 4β-benzylsulphanylepicateehin and catechin activator AgBF₄ afforded procyanidin B-1 in improved yield of 38% over DMTSF activator that afforded 22%. Studies by Van Rensburg et al. (1996, 1997) described successful activation of benzylic C–S bond of a benzylsulphanyldihydrochalcone towards the formation of a C–O bond in the synthesis of dihydroflavonols using AgBF₄. Steynberg et al. (1998) recorded development of methodologies for C–C interflavanyl bond formation under neutral conditions. The optimised protocol involved treating a mixture of 4β-benzenesulphanylepicatechin 2 and catechin 3 in THF with AgBF₄ (2.5 equiv.) for 1 h at 0 °C to obtain procyanidin B-1 in 38% yield (Scheme 1). The formation of 4β-interflavanyl bond is explicable by the thiobenzyl ether being converted by the AgBF₄ into relatively stable carbocationic intermediate allowing regioselective attack of the nucleophile via C-8 where the HOMO displays maximum amplitude and the stereoselectivity by approach from the sterically least hindered side.

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Scheme 1

Interflavanyl bond formation in procyanidins under neutral conditions.

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Oligomers larger than the tetramer are poorly or not accessible. Favourable chain extension protocols involve activation of 4-(benzylthio)catechin and epicatechin by DMTSF or, preferably by AgBF₄. This protocol has exclusive virtue of forming 4 → 8-interflavanyl linked products. On the other hand, a 2-mercaptobenzothiazole is used to avoid the offensive odour associated with 4-thio derivatives. Condensation of 4 and 5 in dry THF in the presence of anhydrous AgBF₄ at 0 °C resulted in the formation of 4β → 8-dimer 6 (56%), (4β → 8)₂-trimer 7 (14%) and 3-O-4-dimer 8 (5%), as presented in Scheme 2. However, the undesired intervention of the 3-hydroxyl group in the chain elongation process could be avoided by protecting this 3-OH group in both the electrophilic 2 and the nucleophilic 3 reaction partners. Additionally, attempts to improve yield with molecular sieves were ineffective. Interestingly, vacuum-drying the AgBF₄ immediately before the reaction afforded a series of oligomers ranging from the trimer to the octamer were isolated in a combined yield of 91%. No 4 → 6-linked products were found (Kozikowski et al., 2003).

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Scheme 2

Synthesis of procyanidin oligomers using the 4-[(2-benzothiazolyl)thio] derivative.

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AgBF₄ was used to activate OH groups to synthesise the ether-linked proanthocyanidins, proteracacinidin and promelacacinidin (Bennie et al., 2000; Foo, 1989; Coetzee et al., 1998a,b). The protocol involved treating a mixture of the epioritin-4β- 9 and 4α-ols 10 in dry THF at 0 °C with AgBF₄ for 90 min under nitrogen before the reaction was quenched with water. After work-up and purification processes including acetylation, the expected products, epioritin-(4β → 4)-epioritin-4α-ol 11 (9%) and epioritin-(4β → 3)-epioritin-4α-ol 12 (8%), accompanied by a C–C-linked compound, epioritin-(4β → 6)-epioritin-4α-ol 13 (7%) were obtained as the octa-O-acetyl derivatives (Scheme 3). Formation of 11 and 12 could be attributed to the activation of the reactive axial C-4 hydroxyl group of 10, coupled with the outstanding stable equatorial benzylic OH group of 9 serving as the ambient nucleophile. On the other hand, the earlier work by Coetzee et al. (1998a,b) using AgBF₄ to activate the free phenolic epioritin-4b-ol 10 towards self-condensation resulted in isolating 12 and 13 from a complex reaction mixture. The stereochemistry of the products can be explained in line with neighbouring group mechanism triggered by interaction of the Lewis acid and the near-axial C-4 hydroxyl group of the flavan-3,4-diol 10 (Coetzee et al., 1998a,b).

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Scheme 3

Synthesis of ether-linked proteracacinidins 11 and 12 and the C–C coupled analogue 13.

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Furthermore, the fact that AgBF₄ activates S-containing leaving groups was utilised to cleave the S–C bond and obtained S-octylethanethioate 16 in the presence of acetyl chloride 15 as a trapping agent. It is thus purported that the silver metal complexed with the carbonyl to assist the reaction. Typical experimental protocol involved treatment of 2-(trimethylsilyl)ethyl sulphide 14 (91.4 mg, 0.37 mmol) and 15 (0.5 mL) in dry dichloromethane (CH₂Cl₂) (2 mL) under argon with AgBF₄ (75 mg, 0.39 mmol) for 5 min. The reaction mixture diluted with CH₂Cl₂ and saturated aqueous NaHCO₃, filtered through celite, the filtrate (CH₂Cl₂) dried over Na₂SO₄ and concentrated to obtain octyl thioacetate in good yield (64.6 mg, 93%) (Scheme 4) (Grundberg et al., 1999).

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Scheme 4

Conversion of 2-(trimethylsilyl)ethyl sulphide into a thioester.

