Vitamin Catalysis: Direct, Photocatalytic Synthesis of Benzocoumarins via ( )-Riboflavin-Mediated Electron Transfer

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1 Supporting Information Vitamin Catalysis: Direct, Photocatalytic Synthesis of Benzocoumarins via ( )-Riboflavin-Mediated Electron Transfer Tobias Morack, Jan B. Metternich and Ryan Gilmour* Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, Münster, Germany Corresponding Author: ryan.gilmour@uni-muenster.de General Information Experimental Section NMR Spectra References S2 S4 S31 S83 S1

2 General Information All chemicals were purchased as reagent grade and used without further purification. Solvents for purification (extraction and chromatography) were purchased as technical grade and distilled on the rotary evaporator prior to use. For column chromatography SiO2 (40-63 μm for Flash-Chromatography, VWR Chemicals) was used as stationary phase. Analytical thin layer chromatography (TLC) was performed on aluminum foil pre-coated with SiO2-60 F254 (Merck) and visualized with a UV-lamp (254 nm) and KMnO4 or CAM solution. Concentration in vacuo was performed at ~10 mbar and 40 C, drying at ~10-2 mbar and room temperature. NMR spectra were measured by the NMR service of the Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster on a Bruker AV300, Bruker AV400, Agilent DD2 500 or an Agilent DD2 600 spectrometer at room temperature. The chemical shifts are referenced to the residual solvent peak as internal standard. The resonance multiplicity is abbreviated as: s (singlet), d (doublet), t (triplet), q (quadruplet), p (pentet), sext (sextet), sep (septet), m (multiplet) and b (broad). Assignments of unknown compounds are based on DEPT, COSY (HH and FF), HMBC, HSQC and NOESY spectra. Melting points were measured on a Büchi B-545 melting-point apparatus in open capillaries. IR spectra were recorded on a Perkin-Elmer 100 FT-IR spectrometer, selected adsorption bands are reported in wavenumbers (cm 1 ) and intensities are reported as: w (weak), m (medium), s (strong) and b (broad). High-resolution mass spectra (HR-ESI) were measured by the MS service of the Insitute for Organic Chemsitry, Westfälische Wilhelms-Universität Münster. Cyclization reactions were performed utilizing a set-up of 4 Winger WEPUV3-S2 UV Power LED Star (Schwarzlicht) 1.2 W lamps (emission spectrum see Figure 1). The forward current per chip was set to 700 ma, the resulting forward voltage was 3.4 V while the resulting radiant flux was 1200 mw. The distance between the reaction vessels and the UV-lamp was set at approximately 0.5 cm for all reactions. S2

3 Relative Intensity 1 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0, Wavelength [nm] Figure 1: Emission spectrum of LED lamp: 402 nm. S3

4 Experimental Section Procedures and analytical data General Procedure A for Esterification and Triflation of Salicylic Acid Derivatives Under an argon atmosphere, the specified salicylic acid (2.00 mmol, 1.0 eq.) was dissolved in DMF (20 ml, 0.1 M) and Cs2CO3 (0.33 g, 1.00 mmol, 0.5 eq.) and MeI (0.1 ml, 2.10 mmol, 1.05 eq.) were added. The resulting mixture was stirred at room temperature for 2 h, before the reaction was quenched by addition of water. The aqueous phase was extracted with EtOAc (3x), and the combined organic layers were washed with water (2x), sat. NaHCO3 (aq., 2x) and sat. NaCl (aq., 1x), before being dried over MgSO4 and concentrated in vacuo. Under argon, the resulting crude product was dissolved in dry DCM (20 ml, 0.2 M) and cooled to -78 C. Triethylamine (0.6 ml, 4.40 mmol, 2.2 eq.) and Tf2O (0.5 ml, 3.00 mmol, 1.5 eq.) were added and the reaction mixture gradually warmed to room temperature before being stirred for 12 h. Et2O was added, the organic layer washed with 1 M HCl (aq., 2x) and sat. NaCl (aq., 1x), the combined organic layers were dried over MgSO4 and concentrated in vacuo. Purification by column chromatography (SiO2) yielded the product. Methyl 5-fluoro-2-(((trifluoromethyl)sulfonyl)oxy)benzoate (24) Prepared according to General Procedure A, 5-fluorosalicylic acid (0.31 g, 2.00 mmol, 1.0 eq.) was converted to 24. Purification by column chromatography (n-pentane/etoac 19:1) yielded the product as a colourless oil (0.21 g, 0.69 mmol, 35%). Rf = 0.80 (n-pentane/etoac 8:2); 1 H NMR (400 MHz, CDCl3): δ = 7.78 (ddd, J = 8.3, 2.8, 0.8 Hz, 1H, H4), (m, 2H, H7/H6), 3.97 (s, 3H, H1) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C2), (d, JCF = Hz, C5), (C8), (d, JCF = 8.0 Hz, C3), (d, JCF = 8.5 Hz, C7), (d, JCF = 23.7 Hz, C6), (d, JCF = 25.6 Hz, C4), (q, JCF = Hz, C9), 53.1 (C1) ppm; 19 F NMR (282 MHz, CDCl3): δ = (s, F9), (td, J = 8.5, 5.9 Hz, F5) ppm; IR (ATR): ῦ = 2959(w), 2920(w), 2851(w), 1734(s), 1622(w), 1595(w), 1490(m), 1427(s), 1305(m), 1281(m), 1249(m), 1207(s), 1141(s), 1069(m), 985(m), 915(w), 871(s), 835(m), 801(m), 782(m), 723(w), 686(w), 670(w) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C9H6F4O5SNa + : ); analytical data in agreement with literature. [1] S4

5 Methyl 2-bromo-5-chlorobenzoate (25) 2-Bromo-5-chlorobenzoic acid (471 mg, 2.00 mmol, 1 eq.) was dissolved in methanol (2.5 ml) and SOCl2 (0.31 ml, 4.20 mmol, 2.1 eq.) was added at 0 C. The resulting mixture was gradually warmed to room temperature and stirred for 18 h. The solvent was removed in vacuo and the product was used without further purification. Methyl 5-methyl-2-(((trifluoromethyl)sulfonyl)oxy)benzoate (26) Prepared according to General Procedure A, 5-methylsalicylic acid (0.30 g, 2.00 mmol, 1.0 eq.) was converted to 26. Purification by column chromatography (n-pentane/etoac 19:1) yielded the product as a colourless oil (0.20 g, 0.68 mmol, 34%). Rf = 0.80 (n-pentane/etoac 8:2); 1 H NMR (400 MHz, CDCl3): δ = 7.88 (d, J = 2.0 Hz, 1H, H4), 7.40 (ddd, J = 8.4, 2.4, 0.7 Hz, 1H, H6), 7.18 (d, J = 8.4 Hz, 1H, H7), 3.96 (s, 3H, H1), 2.42 (s, 3H, H10) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C2), (C8), (C10), (C6), (C4), (C3), (C7), (q, JCF = Hz, C9), 52.8 (C1), 20.9 (C10) ppm; 19 F NMR (282 MHz, CDCl3): δ = (s) ppm; IR (ATR): ῦ = 2957(w), 1730(m), 1680(w), 1611(w), 1491(m), 1423(s), 1302(m), 1249(m), 1204(s), 1167(m), 1139(s), 1075(m), 1009(w), 975(w), 904(m), 868(s), 828(m), 784(m), 770(w), 738(m), 717(m), 685(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C10H9F3O5SNa + : ); analytical data in agreement with literature. [2] Methyl 5-methoxy-2-(((trifluoromethyl)sulfonyl)oxy)benzoate (27) Prepared according to General Procedure A, 5-methoxysalicylic acid (0.34 g, 2.00 mmol, 1.0 eq.) was converted to 27. Purification by column chromatography (n-pentane/etoac 19:1) yielded the product as a colourless oil (0.23 g, 0.73 mmol, 36%). Rf = 0.63 (n-pentane/etoac 8:2); 1 H NMR (400 MHz, CDCl3): δ = 7.54 (d, J = 3.1 Hz, 1H, H4), 7.21 (d, J = 9.0 Hz, 1H, H7), 7.09 (dd, J = 9.0, 3.3 Hz, 1H, H6), 3.96 (s, 3H, H1), 3.87 (s, 3H, H10) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C2), (C5), (C8), (C3), (C7), (C6), (q, JCF = Hz, C9), (C4), 56.1 (C10), 52.9 S5

