Supporting Information

Supporting Information Copper/Silver Cocatalyzed Oxidative Coupling of Vinylarenes with ICH 2 CF 3 or ICH 2 CHF 2 Leading to β-cf 3 /CHF 2 -Substituted Ketones Niannian Yi, Hao Zhang, Chonghui Xu, Wei Deng*, Ruijia Wang, Dongming Peng, Zebing Zeng, and Jiannan Xiang* State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, P. R. China School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, P. R. China Content Page number General information 1 General procedure 1 Mechanistic study 1 Characterization data of products 2 1 H, 13 C and 19 F NMR spectra 10

General information Commercially available reagents were purchased from commercial suppliers and used without further purification. Reactions were monitored by thin layer chromatography (TLC) using silicycle pre-coated silica gel plates. Flash column chromatography was performed over silicycle silica gel (200-300 mesh). 1 H NMR, 13 C NMR and 19 F NMR spectra were recorded on 400 MHz NMR plus spectrometer using residue solvent peaks as internal standards. Infrared spectra were recorded with IR spectrometer and are reported in reciprocal centimeter (cm -1 ). High resolution mass spectra were obtained using GCT-TOF instrument with EI or ESI source. General procedure for the synthesis of 3 and 4 To a sealed tube were added vinylarene (0.75 mmol), ICH 2 CF 3 (0.5 mmol, 105 mg) or ICH 2 CHF 2 (0.5 mmol, 96 mg), Cu(acac) 2 (0.1 mmol, 26 mg), Ag 2 SO 4 (0.1 mmol, 31 mg), Et 3 N (0.5 mmol, 50 mg), TBHP (1.5 mmol, 193 mg, 70% in water) and CH 3 CN (1 ml). Then the tube was stirred at 80 C for 24 h. After completion of the reaction, the resulting mixture was diluted with dichloromethane and washed with water. The separated aqueous phase was washed with CH 2 Cl 2. The combined organic layers were washed with brine, dried over Na 2 SO 4, filtered, and concentrated under vacuo. The crude mixture was purified by column chromatography on silica gel (petroleum ether/ethyl acetate) to afford the desired product 3 or 4. Large-scale synthesis of 3a To a sealed tube were added 4-tert-butylstyrene (15 mmol, 2.4 g), ICH 2 CF 3 (10 mmol, 2.1 g), Cu(acac) 2 (2 mmol, 0.52 g), Ag 2 SO 4 (2 mmol, 0.62 g), Et 3 N (10 mmol, 1.0 g), TBHP (30 mmol, 3.86 g, 70% in water) and CH 3 CN (20 ml). Then the tube was stirred at 80 C for 24 h. After completion of the reaction, the resulting mixture was quenched with saturated Na 2 S 2 O 3 solution and extracted with dichloromethane. The organic layer was washed with water and brine, and the separated aqueous phase was extracted with CH 2 Cl 2. The combined organic layers dried over Na 2 SO 4, filtered, and concentrated under vacuo. The crude mixture was purified by column chromatography on silica gel (petroleum ether/ethyl acetate) to afford the desired product 3a as a white solid (1.56 g, 60% yield). Mechanistic study 1) The reaction of TEMPO and ICH 2 CF 3 under the standard conditions To a sealed tube were added