Supporting Information

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1 Supporting Information Siladifluoromethylation and Difluoromethylation onto C(sp3), C(sp2), and C(sp) Centers Using Ruppert-Prakash Reagent and luoroform Kohsuke Aikawa, Kenichi Maruyama, Junki Nitta, Ryota Hashimoto, and Koichi Mikami* [*] Prof. Dr. K. Mikami, Dr. K. Aikawa, K. Maruyama, J. Nitta, R. Hashimoto Department of Chemical Science and Engineering School of Material and Chemical Technology Tokyo Institute of Technology -okayama, Meguro-ku, Tokyo (Japan) ax: Int. code (+81) Table of Contents General Information 2 Syntheses of Carbamate Substrates 3 General Procedure for Siladifluoromethylation onto C(sp 3 ) Centers 7 General Procedure for Difluoromethylation onto C(sp 3 ) Centers 12 Syntheses of Arylether Substrates 14 General Procedure for Siladifluoromethylation onto C(sp 2 ) Centers 16 Procedures for Transformation of Siladifluoromethylated Products 20 Syntheses of Alkyne Substrates 24 Genaral Procedure for Siladifluoromethylation onto C(sp) Centers 24 Genaral Procedure for Difluoromethylation onto C(sp) Centers 26 References 29 NMR Spectra 30

2 General Information All reactions were conducted in screw-capped test tubes equipped with a magnetic stirring bar under argon atmosphere unless otherwise noted. luoroform and (trifluoromethyl) trimethylsilane (Ruppert-Prakash Reagent; C 3 TMS) were gifted from TSH -TECH. n-butyllithium solution (1.6 M in hexane) was purchased from Sigma-Aldrich and titrated by 2-propanol with 1,10-phenanthroline as an indicator (Sigma-Aldrich #689327). Potassium fluoride was purchased from Morita Chemical Industries, and dried at 130 C under vacuum for 6 hours prior to use. Dehydrated solvents (TH, diethyl ether) were purchased from Kanto Chemical and distilled with GlassContour Solvent Purification System prior to use. ther dehydrated solvents were purchased from Kanto Chemical and used as received. 1 H, 13 C, and 19 NMR spectra were measured on Bruker AV 300M (300 MHz). Chemical shifts were expressed in ppm (parts per million). IR spectra were measured on JASC T/IR-4200 spectrometer. Mass spectra were measured on JEL JMS-T 100CS. TLC plates were purchased from Merck (Silica-gel ). Visualization was accomplished by UV light (254 nm) and potassium permanganate. Silica-gel column chromatography was performed on Kanto Chemical Silica-gel 60N (spherical, neutral). S2

3 Syntheses of Carbamate Substrates Benzhydryl diisopropylcarbamate (1a) H Ni Pr 2 To a solution of sodium hydride (60% dispersion, 5.5 mmol, 220 mg) in TH (20 ml) was added benzhydrol (5.0 mmol, 920 mg) in TH (10 ml) dropwise at 0 C. After the mixture was stirred for 30 min at 0 C, diisopropylcarbamoyl chloride (6.0 mmol, 980 mg) in TH (10 ml) was added at 0 C. After being stirred for 2 h at room temperature, the reaction mixture was poured into a mixture of water and diethyl ether. The aqueous layer was extracted with diethyl ether. The combined organic layers were washed with water and brine, dried over MgS 4 and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography (5% ethyl acetate in hexane) to afford benzhydryl diisopropylcarbamate 1a (95% yield, 1.48 g) as colorless solid. 1 H NMR (300 MHz, CDCl 3 ) δ (m, 10H), 6.89 (s, 1H) 4.02 (brs, 2H), 1.27 (d, 12H, J = 6.3 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), 77.7 (s), 46.1 (brs), 45.7 (brs), 21.4 (brs), 20.7 (brs); TIR (KBr, cm 1 ) 2968, 2931, 1694, 1432, 1432, 1376, 1368, 1314, 1288, 1157, 1132; HRMS (ESI): m/z [M+Na] + calcd for C 20 H 25 NNa 2 : ; found: Benzhydryl diphenylcarbamate (1b) H N 2 The titled compound was prepared from benzhydrol and diphenylcarbamoyl chloride according to procedure as described above the same manner (88% yield, 1.67 g) as colorless solid. 1 H NMR (300 MHz, CDCl 3 ) δ (m, 20H), 6.91 (s, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), (s), (s), (s), (s); TIR (KBr, cm 1 ) 3063, 3031, 1713, 1591, 1491, 1454, 1361, 1280, 1211, 1051, 1024; HRMS (ESI): m/z [M+Na] + calcd for C 26 H 21 NNa 2 : ; found: S3

4 Benzhydryl pyrrolidine-1-carboxylate (1c) N H The titled compound was prepared from benzhydrol and pyrrolidine-1-carbonyl chloride according to procedure as described above the same manner (60% yield, 844 mg) as colorless solid. 1 H NMR (300 MHz, CDCl 3 ) δ (m, 10H), 6.85 (s, 1H), 3.53 (t, 2H, J = 6.3 Hz), 3.40 (t, 2H, J = 6.3 Hz), 1.88 (m, 4H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), 77.1 (s), 46.2 (s), 45.8 (s), 25.7 (s), 24.9 (s); TIR (KBr, cm 1 ) 2937, 2855, 1697, 1427, 1256, 1232, 1146, 1083, 1024; HRMS (ESI): m/z [M+Na] + calcd for C 19 H 21 NNa 2 : ; found: Benzhydryl piperidine-1-carboxylate (1d) N H The titled compound was prepared from benzhydrol and piperidine-1-carbonyl chloride according to procedure as described above the same manner (60% yield, 886 mg) as colorless solid. 1 H NMR (300 MHz, CDCl 3 ) δ (m, 10H), 6.84 (s, 1H), 3.57 (brs, 2H), 3.52 (brs, 2H), 1.58 (brs, 6H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), 77.6 (s), 44.9 (s), 25.6 (s), 24.4 (s); TIR (KBr, cm 1 ) 2937, 2855, 1697, 1427, 1256, 1232, 1146, 1083, 1024; HRMS (ESI): m/z [M+Na] + calcd for C 19 H 21 N- Na 2 : ; found: Benzhydryl morpholine-4-carboxylate (1e) N H The titled compound was prepared from benzhydrol and morpholine-4-carbonyl chloride according to procedure as described above the same manner (87% yield, 1.29 g) as colorless S4

5 solid. 1 H NMR (300 MHz, CDCl 3 ) δ (m, 10H), 6.86 (s, 1H), (m, 8H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), 78.1 (s), 66.6 (s), 44.0 (brs); TIR (KBr, cm 1 ) 2963, 2857, 1703, 1244, 1423, 1277, 1238, 1220, 1116, 1087; HRMS (ESI): m/z [M+Na] + calcd for C 18 H 19 NNa 3 : ; found: Bis(4-methoxyphenyl)methyl diisopropylcarbamate (1f) H Ni Pr 2 Me The titled compound was prepared from bis(4-methoxyphenyl)methanol and diisopropylcarbamoyl chloride according to procedure as described above the same manner (80% yield, 1.49 g) as colorless solid. 1 H NMR (300 MHz, CDCl 3 ) δ 7.27 (d, 4H, J = 8.7 Hz), 6.86 (d, 4H, J = 8.7 Hz), 6.79 (s, 1H), 3.90 (brs, 2H), 3.77 (s, 6H), 1.23 (d, 12H, J = 6.6 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), 77.0 (s), 55.2 (s), 46.3 (brs), 21.6 (brs), 21.0 (brs); TIR (KBr, cm 1 ) 2997, 2967, 2934, 1683, 1652, 1614, 1540, 1513, 1508, 1436, 1288, 1269, 1247, 1173, 1046; HRMS (ESI): m/z [M+Na] + calcd for C 22 H 29 NNa 4 : ; found: Me (4-Chlorophenyl)(phenyl)methyl diisopropylcarbamate (1g) Cl H Ni Pr 2 The titled compound was prepared from (4-chlorophenyl)(phenyl)methanol and diisopropylcarbamoyl chloride according to procedure as described above the same manner as (80% yield, 1.38 g) as colorless solid. 1 H NMR (300 MHz, CDCl 3 ) δ (m, 9H), 6.80 (s, 1H), 3.97 (brs, 2H), 1.23 (d, 12H, J = 6.6 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), (s), (s), (s), 77.0 (s), 46.6 (brs), 45.7 (brs), 21.6 (brs), 20.7 (brs); TIR (KBr, cm 1 ) 2969, 2934, 1694, 1491, 1432, 1368, 1289, 1214, 1157, 1132, S5

