Supporting Information for

Transcript

1 Supporting Information for A ovel Synthesis of luorinated Pyrazoles via Gold(I)-Catalyzed Tandem Aminofluorination of Alkynes in the Presence of Selectfluor Jianqiang Qian, Yunkui Liu,* Jie Zhu, Bo Jiang, and Zhenyuan Xu* State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of Technology, Hangzhou , People s Repubilc of China ykuiliu@zjut.edu.cn; greensyn@zjut.edu.cn Contents General Typical procedure for synthesis of 2 Experimental procedure for synthesis of 2 a Optimization of reaction conditions The change situation of the yields of 2a and 2'a during the S2 S2 S2 S3 5 S6 reaction time Characterization of all products References S6 S15 S15 1 H, 13 C, and 19 MR spectra of all products S16 S88 S1

2 General Unless otherwise stated, all reagents were purchased from commercial suppliers and used without purifications. All experiments were carried out under a nitrogen atmosphere. All solvents for reactions were dried and distilled prior to use according to standard methods. Melting points are uncorrected. The 1 H and 13 C MR spectra were recorded on a Bruker AVACE III 500 at 25 C in CDCl 3 at 500 MHz, 125 MHz, respectively, with TMS as internal standard. 19 MR were recorded on a Varian Inova 400 at 25 C in CDCl 3 at 376 MHz, with C 3 COOH as external standard. Chemical shifts ( ) are expressed in ppm and coupling constants J are given in Hz. The IR spectra were recorded on an T-IR spectrometer. GC-MS experiments were performed with an Agilent 6890 GC system equipped with a 5973 mass-selective detector with EI source, high resolution mass spectra (HRMS) were obtained on a TO MS instrument with EI source. The starting material 1 were synthesized according to reported literatures. 1,2 Typical experimental procedure for synthesis of fluorinated pyrazole 2 1 (0.2 mmol) was added into a solution of Selectfluor (141.7 mg, 0.4 mmol, 2 equiv), ahco 3 (33.6 mg, 0.4 mmol, 2 equiv) and 3 PAuTf 2 (3.7 mg, mmol) in MeC (2 ml) under 2. Then the reaction mixture was stirred at room temperature for 2.0 h. Upon completion, the resulting mixture was diluted with CH 2 Cl 2 (10 ml) and filtered through Celite. After evaporation of the solvent under vacuum, the residue was purified by column chromatography on silica gel ( mesh) using petroleum ether-etoac (10:1) as eluent to give pure 2. Experimental procedure for synthesis of 2 a 1a (0.2 mmol) was added into a solution of 3 PAuTf 2 (3.7 mg, mmol) in MeC (2 ml) under 2. Then the reaction mixture was stirred at room temperature for 2.0 h. Upon completion, the resulting mixture was diluted with CH 2 Cl 2 (10 ml) and filtered through Celite. After evaporation of the solvent under vacuum, the residue was purified by column chromatography on silica gel ( mesh) using petroleum ether-etoac (10:1) as eluent to give pure 2 a in 92 % yield. S2

3 Optimization of Reaction Conditions Table S1. Screening with different bases a H 3 PAuTf 2 (2.5 mol %) Selectfluor (2 equiv) base, MeC, rt, 2.0 h H 1a 2a 2'a entry base 2a/2'a b yield (%, 2a) c 1 none 1.2: K 2 CO 3 1.1: Cs 2 CO 3 1: CH 3 COOa 4.0: a 2 CO 3 6.1: ahco 3 6.2: ahco 3 (1.2 equiv) 3.1: ahco 3 (3.0 equiv) 4.0: ahco 3, Selectfluor (3.0 equiv) 2.6: ahco 3, Selectfluor (1.2 equiv) 1: H 4 HCO 3 5.8: K 1.9: LiOH 2.3: KOH 1: t-buok 1: Et 3 _ d _ d 17 DMAP _ d _ d 18 DABCO _ d _ d a Reactions carried out with 1a (0.2 mmol), Selectfluor (2 equiv), Base (2 equiv) and 3 PAuTf 2 (2.5 mol %) in MeC (2 ml) at rt for 2 h. b Determined by GC. c Isolated yields. d Only a small amount of 2'a was detected. S3

