Electrochemical reduction of a bromo propargyloxy ester at silver cathodes in dimethylformamide

Article abstract of DOI:10.1149/2.0031501jes

Cyclic voltammograms for the reduction of ethyl 2-bromo-3-(3',4'-dimethoxyphenyl)-3-(propargyloxy)propanoate (1) at a silver cathode in dimethylformamide (DMF) containing 0.10 M tetraethylammonium tetrafluoroborate (TEABF4) exhibit several cathodic peaks,

Full text of DOI:10.1149/2.0031501jes

G128
Journal of The Electrochemical Society, 161 (14) G128-G132 (2014)
Electrochemical Reduction of a Bromo Propargyloxy Ester
at Silver Cathodes in Dimethylformamide
Robert J. Henderson,a Nathan R. Buehler,a Erick M. Pasciak,a,∗ Mohammad S. Mubarak,b
and Dennis G. Petersa,∗∗,z
aDepartment of Chemistry, Indiana University, Bloomington, Indiana 47405, USA
bDepartment of Chemistry, The University of Jordan, Amman 11942, Jordan
Cyclic voltammograms for the reduction of ethyl 2-bromo-3-(3ꢀ,4ꢀ-dimethoxyphenyl)-3-(propargyloxy)propanoate (1) at a silver
cathode in dimethylformamide (DMF) containing 0.10 M tetraethylammonium tetrafluoroborate (TEABF4) exhibit several cathodic
peaks, the first of which is attributed to reductive cleavage of the carbon–bromine bond. Controlled-potential (bulk) electrolyses
of 1 at silver gauze electrodes in DMF–0.10 M TEABF4 give rise to four products: cis- and trans-isomers of ethyl 3-(3ꢀ,4ꢀ-
dimethoxyphenyl)-prop-2-enoate (4), ethyl 3-(3ꢀ,4ꢀ-dimethoxyphenyl)propiolate (7), and ethyl 3-(3ꢀ,4ꢀ-dimethoxyphenyl)-3-(prop-
2-yn-1-yloxy)propanoate (8). These products have been identified with the aid of mass spectrometry and nuclear magnetic resonance
spectroscopy. We propose that reduction of 1 involves two-electron cleavage of the carbon–bromine bond to form a carbanion. Then
the latter species eliminates −OCH2C≡CH to afford 4. In addition, −OCH2C≡CH can deprotonate 1 to yield (Z)-ethyl 2-bromo-3-
(3ꢀ,4ꢀ-dimethoxyphenyl)acrylate (5), which is further deprotonated by −OCH2C≡CH to give 7. Alternatively, the carbanion resulting
from the original two-electron reduction of 1 can gain a proton from the medium to form 8.
© The Author(s) 2014. Published by ECS. This is an open access article distributed under the terms of the Creative Commons
Attribution 4.0 License (CC BY, http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse of the work in any
medium, provided the original work is properly cited. [DOI: 10.1149/2.0031501jes] All rights reserved.
Manuscript submitted September 18, 2014; revised manuscript received October 14, 2014. Published October 31, 2014.
In two previous projects1,2 involving collaboration with our lab-
arises via base-promoted rearrangement of 2) was found in mod-
est yield (18–26%). More importantly, the principal product was ethyl
trans-3-(3ꢀ,4ꢀ-dimethoxyphenyl)acrylate (4), although small amounts
of (Z)-ethyl 2-bromo-3-(3ꢀ,4ꢀ-dimethoxyphenyl)acrylate (5) and ethyl
3-(3ꢀ,4ꢀ-dimethoxyphenyl)-2,3-bis(prop-2-yn-1-yloxy)propanoate (6)
were detected.
oratory, electrochemical methods were probed as an avenue to the
synthesis of building blocks for lignans, which comprise a class of
phenylalanine-derived compounds that have attracted considerable at-
tention due to their pharmacological activity and abundance in nature.
In the first of those investigations,1 we examined the reductive in-
tramolecular cyclization of ethyl 2-bromo-3-(3ꢀ,4ꢀ-dimethoxyphenyl)-
3-(propargyloxy)propanoate (1), catalyzed by electrogenerated
nickel(I) tetramethylcyclam, to afford 2-(3ꢀ,4ꢀ-dimethoxyphenyl)-3-
(ethoxycarbonyl)-4-methylenetetrahydrofuran (2) in good yield (72–
85%); the latter species is a desired precursor for the formation of isog-
melinol (a furofuran lignan). In addition, a second product, 2-(3ꢀ,4ꢀ-
dimethoxyphenyl)-3-ethoxycarbonyl-4-methyl-2,5-dihydrofuran (3),
was obtained in significant yield (22–30%).
