The Journal of Organic Chemistry
Article
graphite anode. A solution of 0.1 M NBu4ClO4 in MeCN was used as
a conductive reaction media. To the cathodic chamber were added 1a
(0.16 mmol, 1 equiv) and 8 mL of electrolyte solution. To the anodic
chamber, 2 mL of electrolyte solution was added. The reaction was
performed under the protection of nitrogen at room temperature with
a constant current of 3.3 mA for 4 h (∼3 equiv of electrons). After the
reaction was completed, solvent was removed under reduced pressure
and the resulting crude mixture was analyzed by 1H NMR using 1,3,5-
trimethoxybenzene as an internal standard. The reaction gave ∼43%
1H NMR yield of 2a, ∼86% 1H NMR yield of 3a, and ∼41% 1H NMR
yield of 4a. The structure of 4a was determined by comparison to a
previous report.27 (Note: Due to a large amount of electrolyte in the
Purified by gradient elution (10−40% ethyl acetate/hexanes) column
chromatography on silica gel.
Reaction of 1c (53 mg) at −2.3 V for 4 h produced 2c (27 mg,
81%) and 3a (18 mg, 92%). 1-(3,4,5-trimethoxyphenyl)ethan-1-one
(2c).13,24 Colorless, amorphous solid. Yield: from electrolysis of 1c at
−2.3 V for 4 h. 1H NMR (500 MHz, CDCl3) δ: 7.22 (s, 2H), 3.92 (s,
6H), 3.92 (s, 3H), 2.59 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3)
δ: 196.8, 153.0, 142.5, 132.4, 105.6, 60.8, 56.1, 26. 5. Purified by
gradient elution (10−40% ethyl acetate/hexanes) column chromatog-
raphy on silica gel.
Reaction of 1d (48 mg) at −2.3 V for 4 h, with addition of AcOH
(0.8 mmol, 5 equiv) to the cathodic chamber, produced 2d (24 mg,
82%) and 3a (13 mg, 72%). 3-Hydroxy-1-(4-methoxyphenyl)propan-1-
one (2d).13,24 Colorless, amorphous solid. 1H NMR (500 MHz,
CDCl3) δ: 7.94 (d, 2H, J = 8.9 Hz), 6.94 (d, 2H, J = 8.9 Hz), 4.01 (q,
2H, J = 11.2, 5.6 Hz), 3.88 (s, 3H), 3.18 (t, 2H, J = 5.4 Hz), 2.76 (m,
1H). 13C{1H} NMR (126 MHz, CDCl3) δ: 199.2, 164.0, 130.5, 114.0,
58.4, 55.7, 40.2. Purified by gradient elution (10−50% ethyl acetate/
hexanes) column chromatography on silica gel.
1
crude mixture, the signals in H NMR were distorted to some extent
and the reported yields here were rough estimations.)
General Procedure for Reaction Optimization. Reaction was
performed in a divided cell equipped with a glassy carbon plate
cathode (2 cm2), a graphite anode, and a Ag/AgNO3 reference
electrode. A solution of 0.1 M electrolyte in MeCN was used as a
conductive medium. To the cathodic chamber were added 1a (0.16
mmol, 1 equiv) and 8 mL of electrolyte solution. To the anodic
chamber, 2 mL of reaction solution was added. Bulk electrolysis was
performed under the protection of nitrogen at room temperature with
a constant potential. After the reaction was completed, solvent was
removed under reduced pressure and the resulting crude mixture was
Reaction of 1e (58 mg) at −2.3 V for 4 h, with addition of AcOH
(0.8 mmol, 5 equiv) to the cathodic chamber, produced 2e (29 mg,
85%) and 3b (19 mg, 78%). 1-(3,4-Dimethoxyphenyl)-3-hydroxypro-
pan-1-one (2e).13,24 Colorless, amorphous solid. 1H NMR (500 MHz,
CDCl3) δ: 7.59 (dd, 1H, J = 8.3, 2.0 Hz), 7.52 (s, 1H), 6.90 (d, 1H, J
= 8.4 Hz), 4.02 (q, 2H, J = 11.9, 5.2 Hz), 3.95 (s, 3H), 3.94 (s, 3H),
3.19 (t, 2H, J = 5.4 Hz), 2.73 (t, 1H, J = 6.6 Hz). 13C{1H} NMR (126
MHz, CDCl3) δ: 198.06, 152.6, 148.0, 128.9, 121.9, 109.0, 108.8,
57.3, 55.1, 55.0, 38.8. 2,6-Dimethoxyphenol (3b).13,24 Colorless,
1
analyzed by H NMR using 1,3,5-trimethoxybenzene as an internal
standard. A full optimization table is presented in the SI.
