Esterification of Carboxylic Acids with Aryl Halides via the Merger of Paired Electrolysis and Nickel Catalysis

Article abstract of DOI:10.1021/acs.joc.1c00204

Electrochemistry has been successfully applied in metal catalysis to avoid the usage of chemical redox agents. This strategy proved to be a powerful approach to construct carbon-carbon (C-C) and carbon-heteroatom (C-X) bonds. However, most of the developed methods are based on either anodic oxidation or cathodic reduction, in which a sacrificial reaction occurs at the counter electrode. Paired electrolysis merging with metal catalysis is underdeveloped, wherein both anodic and cathodic processes are taking place simultaneously. Herein, we demonstrated that by using esterification of carboxylic acids with aryl halides via paired electrolysis using nickel as the catalyst the respective aryl esters were obtained in good to excellent yields at room temperature in an undivided electrochemical cell.

Full text of DOI:10.1021/acs.joc.1c00204

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Esterification of Carboxylic Acids with Aryl Halides via the Merger of
Paired Electrolysis and Nickel Catalysis
Lei Wei, Zhen-Hua Wang, Ke-Jin Jiao, Dong Liu, Cong Ma, Ping Fang, and Tian-Sheng Mei*
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ABSTRACT: Electrochemistry has been successfully applied in
metal catalysis to avoid the usage of chemical redox agents. This
strategy proved to be a powerful approach to construct carbon−
carbon (C−C) and carbon−heteroatom (C−X) bonds. However,
most of the developed methods are based on either anodic
oxidation or cathodic reduction, in which a sacrificial reaction
occurs at the counter electrode. Paired electrolysis merging with
metal catalysis is underdeveloped, wherein both anodic and cathodic processes are taking place simultaneously. Herein, we
demonstrated that by using esterification of carboxylic acids with aryl halides via paired electrolysis using nickel as the catalyst the
respective aryl esters were obtained in good to excellent yields at room temperature in an undivided electrochemical cell.
bond formation via paired electrolysis.9 We have always been
interested in Ni-catalyzed electrochemical reactions; we further
questioned whether esterification of carboxylic acids and aryl
halides could be achieved without the use of a sacrificial anode
INTRODUCTION
The organic electrochemical synthesis represents an environ-
mentally friendly method, as caustic stoichiometric chemical
■
redox reagents which are required in the conventional methods
could be reduced or prevented.1 Additionally, electrochemical
(Figure 1c). Aryl esters are commonly encountered in natural
products, pharmaceuticals, and polymers.10 Aryl esters have
methods offer a few advantages over chemical redox agents
also attracted great interest as green and inexpensive arylating
agents for the recent development of metal-catalyzed coupling
reactions via C−O activation.11 The cross-coupling between
aryl halides and carboxylic acids has been achieved using
expensive Pd catalysts, or/and excessive amounts of Ag salt, or
phosphine-based ligand at high temperature.12 Visible-light-
driven formations of the C−O bond have been reported by
several groups using kinds of photocatalysts through energy or
electron transfer.13 However, as the most controllable and
environmentally benign means, electrochemistry has not been
utilized in these transformations.14 Herein, we report
esterification of carboxylic acids and aryl halides via the
merger of paired electrolysis and nickel catalysis (Figure 1d).
Result and Discussion. To initiate the study, we examined
the electrochemical esterification of N-(tert-butoxycarbonyl)-
proline (BocPro-OH) (1a) with 4-bromobenzoic acid methyl
ester (2a) under various reaction conditions. To our delight,
81% isolated yield of the desired product (3a) could be
obtained under constant-current electrolysis at 4.0 mA in the
presence of 10 mol% NiBr2·glyme, 20 mol% d(OMe)bpy, 2
such as tunable redox strength, innocent feature, and
mechanistic investigation. In general, direct electrolysis
presents higher electric potentials and undesired side reactions.
Indirect electrolysis has received special attention since the
reactivity and selectivity could be governed by redox
mediators.2 In particular, the use of organotransition metals
as redox mediators has received tremendous attention since
redox potentials can be tuned via the modification of ligand,
and organotransition-metal-catalyzed reactions are well-devel-
oped. Thereby, various organotransition-metal-catalyzed ano-
dic oxidation has been developed, including C−H functional-
ization,3 and alkene functionalization,4 despite hydrogen being
generated as a byproduct in a cathodic cell (Figure 1a, left).
Organotransition-metal-catalyzed cathodic reduction has been
well-investigated, including reductive carboxylation of electro-
philes5 and couplings of organohalides.6 Unfortunately, the use
of a sacrificial anode is typically required (Figure 1a, right). In
order to maximize the energy efficiency of the electrolysis, the
merger of an organotranisiton metal with paired electrolysis is
an appealing strategy, in which both cathodic reduction and
anodic oxidation of the organometal species take place
simultaneously to generate the desired product (Figure 1b).
However, this promising strategy is underdeveloped, and only
a few examples of the merger of metal catalysis with paired
electrolysis are known.7 For instance, Baran and co-workers
have reported electrochemical amination of aryl halides via the
merger of Ni catalysis with paired electrolysis under mild
reaction conditions.8 Recently, we have also reported C−S
Special Issue: Electrochemistry in Synthetic Organic
Chemistry
Received: January 27, 2021
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© XXXX American Chemical Society
A

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(entries 2−5). The organic or inorganic bases such as collidine,
TMG, KOtBu, and KF were tested. These proved inapplicable
to this transformation (entries 7−10), whereas Cs2CO3 gave
the desired product in 38% yield (entry 6). Control
experiments indicate that NiBr2·glyme and electrical current
are necessary for this reaction (entries 11 and 12).
Next, the scope of the reaction was evaluated under the
optimized reaction conditions. As shown in Scheme 1, arenes
a
Scheme 1. Evaluation of Aryl Bromides
Figure 1. (a) Organotransition-metal-catalyzed anodic oxidation or
cathodic reduction. (b) Organotransition-metal-catalyzed paired
electrolysis. (c) Our hypothesis for esterification. (d) This work.
n
equiv of Bu4NBr, and 3 equiv of K2CO3 in DMA at room
temperature for 10 h (Table 1, entry 1). Variation of catalyst,
ligand, and electrode led to decreased yields or no reaction
a
Table 1. Reaction Optimization with Substrate 1a
b
entry
variation from standard conditions
none
yield (%)
c
1
90 (81)
2
3
4
5
6
7
NiBr2 instead of NiBr2·glyme
2,2-bpy instead of d(OMe)bpy
RVC instead of Graphite
Pt−Pt instead of graphite and Ni foam
Cs2CO3 instead of K2CO3
KF instead of K2CO3
42
58
65
0
38
0
a
Reaction conditions: undivided cell with a Ni-foam electrode (2.0 ×
3.0 cm2) as cathode and a graphite plate (1.0 × 2.0 cm2) as anode, rt,
b
KOtBu instead of K2CO3
2,4,6-collidine instead of K2CO3
TMG instead of K2CO3
no NiBr2·glyme
0
0
0
0
4.0 mA, 10 h. Undivided cell with two platinum electrodes (1.0 × 1.0
8
9
10
11
12
cm2).