Recent publications from our laboratory3–8 and by other research
groups9–24 have dealt with the electrochemistry of halogenated
organic compounds at silver cathodes and have revealed the catalytic
effect of silver on the reductive cleavage of carbon–halogen bonds; the
cited references lead the way to other earlier papers on this topic. For
example, our laboratory discovered quite recently8 that cleavage of
the carbon−chlorine bond of 2-chloro-N-phenylacetamides at a silver
cathode occurs at potentials which are 500–600 mV more positive than
those seen with a glassy carbon electrode. In an earlier paper, Isse and
co-workers14 found that cyclic voltammograms for reduction of ben-
zyl bromide at a silver electrode in an acetonitrile medium exhibit two
cathodic peaks, whereas only one stage of reduction is observed when
a glassy carbon cathode is employed. Using silver cathodes, these au-
thors demonstrated that bulk electrolyses of benzyl bromide at a poten-
tial corresponding to the first voltammetric peak afford mainly biben-
zyl via coupling of benzyl radicals produced by one-electron reduction
of the starting material. On the other hand, electrolyses of benzyl
bromide at a potential corresponding to the second voltammetric peak
resulted in a mixture of bibenzyl and toluene; although toluene was the
A second paper2 was concerned with the direct reduction of
1 at both glassy carbon and reticulated vitreous carbon cathodes
in dimethylformamide (DMF) containing various tetraalkylammo-
nium salts. Interestingly, although 2 was not obtained, 3 (which
∗Electrochemical Society Student Member.
∗∗Electrochemical Society Fellow.
zE-mail: peters@indiana.edu
Downloaded on 2015-06-08 to IP 128.192.114.19 address. Redistribution subject to ECS terms of use (see ecsdl.org/site/terms_use) unless CC License in place (see abstract).

Journal of The Electrochemical Society, 161 (14) G128-G132 (2014)
G129
anticipated product, the formation of bibenzyl was attributed to an effi-
cient solution-phase SN2 reaction between the starting material and the
electrogenerated benzyl carbanion, the latter species arising from a
two-electron process.
For controlled-potential (bulk) electrolyses, working cathodes
(with geometric areas of approximately 20 cm2) were constructed
from silver gauze (Alfa Aesar, 99.9%, 20-mesh, woven from 0.356-
mm-diameter wire).6,8 Careful pretreatment of these electrodes is
crucial to obtain reproducible and complete reduction of a starting
material. Therefore, each electrode was cleaned by immersion in a
room-temperature aqueous slurry (suspension) of solid sodium bicar-
bonate that was simultaneously ultrasonicated for 30 min. Then the
electrode was thoroughly rinsed with distilled, deionized water to re-
move the sodium bicarbonate (and any impurities), after which the
electrode was placed in an oven at 180◦C and atmospheric pressure
for 20 min. Finally, a very brief cathodic polarization of the elec-
trode, after being inserted into the electrolysis cell, serves to activate
the cathode completely. As indicated in the preceding paragraph, the
reference electrode was a saturated cadmium amalgam in DMF;26–28
the auxiliary anode was a graphite rod separated from the cathode
compartment by a medium-porosity sintered-glass disk backed by a
methyl cellulose–DMF–0.10 M TEABF4 plug. Information about the
two-compartment (divided) electrolysis cell, as well as details about
instrumentation and procedures for bulk electrolyses, can be found in
earlier papers.6,31
As part of our ongoing interest in the reduction of halogenated
organic compounds at silver cathodes, we have employed cyclic
voltammetry and controlled-potential (bulk) electrolysis in the present
work to investigate the electrochemical reduction of 1 in dimethyl-
formamide (DMF) containing 0.10 M tetraethylammonium tetrafluo-
roborate (TEABF4). To the best of our knowledge, reduction of 1 at a
silver electrode has not been previously explored. Identities and yields
of the various products, none of which is a carbocyclic compound,
have been established with the aid of 1H and 13C NMR spectroscopy,
gas chromatography (GC) and gas chromatography–mass spectrom-
etry (GC–MS), and high-resolution mass spectrometry (HRMS). Ef-
fects of added proton donors (1,1,1,3,3,3-hexafluoro-2-propanol and
deuterium oxide) on the coulometric n value and product distribution
have been examined, and a set of mechanistic pathways is proposed
to account for the formation of the various products.