6 1089, 1048; HRMS (ESI): m/z [M+Na] + calcd for C 20 H 24 ClNNa 2 : ; found: Naphthalen-2-yl(phenyl)methyl diisopropylcarbamate (1h) H Ni Pr 2 The titled compound was prepared from naphthalen-2-yl(phenyl)methanol and diisopropylcarbamoyl chloride according to procedure as described above the same manner (74% yield, 1.34 g) as colorless solid. 1 H NMR (300 MHz, CDCl 3 ) δ (m, 4H), (m, 8H), 7.04 (s, 1H), 4.02 (brs, 2H), 1.27 (brs, 12H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), (s), (s), (s), (s), (s), (s), (s), (s), (s), (s), 77.9 (s), 46.5 (brs), 45.6 (brs), 21.7 (brs), 20.7 (brs); TIR (KBr, cm 1 ) 2996, 2969, 2933, 1692, 1453, 1435, 1290, 1215, 1188, 1156, 1132, 1047; HRMS (ESI): m/z [M+Na] + calcd for C 24 H 27 NNa 2 : ; found: (E)-1,3-Diphenylallyl diisopropylcarbamate (1i) Ni Pr 2 To a solution of (E)-1,3-diphenylprop-2-en-1-ol (5.0 mmol, 1.05 g) in TH (20 ml) was added potassium hexamethyldisilazide solution (1.0 M in TH, 5.5 mmol, 5.5 ml) dropwise at 78 C. After the mixture was stirred for 10 min at 78 C, diisopropylcarbamoyl chloride (5.5 mmol, 900 mg) in TH (10 ml) was added to the mixture at 78 C. After being stirred for 1 h at 40 C, the reaction mixture was poured into mixture of TH (5 ml) and acetic acid (5 ml). The aqueous layer was extracted with diethyl ether. The combined organic layers were washed with water and brine, dried over MgS 4 and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography (5% ethyl acetate in hexane) to afford (E)-1,3-diphenylallyl diisopropylcarbamate 1i (62% yield, 1.05 g) as colorless oil. 1 H NMR (300 MHz, CDCl 3 ) δ (m, 10H), 6.65 (d, 1H, J = 14.4 Hz), 6.48 (d, 1H, J = 6.6 Hz), 6.41 (dd, 1H, J = 14.4, 6.6 Hz), 4.07 (brs, 2H), 1.27 (d, 12H, J = 6.6 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), (s), S6

7 (s), (s), (s), (s), (s), 76.7 (s), 46.7 (brs), 45.6 (brs), 21.5 (brs), 21.0 (brs); TIR (neat, cm 1 ) 2968, 2933, 1693, 1433, 1284, 1241, 1157, 1132, 1046; HRMS (ESI): m/z [M+Na] + calcd for C 22 H 27 NNa 2 : ; found: General Procedure for Siladifluoromethylation onto C(sp 3 ) Centers To a solution of benzhydryl diisopropylcarbamate 1a (0.10 mmol, 31.1 mg) in TH/diethyl ether (0.5/0.5 ml) was added dropwise n-butyllithium solution (1.6 M in hexane, 0.20 mmol, 125 µl) at 78 C. After the solution was stirred for 30 min at 78 C, C 3 TMS (0.50 mmol, 74 µl) was added at 78 C. After stirring for 2 h at 40 C, the reaction mixture was quenched by mixture of water and ethyl acetate. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over MgS 4, and evaporated under reduced pressure. NMR yield (50%) was determined by using BT as an internal standard. The residue was purified by silica-gel column chromatography (2.5% ethyl acetate in hexane) to isolate difluoro(trimethylsilyl)methylated product 2a (50% yield, 21.7 mg). 2,2-Difluoro-1,1-diphenyl-2-(trimethylsilyl)ethyl diisopropylcarbamate (2a) Ni Pr 2 Colorless liquid. 50% isolated yield (21.7 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.57 (d, 4H, J = 7.2 Hz), (m, 6H), (m, 1H), (m, 1H), 1.27 (d, 6H, J = 6.9 Hz), 1.12 (d, 6H, J = 6.6 Hz), 0.12 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (t, J C- = Hz), (s), 87.6 (t, J C- = 21.7 Hz), 47.3 (s), 45.0 (s), 21.1 (s), 20.3 (s), 3.2 (s); 19 NMR (282 MHz, CDCl 3 ) δ (brs, 2); TIR (neat, cm 1 ) 2966, 2931, 1714, 1428, 1369, 1316, 1045, 1031; HRMS (ESI): m/z [M+Na] + calcd for C 24 H 33 2 NNa 2 Si: ; found: ,2-Difluoro-1,1-diphenyl-2-(trimethylsilyl)ethyl diphenylcarbamate (2b) N 2 Colorless liquid. 31% isolated yield (15.6 mg). 1 H NMR (300 MHz, CDCl 3 ) δ (m, 20H), 0.37 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), S7

8 129.6 (s), (s), (s), (s), (s), (s), (t, J C- = Hz), (s), (s), (s), (s), 88.5 (t, J C- = 22.5 Hz), 3.7 (s); 19 NMR (282 MHz, CDCl 3 ) δ (s, 2); TIR (neat, cm 1 ) 3058, 2955, 2931, 1729, 1592, 1491, 1337, 1301, 1252, 1051; HRMS (ESI): m/z [M+Na] + calcd for C 30 H 29 2 NNa 2 Si: ; found: ,2-Difluoro-1,1-diphenyl-2-(trimethylsilyl)ethyl pyrrolidine-1-carboxylate (2c) N Colorless liquid. 20% isolated yield (8.1 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.58 (d, 4H, J = 7.5 Hz), (m, 6H), 3.64 (t, 2H, J = 6.6 Hz), 3.27 (t, 2H, J = 6.6 Hz), 1.96 (m, 2H), 1.84 (m, 2H), 0.12 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (t, J C- = Hz), (s), 87.4 (t, J C- = 21.7 Hz), 46.4 (s), 46.3 (s), 25.9 (s), 24.8 (s), 3.2 (s); 19 NMR (282 MHz, CDCl 3 ) δ (s, 2); TIR (neat, cm 1 ) 2956, 2876, 1718, 1495, 1447, 1397, 1251, 1447, 1397, 1251, 1175, 1125, 1084; HRMS (ESI): m/z [M+Na] + calcd for C 22 H 27 2 NNa 2 Si: ; found: ,2-Difluoro-1,1-diphenyl-2-(trimethylsilyl)ethyl piperidine-1-carboxylate (2d) N Colorless liquid. 36% isolated yield (15.0 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.58 (d, 4H, J = 6.6 Hz), (m, 6H), 3.67 (brs, 2H), 3.29 (brs, 2H), 1.63 (brs, 3H), 1.48 (brs, 3H), 0.14 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (t, J C- = 3.0 Hz), (s), (t, J C- = Hz), (s), 87.5 (t, J C- = 21.7 Hz), 45.5 (s), 44.8 (s), 26.3 (s), 25.7 (s), 24.4 (s), 3.3 (s); 19 NMR (282 MHz, CDCl 3 ) δ (s, 2); TIR (neat, cm 1 ) 2936, 2856, 1715, 1495, 1445, 1424, 1255, 1230, 1146; HRMS (ESI): m/z [M+Na] + calcd for C 23 H 29 2 NNa 2 Si: ; found: S8

