Decarboxylative Addition of Propiolic Acids with Indoles to Synthesize Bis(indolyl)methane Derivatives with a Pd(II)/LA Catalyst

Article abstract of DOI:10.1021/acs.joc.1c00762

Exploring new protocols for efficient organic synthesis is crucial for pharmaceutical developments. The present work introduces a Pd(II)/LA-catalyzed (LA: Lewis acid) decarboxylative addition reaction for the synthesis of bis(indolyl)methane derivatives. The presence of Lewis acid such as Sc(OTf)3 triggered Pd(II)-catalyzed decarboxylative addition of propiolic acids with indoles to offer the bis(indolyl)methane derivatives in moderate to good yields, whereas neither Pd(II) nor Lewis acid alone was active for this synthesis. The catalytic efficiency of Pd(OAc)2 was highly dependent on the Lewis acidity of the added Lewis acid, that is, a stronger Lewis acid provided a higher yield of the bis(indolyl)methane derivatives. Meanwhile, this Pd(II)/LA-catalyzed decarboxylative addition reaction showed good tolerance toward versatile electron-rich or-deficient substituents on the indole skeleton and on the benzyl ring of propiolic acids. The studies on the in situ 1H NMR kinetics of this Pd(II)/Sc(III) catalysis disclosed the formation of a transient vinyl-Pd(II)/Sc(III) intermediate generated by the pyrrole addition to the alkynyl-Pd(II)/Sc(III) species after decarboxylation, which was scarcely observed before.

Full text of DOI:10.1021/acs.joc.1c00762

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Decarboxylative Addition of Propiolic Acids with Indoles to
Synthesize Bis(indolyl)methane Derivatives with a Pd(II)/LA Catalyst
Miao Zeng, Jing-Wen Xue, Hongwu Jiang, Kaiwen Li, Yunong Chen, Zhuqi Chen, and Guochuan Yin*
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ABSTRACT: Exploring new protocols for efficient organic
synthesis is crucial for pharmaceutical developments. The present
work introduces a Pd(II)/LA-catalyzed (LA: Lewis acid)
decarboxylative addition reaction for the synthesis of bis(indolyl)-
methane derivatives. The presence of Lewis acid such as Sc(OTf)3
triggered Pd(II)-catalyzed decarboxylative addition of propiolic
acids with indoles to offer the bis(indolyl)methane derivatives in
moderate to good yields, whereas neither Pd(II) nor Lewis acid
alone was active for this synthesis. The catalytic efficiency of
Pd(OAc)2 was highly dependent on the Lewis acidity of the added
Lewis acid, that is, a stronger Lewis acid provided a higher yield of the bis(indolyl)methane derivatives. Meanwhile, this Pd(II)/LA-
catalyzed decarboxylative addition reaction showed good tolerance toward versatile electron-rich or -deficient substituents on the
indole skeleton and on the benzyl ring of propiolic acids. The studies on the in situ 1H NMR kinetics of this Pd(II)/Sc(III) catalysis
disclosed the formation of a transient vinyl-Pd(II)/Sc(III) intermediate generated by the pyrrole addition to the alkynyl-Pd(II)/
Sc(III) species after decarboxylation, which was scarcely observed before.
synthesis, defined as Pd(II)/LA catalysis. Up to now, this
strategy has been successful in olefin oxidation, olefin
isomerization, alkyne oxidation, oxidative dehydrogenation,
benzene hydroxylation, nitrile hydration, and oxidative
olefination/annulation of benzamides,6,7 and it has also been
expanded to Ni(II)/LA-catalyzed oxidative S−P bond
formation.8
The present work introduces the application of this Pd(II)/
LA catalysis in decarboxylative addition of propiolic acids to
indoles and pyrroles for the syntheses of bis(indolyl)methane
and bis(pyrrolyl)methane derivatives, in which bis(indolyl)-
methane derivatives have been disclosed to have promising
antibacterial and antifungal activities.9 In the literature, a list of
methodologies was explored to synthesize bis(hetero)methane
derivatives;10 among them, bis(indolyl)methane derivatives
were mainly synthesized through (1) arylation of aryl ketones
followed by addition of indoles (Scheme 1a),11 (2) reductive
alkylation of indoles with aryl ketones and aldehydes (Scheme
1b),12 (3) alkyne addition with indoles (Scheme 1c),13 (4)
Friedel−Crafts alkylation of trifluoromethylated 3-indolylme-
thanols with 2-substituted indoles (Scheme 1d),14 (5)
1. INTRODUCTION
Exploring new methodology for efficient organic synthesis is
among the most attractive topics in chemical science because
of its fantasy in creating new compounds for pharmaceutical
and material applications with it reducing the pollution in
synthesis. In recent years, cooperatively bimetallic catalysis has
received increasing attention in organic synthesis, and Wacker-
type oxidation with inspired Pd(II)/Cu(II) catalysis possibly
represents one of the most attractive bimetallic oxidation
methods in organic synthesis, in which Cu(II) is generally
believed to serve as the oxidant to regenerate the active Pd(II)
species from the reduced Pd(0) in the catalytic cycle.1−3
During the mechanistic studies of redox enzymes with
inorganic models, we observed that increasing the positive
net charge of an active metal ion through protonation can
significantly accelerate its electron transfer rate, which inspired
us to explore Lewis acid-promoted catalytic oxidations with
4,5
̈
redox catalysts (Bronsted acid vs Lewis acid). Following up
this concept, we unexpectedly found that adding certain non-
redox metal ions such as Sc3+ can significantly accelerate
Pd(II)-catalyzed aerobic olefin oxidation to ketone, even much
more efficiently than the corresponding Pd(II)/Cu(II)
catalysis, and the promotional effect was obviously dependent
on the Lewis acidity of the added non-redox metal ions as
Lewis acid.6 This phenomenon has disclosed that in addition
to its redox properties, the Lewis acid properties of the Cu2+
cation may have also played significant roles in Pd(II)/Cu(II)-
catalyzed organic syntheses in certain cases, which inspired us
to explore Lewis acid-promoted Pd(II) catalysis in organic
Received: March 31, 2021
Published: May 31, 2021
https://doi.org/10.1021/acs.joc.1c00762
© 2021 American Chemical Society
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substrates. As shown in Table 1, the expected decarboxylative
addition reaction did not happen using 5 mol % Pd(OAc)2
alone as the catalyst in 1,4-dioxane at 70 °C (Table 1, entry 1);
only the homocoupling product of phenylacetylene was
obtained after Pd(II)-catalyzed decarboxylation of phenyl-
propiolic acid as that in the literature.17 Next, different Lewis
acids were tested as the additives to the Pd(OAc)2 catalyst
(Table 1, entries 2−11). Although adding 10 mol % NaOTf to
Pd(OAc)2 did not provide bis(indolyl)methane as the product,
it was obtained when bivalent metal ions were added as the
Lewis acid (Table 1, entries 2−6). For example, adding
Zn(OTf)2 to Pd(OAc)2 provided 28% yield of 3aa with only
4% yield of α-addition product 4aa; using Cu(OTf)2 as the
source of Lewis acid also provided 26% yield of 3aa with the
yield of 4aa increasing up to 16%. Remarkably, the trivalent
metal ions such as Bi3+, Al3+, Yb3+, Y3+, and Sc3+ exhibited a
much better promotional effect than bivalent metal ions for
3aa synthesis, while the yield of 4aa did not increase too much
(Table 1, entries 7−11), and adding Sc(OTf)3 afforded 3aa in
the highest yield than other trivalent metal ions, giving 80%
yield of 3aa with only 8% of 4aa (Table 1, entry 11). Clearly,
the promotional effects were positively correlated with the
acidity of the added Lewis acids, whereas using Lewis acid
alone was ineffective for this reaction, and the substrate 1a
could not be decarboxylated with Lewis acid alone (Table 1,
entry 16). In addition, this Pd(II)/LA catalysis demonstrated
higher activity in 3aa synthesis in ether-type solvents such as
1,4-dioxane and ethylene glycol diethyl ether than that in other
solvents such as DMSO, MeCN, and HOAc (Table 1, entries
11−15). Notably, combining Lewis acids with Pd(OAc)2 to
generate a Pd(II)/LA catalyst led to no homocoupling product
formation from propionic acid, and no palladium black was
observed after the reaction, whereas both the homocoupling
product and palladium black were clearly observed with
Pd(OAc)2 alone as the catalyst, indicating that in situ
generation of a Pd(II)/LA catalyst led to a distinct reactivity
different from that when using Pd(OAc)2 alone.
The ratio of 1a and 2a substrates and the reaction
temperature were further optimized using Pd(II)/Sc(III) as
the catalyst, and it was found that the ratio of 1/5 between 1a
and 2a provided the best results at the reaction temperature of
70 °C in 1,4-dioxane solvent (Table S1, entries 1−5). Based on
these conditions, the influence of the Pd(II)/Sc(III) ratio on
the catalytic efficiency of the model reaction was next
investigated (Table S2). As shown, in the absence of Sc(OTf)3,
using Pd(OAc)2 alone as a catalyst, only the homocoupling
product of phenylacetylene was obtained (Table S2, entry 1).
Adding Sc(OTf)3 significantly improved the catalytic efficiency
for the decarboxylative addition reaction. Even in the case of
adding 0.5 mol % Sc(OTf)3 to 5 mol % Pd(OAc)2, it also
provided 7% yield of 3aa (Table S2, entry 2). When adding 5
mol % Sc(OTf)3 to 5 mol % Pd(OAc)2, it gave 63% yield of
3aa with trace 4aa formation (Table S2, entry 5), and using 10
mol % Sc(OTf)3 and 5 mol % Pd(OAc)2 provided 3aa in 80%
yield with 8% yield of 4aa formation (Table S2, entry 6);
further increasing the Sc(OTf)3 loading did not provide any
more improvement on catalytic efficiency.
Scheme 1. Synthesis of Bis(indolyl)methanes
oxidative coupling of olefin with indoles (Scheme 1e),15 and so
forth. While all of these methodologies demonstrated their
specific merits in bis(indolyl)methane derivative syntheses, for
example, a Lewis acid-catalyzed reaction such as GaCl3- and
In(OTf)3-catalyzed addition of indoles to alkynes represents a
simple protocol for their syntheses,13c they also face different
challenges such as starting material limits, the structural limits
of the final bis(indolyl)methane product, and so forth.
Decarboxylative coupling is a new protocol for C−C bond
formation in addition to well-known protocols through C−H
and C−X bond activation.16 Herein, we report a Pd(II)/LA-
catalyzed decarboxylative addition of propiolic acids with
indoles and pyrroles to synthesize bis(indolyl)methane and
bis(pyrrolyl)methane derivatives, respectively (Scheme 1f),
which complements our previous oxidative coupling protocol
suitable for electron-deficient olefins.15a Interestingly, the
decarboxylation coupling and the next indole/pyrrole addition
reaction in this work dominantly happened on the olefinic
carbon proximal to the aromatic ring, in which a vinyl-Pd(II)/
Sc(III) complex, generated by pyrrole addition to the alkynyl-
Pd(II)/Sc(III) species after decarboxylation, was observed as
In order to reveal the role of Sc(OTf)3 in catalysis, a series of
control experiments was carried out next under the optimal
conditions (Table 2). As shown, in the absence of Sc(OTf)3,
using Pd(OAc)2 alone as a catalyst, no 3aa or 4aa was detected
(Table 2, entry 1). The product 3aa was generated only when
Pd(OAc)2 and Lewis acid such as Sc(OTf)3 were employed
1
an intermediate through H NMR kinetic studies.
