Nickel-Catalyzed Electrochemical Cyclization of Alkynyl Aryl Iodide and the Domino Reaction with Aldehydes

Article abstract of DOI:10.1021/acs.joc.1c00811

An intramolecular carbometallation of a triple bond promoted by electrochemistry and mediated by nickel catalysis is described. This domino process transforms various aryl halides bearing a propargyl chain into substituted heterocycles in one single operation, with high stereoselectivities and in good to high yields. This reaction, characterized by a cyclic voltammetry set of experiments, proceeds following a syn-exo-dig cyclization process. When run at 80 °C, vinylbenzofuranes that are suitable substrates for cycloaddition reactions are obtained.

Full text of DOI:10.1021/acs.joc.1c00811

pubs.acs.org/joc
Article
Nickel-Catalyzed Electrochemical Cyclization of Alkynyl Aryl Iodide
and the Domino Reaction with Aldehydes
Claire Déjardin, Amaury Renou, Jacques Maddaluno, and Muriel Durandetti*
Cite This: J. Org. Chem. 2021, 86, 8882−8890
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: An intramolecular carbometallation of a triple bond promoted
by electrochemistry and mediated by nickel catalysis is described. This
domino process transforms various aryl halides bearing a propargyl chain into
substituted heterocycles in one single operation, with high stereoselectivities
and in good to high yields. This reaction, characterized by a cyclic
voltammetry set of experiments, proceeds following a syn-exo-dig cyclization
process. When run at 80 °C, vinylbenzofuranes that are suitable substrates for
cycloaddition reactions are obtained.
INTRODUCTION
■
Indisputably, metal-catalyzed coupling reactions are, and now
for years, one of the best ways to complete efficient syntheses
of multifunctionalized scaffolds.1 A typical catalytic cycle
involves an unstable low-valent metal that is generally prepared
in situ from salts of higher oxidation states to be reacted with a
large excess of a reducing agent. But low-valent metals can also
be generated by electrochemical reduction. Thus, the pioneer-
́
ing works by Perichon et al. in 1980 reported interesting
results of electrosynthesis using a sacrificial anode process.2
Combining this technique with nickel catalysis, some of us
have described electrochemical processes allowing cross-
coupling reactions based on the in situ generation of Ni(0).
In particular, we have developed several processes, relying on
the Ni(0)bipy system (resulting from the reduction of
NiBr2bipy), and this catalyst has been shown to be reactive
toward an aryl or vinyl halide.3 The recent revival of
electrosynthesis,4 likely to be related to the development of
easy-to-handle commercial apparatus, has prompted us to re-
explore the possibilities opened by this methodology.5 Our first
results are presented below.
Polycyclic oxygen or nitrogen heterocycles are found in
numerous natural products or valuable building blocks, as
illustrated in Figure 1. Because they give an effective access to
carbon−carbon bonds,6 carbometallation reactions can be
regarded as a perfect showcase. The transition-metal-catalyzed
functionalization of alkynes, which seems to be an easy-to-
adapt transformation, is an attractive, possibly stereoselective
transformation that provides substituted alkenes. In addition to
carbolithiation7 and carbomagnesation,8 palladium has been
widely used in recent decades to carry out this type of
reaction.9 The results presented underneath suggest that a
nickel-based electrochemical system can afford a sustainable
while competitive catalytic method, helping to clear large-scale
Figure 1. Representative polycyclic oxygen or nitrogen heterocycles
found in natural products.
industrial processes from a rare and expensive metal, nowadays
a societal requisite.10
We previously described the carbonickelation of alkynes
followed by direct functionalization of the resulting vinylnickel,
catalyzed by NiBr2bipy. This handy process affords substituted
dihydrobenzofurans, (iso)chromans, indoles, or indanes, in
good to high yields from aryl iodides and a variety of
electrophiles.11 While our original protocol relied on the
chemical reduction of stable Ni(II) complexes by Mn(0),12 it
appeared even simpler and certainly “cleaner” to us to use just
electrons to generate Ni(0). This “minimal” and inexpensive
reductant can indeed be regarded as a perfect alternative to
manganese, avoiding metal powders and extra salt contami-
Received: April 8, 2021
Published: June 11, 2021
https://doi.org/10.1021/acs.joc.1c00811
© 2021 American Chemical Society
J. Org. Chem. 2021, 86, 8882−8890
8882

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
nation. If this attractive scenario casts relatively little doubt on
the electrogeneration of the arylnickel intermediate, two key
questions remain (i) will this elusive reagent be able to
perform the cyclization step in the electrochemical conditions
and (ii) will the second step of the domino process take place,
that is will the transient vinylnickel react with the electrophile
while avoiding its dimerization?
Table 1. Optimization of the Intramolecular
Electrochemical Carbonickelation and Functionalization of
a
1a
We present underneath our investigation on this nickel-
catalyzed electroreductive intramolecular carbonickelation
reaction, as well as its domino version, leading to various
substituted heterocycles (Scheme 1). We also detail the
b
entry
solvent
i (mA)
T (°C)
anode
2a (%)
Scheme 1. Nickel-Catalyzed Electroreductive
Intramolecular Carbonickelation Reaction Followed by a
Barbier-Type Addition on Aldehydes
c
1
2
3
4
5
6
7
8
DMF
DMF
DMF
DMF
DMF
EtOH/DMF 9:1
MeCN/DMF 4:1
THF
100
50
25
25
15
25
25
25
25
25
25
25
50
50
50
r.t.
r.t.
50
50
50
50
50
50
50
Al
Al
Al
Al
Al
Al
Al
Al
Al
Zn
Ni
Al
30
45
d
95 (90)
e
69
93
g
f
9
NMP
DMF
33
53
56
h
10
11
12
h
DMF
DMF
i
62 (48)
a
Reaction conditions unless otherwise specified: 1a (1 mmol),
PhCHO (1.3 mmol), NiBr2bipy (0.10 mmol), NBu4BF4 (0.15 mmol),
and DMF (5 mL). Electrolysis was run under argon, at constant
current intensity until the aromatic halide was totally consumed (2 F/
efficiency and scope of this procedure. In addition, the use of a
simple nickel complex in an undivided cell, with a sacrificial
anode, led us to expect an easy, cheap, little toxic, and
innovative process.
b
mol). NMR yields, based on the initial aryl iodide 1a. Isolated yields
c
in brackets. 26% of the starting material and 44% of vinylH 3a is
d
recovered at the end of electrolysis. 15% of the starting material and
e
RESULTS AND DISCUSSION
40% of 3a is recovered at the end of electrolysis. 15% of the starting
■
material and 15% of 3a is recovered at the end of electrolysis.
At first, different parameters such as the anode, the
temperature, the intensity, and the solvent were studied; the
results are reported in Table 1.
f
g
Reaction is stirred 15 min after the end of electrolysis. Acetal of
h
benzaldehyde is recovered with the starting material. 15% of the
starting material and 30% of 3a are recovered at the end of
The optimization was run with aryl iodide 1a,11 which bears
a simple propargyl chain, and benzaldehyde. Dimethylforma-
mide (DMF), which is generally used when NiBr2bipy is the
catalyst,11,12 immediately gave a very good result: the expected
alcohol 2a, resulting from the domino process cyclization +
nucleophilic addition of the vinylnickel intermediate to
benzaldehyde, was recovered in 90% isolated yields, provided
the reaction was performed at 50 °C and a constant current of
25 mA (Table 1, entry 3). However, running the reaction at 50
or 100 mA revealed that some starting material was left
unconsumed, and the time was too short for the cyclized
vinylnickel intermediate to be added to benzaldehyde, as
evidenced by significant amounts of vinylH 3a recovered
(Table 1, entries 1 and 2). At room temperature, the second
step again seemed to slow down, and the current had to be
decreased to 15 mA to obtain a complete conversion and,
finally, to wait 15 min after electrolysis to obtain good yield of
alcohol 2a (Table 1, entries 4 and 5). Replacement of DMF by
other solvents gave poor results, even in a mixture with DMF
(Table 1, entries 6−9). Finally, we found that an aluminum
rod provides the best anode (Table 1, entries 3−5), and
resorting to Zn instead of Al slows down the process and 1a is
not fully consumed at 2 F/mol, probably because a competitive
Zn2+ reduction occurs during the Ni(II) catalytic cycle (Table
1, entry 10). The same observation was made with a Ni anode
(Table 1, entry 11). Finally, it is interesting to note that the
reaction can take place under air instead of argon, although a
lower yield is obtained, probably due to the loss of the catalyst
i
electrolysis. Reaction is run under air.
during electrolysis. This experimental study led us to apply the
following typical procedure: electrolysis was run in a one-
compartment cell fitted with nickel sponge (area ca. 2 cm2) as
a cathode and an aluminum plate as the anode. NBu4BF4 (0.15
equiv, 0.15 mmol, supporting electrolyte) was dissolved in 5
mL of dry DMF under argon atmosphere, and then NiBr2bipy
(0.10 equiv, 0.10 mmol), aryl iodide 1 (1.0 equiv, 1.0 mmol),
and aldehyde (1.3 equiv, 1.3 mmol) were added. Electrolysis
was run at 50 °C with an oil bath, under argon, at a constant
current intensity of 25 mA until the aromatic halide 1 was
totally consumed (2 F/mol, ∼2 h 15 min).
This process was applied to various aryl iodides 1a−h, easily
prepared from commercially available iodophenol, iodobenzoic
acid, or iodobenzyl bromide.11 Results for the tandem process
with benzaldehyde are given in Table 2. In all cases, the
conversion is complete in 2 F/mol (ca. 2 h 15 min), and the
selectivity of the carbonickelation is totally in favor of exo-dig
syn-addition, whatever the size of the ring (5-, 6-, or 7-
membered). Moreover, the postfunctionalization is efficient,
and the alcohols are obtained in good to excellent yields.
Unfortunately, our isolated yields sometimes look inferior, due
to the dehydration reaction and rearomatization during the
purification on silica gel or alumina column chromatography.
