Relay Catalysis of Bismuth Trichloride and Byproduct Hydrogen Bromide Enables the Synthesis of Carbazole and Benzo[α]carbazoles from Indoles and α-Bromoacetaldehyde Acetals

Article abstract of DOI:10.1002/adsc.201800669

Benzo[α]carbazoles were synthesized from 2-phenylindoles and α-bromoacetaldehyde using bismuth trichloride as a catalyst. The reaction was triggered by a bismuth trichloride-catalyzed Friedel-Crafts alkylation of these two precursors, which provided a tryptaldehyde intermediate that underwent intramolecular olefination to form the final product. Interestingly, the HBr byproduct generated in the upstream step of the reaction catalyzed the following downstream reaction steps, thus creating a byproduct-participated relay catalytic process. Motivated by this mechanism, we developed a three-component reaction of indole, α-bromoacetaldehyde acetal, and 1,3-dicarbonyl compounds. This study offers a straightforward method for synthesizing substituted carbazoles. (Figure presented.).

Full text of DOI:10.1002/adsc.201800669

Title: Relay Catalysis of Bismuth Trichloride and Byproduct
Hydrogen Bromide Enables Synthesis of Carbazole and
Benzo[α]carbazoles from Indoles and α-Bromoacetaldehyde
acetals
Authors: Fengtian Wu, Wenbo Huang, Yiliqi -, Jian Yang, and Yanlong
Gu
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201800669
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10.1002/adsc.201800669
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Relay Catalysis of Bismuth Trichloride and Byproduct
Hydrogen Bromide Enables the Synthesis of Carbazole and
Benzo[]carbazoles from Indoles and -Bromoacetaldehyde
Acetals
Fengtian Wu,a,c Wenbo Huang,a,c Yiliqi,a Jian Yang,a and Yanlong Gua,b*
a
Key Laboratory of Material Chemistry for Energy Conversion and Storage, Ministry of Education, Hubei Key
Laboratory of Material Chemistry and Service Failure, School of Chemistry and Chemical Engineering,
HuazhongUniversity of Science and Technology, 1037 Luoyu road, Hongshan District, Wuhan 430074, People’s
Republic of China
Fax: (+86)-27-8754-4532; phone: (+86)-27-8754-37 32; E-mail: klgyl@hust.edu.cn
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Lanzhou,
b
730000, People’s Republic of China
F. Wu and W. Huang contributed equally to this work.
c
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. Benzo[]carbazoles were synthesized from 2- a byproduct-participated relay catalytic process. Motivated
phenylindoles and -bromoacetaldehyde using bismuth by this mechanism, we developed a three-component
trichloride as a catalyst. The reaction was triggered by a reaction of indole, -bromoacetaldehyde acetal, and 1,3-
bismuth trichloride-catalyzed Friedel–Crafts alkylation of dicarbonyl compounds. This study offers a straightforward
these two precursors, which provided a tryptaldehyde method for synthesizing substituted carbazoles.
intermediate that underwent intramolecular olefination to
form the final product. Interestingly, the HBr byproduct
generated in the upstream step of the reaction catalyzed the
following downstream reaction steps, thus creating
Keywords: Relay catalysis; Waste-mediated reaction;
Carbazole; Benzo[]carbazole; Acid catalysis
methods to prepare these privileged molecules and
their derivatives,[8] current efforts focus on efficient
synthetic methods using readily available chemicals
under user-friendly conditions. In continuation of our
Introduction
Realization of simple and green synthetic procedures
is an important goal in organic synthesis.[1] To
combat the tedious operational procedure associated
with multistep organic synthesis, synthetic chemists
often use one-pot tandem reactions. In this context,
some new catalysis concepts, such as single-catalyst-
driven auto-tandem catalysis (ATC)[2] and relay
catalysis of two distinctive catalysts[3] have emerged
as significant means to facilitate studies of tandem
reactions. ATC and relay catalysis can shorten
reaction steps and minimize material and energy
inputs. This also minimizes waste generation.[4]
Tangentially, the concept of byproduct-induced (or
waste-induced) relay catalysis was recently
described.[5] However, this concept generally requires
a judicious design of both the reaction and the
catalytic systems, and successful examples of this
type of catalysis are rare.[6]
research on aldo-X bifunctional building blocks in
10]
organic synthesis,[9,
we identified the -
haloacetaldehyde as an important reactant because it
is readily available and inexpensive. In -
bromoacetaldehyde, for example, the presence of a
carbonyl group and a bromo substituent makes this
compound a 1,2-biselectrophile. Therefore, it has
been widely used in organic synthesis.[11]
Here, we report for the first time the acid-catalyzed
synthesis of benzo[]carbazoles and carbazoles with
-bromoacetaldehyde acetals and indoles as
substrates. The tryptaldehyde is formed in situ via
Friedel–Crafts alkylation of -bromoacetaldehyde
acetal with indoles, but it is unstable in air. This is
critical to selective synthesis reactions. The
concomitantly formed byproduct hydrogen bromide
generated in the first step of the reaction played an
intriguing role as a catalyst in the second step. This
established an interesting system involving
byproduct-induced relay catalysis.