2. RESULTS AND DISCUSSION
In the initial tests, the condition optimizations were carried out
with phenylpropiolic acid (1a) and indole (2a) as the model
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a
Table 1. Optimization of the Reaction Conditions for the Model Reaction
b
yield (%)
entry
catalyst
additives
solvent
1,4-dioxane
3aa
4aa
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
nd
nd
3
nd
nd
nd
nd
4
16
15
13
trace
trace
8
13
8
nd
trace
nd
NaOTf
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
MeCN
Ba(OTf)2
Mg(OTf)2
Zn(OTf)2
Cu(OTf)2
Bi(OTf)3
Al(OTf)3
Yb(OTf)3
Y(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
6
28
26
38
45
59
61
80
19
70
nd
trace
nd
9
10
11
12
13
14
15
16
ethylene glycol diethyl ether
DMSO
HOAc
1,4-dioxane
a
Reaction conditions: 1a (0.2 mmol), 2a (1.0 mmol), solvent (1.0 mL), Pd(OAc)2 (5 mol %), Lewis acid (10 mol %), Ar balloon, 70 °C, and 12 h.
b
Isolated yield.
a
Table 2. Control Experiments for the Model Reaction
b
yield (%)
entry
catalyst
3aa
4aa
1
2
3
4
5
6
7
Pd(OAc)2
nd
80
30
trace
trace
28
nd
8
20
trace
trace
4
Pd(OAc)2 + Sc(OTf)3
Pd(OAc)2 + HOTf (30 mol %)
Pd(OAc)2 + NaOTf (30 mol %)
Pd(OTf)2
Pd(OAc)2 + Zn(OTf)2
Pd(OAc)2 + Zn(BF4)2
34
5
a
Reaction conditions: 1a (0.2 mmol), 2a (1.0 mmol), 1,4-dioxane (1.0 mL), Pd(OAc)2 (5 mol %), Lewis acid (10 mol %), Ar balloon, 70 °C, and
b
12 h. Isolated yield.
together as a catalyst (Table 2, entry 2), which clearly
supported that adding Lewis acid triggered the catalytic activity
of Pd(OAc)2 for the decarboxylative addition reaction. The
role of the anion in this reaction was also addressed by adding
HOTf or NaOTf instead of the salts of bivalent or trivalent
metal ions. When 30% mol HOTf was added instead of Lewis
acid, the desired product 3aa was formed in only 30% yield;
however, the α-addition byproduct 4aa was also formed in 20%
yield (Table 2, entry 3). Plausibly, the substrate 1a was
unstable under acidic conditions;18 after its decarboxylation,
both the α-addition and β-addition reaction could proceed
feasibly, leading to the low selectivity to 3aa. Adding Sc3+
possibly enhanced the electrophilic properties of the Pd2+
cation (vide infra); thus, the Markovnikov adduct product 3aa
dominated with trace 4aa formation.19 To address whether the
OTf− anion of Sc(OTf)3 played the key role instead of the Sc3+
cation through the ligand exchange between Pd(OAc)2 and
Sc(OTf)3, 30% mol NaOTf was tested as the additives;
however, only trace 3aa was detected as the product (Table 2,
entry 4). In addition, using Pd(OTf)2 as a catalyst also
provided only trace 3aa formation (Table 2, entry 5). When
5% mol Zn(BF4)2 was added instead of Zn(OTf)2, the product
3aa was formed in 34% yield, even higher than 28% yield of
3aa with Zn(OTf)2 as additives (Table 2, entries 6 and 7).
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a
Scheme 2. Substrate Scope of Reactions Using Indole
a
Reaction conditions: 1a (0.2 mmol), 2 (1.0 mmol), Pd(OAc)2 (5 mol %), Sc(OTf)3 (10 mol %), 1,4-dioxane (1 mL), Ar balloon, 70 °C, and 12 h.
b24 h.
Clearly, these results supported that it was the Lewis acid
cation, rather than its counteranion, OTf−, that improved the
catalytic efficiency of Pd(OAc)2 in this decarboxylation
addition reaction, and the promotional effect was positively
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a
correlated with the acidity of the added Lewis acids, as
disclosed in Table 1.
Scheme 3. Scope of Reactions Using Phenylpropiolic Acid
To evaluate the substrate scope of this reaction with a
Pd(OAc)2/Sc(OTf)3 catalyst, a variety of indoles were first
investigated as the substrate in reaction with phenylpropiolic
acid 1a. As summarized in Scheme 2, the reaction proceeded
smoothly to provide bis(indolyl)methanes as the product. The
indole bearing a methyl or methoxy group at the C5 position
reacted smoothly with 1a, giving 71 and 67% yields,
respectively (3ab and 3ac), and it bearing an electron-
withdrawing group at the C5 position also gave similar yields
(3ad and 3af). The C6- and C7-substituted indole derivatives
were also tolerated with this reaction, giving 67 and 76% yields,
respectively (3ag and 3ah). Unfortunately, when the C2-
substituted indoles such as 2-phenylindole and 2-methylindole
were employed as the substrate, no bis(indolyl)methane was
observed, possibly due to the influence of steric hindrance.
Indole having multiple electron-withdrawing groups on the
phenyl ring gave a moderate yield (46%, 3ai). Other functional
group-substituted indoles such as 5-hydroxyindole, 5-cyanoin-
dole, and 5-nitroindole reacting with 1a gave 60, 19, and 20%
yields, respectively (3aj−3al). Interestingly, methyl indole-4-
carboxylate 2m as the substrate gave 17% yield of 3am, which
is a decarboxylative addition product without further addition
of the second 2m substrate, possibly due to the steric
hindrance; remarkably, the formation of this product provided
a valuable mechanistic clue for this Pd(II)/LA catalysis. In
addition, using dimethyl indolizine-1,2-dicarboxylate instead of
indole as the substrate provided 37% yield of bis(indolizinyl)-
methane (3an). Since 3an is not very stable, the real yield of
3an may be higher than 37% in the present study. Pyrrole and
2-methyl-1H-pyrrole also reacted with 1a smoothly, giving 50
and 51% yields of bis(pyrrolyl)methanes (3ao and 3ap),
respectively. Notably, 5,6-dimethoxyindole 2q as the substrate
gave 31% yield of 3aq, which is a new decarboxylative addition
product that was never reported before. Unlike other
substrates, here, the addition reaction occurred at the C2
and C3 positions of the two 2q molecules. In addition, N-
protected indole 2 such as 1-methylindole was also tested as
the substrate, and it showed good reactivity; however, the
expected product was not stable enough to achieve the NMR
analysis.
Next, the scope of phenylpropiolic acid derivatives was
investigated, which is summarized in Scheme 3. The electronic
nature of the phenylpropiolic acid derivatives significantly
affected the yield of bis(indolyl)methane. As shown, phenyl-
propiolic acids with an electron-donating functional group on
the phenyl ring (3ba and 3ca) provided higher yield than those
having an electron-withdrawing group (3da−3ga). Aryl
propiolic acids with a methoxy and methyl group at the
meta position afforded bis(indolyl)methanes 3ha and 3ia in 82
and 65% yields, respectively. Phenylpropiolic acid with
multiple electron-donating groups on the phenyl ring gave
3ja in 88% yield, and naphthyl propiolic acid as the substrate
also gave 3ka in 51% yield. In addition, 2-thiophenyl propiolic
acid as the substrate gave 3la in 42% yield, and the alkyl-
substituted alkynoic acids also gave 3ma and 3na in 27 and
26% yields, respectively. In the literature, Statti even disclosed
the good anti-cancer activity of 3ja, in which 3ja was
synthesized through condensation of 3,4,5-trimethoxyaceto-
phenone with indole in the presence of HCl (26% yield) or
(COOH)2·2H2O/CTAB (62% yield, CTAB: N-cetyl-N,N,N-
trimethylammonium bromide).20 Most recently, Szpilman
a
Reaction conditions: 1 (0.2 mmol), 2a (1.0 mmol), Pd(OAc)2 (5
mol %), Sc(OTf)3 (10 mol %), 1,4-dioxane (1 mL), Ar balloon, 70
°C, and 12 h. 24 h.
b
reported an InCl3-catalyzed vinyl azide reaction with indole
to provide 3ja in 88% yield, where the treatment of vinyl azide
must be done with proper safety precautions.21 Apparently, the
method disclosed in the present study is more attractive than
that in previous studies for 3ja synthesis. Accordingly, the
synthesis of 3ja was carried out next in the gram scale, which
provided 86% yield of 3ja (1.1 g, 86%, Scheme 4), almost
identical to that in Scheme 3, indicating that this new
methodology is potentially applicable in the large-scale
synthesis of 3ja.
In order to investigate the active catalyst in this Pd(II)/LA-
catalyzed decarboxylative addition reaction, the UV−vis
spectra of the Pd(II)/Sc(III) catalyst were investigated,
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To obtain the mechanistic clues for this Pd/LA-catalyzed
decarboxylative addition reaction, a series of control experi-
ments was carried out, as shown in Scheme 5. In the literature,
Lewis acid-catalyzed indole addition of phenylacetylene to give
bis(indolyl)methane products was even reported;13c accord-
ingly, one may suspect that a pathway of Pd(II)-catalyzed
decarboxylation of phenylpropiolic acid to phenylacetylene
followed by Lewis acid-catalyzed indole addition may be
present here. To address this issue, the control experiments
using phenylacetylene instead of phenylpropiolic acid as the
substrate were carried out under the standard conditions, and
the results are summarized in Table S3. As shown, when
phenylacetylene was employed as the substrate, only 15% yield
of the product 3aa was observed with the Pd(II)/Sc(III)
catalyst (Scheme 5, eq 1, also Table S3, entry 1), which is
much lower than that using phenylpropiolic acid as the
substrate (80% yield, Table 1, entry 11), and 31% of
phenylacetylene still remained after the reaction in GC analysis
(Figure S1). In the case of using Sc(OTf)3 alone as a catalyst,
it provided 3aa in only 17% yield (Table S3, entry 2), also
much lower than that using phenylpropiolic acid as the
substrate (80% yield, Table 1, entry 11). Clearly, if Pd(II)-
catalyzed decarboxylation followed by Lewis acid-catalyzed
indole addition happened in this Pd/LA-catalyzed decarbox-
ylative addition reaction, its efficiency should be much lower
than that observed in Table 1. Also, if phenylacetylene was the
intermediate for the product 3aa formation in this reaction,
using phenylacetylene as the reactant should provide a much
higher yield than 15% of 3aa, and it should be completely
converted, not as 31% of phenylacetylene still remained after
Scheme 4. Gram-Scale Synthesis of Bis(indolyl)methane 3ja
which are displayed in Figure 1. As shown, Pd(OAc)2
demonstrated an absorbance band around 400 nm due to
the ligand-to-metal charge transfer from the acetate ligand to
the Pd2+ cation. Adding Sc(OTf)3 to Pd(OAc)2 led to the
generation of a new absorbance band with a maximum near
321 nm, and with increasing the concentration of the Pd(II)/
LA catalyst, the new absorbance band increased proportion-
ately as well (Figure S2), thus indicating the formation of a
new Pd(II) species. The migration of chemical shifts caused by
adding Sc(OTf)3 was also observed in 1H NMR spectra
(Figure 2). As shown in Figure 2b, Pd(OAc)2 alone in DMSO-
d6 reveals a chemical shift of 1.78 ppm, corresponding to the
methyl group of acetate in the Pd3(OAc)6 trimer in which all
of the acetates serve as bridges like those in the literature.22
Adding Sc(OTf)3 to Pd(OAc)2 downshifted the methyl group
of acetate from 1.78 to 1.91 ppm (Figure 2a vs 2b), and a
similar methyl peak of the acetate at δH = 1.91 ppm was also
observed in Pd(II)/Sc(III)-catalyzed decarboxylative addition
reaction in its 1H NMR kinetic studies (vide infra, Figures 3c−
e and S3). Accordingly, a similar hetero-bimetallic Pd(II)/
Sc(III) species having two acetate bridges can be assigned to
this new Pd(II) species and that in our previous studies,7 and
the downshift of the methyl group was caused by the more
positively charged Sc3+ cation in the hetero-bimetallic Pd(II)/
Sc(III) species than the +2 charged Pd2+ cation in the
Pd3(OAc)6 trimer.
1
the reaction. Additionally, in the H NMR kinetic monitoring
of Pd(II)/Sc(III)-catalyzed decarboxylative addition of phenyl-
propiolic acid with pyrrole, no signals of phenylacetylene were
observed to indicate it as the intermediate for this reaction
(Figures S4, S9−S11). Taken together, the pathway of Pd(II)-
catalyzed decarboxylation of phenylpropiolic acid to phenyl-
Figure 1. UV−vis spectra of Pd(OAc)2 and Sc(OTf)3 in 1,4-dioxane.
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1
Figure 2. H NMR spectra of Pd(OAc)2 and Sc(OTf)3 in DMSO-d6 containing 1,4-dioxane (v/v, 0.4/0.2 mL).
1
Figure 3. Selected H NMR spectra of the decarboxylative addition of phenylpropionic acid (1a) to pyrrole (2o) in DMSO-d6 containing 1,4-
dioxane (v/v, 0.4/0.2 mL) at room temperature.
acetylene followed by Lewis acid-catalyzed indole addition
could be clearly excluded here.
