Supporting Information for Regioselective Synthesis of -Bromo--unsaturated Carbonyl Compounds via Photocatalytic -Bromination reactions Dan Wang, Yating Zhao, Chao Yang, Wujiong Xia* †State Key Lab of Urban Water Resource and Environment, the Academy of Fundamental and Interdisciplinary Sciences, Harbin Institute of Technology, Harbin, 150080, E-mail: xiawj@hit.edu.cn Table of contents 1 General information..............................................................................2 2 General Procedure for the visible-light promoted α-bromination of α,β-unsaturated ketones or aldehydes...................................................2 3 General Procedure for the synthesis of α,β-unsaturated ketones or aldehydes..............................................................................................2 3.1 General Procedure for the synthesis of α,β-unsaturated ketones...........................................................................................................2 3.2 Synthesis of aldehyde 7a......................................................................3 4 Characterization of α-bromo-α,β-unsaturated carbonyl compounds....3 5 1 H NMR and 13C NMR spectra............................................................7 6 CV Spectra of 1a and 10a………………………………………..….27 1 1 General Information All reagents were purchased from commercial sources unless otherwise noted. Solvents were dried according to standard procedures prior to use. 1H NMR (600 or 400 MHz) and 13 C NMR (151 MHz) spectra are recorded on a Bruker AV-400 spectrometer in CDCl3. For 1H NMR (600 or 400 MHz), tetramethylsilane (TMS) serverd as internal standard (δ= 0 ppm) and data are reported as follows: chemical shift (in ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad), coupling constant (in Hz), and integration. For 13 C NMR (151 MHz), CDCl3 was used as internal standard (δ= 77.23 ppm) and spectra were obtained with complete proton decoupling. HR-MS spectra were recorded on a Bruker Esquire LC mass spectrometer using electrospray ionization (ESI, TOF). 2 General Procedure for the visible-light promoted -bromination of -unsaturated ketones or aldehydes (1b as an example) A 10 mL round bottom flask was equipped with a magnetic stir bar and was charged with substrate 1a (16.2 mg, 0.1 mmol), carbon tetrabromide (99 mg, 0.3 mmol), CH3CN (1.0 mL) and fac-Ir(ppy)3 (3.3 mg, 0.005 mmol). The reaction mixture was degassed three times by Freeze-Pump-Thaw cycles and then was stirred at room temperature. N2 protected, the mixture was irradiated by blue LEDs (1 W) . After 76 h the reaction was completed (monitored by TLC), the solvent was concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (petroleum ether–EtOAc = 50:1) to afford the desired product 1b (19.8mg, 83%) . 