A Facile and General Approach to 3-((Trifluoromethyl)thio)- 4H-chromen-4-one

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1 A Facile and General Approach to 3-((Trifluoromethyl)thio)- 4H-chromen-4-one Haoyue Xiang and Chunhao Yang* State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, , China. Supporting Information Lists of Contents Experimental Section... 2 Characterization data...4 Crystal Structure Report for 2a Copies of 1 H and 13 C NMR spectra Copies of 19 F NMR spectra of 2a

2 Experimental Section General Experimental Information Unless otherwise noted, all solvents and other reagents are commercially available and used without further purification. All reagents were weighed and handled in air at room temperature. Column chromatography was performed on silica gel (200~300 mesh). NMR spectra were recorded on Brucker AVANCE 300 NMR spectrometer or Brucker AVANCE III 400 NMR spectrometer or Brucker AVANCE III 500 NMR spectrometer or Brucker AVANCE III 600 NMR spectrometer. Chemical shifts were reported in parts per million (ppm, δ). Proton coupling patterns are described as singlet (s), doublet (d), triplet (t), quartet (q), heptet (hept), multipet (m) and broad (br). Low and high-resolution mass spectra (LRMS and HRMS) were recorded on a Finnigan/MAT-95 (EI), Finnigan LCQ/DECA and Micromass Ultra Q-TOF (ESI) spectrometer. Melting points (m.p.) were measured by Büchi 510 melting point apparatus without further corrected. General procedure for the synthesis of compounds 1 Compounds 1 were prepared by the treatment of the corresponding unsubstituted/substituted o-hydroxyacetophenone with N,N-dimethylformamide dimethyl acetal (DMF-DMA), according to a reported protocol. 1 General procedure for the synthesis of 3-((trifluoromethyl)thio-4H-chromen-4-one (2a-2w) To a reaction tube were added AgSCF 3 (0.6 mmol), trichloroisocyanuric acid (TCCA) (0.3 mmol) and THF (2 ml). The mixture was stirred at room temperature for 30 min. Then compounds 1 (0.2 mmol) were added directly and stirred for another 2 hours at room temperature. Afterward, the reaction mixture was filtered through celite and washed with EtOAc. After removing the solvent in vacuo, the residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate = 10/1) to yield the pure products. General procedure for the synthesis of 2ia-2ic 2 A mixture of 2i (0.15 mmol), K 2CO 3 (0.3 mmol), amidines/guanidine (0.15 mmol), and DMSO (2 ml) was heated to 60 and kept at this temperature for 1h. After the reaction was complete, the reaction was cooled to room temperature, and then diluted by water (20 ml). The mixtures was extracted with EtOAc (3 30 ml), washed with water and brine, dried over anhydrous Na 2SO 4 and filtered. The solvent was removed under vacuum. The residue was applied on a silica-gel column (petroleum ether/ethyl acetate = 5/1) to afford products. 2

3 General procedure for the synthesis of 3e A mixture of 3d (0.3 mmol), prepared according to the literature, 3 and N,N-dimethylformamide dimethyl acetal (DMF-DMA) (5 ml) was heated to 120 and kept at this temperature for 2 h. After the reaction was complete, the reaction was cooled to room temperature. The DMF-DMA was removed under vacuum. The residue was applied on a short silica-gel column (CH 2Cl 2/MeOH = 20/1) to give crude (E)-2-(3-(dimethylamino)acryloyl)-1-hydroxy-8- methoxyanthracene-9,10-dione which was used in next step. To a reaction tube were added AgSCF 3 (0.6 mmol), trichloroisocyanuric acid (TCCA) (0.3 mmol) and THF (2 ml). The mixture was stirred at room temperature for 30 min. Then a solution of (E)-2-(3-(dimethylamino)acryloyl)-1- hydroxy-8-methoxyanthracene-9,10-dione in THF (2 ml) was added directly and stirred for another 2 hours at room temperature. Afterward, the reaction mixture was filtered through celite and washed with EtOAc. After removing the solvent in vacuo, the residue was purified by flash column chromatography on silica gel (CH 2Cl 2) to give the pure products as yellow solid, total yield 41%. References (1) Levchenko, K. S.; Semenova, I. S.; Yarovenko, V. N.; Shmelin, P. S.; Krayushkin, M. M. Tetrahedron Lett. 2012, 53, (2) Xiang, H.; Chen, Y.; He, Q.; Xie, Y.; Yang, C. RSC Advances 2013, 3, (3) (a) Sereda, G. A.; Akhvlediani, D. G. Tetrahedron Lett. 2003, 44, 9125; (b) Gattinoni, S.; Merlini, L.; Dallavalle, S. Tetrahedron Lett. 2007, 48,