ICH 2 CF 3 (0.5 mmol, 105 mg), TEMPO (1.0 mmol, 156 mg), Cu(acac) 2 (0.1 mmol, 26 mg), Ag 2 SO 4 (0.1 mmol, 31 mg), Et 3 N (0.5 mmol, 50 mg), TBHP (1.5 mmol, 193 mg, 70% in water) and CH 3 CN (2 ml). Then the tube was stirred at 80 C for 24 h. After completion of the reaction, the resulting mixture was diluted with dichloromethane and washed with water. The separated aqueous phase was washed with CH 2 Cl 2. The combined organic layers were dried over Na 2 SO 4, filtered, and concentrated under vacuo. 19 F NMR analysis of the 1

crude mixture showed that TEMPO-CH 2 CF 3 was formed in 71% yield. EI-MS (m/z, relative intensity): 239 (M +, 11), 224 (100), 156 (71), 124 (27), 109 (68), 69 (80). 19 F NMR (376 MHz, CDCl 3 ) δ -73.37. 2) The reaction of 4-tert-butylstyrene, TEMPO and ICH 2 CF 3 under the standard conditions To a sealed tube were added 4-tert-butylstyrene (0.75 mmol, 120 mg), ICH 2 CF 3 (0.5 mmol, 105 mg), TEMPO (1.0 mmol, 156 mg), Cu(acac) 2 (0.1 mmol, 26 mg), Ag 2 SO 4 (0.1 mmol, 31 mg), Et 3 N (0.5 mmol, 50 mg), TBHP (1.5 mmol, 193 mg, 70% in water) and CH 3 CN (2 ml). Then the tube was stirred at 80 C for 24 h. After completion of the reaction, the resulting mixture was diluted with dichloromethane and washed with water. The separated aqueous phase was washed with CH 2 Cl 2. The combined organic layers were dried over Na 2 SO 4, filtered, and concentrated under vacuo. 19 F NMR analysis of the crude mixture showed that TEMPO-CH 2 CF 3 was formed in 60% yield and 3a was not detected. Characterization data of products 1-(4-(tert-butyl)phenyl)-4,4,4-trifluorobutan-1-one (3a) White solid, 62% yield (80 mg), mp = 66-68 C; 1 H NMR (400 MHz, CDCl 3 ) δ 7.91 (d, J = 8.8 Hz, 2 H), 7.50 (d, J = 8.4 Hz, 2 H), 3.24 (t, J = 7.8 Hz, 2 H), 2.65-2.53 (m, 2 H), 1.35 (s, 9 H); 13 C NMR (100 MHz, CDCl 3 ) δ 195.9, 157.4, 133.6, 128.0, 127.2 (q, J = 274.1 Hz), 125.7, 35.1, 31.0, 28.4 (q, J = 29.4 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -66.44; IR (KBr): 2965, 1683, 1605, 1336, 1142, 1100, 984 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 14 H 18 F 3 O: 259.1304, found: 259.1305. 4,4,4-trifluoro-1-phenylbutan-1-one (3b) 1, 2 White solid, 52% yield (52 mg), mp = 56-58 C; 1 H NMR (400 MHz, CDCl 3 ) δ 7.97 (d, J = 7.6 Hz, 2 H), 7.60 (t, J = 7.2 Hz, 1 H), 7.49 (t, J = 7.6 Hz, 2 H), 3.26 (t, J = 7.8 Hz, 2 H), 2.66-2.54 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 196.3, 136.1, 133.6, 128.8, 128.0, 127.1 (q, J = 273.9 Hz), 31.2 (d, J = 2.2 Hz), 28.3 (q, J = 29.6 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -66.44. 4,4,4-trifluoro-1-(4-fluorophenyl)butan-1-one (3c) 1, 2 2