We have then studied the influence of the nature of the link
between the aryl and the triple bond. Here again, moderate to
8883
https://doi.org/10.1021/acs.joc.1c00811
J. Org. Chem. 2021, 86, 8882−8890

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Table 2. Scope of the Electrochemical Carbonickelation of
Aryl Iodides 1a−h in the Presence of Benzaldehyde
Scheme 2. Proposed Catalytic Cycle
a
0.1 M solution of n-NBu4Br used as the supporting electrolyte
in DMF at room temperature. The cyclic voltammograms of
NiBr2bipy in the absence and presence of 1 equiv of ArI 1a, as
obtained on a gold microelectrode at 200 mV/s, are given in
Figure 2. By itself, the nickel(II) complex shows a quasi-
a
Reaction conditions: 1a−h (1 mmol), benzaldehyde (1.3 mmol),
NiBr2bipy (10 mol %), DMF (5mL), 50 °C, i = 25 mA, and 2 h 15
min. Yields of isolated products are given. NMR yields with respect to
an internal standard based on the initial aryl iodide 1 are given within
brackets.
Figure 2. Cyclic voltammograms in DMF + 0.1 M NBu4Br, at a gold
disc microelectrode (0.25 mm diameter) at v = 0.2 V/s and at r.t
good yields were obtained in the same experimental
conditions, from the corresponding all-carbon (2d, Table 2)
or nitrogenated (2c) alkynes. Note that the reaction tolerates
electron-donating (2g) or -withdrawing (2e,f) substituents on
the aromatic ring and remains highly chemoselective even in
the presence of an ester group. We next checked whether this
process could be scaled up. The reaction was performed on 4
mmol of the easily accessible substrate 1a, using 5 mmol of
benzaldehyde in 10 mL of DMF. To diminish the reaction
time, the electrolysis was run at 50 mA, always with 2F/mol.
Finally, alcohol 2a was isolated in 69% isolated yield (75%
NMR yield) after ≈4 h 30 min.
To explain the catalytic amount of the nickel salt in the case
of this domino sequence cyclization/nucleophilic addition
onto carbonyl, we propose the mechanism depicted in Scheme
2. The first likely step is the in situ generation of Ni(0) by
reduction of nickel(II) at the cathode at −1.15 V/SCE.13 After
oxidative addition, the arylnickel intermediate reacts with the
triple bond and triggers a stereoselective cyclization.11 The
nucleophilic addition of the resulting vinylnickel to benzalde-
hyde occurs, leading to the nickel alkoxide. Then, the nickel
alkoxide transmetallates with Al(III) coming from the
oxidation of the anode14 releasing the nickel(II) salt, which
can be reduced another time.
(purple curve) of (a) 10−2 M NiBr2bipy (blue curve), (b) 10−2
M
M
NiBr2bipy + 1 molar equiv of ArI 1a (red curve), and (c) 10−2
NiBr2bipy + 1 molar equiv of ArI 1a + 1.5 equiv of benzaldehyde
(green curve).
reversible reduction system in DMF at −1.15 V/SCE, with the
consumption of two electrons, giving Ni(0)bipy, which is then
further reduced at −1.9 V/SCE to Ni(0)bipy.− (blue curve).13b
In the presence of 1a, an oxidative addition of electrogenerated
Ni(0) to the aryl halide occurs, leading to a σ-arylnickel(II)
entity, which can be reduced to ArNi(I) either at −1.35 or
−1.5 V/SCE, depending on the complexation state13a (red
curve). Simultaneously, the Ni(II) reduction occurs earlier, in
agreement with a chemical reaction succeeding the electro-
chemical one, and the reoxidation of Ni(0) no longer takes
place (EC mechanism). The addition of benzaldehyde
modifies the curve again: the two peaks corresponding to the
arylnickel(II) reduction disappear and a new system appears at
−1.6 V/SCE, in addition to the reduction of benzaldehyde at
−1.9 V/SCE (green curve).
The scope of this sequence is also defined by the variety of
electrophiles that it can encompass. The results in Table 3
show the reactivity of aryl iodide 1a toward various aldehydes.
It turns out that the process is efficient, whatever the
A cyclic voltammetry study was launched to support our
mechanistic hypotheses. CV experiments were carried out in a
8884
https://doi.org/10.1021/acs.joc.1c00811
J. Org. Chem. 2021, 86, 8882−8890

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
The reaction is highly chemoselective, and no competitive
addition is observed on the ester, nitrile, or ketone groups (4f−
h). Even if the reduction of aromatic aldehydes bearing
electron-withdrawing groups is easy, compared to other
aldehydes (−1.55 V/SCE for p-CF3-PhCHO and −1.45 V/
SCE for p-MeO2C-pHCHO compared to −1.9 V/SCE for
PhCHO),15 and close to the Ni(II) reduction potential (−1.15
V/SCE),13 no pinacolization is observed in these cases.
Addition to aliphatic aldehydes at 80 °C also gave good
NMR yield, but the purification by chromatography on silica or
alumina gel led to severe losses of products (4k−l). Varying
the temperature can afford, with electron-rich aldehydes,
another product, the alcohol 4 can transform directly into the
corresponding diene 5, following a dehydration−aromatization
process, as observed in the case of 5a and 5m and 5n, derived,
respectively, from anisaldehyde, N,N-dimethyl benzaldehyde,
and cinnamaldehyde.
Table 3. Electrochemical Nickel-Catalyzed Cyclization of
Iodoaryl 1a in the Presence of Various Aldehydes
a
Since the 3-vinylbenzofuranes 5 we have prepared exhibit a
peculiar dienic motive, we decided to end up this work by
illustrating their synthetic potential in cycloaddition reactions.
Previous works have shown that such substrates can react in
dearomatizing (4 + 2) cycloadditions under hyperbaric
conditions (Scheme 3).11,16
Scheme 3. Cycloaddition of Benzofurane 5 under
Hyperbaric Conditions
a
Reaction conditions: 1a (1 mmol), aldehyde (1.3 mmol), NiBr2bipy
(10 mol %), DMF (5 mL), 50 °C, i = 25 mA, and 2 h 15 min. Yields
of isolated products are given. NMR yields with respect to an internal
standard based on the initial aryl iodide 1a are given within brackets.
b
Reaction run at 80 °C.
substituent formed by the aromatic aldehyde in ortho, meta, or
para positions. For example, good to excellent NMR yields are
obtained for anisaldehyde, and if the para isomer 4a revealed
to be unstable, the alcohols 4b and 4c could even be efficiently
purified. If aromatic aldehydes bearing electron-donating or
-withdrawing groups are suitable, the best results are obtained
when the reaction is conducted at 80 °C on electron-depleted
substrates. At 50 °C, a mixture of 4 and (Z)-3-ethylidene-2,3-
dihydrobenzofuran 3a was obtained. The formation of this
latter is probably due to the sluggish nucleophilic addition of
the vinylnickel intermediate on the electron-poor aldehydes,
giving its chance, again, to a competitive protonation.
Increasing the temperature to 80 °C allows a total conversion
of the vinylnickel intermediate into the addition products 4.
Thus, 5a was reacted with N-methylmaleimide at room
temperature, under 16 kbar. The cycloaddition is efficient,
allowing a single endo isomer 6a in 65% yield. When 5m is
used under the same hyperbaric conditions, 6m is isolated in a
very good yield of 71% as a single endo isomer. The same
reaction conducted in the presence of t-butyl acrylate as
dienophile leads to the tricyclic adduct in a good yield of 77%
but as a mixture of three isomers. Overall a good endo/exo
selectivity of about 97/3 is observed for 7m but associated
8885
https://doi.org/10.1021/acs.joc.1c00811
J. Org. Chem. 2021, 86, 8882−8890

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
3H, J = 2.3 Hz). 13C{1H} NMR (CDCl3, 75 MHz): δ 159.1, 136.6 (q,
J = 3.7 Hz), 126.8 (q, J = 3.7 Hz), 124.9 (q, J = 33.2 Hz), 123.3 (q, J =
271.3 Hz), 112.1, 86.1, 85.2, 72.8, 57.7, 3.7. 19F NMR (CDCl3, 282
MHz): −61.6; IR (neat): υmax = 1602; 1496; 1324; 1268; 1117; 811;
670 cm−1. MS (CI, methane) 341 (MH+); 214 (base, MH+ − I).
HRMS (CI, methane): theor for C11H9F3IO (M + H+): 340.9650,
meas. 340.9634.
with a moderate regioselectivity of 3/1 for 7m/8m, probably
due to the modest polarization of the diene.
CONCLUSIONS
■
In conclusion, this article describes an easy access to
substituted dihydrobenzofuran, (iso)chroman, indole, or
indane structures by an expedient electrochemical route that
encompasses both a cyclization and a C−C bond formation
step. We report on the first electroreductive catalytic
intramolecular carbonickelation of alkynes that affords, in
fine yields, a set of heterocycles, following a 5-, 6-, or 7-exo-dig
cyclization. This transformation allows in one single syn-
selective step the desired vinylnickel intermediate, which adds
to aldehydes in Barbier conditions. The proposed mechanism
was supported by a cyclic voltammetry set of experiments.
Pushing the investigation further led us to show that the
resulting 3-vinylbenzofuranes, obtained after dehydration of
the alcohols, react with activated olefins to provide the (4 + 2)
cycloaddition products, in high endo/exo selectivity. We believe
that such a procedure presents significant advantages in terms
of sustainable development over the more classical chemical
method developed previously.
1-(But-2-yn-1-yloxy)-2-iodo-4-methylbenzene (1g). Ether 1g
is obtained using 2-iodo-4methylphenol (2.36 g, 10.1 mmol),
potassium carbonate (2.12 g, 15.2 mmol, 1.5 equiv), and 1-bromo-
but-2-yne (1.33 mL, 15.2 mmol, 1.5 equiv) in anhydrous DMF (10
mL) following the Williamson alkylation procedure. We thus obtained
1
2.885 g (10.08 mmol, 100%) of the desired compound 1g. H NMR
(CDCl3, 300 MHz): δ 7.60 (d, 1H, J = 2.1 Hz), 7.09 (dd, 1H, J = 8.4,
2.1 Hz), 6.87 (d, 1H, J = 8.4 Hz), 4.68 (q, 2H, J = 2.3 Hz), 2.26 (s,
3H), 1.84 (t, 3H, J = 2.3 Hz). 13C{1H} NMR (CDCl3, 75 MHz): δ
154.3, 139.6, 132.4, 129.6, 112.7, 86.3, 83.9, 73.8, 57.5, 19.9, 3.6. IR
(neat): υmax = 2966; 2919; 2229; 1599; 1485; 1432; 1226; 1041; 698
cm−1. MS (CI, methane) 286 (M+); 159 (base, M+ − I). HRMS (CI,
methane): theor for C11H11IO (M+): 285.9855, meas. 285.9844.
