ࡱ> y{x7 HbjbjUU .7|7|Bl& & & 8^ d $T,& ( "< < < O O O +++++++$z- /v+-O K O O O +#< < ,###O 8< < +#O +##++< @gc4& !<++$,0T,+0#0+#Supporting Information Directed Deprotonation-Transmetallation as a Route to Substituted Pyridines Gunter Karig, James A. Spencer and Timothy Gallagher* School of Chemistry, University of Bristol, Bristol BS8 1TS UK T.Gallagher@bristol.ac.uk Representative Experimental Procedures. General Procedure A. Formation of Riekes Activated Zinc. A mixture of freshly cut lithium (106 mg, 15.32 mmol) and naphthalene (1.99 g, 15.57 mmol) in dry THF (15 mL) under a nitrogen atmosphere was stirred vigorously at room temperature for 2 hours. 0.95 mL of this solution was removed and transferred to a clean, dry flask, and anhydrous zinc chloride (0.5 M in THF, 0.97 mL, 0.49 mmol) added dropwise over 10 minutes to generate the activated zinc (0.49 mmol). This solution is then ready for immediate use. General Procedure B. Formation of 3-bromo-4-pyridylzinc chloride To diisopropylamine (0.32 mL, 2.32 mmol) in dry THF (5 mL) at 78 (C was added n-butyllithium (1.08 M in hexanes, 2.14 mL, 2.32 mmol) dropwise. The solution was stirred at 78 (C for 10 minutes then allowed to warm to room temperature. A volume of this LDA solution (7.05 mL) was added dropwise over 10 minutes to a solution of 3-bromopyridine (0.19 mL, 1.935 mmol) in dry THF (5 mL) at 95 (C and the resulting solution stirred at 95 (C for 25 minutes. After this time, anhydrous zinc chloride (0.5 M in THF, 3.87 mL, 1.935 mmol) was added dropwise and the solution allowed to warm to room temperature to provide 3-bromo-4-pyridyl zinc chloride (1.94 mmol). General Procedure C. Preparation of 3-bromo-4-substituted 3 and 4-substituted pyridines 4. (See Scheme 1 and Table 1). Illustrated for preparation of 4a.- (i) Cross coupling procedure.- A solution of 4-pyridylzinc chloride (2.7 mmol) was prepared as according to General Procedure B. To this was added iodobenzene (0.11 mL, 1.0 mmol) followed by a solution of Pd(PPh3)4 (57 mg, 0.05 mmol) in dry THF (5 mL) via cannula. The solution was then heated to reflux for 2.5 hours. In a separate flask, Reikes zinc (2.5 mmol) was prepared according to General Procedure A. At this point, work up and isolation gave 3-bromo-4-substituted pyridines 3a-f shown in Table 1. The same procedure was also used to prepare 2-bromo-3-substituted 9 starting from 2-bromopyridine (Scheme 2). (ii) Rieke zinc reduction.- The cross coupling reaction mixture was then added to the freshly prepared active Rieke zinc via cannula and the suspension heated to reflux for 1 hour. The mixture was allowed to cool to room temperature and then quenched by addition of water (10 mL). The organic phase was separated and the aqueous phase extracted with dichloromethane (2 x 10 mL). The combined organic phases were dried (Na2SO4) and the solvent removed in vacuo. The residue was purified by