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Thioglycosides are usually activated by NIS/TfOH or NIS/TMSOTf. The glycosyl acetates are commonly activated by BF₃⋅Et₂O, while the glycosyl donors such as glycosyl bromides, chlorides, trichloracetimidates, and seleno glycosides are normally triggered by freshly activated AgOTf. Unfortunately, the use of AgOTf is limited by the rigours of dehydration processes to obtain a freshly activated AgOTf before a successful reaction could be conducted. Excitingly, AgBF₄ required no prior azeotropic dehydration before usage, and thus makes it preferred reaction promoter over AgOTf in glycosyl synthesis. Accordingly, AgBF₄ has been identified as a facile and excellent promoter for the activation of various glycosyl donors such as glycosyl halides, trichloroacetimidates and thioimidates (Pornsuriyasak and Demchenko, 2006; Kaeothip et al., 2008). Kaeothip et al. (2008), demonstrated that glycosylthioimidate 18 could be selectively activated by AgBF₄ (20–50 mol%) while the S-ethyl moiety of the glycosyl acceptor 17 remained inert. The activated 18 then couples with the 17 to form intermediate dissacharide 19. On addition of 2.0 equiv. of N-iodosuccinimide (NIS), the -SEt moiety of 19 was readily activated, and following the addition of a new acceptor (methoxy glycoside 20) to the reaction system, trisaccharides 21 was afforded in 72% yield (Scheme 5).

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Scheme 5

Synthesis of trisaccharides 21.

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Wang et al. (2013) described AgBF₄-improved synthesis of capuramycin: demonstrating the effectiveness of AgBF₄ in activation of thioglycosides 23 in the mannosylation of uridine derivatives 22. The authors found that α-selective mannosylation of 22 with 23 was only achieved through the combination of NIS and AgBF₄ in CH₂Cl₂ at low concentration (0.05 M) and long reaction time (16 h) to afford 24 exclusively in 90% yield. On investigation of the activity of AgBF₄ on different substrates, treatment of uridine protected by monomethoxydiphenylmethoxylmethyl (MDPM) 22a and thioglycoside 23a with the same NIS/AgBF₄, did not provide the desired product but the starting material 24a was completely consumed to form complex mixtures (Scheme 6) (Kurosu et al., 2009; Wang et al., 2013a,b).

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Scheme 6

AgBF₄ α-selective mannosylation of 22 with thioglycoside 23.

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Reacting a THF solution of 25 at room temperature with AgBF₄ activates an intramolecular Mannich reaction, leading to efficient 5-endo-trig cyclisation to furnish the tetra-cyclic compound 26 with an exo-oriented aldehyde function in 88% yield after 6 h. The reaction protocol involved addition to a THF (6 mL) solution of silyl enol ether 25 (137.7 mg, 0.164 mmol), AgBF₄ (57.6 mg, 0.294 mmol) at room temperature. The mixture was stirred at room temperature for overnight, and quenched with saturated aqueous NaHCO₃ (20 mL) and ethyl acetate (50 mL). After work-up and chromatographic purification, tetracyclic aldehyde 26 (89.6 mg, 88% yield) was obtained as foam (Scheme 7). The AgBF₄ served as an activator of both the electrophilic and nucleophilic moieties leading to the efficient 5-endo-trig cyclisation (Wu et al., 2008, 2009).

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Scheme 7

Construction of the tetra-cyclic ring of quinocarcin.

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3 AgBF₄-promoted oxidative coupling reactions driven by hydride abstraction

AgBF₄ can activate C–H groups between a carbonyl and aryl functional group, affording a novel synthesis of proanthocyanidins 29 and 30 (Scheme 8) from 3-oxo-flavans 27, accessible from readily available flavan-3-ols 28 via Dess-Martin periodinane oxidation, thus circumventing the need for C-4 functionalisation. In contrast to flavan-3-ol based syntheses, where the C-3 configuration determines the C-4 configuration, the 3-oxo-flavans have no stereochemistry on C-3 and the C-2 configuration determines absolute configuration on C-4, giving access to hitherto synthetically unavailable 3,4-cis procyanidins. Standard coupling method involved a solution of tetra-O-methyl-catechin (0.435 mmol) in THF (3 mL), added dropwise to a mixture of AgBF₄ (1.1 mmol) and tetra-O-methyl-3-oxocatechin (0.145 mmol) in THF (3 mL) and refluxed under nitrogen for 4 h. Filtration on SiO₂ and purifying with silica gel TLC yielded the desired products (Achilonu et al., 2008; Achilonu, 2009).

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Scheme 8

Condensation reaction between 27 and 28.

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The requirement of an excess of AgBF₄ and the observation of a silver mirror (reduction of Ag¹ to Ag⁰) may indicate an oxidative mechanism (Scheme 9).

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Scheme 9

Proposed mechanism for oxidative synthesis of 29 and 30 based on the model reaction.

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The BF₄⁻ anion probably assists in stabilising the 4-carbocation C via the quinone methide tautomer E. Another major advantage of this synthesis is that no self-condensation was observed, thus no multiple by-products, as is the case with the conventional syntheses based on a flavan-3-ol with a C-4 leaving group as exemplified by Schemes 2 and 3.