substituted with a variety of functional groups such as ester,
trifluoromethyl, nitrile, chloro, sulfonyl, trifluoromethylthio,
and trifluoromethoxy groups were tolerated (3b−3i), affording
the product in good to excellent yields. In general, aryl
bromides with electron-deficient substituents reacted partic-
ularly well. In addition, various heterocycles, such as
benzofuran, benzothiophene, and indole substrates, are also
subjected to the electrochemical esterification protocol (3o−
3t). Besides, electron-donating groups, such as methylthio and
no electric current
0
a
Reaction conditions: 1a (0.3 mmol), 2a (2.0 equiv), NiBr2·glyme
(10 mol%), d(OMe)bpy (20 mol%), nBu4NBr (2.0 equiv), and DMA
(3 mL), in an undivided cell with a Ni-foam electrode (2.0 × 3.0 cm2)
as cathode and a graphite plate (1.0 × 2.0 cm2) as anode, rt, 4.0 mA,
10 h. Yields were determined by H NMR analysis with CH2Br2 as
an internal standard. Isolated yield in parentheses. RVC = reticulated
b
1
c
vitreous carbon. TMG = tetramethylguanidine.
B
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Scheme 2. Evaluation of Carboxylic Acids
phenoxy, are also accommodated with medium yield (3l and
3m).
Scheme 3. Gram-Scale Experiment
Next, the reactivity of a series of carboxylic acids was
investigated. As shown in Scheme 2, a variety of functional
groups were well-tolerated in the reaction. This protocal is
amenable to a wide range of primary, secondary, tertiary, and
aryl acids (4a−4i). To further showcase the utility of this
protocol, we subjected several drug molecules to the optimized
conditions. Remarkably, chlorambucil containing alkyl chloride
also succeeded in this transformation with the chlorine atoms
intact (4j). With nitrogen and oxygen-containing heterocycles,
oxaprozin (4k) afforded the desired product in good yield.
Carboxylic acids at activated positions, including ibuprofen and
naproxen (4l and 4n), were all converted to their
corresponding esterification analogs.
reductive peaks at −1.61 and −1.89 V versus Ag/AgNO3 in
DMA (red line, Figure 2), and they were all attributed to the
reductive potential of Ni(II)/Ni(I) because of loose
coordination between the ligand and nickel catalyst.15 With
the addition of 1a, the reductive peak increased significantly.
Consequently, we monitored the potentials of the cathode
during electrolysis with a Ag/AgNO3 reference electrode; the
cathode potential stabilized at the range of −1.79 V to −1.92 V
(see Figure S6). Ni(II) could be reduced to Ni(I) facilely
under standard conditions.
Furthermore, the preparative utility of this electrochemical
esterification reaction was demonstrated by using a reaction
containing 5 mmol of substrate 2a, which furnished desired
product 3a in 48% yield (Scheme 3).
A series of cyclic voltammetric analyses were conducted to
gain insight into the mechanism of this electrochemical
esterification reaction (Figures 2 and S2−S6). Compared to
the substrates, the nickel catalyst is more easily reduced to a
lower valency (see Figure S2). In the present of 2 equiv of
d(OMe)bpy, the nickel complex exhibits two quasi-reversible
CONCLUSION
■
In conclusion, we have developed Ni-catalyzed electrochemical
esterification of aryl bromides in an undivided cell at room
temperature. These findings provide a new avenue for
transition-metal-catalyzed cross-coupling reactions. Further
C
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Article
product was purified by column chromatography to furnish the
desired product.
1-(tert-Butyl)-2-(4-(methoxycarbonyl)phenyl)(S)-pyrrolidine-1,2-
dicarboxylate (3a).13c Purified by column chromatography on silica
gel (petroleum ether/ethyl acetate = 10:1) as colorless oil (85.0 mg,
1
81%). H NMR (400 MHz, CDCl3) δ 8.06 (m, 2H), 7.18 (m, 2H),
4.53−4.43(m, 1H), 3.90 (m, 3H), 3.64−3.41 (m, 2H), 2.43−1.91 (m,
4H), 1.46 (m, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ (171.1)
171.0, (166.3) 166.1, (154.4) 154.1, 153.6, 131.2 (131.0), 127.8,
(121.5) 121.1, 80.3, 59.1 (59.0), 52.2 (52.1), (46.6) 46.4, (31.0) 29.9,
28.3, (24.5) 23.7.
1-(tert-Butyl)-2-(4-(ethoxycarbonyl)phenyl)(S)-pyrrolidine-1,2-di-
carboxylate (3b)new. Purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) as colorless oil (60.4 mg,
1
55%). H NMR (400 MHz, CDCl3) δ 8.05 (m, 2H), 7.16 (m, 2H),
4.52−4.42 (m, 1H), 4.38−4.32 (m, 2H), 3.69−3.36 (m, 2H), 2.48−
1.80 (m, 4H), 1.44 (m, 9H), 1.36 (t, J = 7.2, 3H). 13C{1H} NMR
(100 MHz, CDCl3) δ 171.1, 165.7, (154.4) 154.1, 153.6, 131.2
(131.1), 128.2, (121.5) 121.1, (80.3) 80.1, 61.1 (61.0), 59.2 (59.1),
(46.6) 46.5, 31.0 (30.0), 28.4, (24.5) 23.7, 14.3. IR (neat): 2978,
1668, 1412, 1366, 1272, 1159, 888, 772 cm−1. HRMS (ESI): calcd for
C19H25NO6Na [M + Na]+: 386.1574. Found: 386.1578.
Figure 2. Cyclic voltammograms recorded on a glassy carbon
electrode at 100 mVs−1. All potentials are referenced against the Ag/
n
AgNO3 redox couple. (a) DMA containing 0.1 M Bu4NPF6 (black
line). (b) Solution (a) with 10 mM NiBr2·glyme and 20 mM
d(OMe)bpy added (red line). (c) Solution (b) with 10 mM 1a added
(blue line). (d) Solution (c) with 10 mM 1a added (green line). (e)
Solution (d) with 20 mM 1a added (purple line).
1-(tert-Butyl)-2-(4-(trifluoromethyl)phenyl)(S)-pyrrolidine-1,2-di-
carboxylate (3c).13c Purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) as colorless oil (86.2 mg,
1
80%). H NMR (400 MHz, CDCl3) δ 7.72−7.53 (m, 2H), 7.23 (m,
3H), 4.48 (m, 1H), 3.74−3.36 (m, 2H), 2.52−2.24 (m, 1H), 2.21−
1.81 (m, 3H), 1.45 (m, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ
(171.2) 171.1, (154.4) 153.6, (153.2) 153.0, 128.2 (128.0) (q, C−F,
3
2JC−F = 33.4 Hz), 126.8 (126.6) (q, C−F, JC−F = 3.8 Hz), (123.8)
efforts to understand the reaction mechanism are currently
underway in our laboratory.