General Procedure for Electroreductive Carbonickelation−
Nucleoplile Addition, Exemplified with Compound 2a.
Electrolysis was run in a one-compartment cell fitted with nickel
sponge (area ca. 2 cm2) as the cathode and an aluminum plate as the
anode. NBu4BF4 (0.15 equiv, 0.15 mmol, 50 mg) was dissolved in 5
mL of dry DMF under argon atmosphere, then NiBr2bipy (37 mg, 0.1
mmol, 0.1 equiv), 1-(but-2-yn-1-yloxy)-2-iodobenzene (1 mmol, 272
mg, 1 equiv), and benzaldehyde (130 μL, 1.3 equiv) were added. The
electrolysis was run at 50 °C with an oil bath, under argon, at a
constant current intensity of 25 mA until the aromatic halide was
totally consumed (2 F/mol, ∼2 h 15 min). The reaction was
monitored by TLC. Finally, the reaction was diluted with 5 mL of
water and extracted with 3 × 10 mL of ethyl acetate and organic layers
were washed with water.
EXPERIMENTAL SECTION
■
GC analysis was carried out using a 24 m HP-methyl silicon capillary
column. Mass spectra were recorded with a quadrupolar MS
instrument coupled to a gas chromatograph. Elemental analyses
were performed on a Thermo Fisher FLASH 2000. High-resolution
mass spectra were obtained using a Thermo Finnigan MAT95XP
mode. Column chromatography was performed on standard silica gel
(230−400 mesh) or basic alumina. 1H NMR spectra were recorded in
CDCl3 at 300 MHz and 13C NMR spectra were recorded at 75 MHz;
chemical shifts (δ) are given in parts per million (ppm) and the
coupling constants (J) in hertz. IR spectra were recorded by
transmission on an IRFT spectrometer. DMF was stored under
argon. THF was distilled from sodium/benzophenone. The catalyst
precursor NiBr2bipy was prepared separately, according to the
literature.17
(E)-2-(Benzofuran-3(2H)-ylidene)-1-phenylpropan-1-ol (2a).
The pure compound 2a was obtained by recrystallization in pentane
1
(227 mg, 0.90 mmol, 90%) as a white solid. H NMR (CDCl3, 300
MHz): δ 7.58 (d, 1H, J = 7.9 Hz), 7.45 (d, 2H, J = 7.9 Hz), 7.35 (t,
2H, J = 7.9 Hz), 7.29 (d, 1H, J = 7.1 Hz), 7.19 (t, 1H, J = 7.9 Hz),
6.89 (d, 1H, J = 8.0 Hz), 6.88 (t, 1H, J = 7.9 Hz), 6.37 (s, 1H), 5.10
(bs, 2H), 2.00 (s, 1H), 1.61 (s, 3H). 13C{1H} NMR (CDCl3, 75
MHz): δ 128.8 (2C), 128.5, 127.8, 126.0 (2C), 125.0, 124.5, 121.2,
111.1, 75.0, 71.6, 15.0. NMR 2D NOESY correlation between 1.61 (s,
3H) and 5.12 (bs, 2H). MS 234 (M − H2O), 219 (base), 218, 191,
189. Anal. calcd for C17H16O2: C, 80.93; H, 6.39. Found: C, 80.89; H,
6.35.
Compounds 1a, 1b, 1c, 1d, and 1h have been described previously,
and prepared according to our previous reports.11 1e, 1f, and 1g are
prepared following a Williamson alkylation procedure.
The Williamson alkylation procedure, exemplified with 1e. To a
solution of substituted iodophenol (1,39 g, 5 mmol) and K2CO3 (1,05
g, 7.5 mmol, 1.5 equiv) in 10 mL of anhydrous DMF at room
temperature under argon was added 1-bromo-but-2-yne (0.656 mL,
7.5 mmol, 1.5 equiv). The solution was stirred for 30 min and washed
by adding HCl 0.5M (30 mL). The mixture was diluted with Et2O (3
× 15 mL) and washed with 0.5 M NaOH (10 mL) and then NaCl (10
mL). The combined organic layers were dried over MgSO4 and
concentrated. We thus obtained 1,65 g (5.0 mmol, 100%) of the
desired compound 1e.
(Z)-3-Ethylidene-2,3-dihydrobenzofuran (3a). 1H NMR
(CDCl3, 300 MHz): δ 7.34 (dd, 1H, J = 7.5 Hz J = 1.2 Hz), 7.13
(td, 1H, J = 7.5 Hz J = 1.2 Hz), 6.86 (td, 1H, J = 7.6 Hz J = 1.0 Hz),
6.84 (dd, 1H, J = 7.3 Hz J = 1.0 Hz), 5.86 (qt, 1H, J = 7.1 Hz J = 3.6
Hz), 5.10 (bs, 2H), 1.74 (dt, 3H, J = 7.1 Hz J = 1.9 Hz). 13C{1H}
NMR (CDCl3, 75 MHz): δ 163.4, 136.7, 129.5, 126.6, 120.9, 120.4,
111.8, 110.6, 73.9, 15.3. NMR 2D NOESY correlation between 1.74
(dt, 3H, J = 7.1 Hz J = 1.9 Hz) and 5.10 (s, 2H). MS 146 (M+), 131
(base), 115, 103, 77. Anal. calcd for C10H10O: C, 82.16; H, 6.89.
Found: C, 81.77; H, 6.64.
(Z)-2-(Chroman-4-ylidene)-1-phenylpropan-1-ol (2b). The
pure compound 2b was isolated by flash column chromatography
(SiO2, cyclohexane/AcOEt: 95:5) (151 mg, 0.57 mmol, 57%) as a
white solid. 1H NMR (CDCl3, 300 MHz): δ 7.43-7.32 (m, 4H),
7.30−7.26 (m, 2H), 7,17 (td, 1H, J = 8.0 Hz J = 1.5 Hz), 6.86 (dd,
1H, J = 8.0 Hz J = 1.2 Hz), 6.80 (td, 1H, J = 7.8 Hz J = 1.2 Hz), 6.16
(d, 1H, J = 3.9 Hz), 4.43−4.27 (m, 2H), 2.76−2.62 (m, 2H), 1.99 (d,
1H, J = 3.9 Hz), 1.69 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ
154.9, 142.6, 130.3, 130.1, 129.2, 128.7, 128.5 (2C), 127.3, 126.2
(2C), 123.0, 119.9, 116.9, 72.9, 67.7, 28.0, 13.8. NMR 2D NOESY
correlation between 1.68 (s, 3H) and 2.69 (m, 2H). MS 248 (M −
H2O), 233 (base), 215, 205, 171, 131, 91, 77. IR (neat): υmax = 3418,
2976, 2869, 2359, 1486,1449, 1119 cm−1. Mp: 117−118 °C.
1
Methyl 4-(But-2-yn-1-yloxy)-3-iodobenzoate (1e). H NMR
(CDCl3, 300 MHz): δ 8.46 (d, 1H, J = 2.1 Hz), 8.01 (dd, 1H, J = 8.7,
2.1 Hz), 6.99 (d, 1H, J = 8.7 Hz), 4.79 (q, 2H, J = 2.3 Hz), 3.89 (s,
3H), 1.85 (t, 3H, J = 2.3 Hz). 13C{1H} NMR (CDCl3, 75 MHz): δ
165.5, 160.1, 141.1, 131.4, 124.7, 111.7, 85.8, 85.1, 72.9, 57.7, 52.2,
3.8. IR (neat): υmax = 2947; 2241; 1703; 1592; 1436; 1296; 1259; 999
cm−1. HRMS (ESI+): theor for C12H12IO3 (M + H+): 330.9826, meas.
330.9831. Mp: 75−76 °C.
1-(But-2-yn-1-yloxy)-2-iodo-4-(trifluoromethyl)benzene
(1f). Ether 1f is obtained using 2-iodo-4-(trifluoromethyl)phenol
(2.88 g, 10 mmol), potassium carbonate (2.10 g, 15 mmol, 1.5 equiv),
and 1-bromo-but-2-yne (1.31 mL, 15 mmol, 1.5 equiv) in anhydrous
DMF (10 mL) following the Williamson alkylation procedure. We
thus obtained 3.257 g (9.58 mmol, 96%) of the desired compound 1f.
1H NMR (CDCl3, 300 MHz): δ 8.02 (d, 1H, J = 1.7 Hz), 7.58 (d, 1H,
J = 8.6 Hz), 7.03 (d, 1H, J = 8.6 Hz), 4.78 (q, 2H, J = 2.3 Hz), 1.86 (t,
8886
https://doi.org/10.1021/acs.joc.1c00811
J. Org. Chem. 2021, 86, 8882−8890

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(E)-tert-Butyl 3-(1-hydroxy-1-phenylpropan-2-ylidene)-
indoline-1-carboxylate (2c). The pure compound 2c was isolated
by flash column chromatography (SiO2, cyclohexane/AcOEt: 9:1)
987; 807; 749; 698 cm−1. HRMS (EI+): calcd for C18H16O (M −
H2O) 248.1201, found 248.1203. Mp: 128−129 °C.
