Supporting Information Nickel-Catalyzed C sp2 -C sp3 Cross Coupling via C-O Bond Activation Lin Guo, Chien Chi Hsiao, Huifeng Yue, Xiangqian Liu, and Magnus Rueping* Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany Magnus.rueping@rwth-aachen.de I II III IV V VI VII VIII IX General Information Optimization Studies Synthesis of Starting Materials Preparation of B-Alkyl-9-BBN Typical Procedure for the Catalytic Reactions Gram Scale Experiment Spectroscopic Data of Products Synthetic Application Copies of 1 H and 13 C NMR Spectra S1
I. General Information Unless otherwise noted, all commercially available compounds were used as provided without further purification. Solvents for chromatography were technical grade and freshly distilled prior to use. Diisopropyl ether used in reactions was analytical grade and distilled from benzophenone/na. Analytical thin-layer chromatography (TLC) was performed on Merck silica gel aluminium plates with F-254 indicator, visualised by irradiation with UV light. Column chromatography was performed using silica gel (Macherey Nagel, particle size 0.040-0.063 mm). Solvent mixtures are understood as volume/volume. 1 H-NMR and 13 C-NMR were recorded on a Varian AV300, AV400 or AV600 spectrometer in CDCl 3 and are reported relative to the solvents residual 1 H-signal (CHCl 3, δ(h) 7.26). Data are reported in the following order: chemical shift (δ) in ppm; multiplicities are indicated s (singlet), bs (broad singlet), d (doublet), t (triplet), m (multiplet); coupling constants (J) are in Hertz (Hz). Melting points were measured using open glass capillaries in a Buchi SMP-20 apparatus. IR spectra were recorded on a Perkin Elmer-100 spectrometer and are reported in terms of frequency of absorption (cm -1 ). Mass spectra (EI-MS, 70 ev) were conducted on a Finnigan SSQ 7000 spectrometer. HRMS were recorded on a Thermo Scientific LTQ Orbitrap XL spectrometer. S2
II. Optimization Studies Table S1. Effect of solvent a Entry [Ni] Solvent T ( C) Yield of 3a (%) b 1 Ni(COD) 2 THF 80 5 2 Ni(COD) 2 DME 80 0 3 Ni(COD) 2 1,4-dioxane 80 10 4 Ni(COD) 2 Toluene 120 6 5 Ni(COD) 2 i Pr 2 O 120 27 a Reaction conditions: 1a (0.20 mmol), 2a (0.32 mmol), Ni catalyst (8 mol%), ligand (16 mol%), base (1.2 equiv.), i BuOH (2 equiv.), solvent (0.1 M) at the corresponding temperature for 12 h. b NMR yields using 1,3,5- () 3 C 6 H 3 as an internal standard. Table S2. Effect of nickel catalyst utilized a Entry [Ni] Solvent T ( C) Yield of 3a (%) b 1 NiBr 2 i Pr 2 O 100 0 2 NiCl 2 glyme i Pr 2 O 100 0 3 Ni(acac) 2 i Pr 2 O 100 11 4 c Ni(IMes) 2 i Pr 2 O 100 21 5 Ni(COD) 2 i Pr 2 O 100 90 a Reaction conditions: 1a (0.20 mmol), 2a (0.32 mmol), Ni catalyst (8 mol%), ligand (16 mol%), base (1.5 equiv.), solvent (0.1 M) at 100 for 12 h. b NMR yields. c Without ligand. S3
Table S3. Effect of the supporting ligand a Entry [Ni] Ligand (x) T ( C) Yield of 3a (%) b 1 Ni(COD) 2 None 100 0 2 Ni(COD) 2 P t Bu 3 (16) 100 0 3 Ni(COD) 2 PPh 3 (16) 100 0 4 Ni(COD) 2 PCy 3 (16) 100 0 5 Ni(COD) 2 dppe (8) 100 < 5 6 Ni(COD) 2 dppf (8) 100 11 7 Ni(COD) 2 dcype (8) 100 19 8 Ni(COD) 2 dcypf (8) 100 9 9 Ni(COD) 2 SIPr HCl (16) 100 10 10 Ni(COD) 2 IPr HCl (16) 100 90 11 Ni(COD) 2 ICy HCl (16) 100 40 12 Ni(COD) 2 IMes HCl (16) 100 26 13 c Ni(COD) 2 IPr HCl (10) 100 82 a Reaction conditions: 1a (0.20 mmol), 2a (0.32 mmol), Ni catalyst (8 mol%), ligand (x mol%), base (1.5 equiv.), solvent (0.1 M) at 100 for 12 h. b NMR yields. c Ni catalyst (5 mol%). S4
Table S4. Effect of temperature a Entry Solvent T ( C) Yield of 3a (%) b 1 i Pr 2 O 40 trace 2 i Pr 2 O 60 < 5 3 i Pr 2 O 80 18 4 i Pr 2 O 90 70 5 i Pr 2 O 100 90 6 i Pr 2 O 110 97 7 i Pr 2 O 120 87 a Reaction conditions: 1a (0.20 mmol), 2a (0.32 mmol), Ni catalyst (8 mol%), ligand (16 mol%), base (1.5 equiv.), solvent (0.1 M) at the corresponding temperature for 12 h. b NMR yields. Table S5. Effect of base a Entry Base Solvent T ( C) Yield of 3a (%) b 1 Li 2 CO 3 i Pr 2 O 100 0 2 Na 2 CO 3 i Pr 2 O 100 0 3 K 2 CO 3 i Pr 2 O 100 < 5 4 Na 2 HCO 3 i Pr 2 O 100 0 5 K 3 PO 4 i Pr 2 O 100 53 6 CsF i Pr 2 O 100 38 7 NaO t Bu i Pr 2 O 100 36 8 none i Pr 2 O 100 0 a Reaction conditions: 1a (0.20 mmol), 2a (0.32 mmol), Ni catalyst (8 mol%), ligand (x mol%), base (1.5 equiv), solvent (0.1 M) at 100 for 12 h. b NMR yields. S5
Table S6. Effect for protecting groups of phenol derivatives a Entry R Yield of 3a (%) b 1 Ts 98 2 Ms 89 3 SO 2 NEt 2 98 4 CONEt 2 92 5 Boc 75 6 Piv 93 7 Bn 0 8 i Pr 0 9 Et 0 10 Me 0 a Reaction conditions: 1 (0.20 mmol), 2a (0.32 mmol), Ni catalyst (8 mol%), ligand (16 mol%), base (1.5 equiv), solvent (0.1 M) at 110 for 12 h. b NMR yields. S6
Table S7. Effect of alkylboron nuclephile a Entry Alkylboron Ligand (x mol%) Yield of 3 (%) b 1 9 PCy 3 (16) 0 2 9 dcype (8) 0 3 9 IPr HCl (16) 0 4 10 PCy 3 (16) 0 5 10 dcype (8) 0 6 10 IPr HCl (16) 0 a Reaction conditions: 1a (0.20 mmol), 9 or 10 (0.40 mmol), Ni catalyst (8 mol%), ligand (8 or 16 mol%), base (1.5 equiv.), solvent (0.1 M) at the corresponding temperature for 12 h. b NMR yields. S7