1
123.7 (q, C−F, JC−F = 272.9 Hz), (122.0) 121.6, 80.3 (80.1), 59.1
(59.0), (46.6) 46.4, 30.9 (29.9), 28.3, (24.5) 23.64. 19F NMR (376
MHz, CDCl3) δ −62.30, −62.35.
EXPERIMENTAL SECTION
■
2-(3,5-Bis(trifluoromethyl)phenyl)-1-(tert-butyl)(S)-pyrrolidine-
1,2-dicarboxylate (3d)new. Purified by column chromatography on
silica gel (petroleum ether/ethyl acetate = 10:1) as colorless oil (64.1
mg, 50%). 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 12.8 Hz, 1H),
7.60 (d, J = 17.2 Hz, 2H), 4.50 (m, 1H), 3.54 (m, 2H), 2.32 (m, 1H),
2.07 (m, 3H), 1.45 (m, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ
171.0 (170.9), 154.5 (153.5), 151.3 (151.1), (133.1) 132.8 (q, C−F,
General Experimental Section. Commercially available materi-
als were used without further purification. Column chromatography
was performed using either 100−200 mesh or 300−400 mesh silica
gel. Visualization of spots on the TLC plate was accomplished with
UV light (254 nm) and staining over an I2 chamber. All commercial
reagents of the highest purity grade were purchased from TCI, Alfa-
aesar, Adamas-beta, J&K, Bide chemistry, and Energy Chemical. They
were used without further purification unless specified. Nickel(II)
bromide ethylene and glycol dimethyl ether were purchased from
Strem chemicals and used as received. DMA (99.8%, SuperDry) was
1
2JC−F = 34.0 Hz), 122.7 (122.6) (q, C−F, JC−F = 271.0 Hz), 122.5
(122.0), 119.6 (m), (80.5) 80.4, 59.0, 46.6 (46.5), (30.9) 29.8, 28.3,
24.6 (23.7). 19F NMR (376 MHz, CDCl3) δ −63.13, −63.22. IR
(neat): 2982, 1721, 1664, 1420, 1276, 1165, 1124, 1000, 876, 702,
681 cm−1. HRMS (ESI): calcd for C18H19NO4F6Na [M + Na]+:
450.1110. Found: 450.1106.
1
purchased from J&K and was used without further purification. H
NMR and 13C NMR spectra were recorded on Agilent AV 400,
Bruker 400, and Varian Inova 400 (400 and 100 MHz, respectively).
19F NMR spectra were recorded on Agilent AV 400 and Varian Inova
400 (376 MHz) instrument. The peaks were internally referenced to
TMS (0.00 ppm) or residual undeuterated solvent signal. The
following abbreviations were used to explain multiplicities: s = singlet,
d = doublet, t = triplet, q = quartet, m = multiplet, and br = broad.
Infrared spectra were obtained on a Bio-Rad FTS-185 instrument.
High-resolution mass spectra (HRMS) were recorded at the Center
for Mass Spectrometry, Shanghai Institute of Organic Chemistry.
Analytical and spectral data of all those known compounds exactly
match the reported values.
1-(tert-Butyl)-2-(4-cyanophenyl)(S)-pyrrolidine-1,2-dicarboxylate
(3e).13c Purified by column chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) as colorless oil (71.7 mg, 75%). 1H NMR
(400 MHz, CDCl3) δ 7.69 (m, 2H), 7.27 (m, 2H, contains residual
solvent signal of CDCl3), 4.53−4.45 (m, 1H), 3.65−3.44 (m, 2H),
2.46−2.32 (m, 1H), 2.24−1.91 (m, 3H), 1.46 (m, 9H). 13C{1H}
NMR (100 MHz, CDCl3) δ (170.9) 170.8, (154.5) 154.1, (153.8)
153.5, (133.7) 133.6, (122.6) 122.2, (118.2) 118.1, (109.9) 109.7,
(80.4) 80.2, (59.1) 59.0, (46.6) 46.4, 31.0 (29.9), 28.4, (24.6) 23.6.
1-(tert-Butyl)-2-(4-chlorophenyl)(S)-pyrrolidine-1,2-dicarboxy-
late (3f).13c Purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) as colorless oil (51.6 mg,
53%). 1H NMR (400 MHz, CDCl3) δ 7.51−7.31 (m, 2H), 7.07−6.97
(m, 2H), 4.51−4.42 (m, 1H), 3.64−3.41 (m, 2H), 2.43−2.28 (m,
1H), 2.19−1.89 (m, 2H), 1.47−1.45 (m, 9H). 13C{1H} NMR (100
MHz, CDCl3) δ (171.5) 171.4, (154.5) 153.7, (149.2) 149.1, (132.6)
132.4, (131.3) 131.2, (129.6) 129.4, 123.3, (122.9) 122.5, 80.3,
(59.2) 59.1, (46.6) 46.5, 31.0 (30.0), 28.4, (24.6), 23.7.
General Procedure for Electrochemical Esterification. In a
nitrogen-filled glovebox, to an oven-dried 10 mL hydrogenation tube
charged with a stir bar were added aryl bromide 1a−1t (0.6 mmol),
carboxylic acids 2a−2n (64.5 mg, 0.3 mmol), NiBr2·glyme (9.3 mg,
n
0.03 mmol), d(OMe)bpy (13 mg, 0.06 mmol), Bu4NBr (193.5 mg,
0.6 mmol), and K2CO3 (126 mg, 0.9 mmol) to the electrochemical
cell. The tube was installed with a Ni foam (2.0 × 3.0 cm2) as the
cathode and graphite flake (1.0 × 2.0 cm2) as an anode. The reaction
mixture was vigorously stirred and electrolyzed under a constant
current of 4 mA until the complete consumption of the starting
materials as judged by TLC (about 10 h). After the reaction, the
aqueous layer was extracted with EtOAc (3 × 10 mL), and the
combined organics were washed with saturated brine (3 × 20 mL),
dried over Na2SO4, filtered, and concentrated in vacuo. The crude
1-(tert-Butyl)-2-(4-(methylsulfonyl)phenyl)(S)-pyrrolidine-1,2-di-
carboxylate (3g)new. Purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) as colorless oil (99.6 mg,
90%). 1H NMR (400 MHz, CDCl3) δ 8.01−7.95 (m, 2H), 7.36−7.31
(m, 2H), 4.54−4.46 (m, 1H), 3.66−3.45 (m, 2H), 3.07−3.06 (m,
3H), 2.47−2.33 (m, 1H), 2.22−1.94 (m, 3H), 1.48−1.46 (m, 9H).