Carbazoles and benzo[]carbazoles are naturally
occurring heterocycles. They are important and
biologically active pharmaceuticals that are also
widely used in the synthesis of optoelectronic
materials because of their unique electrical and
thermal properties.[7] Although there are many
Results and Discussion
1
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10.1002/adsc.201800669
Advanced Synthesis & Catalysis
This work used 2-phenylindole 1a and -
bromoacetaldehyde ethylene acetal 2a. Initially, the
reaction was performed in acetonitrile at 60 °C. Only
unreacted starting materials were recovered in the
absence of catalyst (Table 1, entry 1). Weak acids,
such as LiBr and H3BO3, cannot initiate this reaction
(entries 2 and 3). Then, some strong acids, such as
[c] 80 °C.
Interestingly, the expected product 3a can be
isolated with 86% yield by increasing the amount of
BiCl3 to 30 mol% (Table 2, entry 1). Here, the ratio
of 2a/1a is 2/1. When the ratio decreased to 1/1, the
yield dropped to 66% (entry 2). Species 3a can also
be formed when 2a is replaced by an acyclic acetal
2b. However, the yield only reached 64% (entry 3).
Similarly, acetals of -chloroacetaldehyde, 2c and 2d,
can also react with 1a. However, the yields of 3a
were slightly lower (entries 4 and 5). The results in
Table 2 also indicated higher yields with ethylene
acetals than with diethyl acetals. This phenomenon
can be explained by the reaction mechanism, which
will be discussed in detail later. We also tried to use
bromoacetaldehyde to replace acetal 2a, but the
reaction was nonselective, and an inseparable mixture
was obtained. This indicated that the use of acetal is
necessary for this reaction. The BiCl3-promoted
reaction of 1a and 2a can also be used for a gram-
scale synthesis of 3a (entry 6).
.
BF3 Et2O, AlCl3, Sc(OTf)3, and para-toluenesulfonic
acid (PTSA) were examined. Although the expected
product 3a can be obtained, the yields were low
(entries 4 to 7). When Bi(OTf)3 was used, the yield of
3a reached 30% after 3 h (entry 8). Encouraged by
this promising result, other commercially available
bismuth salts were then examined.
The reaction using BiCl3 as the catalyst proceeded
well, and 3a can be isolated with 60% yield (entry 9).
BiBr3 and BiI3 can also promote this reaction, but the
yields were not comparable with those using BiCl3
(entries 10 and 11). The effect of solvent was then
investigated. Acetonitrile was the best solvent
followed by nitromethane (entries 12 to 15). Notably,
a small amount of 1a remained unreacted after 3 h of
heating at 60 °C. We also increased the reaction time,
but no further increase in yield was noted (entry 16).
However, a slight yield improvement was observed
by performing the reaction at 80 °C (entry 17).
Thereafter, the reaction was performed at 80 °C.
Table 2. Reactions of 1a with different acetals.[a]
Table 1. Condition optimization for the reaction between
1a and 2a.[a]
Entry
Acetal
2a
Yield (%)
1
2[b]
86
66
64
72
55
83
Entry
1
Catalyst
─
Solvent
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeNO2
DMSO
Toluene
1,4-Dioxane
MeCN
MeCN
Yield (%)
2a
0
3
2b
2
LiBr
Trace
Trace
8
4
2c
3
H3BO3
5
6[c]
2d
.
4
BF3 Et2O
2a
5
AlCl3
Sc(OTf)3
PTSA
Bi(OTf)3
BiCl3
BiBr3
BiI3
10
12
6
[a]
1a: 0.3 mmol, acetal 2a-d: 0.6 mmol, MeCN: 1 mL,
catalyst: 0.09 mmol, 80 °C, 3 h.
[b] 2a: 0.3 mmol.
6
7
[c] 10.0 mmol scale reaction.