3 General Procedure for the synthesis of -unsaturated ketones or aldehydes. 3.1 General procedure for synthesis of α,β-unsaturated ketones 2 OH R O Vinylmagnesium chloride R THF, -78 °C To a cooled (-78 oC) solution of vinylmagnesium chloride (2.0 M in THF, 1.5 mL, 3.0 mmol) and Aldehydrate (2.0 mmol) in THF (10 mL) was added dropwise. The reaction mixture was stirred at -78 oC for 30 min, then quenched by the addition of saturated NH4Cl solution (10 mL) . After separation, the aqueous layer was extracted with Ethyl acetate (2 X 15 mL). The combined organic layers were washed with brine (3 X 15 mL), then dried over Na2SO4. The combined organic layers were concentrated to a residue that was subjected to column chromatography (1:3 EtOAc/hexanes) to give the title compound. OH O MnO2, CH2Cl2 R R 0 °C, 30 min MnO2 (0.87 g, 10 mmol) was added to a flame dried flask, then CH2Cl2 (30 mL) was introduced at room temperature. A solution of the alcohol (1.0 mmol) in CH2Cl2 (5 mL) was added dropwise at 0 oC to the above mixture. The mixture was stirred at 0 o C for 30 min, and filtered though a pad of Celite. The oil residue in the funnel was washed with CH2Cl2 (3 X 15 mL). The residue was purified by flash column chromatography to give ketones. 3.2 Synthesis of aldehyde 7a Ph Ph PCC, CH2Cl2 O 0 °C, 1.5 h 7a OH PCC (2.0 mmol, 432 mg) with same amount celite was added to a flame dried flask, then CH2Cl2 (30 mL) was introduced at room temperature.A solution of the alcohol get in the same way above (210 mg, 1.0mmol) in CH2Cl2 (4 mL) was added dropwise at 0 oC to the above mixture. The mixture was stirred at 0 oC for 1.5h, and filtered though a pad of Celite. The solid residue in the funnel was washed with CH2Cl2 (3 X 20 mL). The residue was purified by flash column chromatography to give product 7a (116 mg, 56%). 4 Characterization of -bromo--unsaturated ketones or aldehydes O O (Z)-2-bromo-3-(2-methoxyphenyl)acrylaldehyde (1b): 1H NMR (400 MHz, CDCl3) δ 9.35 (s, 1H; CHO), 8.35 (d, J=7.7 Br 3 Hz, 1H), 8.32 (s, 1H), 7.47 (t, J=7.9 Hz, 1H), 7.06 (t, J=7.6 Hz, 1H), 6.96 (d, J=8.3 Hz, 1H), 3.91 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 186.28, 157.10, 143.37, 132.08, 129.01, 123.56, 120.91, 119.27, 109.74, 54.69; GC-MS (EI): 242, 240, 211, 209, 161, 131; HRMS (ESI-TOF) Calcd for C10H10BrO2, [M+H]+ 240.9864, Found 240.9874. (Z)-2-bromo-3-phenylacrylaldehyde (2b): 1H NMR (400 MHz, CDCl3) δ 9.34 (s, 1H), 8.00 (d, J=5.5 Hz, 2H), 7.90 (s, 1H), O Br 7.58-7.42 (m, 3H). 