D
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13C{1H} NMR (100 MHz, CDCl3) δ (171.1) 171.0, (154.9) 154.6,
(154.5) 153.6, (138.0) 137.8, (129.3) 129.2, (122.7) 122.3, (80.4)
80.3, (59.1) 59.1, 46.7 (46.5), 44.6, 31.0 (30.0), 28.4, (24.6) 23.7. IR
1-(tert-Butyl)-2-(4-phenoxyphenyl)(S)-pyrrolidine-1,2-dicarboxy-
late (3m)new. Purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) as colorless oil (51.1 mg,
45%). 1H NMR (400 MHz, CDCl3) δ 7.36−7.30 (m, 2H), 7.13−6.98
(m, 7H), 4.53−4.43 (m, 1H), 3.66−3.42 (m, 2H), 2.43−2.29 (m,
1H), 2.20−1.89 (m, 1H), 1.48−1.47 (m, 9H). 13C{1H} NMR (100
MHz, CDCl3) δ 171.8, (157.3) 157.1, 154.9 (154.7), (154.5) 153.7,
(146.3) 146.0, 129.8 (129.8), 123.5 (123.3), (122.6) 122.3, (119.6)
119.6, 118.9 (118.7), 80.2 (80.0), 59.2 (59.1), (46.7) 46.5, 31.1
(30.0), 28.5, (24.5) 23.7. IR (neat): 2977, 1666, 1486, 1414, 1216,
1119, 845, 750, 691 cm−1. HRMS (ESI): calcd for C22H25NO5Na [M
+ Na]+: 406.1613. Found: 406.1625.
(neat): 2973, 1697, 1587, 1398, 1291, 1120, 963, 763, 537, 519 cm−1
.
HRMS (ESI): calcd for C17H23NO6NaS [M + Na]+: 392.1138.
Found: 392.1137.
1-(tert-Butyl)-2-(4-((trifluoromethyl)thio)phenyl)(S)-pyrrolidine-
1,2-dicarboxylate (3h)new. Purified by column chromatography on
silica gel (petroleum ether/ethyl acetate = 10:1) as colorless oil (70.6
mg, 60%). 1H NMR (400 MHz, CDCl3) δ 7.70−7.65 (m, 2H), 7.22−
7.17 (m, 2H), 4.53−4.44 (m, 1H), 3.65−3.43 (m, 2H), 2.44−2.30
(m, 1H), 2.20−1.92 (m, 3H), 1.47 (m, 9H). 13C{1H} NMR (100
MHz, CDCl3) δ (171.2) 171.1, (154.5) 153.6, (153.0) 152.8, 137.8
2-([1,1′-Biphenyl]-4-yl)-1-(tert-butyl)(S)-pyrrolidine-1,2-dicarbox-
ylate (3n)new. Purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) as a white solid (59.5 mg,
1
(137.7), 129.4 (q, C−F, JC−F = 308.4 Hz), (122.7) 122.4, 121.6
(121.3), 80.3 (80.2), 59.2 (59.1), (46.6) 46.5, 31.0 (30.0), 28.4,
(24.6) 23.7. 19F NMR (376 MHz, CDCl3) δ −42.92, −42.99. IR
(neat): 2980, 1720, 1664, 1601, 1416, 1154, 1113, 834, 521 cm−1.
HRMS (ESI): calcd for C17H20NO4F3NaS [M + Na]+: 414.0957.
Found: 414.0948.
1
54%). M.p.: 137.9−139.9 °C. H NMR (400 MHz, CDCl3) δ 7.64−
7.53 (m, 1H), 7.47−7.40 (m, 2H), 7.38−7.32 (m, 1H), 7.22−7.15
(m, 2H), 4.59−4.43 (m, 1H), 3.70−3.41 (m, 2H), 2.46−2.29 (m,
1H), 2.25−1.91 (m, 3H), 1.49 (s, 9H). 13C{1H} NMR (100 MHz,
CDCl3) δ 171.7, (154.4) 153.7, (150.2) 149.9, (140.4) 140.2, 139.1
(138.9), 128.8 (128.7), 128.2 (128.1), 127.4 (127.2), (121.7) 121.4,
80.2 (80.0), 59.2 (59.0), (46.6) 46.4, 31.0 (30.0), 28.4, (24.5) 23.7.
IR (neat): 2958, 2922, 1769, 1704, 1394, 1166, 1118, 923, 865, 759,
688 cm−1. HRMS (ESI): calcd for C22H25NO4Na [M + Na]+:
390.1676. Found: 390.1685.
1-(tert-Butyl)-2-(4-(trifluoromethoxy)phenyl)(S)-pyrrolidine-1,2-
dicarboxylate (3i)new. Purified by column chromatography on silica
gel (petroleum ether/ethyl acetate = 10:1) as colorless oil (43.6 mg,
39%). 1H NMR (400 MHz, CDCl3) δ 7.25−7.19 (m, 2H), 7.16−7.11
(m, 2H), 4.52−4.43 (m, 1H), 3.64−3.42 (m, 2H), 2.43−2.29 (m,
1H), 2.20−1.91 (m, 3H), 1.46 (m, 9H). 13C{1H} NMR (100 MHz,
CDCl3) δ (171.5) 171.4, (154.5) 153.7, (149.0) 148.8, 146.6, (122.8)
122.5, 122.2 (122.1), 120.4 (q, C−F, 1JC−F = 258.5 Hz), 80.3 (80.1),
59.1 (59.0), (46.6) 46.5, 31.0 (30.0), 28.4, (24.5) 23.7. 19F NMR
(376 MHz, CDCl3) δ −58.18. IR (neat): 2980, 1721, 1667, 1510,
1416, 1366, 1154, 888, 592 cm−1. HRMS (ESI): calcd for
C17H20NO5F3Na [M + Na]+: 398.1186. Found: 398.1182.
1-(tert-Butyl)-2-(naphthalen-1-yl)(S)-pyrrolidine-1,2-dicarboxy-
late (3j).16 Purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) as colorless oil (50.5 mg,
50%). 1H NMR (400 MHz, CDCl3) δ 8.06−7.84 (m, 2H), 7.76−7.72
(m, 1H), 7.52−7.43 (m, 3H), 7.28−7.25 (m, 1H, contains residual
solvent signal of CDCl3), 4.73−4.65 (m, 1H), 3.72−3.48 (m, 2H),
2.55−2.28 (m, 2H), 2.21−1.97 (m, 2H), 1.52−1.51 (m, 9H).
13C{1H} NMR (100 MHz, CDCl3) δ (171.8) 171.5, (154.6) 153.9,
2-(Benzo[b]thiophen-6-yl)-1-(tert-butyl)(S)-pyrrolidine-1,2-dicar-
boxylate (3o)new. Purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) as colorless oil (72.0 mg,
70%). 1H NMR (400 MHz, CDCl3) δ 7.80−7.75 (m, 1H), 7.65−7.61
(m, 1H), 7.42−7.37 (m, 1H), 7.30−7.27 (m, 1H), 7.14−7.08 (m,
1H), 4.56−4.46 (m, 1H), 3.66−3.41 (m, 2H), 2.43−2.29 (m, 1H),
2.23−2.13 (m, 1H), 2.09−1.90 (m, 2H), 1.49−1.48 (m, 9H).