III.Synthesis of Starting Materials Aryl pivalates have been prepared via the classical reaction of the free alcohol in the presence of Et 3 N (1.20 equiv), PivCl (1.20 equiv) in dichloromethane at room temperature. 1 Naphthalen-2-yl pivalate (1a) 1 H NMR (600 MHz, CDCl 3 ): δ = 7.88-7.83 (m, 2H), 7.80 (dd, J = 8.0, 1.4 Hz, 1H), 7.54 (d, J = 2.3 Hz, 1H), 7.52-7.43 (m, 2H), 7.20 (dd, J = 8.8, 2.3 Hz, 1H), 1.41 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ = 177.4, 148.9, 133.9, 131.5, 129.4, 127.9, 127.7, 126.6, 125.7, 121.3, 118.5, 39.3, 27.3. Data in accordance with the literature. 1 Naphthalen-1-yl pivalate (1b) 1 H NMR (600 MHz, CDCl 3 ): δ = 7.91-7.87 (m, 2H), 7.75 (d, J = 8.3 Hz, 1H), 7.55-7.50 (m, 2H), 7.48 (t, J = 7.9 Hz, 1H), 7.24 (d, J = 7.5 Hz, 1H), 1.53 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ = 176.1, 146.9, 134.7, 128.1, 127.1, 126.43, 126.40, 125.8, 125.5, 121.1, 118.0, 39.6, 27.5. Data in accordance with the literature. 1 Phenanthren-9-yl pivalate (1c) 1 H NMR (600 MHz, CDCl 3 ): δ = 8.72 (d, J = 8.3 Hz, 1H), 8.67 (d, J = 8.3 Hz, 1H), 7.96 (dd, J = 8.1, 0.6 Hz, 1H), 7.85 (dd, J = 8.1, 0.6 Hz, 1H), 7.73-7.68 (m, 1H), 7.66-7.58 (m, 3H), 7.51 (s, 1H), 1.54 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ = 177.1, 145.3, 131.7, 131.6, 128.9, 128.5, 127.2, 127.1, 126.95, 126.91, 126.4, 123.1, 122.7, 121.8, 117.6, 39.7, 27.5. Data in accordance with the literature. 2 [1,1'-Biphenyl]-4-yl pivalate (1d) 1 H NMR (600 MHz, CDCl 3 ): δ = 7.60-7.54 (m, 4H), 7.46-7.41 (m, 2H), 7.34 (tt, J = 7.2, 1.2 Hz, 1H), 7.13 (d, J = 8.8 Hz, 2H), 1.38 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ = 177.1, 150.5, 140.4, 138.7, 128.8, 128.1, 127.3, 127.1, 121.8, 39.1, 27.1. Data in accordance with the literature. 3 [1,1'-Biphenyl]-3-yl pivalate (1e) 1 H NMR (400 MHz, CDCl 3 ): δ = 7.61-7.54 (m, 2H), 7.47-7.39 (m, 4H), 7.38-7.32 (m, 1H), 7.29-7.26 (m, 1H), 7.08-7.01 (m, 1H), 1.38 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ): S8
δ = 177.1, 151.6, 142.9, 140.3, 129.7, 128.8, 127.7, 127.3, 124.4, 120.3, 39.2, 27.3. Data in accordance with the literature. 4 [1,1'-Biphenyl]-2-yl pivalate (1f) 1 H NMR (600 MHz, CDCl 3 ): δ = 7.45-7.29 (m, 8H), 7.12 (dd, J = 8.0, 1.2 Hz, 1H), 1.16 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ = 176.8, 148.2, 137.6, 135.3, 130.9, 129.3, 128.5, 128.1, 127.4, 126.1, 122.7, 38.9, 27.0. Data in accordance with the literature. 5 4-Methoxynaphthalen-1-yl pivalate (1g) 1 H NMR (600 MHz, CDCl 3 ): δ = 8.27 (d, J = 8.2, 1H), 7.77(d, J = 7.5, 1H), 7.55-7.48 (m, 2H), 7.10 (d, J = 8.2, 1H), 6.77 (d, J = 8.2, 1H), 4.00 (s, 3H), 1.49 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ = 177.5, 153.3, 140.3, 127.7, 127.0, 126.3, 125.7, 122.5, 120.8, 117.6, 103.0, 55.8, 39.5, 27.5. Data in accordance with the literature. 1 7-Methoxynaphthalen-2-yl pivalate (1h) 1 H NMR (400 MHz, CDCl 3 ): δ = 7.75 (dd, J = 15.0, 8.8 Hz, 2H), 7.45 (d, J = 2.1 Hz, 1H), 7.18-7.03 (m, 3H), 3.90 (s, 3H), 1.43 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ): δ = 177.3, 158.3, 149.6, 135.3, 129.3, 129.1, 127.0, 118.8, 118.5, 117.5, 105.7, 55.4, 39.3, 27.3. Data in accordance with the literature. 5 Methyl 6-(pivaloyloxy)-2-naphthoate (1i) 1 H NMR (600 MHz, CDCl 3 ): δ = 8.61 (d, J = 0.6 Hz, 1H), 8.07 (dd, J = 8.6, 1.6 Hz, 1H), 7.96 (d, J = 8.8 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.58 (d, J = 2.1 Hz, 1H), 7.27 (dd, J = 9.1, 2.1 Hz, 1H), 3.98 (s, 3H), 1.41 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ = 177.1, 167.2, 150.7 136.2, 130.94 130.90 130.5, 127.9, 127.3, 126.0, 122.2, 118.5, 52.4 39.3, 27.2. Data in accordance with the literature. 6 6-(Trimethylsilyl)naphthalen-2-yl pivalate (1j) White solid (Mp: 59-60 C). 1 H NMR (600 MHz, CDCl 3 ): δ = 8.00 (s, 1H), 7.85 (d, J = 8.8 Hz, 1H), 7.77 (d, J = 8.1 Hz, 1H), 7.60 (dd, J = 8.1, 1.0 Hz, 1H), 7.50 (d, J = 2.2 Hz, 1H), 7.19 (dd, J = 8.8, 2.2 Hz, 1H), 1.41 (s, 9H), 0.35 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ = 177.3, 149.1, 137.7, 134.1, 133.6, 130.9, 130.6, 129.5, 126.7, 121.3, 118.3, 39.2, 27.3, -1.0. IR (ATR): ~ = 2958, 1746, 1606, 1470, 1373, 1218, 1126, 831, 757 cm -1. MS S9
(EI): m/z (%) = 300.1 (M +, 100), 216.1 (74), 201.0 (94), 57.1 (73). HRMS (ESI) for C 18 H 24 O 2 Si: calculated for [M+Na] + 323.14378, found 323.14374. 4-Acetylphenyl pivalate (1k) 1 H NMR (600 MHz, CDCl 3 ): δ = 7.99 (d, J = 8.6 Hz, 2H), 7.16 (d, J = 8.6 Hz, 2H), 2.60 (s, 3H), 1.37 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ = 197.0, 176.6, 155.0, 134.6, 130.0, 121.8, 39.3, 27.2, 26.7. Data in accordance with the literature. 6 6-(4-Fluorophenyl)naphthalen-2-yl pivalate (1l) White solid (Mp: 110-111 C). 1 H NMR (600 MHz, CDCl 3 ): δ = 7.98 (s, 1H), 7.92-7.82 (m, 2H), 7.72-7.61 (m, 3H), 7.55 (s, 1H), 7.28-7.13 (m, 3H), 1.42 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ = 177.3, 162.6 (d, J C-F = 246.6 Hz), 149.0, 137.4, 137.1 (d, J C-F = 2.7 Hz), 132.9, 131.6, 129.6, 129.0 (d, J = 8.0 Hz), 128.3, 126.2, 125.6, 121.8, 118.3, 115.8 (d, J = 21.4 Hz), 39.3, 27.3. 19 F NMR (564 MHz, CDCl 3 ): δ = - 115.5. IR (ATR): ~ = 2967, 1746, 1594, 1486, 1370, 1222, 1116, 1018, 898, 813 cm -1. MS (EI): m/z (%) = 322.0 (M +, 15), 307.9 (33), 305.9 (32), 223.8 (60), 221.9 (59), 194.8 (50), 192.8 (51), 84.9 (31), 57.1 (100). HRMS (ESI) for C 21 H 19 FO 2 : calculated for [M+Na] + 345.12613, found 345.12640. 2-Methylquinolin-4-yl pivalate (1m) 1 H NMR (600 MHz, CDCl 3 ): δ = 8.10-7.97 (m, 1H), 7.86 (dd, J = 8.4, 1.3 Hz, 1H), 7.71 (ddd, J = 8.4, 6.8, 1.3 Hz, 1H), 7.51 (ddd, J = 8.2, 6.8, 1.3 Hz, 1H), 7.26 (s, 1H), 2.75 (s, 3H), 1.49 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ = 176.0, 160.0, 154.6, 149.6, 130.1, 128.9, 126.1, 121.1, 121.0, 113.7, 39.9, 27.4, 25.7. Data in accordance with the literature. 5 3,4-Dihydronaphthalen-1-yl pivalate (1n) 1 H NMR (600 MHz, CDCl 3 ): δ = 7.21-7.13 (m, 3H), 7.12-7.05 (m, 1H), 5.67 (t, J = 4.7, 1H), 2.87 (t, J = 8.1, 2H), 2.48-2.41 (m, 2H), 1.38 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ = 177.0, 145.9, 136.6, 130.9, 128.0, 127.7, 126.5, 120.7, 115.2, 39.4, 27.7, 27.5, 22.2. Data in accordance with the literature. 1 S10