Monitoring the Reaction Progress by GCMS. Electrolysis of 1a
was performed with NBu4ClO4 at a constant potential of −2.7 V for 6
h. An aliquot reaction solution was taken for GC−MS analysis every
30 min and was reinjected into reaction solution. The concentrations
for each molecule were calculated according to their premade
calibration curves. Tabulated raw data is presented in the SI.
Sodium 2-Methoxyphenoxide (3a′). White solid. Yield: 4 mg
(<10%), from electrolysis of 1a with NaClO4. After the reaction, a
white solid coated on the cathode was isolated. The solid was rinsed
with MeCN (3 mL × 3) and dried over vacuum. The major species in
1
amorphous solid. H NMR (500 MHz, CDCl3) δ: 6.79 (t, 1H, J =
8.6 Hz,), 6.59 (s, 1H), 6.58 (s, 1H), 5.51 (br s, 1H), 3.89 (s, 6H);
13C{1H} NMR (126 MHz, CDCl3) δ: 147.3, 134.9, 119.1, 105.0, 56.3.
Purified by gradient elution (10−50% ethyl acetate/hexanes) column
chromatography on silica gel.
Reaction of 1f (58 mg) at −2.3 V for 4 h, with addition of AcOH
(0.8 mmol, 5 equiv) to the cathodic chamber, produced 2f (28 mg,
74%) and 3a (14 mg, 75%). 3-Hydroxy-1-(3,4,5-trimethoxyphenyl)-
propan-1-one (2f).13,24 Colorless, amorphous solid. Yield: 28 mg
(74%), from electrolysis of 1f at −2.3 V for 4 h, with addition of
1
the crude solid was characterized as 3a′. H NMR (500 MHz, D2O)
δ: 6.90 (dd, 1H, J = 7.9, 1.4 Hz), 6.83−6.79 (dt, 1H, J = 7.8, 1.5 Hz),
6.67−6.65 (dd, 1H, J = 7.8, 1.5 Hz), 6.59−6.55 (dt, 1H, J = 7.8, 1.5
Hz), 3.75 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ: 161.0, 147.9,
121.7, 119.8, 116.1, 112.8, 55.9.
1
AcOH (0.8 mmol, 5 equiv) to the cathodic chamber. H NMR (500
MHz, CDCl3) δ: 7.23 (s, 2H), 4.3 (q, 2H, J = 11.5, 5.7 Hz), 3.93 (s,
9H), 3.21 (t, 2H, J = 5.3 Hz), 2.61 (t, 1H, J = 6.7 Hz). 13C{1H} NMR
(126 MHz, CDCl3) δ: 199.2, 153.1, 143.0, 131.9, 105.6, 61.0, 58.2,
56.3, 40.1. Purified by gradient elution (10−50% ethyl acetate/
hexanes) column chromatography on silica gel.
General Procedure for Electrochemical Reductive Cleavage
of Substrates 1a−1g. The reaction was performed in a divided cell
equipped with a glassy carbon plate cathode (2 cm2), a graphite anode
and a Ag/AgNO3 reference electrode. A solution of 0.1 M NBu4Br in
MeCN was used as a conductive reaction media. To the cathodic
chamber were added 1 (0.16 mmol, 1 equiv) and 8 mL of electrolyte
solution. To the anodic chamber was added 2 mL of electrolyte
solution. Bulk electrolysis was performed under the protection of
nitrogen at room temperature with a constant potential. After the
reaction was completed, solvent was removed under reduced pressure.
The corresponding products 2−4 were purified by column
chromatography on silica gel using ethyl acetate/hexanes.