13C{1H} NMR (100 MHz, CDCl3) δ 171.8, (154.5) 153.8, (147.9)
147.7, 140.3 (140.2), 137.6 (137.5), 126.9 (126.7), 124.1 (124.0),
123.5 (123.4), (118.8) 118.4, (115.0) 114.7, 80.2 (80.0), 59.2 (59.1),
(46.7) 46.5, 31.1 (30.1), 28.5, (24.5) 23.7. IR (neat): 2974, 2879,
1765, 1692, 1461, 1392, 1134, 1084 cm−1. HRMS (ESI): calcd for
C18H21NO4NaS [M + Na]+: 370.1083. Found: 370.1080.
2-(Benzo[b]thiophen-2-yl)-1-(tert-butyl)(S)-pyrrolidine-1,2-dicar-
boxylate (3p)new. Purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) as colorless oil (48.7 mg,
(146.8) 146.4, 134.7 (134.6), 128.1 (127.8), 127.0 (126.7), 126.6
(126.5),126.4, 126.1 (126.1), 125.4 (125.3), 121.7, 121.1, (117.9)
117.6, 80.5 (80.1), 59.3 (59.3), (46.7) 46.5, 31.4 (30.3), 28.5, (24.7)
23.8. HRMS (ESI): calcd for C20H23NO4Na [M + Na]+: 364.1519.
Found: 364.1512.
1
47%). H NMR (400 MHz, CDCl3) δ 7.82−7.67 (m, 2H), 7.48 (s,
0.5H), 7.40−7.34 (m, 2.5H), 4.66−4.53 (m, 1H), 3.73−3.46 (m,
2H), 2.48−2.34 (m, 1H), 2.27−2.20 (m, 1H), 2.13−1.95 (m, 2H),
1.49 (s, 4H), 1.40 (s, 5H). 13C{1H} NMR (100 MHz, CDCl3) δ
(170.6) 170.5, (154.5) 153.7, (140.7) 140.3, (136.9) 136.7, (132.1)
131.9, 125.3 (125.1), 124.4 (124.3), 122.9 (122.8), (120.8) 120.4,
(112.0) 111.4, 80.5 (80.2), 59.4 (59.1), (46.7) 46.5, 31.2 (30.2), 28.5,
28.3, (24.6) 23.8. IR (neat): 2976, 1696, 1651, 1394, 1366, 1158,
1126, 734 cm−1. HRMS (ESI): calcd for C18H21NO4NaS [M + Na]+:
370.1083. Found: 370.1084.
1-(tert-Butyl)-2-(naphthalen-2-yl)(S)-pyrrolidine-1,2-dicarboxy-
late (3k).17 Purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) as a white solid (72.2 mg,
71%). 1H NMR (400 MHz, CDCl3) δ 7.87−7.78 (m, 3H), 7.59−7.56
(m, 1H), 7.51−7.41 (m, 2H), 7.28−7.21 (m, 1H, contains residual
solvent signal of CDCl3), 4.60−4.49 (m, 1H), 3.69−3.43 (m, 2H),
2.46−2.31 (m, 1H), 2.27−2.17 (m, 1H), 2.12−2.03 (m, 1H), 2.00−
1.90 (m, 1H), 1.49 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ
171.8, (154.5) 153.8, (148.5) 148.3, 133.7, 131.5, 129.5 (129.4),
127.8 (127.8), 127.7 (127.6), 126.7 (126.5), 125.8 (125.7), (121.1)
120.7, (118.5) 118.1, 80.3 (80.0), 59.3 (59.2), (46.7) 46.5, 31.1
(30.1), 28.5, (24.6) 23.8. HRMS (ESI): calcd for C20H23NO4Na [M
+ Na]+: 364.1519. Found: 364.1519.
1-(tert-Butyl)-2-(4-(methylthio)phenyl)(S)-pyrrolidine-1,2-dicar-
boxylate (3l)new. Purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) as a white solid (50.0 mg,
50%). M.p.: 76.3−77.4 °C. 1H NMR (400 MHz, CDCl3) δ 7.29−7.24
(m, 2H, contains residual solvent signal of CDCl3), 7.06−7.01 (m,
2H), 4.52−4.42 (m, 1H), 3.65−3.41 (m, 2H), 2.48−2.46 (m, 3H),
2.42−2.28 (m, 1H), 2.20−1.89 (m, 3H), 1.48−1.46 (m, 9H).
13C{1H} NMR (100 MHz, CDCl3) δ 171.6, (154.5) 153.7, (148.6)
1-(tert-Butyl)-2-(dibenzo[b,d]thiophen-4-yl)(S)-pyrrolidine-1,2-
dicarboxylate (3q)new. Purified by column chromatography on silica
gel (petroleum ether/ethyl acetate = 10:1) as colorless oil (72.6 mg,
61%). 1H NMR (400 MHz, CDCl3) δ 8.06−8.04 (m, 1H), 7.95−7.91
(m, 1H), 7.76−7.73 (m, 1H), 7.42−7.36 (m, 3H), 7.27−7.17 (m, 1H,
contains residual solvent signal of CDCl3), 4.61−4.50 (m, 1H), 3.65−
3.38 (m, 2H), 2.45−2.25 (m, 2H), 2.14−1.92 (m, 2H), 1.43 (s, 9H).
13C{1H} NMR (100 MHz, CDCl3) δ 170.6, (154.5) 153.8, (145.6)
145.5, (139.3) 139.1, 138.2 (138.0), (135.6) 135.5, (131.7) 131.5,
127.3 (127.1), 125.5, 124.8 (124.6), 122.9, 122.0 (121.9), (119.6)
119.1, (119.0) 118.9, 80.4 (80.1), 59.3 (59.2), (46.7) 46.5, 31.3
(30.3), 28.5, (24.6) 23.8. IR (neat): 2975, 1717, 1571, 1413, 1158,
1129, 749 cm−1. HRMS (ESI): calcd for C22H23NO4NaS [M + Na]+:
420.1240. Found: 420.1236.
148.3, 135.9 (135.6), 128.0, (122.0) 121.6, 80.2 (80.0), 59.2 (59.1),
(46.6) 46.5, 31.1 (30.0), 28.4, (24.5) 23.7, (16.6) 16.5. IR (neat):
2970, 2920, 1766, 1704, 1487, 1392, 1202, 1167, 938, 860, 810 cm−1.
HRMS (ESI): calcd for C17H23NO4NaS [M + Na]+: 360.1240.
Found: 360.1234.
2-(Benzofuran-5-yl)-1-(tert-butyl)(S)-pyrrolidine-1,2-dicarboxy-
late (3r)new. Purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) as colorless oil (59.6 mg,
60%). 1H NMR (400 MHz, CDCl3) δ 7.64−7.61 (m, 1H), 7.48−7.43
(m, 1H), 7.34−7.30 (m, 1H), 7.03−6.97 (m, 1H), 6.74−6.71 (m,
E
https://doi.org/10.1021/acs.joc.1c00204
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
1H), 4.55−4.45 (m, 1H), 3.66−3.41 (m, 2H), 2.41−2.28 (m, 1H),
2.22−2.13 (m, 1H), 2.09−1.88 (m, 2H), 1.48−1.46 (m, 9H).