Next, when using equal equivalence of indole and 2-methyl-
1H-pyrrole to react with phenylpropiolic acid, the product 3aa
and 5aap were generated in 7 and 9% yields, respectively, and
no product 3ap was observed (Scheme 5, eq 2). As both
observed products contained an indolyl unit and a benzyl unit,
3-(1-phenylvinyl)-1H-indole 5aa was possibly the intermediate
in this reaction, which was also evidenced by the formation of
3am as the product in the abovementioned substrate scope
section (vide supra, Scheme 2). Accordingly, 5aa was
synthesized according to the literature11 and employed as the
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Scheme 5. Experiments for Mechanistic Studies
substrate to react with both indole and 2-methyl-1H-pyrrole,
which gave the product 3aa and 5aap in 23 and 29% yields,
respectively, thus suggesting that 5aa was involved as the
intermediate in this decarboxylative addition reaction (Scheme
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1
Figure 4. H-13C HSQC spectrum of the decarboxylative addition of phenylpropiolic acid (1a) with pyrrole (2o).
5, eq 3). Notably, if indole or 2-methyl-1H-pyrrole was in
much excess than the other, the major product was
bis(indolyl)methane 3aa or bis(pyrrolyl)methane 3ap, respec-
tively (Scheme 5, eqs 4 and 5). When using one equivalent of
indole 2b with indole 2a in excess as the substrate mixture to
react with phenylpropiolic acid, the product 3aa and 3ab were
generated in 38 and 2% yields, respectively, and remarkably,
22% yield of bis(indolyl)methane product 5aab bearing two
different indole rings was generated as a mixed bis(indolyl)-
methane product (Scheme 5, eq 6). Using 5aa as the substrate
to react with indole in the presence of the Pd(II)/Sc(III)
catalyst for 10 min provided bis(indolyl)methane product 3aa
in 99% yield (Scheme 5, eq 7), while the product 3aa was also
obtained in 75% yield when employing Sc(III) alone as a
catalyst (Scheme 5, eq 9). However, no product 3aa was
observed when using Pd(II) alone as a catalyst under the
identical conditions, but a lot of palladium black was observed
after the reaction (Scheme 5, eq 8); in contrast, no palladium
black was observed when using Pd(II)/Sc(III) as a catalyst for
this control experiment (Scheme 5, eq 7). Surprisingly, when
adding 5 mol % Sc(OTf)3 to 5 mol % Pd(OAc)2 as the
catalyst, only 10% yield of 3aa was obtained (Scheme 5, eq
10). In the complimentary tests, the product 3aa could also be
obtained in 27% yield after reaction for 12 h when using
Zn(OTf)2 alone as a catalyst (Table S4); apparently, the
second step is a Lewis acid-catalyzed addition reaction.
its catalysis much less efficient than Sc3+ alone, which is a
Lewis acid-catalyzed addition reaction (Scheme 5, eqs 9 vs 10).
An identical information was also confirmed by comparing the
catalytic efficiencies between Pd(II)/Zn(II) and Zn(II) as a
catalyst, in which Zn(OTf)2 alone as a catalyst offered 27% of
3aa from 5aa and 2a in 12 h, whereas 1:1 ratio of the Pd(II)/
Zn(II) was inactive (Table S4). Taken together, these data
supported that the formation of the heterometallic Pd(II)/LA
species significantly weakened the Lewis acidity of the LA in
the cluster; on the other hand, it should have simultaneously
strengthened the electrophilic properties of the Pd(II) unit in
this Pd(II)/LA species, making it more active in Pd(II)-
catalyzed syntheses, as demonstrated in this decarboxylative
addition reaction and that in previous studies.7
In order to detect the potential intermediate in situ
1
generated in this decarboxylative addition reaction, H NMR
kinetic studies of the Pd(II)/Sc(III)-catalyzed decarboxylative
addition reaction between phenylpropiolic acid (1a) and
pyrrole (2o) were performed, as shown in Figure 3. The
selection of 2o rather than indole in this study was based on
1
the purpose of simplifying the H NMR spectrum in kinetic
studies. The 1H NMR spectra of 1a and 2o in pure DMSO-d6
are displayed in Figure 3a,b. After reaction for 5 min under the
standard conditions, the reaction mixtures of 1a and 2o were
taken out for the 1H NMR examination in DMSO-d6
immediately (Figure 3c), and it was found that large amounts
of 1a and 2o still remained with a set of new peaks observed
(marked in a red circle in Figure 3). After 10 min, these new
peaks grew up quickly, and the peaks of the product 3ao were
also observed as compared with its authentic sample (Figure
3d vs 3g). After 30 min, the set of these new peaks disappeared
with the peaks of the product 3ao growing up (Figure 3e).
Significantly, 1:1 ratio of Pd(II)/Sc(III) was almost inactive
for this second-step reaction, which is an addition reaction,
whereas 1:2 ratio of the Pd(II)/Sc(III) or Sc(III) alone was
highly active for this addition reaction (Scheme 5, eqs 7 and
10). These results indicated that the presence of the Pd(II)
unit in the hetero-bimetallic Pd(II)/Sc(III) species has
weakened the Lewis acidity of the Sc3+ cation, thus making
1
Clearly, this set of new peaks in the H NMR spectrum
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Figure 5. H-1H NOESY spectrum of the decarboxylative addition of phenylpropiolic acid (1a) with pyrrole (2o).
indicated the occurrence of a transient intermediate in the
reaction, which can be transformed to the final product 3ao
with the reaction proceeding.
Sc(III) structure. According to these clues and those from
control experiments, this transient intermediate can be
assigned as a vinyl-Pd(II)/Sc(III) intermediate IV-ao, as
shown in Figure 3.
1
In Figure 3c, the H NMR spectrum of these new peaks
1
shows ABC system peaks with equal intensity in the aromatic
region (δH = 5.94, 6.17, and 7.20 ppm, Figure 3c). After
comparing with the pyrrolyl protons in 2-(1-phenylvinyl)-1H-
pyrrole (5ao) which was independently synthesized according
to the literature as the authentic sample (Figure 3f),23 these
new ABC system peaks can be assigned to the pyrrolyl protons
of the transient intermediate (Figures 3c,f and S5). According
to the 1H NMR assignments of the pyrrolyl unit in 5ao,23 here,
the peak at δH = 7.20 ppm can be assigned to the proton at the
2 position of the pyrrolyl ring in the transient intermediate,
while the peaks at δH = 6.17 and 5.94 ppm can be assigned to
the protons at the 4 and 3 positions, respectively (see also
Figure S5a′,b′ for clear details); the multiple signals of the new
transient intermediate in the aromatic region (δH around 7.40
ppm) can be assigned to its corresponding aromatic protons.
As only one singlet peak (no doublet peak) was observed in
the region of the olefinic proton (δH = 5.47 ppm), it could be
concluded that the transient intermediate was not 5ao.
Compared with the authentic 1H NMR graph of the authentic
5ao sample, the pyrrolyl protons of the transient intermediate
showed a great downshift (see Figure S5 for clear details),
especially for the N−H (downshifted from 11.08 to 12.96
ppm) and the pyrrolyl proton adjacent to the N−H group
(downshifted from 6.82 to 7.20 ppm). It is worth mentioning
To confirm the vinyl-Pd(II)/Sc(III) structure, the H-13C
HSQC experiment was conducted for the mixtures of 1a and
2o after reaction for 5 min under the standard conditions. As
shown in Figure 4, the 1H-13C HSQC spectrum disclosed that
the carbon linked to the singlet proton at δH = 5.47 ppm of the
intermediate IV-ao is in sp2 hybridization having the chemical
shift around 111 ppm, thus confirming that the intermediate
IV-ao is a vinyl-Pd(II) complex. Furthermore, the 1H-1H
NOESY spectrum disclosed that this singlet proton at δH
=
5.47 ppm is correlated with the corresponding aryl proton at
δH = 7.4 ppm of the same intermediate IV-ao (Figure 5), thus
confirming that this proton is cis to the aromatic ring, that is,
Pd(II) and the pyrrolyl ring are cis about the CC bond. The
sharp downshift of the N−H proton from 11.08 to 12.96 ppm
in IV-ao can be attributed to the unsymmetrical η5-
coordination of the Pd2+ cation on the pyrrolyl ring, a
cation−π coordination mode in which the N lone pair of
pyrrolyl contributes a lot in the η5-coordination; such a
cation−π coordination mode similarly causes the downshift of
the neighboring proton of the pyrrolyl nitrogen atom from
6.82 to 7.20 ppm. Because of the unsymmetrical η5-
coordination of the Pd2+ cation on the pyrrolyl ring, the
coplanar geometry of benzyl, alkenyl, and pyrrolyl groups was
broken in this vinyl-Pd(II)/Sc(III) intermediate, thus breaking
the conjugated π bond system, which exists in 5ao.
1
that in the H NMR spectrum of the reaction mixtures, the
methyl group of acetate from the Pd(II)/Sc(III) catalyst
retained the identical chemical shift as that in the H NMR
studies of the catalyst (Figures 2 vs 3), indicating that during
the reaction, the catalyst retained its hetero-bimetallic Pd(II)/
Notably, one of two alkenyl protons in 5ao also appears at
the nearly identical chemical shift of the alkenyl proton in IV-
ao (5.468 vs 5.472 ppm, see Figure S5 for clear details).
Generally, one may expect that the chemical shift of the
1
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1
neighboring proton of the vinyl-Pd(II)/Sc(III) intermediate
should upshift when compared with that in 5ao. This
phenomenon can be rationalized as that while the shielding
effect of the Pd(II) causes the alkenyl proton to upshift, the
breaking of the conjugated π bond system in IV-ao may have
caused the contrast deshielding effect. Two distinct effects
compensated together, resulting in the chemical shift of the
alkenyl proton in IV-ao almost unchanged (5.468 vs 5.472
ppm), while others including pyrrolyl and benzyl protons still
downshifted, as displayed in Figure S5. A similar vinyl-Pd(II)/
Sc(III) intermediate was also observed in the 1H NMR kinetics
when using 3-(4-chlorophenyl)propiolic acid as the substrate
(Figure S6). To the best of our knowledge, except in Pd(II)-
catalyzed C−X (X = Cl, Br, and I) activation of halogenated
alkene, the vinyl-Pd(II) intermediate was scarcely identified in
Pd(II)-catalyzed C−H activation of alkene until now, although
it may occur as an intermediate in many alkene functionaliza-
tion reactions.24
is, indole, the resulting H NMR spectra became complicated
with the disappearance of 1a, indicating the instability of the
resulting decarboxylating intermediate. On the other side, the
signals of indole remained clear after adding the Pd(II)/Sc(III)
catalyst to its deuterated 1,4-dioxane solution, indicating that
the Pd(II)/Sc(III) catalyst did not react directly with indole
under current reaction conditions. Taken together, these clues
indicated that this Pd(II)/Sc(III)-catalyzed decarboxylative
addition of propiolic acids with indoles started from
decarboxylation of propiolic acid rather than activation of
the C−H bond in indole.
Because a pathway of Pd(II)-catalyzed decarboxylation of
phenylpropiolic acid to phenylacetylene followed by Lewis
acid-catalyzed indole addition has been excluded in the present
studies (vide supra), a phenylethynyl-Pd(II)/Sc(III) inter-
mediate may be generated after Pd(II)/Sc(III)-catalyzed
phenylpropiolic acid decarboxylation, and a following pyrrole
addition to this intermediate leads to the observed
intermediate IV-ao formation in Figure 3. However, such a
phenylethynyl-Pd(II)/Sc(III) intermediate was not observed
The 1H NMR kinetic studies of the Pd(II)/Sc(III)-catalyzed
decarboxylative addition reaction between phenylpropiolic acid
(1a) and indole (2a) were also carried out, as shown in Figure
S7. However, no clean intermediate such as IV-ao could be
assigned except that two small new peaks in the olefinic region
(δH = 5.51 and 5.32 ppm, Figure S7) were observed. After
comparing with the alkenyl protons of 3-(1-phenylvinyl)-1H-
indole (5aa) which was independently synthesized according
to the literature as the authentic sample (Figure S7g),11 the
two protons at the chemical shift of 5.51 and 5.32 ppm can be
assigned to the intermediate 5aa, and 5aa reacts feasibly with
the second indole to give the final bis(indolyl)methane
product, as shown in Figure 3. In the case of using indole-4-
carboxylate 2m as the substrate, the mono-adduct product
3am was obtained as the final product due to the steric
hindrance, as demonstrated above (Scheme 2).
1
in H NMR kinetic studies, plausible due to its instability. In
order to address whether the addition of the weakly
nucleophilic indole to the phenylethynyl-Pd(II)/Sc(III)
species can happen or not, a series of controlled experiments
to investigate the nucleophilic addition reactivity of the
plausible phenylethynyl-Pd(II)/Sc(III) were carried out, as
shown in Table S5.