Experimental
Separation, identification, and quantitation of electrolysis
products.— Prior to the start of each controlled-potential (bulk) elec-
trolysis, a known amount of an internal standard (n-undecane) was
added to the solution so that the absolute yield of each product (with
respect to the amount of starting material) could be determined; de-
tails pertaining to this quantitation procedure have been published
elsewhere.32 At the conclusion of a bulk electrolysis, the catholyte
(ca. 20–25 mL) was added to approximately 20 mL of diethyl ether
and washed three times with brine. Then the ether phase was dried
over anhydrous sodium sulfate, filtered to remove the drying agent,
and concentrated by means of rotary evaporation. Gas chromatog-
raphy (GC) and gas chromatography–mass spectrometry (GC−MS)
were employed to separate, identify, and quantitate the various elec-
trolysis products in each ether extract. Each of the gas chromato-
graphic systems (Agilent 7890A instrument) included a 60 m × 0.25
mm i.d. capillary column (Agilent Technologies) with a polyethylene
glycol stationary phase; a flame-ionization detector was utilized for
the GC measurements, whereas an inert mass-selective detector in
electron-ionization mode (70 eV) was used for the GC–MS analyses.
As appropriate, gas chromatographic retention times, along with NMR
and mass spectral data, for the electrolysis products were compared
with those for chemically synthesized authentic samples. Identities of
Reagents.— Each
of
the
following
chemicals
was
used, as received, without further purification: 1,1,1,3,3,3-
hexafluoro-2-propanol (HFIP, Sigma Aldrich, 98%), 3,4-
dimethoxyphenylacetylene (Aldrich, 98%), anhydrous diethyl ether
(EMD Millipore Co., 99%), anhydrous ethanol (Pharmco-AAPER),
anhydrous sodium sulfate (BDH, ACS grade), n-butyllithium
(Aldrich, 2.0 M in cyclohexane), ethyl acetate (Macron, ACS grade),
ethyl chloroformate (Aldrich, 97%), n-hexane (BDH, ACS grade),
hydrochloric acid (Macron, ACS grade), methanol (Macron, ACS
grade), n-undecane (EMD Millipore Co., 99.9+%), ammonium
chloride (Macron, 99.5%), tetrahydrofuran (THF, Macron, ACS
grade), deuterium oxide (D2O, Aldrich, 99.9%), and trans-3,4-
dimethoxycinnamic acid (Aldrich, 99%, as a 19:1 mixture of the
trans and cis compounds).
Dimethylformamide (DMF, EMD Millipore Co., 99.9%) was em-
ployed, without further purification, as the solvent for all electrochem-
ical experiments. Tetraethylammonium tetrafluoroborate (TEABF4,
GFS Chemicals, 98%) served as the supporting electrolyte; prior to
being used, it was recrystallized from methanol–water and stored in
a vacuum oven at 90◦C to remove traces of water. Deoxygenation of
all solutions for cyclic voltammetry and controlled-potential electrol-
yses was accomplished with zero-grade argon (Air Products). Ethyl
2-bromo-3-(3ꢀ,4ꢀ-dimethoxyphenyl)-3-(propargyloxy)propanoate (1)
was prepared according to a published procedure;25 mass and 1H
NMR spectra were in accord with previously reported data.
synthesized compounds were established with the aid of 1H and 13
C
NMR spectroscopy (400- or 500-MHz Varian Inova instrument) and
high-resolution GC–MS (Thermo Electron Corporation instrument)
coupled to a MAT-95XP magnetic-sector mass spectrometer.