9 2,2-Difluoro-1,1-diphenyl-2-(trimethylsilyl)ethyl morpholine-4-carboxylate (2e) N Colorless liquid. 38% isolated yield (15.9 mg). 1 H NMR (300 MHz, CDCl 3 ) δ (m, 4H), (m, 6H), (m, 6H), 3.36 (brs, 2H), 0.14 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (t, J C- = 3.0 Hz), (s), (t, J C- = Hz), (s), 88.0 (t, J C- = 22.5 Hz), 66.8 (s), 45.1 (s), 43.9 (s), 3.3 (s); 19 NMR (282 MHz, CDCl 3 ) δ (s, 2); TIR (neat, cm 1 ) 2962, 2921, 2899, 2857, 1718, 1447, 1421, 1276, 1250, 1238, 1117, 1073; HRMS (ESI): m/z [M+Na] + calcd for C 22 H 27-2NNa 3 Si: ; found: ,2-Difluoro-1,1-bis(4-methoxyphenyl)-2-(trimethylsilyl)ethyl diisopropylcarbamate (2f) Ni Pr 2 Me Colorless solid. 37% isolated yield (18.3 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.51 (d, 4H, J = 9.0 Hz), 6.88 (d, 4H, J = 9.0 Hz), (m, 1H), 3.82 (s, 6H), (m, 1H), 1.27 (d, 6H, J = 6.9 Hz), 1.15 (d, 6H, J = 6.6 Hz), 0.08 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), (t, J C- = Hz), 87.4 (t, J C- = 21.7 Hz), 55.0 (s), 47.1 (s), 44.8 (s), 21.0 (s), 20.2 (s), 3.2 (s); 19 NMR (282 MHz, CDCl 3 ) δ (brs, 2); TIR (KBr, cm 1 ) 2999, 2964, 2908, 2837, 1709, 1610, 1513, 1463, 1317, 1297, 1251, 1180, 1063; HRMS (ESI): m/z [M+Na] + calcd for C 26 H 37 2 N- Na 4 Si: ; found: Me S9

10 1-(4-Chlorophenyl)-2,2-difluoro-1-phenyl-2-(trimethylsilyl)ethyl diisopropylcarbamate (2g) Cl Ni Pr 2 C 2TMS Colorless liquid. 37% isolated yield (17.3 mg). 1 H NMR (300 MHz, CDCl 3 ) δ (m, 3H), (m, 6H), (m, 1H), (m, 1H), (m, 6H), (m, 6H), 0.12 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (t, J C- = 2.2 Hz), (t, J C- = 2.2 Hz), (t, J C- = Hz), 87.2 (t, J C- = 21.7 Hz), 47.4 (s), 45.1 (s), 21.1 (s), 20.3 (s), 3.2 (s); 19 NMR (282 MHz, CDCl 3 ) δ (d, 1, J - = Hz), (d, 1, J - = Hz); TIR (neat, cm 1 ) 2967, 2933, 1714, 1493, 1427, 1316, 1251, 1088, 1045, 1017; HRMS (ESI): m/z [M+Na] + calcd for C 28 H 35 2 NNa 2 Si: ; found: ,2-Difluoro-1-(naphthalen-2-yl)-1-phenyl-2-(trimethylsilyl)ethyl diisopropylcarbamate (2h) Ni Pr 2 C 2TMS Colorless liquid. 26% isolated yield (12.6 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 8.09 (s, 1H), (m, 3H), (m, 3H), (m, 2H), (m, 3H), (m, 1H), (m, 1H), 1.33 (d, 3H, J = 5.1 Hz), 1.31 (d, 3H, J = 4.8 Hz), 1.14 (d, 3H, J = 6.6 Hz), 1.08 (d, 3H, J = 6.6 Hz), 0.10 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), (s), (s), (s), (s), (t, J C- = Hz), (s), (s), (s), (s), (s), (s), 87.9 (t, J C- = 22.5 Hz), 47.3 (s), 45.1 (s), 21.2 (s), 20.3 (s), 2.9 (s); 19 NMR (282 MHz, CDCl 3 ) δ (brd, 1, J - = Hz), (brd, 1, J - = Hz); TIR (KBr, cm 1 ) 2967, 2932, 1713, 1428, 1370, 1315, 1250, 1045; HRMS (ESI): m/z [M+Na] + calcd for C 28 H 35 2 NNa 2 Si: ; found: S10

11 (Z)-4,4-Difluoro-1,3-diphenyl-4-(trimethylsilyl)but-1-en-1-yl diisopropylcarbamate (γ-2i) i Pr 2 N To a solution of (E)-1,3-diphenylallyl diisopropylcarbamate 1i (0.10 mmol, 33.7 mg) in TH (0.5 ml) was added dropwise n-butyllithium solution (1.6 M in hexane, 0.20 mmol, 125 µl) at 78 C. After the solution was stirred for 30 min at 78 C, C 3 TMS (0.50 mmol, 74 µl) was added at 78 C. After stirring for 2 h at 40 C, the reaction mixture was quenched by a mixture of water and ethyl acetate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over MgS 4, and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography (2.5% ethyl acetate in hexane) to isolate difluoro(trimethylsilyl)methylated product γ-2i (50% yield) as colorless liquid. 50% isolated yield (23.0 mg). 1 H NMR (300 MHz, CDCl 3 ) δ (m, 2H), (m, 8H), 6.16 (d, 1H, J = 9.9 Hz), (m, 2H), (m, 1H), (m, 6H), (m, 6H), 0.00 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (t, J C- = 4.5 Hz), (s), (s), (t, J C- = Hz), (s), (s), (s), (s), (s), (t, J C- = 6.7 Hz), 49.1 (t, J C- = 19.5 Hz), 46.6 (s), 46.3 (s), 21.6 (s), 20.5 (s), 4.1 (s); 19 NMR (282 MHz, CDCl 3 ) δ (dd, 1, J - = Hz, J H- = 17.4 Hz), (dd, 1, J - = Hz, J H- = 17.4 Hz); TIR (neat, cm 1 ) 2969, 2935, 1716, 1428, 1369, 1309, 1267, 1253, 1216, 1043; HRMS (ESI): m/z [M+Na] + calcd for C 26 H 35 2 NNa 2 Si: ; found: (E)-1,1-Difluoro-2,4-diphenyl-1-(trimethylsilyl)but-3-en-2-yl diisopropylcarbamate (α-2i) i Pr 2 N This compound could not be isolated because of many impurities. NMR yield (18%) was determined by using BT as an internal standard. 19 NMR (282 MHz, CDCl 3 ) δ (d, 1, J - = Hz), (d, 1, J - = Hz). S11