8
30
60
45
32
42
8
With the optimized conditions in hand, we probed
the scope of reaction with respect to the 2-arylindole
component. Scheme 1 shows that indoles with an
electron-donating group at the C5-position readily
participated in the reaction to produce the
corresponding benzo[]carbazoles in high yields (3b
and 3c). The existence of weak electron-withdrawing
groups, such as fluoro or chloro substituents, in the
indole ring showed no significant effect on the
reaction yield (3d and 3e). However, those containing
strongly electron-withdrawing groups, such as ethyl
2-phenyl-1H-indole-5-carboxylate and 5-nitro-2-
phenyl-1H-indole, failed to participate in the reaction.
The reactions with 1-methyl-2-phenylindole and 1-
ethyl-2-phenylindole proceeded rapidly under
9
10
11
12
13
14
15
16[b]
BiCl3
BiCl3
BiCl3
BiCl3
BiCl3
BiCl3
12
15
65
70
17[c]
[a]
1a: 0.3 mmol, 2a: 0.6 mmol, solvent: 1 mL, catalyst:
0.03 mmol, 60 °C, 3 h.
[b] 6 h.
2
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10.1002/adsc.201800669
Advanced Synthesis & Catalysis
standard conditions, and the expected products
formed with more than 70% yield within 20 min (3f
and 3g). Ester and ether groups and a C-C triple bond
in the indole component can all be delivered into the
benzo[]carbazole products (3h, 3i, and 3j). The
existence of an electron-donating group at the para-
position of the C2-phenyl ring also favored this
transformation (3k and 3l). However, methyl 4-(1H-
not be recovered. Interestingly, by adding 10 mol%
of hydrogen bromide (an acetic acid solution of HBr,
40 wt%), 4a can be readily converted to 3a in
acetonitrile. Further studies revealed that hydrogen
bromide alone can effectively catalyze the
transformation of 4a to 3a. However, hydrogen
bromide cannot effectively catalyze the Friedel–
Crafts-type reaction of 1a and 2a. Aldehydes can
indol-2-yl)benzoate cannot participate in this reaction. react with two molecules of indoles via an acid
Two 2-heteroarylindoles were also used in this
reaction. The 2-(thiophen-2-yl)-1H-indole can be
converted to 10H-thieno[2,3-a]carbazole in 81%
yield via the BiCl3 catalyst (3m). However, the
reaction of 2-(furan-2-yl)-1H-indole and 2a produced
an inseparable mixture, possibly due to the
susceptibility of the furan moiety to acids.
catalyst to form di(indolyl)methanes.[18] In the
presence of PTSA, -bromoacetaldehyde reacted
with 1a in an ethanol solution to yield a
di(indolyl)methane derivative 5a. However, this
compound cannot be converted into 3a via BiCl3 or a
HBr catalyst. This observation precluded the
possibility of considering 5a as an intermediate in the
mechanism.
Scheme 1. Substrate scope of BiCl3-catalyzed reaction
between 2-arylindoles and 2a.
The benzo[]carbazoles are important building
blocks for the synthesis of optoelectrical materials.[12]
Many methods have been developed for synthesis of
these compounds including one-pot oxidative
condensation of -tetralone and phenylhydrazine
hydrochloride,[13] oxidative dehydrogenation of
1,2,3,4-tetrahydro-11H-benzo[]carbazole
either dichlorodicyanoquinone[14] or oxygen over a
catalyst,[15]
palladium-based base-catalyzed
intramolecular C−C bond formation of diarylamines
by SRN1 mechanism,[16] and iron- or platinum-
catalyzed intramolecular C-H amination (see Figure
S1 in electronic supporting information).[17] However,
most of these methods involve the use of expensive
reagents or catalysts and also suffer from the lack of
simplicity. In some cases, the yields and selectivities
are far from satisfactory due to several side reactions.
The BiCl3-catalyzed reaction of 1a and 2a provides a
Scheme 2. Some control experiments.
A plausible mechanism was proposed based on
these data (Scheme 3). The first step is the BiCl3-
catalyzed Friedel–Crafts alkylation of 2a. This
involved activation of 2a and the following
with
nucleophilic attack of 1a to
a
carbocation
intermediate (I). Although the bromomethyl and
acetal sides are both reactive toward 1a with a mild
Lewis acid, the bismuth trichloride,[19] reaction
occurred selectively on the bromomethyl side. This
yielded an acetal intermediate (III) via the formation
reaction of intermediate (II). This process
simultaneously released one molecule of HBr.
Some water exists in the reaction system because
the reagents and solvents are not absolutely dry.
Deacetalization of (III) under acidic conditions
yielded 4a. Finally, 3a was formed via HBr-catalyzed
intramolecular olefination of 4a.[20] Although only
one catalyst was added in the beginning of the
reaction, this process involved relay catalysis of
BiCl3 and HBr. The latter is a byproduct of the first
reaction. Although such concomitant byproduct-
participated relay catalysis has been reported in the
literature,[6, 21] this study is the first to establish relay
cost-effective
route
for
synthesis
of
benzo[]carbazoles.
