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