Colorless oil, 60% yield (66 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 8.00 (dd, J = 8.8, 5.6 Hz, 2 H), 7.15 (t, J = 8.4 Hz, 2 H), 3.22 (t, J = 7.8 Hz, 2 H), 2.64-2.52 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 194.7, 166.0 (d, J = 254.4 Hz), 132.5 (d, J = 3.0 Hz), 130.6 (d, J = 9.5 Hz), 127.1 (q, J = 273.9 Hz), 115.9 (d, J = 21.9 Hz), 31.1 (d, J = 2.2 Hz), 28.3 (q, J = 29.7 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -66.49, -104.28. 1-(4-chlorophenyl)-4,4,4-trifluorobutan-1-one (3d) 1, 2 White solid, 72% yield (85 mg), mp = 65-67 C; 1 H NMR (400 MHz, CDCl 3 ) δ 7.91 (d, J = 8.8 Hz, 2 H), 7.46 (d, J = 8.4 Hz, 2 H), 3.22 (t, J = 7.8 Hz, 2 H), 2.65-2.53 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 195.1, 140.1, 134.4, 129.4, 129.1, 127.0 (q, J = 274.2 Hz), 31.2 (d, J = 2.1 Hz), 28.3 (q, J = 29.6 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -66.44. 1-(4-bromophenyl)-4,4,4-trifluorobutan-1-one (3e) 1, 2 O CF 3 Br White solid, 70% yield (98 mg), mp = 79-80 C; 1 H NMR (400 MHz, CDCl 3 ) δ 7.82 (d, J = 8.4 Hz, 2 H), 7.62 (d, J = 8.0 Hz, 2 H), 3.22 (t, J = 7.8 Hz, 2 H), 2.64-2.52 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 195.3, 134.8, 132.1, 129.5, 128.8, 127.0 (q, J = 273.9 Hz), 31.2 (d, J = 3.0 Hz), 28.2 (q, J = 29.6 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -66.44. 1-(3-bromophenyl)-4,4,4-trifluorobutan-1-one (3f) 1 Colorless oil, 62% yield (86 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 8.08 (s, 1 H), 7.88 (d, J = 8.0 Hz, 1 H), 7.71 (d, J = 8.0 Hz, 1 H), 7.37 (t, J = 7.8 Hz, 1 H), 3.22 (t, J = 7.8 Hz, 2 H), 2.64-2.52 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 194.9, 137.7, 136.4, 131.0, 130.3, 127.0 (q, J = 274.1 Hz), 126.5, 123.1, 31.3 (d, J = 2.9 Hz), 28.2 (q, J = 29.7 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -66.42. 1-(2-chlorophenyl)-4,4,4-trifluorobutan-1-one (3g) 3

Colorless oil, 31% yield (36 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 7.51 (d, J = 7.2 Hz, 1 H), 7.45-7.40 (m, 2 H), 7.35 (t, J = 6.8 Hz, 1 H), 3.24 (t, J = 7.6 Hz, 2 H), 2.65-2.53 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 199.3, 138.2, 132.3, 131.1, 130.7, 129.1, 127.1, 126.8 (q, J = 274.2 Hz), 35.4 (d, J = 2.2 Hz), 28.4 (q, J = 29.9 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -66.44; IR (KBr): 2966, 1690, 1582, 1331, 1142, 976 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 10 H 9 ClF 3 O: 237.0288, found: 237.0286. 4,4,4-trifluoro-1-(p-tolyl)butan-1-one (3h) 1, 2 White solid, 54% yield (58 mg), mp = 78-81 C; 1 H NMR (400 MHz, CDCl 3 ) δ 7.87 (d, J = 8.4 Hz, 2 H), 7.28 (d, J = 8.4 Hz, 2 H), 3.23 (t, J = 7.8 Hz, 2 H), 2.64-2.52 (m, 2 H), 2.42 (s, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ 195.9, 144.5, 133.7, 129.4, 128.1, 127.2 (q, J = 273.9 Hz), 31.0 (d, J = 2.2 Hz), 28.4 (q, J = 29.4 Hz), 21.6; 19 F NMR (376 MHz, CDCl 3 ) δ -66.43. 4,4,4-trifluoro-1-(4-methoxyphenyl)butan-1-one (3i) 1, 2 White solid, 55% yield (63 mg), mp = 61-63 C; 1 H NMR (400 MHz, CDCl 3 ) δ 7.94 (d, J = 8.8 Hz, 2 H), 6.94 (d, J = 8.8 Hz, 2 H), 3.87 (s, 3 H), 3.19 (t, J = 7.8 Hz, 2 H), 2.63-2.51 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 194.8, 163.8, 130.3, 129.2, 127.2 (q, J = 274.2 Hz), 113.8, 55.4, 30.7 (d, J = 2.9 Hz), 28.4 (q, J = 29.4 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -66.43. 