Reaction of 1g (48 mg) at −2.3 V for 4 h in MeCN-d3 produced 2g
(20 mg, 70% yield) and 3a (12 mg, 64%). 1-(4-Methoxyphenyl)-2-
methylpropan-1-one-2-d (2g). Colorless, amorphous solid, > 95% atom
1
D. H NMR (500 MHz, CDCl3) δ: 7.96−7.94 (d, 2H, J = 8.9 Hz),
6.93−6.95 (d, 2H, J = 8.8 Hz), 3.87 (s, 3H), 1.20 (s, 3H). 13C{1H}
NMR (126 MHz, CDCl3) δ: 203.11, 163.3, 130.5, 129.2, 113.7, 55.5,
+
19.2; HRMS (ESI/Q-TOF) m/z: [M + H]+ Calcd for C11H14DO2
180.1129; Found: 180.1117. Purified by gradient elution (10−40%
ethyl acetate/hexanes) column chromatography on silica gel.
Reaction of 1a (44 mg) at −2.7 V for 6 h produced 4a (36 mg,
75%, meso/dl = 44:56) and 3a (17 mg, 86%). 2,3-Bis(4-
methoxyphenyl)butane-2,3-diol (4a). Colorless, amorphous solid.
Reaction of 1a (44 mg) at −2.3 V for 4 h produced 2a (21 mg, 86%
yield) and 3a (18 mg, 92%). 1-(4-methoxyphenyl)ethan-1-one (2a).13,24
Colorless, amorphous solid. 1H NMR (500 MHz, CDCl3) δ: 7.92 (d,
2H, J = 8.9 Hz), 6.92 (d, 2H, J = 8.8 Hz), 3.85 (s, 3H), 2.54 (s, 3H).
13C{1H} NMR (126 MHz, CDCl3) δ: 196.7, 163.4, 130.5, 130.2,
1
meso isomer: H NMR (500 MHz, CDCl3) δ: 7.32−7.10 (m, 4H),
6.89−6.76 (m, 4H), 3.80 (s, 6H), 2.21 (br s, 2H), 1.56 (s, 3H).
13C{1H} NMR (126 MHz, CDCl3) δ: 158.4, 135.7, 128.1, 112.4, 78.5,
55.2, 25.0. dl isomer: 1H NMR (500 MHz, CDCl3) δ: 7.32−7.10 (m,
4H), 6.89−6.76 (m, 4H), 3.81 (s, 6H), 2.48 (br s, 2H), 1.47 (s, 3H).
13C{1H} NMR (126 MHz, CDCl3) δ: 158.5, 136.0, 128.5, 112.5, 78.7,
55.2, 25.2. HRMS (ESI/Q-TOF) m/z: [M + Na]+ Calcd for
113.6, 55.5, 26.4. 2-Methoxyphenol (3a).13,24 Colorless oil. H NMR
1
(500 MHz, CDCl3) δ: 6.96−6.94 (m, 1H), 6.90−6.85 (m, 3H), 5.66
(br s, 1H), 3.89 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ: 146.8,
145.8, 121.5, 120.2, 114.8, 111.0, 55.9. Purified by gradient elution
(10−40% ethyl acetate/hexanes) column chromatography on silica
gel.
+
C18H22NaO4 325.1416; Found: 325.1409. Purified by gradient
Reaction of 1b (48 mg) at −2.3 V for 4 h produced 2b (23 mg,
elution (10−70% ethyl acetate/hexanes) column chromatography
86% yield) and 3a (17 mg, 86%). 1-(3,4-dimethoxyphenyl)ethan-1-one
on silica gel.
(2b).13,24 Colorless, amorphous solid. H NMR (500 MHz, CDCl3)
Reaction of 1b (48 mg) at −2.7 V for 6 h produced 4b (42 mg,
72%, meso/dl = 51:49) and 3a (17 mg, 86%). 2,3-Bis(3,4-
dimethoxyphenyl)butane-2,3-diol (4b). Yellow, amorphous solid. Meso
1
δ: 7.55 (dd, 1H, J = 8.4, 2.1 Hz), 7.51 (m, 1H), 6.87 (d, 1H, J = 8.4
Hz), 3.93 (s, 3H), 3.92 (s, 3H), 2.55 (s, 3H). 13C{1H} NMR (126
MHz, CDCl3) δ: 196.6, 153.1, 148.7, 130.2, 123.0, 109.7, 55.8, 26.1.
1
isomer: H NMR (500 MHz, CDCl3) δ: 6.95−6.95 (m, 2H), 6.90−
F
J. Org. Chem. XXXX, XXX, XXX−XXX