6 (C1) ppm; 19 F NMR (282 MHz, CDCl3): δ = (s) ppm; IR (ATR): ῦ = 2957(w), 2921(w), 2845(w), 1731(s), 1590(w), 1493(m), 1422(s), 1327(m), 1295(s), 1247(s), 1205(s), 1161(s), 1140(s), 1073(m), 704(m), 981(w), 905(m), 866(s), 829(m), 796(m), 781(m), 770(w), 722(w), 690(m), 667(w) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C10H9F3O6SNa + : ); analytical data in agreement with literature. [3] Methyl 6-methyl-2-(((trifluoromethyl)sulfonyl)oxy)benzoate (28) Prepared according to General Procedure A, 6-methylsalicylic acid (0.33 g, 2.00 mmol, 1.0 eq.) was converted to 28. Purification by column chromatography (n-pentane/etoac 19:1) yielded the product as a colourless oil (0.55 g, 1.83 mmol, 93%). Rf = 0.72 (n-pentane/etoac 8:2); 1 H NMR (600 MHz, CDCl3): δ = 7.81 (dd, J = 7.8, 1.3 Hz, 1H, H7), 7.47 (dd, J = 7.7, 1.0 Hz, 1H, H5), 7.34 (t, J = 7.7 Hz, 1H, H6), 3.94 (s, 3H, H1), 2.43 (s, 3H, H10) ppm; 13 C NMR (151 MHz, CDCl3): δ = (C2), (C3), (C5), (C4), (C7), (C6), (C8), (q, JCF = Hz, C9), 52.8 (C1), 16.7 (C10) ppm; 19 F NMR (564 MHz, CDCl3): δ = (s) ppm; IR (ATR): ῦ = 2958(w), 1732(s), 1609(w), 1583(w), 1463(w), 1422(s), 1298(s), 1247(m), 1202(s), 1161(m), 1140(s), 1083(m), 1016(w), 975(w), 889(s), 811(w), 794(m), 775(m), 766(m), 741(w), 721(w) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C10H9F3O5SNa + : ). Methyl 5-bromo-2-(((trifluoromethyl)sulfonyl)oxy)benzoate (29) Prepared according to General Procedure A, 5-bromosalicylic acid (0.43 g, 2.00 mmol, 1.0 eq.) was converted to 29. Purification by column chromatography (n-pentane/etoac 19:1) yielded the product as a colourless oil (0.33 g, 0.90 mmol, 45%). Rf = 0.87 (n-pentane/etoac 8:2); 1 H NMR (400 MHz, CDCl3): δ = 8.21 (d, J = 2.6 Hz, 1H, H4), 7.74 (dd, J = 8.7, 2.6 Hz, 1H, H6), 7.18 (d, J = 8.8 Hz, 1H, H7), 3.97 (s, 3H, H1) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C2), (C8), (C6), (C4), (C3), (C7), (C5), (q, JCF = Hz, C9), 53.2 (C1) ppm; 19 F NMR (282 MHz, CDCl3): δ = (s) ppm; IR (ATR): ῦ = 2958(w), 1733(s), 1600(w), 1568(w), 1477(m), 1427(s), 1395(m), 1291(m), 1270(m), 1249(m), 1208(s), 1169(s), 1137(s), 1092(m), 1076(m), S6

7 967(m), 890(s), 839(s), 783(m), 753(s), 703(w), 674(w) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C9H6BrF3O5SNa + : ). General Procedure B for Suzuki-Miyaura Cross-Coupling A Schlenk pressure tube was charged with the specified aryl halide or aryl triflate (1.0 eq.), the specified aryl boronic acid (1.05 eq.), PdCl2(PPh3)3 (0.025 eq.) and Na2CO3 (2.0 eq.). The tube was evacuated and backfilled with argon (3x) before THF/H2O (1:1, 0.2 M) was added. The tube was evacuated upon slight boiling and backfilled with argon (3x). Afterwards the tube was sealed and stirred at 80 C for 14 h. The reaction was cooled to room temperature, sat. NaCl (aq.) was added and the reaction mixture extracted with EtOAc (3x). The combined organic layers were dried over MgSO4 and concentrated in vacuo. Purification by column chromatography (SiO2) yielded the product. Methyl 4'-(trifluoromethyl)-[1,1'-biphenyl]-2-carboxylate (30) Prepared according to General Procedure B, methyl 2-iodobenzoate (0.23 ml, 1.50 mmol, 1.0 eq.) and 4-(trifluoromethyl)phenylboronic acid (0.30 g, 1.58 mmol, 1.05 eq.) were converted to 30. Purification by column chromatography (n-pentane/etoac 19:1) yielded the product as a colourless oil (0.39 g, 1.37 mmol, 92%). Rf = 0.63 (n-pentane/etoac 9:1); 1 H NMR (600 MHz, CDCl3): δ = 7.91 (ddd, J = 7.8, 1.4, 0.4 Hz, 1H, H7), 7.66 (d, J = 7.9 Hz, 1H, H11), 7.57 (td, J = 7.6, 1.4 Hz, 1H, H5), 7.47 (td, J = 7.6, 1.3 Hz, 1H, H6), 7.42 (d, J = 7.9 Hz, 2H, H10), 7.34 (ddd, J = 7.7, 1.3, 0.4 Hz, 1H, H4), 3.66 (s, 3H, H1) ppm; 13 C NMR (151 MHz, CDCl3): δ = (C2), (q, JCF = 1.4 Hz, C9), (C8), (C5), (C4), (C3), (C7), (q, JCF = 32.5 Hz, C12), (C10), (C6), (q, JCF = 3.8 Hz, C11), (q, JCF = Hz, C13), 52.2 (C1) ppm; 19 F NMR (564 MHz, CDCl3): δ = (td, J = 0.65 Hz) ppm; IR (ATR): ῦ = 2989(w), 2901(w), 1725(s), 1619(w), 1569(w), 1484(w), 1449(w), 1434(w), 1405(m), 1324(s), 1283(m), 1253(m), 1134(m), 1123(s), 1109(s), 1091(s), 1069(s), 1049(m), 1022(m), 1007(m), 963(w), 845(m), 796(w), 766(m), 744(m), 713(w), 670(w) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C15H11O2F3Na + : ); analytical data in agreement with literature. [4] S7

8 Methyl 4'-bromo-[1,1'-biphenyl]-2-carboxylate (31) Prepared according to General Procedure B, methyl 2-iodobenzoate (0.45 ml, 3.00 mmol, 1.0 eq.) and 4-bromophenylboronic acid (0.63 g, 3.15 mmol, 1.05 eq.) were converted to 31. Purification by column chromatography (n-pentane/etoac 98:2) yielded the product as a colourless oil (0.49 g, 1.37 mmol, 56%). Rf = 0.63 (n-pentane/etoac 9:1); 1 H NMR (400 MHz, CDCl3): δ = 7.86 (dd, J = 7.7, 1.3 Hz, 1H, H7), 7.52 (m, 2H, H10/H5), 7.43 (td, J = 7.7, 1.2 Hz, 1H, H6), 7.33 (dd, J = 7.7, 1.0 Hz, 1H, H4), 7.18 (d, J = 8.4 Hz, 2H, H11), 3.67 (s, 3H, H1) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C2), (C9), (C8), (C3), (C10), (C4), (C5), (C7), (C11), (C6), (C12), 52.2 (C1) ppm; IR (ATR): ῦ = 2950(w), 2920(m), 1722(s), 1599(w), 1500(w), 1475(m), 1446(m), 1432(m), 1393(w), 1286(s), 1260(s), 1247(s), 1190(w), 1163(w), 1125(m), 1090(s), 1072(s), 1049(m), 1016(m), 1003(s), 963(w), 880(w), 831(m), 796(w), 760(s), 725(m), 708(m), 675(w) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C14H11O2BrNa + : ); analytical data in agreement with literature. [5] Methyl 4'-fluoro-[1,1'-biphenyl]-2-carboxylate (32) Prepared according to General Procedure B, methyl 2-iodobenzoate (0.23 ml, 1.50 mmol, 1.0 eq.) and 4-fluorophenylboronic acid (0.22 g, 1.58 mmol, 1.05 eq.) were converted to 32. Purification by column chromatography (n-pentane/etoac 19:1) yielded the product as a colourless oil (0.34 g, 1.47 mmol, 98%). Rf = 0.66 (n-pentane/etoac 9:1); 1 H NMR (400 MHz, CDCl3): δ = 7.84 (dd, J = 7.8, 1.0 Hz, 1H, H7), 7.53 (td, J = 7.5, 1.4 Hz, 1H, H5), 7.42 (td, J = 7.6, 1.3 Hz, 1H, H6), 7.34 (dd, J = 7.6, 0.9 Hz, 1H, H4), 7.27 (dd, J = 8.8, 5.3 Hz, 2H, H10), 7.09 (t, J = 8.7 Hz, 2H, H11), 3.66 (s, 3H, H1) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C2), (d, JCF = Hz, C12), (C8), (d, JCF = 3.3 Hz, C9), (C5), (C4), (C3), (C7), (d, JCF = 8.1 Hz, C10), (C6), (d, JCF = 21.5 Hz, C11), 52.1 (C1) ppm; 19 F NMR (564 MHz, CDCl3): δ = (td, J = 8.3, 4.1 Hz) ppm; IR (ATR): ῦ = 2952(w), 1722(s), 1607(m), 1572(w), 1515(m), 1481(m), 1448(m), 1433(m), 1405(w), 1279(s), 1245(s), 1222(s), 1190(m), 1159(m), 1126(m), 1088(s), 1048(m), 1008(m), 963(w), 839(s), S8