First, the stable phenylethynyl-Cu(I) reagent 7a was
synthesized according to the literature.25 Then, a series of
controlled experiments were designed to check its reactivity
with indole in the absence/presence of Pd(OAc)2 and/or
Sc(OTf)3. As shown in Table S5, (1)when using 7a as the
substrate to react directly with indole in HOAc, no product
was detected (Table S5, entry 1), indicating that nucleophilic
addition of indole to the phenylethynyl-Cu(I) moiety is not
accessible; (2) adding Pd(OAc)2 as the catalyst to this reaction
provided 5% yield of 6aa as a homocoupling product with
bulky palladium black formation (Table S5, entry 2), which
may proceed through transmetallation of the phenylethynyl-
Cu(I) with Pd(II) to generate the phenylethynyl-Pd(II)
intermediate, followed by the homocoupling reaction to give
6aa as the product; however, no indole addition product 3aa
was observed, indicating that the nucleophilic addition of
indole to a nucleophilic phenylethynyl-Pd(II) moiety is not
accessible; (3) In the absence of indole, reaction of
phenylethynyl-Cu(I) with Pd(OAc)2 also provided only 7%
yield of 6aa as the homocoupling product (Table S5, entry 4);
(4) using Sc(OTf)3 alone as the catalyst provided 8% yield of
3aa as the indole addition product, which may be explained as
a Lewis acid-catalyzed indole addition reaction under the
reaction conditions (Table S5, entry 3); and (5) Remarkably,
using Pd(OAc)2/Sc(OTf)3 as the catalyst provided 36% yield
of 3aa with 8% yield of 6aa product (Table S5, entry 5), in
which the yield of the indole addition product 3aa was much
higher than that when using Sc(OTf)3 alone as the catalyst,
which cannot be explained as a Sc3+-catalyzed indole addition.
Accordingly, this higher yield of 3aa can be rationalized by the
indole addition to the CC triple bond of the phenylethynyl-
Pd(II)/Sc(III) intermediate, generated by transmetallation of
phenylethynyl-Cu(I) to the Pd(II)/Sc(III) species, which is
more electron-deficient than that in the phenylethynyl-Pd(II)
intermediate, thus making indole addition become accessible,
even though indole is a weakly nucleophilic reagent.
Interestingly, the vinyl-Pd(II)/Sc(III) intermediate was not
observed in decarboxylative addition of propionic acids with
indole, which can be rationalized by that its addition reaction
occurs at the 3 position of indole (unlike at the 2 position of
pyrrole), making it impossible to form an intermediate such as
IV-ao due to the steric hindrance. Without the stabilization of
unsymmetrical η5-coordination of the Pd2+ cation on the
pyrrolyl ring, after its formation, it could be immediately
transformed to the mono-adduct product such as 5aa, which
was traced by the occurrence of its olefinic protons, as shown
in Figure S7, and next, Lewis acid-catalyzed addition of the
second indole to the mono-adduct product happened feasibly
to give the final bis(indolyl)methane product. On the other
hand, in the case of pyrrole as the substrate, because of the
stabilization of the unsymmetrical η5-coordination of the
Pd(II)/Sc(III) intermediate on the pyrrolyl ring, it can be
1
identified as the intermediate in the reaction mixtures by H
NMR studies, and next, Lewis acid-catalyzed direct addition of
pyrrole to this intermediate led to the formation of the final
bis(pyrrolyl)methane product. The absence of the mono-
adduct product such as 5ao was supported by the failure of
1
tracing its olefinic protons in the H NMR kinetic studies, as
shown in Figure 3.
1
In the H NMR kinetics of the semi-reaction, after adding
the Pd(II)/Sc(III) catalyst to the solution of 1a in deuterated
1,4-dioxane at 70 °C, the signals of phenylpropionic acid 1a
1
disappeared gradually in its H NMR spectrum (Figure S8),
indicating that the decarboxylative reaction happened.
However, because of the absence of the other substrate, that
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Due to the instability of the phenylethynyl-Pd(II)/Sc(III)
intermediate, it was also not observed in the abovementioned
phenylethynyl-Cu(I) reaction with Pd(II) or Pd(II)/Sc(III) in
the presence/absence of indole; however, from the clues of the
homocoupling product formation in the presence of Pd-
(OAc)2, it can be reasonably suspected that it can occur
through transmetallation reaction between phenylethynyl-
Cu(I) and Pd(II) or Pd(II)/Sc(III). Remarkably, nucleophilic
addition of indole to a nucleophilic phenylethynyl-Pd(II)
intermediate is not accessible, whereas it is accessible for the
phenylethynyl-Pd(II)/Sc(III) intermediate to generate the 3aa
product, as disclosed (Table S5, entries 2 vs 5). Similarly, in
our decarboxylative addition reaction, using Pd(OAc)2 alone as
the catalyst only provided the homocoupling product without
indole addition product formation, but the homocoupling
product was observed (Table 1, entry 1); however, the
presence of Sc(OTf)3 makes indole addition become
accessible, leading to 80% yield of 3aa with 8% yield of 4aa
formation (Table 1, entry 11), indicating that the CC triple
bond of the phenylethynyl-Pd(II)/Sc(III) intermediate is more
electron-deficient than that of the phenylethynyl-Pd(II), thus
making indole addition become accessible in our studies, even
though indole is a weakly nucleophilic reagent.
reaction. The catalysis was triggered through decarboxylation
of propiolic acid by the Pd(II)/Sc(III) species to generate the
phenylethynyl-Pd(II)/Sc(III) intermediate I. The presence of
the Sc3+ cation makes the Pd2+ cation more electron-deficient,
and the carbon of the α-position in the intermediate I is
partially, positively charged, which makes its CC triple bond
electrophilic addition with substrate 2 or 2″ become accessible
and give the intermediate II and V. For the pyrrole derivatives
2, the addition reaction occurs at the 2 position of the pyrrolyl
ring (Scheme 6, pathway A), which makes the unsymmetrical
η5-coordination of the Pd(II)/Sc(III) intermediate to the
pyrrolyl ring, a cation−π coordination mode in which the N
lone pair of pyrrole contributes a lot in the η5-coordination,
become possible, giving a relatively stable vinyl-Pd(II)/Sc(III)
1
intermediate II, which was successfully identified in H NMR
kinetic studies. Here, releasing the Pd(II)/Sc(III) species from
the intermediate II is not favorable, as no olefinic protons of
the mono-adduct such as 5ao are traced in Figure 3. Thus, the
intermediate II directly reacts with another substrate 2 via
Lewis acid-catalyzed addition to provide the intermediate III.
Then, releasing the Pd(II)/Sc(III) species from the
intermediate III gives the bis(pyrrolyl)methane 3 as the final
product to achieve the catalytic cycle. Unlike the pathway A,
for the indole addition, the reaction preferably occurs at the 3
position of indole derivatives 2″ to give the intermediate V
(Scheme 6, pathway B). Releasing the Pd(II)/Sc(III) species
from the intermediate V generates the mono-adduct product 5,
which was traced by the occurrence of its olefinic protons in
1H NMR kinetic studies (Figure S7). Next, 5 reacts feasibly
with another substrate 2″ via Lewis acid-catalyzed addition to
provide the bis(indolyl)methane as the final product 3″ to
achieve the catalytic cycle.
Accordingly, a simplified mechanism of Pd(II)/Sc(III)-
catalyzed decarboxylative addition of propiolic acids with
indole or pyrrole reaction is proposed in Scheme 6. First, a
hetero-bimetallic Pd(II)/Sc(III) species was in situ generated
as the key active species for the decarboxylative addition
Scheme 6. Proposed Mechanism for the Pd(II)/Sc(III)-
Catalyzed Decarboxylative Addition Reaction
3. CONCLUSIONS
In summary, a new protocol was explored for the synthesis of
bis(indolyl)methane and bis(pyrrolyl)methane derivatives
through decarboxylative addition reaction of propiolic acids
and indoles/pyrroles with a Pd(II)/LA catalyst. It was found
that adding Lewis acid such as Sc(OTf)3 to the Pd(OAc)2
catalyst triggered this catalysis, providing the desired products
in moderate to good yields, whereas neither Pd(II) nor Sc(III)
alone was active for this synthesis. The promotional effect was
highly dependent on the Lewis acidity of the added Lewis acid,
that is, a stronger Lewis acid provided a higher yield. Through
the UV−vis and 1H NMR characterizations, a hetero-bimetallic
Pd(II)/Sc(III) species having two acetate bridges was
proposed as the active species for this catalysis as that in
previous studies, and a vinyl-Pd(II)/Sc(III) intermediate was
identified in 1H NMR kinetic studies of Pd(II)/Sc(III)-
catalyzed decarboxylative addition of pyrrole to phenyl-
propionic acid, which was scarcely identified in Pd(II)-
catalyzed alkene functionalization reaction except in Pd(II)-
catalyzed C−X (X = Cl, Br, and I) activation of halogenated
alkene. In addition, the present work also further convinced
that the presence of Lewis acid can modulate the reactivity and
improve the catalytic efficiency of a redox metal ion such as
Pd(II), thus providing a new strategy for the catalyst design of
these transition metal ion-mediated organic syntheses.
4. EXPERIMENTAL SECTION
4.1. Materials and Analytical Methods. All reagents were
purchased from commercial suppliers and used without further
purification. The propiolic acids 2b−2m and intermediate 5aa were
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synthesized following the literature with modifications.11,26 UV−vis
spectra were collected on an Agilent Technologies Cary-8454 UV−vis
spectrometer. The reactions were monitored by TLC with Haiyang
GF-254 silica gel plates (Qingdao Haiyang Chemical Industry Co.
Ltd, Qingdao, China) using UV light and bromocresol green as
visualizing agents as needed. Flash column chromatography was
the solvent was removed under reduced pressure. After purification by
column chromatography (SiO2, PE/EA = 40:1), it afforded 5ao (21.9
mg, 66% yield) as a yellowish oil.
4.6.1. 3,3′-(1-Phenylethane-1,1-diyl)bis(1H-indole) (3aa). 3-Phe-
nylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and indole (2a) (117.2
mg, 1.0 mmol) afforded 3,3′-(1-phenylethane-1,1-diyl)bis(1H-indole)
(3aa) (53.8 mg, 0.16 mmol, 80% yield); yellowish solid (petroleum
1
performed using a 200−300-mesh silica gel at increased pressure. H
1
NMR spectra and 13C NMR spectra were, respectively, recorded on
ether/ethyl acetate = 5/1); melting point: 190−192 °C; H NMR
Bru
̈
ker AV-400 spectrometers and Bru
̈
ker AV-600 spectrometers.
(400 MHz, CDCl3): δ 7.51 (s, 2H), 7.34 (d, J = 7.0 Hz, 2H), 7.28 (d,
J = 8.0 Hz, 2H), 7.23−7.14 (m, 5H), 7.08 (t, J = 7.5 Hz, 2H), 6.89 (t,
J = 7.5 Hz, 2H), 6.42 (d, J = 1.7 Hz, 2H), 2.30 (s, 3H); 13C{1H}
NMR (101 MHz, CDCl3): δ 148.1, 137.1, 128.2, 127.9, 126.5, 125.9,
124.7, 123.5, 122.2, 121.6, 119.0, 111.3, 43.8, 28.9; HRMS (APCI)
m/z: [M − H]− calcd for C24H20N2, 335.1554; found, 335.1550.
4.6.2. 3,3′-(1-Phenylethane-1,1-diyl)bis(5-methoxy-1H-indole)
(3ab). 3-Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and 5-
methoxy-1H-indole (2b) (147 mg, 1.0 mmol) afforded 3,3′-(1-
phenylethane-1,1-diyl)bis(5-methoxy-1H-indole) (3ab) (53.8 mg,
0.142 mmol, 71% yield); yellowish solid (petroleum ether/ethyl
Chemical shifts (δ) were expressed in ppm with TMS as the internal
standard, and coupling constants (J) were reported in Hz. High-
resolution mass spectra were obtained on a mass spectrometer using
APCI FT-ICR mass spectrometry. Melting points were collected on
an INESA automatic melting point tester (WRS-1C).
4.2. General Procedure for the Synthesis of 3. In a typical
procedure, Pd(OAc)2 (2.2 mg, 0.01 mmol) and Sc(OTf)3 (9.9 mg,
0.02 mmol) were dissolved in 1,4-dioxane (1 mL) in a glass tube.
Then, propiolic acids 1 (0.2 mmol) and indole derivatives 2 (1.0
mmol) were added in the glass tube connected with an Ar balloon.
The reaction mixtures were heated in an oil bath with stirring at 70 °C
for 12 h. After the reaction, the solvent was removed under reduced
pressure. The raw product was purified by column chromatography
on a silica gel (petroleum ether/EtOAc: 1/1−20/1) to give the
desired product 3.