3,4-Dihydronaphthalen-2-yl pivalate (1o) 1 H NMR (600 MHz, CDCl 3 ): δ = 7.17-7.09 (m, 3H), 7.01 (d, J = 7.1 Hz, 1H), 6.20 (s, 1H), 3.00 (t, J = 8.3 Hz, 2H), 2.49 (t, J = 8.3 Hz, 2H), 1.31 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ = 176.8, 151.3, 133.4, 133.3, 127.3, 126.7, 126.6, 126.2, 114.5, 39.0, 28.6, 27.2, 26.3. Data in accordance with the literature. 7 2,2-Diphenylvinyl pivalate (1p) 1 H NMR (600 MHz, CDCl 3 ): δ = 7.62 (s, 1H), 7.39-7.26 (m, 10H), 1.21 (s, 9H). 13 C NMR (150 MHz, CDCl 3 ): δ = 175.5, 139.1, 136.8, 132.8, 130.1, 128.44, 128.40, 128.0, 127.6, 127.5, 127.4, 38.9, 27.0. Data in accordance with the literature. 8 S11
IV. Preparation of B-Alkyl-9-BBNs The B-alkyl-9-BBN could be generated in situ from the corresponding alkenes with 9-BBN dimer. As mentioned in Fu s paper, 9 in a nitrogen-filled glovebox the corresponding olefin (0.32 mmol) was added to 9-BBN dimer (39.0 mg, 0.16 mmol) in a 10-mL vial equipped with a stirring bar. Diisopropyl ether (1.0 ml) was added and then the vial was capped and removed from the glovebox. The reaction mixture was stirred at 60 C for 1.5 h, and allowed to cool to room temperature. The vial was then taken back into the glovebox and could be directly used in the catalytic reactions. V. Typical Procedure for the Catalytic Reactions In a nitrogen-filled glovebox, an oven-dried sealed tube containing a stirring bar was charged with aryl pivalate substrate (0.20 mmol), yellow Ni(COD) 2 (4.4 mg, 8 mol%), IPr. HCl ligand (13.6 mg, 16 mol%), cesium carbonate (97.7 mg, 0.30 mmol) and freshly distilled diisopropyl ether (1.0 ml). Subsequently, the B-alkyl-9-BBN solution was added via syringe, and the reaction mixture was stirred at 110 C for 12 h. Upon purification via column chromatography the pure product was obtained after solvent removal. S12
VI. Gram Scale Experiment In a nitrogen-filled glovebox, 1-allyl-4-methoxybenzene (1.08 ml, 7.01 mmol) was added to 9-BBN dimer (854.1 mg, 3.50 mmol) in a 100-mL sealed tube equipped with a stirring bar. Distilled diisopropyl ether (21.9 ml) was added and then the tube was capped and removed from the glovebox. The reaction mixture was stirred at 60 C for 1.5 h, allowed to cool to room temperature, and then taken back into the glovebox. Another 100-mL oven-dried sealed tube containing a stirring bar was charged with naphthalen-2-yl pivalate (1a, 1.00 g, 4.38 mmol), yellow Ni(COD) 2 (24.0 mg, 2 mol%), IPr. HCl ligand (74.4 mg, 4 mol%), cesium carbonate (2.14 g, 6.57 mmol) in the glovebox. Subsequently, the prepared B-alkyl-9-BBN solution was added via syringe, and the reaction mixture was stirred at 110 C for 68 h. After it was cooled down to room temperature, the reaction mixture was extracted three times with ethyl acetate. The combined organic layer was washed with brine, dried over Na 2 SO 4, and then filtrated. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography (eluent: pure hexane to 50:1 hexane:etoac) to afford the corresponding product 3a as a white solid in 46% yield. S13
VII. Spectroscopic Data of Products 2-(3-(4-Methoxyphenyl)propyl)naphthalene (3a) As for general procedure, starting from naphthalen-2-yl pivalate (45.7 mg, 0.20 mmol), the product was isolated as white solid after flash chromatography on silica gel (50:1 hexane:etoac), 51.3 mg (93%). Mp: 53-54 C; 1 H NMR (600 MHz, CDCl 3 ): δ = 7.85-7.76 (m, 3H), 7.63 (s, 1H), 7.50-7.41 (m, 2H), 7.35 (d, J = 8.4 Hz, 1H), 7.14 (d, J = 8.3 Hz, 2H), 6.86 (d, J = 8.3 Hz, 2H), 3.81 (s, 3H), 2.82 (t, J = 7.7 Hz, 2H), 2.65 (t, J = 7.7 Hz, 2H), 2.08-2.01 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 157.8, 139.9, 134.4, 133.7, 132.0, 129.4, 127.9, 127.7, 127.47, 127.45, 126.5, 125.9, 125.1, 113.8, 55.3, 35.6, 34.6, 33.2; IR (ATR): ~ = 2931, 2852, 1696, 1607, 1509, 1452, 1244, 1181, 1027, 813, 743 cm -1 ; MS (EI): m/z (%) = 276.0 (M +, 77), 141.8 (100), 133.9 (34), 120.9 (47); HRMS (EI) for C 20 H 20 O: calculated for [M] + 276.15142, found 276.15082. 1-(3-(4-Methoxyphenyl)propyl)naphthalene (3b) As for general procedure, starting from naphthalen-1-yl pivalate (45.7 mg, 0.20 mmol), the product was isolated as colorless oil after flash chromatography on silica gel (50:1 hexane:etoac), 50.2 mg (91%). 1 H NMR (400 MHz, CDCl 3 ): δ = 8.00-7.96 (m, 1H), 7.89-7.84 (m, 1H), 7.72 (d, J = 8.1 Hz, 1H), 7.52-7.45 (m, 2H), 7.41 (t, J = 7.6 Hz, 1H), 7.34 (d, J = 6.9 Hz, 1H), 7.16 (d, J = 8.5 Hz, 2H), 6.86 (d, J = 8.5 Hz, 2H), 3.81 (s, 3H), 3.11 (t, J = 7.6 Hz, 2H), 2.72 (t, J = 7.6 Hz, 2H), 2.13-2.03 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ): δ = 157.8, 138.6, 134.3, 134.0, 132.0, 129.4, 128.8, 126.6, 126.0, 125.8, 125.6, 125.5, 123.9, 113.8, 55.4, 35.0, 32.6; IR (ATR): ~ = 2933, 2858, 1609, 1510, 1459, 1243, 1176, 1034, 779, 731 cm -1 ; MS (EI): m/z (%) = 276.1 (M +, 100), 141.9 (43), 133.9 (47), 120.9 (45); HRMS (EI) for C 20 H 20 O: calculated for [M] + 276.15142, found 276.15114. S14
9-(3-(4-Methoxyphenyl)propyl)phenanthrene (3c) As for general procedure, starting from phenanthren-9-yl pivalate (55.6 mg, 0.20 mmol), the product was isolated as white solid after flash chromatography on silica gel (50:1 hexane:etoac), 51.5 mg (79%). Mp: 80-81 C; 1 H NMR (600 MHz, CDCl 3 ): δ = 8.75 (dd, J = 8.1, 0.6 Hz, 1H), 8.67 (dd, J = 8.1, 0.6 Hz, 1H), 8.05 (dd, J = 7.7, 1.2 Hz, 1H), 7.84 (dd, J = 7.7, 1.2 Hz, 1H), 7.69-7.57 (m, 5H), 7.18 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H), 3.82 (s, 3H), 3.15 (t, J = 7.6 Hz, 2H), 2.77 (t, J = 7.6 Hz, 2H), 3.21-3.11 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 157.8, 136.5, 134.3, 132.0, 131.3, 130.8, 129.7, 129.5, 128.1, 126.7, 126.5, 126.2, 126.1, 126.0, 124.5, 123.3, 122.5, 113.8, 55.3, 35.1, 32.9, 32.0; IR (ATR): ~ = 3347, 2944, 2719, 1676, 1598, 1466, 1256, 1142, 1028, 806, 748 cm -1 ; MS (EI): m/z (%) = 326.0 (M +, 54), 192.0 (100), 133.9 (79); HRMS (EI) for C 24 H 22 O: calculated for [M] + 326.16707, found 326.16689. 