12 (2,2-Difluoroethene-1,1-diyl)dibenzene (3a) This compound exhibited the same 19 NMR spectra as reported before. [1] NMR yield (49%) was determined by using BT as an internal standard. 19 NMR (282 MHz, CDCl 3 ) δ 87.8 (s, 2). 4,4-Difluoro-1,3-diphenyl-4-(trimethylsilyl)butan-1-one (4) To a solution of (Z)-4,4-difluoro-1,3-diphenyl-4-(trimethylsilyl)but-1-en-1-yl diisopropylcarbamate γ-2i (0.10 mmol, 45.9 mg) in toluene (1.0 ml) was added trimethylsilyl trifluoromethanesulfonate (0.30 mmol, 54 µl) dropwise. After the mixture was stirred for 12 h at 60 C, the reaction mixture was poured into mixture of water and diethyl ether. The aqueous layer was extracted with diethyl ether. The combined organic layers were washed with water and brine, dried over MgS 4 and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography (5% ethyl acetate in hexane) to afford 4,4-difluoro-1,3-diphenyl-4-(trimethylsilyl)butan-1-one 4 (80% yield) as colorless liquid. 80% isolated yield (26.6 mg). 1 H NMR (300 MHz, CDCl 3 ) δ (m, 2H), (m, 8H), (m, 1H), 3.73 (d, 1H, J = 17.4, 3.3 Hz), 3.51 (dd, 1H, J = 17.4, 9.3 Hz), 0.12 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), (s), (t, J C- = Hz), (s), (s), (s), 47.2 (t, J C- = 19.5 Hz), 37.5 (t, J C- = 6.7 Hz), 4.3 (s); 19 NMR (282 MHz, CDCl 3 ) δ (d, 1, J - = Hz), (dd, 1, J - = 313.3, 33.8 Hz); TIR (neat, cm 1 ) 2958, 2927, 1732, 1688, 1496, 1455, 1449, 1361, 1276, 1252, 1213, 1023, 973; HRMS (ESI): m/z [M+Na] + calcd for C 19 H 22 2 NaSi: ; found: General Procedure for Difluoromethylation onto C(sp 3 ) Centers To a solution of benzhydryl diisopropylcarbamate 1a (0.10 mmol, 31.1 mg) in TH (1 ml) was added dropwise n-butyllithium solution (1.6 M in hexane, 0.20 mmol, 125 µl) at 78 C. After the solution was stirred for 30 min at 78 C, excess amount (ca. 10 mmol) of C 3 H was bubbled into the mixture at 78 C. After stirring for 2 h at 78 C, the reaction mixture was quenched by mixture of water and ethyl acetate. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over MgS 4, and evaporated under reduced pressure. S12

13 The residue was purified by silica-gel column chromatography (5% ethyl acetate in hexane) to isolate difluoromethylated product 5a (28% yield) as colorless solid. 2,2-Difluoro-1,1-diphenylethyl diisopropylcarbamate (5a) Ni Pr 2 C 2 H Colorless solid. 28% isolared yield (10.1 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.35 (s, 10H), 7.33 (t, 1H, J H- = 57.3 Hz), 4.15 (brs, 1H), 3.79 (brs, 1H), 1.34 (d, 6H, J = 6.3 Hz), 1.16 (d, 6H, J = 6.1 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), (t, J C- = Hz), 84.2 (t, J C- = 22.7 Hz), 46.7 (s), 46.2 (s), 21.5 (s), 20.4 (s); 19 NMR (282 MHz, CDCl 3 ) δ (d, 2, J H- = 57.1 Hz); TIR (KBr, cm 1 ) 3064, 3005, 2965, 2871, 1703, 1657, 1600, 1434, 1325, 1279; HRMS (ESI): m/z [M+Na] + calcd for C 21 H 25 2 NNa 2 : ; found: S13

14 Syntheses of Arylether Substrates Arylethers 6a, 6d, and 6g-j were synthesized by the reaction of corresponding phenols and chloromethyl methyl ether in the presence of sodium hydride as base according to previous report. [3] Arylethers 6b and 6e were synthesized by the reaction of corresponding phenols and 2-methoxyethoxymethyl chloride (MEM-chloride) in the presence of sodium hydride as base. Arylethers 6c and 6f were synthesized by the reaction of corresponding phenols and chloromethyl ethyl ether in the presence of sodium hydride as base. Arylethers 6b, 6c, 6e, and 6j are unknown compounds. ysical properties of these compounds are described below. General Procedure for Syntheses of Arylether Substrates To a solution of sodium hydride (60% dispersion, 5.5 mmol, 220 mg) in TH (20 ml) was added phenol derivative (5.0 mmol) in TH (10 ml) dropwise at 0 C. After the mixture was stirred for 30 min at 0 C, chloromethyl methyl ether (5.5 mmol, 414 ml) was added at 0 C. After being stirred for 2 h at room temperature, the reaction mixture was poured into a mixture of water and diethyl ether. The aqueous layer was extracted with diethyl ether. The combined organic layers were washed with water and brine, dried over MgS 4, and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography (5% ethyl acetate in hexane) to afford 6b, 6c, 6e, and 6j as colorless liquid. 1-((2-Methoxyethoxy)methoxy)-4-(trifluoromethyl)benzene (6b) Me 3 C Colorless liquid. 72% isolated yield (900 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.54 (d, 2H, J = 8.7 Hz), 7.13 (d, 2H, J = 8.6 Hz), 5.31 (s, 2H), (m, 2H), (m, 2H), 3.37 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (q, J C- = 3.7 Hz), (q, J C- = Hz), (q, J C- = 32.4 Hz), (s), 93.2 (s), 71.5 (s), 67.9 (s), 58.9 (s); 19 NMR (282 MHz, CDCl 3 ) δ 61.7 (s, 3); TIR (neat, cm 1 ) 2933, 2821, 1616, 1518, 1328, 1236, 1162, 989, 840, 591; HRMS (APCI): m/z [M H] calcd for C 11 H : ; found: S14

15 1-(Ethoxymethoxy)-4-(trifluoromethyl)benzene (6c) 3 C Colorless liquid. 80% isolated yield (620 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.54 (d, 2H, J = 8.7 Hz), 7.11 (d, 2H, J = 8.6 Hz), 5.26 (s, 2H), 3.73 (q, 2H, J = 7.1 Hz), 1.22 (t, 3H, J = 7.1 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (q, J C- = 3.7 Hz), (q, J C- = Hz), (q, J = 32.5 Hz), (s), 92.9 (s), 64.5 (s), 14.9 (s); 19 NMR (282 MHz, CDCl 3 ) δ 61.8 (s, 3); TIR (neat, cm 1 ) 2980, 2898, 1617, 1519, 1327, 1162, 1108, 989, 840, 620; HRMS (APCI): m/z [M H] calcd for C 10 H : ; found: Chloro-4-((2-methoxyethoxy)methoxy)benzene (6e) Me Cl Colorless liquid. 85% isolated yield (921 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.18 (d, 2H, J = 9.0 Hz), 6.94 (d, 2H, J = 9.0 Hz), 5.17 (t, 2H, J = 1.5 Hz), (m, 2H), (m, 2H), 3.31 (t, 3H, J = 1.6 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), 93.5 (s), 71.5 (s), 67.7 (s), 58.9 (s); TIR (neat, cm 1 ) 2925, 2889, 1595, 1492, 1291, 1225, 1103, 999, 828, 624; HRMS (APCI): m/z [M H] calcd for C 10 H 12 C- l 3 : ; found: Chloro-4-(methoxymethoxy)naphthalene (6j) Me Cl Colorless liquid. 82% isolated yield (913 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 8.30 (d, 1H, J = 8.3 Hz), 8.22 (d, 1H, J = 8.4 Hz), 7.62 (t, 1H, J = 7.4 Hz), 7.55 (t, 1H, J = 7.5 Hz), 7.46 (d, 1H, J = 8.2 Hz), 7.03 (d, 1H, J = 8.2 Hz), 5.38 (s, 2H), 3.54 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), (s), (s), (s), (s), (s), 94.9 (s), 56.3 (s); TIR (neat, cm 1 ) 2955, 2899, 1594, 1376, 1258, 1148, 1057, 927, 761, 640; HRMS (ESI): m/z [M+Cl] calcd for C 12 H 11 Cl 2 2 : ; found: S15

