Nucleophilic Trifluoromethylation of Unactivated Arenes Jack A Pike, James W Walton

Transcription

1 Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 07 Nucleophilic Trifluoromethylation of Unactivated Arenes Jack A Pike, James W Walton Table of contents:. NMR Spectra for Photolysis of Complex. Experimental Detail and Product Characterisation 3. NMR Spectra of Products 4. HPLC Method and Traces 5. Crystal and Structural Refinement Data for Complex. NMR Spectra for Photolysis of Complex CF 3 h CD 3 CN 7 h CF 3 [Cp(MeCN) 3 ] 7 hr 8 hr 3 hr 90 min 30 min 0 min 0 min f (ppm) Figure S. Stacked H-NMR spectra (CD 3 CN, 98 K, 400 MHz) for the photolysis of complex.

2 . Experimental Detail and Product Characterisation General Information Commercially available reagents were used as received from suppliers. Solvents were laboratory grade and dried using an appropriate drying agent when required. Prior to use, KF was oven dried at 00 C for 48 h. Reactions requiring anhydrous conditions were carried out under an atmosphere of dry argon using Schlenk-line techniques. Where appropriate, solvents were sparged with argon or degassed using the freeze-thaw cycle method. Thin-layer chromatography was carried out on silica plates (Merck 5554) or neutral alumina plates (Merck Art 5550) and visualized under UV (54/365 nm) irradiation or by staining with potassium permanganate solutions. Preparative column chromatography was carried out using silica (Merck Silica Gel 60, mesh) or neutral alumina (Merck Aluminium Oxide 90, activity II-III, 7030 mesh), pre-soaked in ethyl acetate. NMR spectra (H, 3C, 9F) were recorded on a Varian VXR-400 spectrometer (H at Hz, 3 C at MHz, 9F at MHz) or a Varian VNMRS-700 spectrometer (H at MHz, 3C at MHz). Spectra were recorded at 95 K in commercially available deuterated solvents and referenced internally to the residual solvent proton resonances. Electrospray and high resolution mass spectrometry were performed on a Thermo-Finnigan LTQ FT system using acetonitrile as the carrier solvent 4 3 NO 5 [(η 6 -nitrobenzene)(η 5 -cyclopentadienyl)] () To a solution of nitrobenzene (63 mg, 53 µl, mmol,. equiv) in degassed,- dichloroethane (9 ml) at 80 C was added [(NCMe) 3 Cp] (00 mg, 0.46 mmol). The resulting solution was heated to reflux for 6 hours under an inert atmosphere, allowed to cool to room temperature and filtered. The filtrate was concentrated in vacuo, redissolved in a minimum of MeCN and added dropwise to Et O. The green solid was isolated by filtration,

3 rinsed with ether, dissolved in MeCN, concentrated in vacuo and dried under vacuum to give the title compound as a light brown solid (87 mg, 93%); δ H (acetone-d 6 ) 7.46 (H, dt, 3 J H-H 6.0 Hz, 4 J H-H.0 Hz, H ), 6.79 (H, tt, 3 J H-H 6.0 Hz, 4 J H-H.0 Hz, H 3 ), 6.70 (H, tt, 3 J H-H 6.0 Hz, 4 J H-H.0 Hz, H 4 ) 5.78 (5H, s, H 5 ); δ C (acetone-d 6 ).4 (C, s, C ), 88.5 (C, s, C 4 ), 86.5 (C, s, C 3 ), 83.7 (5C, s, C 5 ), 8.9 (C, s, C ); δ P (acetone-d 6 ) (sept., J P-F 707 Hz); m/z (HRMS + ) [M- ] + (C H 0 NO 96 requires ); Anal. Found (Expected): C (30.43); H.34 (.3); N 3.37 (3.3) CF3 6 [(η 6 -α,α,α-trifluorotoluene)(η 5 -cyclopentadienyl)] () [(η 6 -nitrobenzene)(η 5 -cyclopentadiene)] (00 mg, 0.30 mmol) was dissolved in anhydrous DMF (5 ml). Oven dried potassium fluoride (5 mg, 0.53 mmol,. equiv) and trimethyl(trifluoromethyl)silane (36 mg, 37.4 µl, 0.53 mmol,. equiv) were added. The mixture was stirred at 0 C under argon atmosphere for 8 hours. Purification by column chromatography (silica, acetonitrile : 5% MeOH) gave the title compound as a brown solid (33 mg, 3%); δ H (acetone-d 6 ) (H, dt, 3 J H-H 6.0 Hz, 4 J H-H.0 Hz, 4 J H-H.5 Hz H 3 ), (3H, m, H 4 and 5 ), 5.70 (5H, s, H 6 ); δ C (acetone-d 6 ) 3. (C, q, J C-F 74 Hz, C ), 9.8 (C, q, J C-F 38 Hz, C ), 87.8 (C, s, C 5 ), 86. (C, s, C 4 ), 83.6 (C, q, 3 J C-F 3 Hz, C 3 ), 8.6 (5C, s, C 6 ); δ F (acetone-d 6 ) (3F, s, F arene ), -7.6 (6F, d, J F-P 707 Hz, F counterion ); m/z (HRMS + ) [M- ] + (C H 0 F 96 3 requires ) R f = 0.7 (silica, acetonitrile : 5% MeOH); Anal. Found (Expected): C 3.69 (3.5); H. (.0); N 0.6 (0.00). 5 CF H 7 NO 8 [(η 5 --nitro--trifluoromethylcyclohexadienyl)(η 5 -cyclopentadiene)] (3)

