Highly Selective Pd-Catalyzed Direct C-F Bond Arylation of Polyfluoroarenes

Supporting Information for Highly Selective Pd-Catalyzed Direct C-F Bond Arylation of Polyfluoroarenes Zhi-Ji Luo, Hai-Yang Zhao, and Xingang Zhang* Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, 345 Lingling Lu, Shanghai 200032 (China) xgzhang@mail.sioc.ac.cn S1

List of Contents 1. Materials and Methods... 3 2. Optimization of Palladium Catalyzed Cross-Coupling of Pentafluorobenzene 1a With Phenylboronic Acid 2a.... 4 3. Mechanistic Study... 7 4. General Procedure for Palladium Catalyzed Cross-Coupling of Polyfluoroarenes with Aryboronic Acids... 9 5. Characterization Data for Arylated Polyfluoroarenes 3 and 4... 9 6. Sequential C-F Bond Activation of Polyfluoroarenes... 22 7. Preparation of Liquid Crystal Molecule... 25 8. References... 26 9. Copies of 1 H NMR, 13 C NMR, and 19 F NMR Spectra of Compounds 3-6, 8, 10, and 11... 28 S2

1. Materials and Methods General Information: 1 H NMR and 13 C NMR spectra were recorded on a Bruker AM400 spectrometer and are calibrated using residual undeuterated solvent (CHCl3 at 7.26 ppm 1 H NMR, 77.60 ppm 13 C NMR; CD2Cl2 at 5.32 ppm 1 H NMR, 54.00 ppm 13 C NMR). (CFCl3 as an external standard and low field is positive). Chemical shifts (δ) are reported in ppm, and coupling constants (J) are in Hertz (Hz). The following abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad. NMR yield was determined by 19 F NMR using fluorobenzene as an internal standard before working up the reaction. Materials: All reagents were used as received from commercial sources, unless specified otherwise, or prepared as described in the literature. Cs2CO3 was milled and weighed under Ar atmosphere. Pd(OAc)2 were purchased from Strem Chemicals and used as received. BrettPhos was purchased from Adams and used as received. Toluene was distilled from sodium and benzophenone before use. Pentane was distilled from CaH2. Compounds 1 were prepared according to the literature procedure, 1d [1], 1e [2], 1h [2], 1o [1], 1q [2]. Pd(CH2SiMe3)2(COD) [3] was prepared according to the literature procedure and the rude product was crystallized from acetone (in freezer, -30 o C) affording crystalline Pd(CH2SiMe3)2(COD). S3

2. Optimization of Palladium Catalyzed Cross-Coupling of Pentafluorobenzene 1a With Phenylboronic Acid 2a. To a 25 ml of Schlenk tube were added phenylboronic acid 2a (1.0-2.0 equiv), [Pd]-catalyst (x mol %), P-ligand (y mol %) and base (1.0-2.0 equiv) under Ar atmosphere, followed by addition of pentafluorobenzene 1a (0.3 mmol, 1.0 equiv) and solvent (2 ml). The tube was screw-capped and heated to 80-120 º C (oil bath). After stirring for 12 h, the reaction mixture was cooled to room temperature and fluorobenzene (1.0 equiv) was added. The yield was determined by 19 F NMR before working up. If necessary, the reaction mixture was diluted with dichloromethane, filtered through a pad of Celite and concentrated. The residue was purified with silica gel chromatography (petroleum) to provide 3a/3a as a white solid. S4

Table S1. Ligand Effect on Palladium Catalyzed Cross-Coupling of 1a with 2a a Entry Pd(OAc)2 (x) L (y) S5 yield 1a 3a 3a 1 2.5 L1 (5) 99 nd nd 2 2.5 L2 (5) 99 nd nd 3 2.5 L3 (5) 100 nd nd 4 2.5 L4 (5) 99 nd nd 5 2.5 L5 (5) 96 3 nd 6 2.5 L6 (5) 99 nd nd 7 2.5 L7 (5) 100 nd nd 8 2.5 L8 (5) 78 20 trace 9 2.5 L9 (5) 99 nd nd 10 2.5 L10 (5) 0 94 (90) 5 (4) 11 2.5 L11 (5) 100 nd nd 12 2.5 L12 (2.5) 99 nd nd 13 2.5 L13 (2.5) 100 nd nd 14 2.5 L14 (2.5) 100 nd nd 15 2.5 L10 (2.5) 21 72 5 16 1.25 L10 (2.5) 12 83 5 17 2.5 none 100 nd nd a Reaction conditions (unless otherwise specified): 1a (0.3 mmol, 1.0 equiv), 2a (0.6 mmol, 2.0 equiv), Cs2CO3 (2.0 equiv), toluene (2 ml). b Determined by 19 F NMR using fluorobenzene as an internal standard and number in parenthesis is isolated yield.

Table S2. Screening of Solvents and Bases for Palladium Catalyzed Cross-Coupling of 1a with 2a a Entry Solvent Base yield 1a 3a 3a 1 dioxane Cs2CO3 13 50 4 2 DMF Cs2CO3 20 nd nd 3 DMSO Cs2CO3 39 49 2 4 toluene CsF nd 71 4 5 toluene KF 76 10 nd 6 toluene Na2CO3 99 nd nd 7 toluene K2CO3 69 29 2 8 toluene K3PO4 59 34 2 a Reaction conditions (unless otherwise specified): 1a (0.3 mmol, 1.0 equiv), 2a (0.6 mmol, 2.0 equiv), base (2.0 equiv), solvent (2 ml). b Determined by 19 F NMR using fluorobenzene as an internal standard. S6

Table S3. Screening of Palladium Sources and Reaction Temperature for Palladium Catalyzed Cross-Coupling of 1a with 2a a Entry [Pd] Temp ( º C) yield 1a 3a 3a 1 Pd(OAc)2 120 0 94(90) 5(4) 1 Pd(OAc)2 100 4 89 5 2 Pd(OAc)2 80 23 72 4 3 PdCl2 120 98 1 nd 4 Pd(COD)Cl2 120 0 88 5 5 Pd(PPh3)Cl2 120 99 trace nd 6 Pd2(dba)3 120 81 8 trace 7 Pd(PPh3)4 120 99 nd nd 8 none 120 100 nd nd a Reaction conditions (unless otherwise specified): 1a (0.3 mmol, 1.0 equiv), 2a (0.6 mmol, 2.0 equiv), base (2.0 equiv), solvent (2 ml). b Determined by 19 F NMR using fluorobenzene as an internal standard and number in parenthesis is an isolated yield. 3. Mechanistic Study Preparation of (BrettPhos)Pd(C6F4CO2Me)F (11) Procedure: A 25 ml of Schlenck tube equipped with a magnetic stir bar was charged with Pd(CH2SiMe3)2(cod) (77.8 mg, 0.2 mmol, 1.0 equiv), (90.4 mg, 0.4 mmol, 2.0 equiv) and BrettPhos (107.2 mg, 0.2 mmol, 1.0 equiv) in glove box, toluene (4 ml) was then added. After stirring for 4 h at 40 o C, the volatiles was removed under vaccum, the residue was washed with pentane (10.0 ml S7