4.3. General Procedure for the Controlled Experiments
with Phenylacetylene as the Substrate. In a typical procedure,
Pd(OAc)2 (2.2 mg, 0.01 mmol) and Sc(OTf)3 (9.9 mg, 0.02 mmol)
were dissolved in 1,4-dioxane (1 mL) in a glass tube. Then,
phenylacetylene 6a (20.4 mg, 0.2 mmol) and indole 2a (117.1 mg, 1.0
mmol) were added in the glass tube connected with an Ar balloon.
The reaction mixtures were heated in an oil bath with stirring at 70 °C
for 12 h. After the reaction, the solvent was removed under reduced
pressure. The raw product was purified by column chromatography
on a silica gel (petroleum ether/EtOAc: 1/1−100/1) to give the
desired product 3aa and 6aa.
4.4. General Procedure for the Controlled Experiments
with Phenylethynyl-Cu(I) Reagent as the Substrate. In a typical
procedure, Pd(OAc)2 (2.2 mg, 0.01 mmol) and Sc(OTf)3 (9.9 mg,
0.02 mmol) were dissolved in 1,4-dioxane (1 mL) in a glass tube.
Then phenylethynyl-Cu(I) 7a (32.9 mg, 0.2 mmol) and indole 2a
(117.1 mg, 1.0 mmol) were added in the glass tube connected with an
Ar balloon. The reaction mixtures were heated in an oil bath with
stirring at 70 °C for 12 h. After the reaction, the solvent was removed
under reduced pressure. The raw product was purified by column
chromatography on a silica gel (petroleum ether/EtOAc: 1/1−100/
1) to give the desired product 3aa and 6aa.
4.5. General Procedure for the Synthesis of 3-(1-Phenyl-
vinyl)-1H-indole (5aa). According to the literature,11 under N2, 1-
(1H-indol-3-yl)ethan-1-one (5 mmol, 0.8 g) was added in dry THF
(20 mL) at 0 °C; then, ArMgBr (12.5 mmol, 1.0 M solution in THF)
was added dropwisely. The reaction mixtures were warmed to 50 °C
and stirred at the same temperature for 12 h. Then, the reaction
mixtures were cooled to 0 °C, and a saturated aqueous NH4Cl
solution (20 mL) was added dropwisely. After the organic layer was
separated, the aqueous layer was extracted with Et2O (2 × 50 mL).
The combined organic layers were dried over anhydrous Na2SO4,
filtered, and concentrated. The resulting residues were dissolved in
CH2Cl2 (25 mL), to which was added anhydrous MgSO4 (2.5 g)
followed by a silica gel (200−300 mesh particle size, 2.5 g). The
mixtures were then stirred at room temperature for 5 h, then filtered,
and washed with Et2O. The filtrate was concentrated, and the
resulting residues were purified by silica gel chromatography to afford
the desired 5aa as a white solid alkene product 5aa (910 mg, 83%
yield).
1
acetate = 4/1); melting point: 259−261 °C; H NMR (400 MHz,
CDCl3): δ 10.66 (d, J = 1.9 Hz, 2H), 7.33 (d, J = 7.3 Hz, 2H), 7.24
(d, J = 8.8 Hz, 4H), 7.17 (d, J = 7.2 Hz, 1H), 6.77 (d, J = 2.5 Hz, 2H),
6.65 (dd, J = 8.8, 2.4 Hz, 2H), 6.43 (d, J = 2.3 Hz, 2H), 3.45 (s, 6H),
2.20 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6): δ 152.6, 148.6,
132.7, 128.3, 128.0, 126.9, 126.0, 124.6, 122.8, 112.4, 110.5, 103.8,
55.5, 43.5, 29.5; HRMS (APCI) m/z: [M − H]− calcd for
C26H24N2O2, 395.1765; found, 395.1761.
4.6.3. 3,3′-(1-Phenylethane-1,1-diyl)bis(5-methyl-1H-indole)
(3ac). 3-Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and 5-
methyl-1H-indole (2c) (131.2 mg, 1.0 mmol) afforded 3,3′-(1-
phenylethane-1,1-diyl)bis(5-methyl-1H-indole) (3ac) (48.8 mg,
0.134 mmol, 67% yield); yellowish solid (petroleum ether/ethyl
1
acetate = 4/1); melting point: 218−220 °C; H NMR (400 MHz,
CDCl3): δ 7.66 (s, 2H), 7.37 (d, J = 7.2 Hz, 2H), 7.21 (dd, J = 14.3,
7.8 Hz, 5H), 7.12 (s, 2H), 6.95 (d, J = 8.1 Hz, 2H), 6.47 (d, J = 1.8
Hz, 2H), 2.34 (s, 3H), 2.29 (s, 6H); 13C{1H} NMR (101 MHz,
DMSO-d6): δ 148.9, 136.0, 128.2, 128.0, 126.7, 126.5, 126.0, 124.1,
122.9, 122.6, 121.2, 111.8, 43.7, 29.4, 21.9; HRMS (APCI) m/z: [M
− H]− calcd for C26H24N2, 363.1867; found, 363.1856.
4.6.4. 3,3′-(1-Phenylethane-1,1-diyl)bis(5-chloro-1H-indole)
(3ad). 3-Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and 5-
chloro-1H-indole (2d) (151.6 mg, 1.0 mmol) afforded 3,3′-(1-
phenylethane-1,1-diyl)bis(5-chloro-1H-indole) (3ad) (52.7 mg, 0.13
mmol, 65% yield); yellowish solid (petroleum ether/ethyl acetate =
1
5/1); melting point: 129−131 °C; H NMR (400 MHz, CDCl3): δ
7.80 (s, 2H), 7.21 (d, J = 7.0 Hz, 2H), 7.11 (dd, J = 23.4, 10.5 Hz,
7H), 6.96 (d, J = 8.6 Hz, 2H), 6.48 (d, J = 1.8 Hz, 2H), 2.17 (s, 3H);
13C{1H} NMR (101 MHz, DMSO-d6): δ 148.0, 136.0, 128.3, 128.0,
127.5, 126.4, 125.7, 123.1, 122.7, 121.1, 120.2, 113.7, 43.4, 29.7;
HRMS (APCI) m/z: [M − H]− calcd for C24H18Cl2N2, 403.0774;
found, 403.0773.
4.6.5. 3,3′-(1-Phenylethane-1,1-diyl)bis(5-bromo-1H-indole)
(3ae). 3-Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and 5-
bromo-1H-indole (2e) (196 mg, 1.0 mmol) afforded 3,3′-(1-
phenylethane-1,1-diyl)bis(5-bromo-1H-indole) (3ae) (63.3 mg,
0.128 mmol, 64% yield); yellowish solid (petroleum ether/ethyl
1
acetate = 10/1); melting point: 251−253 °C; H NMR (400 MHz,
DMSO-d6): δ 11.11 (s, 2H), 7.36 (d, J = 9.1 Hz, 2H), 7.28 (d, J = 4.2
Hz, 4H), 7.21 (dd, J = 8.4, 4.1 Hz, 1H), 7.14−7.09 (m, 4H), 6.86 (d, J
= 2.4 Hz, 2H), 2.20 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6): δ
148.0, 136.2, 128.3, 128.2, 128.00, 126.4, 125.5, 123.6, 123.2, 122.6,
114.2, 111.2, 43.4, 29.7; HRMS (APCI) m/z: [M − H]− calcd for
C24H18Br2N2, 490.9764; found, 490.9754.
4.6.6. 3,3′-(1-Phenylethane-1,1-diyl)bis(5-fluoro-1H-indole)
(3af). 3-Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and 5-
fluoro-1H-indole (2f) (135.1 mg, 1.0 mmol) afforded 3,3′-(1-
phenylethane-1,1-diyl)bis(5-fluoro-1H-indole) (3af) (47.7 mg, 0.128
mmol, 64% yield); yellowish solid (petroleum ether/ethyl acetate =
4.6. General Procedure for the Synthesis of 2-(1-Phenyl-
vinyl)-1H-pyrrole (5ao). According to the literature,23 a NMR tube
was charged with 21.5 μL (196 μmol; 1 equiv) of phenylacetylene and
0.56 mL of acetonitrile. Then, 67.9 μL (979 μmol; 5 equiv) of pyrrole
and 3.4 mg (4 μmol; 0.02 equiv) of IPrAuNTf2 were next added in
the NMR tube. The reaction was terminated after reaction 5 h, and
1
5/1); melting point: 142−144 °C; H NMR (400 MHz, CDCl3): δ
7.89 (s, 2H), 7.34 (d, J = 7.3 Hz, 2H), 7.27−7.16 (m, 5H), 6.86 (dd, J
8345
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Article
= 16.2, 9.3 Hz, 4H), 6.67 (s, 2H), 2.26 (s, 3H); 13C{1H} NMR (101
MHz, DMSO-d6): δ 157.4 (d, JC−F = 4.7 Hz), 148.1, 134.1, 128.1 (d,
phenylethane-1,1-diyl)bis(5-nitro-1H-indole) (3al) (17.1 mg, 0.04
mmol, 20% yield); yellowish solid (petroleum ether/ethyl acetate =
2/1); melting point: 199−201 °C; 1H NMR (400 MHz, DMSO-d6):
δ 11.73 (d, J = 1.6 Hz, 2H), 7.93 (d, J = 2.3 Hz, 1H), 7.91 (d, J = 2.3
Hz, 1H), 7.89 (d, J = 2.2 Hz, 2H), 7.57 (s, 1H), 7.55 (s, 1H), 7.32 (d,
J = 4.2 Hz, 4H), 7.26 (dd, J = 8.3, 4.1 Hz, 1H), 7.18 (d, J = 2.4 Hz,
2H), 2.30 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6): δ 147.4,
140.8, 140.3, 128.6, 127.9, 126.8, 125.6, 125.3, 117.8, 116.8, 112.8,
43.5, 30.3; HRMS (APCI) m/z: [M − H]− calcd for C24H18N4O4,
425.1255; found, 425.1245.
4.6.13. Methyl 3-(1-Phenylvinyl)-1H-indole-4-carboxylate (3am).
3-Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and methyl 1H-
indole-4-carboxylate (2m) (175.2 mg, 1.0 mmol) afforded methyl 3-
(1-phenylvinyl)-1H-indole-4-carboxylate (3am) (9.4 mg, 0.034 mmol,
17% yield); yellowish solid (petroleum ether/ethyl acetate = 5/1);
melting point: 222−224 °C; 1H NMR (400 MHz, CDCl3): δ 8.48 (s,
1H), 7.58 (dd, J = 8.1, 0.9 Hz, 1H), 7.51 (dd, J = 7.4, 0.9 Hz, 1H),
7.39 (d, J = 2.5 Hz, 1H), 7.37−7.33 (m, 2H), 7.25 (dd, J = 8.8, 6.9
Hz, 4H), 5.69 (d, J = 1.5 Hz, 1H), 5.38 (d, J = 1.5 Hz, 1H), 3.42 (s,
3H); 13C{1H} NMR (101 MHz, DMSO-d6): δ 168.4, 144.2, 141.0,
137.9, 128.6, 128.4, 127.7, 126.6, 124.7, 123.2, 121.6, 120.9, 116.7,
116.2, 111.7, 51.3; HRMS (APCI) m/z: [M + H]+ calcd for
C18H15NO2, 278.1176; found, 278.1177.
4.6.14. Dimethyl 3,3′-(1-Phenylethane-1,1-diyl)bis(indolizine-1-
carboxylate) (3an). 3-Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol)
and methyl indolizine-1-carboxylate (2n) (175.2 mg, 1.0 mmol)
afforded dimethyl 3,3′-(1-phenylethane-1,1-diyl)bis(indolizine-1-car-
boxylate) (3an) (33.5 mg, 0.074 mmol, 37% yield); yellowish solid
(petroleum ether/ethyl acetate = 10/1); melting point: 297−299 °C;
1H NMR (400 MHz, DMSO-d6): δ 8.14 (d, J = 7.9 Hz, 2H), 7.64 (s,
2H), 7.37 (d, J = 6.3 Hz, 3H), 7.12 (s, 4H), 6.84 (s, 2H), 6.66 (d, J =
5.4 Hz, 2H), 3.76 (d, J = 4.4 Hz, 6H), 2.36 (s, 3H); 13C{1H} NMR
(101 MHz, DMSO-d6): δ 164.5, 142.5, 136.9, 129.3, 128.3, 128.0,
125.8, 123.2, 119.5, 116.6, 113.2, 102.4, 51.2, 45.3, 25.4; HRMS
(APCI) m/z: [M + H]+ calcd for C28H24N2O4, 453.1809; found,
453.1802.