Electrodes, cells, and instrumentation.— For cyclic voltammetry,
we fabricated circular, planar glassy carbon and silver working elec-
trodes (with geometric areas of 0.071 cm2) by fitting short lengths
of either a glassy carbon rod (Grade GC-20, 3.0-mm-diameter, Tokai
Electrode Manufacturing Company, Tokyo, Japan) or a silver rod
(3.0-mm-diameter, 99.9% purity, Alfa Aesar) into a machined teflon
tube. A stainless-steel pole (3.0-mm-diameter), pressed into the op-
posite end of the machined teflon tube, provided electrical connec-
tion to these working electrodes. Before each cyclic voltammogram
was recorded, the working electrodes were cleaned on a Master-Tex
(Buehler) polishing pad with an aqueous suspension of 0.050-μm alu-
mina, followed by rinsing with deionized water and ultrasonication
in DMF. A coil of platinum wire served as the auxiliary (counter)
electrode. All potentials reported in this paper are given with respect
to a reference electrode consisting of a cadmium-saturated mercury
amalgam in DMF saturated with both cadmium chloride and sodium
chloride; this electrode has a potential of –0.76 V versus the aqueous
saturated calomel electrode (SCE) at 25◦C.26–28 Cells, instrumenta-
tion, and procedural details for cyclic voltammetry are described in
previous publications.6,29,30
Synthesis of ethyl trans-3-(3ꢀ,4ꢀ-dimethoxyphenyl)acrylate (trans-
4).— To 1 mL of concentrated hydrochloric acid in 50 mL of anhy-
drous ethanol was added trans-3,4-dimethoxycinnamic acid (1.1 g,
4.7 mmol), and this solution was refluxed overnight. Rotary evapo-
ration was used to remove the ethanol, and the resulting solid was
recrystallized from a hot methanol–water mixture to afford the de-
sired product (actually a 19:1 mixture of trans and cis species). We
confirmed the identity of trans-4 by spectroscopic methods: 1H NMR
(400 MHz, CDCl3) δ 7.63 (d, J = 15.6 Hz, 1H, CCH=C), 7.11 (dd, J
= 2.0, 8.4 Hz, 1H, aromatic H), 7.06 (d, J = 1.6 Hz, 1H, aromatic H),
6.87 (d, J = 8.4 Hz, 1H, aromatic H), 6.32 (d, J = 16.0 Hz, 1H, C=
CH–C), 4.19 (q, J = 7.2 Hz, 2H, OCH2), 3.92 (s, 6H, OCH3), 1.34 (t,
J = 6.8 Hz, 3H, CH3); MS (70 eV) m/z 236, M+ (100%); 191, [M –
OCH2CH3]+ (57%); 164, [M – CO2CH2CH3]+ (25%). These results
are in agreement with the literature.2,33
Synthesis of ethyl 3-(3ꢀ,4ꢀ-dimethoxyphenyl)propiolate (7).— A
solution of 3,4-dimethoxyphenylacetylene (1.0 g, 6.2 mmol) in dry
THF (10 mL) was prepared and cooled to –5◦C in an ice–salt bath;
to this solution, n-butyllithium (2.0 M in cyclohexane, 3.3 mL,
Downloaded on 2015-06-08 to IP 128.192.114.19 address. Redistribution subject to ECS terms of use (see ecsdl.org/site/terms_use) unless CC License in place (see abstract).

G130
Journal of The Electrochemical Society, 161 (14) G128-G132 (2014)
6.2 mmol) was added, and the cooled mixture was stirred for 10
min. Then the solution was allowed to warm to room temperature and
was stirred for 1 h. A dry ice–acetone bath was used to cool the mix-
ture to –78◦C, ethyl chloroformate (0.67 g, 6.2 mmol) was added, and
the solution was stirred at this temperature for 30 min. Next, the tem-
perature of the mixture was raised to 0◦C and the solution was stirred
for an additional 1 h. Saturated aqueous ammonium chloride solution
was added to quench the reaction and the mixture was extracted with
ethyl acetate, after which the organic phase was washed three times
with brine, dried over anhydrous sodium sulfate, concentrated under
reduced pressure, and introduced into a silica-gel chromatographic
column which was eluted with 20:1 hexane:ethyl acetate to afford the
desired product as a colorless oil: 1H NMR (500 MHz, CDCl3) δ 7.23
(d, J = 9.5 Hz, aromatic H), 7.08 (s, 1H, aromatic H), 6.85 (d, J =
8.5 Hz, 1H, aromatic H), 4.30 (q, J = 7.5 Hz, 2H, OCH2), 3.89 (s,
3H, OCH3), 3.92 (s, 3H, OCH3), 1.36 (t, J = 6.8 Hz, 3H, CH3); 13
C
NMR (125 MHz, CDCl3) δ 14.1, 56.0, 62.0, 79.9, 87.0, 111.1, 111.5,
115.3, 127.3, 148.8, 151.5; HRMS (ESI, 70 eV) m/z: calculated for
C13H14O4 [M]+ 234.0892, found 234.0886.