13C{1H} NMR (100 MHz, CDCl3) δ (172.1) 172.0, (154.5) 153.8,
152.6, 146.4 (146.4), (146.2) 146.2, 128.1 (128.0), (118.0) 117.6,
(113.6) 113.3, 111.9 (111.7), 106.9, 80.2 (80.0), 59.2 (59.1), (46.7)
46.5, 31.1 (30.1), 28.5, (24.5) 23.7. IR (neat): 2977, 2881, 1749,
1667, 1394, 1366, 1156, 1127, 762, 732 cm−1. HRMS (ESI): calcd for
C18H21NO5Na [M + Na]+: 354.1312. Found: 354.1312.
1H), 2.57−2.42 (m, 1H), 2.06−1.92 (m, 4H), 1.85−1.69 (m, 4H).
13C{1H} NMR (100 MHz, CDCl3) δ 175.2, 172.9, 166.2, 154.4,
131.0, 127.5, 121.5, 52.1, 51.6, 42.4, 42.2, 40.7, 40.4, 27.8, 25.8. IR
(neat): 2951, 2919, 2849, 1752, 1723, 1270, 1203, 1128, 1107, 1023,
750 cm−1. HRMS (ESI): calcd for C17H20O6Na [M + Na]+: 343.1152.
Found: 343.1154.
Methyl-4-((1-phenylcyclopentane-1-carbonyl)oxy)benzoate
(4e)new. Purified by column chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) as a white solid (79.4 mg, 82%). M.p.:
2-(1-(tert-Butoxycarbonyl)-1H-indol-3-yl)-1-(tert-butyl)(S)-pyrro-
lidine-1,2-dicarboxylate (3s)new. Purified by column chromatography
on silica gel (petroleum ether/ethyl acetate = 10:1) as colorless oil
1
85.2−86.6 °C. H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.8 Hz,
2H), 7.47 (d, J = 7.6 Hz, 2H), 7.36 (m, 2H), 7.32−7.23 (m, 1H,
contains residual solvent signal of CDCl3), 6.97 (d, J = 8.8 Hz, 2H),
3.88 (s, 3H), 2.79 (m, 2H), 2.06 (m, 2H), 1.83 (m, 4H). 13C{1H}
NMR (100 MHz, CDCl3) δ 174.0, 166.3, 154.8, 142.3, 131.0, 128.5,
127.5, 127.1, 126.8, 121.3, 59.4, 52.1, 36.0, 23.6. IR (neat): 2954,
2924, 1747, 1720, 1275, 1196, 1096, 694 cm−1. HRMS (ESI): calcd
for C20H21O4 [M + H]+: 325.1434. Found: 325.1433.
1
(18.1 mg, 14%). H NMR (400 MHz, CDCl3) δ 8.16 (bra, 1H),
7.83−7.72 (m, 1H), 7.55−7.47 (m, 1H), 7.34 (q, J = 8.4 Hz, 1H),
7.27−7.21 (m, 1H, contains residual solvent signal of CDCl3), 4.66−
4.49 (m, 1H), 3.71−3.44 (m, 2H), 2.47−2.31 (m, 1H), 2.24−1.92
(m, 3H), 1.69−1.61 (m, 9H), 1.48 (s, 4H), 1.39 (s, 5H). 13C{1H}
NMR (100 MHz, CDCl3) δ (170.4) 170.3, (154.5) 153.8, 149.7,
(133.3) 133.2, (132.9) 132.7, 125.4 (125.2), (123.6) 123.3, 122.8
(122.7), (117.8) 117.5, 115.3 (115.2), (114.4) 113.9, 84.0 (83.8),
80.4 (80.2), 59.3 (59.0), (46.7) 46.5, 31.2 (30.2), 28.5, 28.3, 28.2,
(24.5) 23.8. IR (neat): 2957, 2924, 1695, 1587, 1524, 1367, 1249,
1151, 755 cm−1. HRMS (ESI): calcd for C23H30N2O6Na [M + Na]+:
453.1996. Found: 453.2003.
2-(4-(9H-Carbazol-9-yl)phenyl)-1-(tert-butyl)(S)-pyrrolidine-1,2-
dicarboxylate (3t)new. Purified by column chromatography on silica
gel (petroleum ether/ethyl acetate = 10:1) as colorless oil (121.0 mg,
90%). 1H NMR (400 MHz, CDCl3) δ 8.17−8.15 (m, 2H), 7.61−7.56
(m, 2H), 7.45−7.28 (m, 8H), 4.62−4.52 (m, 1H), 3.73−3.48 (m,
2H), 2.50−2.36 (m, 1H), 2.28−2.19 (m, 1H), 2.15−1.98 (m, 2H),
1.54 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ (171.7) 171.6,
(154.6) 153.8, (149.7) 149.5, (140.9) 140.9, 135.4 (135.2), 128.3
(128.1), 126.1 (126.0), 123.4 (123.4), (123.0) 122.7, 120.4 (120.3),
120.1 (120.0), (109.7) 109.7, 80.4 (80.2), 59.3 (59.2), (46.7) 46.5,
31.2 (30.1), 28.5, (24.6) 23.8. IR (neat): 2976, 1665, 1515, 1452,
1414, 1366, 1229, 1159, 910, 834, 749, 724 cm−1. HRMS (ESI): calcd
for C28H28N2O4Na [M + Na]+: 479.1941. Found: 479.1939.
Methyl-4-((3-(m-tolyl)propanoyl)oxy)benzoate (4a)new. Purified
by column chromatography on silica gel (petroleum ether/ethyl
acetate = 10:1) as a white solid (44.7 mg, 50%). M.p.: 72.8−74.6 °C.
1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 8.8 Hz, 2H), 7.22 (t, J =
7.6 Hz, 1H), 7.12−7.03 (m, 5H), 3.91 (s, 3H), 3.05 (t, J = 7.6 Hz,
2H), 2.89 (t, J = 8.0 Hz, 2H), 2.35 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3) δ 170.9, 166.3, 154.3, 139.9, 138.3, 131.2, 129.2, 128.6,
127.7, 127.3, 125.4, 121.6, 52.2, 36.1, 30.8, 21.4. IR (neat): 2952,
2918, 2849, 1746, 1719, 1602, 1437, 1376, 1273, 1220, 1145, 1105
cm−1. HRMS (ESI): calcd for C18H18O4Na [M + Na]+: 321.1097.
Found: 321.1097.
Methyl-4-(2-((3r,5r,7r)-adamantan-1-yl)acetoxy)benzoate
(4b)new. Purified by column chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) as a white solid (53.7 mg, 55%). M.p.:
100.5−101.2 °C. 1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 8.8 Hz,
2H), 7.16 (d, J = 8.8 Hz, 2H), 3.91 (s, 3H), 2.32 (s, 2H), 2.09−1.97
(m, 3H), 1.76−1.65 (m, 12H). 13C{1H} NMR (100 MHz, CDCl3) δ
169.6, 166.4, 154.4, 131.1, 127.6, 121.8, 52.2, 48.7, 42.5, 36.7, 33.3,
28.6. IR (neat): 2897, 2846, 1751, 1721, 1599, 1273, 1185, 1156,
1094 cm−1. HRMS (ESI): calcd for C20H25O4 [M + H]+: 329.1747.