4 Table S2. Screening with different solvents a H 3 PAuTf 2 (2.5 mol %) Selectfluor (2 equiv) solvent, rt, 2.0 h H 1a 2a 2'a entry solvent 2a/2'a b Yield (%, 2a) c 1 MeO 2 1: TH _ d _ d 3 MeC 6.2: MeC/H 2 O = 20:1 2.1: CH 2 Cl 2 1: ,4-Dioxane _ d _ d 7 Pyridine 1:9 6 8 EtOH _ d _ d 9 DM _ d _ d 10 MeC/H 2 O = 20:1, no base _ e trace a Reactions carried out with 1a (0.2 mmol), Selectfluor (2 equiv), 3 PAuTf 2 (2.5 mol %) and ahco 3 (2 equiv) in solvent (2 ml) at rt for 2 h. b Determined by GC. c Isolated yields. d Only a large quantity of 2'a was detected. e Only 2'a was isolated in 72% yield. S4

5 Table S3. Screening with different catalysts a H catalyst (2.5 mol %) Selectfluor (2 equiv) ahco 3 (2 equiv), MeC rt, 2.0 h H 1a 2a 2'a entry catalyst 2a/2'a b yield (%, 2a) c 1 AuCl 1: PAuCl 5.3: AuCl 3 1: AuCl/AgOTf 1.8: PAuCl/AgOTf 3.8: AuCl 3 /3AgOTf 1.6: AuCl 3 /3AgTf 2 4.7: AuCl/AgTf 2 3.1: PAuTf 2 6.2: PAuCl /AgTf 2 6.2: PAuTf 2, (C 6 H 5 SO 2 ) 2 (2.0 equiv) 1: PAuTf 2 6.1:1 79 d 13 IMesAuTf 2 3.6: PAuCl/AgSb 6 1: PAuCl/Ag 5.9: PAuCl/AgC 4.1: PAuCl/AgO 2 1.9: AgTf 2 1.5: PdCl 2 1.1: ecl 3 2.5: CuI 1.6: none _ e _ e a Reactions carried out with 1a (0.2 mmol), Selectfluor (2 equiv), ahco 3 (2 equiv) and catalyst (2.5 mol %) in MeC (2 ml) at rt for 2 h. b Determined by GC. c Isolated yield. d Reaction temperature at 40 o C. e Both 2a and 2'a were not detected. S5

6 Table S4. The change situation of the yields of 2a and 2'a during the reaction time Time(h) t a Yield(%) 2 a Yield (%) Time (h) IGURE 1. Plots of the yields of 2a and 2 a against reaction time (h) for the gold-catalyzed aminofluorination of 1a. Curve a and b represent the change situation of the yield of 2a and 2 a with the reaction time, respectively. a b Characterization of all products (1) 4-luoro-3-methyl-1,5-diphenyl-1H-pyrazole (2a) 3 Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (40.8 mg, 81%); R f = 0.49; IR (neat): = 3060, 2927, 2862, 1596, 1503, 1448, 1372 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 5H), (m, 5H), 2.39 (s, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 140.1, (d, J = 11.3 Hz), 129.0, (d, J = 2.5 Hz), 128.5, 128.4, (d, J = 22.5 Hz), (d, J = 3.8 Hz), 127.3, 124.7, 10.0 (d, J = 2.5 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 252(100) [M + ], 231(21), 180(13), 108(9), 77(35). (2) 4-luoro-3-methyl-1-phenyl-5-p-tolyl-1H-pyrazole (2b) S6