Figure 1. Cyclic voltammograms recorded at 100 mV s−1 for reduction of
2.0 mM 1 at a silver cathode (curve A, solid line) and a glassy carbon cathode
(curve B, dashed line) in oxygen-free DMF containing 0.10 M TEABF4; each
electrode had an area of 0.071 cm2. Curve A was scanned from 0 to –1.5 to
0 V, and curve B was scanned from 0 to –2.0 to 0 V. Potentials are given with
respect to a reference electrode consisting of a cadmium-saturated mercury
amalgam in contact with DMF saturated with both cadmium chloride and
sodium chloride; this electrode has a potential of –0.76 V versus an aqueous
saturated calomel electrode (SCE) at 25◦C.
at potentials corresponding to the first peak, as will be discussed later
when we consider mechanistic aspects of the reduction of 1 at silver.
Shown in Figure 2 is a comparison of the cyclic voltammetric
behavior of 2.0 mM solutions of 1 in the absence and presence of a
proton donor (1,1,1,3,3,3-hexafluoro-2-propanol, HFIP). Both cyclic
voltammograms were recorded at a scan rate of 100 mV s−1 in DMF
containing 0.10 M TEABF4 and either no HFIP (curve A, solid line)
or 20 mM HFIP (curve B, dashed line). In the presence of HFIP, all
stages in the reduction of 1 are shifted dramatically toward less nega-
tive potentials: (a) the first peak shifts from –0.67 to –0.08 V and (b)
the second set of cathodic peaks coalesces and shifts from ca. −1.30 to
−0.91 V. These large shifts in peak potentials are believed to be the
result of protonation of the ester moiety of 1, which draws electron
density away from the carbon–bromine bond. A referee suggested
an alternate way to view the effect of the added proton donor. Ac-
cordingly, the first event in the reduction of 1 involves addition of
Identification and characterization of ethyl 3-(3ꢀ,4ꢀ-
dimethoxyphenyl)-3-(prop-2-yn-1-yloxy)propanoate
(8).— We
confirmed one of the electrolysis products as the title compound
by means of mass spectrometry: MS (70 eV) m/z 292, M+ (23%);
253, [M – CH2C≡CH]+ (20%); 236, [M – HOCH2C≡CH]+ (42%);
205, [M – CH2CO2CH2CH3]+ (98%); 191, [M – CH2CO2CH2CH3
– CH2]+ (22%) 165, [M – CO2CH2CH3 – OCH2C≡CH]+ (100%);
HRMS (ESI, 70 eV) m/z: calculated for C16H20NaO5 [M + Na]+
315.1208; found 315.1194.
Results and Discussion
Cyclic voltammetric behavior of ethyl 2-bromo-3-(3ꢀ,4ꢀ-
dimethoxyphenyl)-3-(propargyloxy)propanoate (1).— Displayed in
Figure 1 is a cyclic voltammogram recorded at 100 mV s−1 for the
direct reduction of a 2.0 mM solution of 1 at a silver cathode (curve A,
solid line) in oxygen-free DMF containing 0.10 M tetraethylammo-
nium tetrafluoroborate (TEABF4). For comparison, a cyclic voltam-
mogram for reduction of 1 at a glassy carbon electrode under the same
conditions is included in this figure (curve B, dashed line). For each
electrode, the first peak (–0.67 V for silver and –0.75 V for glassy
carbon) is highly reproducible and is assigned to the irreversible two-
electron reductive cleavage of the carbon–bromine bond of 1. It is
interesting to note that cleavage of the carbon–bromine bond is easier
at silver than at glassy carbon by 80 mV, a finding in accord with
the recognized electrocatalytic ability of silver to promote cleavage
of carbon–halogen bonds. With respect to curve A, we attribute the
peaks at more negative potentials to the reduction of products formed
Figure 2. Cyclic voltammograms recorded at 100 mV s−1 for reduction of
2.0 mM 1 at a silver cathode (area of 0.071 cm2) in oxygen-free DMF con-
taining 0.10 M TEABF4 and in the absence of HFIP (curve A, solid line) and
in the presence of 20 mM HFIP (curve B, dashed line). Curve A was scanned
from 0 to –1.5 to 0 V; curve B was scanned from 0 to –1.2 to 0 V. Potentials are
given with respect to a reference electrode consisting of a cadmium-saturated
mercury amalgam in contact with DMF saturated with both cadmium chlo-
ride and sodium chloride; this electrode has a potential of –0.76 V versus an
aqueous saturated calomel electrode (SCE) at 25◦C.