4-(3-(4-Methoxyphenyl)propyl)-1,1'-biphenyl (3d) As for general procedure, starting from [1,1'-biphenyl]-4-yl Ph pivalate (50.8 mg, 0.20 mmol), the product was isolated as colorless solid after flash chromatography on silica gel (50:1 hexane:etoac), 45.3 mg (75%). Mp: 36-37 C; 1 H NMR (600 MHz, CDCl 3 ): δ = 7.60-7.58 (m, 2H), 7.53-7.51 (m, 2H), 7.45-7.41 (m, 2H), 7.35-7.31 (m, 1H), 7.28-7.25 (m, 2H), 7.13 (d, J = 8.6 Hz, 2H), 6.87-6.83 (m, 2H), 3.80 (s, 3H), 2.69 (t, J = 7.7 Hz, 2H), 2.64 (t, J = 7.7 Hz, 2H), 2.01-1.94 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 157.8, 141.6, 141.2, 138.7, 134.4, 129.4, 128.9, 128.8, 127.11, 127.06, 113.8, 55.4, 35.1, 34.6, 33.2; IR (ATR): ~ = 2929, 2855, 1606, 1504, 1241, 1176, 1114, 1032, 824, 756, 700 cm -1 ; MS (EI): m/z (%) = 302.0 (M +, 9), 148.9 (28), 120.8 (100); HRMS (EI) for C 22 H 22 O: calculated for [M] + 302.16707, found 302.16735. 3-(3-(4-Methoxyphenyl)propyl)-1,1'-biphenyl (3e) As for general procedure, starting from [1,1'-biphenyl]-3-yl pivalate Ph (50.8 mg, 0.20 mmol), the product was isolated as colorless oil after S15
flash chromatography on silica gel (50:1 hexane:etoac), 42.9 mg (71%). 1 H NMR (600 MHz, CDCl 3 ): δ = 7.61 (d, J = 7.6 Hz, 2H), 7.48-7.41 (m, 4H), 7.39-7.32 (m, 2H), 7.19 (d, J = 7.5 Hz, 1H), 7.13 (d, J = 8.6 Hz, 2H), 6.85 (d, J = 8.6 Hz, 2H), 3.81 (s, 3H), 2.72 (t, J = 7.7 Hz, 2H), 2.65 (t, J = 7.7 Hz, 2H), 2.03-1.96 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 157.8, 142.9, 141.5, 141.3, 134.4, 129.4, 128.8, 127.5, 127.4, 127.3, 127.2, 124.7, 113.8, 55.3, 35.6, 34.6, 33.3; IR (ATR): ~ = 3029, 2930, 2855, 2111, 1743, 1607, 1510, 1456, 1244, 1175, 1106, 1033, 802, 754, 698 cm -1 ; MS (EI): m/z (%) = 302.6 (M +, 2), 121.3 (100); HRMS (ESI) for C 22 H 22 ONa: calculated for [M+Na] + 325.15629, found 325.15659. 2-(3-(4-Methoxyphenyl)propyl)-1,1'-biphenyl (3f) As for general procedure, starting from [1,1'-biphenyl]-2-yl pivalate Ph (50.8 mg, 0.20 mmol), the product was isolated as colorless oil after flash chromatography on silica gel (50:1 hexane:etoac), 32.0 mg (53%). 1 H NMR (600 MHz, CDCl 3 ): δ = 7.42-7.33 (m, 3H), 7.32-7.20 (m, 6H), 6.96 (d, J = 8.6 Hz, 2H), 6.78 (d, J = 8.6 Hz, 2H), 3.79 (s, 3H), 2.63 (t, J = 7.7 Hz, 2H), 2.46 (t, J = 7.7 Hz, 2H), 1.80-1.73 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 157.7, 142.0, 141.9, 139.9, 134.3, 130.1, 129.32, 129.26, 129.2, 128.1, 127.4, 126.8, 125.7, 113.7, 55.3, 34.8, 33.1, 32.7; IR (ATR): ~ = 3058, 3023, 2930, 2857, 2318, 2085, 1737, 1609, 1510, 1457, 1243, 1176, 1035, 826, 750, 701 cm -1 ; MS (EI): m/z (%) = 302.7 (M +, 21), 121.4 (100); HRMS (ESI) for C 22 H 22 ONa: calculated for [M+Na] + 325.15629, found 325.15659. 1-Methoxy-4-(3-(4-methoxyphenyl)propyl)naphthalene (3g) As for general procedure, starting from 4-methoxynaphthalen-1-yl pivalate (51.7 mg, 0.20 mmol), the product was isolated as colorless oil after flash chromatography on silica gel (40:1 hexane:etoac), 35.5 mg (58%). 1 H NMR (600 MHz, CDCl 3 ): δ = 8.31 (d, J = 8.5 Hz, 1H), 7.91 (d, J = 8.2 Hz, 1H), 7.53-7.45 (m, 2H), 7.22 (d, J = 7.8 Hz, 1H), 7.14 (d, J = 8.5 Hz, 2H), 6.85 (d, J = 8.5 Hz, 2H), 6.75 (d, J = 7.8 Hz, 1H), 3.99 (s, 3H), 3.80 (s, 3H), 3.02 (t, J = 7.6 Hz, 2H), 2.70 (t, J = 7.6 Hz, 2H), 2.07-2.01 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 157.8, 154.1, 134.5, 132.7, 130.4, 129.4, 126.3, 126.0, 125.6, 124.8, 123.7, 122.6, 113.8, S16
103.4, 55.5, 55.3, 35.0, 32.6, 32.1; IR (ATR): ~ = 2930, 1601, 1507, 1259, 1182, 1043, 826, 603 cm -1 ; MS (EI): m/z (%) = 306.0 (M +, 100), 170.9 (77), 127.8 (20), 120.9 (20); HRMS (ESI) for C 21 H 22 O 2 : calculated for [M+Na] + 329.15120, found 329.15112. 2-Mthoxy-7-(3-(4-methoxyphenyl)propyl)naphthalene (3h) MeO As for general procedure, starting from 7-methoxynaphthalen-2-yl pivalate (51.7 mg, 0.20 mmol), the product was isolated as light yellow solid after flash chromatography on silica gel (50:1 hexane:etoac), 53.8 mg (88%). Mp: 81-82 C; 1 H NMR (600 MHz, CDCl 3 ): δ = 7.71 (dd, J = 8.3, 4.9 Hz, 2H), 7.54 (s, 1H), 7.20 (d, J = 8.3 Hz, 1H), 7.13 (d, J = 8.4 Hz, 2H), 7.12-7.09 (m, 2H), 6.86 (d, J = 8.4 Hz, 2H), 3.93 (s, 3H), 3.81 (s, 3H), 2.80 (t, J = 7.6 Hz, 2H), 2.65 (t, J = 7.6 Hz, 2H), 2.06-2.00 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 157.77, 157.75, 140.5, 134.8, 134.4, 129.4, 129.2, 127.6, 127.5, 125.5, 125.2, 117.9, 113.8, 105.5, 55.3, 35.6, 34.6, 33.2; IR (ATR): ~ = 3005, 2930, 2851, 1608, 1509, 1458, 1247, 1212, 1174, 1027, 834, 740 cm -1 ; MS (EI): m/z (%) = 306.1 (M +, 49), 172.0 (100); HRMS (ESI) for C 21 H 22 O 2 : calculated for [M+Na] + 329.15120, found 329.15131. Methyl 6-(3-(4-methoxyphenyl)propyl)-2-naphthoate (3i) As for general procedure, starting from methyl MeO O 6-(pivaloyloxy)-2-naphthoate (57.2 mg, 0.20 mmol), the product was isolated as white solid after flash chromatography on silica gel (30:1 hexane:etoac), 47.4 mg (71%). Mp: 82-83 C; 1 H NMR (600 MHz, CDCl 3 ): δ = 8.57 (s, 1H), 8.03 (dd, J = 8.5, 1.5 Hz, 1H), 7.87 (d, J = 8.5 Hz, 1H), 7.80 (d, J = 8.5 Hz, 1H), 7.65 (s, 1H), 7.39 (dd, J = 8.5, 1.5 Hz, 1H), 7.12 (d, J = 8.6 Hz, 2H), 6.84 (d, J = 8.6 Hz, 2H), 3.98 (s, 3H), 3.79 (s, 3H), 2.82 (t, J = 7.6 Hz, 2H), 2.64 (t, J = 7.6 Hz, 2H), 2.08-1.99 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 167.5, 157.9, 142.9, 135.9, 134.2, 131.1, 130.9, 129.40, 129.36, 128.3, 127.7, 126.7, 126.4, 125.4, 113.8, 55.4, 52.3, 35.7, 34.6, 33.0; IR (ATR): ~ = 2931, 2853, 1712, 1619, 1506, 1281, 1185, 1028, 904, 823, 588 cm -1 ; MS (EI): m/z (%) = 334.0 (M +, 100), 200.0 (44), 133.9 (86), 120.9 (89); HRMS (EI) for C 22 H 22 O 3 : calculated for [M] + 334.15689, found 334.15665. S17
