Nickel-Catalyzed Denitrogenative Cross-Coupling Reaction of 1,2,3- Benzotriazin-4(3H)-ones with Organoboronic Acids: An Easy Access to Ortho-Arylated and Alkenylated Benzamides Madasamy Hari Balakrishnan a, Kotturaja Sathriyan a and Subramaniyan Mannathan a,b * a SRM Research Institute, SRM Institute of Science and Technology (formerly known as SRM University), Kattankulathur, Chennai 603203, India b Department of Chemistry, SRM University-AP, Amaravati 522502, Andhra Pradesh, India. Email: mannathan.s@srmap.edu.in Supporting Information Table of Contents Page S2 S4 Page S5 Page S5 Page S6 S17 Experimental Section Effect of Solvents References 1 H NMR, 13 C NMR and HRMS data S1
Experimental Section: All experiments were carried out in oven-dried glassware, in an atmosphere of nitrogen, unless specified otherwise, by standard Schenk techniques. All the solvents used for extraction, filtration and flash chromatography were used without further purification. All reagents were purchased from Sigma-Aldrich, Alfa Aesar or Avra and were used without further purification. Flash column chromatography was performed on 100-200 mesh silica gel. 1 H-, and 13 C NMR spectroscopy was performed on Bruker BBFO (500 MHz) spectrometer. Chemical shifts were determined relative to the residual solvent peaks (CHCl3, δ = 7.26 ppm for 1 H NMR, δ = 77.0 ppm for 13 C NMR). The mass spectra (ESI-MS) were recorded on an Agilent 6200 Series TOF LC/MS spectrometer. Ni(cod)2 were purchased from Sigma Aldrich and used. The starting materials, benzotriazin-4(3h)-ones 1a-f 1, 1j 1, 1g-h 2, 3, 1i 4 were prepared according to literature procedure. Organo boronic acids 2 are purchased from spectrochem, sigma aldrich and Alfa Aesar, and used. Tri n-butyl phosphine was purchased from Alfa Aesar and used. General preparation of ortho-arylated benzamides (3) A sealed tube containing 1,2,3-benzotriazin-4(3H)-ones 1 (0.40 mmol), Ni(cod)2 (0.040 mmol), P(n-Bu)3 (0.080 mmol), Na2CO3 (0.40 mmol) and organo boronic acid 2 (0.60 mmol) was evacuated and purged with nitrogen gas three times. To this mixture, dry 1,4-dioxane (2 ml) was added via syringe under nitrogen atmosphere at room temperature and stirred for 2 min. The seal tube was then placed in a preheated oil bath at 80 C for 12 h. After completion of reaction the mixture was cooled and diluted with Ethyl acetate (10 ml). The mixture was filtered through a Celite and silica gel pad and was washed with Ethyl acetate (3 10 ml). The filtrate was concentrated and the residue was purified by silica gel column chromatography using suitable eluent to afford the desired pure product 3. S2
Procedure for the preparation of ortho-arylated benzamides 3a (1.00 mmol scale) A sealed tube containing 1,2,3-benzotriazin-4(3H)-ones 1a (253 mg, 1.0 mmol), Ni(cod)2 (27.6 mg, 0.1 mmol), P(n-Bu)3 (40 mg, 0.2 mmol), Na2CO3 (106 mg, 1 mmol) and organo boronic acid 2a (183 mg, 1.5 mmol) was evacuated and purged with nitrogen gas three times. To this mixture, dry 1,4-dioxane (3 ml) was added via syringe under nitrogen atmosphere at room temperature and stirred for 2 min. The seal tube was then placed in a preheated oil bath at 80 C for 12 h. After completion of reaction, the mixture was cooled and diluted with Ethyl acetate (10 ml). The mixture was filtered through a Celite and silica gel pad and was washed with Ethyl acetate (3 10 ml). The filtrate was concentrated and the residue was purified by silica gel column chromatography using hexane/ethyl acetate (85/15) as eluent to afford the desired pure product 3a (267 mg, 88 % yield). General procedure for the preparation of fluorenones (7) Fluorenones (7) has been prepared according to the literature procedure 4. Ortho-arylated benzamides 3a (121 mg, 0.40 mmol scale reaction) and (CF3CO)2O (3 ml) were taken in a sealed pressure tube. The reaction mixture was allowed to stir at 100 C for 2 h. Then, the reaction mixture was refluxed in the presence of conc. HCl (1.5 ml) at 100 C for additional 1 h. After completion of the reaction, the reaction mixture was allowed to cool to room temperature and was extracted with ethyl acetate, washed with water and brine, and dried with anhydrous Na2SO4. The filtrate was concentrated and the residue was purified through a silica gel column chromatography using hexanes and ethyl acetate as eluent to give pure 7a (64 mg, S3