4) to remove unreacted methyl 2,3,4,5,6-pentafluorobenzoate and BrettPhos, then dried under vacuum to give (BrettPhos)Pd(C6F4CO2Me)F (11) (108.0 mg, 62 % yield) as a pale yellow solid. Single crystal of complex 11 was obtained by vapor diffusion of pentane into DCM solution of 11. 1 H NMR (400 MHz, CD2Cl2) δ 7.12 (s, 2H), 6.94 (s, 2H), 3.87 (s, 3H), 3.86 (s, 3H), 3.42 (s, 3H), 2.97 (hept, J = 6.9 Hz, 1H), 2.59 2.52 (m, 4H), 1.89 1.76 (m, 4H), 1.73 1.65 (m, 6H), 1.63 (d, J = 6.7 Hz, 6H), 1.31 (d, J = 6.9 Hz, 6H), 1.29 1.15 (m, 7H), 1.14 1.02 (m, 3H), 0.86 (d, J = 6.6 Hz, 6H). 19 F NMR (376 MHz, CD2Cl2) δ -115.72 (d, J = 23.4 Hz), -142.14 (d, J = 20.2 Hz), -214.96 (d, J = 182.2 Hz). 31 P NMR (162 MHz, CD2Cl2) δ 51.81 (d, J = 182.2 Hz). 13 C NMR (101 MHz, CD2Cl2) δ 162.1 161.9 (m), 160.9, 154.8, 154.6, 152.4 (d, J = 16.2 Hz), 148.5 (dm, J = 224.6 Hz), 144.1(dm, J = 260.8 Hz), 137.9 (d, J = 16.6 Hz), 125.7 125.5 (m), 125.3 125.1 (m), 124.5, 114.7, 112.7 (d, J = 3.3 Hz), 111.9 (d, J = 4.6 Hz), 108.7 108.1 (m), 55.7, 55.0, 53.0, 37.5 (d, J = 29.2 Hz), 35.3, 32.2, 29.7, 29.5 (d, J = 3.3 Hz), 28.3 (d, J = 11.9 Hz), 27.7 (d, J = 13.8 Hz), 26.6, 25.0, 24.8, 24.4. IR (thin film) max 2929, 2855, 1736, 1436, 1289, 960, 742, 640 cm -1. MALDI-TOF-MS: m/z (%) 849 (BrettPhos)Pd(C6F4CO2Me) + (100), 642 ((BrettPhos)Pd) 2+. Stoichiometric Reaction of (BrettPhos)Pd(C6F4CO2Me)F (11) with phenylboronic acid 2a Procedure: A 25 ml of Schlenck tube equipped with a magnetic stir bar was charged with PhB(OH)2 (12.2 mg, 0.1 mmol, 1.0 equiv), Cs2CO3 (32.6 mg, 0.1 mmol, 1.0 equiv) and (BrettPhos)Pd(C6F4CO2Me)F (11) (86.9 mg, 0.1 mmol, 1.0 equiv) in glove box, followed by toluene (2 ml). The tube was screw capped and put into an oil bath (preheated to 40 o C). After stirring for 8 h, the reaction mixture was cooled to room temperature, diluted with DCM, filtered through a pad of Celite and concentrated. The residue was purified with silica gel chromatography (Petroleum / Ethyl acetate= 40:1) to provide pure product 4o (18.0 mg, 63 % yield). S8

(BrettPhos)Pd(C6F4CO2Me)F (11) Catalyzed Cross-Coupling of 2a with methyl 2,3,4,5,6-pentafluorobenzoate 1p To a septum capped 25 ml of Schlenck tube were added phenylboronic acid (36.6 mg, 0.3 mmol, 1.0 equiv), methyl 2,3,4,5,6-pentafluorobenzoate (67.8 mg, 0.3 mmol, 1.0 equiv), Cs2CO3 (97.8 mg, 0.3 mmol, 1.0 equiv), and (BrettPhos)Pd(C6F4CO2Me)F (11) (6.5 mg, 2.5% mmol) in glove box, followed by toluene (2 ml). The tube was screw capped and put into an oil bath (preheated to 120 o C). After stirring for 12 h, the reaction mixture was cooled to room temperature, diluted with DCM, filtered through a pad of Celite and concentrated. The residue was purified with silica gel chromatography (Petroleum / Ethyl acetate= 40:1) to provide pure product 4o (72.8 mg, 63 % yield). 4. General Procedure for Palladium Catalyzed Cross-Coupling of Polyfluoroarenes with Aryboronic Acids To a septum capped 25 ml of Schlenck tube were added Pd(OAc)2 (1.7 mg, 2.5 mol%), arylboronic acid (0.6 mmol, 2.0 equiv), BrettPhos (8.1 mg, 5 mol%), and Cs2CO3 ( 195.5 mg, 2.0 equiv) under Ar, followed by toluene (2.0 ml) and polyfluoroarene (0.3 mmol, 1.0 equiv). The tube was screw capped and put into an oil bath (preheated to 120 o C). After stirring for 12 h, the reaction mixture was cooled to room temperature, and diluted with DCM, filtered through a pad of Celite and concentrated. The residue was purified with silica gel chromatography to provide pure product 3 or 4. And the ratio of the major product 3a to the isomer 3a was determined by 19 F NMR analysis of the isolated product 3. 5. Characterization Data for Arylated Polyfluoroarenes 3 and 4 2,3,5,6-Tetrafluorobiphenyl (3a). [Known compound 4 ]: The product 3a contains a small amount of regioisomer 3a (3a, 61.1 mg, 90% yield; 3a, 2.7 mg, 4% yield) as a white solid was purified with S9

silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 7.54 7.42 (m, 5H), 7.07 (tt, J = 9.7, 7.4 Hz, 1H). 19 F NMR (376 MHz, CDCl3) δ -139.0-139.2 (m, 2F), -142.2-145.3 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 146.6 (dm, J = 245.4 Hz), 144.7 (dm, J = 245.1 Hz), 130.7 (t, J = 2.1 Hz), 129.8, 129.2, 128.0, 122.1 (t, J = 13.7 Hz), 105.4 (t, J = 22.7 Hz). 2,3,5,6-Tertrafluoro-4 -methoxy-1,1 -biphenyl (3b). [Known compound 5 ]: The product 3b contains a small amount of regioisomer 3b (3b, 66.9 mg, 87% yield; 3b, 2.3 mg, 3% yield) as a white solid was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 8.5 Hz, 2H), 7.07 6.95 (m, 3H), 3.87 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ -139.4-139.5 (m, 2F), -144.2-144.4 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 160.8, 146.8 (dm, J = 245.1 Hz), 144.3 (dm, J = 246.4 Hz), 132.0, 121.8 (t, J = 16.9 Hz), 120.1, 114.7, 104.8 (t, J = 22.8 Hz), 55.8. 2,3,5,6-Tertrafluoro-3,5 -dimethyl-1,1 -biphenyl (3c). The product 3c contains a small amount of regioisomer 3c (3c, 48.0 mg, 63% yield; 3c, 3.1 mg, 4% yield) as a white solid (mp. 41-43 o C) was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 7.10 (s, 1H), 7.06 (s, 2H), 7.05-6.99 (m, 1H), 2.38 (s, 6H). 19 F NMR (376 MHz, CDCl3) -139.4-139.5 (m, 2F), -143.6-143.7 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 146.7 (dm, J = 248.5 Hz), 144.3 (dm, J = 247.5 Hz), 138.8, 131.5, 128.3, 127.8, 122.4 (t, J = 16.8 Hz), 105.1 (t, J = 22.8 Hz), 21.8. IR (thin film) max 1643, 1602, 1493, 1447 cm -1. MS (EI): m/z (%) 254 (M + ), 241 (100). HRMS: Calcd. for C14H10F4: 254.0719; Found: 254.0718. S10