(6-(3-(4-Methoxyphenyl)propyl)naphthalen-2-yl)trimethylsilane (3j) As for general procedure, starting from Me 3 Si 6-(trimethylsilyl)naphthalen-2-yl pivalate (60.1 mg, 0.20 mmol), the product was isolated as colorless oil after flash chromatography on silica gel (pure hexane), 48.7mg (70%). H NMR (600 MHz, CDCl 3 ): δ = 7.98 (s, 1H), 7.77 (t, J = 7.8 Hz, 2H), 7.61-7.57 (m, 2H), 7.34 (d, J = 8.3 Hz, 1H), 7.12 (d, J = 8.5 Hz, 2H), 6.85 (d, J = 8.5 Hz, 2H), 3.80 (s, 3H), 2.81 (t, J = 7.6 Hz, 2H), 2.63 (t, J = 7.6 Hz, 2H), 2.05-1.99 (m, 2H), 0.35 (s, 9H); 3 C NMR (150 MHz, CDCl 3 ): δ = 157.8, 140.4, 137.0, 134.4, 133.9, 133.6, 131.6, 129.9, 129.4, 128.0, 127.5, 126.6, 126.3, 113.8, 55.3, 35.6, 34.6, 33.2, -1.0; IR (ATR): ~ = 2937, 2311, 2093, 1739, 1611, 1509, 1457, 1245, 1087, 1036, 830, 753 cm -1 ; MS (EI): m/z (%) = 348.1 (M +, 100), 214.0 (50), 120.9 (27); HRMS (ESI) for C 23 H 28 OSi: calculated for [M+Na] + 371.18016, found 371.18027. 1-(4-(3-(4-Mthoxyphenyl)propyl)phenyl)ethanone (3k) As for general procedure, starting from 4-acetylphenyl Me O pivalate (44.1 mg, 0.20 mmol), the product was isolated as colorless oil after flash chromatography on silica gel (16:1 hexane:etoac), 33.3 mg (62%). 1 H NMR (600 MHz, CDCl 3 ): δ = 7.88 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 8.3 Hz, 2H), 7.09 (d, J = 8.6 Hz, 2H), 6.84 (d, J = 8.5 Hz, 2H), 3.79 (s, 3H), 2.69 (t, J = 7.6 Hz, 2H), 2.62-2.57 (m, 5H), 2.00-1.89 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 198.0, 157.9, 148.3, 135.1, 134.0, 129.4, 128.7, 128.6, 113.8, 55.3, 35.4, 34.5, 32.9, 26.7; IR (ATR): ~ = 2925, 1678, 1605, 1264, 1185, 1059, 825, 666 cm -1 ; MS (EI): m/z (%) = 268.0 (M +, 43), 120.9 (100); HRMS (ESI) for C 18 H 20 O 2 : calculated for [M+Na] + 291.13555, found 291.13556. 2-(4-Fluorophenyl)-6-(3-(4-methoxyphenyl)propyl)naphthalene (3l) As for general procedure, starting from 6-(4-fluorophenyl)naphthalen-2-yl pivalate (64.5 mg, F S18
0.20 mmol), the product was isolated as white solid after flash chromatography on silica gel (40:1 hexane:etoac), 46.6 mg (63%). Mp: 74-75 C; 1 H NMR (600 MHz, CDCl 3 ): δ = 7.95 (s, 1H), 7.83 (dd, J = 14.8, 8.4 Hz, 2H), 7.69-7.63 (m, 4H), 7.37 (dd, J = 8.4, 1.5 Hz, 1H), 7.17 (t, J = 8.7 Hz, 2H), 7.13 (d, J = 8.5 Hz, 2H), 6.85 (d, J = 8.5 Hz, 2H), 3.80 (s, 3H), 2.82 (t, J = 7.6 Hz, 2H), 2.65 (t, J = 7.6 Hz, 2H), 2.08-2.00 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 162.5 (d, J C-F = 246.4 Hz), 157.8, 140.2, 137.4 (d, J C-F = 2.9 Hz), 136.9, 134.4, 132.8, 132.2, 129.4, 128.9 (d, J C-F = 7.9 Hz), 128.14, 128.10, 128.06, 126.3, 125.5 (d, J C-F = 3.3 Hz), 115.76 (d, J C-F = 21.4 Hz), 113.8, 55.3, 35.6, 34.6, 33.1; 19 F NMR (564 MHz, CDCl 3 ): δ = - 115.9; IR (ATR): ~ = 3002, 2928, 2852, 1751, 1602, 1508, 1457, 1238, 1036, 886, 815, 699 cm -1 ; MS (EI): m/z (%) = 370.1 (M +, 93), 236.0 (100), 120.9 (65); HRMS (ESI) for C 26 H 23 FO: calculated for [M] + 370.17329, found 370.17275. 4-(3-(4-Methoxyphenyl)propyl)-2-methylquinoline (3m) As for general procedure, starting from 2-methylquinolin-4-yl pivalate N Me (48.7 mg, 0.20 mmol), the product was isolated as colorless oil after flash chromatography on silica gel (8:1 hexane:etoac), 48.9 mg (84%). 1 H NMR (600 MHz, CDCl 3 ): δ = 8.02 (d, J = 8.2 Hz, 1H), 7.89 (d, J = 8.2 Hz, 1H), 7.67-7.63 (m, 1H), 7.48-7.44 (m, 1H), 7.13 (d, J = 8.6 Hz, 2H), 7.12 (s, 1H), 6.85 (d, J = 8.6 Hz, 2H), 3.80 (s, 3H), 3.03 (t, J = 7.8 Hz, 2H), 2.73-2.68 (m, 5H), 2.09-2.03 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 158.7, 157.9, 148.2, 148.1, 133.7, 129.40, 129.38, 129.1, 125.8, 125.5, 123.4, 121.7, 113.9, 55.3, 34.9, 31.8, 31.5, 25.4; IR (ATR): ~ = 2999, 2933, 2859, 1603, 1510, 1456, 1243, 1177, 1033, 830, 760 cm -1 ; MS (EI): m/z (%) = 291.1 (M +, 100), 290.1 (67), 133.9 (79), 120.9 (79); HRMS (ESI) for C 20 H 21 NO: calculated for [M+H] + 292.16959, found 292.16934. 4-(3-(4-Methoxyphenyl)propyl)-1,2-dihydronaphthalene (3n) As for general procedure, starting from 3,4-dihydronaphthalen-1-yl pivalate (46.0 mg, 0.20 mmol), the product was isolated as colorless oil after flash chromatography on silica gel (50:1 hexane:etoac), 28.4 mg (51%). 1 H NMR (600 MHz, CDCl 3 ): δ = 7.20-7.17 (m, 2H), 7.15-7.09 (m, 4H), 6.83 (d, J = 8.5 Hz, 2H), 5.86 (t, J = 4.5 Hz, 1H), 3.79 (s, 3H), 2.74 (t, J = 7.7 Hz, S19
2H), 2.63 (t, J = 7.7 Hz, 2H), 2.47 (t, J = 7.7 Hz, 2H), 2.31-2.20 (m, 2H), 1.88-1.80 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 157.7, 136.9, 136.3, 135.0, 134.6, 129.4, 127.6, 126.6, 126.3, 125.0, 122.7, 113.8, 55.4, 34.9, 32.2, 30.4, 28.6, 23.2; IR (ATR): ~ = 2929, 2859, 2834, 1727, 1510, 1455, 1244, 1036, 813, 739 cm -1 ; MS (EI): m/z (%) = 278.0 (M +, 14), 133.9 (100); HRMS (EI) for C 20 H 22 O: calculated for [M] + 278.16707, found 278.16641. 3-(3-(4-Methoxyphenyl)propyl)-1,2-dihydronaphthalene (3o) As for general procedure, starting from 3,4-dihydronaphthalen-2-yl pivalate (46.0 mg, 0.20 mmol), the product was isolated as colorless oil after flash chromatography on silica gel (50:1 hexane:etoac), 37.8 mg (68%). 1 H NMR (600 MHz, CDCl 3 ): δ = 7.18-7.07 (m, 5H), 7.00 (d, J = 7.4 Hz, 1H), 6.90-6.84 (m, 2H), 6.25 (s, 1H), 3.81 (s, 3H), 2.82 (t, J = 8.2 Hz, 2H), 2.62 (t, J = 8.2 Hz, 2H), 2.26 (q, J = 7.4 Hz, 4H), 1.88-1.80 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 157.8, 142.0, 135.0, 134.51, 134.50, 129.4, 127.2, 126.5, 126.1, 125.4, 122.5, 113.8, 55.3, 37.0, 34.7, 29.6, 28.3, 27.4; IR (ATR): ~ = 2915, 2339, 2093, 1745, 1616, 1479, 1236, 1036, 763 cm -1 ; MS (EI): m/z (%) = 278.7 (M +, 47), 134.4 (100), 121.4 (72); HRMS (ESI) for C 20 H 22 ONa: calculated for [M+Na] + 301.15629, found 301.15646. (5-(4-Methoxyphenyl)pent-1-ene-1,1-diyl)dibenzene (3p) As for general procedure, starting from 2,2-diphenylvinyl pivalate (56.1 mg, 0.20 mmol), the product was isolated as colorless oil after flash chromatography on silica gel (50:1 hexane:etoac), 38.1 mg (58%). 1 H NMR (400 MHz, CDCl 3 ): δ = 7.42-7.14 (m, 10H), 7.05 (d, J = 8.6 Hz, 2H), 6.81 (d, J = 8.6 Hz, 2H), 6.11 (t, J = 7.5 Hz, 1H), 3.79 (s, 3H), 2.56 (t, J = 7.7 Hz, 2H), 2.22-2.14 (m, 2H), 1.80-1.70 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ): δ = 157.7, 142.9, 142.0, 140.3, 134.5, 130.0, 129.8, 129.3, 128.2, 128.1, 127.3, 126.92, 126.88, 113.8, 55.3, 34.6, 32.0, 29.4; IR (ATR): ~ = 3056, 3024, 2925, 2855, 2323, 2083, 1734, 1609, 1510, 1446, 1298, 1244, 1176, 1033, 909, 809, 762, 732, 698 cm -1 ; MS (EI): m/z (%) = 328.7 (M +, 14), 121.4 (100); HRMS (ESI) for C 24 H 24 ONa: calculated for [M+Na] + 351.17194, found 351.17255. S20