7 Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (45.2 mg, 85%); R f = 0.46; IR (neat): = 3032, 2926, 2866, 1598, 1509, 1448, 1371 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 2H), (m, 3H), 7.16 (m, 4H), 2.40 (s, 3H), 2.37 (s, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 140.0, 138.5, (d, J = 12.5 Hz), (d, J = 5.0 Hz), 129.3, 129.0, (d, J = 1.3 Hz), (d, J = 21.3 Hz), 127.3, 124.8, 21.3, 10.0 (d, J = 2.5 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC- MS (EI, 70eV): m/z (%) = 266(100) [M + ], 245(17), 219(5), 194(10), 77(24); HRMS (EI) for C 17 H 15 2 : calcd , found (3) 4-luoro-5-(4-methoxyphenyl)-3-methyl-1-phenyl-1H-pyrazole (2c) O Purification by column chromatography (petroleum ether/etoac, 6/1) as a yellow oil (45.7 mg, 81%); R f = 0.44; IR (neat): = 3056, 2927, 2845, 1607, 1510, 1447, 1371, 1251, 1154 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 2H), (m, 3H), 7.18 (d, J = 8.5 Hz, 2H), 6.88 (d, J = 9.0 Hz, 2H), 3.83 (s, 3H), 2.38 (s, 3H); 13 C MR (CDCl 3, 125 MHz): δ 159.6, (d, J = Hz), 140.2, (d, J = 11.3 Hz), (d, J = 1.3 Hz), 128.9, (d, J = 22.5 Hz), 127.2, 124.7, (d, J = 3.8 Hz), 114.1, 55.2, 10.1 (d, J = 2.5 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 282(100) [M + ], 267(31), 239(5), 210(5), 77(9); HRMS (EI) for C 17 H 15 2 O: calcd , found (4) 4-luoro-5-(2-methoxyphenyl)-3-methyl-1-phenyl-1H-pyrazole (2d) O Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (46.8 mg, 83%); R f = 0.30; IR (neat): = 3065, 3006, 2934, 2841, 1594, 1499, 1464, 1372 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 1H), (m, 6H), 7.02 (dd, J 1 =7.0, J 2 = 8.0 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 3.43 (s, 3H), 2.40 (s, 3H); 13 C MR (CDCl 3, 125 MHz): δ 156.7, (d, J = Hz), 141.0, (d, J = 11.3 Hz), (d, J = Hz), 131.4, 130.8, 128.6, (d, J = 23.8 Hz), 123.0, 120.8, (d, J = 2.5 Hz), 111.4, 55.0, 10.1 (d, J = 2.5 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 282(100) [M + ], 261(23), 220(22), 118(11), 77(29); HRMS (EI) for C 17 H 15 2 O: calcd , found S7

8 (5) 5-(4-Ethoxyphenyl)-4-fluoro-3-methyl-1-phenyl-1H-pyrazole (2e) O Purification by column chromatography (petroleum ether/etoac, 6/1) as a yellow oil (47.3 mg, 80%); R f = 0.53; IR (neat): = 3062, 2978, 2927, 1606, 1512, 1372, 1248 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 2H), (m, 3H), 7.16 (d, J = 8.5 Hz, 2H), (d, J = 8.5 Hz, 2H), 4.05 (q, J =7.0 Hz, 2H), 2.38 (s, 3H), 1.43 (t, J = 7.0 Hz, 3H); 13 C MR (CDCl 3, 125 MHz): δ 159.0, (d, J = Hz), 140.2, (d, J = 11.3 Hz), (d, J = 2.5 Hz), 128.9, (d, J = 23.8 Hz), 127.1, 124.7, (d, J = 2.5 Hz), 114.6, 63.5, 14.8, 10.1 (d, J = 2.5 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 296(100) [M + ], 267(47), 247(9), 196(8), 77(21); HRMS (EI) for C 18 H 17 2 O: calcd , found (6) 5-(4-Ethylphenyl)-4-fluoro-3-methyl-1-phenyl-1H-pyrazole (2f) Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (40.8 mg, 73%); R f = 0.44; IR (neat): = 3057, 2966, 2929, 2871, 1598, 1507, 1453, 1370 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 2H), (m, 3H), (m, 4H), 2.67 (q, J = 8.0 Hz, 2H), 2.39 (s, 3H), 1.25 (t, J = 7.8 Hz, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 144.6, 140.1, (d, J = 11.3 Hz), (d, J = 5.0 Hz), 128.9, (d, J = 2.5 Hz), (d, J = 21.3 Hz), 128.1, 127.2, 124.7, 28.6, 15.2, 10.0 (d, J = 2.5 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 280(100) [M + ], 265(91), 251(4), 231(4), 77(20); HRMS (EI) for C 18 H 17 2 : calcd , found (7) 4-luoro-3-methyl-5-(4-pentylphenyl)-1-phenyl-1H-pyrazole (2g) Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (48.2 mg, 75%); R f = 0.38; IR (neat): = 3056, 2928, 2860, 1595, 1510, 1453, 1372 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 2H), (m, 3H), (m, 4H), 2.61 (t, J = 7.8 Hz, 2H), 2.39 (s, 3H), (m, 2H), (m, 4H), 0.91 (t, J = 7.0 Hz, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 143.4, 140.2, (d, J = 11.3 Hz), 128.9, (d, J = 2.5 Hz), 128.6, (d, J = 21.3 Hz), 127.2, (d, J = 3.8 Hz), 124.7, 35.7, 31.5, 30.8, 22.5, 14.0, 10.1 (d, J = 2.5 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS S8