4-(4,4,4-trifluorobutanoyl)phenyl acetate (3j) White solid, 40% yield (52 mg), mp = 87-88 C; 1 H NMR (400 MHz, CDCl 3 ) δ 8.00 (d, J = 8.4 Hz, 2 H), 7.21 (d, J = 8.4 Hz, 2 H), 3.23 (t, J = 7.8 Hz, 2 H), 2.65-2.52 (m, 2 H), 2.32 (s, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ 195.0, 168.7, 154.7, 133.6, 129.6, 127.1 (q, J = 274.1 Hz), 121.9, 31.1 (d, J = 2.9 Hz), 28.3 (q, J = 29.6 Hz), 21.1; 19 F NMR (376 MHz, CDCl 3 ) δ -66.44; IR (KBr): 2968, 1738, 1687, 1601, 1339, 1140, 1107, 981 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 12 H 12 F 3 O 3 : 261.0733, found: 261.0735. 4,4,4-trifluoro-1-(naphthalen-2-yl)butan-1-one (3k) 1, 2 4

White solid, 46% yield (58 mg), mp = 88-90 C; 1 H NMR (400 MHz, CDCl 3 ) δ 8.47 (s, 1 H), 8.04-7.97 (m, 2 H), 7.90 (t, J = 8.6 Hz, 2 H), 7.64-7.56 (m, 2 H), 3.39 (t, J = 7.8 Hz, 2 H), 2.72-2.60 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 196.2, 135.7, 133.4, 132.4, 129.8, 129.6, 128.7, 128.6, 127.8, 127.2 (q, J = 273.9 Hz), 126.9, 123.5, 31.2 (d, J = 2.9 Hz), 28.4 (q, J = 29.4 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -66.32. 4,4,4-trifluoro-1-(pyridin-4-yl)butan-1-one (3l) O N CF 3 Pale yellow oil, 48% yield (48 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 8.82 (d, J = 5.6 Hz, 2 H), 7.72 (d, J = 6.0 Hz, 2 H), 3.25 (t, J = 7.6 Hz, 2 H), 2.65-2.53 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 195.8, 151.1, 141.7, 126.8 (q, J = 274.1 Hz), 120.8, 31.5 (d, J = 3.0 Hz), 28.0 (q, J = 29.9 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -66.51; IR (KBr): 3043, 2925, 1700, 1550, 1336, 1149, 1102, 979 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 9 H 9 F 3 ON: 204.0630, found: 204.0630. 1-(9H-carbazol-9-yl)-4,4,4-trifluorobutan-1-one (3m) White solid, 25% yield (36 mg), mp = 102-104 C; 1 H NMR (400 MHz, CDCl 3 ) δ 8.16 (d, J = 8.4 Hz, 2 H), 7.99 (d, J = 7.6 Hz, 2 H), 7.49 (t, J = 7.8 Hz, 2 H), 7.40 (t, J = 7.4 Hz, 2 H), 3.38 (t, J = 8.0 Hz, 2 H), 2.84-2.72 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 169.8, 138.2, 127.5, 126.8 (q, J = 274.1 Hz), 126.5, 124.0, 119.9, 116.3, 32.0 (d, J = 2.9 Hz), 29.3 (q, J = 29.6 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -66.23; IR (KBr): 3056, 2926, 1693, 1445, 1346, 1135, 1103, 984 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 16 H 13 F 3 ON: 292.0943, found: 292.0939. 4,4,4-trifluoro-1-(2-methoxyphenyl)butan-1-one (3n) 3 O OMe Pale yellow oil, 32% yield (37 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 7.76 (d, J = 7.6 Hz, 1 H), 7.49 (t, J = 8.0 Hz, 1 H), 7.04-6.97 (m, 2 H), 3.93 (s, 3 H), 3.26 (t, J = 8.0 Hz, 2 H), 2.60-2.48 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 198.3, 158.9, 134.1, 130.5, 127.2 (q, J = 274.1 Hz), 126.9, 120.7, 111.5, 55.4, 36.3 (d, J = 2.2 Hz), 28.6 (q, J = 29.2 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -66.41. CF 3 1-(2,5-dimethylphenyl)-4,4,4-trifluorobutan-1-one (3o) 5