2-(3-Phenylpropyl)naphthalene (4a) As for general procedure, starting from naphthalen-2-yl pivalate (45.7 mg, 0.20 mmol), the product was isolated as colorless oil after flash chromatography on silica gel (pure hexane), 39.8 mg (81%). 1 H NMR (600 MHz, CDCl 3 ): δ = 7.85-7.79 (m, 3H), 7.65 (s, 1H), 7.51-7.42 (m, 2H), 7.37 (d, J = 8.2, 1H), 7.33 (t, J = 7.6 Hz, 2H), 7.25-7.21 (m, 3H), 2.85 (t, J = 7.7 Hz, 2H), 2.73 (t, J = 7.7 Hz, 2H), 2.13-2.05 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 142.3, 139.9, 133.7, 132.1, 128.5, 128.4, 127.9, 127.7, 127.5, 127.4, 126.5, 125.9, 125.8, 125.2, 35.7, 35.5, 32.9; IR (ATR): ~ = 3029, 2929, 2856, 2323, 2100, 1740, 1449, 1365, 1216, 813, 742, 700 cm -1 ; MS (EI): m/z (%) = 246.0 (M +, 58), 141.9 (100); Data in accordance with the literature. 10 2-(3-(p-Tolyl)propyl)naphthalene (4b) As for general procedure, starting from naphthalen-2-yl pivalate Me (45.7 mg, 0.20 mmol), the product was isolated as white solid after flash chromatography on silica gel (pure hexane), 45.3 mg (87%). Mp: 45-46 C; 1 H NMR (600 MHz, CDCl 3 ): δ = 7.84-7.78 (m, 3H), 7.64 (s, 1H), 7.49-7.42 (m, 2H), 7.36 (d, J = 8.4 Hz, 1H), 7.15-7.11 (m, 4H), 2.84 (t, J = 7.7 Hz, 2H), 2.68 (t, J = 7.7 Hz, 2H), 2.35 (s, 3H), 2.10-2.02 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 139.9, 139.2, 135.3, 133.7, 132.0, 129.1, 128.4, 127.9, 127.7, 127.48, 127.46, 126.5, 125.9, 125.1, 35.6, 35.1, 33.0, 21.1; IR (ATR): ~ = 3039, 2927, 2858, 1510, 1447, 808, 745 cm -1 ; MS (EI): m/z (%) = 260.1 (M +, 68), 141.9 (100); HRMS (EI) for C 20 H 20 : calculated for [M] + 260.15650, found 260.15583. 2-(3-(3,4-Dimethoxyphenyl)propyl)naphthalene (4c) As for general procedure, starting from naphthalen-2-yl pivalate (45.7 mg, 0.20 mmol), the product was isolated as white solid after flash chromatography on silica gel (16:1 hexane:etoac), 55.1 mg (90%). Mp: 44-45 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 7.84-7.76 (m, 3H), 7.63 (s, 1H), S21
7.49-7.40 (m, 2H), 7.35 (dd, J = 8.4, 1.4 Hz, 1H), 6.82 (d, J = 8.1 Hz, 1H), 6.78-6.70 (m, 2H), 3.88 (s, 3H), 3.87 (s, 3H), 2.83 (t, J = 7.7 Hz, 2H), 2.65 (t, J = 7.7 Hz, 2H), 2.10-2.00 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ): δ = 148.9, 147.2, 139.9, 135.0, 133.7, 132.1, 127.9, 127.7, 127.4, 126.5, 126.0, 125.2, 120.3, 111.9, 111.3, 56.0, 55.9, 35.6, 35.1, 33.1; IR (ATR): ~ = 2931, 2852, 1725, 1594, 1510, 1454, 1247, 1141, 1027, 808, 750 cm -1 ; MS (EI): m/z (%) = 306.1 (M +, 100), 163.9 (42); HRMS (ESI) for C 21 H 22 O 2 : calculated for [M] + 306.16198, found 306.16197. 2-(3-(4-Fluorophenyl)propyl)naphthalene (4d) As for general procedure, starting from naphthalen-2-yl pivalate F (45.7 mg, 0.20 mmol), the product was isolated as white solid after flash chromatography on silica gel (50:1 hexane:etoac), 39.1 mg (74%). Mp: 43-44 C; 1 H NMR (600 MHz, CDCl 3 ): δ = 7.84-7.77 (m, 3H), 7.62 (s, 1H), 7.49-7.41 (m, 2H), 7.34 (d, J = 8.3 Hz, 1H), 7.18-7.13 (m, 2H), 6.99 (t, J = 8.5 Hz, 2H), 2.82 (t, J = 7.7 Hz, 2H), 2.67 (t, J = 7.7 Hz, 2H), 2.09-1.99 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 161.3 (d, J C-F = 243.2 Hz), 139.7, 137.9 (d, J C-F = 3.0 Hz), 133.7, 132.1, 129.8 (d, J C-F = 7.7 Hz), 128.0, 127.7, 127.5, 127.4, 126.5, 126.0, 125.2, 115.1 (d, J C-F = 21.0 Hz), 35.5, 34.7, 33.1; 19 F NMR (564 MHz, CDCl 3 ): δ = - 177.9; IR (ATR): ~ = 3050, 2926, 2855, 2105, 1600, 1507, 1456, 1220, 1155, 817, 744 cm -1 ; MS (EI): m/z (%) = 264.1 (M +, 73), 141.9 (100); HRMS (ESI) for C 19 H 17 F: calculated for [M] + 264.13143, found 264.13092. 2-(3-(4-(Trifluoromethyl)phenyl)propyl)naphthalene (4e) As for general procedure, starting from naphthalen-2-yl pivalate CF 3 (45.7 mg, 0.20 mmol), the product was isolated as white solid after flash chromatography on silica gel (pure hexane), 36.4 mg (58%). Mp: 38-39 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 7.85-7.77 (m, 3H), 7.63 (s, 1H), 7.56 (d, J = 8.0 Hz, 2H), 7.50-7.42 (m, 2H), 7.37-7.28 (m, 3H), 2.84 (t, J = 7.7 Hz, 2H), 2.75 (t, J = 7.7 Hz, 2H), 2.14-2.02 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ): δ = 146.4, 139.4, 133.7, 132.1, 128.8, 128.7 (q, J C-F = 37.2 Hz), 128.1, 127.7, 127.5, 127.3, 126.6, 126.1, 125.3 (q, J C-F = 3.8 Hz), 125.29, 124.5 (q, J C-F = 265.1 Hz), 35.5, 35.3, 32.6; 19 F NMR (376 MHz, CDCl 3 ): δ = - 62.3 (s, CF 3 ); IR (ATR): ~ = 3049, 2934, 2860, 1740, 1614, 1321, S22
