Compound 3a

View in PubChem | in situ 11B NMR | in situ 19F NMR | 1H NMR | 11B {1H} NMR | 19F NMR | Q-Exactive MS | Q-Exactive MS | MDL Molfile | ChemDraw

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

Synthesis of 4-pentafluorophenyl(hydroxymethyl) benzene: a solution of 4-pentafluorophenyl benzaldehyde (0.900 g, 3.30 mmol) and sodium borohydride (0.150 g, 3.96 mmol) in 14 mL tetrahydrofuran and 7 mL ethanol was prepared and placed under a positive nitrogen flow. The mixture was stirred at room temperature for 24 hours. The resulting dark solution was diluted with water (30 mL) and extracted with methylene chloride (30 mL). The organic layer was washed three times with H₂O, dried over MgSO₄, and filtered through Celite. The solvent was then dried in vacuo. The residue was purified by flash chromatography (eluent: DCM; R_f = 0.4) through a silica column, using UV light for TLC visualization. The resulting solution was dried under vacuum, providing 4-pentafluorophenyl(hydroxymethyl) benzene as a white solid (0.705 g, 78%). ¹H NMR (400 MHz, CDCl₃): δ 7.49 (d, 2H, Ar), 7.42 (d, 2H, Ar), 4.76 (d, 2H, CH₂OH), 2.05 (t, 1H, CH₂OH). ¹³C{¹H} NMR (126 MHz, CDCl₃): δ 144.3, 142.3, 140.6, 138.1, 130.5, 127.2, 126.3, 115.8, 64.9. ¹⁹F NMR (376 MHz, CDCl₃): δ -143.3 (q, 2F, -ortho), -155.5 (t, 1F, -para), -162.2 (m, 2F, -meta).

Synthesis of 4-pentafluorophenyl(bromomethyl) benzene: a flask containing 4-pentafluorophenyl(hydroxymethyl) benzene (1.00 g, 3.65 mmol) was purged with nitrogen and 30 mL of dry methylene chloride was charged into the flask. The solution was placed in ice bath and PBr₃ (346 µL, 3.65 mmol) was added via syringe. The reaction mixture was stirred overnight, during which time the mixture turned yellow. The resulting mixture was then diluted with 100 mL distilled H₂O. The organic layer was separated and washed 3 times with saturated NaCl solution. Organic layer was collected and dried over MgSO₄, then filtered through Celite. Solvent was evaporated and the residue was purified by flash chromatography (hexane/CH₂Cl₂, 2:1; R_f = 0.75) through a silica column, using UV light for TLC visualization. The resulting solution was dried under vacuum, providing 4-pentafluorophenyl(bromomethyl) benzene as a white solid (0.773 g, 63%). ¹H NMR (400 MHz, CDCl₃): δ 7.53 (d, 2H, Ar), 7.42 (d, 2H, Ar), 4.54 (s, 2H, CH₂Br). ¹³C{¹H} NMR (126 MHz, CDCl₃): δ 144.3, 140.7, 139.1, 138.0, 130.7, 129.5, 126.6, 115.4, 32.6. ¹⁹F NMR (376 MHz, CDCl₃): δ -143.1 (q, 2F, -ortho), -155.1 (t, 1F, -para), -162.0 (m, 2F, -meta).