90 % yield). 7b-c were prepared by following the same procedure mentioned above with 3c and 3b as starting material accordingly. Procedure for the preparation of 4-Methoxy-N-((4'-methoxy-[1,1'-biphenyl]-2- yl)methyl)aniline (8) 4-Methoxy-N-((4'-methoxy-[1,1'-biphenyl]-2-yl)methyl)aniline 8 was prepared according to the literature procedure 6. In a sealed pressure tube LiAlH4 (39 mg, 1.2 mmol) was suspended in dry THF (3mL). To this 3b (133 mg, 0.4 mmol) in THF solution was added drop wisely for 15 minutes at room temperature under nitrogen atmosphere. Then, the reaction mixture was stirred at 80 C for 3 h and it was cooled to 0-5 C and quenched with 15% NaOH solution (10 ml) and filtered through celite bed. The celite bed washed with ethylacetate (5mL) 3 times. The filtrate was extracted with ethyl acetate (10 ml) 2 times. The ethyl acetate layers were combined and dried with anhydrous sodium sulphate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography with hexane and ethyl acetate as eluent to afford pure product 8 (108 mg, 85 % yield) S4
Table-1: Effect of Solvents a Entry Solvent 3a Yield (%) b 4a 1 1,4-Dioxane 95 (92) c 5 2 THF 91 7 3 Toluene 47 35 4 ACN 54 8 5 DCE 43 7 a All the reactions were carried out using 1a (0.40 mmol), 2a (0.60 mmol), Ni(cod)2 (0.04 mmol), P(n-Bu)3 (0.08 mmol), sodium carbonate (0.40 mmol) and solvent 1.5 ml (dry) at 80 C and 12 h under N2. b GC yields. c Isolated yield. References 1. Miura, T.; Morimoto, M.; Yamauchi, M.; Murakami, M. J. Org. Chem. 2010, 75, 5359 5362. 2. Wang H.; Yu; S. Org. Lett. 2015, 17, 4272 4275. 3. Rama, N. H.; saeed, A.; Iqbal, R. J. Sci. I. R. Iran. 1997, 8, 39-41. 4. Vijaykumar, H.; Nitinkumar, U.; Murakami, M. Cheng, C. H. Adv. Synth. Catal. 2017, 2, 284-289. 5. Ravi Kiran, C; Jeganmohan, M.; Org. Lett. 2012, 14, 5246 5249. 6. Micovic, V.; Mihailovic, M. J. Org. Chem. 1953, 18, 1190 1200. S5
Spectral data of 1 H, 13 C NMR N-(4-Methoxyphenyl)-[1,1'-biphenyl]-2-carboxamide (3a) White fine solid (111 mg, 92% yield); mp: 152-153 C; 1 H NMR (500 MHz, CDCl3) δ 7.87 (d, J = 7.6 Hz, 1H), 7.53 (td, J = 7.5, 1.1 Hz, 1H), 7.51 7.36 (m, 7H), 7.04 6.95 (m, 2H), 6.77 (dd, J = 9.9, 6.3 Hz, 3H), 3.75 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.0, 156.4, 140.0, 139.4, 135.3, 130.5, 130.2, 129.5, 128.9, 128.8, 128.0, 127.8, 121.8, 113.9, 55.4; HRMS calculated for C20H18NO2 [M+H] + : 304.1332, found 304.1330; Purification: Flash chromatography; Eluent: hexane/etoac = 85/15. 4'-Methoxy-N-(4-methoxyphenyl)-[1,1'-biphenyl]-2-carboxamide (3b) White fine solid (126 mg, 95% yield); mp:133-134 C; 1 H NMR (500 MHz, CDCl3) δ 7.80 (d, J = 7.5 Hz, 1H), 7.49 (t, J = 7.3 Hz, 1H), 7.40 (dd, J = 15.1, 7.9 Hz, 4H), 7.07 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.5 Hz, 3H), 6.77 (d, J = 8.8 Hz, 2H), 3.81 (s, 3H), 3.74 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.3, 159.4, 156.4, 139.0, 135.2, 132.1, 130.6, 130.4, 130.2, 129.9, 129.3, 127.3, 121.8, 114.2, 113.9, 55.3, 55.3.; HRMS calculated for C21H20NO3 [M+H] + : 334.1438, found 334.1441; Purification: Flash chromatography; Eluent: hexane/etoac = 8/2. S6
N-(4-Methoxyphenyl)-4'-methyl-[1,1'-biphenyl]-2-carboxamide (3c) White fine solid (113 mg, 89% yield); mp:147-148 C; 1 H NMR (500 MHz, CDCl3) δ 7.81 7.74 (m, 1H), 7.44 (ddd, J = 7.5, 4.5, 1.4 Hz, 1H), 7.37 (ddd, J = 7.5, 4.4, 1.3 Hz, 1H), 7.35 7.31 (m, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.18 (dd, J = 8.1, 5.5 Hz, 2H), 7.00 6.92 (m, 2H), 6.77 (s, 1H), 6.73 6.66 (m, 2H), 3.68 (s, 3H), 2.32 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.1, 156.4, 139.4, 137.8, 137.0, 135.2, 130.7, 130.5, 130.2, 129.5, 129.4, 128.7, 127.6, 121.7, 113.9, 55.4, 21.1; HRMS calculated for C21H20NO2 [M+H] + : 318.1489, found 318.1482; Purification: Flash chromatography; Eluent: hexane/etoac = 8/2. N-(4-Methoxyphenyl)-3'-methyl-[1,1'-biphenyl]-2-carboxamide (3d) White solid (107 mg, 85% yield); mp:118-119 C; 1 H NMR (500 MHz, CDCl3) δ 7.83 (dd, J = 7.7, 1.2 Hz, 1H), 7.50 (td, J = 7.5, 1.3 Hz, 1H), 7.43 (td, J = 7.5, 1.2 Hz, 1H), 7.39 (dd, J = 7.5, 1.0 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H), 7.28 7.22 (m, 2H), 7.20 (d, J = 7.5 Hz, 1H), 7.03 6.96 (m, 2H), 6.92 (s, 1H), 6.77 6.72 (m, 2H), 3.73 (s, 3H), 2.34 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.1, 156.4, 139.9, 139.5, 138.5, 135.1, 130.5, 130.4, 130.1, 129.4, 129.4, 128.7, 128.6, 127.6, 125.8, 121.8, 113.8, 55.3, 21.3; HRMS calculated for C21H20NO2 [M+H] + : 318.1489, found 318.1488; Purification: Flash chromatography; Eluent: hexane/etoac = 8/2. S7