Colorless oil, 29% yield (33 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 7.47 (s, 1 H), 7.22 (d, J = 7.6 Hz, 1 H), 7.15 (d, J = 8.0 Hz, 1 H), 3.18 (t, J = 7.6 Hz, 2 H), 2.63-2.51 (m, 2 H), 2.46 (s, 3 H), 2.38 (s, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ 199.8, 136.5, 135.5, 135.4, 132.6, 132.1, 129.1, 127.1 (q, J = 274.2 Hz), 33.6 (d, J = 2.2 Hz), 28.4 (q, J = 29.2 Hz), 20.9, 20.8; 19 F NMR (376 MHz, CDCl 3 ) δ -66.35; IR (KBr): 2961, 1689, 1585, 1338, 1147, 986 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 12 H 14 F 3 O: 231.0994, found: 231.0991. 1-(4-(tert-butyl)phenyl)-4,4-difluorobutan-1-one (4a) White solid, 46% yield (55 mg), mp = 35-37 C; 1 H NMR (400 MHz, CDCl 3 ) δ 7.92 (d, J = 8.0 Hz, 2 H), 7.49 (d, J = 8.0 Hz, 2 H), 6.01 (tt, J = 56.8, 4.2 Hz, 1 H), 3.17 (t, J = 7.2 Hz, 2 H), 2.36-2.23 (m, 2 H), 1.35 (s, 9 H); 13 C NMR (100 MHz, CDCl 3 ) δ 197.4, 157.2, 133.8, 127.9, 125.6, 116.6 (t, J = 237.3 Hz), 35.1, 31.0, 30.7 (t, J = 5.1 Hz), 28.4 (t, J = 21.5 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -116.98 (dt, J = 57.1, 17.7 Hz); IR (KBr): 2964, 1687, 1608, 1462, 1367, 1119, 1053 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 14 H 19 F 2 O: 241.1398, found: 241.1395. 4,4-difluoro-1-phenylbutan-1-one (4b) Colorless oil, 45% yield (41 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 7.97 (d, J = 7.6 Hz, 2 H), 7.58 (t, J = 7.4 Hz, 1 H), 7.48 (t, J = 7.6 Hz, 2 H), 6.02 (tt, J = 56.8, 4.0 Hz, 1 H), 3.18 (t, J = 7.2 Hz, 2 H), 2.37-2.23 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 197.7, 136.3, 133.4, 128.7, 127.9, 116.5 (t, J = 237.3 Hz), 30.7 (t, J = 5.2 Hz), 28.3 (t, J = 21.8 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -117.05 (dt, J = 56.2, 17.9 Hz); IR (KBr): 3062, 2960, 1689, 1602, 1456, 1369, 1122, 1047 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 10 H 11 F 2 O: 185.0772, found: 185.0771. 4,4-difluoro-1-(4-fluorophenyl)butan-1-one (4c) Colorless oil, 50% yield (50 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 7.99 (dd, J = 7.6, 5.6 Hz, 2 H), 7.14 (t, J = 8.2 Hz, 2 H), 6.01 (tt, J = 56.8, 4.0 Hz, 1 H), 3.15 (t, J = 7.2 Hz, 2 H), 2.35-2.22 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 196.1, 165.8 (d, J = 253.7 Hz), 132.8 (d, J = 2.9 Hz), 130.6 (d, J = 9.4 Hz), 116.4 (t, J = 237.3 Hz), 115.8 (d, J = 21.9 Hz), 30.6 (t, J = 5.5 Hz), 28.3 (t, J = 21.9 6

Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -104.65 (m, 1 F), -117.16 (dt, J = 57.1, 18.4 Hz, 2 F); IR (KBr): 2932, 1690, 1602, 1505, 1366, 1125, 1051 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 10 H 10 F 3 O: 203.0678, found: 203.0676. 