4 Characterization Data 3-((Trifluoromethyl)thio)-4H-chromen-4-one (2a) White solid 47 mg (94%). Mp H NMR (300 MHz, Chloroform-d) δ 8.39 (s, 1H), 8.29 (d, J = 7.3 Hz, 1H), 7.75 (t, J = 7.7 Hz, 1H), 7.50 (t, J = 7.9 Hz, 2H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , (q, J = Hz), , , , , F NMR (471 MHz, Chloroform-d) δ HRMS (EI + ) calculated for C 10H 5F 3O 2S, ; found, Methyl-3-((trifluoromethyl)thio)-4H-chromen-4-one (2b) White solid 48 mg (92%). Mp H NMR (300 MHz, Chloroform-d) δ 8.36 (s, 1H), 8.06 (d, J = 2.2 Hz, 1H), 7.54 (dd, J = 8.6, 2.2 Hz, 1H), 7.40 (d, J = 8.6 Hz, 1H), 2.47 (s, 3H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , (q, J = Hz), , , , , HRMS (EI + ) calculated for C 11H 7F 3O 2S, ; found, Ethyl-3-((trifluoromethyl)thio)-4H-chromen-4-one (2c) White solid 51 mg (93%). Mp H NMR (300 MHz, Chloroform-d) δ 8.37 (s, 1H), 8.08 (d, J = 2.2 Hz, 1H), 7.57 (dd, J = 8.6, 2.3 Hz, 1H), 7.42 (d, J = 8.6 Hz, 1H), 2.77 (q, J = 7.6 Hz, 2H), 1.28 (t, J = 7.6 Hz, 3H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , (q, J = Hz), , , , , 27.88, HRMS (EI + ) calculated for C 12H 9F 3O 2S, ; found, Propyl-3-((trifluoromethyl)thio)-4H-chromen-4-one (2d) White solid 49 mg (85%). Mp H NMR (300 MHz, Chloroform-d) δ 8.37 (s, 1H), 8.07 (d, J = 2.3 Hz, 1H), 7.55 (dd, J = 8.6, 2.2 Hz, 1H), 7.42 (d, J = 8.6 Hz, 1H), 2.71 (t, J = 7.6 Hz, 2H), 1.69 (h, J = 7.4 Hz, 2H), 0.94 (t, J = 7.4 Hz, 3H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , (q, J = Hz), , , , , 36.85, 23.86, HRMS (EI+) calculated for C 13H 11F 3O 2S, ; found, Isopropyl-3-((trifluoromethyl)thio)-4H-chromen-4-one (2e) 4