The use of silver as an oxidation agent has been summarised (Álvarez-Corral et al., 2008; Weibel et al., 2008) and will not be comprehensively reviewed here. Hirao et al. (2000), described oxidant-induced coupling reaction between organozinc compounds. Studies have shown cross-coupling reactions of organozinc reagents promoted by transition metal salts as versatile synthetic tools in organic syntheses (Oshima, 1991; Erdik, 1992). AgBF₄ is a useful oxidising agent that gives cross-coupling compound, probably via a one-electron oxidation process. When 6.0 equiv. of AgBF₄ was used instead of the oxovanadium(V) compound, selective cross-coupling reaction between alkyl groups and o-methoxy-substituted aryl groups occurred. Metal silver, Ag(0), was detected in the reaction mixture, suggesting that the cross-coupling reaction is induced by one-electron oxidation with Ag(I). Typical protocol includes the cross-coupling of organo-zinc compounds (Hirao et al., 2000), where the mild nature of AgBF₄ gave good yields. In their representative procedure, n-BuLi (0.75 mmol, 0.49 mL, 1.54 M in hexane) was added to a stirred solution of arylbromide 39 (0.68 mmol) in dry ether (1.4 mL) under argon at room temperature to generate the corresponding aryllithium. After 10 min at room temperature, Et₂-Zn (0.75 mmol, 0.75 mL, 1.0 M in hexane) was added drop-wise to the resulting solution at 0 °C. Ten minutes later, at the same temperature, the resulting solution containing intermediate compound A was added to a solution of AgBF₄ (801 mg, 4.1 mmol, 6.0 equiv.) in dry ether at 0 °C. The mixture was stirred for 2 h at room temperature. After work-up and purification by column chromatography on silica gel, 32 (65 mg, 70%) and 33 (3 mg, 4%) were obtained (Scheme 10).

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Scheme 10

Cross-coupling reaction of triorgano-zincates A using AgBF₄.

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4 AgBF₄-promoted synthesis driven by halide abstraction

A novel synthetic approach to synthesise carbapenems utilising aza-Cope-Mannich cyclisation was recorded in 1995 (Sakurai et al., 1995). The success of this preparation involved the introduction of a carbon nucleophile into the azetidinones with a leaving group at C-4; suitable for generation of acyliminium intermediate. Authors’ first attempt was introducing acetoxy moiety in the C-4 of 34 and several trials to activate the acetoxy group using a variety of acetoxy activating promoters (Me₃SiOSO₂CF₃, Bu^tMe₂SiOSO₂CF₃, BF₃⋅OEt₂) did not yield the desired carbapenem. With chloride as leaving group on the C-4 of 34, AgBF₄ was found to be a suitable silver salt to activate cyclisation of the compound after several attempts using a variety of other silver salts with non-nucleophilic counter anions. The reaction procedure includes treating 34 with AgBF₄ in CH₂Cl₂ at −78 °C to obtain the desired carbapenam 35 in 33% as a single isomer (Scheme 11). A plausible mechanism for the AgBF₄ catalysed alkene-aza-Cope-Mannich cyclisation is presented in Scheme 12.

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Scheme 11

Synthesis of carbapenems using aza-Cope Mannich cyclisation.

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Scheme 12

Plausible mechanism for the AgBF₄-catalysed alkene-aza-Cope-Mannich cyclisation of 34.

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A concise route to a morphinan ring system 37 through silver-promoted reactions has been described (Broka and Gerlits, 1988). It relies on the intramolecular trapping of an aziridinium cation generated in situ by the treatment of 36 with AgBF₄ or AgSbF₆ in toluene. Attempted treatment of unprotected carbonyl group of pyrrolidine 36a and 1,2,2,6,6-pentamethylpiperidine (PMP) with AgBF₄ produced 37a, while reaction of the trimethylsilyl enol ether of the 36a with AgBF₄ also failed to lead to desired product 37. Interestingly, treatment of a solution of dimethyl-tert-butylsilyl (TBDMS) enol ether 36 (54 mg, 0.13 mmol) in 3 mL of toluene with AgBF₄ (56 mg, 0.29 mmol) in 2 mL of toluene afforded the desired compound 37 (19 mg, 56%) after purification on preparative silica gel (eluting with 12% MeOH/CH₂Cl₂) (Scheme 13). The immediate formation of AgCl precipitate is purported to drive the reaction forward. When THF or CH₃CN solvent is used, lower yield of 37 was obtained. Using AgSbF₆ in toluene gave better yield (64%). However, treatment of 36 with AgOAc or AgF failed to afford 37.

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Scheme 13

AgBF₄-mediated synthesis of morphinans.

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Kuehne et al. (1991) recorded successful enantioselective synthesis of vinblastine, a naturally occurring bioactive binary indole-indoline alkaloid. Here, we summarised accessing the compound via the synthesis of the intermediate promoted by AgBF₄. The authors established that treating 5 mL dry acetone solution of chloroimine 38 (∼100 mg, 0.14 mmol) and vindoline hydrofluoroborate (63 mg, 0.95 equiv.) with 0.05 mL (2 equiv.) of tetrafluoroboric acid-diethyl ether complex. After 5 min, AgBF₄ (56 mg, 2 equiv.) in 2 mL dry acetone was added. After another 5 min, 10 mL of 10% aqueous ammonium hydroxide was added to the heterogenous reaction mixture. Tetracyclic C16′–C14′ parf indolenine 39 was obtained as white foam after work-up and concentration under pressure (Scheme 14).