1-(4-chlorophenyl)-4,4-difluorobutan-1-one (4d) Colorless oil, 52% yield (56 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 7.90 (d, J = 8.4 Hz, 2 H), 7.44 (d, J = 8.4 Hz, 2 H), 6.01 (tt, J = 56.8, 4.0 Hz, 1 H), 3.15 (t, J = 7.2 Hz, 2 H), 2.35-2.22 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 196.5, 139.8, 134.6, 129.3, 128.9, 116.3 (t, J = 236.9 Hz), 30.7 (t, J = 5.4 Hz), 28.2 (t, J = 21.5 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -117.16 (dt, J = 57.1, 18.4 Hz); IR (KBr): 2935, 1688, 1592, 1498, 1367, 1118, 1056 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 10 H 10 ClF 2 O: 219.0382, found: 219.0380. 1-(4-bromophenyl)-4,4-difluorobutan-1-one (4e) Colorless oil, 50% yield (65 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 7.83 (d, J = 8.0 Hz, 2 H), 7.62 (d, J = 8.4 Hz, 2 H), 6.01 (tt, J = 56.8, 4.0 Hz, 1 H), 3.15 (t, J = 7.2 Hz, 2 H), 2.36-2.22 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 196.7, 135.0, 132.0, 129.5, 128.6, 116.3 (t, J = 237.3 Hz), 30.7 (t, J = 5.1 Hz), 28.2 (t, J = 21.9 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -117.18 (dt, J = 57.1, 17.7 Hz); IR (KBr): 2960, 1692, 1590, 1489, 1364, 1121, 1052 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 10 H 10 BrF 2 O: 262.9877, found: 262.9874. 1-(3-bromophenyl)-4,4-difluorobutan-1-one (4f) Colorless oil, 52% yield (68 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 8.09 (s, 1 H), 7.88 (d, J = 7.6 Hz, 1 H), 7.71 (d, J = 8.0 Hz, 1 H), 7.36 (t, J = 7.8 Hz, 1 H), 6.01 (tt, J = 56.8, 4.0 Hz, 1 H), 3.16 (t, J = 7.2 Hz, 2 H), 2.36-2.23 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 196.4, 138.0, 136.2, 131.0, 130.3, 126.5, 123.0, 116.3 (t, J = 237.7 Hz), 30.9 (t, J = 5.1 Hz), 28.2 (t, J = 21.8 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -117.18 (dt, J = 56.0, 17.7 Hz); IR (KBr): 3066, 2931, 1687, 1587, 1478, 1361, 1119, 1058 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 10 H 10 BrF 2 O: 262.9877, found: 262.9875. 1-(2-chlorophenyl)-4,4-difluorobutan-1-one (4g) 7

Colorless oil, 26% yield (28 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 7.49 (d, J = 7.6 Hz, 1 H), 7.44-7.38 (m, 2 H), 7.34 (t, J = 7.6 Hz, 1 H), 6.00 (tt, J = 56.8, 4.2 Hz, 1 H), 3.15 (t, J = 7.2 Hz, 2 H), 2.36-2.22 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 200.9, 138.6, 132.0, 130.9, 130.6, 128.9, 127.0, 116.2 (t, J = 237.7 Hz), 35.1 (t, J = 5.1 Hz), 28.5 (t, J = 21.9 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -117.02 (dt, J = 57.1, 17.7 Hz); IR (KBr): 2963, 1691, 1588, 1369, 1121, 1055 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 10 H 10 ClF 2 O: 219.0382, found: 219.0381. 4,4-difluoro-1-(p-tolyl)butan-1-one (4h) White solid, 43% yield (42 mg), mp = 40-42 C; 1 H NMR (400 MHz, CDCl 3 ) δ 7.87 (d, J = 8.0 Hz, 2 H), 7.27 (d, J = 8.4 Hz, 2 H), 6.01 (tt, J = 56.8, 4.0 Hz, 1 H), 3.16 (t, J = 7.2 Hz, 2 H), 2.42 (s, 3 H), 2.35-2.22 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 197.4, 144.2, 133.9, 129.3, 128.1, 116.6 (t, J = 237.0 Hz), 30.6 (t, J = 5.4 Hz), 28.4 (t, J = 21.5 Hz), 21.6; 19 F NMR (376 MHz, CDCl 3 ) δ -117.02 (dt, J = 57.1, 17.7 Hz); IR (KBr): 2957, 1683, 1602, 1456, 1360, 1115, 1056 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 11 H 13 F 2 O: 199.0928, found: 199.0924. 