9 817(m), 797(w), 765(s), 735(m), 705(m), 694(m), 674(m), 663(m), 654(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C14H11O2Na + : ). Methyl 4'-(tert-butyl)-[1,1'-biphenyl]-2-carboxylate (33) 1.50 mmol, quant.). Prepared according to General Procedure B, methyl 2-iodobenzoate (0.23 ml, 1.50 mmol, 1.0 eq.) and 4-bromophenylboronic acid (0.28 g, 1.58 mmol, 1.05 eq.) were converted to 33. Purification by column chromatography (npentane/etoac 19:1) yielded the product as a white solid (0.41 g, Rf = 0.73 (n-pentane/etoac 9:1); 1 H NMR (600 MHz, CDCl3): δ = 7.80 (dd, J = 8.1, 1.5 Hz, 1H, H7), 7.52 (td, J = 7.5, 1.3 Hz, 1H, H5), 7.42 (d, J = 8.6 Hz, 2H, H11), (m, 2H, H6/H4), 7.26 (d, J = 8.7 Hz, 2H, H10), 3.65 (s, 3H, H1), 1.37 (s, 9H, H14) ppm; 13 C NMR (151 MHz, CDCl3): δ = (C2), (C12), (C8), (C9), (C5), (C3), (C6/C4), (C7), (C10), (C6/C4), (C11), 52.1 (C1), 34.7 (C13), 31.5 (C14) ppm; IR (ATR): ῦ = 3059(w), 3027(w), 2954(m), 2869(w), 1727(s), 1688(w), 1595(w), 1574(w), 1515(w), 1480(m), 1434(m), 1398(w), 1365(w), 1300(w), 1287(m), 1279(m), 1249(s), 1192(m), 1163(w), 1134(m), 1115(m), 1087(s), 1049(m), 1029(w), 1004(m), 986(w), 969(w), 960(w), 924(w), 891(w), 834(s), 796(m), 767(s), 742(s), 713(s), 687(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C18H20O2Na + : ); Mp.: C. Methyl 4'-methoxy-[1,1'-biphenyl]-2-carboxylate (34) 1.42 mmol, 95%). Prepared according to General Procedure B, methyl 2-iodobenzoate (0.23 ml, 1.50 mmol, 1.0 eq.) and 4-methoxyphenylboronic acid (0.24 g, 1.58 mmol, 1.05 eq.) were converted to 34. Purification by column chromatography (npentane/etoac 19:1) yielded the product as a colourless oil (0.35 g, Rf = 0.36 (n-pentane/etoac 9:1); 1 H NMR (400 MHz, CDCl3): δ = 7.79 (dd, J = 8.1, 0.9 Hz, 1H, H4), 7.51 (td, J = 7.4, 1.4 Hz, 1H, H6), 7.38 (t, J = 7.5 Hz, 2H, H5/H7) 7.25 (d, J = 8.7 Hz, 2H, H10), 6.94 (d, J = 8.7 Hz, 2H, H11), 3.85 (s, 3H, H13), 3.67 (s, 3H, S9

10 H1) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C2), (C12), (C8), (C9), (C6), (C3), (C5), (C4), (C10), (C7) (C11), 55.4 (C13), 52.1 (C1) ppm; IR (ATR): ῦ = 2951(w), 2937(w), 1718(s), 1611(m), 1580(w), 1517(m), 1480(m), 1463(m), 1447(m), 1284(s), 1243(s), 1178(m), 1126(m), 1087(s), 1087(m), 1037(m), 1018(m), 1001(m), 964(w), 881(w), 835(m), 764(s), 733(m), 712(m), 657(w) cm -1 ; HR-ESI- MS: m/z: ([M+Na] +, calcd. for C15H14O3Na + : ); analytical data in agreement with literature. [6] Methyl 4-fluoro-[1,1'-biphenyl]-2-carboxylate (35) Prepared according to General Procedure B, 24 (0.17 g, 0.56 mmol, 1.0 eq.) and phenylboronic acid (0.07 g, 0.59 mmol, 1.05 eq.) were converted to 35. Purification by column chromatography (npentane/etoac 19:1) yielded the product as a colourless oil (0.10 g, 0.44 mmol, 79%). Rf = 0.83 (n-pentane/etoac 8:2); 1 H NMR (400 MHz, CDCl3): δ = 7.53 (dd, J = 9.0, 2.8 Hz, 1H, H4), (m, 4H, H12/H11/H7), (m, 3H, H10/H6), 3.65 (s, 3H, H1) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C2), (d, JCF = Hz, C5), (C9), (C8), (d, JCF = 7.6 Hz, C7), (d, JCF = 6.1 Hz, C3), (C10) (C11), (C12), (d, JCF = 21.6 Hz, C6), (d, JCF = 22.0 Hz, C4), 52.3 (C1) ppm; 19 F NMR (282 MHz, CDCl): δ = ppm; IR (ATR): ῦ = 3068(w), 3029(w), 2952(w), 1721(s), 1609(w), 1587(w), 1507(w), 1479(s), 1447(m), 1436(m), 1410(m), 1301(s), 1281(m), 1265(m), 1240(s), 1196(s), 1127(m), 1075(m), 1038(w), 1010(m), 986(m), 902(m), 882(m), 832(m), 795(m), 786(m), 766(s), 735(m), 704(s), 673(w) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C14H11O2Na + : ); analytical data in agreement with literature. [7] Methyl 4-chloro-[1,1'-biphenyl]-2-carboxylate (36) Prepared according to General Procedure B, 25 (0.50 g, 2.00 mmol, 1.0 eq.) and phenylboronic acid (0.26 g, 2.10 mmol, 1.05 eq.) were converted to 36. Purification by column chromatography (npentane/etoac 19:1) yielded the product as a colourless oil (0.34 g, 1.39 mmol, 69%). S10

11 Rf = 0.83 (n-pentane/etoac 8:2); 1 H NMR (400 MHz, CDCl3): δ = 7.75 (d, J = 2.3 Hz, 1H, H4), 7.43 (dd, J = 8.3, 2.3 Hz, 1H, H6), (m, 3H, H12/H11), 7.23 (d, J = 6.5 Hz, 1H, H7), (m, 2H, H10), 3.58 (s, 3H, H1) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C2), (C8), (C9), (C5), (C3), (C7), (C6), (C4), (C10), (C11), (C12), 52.3 (C1) ppm; IR (ATR): ῦ = 3027(w), 2950(w), 1722(s), 1592(w), 1559(w), 1472(m), 1434(m), 1395(w), 1278(s), 1239(s), 1190(w), 1142(m), 1107(m), 1087(m), 1037(w), 1008(w), 971(m), 895(w), 853(m), 832(m), 789(w), 768(s), 727(w), 701(s), 657(w) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C14H11ClO2Na + : ). Methyl 4-methyl-[1,1'-biphenyl]-2-carboxylate (37) Prepared according to General Procedure B, 26 (0.20 g, 0.67 mmol, 1.0 eq.) and phenylboronic acid (0.09 g, 0.70 mmol, 1.05 eq.) were converted to 37. Purification by column chromatography (npentane/etoac 19:1) yielded the product as a colourless oil (0.15 g, 0.66 mmol, 99%). Rf = 0.83 (n-pentane/etoac 8:2); 1 H NMR (500 MHz, CDCl3): δ = (m, 1H, H4), (m, 2H, H11), (m, 2H, H12/H6), (m, 3H, H10/H7), 3.62 (s, 3H, H1), 2.42 (s, 3H, H13) ppm; 13 C NMR (126 MHz, CDCl3): δ = (C2), (C9), (C8), (C5), (C6), (C3), (C7), (C4), (C10), (C11), (C12), 52.0 (C1), 21.1 (C13) ppm; IR (ATR): ῦ = 3026(w), 2949(w), 2920(w), 1718(s), 1612(w), 1562(w), 1481(m), 1434(m), 1402(w), 1296(s), 1244(m), 1204(s), 1143(m), 1090(m), 1037(w), 1009(m), 976(w), 914(w), 882(w), 830(m), 791(m), 765(s), 732(w), 700(s), 676(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C15H14O2Na + : ); analytical data in agreement with literature. [8] Methyl 4-methoxy-[1,1'-biphenyl]-2-carboxylate (38) Prepared according to General Procedure B, 27 (0.22 g, 0.70 mmol, 1.0 eq.) and phenylboronic acid (0.09 g, 0.74 mmol, 1.05 eq.) were converted to 38. Purification by column chromatography (n-pentane/etoac 19:1) yielded the product as a colourless oil (0.14 g, 0.59 mmol, 84%). S11