9 (EI, 70eV): m/z (%) = 322(66) [M + ], 265(100), 251(2), 204(2), 77(8); HRMS (EI) for C 21 H 23 2 : calcd , found (8) 5-(4-Chlorophenyl)-4-fluoro-3-methyl-1-phenyl-1H-pyrazole (2h) Cl Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow solid (36.7 mg, 64%); mp ºC; R f = 0.57; IR (KBr): = 3061, 2928, 2861, 1594, 1500, 1441, 1370 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 5H), 7.26 (d, J = 8.5 Hz, 2H), 7.18 (d, J = 8.5 Hz, 2H), 2.38 (s, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 139.7, (d, J = 11.3 Hz), 134.5, (d, J = 2.5 Hz), 129.2, 128.9, 127.6, (d, J = 22.5 Hz), (d, J = 3.8 Hz), 124.8, 10.0 (d, J = 1.3 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 286(100) [M + ], 265(14), 250(5), 108(8), 77(31); HRMS (EI) for C 16 H 12 Cl 2 : calcd , found (9) 5-(2-Chlorophenyl)-4-fluoro-3-methyl-1-phenyl-1H-pyrazole (2i) Cl Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow-brown solid (41.8 mg, 73%); mp ºC; R f = 0.49; IR (KBr): = 3065, 2928, 2862, 1594, 1508, 1447, 1369 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 5H), (m, 3H), 7.08 (d, J = 7.5 Hz, 1H), 2.39 (s, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 139.7, (d, J = 11.3 Hz), 134.5, 129.8, (d, J = 3.8 Hz), 129.1, (d, J = 2.5 Hz), 128.5, 127.6, (d, J = 2.5 Hz), (d, J = 21.3 Hz), 124.8, 10.0 (d, J = 2.5 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 286(100) [M + ], 265(21), 250(7), 214(10), 77(37); HRMS (EI) for C 16 H 12 Cl 2 : calcd , found (10) 5-(4-Bromophenyl)-4-fluoro-3-methyl-1-phenyl-1H-pyrazole (2j) Br Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (45.6 mg, 69%); R f = 0.51; IR (neatr): = 3060, 2928, 2864, 1595, 1499, 1435, 1369 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 2H), (m, 3H), 7.26 (m, J = 8.5 Hz, 2H), 7.12 (d, J = 8.5 Hz, 2H), 2.38 (s, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 139.8, (d, J = 11.3 Hz), 131.9, (d, J = 1.3 Hz), S9

10 129.1, 127.5, (d, J = 22.5 Hz), (d, J = 5.0 Hz), 124.8, 122.7, 10.0 (d, J = 2.5 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 330(100) [M + ], 311(14), 250(10), 118(17), 77(52); HRMS (EI) for C 16 H 12 Br 2 : calcd , found (11) 4-luoro-3-methyl-1-phenyl-5-(thiophen-2-yl)-1H-pyrazole (2k) S Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow-brown oil (44.8 mg, 87%); R f = 0.49; IR (neat): = 3072, 2928, 2861, 1597, 1505, 1453, 1373 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 6H), (m, 2H), 2.37 (s, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 139.7, (d, J = 11.3 Hz), 129.1, 128.3, (d, J = 2.5 Hz), 127.2, 127.0, 125.9, (d, J = 22.5 Hz), (d, J = Hz), 10.0 (d, J = 3.8 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 258(100) [M + ], 237(20), 216(9), 186(11), 77(29); HRMS (EI) for C 14 H 11 2 S: calcd , found (12) 5-Butyl-4-fluoro-3-methyl-1-phenyl-1H-pyrazole (2l) Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (36.1 mg, 78%); R f = 0.33; IR (neat): = 3065, 2958, 2930, 2866, 1599, 1509, 1460, 1381 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 2H), (m, 3H), 2.68 (t, J = 7.5 Hz, 2H), 2.3 (s, 3H), (m, 2H), (m, 2H), 0.86 (t, J = 7.5 Hz, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 140.1, (d, J = 11.3 Hz), 129.1, (d, J = 23.8 Hz), 127.7, 125.1, 30.0, 23.4 (d, J = 3.8 Hz), 22.2, 13.6, 9.9; 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 232(67) [M + ], 203(15), 190(100), 169(16), 77(29); HRMS (EI) for C 14 H 17 2 : calcd , found (13) 5-Benzyl-4-fluoro-3-methyl-1-phenyl-1H-pyrazole (2m) Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (39.3 mg, 74%); R f = 0.44; IR (neat): = 3062, 3031, 2935, 2856, 1600, 1505, 1455, 1380 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 3H), (m, 4H), (m, 1H), 7.08 (d, J = 7.5 Hz, 2H), 4.02 (s, 2H), 2.34 (s, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 139.4, 137.3, (d, J = 11.3 Hz), S10