(Z)-2-(3,4-Dihydrobenzo[b]oxepin-5(2H)-ylidene)-1-phenyl-
propan-1-ol (2h). The pure compound 2h was isolated by flash
column chromatography (SiO2, cyclohexane/Et2O 8:2) (123 mg, 0.44
mmol, 44%) as a white solid. 1H NMR (DMSO, 300 MHz, 60 °C): δ
7.16−7.41 (m, 7H), 6.97−7.03 (m, 2H), 5.42 (d, 1H, J = 4.1 Hz),
5.18 (d, J = 4.1 Hz, 1H), 4.23 (bs, 1H), 3.95 (bs, 1H), 2.68 (bs, 1H),
2.19 (bs, 1H), 1.78−2.01 (m, 2H), 1.56 (s, 3H). 13C{1H} NMR
(CDCl3, 75 MHz): δ 157.7, 142.9, 136.9, 134.6, 133.2, 129.7, 128.5,
128.2 (2C), 126.7, 125.3, 123.3, 121.5 (2C), 73.3, 72.4, 30.6, 29.5,
11.8. NMR 2D NOESY correlation between 1.56 (s, 3H) and 1.78−
2.01 (m, 2H). MS: 280 (M+), 262 (M − H2O), 247 (M − H2O −
CH3), 147 (base). IR (neat): υmax = 3424, 3025, 2930, 1599, 1480,
1228, 1054, 1008 cm−1. HRMS (EI): calcd for C19H20O2 280.1463,
found 280.1477. Mp: 92−94 °C.
1
(232 mg, 0.66 mmol, 66%) as a white solid. H NMR (CDCl3, 300
MHz): δ 7.92 (sl, 1H), 7.57 (d, 1H, J = 7.8 Hz), 7.43 (d, 2H, J = 7.4
Hz), 7.30−7.35 (m, 3H), 7.21 (d, 1H, J = 8.1 Hz), 6.93 (td, 1H, J =
7.8 Hz J = 0.9 Hz), 6.38 (s, 1H), 4.53 (s, 2H), 1.99 (bs, 1H), 1.68 (t,
3H, J = 1.7 Hz), 1.60 (bs, 9H).13C{1H} NMR (CDCl3, 75 MHz): δ
151.9, 145.8, 141.5, 130.5, 129.7, 128.8, 128.4 (2C), 127.3, 127.0,
125.8 (2C), 123.9, 122.4, 115.3, 81.2, 70.6, 53.0, 28.5 (3C), 15.2.
NMR 2D NOESY correlation between 1.65 (s, 3H) and 4.34−4.50
(m, 2H). MS 350 (M+ − H), 349, 233 (base), 218. IR (neat): υmax
=
3412, 3052, 2980, 1703, 1472, 1383, 1163, 725 cm−1. Anal. Calcd for
C22H25NO3: C, 75.19; H, 7.17; N, 3.99. Found: C, 74.91; H, 7.69; N,
3.90.
(Z)-2-(1,2-Dihydroinden-3-ylidene)-1-phenylpropan-1-ol
(2d). The pure compound 2d was isolated by flash column
chromatography (SiO2, cyclohexane/AcOEt: 97:3) (100 mg, 0.40
mmol, 40%) as a yellow oil. 1H NMR (CDCl3, 300 MHz): δ 7.53 (d,
1H, J = 7.5 Hz), 7.45−7.56 (m, 2H), 7.14−7.39 (m, 6H), 6.37 (d,
1H, J = 3.9 Hz), 2.98−3.03 (m, 2H), 2.74−2.89 (m, 2H), 2.35 (d,
1H, J = 3.9 Hz), 1. 72 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3): δ
148.1, 142.1, 140.3, 140.2, 130.0, 128.4 (2C), 127.5, 127.1, 126.5,
126.0 (2C), 125.5, 124.5, 71.8, 31.8, 30.2, 15.4. NMR 2D NOESY
correlation between 1.72 (s, 3H) and 2.74−2.89 (m, 2H) and
between 6.37 (d, 1H, J = 3.9 Hz) and 7.53 (d, 1H, J = 7.5 Hz). MS
(E)-2-(Benzofuran-3(2H)-ylidene)-1-(4-methoxyphenyl)-
propan-1-ol (4a). The pure compound 4a was isolated by reversed-
phase columns (water/acetonitrile: 54/46) (141 mg, 0.50 mmol,
50%) as a yellow solid. 1H NMR (CDCl3, 300 MHz): δ 7.54 (d, 1H, J
= 7.9 Hz), 7.36 (d, 2H, J = 8.8 Hz), 7.18 (t, 1H, J = 7.7 Hz), 6.85−
6.91 (m, 4H), 6.29 (d, 1H, J = 3.5 Hz), 5.09 (m, 2H), 3.80 (s, 3H),
1.97 (d, 1H, J = 3.5 Hz), 1.62 (t, 3H, J = 1.7 Hz). 13C{1H} NMR
(CDCl3, 75 MHz): δ 164.7, 159.1, 133.7, 132.5, 129.6, 128.5, 127.1
(2C), 124.7, 124.3, 120.9, 114.0 (2C), 110.8, 74.7, 71.2, 55.4, 14.8.
NMR 2D NOESY correlation between 1.62 (t, 3H, J = 3.0 Hz) and
5.09 (m, 2H) and between 6.26 (s, 1H) and 7.54 (d, 1H, J = 7.9 Hz).
MS: 280 (M+), 262 (M − H2O), 247 (M − H2O − CH3), 147 (base).
IR (neat): υmax = 3492, 2911, 1240, 1023 cm−1. HRMS (API+): calcd
for C18H17O2 (M − H2O + H+) 265.1229, found 265,1233. Mp:
132−133 °C.
(E)-2-(Benzofuran-3(2H)-ylidene)-1-(3-methoxyphenyl)-
propan-1-ol (4b). The pure compound 4b was obtained by
recrystallization in pentane (195 mg, 0.69 mmol, 69%) as a cream
solid. 1H NMR (CDCl3, 300 MHz): δ 7.58 (d, 1H, J = 7.7 Hz), 7.24−
7.30 (m, 1H), 7.19 (t, 1H, J = 7.5 Hz), 6.97−7.05 (m, 2H), 6.86−
6.95 (m, 2H), 6.78−6.84 (m, 1H), 6.33 (s, 1H), 5.08 (bs, 2H), 3.80
(s, 3H), 2.07 (s, 1H), 1.60 (s, 3H). 13C{1H} NMR (CDCl3, 75
MHz): δ 164.8, 160.0, 143.4, 133.1, 129.8, 129.6, 128.1, 124.7, 124.2,
120.9, 118.1, 112.8, 111.6, 110.9, 74.7, 71.3, 55.4, 14.7. NMR 2D
NOESY correlation between 1.60 (s, 3H) and 5.08 (m, 2H). IR
(neat): υmax = 3489, 1585, 1462, 1435, 1136, 1050, 1022 cm−1.
HRMS (API+): calcd for C18H17O2 (M + H+ − H2O) 265.1229,
found 265.1225. Mp: 129−130 °C.
250 (M+), 232 (M+ − H2O), 217 (base), 202, 115. IR (neat): υmax
=
3405, 2919, 1447, 1016, 754 cm−1. HRMS (EI): calcd for C18H16 (M
− H2O) 232.1252, found 232.1260.
Methyl (E)-3-(1-Hydroxy-1-phenylpropan-2-ylidene)-2,3-di-
hydrobenzofuran-5-carboxylate (2e). The pure compound 2e
was obtained by recrystallization in pentane (240 mg, 0.77 mmol,
77%) as a cream solid. 1H NMR (CDCl3, 300 MHz): δ 8.32 (d, 1H, J
= 1.7 Hz), 7.93 (dd, 1H, J = 8.5Hz J = 1.7 Hz), 7.42−7.47 (m, 2H),
7.32−7.38 (m, 2H), 7.27−7.31 (m, 1H), 6.90 (d, 1H, J = 8.5 Hz),
6.42 (s, 1H), 5.16 (m, 2H), 3.86 (s, 3H), 2.20 (s, 1H), 1.62 (t, 3H, J =
1.9 Hz). 13C{1H} NMR (CDCl3, 75 MHz): δ 168.5, 167.0, 141.6,
132.2, 131.2, 130.3, 128.7 (2C), 127.7, 125.9, 125.8 (2C), 125.1,
123.0, 110.5, 75.8, 71.3, 52.2, 15.0. NMR 2D NOESY correlation
between 1.62 (t, 3H, J = 1.9 Hz) and 5.16 (m, 2H). IR (neat): υmax
=
3472; 2949; 1695; 1588; 1482; 1433; 1363; 1328; 1295; 1243; 1114;
1100; 987; 841; 706 cm−1. HRMS (API+): calcd for C19H17O3 (M −
H2O+H+) 293.1172, found 293.1175. Mp: 151−152 °C.
(E)-1-Phenyl-2-(5-(trifluoromethyl)benzofuran-3(2H)-
ylidene)propan-1-ol (2f). The pure compound 2f was isolated by
flash column chromatography (neutralized alumina, cyclohexane/
AcOEt: 95:5) (112 mg, 0.35 mmol, 35%) as a yellow solid. 1H NMR
(300 MHz, CDCl3): δ 7.82 (s, 1H), 7.42−7.47 (m, 3H), 7.27−7.40
(m, 3H), 6.94 (d, J = 8.5Hz, 1H), 6.29 (s, 1H), 5.17 (m, 2H), 2.09 (s,
1H), 1.64 (t, 3H, J = 1.9 Hz). 13C{1H} NMR (CDCl3, 75 MHz): δ
167.0, 141.3, 131.2, 130.8, 128.8 (2C), 127.9, 127.2 (q, J = 3.9 Hz),
125.8 (2C), 125.3, 124.3 (q, J = 271.2 Hz), 123.3 (q, J = 32.5 Hz),
121.5 (q, J = 3.9 Hz), 110.8, 75.6, 71.5, 15.2. 19F NMR (CDCl3, 282
MHz): −61.16. NMR 2D NOESY correlation between 1.64 (t, 3H, J
= 1.9 Hz) and 5.16 (m, 2H). IR (neat): υmax = 3290; 3076; 3034;