12 Rf = 0.70 (n-pentane/etoac 8:2); 1 H NMR (500 MHz, CDCl3): δ = (m, 2H, H11), (m, 1H, H4), (m, 4H, H12/H10/H7), 7.07 (dd, J = 8.5, 2.8 Hz, 1H, H6), 3.88 (s, 3H, H13), 3.63 (s, 3H, H1) ppm; 13 C NMR (126 MHz, CDCl3): δ = (C2), (C5), (C9), (C8), (C7), (C3), (C10), (C11), (C12), (C6), (C4), 55.7 (C13), 52.1 (C1) ppm; IR (ATR): ῦ = 3000(w), 2950(w), 2837(w), 1718(s), 1607(m), 1580(w), 1564(w), 1508(m), 1481(s), 1464(m), 1434(s), 1413(m), 1319(m), 1288(s), 1243(s), 1225(s), 1182(m), 1136(m), 1090(m), 1048(s), 1007(m), 983(m), 876(m), 829(m), 786(m), 767(s), 732(m), 703(s) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C15H14O3Na + : ); analytical data in agreement with literature. [9] Methyl 6-methyl-[1,1'-biphenyl]-2-carboxylate (39) Prepared according to General Procedure B, 28 (0.55 g, 1.85 mmol, 1.0 eq.) and phenylboronic acid (0.23 g, 1.95 mmol, 1.05 eq.) were converted to 39. Purification by column chromatography (n-pentane/etoac 19:1) yielded the product as a colourless oil (0.36 g, 1.57 mmol, 85%). Rf = 0.81 (n-pentane/etoac 8:2); 1 H NMR (500 MHz, CDCl3): δ = 7.69 (dd, J = 7.8, 1.4 Hz, 1H, H4), 7.40 (m, 3H, H11/H6), 7.35 (d, J = 7.0 Hz, 1H, H12), 7.32 (t, J = 7.7 Hz, 1H, H5), 7.17 (dd, J = 7.6, 0.8 Hz, 2H, H10), 3.54 (s, 3H, H1), 2.11 (s, 3H, H13) ppm; 13 C NMR (126 MHz, CDCl3): δ = (C2), (C8), (C9), (C7), (C6), (C3), (C10), (C11), (C5), (C4), (C12), 51.9 (C1), 20.8 (C13) ppm; IR (ATR): ῦ = 3061(w), 2950(w), 1717(s), 1593(w), 1497(w), 1458(m), 1433(m), 1378(w), 1290(s), 1266(s), 1231(w), 1191(m), 1174(m), 1136(s), 1094(m), 1074(m), 1009(m), 976(w), 934(w), 916(w), 875(w), 847(w), 809(w), 793(w), 758(s), 743(s), 729(m), 700(s), 660(w) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C15H14O2Na + : ). Methyl 4''-bromo-[1,1':4',1''-terphenyl]-2-carboxylate (40) 0.29 mmol, 10%). Prepared according to General Procedure B, methyl 2-iodobenzoate (0.45 ml, 3.00 mmol, 1.0 eq.) and 4-bromophenylboronic acid (0.63 g, 3.15 mmol, 1.05 eq.) were converted to 40. Purification by column chromatography (npentane/etoac 98:2) yielded the product as a white solid (0.11 g, S12

13 Rf = 0.55 (n-pentane/etoac 9:1); 1 H NMR (600 MHz, CDCl3): δ = 7.87 (ddd, J = 7.8, 1.4, 0.5 Hz, 1H, H7), 7.61 (d, J = 8.6 Hz, 2H, H11), 7.59 (d, J = 8.7 Hz, 2H, H15), 7.56 (td, J = 7.6, 1.4 Hz, 1H, H5), 7.52 (d, J = 8.7 Hz, 2H, H14), 7.44 (td, J = 7.6, 1.3 Hz, 1H, H6), (m, 3H, H10/H4), 3.70 (s, 3H, H1) ppm; 13 C NMR (151 MHz, CDCl3): δ = (C2), (C8), (C9), (C13), (C12), (C15), (C5), (C4), (C3), (C7), (C10), (C14), (C6), (C11), (C16), 52.1 (C1) ppm; IR (ATR): ῦ = 3028(w), 2952(w), 2925(w), 2852(w), 1923(w), 1718(s), 1595(w), 1568(w), 1478(m), 1431(m), 1406(w), 1387(w), 1286(m), 1274(s), 1259(s), 1249(s), 1189(m), 1132(m), 1093(s), 1074(m), 1052(m), 1002(s), 969(w), 959(w), 855(w), 829(w), 815(s), 802(s), 770(s), 740(s), 720(m), 710(m), 663(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C20H15O2BrNa + : ); Mp.: C; analytical data in agreement with literature. [10] Methyl 4-phenyl-[1,1'-biphenyl]-2-carboxylate (41) Prepared according to General Procedure B, 29 (0.29 g, 0.80 mmol, 1.0 eq.) and phenylboronic acid (0.10 g, 0.84 mmol, 1.05 eq.) were converted to 41. Purification by column chromatography (n-pentane/etoac 19:1) yielded the product as a colourless oil (0.07 g, 0.26 mmol, 32%). Rf = 0.80 (n-pentane/etoac 8:2); 1 H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 1.9 Hz, 1H, H4), 7.76 (dd, J = 8.0, 2.0 Hz, 1H, H6), (m, 2H, H14), (m, 3H, H10/H7), (m, 6H, H16/H15/H12/H11), 3.67 (s, 3H, H1) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C2), (C13), (C5), (C9), (C8), (C3), (C7), (C6), (C10), (C4), (C15/C11), (C15/11), (C16/C12), (C16/C12), (C14), 52.2 (C1) ppm; IR (ATR): ῦ = 3026(w), 2948(w), 1721(s), 1600(w), 1476(m), 1451(m), 1434(m), 1395(w), 1311(m), 1238(s), 1146(m), 1090(m), 1054(m), 1008(w), 969(w), 902(w), 844(m), 791(w), 757(s), 699(s), 675(w) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C20H16O2Na + : ); analytical data in agreement with literature. [11] S13

14 Methyl 2-(pyridin-3-yl)benzoate (42) Prepared according to General Procedure B, methyl 2-iodobenzoate (0.23 ml, 1.50 mmol, 1.0 eq.) and 3-pyridinylboronic acid (0.19 g, 1.58 mmol, 1.05 eq.) were converted to 42. Purification by column chromatography (n-pentane/etoac 1:1) yielded the product as a colourless oil (0.25 g, 1.19 mmol, 79%). Rf = 0.27 (n-pentane/etoac 1:1); 1 H NMR (400 MHz, CDCl3): δ = 8.59 (dd, J = 4.8, 1.3 Hz, 1H, H12), 8.55 (d, J = 1.6 Hz, 1H, H13), 7.94 (dd, J = 7.8, 1.0 Hz, 1H, H7), 7.63 (ddd, J = 7.8, 2.3, 1.7 Hz, 1H, H10), 7.58 (td, J = 7.5, 1.4 Hz, 1H, H5), 7.47 (td, J = 7.7, 1.4 Hz, 1H, H6), (m, 2H, H11/H4), 3.67 (s, 3H, H1) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C2), (C13), (C12), (C8), (C9), (C10), (C5), (C4), (C7), (C3), (C6), (C11), 52.2 (C1) ppm; IR (ATR): ῦ = 2951(m), 2921(m), 1721(s), 1600(w), 1576(w), 1469(m), 1446(m), 1433(m), 1409(m), 1288(s), 1256(s), 1189(m), 1126(m), 1090(s), 1057(m), 1027(m), 1001(m), 958(w), 811(m), 759(s), 712(s), 671(w) cm -1 ; HR-ESI-MS: m/z: ([M+H] +, calcd. for C13H11NO2H + : ); analytical data in agreement with literature. [12] General Procedure C for the Saponification of Methyl biphenyl-2-carboxylates The specified methyl biphenyl-2-carboxylate (1.0 eq.) was dissolved in methanol (0.25 M) and aq. NaOH (1 M, 4.0 eq.) was added. The mixture was heated at 50 C for 14 h, before the solvent was removed in vacuo and the crude product was dissolved in aq. HCl (1 M)/EtOAc (1:1). The aqueous layer was extracted with EtOAc (3x) and the combined organic layer were dried over MgSO4 and concentrated in vacuo to give the specified product. 4'-Trifluoromethyl-[1,1'-biphenyl]-2-carboxylic acid (43) Prepared according to General Procedure C, 30 (360 mg, 1.29 mmol) was converted to 43, yielding the product as an off-white solid (347 mg, 1.30 mmol, quant.). Rf = 0.63 (DCM/MeOH 9:1); 1 H NMR (500 MHz, CDCl3): δ = 8.03 (ddd, J = 7.8, 1.4, 0.4 Hz, 1H, H3), 7.64 (d, J = 8.0 Hz, 2H, H10), 7.61 (td, J = 7.5, 1.4 Hz, 1H, H5), 7.49 (td, S14