flash chromatography with silica gel (EtOAc-petrol) to give, 4a (126 mg, 81 %) as a colourless solid which was recrystallised from hexane m.p. 71-72 (C (lit. 73-74 (C). General Procedure D. Heck Reaction (See Tables 2 and 3) Preparation of 5f: Bromopyridine 3b (0.112g, 0.4 mmol) was dissolved in dry acetonitrile (6 mL) in a resealable tube. Pd(OAc)2 (2 mg, 0.01 mmol), P(o-Tol)3 (6 mg, 0.02 mmol), NEt3 (0.3 mL, 2.1 mmol) and ethyl acrylate (70 (L, 0.64 mmol) were added under nitrogen and the tube was sealed and heated to 125 (C for 20 h. The mixture was cooled to room temperature, diluted with water, extracted with CH2Cl2 and dried (MgSO4). Chromatography on silica gel (EtOAc-petrol) gave 5f (62 mg, 5 3%) as a pale yellow solid. Characterization data are described below. General Procedure E. Suzuki Reaction (See Tables 2 and 3)- Preparation of 5a: To a solution of 3b (0.112g, 0.4 mmol) in toluene (5 mL) and EtOH (1 mL) were added 4-methylbenzeneboronic acid (82 mg, 0.6 mmol), Pd(PPh3)4 (23 mg, 0.02 mmol) and 2M aq. Na2CO3 (2 mL). The mixture was vigorously stirred and heated at reflux for 1h. The mixture was diluted with water, extracted with diethyl ether, the extracts were washed with aq. NaHCO3 and dried (MgSO4). Chromatography on silica (EtOAc-petrol) gave 5a (114 mg, 98 %) as a yellow solid. Characterization data are described below. General Procedure F. Metallation of 2-bromopyridine using LTMP, (see Scheme 3) Preparation of 8a and 10a: To tetramethylpiperidine (0.22 mL, 1.3 mmol) in dry THF (4 mL) was dropped nBuLi (1.5 M in hexane, 0.83 mL, 1.25 mmol) at 0(C. The solution was stirred for 25 min and then dropwise added to 2-bromopyridine (0.12 mL, 1.25 mmol) in THF (4 mL) at -78(C. After 20 min at that temperature, ZnCl2 (170 mg, 1.25 mmol) in THF (1 mL) was added and a precipitate formed. The mixture was allowed to warm to room temperature and 4-iodoanisol (117 mg, 0.5 mmol) in THF (2 mL), followed by Pd(PPh3)4 (30 mg, 0.025 mmol) was added. The solution was heated to reflux for 2h. After aqueous work-up, Chromatography on silica (EtOAc-petrol) yielded 10a (30 mg) as a colourless solid, followed by 8a (81 mg) as a yellow oil. Total yield 111 mg (84 %). Characterization data are described below. Characterization Data for Compounds Reported (compounds were recrystallised from hexanes unless otherwise stated) 3a m.p. 75-76 (C; Rf = 0.46 (1:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.79 (s, 1H), 8.51 (d, J = 4.9, 1H), 7.41 (d, J = 8.9, 2H), 7.25 (d, J = 4.9, 1H), 6.99 (d, J = 8.9, 2H), 3.87 (s, 3H); 13C NMR (68 MHz, CDCl3) ( 160.2, 152.6, 149.4, 148.3, 130.6, 130.3, 125.7, 121.0, 113.9, 55.4; MS (EI) m/z 265 (68, M+), 264 (8), 263 (70, M+), 220 (10), 83 (100); HRMS (EI) m/z calcd for C12H1081BrNO 264.9925 (M+), found 264.9922. 