4 [(η 6 -nitrobenzene)(η 5 -cyclopentadiene)] (00 mg, 0.30 mmol) was dissolved in anhydrous DMF (5 ml). Oven dried potassium fluoride (5 mg, 0.53 mmol,. equiv) and trimethyl(trifluoromethyl)silane (36 mg, 37.4 µl, 0.53 mmol,. equiv) was added. The mixture was stirred at 0 C under argon atmosphere for 8 hours. Purification by column chromatography (silica, pet. ether : 0% EtOAc) gave the title compound as a yellow oil (7 mg, 3%); δ H (acetone-d 6 ) 6.9 (H, td, 3 J H-H 5.5 Hz, 4 J H-H.5 Hz, H 5 ), 6.09 (H, ddd, 3 J H-H 5.5 Hz, 4 J H-H.5 Hz, 4 J H-H 0.5 Hz, H 6 ), 5.09 (H, t, 3 J H-H 5.5 Hz, H 4 ), 4.96 (5H, s, H 8 ), 4.48 (H, qdd, 3 J H-F 8.0 Hz, 3 J H-H 6.5 Hz, 4 J H-H.5 Hz, H ), 3.76 (H, dt, 3 J H-H 6.0 Hz, 4 J H-H.5 Hz, H 3 ); δ C (acetone-d 6 ) 4. (C, q, J C-F 87 Hz, C ), 8.0 (C, s, C 4 ), 80.6 (C, s, C 5 ), 79.4 (5C, s, C 8 ), 75. (C, s, C 6 ), 6.0 (C, m, C 7 ), 43.4 (C, q, J C-F 9 Hz, C ), 8.3 (C, q, J C-F Hz, C 3 ); δ F (acetone-d 6 ) (3F, d, 3 J F-H 8.0 Hz); m/z (HRMS + ) [M+H] + (C H F 3 NO 96 requires ), [M-NO ] + (C H 0 F 96 3 requires ), R f = 0.8 (silica, pet. ether : 0% EtOAc); t R (RP-HPLC) column : 3.36 min, purity >99%; column : 3.56 min, purity >99%. NO 3 4 CF 3 -Trifluoromethyl-nitrobenzene To an oven dried Schlenk tube, [(η 5 --nitro--trifluoromethylcyclohexadienyl)(η 5 - cyclopentadiene)] (0 mg, 55.8 µmol) was added and dissolved in anhydrous deuterated acetonitrile ( ml). To this,,3-dichloro-5,6-dicyano-,4-benzoquinone (5 mg, 66.9 µmol,. equiv) was added and the mixture was stirred at room temperature for 4 hours. H- and 9 F-NMR showed confirmation of quantitative conversion to free arene using an external standard of α,α,α-trifluorotoluene (0 mg, quantitative); δ H (acetonitile-d 3 ) 8.00 (H, m), 7.96 (H, m), 7.89 (H, m); δ F (acetonitrile-d 3 ) -60. (3F, m). CF 3 3