J
C−F = 18.5 Hz), 126.6 (d, JC−F = 9.8 Hz), 126.3, 125.9, 123.1 (d, JC−F
= 4.7 Hz), 113.0 (d, JC−F = 9.9 Hz), 109.2 (d, JC−F = 26.3 Hz), 105.7,
105.5, 43.3, 29.5; 19F NMR (376 MHz, DMSO-d6): δ −125.3 (td, J =
9.8, 4.5 Hz); HRMS (APCI) m/z: [M − H]− calcd for C24H18F2N2,
371.1365; found, 371.1357.
4.6.7. 3,3′-(1-Phenylethane-1,1-diyl)bis(6-methyl-1H-indole)
(3ag). 3-Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and 6-
methyl-1H-indole (2g) (131.2 mg, 1.0 mmol) afforded 3,3′-(1-
phenylethane-1,1-diyl)bis(6-methyl-1H-indole) (3ag) (50.3 mg,
0.138 mmol, 69% yield); yellowish solid (petroleum ether/ethyl
1
acetate = 5/1); melting point: 221−223 °C; H NMR (400 MHz,
CDCl3): δ 7.50 (s, 2H), 7.28 (d, J = 7.7 Hz, 2H), 7.15−7.06 (m, 5H),
6.97 (s, 2H), 6.67 (d, J = 8.2 Hz, 2H), 6.36 (d, J = 1.8 Hz, 2H), 2.32
(s, 6H), 2.21 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6): δ 148.9,
137.9, 130.1, 128.0, 127.7, 125.7, 124.5, 123.3, 122.9, 121.1, 120.0,
111.5, 43.5, 29.1, 21.1; HRMS (APCI) m/z: [M − H]− calcd for
C26H24N2, 363.1867; found, 363.1857.
4.6.8. 3,3′-(1-Phenylethane-1,1-diyl)bis(7-methyl-1H-indole)
(3ah). 3-Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and 7-
methyl-1H-indole (2h) (131.2 mg, 1.0 mmol) afforded 3,3′-(1-
phenylethane-1,1-diyl)bis(7-methyl-1H-indole) (3ah) (55.4 mg,
0.152 mmol, 76% yield); yellowish solid (petroleum ether/ethyl
1
acetate = 5/1); melting point: 224−226 °C; H NMR (400 MHz,
CDCl3): δ 7.35 (s, 2H), 7.25 (d, J = 6.8 Hz, 2H), 7.12−7.05 (m, 5H),
6.84 (d, J = 6.9 Hz, 2H), 6.77 (t, J = 7.5 Hz, 2H), 6.24 (d, J = 2.0 Hz,
2H), 2.29 (s, 6H), 2.21 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-
d6): δ 148.8, 136.9, 128.1, 127.8, 126.2, 125.8, 123.8, 123.5, 121.4,
121.0, 119.2, 118.5, 43.6, 29.2, 16.9; HRMS (APCI) m/z: [M − H]−
calcd for C26H24N2, 363.1867; found, 363.1859.
4.6.9. 3,3′-(1-Phenylethane-1,1-diyl)bis(5,6-dichloro-1H-indole)
(3ai). 3-Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and 5,6-
dichloro-1H-indole (2i) (186 mg, 1.0 mmol) afforded 3,3′-(1-
phenylethane-1,1-diyl)bis(5,6-dichloro-1H-indole) (3ai) (43.6 mg,
0.092 mmol, 46% yield); yellowish solid (petroleum ether/ethyl
1
acetate = 4/1); melting point: 185−187 °C; H NMR (600 MHz,
4.6.15. 2,2′-(1-Phenylethane-1,1-diyl)bis(1H-pyrrole) (3ao). 3-
Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and 1H-pyrrole
(2o) (67.1 mg, 1.0 mmol) afforded 2,2′-(1-phenylethane-1,1-
diyl)bis(1H-pyrrole) (3ao) (23.6 mg, 0.1 mmol, 50% yield);
yellowish solid (petroleum ether/ethyl acetate = 5/1); melting
DMSO-d6): δ 11.20 (s, 2H), 7.62 (s, 2H), 7.30−7.20 (m, 5H), 7.05
(s, 2H), 6.95 (d, J = 2.4 Hz, 2H), 2.19 (s, 3H); 13C{1H} NMR (101
MHz, DMSO-d6): δ 147.6, 136.4, 135.9, 128.4, 126.8, 126.3, 125.2,
122.6, 121.7, 121.0, 119.9, 113.7, 43.2, 29.7; HRMS (APCI) m/z: [M
− H]− calcd for C24H16Cl4N2, 470.9995, found, 470.9987.
1
point: 221−223 °C; H NMR (400 MHz, CDCl3): δ 7.80 (s, 2H),
4.6.10. 3,3′-(1-Phenylethane-1,1-diyl)bis(1H-indol-5-ol) (3aj). 3-
Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and 1H-indol-5-ol
(2j) (133.2 mg, 1.0 mmol) afforded 3,3′-(1-phenylethane-1,1-
diyl)bis(1H-indol-5-ol) (3aj) (44.2 mg, 0.12 mmol, 60% yield);
yellowish solid (petroleum ether/ethyl acetate = 3/1); melting point:
7.28 (s, 1H), 7.24 (d, J = 7.0 Hz, 2H), 7.15−7.10 (m, 2H), 6.68 (d, J
= 1.4 Hz, 2H), 6.18 (dd, J = 5.8, 2.8 Hz, 2H), 5.98 (d, J = 3.3 Hz,
2H), 2.04 (d, J = 15.0 Hz, 3H); 13C{1H} NMR (101 MHz, DMSO-
d6): δ 149.3, 138.0, 128.1, 127.6, 126.3, 117.6, 106.7, 106.4, 44.7,
28.5; HRMS (APCI) m/z: [M − H]− calcd for C16H16N2, 235.1241;
found, 235.1241.
1
191−193 °C; H NMR (400 MHz, DMSO-d6): δ 10.48 (d, J = 2.2
Hz, 2H), 8.42 (s, 2H), 7.34−7.30 (m, 2H), 7.25 (t, J = 7.6 Hz, 2H),
7.19−7.15 (m, 2H), 7.13 (s, 1H), 6.59 (d, J = 2.5 Hz, 2H), 6.54 (d, J
= 2.3 Hz, 1H), 6.52 (d, J = 2.3 Hz, 1H), 6.49 (d, J = 2.2 Hz, 2H), 2.17
(s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6): δ 149.9, 132.1, 128.2,
128.0, 127.2, 124.4, 122.3, 112.2, 111.3, 105.8, 43.5, 28.9; HRMS
(APCI) m/z: [M − H]− calcd for C24H20N2O2, 367.1452; found,
367.1455.
4.6.16. 5,5′-(1-Phenylethane-1,1-diyl)bis(2-methyl-1H-pyrrole)
(3ap). 3-Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and 2-
methyl-1H-pyrrole (2p) (81.1 mg, 1.0 mmol) afforded 5,5′-(1-
phenylethane-1,1-diyl)bis(2-methyl-1H-pyrrole) (3ap) (27 mg, 0.102
mmol, 51% yield); yellowish solid (petroleum ether/ethyl acetate =
1
5/1); melting point: 161−162 °C; H NMR (400 MHz, CDCl3): δ
7.51 (s, 2H), 7.28 (s, 1H), 7.23 (d, J = 6.9 Hz, 2H), 7.17−7.13 (m,
2H), 5.85−5.74 (m, 4H), 2.20 (s, 6H), 1.99 (s, 3H); 13C{1H} NMR
(101 MHz, DMSO-d6): δ 149.7, 136.6, 128.0, 127.6, 126.7, 126.2,
106.2, 104.5, 44.6, 28.5, 13.4; HRMS (APCI) m/z: [M − H]− calcd
for C18H20N2, 263.1554; found, 263.1554.
4.6.11. 3,3′-(1-Phenylethane-1,1-diyl)bis(1H-indole-5-carboni-
trile) (3ak). 3-Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and
1H-indole-5-carbonitrile (2k) (142.2 mg, 1.0 mmol) afforded 3,3′-(1-
phenylethane-1,1-diyl)bis(1H-indole-5-carbonitrile) (3ak) (14.7 mg,
0.038 mmol, 19% yield); yellowish solid (petroleum ether/ethyl
4.6.17. 3-(1-(5,6-Dimethoxy-1H-indol-2-yl)-1-phenylethyl)-5,6-
dimethoxy-1H-indole (3aq). 3-Phenylpropiolic acid (1a) (29.2 mg,
0.2 mmol) and 5,6-dimethoxy-1H-indole (2q) (177.1 mg, 1.0 mmol)
afforded 3-(1-(5,6-dimethoxy-1H-indol-2-yl)-1-phenylethyl)-5,6-di-
methoxy-1H-indole (3aq) (28.3 mg, 0.062 mmol, 31% yield);
yellowish solid (petroleum ether/ethyl acetate = 5/1); melting
1
acetate = 2/1); melting point: 261−263 °C; H NMR (400 MHz,
CDCl3): δ 8.50 (s, 2H), 7.76 (s, 1H), 7.54 (s, 1H), 7.41 (d, J = 4.1
Hz, 2H), 7.36 (t, J = 7.7 Hz, 3H), 7.30 (d, J = 2.4 Hz, 3H), 7.18 (s,
1H), 6.87 (d, J = 1.8 Hz, 2H), 2.32 (s, 3H); 13C{1H} NMR (101
MHz, DMSO-d6): δ 147.7, 139.3, 128.5, 128.0, 126.7, 126.6, 126.3,
126.1, 123.9, 123.8, 121.2, 113.6, 100.7, 43.4, 29.9; HRMS (APCI)
m/z: [M − H]− calcd for C26H18N4, 385.1459; found, 385.1448.
4.6.12. 3,3′-(1-Phenylethane-1,1-diyl)bis(5-nitro-1H-indole)
(3al). 3-Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol) and 5-
nitro-1H-indole (2l) (162.1 mg, 1.0 mmol) afforded 3,3′-(1-
1
point: 385−387 °C; H NMR (400 MHz, DMSO-d6): δ 10.61 (s,
1H), 10.43 (s, 1H), 7.31−7.17 (m, 5H), 6.94 (s, 1H), 6.87 (s, 1H),
6.83 (s, 1H), 6.71 (d, J = 2.3 Hz, 1H), 6.17 (s, 1H), 5.78 (d, J = 1.7
Hz, 1H), 3.72 (d, J = 4.3 Hz, 6H), 3.69 (s, 3H), 3.28 (s, 3H), 2.15 (s,
3H); 13C{1H} NMR (101 MHz, DMSO-d6): δ 148.3, 146.5, 146.2,
8346
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1
145.1, 144.6, 143.9, 131.8, 131.2, 128.1, 128.0, 126.3, 122.4, 122.1,
120.6, 119.4, 103.9, 103.2, 100.2, 95.7, 95.6, 56.7, 56.2, 56.1, 56.1,
44.5, 28.9; HRMS (APCI) m/z: [M − H]− calcd for C28H28N2O4,
455.1976; found, 455.1971.
5/1); melting point: 112−114 °C; H NMR (400 MHz, CDCl3): δ
7.81 (s, 2H), 7.37−7.28 (m, 6H), 7.23 (d, J = 2.6 Hz, 2H), 7.13 (t, J =
7.4 Hz, 2H), 6.94 (t, J = 7.5 Hz, 2H), 6.58 (d, J = 1.8 Hz, 2H), 2.31
(s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6): δ 147.2, 137.1, 130.9,
130.0, 126.2, 124.1, 123.4, 121.9, 121.7, 119.8, 119.1, 111.3, 43.5,
28.7; HRMS (APCI) m/z: [M − H]− calcd for C24H19BrN2,
413.0659; found, 413.0654.
4.6.18. 3,3′-(1-(4-Methoxyphenyl)ethane-1,1-diyl)bis(1H-indole)
(3ba). 3-(4-Methoxyphenyl)propiolic acid (1b) (35.2 mg, 0.2
mmol) and 1H-indole (2a) (117.2 mg, 1.0 mmol) afforded 3,3′-(1-
(4-methoxyphenyl)ethane-1,1-diyl)bis(1H-indole) (3ba) (52.5 mg,
0.156 mmol, 78% yield); yellowish solid (petroleum ether/ethyl
4.6.24. 3,3′-(1-(3-Methoxyphenyl)ethane-1,1-diyl)bis(1H-indole)
(3ha). 3-(3-Methoxyphenyl)propiolic acid (1h) (35.2 mg, 0.2
mmol) and 1H-indole (2a) (117.2 mg, 1.0 mmol) afforded 3,3′-(1-
(3-methoxyphenyl)ethane-1,1-diyl)bis(1H-indole) (3ha) (60 mg,
0.164 mmol, 82% yield); yellowish solid (petroleum ether/ethyl
1
acetate = 4/1); melting point: 225−227 °C; H NMR (400 MHz,
CDCl3): δ 7.71 (s, 2H), 7.30 (d, J = 7.8 Hz, 3H), 7.24 (s, 2H), 7.09
(t, J = 7.2 Hz, 3H), 6.91 (t, J = 7.3 Hz, 2H), 6.72 (d, J = 8.3 Hz, 2H),
6.49 (s, 2H), 3.71 (s, 3H), 2.28 (s, 3H); 13C{1H} NMR (101 MHz,
DMSO-d6): δ 157.5, 141.1, 137.5, 129.0, 126.5, 123.7, 123.5, 121.4,
120.7, 118.0, 112.9, 111.6, 56.7, 42.8, 29.0; HRMS (APCI) m/z: [M
− H]− calcd for C25H22N2O, 365.1659; found, 365.1647.