2,3,5,6-Tetrafluoro-1,1':2',1''-terphenyl (3d). [Known compound 6 ]: The product 3d contains a small amount of regioisomer 3d (3d, 82.5 mg, 91% yield; 3d, 1.8 mg, 2% yield) as a white solid was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 7.58 7.45 (m, 3H), 7.39 7.34 (m, 1H), 7.28 7.23 (m, 3H), 7.18 7.13 (m, 2H), 6.95 (tt, J = 9.7, 7.3 Hz, 1H). 19 F NMR (376 MHz, CDCl3) δ -139.6-139.9 (m, 2F), -141.0-14.3 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 146.3 (dm, J = 248.8 Hz), 144.3 (dm, J = 246.8 Hz), 143.4, 141.0, 131.5, 130.9, 130.2, 129.2, 128.6, 127.9, 127.9, 126.6, 122.2 (t, J = 19.0 Hz), 105.6 (t, J = 22.7 Hz). 1-(2,3,5,6-Tetrafluorophenyl)naphthalene (3e). The product 3e contains a small amount of regioisomer 3e (3e, 45.6 mg, 55% yield; 3e, 4.1 mg, 5% yield) as a white solid (mp. 63-65 o C) was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.2 Hz, 1H), 7.93 (d, J = 7.9 Hz, 1H), 7.61 7.43 (m, 5H), 7.23 7.11 (m, 1H). 19 F NMR (376 MHz, CDCl3) δ -138.9-139.0 (m, 2F), -140.1-140.2 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 147.0 (dm, J = 247.3 Hz), 144.5 (dm, J = 246.9 Hz), 134.2, 132.0, 130.5, 129.28 (s), 129.1, 127.5, 126.9, 125.8, 125.5, 125.3, 120.8 (t, J = 19.8 Hz), 106.1 (t, J = 22.6 Hz). IR (thin film) max 1606, 1489 cm -1. MS (EI): m/z (%) 276 (M + ), (100). HRMS: Calcd. for C16H8F4: 276.0562; Found: 276.0560. 2-(2,3,5,6-Tetrafluorophenyl)naphthalene (3f). [Known compound 7 ]: The product 3f contains a small amount of regioisomer 3f (3f, 69.6 mg, 84% yield; 3f, 3.3 mg, 4% yield) as a white solid was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 8.00 7.97 (m, 2H), 7.93 7.89 (m, 2H), 7.60 7.51 (m, 3H), 7.17 7.06 (m, 1H). 19 F NMR (376 MHz, CDCl3) δ -139.0-139.1 (m, 2F), -143.6-143.8 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 146.9 (dm, J = S11

245.4 Hz), 144.8 (dm, J = 245.3 Hz), 133.8, 133.6, 130.6, 128.9, 128.8, 128.3, 127.7, 127.2, 125.4, 122.0 (t, J = 16.3 Hz), 105.5 (t, J = 22.7 Hz). 2,3,4,5,6-Pentafluoro-1,1 -biphenyl (3g). [Known compound 8 ]: The product 3g contains a small amount of regioisomer 3g (3g, 47.6 mg, 65% yield; 3g, 2.2 mg, 3% yield) as a white solid was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 7.49 7.42 (m, 2H), 7.19 (t, J = 8.7 Hz, 2H), 7.13 7.02 (m, 1H). 19 F NMR (376 MHz, CDCl3) δ -111.5-111.6 (m, 1F), -138.9-139.0 (m, 2F), -143.8-144.3 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 160.8 (d, J = 250.7 Hz), 146.8 (dm, J = 249.0Hz), 144.4 (dm, J = 250.2Hz), 132.6 (d, J = 8.4 Hz), 123.9, 121.1, 116.4 (d, J = 21.9 Hz), 105.6 (t, J = 22.7 Hz). 2,3,5,6-Tetrafluoro-4'-(trifluoromethyl)-1,1'-biphenyl (3h). [Known compound 5 ]: The product 3h contains a small amount of regioisomer 3h (3h, 68.0 mg, 77% yield; 3h, 3.5 mg, 4% yield) as a white solid was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.3 Hz, 2H), 7.58 (d, J = 8.3 Hz, 2H), 7.18 7.06 (m, 1H). 19 F NMR (376 MHz, CDCl3) δ -62.9 (s, 3F), -138.3-138.4 (m, 2F), -143.6-143.8 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 146.9 (dm, J = 249.9 Hz), 144.2 (dm, J = 249.3 Hz), 132.1, 131.8, 131.2 (t, J = 2.1 Hz), 126.2 126,1 (m), 124.4 (q, J = 273.6 Hz), 120.6 (t, J = 20.5 Hz), 106.4 (t, J = 22.6 Hz). 2,3,5,6-Tertrafluoro-4 -trifluoromethoxy-1,1 -biphenyl (3i). The product 3i contains a small S12

amount of regioisomer 3i (3i, 72.5 mg, 78% yield; 3i, 1.9 mg, 2% yield) as a colorless oil was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 7.54 (t, J = 8.0 Hz, 1H), 7.46 7.40 (m, 1H), 7.39 7.31 (m, 2H), 7.18 7.06 (m, 1H). 19 F NMR (376 MHz, CDCl3) δ -58.1 (t, J = 10.2 Hz, 3F), -138.6-138.8 (m, 2F), -143.7-144.0 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 149.9 (d, J = 1.8 Hz), 146.7 (dm, J = 261.4), 144.5 (dm, J = 267.9), 130.6, 129.8, 129.2 (t, J = 2.1 Hz), 123.4, 122.4, 122.3, 121.1 (q, J = 259.1 Hz), 120.5 (t, J = 16.3 Hz), 106.2 (t, J = 22.8 Hz). IR (thin film) max 1611, 1584, 1495, 1455, 1255, 1207, 1172 cm -1. MS (EI): m/z (%) 310 (M + ), (100). HRMS: Calcd. for C13H5OF7: 310.0229; Found: 310.0233. Ethyl 4-(2',3',5 ',6'-tetrafluorophenyl)benzoate (3j). [Known compound 9 ]: The product 3j contains a small amount of regioisomer 3j (3j, 51.0 mg, 57% yield; 3j, 2.7 mg, 3% yield) was purified with silica gel chromatography (Petroleum / Ethyl acetate = 20:1) as a white solid. 1 H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 8.1 Hz, 2H), 7.54 (d, J = 8.1 Hz, 2H), 7.17 7.05 (m, 1H), 4.42 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.1 Hz, 3H). 19 F NMR (376 MHz, CDCl3) δ -138.6-138.7 (m, 2F), -143.4-143.6 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 166.5, 146.9 (dm, J = 253.4 Hz), 144.1 (dm, J = 254.4 Hz), 132.4, 131.7, 130.7 (t, J = 2.1 Hz), 130.3, 121.1, 106.1 (t, J = 22.6 Hz), 61.8, 14.9. 2-Methoxyl-5-[2,3,5,6 -tetrafluorophenyl]pyridine (3k). The product 3k contains a small amount of regioisomer 3k (3k, 32.4 mg, 42% yield; 3k, 2.3 mg, 3% yield) as a white solid (mp. 70-72 o C) was purified with silica gel chromatography (Petroleum / Dichloromethane = 30:1). 1 H NMR (400 MHz, CDCl3) δ 8.29 (s, 1H), 7.68 (dd, J = 8.6, 1.1 Hz, 1H), 7.13 7.03 (m, 1H), 6.88 (d, J = 8.6 Hz, 1H), 4.00 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ -138.6-138.8 (m, 2F), -143.6-144.3 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 165.0, 148.6 (t, J = 3.1 Hz), 146.8 (dm, J = 233.9 Hz), 144.4 (dm, J = S13

233.1 Hz), 140.8 140.2 (m), 117.3 (d, J = 2.2 Hz), 111.6, 109.8, 105.6 (t, J = 23.1 Hz), 54.3. IR (thin film) max 1607, 1492, 1456 cm -1. MS (EI): m/z (%) 257 (M + ), (100). HRMS: Calcd. for C12H7NF4O: 257.0464; Found: 257.0458. 9-(2',3',5',6'-Tetrafluoro[1,1'-biphenyl]-4-yl)-carbazole (3l). The product 3l contains a small amount of regioisomer 3l (3l, 59.9 mg, 51% yield; 3l, 4.7 mg, 4% yield) as a white solid (mp. 154-156 o C) was purified with silica gel chromatography (Petroleum / Dichloromethane= 50:1). 1 H NMR (400 MHz, CDCl3) δ 8.27 (s, 1H), 8.18 (d, J = 7.7 Hz, 1H), 7.71 7.56 (m, 4H), 7.55 7.48 (m, 3H), 7.48 7.40 (m, 2H), 7.34 (t, J = 6.8 Hz, 1H), 7.15 7.02 (m, 1H). 19 F NMR (376 MHz, CDCl3) δ -139.2-139.7 (m, 2F), -144.0-144.3 (m, 2F). 13 C NMR (101 MHz,CDCl3) δ 147.0 (dm, J = 247.3 Hz), 144.4 (dm, J = 247.3 Hz), 141.7 (d, J = 34.6 Hz), 137.9, 130.6, 128.3 (d, J = 4.5 Hz), 127.7, 127.1, 123.8 (d, J = 48.5 Hz), 122.9 (d, J = 1.9 Hz), 121.0 (d, J = 1.7 Hz), 119.3, 110.5 (d, J = 11.7 Hz), 104.8 (t, J = 22.8 Hz). IR (thin film) max 1599, 1501, 1445 cm -1. MS (EI): m/z (%) 391 (M + ), (100). HRMS: Calcd. for C24H13NF4: 391.0984; Found: 391.0996. 4'-(Diphenylamino)-2,3,5,6-tetrafluoro-1,1'-biphenyl (3m). The product 3m contains a small amount of regioisomer 3m (3m, 76.7 mg, 65% yield; 3m, 3.5 mg, 3% yield) as a white solid (mp. 90-92 o C) was purified with silica gel chromatography (Petroleum / Dichloromethane = 100:1). 1 H NMR (400 MHz, CDCl3) δ 7.30 (t, J = 7.8 Hz, 6H), 7.20-7.15 (m, 4H), 7.14 7.10 (m, 2H), 7.08 (t, J = 7.4 Hz, 2H), 7.00 (m, 1H). 19 F NMR (376 MHz, CDCl3) δ -139.4-139.5 (m, 2F), -144.1-144.3 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 149.2, 147.8, 146.8 (dm, J = 248.3 Hz), 144.4 (dm, J = 247.1 Hz), 131.5, 130.0, 125.8, 124.3, 122.4, 121.8 (t, J = 16.5 Hz), 120.7, 104.7 (t, J = 22.8 Hz). S14