Found: 329.1743.
Methyl-4-((1-phenylcyclopropane-1-carbonyl)oxy)benzoate
(4f)new. Purified by column chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) as a white solid (23.5 mg, 27%). M.p.:
1
99.1−101.6 °C. H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 8.8 Hz,
2H), 7.49−7.42 (m, 2H), 7.39−7.32 (m, 2H), 7.32−7.27 (m, 1H),
7.10 (d, J = 8.8 Hz, 2H), 3.89 (s, 4H), 1.79 (m, 2H), 1.38 (m, 2H).
13C{1H} NMR (100 MHz, CDCl3) δ 172.8, 166.3, 154.7, 138.7,
131.0, 130.6, 128.4, 127.6, 127.5, 121.5, 52.2, 29.3, 17.5. IR (neat):
2919, 2849, 1716, 1275, 1198, 1164, 1138, 1110, 1087 cm−1. HRMS
(ESI): calcd for C18H17O4 [M + H]+: 297.1121. Found: 297.1126.
4-(Methoxycarbonyl)phenyl-4-fluorobenzoate (4g).13a Purified
by column chromatography on silica gel (petroleum ether/ethyl
acetate = 10:1) as a white solid (60.7 mg, 74%). 1H NMR (400 MHz,
CDCl3) δ 8.22 (m, 2H), 8.12 (d, J = 8.8 Hz, 2H), 7.30 (d, J = 8.8 Hz,
2H), 7.19 (m, 2H), 3.93 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3)
δ 166.3 (d, C−F, 1JC−F = 256.5 Hz), 166.3, 163.6, 154.4, 132.9 (d, C−
3
4
F, JC−F = 9.5 Hz), 131.2, 127.9, 125.3 (d, C−F, JC−F = 2.9 Hz),
121.7, 115.9 (d, C−F, JC−F = 22.1 Hz), 52.2. 19F NMR (376 MHz,
2
CDCl3) δ −103.77.
4-(Methoxycarbonyl)phenyl-3-methylbenzoate (4h).18 Purified
by column chromatography on silica gel (petroleum ether/ethyl
acetate = 10:1) as a white solid (43.3 mg, 53%). 1H NMR (400 MHz,
CDCl3) δ 8.13 (d, J = 8.4 Hz, 2H), 8.00 (m, 2H), 7.49−7.37 (m, 2H),
7.30 (d, J = 8.8 Hz, 2H), 3.93 (s, 3H), 2.45 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3) δ 166.3, 164.8, 154.7, 138.5, 134.6, 131.2, 130.7,
129.0, 128.5, 127.7, 127.4, 121.8, 52.2, 21.3. HRMS (ESI): calcd for
C16H15O4 [M + H]+: 271.0965. Found: 271.0965.
Methyl-4-(benzoyloxy)benzoate (4i).13c Purified by column
chromatography on silica gel (petroleum ether/ethyl acetate =
10:1) as a white solid (30.7 mg, 40%). 1H NMR (400 MHz,
CDCl3) δ 8.21 (d, J = 7.2 Hz, 2H), 8.13 (d, J = 8.8 Hz, 2H), 7.66 (m,
1H), 7.57−7.50 (m, 2H), 7.31 (d, J = 8.8 Hz, 2H), 3.93 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 166.3, 164.6, 154.6, 133.9,
131.2, 130.2, 129.1, 128.6, 127.7, 121.7, 52.2.
Methyl-4-((4-(4-(bis(2-chloroethyl)amino)phenyl)butanoyl)oxy)-
benzoate (4j)new. Purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) as colorless oil (54.0 mg,
41%). 1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 8.8 Hz, 2H), 7.13
(m, 4H), 6.65 (d, J = 8.8 Hz, 2H), 3.92 (s, 4H), 3.67 (m, 8H), 2.62
(m, 4H), 2.05 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 171.4,
166.3, 154.3, 144.4, 131.1, 130.1, 129.7, 127.6, 121.5, 112.2, 53.5,
52.2, 40.5, 33.9, 33.6, 26.5. IR (neat): 2951, 1756, 1719, 1604, 1517,
1275, 1199, 1160, 1101 cm−1. HRMS (ESI): calcd for C22H26NO4Cl2
[M + H]+: 438.1233. Found: 438.1231.
Methyl-4-((3-(4,5-diphenyloxazol-2-yl)propanoyl)oxy)benzoate
(4k)new. Purified by column chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) as colorless oil (81.0 mg, 63%). 1H NMR
(400 MHz, CDCl3) δ 8.06 (d, J = 8.8 Hz, 2H), 7.65 (m, 2H), 7.59
(m, 2H), 7.36 (m, 6H), 7.20 (d, J = 8.8 Hz, 2H), 3.91 (s, 3H), 3.31
(m, 2H), 3.19 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 169.1,
165.3, 160.2, 153.2, 144.6, 134.2, 131.3, 130.1, 127.9, 127.7, 127.6,
127.5, 127.1, 126.8, 126.7, 125.5, 120.5, 51.2, 30.2, 22.4. IR (neat):
4-(Methoxycarbonyl)phenyl-tetrahydro-2H-pyran-4-carboxylate
(4c).13a Purified by column chromatography on silica gel (petroleum
ether/ethyl acetate = 10:1) as a white solid (37.0 mg, 47%). 1H NMR
(400 MHz, CDCl3) δ 8.07 (d, J = 8.8 Hz, 2H), 7.16 (d, J = 8.8 Hz,
2H), 4.03 (dt, J = 11.6, 3.6 Hz, 2H), 3.91 (s, 3H), 3.56−3.45 (td, J =
11.2, 2.8 Hz, 2H), 2.82 (tt, J = 10.8, 4.4 Hz, 1H), 2.06−1.85 (m, 4H).
13C{1H} NMR (100 MHz, CDCl3) δ 172.4, 166.3, 154.3, 131.2,
127.8, 121.5, 67.0, 52.2, 40.3, 28.5.
1-(4-(Methoxycarbonyl)phenyl)-4-methyl-(1s,4s)-cyclohexane-
1,4-dicarboxylate (4d)new. Purified by column chromatography on
silica gel (petroleum ether/ethyl acetate = 10:1) as colorless oil (15.4
1
mg, 16%). H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 8.8 Hz, 2H),
7.12 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 3.67 (s, 3H), 2.77−2.69 (m,
F
https://doi.org/10.1021/acs.joc.1c00204
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
2949, 1716, 1605, 1435, 1274, 1162, 1110, 762, 694 cm−1. HRMS
(ESI): calcd for C26H22NO5 [M + H]+: 428.1493. Found: 428.1499.