3'-Fluoro-N-(4-methoxyphenyl)-[1,1'-biphenyl]-2-carboxamide (3e) White solid (91 mg, 71% yield); mp:162-163 C; 1 H NMR (500 MHz, CDCl3) δ 7.81 (d, J = 7.6 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 7.49 (t, J = 7.5 Hz, 1H), 7.41 (d, J = 7.4 Hz, 1H), 7.40 7.34 (m, 1H), 7.25 (d, J = 6.3 Hz, 1H), 7.21 (d, J = 9.5 Hz, 1H), 7.08 (dd, J = 12.2, 5.7 Hz, 3H), 6.84 (s, 1H), 6.79 (d, J = 8.9 Hz, 2H), 3.76 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.03, 162.84 (d, JC-F = 247.5 Hz), 156.66, 142.16 (d, JC-F = 7.7 Hz), 138.18, 135.66, 130.60, 130.41 (d, JC-F = 2.6 Hz), 130.36, 130.14, 129.19, 128.28, 124.62 (d, J = 2.8 Hz), 121.93, 115.68 (d, J = 21.9 Hz), 114.87 (d, JC-F = 20.9 Hz), 114.07, 55.43; HRMS calculated for C20H17NO2F1 [M+H] + : 322.1238, found 322.1239; Purification: Flash chromatography; Eluent: toluene/diethyl ether = 85/15. 4'-Fluoro-N-(4-methoxyphenyl)-[1,1'-biphenyl]-2-carboxamide (3f) White fine solid (102 mg, 80% yield); mp: 167-168 C; 1 H NMR (500 MHz, CDCl3) δ 7.79 (d, J = 7.6 Hz, 1H), 7.52 (td, J = 7.5, 1.4 Hz, 1H), 7.49 7.42 (m, 3H), 7.39 (dd, J = 7.6, 1.0 Hz, 1H), 7.15 7.06 (m, 4H), 6.88 (s, 1H), 6.83 6.75 (m, 2H), 3.76 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.1, 162.5 (d, JC-F = 247.9 Hz), 156.6, 138.3, 135.9, 135.6, 130.5 (d, JC-F = 10.0 Hz), 130.3 (d, JC-F = 15.8 Hz), 129.1, 127.9, 121.7, 115.9, 115.7, 114.0, 55.4; HRMS calculated for C20H17NO2F [M+H] + : 322.1238, found 322.1236. Purification: Flash chromatography; Eluent: hexane/etoac = 75/25. S8
N-(4-Methoxyphenyl)-4'-(trifluoromethyl)-[1,1'-biphenyl]-2-carboxamide (3g) White solid (108 mg, 73% yield); mp:185-186 C; 1 H NMR (500 MHz, CDCl3) δ 7.77 (d, J = 7.6 Hz, 1H), 7.67 (d, J = 8.2 Hz, 2H), 7.59 (d, J = 8.5 Hz, 2H), 7.55 (dd, J = 7.5, 1.4 Hz, 1H), 7.49 (dd, J = 10.8, 4.2 Hz, 1H), 7.43 (dd, J = 7.6, 1.1 Hz, 1H), 7.10 7.04 (m, 2H), 6.92 (s, 1H), 6.82 6.75 (m, 2H), 3.76 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 166.9, 156.7, 143.6, 138.1, 135.9, 130.6, 130.3, 130.2, 129.9 (d, JC-F = 32.8 Hz), 129.0, 128.9, 128.4, 125.6 (d, JC- F = 3.7 Hz), 124.0 (d, JC-F = 272.2 Hz), 121.8, 114.0, 55.4; HRMS calculated for C21H17NO2F3 [M+H] + : 372.1206, found 372.1204. Purification: Flash chromatography; Eluent: hexane/etoac = 8/2. 2-(Benzofuran-2-yl)-N-(4-methoxyphenyl)benzamide (3h) Light brown solid (86 mg, 63% yield); mp: 173-174 C; 1 H NMR (500 MHz, DMSO) δ 10.37 (d, J = 6.4 Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.69 7.52 (m, 6H), 7.49 (d, J = 8.2 Hz, 1H), 7.36 7.28 (m, 1H), 7.24 (dd, J = 10.9, 4.0 Hz, 1H), 7.17 (d, J = 3.1 Hz, 1H), 7.00 6.88 (m, 2H), 3.75 (s, 3H); 13 C NMR (126 MHz, DMSO) δ 167.7, 156.0, 154.6, 154.1, 136.6, 132.7, 130.0, 129.2, 129.0, 128.4, 127.8, 127.3, 125.2, 123.6, 121.8, 121.8, 114.3, 111.4, 104.7, 55.6; HRMS calculated for C22H18NO3 [M+H] + : 344.1281, found 344.1278. Purification: Flash chromatography; Eluent: hexane/etoac = 7/3. S9
N-(4-Methoxyphenyl)-2-(thiophen-2-yl)benzamide (3i) White fine solid (111 mg, 90% yield); mp: 124-125 C; 1 H NMR (500 MHz, CDCl3) δ 7.79 7.73 (m, 1H), 7.55 7.42 (m, 3H), 7.38 (dd, J = 5.1, 1.1 Hz, 1H), 7.25 7.17 (m, 3H), 7.13 (s, 1H), 7.11 7.05 (m, 1H), 6.86 6.77 (m, 2H), 3.77 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.0, 156.5, 140.9, 135.9, 131.7, 130.7, 130.6, 130.2, 129.0, 128.2, 127.9, 127.1, 126.7, 121.9, 114.0, 55.4; HRMS calculated for C18H16NO2S [M+H] + : 310.0896, found 310.0886. Purification: Flash chromatography; Eluent: hexane/etoac = 85/15. (E)-N-(4-Methoxyphenyl)-2-styrylbenzamide (3j) Light yellow solid (110 mg, 84% yield); mp: 182-183 C; 1 H NMR (500 MHz, CDCl3) δ 7.73 (d, J = 7.9 Hz, 1H), 7.61 (d, J = 7.6 Hz, 1H), 7.57 7.44 (m, 7H), 7.34 (dd, J = 14.0, 7.1 Hz, 3H), 7.30 7.23 (m, 1H), 7.10 (d, J = 16.2 Hz, 1H), 6.89 (d, J = 8.9 Hz, 2H), 3.81 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.3, 156.6, 136.8, 135.7, 135.5, 131.9, 130.9, 130.5, 128.7, 128.0, 127.8, 127.6, 126.8, 126.4, 125.6, 121.7, 114.2, 55.4; HRMS calculated for C22H20NO2 [M+H] + : 330.1489, found 330.1482. Purification: Flash chromatography; Eluent: hexane/etoac = 85/15. (E)-N-(4-Methoxyphenyl)-2-(4-methylstyryl)benzamide (3k) S10