IR (thin film) max 1589, 1515, 1488, 1447 cm -1. MS (EI): m/z (%) 393 (M + ), (100). HRMS: Calcd. for C24H15NF4: 393.1141; Found: 393.1135. 9,9-Dimethyl-2-(2,3,5,6 -tetrafluorophenyl)fluorene (3n). The product 3n contains a small amount of regioisomer 3n (3n, 76.0 mg, 74% yield; 3n, 4.1 mg, 4% yield) as a white solid (mp. 156-158 o C) was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 7.8 Hz, 1H), 7.80 7.74 (m, 1H), 7.53 (s, 1H) 7.50 7.43 (m, 2H), 7.40 7.33 (m, 2H), 7.13 7.02 (m, 1H), 1.53 (s, 6 H). 19 F NMR (376 MHz, CDCl3) δ -139.3-139.4 (m, 2F), -143.6-143.8 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 154.5, 154.4, 146.8 (dm, J = 251.6 Hz), 144.8 (dm, J = 249.8 Hz), 140.8, 138.9, 129.6, 128.5, 127.7, 126.6, 125.1, 123.3, 122.5 (t, J = 16.3 Hz), 121.0, 120.6, 105.1 (t, J = 22.7 Hz), 47.6, 27.6. IR (thin film) max 2968, 1646, 1501, 1464 cm -1. MS (EI): m/z (%) 342 (M + ), 327 (100). HRMS: Calcd. for C21H14F4: 342.1032; Found: 342.1022. 3-(2,3,5,6 -Tetrafluorophenyl)dibenzothiophene (3o). The product 3o contains a small amount of regioisomer 3o (3o, 56.8 mg, 57% yield; 3o, 3.0 mg, 3% yield) as a white solid (mp. 137-139 o C) was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 8.28 (d, J = 7.9 Hz, 1H), 8.23 8.18 (m, 1H), 7.86 7.80 (m, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.54 7.46 (m, 2H), 7.46 7.41 (m, 1H), 7.25 7.13 (m, 1H). 19 F NMR (376 MHz, CDCl3) δ -138.2-138.3 (m, 2F), -139.9-140.0 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 146.8 (dm, J = 249.7 Hz), 144.6 (dm, J = 249.5 Hz), 140.8, 139.6, 136.9, 136.0, 129.2, 127.8, 125.2, 125.2, 123.3, 123.1, 123.0 (t, J = 2.4 Hz), 122.4, 120.4 (t, J = 18.5 Hz), 106.7 (t, J = 22.6 Hz). IR (thin film) max 2919, 1577, 1538, 1431 cm -1. MS (EI): m/z (%) 332 (M + ), (100). HRMS: Calcd. for C18H8SF4: 332.0283; Found: 332.0278. S15

Cyclopent-1 -en-1 -yl-2,3,5,6-tetrafluoro benzene (3p). The product 3p contains a small amount of regioisomer 3p (3p, 32.4 mg, 50% yield; 3p, 2.6 mg, 4% yield) as a colorless oil was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 6.97 6.85 (m, 1H), 6.27 (s, 1H), 2.77 (dd, J = 14.9, 7.8 Hz, 2H), 2.64 2.47 (m, 2H), 2.07 1.95 (m, 2H). 19 F NMR (376 MHz, CDCl3) δ -140.2-140.4 (m, 2F), -140.9-141.1 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 146.7 (dm, J = 244.2 Hz), 144.8 (dm, J = 248.7 Hz), 137.4 (t, J = 4.3 Hz), 131.0, 125.2, 104.1 (t, J = 22.8 Hz), 36.0 (t, J = 3.4 Hz), 33.9, 24.0. IR (thin film) max 2967, 1712, 1492, 1461 cm -1. MS (EI): m/z (%) 216 (M + ), (100). HRMS: Calcd. for C11H8F4: 216.0562; Found: 216.0565. 2,3,4,5,6-Pentafluorobiphenyl (4a). [Known compound 5 ]: The product (38.1 mg, 52% yield) as a white solid was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDC3) δ 7.56 7.36 (m, 5H). 19 F NMR (376 MHz, CDCl3) δ -143.3 (dd, J = 24.2, 9.4 Hz, 2F), -155.7 (t, J = 21.9 Hz, 1F), -162.3 (td, J = 23.2, 8.5 Hz, 2F). 13 C NMR (101 MHz, CDCl3) δ 144.8 (dm, J = 248.5 Hz), 141.1 (dm, J = 251.8 Hz), 138.5 (dm, J = 254.8 Hz), 130.7, 129.9, 129.3, 127.0, 116.6(td, J = 17.8, 4.5 Hz). 2,3,5,6-Tetrafluoro-4-(trifluoromethyl)-1,1 -biphenyl (4b). [Known compound 5 ]: The product (71.4 mg, 81% yield) as a white solid was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 7.60 7.43 (m, 5H). 19 F NMR (376 MHz, CDCl3) δ -56.3 (t, J = 21.6 Hz, 3F), -140.6-141.0 (m, 2F), -141.6 (td, J = 15.4, 5.5 Hz, 2F). 13 C NMR (101 MHz, CDCl3) δ 145.1 (dm, J = 254.1 Hz), 144.7 (dm, J = 251.6 Hz), 130.6, 130.5 (t, J = 2.1 Hz), 129.4, 126.6, 125.5 (t, J = 16.0 Hz), 121.1 (q, J = 275.2 Hz), 109.7 108.8 (m). S16