15 J = 7.7, 1.4 Hz, 1H, H4), 7.43 (d, J = 7.9 Hz, 2H, H9), 7.33 (ddd, J = 7.6, 1.2, 0.4 Hz, 1H, H6) ppm; 13 C NMR (126 MHz, CDCl3): δ = (C1), (q, JCF = 1.4 Hz, C8), (C7), (C5), (C6), (C3), (q, JCF = 32.4 Hz, C11), (C9), (C2), (C4), (q, JCF = 3.7 Hz, C10), (q, JCF = Hz, C12) ppm; 19 F NMR (470 MHz, CDCl3): δ = ppm; IR (ATR): ῦ = 3001(w), 2953(w), 2901(w), 2590(w), 1683(s), 1618(w), 1599(w), 1570(w), 1478(w), 1453(w), 1428(w), 1403(w), 1314(s), 1292(s), 1272(m), 1239(m), 1187(w), 1170(s), 1158(s), 1124(s), 1109(s), 1066(s), 1047(m), 1020(w), 1006(m), 963(w), 935(m), 880(w), 846(s), 802(w), 792(w), 765(s), 741(s), 709(m), 663(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C14H9O2F3Na + : ); Mp.: C; analytical data in agreement with literature. [13] 4'-Bromo-[1,1'-biphenyl]-2-carboxylic acid (44) Prepared according to General Procedure C, 31 (463 mg, 1.59 mmol) was converted to 44, yielding the product as a white solid (441 mg, 1.59 mmol, quant.). Rf = 0.34 (DCM/MeOH 9:1); 1 H NMR (400 MHz, CDCl3): δ = 7.99 (dd, J = 7.8, 1.1 Hz, 1H, H3), 7.58 (td, J = 7.6, 1.4 Hz, 1H, H5), 7.52 (d, J = 8.5 Hz, 2H, H10), 7.45 (td, J = 7.7, 1.3 Hz, 1H, H4), 7.32 (dd, J = 7.7, 0.9 Hz, 1H, H6), 7.20 (d, J = 8.5 Hz, 2H, H9) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C1), (C7), (C8), (C5), (C10), (C6), (C3), (C9), (C2), (C4), (C11) ppm; IR (ATR): ῦ = 2818(w), 2643(w), 2538(w), 1902(w), 1676(s), 1598(m), 1589(m), 1574(m), 1497(w), 1474(m), 1453(s), 1413(m), 1390(m), 1305(s), 1291(s), 1260(s), 1181(w), 1163(m), 1140(m), 1100(w), 1068(m), 1048(w), 1016(w), 1102(m), 941(m), 888(m), 826(s), 806(m), 755(s), 718(s), 703(s), 668(s) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C13H9O2BrNa + : ); Mp.: C; analytical data in agreement with literature. [14] 4'-Fluoro-[1,1'-biphenyl]-2-carboxylic acid (45) Prepared according to General Procedure C, 32 (315 mg, 1.37 mmol) was converted to 45, yielding the product as a white solid (297 mg, 1.37 mmol, quant.). S15

16 Rf = 0.42 (DCM/MeOH 9:1); 1 H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 7.2 Hz, 1H, H3), 7.57 (t, J = 7.5 Hz, 1H, H5), 7.44 (t, J = 7.3 Hz, 1H, H4), 7.34 (d, J = 7.5 Hz, 1H, H6), 7.29 (dd, J = 8.5, 5.4 Hz, 2H, H9), 7.08 (t, J = 8.7 Hz, 2H, H10) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C1), (d, JCF = Hz, C11), (C7), (d, JCF = 3.2 Hz, C8), (C5), (C6), (C3), (d, JCF = 8.3 Hz, C9), (C2), (C4), (d, JCF = 21.4 Hz, C10) ppm; 19 F NMR (282 MHz, CDCl3): δ = ppm; IR (ATR): ῦ = 2900(w), 2820(w), 2650(w), 2540(w), 1687(s), 1607(w), 1598(m), 1512(m), 1483(m), 1453(m), 1401(m), 1307(m), 1295(s), 1282(m), 1259(m), 1214(s), 1162(m), 1146(w), 1136(w), 1093(m), 1048(w), 1018(w), 1008(w), 992(w), 905(m), 884(w), 838(s), 825(m), 800(s), 762(s), 727(m), 715(m), 706(m) cm -1 ; HR-ESI-MS: m/z: ([M-H], calcd. for C13H9FO2 : ); Mp.: C; analytical data in agreement with literature. [14] 4'-(tert-Butyl)-[1,1'-biphenyl]-2-carboxylic acid (46) Prepared according to General Procedure C, 33 (389 mg, 1.45 mmol) was converted to 46, yielding the product as an off-white solid (370 mg, 1.45 mmol, quant.). Rf = 0.60 (DCM/MeOH 9:1); 1 H NMR (400 MHz, CDCl3): δ = 7.95 (dd, J = 7.8, 1.1 Hz, 1H, H3), 7.55 (td, J = 7.6, 1.4 Hz, 1H, H5), (m, 4H, H10/H6/H4), 7.29 (d, J = 8.5 Hz, 2H, H9), 1.36 (s, 9H, H13) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C1), (C11), (C7), (C8), (C5), (C4), (C3), (C2), (C9), (C6), (C10), 34.7 (C12), 31.5 (C13) ppm; IR (ATR): ῦ = 2960(m), 2866(w), 2634(w), 2573(w), 1699(m), 1678(s), 1598(m), 1575(w), 1515(w), 1482(m), 1451(m), 1422(w), 1400(m), 1361(w), 1291(s), 1253(s), 1201(w), 1166(w), 1140(m), 1119(w), 1093(m), 1051(w), 1028(w), 1002(w), 960(w), 932(m), 831(s), 802(m), 759(s), 740(s), 705(m), 682(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C17H18O2Na + : ); Mp.: C; analytical data in agreement with literature. [14] S16

17 4'-Methoxy-[1,1'-biphenyl]-2-carboxylic acid (47) Prepared according to General Procedure C, 34 (320 mg, 1.32 mmol) was converted to 47, yielding the product as an off-white solid (302 mg, 1.32 mmol, quant.). Rf = 0.43 (DCM/MeOH 9:1); 1 H NMR (400 MHz, CDCl3): δ = 7.93 (dd, J = 7.8, 1.1 Hz, 1H, H3), 7.55 (td, J = 7.5, 1.4 Hz, 1H, H5), 7.38 (m, 2H, H6/H4), 7.28 (d, J = 8.8 Hz, 2H, H9), 6.93 (d, J = 8.8 Hz, 2H, H10), 3.85 (s, 3H, H12) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C1), (C11), (C7), (C8), (C5), (C6), (C3), (C9), (C2), (C4), (C10), 55.4 (C12) ppm; IR (ATR): ῦ = 3001(w), 2959(w), 2932(w), 2838(w), 2542(w), 1675(s), 1609(m), 1587(m), 1578(w), 1566(w), 1513(m), 1481(m), 1453(s), 1440(m), 1426(w), 1405(w), 1302(s), 1240(s), 1178(s), 1139(m), 1112(m), 1090(m), 1048(m), 1016(m), 1034(s), 1016(m), 1000(m), 938(m), 836(s), 820(s), 795(m), 760(s), 730(s), 718(m), 704(s) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C14H12O3Na + : ); Mp.: C; analytical data in agreement with literature. [14] 4-Fluoro-[1,1'-biphenyl]-2-carboxylic acid (48) Prepared according to General Procedure C, 35 (103 mg, 0.45 mmol) was converted to 48, yielding the product as a white solid (78 mg, 0.36 mmol, 80%). Rf = 0.41 (DCM/MeOH 9:1); 1 H NMR (600 MHz, CDCl3): δ = 7.64 (dd, J = 9.1, 2.7 Hz, 1H, H3), (m, 4H, H11/H10/H6), (m, 3H, H9/H5) ppm; 13 C NMR (151 MHz, CDCl3): δ = (C1), (d, JCF = Hz, C4), (C8), (d, JCF = 3.2 Hz, C7), (d, JCF = 7.5 Hz, C6), (C2), (C9), (C10), (C11), (d, JCF = 20.8 Hz, C5), (d, JCF = 23.4 Hz, C3) ppm; 19 F NMR (564 MHz, CDCl3): δ = (td, J = 8.6, 5.7 Hz) ppm; IR (ATR): ῦ = 2920(m), 2852(w), 2571(w), 1690(s), 1610(w), 1582(m), 1510(w), 1478(m), 1448(m), 1440(m), 1301(s), 1287(m), 1258(m), 1203(m), 1158(w), 1130(m), 1075(w), 1011(m), 930(m), 919(m), 888(m), 841(m), 773(s), 766(s), 734(m), 705(s), 665(m) cm -1 ; HR-ESI-MS: m/z: ([M-H], calcd. for C13H9FO2 : ); Mp.: C. S17