Methyl-4-((2-(4-isobutylphenyl)propanoyl)oxy)benzoate (4l).13c
Purified by column chromatography on silica gel (petroleum ether/
Chinese Academy of Sciences, Chinese Academy of Sciences,
Shanghai 200032, China; orcid.org/0000-0002-4985-
1071; Email: mei7900@sioc.ac.cn
1
ethyl acetate = 10:1) as colorless oil (33.7 mg, 33%). H NMR (400
Authors
MHz, CDCl3) δ 8.03 (d, J = 8.8 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H),
7.15 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.8 Hz, 2H), 3.95 (q, J = 7.2 Hz,
1H), 3.90 (s, 3H), 2.48 (d, J = 7.2 Hz, 2H), 1.94−1.80 (m, 1H), 1.61
(d, J = 7.2 Hz, 3H), 0.92 (d, J = 6.8 Hz, 6H). 13C{1H} NMR (100
MHz, CDCl3) δ 172.7, 166.3, 154.5, 141.0, 136.9, 131.0, 129.6, 127.6,
127.2, 121.4, 52.1, 45.3, 45.0, 30.2, 22.4, 18.4.
Lei Wei − State Key Laboratory of Organometallic Chemistry,
Center for Excellence in Molecular Synthesis, Shanghai
Institute of Organic Chemistry, University of Chinese
Academy of Sciences, Chinese Academy of Sciences, Shanghai
200032, China
Zhen-Hua Wang − State Key Laboratory of Organometallic
Chemistry, Center for Excellence in Molecular Synthesis,
Shanghai Institute of Organic Chemistry, University of
Chinese Academy of Sciences, Chinese Academy of Sciences,
Shanghai 200032, China
Ke-Jin Jiao − State Key Laboratory of Organometallic
Chemistry, Center for Excellence in Molecular Synthesis,
Shanghai Institute of Organic Chemistry, University of
Chinese Academy of Sciences, Chinese Academy of Sciences,
Shanghai 200032, China
4-(Methoxycarbonyl)phenyl-2-acetoxybenzoate (4m)new. Puri-
fied by column chromatography on silica gel (petroleum ether/ethyl
acetate = 10:1) as a white solid (46.2 mg, 50%). M.p.: 114.4−117.8
°C. 1H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 8.0 Hz, 1H), 8.12 (d,
J = 8.8 Hz, 2H), 7.66 (t, J = 8.0 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H),
7.26 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 1H), 3.93 (s, 3H), 2.31
(s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 169.7, 166.2, 162.3,
154.1, 151.3, 134.9, 132.2, 131.3, 128.0, 126.2, 124.1, 122.1, 121.7,
52.2, 21.0. IR (neat): 2956, 2920, 1739, 1279, 1244, 1175, 1110,
1038, 1010, 751 cm−1. HRMS (ESI): calcd for C17H14O6Na [M +
Na]+: 337.0683. Found: 337.0679.
Dong Liu − State Key Laboratory of Organometallic
Chemistry, Center for Excellence in Molecular Synthesis,
Shanghai Institute of Organic Chemistry, University of
Chinese Academy of Sciences, Chinese Academy of Sciences,
Shanghai 200032, China
Cong Ma − State Key Laboratory of Organometallic
Chemistry, Center for Excellence in Molecular Synthesis,
Shanghai Institute of Organic Chemistry, University of
Chinese Academy of Sciences, Chinese Academy of Sciences,
Shanghai 200032, China; orcid.org/0000-0001-7568-
1347
Ping Fang − State Key Laboratory of Organometallic
Chemistry, Center for Excellence in Molecular Synthesis,
Shanghai Institute of Organic Chemistry, University of
Chinese Academy of Sciences, Chinese Academy of Sciences,
Shanghai 200032, China; orcid.org/0000-0002-3421-
2613
Methyl-(S)-4-((2-(6-methoxynaphthalen-2-yl)propanoyl)oxy)-
benzoate (4n)new. Purified by column chromatography on silica gel
(petroleum ether/ethyl acetate = 10:1) as a white solid (87.2 mg,
80%). M.p.: 165.8−166.7 °C. 1H NMR (400 MHz, CDCl3) δ 8.01 (d,
J = 8.8 Hz, 2H), 7.75 (m, 3H), 7.53−7.46 (m, 1H), 7.21−7.12 (m,
2H), 7.07 (d, J = 8.8 Hz, 2H), 4.11 (q, J = 7.2 Hz, 1H), 3.93 (s, 3H),
3.89 (s, 3H), 1.70 (d, J = 7.2 Hz, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 172.6, 166.2, 157.8, 154.4, 134.7, 133.8, 131.0, 129.2, 128.9,
127.6, 127.4, 126.1, 125.9, 121.4, 119.1, 105.5, 55.2, 52.1, 45.5, 18.4.
IR (neat): 2956, 2917, 1749, 1719, 1604, 1433, 1278, 1260, 1163,
1065, 1015, 798 cm−1. HRMS (ESI): calcd for C22H21O5 [M + H]+:
365.1384. Found: 365.1387.
Gram-Scale Synthesis. In a nitrogen-filled glovebox, to a dried
100 mL hydrogenation tube equipped with a stir bar, the following
were added to the electrochemical cell: aryl bromide 1a (2.15 g, 10.0
mmol), N-Boc-D-proline 2a (1.07 g, 5.0 mmol), NiBr2·glyme (154
n
mg, 0.5 mmol), d(OMe)bpy (216 mg, 1 mol), Bu4NBr (1.3 g, 4
mmol), K2CO3 (1.38 g, 10 mmol), and DMA (20 mL). The tube was
installed a Ni foam (4.0 × 8.0 cm2) as the cathode and graphite flake
(2.0 × 2.0 cm2) as the anode. Then the reaction mixture was
electrolyzed under a constant current of 15 mA for 24 h. After the
reaction, the aqueous layer was extracted with EtOAc (3 × 50 mL),
and the combined organics were washed with saturated brine (3 ×
100 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The
resulting residue was purified by silica gel flash chromatography to
give product 3a as white solid with 48% yield.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00204
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
Electrochemical Procedure for Cyclic Voltammetry. Cyclic
voltammograms were recorded with a CHI660E potentiostat at room
■
This work was financially supported by the Strategic Priority
Research Program of the Chinese Academy of Sciences (Grant
XDB20000000), the “1000-Youth Talents Plan”, NSF of China
(Grant 21572245, 21772222, and 21772220), and S&TCSM
of Shanghai (Grants 17JC1401200 and 18JC1415600).
n
temperature in DMA. Bu4NPF6 (0.1 M) was used as the supporting
electrolyte, and a glass carbon electrode was used as the working
electrode. The auxiliary electrode was a Pt sheet. All potentials were
referenced against the Ag/AgNO3 redox couple. The scan rate was
100 mV s−1.
REFERENCES
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
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AUTHOR INFORMATION
Corresponding Author
Tian-Sheng Mei − State Key Laboratory of Organometallic
Chemistry, Center for Excellence in Molecular Synthesis,
Shanghai Institute of Organic Chemistry, University of
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