High Yield C-Derivatization of Weakly Coordinating Carborane Anions

Abstract

Unlike the “parent” carborane anion CHB₁₁H₁₁⁻, halogenated carborane anions such as CHB₁₁H₅Br₆⁻ can be readily C-functionalized in high yield and purity, enhancing their utility as weakly coordinating anions.

B-halogenated icosahedral carborane anions such as CHB₁₁H₅X₆⁻ and CHB₁₁X₁₁⁻ (X = halogen) (Figure 1) are particularly useful members of a class of exceptionally inert, weakly coordinating anions^1–5 whose versatility might be further tailored by suitable C-derivatization chemistry. Long-chain hydrocarbon “tails” formed by C-alkylation should lower the lattice energies of salts, increase their solubilities in low dielectric solvents and allow better exploitation of reactive cations in catalysis. Applications in surfactant chemistry can also be envisioned. Similarly, C-fluorocarbon tails should improve the solubility of carborane ion pairs in fluorocarbon solvents, where catalytic applications have been reported.⁶ Attachment of a carborane anion to a polymer has allowed exploitation of immobilization chemistry in cation-selective sensor technology.⁷ C-arylation takes advantage of the unique scaffold of a carborane anion in rigid rod supramolecular chemistry.^8,9

Figure 1.

Carborane anions CHB₁₁H₅X₆⁻ and CHB₁₁X₁₁⁻ (gray = C, white = H, red = H or halogen, green = halogen).

Despite these promising applications, the C-derivatization chemistry of carborane anions has progressed rather slowly. Most work has been performed on the “parent” carborane anion, CHB₁₁H₁₁⁻, but is frequently hampered by modest yields and difficult separations from starting material. Being ionic rather than neutral, the chromatographic separation of different carborane anions is not trivial on a synthetic scale. The activation of CHB₁₁H₁₁⁻ via C-lithiation with butyl lithium appears to be essentially quantitative¹⁰ but the partial regeneration of starting material during subsequent reactions with electrophiles is common, despite careful control of conditions. Alkylation of 1-Li-CB₁₁H₁₁⁻ with alkyl halides gives mixed results. While the yields for methylations are frequently quite high,^2,11–14 they drop to 63% for ethylation of CHB₁₁H₁₁⁻ and are even lower for most other alkylations, silylations, phosphinations and metallations.^2,10 The yields of C-monohalogenated products, 1-X-CB₁₁H₁₁⁻, have been raised to 81–96% by careful attention to conditions but chromatography purification is still recommended for most derivatives.¹¹

We now report that when these C-functionalization reactions are performed on an already halogenated carborane anion such as CHB₁₁H₅Br₆⁻, rather than on the unfunctionalized parent CHB₁₁H₁₁⁻, isolated yields are generally excellent and compound purity is sufficiently high that chromatographic purification is unnecessary. High yield C-cyanation of undecahalogenated carboranes has very recently been reported.¹⁵ These findings makes sense within the context of known carborane reactivity patterns. ² C-lithiation is a deprotonation reaction and the C-H bond in B-halogenated carborane anions is more acidic than in the parent CHB₁₁H₁₁⁻. This is borne out by DFT theory at the B3LYP/6-311+G(d,p) level using dimethylsulfoxide in the IEFPCM solvation model. A 16 kcal.mole⁻¹ decrease in acidity of the C-H bond between CHB₁₁H₅Br₆⁻ and CHB₁₁H₁₁⁻ is calculated. Similarly, the electron withdrawing effect of B-halogen substituents will more favorably polarize the Li-C bond in 1-Li-CB₁₁H₅Br₆⁻ towards clean replacement of Li⁺ by an electrophile.

Scheme 1 summarizes the representative C-functionalization chemistry reported in the present work.

Scheme 1.

C-functionalization of the 1-Li–CB₁₁H₅Br₆⁻ anion (o denotes boron vertex).

For convenience and solubility reasons, the preferred starting material is the dilithio derivative Li[1-Li-CB₁₁H₅Br₆], conveniently prepared from the Me₃NH⁺ salt and 2 equiv. of butyl lithium.¹⁶ Trialkylsilyl, allyl, benzyl (including Merrifield resin), perfluoroaryl and perfluoroallenyl electrophiles, supplied as halides, illustrate the scope of the reactivity. When performed in a careful manner, isolated yields were >90%. Products were isolated by straightforward solvent extractions, avoiding tedious HPLC protocols. Excellent product purity was indicated both by clean NMR and IR spectroscopies as well as the absence of starting material in anionic mode electrospray mass spectrometry.

There is every reason to believe that the same efficient C-functionalization chemistry can be applied to other halogenated carborane anions.