5 α,α,α-trifluorotoluene To a quartz NMR tube, [(η 6 -α,α,α-trifluorotoluene)(η 5 -cyclopentadienyl)] (0 mg, 43.7 µmol) was added and dissolved in anhydrous deuterated acetonitrile (0.8 ml). The mixture was irradiated under UV lamp (365 mn, 36 W) for 7 hours to give the title compound in a quantitative conversion (see NMR spectrum S). δ H (acetonitile-d 3 ) 7.73 (H, m, H ), 7.68 (H, t, 3 J H-H 7.5, H 3 ) 7.60 (H, t, 3 J H-H 7.5, H ); δ F (acetonitrile-d 3 ) -63. (3F, m) NO [(η 6-4-nitrotoluene)(η 5 -cyclopentadienyl)] To a solution of 4-nitrotoluene (9 mg, 0.38 mmol,. equiv) in degassed,-dichloroethane (4 ml) at 80 C was added [(NCMe) 3 Cp] (50 mg, 0.5 mmol). The resulting solution was heated to reflux for 6 hours, allowed to cool to room temperature and filtered. The filtrate was concentrated in vacuo, redissolved in a minimum of MeCN and added dropwise to Et O. The light brown precipitate was isolated by filtration, rinsed with ether, dissolved in MeCN, concentrated in vacuo and dried under vacuum to give the title compound as a light brown solid (56 mg, 9%). δ H (acetone-d 6 ) 7.39 (H, d, 3 J H-H 6.5 Hz, H ), 6.77 (H, d, 3 J H-H 6.5 Hz, H 3 ), 5.73 (5H, s, H 6 ),.54 (3H, s, H 5 ); δ C (acetone-d 6 ) 0.5 (C, s, C ), 05.8 (C, s, C 4 ), 88.6 (C, s, C 3 ), 87.6 (C, s, C 5 ), 83.3 (5C, s, C 6 ), 7.9 (C, s, C ); δ P (acetone-d 6 ) (sept, J P-F 73 Hz); δ F (acetone-d 6 ) -7. (d, J F-P 73 Hz); m/z (HRMS + ) [M ] + (C H NO 96 requires ); Anal. Found (Expected): C 3.38 (3.5); H.7 (.70); N 3.30 (3.) CN 6 [(η 6 -benzonitrile)(η 5 -cyclopentadienyl)] To a solution of benzonitrile (6 mg, 6 µl, 0.53 mmol,. equiv) in degassed,- dichloroethane (6 ml) at 80 C was added [(NCMe) 3 Cp] (00 mg, 0.30 mmol). The