18 4-Chloro-[1,1'-biphenyl]-2-carboxylic acid (49) Prepared according to General Procedure C, 36 (340 mg, 1.38 mmol) was converted to 49, yielding the product as a white solid (267 mg, 1.15 mmol, 83%). Rf = 0.50 (DCM/MeOH 9:1); 1 H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 2.3 Hz, 1H, H3), 7.53 (dd, J = 8.3, 2.3 Hz, 1H, H5), (m, 3H, H11/H9), (m, 3H, H10/H6) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C1), (C7), (C8), (C2), (C6), (C5), (C4), (C3), (C10), (C9), (C11) ppm; IR (ATR): ῦ = 2853(w), 2652(w), 2563(w), 1683(s), 1595(w), 1558(w), 1474(m), 1438(m), 1388(w), 1303(s), 1258(m), 1154(w), 1108(m), 1096(w), 1073(w), 1034(w), 1008(w), 996(w), 943(m), 916(m), 898(m), 861(m), 838(s), 792(w), 768(s), 751(s), 723(m), 701(s), 674(m), 655(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C13H9ClO2Na + : ); Mp.: C. 4-Methyl-[1,1'-biphenyl]-2-carboxylic acid (50) Prepared according to General Procedure C, 37 (132 mg, 0.58 mmol) was converted to 50, yielding the product as a white solid (104 mg, 0.49 mmol, 84%). Rf = 0.66 (DCM/MeOH 9:1); 1 H NMR (400 MHz, CDCl3): δ = 7.77 (dd, J = 1.3, 0.5 Hz, 1H, H3), (m, 3H, H9/H5), (m, 3H, H11/H10), 7.26 (d, J = 7.8 Hz, 1H, H6), 2.43 (s, 3H, H12) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C1), (C8), (C7), (C4), (C5), (2C, C6/C3), (C2), (C10), (C9), (C11), 21.0 (C12) ppm; IR (ATR): ῦ = 3028(w), 2855(m), 2668(w), 2583(m), 1676(s), 1611(m), 1561(w), 1481(m), 1436(m), 1307(s), 1273(m), 1252(m), 1216(m), 1146(w), 1101(w), 1073(w), 1009(m), 950(m), 917(m), 903(m), 836(s), 795(w), 768(s), 734(m), 701(s), 667(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C14H12O2Na + : ); Mp.: C; analytical data in agreement with literature. [14] S18

19 4-Methoxy-[1,1'-biphenyl]-2-carboxylic acid (51) Prepared according to General Procedure C, 38 (134 mg, 0.54 mmol) was converted to 51, yielding the product as a white solid (120 mg, 0.53 mmol, 95%). Rf = 0.59 (DCM/MeOH 9:1); 1 H NMR (400 MHz, CDCl3): δ = 7.46 (d, J = 2.8 Hz, 1H, H3), (m, 6H, H11/H10/H9/H6), 7.11 (dd, J = 8.5, 2.8 Hz, 1H, H5), 3.88 (s, 3H, H12) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C1), (C4), (C8), (C7), (C6), (C2), (C9), (C10), (C11), (C5), (C3), 55.7 (C12) ppm; IR (ATR): ῦ = 3676(w), 2988(m), 2967(m), 2901(w), 2564(m), 1681(s), 1604(m), 1582(w), 1565(w), 1508(w), 1484(m), 1471(m), 1451(m), 1427(s), 1394(m), 1319(m), 1306(m), 1271(m), 1231(s), 1255(s), 1186(m), 1138(m), 1075(m), 1067(m), 1043(s), 1032(m), 1006(m), 995(w), 936(m), 914(m), 862(m), 843(s), 792(w), 772(s), 752(s), 730(m), 701(s), 660(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C14H12O3Na + : ); Mp.: C; analytical data in agreement with literature. [15] 6-Methyl-[1,1'-biphenyl]-2-carboxylic acid (52) Prepared according to General Procedure C, 39 (340 mg, 1.50 mmol) was converted to 52, yielding the product as a beige solid (320 mg, 1.50 mmol, quant.). Rf = 0.45 (DCM/MeOH 9:1); 1 H NMR (500 MHz, CDCl3): δ = 7.78 (d, J = 7.8 Hz, 1H, H3), 7.44 (d, J = 7.7 Hz, 1H, H5), 7.38 (tt, J = 8.0, 1.9 Hz, 2H, H10), 7.34 (dt, J = 7.3, 1.6 Hz, 1H, H11), 7.32 (t, J = 7.7 Hz, 1H, H4), 7.15 (dd, J = 8.1, 1.4 Hz, 2H, H9), 2.09 (s, 3H, H12) ppm; 13 C NMR (126 MHz, CDCl3): δ = (C1), (C7), (C8), (C2), (C5), (C6), (C9), (C10), (C3), (C4), (C11), 20.9 (C12) ppm; IR (ATR): ῦ = 2919(w), 2671(w), 2564(w), 1683(s), 1591(w), 1496(w), 1459(w), 1441(m), 1413(m), 1378(w), 1298(s), 1186(m), 1153(m), 1102(w), 1074(w), 1036(w), 1008(w), 922(m), 811(m), 770(m), 760(s), 735(s), 716(m), 698(s) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C14H12O2Na + : ); Mp.: C. S19

20 4''-Bromo-[1,1':4',1''-terphenyl]-2-carboxylic acid (53) Prepared according to General Procedure C, 40 (105 mg, 0.29 mmol) was converted to 53, yielding the product as a white solid (98 mg, 0.28 mmol, 97%). Rf = 0.41 (DCM/MeOH 9:1); 1 H NMR (400 MHz, CD3OD): δ = 7.83 (dd, J = 7.8, 1.0 Hz, 1H, H3), 7.64 (d, J = 8.5 Hz, 2H, H10), (m, 4H, H14/13), 7.56 (dd, J = 7.5, 1.5 Hz, 1H, H5), 7.46 (td, J = 7.7, 1.3 Hz, 1H, H4), (m, 3H, H9/6) ppm; 13 C NMR (101 MHz, CD3OD): δ = (C1), (C7), (C8), (C12), (C11), (C2), (C14/13), (C5), (C6), (C3), (C9), (C14/13), (C4), (C10), (C15) ppm; IR (ATR): ῦ = 2853(w), 2648(w), 2565(w), 1910(w), 1683(s), 1596(m), 1568(w), 1475(m), 1452(m), 1407(m), 1381(m), 1293(s), 1248(m), 1200(w), 1139(w), 1093(w), 1075(m), 1002(s), 944(m), 854(m), 819(s), 804(m), 760(s), 739(m), 704(m), 660(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C19H13O2BrNa + : ); Mp.: C. [1,1':4',1''-Terphenyl]-2'-carboxylic acid (54) Prepared according to General Procedure C, 41 (78 mg, 0.27 mmol) was converted to 54, yielding the product as an offwhite solid (52 mg, 0.19 mmol, 70%). Rf = 0.52 (DCM/MeOH 9:1); 1 H NMR (400 MHz, CDCl3): δ = 8.19 (d, J = 1.9 Hz, 1H, H3), 7.80 (dd, J = 8.0, 2.0 Hz, 1H, H5), 7.66 (dd, J = 8.3, 1.3 Hz, 2H, H13), (m, 9H, H15/H14/H11/H10/H9/H6) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C1), (C7), (C8), (C4), (C12), (C6), (C5), (C3), (C14/C13/C11/C9), (C14/C13/C11/C10/C9), (C15/C14), (C15/C14), (C2), (C14/C13/C11/C10/C9) ppm; IR (ATR): ῦ = 2973(w), 2921(w), 2632(w), 2544(w), 1726(w), 1685(s), 1599(w), 1581(w), 1557(w), 1479(m), 1452(m), 1443(w), 1409(m), 1297(m), 1252(s), 1186(w), 1153(w), 1101(w), 1076(m), 1036(w), 1027(w), 1007(w), 968(w), 918(m), 905(m), 857(m), 838(m), 789(s), 760(s), 702(s), 690(s), 666(s) cm -1 ; HR-ESI-MS: m/z: S20