Experimental

All experimental manipulations were carried out using standard drybox or Schlenk tube inert atmospheric techniques. Spectrochemical grade tetrahydrofuran (THF), acetonitrile and diethylether (Fischer) were distilled from sodium/benzophenone. Cs(CHB₁₁H₅Br₆) was prepared as previously described. ¹ Other commercially available chemicals were reagent grade and were degassed and dried over 4A molecular sieves for 1 week prior to use. All solvent evaporations were performed at reduced pressure on a rotary evaporator. ¹¹B, ¹H, ¹⁹F and ³¹P NMR spectra were obtained on a Bruker Avance 300 MHz spectrometer. ¹¹B chemical shifts were referenced to BF₃-OEt₂ as an external reference in a capillary within the sample tube. ¹H chemical shifts were measured relative to internal residual protons from the lock solvent and referenced to (CH₃)₄Si (0.0 ppm). ¹⁹F chemical shifts were referenced to CFCl₃ (0.0 ppm). ³¹P chemical shifts were referenced to 85% aqueous H₃PO₄ (0.0 ppm) in a capillary. Electrospray ionization mass spectrometry data were obtained on an Agilent 6200 LC TOF in anionic mode. IR data were recorded on a Perkin Elmer Spectrum 100 Series as KBr pellets.

DFT calculations were carried out on CB₁₁H₁₂⁻ and CHB₁₁H₅Br₆⁻ at B3LYP/6-311+G(d,p) level with the Gaussian 03 system of programs. The intrinsic gas phase acidities of the carborane anions were calculated according to the following thermodynamic heterolytic equilibrium, analogous to work^17,18 on neutral species:

$${\text{HA}}^{-}\to {\mathrm{A}}^{2-}+{\mathrm{H}}^{+}$$

The absence of imaginary frequencies was taken as the criterion of a true minimum. The gas phase values of ΔG_acidwere then recalculated using the IEFPCM solvation model with DMSO as a solvent. The resultant ΔG_acid values were: CB₁₁H₁₂⁻ = 325.75 and CHB₁₁H₅Br₆⁻ = 309.58 kcal.mol⁻¹.

[Me₃NH][closo-1-H-CB₁₁H₅Br₆]

[Cs][CHB₁₁H₅Br₆] (8.27 g, 11 mmole) was suspended in deionized water (325 mL) and the suspension heated to boiling to effect dissolution. The hot solution was filtered through a medium porosity frit and the filtrate reheated to boiling. [Me₃NH]Cl (3.15 g, 33 mmole) was added, resulting in a thick white precipitate. The solution was allowed to stir at a gentle boil for 5 min. before being removed from heat. After cooling to room temperature, the suspension was further cooled in an ice bath. After 30 min., the suspension was filtered onto a 30 mL fine porosity frit and washed with aliquots of deionized water (300 mL). After air drying overnight, the product was transferred to a glass vial, dried overnight in a convection oven at 95° C (7.24 g (97%) and stored in a drybox.

Li[closo-1-Li-CB₁₁H₅Br₆]

In a typical reaction, [Me₃NH][closo-1-H-CB₁₁H₅Br₆] (0.1–3 g) was dissolved in sufficient THF (~10 mL/g) to give a clear solution. Butyl lithium in hexanes (1.6 M, 2.1 molar equivalents) was then added dropwise over the course of minutes, maintaining a clear solution. If a white precipitate formed, additional THF was added to effect dissolution. The solvent volume was then reduced under vacuum by ca. 50% to remove butane and trimethylamine. THF was added to redissolve any white precipitate and the clear solution was immediately used for subsequent reactions.

[Me₄N][closo-1-Me₃Si-CB₁₁H₅Br₆]

To a THF solution of Li[1-Li-CB₁₁H₅Br₆] generated from [Me₃NH][CHB₁₁H₅Br₆] (0.1251g, 0.185 mmol), Me₃SiCl (~.5 mL) was added dropwise over 5 min. After stirring for 24 hrs, the flask was removed from the inert atmosphere and the solvent evaporated. The resulting white solid was dissolved in water (45 mL) transferred to a beaker. A pellet of sodium hydroxide was added to neutralize any remaining Me₃SiCl and acidic byproducts. The solution was heated to boiling and filtered while hot using a fine frit. The resulting clear solution was reduced in volume to 20 mL by boiling and Me₄NCl (200 mg, 1.8 mmol) was added. A white precipitate formed which was isolated by filtration onto a fine frit, washed with water and vacuum dried (0.135 g, 88%). ¹H NMR (d₆-acetone): δ 3.46 [s, 12H, Me₄N], 0.096 ppm [s, 9H, Me₃Si]. ¹¹B NMR: +0.49 [s, 1B, B(12)], −7.52 [s, 5B, B(7–11)], − 17.49 ppm, [d, 5B, B(2–6), J_BH 503.2 Hz]. M/z: calcd. for Me₃Si-CB₁₁H₅Br₆⁻ 688.7000, found 688.6996.