1
acetate = 4/1); melting point: 211−213 °C; H NMR (400 MHz,
CDCl3): δ 7.60 (s, 2H), 7.31 (d, J = 7.8 Hz, 2H), 7.20 (d, J = 8.3 Hz,
2H), 7.10 (dd, J = 16.9, 8.5 Hz, 3H), 6.91 (dd, J = 17.4, 10.3 Hz, 4H),
6.71 (d, J = 8.4 Hz, 1H), 6.42 (s, 2H), 3.63 (s, 3H), 2.25 (d, J = 28.4
Hz, 3H); 13C{1H} NMR (101 MHz, DMSO-d6): δ 157.4, 140.9,
137.5, 129.1, 126.5, 123.7, 123.6, 121.5, 120.9, 118.3, 113.3, 112.0,
55.3, 42.9, 29.7; HRMS (APCI) m/z: [M − H]− calcd for
C25H22N2O, 365.1659; found, 365.1651.
4.6.19. 3,3′-(1-(p-Tolyl)ethane-1,1-diyl)bis(1H-indole) (3ca). 3-(p-
Tolyl)propiolic acid (1c) (32 mg, 0.2 mmol) and 1H-indole (2a)
(117.2 mg, 1.0 mmol) afforded 3,3′-(1-(p-tolyl)ethane-1,1-diyl)bis-
(1H-indole) (3ca) (50.5 mg, 0.144 mmol, 72% yield); yellowish solid
(petroleum ether/ethyl acetate = 5/1); melting point: 105−107 °C;
1H NMR (400 MHz, CDCl3): δ 7.61 (s, 2H), 7.30 (d, J = 7.7 Hz,
2H), 7.24 (d, J = 7.6 Hz, 4H), 7.10 (t, J = 7.2 Hz, 2H), 7.01 (d, J = 7.3
Hz, 2H), 6.91 (d, J = 7.0 Hz, 2H), 6.48 (s, 2H), 2.36−2.16 (m, 6H);
13C{1H} NMR (101 MHz, DMSO-d6): δ 145.6, 137.5, 134.7, 128.2,
4.6.25. 3,3′-(1-(m-Tolyl)ethane-1,1-diyl)bis(1H-indole) (3ia). 3-
(m-Tolyl)propiolic acid (1i) (32 mg, 0.2 mmol) and 1H-indole (2a)
(117.2 mg, 1.0 mmol) afforded 3,3′-(1-(m-tolyl)ethane-1,1-diyl)bis-
(1H-indole) (3ia) (45.6 mg, 0.13 mmol, 65% yield); yellowish solid
(petroleum ether/ethyl acetate = 5/1); melting point: 107−109 °C;
1H NMR (400 MHz, CDCl3): δ 7.61 (s, 2H), 7.31 (d, J = 8.0 Hz,
2H), 7.26−7.19 (m, 3H), 7.11 (dd, J = 14.5, 7.2 Hz, 4H), 6.98 (d, J =
7.1 Hz, 1H), 6.90 (t, J = 7.5 Hz, 2H), 6.47 (d, J = 1.7 Hz, 2H), 2.31
(s, 3H), 2.21 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6): δ 148.0,
137.2, 137.1, 128.7, 127.7, 126.6, 126.5, 124.8, 123.5, 122.2, 121.5,
118.9, 111.2, 43.7, 28.8, 21.8; HRMS (APCI) m/z: [M − H]− calcd
for C25H22N2, 349.1710; found, 349.1701.
4.6.26. 3,3′-(1-(3,4,5-Trimethoxyphenyl)ethane-1,1-diyl)bis(1H-
indole) (3ja). 3-(3,4,5-Trimethoxyphenyl)propiolic acid (1j) (47.2
mg, 0.2 mmol) and 1H-indole (2a) (117.2 mg, 1.0 mmol) afforded
3,3′-(1-(3,4,5-trimethoxyphenyl)ethane-1,1-diyl)bis(1H-indole) (3ja)
(75.0 mg, 0.176 mmol, 88% yield); yellowish solid (petroleum ether/
127.9, 126.5, 123.5, 121.4, 120.7, 118.0, 111.6, 43.1, 29.0, 18.2;
HRMS (APCI) m/z: [M − H]− calcd for C25H22N2, 349.1710; found,
349.1710.
4.6.20. 3,3′-(1-(4-(Trifluoromethyl)phenyl)ethane-1,1-diyl)bis-
(1H-indole) (3da). 3-(4-(Trifluoromethyl)-phenyl)propiolic acid
(1d) (42.8 mg, 0.2 mmol) and 1H-indole (2a) (117.2 mg, 1.0
mmol) afforded 3,3′-(1-(4-(trifluoromethyl)phenyl)ethane-1,1-diyl)-
bis(1H-indole) (3da) (54.2 mg, 0.134 mmol, 67% yield); yellowish
solid (petroleum ether/ethyl acetate = 5/1); melting point: 95−97
°C; 1H NMR (400 MHz, CDCl3): δ 7.81 (s, 2H), 7.46 (q, J = 8.6 Hz,
4H), 7.27 (dd, J = 12.2, 8.2 Hz, 4H), 7.13 (t, J = 7.5 Hz, 2H), 6.93 (t,
J = 7.5 Hz, 2H), 6.54 (d, J = 1.5 Hz, 2H), 2.33 (s, 3H); 13C{1H}
NMR (101 MHz, DMSO-d6): δ 153.4, 137.5, 128.8, 126.2, 124.6,
123.8, 122.4, 121.1, 120.9, 118.4, 111.9, 43.8, 29.0; HRMS (APCI)
m/z: [M − H]− calcd for C25H19F3N2, 403.1428; found, 403.1417.
4.6.21. 3,3′-(1-(4-Fluorophenyl)ethane-1,1-diyl)bis(1H-indole)
(3ea). 3-(4-Fluorophenyl)propiolic acid (1e) (32.8 mg, 0.2 mmol)
and 1H-indole (2a) (117.2 mg, 1.0 mmol) afforded 3,3′-(1-(4-
fluorophenyl)ethane-1,1-diyl)bis(1H-indole) (3ea) (48.2 mg, 0.136
mmol, 68% yield); yellowish solid (petroleum ether/ethyl acetate =
1
ethyl acetate = 4/1); melting point: 386−388 °C; H NMR (400
MHz, DMSO-d6): δ 10.77 (s, 2H), 7.33 (d, J = 8.1 Hz, 2H), 7.10 (d, J
= 8.0 Hz, 2H), 6.98 (t, J = 7.6 Hz, 2H), 6.79−6.74 (m, 4H), 6.63 (s,
2H), 3.63 (s, 3H), 3.50 (s, 6H), 2.21 (s, 3H); 13C{1H} NMR (101
MHz, DMSO-d6): δ 152.3, 144.5, 137.4, 136.3, 126.5, 123.8, 123.2,
121.5, 120.9, 118.3, 112.0, 106.5, 60.5, 56.2, 43.8, 29.7; HRMS
(APCI) m/z: [M − H]− calcd for C27H26N2O3, 425.1871; found,
425.1867.
1
5/1); melting point: 122−123 °C; H NMR (400 MHz, CDCl3): δ
4.6.27. 3,3′-(1-(Naphthalen-2-yl)ethane-1,1-diyl)bis(1H-indole)
(3ka). 3-(Naphthalen-2-yl)propiolic acid (1k) (39.2 mg, 0.2 mmol)
and 1H-indole (2a) (117.2 mg, 1.0 mmol) afforded 3,3′-(1-
(naphthalen-2-yl)ethane-1,1-diyl)bis(1H-indole) (3ka) (39.4 mg,
0102 mmol, 51% yield); yellow solid (petroleum ether/ethyl acetate
7.70 (s, 2H), 7.33−7.23 (m, 6H), 7.11 (t, J = 7.5 Hz, 2H), 6.89 (dt, J
= 17.1, 8.0 Hz, 4H), 6.49 (d, J = 1.4 Hz, 2H), 2.30 (s, 3H); 13C{1H}
NMR (101 MHz, CDCl3): δ 162.4 (d, JC−F = 252.5 Hz), 159.9, 143.8
(d, JC−F = 3.0 Hz), 137.2, 129.7 (d, JC−F = 7.7 Hz), 126.3, 124.5,
123.4, 122.0, 121.7, 119.1, 114.5 (d, JC−F = 21.2 Hz), 111.3, 43.4,
29.0; 19F NMR (376 MHz, CDCl3): δ −117.9 (td, J = 8.9, 4.5 Hz);
HRMS (APCI) m/z: [M − H]− calcd for C24H19FN2, 353.1460;
found, 353.1450.
1
= 7/1); melting point: 266−268 °C; H NMR (400 MHz, DMSO-
d6): δ 10.83 (d, J = 1.7 Hz, 2H), 7.83 (dd, J = 7.9, 5.7 Hz, 2H), 7.77−
7.68 (m, 2H), 7.49 (dd, J = 8.7, 1.8 Hz, 1H), 7.46−7.39 (m, 2H), 7.36
(d, J = 8.1 Hz, 2H), 7.11 (d, J = 8.1 Hz, 2H), 7.00 (dd, J = 11.2, 3.9
Hz, 2H), 6.78−6.71 (m, 4H), 2.34 (s, 3H); 13C{1H} NMR (101
MHz, DMSO-d6): δ 146.4, 137.5, 133.2, 131.9, 128.4, 127.7, 127.6,
127.3, 126.5, 126.2, 125.9, 125.6, 124.0, 123.1, 121.4, 121.0, 118.5,
112.1, 43.8, 29.4; HRMS (APCI) m/z: [M − H]− calcd for C28H22N2,
385.1710; found, 385.1709.
4.6.22. 3,3′-(1-(4-Chlorophenyl)ethane-1,1-diyl)bis(1H-indole)
(3fa). 3-(4-Chlorophenyl)propiolic acid (1f) (36.1 mg, 0.2 mmol)
and 1H-indole (2a) (117.2 mg, 1.0 mmol) afforded 3,3′-(1-(4-
chlorophenyl)ethane-1,1-diyl)bis(1H-indole) (3fa) (32.5 mg, 0.092
mmol, 46% yield); yellowish solid (petroleum ether/ethyl acetate =
1
5/1); melting point: 106−108 °C; H NMR (400 MHz, CDCl3): δ
4.6.28. 3,3′-(1-(Thiophen-2-yl)ethane-1,1-diyl)bis(1H-indole)
(3la). 3-(Thiophen-2-yl)propiolic acid (1l) (30.4 mg, 0.2 mmol)
and 1H-indole (2a) (117.2 mg, 1.0 mmol) afforded 3,3′-(1-
(thiophen-2-yl)ethane-1,1-diyl)bis(1H-indole) (3la) (28 mg, 0.082
mmol, 42% yield); yellowish solid (petroleum ether/ethyl acetate =
7.74 (s, 2H), 7.28 (d, J = 7.2 Hz, 6H), 7.18−7.10 (m, 4H), 6.93 (t, J =
7.5 Hz, 2H), 6.52 (d, J = 1.6 Hz, 2H), 2.29 (s, 3H); 13C{1H} NMR
(101 MHz, DMSO-d6): δ 146.7, 137.1, 131.6, 129.6, 127.9, 126.3,
124.2, 123.4, 122.0, 121.7, 119.1, 111.3, 43.5, 28.8; HRMS (APCI)
m/z: [M − H]− calcd for C24H19ClN2, 369.1164; found, 369.1154.