21 ([M-H], calcd. for C19H14O2 : ); Mp.: C; analytical data in agreement with literature. [13] 2-(Pyridin-3-yl)benzoic acid (55) Prepared according to General Procedure C, 42 (230 mg, 1.08 mmol) was converted to 55. After the reaction was being cooled to room temperature the ph was adjusted to 5 by addition of aq. HCl (1M) and extracted with EtOAc (7x). The combined organic layers were dried over MgSO4 and concentrated in vacuo yielding the product as an off-white solid (140 mg, 0.70 mmol, 65%). Rf = 0.25 (DCM/MeOH 9:1); 1 H NMR (400 MHz, d6-dmso): δ = 8.64 (bs, 1H, H12), 7.86 (dd, J = 7.7, 1.2 Hz, 1H, H3), 7.77 (d, J = 7.8 Hz, 1H, H9), 7.64 (td, J = 7.6, 1.4 Hz, 1H, H5) (m, 2H, H10/4), 7.41 (dd, J = 7.7, 1.0 Hz, 1H, H6), obscured (H11) ppm; 13 C NMR (101 MHz, d6-dmso): δ = (C1), (C12), (C7), (C9), (C5), (C2), (C6), (C3), (C4), obscured (C11/10/8) ppm; IR (ATR): ῦ = 3070(w), 2922(w), 2853(w), 2411(bw), 1679(m), 1601(m), 1473(w), 1414(m), 1269(m), 1192(m), 1130(m), 1047(s), 1010(s), 951(s), 934(m), 809(s), 753(s), 716(m), 700(s), 661(s) cm -1 ; HR- ESI-MS: m/z: ([M+H] +, calcd. for C12H10NO2H + : ); Mp.: C. analytical data in agreement with literature. [16] General Procedure D for ( )-Riboflavin Catalysed Oxidative Cyclisation of Biphenyl-2- Carboxylic Acids The specified carboxylic acid (0.10 mmol, 1.0 eq.) and ( )-riboflavin (1.9 mg, mmol, 0.05 eq.) were suspended in MeOH (1.5 ml). The solution was purged with oxygen (balloon) for 5 min and the mixture was stirred for the specified time under an atmosphere of oxygen and UV-light irradiation (402 nm). After every 12 h another portion of ( )-riboflavin (1.9 mg, mmol, 0.05 eq.) was added. Afterwards, the solvent was removed in vacuo and the crude was purified by column chromatography (SiO2, n-pentane/etoac 98:2 9:1) to yield the specified product. S21

22 6H-Benzo[c]chromen-6-one (10) Prepared according to General Procedure D, [1,1'-biphenyl]-2- carboxylic acid (20 mg, 0.1 mmol) was converted to 10 in 24 h yielding the product as a white solid (16 mg, mmol, 84%). Rf = 0.58 (n-pentane/etoac 8:2); 1 H NMR (400 MHz, CDCl3): δ = (m, 1H, H3), (m, 1H, H6), 8.06 (dd, J = 7.9, 1.6 Hz, 1H, H9), (m, 1H, H5), 7.58 (ddd, J = 8.3, 7.3, 1.1 Hz, 1H, H4), 7.48 (ddd, J = 8.5, 7.1, 1.5 Hz, 1H, H11), (m, 2H, H12/10) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C1), (C13), (C5), (C7), (C3), (C11), (C4), (C10), (C9), (C6), (C2), (C8), (C12) ppm; IR (ATR): ῦ = 3068(w), 3034(w), 2925(w), 1965(w), 1919(w), 1784(w), 1760(w), 1724(s), 1606(s), 1567(w), 1505(w), 1484(m), 1455(m), 1433(m), 1336(w), 1321(w), 1303(m), 1284(w), 1263(m), 1237(m), 1204(m), 1158(w), 1127(w), 1092(s), 1076(s), 1032(s), 1008(w), 958(w), 938(w), 895(m), 875(w), 852(w), 788(w), 742(s), 717(s), 680(s), 659(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C13H8O2Na + : ); Mp.: C; analytical data in agreement with literature. [14] As a representative example, this reaction was repeated on a 1 mmol scale: A 10 ml round-bottomed flask was charged with [1,1'-biphenyl]-2-carboxylic acid (198 mg, 1.0 mmol, 1.0 eq.), ( )-riboflavin (18.8 mg, 0.05 mmol, 0.05 eq.), and MeOH (7.5 ml). The reaction vessel was sealed with a septum, purged with oxygen (balloon) for 10 min and irradiated at 402 nm for 24 h at ambient temperature. After this time, a second portion ( )- riboflavin (18.8 mg, 0.05 mmol, 0.05 eq.) was added and the reaction was irradiated for another 24 h. Afterwards, the solvent was removed in vacuo and the crude was purified by column chromatography (SiO2, n-pentane/etoac 98:2 9:1) to yield the product as a white solid (123 mg, 0.63 mmol, 63%). S22

23 3-(Trifluoromethyl)-6H-benzo[c]chromen-6-one (11) Prepared according to General Procedure D, 43 (27 mg, 0.1 mmol) was converted to 11 in 36 h yielding the product as a white solid (12 mg, mmol, 45%). Rf = 0.33 (n-pentane/etoac 9:1); 1 H NMR (600 MHz, CDCl3): δ = 8.44 (ddd, J = 7.9, 1.3, 0.3 Hz, 1H, H3), 8.19 (d, J = 8.3 Hz, 1H, H9), 8.17 (d, J = 8.1 Hz, 1H, H6), 7.89 (td, J = 7.7, 1.4 Hz, 1H, H5), 7.68 (td, J = 7.3, 1.1 Hz, 1H, H4), 7.63 (d, J = 1.2 Hz, 1H, H12), 7.59 (dd, J = 8.3, 1.2 Hz, 1H, H10) ppm; 13 C NMR (151 MHz, CDCl3): δ = (C1), (C13), (C5), (C8), (q, JCF = 33.5 Hz, C11), (C3), (C4), (C9), (q, JCF = Hz, C14), (C6), (C2), (C7), (q, JCF = 3.8 Hz, C10), (q, JCF = 4.0 Hz, C12) ppm; 19 F NMR (564 MHz, CDCl3): δ = ppm; IR (ATR): ῦ = 3084(w), 2852(w), 1728(s), 1706(m), 1627(w), 1608(m), 1522(w), 1485(w), 1461(w), 1407(m), 1334(m), 1320(m), 1270(m), 1234(m), 1206(m), 1168(m), 1159(m), 1141(s), 1108(s), 1081(m), 1070(s), 1036(m), 991(m), 967(w), 936(m), 873(m), 831(m), 812(w), 790(w), 770(s), 753(w), 721(s), 706(m), 692(m), 681(s), 658(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C14H7O2F3Na + : ); Mp.: C; analytical data in agreement with literature. [14] 3-Bromo-6H-benzo[c]chromen-6-one (12) Prepared according to General Procedure D, 44 (28 mg, 0.1 mmol) was converted to 12 in 24 h yielding the product as a white solid (19 mg, mmol, 69%). Rf = 0.66 (n-pentane/etoac 8:2); 1 H NMR (600 MHz, CDCl3): δ = 8.37 (dd, J = 7.9, 1.4 Hz, 1H, H3), 8.06 (d, J = 8.1 Hz, 1H, H6), 7.90 (d, J = 8.4 Hz, 1H, H9), 7.83 (td, J = 7.3, 1.4 Hz, 1H, H5), 7.60 (td, J = 7.8, 1.4 Hz, 1H, H4), 7.51 (d, J = 2.0 Hz, 1H, H12), 7.45 (dd, J = 8.5, 2.0 Hz, 1H, H10) ppm; 13 C NMR (151 MHz, CDCl3): δ = (C1), (C13), (C5), (C7), (C3), (C4), (C10), (C9), (C11), (C6), (C2), (C12), (C8) ppm; IR (ATR): ῦ = 3074(w), 2923(w), 2853(w), 1745(s), 1595(s), 1473(m), 1451(m), 1394(m), 1331(w), 1314(w), 1303(m), 1265(m), 1255(s), 1227(m), 1202(m), 1164(w), 1141(m), 1112(w), 1098(m), 1063(s), 1027(m), 1005(m), 960(w), 916(m), S23