[Me₄N][closo-1-iPr₃Si-CB₁₁H₅Br₆]

This was prepared from [Me₃NH][CHB₁₁H₅Br₆] (0.1467g, 0.217 mmol) and iPr₃SiCl in a similar manner to [Me₄N][closo-1-Me₃Si-CB₁₁H₅Br₆] above except that the crude product was extracted into diethylether (45 mL) for the initial filtration before dissolving in water (30 mL). Yield: 0.173g, 94%). ¹H NMR (d₆-acetone): δ 3.46 [s, 12H, Me₄N], 1.17 [m, 21H, i-Pr3Si]. ¹¹B NMR: 1.21 [s, 1B, B(12)], −7.70 [s. 5B, B(7–11)], −16.82 [d, 5B, B(2–6), J_BH 498.3 Hz]. M/z: calcd. for (iPr)₃Si-CB₁₁H₅Br₆⁻ 772.7939, found 772.7930.

[Me₄N][closo-1-C₃H₅-CB₁₁H₅Br₆]

To THF solution of Li[1-Li-CB₁₁H₅Br₆] generated from [Me₃NH][CHB₁₁H₅Br₆] (0.1525g, 0.225 mmol) was added allyl iodide (~1mL) dropwise over the course of 5 mins. Light was excluded by wrapping the flask in Al foil and the reaction stirred for 24 hours before exposing to air and evaporating the solvent to dryness. The white solid was dissolved in water (45mL) yielding a clear solution which was transferred to a beaker, boiled and filtered hot through a fine frit. The resulting solution was reduced in volume to 20 mL before adding Me₄NCl (200 mg, 1.8 mmol) which yielded a white precipitate which was isolated on a fine frit, washed with water and vacuum dried (0.152 g, 92%). ¹H NMR (d₆-acetone): δ 3.46 [s, 12H, Me₄N], 2.57 [d, 2H, methylene, J_H 7.2 Hz], 4.99 [m, 2H, vinyl], 5.63 [m, 1H, vinyl]. ¹¹B NMR: −2.29 [s, 1B, B(12)], −8.85 [s. 5B, B(7–11)], −16.97 [d, 5B, B(2–6), J_BH 522 Hz ]. M/z: calcd. for C₃H₅-CB₁₁H₅Br₆⁻ 656.6917, found 656.6913.

[Me₄N][closo-1-CH₂(C₆H₅)-CB₁₁H₅Br₆]

This was prepared from Li[1-Li-CB₁₁H₅Br₆] generated from [Me₃NH][CHB₁₁H₅Br₆] (0.1401g, 0.207 mmol) and benzyl bromide (~0.25 mL) in a similar manner to [Me₄N][closo-1-C₃H₅-CB₁₁H₅Br₆] above (0.243g, 90%). ¹H NMR (d₆-acetone): δ 3.46 [s, 12H, Me₄N], 3.15 [s, 2H, methylene], 7.12 [m, 2H, phenyl], 7.27 [m, 3H, phenyl]. ¹¹B NMR: −2.29 [s, 1B, B(12)], −8.79 [s. 5B, B(7–11)], −16.84 [d, 5B, B(2–6), J_BH 501.8 Hz]. M/z: calcd. for C₇H₇-CB₁₁H₅Br₆⁻ 706.7074, found 706.7061.

Li[closo-1-(t-butyl)₂P-CB₁₁H₅Br₆]

This was prepared from Li[1-Li-CB₁₁H₅Br₆] generated from [Me₃NH][CHB₁₁H₅Br₆] (0.2350g, 0.347 mmol) and di-t-butylchlorophosphine (.065 mL). The reaction was allowed to stir for 1 hour at room temperature followed by removal of ca. 85% of the solvent. Only NMR data were collected due to the extreme sensitivity of the product to oxygen. ¹H NMR (d₃-acetonitrile): δ 1.18 [d, 18 H, t-butyl, J_PH 32.2 Hz]. ^31P NMR: −151.40 [s, 1P]. ¹¹B NMR: −1.13 [s, 1B, B(12)], −8.69 [s. 5B, B(7–11)], −15.20 [d, 5B, B(2–6), J_BH 551.9 Hz].

[Me₄N][closo-1-C₆F₅-CB₁₁H₅Br₆]

This was prepared from Li[1-Li-CB₁₁H₅Br₆] generated from [Me₃NH][CHB₁₁H₅Br₆] (0.2708 g, 0.400 mmol) and C₆F₆ (~1 mL) in a similar manner to [Me₄N][closo-1-Me₃Si-CB₁₁H₅Br₆] above, except that the crude yellow product was extracted into diethylether (45 mL) for the initial filtration before dissolving in water (45 mL). (If a large excess of C₆F₆ is not used, multiple substitution occurs). Yield of off-white solid (0.323 g, 94%). ₁₁B NMR: +.049 [s, 1B, B(12)], −8.55 [s. 5B, B(7–11)], −15.85 [d, 5B, B(2–6), J_BH 495.9 Hz]. ¹⁹F NMR: −133.53 [broad, o-F], −154.70 [tt, p-F, J_FF 22.9, 5.1 Hz], −162.9531 [m, m-F]. M/z: calcd. for C₆F₅-CB₁₁H₅Br₆⁻ 782.6446, found 782.6459.