3b Recrystallised from methanol m.p. 141-142 (C; 1H NMR (270 MHz, CD2Cl2) ( 8.85 (s, 1 H), 8.60 (d, J=4.9 Hz, 1 H), 8.32 (d, J= 8.9 Hz, 2 H), 7.63 (d, J=8.9 Hz, 2 H), 7.30 (d, J=4.9 Hz, 1 H); 13C NMR (75 MHz, CDCl3) ( 152.6, 148.4, 148.2, 147.8, 144.3, 130.0, 125.16, 123.7, 120.4; MS (EI) m/z 280 (M+, 81Br, 75 %), 278 (M+, 79Br, 73 %), 264 (10), 250 (13), 153 (100), 126 (78); HRMS (EI) m/z calcd for C11H779BrN2O2 277.9691 (M+), found: 277.9690. 3c m.p. 117-118 (C; 1H NMR (300 MHz, CDCl3) ( 8.91 (br s, 1 H), 8.66 (br s, 1 H), 7.83 (m, 1 H), 7.73 (m, 1H), 7.59 (m, 1H), 7.43 (m, 1H), 7.34 (m, 1H); m/z (CI) 261 (MH+, 81Br, 88 %), 259 (MH+, 79Br, 90 %), 85 (100), 83 (96), 71 (42), 57 (62); HRMS (CI) m/z calcd for C12H879BrN2 (MH+) 258.9871, found 258.9875. Anal Calcd for C12H8BrN C, 55.63; H, 2.72; N, 10.81. Found: C, 56.04; H, 2.57; N 10.86. 3d This compound had identical data to that reported ( ADDIN ENBbu Comins, D. L.; Mantlo, N. B. J. Heterocycl. Chem. 1983, 20, 1239-1243). 3e m.p. 74-75 (C; 1H NMR (300 MHz, CDCl3) ( 8.76 (s, 1 H), 8.56 (d, J=5.0 Hz, 1 H), 7.37-7.19 (m, 6 H), 5.90 (broad s, 1 H), 5.33 (broad s, 1 H); 13C NMR (75 MHz, CDCl3) ( 152.2, 150.6, 148.1, 146.8, 138.1, 128.6, 128.3, 126.6, 126.1, 121.7, 117.3; m/z (CI) 262 (MH+, 81Br, 90 %), 260 (MH+, 79Br, 100 %), 180 (90), 83 (32), 57 (42); HRMS (CI) m/z calcd for C13H1179BrN requires 260.0075 (MH+), found 260.0073; Anal Calcd for C13H11BrN C, 60.02; H, 3.87; N, 5.38. Found: C, 59.81; H, 3.55; N 5.05. 3f. Recrystallised from hexane m.p. 80-82 (C; 1H NMR (270 MHz, CDCl3) (amide rotomers were evident and 13C NMR spectrum was poorly resolved) ( 8.70 (m, 1 H), 8.46 (m, 1 H), 7.50 (d, J=5.0 Hz, 0.5 H), 7.22 (m, 0.5 H), 7.18 (m, 0.5 H), 7.12 (d, J=4.6 Hz, 0.5 H), 5.79 (m, 1 H) 4.80 (dd, J=14.1, 1.3 Hz, 0.5 H), 4.67 (m, 1 H), 4.56 (m, 1 H), 4.47 (dd, J=6.3, 1.6 Hz, 0.5 H), 4.30 (dd, J=6.3, 1.3 Hz, 0.5 H), 4.24 (dd, J=13.8, 1.6 Hz, 0.5 H), 2.64-1.62 (m, 8 H); MS (CI) 351 (MH+, 90 %, 81Br), 349 (MH+, 100 %, 79Br), 305 (95), 307 (100), 227 (50), 85 (82); HRMS (CI) ) m/z calcd for C16H1879BrN2O2 349.0552 (MH+) 349.0456. 4a This compound had identical data to that reported by Comins ( ADDIN ENBbu Comins, D. L.; Mantlo, N. B. J. Heterocycl. Chem. 1983, 20, 1239-1243). 4b This compound had identical data to that reported (Ishikara, M.; Ohta, T.; Terashima, M. Chem. Pharm. Bull. 1985, 33, 4755) 5a m.p. 136-137(C; Rf = 0.30 (1:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.70 (s, 1H), 8.67 (d, J = 4.9, 1H), 8.13 (d, J = 8.9, 2H), 7.30-7.37 (m, 1H), 7.34 (d, J = 9.2, 2H), 7.10 (d, J = 7.9, 2H), 7.00 (d, J = 8.2, 2H), 2.34 (s, 3H); 13C NMR (68 MHz, CDCl3) ( 151.4, 148.8, 147.3, 145.6, 145.3, 137.9, 135.8, 133.8, 130.3, 129.7, 129.4, 124.0, 123.6, 21.2; MS (EI) m/z 291 (41), 290 (100, M+), 273 (35), 243 (55), 229 (45); HRMS (EI) m/z calcd for C18H14N2O2 290.1055 (M+), found 290.1050. 