2933; 1658; 1613; 1494; 1452; 1319; 1280; 1246; 1102; 1064; 994
cm−1. HRMS (EI): calcd for C18H13F3O (M − H2O) 302.0918, found
302.0924. Mp: 84−85 °C.
(E)-2-(5-Methylbenzofuran-3(2H)-ylidene)-1-phenylpropan-
1-ol (2g). The pure compound 2g was obtained by recrystallization in
pentane (162 mg, 0.61 mmol, 61%) as a cream solid. 1H NMR
(CDCl3, 300 MHz): δ 7.40−7.50 (m, 3H), 7.33−7.39 (m, 2H),
7.27−7.32 (m, 1H), 7.00 (d, 1H, J = 8.2 Hz), 6.80 (d, 1H, J = 8.2
Hz), 6.39 (s, 1H), 5.06 (m, 2H), 2.28 (s, 3H), 2.13 (s, 1H), 1.57 (t,
3H, J = 1.9 Hz); 13C{1H} NMR (CDCl3, 75 MHz): δ 162.9, 141.7,
133.3, 130.4, 130.1, 128.6 (2C), 127.9, 127.4, 125.7 (2C), 124.6,
124.5, 110.4, 74.9, 71.3, 21.2, 14.7. NMR 2D NOESY correlation
(E)-2-(Benzofuran-3(2H)-ylidene)-1-(2-methoxyphenyl)-
propan-1-ol (4c). The pure compound 4c was obtained by
recrystallization in pentane (254 mg, 0.90 mmol, 90%) as a cream
solid. 1H NMR (CDCl3, 300 MHz): δ 7.44 (d, 1H, J = 7.6 Hz), 7.34
(dd, 1H, J = 7.5, 1.4 Hz), 7.25−7.31 (m, 1H), 7.13 (t, 1H, J = 7.7
Hz), 6.91−6.97 (m, 2H), 6.79−6.87 (m, 2H), 6.42 (s, 1H), 5.12 (m,
2H), 3.83 (s, 3H), 2.93 (s, 1H), 1.74 (t, 3H, J = 1.9 Hz). 13C{1H}
NMR (CDCl3, 75 MHz): δ 164.7, 157.4, 132.7, 129.6, 129.2, 128.9,
127.2, 126.8, 125.2, 124.9, 120.9, 120.7, 110.6, 110.3, 74.8, 68.7, 55.4,
15.5. NMR 2D NOESY correlation between 1.74 (t, 3H, J = 1.9 Hz)
and 5.12 (m, 2H). IR (neat): υmax = 3482, 2935, 2840, 1598, 1586,
1463, 1239, 1118, 744 cm−1. HRMS (API+): calcd for C18H17O2 (M +
H+ − H2O) 265.1229, found 265.1227. Mp: 126−127 °C.
(E)-2-(Benzofuran-3(2H)-ylidene)-1-(4-(tert-butyl)phenyl)-
propan-1-ol (4d). The pure compound 4d was isolated by flash
column chromatography (neutralized alumina, cyclohexane/AcOEt:
1
95:5) (92 mg, 0.30 mmol, 30%) as a yellow solid. H NMR (CDCl3,
300 MHz): δ 7.57 (d, 1H, J = 7.8 Hz), 7.37 (s, 4H), 7.18 (td, 1H, J =
7.8 1.2 Hz), 6.84−6.91 (m, 2H), 6.33 (bs, 1H), 5.09 (m, 2H), 2.08
(bs, 1H), 1.63 (t, 3H, J = 1.7 Hz), 1.32 (s, 9H). 13C{1H} NMR
(CDCl3, 75 MHz): δ 164.8, 150.5, 138.6, 132.6, 129.6, 128.5, 125.5
(4C), 124.8, 124.3, 120.9, 110.8, 74.8, 71.4, 34.6, 31.5 (3C), 14.8.
NMR 2D NOESY correlation between 1.64 (t, 3H, J = 1.7 Hz) and
5.10 (m, 2H). IR (neat): υmax = 3494, 2961, 2869, 1584, 1463, 1364,
1215, 1107, 1027, 987, 749 cm−1. HRMS (ESI): calcd for C21H23O2
(M − H+) 307.1698, found 307.1691. Mp: 133−134 °C.
between 1.57 (t, 3H, J = 1.9 Hz) and 5.06 (m, 2H). IR (neat): υmax
=
3457; 3058; 3029; 2927; 1489; 1449; 1395; 1306; 1208; 1025; 1117;
8887
https://doi.org/10.1021/acs.joc.1c00811
J. Org. Chem. 2021, 86, 8882−8890

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(E)-2-(Benzofuran-3(2H)-ylidene)-1-(4-fluorophenyl)-
propan-1-ol (4e). The pure compound 4e was obtained by
recrystallization in pentane (165 mg, 0.61 mmol, 61%) as a cream
solid. 1H NMR (CDCl3, 300 MHz): δ 7.55 (d, 1H, J = 7.7 Hz), 7.39−
7.43 (m, 2H), 7.17−7.22 (m, 1H), 7.00−7.06 (m, 2H), 6.84−6.92
(m, 2H), 6.34 (s, 1H), 5.09 (m, 2H), 1.98 (bs, 1H), 1.59 (t, 3H, J =
1.8 Hz). 13C{1H} NMR (CDCl3, 75 MHz): δ 164.9, 161.9 (d, J =
246.1 Hz), 133.3, 129.9, 128.9 (d, J = 8.7 Hz), 127.5 (d, 2C, J = 9.7
Hz), 124.6, 124.2, 121.0, 116.7, 115.4 (d, 2C, J = 19.4 Hz), 111.0,
74.7, 71.0, 14.6. 19F NMR (CDCl3, 282 MHz): −115.40. NMR 2D
NOESY correlation between 1.59 (t, 3H, J = 1.8 Hz) and 5.09 (m,
2H). IR (neat): υmax = 3469, 2910, 1653, 1602, 1508, 1464, 1377,
1222, 1156, 1016, 748 cm−1. HRMS (API+): calcd for C17H14OF (M
+ H+ − H2O) 253.1029, found 253.1027. Mp: 138−139 °C.
(E)-2-(Benzofuran-3(2H)-ylidene)-1-(4-(trifluoromethyl)-
phenyl)-1-ol (4j). The pure compound 4j was obtained by
recrystallization in pentane (86 mg, 0.27 mmol, 27%) as a cream
solid. H NMR (CDCl3, 300 MHz): δ 7.55−7.62 (m, 5H), 7.22 (td,
1
1H, J = 7.8 1.0 Hz), 6.87−6.94 (m, 2H), 6.42 (s, 1H), 5.09 (m, 2H),
2.17 (bs, 1H), 1.56 (t, 3H, J = 1.9 Hz). 13C{1H} NMR (CDCl3, 75
MHz): δ 165.0, 145.6, 133.9, 130.1, 129.8 (q, J = 31.5 Hz), 127.4,
126.1 (2C), 125.6 (q, J = 3.8Hz, 2C), 124.4, 124.2 (q, J = 247.7 Hz),
124.0, 121.1, 111.1, 74.7, 71.0, 14.6. 19F NMR (CDCl3, 282 MHz):
−62.40. NMR 2D NOESY correlation between 1.56 (t, 3H, J = 1.9
Hz) and 5.09 (m, 2H). IR (neat): υmax = 3479; 1621; 1465; 1323;
1115; 1067; 742 cm−1. HRMS (ESI): calcd for C18H14O2F3 (M −
H+) 319.0946, found 319.0959. Mp: 148−149 °C.
(E)-2-(Benzofuran-3(2H)-ylidene)propan-1-ol (4k). The pure
compound 4k was isolated by flash column chromatography
(neutralized alumina, cyclohexane/AcOEt: 95:5) (35 mg, 0.20
(E)-Methyl 4-(2-(Benzofuran-3(2H)-ylidene)-1-
hydroxypropyl)benzoate (4f). The pure compound 4f was isolated
by flash column chromatography (neutralized alumina, cyclohexane/
1
mmol, 20%) as a white solid. H NMR (CDCl3, 300 MHz): δ 7.57
1
AcOEt: 9:1) (186 mg, 0.60 mmol, 60%) as a yellow solid. H NMR
(d, 1H, J = 7.7 Hz), 7.16 (t, 1H, J = 7.8 Hz), 6.84−6.93 (m, 2H), 5.04
(m, 2H), 4.49 (bs, 2H), 1.83 (t, 3H, J = 1.8 Hz), 1.69 (bs, 1H).
13C{1H} NMR (CDCl3, 75 MHz,): δ 164.5, 133.2, 129.5, 125.7,
124.8, 124.3, 120.9, 110.6, 74.6, 63.5, 19.0. NMR 2D NOESY
correlation between 1.85 (t, 3H, J = 1.8 Hz) and 5.06 (m, 2H). IR
(neat): υmax = 3204, 2924, 1668, 1601, 1585, 1463, 1242, 1212, 1112,
1000, 986, 742 cm−1. HRMS (EI): calcd for C11H10O1 (M − H2O +
H+) 158.0732, found 158.0736. Mp: 90−91 °C.
(CDCl3, 300 MHz): δ 8.02 (d, 2H, J = 8.3 Hz), 7.60 (d, 1H, J = 7.7
Hz), 7.52 (d, 2H, J = 8.3 Hz), 7.21 (td, 1H, J = 7.8 1.5 Hz), 6.87−
6.94 (m, 2H), 6.42 (d, 1H, J = 3.3 Hz), 5.09 (m, 2H), 3.91 (s, 3H),
2.07 (d, 1H, J = 3.3 Hz), 1.56 (t, 3H, J = 2.1 Hz). 13C{1H} NMR
(CDCl3, 75 MHz): δ 167.1, 164.9, 146.9, 133.6, 130.0, 129.8 (2C),
129.3, 127.6, 125.8 (2C), 124.5, 124.0, 121.0, 111.0, 74.7, 71.1, 52.2,
14.6. NMR 2D NOESY correlation between 1.56 (t, 3H, J = 1.8 Hz)
and 5.09 (m, 2H). IR (neat): υmax = 3469, 2908, 1896, 1603, 1508,
1464, 1377, 1222, 1156, 1017, 748 cm−1. HRMS (API+): calcd for
C19H17O3 (M + H+ − H2O) 293.1178, found 293.1174. Mp: 100−
101 °C.