Light yellow solid (116 mg, 85% yield); mp:189-190 C; 1 H NMR (500 MHz, CDCl3) δ 7.64 (d, J = 7.8 Hz, 1H), 7.54 (d, J = 6.9 Hz, 1H), 7.41 (dt, J = 15.8, 7.6 Hz, 5H), 7.32 (d, J = 8.0 Hz, 2H), 7.26 (t, J = 7.4 Hz, 1H), 7.07 (d, J = 7.9 Hz, 2H), 7.00 (d, J = 16.3 Hz, 1H), 6.82 (d, J = 8.9 Hz, 2H), 3.74 (s, 3H), 2.28 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.3, 156.6, 138.1, 135.8, 135.3, 134.0, 131.9, 130.9, 130.5, 129.4, 127.8, 127.4, 126.7, 126.4, 124.5, 121.7, 114.2, 55.4, 21.2; HRMS calculated for C23H22NO2 [M+H] + : 344.164 found 344.1645; Purification: Flash chromatography; Eluent: toluene/diethyl ether = 85/15. (E)-N-(4-Methoxyphenyl)-2-(4-methoxystyryl)benzamide (3l) Light yellow solid (125 mg, 87% yield); mp: 192-193 C; 1 H NMR (500 MHz, CDCl3) δ 7.69 (d, J = 7.9 Hz, 1H), 7.60 (dd, J = 7.6, 0.8 Hz, 1H), 7.54 7.49 (m, 2H), 7.47 7.35 (m, 5H), 7.31 (t, J = 8.0 Hz, 1H), 7.08 7.00 (m, 1H), 6.88 (dd, J = 11.7, 8.8 Hz, 4H), 3.81 (s, 3H), 3.81 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.3, 159.6, 156.6, 135.9, 135.2, 131.4, 130.9, 130.5, 129.6, 128.0, 127.8, 127.2, 126.2, 123.4, 121.7, 114.2, 114.1, 55.5, 55.3; HRMS calculated for C23H22NO3 [M+H] + : 360.1594, found 360.1596; Purification: Flash chromatography; Eluent: toluene/diethyl ether = 8/2. (E)-N-(4-Methoxyphenyl)-2-(pent-1-en-1-yl)benzamide (3m) Light brown solid (97 mg, 82% yield); mp: 100-101 C; 1 H NMR (500 MHz, CDCl3) δ 7.61 7.47 (m, 5H), 7.39 (t, J = 7.6 Hz, 1H), 7.27 (dt, J = 7.4, 3.4 Hz, 1H), 7.03 6.85 (m, 2H), 6.75 (d, J = 15.7 Hz, 1H), 6.30 6.16 (m, 1H), 3.81 (s, 3H), 2.20 (q, J = 7.2 Hz, 2H), 1.48 (dd, J = 14.7, 7.4 Hz, 2H), 0.93 (t, J = 7.4 Hz, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.3, 156.4, 136.0, 134.7, 134.7, 131.0, 130.3, 127.7, 127.2, 126.9, 126.6, 121.5, 114.1, 55.4, 35.2, 22.4, 13.7; S11
HRMS calculated for C19H22NO2 [M+H] + : 296.1645, found 296.164; Purification: Flash chromatography; Eluent: hexane/etoac = 75/25. 4'-Methoxy-N-phenyl-[1,1'-biphenyl]-2-carboxamide (3n) White solid (103 mg, 85% yield); mp: 143-144 C; 1 H NMR (500 MHz, CDCl3) δ 7.86 (d, J = 7.6 Hz, 1H), 7.55 7.49 (m, 1H), 7.45 (d, J = 7.5 Hz, 1H), 7.44 7.36 (m, 2H), 7.23 (d, J = 7.5 Hz, 2H), 7.17 (d, J = 7.7 Hz, 2H), 7.06 (t, J = 7.3 Hz, 1H), 6.97 (d, J = 8.6 Hz, 3H), 3.83 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.3, 159.5, 139.1, 137.6, 135.1, 132.0, 130.6, 130.3, 130.0, 129.5, 128.8, 127.5, 124.3, 119.9, 114.4, 55.3; HRMS calculated for C20H18NO2 [M+H] + : 304.1332, found 304.1336; Purification: Flash chromatography; Eluent: hexane/etoac = 85/15. 4'-Methoxy-N-(p-tolyl)-[1,1'-biphenyl]-2-carboxamide (3o) White solid (111 mg, 88% yield); mp: 129-130 C; 1 H NMR (500 MHz, CDCl3) δ 7.83 (d, J = 7.7 Hz, 1H), 7.49 (td, J = 7.4, 1.0 Hz, 1H), 7.44 7.37 (m, 4H), 7.08 7.01 (m, 4H), 6.95 (t, J = 5.8 Hz, 3H), 3.81 (s, 3H), 2.27 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.3, 159.4, 139.0, 135.2, 135.0, 133.9, 132.1, 130.4, 130.2, 129.9, 129.4, 129.2, 127.3, 120.0, 114.3, 55.3, 20.8; HRMS calculated for C21H20NO2 [M+H] + : 318.1489, found 318.1490; Purification: Flash chromatography; Eluent: hexane/etoac = 88/12. S12