16 General Procedure for Siladifluoromethylation onto C(sp 2 ) Centers To a solution of 1-(methoxymethoxy)-4-(trifluoromethyl)benzene 6a (0.20 mmol, 41.2 mg) in TH (1.0 ml) was added n-butyllithium solution (1.6 M in hexane, 0.20 mmol, 125 µl) at 78 C. After stirred for 2 h at the same temperature, C 3 TMS (0.24 mmol, 36 µl) was added. After stirred for 5 minutes, the reaction was quenched with water. The organic layer was extracted with diethyl ether, washed with brine, and dried over anhydrous MgS 4. After filtration, the solvent was removed under reduced pressure. NMR yield (57%) was determined by using BT as an internal standard. The residue was purified by silica-gel column chromatography (5% dichloromethane in hexane) to afford 7a as colorless liquid. The isolated yields after silica-gel column chromatography were generally lower than the corresponding NMR yields because it was difficult to separate the product from substrate and byproducts. (Difluoro(2-(methoxymethoxy)-5-(trifluoromethyl)phenyl)methyl)trimethylsilane (7a) Me 3 C Colorless liquid. 57% NMR yield. 55% isolated yield (37.4 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.70 (s, 1H), 7.60 (d, 1H, J = 8.6 Hz), 7.28 (d, 1H, J = 9.0 Hz), 5.23 (s, 2H), 3.50 (s, 3H), 0.19 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (t, J C- = 4.9 Hz), (t, J C- = 20.5 Hz), (s), (t, J C- = Hz), (q, J C- = Hz), (q, J C- = 32.8 Hz), (m), (s), 94.5 (s), 56.5 (s), 3.8 (s); 19 NMR (282 MHz, CDCl 3 ) δ 61.9 (s, 3), (s, 2); TIR (neat, cm 1 ) 2963, 2906, 1620, 1506, 1334, 1280, 1132, 987, 966, 849; HRMS (APCI): m/z [M H] calcd for C 13 H Si: ; found: (Difluoro(2-((2-methoxyethoxy)methoxy)-5-(trifluoromethyl)phenyl)methyl)trimethylsilane (7b) Me 3 C 47% NMR yield. 19 NMR (282 MHz, CDCl 3 ) δ 61.9 (s, 3), (s, 2). This compund could not be isolated from impurities. After desilylation (treatment with 10 mol% potassium carbonate in methanol at room temperature for 1 h), the obtained product could be identified with the expected desilylated compound 7b-H. S16

17 2-(Difluoromethyl)-1-((2-methoxyethoxy)methoxy)-4-(trifluoromethyl)benzene (7b-H) Me 3 C C 2 H Colorless liquid. 35% isolated yield (2 steps, 21.0 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.82 (s, 1H), 7.66 (d, 1H, J = 7.9 Hz), 7.31 (d, 1H, J = 8.5 Hz), 6.93 (t, 1H, J H- = 55.2 Hz), 5.38 (s, 2H), 3.82 (t, 2H, J = 4.5 Hz), 3.54 (t, 2H, J = 4.5 Hz), 3.35 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ (t, J C- = 5.2 Hz), (t, J C- = 1.9 Hz), (q, J C- = Hz), (q, J C- = 33.2 Hz), (t, J C- = 22.6 Hz), (m), (s), (t, J C- = Hz), 93.4 (s), 71.4 (s), 68.3 (s), 58.9 (s); 19 NMR (282 MHz, CDCl 3 ) δ 62.0 (s, 3), (d, 2, J H- = 55.0 Hz); TIR (neat, cm 1 ) 2931, 2896, 1626, 1509, 1333, 1276, 1125, 978, 905, 830; HRMS (ESI): m/z [M+Na] + calcd for C 12 H 13 5 Na 3 : ; found: ((2-(Ethoxymethoxy)-5-(trifluoromethyl)phenyl)difluoromethyl)trimethylsilane (7c) 3 C Colorless liquid. 49% NMR yield. 29% isolated yield (19.9 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.68 (s, 1H), 7.59 (d, 1H, J = 8.8 Hz), 7.29 (d, 1H, J = 8.7 Hz), 5.27 (s, 2H), 3.74 (q, 2H, J = 7.1 Hz), 1.23 (t, 3H, J = 7.1 Hz), 0.17 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (t, J C- = 4.6 Hz), (t, J C- = 20.2 Hz), (m), (t, J C- = Hz), (q, J C- = Hz), (q, J C- = 32.8 Hz), (s), 93.2 (s), 65.0 (s), 15.0 (s), 3.7 (s); 19 NMR (282 MHz, CDCl 3 ) δ 61.8 (s, 3), (s, 2); TIR (neat, cm 1 ) 2979, 2903, 1619, 1506, 1335, 1278, 1125, 985, 965, 849; HRMS (APCI): m/z [M+Na] + calcd for C 14 H 19 5 Na 2 Si: ; found: ((5-Chloro-2-(methoxymethoxy)phenyl)difluoromethyl)trimethylsilane (7d) Me Cl Colorless liquid. 40% NMR yield. 36% isolated yield (21.2 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.36 (d, 1H, J = 2.5 Hz), 7.24 (dd, 1H, J = 8.9, 2.6 Hz), 7.09 (d, 1H, J = 8.8 Hz), 5.11 (s, 2H), 3.46 (s, 3H), 0.15 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (t, J C- = 5.2 Hz), (s), (s), (t, J C- = 20.1 Hz), (s), (t, J C- = Hz), (s), 95.0 (s), 56.4 (s), 3.6 (s); 19 NMR (282 MHz, CDCl 3 ) δ (s, 2); TIR S17

18 (neat, cm 1 ) 2960, 2904, 1598, 1486, 1397, 1242, 1159, 989, 964, 848; HRMS (APCI): m/z [M+Na] + calcd for C 12 H 17 Cl 2 Na 2 Si: ; found: ((5-Chloro-2-((2-methoxyethoxy)methoxy)phenyl)difluoromethyl)trimethylsilane (7e) Me Cl 38% NMR yield. 19 NMR (282 MHz, CDCl 3 ) δ (s, 2). This compund could not be isolated from impurities. After desilylation (treatment with 10 mol% potassium carbonate in methanol at room temperature for 1 h), the obtained product could be identified with the expected desilylated compound 7e-H. 4-Chloro-2-(difluoromethyl)-1-((2-methoxyethoxy)methoxy)benzene (7e-H) Me Cl C 2 H Colorless liquid. 14% isolated yield (2 steps, 7.5 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.52 (s, 1H), 7.35 (d, 1H, J = 8.9 Hz), 7.17 (dm, 1H, J = 8.9 Hz), 6.89 (t, 1H, J H- = 55.3 Hz), 5.30 (s, 2H), (m, 2H), (m, 2H), 3.36 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ (t, J C- = 5.8 Hz), (s), (s), (t, J C- = 6.1 Hz), (t, J C- = 22.3 Hz), (s), (t, J C- = Hz), 93.7 (s), 71.4 (s), 68.1 (s), 59.0 (s); 19 NMR (282 MHz, CDCl 3 ) δ (d, 2, J H- = 55.8 Hz); TIR (neat, cm 1 ) 2926, 2888, 1605, 1490, 1383, 1239, 1105, 984, 887, 820; HRMS (ESI): m/z [M+H] + calcd for C 11 H 14 Cl 2 3 : ; found: ((5-Chloro-2-(ethoxymethoxy)phenyl)difluoromethyl)trimethylsilane (7f) Cl Colorless liquid. 36% NMR yield. 20% isolated yield (12.3 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.38 (s, 1H), 7.28 (d, 1H, J = 8.8 Hz), 7.15 (d, 1H, J = 8.8 Hz), 5.18 (d, 2H, J = 1.2 Hz), 3.73 (dq, 2H, J = 6.9, 1.2 Hz), 1.23 (td, 3H, J = 7.1, 1.3 Hz), 0.16 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (t, J C- = 5.0 Hz), (s), (t, J C- = 20.0 Hz), (s), (t, J C- = Hz), (t, J C- = 11.4 Hz), (s), 93.6 (s), 64.7 (s), 15.0 (s), 3.7 (s); 19 NMR (282 MHz, CDCl 3 ) δ (s, 2); TIR (neat, cm 1 ) 2978, 2901, 1487, 1398, 1236, 1200, 1109, 986, 964, 848; HRMS (APCI): m/z [M+Na] + calcd for C 13 H 19 Cl 2 Na 2 Si: ; found: S18