1-[5-(2,3,5,6-Tetrafluoro-1,1 -biphenyl)thiophen-2-yl]ethanone (4c). The product (84.1 mg, 80% yield) as a white solid (mp. 200-202 o C) was purified with silica gel chromatography (Petroleum / Dichloromethane = 2:1). 1 H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 4.1 Hz, 1H), 7.64 (d, J = 4.0 Hz, 1H), 7.56 7.44 (m, 5H), 2.62 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ -139.6 (dd, J = 20.6, 10.5 Hz, 2F), -143.6 (dd, J = 13.1, 2.6 Hz, 2F). 13 C NMR (101 MHz, CDCl3) δ 190.2, 144.6 (dm, J = 250.6 Hz), 144.4 (dm, J = 249.0 Hz), 135.8, 132.2, 131.0, 130.3, 129.6, 128.9, 128.5, 127.1, 120.6, 109.0, 27.1. IR (thin film) max 1650, 1473, 1439 cm -1. MS (EI): m/z (%) 350 (M + ), 335 (100). HRMS: Calcd. for C18H10OSF4: 350.0388; Found: 350.0397. 4-Butyl-2',3',5',6'-tetrafluoro-4'-(4-cyanophenyl)biphenyl (4d). The product (104.6 mg, 91% yield) as a white solid (mp. 153-155 o C) was purified with silica gel chromatography (Petroleum / Dichloromethane = 5:1). 1 H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.1 Hz, 2H), 7.65 (d, J = 8.1 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 2.69(t, J = 8.0 Hz, 2H), 1.72 1.61 (m, 2H), 1.46 1.35 (m, 2H), 0.96 (t, J = 7.3 Hz, 3H). 19 F NMR (376 MHz, CDCl3) δ -143.4 (dd, J = 22.6, 12.4 Hz, 2F), -144.3 (dd, J = 22.6, 12.4 Hz, 2F). 13 C NMR (101 MHz, CDCl3) δ 145.1, 144.9 (dm, J = 248.3 Hz), 144.6 (dm, J = 249.6 Hz), 132.8, 131.5 (t, J = 2.2 Hz), 130.5, 129.3, 124.7, 121.7 (t, J = 16.7 Hz), 118.8, 117.7 (t, J = 16.1 Hz), 113.5, 109.5, 36.1, 34.0, 30.3, 23.0. IR (thin film) max 2927, 2241, 1610, 1469, 1401 cm -1. MS (EI): m/z (%) 383 (M + ), 340 (100). HRMS: Calcd. for C23H17NF4: 383.1297; Found: 383.1299. 2,3,4,5-Tetrafluoro-6-nitrobiphenyl (4e). [Known compound 10 ]: The product (69.1 mg, 85% yield) as a white solid was purified with silica gel chromatography (Petroleum / Dichloromethane = 10:1). S17

1 H NMR (400 MHz, CDCl3) δ 7.53 7.44 (m, 3H), 7.35 7.28 (m, 2H). 19 F NMR (376 MHz, CDCl3) δ -137.7 (ddd, J = 22.4, 10.8, 3.6 Hz, 1F), -147.3 (ddd, J = 21.6, 10.8, 5.1 Hz, 1F), -149.4(ddd, J = 22.4, 20.5, 5.2 Hz, 1F), -152.3 ( ddd, J = 21.6, 20.7, 3.5 Hz, 1F). 13 C NMR (101 MHz, CDCl3) δ144.7 (dm, J = 251.7 Hz), 142.7 (dm, J = 260.5 Hz), 141.4 (dm, J = 261.1 Hz), 139.6 (dm, J = 257.5 Hz), 136.4 135.8 (m), 130.7, 129.7, 129.6, 127.2, 121.7 121.1 (m). 2,3,5,6-Tetrafluoro-4-phenyl-pyridine (4f). [Known compound 5 ]: The product (34.1 mg, 50% yield) as a white solid was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 7.59 7.50 (m, 5H). 19 F NMR (376 MHz, CDCl3) δ -90.8 (dd, J = 29.3, 13.8 Hz, 2F), -145.2 (dd, J = 29.2, 13.8 Hz, 2F). 13 C NMR (101 MHz, CDCl3) δ 144.60 (dm, J = 249.1 Hz), 139.81 (dm, J = 251.6 Hz), 134.03 (t, J = 16.0 Hz), 131.13, 130.32, 129.52, 126.49. 4'-(4-tert-Butylphenyl)-2-(2',3',5',6'-tetrafluorophenyl)quinoline (4g). The product (93.3 mg, 76% yield) as a white solid (mp. 167-169 o C) was purified with silica gel chromatography (Petroleum / Dichloromethane = 30:1). 1 H NMR (400 MHz, CDCl3) δ 8.33 (d, J = 8.5 Hz, 1H), 8.20 (d, J = 8.5 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.81 (t, J = 7.6 Hz, 1H), 7.65 (t, J = 7.3 Hz, 2H), 7.55 (d, J = 8.3 Hz, 2H), 7.48 (d, J = 8.3 Hz, 2H), 1.39 (s, 9H). 19 F NMR (376 MHz, CDCl3) δ -143.8 (dd, J = 22.9, 12.3 Hz, 2F), -144.2 (dd, J = 22.6, 12.3 Hz, 2F). 13 C NMR (101 MHz, CDCl3) δ 153.0, 148.8, 148.7, 145.3 (dm, J = 232.6 Hz), 144.8 (dm, J = 230.9 Hz), 137.3, 130.7, 130.4, 128.2, 128.1, 128.1, 126.2, 125.0, 123.4, 35.4, 31.8. IR (thin film) max 2963, 1597, 1471, 1404 cm -1. MS (EI): m/z (%) 409 (M + ), 394 (100). HRMS: Calcd. for C25H19NF4: 409.1454; Found: 409.1466. S18

1-(1',3',4'-Trifluorophenyl)naphthalene (4h). The product (51.1 mg, 66% yield) as a white solid (mp. 120-122 o C) was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.95 (d, J = 8.5 Hz, 1H), 7.91-7.89 (m, 2H), 7.59 7.51 (m, 3H), 7.17 (qd, J = 9.2, 5.0 Hz, 1H), 7.02 6.92 (m, 1H). 19 F NMR (376 MHz, CDCl3) δ -119.5-119.7 (m, 1F), -137.7 (dd, J = 21.4, 8.4 Hz, 1F), -141.9-142.1 (m, 1F). 13 C NMR (101 MHz, CDCl3) δ 155.4 (dm, J = 242.7 Hz), 148.1 (dm, J = 256.5 Hz), 147.5(dm, J = 246.1 Hz), 133.0, 129.9, 128.3, 127.0, 127.7, 127.3, 126.8, 126.4, 125.7, 120.3 (dd, J = 20.7, 15.1 Hz), 115.7 (dd, J = 19.6, 9.8 Hz), 110.9 (ddd, J = 25.4, 6.5, 4.2 Hz). IR (thin film) max 1482 cm -1. MS (EI): m/z (%) (M + ), 258 (100). HRMS: Calcd. for C16H9F3: 258.0656; Found: 258.0657. 2,3,5-Trifluoro-6-nitrobiphenyl (4i). [Known compound 10 ]: The product (60.8 mg, 80% yield) as a white solid was purified with silica gel chromatography (Petroleum / Dichloromethane = 20:1). 1 H NMR (400 MHz, CDCl3) δ 7.53 7.44 (m, 3H), 7.39 7.31 (m, 2H), 7.17 (td, J = 9.1, 6.2 Hz, 1H). 19 F NMR (376 MHz, CDCl3) δ -124.1 (ddd, J = 14.0, 8.8, 5.3 Hz, 1F), -126.3 (ddd, J = 22.0, 9.2, 5.2 Hz, 1F), -140.8 (ddd, J = 22.0, 14.1, 5.4 Hz, 1F). 13 C NMR (101 MHz, CDCl3) δ 152.2 (ddd, J=259.8, 14.3, 12.1 Hz), 150.2 (ddd, J = 258.2, 12.1, 4.1 Hz), 144.7 (ddd, J= 250.8, 14.3, 4.1 Hz), -136.4-136.0 (m), 130.5, 129.6, 129.4 (d, J = 1.1 Hz), 128.2, 127.3 (d, J = 18.4 Hz), 106.3 (dd, J = 24.7, 22.7 Hz). 3',4'-Methylenedioxy-2,3-difluoro-6-nitrophenyl (4j). The product (46.1 mg, 55% yield) as a white solid (mp. 116-118 o C) was purified with silica gel chromatography (Petroleum / Dichloromethane = 5:1). 1 H NMR (400 MHz, CDCl3) δ 7.70 7.61 (m, 1H), 7.25 7.13 (m, 1H), 6.83 (d, J = 7.9 Hz, S19