N-(4-Chlorophenyl)-4'-methoxy-[1,1'-biphenyl]-2-carboxamide (3p) White solid (97 mg, 72% yield); mp: 146-147 C; 1 H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.4 Hz, 1H), 7.51 (t, J = 7.3 Hz, 1H), 7.47 7.33 (m, 4H), 7.18 (d, J = 8.6 Hz, 2H), 7.14 7.02 (m, 3H), 6.95 (d, J = 8.4 Hz, 2H), 3.82 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.3, 159.5, 139.1, 136.1, 134.7, 131.9, 130.7, 130.3, 129.9, 129.5, 129.2, 128.8, 127.5, 121.0, 114.4, 55.3; HRMS calculated for C 20H 17NO 2Cl [M+H] + : 338.0942, found 338.0940; Purification: Flash chromatography; Eluent: hexane/etoac = 83/17. N-Cyclopentyl-4'-methoxy-[1,1'-biphenyl]-2-carboxamide (3q) White solid (108 mg, 92% yield); mp: 123-124 C; 1 H NMR (500 MHz, CDCl3) δ 7.70 (dd, J = 7.7, 1.2 Hz, 1H), 7.46 7.41 (m, 1H), 7.38 (dd, J = 7.6, 1.2 Hz, 1H), 7.35 7.30 (m, 3H), 6.97 6.93 (m, 2H), 5.19 (d, J = 7.4 Hz, 1H), 4.40 4.16 (m, 1H), 3.84 (s, 3H), 1.81 1.72 (m, 2H), 1.52 1.41 (m, 2H), 1.39 1.31 (m, 2H), 1.09 0.99 (m, 2H); 13 C NMR (126 MHz, CDCl3) δ 168.7, 159.3, 138.9, 135.7, 132.5, 130.0, 129.8, 128.8, 127.1, 114.0, 55.3, 51.2, 32.4, 23.3; HRMS calculated for C19H22NO2 [M+H] + : 296.1645 found 296.1644. Purification: Flash chromatography; Eluent: hexane/etoac = 7/3. N-Cyclohexyl-4'-methoxy-[1,1'-biphenyl]-2-carboxamide (3r) S13
White solid (108 mg, 88% yield); mp: 143-144 C; 1 H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 7.5 Hz, 1H), 7.44 (td, J = 7.4, 0.8 Hz, 1H), 7.36 (dt, J = 15.4, 3.7 Hz, 4H), 6.95 (d, J = 8.6 Hz, 2H), 5.16 (d, J = 7.8 Hz, 1H), 3.84 (s, 3H), 3.81 3.72 (m, 1H), 1.71 1.61 (m, 2H), 1.51 (d, J = 10.6 Hz, 3H), 1.33 1.20 (m, 2H), 1.04 (tdd, J = 12.4, 9.5, 3.3 Hz, 1H), 0.79 (td, J = 12.9, 2.8 Hz, 2H); 13 C NMR (126 MHz, CDCl3) δ 168.4, 159.3, 138.9, 135.9, 132.5, 130.0, 129.8, 129.8, 128.7, 127.1, 114.0, 55.3, 48.1, 32.4, 25.3, 24.4; HRMS calculated for C20H24NO2 [M+H] + : 310.1802 found 310.1795. Purification: Flash chromatography; Eluent: hexane/etoac = 7/3. N-(4-Methoxyphenyl)-4-methyl-[1,1'-biphenyl]-2-carboxamide (3s) White solid (105 mg, 71% yield); mp:147-148 C; 1 H NMR (500 MHz, CDCl3) δ 7.70 7.69 (m, 1H), 7.47 7.37 (m, 6H), 7.33 (dt, J = 14.2, 4.5 Hz, 2H), 7.00 6.97 (m, 2H), 6.78 6.74 (m, 3H), 3.75 (s, 3H), 2.44 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.2, 156.4, 139.9, 137.8, 136.5, 135.0, 131.3, 130.5, 130.2, 130.0, 128.8, 128.8, 127.8, 121.8, 113.9, 55.4, 21.0; HRMS calculated for C21H20NO2 [M+H] + : 318.1489 found 318.1491; Purification: Flash chromatography; Eluent: toluene/thf = 95/5. 4-Fluoro-N-(4-methoxyphenyl)-[1,1'-biphenyl]-2-carboxamide (3t) White solid (83 mg, 65% yield); mp: 162-163 C; 1 H NMR (500 MHz, CDCl3) δ 7.62 (dd, J = 9.0, 2.7 Hz, 1H), 7.48 7.42 (m, 5H), 7.40 (dd, J = 8.5, 5.4 Hz, 1H), 7.25 7.20 (m, 1H), 7.00 6.95 (m, 2H), 6.79 6.74 (m, 3H), 3.76 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 165.54, 162.21 (d, JC-F = 248.7 Hz), 156.7, 139.1, 137.0, 135.5, 132.1 (d, J = 7.8 Hz), 130.2, 129.1, 128.9, 128.2, 121.2, 117.7 (d, JC-F = 21.3 Hz), 116.5 (d, J = 23.1 Hz), 114.0, 55.4; HRMS S14
calculated for C20H17NO2F [M+H] + : 322.1238 found 322.1239; Purification: Flash chromatography; Eluent: toluene/thf = 98/2. 4'-Methoxy-4-morpholino-N-(p-tolyl)-[1,1'-biphenyl]-2-carboxamide (3u) Light brown solid (116 mg, 72% yield); 1 H NMR (500 MHz, CDCl3) δ 7.39 (d, J = 2.7 Hz, 1H), 7.38 7.34 (m, 2H), 7.30 (d, J = 8.5 Hz, 1H), 7.06 7.01 (m, 5H), 6.96 6.91 (m, 3H), 3.82 (s, 3H), 3.89 3.87 (m, 4H), 3.27 3.23 (m, 4H), 2.28 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 167.4, 159.1, 150.3, 135.7, 135.0, 134.0, 132.0, 131.2, 130.1, 130.0, 129.3, 119.9, 117.5, 115.9, 114.3, 66.7, 55.3, 48.8, 20.8; HRMS calculated for C25H27N2O3 403.2016 found 403.2021; Purification: Flash chromatography; Eluent: CHCl3/diethyl ether = 95/5. 4,4',5-Trimethoxy-N-(p-tolyl)-[1,1'-biphenyl]-2-carboxamide (3v) Light yellow solid (117 mg, 77% yield); 1 H NMR (500 MHz, CDCl3) δ 7.50 (s, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.05 6.96 (m, 6H), 6.92 (s, 1H), 6.81 (s, 1H), 3.97 (s, 3H), 3.94 (s, 3H), 3.84 (s, 3H), 2.27 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 166.4, 159.5, 150.5, 148.3, 135.2, 133.8, 132.6, 132.2, 130.3, 129.3, 127.0, 119.8, 114.5, 112.9, 112.5, 56.1, 56.1, 55.4, 20.8; HRMS calculated for C23H24NO4 [M+H] + : 378.1700 found 378.1705; Purification: Flash chromatography; Eluent: DCM/THF = (98/2) S15