[Me₄N][closo-1-C₆F₁₁-CB₁₁H₅Br₆]

This was prepared from Li[1-Li-CB₁₁H₅Br₆] generated from [Me₃NH][CHB₁₁H₅Br₆] (0.3051 g, 0.451 mmol and perfluoro-1-hexene (0.150 g, 0.5 mmol) in a similar manner to [Me₄N][closo-1-Me₃Si-CB₁₁H₅Br₆] above except that the crude brown product was extracted into diethylether (45 mL) for the initial filtration before evaporation and dissolution in water (45 mL). An additional extraction of the final product into dichloromethane (10 mL) followed filtration through a fine frit and evaporation of solvent gave an oil that solidified to a brown solid (0.3682 g, 91.1%). ¹¹B NMR: +0.049 [s, 1B, B(12)], −8.55 [s. 5B, B(7–11)], −15.85 [d, 5B, B(2–6), J_BH 487.5 Hz]. ¹⁹F NMR: −157.73 [d, alkene, J_FF 144.5 Hz], −146.70 [d, alkene, J_FF 137.37 Hz], - 127.70 [m, CF₂], −118.75 [m, CF₂], −84.67 [dd, CF₂, J_FF 31.7, 9.93 Hz], −80.73[t, CF₃, J_FF 8.6 Hz]. M/z: calcd. for C₆F₁₁CB₁₁H₅Br₆⁻ 896.6351, found 893.6390.

[Me₄N][closo-1-C₃F₅-CB₁₁H₅Br₆]

Extreme care should be exercised when confining hexafluoropropene (B.Pt. −28° C) to glass Schlenkware. All reactions must be maintained at dry ice temperatures to avoid explosion. In heavy walled Schlenkware, hexafluoropropene (~1mL) was pre-condensed at −78 °C then transferred to a heavy walled reaction vessel at dry ice temperature containing THF (5 mL) and Li[closo-1-Li-CB₁₁H₅Br₆] generated from [Me₃NH][CHB₁₁H₅Br₆] (0.4510 g, 0.666 mmol). The resulting yellow solution was allowed to stir for 3 hours before gradually removing the excess hexafluoropropene under vacuum. The reaction was then allowed to warm to room temperature and the solvent removed under reduced pressure to give a colorless residue. This was extracted into diethylether (50 mL), filtered through a fine frit and the filtrate evaporated to dryness. The crude product was dissolved in water (35 mL) and Me₄NCl (200 mg, 1.8 mmol) was added. The resulting white precipitate was isolated by filtration onto a fine frit, washed with water and vacuum dried (0.4608 g, 92.7%). ¹¹B NMR: +1.82 [s, 1B, B(12)], −8.60 [s. 5B, B(7–11)], −17.52 [d, 5B, B(2–6), J_BH 504.2 Hz]. ¹⁹F NMR: −67.56 [dd, CF₂(sp³), J_FF 23.5, 10.7 Hz], −122.60 [dm, CF, J_FF 146.1, 23.7 Hz], −160.60 [d, CF₂(sp²), J_FF 145.3 Hz]. M/z: calcd. for C₃F₅CB₁₁H₅Br₆⁻ 746.6446, found 746.6458.

Cs[closo-1-Merrifield Peptide Resin-CB₁₁H₅Br₆]

To THF solution [Li][1-Li-CB₁₁H₅Br₆] generated from [Me₃NH][CHB₁₁H₅Br₆] (0.2330 g, 0.344 mmol) was added Merrifield’s Peptide Resin (0.185g, 1.95 mmol Cl/g, 1.05 equiv.) was added. The reaction was allowed to stir for 1 week yielding a yellow powder which was filtered onto a medium frit and was washed thoroughly with 3 aliquots of THF (50 mL). All filtrates were collected and the solvent evaporated. To the residue, deionized water (20 mL) was added. ¹¹B NMR of this solution showed no detectable signals. To the filtrate, 2 drops of HNO₃ were added, followed AgNO₃ (1 mL, 0.5 M). The resulting white precipitate of AgCl was filtered onto a fine frit and dried (0.048g, 0.99 equiv.). The resin was suspended in water and CsCl (1 g, 6 mmol) added. The suspension was stirred for 1 day before collecting the resin by filtration onto a medium frit and washing with water. The faintly pale product was oven dried for 2 hours at 90° C before obtaining an IR spectrum.