1H), 6.71 (d, J = 7.8 Hz, 1H), 6.68 (d, J = 7.9 Hz, 1H), 5.99 (s, 2H). 19 F NMR (376 MHz, CDCl3) δ -127.7 (ddd, J = 21.8, 8.6, 4.3 Hz, 1F), -134.6 (dd, J = 21.7, 7.2 Hz, 1F). 13 C NMR (101 MHz, CDCl3) δ 153.6 (dd, J = 259.7, 14.1 Hz), 149.1 (s), 148.7 (dd, J = 252.6, 13.4 Hz), 148.6, 146.2, 127.9 (d, J = 16.9 Hz), 123.2 (d, J = 1.2 Hz), 122.9 (d, J = 2.1 Hz), 120.9 (dd, J = 8.0, 4.5 Hz), 116.7 (d, J = 19.1 Hz), 109.8, 109.3, 102.1. IR (thin film) max 1543, 1519, 1504, 1478 cm -1. MS (EI): m/z (%) 279 (M + ), (100). HRMS: Calcd. for C13H7F2NO4: 279.0343; Found: 279.0330. Methyl 2-(p-methoxylphenyl)-3,6-difluorofluorobenzoate (4k). The product (73.4 mg, 88% yield) as a colorless oil was purified with silica gel chromatography (Petroleum / Ethyl acetate = 20:1). 1 H NMR (400 MHz, CDCl3) δ 7.26 (d, J = 8.2 Hz, 2H), 7.19 7.10 (m, 1H), 7.09 7.00 (m, 1H), 6.94 (d, J = 8.2 Hz, 2H), 3.82 (s, 3H), 3.65 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ -120.5-121.6 (m, 1F), -120.9-121.0 (m, 1F). 13 C NMR (101 MHz, CDCl3) δ 165.5 (d, J = 2.8 Hz), 160.2, 157.2, 157.1, 154.8 (d, J = 1.2 Hz), 154.7 (d, J = 7.1 Hz), 131.0 (d, J = 1.6 Hz), 129.5 (dd, J = 19.6, 3.4 Hz), 125.1 (d, J = 1.6 Hz), 123.9 (dd, J = 18.7, 3.0 Hz), 117.5 (dd, J = 269.7, 9.0 Hz), 117.3 (dd, J = 267.6, 8.6 Hz), 114.4, 55.7, 53.1. IR (thin film) max 2967, 1738, 1611, 1516, 1436 cm -1. MS (EI): m/z (%) 278 (M + ), (100). HRMS: Calcd. for C15H12F2O3: 278.0755; Found: 278.0764. 4-(p-Methoxylphenyl)-3,5-difluorobenzonitrile (4l). The product (64.7 mg, 88% yield) as a white solid (mp. 141-143 o C) was purified with silica gel chromatography (Petroleum / Dichloromethane = 2:1). 1 H NMR (400 MHz, CDCl3) δ 7.45 7.38 (m, 2H), 7.34 7.27 (m, 2H), 7.05 6.98 (m, 2H), 3.87 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ -110.6-110.7 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 160.8, 160.4 (dd, J =253.5, 7.9 Hz), 131.9 (t, J = 2.2 Hz), 124.4 (t, J = 18.2 Hz), 119.6, 117.2 (t, J = 3.3 Hz), 116.7 116.1 (m), 114.6, 112.0 (t, J = 12.2 Hz), 55.8. IR (thin film) max 2239, 1611, 1577, 1554, 1523, 1444 cm -1. MS (EI): m/z (%) 245 (M + ), (100). HRMS: Calcd. for C14H9F2NO: 245.0652; Found: 245.0649. S20

1,2,4,5-Tetrafluoro-3-(4-tert-butylphenyl)-6-[2',3',5',6'-tetrafluoro-4'-(4-tert-butylphenyl)phenyl ]benzene (4m). The product (111.4 mg, 66% yield) as a white solid (mp. 255-257 o C) was purified with silica gel chromatography (Petroleum). 1 H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.5 Hz, 4H), 7.49 (d, J = 8.5 Hz, 4H), 1.39 (s, 18H). 19 F NMR (376 MHz, CDCl3) δ -138.7-138.9 (m, 4F), -142.8-143.2 (m, 4F). 13 C NMR (101 MHz, CDCl3) δ 153.3, 145.2 (dm, J = 246.6 Hz), 144.8 (dm, J = 247.3 Hz), 130.4, 126.3, 124.6, 123.2 (t, J = 16.7 Hz), 35.4, 31.8. IR (thin film) max 2963, 1467 cm -1. MS (EI): m/z (%) 562 (M + ), 547 (100). HRMS: Calcd. for C32H26F8: 562.1907; Found: 562.1912. 2,5-Bis[2',3',5',6'-tetrafluoro-4'-(4-tert-butylphenyl)phenyl]thiophene (4n). The product (179.9 mg, 93% yield) as a white solid (mp. 246-248 o C) was purified with silica gel chromatography (Petroleum / Dichloromethane = 20:1). 1 H NMR (400 MHz, CDCl3) δ 7.75 (s, 2H), 7.54 (d, J = 8.2 Hz, 4H), 7.48 (d, J = 8.2 Hz, 4H), 1.39 (s, 18H). 19 F NMR (376 MHz, CDCl3) δ -140.2 (dd, J = 21.7, 11.1 Hz, 4F), -144.1 (dd, J = 21.8, 11.3 Hz, 4F). 13 C NMR (101 MHz, CDCl3) δ 153.1, 145.1 (dm, J = 247.4 Hz), 144.6 (dm, J = 246.3 Hz), 131.3, 130.7 (t, J = 6.2 Hz), 130.4, 126.2, 124.8, 120.2 119.6 (m), 112.9, 35.4, 31.8. IR (thin film) max 2962, 1474, 1401 cm -1. MS (EI): m/z (%) 644 (M + ), (100). HRMS: Calcd. for C36H28SF8: 644.1784; Found: 644.1783. S21

6. Sequential C-F Bond Activation of Polyfluoroarenes Gram-Scale Synthesis of 4o. Methyl 2,3,5,6-tetrafluoro-[1,1'-biphenyl]-4-carboxylate (4o). To a septum capped 100 ml of Schlenck tube were added phenylboronic acid (1.10 g, 9.0 mmol, 1.5 equiv), BrettPhos (161.0 mg, 5 mol%), Pd(OAc)2 (33.6 mg, 2.5 mol%), and Cs2CO3 (2.93 g, 9.0 mmol, 1.5 equiv) under Ar, followed by toluene (30 ml) and fluoroarene 1p (1.36 g, 6.0 mmol, 1.0 equiv). The tube was screw capped and put into an oil bath (preheated to 120 o C). After stirring for 12 h, the reaction mixture was cooled to room temperature, and diluted with DCM, filtered through a pad of Celite and concentrated. The residue was purified with silica gel chromatography (Petroleum / Ethyl acetate = 20:1) to provide pure 4o (1.47 g, 86 % yield) white solid (mp. 103-105 o C). Data for compound 4o: 1 H NMR (400 MHz, CDCl3) δ 7.56 7.44 (m, 5H), 4.01 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ -139.6 (td, J = 15.5, 4.6 Hz, 2F), -142.6 (td, J = 15.3, 4.1 Hz, 2F). 13 C NMR (101 MHz, CDCl3) δ 161.5 160.6 (m), 145.6 (dm, J = 258.3 Hz), 144.5 (dm, J = 250.7 Hz), 130.6 (t, J = 2.1 Hz), 130.3, 129.3, 127.1, 124.4, 111.8, 53.8. IR (thin film) max 1731, 1655, 1477, 1438, 1319, 1030, 982 cm -1.MS (EI): m/z (%) 284 (M + ), (100). HRMS: Calcd. for C14H8F4O2: 284.0460; Found: 284.0462. Preparation of Compound 5 Methyl 2',5',6'-trifluoro-4''-methoxy-[1,1':3',1''-terphenyl]-4'-carboxylate (5). A 25 ml of Schlenck tube equipped with a magnetic stir bar was charged with 4o (85.3 mg, 0.3 mmol, 1.0 equiv ), 4-methoxyphenylboronic acid (91.2 mg, 0.6 mmol, 2.0 equiv ), Pd(OAc)2 (1.7 mg, 2.5 S22