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Scheme 14

Synthesis of indolenine 39.

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Formation of Lewis salts-promoted C-linked glycosyl compounds through alkyne transfer to the anomeric centre of 2-azido-2-deoxy sugars has been described. However, the use of ZnCl, TiCl₄, BF₃⋅Et₂O, trimethyltriflate, etc. promoters in alkynylation of sugar bromides by alkynylstannanes are notorious for not giving clean reactions, consequently afford poor α-selectivity and low yields. According to Leteux and Veyrières (1994), coupling of 6-acetyl-azido-3,4-di-O-benzyl-2-deoxy-α-d-galactopyranosylbromide 40 with various alkynyltributylstannanes in the presence of silver AgBF₄ yields the corresponding stable α, β-C-(d-galactopyranosyl)alkynes. The AgBF₄ (2 mol. equiv.) was found to initiate a smooth and clean coupling reactions at 0 °C. The authors’ typical reaction methodology involved stirring a mixture of bromide 40 (1.96 g, 4 mmol), tributyl(oct-1-ynyl)stannane (7.98 g, 20 mmol) and 3 Å molecular sieves (1 g) in dry 1,2-dichloroethane (12 cm³) at room temperature under argon for 30 min. Then the reaction mixture was cooled to −30 °C, followed by rapid addition of dry AgBF₄ (1.56 g, 8 mmol). Thereafter, the temperature was allowed to rise slowly to 0 °C and stirring continued at the same temperature overnight. After work-up and flash chromatography, the α-C-glycoside 41 (1.08 g, 52%) and β-C-glycoside 42 (218 mg, 10%) were obtained (Scheme 15).

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Scheme 15

Synthesis of α-C-glycopyranosides via AgBF₄-promoted alkynylation at the anomeric centre.

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Fréchet and Baer (1975) established that subjecting the CH₂Cl₂ solutions of halides 43, 46 and 47 to methanolysis in the presence of AgBF₄ and excess of methanol, stereoselectively produces ratios of anomeric glycosides, respectively. Galactopyranosylbromide 44 afforded the methyl α- and β-glycosides 44 and 45 in the ratio of (5:95) (Scheme 16). Use of n-Bu^tNBr catalyst afforded 44 and 45 α/β ratio of 70:30, while Hg(CN)₂ catalyst gave 3:97. The 2,3-di-O-benzyl-5,6-di-O-p-nitrobenzoyl-β-d-galactofuranosyl bromide 46 gave product 48 (methyl 2,3,5.6-tetra-O-benzyl-α-d-galactofuranoside) with α/β ratio of (95:5), while the β-d-galactofuranosyl chloride 47 yielded the same product with α/β ratio of (100:0) and using catalyst n-Bu^tNBr or Hg(CN)₂ did not make any difference in α/β ratio of product 48 (Scheme 17). In their representative reaction protocol, AgBF₄ (about 95 mg) was added in one portion to a cooled (−78 °C) CH₂Cl₂ solution (10 mL) of glycosyl halide (160 mg) and the reaction mixture was stirred in the dark for 10 min. Methanol (0.5 mL) was introduced and stirring continued for 1 h. After purification, the ratio of anomeric glycosides in the residue was determined by measuring the intensity of the methoxy proton resonances of the ¹H NMR spectrum.

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Scheme 16

Methanolysis of 2–o-benzylated d-galactopyranosyl halides.

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Scheme 17

Methanolysis of 2–o-benzylated d-galactofuranosyl halides.

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AgBF₄ has been used to activate trimethylsilylenols as nucleophiles in substitution reactions. In a study (Padwa and Ishida, 1991), 2,3-diiodo-1-(phenylsulphonyl)-1-propene 49 and (cyclohex-1-enyloxy)trimethylsilane 50 were treated at 25 °C in methylene chloride (0.05 M), with 2.0 equiv. of AgBF₄ to effect S_N2 displacement of the terminal halide of 49 and iodo-(phenylsulphonyl) ketone 51 was obtained in 71% yield. Addition of triethylamine in THF at 25 °C cyclised the ketone compound to form the 2-phenylsulphonylmethyl substituted furan 52 (Scheme 18). Other Lewis acids (TiCl₄ and ZnCl) reacted with 49 and 50 led only to the destruction of 50 and 49 was recovered unchanged.

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Scheme 18

Synthesis of substituted furan 52.