5 White solid 49 mg (85%). Mp H NMR (300 MHz, Chloroform-d) δ 8.37 (s, 1H), 8.11 (d, J = 2.3 Hz, 1H), 7.61 (dd, J = 8.7, 2.3 Hz, 1H), 7.43 (d, J = 8.7 Hz, 1H), 3.05 (hept, J = 7.2 Hz, 1H), 1.30 (d, J = 6.9 Hz, 6H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , (q, J = Hz), , , , , 33.34, HRMS (EI + ) calculated for C 13H 11F 3O 2S, ; found, Methoxy-3-((trifluoromethyl)thio)-4H-chromen-4-one (2f) White solid 48 mg (87%). Mp H NMR (300 MHz, Chloroform-d) δ 8.37 (s, 1H), 7.62 (d, J = 3.2 Hz, 1H), 7.44 (d, J = 9.1 Hz, 1H), 7.31 (dd, J = 9.3, 3.1 Hz, 1H), 3.91 (s, 3H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , (q, J = Hz), 124.1, , , , , HRMS (EI + ) calculated for C 11H 7F 3O 3S, ; found, Fluoro-3-((trifluoromethyl)thio)-4H-chromen-4-one (2g) White solid 44 mg (84%). Mp H NMR (300 MHz, Chloroform-d) δ 8.39 (s, 1H), 7.91 (dd, J = 8.0, 2.9 Hz, 1H), (m, 2H). 13 C NMR (126 MHz, Chloroform-d) δ , , (d, J = Hz), , (q, J = Hz), (d, J = 7.6 Hz), (d, J = 25.5 Hz), (d, J = 8.3 Hz), (d, J = 24.2 Hz), HRMS (EI + ) calculated for C 10H 4F 4O 2S, ; found, Chloro-3-((trifluoromethyl)thio)-4H-chromen-4-one (2h) White solid 53 mg (95%). Mp H NMR (300 MHz, Chloroform-d) δ 8.39 (s, 1H), 8.23 (d, J = 2.6 Hz, 1H), 7.68 (dd, J = 9.0, 2.6 Hz, 1H), 7.48 (d, J = 8.9 Hz, 1H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , (q, J = Hz), , , , HRMS (EI + ) calculated for C 10H 4ClF 3O 2S, ; found, Bromo-3-((trifluoromethyl)thio)-4H-chromen-4-one (2i) White solid 58 mg (90%). Mp H NMR (300 MHz, Chloroform-d) δ (m, 2H), (m, 1H), 7.41 (d, J = 8.9 Hz, 1H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , (q, J = Hz), , , , HRMS (EI + ) calculated for C 10H 4BrF 3O 2S, ; found, Nitro-3-((trifluoromethyl)thio)-4H-chromen-4-one (2j) White solid 30 mg (52%). Mp H NMR (500 MHz, Chloroform-d) δ 9.14 (d, J = 2.7 Hz, 1H), 8.59 (dd, J = 9.2, 5

6 2.8 Hz, 1H), 8.46 (s, 1H), 7.71 (d, J = 9.2 Hz, 1H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , (q, J = Hz), , , , HRMS (EI + ) calculated for C 10H 4F 3NO 4S, ; found, Methoxy-3-((trifluoromethyl)thio)-4H-chromen-4-one (2k) White solid 47 mg (85%). Mp H NMR (300 MHz, Chloroform-d) δ 8.31 (s, 1H), 8.17 (d, J = 8.9 Hz, 1H), 7.03 (dd, J = 8.9, 2.3 Hz, 1H), 6.87 (d, J = 2.4 Hz, 1H), 3.92 (s, 3H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , (q, J = Hz), , , , , , HRMS (EI + ) calculated for C 11H 7F 3O 3S, ; found, Ethyl-3-((trifluoromethyl)thio)-4H-chromen-4-one (2l) White solid 49 mg (89%). Mp H NMR (300 MHz, Chloroform-d) δ 8.35 (s, 1H), 8.18 (d, J = 8.0 Hz, 1H), (m, 2H), 2.80 (q, J = 7.6 Hz, 2H), 1.30 (t, J = 7.6 Hz, 3H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , (q, J = Hz), , , , , , 28.53, HRMS (EI + ) calculated for C 12H 9F 3O 2S, ; found, Bromo-3-((trifluoromethyl)thio)-4H-chromen-4-one (2m) White solid 46 mg (71%). Mp H NMR (300 MHz, Chloroform-d) δ 8.35 (s, 1H), 8.14 (d, J = 8.6 Hz, 1H), 7.71 (s, 1H), 7.62 (d, J = 8.5 Hz, 1H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , (q, J = Hz), , , , HRMS (EI + ) calculated for C 10H 4BrF 3O 2S, ; found, Chloro-3-((trifluoromethyl)thio)-4H-chromen-4-one (2n) White solid 46 mg (82%). Mp H NMR (300 MHz, Chloroform-d) δ 8.36 (s, 1H), 8.22 (d, J = 8.6 Hz, 1H), 7.53 (d, J = 1.9 Hz, 1H), 7.46 (dd, J = 8.6, 2.0 Hz, 1H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , (q, J = Hz), , , , , HRMS (EI + ) calculated for C 10H 4ClF 3O 2S, ; found, ,7-Dimethoxy-3-((trifluoromethyl)thio)-4H-chromen-4-one (2o) White solid 51 mg (83%). Mp H NMR (300 MHz, Chloroform-d) δ 8.32 (s, 1H), 7.57 (s, 1H), 6.89 (s, 1H), 3.98 (s, 3H), 3.98 (s, 3H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , (q, J = Hz), , , , 99.23, 56.10, HRMS (EI + ) calculated for C 12H 9F 3O 4S, ; found,