11 129.1, 128.7, 128.1, 127.9, (d, J = 25.0 Hz), 126.7, 125.1, 29.4 (d, J = 2.5 Hz), 10.0 (d, J = 2.5 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 266(100) [M + ], 251(9), 189(25), 91(12), 77(19); HRMS (EI) for C 17 H 15 2 : calcd , found (14) 5-tert-Butyl-4-fluoro-3-methyl-1-phenyl-1H-pyrazole (2n) Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (34.8 mg, 75%); R f = 0.47; IR (neat): = 3063, 2967, 2874, 1598, 1508, 1371, 1291 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 3H), (m, 2H), 2.25 (s, 3H), 1.22 (d, J = 1.5 Hz, 9H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 142.5, (d, J = 17.5 Hz), (d, J = 13.8 Hz), 129.0, 128.7, 128.6, 32.4 (d, J = 3.8 Hz), 30.2 (d, J = 3.8 Hz), 9.8 (d, J = 2.5 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 232(41) [M + ], 217(100), 197(2), 182(4), 77(12). HRMS (EI) for C 14 H 17 2 : calcd , found (15) 4-luoro-3-methyl-1-phenyl-5-(trimethylsilyl)-1H-pyrazole (2o) Si Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (21.4 mg, 43%); R f = 0.48; IR (neat): = 3062, 2960, 2862, 1600, 1505, 1406, 1256 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 3H), (m, 2H), 2.31 (s, 3H), 0.14 (d, J = 1.0 Hz, 9H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 142.6, (d, J = 13.8 Hz), 128.8, 128.3, (d, J = 30.0 Hz), 126.2, 9.4 (d, J = 2.5 Hz), -0.8; 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 248(83) [M + ], 233(100), 218(5), 171(21), 130(13), 77(47). HRMS (EI) for C 13 H 17 2 Si: calcd , found (16) 3-Ethyl-4-fluoro-1,5-diphenyl-1H-pyrazole (2p) Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (35.6 mg, 67%); R f = 0.47; IR (neat): = 3060, 2970, 2928, 2861, 1596, 1506, 1449, 1379, 1336 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 5H), (m, 5H), 2.79 (q, J = 7.5 Hz, 2H), 1.36 (t, J = 7.8 Hz, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), (d, J = 10.0 Hz), 140.1, 129.0, (d, J = 2.5 Hz), 128.6, 128.4, (d, J = 22.5 Hz), (d, J = 5.0 Hz), 127.3, 124.8, 18.8 (d, J = S11

12 2.5 Hz), 12.9; 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 266(100) [M + ], 251(33), 231(2), 180(8), 77(33); HRMS (EI) for C 17 H 15 2 : calcd , found (17) 4-luoro-1,5-diphenyl-3-propyl-1H-pyrazole (2q) Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (35.2 mg, 63%); R f = 0.51; IR (neat): = 3061, 2962, 2931, 2872, 1594, 1505, 1451, 1377 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 5H), (m, 5H), 2.75 (t, J = 7.5 Hz, 2H), (m, 2H), 1.06 (t, J = 7.3 Hz, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), (d, J = 11.3 Hz), 140.1, 128.9(2C), 128.5, 128.3, (d, J = 21.3 Hz), (d, J = 3.8 Hz), 127.2, 124.8, 27.3 (d, J = 3.8 Hz), 22.0, 14.0; 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%)= 280(25) [M + ], 265(8), 252(100), 180(4), 77(21); HRMS (EI) for C 18 H 17 2 : calcd , found (18) 4-luoro-1,5-diphenyl-1H-pyrazole (2r) H Purification by column chromatography (petroleum ether/etoac, 10/1) as a colorless oil (42.8 mg, 90%); R f = 0.44; IR (neat): = 3065, 2925, 2854, 1596, 1551, 1508, 1476, 1444, 1381 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 6H), (m, 4H), 6.09 (d, J = 5.5 Hz, 1H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 144.7, 139.4, 129.9, 128.9, 128.8, 128.7, 128.6, 127.5, 125.2, 91.7 (d, J = 23.8 Hz); 19 MR (CDCl 3, 376 MHz): δ (d, J = 6.0 Hz); GC-MS (EI, 70eV): m/z (%) = 238(100) [M + ], 210(12), 190(12), 135(3), 77(15); HRMS (EI) for C 15 H 11 2 : calcd , found (19) 3-tert-Butyl-4-fluoro-1,5-diphenyl-1H-pyrazole (2s) t-bu Purification by column chromatography (petroleum ether/etoac, 10/1) as a pale-yellow solid (37.7 mg, 64%); mp ºC; R f = 0.45; IR (KBr): = 3047, 2990, 2969, 2875, 1596, 1554, 1499, 1482, 1451, 1365 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ 7.92 (d, J = 8.0 Hz, 2H), (m, 3H), (m, 4H), 7.33 (t, J = 7.3 Hz, 1H), 1.28 (d, J = 15.0 Hz, 9H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = S12