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A convenient, mild and one-step synthesis of α-fluorocarbonyl compounds, involving only reaction of the appropriate α-bromo compound with AgBF₄ in ether has been reported. The fluoride in the BF₄⁻ anion component of AgBF₄ can liberate as an F⁻ nucleophile. Following this line of thought, α-fluorocarbonyl molecules 54 were prepared via substitution of carbonyl α-bromo substituents (Scheme 19), presumably via neighbouring group participation by the carbonyl oxygen (Scheme 20) to obtain α-fluorocarbonyl compounds (Fry and Migron, 1979). The authors noted that the reaction is not applicable to terminal bromides or chloroketones. Again, reactions carried out in nucleophilic solvents (methanol) yield the corresponding α-methoxy ketone. Representative protocol involves the reaction of 1.65 g (0.01 mol.) of 2-bromo-2-methyl-3-butanone and 1.95 g (0.01 mol.) of AgBF₄ overnight at room temperature in 70 mL of dry ether. After work-up and purification, 54 was obtained in 87% yield.

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Scheme 19

Synthesis of α-fluorocarbonyl compounds 54.

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Scheme 20

Proposed reaction mechanism for α-fluorocarbonyl compounds.

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The role of BF₄⁻ in stabilisation of intermediate carbocations is demonstrated by using AgBF₄ to heterolyse a C–Cl bond (Schmitt et al., 2013). The precipitation of AgCl probably plays a thermodynamic role in driving the reaction forward (Scheme 21).

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Scheme 21

Synthesis of a BF₄⁻ stabilised intermediate carbocation.

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An efficient two-step synthesis of trifluoromethyl sulphides using inorganic fluorides (CsF, HF, HgF₂, AgBF₄, etc.) has been described. BF₄⁻ anion from AgBF₄ salt participation in fluorination reactions is the synthesis of trifluoromethyl sulphides has been demonstrated (Suda and Hino, 1981). The procedure involved treatment of an aprotic solution of mercaptan 57 with a base (NaH), and thereafter with CF₂Br₂ or CF₂BrCl. The resulting bromodifluoromethylsulphide 58 was subsequently treated with AgBF₄ to obtain the desired trifluoromethyl sulphide 59 in moderate yield (41%) (Scheme 22).

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Scheme 22

AgBF₄-mediated synthesis of trifluoromethyl sulphide.

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Bloodworth and Bowyer (1987) reported a mild, convenient halogen-exchange route to gem-difluorides and trifluorides as promoted by AgBF₄. The AgBF₄ promotes conversion of dihalides and trihalides into their corresponding fluorides at room or sub-ambient temperatures in moderate to good yields. The exchange-fluorination protocol involved treating substrates 60 or 62 with AgBF₄ (1.1 M equiv. per halide) in CH₂Cl₂ for 1 h at room temperature afforded 35–84% yields after appropriate work-up (Scheme 23). The author suggested that the reactions proceeded via cationic intermediates, generated by silver-induced halogenation, which went fluorination by BF₄⁻ anion as demonstrated by the proposed mechanism in Scheme 24.

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Scheme 23

Exchange-fluorination by reaction with AgBF₄.

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Scheme 24

Mechanism of exchange-fluorination by reaction with AgBF₄.

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5 AgBF₄-promoted halogenation reactions

AgBF₄ activates alkyne moieties via π-complexes, as exemplified in the regio- and stereoselective difunctional synthesis of (Z)-β-haloenol acetates from terminal alkynes (Scheme 25) (Chen et al., 2010). There are few catalytic methods to synthesise the haloenols (OC = CX) bond in one step from terminal alkynes (Barluenga et al., 1990). Out of the reaction promoters (CuI, Pd(OAc)₂, FeCl₃, HBF₄, AgBF₄) used, only AgBF₄ could afford the corresponding product in 90% yield; others did not proceed without AgBF₄. Actic anhydride was the favourable solvent. DMF and 1,4-dioxane afforded products in lower yield. Representative protocol involved reaction of phenylacetylene 64 (1.0 mmol) and an N-halosuccinimide (NXS) (1.2 mmol) in acetic anhydride (2 mL) in the presence of AgBF₄ (5 mol%) at 120 °C for 12 h affords 60–90% yield of (Z)-β-haloenol acetate compounds 65. These vinyl halides are important starting materials for transition-metal-catalysed cross-coupling reactions and halogen-metal exchange reactions (Chen et al., 2011).

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Scheme 25

Highly regio- and stereo-selective synthesis of (Z)-β-haloenol acetates.

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In 2012, Chen et al. disclosed the first transition-metal-catalysed electrophilic cascade cyclisation reaction of benzodiyne 66 with NXS and AgBF₄, which affords halo-containing benzo[a]fluorenols A at room temperature (10 °C) in moderate to good yields (Scheme 26). Initial reaction attempts on 66 using an electrophile NXS, did not trigger reaction in the presence of catalysts FeCl₃, FeCl.6H₂O, CuI, In(OTf)₃ or NiCl₂(PPh₃)₂. Further investigation using silver salts as catalyst revealed that AgBF₄ was the best reaction promoter compared with Ag₂CO₃, AgF, AgNO₃, and AgSbF₆. Optimised reaction condition involved treating a solution of benzodiyne 66 (0.20 mmol) in CH₂Cl₂ (1.0 mL) with a mixture of N-iodosuccinimide (0.24 mmol) and AgBF₄ (0.01 mmol) in CH₂Cl₂ (0.5 mL) at 10 °C under nitrogen. After 12 h, the reaction mixture was quenched with a saturated ammonium chloride solution (3 mL) and flash column chromatography (ethyl acetate/n-hexane, 1:50) afforded 67 (76%) as a light yellow solid. A plausible mechanism is depicted in Scheme 27.