19 (Difluoro(2-(methoxymethoxy)-4-(trifluoromethyl)phenyl)methyl)trimethylsilane (7g) 3 C Me Colorless liquid. 53% NMR yield. 35% isolated yield (23.0 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.52 (d, 1H, J = 8.1 Hz), 7.42 (s, 1H), 7.31 (d, 1H, J = 8.1 Hz), 5.21 (s, 2H), 3.51 (s, 3H), 0.18 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (q, J C- = 32.3 Hz), (t, J C- = 19.7 Hz), (t, J C- = 20.7 Hz), (t, J C- = Hz), (q, J C- = Hz), (s), 94.9 (s), 56.5 (s), 3.8 (s); 19 NMR (282 MHz, CDCl 3 ) δ 62.8 (s, 3), (s, 2); TIR (neat, cm 1 ) 2963, 2906, 1619, 1508, 1432, 1330, 1160, 1134, 985, 847; HRMS (APCI): m/z [M+Na] + calcd for C 13 H 17 5 Na 2 Si: ; found: ((2-Chloro-6-(methoxymethoxy)phenyl)difluoromethyl)trimethylsilane (7h) Me Cl Colorless liquid. 29% NMR yield. 20% isolated yield (11.8 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.20 (dd, 1H, J = 8.4, 7.8 Hz), (m, 2H), 5.14 (s, 2H), 3.50 (s, 3H), 0.23 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (t, J C- = 4.8 Hz), (t, J C- = 4.0 Hz ), (s), (t, J C- = Hz), (s), (t, J C- = 19.1 Hz), (s), 95.4 (s), 56.5 (s), 3.2 (s); 19 NMR (282 MHz, CDCl 3 ) δ (s, 2); TIR (neat, cm 1 ) 2959, 2929, 1589, 1451, 1253, 1161, 1077, 991, 844; HRMS (APCI): m/z [M+Na] + calcd for C 12 H 17 Cl 2 Na 2 Si: ; found: ((2,3-Dichloro-6-(methoxymethoxy)phenyl)difluoromethyl)trimethylsilane (7i) Me Cl Cl Colorless liquid. 51% NMR yield. 50% isolated yield (32.9 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.42 (d, 1H, J = 9.0 Hz), 7.39 (d, 1H, J = 9.0 Hz), 5.13 (s, 2H), 3.50 (s, 3H), 0.24 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (t, J C- = Hz), (t, J C- = 38.6 Hz), (s), 95.6 (s), 56.6 (s), 3.1 (s); 19 NMR (282 MHz, CDCl 3 ) δ (s, 2); TIR (neat, cm 1 ) 2966, 2906, 1578, 1458, 1254, 1199, 1144, 1085, 977, 850; HRMS (APCI): m/z [M+H] + calcd for C 12 H 17 Cl Si: S19

20 ; found: ((4-Chloro-1-(methoxymethoxy)naphthalen-2-yl)difluoromethyl)trimethylsilane (7j) Me Cl 30% NMR yield. 19 NMR (282 MHz, CDCl 3 ) δ (s, 2). This compund could not be isolated from impurities. After desilylation (treatment with 10 mol% potassium carbonate in methanol at room temperature for 1 h), the obtained product could be identified with the expected desilylated compound 7j-H. 4-Chloro-2-(difluoromethyl)-1-(methoxymethoxy)naphthalene (7j-H) Me Cl C 2 H Colorless solid. 26% isolated yield (2 steps, 14.2 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 8.29 (d, 1H, J = 8.3 Hz), 8.17 (d, 1H, J = 8.2 Hz), 7.77 (s, 1H), (m, 2H), 7.15 (t, 1H, J H- = 55.2 Hz), 5.19 (s, 2H), 3.66 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ (t, J C- = 7.4 Hz), (s), (s), (s), (s), (s), (s), (t, J C- = 23.2 Hz), (s), (t, J C- = 4.7 Hz), (t, J C- = Hz), (s), 58.1 (s); 19 NMR (282 MHz, CDCl 3 ) δ (d, 2, J H- = 55.3 Hz); TIR (KBr, cm 1 ) 2954, 2932, 1601, 1357, 1200, 1164, 1059, 1028, 919, 765; HRMS (ESI): m/z [M H] calcd for C 13 H 10 Cl 2 2 : ; found: Procedures for Transformation of Siladifluoromethylated Products 2-(1,1-Difluoroethyl)-1-(methoxymethoxy)-4-(trifluoromethyl)benzene (8) Me 3 C Me Iodomethane (0.30 mmol, 19 µl) and anhydrous potassium fluoride (0.30 mmol, 17.4 mg) were dissolved in DM (1 ml). To the resulting solution was added a solution of 7a (0.10 mmol, 32.8 mg) in DM (0.5 ml). The mixture was heated at 80 C for 2 h. The solution was allowed to cool to room temperature, and water (1 ml) was added. The organic S20

21 layer was extracted with diethyl ether, washed with brine, and then dried over MgS4. After filtration, the solvent was removed under reduced pressure. The residue was purified by silica-gel column chromatography (5% dichloromethane in hexane) to afford 8 as colorless liquid. The isolated yield after silica-gel column chromatography was lower than the NMR yield because it was difficult to separate the product from protodesilylated byproduct. 60% NMR yield. 29% isolated yield (7.8 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.80 (s, 1H), 7.63 (d, 1H, J = 8.2 Hz), 7.27 (d, 1H, J = 8.0 Hz), 5.30 (s, 2H), 3.50 (s, 3H), 2.03 (t, 3H, J H- = 18.7 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (t, J C- = 26.1 Hz), (q, J C- = Hz), (m), (q, J C- = 33.0 Hz), (t, J C- = Hz), (s), 56.5 (s), 24.5 (t, J C- = 28.3 Hz); 19 NMR (282 MHz, CDCl 3 ) δ 61.9 (s, 3), 87.9 (q, 2, J H- = 18.3 Hz); TIR (neat, cm 1 ) 2965, 2856, 1624, 1507, 1338, 1280, 1127, 983, 930, 829; HRMS (ESI): m/z [M+H] + calcd for C 11 H : ; found: Ethyl 2,2-difluoro-2-(2-(methoxymethoxy)-5-(trifluoromethyl)phenyl)acetate (9) Me 3 C Ethyl chloroformate (0.30 mmol, 29 µl) and anhydrous potassium fluoride (0.30 mmol, 17.4 mg) were dissolved in DM (1 ml). To the resulting solution was added a solution of 7a (0.10 mmol, 32.8 mg) in DM (0.5 ml). The mixture was heated at 100 C for 2 h. The solution was allowed to cool to room temperature, and water (1 ml) was added. The organic layer was extracted with diethyl ether, washed with brine, and then dried over MgS4. After filtration, the solvent was removed under reduced pressure. The residue was purified by silica-gel column chromatography (10% dichloromethane in hexane) to afford 9 as red liquid. 50% NMR yield. 34% isolated yield (11.6 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.92 (d, 1H, J = 1.9 Hz), 7.82 (dd, 1H, J = 8.7, 1.6 Hz), 7.27 (d, 1H, J = 8.4 Hz), 5.21 (s, 2H), 4.34 (q, 2H, J = 7.1 Hz), 3.45 (s, 3H), 1.32 (t, 3H, J = 7.1 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ (t, J C- = 33.4 Hz), (t, J C- = 4.0 Hz), (s), (m), (q, J C- = 33.1 Hz) (q, J C- = Hz), (t, J C- = 24.5 Hz), (t, J C- = Hz), 94.4 (s), 63.0 (s), 56.5 (s), 13.9 (s); 19 NMR (282 MHz, CDCl 3 ) δ 62.0 (s, 3), (s, 2); TIR (neat, cm 1 ) 2966, 2936, 1778, 1625, 1509, 1336, 1278, 1230, 1123, 1093; HRMS (APCI): m/z [M+Na] + calcd for C 13 H 13 5 Na 4 : ; found: S21