13 248.8 Hz), 142.5, (d, J = 8.8 Hz), (d, J = 18.8 Hz), (d, J = 3.8 Hz), 129.3, 128.8, 128.7, 128.5, 127.9, (d, J = 3.8 Hz), 32.7 (d, J = 3.8 Hz), 30.3 (d, J = 3.8 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 294(54) [M + ], 279(100), 243(3), 132(3), 77(10). HRMS (EI) for C 19 H 19 2 : calcd , found (20) 1-(2,4-Dichlorophenyl)-4-fluoro-5-phenyl-1H-pyrazole (2t) Cl Cl H Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (50.3 mg, 82%); R f = 0.46; IR (neat): = 3071, 2927, 2859, 1554, 1507, 1480, 1389 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ 7.45 (d, J = 2.0 Hz, 1H), (m, 5H), (m, 2H), 6.15 (d, J = 5.5 Hz, 1H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 147.0, 136.0, 135.7, 133.5, 130.9, 130.3, 129.2, 129.1, 128.7, 128.0, 127.9, 90.9 (d, J = 23.8 Hz); 19 MR (CDCl 3, 376 MHz): δ (d, J = 6.0 Hz); GC-MS (EI, 70eV): m/z (%) = 306(60) [M + ], 271(100), 236(60), 109(18), 77(24); HRMS (EI) for C 15 H 9 Cl 2 2 : calcd , found (21) 1-(2,4-Dichlorophenyl)-4-fluoro-3-methyl-5-phenyl-1H-pyrazole (2u) Cl Cl Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (35.9 mg, 56%); R f = 0.48; IR (neat): = 3061, 2927, 2859, 1592, 1494, 1380, 1309, 1153 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ 7.45 (d, J = 2.5 Hz, 1H), (m, 5H), (m, 2H), 2.39 (s, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), (d, J = 11.3 Hz), 136.7, 135.5, 133.2, 130.8, 130.3, (d, J = 21.3 Hz), 128.7, 128.6, 127.9, (d, J = 3.8 Hz), 10.1 (d, J = 1.3 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 320(100) [M + ], 285(42), 265(56), 250(64), 109(28), 77(37); HRMS (EI) for C 16 H 11 Cl 2 2 : calcd , found (22) 4-luoro-3-methyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole (2v) S13