mol%), BrettPhos (8.1 mg, 5 mol%), and Cs2CO3 (195.5 mg, 2.0 equiv) in the glove box. Toluene (2 ml) was then added. The tube was screw capped and put into an oil bath (preheated to 120 o C). After stirring for 12 h, the reaction mixture was cooled to room temperature, and diluted with DCM, filtered through a pad of Celite and concentrated. The product 5 (73.7 mg, 68% yield) as a white solid (mp. 62-64 o C) was purified with silica gel chromatography (Petroleum / Ethyl acetate = 20:1). Data for compound 5: 1 H NMR (400 MHz,CDCl3) δ 7.53 7.42 (m, 5H), 7.30 (d, J = 8.6 Hz, 2H), 6.97 (d, J = 8.6 Hz, 2H), 3.85 (s, 3H), 3.71 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ -120.4 (dd, J = 15.1, 4.1 Hz, 1F), -138.0 (dd, J = 22.6, 4.5 Hz, 1F), -143.6 (dd, J = 22.6, 15.2 Hz, 1F). 13 C NMR (101 MHz, CDCl3) δ 164.5 (t, J = 3.5 Hz), 160.3, 152.5 (dm, J = 246.4 Hz), 147.3 (dm, J = 252.5 Hz), 145.4 (dm, J = 251.9 Hz), 131.2 (d, J = 1.0 Hz), 130.7 (t, J = 1.9 Hz), 129.6, 129.1, 128.4 (d, J = 1.9 Hz), 124.7 (m), 124.6, 123.4 (dd, J = 15.0, 3.7 Hz), 122.3 (dd, J = 22.5, 15.0 Hz), 114.4, 55.8 53.4. IR (thin film) max 1735, 1614, 1522, 1469, 1434 cm -1. MS (EI): m/z (%) 372 (M + ), (100). HRMS: Calcd. for C21H15F3O3: 372.0973; Found: 372.0968. Reaction of 1q with Arylboronic Acid 2-(4'-Methoxyl-2,3,5,6-tetrafluoro-[1,1'-biphenyl]-4-yl)pyridine (4p). The product (85.0 mg, 85% yield on a 0.3 mmol scale) as a white solid (mp. 162-164 o C) was purified with silica gel chromatography (Petroleum / Ethyl acetate = 30:1). 1 H NMR (400 MHz,CDCl3) δ 8.80 (d, J = 4.1 Hz, 1H), 7.85 (t, J = 7.7 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.46 (d, J = 8.5 Hz, 2H), 7.39 (dd, J = 6.8, 5.0 Hz, 1H), 7.04 (d, J = 8.7 Hz, 2H), 3.87 (d, J = 8.6 Hz, 3H). 19 F NMR (376 MHz, CDCl3) δ -144.4 (dd, J = 22.5, 12.1 Hz, 2F), -144.7 (dd, J = 22.5, 12.2 Hz, 2F). 13 C NMR (101 MHz, CDCl3) δ 160.8, 150.6, 148.5, 145.1 (dm, J = 248.1 Hz), 144.5 (dm, J = 253.1 Hz), 137.1, 132.0 (t, J = 2.2 Hz), 126.5 (t, J = 1.7 Hz), 124.1, 121.2, 119.9, 118.9 (t, J = 16.67 Hz), 114.7, 55.9. IR (thin film) max 1609, 1521, 1464 cm -1. MS (EI): m/z (%) 333 (M + ), (100). HRMS: Calcd. for C18H11ONF4: 333.0777; Found: 333.0775. S23

Borylation of Compound 4p 2-[2-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-4-(p-methoxylphenyl)-3,5,6-tri-fluoropheny l]-pyridine (6). The reaction was conducted according to the literature. [11] To a septum capped 25 ml of Schlenck tube were added 4q (100.0 mg, 0.3 mmol, 1.0 equiv) and (Bpin)2 (152.4 mg, 0.6 mmol, 2.0 equiv), KOAc (58.9 mg, 0.6 mmol, 2.0 equiv), [Rh(COD)2]BF4 (6.1 mg, 5 mol %) and dioxane (2 ml) under Ar. The tube was screw capped and put into an oil bath (preheated to 80 o C). After stirring for 12 h, the reaction mixture was cooled to room temperature, and diluted with DCM, filtered through a pad of Celite and concentrated. The product (111.2 mg, 84% yield) as a white solid (mp. 186-188 o C) was purified with silica gel chromatography (Petroleum / Ethyl acetate = 1:1). Data for compound 6: 1 H NMR (400 MHz, CDCl3) δ 8.68 (d, J = 5.4 Hz, 1H), 8.12 8.03 (m, 2H), 7.51 (td, J = 5.7, 2.9 Hz, 1H), 7.45 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H), 1.42 (s, 12H). 19 F NMR (376 MHz, CDCl3) δ -111.0 (dd, J = 20.7, 5.8 Hz, 1F), -139.3 (dd, J = 21.5, 6.1 Hz, 1F), -147.0 (t, J = 21.0 Hz, 1F). 13 C NMR (101 MHz, CDCl3) δ 160.2, 156.5 (dm, J = 244.1 Hz), 151.1, 148.5 (dm, J = 247.5 Hz), 145.5 (dm, J = 251.8), 143.4, 143.2, 131.9, 124.9 124.5 (m), 124.4, 123.2 (dd, J = 25.1, 14.8 Hz), 122.5, 122.4, 121.6, 81.7, 55.7, 28.0 (d, J = 2.4 Hz), 28.0, 24.9. IR (thin film) max 2985, 1612, 1518, 1483, 1442 cm -1. MS (DART): m/z (%) 442 (M+H + ), (100). HRMS of (M+H + ): Calcd. for C24H24BF3NO3: 442.1796; Found: 442.1796. S24

7. Preparation of Liquid Crystal Molecule 3,5-Difluoro-4-[4-(4-n-propylcyclohexyl)phenyl]benzonitrile (8). To a septum capped 100 ml of Schlenck tube were added Pd(OAc)2 (25.5 mg, 2.5 mol%), p-(4-propylcyclohexyl)phenylboronic acid (7) (2.21 g, 9.0 mmol, 2.0 equiv), BrettPhos (121.5 mg, 5 mol%), and Cs2CO3 (2.29 g, 9.0 mmol, 2.0 equiv) under Ar, followed by toluene (20 ml) and 3,4,5-trifluorobenzonitrile (1m) (0.71 g, 4.5 mmol, 1.0 equiv). The tube was screw capped and put into an oil bath (preheated to 120 o C). After stirring for 12 h, the reaction mixture was cooled to room temperature, and diluted with DCM, filtered through a pad of Celite and concentrated. The product (1.33 g, 87% yield) as a white solid (mp. 116-117 o C) was purified with silica gel chromatography (Petroleum / Ethyl acetate = 20:1). Data for compound 8: 1 H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 8.3 Hz, 2H), 7.36 7.28 (m, 4H), 2.60 2.47 (m, 1H), 1.91 (t, J = 14.7 Hz, 4H), 1.55 1.43 (m, 2H), 1.41 1.29 (m, 3H), 1.27 1.19 (m, 2H), 1.14 1.00 (m, 2H), 0.91 (t, J = 7.2 Hz, 3H). 19 F NMR (376 MHz, CDCl3) δ -110.3-110.4 (m, 2F). 13 C NMR (101 MHz, CDCl3) δ 161.7 (d, J = 7.9 Hz), 159.2 (d, J = 7.8 Hz), 149.8, 130.5, 127.6, 124.9, 117.2, 116.8 115.7 (m), 112.4 (t, J = 12.2 Hz), 45.0, 40.2, 37.5, 34.7, 34.0, 20.6, 14.9. R (thin film) max 2920, 2235, 1612, 1572, 1552, 1519, 1407 cm -1. MS (EI): m/z (%) 339 (M + ), 241 (100). HRMS: Calcd. for C22H23F2N: 339.1799; Found: 339.1805. 3-(3,5-Difluoro-4-(4-(4-n-propylcyclohexyl)phenyl)phenyl)-5-(trifluoromethyl)-1,2,4-oxadiazole (10). According to the literature, [12] compound 8 (0.34 g, 1.0 mmol, 1.0 equiv), 50% aqueous solution of hydroxylamine (2.0 mmol, 2.0 equiv.) and ethanol (20 ml) were added into a 100 ml S25

