In Situ Anodically Oxidized BMIm-BF4: A Safe and Recyclable BF3 Source

The anodic oxidation of 1-butyl-3-methylimidazolium tetrafluoroborate (BMIm-BF4) efficiently generates BF3 from BF4–. This Lewis acid, strongly bound to the ionic liquids, can be efficiently used in classical BF3-catalyzed reactions. We demonstrated the BF3/BMIm-BF4 reactivity in four reactions, namely, a domino Friedel–Crafts/lactonization of phenols, the Povarov reaction, the Friedel–Crafts benzylation of anisole, and the multicomponent synthesis of tetrahydro-11H-benzo[a]xanthen-11-ones. In comparison with literature data using BF3-Et2O in organic solvents, in all the presented cases, analogous or improved results were obtained. Moreover, the noteworthy advantages of the developed method are the in situ generation of BF3 (no storing necessity) in the required amount, using only the electron as redox reagent, and the recycling of BMIm-BF4 for multiple subsequent runs.

B oron trifluoride is a well-known Lewis acid, often used in organic synthesis to carry out many acid-catalyzed transformations. 1 Although this reagent is very common, its use may face problems and small accidents due to its high reactivity and volatility. Additionally, this gas is highly toxic and corrosive and has a suffocating odor. 2 To make BF 3 easier to handle, liquid etherate complexes, consisting of a 1:1 molar ratio of BF 3 and ether (usually dimethyl or diethyl), are used and dissociated under appropriate temperature and pressure conditions. 3 Nonetheless, these compounds show corrosive properties and flammability, so it is necessary to use them under a hood, wearing nitrile gloves and eye protection. 4 Moreover, they are sensitive to humidity and form acidic fumes in moist air.
The in situ generation of BF 3 in the exact amount needed minimizes these problems.
Organic electrochemistry can help with this scope. 5 In fact, BF 3 can be easily obtained by anodic oxidation of the BF 4 − anion (Scheme 1). 6 When using electrochemistry, the reagent is the electron (inherently nonpolluting and cheap), very easy to dose simply by closing or opening the electrical circuit.
The conductivity of the solution is normally ensured by a supporting electrolyte in high concentration (up to 0.5 M). The need of such salt in solution (one of the criticisms to organic electrochemistry raised by organic chemists) can be overcome by using an ionic liquid (IL) as both solvent and supporting electrolyte.
ILs are liquid salts formed by a large, nonsymmetrical organic cation and (usually) a noncoordinating anion (organic or inorganic). 7 Their use as solvents in organic transformations is growing in the past years, due to their ability to solubilize organic and inorganic compounds and, mainly, to their virtually null volatility, allowing for their easy recovery. 8 In organic electrochemistry, they can be used as supporting electrolytes or also as solvents, permitting carrying out electrolyses and, after workup, to recover the IL. 9 In this context, the most frequently used class of ILs is the imidazolium one, which are cheap, liquid in a wide range of temperatures, and possess good solvating properties. Nevertheless, imidazolium ILs are in some cases reactive under electrochemical conditions. 10 In fact, the cathodic limit of an imidazolium IL (unsubstituted at the 2-position) is usually the C2−H bond scission with formation of the corresponding Nheterocyclic carbene (NHC), widely exploited, 6,11 while the anodic limit is the oxidation of the anion. In the case of 1-butyl-3-methylimidazolium tetrafluoroborate (BMIm-BF 4 ), the oxidation of the anion forms BF 3 , 6 as previously stated (Scheme 1). The relatively high potential for BF 3 generation prevents the presence of electroactive substrates in solution during electrolysis (see cyclic voltammetries in the Supporting Information). We were interested in an alternative, less dangerous source of BF 3 , generated in situ and thus not stored. The electrochemical oxidation of BF 4 − in IL seemed the good choice, and we carried out some classical BF 3catalyzed reactions in anodically oxidized BMIm-BF 4 , being this IL really easy to recycle after ethereal extraction. In order to avoid interferences from the cathodically generated NHC, a divided cell was used.
The advantages in this BF 3 source can be summarized in • in situ generation, avoiding the storage (simple galvanostatic electrolysis) • easy to dose (current on/off) • no fumes production (strong interaction with IL) • no particular sensitivity to moisture (IL as moist protector) • easy IL recovery and multiple recycling after ethereal extraction The main disadvantage derives from the use of the IL, i.e., the low solubility of apolar molecules.