Downloaded on 2015-06-08 to IP 128.192.114.19 address. Redistribution subject to ECS terms of use (see ecsdl.org/site/terms_use) unless CC License in place (see abstract).

Journal of The Electrochemical Society, 161 (14) G128-G132 (2014)
G131
potential (bulk) electrolyses of 1 were performed at silver gauze
cathodes in DMF–0.10 M TEABF4. To ensure complete electrol-
ysis of 1 and to preclude reduction of any products, the cathode
potential was held at −0.80 V, which is consistent with the cyclic
voltammogram displayed in Figure 1, curve A. Table I summarizes
the coulometric n values and the product distributions obtained from
at least two separate experiments. No starting material was detected
at the end of any electrolysis, and the total yield of 99% provides
evidence that we were able to account for all of the products. As
shown by the first entry in Table I, essentially equal yields of an alkene
(cis- and trans-4) and an alkyne (7) were found and the coulometric
n value was 1.0; as explained in the discussion of mechanism below,
this n value arises because one-half of the starting material engages in
a two-electron process, whereas the other half of the starting material
undergoes a purely chemical reaction. With respect to 4, the 4:1
trans:cis ratio is not surprising, as the trans-isomer is more stable. In
another experiment in which the initial concentration of 1 was raised
to 10.0 mM, the n value, the cis-trans ratio, and the ratio of yields of
products 4 and 7 were not significantly affected.
Table I. Coulometric data and product distributions for
direct reduction of ethyl 2-bromo-3-(3ꢀ,4ꢀ-dimethoxyphenyl)-3-
(propargyloxy)propanoate (1) at silver gauze cathodes held at –0.80
V in DMF containing 0.10 M TEABF4.
Product distribution (%)a
[1] (mM) HFIP (mM)b nc cis-4 trans-4
7
8
Total
5.0
5.0
0
50.0
1.0
10
40
62
49
NDd
35
99
97
2.0 TRe
NDd
aYield expressed as the percentage of 1 incorporated into each prod-
uct; 4 = ethyl 3-(3ꢀ,4ꢀ-dimethoxyphenyl)acrylate; 7 = ethyl 3-(3ꢀ,4ꢀ-
dimethoxyphenyl)propiolate; 8 = ethyl 3-(3ꢀ,4ꢀ-dimethoxyphenyl)-3-
(prop-2-yn-1-yloxy)propanoate.
bHFIP = 1,1,1,3,3,3-hexafluoro-2-propanol.
cAverage number of electrons per molecule of 1.
dND = species was not detected.
eTR = a trace (<1%) of the species was detected.
Entry 2 in Table I shows the results of bulk electrolyses of 1 done at
–0.80 V in the presence of a tenfold excess of a proton donor (HFIP).
For these experiments, the n value was 2.0 and the products were
trans-4 (62%) and 8. Thus, when a proton donor is introduced, no 7 is
formed, but 8 (a species undetected in experiments performed in the
absence of a proton donor) is produced.
an electron to a LUMO that is a combination of the carbon–bromine
σ* orbital and the carbonyl π* orbital; protonation of the carbonyl
moiety would lower the energy of the π* orbital as well as the energy
of the combined LUMO which, by pulling electron density away from
the carbon–bromine bond, would shift its reduction potential to a less
negative value.
Controlled-potential electrolysis of ethyl 2-bromo-3-(3ꢀ,4ꢀ-
Mechanistic aspects of the reduction of ethyl 2-bromo-3-(3ꢀ,4ꢀ-
dimethoxyphenyl)-3-(propargyloxy)propanoate (1).— Controlled-
dimethoxyphenyl)-3-(propargyloxy)propanoate (1).— Scheme
1
Scheme 1. Proposed mechanistic steps for direct
electrochemical reduction of bromo propargyloxy es-
ter 1 at a silver cathode. Note that the only hydrogen
atoms specifically shown among the various inter-
mediates are those removed as protons via reaction
with −OCH2C≡CH.