9H-Fluoren-9-one (7a) Light yellow solid (65 mg, 90% yield); m.p. 83-84 C; 1 H NMR (500 MHz, CDCl3) δ 7.65 (d, J = 6.2 Hz, 2H), 7.50 (dd, J = 12.7, 7.3 Hz, 4H), 7.28 (t, J = 9.3 Hz, 2H); 13 C NMR (126 MHz, CDCl3) δ 193.9, 144.3, 134.6, 134.1, 129.0, 124.2, 120.2; HRMS calculated for C13H9O [M+H] + : 181.0648 found 181.0643; Purification: Flash chromatography; Eluent: Hexane/EtOAc = 95/5. 2-Methyl-9H-fluoren-9-one (7b) Light yellow solid (68 mg, 88 % yield); m.p. 87-88 C; 1 H NMR (500 MHz, CDCl3) δ 7.63 (d, J = 7.3 Hz, 1H), 7.48 7.45 (m, 3H), 7.40 7.38 (m, 1H), 7.29 7.26 (m, 1H), 7.26 7.23 (m, 1H), 2.37 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 194.2, 144.6, 141.8, 139.2, 135.1, 134.6, 134.3, 134.2, 128.5, 125.0, 124.2, 120.1, 119.9, 21.3; HRMS calculated for C14H11O [M+H] + : 195.0804, found 195.0798; Purification: Flash chromatography; Eluent: Hexane/EtOAc = 95/5. 2-Methoxy-9H-fluoren-9-one (7c) Bright yellow solid (75 mg, 90% yield); m.p. 78-79 C; 1 H NMR (500 MHz, CDCl3) δ 7.58 (d, J = 7.3 Hz, 1H), 7.42 (t, J = 7.4 Hz, 1H), 7.37 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.1 Hz, 2H), 6.96 (dd, J = 8.1, 1.6 Hz, 1H), 3.84 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 193.7, 160.7, 144.7, 136.8, 135.8, 134.7, 134.2, 127.7, 124.2, 121.2, 120.1, 119.5, 109.2, 55.6; HRMS S16
calculated for C14H11O2 [M+H] + : 211.0754 found 211.0745; Purification: chromatography; Eluent: Hexane/EtOAc = 95/5. Flash 4-Methoxy-N-((4'-methoxy-[1,1'-biphenyl]-2-yl)methyl)aniline (8) Brown oily liquid (108 mg, 85% yield); 1 H NMR (500 MHz, CDCl3) δ 7.50 (dq, J = 7.1, 3.6 Hz, 1H), 7.33 (dt, J = 6.9, 3.1 Hz, 4H), 7.28 (dd, J = 5.4, 3.7 Hz, 1H), 6.97 6.94 (m, 2H), 6.76 6.72 (m, 2H), 6.52 6.48 (m, 2H), 4.20 (s, 2H), 3.85 (s, 3H), 3.73 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 158.7, 152.0, 142.2, 141.3, 136.6, 133.2, 130.3, 130.0, 128.7, 127.3, 127.2, 114.7, 114.1, 113.6, 55.7, 55.2, 47.2; HRMS calculated for C21H22NO2 [M+H] + : 322.1238 found 322.1239; Purification: Flash chromatography; Eluent: Hexane/EtOAc = 75/25. S17
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 1H NMR 3a 3.13 2.94 2.07 8.15 1.00 3.75 6.75 6.77 6.78 6.78 6.98 6.99 6.99 7.00 7.01 7.01 7.26 7.40 7.41 7.42 7.43 7.45 7.46 7.47 7.49 7.49 7.52 7.52 7.53 7.54 7.55 7.55 7.87 7.88
13C NMR 3a 167.07 156.49 140.00 139.44 135.34 130.55 130.25 129.50 128.92 128.82 128.03 127.86 121.84 113.96 77.25 77.00 76.75 55.40 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 1H NMR 3b 2.77 2.82 2.04 2.99 1.97 3.85 0.99 1.00 3.74 3.81 6.76 6.77 6.94 6.96 7.06 7.08 7.25 7.38 7.39 7.41 7.42 7.47 7.49 7.50 7.79 7.81
13C NMR3b 167.35 159.41 156.42 139.04 135.23 132.14 130.66 130.43 130.23 129.96 129.32 127.36 121.81 114.28 113.93 77.25 77.00 76.75 55.36 55.31 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0-10
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 1H NMR 3c 3.01 3.04 2.01 0.99 2.07 2.38 3.02 1.05 1.06 1.00 2.32 3.68 6.68 6.69 6.69 6.70 6.70 6.71 6.77 6.94 6.95 6.95 6.96 6.97 6.97 7.16 7.18 7.18 7.28 7.30 7.32 7.32 7.33 7.33 7.36 7.37 7.37 7.38 7.39 7.42 7.42 7.43 7.44 7.77 7.77 7.78 7.79 7.79
13C NMR 3c 167.17 156.46 139.47 137.86 137.04 135.29 130.73 130.50 130.29 129.59 129.46 128.71 127.61 121.78 113.96 77.25 77.00 76.75 55.41 21.16 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 1H NMR 3d 3.09 3.19 2.10 1.07 2.08 1.10 2.20 1.12 2.21 1.04 1.00 2.34 3.73 6.74 6.74 6.75 6.76 6.92 6.98 6.99 7.00 7.00 7.19 7.21 7.24 7.26 7.27 7.30 7.31 7.33 7.38 7.39 7.40 7.40 7.43 7.43 7.44 7.44 7.48 7.48 7.49 7.50 7.82 7.82 7.84 7.84
13C NMR 3d 167.11 156.40 139.90 139.56 138.56 135.18 130.57 130.41 130.15 129.47 129.41 128.73 128.67 127.65 125.85 121.89 113.87 77.25 77.00 76.75 55.32 21.32 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 1H NMR 3e 3.26 2.10 0.89 3.09 2.78 2.11 1.08 1.04 1.00 3.76 6.79 6.80 6.84 7.07 7.07 7.08 7.10 7.20 7.22 7.25 7.26 7.37 7.38 7.39 7.41 7.42 7.47 7.49 7.50 7.53 7.54 7.56 7.80 7.82
-10 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 13C NMR 3e 55.43 76.75 77.00 77.25 114.07 114.79 114.95 115.59 115.77 121.93 124.61 124.63 128.28 129.19 130.14 130.36 130.40 130.42 130.60 135.66 138.18 142.13 156.66 161.86 163.83 167.03
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 1H NMR 3f 3.22 2.05 0.96 4.10 1.06 3.06 1.04 1.00 3.76 6.78 6.78 6.79 6.80 6.80 6.81 6.88 7.08 7.08 7.09 7.10 7.10 7.12 7.13 7.14 7.26 7.38 7.39 7.40 7.40 7.43 7.43 7.44 7.45 7.46 7.47 7.47 7.51 7.51 7.52 7.52 7.54 7.54 7.78 7.80