5b Recrystallised from toluene m.p. 181-182 (C; 1H NMR (300 MHz, CDCl3) d 8.73 (m, 2 H), 8.15 (d, J= 8.8 Hz, 2 H), 7.46-7.26 (m, 6 H), 7.13 (m, 2 H); m/z (CI) 277 (MH+, 100 %), 247 (32), 85 (20); HRMS (CI) calcd for C17H13N2O2 requires 277.0977 (MH+), found: 277.0975. 5c m.p. 135-136 (C; Rf = 0.20 (1:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.75 (d, J = 5.3, 1H), 8.71 (s, 1H), 8.16 (d, J = 8.9, 2H), 7.58 (d, J = 8.0, 2H), 7.39 (d, J = 5.3, 1H), 7.34 (d, J = 8.9, 2H), 7.28 (d, J = 8.0, 2H); 13C NMR (68 MHz, CDCl3) ( 151.1, 149.8, 147.6, 145.6, 144.7, 140.5, 140.5, 134.4, 130.3, 125.7, 124.2, 123.8, 121.0 (CF3 was not observed); MS (EI) m/z 344 (58, M+), 314 (18), 298 (25), 83 (100); HRMS (EI) m/z calcd for C18H11F3N2O2 344.0773 (M+), found 344.0764. 5d m.p. 95-96 (C; Rf = 0.30 (1:1 hex/EtOAc); 1H NMR `(270 MHz, CDCl3) ( 8.69 (d, J = 4.9, 1H), 8.67 (d, J = 0.6, 1H), 8.15 (d, J = 8.9, 2H), 7.34 (d, J = 8.9, 2H), 7.33 (dd, J = 4.9, 0.6, 1H), 7.21 (dd, J = 3.3, 2.0, 1H), 6.21-6.27 (m, 2H), 1.25 (s, 9H); 13C NMR (75 MHz, CDCl3) ( 150.9, 149.5, 148.0, 147.2, 146.3, 145.4, 129.3, 128.9, 128.6, 123.3, 123.0, 122.8, 116.5, 111.0, 83.8, 77.2, 28.0, 27.5 (some duplication of signals was apparent and was attributed to amide resonance); MS (EI) m/z 365 (3, M+), 309 (10), 265 (100), 218 (55); HRMS (EI) m/z calcd for C20H19N3O4 365.1376 (M+), found 365.1386. 5e Colorless oil; Rf = 0.48 (1:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.58 (d, J = 0.6, 1H), 8.56 (d, J = 4.9, 1H), 7.29 (dd, J = 5.2, 0.6, 1H), 7.02-7.12 (m, 6H), 6.79 (d, J = 8.6, 2H), 3.79 (s, 3H), 2.34 (s, 3H); 13C NMR (68 MHz, CDCl3) ( 159.4, 151.2, 148.5, 147.3, 137.0, 135.7, 135.1, 131.1, 130.6, 129.7, 129.1, 124.5, 113.8, 55.3, 21.2; MS (EI) m/z 276 (35), 275 (100, M+), 274 (34), 260 (42), 244 (26); HRMS (EI) m/z calcd for C19H17NO 275.1310 (M+), found 275.1306. 5f mp 112-113 (C; Rf = 0.18 (1:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.94 (s, 1H), 8.70 (d, J = 4.9, 1H), 8.36 (d, J = 8.9, 2H), 7.55 (d, J = 15.8, 1H), 7.54 (d, J = 8.9, 2H), 7.31 (dd, J = 4.9, 0.6, 1H), 6.51 (d, J = 15.8, 1H), 4.24 (q, J = 7.2, 2H), 1.31 (t, J = 7.2, 3H); 13C NMR (68 MHz, CDCl3) ( 165.9, 150.6, 148.9, 148.1, 146.8, 143.8, 139.1, 130.2, 128.5, 124.0, 123.9, 122.4, 60.9, 14.3; MS (EI) m/z 298 (<1, M+), 269 (3), 253 (30), 225 (82), 179 (100); HRMS (EI) m/z calcd for C16H14N2O4 298.0954 (M+), found 298.0941. 5g Colorless oil; Rf = 0.06 (1:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 9.03 (s, 1H), 8.68 (d, J = 2.3, 1H), 8.63 (d, J = 5.8, 1H), 8.34 (d, J = 8.9, 2H), 7.14-7.71 (m, 8H); MS (EI) m/z 302 (100, M-H+), 272 (10), 256 (56), 225 (44); HRMS (EI) m/z calcd for C18H12N3O2 302.0930 (M-H+), found 302.0923. 5f mp 76-78 (C; Rf = 0.32 (1:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.85 (s, 1H), 8.58 (d, J = 5.3, 1H), 7.72 (d, J = 16.1, 1H), 7.24-7.32 (m, 3H), 7.01 (d, J = 8.6, 2H), 6.48 (d, J = 16.1, 1H), 4.24 (q, J = 7.2, 2H), 3.87 (s, 3H), 1.31 (t, J = 7.2, 3H); 13C NMR (68 MHz, CDCl3) ( 166.4, 160.3, 150.2, 149.0, 148.7, 141.0, 130.7, 129.6, 128.7, 124.2, 120.7, 114.3, 60.6, 55.4, 14.3; MS (EI) m/z 283 (38, M+), 238 (15), 210 (100), 167 (60); HRMS (EI) m/z calcd for C17H17NO3 283.1208 (M+), found 283.1208. 