Downloaded on 2015-06-08 to IP 128.192.114.19 address. Redistribution subject to ECS terms of use (see ecsdl.org/site/terms_use) unless CC License in place (see abstract).

G132
Journal of The Electrochemical Society, 161 (14) G128-G132 (2014)
provides a sequence of mechanistic steps that can account for the
electrochemical behavior of 1 at a silver electrode. In the first step, 1
accepts a pair of electrons, accompanied by expulsion of a bromide
ion, to give an intermediate carbanion 9 (reaction 1). Once formed,
9 triggers the formation of the observed final products (4, 7, and 8).
Interestingly, the absence of carbocyclic products such as 2-(3ꢀ,4ꢀ-
dimethoxyphenyl)-3-(ethoxycarbonyl)-4-methylenetetrahydrofuran
(2) or 2-(3ꢀ,4ꢀ-dimethoxyphenyl)-3-ethoxycarbonyl-4-methyl-2,5-
dihydrofuran (3) indicates, in contrast to earlier work,1,2 that
intramolecular cyclization of a radical intermediate (arising from
one-electron reduction of 1) is an irrelevant process when 1 is reduced
at a silver cathode. Furthermore, if a radical intermediate were to be
formed, we suggest that it would be anchored by its acetylenic moiety
or by its two oxygen atoms to the surface of the silver electrode and
that it would immediately accept another electron to yield 9. When
bulk electrolysis of a 5.0 mM solution of 1 was carried out at a silver
gauze cathode in DMF–0.10 M TEABF4 containing 500 mM D2O,
no 8 was detected; this observation implies that 9 is a short-lived
intermediate and that a proton donor more potent than water is needed
to trap 9. In the absence of a sufficiently strong acid, 9 eliminates
the propargyloxy anion to yield 4 (reaction 2). We propose that the
released propargyloxy anion, acting as a base, attacks unreduced 1 to
afford 5 (reaction 3); it is the occurrence of this latter reaction that is
responsible for the coulometric n value of 1 (when bulk electrolysis
of 1 is conducted in the absence of a potent proton donor), since
essentially half of the starting material is consumed by this reaction.
Subsequent base-promoted removal of a proton from 5, followed by
immediate loss of bromide, yields 7 (reaction 4). Evidence supporting
the occurrence of reactions 3 and 4 was obtained by addition of
an excess of NaOH to a 5.0 mM solution of 1 in DMF–0.10 M
TEABF4 that was stirred for 20 min at room temperature. When
this solution was subjected to the usual post-electrolysis extraction
and analysis protocol, the presence of 7 was confirmed by means of
GC–MS. Furthermore, very small amounts of prop-2-yn-1-ol (arising
from protonation of −OCH2C≡CH during the diethyl ether–water
extraction of the catholyte) were detected in the ether phase by
means of GC–MS; however, most of the prop-2-yn-1-ol is lost to the
aqueous phase, so we did not attempt to quantitate this species.
When HFIP is added to the system, the electrogenerated bases
are protonated and no base-promoted eliminations (reactions 3 and
4) occur, which results in the absence of 7. An acidic environment
(containing HFIP) causes protonation of electrogenerated anion 9 to
give 8 (reaction 5). Our proposed mechanistic steps, whereby 4 and 8
are produced, both proceed via an overall two-electron process, which
is in agreement with the observed n value of 2 when electrolyses of 1
are carried out in the presence of HFIP.
the gift of a generous quantity of compound 1. High-resolution mass
analyses were performed in the Indiana University Mass Spectrometry
Facility; the HRMS system was purchased with funds provided by the
National Institutes of Health Grant No. 1S10RR016657-01.
References
1. A. P. Esteves, D. M. Goken, L. J. Klein, M. A. Lemos, M. J. Medeiros, and
D. G. Peters, J. Org. Chem., 68, 1024 (2003).
2. A. P. Esteves, D. M. Goken, L. J. Klein, M. J. Medeiros, and D. G. Peters, J. Elec-
troanal. Chem., 560, 161 (2003).
3. A. A. Peverly, J. A. Karty, and D. G. Peters, J. Electroanal. Chem., 692, 66
(2013).
4. A. A. Peverly, E. M. Pasciak, L. M. Strawsine, E. R. Wagoner, and D. G. Peters, J.
Electroanal. Chem., 704, 227 (2013).