13C NMR (151 MHz, CDCl3) δ 187.17, 149.33, 132.94, 131.66, 131.01, 128.82, 124.28. GC-MS (EI): 212, 210, 184, 182, 155; HRMS (ESI-TOF) Calcd for C9H8BrO, [M+H]+ 210.9768, Found 210.9759. (Z)-2-bromo-3-(4-methoxyphenyl)acrylaldehyde (3b): 1H NMR (400 MHz, CDCl3) δ 9.32 (s, 1H), 8.06 (d, J=8.0 Hz, 2H), O Br 7.84 (s, 1H), 7.02 (d, J=8.0 Hz, 2H), 3.91 (s, 3H). 13C NMR O (151 MHz, CDCl3) δ 187.09, 162.41, 149.06, 133.38, 125.64, 121.65, 114.30, 55.54. GC-MS (EI): 242, 240, 225, 211,209; HRMS (ESI-TOF) Calcd for C10H10BrO2, [M+H]+ 240.9864, Found 240.9871. (Z)-2-bromo-3-(4-fluorophenyl)acrylaldehyde (4b): 1H NMR O (400 MHz, CDCl3) δ 9.34 (s, 1H), 8.10-8.00 (m, 2H), 7.86 (s, Br F 1H), 7.19 (t, J=8.2 Hz, 2H). 13C NMR (151 MHz, CDCl3) δ 186.92 (s, -CHO), 164.35 (d, J=254.9 Hz, CAr), 147.69 (s, =CH), 133.30 (d, J= 8.8 Hz, CAr), 129.20 (d, J=3.4 Hz, CAr), 123.96 (s, =CBr), 116.12 (d, J=21.9 Hz, CAr). GC-MS (EI): 230, 228, 211, 209, 133; HRMS (ESI-TOF) Calcd for C9H7BrFO, [M+H]+ 228.9664, Found 228.9673. (Z)-2-bromo-3-(4-chlorophenyl)acrylaldehyde (5b):1H NMR O (600 MHz, CDCl3) δ 9.35 (s, 1H), 7.96 (d, J=8.1 Hz, 2H), 7.86 Br (s, 1H), 7.47 (d, J=8.1 Hz, 2H). 13C NMR (151 MHz, CDCl3) δ Cl 186.83, 147.46, 137.69, 132.12, 131.36, 129.20, 124.80. GC-MS (EI): 246, 244, 211, 165, 136; HRMS (ESI-TOF) Calcd for C9H7BrClO, [M+H]+ 244.9369, Found 244.9374. (Z)-2-bromo-3-(3-chlorophenyl)acrylaldehyde (6b):1H NMR Cl (600 MHz, CDCl3) δ 9.35 (s, 1H), 8.01 (s, 1H), 7.85 (d, J=6.2 O Br Hz, 2H), 7.48 (d, J=8.5 Hz, 1H), 7.43 (t, J=15.4, 7.4 Hz, 1H). 13 C NMR (151 MHz, CDCl3) δ 186.78, 147.15, 134.81, 134.58, 131.38, 130.38, 130.03, 128.96, 125.62. GC-MS (EI): 246, 244, 233, 209, 154; HRMS (ESI-TOF) Calcd for C9H7BrClO, [M+H]+ 244.9369, Found 244.9381. (Z)-3-([1,1'-biphenyl]-2-yl)-2-bromoacrylaldehyde (7b): 1H O Br NMR (600 MHz, CDCl3) δ 9.21 (s, 1H), 8.24 (d, J=7.6 Hz, 1H), Ph 7.81 (s, 1H), 7.61-7.42 (m, 6H), 7.34 (dd, J=7.4, 1.7 Hz, 13 2H). C NMR (151 MHz, CDCl3) δ 186.87, 149.56, 143.41, 139.61, 131.24, 130.80, 130.23, 129.77, 129.52, 128.52, 128.14, 127.18, 125.95. GC-MS (EI): 288, 286, 207, 178, 152; HRMS (ESI-TOF) Calcd for C15H12BrO, [M+H]+ 287.0072, Found 287.0081. 4 (Z)-2-bromo-3-(2-nitrophenyl)acrylaldehyde (8b):1H NMR NO2 (600 MHz, CDCl3) δ 9.49 (s, 1H), 8.35 (s, 1H), 8.27 (d, J = 8.3 O Br Hz, 1H), 7.80 – 7.77 (m, 2H), 7.69 – 7.65 (m, 1H). 13 C NMR (151 MHz, CDCl3) δ 186.10, 146.74, 146.49, 133.88, 131.02, 130.87, 129.57, 128.11, 125.19. GC-MS (EI): 257, 255, 176, 148, 119; HRMS (ESI-TOF) Calcd for C9H7BrNO3, [M+H]+ 255.9609, Found 255.9612. O O2N Br (Z)-2-bromo-3-(4-nitrophenyl)acrylaldehyde (9b): 1H NMR (400 MHz, CDCl3) δ 9.41 (s, 1H), 8.34 (d, J = 8.7 Hz, 2H), 8.12 (d, J = 8.7 Hz, 2H), 7.97 (s, 1H). 