8a colorless oil; Rf = 0.38 (4:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.34 (dd, J = 4.6, 2.0, 1H), 7.58 (dd, J = 7.6, 2.0, 1H), 7.41 (ddd, J = 7.6, 2.0, 1.7, 1H), 7.30 (dd, J = 7.6, 4.9, 1H), 7.18 (dd, J = 7.6, 1.7, 1H), 7.07-6.96 (m, 2H), 3.78 (s, 3H); 13C NMR (68 MHz, CDCl3) ( 156.6, 148.6, 144.0, 139.7, 137.2, 130.8, 130.1, 128.2, 122.4, 120.5, 111.2, 55.6; MS (EI) m/z 266 (5), 265 (31, M+), 264 (5), 263 (33, M+), 184 (100), 169 (74); HRMS (EI) m/z calcd for C12H1081BrNO 264.9925 (M+), found 264.9918. 8b. This compound has been described in the patent literature: Union Carbide Corp.; DE 2052536; 1970 (Chem. Abstr. 75; 35756) Rf = 0.30 (4:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.37 (dd, J = 4.9, 2.0, 1H), 7.62 (dd, J = 7.6, 2.0, 1H), 7.39-7.50 (m, 5H), 7.33 (dd, J = 7.6, 4.9, 1H); 13C NMR (75 MHz, CDCl3) ( 148.7, 142.3, 139.7, 139.1, 138.9, 129.3, 128.3, 128.3, 122.7; MS (EI) m/z 235 (55, M+), 234 (7), 233 (52, M+), 154 (94), 83 (100); HRMS (EI) m/z calcd for C11H881BrN 234.9819 (M+), found 234.9813. 8c mp 170-172(C; Rf = 0.16 (4:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.46 (dd, J = 4.6, 1.7, 1H), 8.33 (d, J = 8.9, 2H), 7.60-7.67 (m, 3H), 7.41 (dd, J = 7.6, 4.6, 1H); 13C NMR (75 MHz, CDCl3) ( 149.9, 147.7, 145.2, 141.6, 138.8, 137.7, 130.4, 123.6, 122.9; MS (EI) m/z 281 (20), 280 (95, M+), 279 (21), 278 (96, M+), 199 (86), 153 (100); HRMS (EI) m/z calcd for C11H781BrN2O2 279.9670 (M+), found 279.9678. 9a Colorless oil; Rf = 0.42 (1:1 hex/EtOAc); 1H NMR (300 MHz, CDCl3) ( 8.66 (dd, J = 4.8, 1.8, 1H), 7.66 (dd, J = 7.7, 1.8, 1H), 7.21-7.32 (m, 2H), 7.23 (d, J = 8.1, 2H), 7.14 (dd, J = 7.5, 1.8, 1H), 7.00 (dd, J = 8.4, 0.7, 2H), 6.94 (td, J = 7.5, 1.1, 1H), 6.78 (dd, J = 8.3, 1.1, 1H), 3.40 (s, 3H), 2.28 (s, 3H); 13C NMR (75 MHz, CDCl3) ( 158.1, 156.2, 148.2, 139.0, 138.1, 137.2, 132.6, 131.2, 129.3, 129.1, 128.7, 128.2, 121.5, 120.7, 111.1, 55.1, 21.2; MS (EI) m/z 276 (28), 275 (94, M+), 274 (100), 260 (45), 244 (77); HRMS (EI) m/z calcd for C19H17NO 275.1310 (M+), found 275.1299. 9b Colorless oil; Rf = 0.66 (1:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.62 (dd, J = 4.6, 1.6, 1H), 7.61 (dd, J = 7.6, 1.6, 1H), 7.52 (d, J = 15.5, 1H), 7.41 (ddd, J = 8.3, 2.0, 1.7, 1H), 7.32 (dd, J = 7.9, 4.6, 1H), 7.15 (dd, J = 7.6, 2.0, 1H), 7.05 (d, J = 15.5, 1H), 6.98-7.08 (m, 2H), 4.19 (q, J = 7.2, 2H), 3.75 (s, 3H), 1.26 (t, J = 7.2, 3H); 13C NMR (68 MHz, CDCl3) ( 167.1, 156.6, 150.8, 148.6, 141.8, 138.8, 135.2, 131.4, 130.1, 126.8, 123.8, 122.5, 120.9, 111.3, 60.3, 55.5, 14.3; MS (EI) m/z 285 (16), 284 (70, M+H+), 283 (10, M+), 238 (100), 210 (78); HRMS (EI) m/z calcd for C17H17NO3 283.1208 (M+), found 283.1206. 