1115, 820, 746 cm -1 ; MS (EI): m/z (%) = 314.0 (M +, 88), 141.9 (100), 140.9 (62); HRMS (EI) for C 20 H 17 F 3 : calculatedfor [M] + 314.12824, found 314.12791. 5-(3-(Naphthalen-2-yl)propyl)benzo[d][1,3]dioxole (4f) O O As for general procedure, starting from naphthalen-2-yl pivalate (45.7 mg, 0.20 mmol), the product was isolated as colorless oil after flash chromatography on silica gel (50:1 hexane:etoac), 53.4 mg (92%). 1 H NMR (600 MHz, CDCl 3 ): δ = 7.83-7.76 (m, 3H), 7.62 (s, 1H), 7.48-7.40 (m, 2H), 7.33 (d, J = 8.4 Hz, 1H), 6.74 (d, J = 7.9 Hz, 1H), 6.70 (s, 1H), 6.67-6.63 (m, 1H), 5.93 (s, 2H), 2.80 (t, J = 7.7 Hz, 2H), 2.62 (t, J = 7.7 Hz, 2H), 2.05-1.97 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 147.6, 145.6, 139.8, 136.2, 133.7, 132.0, 127.9, 127.7, 127.5, 127.4, 126.5, 126.0, 125.2, 121.2, 109.0, 108.2, 100.8, 35.5, 35.2, 33.2; IR (ATR): ~ = 2926, 2321, 2095, 1728, 1605, 1487, 1365, 1243, 1114, 1037, 933, 803, 745 cm -1 ; MS (EI): m/z (%) = 290.0 (M +, 100), 147.9 (43), 141.9 (45); HRMS (EI) for C 20 H 18 O 2 : calculated for [M] + 290.13068, found 290.13067. 2-(4-Phenylbutyl)naphthalene (4g) As for general procedure, starting from naphthalen-2-yl pivalate (45.7 mg, 0.20 mmol), the product was isolated as white solid after flash chromatography on silica gel (pure hexane), 42.1 mg (81%). Mp: 73-74 C; 1 H NMR (400 MHz, CDCl 3 ): δ = 7.84-7.75 (m, 3H), 7.61 (s, 1H), 7.50-7.38 (m, 2H), 7.34 (dd, J = 8.4, 1.5 Hz, 1H), 7.31-7.27 (m, 2H), 7.21-7.17 (m, 3H), 2.82 (t, J = 7.3 Hz, 2H), 2.67 (t, J = 7.3 Hz, 2H), 1.83-1.67 (m, 4H); 13 C NMR (100 MHz, CDCl 3 ): δ = 142.6, 140.1, 133.7, 132.0, 128.5, 128.3, 127.9, 127.7, 127.5, 127.5, 126.4, 125.9, 125.7, 125.1, 36.0, 35.9, 31.2, 31.0; IR (ATR): ~ = 3030, 2927, 2853, 1596, 1492, 1458, 816, 737 cm -1 ; MS (EI): m/z (%) = 260.1 (M +, 86), 140.9 (100), 90.9 (71); HRMS (ESI) for C 20 H 20 : calculated for [M] + 260.15650, found 260.15655. S23
1-(3-(Naphthalen-2-yl)propyl)-1H-indole (4h) As for general procedure, starting from naphthalen-2-yl pivalate N (45.7 mg, 0.20 mmol), the product was isolated as yellow oil after flash chromatography on silica gel (40:1 hexane:etoac), 31.4 mg (56%). 1 H NMR (600 MHz, CDCl 3 ): δ = 7.87-7.76 (m, 3H), 7.68 (d, J = 7.9 Hz, 1H), 7.62 (s, 1H), 7.52-7.43 (m, 2H), 7.33 (d, J = 8.3 Hz, 2H), 7.23 (t, J = 7.6 Hz, 1H), 7.17-7.10 (m, 2H), 6.55 (d, J = 3.1 Hz, 1H), 4.19 (t, J = 7.6 Hz, 2H), 2.82 (t, J = 7.6 Hz, 2H), 2.36-2.27 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 138.5, 136.0, 133.6, 132.2, 128.7, 128.2, 127.8, 127.7, 127.5, 127.1, 126.7, 126.1, 125.4, 121.5, 121.1, 119.3, 109.5, 101.2, 45.7, 33.2, 31.4; IR (ATR): ~ = 3049, 2926, 1306, 1189, 1042, 887, 616 cm -1 ; MS (EI): m/z (%) = 285.0 (M +, 84), 140.9 (37), 130.9 (58), 129.9 (100), 114.9 (46); HRMS (ESI) for C 21 H 19 N: calculated for [M+H] + 286.15903, found 286.15906. 2-(3-Phenoxypropyl)naphthalene (4i) As for general procedure, starting from naphthalen-2-yl pivalate O (45.7 mg, 0.20 mmol), the product was isolated as white solid after flash chromatography on silica gel (pure hexane), 35.1 mg (67%). Mp: 68-69 C; 1 H NMR (600 MHz, CDCl 3 ): δ = 7.85-7.74 (m, 3H), 7.66 (s, 1H), 7.49-7.41 (m, 2H), 7.38 (d, J = 8.1 Hz, 1H), 7.29 (t, J = 7.5 Hz, 2H), 6.98-6.88 (m, 3H), 4.01 (t, J = 6.0 Hz, 2H), 3.00 (t, J = 7.4 Hz, 2H), 2.25-2.16 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 159.1, 139.1, 133.7, 132.1, 129.5, 128.1, 127.7, 127.5, 127.4, 126.6, 126.0, 125.3, 120.7, 114.6, 66.8, 32.4, 30.9; IR (ATR): ~ = 2957, 2921, 1727, 1596, 1473, 1243, 1035, 820, 746, 695 cm -1 ; MS (EI): m/z (%) = 262.1 (M +, 100), 168.0 (37), 142.0 (66), 141.0 (81); HRMS (EI) for C 19 H 18 O: calculated for [M] + 262.13577, found 262.13583. 2-(2-Methyl-3-phenylpropyl)naphthalene (4j) Me As for general procedure, starting from naphthalen-2-yl pivalate (45.7 mg, 0.20 mmol), the product was isolated as colorless oil after flash chromatography on silica gel (pure hexane), 24.4 mg (47%). 1 H NMR (600 MHz, CDCl 3 ): δ = 7.83-7.75 (m, 3H), 7.60 (s, 1H), 7.48-7.40 (m, 2H), 7.32-7.27 (m, 3H), 7.22-7.16 (m, 3H), 2.86 (dd, J S24
= 13.4, 5.9 Hz, 1H), 2.74 (dd, J = 13.4, 5.9 Hz, 1H), 2.58 (dd, J = 13.5, 8.3 Hz, 1H), 2.47 (dd, J = 13.4, 8.3 Hz, 1H), 2.20-2.12 (m, 1H), 0.87 (d, J = 6.6 Hz, 3H); 13 C NMR (150 MHz, CDCl 3 ): δ = 141.3, 138.9, 133.6, 132.1, 129.3, 128.3, 128.0, 127.8, 127.7, 127.5, 127.4, 125.91, 125.85, 125.2, 43.6, 43.5, 37.2, 19.3; IR (ATR): ~ = 3033, 2919, 2319, 2097, 1740, 1451, 1367, 1219, 810, 740, 700 cm -1 ; MS (EI): m/z (%) = 260.1 (M +, 52), 142.0 (100), 141.0 (55), 90.9 (42); HRMS (EI) for C 20 H 20 : calculated for [M] + 260.15650, found 260.15626. 2-(3-Cyclohexylpropyl)naphthalene (4k) As for general procedure, starting from naphthalen-2-yl pivalate (45.7 mg, 0.20 mmol), the product was isolated as colorless oil after flash chromatography on silica gel (pure hexane), 39.8 mg (79%). 1 H NMR (600 MHz, CDCl 3 ): δ = 7.82-7.74 (m, 3H), 7.61 (s, 1H), 7.46-7.39 (m, 2H), 7.33 (dd, J = 8.3, 1.6 Hz, 1H), 2.75 (t, J = 7.7 Hz, 2H), 1.75-1.66 (m, 7H), 1.30-1.19 (m, 8H); 13 C NMR (150 MHz, CDCl 3 ): δ = 140.6, 133.7, 132.0, 127.8, 127.7, 127.53, 127.47, 126.3, 125.9, 125.0, 37.7, 37.3, 36.5, 33.5, 28.8, 26.8, 26.5; IR (ATR): ~ = 2920, 2849, 2114, 1448, 1261, 811, 742 cm -1 ; MS (EI): m/z (%) = 252.1 (M +, 75), 142.0 (94), 141.0 (100); HRMS (EI) for C 19 H 24 : calculated for [M] + 252.18780, found 252.18715. 2-Otylnaphthalene (4l) As for general procedure, starting from naphthalen-2-yl pivalate (45.7 mg, 0.20 mmol), the product was isolated as colorless oil after flash chromatography on silica gel (pure hexane), 29.8 mg (62%). 1 H NMR (600 MHz, CDCl 3 ): δ = 7.82-7.75 (m, 3H), 7.61 (s, 1H), 7.47-7.39 (m, 2H), 7.34 (dd, J = 8.4, 1.6 Hz, 1H), 2.77 (t, J = 7.7 Hz, 2H), 1.74-1.68 (m, 2H), 1.42-1.20 (m, 10H), 0.88 (t, J = 7.0 Hz, 3H); 13 C NMR (150 MHz, CDCl 3 ): δ = 140.6, 133.7, 132.0, 127.8, 127.7, 127.54, 127.46, 126.3, 125.9, 125.0, 36.2, 32.0, 31.5, 29.6, 29.5, 29.4, 22.8, 14.2; IR (ATR): ~ = 3048, 2923, 2855, 1740, 1455, 1367, 1217, 810, 741 cm -1 ; MS (EI): m/z (%) = 240.1 (M +, 73), 141.9 (91), 140.9 (100); Data in accordance with the literature. 11 S25