Synthesis of 3: compound 1 (75.0 mg, 0.092 mmol) was added to a 10 mL glass microwave vial and transferred out of a nitrogen-filled glovebox, opened to the air, and dissolved in 1.5 mL acetonitrile. N,N-diisopropylethylamine (0.3 mL, 1.73 mmol) and 4-pentafluorophenyl(bromomethyl) benzene (0.8334 g, 2.47 mmol) were added along with a flea micro stir bar, the vial was sealed with a PTFE/silicone cap, and the mixture was heated at 140 °C with stirring in the microwave for 30 minutes. The volatiles were removed via rotary evaporation, and the remaining reagent was eluted first through a slurry-packed silica gel column with 80/20 hexanes/CH₂Cl₂, and the pink/purple product mixture was eluted with acetone followed by CH₂Cl₂. Note: The eluted fraction containing the reagent ligand can be purified by eluting through a silica column with 90/10 hexanes/CH₂Cl₂, and after drying thoroughly it can be used for subsequent synthesis of 3 . Recycling the ligand in this manner can minimize unnecessary repetition of ligand synthesis. The volatiles were removed via rotary evaporation, and the remaining charged 2-/1- product mixture was dissolved in 5 mL 90/10 EtOH/MeCN. FeCl₃∙6H₂O (0.3 g, 1.11 mmol) was added and the mixture was left to stir for 24 hours. Following oxidation, the solvent mixture was removed via rotary evaporation, and a red-orange band containing the neutral product was separated from the FeCl₃∙6H₂O through a slurry-packed silica gel column with CH₂Cl₂. The CH₂Cl₂ was removed via rotary evaporation and the final neutral product 2 was dried under high vacuum to obtain an isolated yield of 266.5 mg (85%). Compound 2 is a dark red-orange solid. ¹H NMR (500 MHz, CD₂Cl₂): δ 7.21 - 7.33 (m, 48H, C₆H₄), 5.50 (s, 24H, OCH₂). ¹¹B{¹H} NMR (128 MHz, CD₂Cl₂): δ 42.4. ¹⁹F NMR (376 MHz, CD₂Cl₂): δ -144.2 (q, 24F, -ortho), -156.5 (t, 12F, -para), -163.4 – -163.5 (m, 24F, -meta). HRMS (Q-Exactive Plus): m/z calculated for C₁₆₅H₇₂B₁₂F₆₀O₁₂ (M^-), 3407.5289 Da; found, 3407.5278 Da. X-ray quality crystals of 3 were grown from a cooling solution of boiling 1:1 EtOH:MeOH.

Synthesis of 3a: 3 (10.0 mg, 0.0029 mmol) and K₂CO₃ (22.0 mg, 0.159 mmol) were added along with a flea micro stir bar to a 4-mL glass vial, which was then sealed with a PTFE/silicone cap under ambient conditions. The vial was then purged and backfilled with N₂ three times before being transferred into the glovebox. In the glovebox, the vial was opened and 300 µL anhydrous DMF was added, followed by 1-hexanethiol (5.42 µL, 0.038 mmol). The vial was sealed again and set to stir at 400 rpm for 7 hours. The vial was transferred out of the glovebox, and its contents were transferred into an NMR tube for in situ ¹⁹F NMR spectroscopy to ensure nearly quantitative conversion and in situ ¹¹B NMR spectroscopy to ensure structural integrity of the cluster. The crude mixture was then transferred into a 20-mL glass vial and lyophilized for solvent removal. A 5 ¾” glass Pasteur pipet column was prepared using glass wool and 4” of silica gel, and the pipet was flushed with triethylamine (2X column volumes). The crude product mixture containing 3a was loaded onto the column with 80/20 hexanes/ethyl acetate (sonication was used to aid dissolution), and the remaining reagent was eluted with 80/20 hexanes/ethyl acetate. A very slightly yellow band containing 3a was eluted with MeCN, and the fractions containing 3a (as assessed by TLC) were combined and volatiles were removed via rotary evaporation followed by lyophilization overnight to obtain an isolated yield of 12.2 mg (87%). ¹H NMR (400 MHz, CD₃CN): δ 7.64 – 7.50 (br m, 24H, OCH₂-Ar), 7.25 – 7.15 (br m, 24H, OCH₂-Ar), 5.60 (br s, 24H, OCH₂), 3.06 (q, 12H, [(CH₃CH₂)₃NH]⁺), 2.93 (t, 24H, SCH₂), 1.61 - 1.49 (m, 24H, SCH₂CH₂), 1.44 – 1.34 (br m, 24H, S(CH₂)2(CH2)3CH3), 1.30 – 1.21 (br m, 48H, S(CH2)2(CH2)3CH3), 1.18 (t, 18H, [(CH3CH2)3NH]+), 0.89 – 0.80 (m, 36H, S(CH2)5CH3). 11B{1H} NMR (128 MHz, CD3CN): δ -15.1. 19F NMR (376 MHz, CD3CN): δ -136.7 (q, 24F, -meta), -145.2 (q, 24F, -ortho). HRMS (Q-Exactive Plus): m/z calculated for C228H228B12F48O12S12 (M2-), 2292.7115 Da; found, 2292.7157 Da.