10a Colorless oil; Rf = 0.46 (4:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.36 (dd, J = 5.2, 0.7, 1H), 7.67 (dd, J = 1.5, 0.7, 1H), 7.43 (dd, J = 5.2, 1.5, 1H), 7.37-7.41 (m, 1H), 7.31 (dd, J = 7.6, 2.0, 1H), 7.09-6.98 (m, 2H), 3.84 (s, 3H); 13C NMR (68 MHz, CDCl3) ( 156.6, 149.6, 149.3, 142.2, 130.8, 130.4, 128.4, 126.3, 123.5, 121.2, 111.6, 55.7; MS (EI) m/z 266 (14), 265 (97, M+), 264 (15), 263 (100, M+), 184 (63), 169 (98); HRMS (EI) m/z calcd for C12H1081BrNO 264.9925 (M+), found 264.9918. 10b This compound has been reported previously: Case; Kasper; J. Amer. Chem. Soc. 1956, 78; 5842; Rf = 0.36 (4:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.41 (d, J = 5.3, 1H), 7.71 (d, J = 1.3, 1H), 7.57-7.65 (m, 2H), 7.43-7.55 (m, 4H); 13C NMR (75 MHz, CDCl3) ( 151.3, 150.5, 142.9, 136.7, 129.7, 129.3, 125.9, 120.9 (in this case, only 6 mg were isolated and no quaternary carbons could be observed in the 13C spectrum); MS (EI) m/z 236 (10), 235 (85, M+), 234 (11), 233 (84, M+), 154 (100), 127 (52); HRMS (EI) m/z calcd for C11H881BrN 234.9819 (M+), found 234.9809. 10c 185 (C (decomp); Rf = 0.20 (4:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.50 (dd, J = 5.0, 0.7, 1H), 8.37 (d, J = 8.9, 2H), 7.77 (d, J = 8.9, 2H), 7.74 (dd, J = 1.7, 0.7, 1H), 7.49 (dd, J = 5.3, 1.7, 1H); 13C NMR (75 MHz, CDCl3) ( 150.8, 128.1, 126.1, 124.5, 120.9; MS (EI) m/z 281 (15), 280 (84, M+), 279 (15), 278 (86, M+), 199 (100), 153 (75); HRMS (EI) m/z calcd for C11H781BrN2O2 279.9670 (M+), found 279.9674. 10d Isolated as an 1:3 but inseparable mixture together with the 2-bromo-3-(4-methoxyphenyl)pyridine. Signals (1H NMR) associated with 10d (minor component) are indicated with a prime mark ('). 13C NMR data are reported as observed. Rf = 0.40 (4:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.32-8.37 (m, 1H/1H'), 7.54-7.67 (m, 2H/1H'), 7.41 (dd, J = 5.0, 1.7, 1H'), 7.36 (d, J = 8.9, 2H), 7.29 (dd, J = 7.6, 4.6, 2H'), 6.95-7.03 (m, 2H/2H'), 3.86 (s, 3H/3H'); 13C NMR (75 MHz, CDCl3) ( 160.9, 159.5, 150.7, 150.3, 150.2, 148.3, 148.2, 142.9, 142.6, 139.3, 139.0, 131.1, 130.5, 128.7, 128.2, 125.0, 125.0, 122.7, 120.2, 120.1, 114.6, 113.6, 55.3, 55.2; MS (EI) m/z 266 (14), 265 (98, M+), 264 (15), 263 (100, M+), 184 (57),169 (27); HRMS (EI) m/z calcd for C12H1081BrNO 264.9925 (M+), found 264.9922. 11 Colorless oil; Rf = 0.60 (1:1 hex/EtOAc); 1H NMR (270 MHz, CDCl3) ( 8.68 (dd, J = 5.3, 0.7, 1H), 7.92 (d, J = 7.9, 2H), 7.86 (dd, J = 1.6, 0.7, 1H), 7.36-7.42 (m, 3H), 7.28 (d, J = 7.9, 2H), 6.96-7.11 (m, 2H), 3.83 (s, 3H), 2.40 (s, 3H); 13C NMR (68 MHz, CDCl3) ( 157.5, 156.7, 149.2, 147.2, 138.8, 137.0, 130.5, 130.0, 129.5, 128.3, 127.0, 122.7, 121.2, 121.1, 115.3, 111.6, 55.7, 21.3; MS (EI) m/z 277 (35), 276 (100, M+H+), 275 (59, M+), 274 (45), 260 (30); HRMS (EI) m/z calcd for C19H17NO 275.1310 (M+), found 275.1318. 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