24 884(w), 854(m), 813(m), 795(w), 787(m), 761(s), 708(s), 675(m), 682(s) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C13H7O2BrNa + : ); Mp.: C; analytical data in agreement with literature. [14] 3-Fluoro-6H-benzo[c]chromen-6-one (13) Prepared according to General Procedure D, 45 (22 mg, 0.1 mmol) was converted to 13 in 36 h yielding the product as a white solid (16 mg, mmol, 72%). Rf = 0.59 (n-pentane/etoac 8:2); 1 H NMR (400 MHz, CDCl3): δ = 8.38 (dd, J = 8.0, 0.9 Hz, 1H, H3), 8.03 (m, 2H, H9/H6), 7.83 (td, J = 7.8, 1.4 Hz, 1H, H5), 7.58 (td, J = 7.6, 1.2 Hz, 1H, H4), 7.08 (m, 2H, H12/H10) ppm; 13 C NMR (101 MHz, CDCl3): δ = (d, JCF = Hz, C11), (C1), (d, JCF = 12.4 Hz, C13), (C5), (C7), (C3), (C4), (d, JCF = 10.1 Hz, C9), (C6), (C2), (d, JCF = 3.5 Hz, C8), (d, JCF = 22.6 Hz, C12), (d, JCF = 25.2 Hz, C10) ppm; 19 F NMR (282 MHz, CDCl3): δ = ppm; IR (ATR): ῦ = 3074(w), 2923(w), 1745(s), 1607(s), 1516(m), 1478(m), 1456(m), 1414(m), 1338(w), 1308(m), 1273(s), 1262(s), 1216(w), 1153(s), 1098(s), 1074(s), 1030(m), 1008(m), 978(m), 938(w), 875(m), 855(w), 827(m), 813(m), 790(w), 762(s), 755(s), 712(s), 681(s) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C13H7O2FNa + : ); Mp.: C; analytical data in agreement with literature. [14] 3-(tert-Butyl)-6H-benzo[c]chromen-6-one (14) Prepared according to General Procedure D, 46 (25 mg, 0.1 mmol) was converted to 14 in 24 h yielding the product as a white solid (20 mg, mmol, 78%). Rf = 0.57 (n-pentane/etoac 9:1); 1 H NMR (500 MHz, CDCl3): δ = 8.38 (dd, J = 7.8, 0.9 Hz, 1H, H3), 8.08 (d, J = 8.1 Hz, 1H, H6), 7.97 (d, J = 9.0 Hz, 1H, H9), 7.80 (td, J = 7.7,1.4 Hz, 1H, H5), 7.55 (td, J = 7.6, 1.0 Hz, 1H, H4), (m, 2H, H12/H10), 1.37 (s, 9H, H15) ppm; 13 C NMR (126 MHz, CDCl3): δ = (C1), (C11), (C13), (C7), (C5), (C3), (C4), (C9), (C10), (C6), (C2), S24

25 (C8), (C12), 35.2 (C14), 31.2 (C15) ppm; IR (ATR): ῦ = 3663(w), 2968(m), 2951(m), 2902(m), 1731(s), 1620(m), 1608(m), 1558(w), 1477(m), 1456(m), 1409(m), 1395(m), 1354(m), 1334(w), 1310(m), 1298(m), 1263(s), 1229(m), 1199(m), 1153(w), 1095(s), 1076(s), 1031(s), 949(w), 906(w), 864(m), 841(w), 819(w), 787(w), 771(s), 722(s), 684(m) cm -1 ; HR- ESI-MS: m/z: ([M+Na] +, calcd. for C17H16O2Na + : ); Mp.: C; analytical data in agreement with literature. [14] 3-Methoxy-6H-benzo[c]chromen-6-one (15) Prepared according to General Procedure D, 47 (23 mg, 0.1 mmol) was converted to 15 in 24 h yielding the product as a white solid (11 mg, mmol, 48%). Rf = 0.58 (n-pentane/etoac 8:2); 1 H NMR (400 MHz, CDCl3): δ = 8.35 (dd, J = 8.0, 0.9 Hz, 1H, H3), 8.00 (d, J = 8.0 Hz, 1H, H6), 7.94 (d, J = 8.9 Hz, 1H, H10), 7.78 (td, J = 7.5, 1.5 Hz, 1H, H5), 7.50 (td, J = 7.5, 1.0 Hz, 1H, H4), 6.91 (dd, J = 8.8, 2.5 Hz, 1H, H9), 6.86 (d, J = 2.5 Hz, 1H, H12), 3.88 (s, 3H, H14) ppm; 13 C NMR (101 MHz, CDCl3): δ = (C11/C1), (C13), (C7), (C5), (C3), (C4), (C10), (C6), (C2), (C9), (C8), (C12), 55.8 (C14) ppm; IR (ATR): ῦ = 3003(w), 2989(w), 2922(w), 1730(s), 1619(s), 1609(s), 1521(w), 1476(m), 1468(m), 1458(m), 1437(m), 1416(m), 1348(m), 1331(w), 1315(m), 1277(m), 1265(s), 1218(m), 1197(s), 1163(s), 1130(m), 1108(m), 1099(s), 1074(m), 1031(s), 1004(m), 962(m), 944(w), 871(w), 852(m), 834(m), 816(m), 807(m), 760(s), 710(s), 679(s), 658(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C14H10O3Na + : ); Mp.: C; analytical data in agreement with literature. [14] 8-Fluoro-6H-benzo[c]chromen-6-one (16) Prepared according to General Procedure D, 48 (22 mg, 0.1 mmol) was converted to 16 in 24 h yielding the product as a white solid (19 mg, mmol, 90%). S25

26 Rf = 0.72 (n-pentane/etoac 8:2); 1 H NMR (500 MHz, CDCl3): δ = 8.12 (dd, J = 8.9, 4.9 Hz, 1H, H6), 8.04 (dd, J = 8.5, 2.7 Hz, 1H, H3), 8.00 (dd, J = 8.0, 1.5 Hz, 1H, H9), 7.54 (ddd, J = 8.8, 7.9, 2.8 Hz, 1H, H5), 7.48 (ddd, J = 8.5, 7.2, 1.5 Hz, 1H, H11), (m, 2H, H12/H10) ppm; 13 C NMR (126 MHz, CDCl3): δ = (d, JCF = Hz, C4), (d, JCF = 3.3 Hz, C1), (d, JCF = 1.0 Hz, C13), (d, J = 2.9 Hz, C7), (d, JCF = 0.7 Hz, C11), (C10), (d, JCF = 7.9 Hz, C6), (d, JCF = 8.1 Hz, C2), (d, JCF = 23.1 Hz, C5), (d, JCF = 0.7 Hz, C9), (C12), (d, JCF = 1.0 Hz, C8), (d, JCF = 23.4 Hz, C3) ppm; 19 F NMR (470 MHz, CDCl3): δ = (td, J = 8.2, 4.8 Hz) ppm; IR (ATR): ῦ = 3081(w), 2971(w), 2923(w), 1720(s), 1608(m), 1508(m), 1479(s), 1454(m), 1410(m), 1380(w), 1333(m), 1307(m), 1273(s), 1233(s), 1196(m), 1156(m), 1126(w), 1107(m), 1066(s), 1008(w), 930(s), 898(w), 874(s), 828(s), 749(s), 732(m), 723(s), 653(m) cm -1 ; HR- ESI-MS: m/z: ([M+Na] +, calcd. for C13H7O2FNa + : ); Mp.: C; analytical data in agreement with literature. [17] 8-Chloro-6H-benzo[c]chromen-6-one (17) Prepared according to General Procedure D, 49 (23 mg, 0.1 mmol) was converted to 17 in 24 h yielding the product as a white solid (18 mg, mmol, 79%). Rf = 0.43 (n-pentane/etoac 8:2); 1 H NMR (500 MHz, CDCl3): δ = 8.34 (d, J = 2.3 Hz, 1H, H3), 8.05 (dd, J = 8.6, 0.4 Hz, 1H, H6), 8.00 (dd, J = 8.4, 1.5 Hz, 1H, H9), 7.76 (ddd, J = 8.6, 2.3, 0.3 Hz, 1H, H5), 7.49 (dd, J = 7.1, 1.5 Hz, 1H, H11), (m, 2H, H12/H10) ppm; 13 C NMR (126 MHz, CDCl3): δ = (C1), (C13), (C5), (C4), (C7), (C11), (C3), (C10), (C6), (C9), (C2), (C12), (C8) ppm; IR (ATR): ῦ = 3077(w), 2923(w), 1718(s), 1624(w), 1604(s), 1559(w), 1503(w), 1472(m), 1452(m), 1401(m), 1344(w), 1308(s), 1275(m), 1249(m), 1200(m), 1160(m), 1141(m), 1115(m), 1077(m), 1044(w), 1004(w), 942(w), 905(m), 892(m), 857(w), 828(s), 782(w), 749(s), 730(m), 689(m), 683(m) cm -1 ; HR-ESI-MS: m/z: ([M+Na] +, calcd. for C13H8O2ClNa + : ); Mp.: C. S26