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Scheme 26

Synthesis of halo-substituted benzo[a]fluorenols.

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Scheme 27

Mechanism for AgBF₄ catalysed sequential electrophilic cyclisation reaction.

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Wang et al., 2013 reported efficient and regioselective fluorination of arenes under various silver-mediated conditions by intercepting the putative silver-complexed aryne intermediates with anions such as ⁻F, ⁻CF₃, or ⁻SCF₃. Exploring the reactivity of fluorinating agents and solvents, the author’s initial investigation showed that AgBF₄ in a polar solvent (toluene) was most effective at promoting the fluorination but ineffective in acetonitrile. AgF afforded 20% yield in acetonitrile, while AgSbF₆, CuF, Cu(MeCN)₄BF₄, Cu(MeCN)₄PF₆, or [(Au₃)(PPh₃)₃]BF₄ did not afford any product in both toluene and acetonitrile. The general procedure for the stoichiometric fluorination reaction involved dissolving 68 (0.1 mmol) and AgBF₄ (0.15 mmol) in 5.0 mL of toluene under an inert atmosphere, and stirring the mixture at 90 °C for 2 h. Thereafter, the crude reaction mixture was filtered through a small column packed with silica gel and the required product 69 (96% yield) was isolated by column chromatography on silica gel (Scheme 28). A proposed reaction mechanism is shown in Scheme 29.

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Scheme 28

Synthesis of compound 69.

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Scheme 29

A proposed reaction mechanism for compound 69a.

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In 2011, Tang and Ritter described direct electrophilic fluorination of aryltrialkoxysilanes with N-Chloromethylfluorotriethylenediammoniumbis(tetra-fluoroborate) fluorinating agent 71 in the presence a silver(I) salt promoter to give functionalised aryl fluorides. The authors established that reaction of 71 and 4-(biphenyl)trethoxysilane 70 gave 4-biphenyl fluoride 72 in less than 4% yield, but on addition of Ag(I) salts (Ag₂O, AgOAc, AgBF₄, AgPF₆, AgF, etc.) regioselective fluorination was observed and Ag₂O gave the highest yield of the expected product (4-Fluorobiphenyl) 72 (14.3 mg, 83%). Following the optimised reaction procedure, the general protocol involved addition to aryl silane (0.100 mmol, 1.00 equiv.) in acetone (2.0 mL) at 23 °C AgBF₄ (0.300 mmol, 2.00 equiv.), barium oxide (17.2 mg, 0.110 mmol), and 71 (70.8 mg, 0.200 mmol). The reaction mixture was stirred for 2 h at 90 °C, cooled to 23 °C, worked up and purified to obtain the desired product in 11% yield (Scheme 30).

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Scheme 30

Silver-mediated synthesis of 4-fluoro-biphenyl.

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In addition to the reactivities of AgBF₄ described above, an effective electrophilic trifluoromethylating reagent, (trifluoromethyl)dibenzotellurophenium salt 75 (Scheme 33), was developed (Wang et al., 2010; Shibata et al., 2010). Treatment of telluride 73 with an equimolar mixture of triflic anhydride and DMSO at 0 °C, followed by anion exchange with AgBF₄ (Umemoto and Ishihara, 1993) afforded the Umemoto salt 75. Synthesised trifluoromethylated arenes 77 were obtained by reacting substituted arenes 76 with Umemoto reagents 75, Pd(OAc)₂ and Cu(OAc)_2, at 110 °C in a mixture of dichloroethane and 10 equiv. of trifluoroacetic acid to afford 53–88% yield of 77 (Scheme 31) (Shibata et al., 2010).

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Scheme 31

Synthesis of Umemoto reagent and ortho-trifluoromethylation of heterocycle-substituted arenes.

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6 Heterocyclisation reactions promoted by AgBF₄

In 2005, Luo et al. reported the first example of an efficient silver-catalysed regioselective domino reaction between anilines and alkynes to obtain polysubstituted 1,2-dihydroquinolines. In their initial studies, they explored hydroamination of unactivated alkynes by anilines with a gold/silver catalyst system (e.g. AuCl₃/AgOTf), to obtain amines in high yields. Subsequently, examination of AgOTf catalyst alone and Au catalyst alone did not provide these products. Combination of AgBF₄/HBF₄ gave the expected product in good yield. Thus, the optimised reaction conditions involve treating phenylacetylene 78 (1.0 mmol) and phenylamine 79 (4.0 mmol) with AgBF₄ (9.7 mg, 0.05 mmol), hydrogen tetrafluoroborate (HBF₄) (11.2 mg 0.07 mmol) and trifluoroboronetherate (BF₃⋅Et₂O) (11.3 mg, 0.08 mmol) as co-catalysts, for 12 h at 160–190 °C gave 80 in 77% yield (Scheme 32). A proposed mechanism is given in Scheme 33 below.