14 O 2 Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow soild (38.1 mg, 64%); mp ºC; R f = 0.45; IR (neat): = 3085, 2931, 2857, 1598, 1518, 1448, 1343 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 2H), (m, 5H), (m, 2H), 2.40 (s, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), 145.7, 144.8, (d, J = 12.5 Hz), 129.3, 129.1, (d, J = 2.5 Hz), (d, J = 23.8 Hz), (d, J = 3.8 Hz), 124.5, 123.7, 10.1 (d, J = 2.5 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 297(100) [M + ], 276(8), 250(20), 179(6), 77(10); HRMS (EI) for C 16 H 12 3 O 2 : calcd , found (23) 4-luoro-1,3-dimethyl-5-phenyl-1H-pyrazole (2w) Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (18.6 mg, 49%); R f = 0.51; IR (neat): = 3060, 2928, 2856, 1586, 1533, 1501, 1454, 1372 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 2H), (m, 3H), 3.80 (s, 3H), 2.30 (s, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), (d, J = 11.3 Hz), 129.2, 129.0, 128.9, 128.8, (d, J = 3.8 Hz), 37.9, 9.8 (d, J = 1.3 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 190(100) [M + ], 175(5), 146(8), 118(15), 77(13). HRMS (EI) for C 11 H 11 2 : calcd , found (24) 4-luoro-3-methyl-5-phenyl-1H-pyrazole (2x) H Purification by column chromatography (petroleum ether/etoac, 1/1) as a pale yellow soild (15.8 mg, 45%); mp ºC; R f = 0.51; IR (KBr): = 3060, 2922, 2857, 1616, 1533, 1503, 1459 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ 7.75 (d, J = 8.0 Hz, 2H), 7.42 (t, J = 7.8 Hz, 2H), 7.34 (m, 1H), 7.0 (br. s, 1H), 2.27 (s, 3H); 13 C MR (CDCl 3, 125 MHz): δ (d, J = Hz), (d, J = 11.3 Hz), (d, J = 20.0 Hz), (d, J = 3.8 Hz), 128.8, 128.1, (d, J = 3.8 Hz), 8.6 (d, J = 2.5 Hz); 19 MR (CDCl 3, 376 MHz): δ (s); GC-MS (EI, 70eV): m/z (%) = 176(100) [M + ], 161(3), 146(7.0), 108(11), 77(19); HRMS (EI) for C 10 H 9 2 : calcd , found S14

15 (25) 3-Methyl-1,5-diphenyl-1H-pyrazole (2'a) 4 H Purification by column chromatography (petroleum ether/etoac, 10/1) as a yellow oil (43.1 mg, 92%); R f = 0.32; IR (neat): = 3058, 2958, 2927, 2868, 1598, 1501, 1451, 1369 cm -1 ; 1 H MR (CDCl 3, 500 MHz): δ (m, 8H), (m, 2H), 6.34 (s, 1H), 2.41 (s, 3H); GC-MS (EI, 70eV): m/z (%) = 234(100) [M + ], 218(17), 192(13), 165(13), 77(27). References: 1. Aldeco-Pérez, E. J.; Álvarez-Toledano, C.; Toscano, A.; García-Estrada, J. G.; Penieres-Carrillo, J. G. Tetrahedron Lett. 2008, 49, Zanka, A.; Uematsu, R.; Morinaga, Y.; Yasuda, H.; Yamazaki, H. Organic Process Research & Development 1999, 3, Joseph, C. S.; Carl, L. B.; W. David, L. J. luorine Chem. 2002, 118, Exier-Boullet,.; Klein, B.; Hamelin, J. Synthesis. 1986, 5, 409. S15

16 1 H, 13 C, and 19 MR spectra of all products 2a S16

17 2a S17

18 2a S18

19 2b S19

20 2b S20

21 2b S21

22 O 2c S22

23 O 2c S23

24 O 2c S24

25 O 2d S25

26 O 2d S26

27 O 2d S27

28 O 2e S28

29 O 2e S29

30 O 2e S30

31 2f S31

32 2f S32

33 2f S33

34 2g S34

35 2g S35

36 2g S36

37 Cl 2h S37

38 Cl 2h S38

39 Cl 2h S39

40 Cl 2i S40

41 Cl 2i S41

42 Cl 2i S42

43 Br 2j S43

44 Br 2j S44

45 Br 2j S45

46 S 2k S46

47 S 2k S47

48 S 2k S48

49 2l S49

50 2l S50

51 2l S51

52 2m S52

53 2m S53

54 2m S54

55 2n S55

56 2n S56

57 2n S57

58 Si 2o S58

59 Si 2o S59

60 Si 2o S60

61 2p S61

62 2p S62

63 2p S63

64 2q S64

65 2q S65

66 2q S66

67 2r H S67

68 2r H S68

69 2r H S69

70 2s t-bu S70

71 2s t-bu S71

72 2s t-bu S72

73 Cl Cl 2t H S73

74 Cl Cl 2t H S74

75 Cl Cl 2t H S75

76 Cl Cl 2u S76

77 Cl Cl 2u S77

78 Cl Cl 2u S78

79 O 2 2v S79

80 O 2 2v S80

81 O 2 2v S81

82 2w S82

83 2w S83

84 2w S84

85 H 2x S85

86 H 2x S86

87 H 2x S87

88 H 2'a S88