22 2,2-Difluoro-2-(2-(methoxymethoxy)-5-(trifluoromethyl)phenyl)-1-phenylethan-1-ol (10) Me H 3 C Benzaldehyde (0.30 mmol, 30 µl) and anhydrous potassium fluoride (0.30 mmol, 17.4 mg) were dissolved in DM (1 ml). To the resulting solution was added a solution of 7a (0.10 mmol, 32.8 mg) in DM (0.5 ml). The mixture was heated at 60 C for 3 h. The solution was allowed to cool to room temperature, and water (1 ml) was added. The organic layer was extracted with diethyl ether, washed with brine, and then dried over MgS4. After filtration, the solvent was removed under reduced pressure. The residue was purified by silica-gel column chromatography (10% ethyl acetate in hexane) to afford 10 as colorless liquid. 65% NMR yield. 65% isolated yield (23.5 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.61 (d, 1H, J = 8.4 Hz), 7.50 (s, 1H), 7.29 (brs, 5H), 7.26 (d, 1H), 5.47 (t, 1H, J H- = 11.7 Hz), 5.28 (s, 2H), 3.53 (s, 3H), 2.86 (brs, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (t, J C- = 44.4 Hz), (m), (t, J C- = 23.3 Hz), (q, J C- = Hz), (q, J C- = 33.1 Hz), (s), (s), (s), 94.6 (s), 75.1 (t, J C- = 27.6 Hz), 56.7 (s); 19 NMR (282 MHz, CDCl 3 ) δ 62.0 (s, 3), (d, 2, J H- = 12.2 Hz); TIR (neat, cm 1 ) 3451, 2962, 2940, 1624, 1336, 1281, 1129, 977, 700; HRMS (APCI): m/z [M+Na] + calcd for C 17 H 15 5 Na 3 : ; found: (Difluoro(2-(methoxymethoxy)-5-(trifluoromethyl)phenyl)methyl)(phenyl)sulfane (11) Me 3 C S Diphenyl disulfide (0.30 mmol, 65.5 mg) and anhydrous potassium fluoride (0.30 mmol, 17.4 mg) were dissolved in DM (1 ml). To the resulting solution was added a solution of 7a (0.10 mmol, 32.8 mg) in DM (0.5 ml). The mixture was heated at 80 C for 2 h. The solution was allowed to cool to room temperature, and water (1 ml) was added. The organic layer was extracted with diethyl ether, washed with brine, and then dried over MgS4. After filtration, the solvent was removed under reduced pressure. The residue was purified by silica-gel column chromatography (5% dichloromethane in hexane) to afford 11 as colorless liquid. 58% NMR yield. 43% isolated yield (15.7 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.63 (d, S22

23 1H, J = 8.7 Hz), 7.56 (s, 1H), 7.55 (d, 2H, J = 7.4 Hz), (m, 1H), , (m, 2H),7.31, (d, 1H, J = 8.8 Hz), 5.36 (s, 2H), 3.58 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (s), (s), (s), (s), (t, J C- = Hz), (q, J C- = Hz), (t, J C- = 25.2 Hz), (m), (q, J C- = 33.2 Hz), (s), 94.2 (s), 56.7 (s); 19 NMR (282 MHz, CDCl 3 ) δ 62.0 (s, 3), 71.6 (s, 2); TIR (neat, cm 1 ) 2963, 2934, 1621, 1507, 1337, 1281, 1126, 982, 905, 692; HRMS (ESI): m/z [M+H] + calcd for C 16 H S: ; found: (Difluoro(2-(methoxymethoxy)-5-(trifluoromethyl)phenyl)methyl)-2,3,4,5,6-pentafluorobenzene (12) Me 3 C Hexafluorobenzene (0.30 mmol, 34 µl) and anhydrous potassium fluoride (0.30 mmol, 17.4 mg) were dissolved in DM (1 ml). To the resulting solution was added a solution of 7a (0.10 mmol, 32.8 mg) in DM (0.5 ml). The mixture was heated at 60 C for 2 h. The solution was allowed to cool to room temperature, and water (1 ml) was added. The organic layer was extracted with diethyl ether, washed with brine, and then dried over MgS4. After filtration, the solvent was removed under reduced pressure. The residue was purified by silica-gel column chromatography (5% dichloromethane in hexane) to afford 12 as colorless solid. 69% NMR yield. 50% isolated yield (21.1 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 8.03 (s, 1H), 7.71 (d, 1H, J = 8.4 Hz), 7.23 (d, 1H, J = 8.6 Hz), 5.16 (s, 2H), 3.33 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (m), (m), (m), (m), (m), (m), (t, J C- = 1.8 Hz), (t, J C- = 26.3 Hz), (q, J C- = Hz), (br), (q, J C- = 33.4 Hz), (t, J C- = Hz), (s), 94.1 (s), 56.4 (s); 19 NMR (282 MHz, CDCl 3 ) δ 62.0 (s, 3), 89.6 (t, 2, J - = 24.8 Hz), (dd, 2, J - = 42.1, 19.9 Hz), (t, 1, J - = 20.1 Hz), (t, 2, J - = 18.4 Hz); TIR (KBr, cm 1 ) 2972, 2943, 1626, 1508, 1335, 1222, 1127, 928, 683, 608; HRMS (APCI): m/z [M+Cl] calcd for C 16 H 8 Cl 10 2 : ; found: S23

24 Syntheses of Alkyne Substrates 1-Chloro-4-ethynylbenzene, tert-butyldimethylsilylacetylene, and triisopropylsilylacetylene were purchased from Tokyo Chemical Industries or Wako Pure Chemical Industries. 2-Ethynylnaphthalene and 6-methoxy-2-ethynylnaphthalene were synthesized by Corey-uchs alkyne synthesis reaction referred to the literature. [4] 3-Ethynylquinoline and methyl 4-ethynylbenzoate were synthesized by Sonogashira coupling reaction referred to the literature. [5] Genaral Procedure for Siladifluoromethylation onto C(sp) Centers To a solution of 2-ethynylnaphthalene 13a (0.20 mmol, 30.4 mg) in TH (1.0 ml) was added n-butyllithium solution (1.6 M in hexane, 0.20 mmol, 125 µl) at 78 C. After stirred for 5 minutes at that temperature, C 3 TMS (0.20 mmol, 30 µl) was added. After stirred for 5 minutes at that temperature, the reaction was quenched with water. The organic layer was extracted with diethyl ether, washed with brine, and dried over anhydrous MgS 4. After filtration, the solvent was removed under reduced pressure. NMR yield (40%) was determined by using BT as an internal standard. The residue was purified by preparative TLC (hexane/ dichloromethane = 5/1 as an eluent) to afford 14a as colorless solid. The isolated yields were generally lower than the corresponding NMR yields because it was difficult to separate the product from substrate and byproducts. (1,1-Difluoro-3-(naphthalen-2-yl)prop-2-yn-1-yl)trimethylsilane (14a) Colorless solid. 40% NMR yield. 28% isolated yield (22.0 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 8.03 (s, 1H), (m, 3H), (m, 3H), 0.33 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (t, J C- = 3.5 Hz), (s), (t, J C- = 2.7 Hz), (s), (s), (s), (s), (t, J C- = Hz), (t, J C- = 3.8 Hz), 91.4 (t, J C- = 9.2 Hz), 82.4 (t, J C- = 31.3 Hz), 4.9 (s); 19 NMR (282 MHz, CDCl 3 ) δ (s, 2); TIR (KBr, cm 1 ) 3060, 2962, 2926, 2854, 2221, 1254, 1072, 972, 848, 817, 747; HRMS (APCI): m/z [M+H] + calcd for C 16 H 17 2 Si: ; found: S24