4.6.23. 3,3′-(1-(4-Bromophenyl)ethane-1,1-diyl)bis(1H-indole)
(3ga). 3-(4-Bromophenyl)propiolic acid (1g) (45 mg, 0.2 mmol)
and 1H-indole (2a) (117.2 mg, 1.0 mmol) afforded 3,3′-(1-(4-
bromophenyl)ethane-1,1-diyl)bis(1H-indole) (3ga) (33.2 mg, 0.08
mmol, 40% yield); yellowish solid (petroleum ether/ethyl acetate =
1
5/1); melting point: 168−170 °C; H NMR (400 MHz, CDCl3): δ
7.71 (s, 2H), 7.36 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 7.11
(t, J = 7.3 Hz, 3H), 6.93 (t, J = 7.5 Hz, 2H), 6.86 (s, 2H), 6.63 (d, J =
1.8 Hz, 2H), 2.38 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6): δ
154.6, 137.1, 126.2, 126.1, 125.0, 124.6, 123.6, 123.1, 121.9, 121.6,
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Article
119.1, 111.3, 41.9, 30.3; HRMS (APCI) m/z: [M − H]− calcd for
C22H18N2S, 341.1118; found, 341.1116.
(m, 2H), 7.32−7.27 (m, 2H), 7.26−7.21 (m, 2H), 7.21−7.15 (m,
1H), 7.02−6.95 (m, 1H), 6.84 (dd, J = 8.8, 2.4 Hz, 1H), 6.75 (d, J =
2.4 Hz, 1H), 6.66 (d, J = 2.6 Hz, 1H), 6.63 (d, J = 2.5 Hz, 1H), 3.64
(s, 3H), 2.39 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ 153.2,
147.9, 137.1, 132.3, 128.1, 127.8, 126.9, 126.5, 125.8, 124.6, 124.4,
124.0, 123.5, 122.1, 121.5, 118.9, 111.7, 111.5, 111.2, 104.2, 55.8,
43.7, 28.7; HRMS (APCI) m/z: [M − H]− calcd for C25H22N2O,
365.1659; found, 365.1653.
4.6.29. 3,3′-(Propane-2,2-diyl)bis(1H-indole) (3ma). But-2-ynoic
acid (1m) (16.8 mg, 0.2 mmol) and 1H-indole (2a) (117.2 mg, 1.0
mmol) afforded 3,3′-(propane-2,2-diyl)bis(1H-indole) (3ma) (14.8
mg, 0.054 mmol, 27% yield); yellowish solid (petroleum ether/ethyl
1
acetate = 6/1); melting point: 165−168 °C; H NMR (400 MHz,
CDCl3): δ 7.92 (s, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.1 Hz,
2H), 7.07 (t, J = 7.4 Hz, 4H), 6.88 (t, J = 7.5 Hz, 2H), 1.92 (s, 6H);
13C{1H} NMR (101 MHz, DMSO-d6): δ 137.5, 126.5, 124.2, 121.2,
120.7, 120.7, 118.0, 111.8, 34.6, 30.5; HRMS (APCI) m/z: [M − H]−
calcd for C19H18N2, 273.1397; found, 273.1400.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00762.
■
sı
4.6.30. 3,3′-(Butane-2,2-diyl)bis(1H-indole) (3na). Pent-2-ynoic
acid (1n) (19.6 mg, 0.2 mmol) and 1H-indole (2a) (117.2 mg, 1.0
mmol) afforded 3,3′-(butane-2,2-diyl)bis(1H-indole) (3na) (15 mg,
0.052 mmol, 26% yield); yellowish solid (petroleum ether/ethyl
General methods, optimizations of reaction conditions,
1
and H NMR, 13C NMR, and HRMS spectra (PDF)
1
acetate = 6/1); melting point: 179−181 °C; H NMR (400 MHz,
CDCl3): δ 7.82 (s, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.1 Hz,
2H), 6.98 (t, J = 5.9 Hz, 4H), 6.76 (t, J = 7.5 Hz, 2H), 2.33 (q, J = 7.3
Hz, 2H), 1.73 (s, 3H), 0.68 (t, J = 7.3 Hz, 3H); 13C{1H} NMR (101
MHz, DMSO-d6): δ 137.5, 126.5, 123.0, 122.0, 120.7, 120.6, 117.9,
111.7, 38.2, 32.6, 26.6, 9.3; HRMS (APCI) m/z: [M − H]− calcd for
C20H20N2, 287.1554; found, 287.1556.
AUTHOR INFORMATION
Corresponding Author
■
Guochuan Yin − School of Chemistry and Chemical
Engineering, Key Laboratory of Material Chemistry for
Energy Conversion and Storage (Huazhong University of
Science and Technology), Ministry of Education, Hubei Key
Laboratory of Material Chemistry and Service Failure,
Huazhong University of Science and Technology, Wuhan
430074, PR China; orcid.org/0000-0003-1003-8478;
Email: gyin@hust.edu.cn
4.6.31. 3-(1-(5-Methyl-1H-pyrrol-2-yl)-1-phenylethyl)-1H-indole
(5aap). 3-(1-Phenylvinyl)-1H-indole (5aa) (21.9 mg, 0.1 mmol),
1H-indole (2a) (11.7 mg, 0.1 mmol), and 2-methyl-1H-pyrrole (2o)
(8.1 mg, 0.1 mmol) afforded 3-(1-(5-methyl-1H-pyrrol-2-yl)-1-
phenylethyl)-1H-indole (5aap) (8.7 mg, 0.029 mmol, 29% yield);
yellowish solid (petroleum ether/ethyl acetate = 6/1); melting point:
1
171−173 °C; H NMR (400 MHz, DMSO-d6): δ 10.82 (s, 1H),
10.11 (s, 1H), 7.33 (d, J = 8.1 Hz, 1H), 7.26−7.15 (m, 5H), 6.98 (t, J
= 7.5 Hz, 1H), 6.88 (d, J = 8.0 Hz, 1H), 6.74 (dd, J = 10.0, 4.8 Hz,
2H), 5.53 (s, 1H), 5.32 (s, 1H), 2.13 (s, 3H), 2.07 (s, 3H); 13C{1H}
NMR (101 MHz, DMSO-d6): δ 149.0, 137.4, 137.3, 128.0, 127.9,
126.5, 126.5, 126.1, 123.7, 123.6, 121.3, 120.9, 118.4, 111.9, 106.3,
104.6, 43.9, 28.9, 13.4; HRMS (APCI) m/z: [M − H]− calcd for
C21H20N2, 299.1554; found, 299.1546.
4.6.32. 2-(1-Phenylvinyl)-1H-pyrrole (5ao). Yellowish oil (petro-
leum ether/ethyl acetate = 40/1, 21.9 mg, 66% yield); 1H NMR (400
MHz, DMSO-d6): δ 11.08 (s, 1H), 7.42−7.35 (m, 5H), 6.83 (d, J =
1.5 Hz, 1H), 6.05−5.97 (m, 1H), 5.84 (t, J = 3.5 Hz, 1H), 5.47 (s,
1H), 4.99 (s, 1H); 13C{1H} NMR (101 MHz, DMSO-d6): δ 141.6,
141.3, 131.6, 128.6, 128.5, 128.2, 120.1, 109.7, 108.7, 108.6.
4.6.33. 3,3′-(2-Phenylethane-1,1-diyl)bis(1H-indole) (4aa).19 It is
a known byproduct in 3 synthesis, as shown in Section 4.2 (4aa, 5.38
mg, 0.016 mmol, 8% yield): yellowish oil (petroleum ether/ethyl
acetate = 5/1); 1H NMR (400 MHz, CDCl3): δ 7.88 (s, 2H), 7.47 (d,
J = 7.9 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 7.12 (t, J = 7.5 Hz, 2H),
6.96 (q, J = 6.6 Hz, 7H), 6.64−6.50 (m, 2H), 4.84 (t, J = 7.2 Hz, 1H),
3.40 (d, J = 7.3 Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3): δ 144.8,
136.6, 130.4, 127.0, 126.1, 122.0, 119.7, 119.6, 119.2, 118.8, 115.8,
111.2, 37.2, 34.5.
Authors
Miao Zeng − School of Chemistry and Chemical Engineering,
Key Laboratory of Material Chemistry for Energy
Conversion and Storage (Huazhong University of Science
and Technology), Ministry of Education, Hubei Key
Laboratory of Material Chemistry and Service Failure,
Huazhong University of Science and Technology, Wuhan
430074, PR China
Jing-Wen Xue − School of Chemistry and Chemical
Engineering, Key Laboratory of Material Chemistry for
Energy Conversion and Storage (Huazhong University of
Science and Technology), Ministry of Education, Hubei Key
Laboratory of Material Chemistry and Service Failure,
Huazhong University of Science and Technology, Wuhan
430074, PR China
Hongwu Jiang − School of Chemistry and Chemical
Engineering, Key Laboratory of Material Chemistry for
Energy Conversion and Storage (Huazhong University of
Science and Technology), Ministry of Education, Hubei Key
Laboratory of Material Chemistry and Service Failure,
Huazhong University of Science and Technology, Wuhan
430074, PR China
Kaiwen Li − School of Chemistry and Chemical Engineering,
Key Laboratory of Material Chemistry for Energy
Conversion and Storage (Huazhong University of Science
and Technology), Ministry of Education, Hubei Key
Laboratory of Material Chemistry and Service Failure,
Huazhong University of Science and Technology, Wuhan
430074, PR China
4.6.34. 3-(1-Phenylvinyl)-1H-indole (5aa). Yellowish oil (petro-
1
leum ether/ethyl acetate = 5/1, 910 mg, 83% yield); H NMR (400
MHz, CDCl3): δ 7.95 (d, J = 63.7 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H),
7.46 (d, J = 3.8 Hz, 2H), 7.37−7.27 (m, 4H), 7.20 (t, J = 7.5 Hz, 1H),
7.08 (dd, J = 12.9, 4.8 Hz, 2H), 5.58 (s, 1H), 5.42 (s, 1H). 13C{1H}
NMR (101 MHz, CDCl3): δ 143.3, 142.5, 136.6, 128.2, 127.7, 126.3,
124.4, 122.3, 120.8, 120.1, 118.1, 112.2, 111.3.
4.6.35. 1,4-Diphenylbuta-1,3-diyne (6aa).17 It is a byproduct in
3aa synthesis, as shown in Section 4.3 (6aa, 5.7 mg, 0.016 mmol, 14%
1
yield): White solid (petroleum ether/ethyl acetate = 1/0); H NMR
(400 MHz, CDCl3): δ 7.59−7.53 (m, 4H), 7.43−7.34 (m, 6H).
4.6.36. 3-(1-(1H-Indol-3-yl)-1-phenylethyl)-5-methoxy-1H-indole
(5aab). 3-Phenylpropiolic acid (1a) (29.2 mg, 0.2 mmol), 1H-indole
(2a) (58.5 mg, 0.5 mmol), and 5-methoxy-1H-indole (2b) (14.7 mg,
0.1 mmol) afforded 3-(1-(1H-indol-3-yl)-1-phenylethyl)-5-methoxy-
1H-indole (5aab) (16.1 mg, 0.044 mmol, 22% yield); Back oil
(petroleum ether/ethyl acetate = 8/1); 1H NMR (400 MHz, CDCl3):
δ 7.84 (s, 1H), 7.78−7.73 (m, 1H), 7.49−7.41 (m, 2H), 7.40−7.34
Yunong Chen − School of Chemistry and Chemical
Engineering, Key Laboratory of Material Chemistry for
Energy Conversion and Storage (Huazhong University of
Science and Technology), Ministry of Education, Hubei Key
Laboratory of Material Chemistry and Service Failure,
Huazhong University of Science and Technology, Wuhan
430074, PR China
8348
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Article
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Asymmetric Arylation of 3-Indolylmethanols: Enantioselective Syn-
thesis of 3,3′-Bis(indolyl)oxindoles with High Atom Economy.
ChemCatChem 2015, 7, 1211−1221. (g) Zhou, L.-J.; Zhang, Y.-C.;
Zhao, J.-J.; Shi, F.; Tu, S.-J. Organocatalytic Arylation of 3-
Indolylmethanols via Chemo- and Regiospecific C6-Functionalization
of Indoles. J. Org. Chem. 2014, 79, 10390−10398.
Zhuqi Chen − School of Chemistry and Chemical Engineering,
Key Laboratory of Material Chemistry for Energy
Conversion and Storage (Huazhong University of Science
and Technology), Ministry of Education, Hubei Key
Laboratory of Material Chemistry and Service Failure,
Huazhong University of Science and Technology, Wuhan
430074, PR China; orcid.org/0000-0002-0503-9671
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00762
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was financially supported by the National Natural
Science Foundation of China (nos. 21573082 and 21872059)
and the Graduates′ Innovation Fund of Huazhong University
of Science and Technology (no. 5003013019). The NMR and
HRMS analyses were performed in the Analytical and Testing
Center of the Huazhong University of Science and
Technology.
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