4,4-difluoro-1-(4-methoxyphenyl)butan-1-one (4i) Colorless oil, 43% yield (46 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 7.94 (d, J = 8.0 Hz, 2 H), 6.93 (d, J = 8.0 Hz, 2 H), 6.00 (tt, J = 56.8, 4.2 Hz, 1 H), 3.86 (s, 3 H), 3.12 (t, J = 7.2 Hz, 2 H), 2.34-2.20 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 196.2, 163.6, 130.2, 129.4, 116.6 (t, J = 237.0 Hz), 113.7, 55.4, 30.3 (t, J = 5.1 Hz), 28.4 (t, J = 21.5 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -116.97 (dt, J = 57.1, 17.8 Hz); IR (KBr): 2965, 1680, 1606, 1472, 1369, 1122, 1064 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 11 H 13 F 2 O 2 : 215.0878, found: 215.0876. 4-(4,4-difluorobutanoyl)phenyl acetate (4j) White solid, 30% yield (36 mg), mp = 62-64 C; 1 H NMR (400 MHz, CDCl 3 ) δ 8.00 (d, J = 8.4 Hz, 2 H), 7.20 (d, J = 8.4 Hz, 2 H), 6.01 (tt, J = 56.8, 4.0 Hz, 1 H), 3.16 (t, J = 7.2 Hz, 2 H), 2.35-2.22 (m, 5 H); 13 C NMR (100 MHz, CDCl 3 ) δ 196.5, 168.7, 154.5, 133.9, 129.6, 121.9, 116.4 (t, J = 237.0 Hz), 30.7 (t, J = 5.1 Hz), 28.2 (t, J = 21.9 Hz), 21.0; 19 F NMR (376 MHz, CDCl 3 ) δ 8

-117.12 (dt, J = 57.1, 17.7 Hz); IR (KBr): 2961, 1735, 1683, 1595, 1362, 1125, 1058 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 12 H 13 F 2 O 3 : 243.0827, found: 243.0824. 4,4-difluoro-1-(naphthalen-2-yl)butan-1-one (4k) White solid, 35% yield (40 mg), mp = 63-65 C; 1 H NMR (400 MHz, CDCl 3 ) δ 8.48 (s, 1 H), 8.03-7.95 (m, 2 H), 7.89 (t, J = 8.0 Hz, 2 H), 7.63-7.55 (m, 2 H), 6.07 (tt, J = 56.8, 4.2 Hz, 1 H), 3.32 (t, J = 7.2 Hz, 2 H), 2.43-2.29 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 197.6, 135.6, 133.6, 132.4, 129.7, 129.5, 128.6, 128.5, 127.7, 126.8, 123.5, 116.5 (t, J = 237.3 Hz), 30.8 (t, J = 5.1 Hz), 28.4 (t, J = 21.5 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -116.95 (dt, J = 57.1, 17.7 Hz); IR (KBr): 2968, 1685, 1442, 1368, 1121, 1065 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 14 H 13 F 2 O: 235.0928, found: 235.0923. 4,4-difluoro-1-(pyridin-4-yl)butan-1-one (4l) Pale yellow oil, 42% yield (38 mg); 1 H NMR (400 MHz, CDCl 3 ) δ 8.79 (d, J = 4.4 Hz, 2 H), 7.71 (d, J = 4.4 Hz, 2 H), 6.00 (tt, J = 56.8, 4.0 Hz, 1 H), 3.17 (t, J = 7.2 Hz, 2 H), 2.35-2.22 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 197.3, 150.9, 142.0, 120.8, 116.0 (t, J = 237.3 Hz), 31.0 (t, J = 5.4 Hz), 27.8 (t, J = 21.8 Hz); 19 F NMR (376 MHz, CDCl 3 ) δ -117.35 (dt, J = 57.1, 17.7 Hz); IR (KBr): 3046, 2932, 1698, 1516, 1362, 1125, 1056 cm -1 ; HRMS (ESI): m/z [M + H] + calcd for C 9 H 10 F 2 ON: 186.0724, found: 186.0722. References 1. Yang, T. P.; Li, Q.; Lin, J. H.; Xiao, J. C. Chem. Commun. 2014, 50, 1077. 2. Park, S.; Joo, J. M.; Cho, E. J. Eur. J. Org. Chem. 2015, 4093. 3. He, X. P.; Shu, Y. J.; Dai, J. J.; Zhang, W. M.; Feng, Y. S.; Xu, H. J. Org. Biomol. Chem. 2015, 13, 7159. 9