(E)-2-(Benzofuran-3(2H)-ylidene)hexan-3-ol (4l). The pure
compound 4l was isolated by flash column chromatography
(neutralized alumina, cyclohexane/AcOEt: 95:5) (65 mg, 0.30
1
mmol, 30%) as a yellow oil. H NMR (CDCl3, 300 MHz): δ 7.45
(E)-4-(2-(Benzofuran-3(2H)-ylidene)-1-hydroxypropyl)-
benzonitrile (4g). The pure compound 4g was isolated by flash
column chromatography (neutralized alumina, cyclohexane/AcOEt:
(d, 1H, J = 7.3 Hz), 7.14 (td, 1H, J = 7.8 1.1 Hz), 6.87 (td, 1H, J = 7.6
1.1 Hz), 6.85 (d, 1H, J = 8.0 Hz), 5.11−5.15 (m, 1H), 5.00 (bs, 2H),
1.94 (bs, 1H), 1.69 (t, 3H, J = 1.8 Hz), 1.27−1.62 (m, 4H), 0.97 (t,
3H, J = 7.1 Hz). 13C{1H} NMR (CDCl3, 75 MHz): δ 164.5, 131.0,
129.8, 129.1, 124.8, 124.5, 120.7, 110.6, 74.6, 70.1, 37.0, 19.1, 14.2,
14.1. NMR 2D NOESY correlation between 1.69 (t, 3H, J = 1.8 Hz)
and 5.00 (m, 2H) and between 5.11−5.15 (m, 1H) and 7.45 (d, 1H, J
= 7.3 Hz). IR (neat): υmax = 3492, 2957, 2929, 2870, 1710, 1600,
1585, 1465, 1454, 1226, 985, 748 cm−1. HRMS (EI): calcd for
C14H16O1 (M − H2O) 200.1201, found 200.1207.
(E)-3-(1-(4-Methoxyphenyl)prop-1-en-2-yl)benzofuran (5a).
The pure compound 5a was isolated by flash column chromatography
(SiO2, cyclohexane/AcOEt: 95:5) (106 mg, 0.40 mmol, 40%) as a
yellow oil. 1H NMR (CDCl3, 300 MHz): δ 7.93 (dd, 1H, J = 7.5 1.9
Hz), 7.71 (s, 1H), 7.52 (dd, 1H, J = 7.5 1.9 Hz), 7.28−7.37 (m, 4H),
7.09 (bs, 1H), 6.94 (d, 2H, J = 8.8 Hz), 3.85 (s, 3H), 2.30 (d, 3H, J =
1.3 Hz). 13C{1H} NMR (CDCl3, 75 MHz): δ 158.4, 156.0, 142.1,
130.49 (2C), 130.46, 127.5, 127.2, 126.0, 124.7, 124.5, 122.9, 121.5,
113.8 (2C), 111.8, 55.3, 17.8. NMR 2D NOESY correlation between
2.30 (d, 3H, J = 3.0 Hz) and 7.32−7.36 (m, 4H) and between 2.30 (d,
3H, J = 3.0 Hz) and 7.71 (s, 1H). IR (neat): υmax = 2917, 1507, 1244,
1026 cm−1. HRMS (API+): calcd for C18H16O2 264.1150, found
264.1159.
1
9:1) (59 mg, 0.21 mmol, 21%) as a yellow solid. H NMR (CDCl3,
300 MHz): δ 7.55−7.66 (m, 5H), 7.21−7.23 (m, 1H), 6.88−6.94 (m,
2H), 6.42 (s, 1H), 5.09 (m, 2H), 2.07 (s, 1H), 1.54 (t, 3H, J = 1.9
Hz). 13C{1H} NMR (CDCl3, 75 MHz): δ 165.0, 147.0, 134.1, 132.4
(2C), 130.2, 130.0, 127.0, 126.5 (2C), 124.3, 123.9, 121.1, 119.0,
111.2, 74.7, 70.8, 14.5. NMR 2D NOESY correlation between 1.54 (t,
3H, J = 1.9 Hz) and 5.09 (m, 2H). IR (neat): υmax = 3468, 2910,
1653, 1603, 1508, 1464, 1377, 1222, 1156, 1115, 748 cm−1. HRMS
(API+): calcd for C18H14NO (M + H+ − H2O) 260.1075, found
260.1082. Mp: 139−140 °C.
(E)-1-(4-(2-(Benzofuran-3(2H)-ylidene)-1-hydroxypropyl)-
phenyl)ethan-1-one (4h). The pure compound 4h was isolated by
flash column chromatography (neutralized alumina, cyclohexane/
1
AcOEt: 9:1) (41 mg, 0.14 mmol, 14%) as a yellow oil. H NMR
(CDCl3, 300 MHz,): δ 7.93 (d, 2H, J = 8.3 Hz), 7.59 (d, 1H, J = 7.6
Hz), 7.54 (d, 2H, J = 8.3 Hz), 7.21 (td, 1H, J = 7.8 1.1 Hz), 6.86−
6.93 (m, 2H), 6.41 (bs, 1H), 5.07 (m, 2H), 2.59 (s, 3H), 2.32 (bs,
1H), 1.55 (t, 3H, J = 2.1 Hz). 13C{1H} NMR (CDCl3, 75 MHz,): δ
198.0, 164.9, 147.0, 136.4, 133.7, 130.0, 128.7 (2C), 127.5, 126.0
(2C), 124.5, 124.0, 121.0, 111.1, 74.7, 71.1, 26.8, 14.6. NMR 2D
NOESY correlation between 1.56 (t, 3H, J = 2.1 Hz,) and 5.10 (m,
2H). IR (neat): υmax = 3488, 2923, 2857, 1686, 1606, 1461, 1359,
1266, 1077, 747 cm−1. HRMS (ESI+): calcd for C19H17O2 (M + H+ −
H2O) 277.1229, found 277.1219. Mp: 125−126 °C.
(E)-2-((Benzofuran-3-yl)prop-1-en-1-yl)-N, N-dimethylani-
line (5m). The pure compound 5m was isolated by flash column
chromatography (neutralized alumina, cyclohexane) (125 mg, 0.45
1
mmol, 45%) as a white solid. H NMR (CDCl3, 300 MHz): δ 7.93
(dd, 1H, J = 6.4 1.8 Hz), 7.69 (s, 1H), 7.51 (d, 1H, J = 7.2 Hz), 7.25−
7.34 (m, 4H), 7.06 (s, 1H), 6.77 (d, 2H, J = 8.6 Hz), 3.00 (s, 6H),
2.32 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 156.1, 149.3,
141.9, 130.4 (2C), 127.9, 126.29, 126.25, 125.8, 125.2, 124.4, 122.9,
121.7, 112.3 (2C), 111.8, 40.7 (2C), 18.1. NMR 2D NOESY
correlation between 2.32 (s, 3H) and 6.77 (d, 2H, J = 8.4 Hz). IR
(neat): υmax = 3137, 3030, 2983, 2911, 2853, 2792, 1603, 1449, 1336,
1224, 744 cm−1. HRMS (ESI+): calcd for C19H20NO (M + H+)
278.1545, found 278.1541. Mp: 88−89 °C.
3-((2Z,4E)-5-Phenylpenta-2,4-dien-2-yl)benzofuran (5n).
The pure compound 5n was isolated by flash column chromatography
(neutralized alumina, cyclohexane) (96 mg, 0.37 mmol, 37%) as a
yellow oil. 1H NMR (CDCl3, 300 MHz): δ 7.93−8.00 (m, 1H), 7.71
(s, 1H), 7.51−7.55 (m, 1H), 7.47−7.51 (m, 2H), 7.32−7.39 (m, 4H),
(E)-2-(Benzofuran-3(2H)-ylidene)-1-(4-(methylsulfonyl)-
phenyl)propan-1-ol (4i). The pure compound 4i was isolated by
flash column chromatography (neutralized alumina, Toluene/AcOEt
1
9:1) (36 mg, 0.11 mmol, 11%) as a white solid. H NMR (CDCl3,
300 MHz): δ 7.87 (d, 2H, J = 8.3 Hz), 7.63 (d, 2H, J = 8.3 Hz), 7.57
(d, 1H, J = 7.9 Hz), 7.21 (td, 1H, J = 7.8 1.1 Hz), 6.86−6.95 (m, 2H),
6.42 (bs, 1H), 5.06 (m, 2H), 3.03 (s, 3H), 2.63 (bs, 1H), 1.56 (t, 3H,
J = 1.2 Hz). 13C{1H} NMR (CDCl3, 75 MHz): δ 164.9, 148.2, 139.4,
134.0, 130.2, 127.6 (2C), 127.1, 126.8 (2C), 124.3, 123.9, 121.1,
111.1, 74.7, 70.7, 44.6, 14.5. NMR 2D NOESY correlation between
1.56 (t, 3H, J = 1.2 Hz) and 5.10 (m, 2H). IR (neat): υmax = 3431;
2921; 1603; 1464; 1321; 1299; 1141; 959; 742 cm−1. HRMS (ESI−):
calcd for C18H17O4S (M − H+) 329.0848, found 329.0847. Mp: 155−
156 °C.
8888
https://doi.org/10.1021/acs.joc.1c00811
J. Org. Chem. 2021, 86, 8882−8890

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
1
7.26 (d, 1H, J = 1.1 Hz), 7.25 (d, 1H, J = 15.4 Hz), 6.94 (d, 1H, J =
11.0 Hz), 6.72 (d, 1H, J = 15.4 Hz), 2.31 (d, 3H, J = 1.1 Hz).
13C{1H} NMR (CDCl3, 75 MHz): δ 156.1, 142.5, 137.8, 132.7, 128.9,
128.8 (2C), 127.6, 127.3, 126.5 (2C), 125.8, 125.3, 124.6, 124.2,
123.1, 121.7, 111.9, 16.7. NMR 2D NOESY correlation between 2.30
(s, 3H) and 7.71 (s, 1H) and between 2.30 (s, 3H) and 7.25 (d, 1H, J
= 15.4 Hz). IR (neat): υmax = 3070, 3023, 2919, 1765, 1615, 1477,
1461, 1378, 1330, 1288, 1231, 1135, 1079, 747 cm−1. HRMS (EI):
calcd for C19H16O 260.1201, found 260.1195.
General Procedure for Cycloaddition Exemplified with
Compound 6a endo. The reaction was realized from diene 5a
(0.129 g, 0.49 mmol, 1 equiv) and N-methylmaleimide (0.108 g, 0.98
mmol, 2 equiv) in solution in THF (5 mL). After 24 h under
hyperbaric conditions (16 Kbar) at room temperature, the solvent was
concentrated, and the crude solid was purified by column
chromatography.