7 6,7-Dimethyl-3-((trifluoromethyl)thio)-4H-chromen-4-one (2p) White solid 47mg (86%). Mp H NMR (300 MHz, Chloroform-d) δ 8.33 (s, 1H), 7.99 (s, 1H), 7.26 (s, 1H), 2.40 (s, 3H), 2.36 (s, 3H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , (q, J = Hz), , , , , 19.98, HRMS (EI + ) calculated for C 12H 9F 3O 2S, ; found, Chloro-7-methyl-3-((trifluoromethyl)thio)-4H-chromen-4-one (2q) White solid 50 mg (85%). Mp H NMR (300 MHz, Chloroform-d) δ 8.35 (s, 1H), 8.21 (s, 1H), 7.39 (s, 1H), 2.52 (s, 3H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , (q, J = Hz), , , , , HRMS (EI + ) calculated for C 11H 6ClF 3O 2S, ; found, ,8-Dimethyl-3-((trifluoromethyl)thio)-4H-chromen-4-one (2r) White solid 40 mg (74%). Mp H NMR (300 MHz, Chloroform-d) δ 8.40 (s, 1H), 7.90 (d, J = 2.2 Hz, 1H), 7.38 (d, J = 2.2 Hz, 1H), 2.46 (s, 3H), 2.42 (s, 3H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , (q, J = Hz), , , , , 20.94, HRMS (EI + ) calculated for C 12H 9F 3O 2S, ; found, Bromo-6-chloro-3-((trifluoromethyl)thio)-4H-chromen-4-one (2s) White solid 50 mg (70%). Mp H NMR (300 MHz, Chloroform-d) δ 8.46 (s, 1H), 8.20 (d, J = 2.5 Hz, 1H), 7.95 (d, J = 2.5 Hz, 1H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , (q, J = Hz), , , HRMS (EI + ) calculated for C 10H 3BrClF 3O 2S, ; found, ((Trifluoromethyl)thio)-4H-benzo[h]chromen-4-one (2t) White solid 49 mg (82%). Mp H NMR (500 MHz, Chloroform-d) δ 8.59 (s, 1H), 8.48 (d, J = 8.2 Hz, 1H), 8.21 (d, J = 8.7 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 8.7 Hz, 1H), (m, 2H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , (q, J = Hz), , , , , , , , , HRMS (EI + ) calculated for C 14H 7F 3O 2S, ; found, Phenyl-3-((trifluoromethyl)thio)-4H-chromen-4-one (2u) 7