round-bottom flask with the condense tube. After refluxing for 24 h, the reaction mixture was cooled to 0 o C with a white precipitate formation. The solid was collected by filtration, washed with water, dried under vaccum, and used without further purification to give compound 9 (0.25 g, 68% yield) as a white solid. According to the literature, [13] compound 9 (111.7 mg, 0.3 mmol, 1.0 equiv), trifluoroacetic anhydride (130 L, 3.0 mmol, 10.0 equiv) and anhydrous toluene (5 ml) were added into a 25 ml of three-necked round-bottom flask with the condense tube under Ar. The reaction mixture was refluxed for 10 h, and was then cooled to room temperature. The volatiles was removed under vaccum, the residue was washed with brine, and extracted with ethyl acetate (3 20 ml). The combined organic layers were evaporated. The residue was purified with silica gel chromatography (Petroleum) to give the product 10 (114.8 mg, 85% yield) as a white solid. Data for compound 10: 1 H NMR (400 MHz,CDCl3) δ 7.79 7.70 (m, 2H), 7.43 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.2 Hz, 2H), 2.58 2.48 (m, 1H), 2.00 1.81 (m, 4H), 1.52 1.42 (m, 2H), 1.40 1.26 (m, 5H), 1.14 0.99 (m, 2H), 0.90 (t, J = 7.2 Hz, 3H). 19 F NMR (376 MHz, CDCl3) δ -65.4 (s, 3F), -111.7 (d, J = 7.3 Hz, 2F). 13 C NMR (101 MHz, CDCl3) δ 167.6, 160.3 (dd, J = 251.4, 7.7 Hz), 148.8, 130.0, 126.9, 125.2, 125.1, 124.3 123.9 (m), 122.5, 118.5 (q, J = 275.2 Hz), 111.5 111.0(m), 44.5, 39.7, 37.0, 34.2, 33.5, 20.0, 14.4. R (thin film) max 2919, 1577, 1537, 1431, 1324 cm -1. MS (ESI): m/z (%) 473 (M+Na + ). HRMS: Calcd. for C24H23F5N2O: 450.1731; Found: 450.1725. 8. References (1) Do, H.-Q.; Daugulis, O. J. Am. Chem. Soc. 2008, 130, 1128. (2) He, C. Y.; Fan, S.; Zhang, X. J. Am. Chem. Soc. 2010, 132, 12850. (3) Pan, Y.; Young, G. B. J. Organomet. Chem. 1999, 577, 257. (4) Wei, Y.; Kan, J.; Wang, M.; Su, W.; Hong, M. Org. Lett. 2009, 11, 3346. (5) Li, H.; Liu, J.; Sun, C. L.; Li, B. J.; Shi, Z.-J.; Org. Lett. 2011, 13, 276. (6) Li, Z.; Twieg, R. J. Chem. Eur. J. 2015, 21, 15534. (7) Lin, X.; You, Y.; Weng, Z. J. Fluorine Chem. 2014, 165, 76. (8) Frohn, H. J.; Adonin, N. Y.; Bardin, V. V.; Starichenko, V. F. J. Fluorine Chem. 2002, 117, 115. (9) Sardzinski, L. W.; Wertjes, W. C.; Schnaith, A. M.; Kalyani, D. Org. Lett. 2015, 17, 1256. (10) Cargill, M. R.; Sandford, G.; Tadeusiak, A. J.; Yufit, D. S.; Howard, J. A. K.; Kilickiran, P.; S26

Nelles, G. J. Org. Chem. 2010, 75, 5860. (11) Guo, W. H.; Min, Q. Q.; Gu, J. W.; Zhang, X. Angew. Chem. Int. Ed. 2015, 54, 9075. (12) Li, Y.; Zhu, H.; Chen, K.; Liu, R.; Khallaf, A.; Zhang, X.; Ni, J. Org. Biomol. Chem. 2013, 11, 3979. (13) Guo, J.; Hua, R.; Sui, Y.; Cao, J. Tetrahedron Lett. 2014, 55, 1557. S27

9. Copies of 1 H NMR, 13 C NMR, and 19 F NMR Spectra of Compounds 3-6, 8, 10 and 11 2,3,5,6-Tetrafluorobiphenyl (3a). S28

2,3,5,6-Tertrafluoro-4 -methoxy-1,1 -biphenyl (3b). S29

2,3,5,6-Tertrafluoro-3,5 -dimethyl-1,1 -biphenyl (3c). S31

2,3,5,6-Tetrafluoro-1,1':2',1''-terphenyl (3d). S32

1-(2,3,5,6-Tetrafluorophenyl)naphthalene (3e). S34

2-(2,3,5,6-Tetrafluorophenyl)naphthalene (3f). S35

2,3,4,5,6-Pentafluoro-1,1 -biphenyl (3g). S37

2,3,5,6-Tetrafluoro-4'-(trifluoromethyl)-1,1'-biphenyl (3h). S38

2,3,5,6-Tertrafluoro-4 -trifluoromethoxy-1,1 -biphenyl (3i). S40

Ethyl 4-(2',3',5 ',6'-tetrafluorophenyl)benzoate (3j). S41

2-Methoxyl-5-[2,3,5,6 -tetrafluorophenyl]pyridine (3k). S43

9-(2',3',5',6'-Tetrafluoro[1,1'-biphenyl]-4-yl)-carbazole (3l). S44

4'-(Diphenylamino)-2,3,5,6-tetrafluoro-1,1'-biphenyl (3m). S46

9,9-Dimethyl-2-(2,3,5,6 -tetrafluorophenyl)fluorene (3n). S47

3-(2,3,5,6 -Tetrafluorophenyl)dibenzothiophene (3o) S49

Cyclopent-1 -en-1 -yl-2,3,5,6-tetrafluoro benzene (3p). S50

2,3,4,5,6-Pentafluorobiphenyl (4a). S52

2,3,5,6-Tetrafluoro-4-(trifluoromethyl)-1,1 -biphenyl (4b). S53

1-[5-(2,3,5,6-Tetrafluoro-1,1 -biphenyl)thiophen-2-yl]ethanone (4c). S55

4-Butyl-2',3',5',6'-tetrafluoro-4'-(4-cyanophenyl)biphenyl (4d). S56

2,3,4,5-Tetrafluoro-6-nitrobiphenyl (4e). S58

2,3,5,6-Tetrafluoro-4-phenyl-pyridine (4f). S59

4'-(4-tert-Butylphenyl)-2-(2',3',5',6'-tetrafluorophenyl)quinoline (4g). S61

1-(1',3',4'-Trifluorophenyl)naphthalene (4h). S62

2,3,5-Trifluoro-6-nitrobiphenyl (4i). S64

3',4'-Methylenedioxy-2,3-difluoro-6-nitrophenyl (4j). S65

Methyl 2-(p-methoxylphenyl)-3,6-difluorofluorobenzoate (4k). S67

4-(p-Methoxylphenyl)-3,5-difluorobenzonitrile (4l). S68

1,2,4,5-Tetrafluoro-3-(4-tert-butylphenyl)-6-[2',3',5',6'-tetrafluoro-4'-(4-tert-butylphenyl)phenyl ]benzene (4m). S70

2,5-Bis[2',3',5',6'-tetrafluoro-4'-(4-tert-butylphenyl)phenyl]thiophene (4n). S71

Methyl 2,3,5,6-tetrafluoro-[1,1'-biphenyl]-4-carboxylate (4o). S73

Methyl 2',5',6'-trifluoro-4''-methoxy-[1,1':3',1''-terphenyl]-4'-carboxylate (5). S74

2-(4'-Methoxyl-2,3,5,6-tetrafluoro-[1,1'-biphenyl]-4-yl)pyridine (4p). S76

2-[2-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-4-(p-methoxylphenyl)-3,5,6-tri-fluoropheny l]-pyridine (6). S77

3,5-Difluoro-4-[4-(4-n-propylcyclohexyl)phenyl]benzonitrile (8). S79

3-(3,5-Difluoro-4-(4-(4-n-propylcyclohexyl)phenyl)phenyl)-5-(trifluoromethyl)-1,2,4-oxadiazole (10). S80

Compound (11) S82