Cycloadduct (8m endo). H NMR (CDCl3, 300 MHz): δ 7.48
(dd, 1H, J = 7.6 1.4 Hz), 7.18 (td, 1H, J = 7.7 1.4 Hz), 7.06 (d, 2H, J
= 8.7 Hz), 6.94 (td, 1H, J = 7.5 1.1 Hz), 6.90 (d, 1H, J = 7.7 Hz), 6.66
(d, 2H, J = 8.7 Hz), 4.98−4.90 (m, 1H), 3.93 (s, 1H), 2.92 (s, 6H),
2.76 (t, 1H, J = 4.8 Hz), 2.57−2.50 (m, 1H), 2.05 (td, 1H, J = 11.8
4.8 Hz), 1.84 (d, 3H, J = 2.5 Hz), 1.47 (s, 9H). 13C{1H} NMR
(CDCl3, 75 MHz): δ 173.6, 162.3, 149.6, 132.1, 131.5, 129.3 (2C),
128.7, 128.2, 127.0, 124.1, 120.9, 112.8 (2C), 110.3, 81.1, 80.6, 47.2,
46.8, 40.8 (2C), 28.2 (3C), 25.1, 18.3. NMR 2D NOESY correlation
between 4.98−4.90 (m, 1H) and 2.57−2.50 (m, 1H) and between
3.93 (s, 1H) and 2.76 (t, 1H, J = 4.8 Hz). IR (neat): υmax = 2974,
2800, 1723, 1611, 1518, 1458, 1367, 1340, 1217, 1146, 1020, 829,
816, 748. HRMS (ESI+): calcd for C26H32NO3 (M + H+) 406.2377,
found 406.2363.
ASSOCIATED CONTENT
■
Cycloadduct (6a endo). The pure compound 6a was isolated by
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00811.
flash column chromatography (SiO2, cyclohexane/AcOEt: 80/20)
1
(120 mg, 0.32 mmol, 65%) as a yellow solid. H NMR (CDCl3, 300
MHz): δ 7.52 (d, 2H, J = 8.6 Hz), 7.48 (d, 1H, J = 7.9 Hz), 7.20 (t,
1H, J = 7.9 Hz), 7.02 (d, 1H, J = 8.0 Hz), 6.94 (d, 2H, J = 8.6 Hz),
6.92 (t, 1H, J = 8.4 Hz), 5.36−5.29 (m, 1H), 3.84 (s, 3H), 3.81 (t,
1H, J = 8.4 Hz), 3.54−3.49 (m, 2H), 2.78 (s, 3H), 1.92 (d, 3H, J = 2.4
Hz). 13C{1H} NMR (CDCl3, 75 MHz): δ 176.7, 173.6, 163.4, 158.8,
132.0 (2C), 130.9, 129.6, 129.2, 129.1, 124.0, 123.4, 121.3, 113.6
(2C), 110.9, 80.2, 55.4, 47.7, 44.2, 43.6, 25.1, 17.0. NMR 2D NOESY
correlation between 3.54−3.51 (m, 2H) and 5.36−5.32 (m, 1H) and
between 3.83 (t, 1H, J = 8.4 Hz) and 5.36−5.32 (m, 1H). IR (neat):
υmax = 2929, 2835, 1777, 1699, 1513, 1462, 1434, 1384, 1306, 1248,
1182, 1110, 1032, 1003, 752. HRMS (ESI+): calcd for C23H22NO4
(M + H+) 376.1543, found 376.1549. Mp: 208−209 °C.
1H and 13C NMR spectra of the new compounds (PDF)
AUTHOR INFORMATION
■
Corresponding Author
Muriel Durandetti − Normandie Univ, UNIROUEN, INSA
Rouen, CNRS, Laboratoire COBRA (UMR 6014 & FR
3038), 76000 Rouen, France; orcid.org/0000-0002-
5136-9655; Email: muriel.durandetti@univ-rouen.fr
Authors
Cycloadduct (6m endo). The pure compound 6m was isolated by
flash column chromatography (SiO2, cyclohexane/AcOEt: 80/20)
Claire Déjardin − Normandie Univ, UNIROUEN, INSA
Rouen, CNRS, Laboratoire COBRA (UMR 6014 & FR
3038), 76000 Rouen, France
Amaury Renou − Normandie Univ, UNIROUEN, INSA
Rouen, CNRS, Laboratoire COBRA (UMR 6014 & FR
3038), 76000 Rouen, France
Jacques Maddaluno − Normandie Univ, UNIROUEN, INSA
Rouen, CNRS, Laboratoire COBRA (UMR 6014 & FR
3038), 76000 Rouen, France
1
(135 mg, 0.35 mmol, 71%) as a white solid. H NMR (CDCl3, 300
MHz): δ 7.47 (d, 1H, J = 8.7 Hz), 7.44 (d, 2H, J = 8.7 Hz), 7.18 (t,
1H, J = 7.6 Hz), 7.01 (d, 1H, J = 8.4 Hz), 6.91 (t, 1H, J = 7.7 Hz),
6.76 (d, 2H, J = 8.7 Hz), 5.32−5.28 (m, 1H), 3.77 (t, 1H, J = 7.7 Hz),
3.45 (t, 1H, J = 3.4 Hz), 3.43 (bs, 1H), 2.98 (s, 6H), 2.77 (s, 3H),
1.94 (d, 3H, J = 1.6 Hz). 13C{1H} NMR (CDCl3, 75 MHz): δ 176.7,
173.7, 163.3, 149.6, 131.6 (2C), 130.5, 129.7, 129.3, 124.7, 124.1,
123.3, 121.1, 112.0 (2C), 110.7, 80.2, 47.6, 44.2, 43.6, 40.6 (2C),
25.0, 17.0. NMR 2D NOESY correlation between 5.38−5.29 (m, 1H)
and 3.81 (t, 1H, J = 7.7 Hz) and between 5.38−5.29 (m, 1H) and
3.49−3.47 (m, 2H). IR (neat): υmax = 2888, 2800, 1690, 1607, 1520,
1462, 1436, 1389, 1339, 1217, 1150, 1029, 824, 744. HRMS (ESI+):
calcd for C24H25N2O3 (M + H+) 389.1860, found 389.1847. Mp:
221−222 °C.
Cycloaddition in the Presence of t-Butyl Acrylate. The
cycloaddition reaction is conducted in similar conditions (16 kbar,
room temperature) in the presence of t-butyl acrylate as dienophile
and leads to the tricyclic adducts 7m endo/7m exo/8m endo in a good
isolated yield of 77% but as a mixture of three inseparable isomers in a
ratio of 70/3/27. A fraction of the pure compound 8m endo is isolated
by flash column chromatography (SiO2, cyclohexane/AcOEt: 98/2)
(21 mg, 0.052 mmol, 13%) as a colorless oil.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00811
Author Contributions
All authors have given approval to the final version of the
manuscript.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This study was funded by the European France-(Manche)-
England cross-border cooperation program INTERREG V A
“LABFACT”, co-financed by ERDF. The authors also thank
Normandie Université, CNRS, INSA Rouen, Carnot I2C, the
LabEx SynOrg (ANR-11-LABX-0029), and the Région
Normandie for their financial support to our general research
projects.
Cycloadduct (7m endo). 1H NMR (CDCl3, 300 MHz): δ 7.45 (d,
1H, J = 7.9 Hz), 7.19 (t, 1H, J = 7.7 Hz), 7.07 (d, 2H, J = 8.6 Hz),
6.90−6.97 (m, 2H), 6.61 (d, 2H, J = 8.6 Hz), 4.97−5.09 (m, 1H),
3.81 (dd, 1H, J = 6.6 2.4 Hz), 2.94−3.02 (m, 1H), 2.89 (s, 6H),
2.37−2.44 (m, 1H), 2.19 (q, 1H, J = 12.1 Hz), 1.75 (d, 3H, J = 2.5
Hz), 1.28 (s, 9H). 13C{1H} NMR (CDCl3, 75 MHz): δ 171.6, 162.5,
150.0, 132.0, 130.8 (2C), 129.2, 128.9, 127.6, 126.8, 124.0, 120.9,
112.4 (2C), 110.4, 83.2, 80.6, 48.4, 44.8, 40.8 (2C), 28.1 (3C), 24.9,
17.9. NMR 2D NOESY correlation between 4.97−5.09 (m, 1H) and
2.94−3.02 (m, 1H), between 4.97−5.09 (m, 1H) and 2.37−2.44 (m,
1H) and between 3.81 (dd, 1H, J = 6.6 2.4 Hz) and 2.94−3.02 (m,
1H). IR (neat): υmax = 2974, 2884, 1724, 1612, 1519, 1457, 1366,
1339, 1223, 1151, 1022, 820, 747. HRMS (ESI+): calcd for
C26H32NO3 (M + H+) 406.2377, found 406.2383.
REFERENCES
■
(1) (a) Fu, G. C. Transition-Metal Catalysis of Nucleophilic
Substitution Reactions: A Radical Alternative to SN1 and SN2
Processes. ACS Cent. Sci. 2017, 3, 692−700. (b) Dong, Z.; Ren, Z.;
Thompson, S. J.; Xu, Y.; Dong, G. Transition-Metal-Catalyzed C−H
Alkylation Using Alkenes. Chem. Rev. 2017, 117, 9333−9403.
8889
https://doi.org/10.1021/acs.joc.1c00811
J. Org. Chem. 2021, 86, 8882−8890

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(2) Chaussard, J.; Folest, J. C.; Nédélec, J. Y.; Périchon, J.; Sibille, S.;
Troupel, M. Use of Sacrificial Anodes in Electrochemical Function-
alization of Organic Halides. Synthesis 1990, 1990, 369−381.
(3) (a) Durandetti, M.; Sibille, S.; Nédélec, J.-Y.; Périchon, J. A
Novel Method of Arylation of α-Chloroketones. Synth. Commun.
1994, 145−151. (b) Durandetti, M.; Périchon, J. Nickel-Catalyzed
Electrochemical Couplings of Aryl, Heteroaryl or vinyl Halides with
Activated Alkyl Halides: Synthetic and Stereochemical Aspects.
Synthesis 2004, 3079−3083.