The examples considered (Scheme 2) are intended to demonstrate the efficiency of this system in classical BF 3catalyzed reactions, and thus no extensive studies for the optimization of yields and reaction scope are reported. It should be underlined that, when more than one reaction was carried out on a particular substrate, the same IL was used in all reactions, recycled after ethereal extraction and submitted to a new anodic oxidation. To the best of our knowledge, anodically generated BF 3 in IL was used only in one paper 12 reporting the BF 3 induced Michael addition of a 1,3-dicarbonyl compound to methyl vinyl ketone, without IL recycling.

Scheme 2. Exploited BF 3 -Catalyzed Reactions
As reported in Table 1, high yields in products 3a−c (entries 5−7) were obtained using a 30% maximum of catalyst (calculated admitting a 100% current yield), comparable with those obtained in the literature using the best experimental conditions, i.e., TiCl 4 as Lewis acid (entries 9−11). A direct comparison with literature data can be made considering entries 3 and 8, in which the same phenol (1a), amount of BF 3 (30%), reaction time and temperature were used. 3a was obtained in 56% in IL (with a 19% of intermediate 4a) with respect to 36% of 3a obtained in CH 2 Cl 2 . Also in this case, BMIm-BF 4 demonstrated to be a solvent suitable for reactions involving dipolar intermediates. 11d Additionally, from the high yield using 30% of BF 3 , we can infer that the IL acts as an efficient solvent to bind this volatile reagent and ensures the reiteration of the catalytic cycle. Moreover, the eco-friendly character of this reaction in IL is demonstrated not only by the use of electricity to generate the catalyst but also by the use of the same IL sample in five subsequent runs (entries 1−5), without reactivity loss.
We tested the electrogenerated BF 3 /BMIm-BF 4 system in this reaction, the imine being obtained in quantitative yield by simple addition of aniline 5 and benzaldehyde 6 to the IL (a noteworthy dehydrating agent). As reported in Table 2, this reaction works well using a theoretical 25% amount of BF 3 (with respect to the imine), in the presence of 3 equiv of dihydropyran 7. High yields of compounds 8a−c were obtained (96%, 89%, and 69% yields, entries 2, 7, and 8, respectively). In all the cases in this work, the yields obtained are higher when compared with analogous literature data (entry 10). 14 Moreover, the cis isomer was synthesized preferentially, in accordance with other methodologies which employ Lewis acids in classical organic solvents 15 and with opposite diastereoselectivity observed by using I 2 as catalyst (Table 2, entry 11). 16 Also in this case, it was possible to reuse the same ionic liquid (entries 1−5, Table 2) in subsequent runs without reactivity loss.
The third reaction considered is the Friedel−Crafts benzylation of anisole 10 with benzyl alcohol 9 (Table 3), in which anisole is monobenzylated in the ortho or para positions (the meta isomer being present only in traces). 17 Good yields in benzylated anisole 11 were obtained using a stoichiometric (69%, entry 3) or overstoichiometric (80%, entry 5) amount of catalyst. Moreover, milder reaction conditions were used, with respect to the literature (r.t. vs 65−80°C, Table 3), and more importantly, the efficient recycling of the IL was demonstrated (entries 1−5).
The literature data here reported for comparison (entry 6, Table 3) showed that the thermodynamic favorite product p-11 can be obtained using a very large excess of anisole (10 to 9: 18/1) at 80°C. The positive effect of an imidazolium IL as solvent in this reaction, involving charged species as intermediates, is confirmed by literature data, besides the results obtained in this work (Table 3, entry 7). 18 The last example is the multicomponent synthesis of tetrahydro-11H-benzo[a]xanthen-1-one 13 from benzaldehyde 6, 2-naphthol 1c, and dimedone 12 ( Table 4).
In conclusion, we efficiently in situ generated BF 3 via direct anodic oxidation of BMIm-BF 4 solutions. By simply using electrons as redox reagents, precise control of the amount of formed BF 3 could be reached and the anolyte could be used directly to carry out organic reactions. This setup was successfully applied to four classically BF 3 -catalyzed transformations, affording similar or improved yields compared with literature results. Moreover, the eco-friendly nature of the developed methodology was demonstrated by the recycling of the IL, which was submitted to up to five subsequent runs without any reactivity loss. We believe that this could be a safer and easier approach to handle this toxic and volatile reagent without storing need and to carry out organic transformations in a sustainable way.