VIII. Synthetic Application 9-BBN PivO OTs 5 PhB(OH) 2 (2.0 equiv) Pd(OAc) 2 (2.0 mol%) XPhos (5.0 mol%) K 3 PO 4 (3.0 equiv) t BuOH, 90 C, 12 h PivO 6, 88% Me (1.6 equiv) Ni(COD) 2 (8.0 mol%) IPr.HCl (16.0 mol%) Cs 2 CO 3 (1.5 equiv) i Pr 2 O, 120 C, 40 h Me LiCH 2 SiMe 3 (1.3 equiv) Ni(COD) 2 (5.0 mol%) Me Toluene, 80 C, 5 h SiMe 3 7, 56% 8, 86% 3-Methoxy-5-(tosyloxy)phenyl pivalate (5) was synthesized from 3,5-dihydroxyanisole according to the literature method. 12 Synthesis of 5-methoxy-[1,1'-biphenyl]-3-yl pivalate (6) An oven-dried Schlenk tube containing a stirring bar was charged with 5 (61.7 mg, 0.20 mmol), phenylboronic acid (48.8 mg, 0.40 mmol), Pd(OAc) 2 (0.9 mg, 0.004 mmol), XPhos (4.8 mg, 0.01 mmol) and K 3 PO 4 (127 mg, 0.60 mmol). The tube was degassed three times. Then 2.0 ml of t BuOH was charged and the reaction was stirred at 90 C for 12 h. The mixture was cooled to room temperature, quenched with saturated aqueous NH 4 Cl and extracted with ethyl acetate. The organic layer was concentrated under vacuum and the product 6 was purified by flash column chromatography and obtained as a light yellow oil. 13 1 H NMR (600 MHz, CDCl 3 ): δ = 7.60-7.56 (m, 2H), 7.43 (t, J = 7.7 Hz, 2H), 7.36 (t, J = 7.4 Hz, 1H), S26
7.01-6.99 (m, 1H), 6.91-6.88 (m, 1H), 6.63-6.60 (m, 1H), 3.86 (s, 3H), 1.39 (s, 9H); 13 C NMR (150 MHz, CDCl 3 ): δ = 177.1, 160.7, 152.4, 143.5, 140.4, 128.8, 127.8, 127.3, 112.9, 110.6, 106.2, 55.6, 39.2, 27.2; IR (ATR): ~ = 2962, 2316, 2100, 1747, 1595, 1462, 1247, 1120, 1052, 857, 759, 692 cm -1 ; MS (EI): m/z (%) = 285.1 (83), 284.0 (M +, 100); HRMS (ESI) for C 18 H 20 O 3 : calculated for [M+Na] + 307.13047, found 307.13065. Synthesis of 3-methoxy-5-(3-(p-tolyl)propyl)-1,1'-biphenyl (7) In a nitrogen-filled glovebox, an oven-dried sealed tube containing a stirring bar was charged with 6 (56.8 mg, 0.20 mmol), yellow Ni(COD) 2 (4.4 mg, 8 mol%), IPr. HCl ligand (13.6 mg, 16 mol%), cesium carbonate (97.7 mg, 0.30 mmol) and freshly distilled diisopropyl ether (1.0 ml). Subsequently, the B-alkyl-9-BBN solution was added via syringe, and the reaction mixture was stirred at 120 C for 40 h. Upon purification via column chromatography the pure product 7 was obtained as a light yellow oil after solvent removal. 1 H NMR (600 MHz, CDCl 3 ): δ = 7.61-7.57 (m, 2H), 7.44 (t, J = 7.7 Hz, 2H), 7.35 (t, J = 7.4 Hz, 1H), 7.14-7.07 (m, 4H), 7.02 (s, 1H), 6.98-6.95 (m, 1H), 6.74 (s, 1H), 3.86 (s, 3H), 2.72-2.63 (m, 4H), 2.33 (s, 3H), 2.04-1.96 (m, 2H); 13 C NMR (150 MHz, CDCl 3 ): δ = 160.0, 144.4, 142.7, 141.4, 139.2, 135.3, 129.1, 128.8, 128.4, 127.4, 127.3, 120.1, 113.1, 110.2, 55.4, 35.7, 35.1, 33.0, 21.1; IR (ATR): ~ = 3006, 2929, 2857, 2326, 2087, 1894, 1722, 1592, 1509, 1455, 1336, 1213, 1154, 1058, 855, 760, 698 cm -1 ; MS (EI): m/z (%) = 316.1 (M +, 81), 198.0 (100); HRMS (EI) for C 23 H 24 O: calculated for [M] + 316.18272, found 316.18255. S27
Synthesis of trimethyl((5-(3-(p-tolyl)propyl)-[1,1'-biphenyl]-3-yl)methyl)silane (8) Me LiCH 2 SiMe 3 (1.3 equiv) Ni(COD) 2 (5.0 mol%) Me Toluene, 80 C, 5 h SiMe 3 7 8, 86% An oven-dried, argon-flushed Schlenk tube was charged with 7 (31.6 mg, 0.1 mmol) and yellow Ni(COD) 2 (1.4 mg, 5 mol%). The tube was immediately sealed and again flushed with argon. Subsequently, freshly distilled toluene (1.5 ml) and a LiCH 2 SiMe 3 solution in pentane (1.0 M) were added and the mixture was stirred for 5 h at 80 C. Upon purification via column chromatography the pure product 8 was obtained as colorless oil after solvent removal. 14 1 H NMR (600 MHz, CDCl 3 ): δ = 7.60-7.56 (m, 2H), 7.42 (t, J = 7.6 Hz, 2H), 7.33 (t, J = 7.4 Hz, 1H), 7.14-7.08 (m, 5H), 7.05 (s, 1H), 6.82 (s, 1H), 2.70-2.61 (m, 4H), 2.33 (s, 3H), 2.13 (s, 2H), 2.01-1.94 (m, 2H), 0.03 (s, 9H); 13 C NMR (150 MHz, CDCl 3 ): δ = 142.6, 141.8, 141.1, 140.9, 139.4, 135.2, 129.1, 128.7, 128.4, 127.4, 127.3, 127.0, 124.5, 123.3, 35.6, 35.2, 33.3, 27.2, 21.1, -1.7; IR (ATR): ~ = 2927, 2317, 2097, 1593, 1440, 1246, 1155, 845, 695 cm -1 ; MS (EI): m/z (%) = 372.2 (M +, 64), 254.1 (69), 72.9 (100); HRMS (ESI) for C 26 H 32 Si: calculated for [M+Na] + 395.21655, found 395.21613. S28
References: 1. Quasdorf, K. W.; Tian, X.; Garg, N. K. J. Am. Chem. Soc. 2008, 130, 14422. 2. Shimasaki, T.; Tobisu, M.; Chatani, N. Angew. Chem., Int. Ed. 2010, 49, 2929. 3. Takise, R.; Muto, K.; Yamaguchi, J.; Itami, K. Angew. Chem., Int. Ed. 2014, 53, 6791. 4. Xiao, B.; Fu, Y.; Xu, J.; Gong, T.-J.; Dai, J.-J.; Yi, J.; Liu, L. J. Am. Chem. Soc. 2010, 132, 468. 5. Zarate, C.; Martin, R. J. Am. Chem. Soc. 2014, 136, 2236. 6. Gogsig, T. M.; Kleimark, J.; Nilsson, L.; Sten, O.; Korsager, S.; Lindhardt, A. T.; Norrby, P.; Skrydstrup, T. J. Am. Chem. Soc. 2012, 134, 443. 7. Li, B.-J.; Xu, L.; Wu, Z.-H.; Guan, B.-T.; Sun, C.-L.; Wang, B.-Q.; Shi, Z.-J. J. Am. Chem. Soc. 2009, 131, 14656. 8. Kinuta, H.; Hasegawa, J.; Tobisu, M.; Chatani, N. Chem. Lett. 2015, 44, 366. 9. Saito, B.; Fu, G. C. J. Am. Chem. Soc. 2007, 129, 9602. 10. Sugimoto, A.; Sakamoto, S.; Suyama, K.; Yoneda, S. Bull. Chem. Soc. Jpn. 1986, 59, 1626. 11. Britton, M.; Fawthrop, S.; Gillies, D.; Sutcliffe, L.; Wu, X.; Smirnov, A. Magn. Reson. Chem. 1997, 35, 493. 12. Zhao, F.; Zhang, Y.-F.; Wen, J.; Yu, D.-G.; Wei, J.-B.; Xi, Z.-F.; Shi, Z.-J. Org. Lett. 2013, 15, 3230. 13. Nguyen, H. N.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 11818. 14. Leiendecker, M.; Hsiao, C.-C.; Guo, L.; Alandini, N.; Rueping, M. Angew. Chem., Int. Ed. 2014, 53, 12912. S29
IX. Copies of 1 H and 13 C NMR Spectra S30
S31
S32
3a 3a S33
3b 3b S34
3c 3c S35
Ph 3d Ph 3d S36
Ph 3e Ph 3e S37
Ph 3f Ph 3f S38
3g 3g S39
MeO 3h MeO 3h S40
MeO O 3i MeO O 3i S41
Me 3 Si 3j Me 3 Si 3j S42
Me O 3k Me O 3k S43
F 3l F 3l S44
F 3l S45
N Me 3m N Me 3m S46
3n 3n S47
3o 3o S48
3p 3p S49
4a 4a S50
4b Me 4b Me S51
4c 4c S52
4d F 4d F S53
4d F S54
4e CF 3 4e CF 3 S55
4e CF 3 S56
O O 4f O O 4f S57
Ph 4g Ph 4g S58
N 4h N 4h S59
OPh 4i OPh 4i S60
Me 4j Me 4j S61
4k 4k S62
4l 4l S63
Ph PivO 6 Ph PivO 6 S64
Me 7 Me 7 S65
Me SiMe 3 8 Me SiMe 3 8 S66