13C NMR (151 MHz, CDCl3) δ 186.42, 148.69, 145.32, 138.89, 131.29, 127.91, 123.88. GC-MS (EI): 257, 255, 240, 238, 176; HRMS (ESI-TOF) Calcd for C9H7BrNO3, [M+H]+ 255.9609, Found 255.9617. 1-([1,1'-biphenyl]-2-yl)-2-bromoprop-2-en-1-one (10b): 1H Ph O NMR (600 MHz, CDCl3) δ 7.63-7.56 (m, 1H), 7.53-7.37 (m, 8H), 6.26 (d, J=2.3 Hz, 1H), 6.17 (d, J=2.3 Hz, 1H). 13C NMR Br (151 MHz, CDCl3) δ 192.71 , 141.02 , 139.99 , 136.76 , 132.49 , 132.40 , 131.09 , 129.98 , 128.91 , 128.83 , 128.80 , 127.85 , 127.41. GC-MS (EI): 288, 286, 207, 181, 152; HRMS (ESI-TOF) Calcd for C15H12BrO, [M+H]+ 287.0072, Found 287.0083. 2-bromo-1-phenylprop-2-en-1-one (11b): 1H NMR (600 MHz, O CDCl3) δ 7.82 (d, J=1.1 Hz, 1H), 7.81 (d, J=1.3 Hz, 1H), 7.63 – Br 7.58 (m, 1H), 7.48 (dd, J=10.9, 4.7 Hz, 2H), 6.55 (d, J=2.4 Hz, 1H), 6.48 (d, J=2.4 Hz, 1H). 13C NMR (151 MHz, CDCl3) δ 190.22 , 135.15 , 133.23 , 130.32 , 129.79 , 129.62 , 128.56. GC-MS (EI): 212, 210, 185, 131, 105; HRMS (ESI-TOF) Calcd for C9H8BrO, [M+H]+ 210.9759, Found 210.9763. 2-bromo-1-(o-tolyl)prop-2-en-1-one (12b): 1H NMR (400 O MHz, CDCl3) δ 7.38 (t, J=7.5 Hz, 1H), 7.33 (d, J=7.5 Hz, 1H), Br 7.28-7.21 (m, 2H), 6.63 (d, J=1.7 Hz, 1H), 6.43 (d, J=1.8 Hz, 1H), 2.34 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 191.90, 137.01, 136.19, 133.38, 132.80, 131.18, 130.90, 128.29, 125.32, 19.82. GC-MS (EI): 226, 224, 145, 119, 91; HRMS (ESI-TOF) Calcd for C10H10BrO, [M+H]+ 224.9915, Found 224.9924. 2-bromo-1-(2-bromophenyl)prop-2-en-1-one (13b): 1H NMR Br O (600 MHz, CDCl3) δ 7.62 (m, 1H), 7.40 (td, J= 7.5, 1.1 Hz, 1H), 7.35 (td, J=7.7, 1.8 Hz, 1H), 7.31 (m, 1H), 6.69 (d, J=2.5 Hz, Br 1H), 6.47 (d, J=2.5 Hz, 1H). 13C NMR (151 MHz, CDCl3) δ 5 189.67, 138.61, 134.56, 133.33, 131.71, 131.52, 128.77, 127.25, 119.48. GC-MS (EI): 292, 290, 288, 183, 155; HRMS (ESI-TOF) Calcd for C9H7Br2O, [M+H]+ 290.8843, Found 290.8854. 2-bromo-1-(2,4-dimethylphenyl)prop-2-en-1-one (14b): 1H O NMR (400 MHz, CDCl3) δ 7.27 (d, J=9.6 Hz, 1H), 7.08 (s, 1H), 7.04 (d, J=7.8 Hz, 1H), 6.58 (d, J=2.1 Hz, 1H), 6.42 (d, J=2.1 Br Hz, 1H), 2.36 (s, 3H), 2.34 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 191.77, 141.55, 137.62, 133.07, 132.78, 132.45, 132.11, 129.03, 125.93, 21.41, 19.97. GC-MS (EI): 240, 238, 159, 133, 105; HRMS (ESI-TOF) Calcd for C11H12BrO, [M+H]+ 239.0072, Found 239.0081. 