8 White solid 58 mg (90%). Mp H NMR (300 MHz, Chloroform-d) δ 8.48 (d, J = 2.3 Hz, 1H), 8.41 (s, 1H), 7.97 (dd, J = 8.7, 2.4 Hz, 1H), (m, 2H), 7.58 (d, J = 8.7 Hz, 1H), (m, 2H), (m, 1H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , , , (q, J = Hz), , , , , , HRMS (EI+) calculated for C 16H 9F 3O 2S, ; found, (4-Methoxyphenyl)-3-((trifluoromethyl)thio)-4H-chromen-4-one (2v) White solid 62 mg (88%). Mp H NMR (300 MHz, Chloroform-d) δ 8.42 (d, J = 2.5 Hz, 1H), 8.40 (s, 1H), 7.93 (dd, J = 8.7, 2.4 Hz, 1H), (m, 3H), 7.01 (d, J = 8.4 Hz, 2H), 3.86 (s, 3H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , , , (q, J = Hz), , , , , , , HRMS (EI + ) calculated for C 17H 11F 3O 3S, ; found, Methyl 4-(4-oxo-3-((trifluoromethyl)thio)-4H-chromen-6-yl)benzoate (2w) White solid 67 mg (88%). Mp H NMR (500 MHz, Chloroform-d) δ 8.53 (d, J = 2.4 Hz, 1H), 8.45 (s, 1H), 8.17 (d, J = 8.3 Hz, 2H), 8.02 (dd, J = 8.7, 2.4 Hz, 1H), (m, 2H), 7.64 (d, J = 8.7 Hz, 1H), 3.98 (s, 3H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , , , , , (q, J = Hz), , , , , , HRMS (EI + ) calculated for C 18H 11F 3O 4S, ; found, Bromo-2-(2-(p-tolyl)-5-((trifluoromethyl)thio)pyrimidin-4-yl)phenol (2ia) Yellow solid 50 mg (76%). Mp H NMR (300 MHz, Chloroform-d) δ (s, 1H), 9.12 (s, 1H), 8.30 (d, J = 8.0 Hz, 2H), 8.10 (d, J = 2.4 Hz, 1H), 7.52 (dd, J = 8.9, 2.5 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.00 (d, J = 8.8 Hz, 1H), 2.46 (s, 3H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , , , , , , (q, J = Hz), , , , , HRMS (EI + ) calculated for C 18H 12BrF 3N 2OS, ; found, Bromo-2-(2-cyclopropyl-5-((trifluoromethyl)thio)pyrimidin-4-yl)phenol (2ib) Yellow oil 44 mg (75%). Mp H NMR (300 MHz, Chloroform-d) δ (s, 1H), 8.89 (s, 1H), 8.11 (d, J = 2.4 8

9 Hz, 1H), 7.47 (dd, J = 8.8, 2.4 Hz, 1H), 6.94 (d, J = 8.8 Hz, 1H), 2.31 (p, J = 6.5 Hz, 1H), 1.27 (d, J = 6.5 Hz, 4H). 13 C NMR (126 MHz, Chloroform-d) δ , , , , , , (q, J = Hz), , , , , 18.44, HRMS (EI + ) calculated for C 14H 10BrF 3N 2OS, ; found, (2-Amino-5-((trifluoromethyl)thio)pyrimidin-4-yl)-4-bromophenol (2ic) Yellow solid 24 mg (44%). Mp H NMR (500 MHz, DMSO-d 6) δ (s, 1H), 8.47 (s, 1H), (m, 4H), 6.89 (d, J = 8.7 Hz, 1H). 13 C NMR (126 MHz, DMSO-d 6) δ , , , , , , (q, J = Hz), , , , HRMS (EI + ) Calculated for C 11H 7BrF 3N 3OS, ; found, Methoxy-3-((trifluoromethyl)thio)-4H-naphtho[2,3-h]chromene-4,7,12-trione (3e) Yellow solid 50 mg (41%). Mp H NMR (400 MHz, Chloroform-d) δ (m, 2H), 8.33 (d, J = 8.3 Hz, 1H), (m, 2H), 7.40 (d, J = 8.5 Hz, 1H), 4.07 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ , , , , , , , , , , (q, J = Hz), , , , , , , , HRMS (EI + ) Calculated for C 19H 9F 3O 5S, ; found,