13C NMR 3f 167.18 163.55 161.58 156.60 138.34 135.96 135.63 130.46 130.39 129.17 127.91 121.77 115.91 115.74 114.07 77.25 77.00 76.75 55.42 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 1H NMR 3g 3.03 1.99 1.98 1.04 1.15 3.02 1.99 1.00 3.76 6.78 6.78 6.79 6.79 6.92 7.06 7.07 7.07 7.08 7.42 7.42 7.43 7.44 7.48 7.48 7.50 7.51 7.54 7.55 7.56 7.56 7.58 7.59 7.67 7.68 7.76 7.78
13C NMR 3g 166.99 156.73 143.67 138.16 135.91 130.66 130.32 130.23 130.08 129.82 129.07 128.95 128.48 125.69 125.66 121.82 114.09 77.25 77.00 76.75 55.42 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0-10
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5 1H NMR 3h 2.93 1.94 0.88 0.98 1.01 0.94 5.81 1.00 1.00 2.50 2.51 2.51 3.34 3.35 3.36 3.38 3.75 6.92 6.93 6.93 6.94 6.94 7.17 7.18 7.24 7.25 7.25 7.29 7.31 7.31 7.48 7.50 7.54 7.55 7.56 7.57 7.57 7.59 7.60 7.61 7.61 7.63 7.63 7.64 7.65 7.96 7.98 10.36 10.37
0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 1C NMR 3h 39.48 39.65 39.82 39.99 40.15 40.32 40.49 55.66 104.79 111.42 114.35 121.83 121.88 123.63 125.27 127.33 127.83 128.45 129.04 129.27 130.07 132.74 136.60 154.19 154.60 156.05 167.71
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 1H NMR 3i 3.00 2.03 1.06 1.00 3.04 1.02 3.27 1.00 3.77 6.81 6.82 6.83 7.07 7.08 7.08 7.09 7.19 7.20 7.20 7.21 7.21 7.26 7.38 7.38 7.39 7.39 7.44 7.45 7.46 7.47 7.49 7.49 7.50 7.50 7.51 7.51 7.76 7.76 7.77
13C NMR 3i 167.05 156.57 140.95 131.72 130.63 130.29 129.07 128.26 127.93 127.19 126.71 121.91 114.06 77.25 77.00 76.75 55.42 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 1H NMR 3j 3.04 2.01 0.96 1.76 2.95 6.93 0.97 1.00 3.81 6.88 6.90 7.08 7.11 7.25 7.26 7.28 7.32 7.33 7.35 7.36 7.46 7.47 7.49 7.50 7.52 7.52 7.56 7.60 7.62 7.72 7.73
13 NMR 3j 167.30 156.65 136.85 135.71 135.51 131.91 130.94 130.57 128.71 128.07 127.81 127.61 126.80 126.48 125.65 121.78 114.25 77.25 77.00 76.75 55.49 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 1H NMR 3k 3.30 3.17 2.02 1.07 2.03 1.09 2.20 5.15 1.06 1.00 2.28 3.74 6.81 6.83 6.99 7.02 7.06 7.08 7.19 7.25 7.26 7.28 7.31 7.33 7.38 7.39 7.41 7.42 7.43 7.44 7.53 7.55 7.63 7.65
13C NMR 3k 167.34 156.63 138.10 135.84 135.38 134.06 131.94 130.95 130.56 129.43 127.88 127.44 126.72 126.43 124.58 121.76 114.25 77.25 77.00 76.75 55.49 21.27 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 1H NMR 3l 6.03 4.39 1.08 1.14 4.56 2.69 1.05 1.00 3.81 3.81 6.86 6.88 6.88 6.90 7.26 7.30 7.32 7.33 7.37 7.40 7.42 7.44 7.45 7.47 7.47 7.50 7.51 7.52 7.69 7.70
13C NMR 3l 167.39 159.61 156.60 135.97 135.23 131.49 130.98 130.54 129.67 128.08 127.87 127.24 126.29 123.43 121.73 114.24 114.13 77.25 77.00 76.75 55.50 55.30 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 1H NMR 3m 3.25 2.11 2.12 3.20 1.00 1.03 2.06 1.30 1.15 5.10 0.92 0.93 0.95 1.46 1.47 1.49 1.50 2.18 2.19 2.21 2.22 3.81 6.20 6.21 6.23 6.24 6.26 6.73 6.76 6.89 6.89 6.90 7.25 7.26 7.26 7.27 7.28 7.28 7.37 7.39 7.41 7.49 7.50 7.51 7.52 7.55 7.55 7.56
13C NMR 3m 167.39 156.49 136.06 134.77 134.74 131.09 130.34 127.72 127.26 126.93 126.67 121.52 114.18 77.25 77.00 76.75 55.47 35.20 22.44 13.73 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 1H NMR 3n 3.16 3.08 1.11 2.00 2.92 4.12 1.06 1.00 3.83 6.96 6.98 7.04 7.06 7.07 7.16 7.18 7.23 7.24 7.26 7.39 7.40 7.41 7.42 7.43 7.44 7.46 7.50 7.50 7.52 7.52 7.53 7.86 7.87
13C NMR 3n 167.36 159.55 139.14 137.60 135.15 132.08 130.65 130.38 130.03 129.54 128.85 127.50 124.37 119.92 114.43 77.25 77.00 76.75 55.38 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 1H NMR 3o 3.18 3.16 3.01 4.08 4.03 1.23 0.99 2.27 3.81 6.94 6.96 6.96 7.02 7.04 7.05 7.06 7.06 7.25 7.38 7.38 7.39 7.40 7.42 7.43 7.43 7.48 7.48 7.49 7.50 7.51 7.51 7.82 7.83
13C NMR 3o 167.31 159.44 139.07 135.24 135.02 133.97 132.10 130.49 130.28 129.97 129.41 129.29 127.39 120.00 114.33 77.25 77.00 76.75 55.32 20.80 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 1H NMR 3p 3.08 2.10 3.02 2.02 4.05 1.13 1.00 3.82 6.94 6.96 7.07 7.09 7.12 7.17 7.19 7.26 7.36 7.38 7.40 7.42 7.44 7.50 7.51 7.53 7.80 7.81