■ EXPERIMENTAL SECTION
General Infomation. All chemicals were commercial (Fluorochem, Aldrich) and used without further purification. BMIm-BF 4 (1-butyl-3-methylimidazolium tetrafluoroborate, Iolitec) was kept at 40°C under vacuum for 3 h before use. 1 H and 13 C spectra were recorded at ambient temperature on a Bruker Avance spectrometer (400 MHz) or with a Gemini Varian spectrometer (300 MHz), using the solvent as internal standard. The chemical shifts (δ) are given in ppm relative to TMS. GC−MS analyses have been run on an HP 5892 series II GC, equipped with a 5% phenyl silicone 30m × 0.25 mm × 25 mm capillary column and coupled to an HP 5972 MSD instrument operating at 70 eV. Flash column chromatography was carried out using a Merck 60 kieselgel (230−400 mesh) under pressure. Starting compounds 1,2,5,6,7,9,10, and 12 were commercially available (Sigma-Aldrich) and used as received.
General Procedure for Electrochemical BF 3 Production. All the experiments were carried out in a homemade divided glass cell separated through a porous glass plug; Pt spirals (apparent area 0.8 cm 2 ) were used as anode and cathode. Electrolyses were performed at constant current (I = 10 mA cm −2 ), at room temperature, under a nitrogen atmosphere, using an Amel Model 552 potentiostat equipped with an Amel Model 731 integrator. 3.0 mL of BMImBF 4 was put in the anodic compartment, 1.0 mL of BMImBF 4 in the cathodic one. After a predetermined number of Coulombs (as reported in tables) passed through the electrolysis cell, the current was switched off, the cathodic compartment was removed, and the reagents were added to the anolyte under an inert atmosphere, as specified below. At the end of the reaction, the anolyte was extracted with diethyl ether (3 × 10 mL). The solvent was eliminated from the combined organic phases under reduced pressure, the crude was analyzed by 1 H NMR, and then the products were purified by flash column chromatography.
When the same anolyte was reused in subsequent electrolyses/ experiments, prior to its reuse it, was kept under vacuum for 30 min to eliminate diethyl ether residues.
All products were known, and their spectral data were in accordance with those reported in the literature.
Friedel−Crafts/Lactonization Reaction. The electrolysis was carried out as previously reported, and after the number of Coulombs reported in Table 1, the current was switched off. Then phenol 1 (0.5 Anisole 10 (amount as in table) and benzyl alcohol 9 (0.5 mmol) were added to the anodically generated BF 3 /BMIm-BF 4 (footnote a of Table 1). The mixture was stirred at r.t. for 4 h and then extracted with diethyl ether. b 9 to 10, molar ratio. c Amount of electrogenerated BF 3 with respect to starting 9, admitting a 100% current efficiency (96.   19 4-Cl 20, BF 3 -Et 2 O/EtOH, 80°C, 45 min 80% (13b) a 2-Naphthol 1c (0.5 mmol), benzaldehyde 6 (0.5 mmol), and dimedone 12 (0.5 mmol) were added to the anodically generated BF 3 /BMIm-BF 4 (footnote a of Table 1). The mixture was stirred (time and temperature as in table) and then extracted with diethyl ether. b Amount of electrogenerated BF 3 with respect to starting 2-naphthol, admitting a 100% current efficiency (96.5 C: 1 mmol of BF 3 ). c Isolated yields after column chromatography. d Entries 1−3: the same recycled IL was used. e Entries 4 and 5: the same recycled IL was used.
Povarov Reaction. Imine Synthesis. Amine 5 (0.5 mmol, 1 equiv) and aldehyde 6 (0.5 mmol, 1 equiv) were added to 0.5 mL of BMIm-BF 4 and kept under stirring at room temperature for 1 h. Then the mixture was extracted with diethyl ether (3 × 3 mL). The solvent was eliminated from the combined organic phases under reduced pressure, and the imine was used without purification (after 1 H NMR control spectrum) in the Povarov reaction.