6 resulting solution was heated to reflux for 6 hours, allowed to cool to room temperature and filtered. The filtrate was concentrated in vacuo, redissolved in a minimum of MeCN and added dropwise to Et O. The light brown precipitate was isolated by filtration, rinsed with ether, dissolved in MeCN, concentrated in vacuo and dried under vacuum to give the title compound as a light brown solid (85 mg, 89%). δ H (acetone-d 6 ) 6.89 (H, dt, 3 J H-H 6.0 Hz, 4 J H-H.5 Hz, H 3 ), 6.65 (H, tt, 3 J H-H 6.0 Hz, 4 J H-H.5 Hz, H 4 ), 6.6 (H, 3 J H-H 6.0 Hz, 4 J H-H.5 Hz, H 5 ), 5.77 (5H, s, H 6 ); δ C (acetone-d 6 ) 5.3 (C, s, C ), 88.6 (C, s, C 3 ), 87.6 (C, s, C 5 ), 86.7 (C, s, C 4 ), 83.3 (5C, s, C 6 ), 7.9 (C, s, C ); δ P (acetone-d 6 ) (sept, J P-F 73 Hz); δ F (acetone- D 6 ) -7. (d, J F-P 73 Hz); m/z (HRMS + ) [M ] + (C H 0 N 96 requires ); Anal. Found (Expected): C (34.79); H.56 (.43); N 3.43 (3.38). 5 9 CF H 7 CN 8 [(η 5 --cyano--trifluoromethylcyclohexadienyl)(η 5 -cyclopentadiene)](4b) [(η 6 -benzonitrile)(η 5 -cyclopentadiene)] (0 mg, 48.3 µmol) was dissolved in anhydrous DMF (3 ml). Oven dried potassium fluoride (4 mg, 53. µmol,. equiv) and trimethyl(trifluoromethyl)silane (8 mg, 9 µl, 53. µmol,. equiv) was added. The mixture was stirred at 0 C under argon atmosphere for 8 hours. Purification by column chromatography (silica, pet. ether : 0% EtOAc) gave the title compound as a brown oil (6 mg, 0%). δ H (acetone-d 6 ) 6.3 (H, td, 3 J H-H 5.5 Hz, 4 J H-H.0 Hz, H 5 ), 5.5 (H, d, 3 J H-H 5.5 Hz, H 6 ), 5.05 (5H, s, H 9 ), 4.94 (H, t, 3 J H-H 5.5 Hz, H 4 ), 3.48 (H, qdd, 3 J H-F 7.5 Hz, 3 J H-H 5.5 Hz, 4 J H-H.5 Hz, H ), 3.33 (H, t, 3 J H-H 5.5 Hz, H 3 ); δ C (acetone-d 6 ) 4. (C, q, J C-F 86 Hz, C ), 3. (C, m, C 8 ), 8.9 (C, s, C 5 ), 80.4 (C, s, C 4 ), 79.0 (5C, s, C 9 ), 78.8 (C, s, C 6 ), 44. (C, q, J C-F 9 Hz, C ), 4. (C, q, J C-F Hz, C 3 ), 7.07 (C, s, C 7 ); δ F (acetone-d 6 ) (3F, d, 3 J F-H 8.0 Hz); m/z (HRMS + ) [M+H] + (C 3 H F 3 N 96 requires ), R f = 0.4 (silica, pet. ether : 0% EtOAc).

7 4 3 5 O OH 6 [(η 6 -carboxybenzene)(η 5 -cyclopentadienyl)] To a solution of benzoic acid (7 mg, 0.38 mmol,. equiv) in degassed,-dichloroethane (6 ml) at 80 C was added [(NCMe) 3 Cp] (50 mg, 0.5 mmol). The resulting solution was heated to reflux for 6 hours, allowed to cool to room temperature and filtered. The filtrate was concentrated in vacuo, redissolved in a minimum of MeCN and added dropwise to Et O. The light brown precipitate was isolated by filtration, rinsed with ether, dissolved in MeCN, concentrated in vacuo and dried under vacuum to give the title compound as a light brown solid (47 mg, 94%). δ H (acetone-d 6 ) 6.88 (H, d, 3 J H-H 6.0 Hz, H 3 ), 6.56 (H, t, 3 J H-H 6.0 Hz, H 4 ), 6.53 (H, 3 J H-H 6.0 Hz, H 5 ), 5.60 (5H, s, H 6 ); δ C (acetone-d 6 ) 65.3 (C, s, C ), 88.5 (C, s, C ), 87.3 (C, s, C 5 ), 86.7 (C, s, C 4 ), 86.5 (C, s, C 3 ), 8.8 (5C, s, C 6 ); δ P (acetone-d 6 ) (sept, J P-F 73 Hz); δ F (acetone-d 6 ) -7. (d, J F-P 73 Hz); m/z (HRMS + ) [M ] + (C H O 96 requires ); Anal. Found (Expected) for C H F 6 O P.(MeCN) 0.5 : C (33.6); H.70 (.63); N 0.7 (0.48) Cl 6 [(η 6-4-chlorotoluene)(η 5 -cyclopentadienyl)] To a solution of 4-chlorotoluene (48 mg, 45 µl, mmol,. equiv) in degassed,- dichloroethane (8 ml) at 80 C was added [(NCMe) 3 Cp] (50 mg, mmol). The resulting solution was heated to reflux for 6 hours, allowed to cool to room temperature and filtered. The filtrate was concentrated in vacuo, redissolved in a minimum of MeCN and added dropwise to Et O. The light brown precipitate was isolated by filtration, rinsed with ether, dissolved in MeCN, concentrated in vacuo and dried under vacuum to give the title compound