13C NMR 3p 167.36 159.56 139.15 136.18 134.76 131.95 130.79 130.37 129.99 129.50 129.27 128.82 127.51 121.04 114.41 77.25 77.00 76.75 55.37 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 1H NMR 3q 2.14 2.32 2.20 2.11 3.26 1.02 1.00 2.07 4.21 1.07 1.00 1.01 1.01 1.02 1.02 1.03 1.04 1.05 1.05 1.06 1.06 1.07 1.07 1.26 1.31 1.32 1.33 1.34 1.34 1.36 1.37 1.37 1.38 1.41 1.42 1.43 1.43 1.44 1.45 1.45 1.46 1.47 1.47 1.73 1.73 1.73 1.74 1.74 1.75 1.77 1.78 1.78 1.79 1.79 3.84 4.16 4.18 4.19 4.20 5.18 5.20 6.94 6.94 6.95 6.96 6.96 6.97 7.27 7.30 7.31 7.31 7.31 7.32 7.32 7.33 7.34 7.34 7.35 7.35 7.36 7.37 7.37 7.38 7.38 7.42 7.42 7.43 7.44 7.45 7.45 7.69 7.69 7.70 7.71
13C NMR 3q 168.79 159.34 138.92 135.74 132.57 130.00 129.84 128.82 127.16 114.00 77.25 77.00 76.75 55.35 51.24 32.49 23.33 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 1H NMR 3r 2.13 1.10 2.27 3.13 2.11 0.76 1.08 3.07 0.96 2.03 4.10 1.04 1.00 0.75 0.75 0.78 0.81 0.83 0.84 1.03 1.03 1.05 1.05 1.06 1.22 1.23 1.25 1.26 1.28 1.29 1.31 1.49 1.52 1.64 1.65 1.66 1.67 1.68 1.87 3.73 3.74 3.75 3.75 3.77 3.78 3.79 3.79 3.80 3.84 5.15 5.17 6.94 6.96 7.27 7.31 7.33 7.35 7.37 7.39 7.39 7.42 7.42 7.44 7.44 7.46 7.46 7.67 7.69
13C NMR 3r 168.49 159.35 138.91 135.92 132.59 130.06 129.88 129.83 128.78 127.15 114.01 77.25 77.00 76.75 55.37 48.13 32.40 25.33 24.45 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0-10
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 1H NMR 3s 3.29 3.10 3.17 2.20 2.09 5.34 1.00 2.44 3.75 6.75 6.76 6.77 6.97 6.99 7.26 7.31 7.32 7.33 7.34 7.38 7.40 7.40 7.40 7.42 7.42 7.43 7.43 7.44 7.44 7.45 7.45 7.45 7.46 7.47 7.47 7.69 7.69 7.69
13C NMR 3s 167.26 156.46 139.98 137.84 136.59 135.09 131.33 130.57 130.20 130.04 128.89 128.87 127.83 121.85 113.95 77.25 77.00 76.75 55.40 21.00 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0-10
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 1H NMR 3t 3.09 2.93 1.97 3.22 5.95 0.98 3.76 6.75 6.76 6.77 6.77 6.78 6.96 6.96 6.97 6.98 6.98 7.22 7.22 7.23 7.24 7.25 7.25 7.26 7.38 7.39 7.40 7.41 7.42 7.43 7.43 7.44 7.44 7.44 7.45 7.46 7.46 7.61 7.61 7.62 7.63
0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 13C NMR 3t 55.45 76.78 77.04 77.29 114.05 116.48 116.66 117.61 117.78 121.92 128.27 128.95 129.10 130.23 132.14 132.20 135.55 137.04 139.10 156.70 161.22 163.20 165.54
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 1H NMR 3u 3.00 4.03 3.01 4.06 3.06 5.09 1.05 2.01 1.04 2.28 3.24 3.25 3.26 3.82 3.87 3.88 3.89 6.92 6.93 6.94 6.95 6.95 7.01 7.03 7.03 7.04 7.05 7.06 7.26 7.29 7.31 7.35 7.36 7.37 7.37 7.39 7.39
13C NMR 3u 167.44 159.16 150.38 135.73 135.03 134.01 132.00 131.29 130.19 130.03 129.32 119.99 117.54 115.99 114.36 77.25 77.00 76.75 66.77 55.37 48.85 20.83 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10
1H NMR 3v 7.50 7.39 7.37 7.26 7.04 7.02 7.00 6.99 6.98 6.98 6.92 6.81 0.95 1.92 6.07 0.95 0.98 3.07 3.04 3.00 2.92 3.97 3.94 3.84 2.27 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
13 C NMR 3v 166.42 159.54 150.51 148.31 135.22 133.83 132.68 132.23 130.32 129.33 127.02 119.81 114.53 112.96 112.59 77.30 77.05 76.79 56.12 56.11 55.47 20.84 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10
1H NMR 7a 7.66 7.65 7.52 7.51 7.50 7.48 7.30 7.29 7.26 2.00 4.13 2.29 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
13C NMR 7a 193.93 144.39 134.66 134.10 129.04 124.28 120.28 77.25 77.00 76.75 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0-10
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 1H NMR 7b 3.22 2.44 1.02 2.96 1.00 2.37 7.23 7.24 7.25 7.25 7.25 7.25 7.26 7.27 7.27 7.27 7.28 7.29 7.39 7.40 7.45 7.45 7.46 7.46 7.47 7.62 7.63
13C NMR 7b 194.24 144.63 141.80 139.26 135.11 134.63 134.37 134.23 128.57 125.01 124.22 120.12 119.98 77.25 77.00 76.75 21.35 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
1H NMR 7c 1.00 3.09 2.04 1.03 7.59 7.57 7.43 7.42 7.40 7.38 7.36 7.26 7.20 7.18 6.97 6.96 6.95 6.95 3.84 3.24 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
13C NMR 7c 193.78 160.74 144.79 136.89 135.80 134.77 134.21 127.78 124.22 121.26 120.14 119.50 109.29 77.25 77.00 76.75 55.63 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 1H NMR 8 3 3 2 2 2 2 5 1 3.72 3.84 4.19 6.48 6.50 6.72 6.74 6.93 6.95 7.24 7.26 7.27 7.27 7.28 7.28 7.30 7.30 7.31 7.31 7.32 7.33 7.48 7.48 7.49 7.49
13C NMR 8 158.79 152.07 142.20 141.35 136.66 133.22 130.31 130.08 128.78 127.35 127.21 114.75 114.15 113.69 77.25 77.00 76.75 55.76 55.26 47.20 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0