10 Crystal Structure Report for 2a A specimen of C 10H 5F 3O 2S, approximate dimensions mm mm mm, was used for the X-ray crystallographic analysis. The X-ray intensity data were measured. The total exposure time was 4.02 hours. The frames were integrated with the Bruker SAINT software package using a narrow-frame algorithm. The integration of the data using a monoclinic unit cell yielded a total of 6373 reflections to a maximum θ angle of (0.76 Å resolution), of which 2218 were independent (average redundancy 2.873, completeness = 96.5%, R int = 4.25%, R sig = 5.33%) and 1229 (55.41%) were greater than 2σ(F 2 ). The final cell constants of a = (9) Å, b = 4.925(3) Å, c = (8) Å, β = 95.46(4), volume = 969.5(11) Å 3, are based upon the refinement of the XYZ-centroids of 1238 reflections above 20 σ(i) with < 2θ < Data were corrected for absorption effects using the multi-scan method (SADABS). The ratio of minimum to maximum apparent transmission was The calculated minimum and maximum transmission coefficients (based on crystal size) are and The structure was solved and refined using the Bruker SHELXTL Software Package, using the space group P 1 21/c 1, with Z = 4 for the formula unit, C 10H 5F 3O 2S. The final anisotropic full-matrix least-squares refinement on F 2 with 145 variables converged at R1 = 5.27%, for the observed data and wr2 = 23.71% for all data. The goodness-of-fit was The largest peak in the final difference electron density synthesis was e - /Å 3 and the largest hole was e - /Å 3 with an RMS deviation of e - /Å 3. On the basis of the final model, the calculated density was g/cm 3 and F(000), 496 e -. The crystal structure of 2a has been deposited at the Cambridge Crystallographic Data Center and allocated the reference no. CCDC

11 1H NMR and 13 C NMR spectra: 1H NMR spectrum of 2a 13C NMR spectrum of 2a 11

12 1H NMR spectrum of 2b 13C NMR spectrum of 2b 12

13 1H NMR spectrum of 2c 13C NMR spectrum of 2c 13

14 1H NMR spectrum of 2d 13C NMR spectrum of 2d 14

15 1H NMR spectrum of 2e 13C NMR spectrum of 2e 15

16 1H NMR spectrum of 2f 13C NMR spectrum of 2f 16

17 1H NMR spectrum of 2g 13C NMR spectrum of 2g 17

18 1H NMR spectrum of 2h 13C NMR spectrum of 2h 18

19 1H NMR spectrum of 2i 13C NMR spectrum of 2i 19

20 1H NMR spectrum of 2j 13C NMR spectrum of 2j 20

21 1H NMR spectrum of 2k 13C NMR spectrum of 2k 21

22 1H NMR spectrum of 2l 13C NMR spectrum of 2l 22

23 1H NMR spectrum of 2m 13C NMR spectrum of 2m 23

24 1H NMR spectrum of 2n 13C NMR spectrum of 2n 24

25 1H NMR spectrum of 2o 13C NMR spectrum of 2o 25

26 1H NMR spectrum of 2p 13C NMR spectrum of 2p 26

27 1H NMR spectrum of 2q 13C NMR spectrum of 2q 27

28 1H NMR spectrum of 2r 13C NMR spectrum of 2r 28

29 1H NMR spectrum of 2s 13C NMR spectrum of 2s 29

30 1H NMR spectrum of 2t 13C NMR spectrum of 2t 30

31 1H NMR spectrum of 2u 13C NMR spectrum of 2u 31

32 1H NMR spectrum of 2v 13C NMR spectrum of 2v 32

33 1H NMR spectrum of 2w 13C NMR spectrum of 2w 33

34 1H NMR spectrum of 2ia 13C NMR spectrum of 2ia 34

35 1H NMR spectrum of 2ib 13C NMR spectrum of 2ib 35

36 1H NMR spectrum of 2ic 13C NMR spectrum of 2ic 36

37 1H NMR spectrum of 3e 13C NMR spectrum of 3e 37

38 19F NMR spectrum of 2a 38