2-bromo-1-(2,5-dimethoxyphenyl)prop-2-en-1-one (15b): 1H O MeO NMR (600 MHz, CDCl3) δ 7.02 – 6.96 (m, 1H), 6.92 – 6.84 (m, Br OMe 2H), 6.53 (d, J = 2.2 Hz, 1H), 6.50 (d, J = 2.2 Hz, 1H), 3.78 (s, 3H), 3.77 (s, 3H).13C NMR (151 MHz, CDCl3) δ 189.87, 153.35, 151.41, 132.04, 131.85, 127.07, 118.06, 114.22, 113.04, 56.40, 55.88. GC-MS (EI): 272, 270, 191, 165, 107; HRMS (ESI-TOF) Calcd for C11H12BrO3, [M+H]+ 270.9970, Found 270.9974. 2-bromo-1-(p-tolyl)prop-2-en-1-one (16b): 1H NMR (600 O MHz, CDCl3) δ 7.74 (d, J=8.2 Hz, 2H), 7.27 (d, J=7.9 Hz, 2H), Br 6.49 (d, J=2.4 Hz, 1H), 6.43 (d, J=2.4 Hz, 1H), 2.43 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 189.95, 144.33, 132.36, 130.04, 129.45, 129.36, 129.27, 21.74. GC-MS (EI): 226, 224, 172, 145, 119; HRMS (ESI-TOF) Calcd for C10H10BrO, [M+H]+ 224.9915, Found 224.9923. 2-bromo-1-(4-fluorophenyl)prop-2-en-1-one (17b): 1H NMR O (600 MHz, CDCl3) δ 7.90-7.85 (m, 2H), 7.16 (t, J=8.6 Hz, 2H), Br 6.51 (d, J=2.4 Hz, 1H), 6.44 (d, J=2.4 Hz, 1H). 13C NMR (151 F MHz, CDCl3) δ 188.80 (-CHO), 165.85 (d, J=255.8 Hz, CAr), 132.53 (d, J =9.4 Hz, CAr), 131.22 (d, J=3.0 Hz, CAr), 129.57 (=CH), 128.92 (-CBr), 115.86 (d, J=22.0 Hz, CAr). GC-MS (EI): 230, 228, 149, 123, 95; HRMS (ESI-TOF) Calcd for C9H7BrFO, [M+H]+ 228.9664, Found 228.9673. 2-bromo-1-(4-(tert-butyl)phenyl)prop-2-en-1-one (18b): 1H O NMR (400 MHz, CDCl3) δ 7.78 (d, J=8.4 Hz, 2H), 7.48 (d, Br J=8.3 Hz, 2H), 6.49 (d, J=2.1 Hz, 1H), 6.45 (d, J=2.1 Hz, 1H), t-Bu 1.35 (s, 9H). 13C NMR (151 MHz, CDCl3) δ 189.90, 157.23, 132.29, 129.89, 129.51, 129.49, 125.57, 35.22, 31.09. GC-MS (EI): 268, 266, 253, 210, 161; HRMS (ESI-TOF) Calcd for C13H16BrO, [M+H]+ 267.0385, Found 267.0394. 1-(benzo[d][1,3]dioxol-6-yl)-2-bromoprop-2-en-1-one (19b): O O O Br 1 H NMR (600 MHz, CDCl3) δ 7.48 (d, J = 8.3 Hz, 1H), 7.35 (s, 1H), 6.87 (d, J = 7.9 Hz, 1H), 6.41 (d, J = 1.6 Hz, 1H), 6.38 (d, 6 1H), 6.07 (s, 2H). 13 C NMR (151 MHz, CDCl3) δ 188.64, 152.37, 148.20, 129.10, 128.53, 128.04, 126.82, 109.57, 108.00, 102.06. GC-MS (EI): 256, 254, 149, 135, 121; HRMS (ESI-TOF) Calcd for C10H8BrO3, [M+H]+ 254.9657, Found 254.9660. 5 1H NMR and 13C NMR spectra Compound 1b 7 Compound 2b 8 Compound 3b 9 Compound 4b 10 Compound 5b 11 Compound 6b 12 Compound 7b 13 Compound 8b 14 Compound 9b 15 Compound 10b 16 Compound 11b 17 Compound 12b 18 Compound 13b 19 Compound 14b 20 Compound 15b 21 Compound 16b 22 Compound 17b 23 Compound 18b 24 Compound 19b 25 26 6 CV Spectra of 1a and 10a 0.00002 O 0.0001 Ph O 0.00001 O Current (A) Current (A) 0.0000 -0.0001 -0.0002 0.00000 -0.00001 -0.00002 -0.0003 -0.00003 -0.0004 -2.5 -2.0 -1.5 -1.0 -0.5 0.0 0.5 1.0 1.5 2.0 -2.5 Voltage (V vs. SCE) -2.0 -1.5 -1.0 -0.5 0.0 0.5 Voltage (V vs. SCE) 27 1.0 1.5 2.0