8 as a light brown solid (47 mg, 97%). δ H (acetone-d 6 ) (H, m, H ), (H, m, H 3 ), 5.63 (5H, s, H 6 ),.4 (3H, s, H 5 ); δ C (acetone-d 6 ) 04.7 (C, s, C ), 0.6 (C, s, C 4 ), 87. (C, s, C /3 ), 86.9 (C, s, C /3 ), 83.0 (5C, s, C 6 ), 0.0 (C, s, C 5 ); δ P (acetone-d 6 ) (sept, J P-F 73 Hz); δ F (acetone-d 6 ) -7. (d, J F-P 73 Hz); m/z (HRMS + ) [M ] + (C H 35 Cl 96 requires ) [(η 6 -toluene)(η 5 -cyclopentadienyl)] To a solution of toluene (4 mg, 7 µl, 0.53 mmol,. equiv) in degassed,-dichloroethane (5 ml) at 80 C was added [(NCMe) 3 Cp] (00 mg, 0.30 mmol). The resulting solution was heated to reflux for 6 hours, allowed to cool to room temperature and filtered. The filtrate was concentrated in vacuo, redissolved in a minimum of MeCN and added dropwise to Et O. The light brown precipitate was isolated by filtration, rinsed with ether, dissolved in MeCN, concentrated in vacuo and dried under vacuum to give the title compound as a light brown solid (87 mg, 94%). δ H (acetone-d 6 ) (H, m, H 3 ), (H, m, H 4 ), (H, m, H 5 ) 5.5 (5H, s, H 6 ),.39 (3H, s, H ); δ C (acetone-d 6 ) 0.6 (C, s, C ), 87. (C, s, C 3 ), 85.4 (C, s, C 4 ), 84.7 (C, s, C 5 ), 80.5 (5C, s, C 6 ), 9.7 (C, s, C ); δ P (acetone-d 6 ) (sept, J P-F 73 Hz); δ F (acetone-d 6 ) -7. (d, J F-P 73 Hz); m/z (ESI + ) [M- ] + (C H 96 3 requires ). Anal. Found (Expected): C (35.74); H 3.36 (3.5); N 0.3 (0.00). [(η 6 -benzene)(η 5 -cyclopentadienyl)] The reaction is a modification of the existing literature procedure. A 00 ml oven dried roundbottom flask equipped with a stir-bar was charged with finely ground potassium carbonate (0.83 g, 6.00 mmol, 6.0 equiv) and the flask flame-dried under vacuum. After

9 cooling to room temperature, the flask was further charged with [(C 6 H 6 )Cl ] (0.50 g,.00 mmol) and a reflux condenser added. Ethanol (30 ml) was then added, followed by freshly cracked cyclopentadiene (.5 ml, 8.0 mmol, 8 equiv). The resulting heterogeneous brown mixture was then warmed to 85 C with rapid stirring. After approximately 6 h, the reaction mixture was cooled to room temperature and filtered through a plug of Celite, and the Celite rinsed with a further 5 ml of ethanol. The dark yellow filtrate was concentrated to 0 ml, then an aqueous solution of NH 4 (0.68 g, 4.0 mmol, 4. equiv, in 0 ml of H O) was added, resulting in the immediate formation of a tan precipitate. The remaining ethanol was removed under reduced pressure and the resulting suspension cooled for several hours. The mixture was then filtered and the tan solid dried under vacuum. The crude product was subsequently dissolved in a minimum of acetonitrile and diethyl ether added dropwise until precipitate formation was no longer observed. This mixture was cooled for several hours before being filtered to give the title compound as a light brown solid 0.78 g (9%). The product is spectroscopically identical to the known [(η 6 -C 6 H 6 )(C 5 H 5 )]PF 6 and is pure by H NMR spectroscopy to the limits of detection. δ H (acetone-d 6 ) 6.36 (6H, s, H ), 5.56 (5H, s, H ). 4 3 F 5 [(η 6 -fluorobenzene)(η 5 -cyclopentadienyl)] To a solution of fluorobenzene (48 mg, 47 µl, mmol,. equiv) in degassed,- dichloroethane (9 ml) at 80 C was added [(NCMe) 3 Cp] (00 mg, 0.46 mmol). The resulting solution was heated to reflux for 6 hours under an inert atmosphere, allowed to cool to room temperature and filtered. The filtrate was concentrated in vacuo, redissolved in a minimum of MeCN and added dropwise to Et O. The brown precipitate was isolated by filtration, rinsed with ether, dissolved in MeCN, concentrated in vacuo and dried under vacuum to give the title compound as a brown solid (53 mg, 8%); δ H (acetone-d 6 ) 6.8 (H, dd, 3 J H-H 6.0 Hz, 3 J H-F 4.5 Hz, H ), 6.47 (H, td, 3 J H-H 6.0 Hz, 4 J H-F 4.0 Hz, H 3 ), 6.7 (H, td, 3 J H-H 6.0 Hz, 5 J H-F 3.5 Hz, H 4 ) 5.65 (5H, s, H 5 ); δ C (acetone-d 6 ) 36.9 (C, d, J C-F 76 Hz, C ), 85. (C, s, C 4 ), 84.9 (C, d, 3 J C-F 6 Hz, C 3 ), 8.6 (5C, s, C 5 ), 77.4 (C, d, J C-F Hz, C ); δ F