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Scheme 32

A silver-catalysed efficient synthesis of 1,2-dihydroquinoline derivatives.

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Scheme 33

Proposed mechanism for the synthesis of 80.

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Liu and co-workers (2010) reported an efficient one-pot silver-catalysed and phenyliodine diacetate (PIDA)-mediated synthesis of poly-substituted pyrroles, in which dimethyl but-2-ynedioate 81 was treated with various amines 83 to afford, via tandem reactions, corresponding pyrroles in moderate to excellent isolated yields of 53–89% (Liu et al., 2010). The initial studies involved examining various silver catalysts (AgBF₄, AgOTf, AgNO₃, and Ag₂CO₃) by heating mixtures of 81 and 83 using PIDA as the oxidant in dioxane at 100 °C to obtain the expected product, tetramethyl 1-benzyl-1H-pyrrole-2,3,4,5-tetracarboxylate 84. AgBF₄ showed the highest activity for the reaction. They established a facile and highly efficient C–N and C–C bond formation method to construct a direct pyrrole framework (Scheme 34) as described by the proposed reaction mechanism (Scheme 35).

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Scheme 34

Synthesis of poly-substituted pyrroles from various alkynoates and amines.

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Scheme 35

A plausible mechanism for the addition/oxidative cyclisation reaction leading to the formation of 84.

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Tang et al. (2010) reported the ammonolysis-cyclisation tandem reactions of various 2-alkynylbenzenamines 85 with tetra-alkyl-thiuram disulphides 86 in the presence of silver catalysts to afford the corresponding 4-methylene-4H-benzo[d][1,3]thiazin-2-amines 87 in moderate to good yields. They evaluated a series of catalysts such as AgOTf, AgBF₄, AgSbF₆, AgOAc, Cu(OTf)₂ and Pd(OAc)₂; solvents such as N-methylpyrrolidine (NMP), toluene, acetronitrile, dichloroethane and DMSO, and temperature from 60 to 120 °C. Interestingly, the studies revealed that AgBF₄ was the most effective in terms of yield, 88% at 80 °C after 36 h (Scheme 36). Notably, they discovered that electron-rich aryl groups provided good yields, whereas electron-withdrawing acetyl- or trifluoromethyl-substituted aryl groups lowered the yields. Thus, the general procedure involved reaction of 2-alkynylbenzenamines 85 (0.5 mmol), tetra-alkyl-thiuram disulphides 86 (0.5 mmol), AgBF₄ (0.05 mmol), and DMSO (1 mL) at 80 °C for 36 h. After work-up and chromatographic purification, pale yellow solid was obtained in 88% yield (Z/E = 90:10).

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Scheme 36

Synthesis of 4-methylene-4H-benzo[d][1,3]thiazin-2-amines.

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Recent reports (Ko et al., 2013) show that stable bis-cyclometallated gold(III) catalysts L exhibit high catalytic activity in organic synthesis via gold–silver dual catalysis for substrate activation. They also purported that silver salts are able to work synergistically with bis-cyclometallated gold(III) complexes in the indole alkylation. Thus, treating alkynyl alcohol 88 and indole 89 at room temperature for 2 h with a combination of L (2.5 mol%) and AgBF₄ (5 mol%) as reaction promoter, gave alkylated indole 90 isolated in 80% yield (Scheme 37). Reaction of L in combination with Zn(OTf)₂ or Yb(OTf)₃ also catalyses the reaction to afford 76% and 39% isolated yields, respectively. However, poor yields (10–13%) or no product formation was found when only a single metal catalyst was used.

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Scheme 37

Gold-silver dual catalysed cyclisation–addition reactions of alkynyl alcohol 88 and substituted indoles 89.

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AgBF₄ has also been used to generate carbenes from diazo compounds (Xia et al., 2011). Several Ag(I)-containing catalysts were tried for the synthesis of 2,3-dihydrofurans 93, from 2-diazo-5,5-dimethylcyclohexanedione 91 and styrene 92. In the reaction, using Ag₂O, Ag₂CO₃, AgNO₃, AgClO₄, or AgOSO₂CF₃ at 70 °C for 10 h gave no cycloadducts, also with AgBF₄ (10 mol%) in CH₂Cl₂, THF or CH₃CN solvent at room temperature for 48 h gave no cycloadduct. However, when toluene was used for the same reaction, the expected product 93 was produced in 22% yield. Raising the temperature to 70 °C increased the yield to 47%, and by using the ionic liquid, 1-butyl-3-methylimidazolium tetra-fluoroborate ([Bmim]BF₄), as a co-catalyst, the yield was increased to 71%. The general procedure for the synthesis involves addition of AgBF₄ (0.10 mmol) and (Bmim)BF₄ (0.1 mL) to a solution of cyclic diazodicarbonyl 91 (1.0 mmol) and the corresponding olefin 92 (5.0 mmol) in toluene (2.0 mL) at room temperature. The reaction mixture was stirred at room temperature for 24 h, or at 70 °C for 5 h (Scheme 38), and the mechanism is given in Scheme 39.