25 (3-(4-Chlorophenyl)-1,1-difluoroprop-2-yn-1-yl)trimethylsilane (14b) Cl Colorless liquid. 37% NMR yield. 29% isolated yield (15.0 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.42 (d, 2H, J = 8.3 Hz), 7.33 (d, 2H, J = 8.5 Hz), 0.28 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (t, J C- = 3.1 Hz), (s), (t, J C- = Hz), (t, J C- = 3.8 Hz), 89.7 (t, J C- = 9.2 Hz), 83.1 (t, J C- = 31.3 Hz), 5.0 (s); 19 NMR (282 MHz, CDCl 3 ) δ (s, 2); TIR (neat, cm 1 ) 2964, 2904, 2226, 1489, 1254, 1080, 975, 850, 829, 756; HRMS (APCI): m/z [M+H] + calcd for C 12 H 14 Cl 2 Si: ; found: (3,3-Difluoro-3-(trimethylsilyl)prop-1-yn-1-yl)quinoline (14c) N Brown solid. 38% NMR yield. 33% isolated yield (18.2 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 8.92 (s, 1H), 8.31 (s, 1H), 8.11 (d, 1H, J = 8.3 Hz), (m, 2H), (m, 1H), 0.33 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (t, J C- = 2.7 Hz), (s), (t, J C- = 3.3 Hz), (s), (s), (s), (s), (s), (t, J C- = Hz), (t, J C- = 3.8 Hz), 88.0 (t, J C- = 9.0 Hz), 85.3 (t, J C- = 31.5 Hz), 4.9 (s); 19 NMR (282 MHz, CDCl 3 ) δ (s, 2); TIR (KBr, cm 1 ) 3060, 3020, 2966, 2223, 1490, 1254, 1071, 966, 853, 754; HRMS (APCI): m/z [M+H] + calcd for C 15 H 16 2 NSi: ; found: tert-butyl(3,3-difluoro-3-(trimethylsilyl)prop-1-yn-1-yl)dimethylsilane (14d) TBS Colorless liquid. 63% NMR yield. 51% isolated yield (26.8 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 0.97 (s, 9H), 0.25 (s, 9H), 0.18 (s, 6H); 13 C NMR (75 MHz, CDCl 3 ) δ (t, J C- = Hz), 98.4 (t, J C- = 29.6 Hz), 96.0 (t, J C- = 7.4 Hz), 26.0 (s), 25.9 (s), 16.4 (s), 5.1 (t, J C- = 1.4 Hz); 19 NMR (282 MHz, CDCl 3 ) δ (s, 2); TIR (neat, cm 1 ) 2956, 2931, 2859, 2153, 1471, 1254, 1099, 982, 844, 778; HRMS (APCI): m/z [M+H] + calcd for C 12 H 25 2 Si 2 : ; found: S25

26 (1,1-Difluoro-3-(triisopropylsilyl)prop-2-yn-1-yl)trimethylsilane (14e) TIPS Colorless liquid. 68% NMR yield. 48% isolated yield (29.2 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 1.11 (m, 21H), 0.26 (s, 9H); 13 C NMR (75 MHz, CDCl 3 ) δ (t, J C- = Hz), 99.7 (t, J C- = 29.6 Hz), 94.0 (t, J C- = 7.4 Hz), 18.5 (s), 11.0 (s), 5.0 (s); 19 NMR (282 MHz, CDCl 3 ) δ (s, 2); TIR (neat, cm 1 ) 2960, 2946, 2869, 2342, 1732, 1465, 1254, 1098, 981, 849; HRMS (APCI): m/z [M+H] + calcd for C 15 H 31 2 Si 2 : ; found: Genaral Procedure for Difluoromethylation onto C(sp) Centers The reaction was performed under fluoroform atmosphere using a balloon. To a solution of 2-ethynylnaphthalene 13a (0.10 mmol, 15.2 mg) in TH (1.0 ml) was added LHMDS solution (1.0 M in TH, 0.20 mmol, 200 µl) at 78 C. After stirred for 2 h, the reaction was quenched with water. The organic layer was extracted with diethyl ether, washed with brine, and dried over anhydrous MgS 4. After filtration, the solvent was removed under reduced pressure. NMR yield (57%) was determined by using BT as an internal standard. The residue was purified by preparative TLC (hexane/dichloromethane = 5/1 as an eluent) to afford 15a as colorless solid. The isolated yields were generally lower than the corresponding NMR yields because it was difficult to separate the product from substrate and byproducts. 2-(3,3-Difluoroprop-1-yn-1-yl)naphthalene (15a) C 2 H Colorless solid. 57% NMR yield. 42% isolated yield (8.5 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 8.08 (s, 1H), (m, 3H), (m, 3H), 6.47 (t, 1H, J H- = 55.1 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (t, J C- = 2.9 Hz), (s), (s), (s), (s), (s), (s), (s), (t, J C- = 3.2 Hz), (t, J C- = Hz), 88.8 (t, J C- = 7.2 Hz), 79.9 (t, J C- = 33.8 Hz); 19 NMR (282 MHz, CDCl 3 ) δ (d, 2, J H- = 55.0 Hz); TIR (KBr, cm 1 ) 3061, 2962, 2925, 2853, 2238, 1595, 1500, 1374, 1087, 1037; HRMS (APCI): m/z [M+H] + calcd for C 13 H 9 2 : ; found: S26

27 2-(3,3-Difluoroprop-1-yn-1-yl)-6-methoxynaphthalene (15b) C 2 H Me Colorless solid. 43% NMR yield. 40% isolated yield (9.3 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 7.99 (s, 1H), (m, 2H), 7.48 (dd, 1H, J = 8.5, 1.5 Hz), 7.19 (dd, 1H, J = 9.0, 2.5 Hz), 7.12 (d, 1H, J = 2.3 Hz), 6.46 (t, 1H, J H- = 55.2 Hz), 3.93 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (s), (t, J C- = 2.9 Hz), (s), (t, J C- = 2.3 Hz), (s), (s), (s), (t, J C- = 3.3 Hz), (s), (t, J C- = Hz), 89.2 (t, J C- = 7.3 Hz), 79.4 (t, J C- = 33.6 Hz), 55.4 (s); 19 NMR (282 MHz, CDCl 3 ) δ (d, 2, J H- = 55.1 Hz); TIR (KBr, cm 1 ) 3060, 2963, 2935, 2851, 2231, 1627, 1601, 1487, 1381, 1256, 1089, 1025; HRMS (ESI): m/z [M+Na] + calcd for C 14 H 10 2 N- a: ; found: Methyl 4-(3,3-difluoroprop-1-yn-1-yl)benzoate (15c) C 2 H Me 2 C Yellow solid. 63% NMR yield. 52% isolated yield (10.9 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 8.04 (d, 2H, J = 8.5 Hz), 7.59 (d, 2H, J = 8.5 Hz), 6.42 (t, 1H, J H- = 54.7 Hz), 3.93 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ (s), (t, J C- = 2.5 Hz), (s), (s), (t, J C- = 3.2 Hz), (t, J C- = Hz), 87.2 (t, J C- = 7.2 Hz), 82.0 (t, J C- = 33.9 Hz), 52.4 (s); 19 NMR (282 MHz, CDCl 3 ) δ (d, 2, J H- = 55.0 Hz); TIR (KBr, cm 1 ) 2955, 2930, 2853, 2253, 1942, 1732, 1606, 1437, 1371, 1279; HRMS (APCI): m/z [M+H] + calcd for C 11 H : ; found: (3,3-Difluoroprop-1-yn-1-yl)quinoline (15d) C 2 H N Brown solid. 45% NMR yield. 39% isolated yield (7.9 mg). 1 H NMR (300 MHz, CDCl 3 ) δ 8.95 (d, 1H, J = 1.8 Hz), 8.35 (d, 1H, J = 1.0 Hz), 8.12 (d, 1H, J = 8.4 Hz), (m, 2H), (m, 1H), 6.48 (t, 1H, J H- = 54.7 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ (t, J C- = 2.3 Hz), (s), (t, J C- = 2.7 Hz), (s), (s), (s), S27