(4) (a) Yan, M.; Kawamata, Y.; Baran, P. S. Synthetic Organic
Electrochemical Methods Since 2000: On the Verge of a Renaissance.
Chem. Rev. 2017, 117, 13230−13319. (b) Ghosh, M.; Shinde, V. S.;
Rueping, M. A review of asymmetric synthetic organic electro-
chemistry and electrocatalysis: concepts, applications, recent develop-
ments and future directions. Beilstein J. Org. Chem. 2019, 15, 2710−
2746. (c) Perkins, R. J.; Hughes, A. J.; Weix, D. J.; Hansen, E. C.
Metal-Reductant-Free Electrochemical Nickel-Catalyzed Couplings of
Aryl and Alkyl Bromides in Acetonitrile. Org. Process Res. Dev. 2019,
23, 1746−1751.
(5) (a) Jiao, K. J.; Liu, D.; Ma, H. X.; Qiu, H.; Fang, P.; Mei, T. S.
Nickel-Catalyzed Electrochemical Reductive Relay Cross-Coupling of
Alkyl Halides to Aryl Halides. Angew. Chem., Int. Ed. 2020, 59, 6520−
6524. (b) Truesdell, B. L.; Hamby, T. B.; Sevov, C. S. General
C(sp2)−C(sp3) Cross-Electrophile Coupling Reactions Enabled by
Overcharge Protection of Homogeneous Electrocatalysts. J. Am.
Chem. Soc. 2020, 142, 5884−5893. (c) Minteer, S. D.; Baran, P.
Electrifying Synthesis: Recent Advances in the Methods, Materials,
and Techniques for Organic Electrosynthesis. Acc. Chem. Res. 2020,
53, 545−546. (d) Zhang, S.-K.; Samanta, R. C.; Del Vecchio, A.;
Ackermann, L. Evolution of High-Valent Nickela-Electrocatalyzed C−
H Activation: From Cross(-Electrophile)-Couplings to Electro-
oxidative C−H Transformations. Chem. - Eur. J. 2020, 26, 10936−
10947. (e) Kumar, G. S.; Peshkov, A.; Brzozowska, A.; Nikolaienka,
P.; Zhu, C.; Rueping, M. Nickel-Catalyzed Chain-Walking Cross-
Electrophile Coupling of Alkyl and Aryl Halides and Olefin
Hydroarylation Enabled by Electrochemical Reduction. Angew.
Chem., Int. Ed. 2020, 59, 6513−6519. (f) Ang, N. W. J.;
Ackermann, L. Electroreductive Nickel-Catalyzed Thiolation: Effi-
cient Cross-Electrophile Coupling for C−S Formation. Chem. - Eur. J.
2021, 27, 4883−1887. (g) Gandeepan, P.; Finger, L. H.; Meyer, T.
H.; Ackermann, L. 3d metallaelectrocatalysis for resource economical
syntheses. Chem. Soc. Rev. 2020, 49, 4254−4272.
K.; Liu, Z.; Larock, R. C. Synthesis of Indenes by the Palladium-
Catalyzed Carboannulation of Internal Alkynes. Org. Lett. 2005, 7,
4963−4966. (d) Yanada, R.; Obika, S.; Inokuma, T.; Yanada, K.;
Yamashita, M.; Ohta, S.; Takemoto, Y. Stereoselective Synthesis of 3-
Alkylideneoxindoles via Palladium-Catalyzed Domino Reactions. J.
Org. Chem. 2005, 70, 6972−6975. (e) Shintani, R.; Yamagami, T.;
Hayashi, T. Rhodium-Catalyzed Multicomponent-Coupling Reactions
Involving a Carborhodation−Cross-Coupling Sequence. Org. Lett.
2006, 8, 4799−4801.
(10) (a) Hodgson, D. M.; Wells, C. Chromium(II)-mediated
nickel(II)-catalysed cyclisations of (iodoaryl)-substituted alkynes and
alkynals. Tetrahedron Lett. 1994, 35, 1601−1604. (b) Studemann, T.;
̈
Knochel, P. New Nickel-Catalyzed Carbozincation of Alkynes: A
Short Synthesis of (Z)-Tamoxifen. Angew. Chem., Int. Ed. 1997, 36,
93−95. (c) Ikeda, S.-i.; Cui, D.-M.; Sato, Y. Nickel-Catalyzed
Asymmetric Multiple-Component Tandem Coupling. Effects of
Simple Monodentate Oxazolines as Chiral Ligands. J. Am. Chem.
Soc. 1999, 121, 4712−4713. (d) Rayabarapu, D. K.; Cheng, C. H.
Nickel-catalyzed regioselective carbocyclization of ortho-halophenyl
ketones with propiolates: an efficient route to disubstituted indenols.
Chem. Commun. 2002, 942−943. (e) Bottcher, S. E.; Hutchinson, L.
E.; Wilger, D. J. Nickel-Catalyzed anti-Selective Alkyne Functionaliza-
tion Reactions. Synthesis 2020, 52, 2807−2820. (f) Liu, W.; Kong, W.
Ni-Catalyzed stereoselective difunctionalization of alkynes. Org. Chem.
Front. 2020, 7, 3941−3955.
(11) Durandetti, M.; Hardou, L.; Lhermet, R.; Rouen, M.;
Maddaluno, J. Synthetic Applications of the Nickel-Catalyzed
Cyclisation of Alkynes Combined with Addition Reactions in a
Domino Process. Chem. - Eur. J. 2011, 17, 12773−12783.
(12) Durandetti, M.; Gosmini, C.; Périchon, J. Ni-Catalysed
Activation of α-Chloroesters: A simple Method for the Synthesis of
α-Arylesters and β-Hydroxyesters. Tetrahedron 2007, 63, 1146−1153.
(13) (a) Durandetti, M.; Devaud, M.; Périchon, J. Investigation of
the reductive coupling of aryl halides and/or ethyl chloroacetate
electrocatalyzed by the precursor NiX2(bpy) with X− = Cl−, Br− or
−
MeSO3 and bpy = 2,2′-dipyridyl. New J. Chem. 1996, 20, 659−667.
(b) Cannes, C.; Labbé, E.; Durandetti, M.; Devaud, M.; Nédélec, J.-Y.
Nickel-catalyzed electrochemical homocoupling of alkenyl halides.
Rates and mechanisms. J. Electroanal. Chem. 1996, 412, 85−93.
(14) Durandetti, M.; Meignein, C.; Périchon, J. Iron-Mediated
Electrochemical Reaction of α-Chloroesters with Carbonyl Com-
pounds. Org. Lett. 2003, 5, 317−320.
(15) Durandetti, M.; Nédélec, J.-Y.; Périchon, J. An Electrochemical
Coupling of Organic Halide with Aldehydes, Catalytic in Chromium
and Nickel Salts. The Nozaki-Hiyama-Kishi Reaction. Org. Lett. 2001,
3, 2073−2076.
(16) Le Strat, F.; Vallette, H.; Toupet, L.; Maddaluno, J. Access to
Tri- and Tetracyclic Structures by Thermally Promoted and High-
Pressure-Promoted [4 + 2] Cycloadditions of 2-, 3- or 4-Vinyl-
Substituted Binuclear Heterocycles. Eur. J. Org. Chem. 2005, 5296−
5305.
(6) (a) Marek, I.; Chinkov, N.; Banon-Tenne, D. Metal-Catalyzed
Cross-Coupling Reactions; Diederich, F.; de Meijere, A., Eds.; Wiley-
VCH: Stuttgart, 2004; Chapter 7, pp 395−478. (b) Hogan, A.-M. L.;
O’Shea, D. F. Synthetic applications of carbolithiation trans-
formations. Chem. Commun. 2008, 3839−3851.
(7) (a) Bailey, W. F.; Ovaska, T. V.; Leipert, T. K. Preparation and
facile cyclization of 5-alkyn-1-yllithiums. Tetrahedron Lett. 1989, 30,
3901−3904. (b) Wu, G.; Cederbaum, F. E.; Neghishi, E.-I.
Stereoselective cyclic carbolithiation of alkyne derivatives. A stereo-
selective synthesis of exocyclic alkenes. Tetrahedron Lett. 1990, 31,
493−496. (c) Bailey, W. F.; Ovaska, T. V. Cyclization of acetylenic
alkyllithiums. J. Am. Chem. Soc. 1993, 115, 3080−3090. (d) Lhermet,
R.; Ahmad, M.; Fressigné, C.; Silvi, B.; Durandetti, M.; Maddaluno, J.
Carbolithiation of Chloro-substituted alkynes: a New Access to Vinyl
Carbenoids. Chem. - Eur. J. 2014, 20, 10249−10254. (e) Lhermet, R.;
Ahmad, M.; Hauduc, C.; Fressigné, C.; Durandetti, M.; Maddaluno, J.
Intramolecular Carbolithiation of Heterosubstituted Alkynes: An
Experimental and Theoretical Study. Chem. - Eur. J. 2015, 21, 8105−
8111.
(17) (a) Uchino, M.; Asagi, K.; Yamamoto, A.; Ikeda, S. Preparation
and properties of aryl(dipyridyl)nickel halide complexes. J. Organomet.
Chem. 1975, 84, 93−103. (b) Dunach, E.; Périchon, J. Electro-
̃
chemical carboxylation of terminal alkynes catalyzed by nickel
complexes: unusual regioselectivity. J. Organomet. Chem. 1988, 352,
239−246.
(8) Fujikura, S.; Inoue, M.; Utimoto, K.; Nozaki, H. Intramolecular
carbometallation of grignard reagents having the terminal trimethylsi-
lylacetylene group. Tetrahedron Lett. 1984, 25, 1999−2002.
(9) (a) Larock, R. C.; Doty, M. J.; Han, X. Synthesis of Isocoumarins
and α-Pyrones via Palladium-Catalyzed Annulation of Internal
Alkynes. J. Org. Chem. 1999, 64, 8770−8779. (b) Zeni, G.; Larock,
R. C. Synthesis of Heterocycles via Palladium π-Olefin and π-Alkyne
Chemistry. Chem. Rev. 2004, 104, 2285−2309. (c) Zhang, D.; Yum, E.
8890
https://doi.org/10.1021/acs.joc.1c00811
J. Org. Chem. 2021, 86, 8882−8890