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Scheme 38

Synthesis of 2,3-dihydrofurans 93.

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Scheme 39

Proposed reaction mechanism to afford the 2,3-dihydrofuran.

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7 AgBF₄-promoted strained-ring-opening and cyclisation reactions

Banwell and co-workers (2001) used AgBF₄ to open cyclopropane rings and to trap the resulting allylic cation with carbamate nitrogen to synthesise maritinamine via an arylated hexahydroindole 95 (64%) from 6,6-dichlorobicyclo[3.1.0]hexane 94. Subjecting 94 to reaction with AgBF₄ in THF at 40 °C resulted in smooth electrocyclic ring-opening of the gem-dihalocyclopropane and accompanying π-allyl cation cyclisation to afford the 95 in yields of 65–75%. Typical reaction procedure involves treating a stirred THF (5 mL) solution of 94 (90 mg, 0.20 mmol) with AgBF₄ (230 mg, 1.2 mmol) at 40 °C for 21 h. After appropriate work-up and concentration under reduced pressure, the resulting pale-yellow oil was re-dissolved in THF (2 mL) and triethylamine (0.19 mL, 1.4 mmol) added. The reaction was stirred for 10 min, treated with di-tert-butyl dicarbonate (120 mg, 0.54 mmol), and again stirred at 18 °C for 15 h. Work-up and flash chromatographic purification gave carbamate 95 (60 mg, 72%) as a clear, colourless oil. This conversion predictably involves sequence of silver-ion-induced electrocyclic ring-opening of the three membered ring and trapping of the resulting allylic cation by pendant carbamate nitrogen. The formation of maritinamine 97 took two more reaction steps (Scheme 40) (Banwell et al., 2001).

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Scheme 40

Synthesis of epi-maritinamine 97.

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Another example of AgBF₄-mediated cyclopropane ring opening and trapping of the intermediate cation with indole is the synthesis of a diastereoisomeric mixture of 101 in 59% combined yield (Scheme 41) (Banwell, 2008; Banwell et al., 2006).

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Scheme 41

Synthesis of hapalindole C.

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A significant part of the successful synthesis of ent-erythramine 105 involves the spirocyclisation of gem-dichlorocyclopropane 102 (mixture of diastereoisomers). Successive treatment of THF solution of 102 at −40 to 0 °C with lithium hexamethyldisilazide (LiHMDS) and the resulting conjugate base with AgBF₄ at 0–45 °C, gave a diastereoisomeric mixture of desired spirocyclisation products. It was purported that deprotonation step with LiHMDS, and treatment with Pb(PPh₃)₄ and dimedone resulted in cleavage of the Alloc-group, and thus afforded products 103 (26%) and its C-3 epimer 104 (30%). Omitting the deprotonation step resulted to dramatic drop in spirocyclisation products, presumably because of the reduced nucleophilicity of the carbamate nitrogen, which could be likened to Boc-protection of the amine group and no spirocyclisation product was detected (Banwell, 2008; Stanislawsk et al., 2006). Completion of the synthesis of erythramine 105 took three further steps (Scheme 42).

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Scheme 42

Synthesis of (-)-erythramine 105.

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Paquette and Stowell (1971) reported silver(I) ion-catalysed rearrangement of strained σ-bond to synthesise pentacyclo[3.3.2.0.0.3.0]dec-9-ene (snoutene) 108. Notably, such metal ion catalysed molecular rearrangements have revealed that Ag(I) ions can complex with strained σ bonds (those endowed with enhanced p character) to an extent sufficient to permit the operation of otherwise thermally forbidden chemical transpositions. At the onset of this study, an excess amount of AgBF₄ was added to dilute deuteriochloroform solutions of 106 at nmr probe temperature (∼40 °C). In less than 3 min quantitative conversion to 107 was obtained. For preparative purposes, an acetone solution of 106 in the presence of catalytic amounts of AgBF₄ was refluxed for 2 h. The crystalline ester was saponified and the derived diacid was electrolytically decarboxylated to give snoutene 108 in 17% yield (Scheme 43).

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Scheme 43

Synthesis of snoutene 108.

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8 Conclusions

A plethora of carbon–carbon and carbon–heteroatom bonds formation promoted by silver tetra-fluoroborate has a long history. Over the years, there have been positive improvements geared towards better understanding of the reaction mechanisms and the associated influence of the reaction conditions on yields and products. Accordingly, AgBF₄ salt has become useful transition metal promoter that mediates a variety of reactions through its ability to complex with and activates electron-rich atoms and bonds under mild conditions. The BF₄⁻ anion has been found valuable in stabilising intermediate cation for smooth nucleophilic attack. The anion also participates in complexing with strained σ-bonds with enhanced p character to activate the reaction, and has demonstrated fascinating ability to liberate F⁻ nucleophile to fluorinate compound. It is therefore plausible to conclude that AgBF₄ is a promoter of some intriguing reactions: a versatile and efficient promoter for carbon–carbon and carbon-heteroatom bond formation.

Author contributions

MCA prepared the manuscript and DOU participated in discussions of views represented in the paper.

Conflicts of interest

The authors have no competing financial interests.