5. E. R. Wagoner and D. G. Peters, J. Electrochem. Soc., 160, G135 (2013).
6. L. M. Strawsine, M. S. Mubarak, and D. G. Peters, J. Electrochem. Soc., 160, G3030
(2013).
7. E. R. Wagoner, C. P. Baumberger, A. A. Peverly, and D. G. Peters, J. Electroanal.
Chem., 713, 136 (2014).
8. E. M. Pasciak, A. Sengupta, M. S. Mubarak, K. Raghavachari, and D. G. Peters,
Electrochim. Acta, 127, 159 (2014).
9. S. Rondinini and A. Vertova, Electrochim. Acta, 49, 4035 (2004).
10. G. Fiori, S. Rondinini, G. Sello, A. Vertova, M. Cirja, and L. Conti, J. Appl. Elec-
trochem., 35, 363 (2005).
11. L. Falciola, A. Gennaro, A. A. Isse, P. R. Mussini, and M. Rossi, J. Electroanal.
Chem., 593, 47 (2006).
12. A. A. Isse, L. Falciola, P. R. Mussini, and A. Gennaro, Chem. Commun., 344
(2006).
13. A. A. Isse, A. De Giusti, and A. Gennaro, Tetrahedron Lett., 47, 7735
(2006).
14. A. A. Isse, A. De Giusti, A. Gennaro, L. Falciola, and P. R. Mussini, Electrochim.
Acta, 51, 4956 (2006).
15. A. A. Isse, S. Gottardello, C. Durante, and A. Gennaro, Phys. Chem. Chem. Phys.,
10, 2409 (2008).
16. O. Scialdone, A. Galia, G. Errante, A. A. Isse, A. Gennaro, and G. Filardo, Elec-
trochim. Acta, 53, 2514 (2008).
17. O. Scialdone, A. Galia, G. Filardo, A. A. Isse, and A. Gennaro, Electrochim. Acta,
54, 634 (2008).
18. P. Poizot, L. Laffont-Dantras, and J. Simonet, Electrochem. Commun., 10, 864
(2008).
19. P. Poizot, L. Laffont-Dantras, and J. Simonet, J. Electroanal. Chem., 624, 52
(2008).
20. J. Simonet, J. Electroanal. Chem., 632, 30 (2009).
21. A. A. Isse, G. Sandona`, C. Durante, and A. Gennaro, Electrochim. Acta, 54, 3235
(2009).
22. A. A. Isse, G. Berzi, L. Falciola, M. Rossi, P. R. Mussini, and A. Gennaro, J. Appl.
Electrochem., 39, 2217 (2009).
23. C. Durante, A. A. Isse, G. Sandona`, and A. Gennaro, Appl. Catal., B, 88, 479 (2009).
24. O. Scialdone, C. Guarisco, A. Galia, and R. Herbois, J. Electroanal. Chem., 641, 14
(2010).
25. S. C. Roy and S. Adhikari, Tetrahedron, 49, 8415 (1993).
26. L. W. Marple, Anal. Chem., 39, 844 (1967).
27. C. W. Manning and W. C. Purdy, Anal. Chim. Acta, 51, 124 (1970).
28. J. L. Hall and P. W. Jennings, Anal. Chem., 48, 2026 (1976).
29. K. L. Vieira and D. G. Peters, J. Electroanal. Chem., 196, 93 (1985).
30. J. A. Cleary, M. S. Mubarak, K. L. Vieira, M. R. Anderson, and D. G. Peters, J.
Electroanal. Chem., 198, 107 (1986).
31. P. Vanalabhpatana and D. G. Peters, J. Electrochem. Soc., 152, E222 (2005).
32. W. A. Pritts, K. L. Vieira, and D. G. Peters, Anal. Chem., 65, 2145 (1993).
33. L. H. Klemm and D. R. Olson, J. Org. Chem., 38, 3390 (1973).
Acknowledgments
We thank Professor Maria J. Medeiros (Centro de Qu´ımica/IBQF,
Universidade do Minho, Largo do Pac¸o, 4700-320 Braga, Portugal) for
Downloaded on 2015-06-08 to IP 128.192.114.19 address. Redistribution subject to ECS terms of use (see ecsdl.org/site/terms_use) unless CC License in place (see abstract).