10 (acetone-d 6 ) -7.6 (6F, d, J F-P 707 Hz, F counterion ), (F, m, F arene ); δ P (acetone-d 6 ) (sept., J P-F 707 Hz); m/z (HRMS + ) [M- ] + (C H 0 F 96 requires ). Anal. Found (Expected): C 3.56 (3.44); H.5 (.48); N 0.5 (0.00).

11 3. NMR spectra of Products NO H NMR CO(CD 3 ) 400 MHz

12 f (ppm) CF 3 H NMR CO(CD 3 ) 400 MHz

13 CF 3 H NO H NMR CO(CD 3 ) 400 MHz

14 NO H NMR CO(CD 3 ) 400 MHz

15 CN P H NMR CO(CD 3 ) 400 MHz

16 O OH H NMR CO(CD 3 ) 400 MHz

17 Cl H NMR CO(CD 3 ) 400 MHz

18 F PF H NMR CO(CD 3 ) 400 MHz 4. HPLC Methods and Traces : Chromatograms of complex 3 were analysed using a Waters Arc HPLC system with PDA detector. Gradient analysis 90% water, 0% acetonitrile minutes---> 95% Acetonitrile, 5% water through column (Waters Coretecs C8.7um 4.6x50mm column ) and column (ACE Excel 3um, C8PFP, 4.6x50mm). Complex 3, column :

19 Complex 3, column : 5 Crystal and Structural Refinement Data for Complex The X-ray single crystal data have been collected using λmokα radiation (λ =0.7073Å) on an Agilent XCalibur (Sapphire-3 CCD detector, fine-focus sealed tube, graphite monochromator) diffractometer equipped with a Cryostream (Oxford Cryosystems) openflow nitrogen cryostat at the temperature 0.0()K. The structure was solved by direct method and refined by full-matrix least squares on F for all data using Olex [3] and SHELXTL [4] software. All non-hydrogen atoms were refined anisotropically, hydrogen

20 atoms were placed in the calculated positions and refined in riding mode. Crystal data and parameters of refinement are listed in Table S. Crystallographic data for the structure have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication CCDC Table S. Crystal data and structure refinement for Empirical formula C H 0 NO x Formula weight Temperature/K 0.0 Crystal system monoclinic Space group P /n a/å 8.760(6) b/å.47() c/å 3.874(3) α/ β/ (8) γ/ Volume/Å (5) Z 4 ρ calc g/cm 3.3 μ/mm -.35 F(000) Crystal size/mm Radiation MoKα (λ = ) Θ range for data collection/ 4.48 to 60 Index ranges - h, -7 k 7, -8 l 8 Reflections collected 0965 Independent reflections 3953 [R int = , R sigma = 0.043] Data/restraints/parameters 3953/0/99 Goodness-of-fit on F.073 Final R indexes [I>=σ (I)] R = , wr = Final R indexes [all data] R = , wr = Largest diff. peak/hole / e Å -3.9/-0.95

21 References B. M. Trost and C. M. Older, Organometallics, 00,, T. P. Gill and K. R. Mann, Organometallics, 98,, O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and H. Puschmann, J. Appl. Cryst. (009), 4, G.M. Sheldrick, Acta Cryst. (008), A64, -.