Additional experiments were performed to identify
the mechanism of this reaction (Scheme 2).
Performing the model reaction at 50 °C not only
resulted in a yield drop of 3a but also enabled us to
isolate a tryptaldehyde-type product 4a. Treatment of
4a in the presence of a BiCl3 catalyst did not produce
3a. However, most of 4a decomposed, and it could
3
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10.1002/adsc.201800669
Advanced Synthesis & Catalysis
Scheme 3. Plausible mechanism of the model reaction.
catalysis of two different acid catalysts based on this
concept. The high nucleophilicity of 2-phenylindole
1a is conceivably the key for rendering the model
reaction possible, and this enables rapid trapping of
carbocation intermediate (I). Such trapping forms a
tryptaldehyde-type intermediate (III). The cyclic
acetal 2a is relatively stable compared with acyclic
acetal 2b. With acetal 2a, the acetal group can last for
a longer time without decomposition. Thus, Friedel–
Crafts alkylation of 2a with 1a smoothly proceeded
via the BiCl3 Lewis acid.
To support this relay catalysis-based mechanism,
some hydrogen bromide scavengers, such as betaine,
1,8-bis(dimethylamino)naphthalene (proton sponge),
and γ-butyrolactone, were added respectively in the
reaction of 1a and 2a. Betaine can react with one
equivalent of hydrogen bromide to form betaine
hydrobromide.[22] Species 3a was barely formed in
the presence of betaine. A similar result was obtained
with the proton sponge (Scheme 4). Betaine can
hamper the acid catalyst, and the reaction was also
studied in the presence of betaine hydrobromide.
Here, 3a formed slowly, and the yield reached 11%
after 6 h of reaction. The γ-butyrolactone can react
with hydrogen bromide to form 4-bromobutyric
acid.[23] The presence of γ-butyrolactone imposed a
negative effect on the reaction. As a result, the yield
of 3a decreased to 25%. 4-Bromobutyric acid can be
detected by GC-MS analysis. These results imply that
the concomitant byproduct, hydrogen bromide,
ensured the success of synthesizing 3a from 1a and
2a.
Scheme 4. Control experiments with HBr scavengers.
With this understanding of the relay catalysis-
based mechanism, we next attempted to develop
other tandem reactions of C3-unsubstituted indole
and -bromoacetaldehyde acetals. We primarily
searched for a suitable reagent that could trap the
generated
tryptaldehyde-type
intermediate.
Tryptaldehyde is a commercially available compound,
it is not stable and should be placed in a glovebox
under nitrogen to prevent oxidization to acid.[24] The
combination of the BiCl3 catalyst and indole/2a thus
offers an ideal method for generating in situ
tryptaldehyde. Theoretically, tryptaldehyde possesses
two reactive sites: (i) an aldehyde as an electrophilic
center; and (ii) the C2 position of the indole ring as a
nucleophilic site.[25] To meet this reactivity, a dual
nucleophilic and electrophilic bifunctional building
block should be used. The 1,3-dicarbonyl compounds
may be feasibly used for such purpose because they
are easily available and contain both nucleophilic and
electrophilic sites.[26] Therefore, a three-component
reaction of indole 1b, 2a, and ethyl acetoacetate 6a
was investigated. In this reaction, we expected 6a to
trap the generated tryptaldehyde to form a carbazole
derivative 7a.
Table 3 shows that no reaction occurred in the
absence of catalyst (entry 1). The reaction over 15
mol% of the BiCl3 catalyst proceeded very well and
produced the expected carbazole 7a in 92% yield
(entry 2). By using HBr as the catalyst, 7a was
obtained with 5% yield (entry 3). Under identical
conditions, the use of PTSA and FeCl3 resulted in a
significant yield drop due to the formation of
considerable amounts of inseparable byproducts
(entries 4 and 5). The reaction was also affected by
the amount of BiCl3 catalyst, ratio of substrate,
reaction temperature, and running time (entries 6 to
9). Thus, the reaction conditions indicated in entry 2
4
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10.1002/adsc.201800669
Advanced Synthesis & Catalysis
in Table 3 appeared to be appropriate for this
reaction.
with the aid of either BiCl3 or HBr catalyst, species
8a and 8a′ can react with 1b to yield 7a. Impressively,
in all these cases, formation of by-product 9a is
obvious. However, no 9a can be detected in the
When the reaction was performed at 50 °C,
tryptaldehyde ethylene acetal 4b′ can be isolated in
8% yield (Table 3, entry 8). We therefore speculated
that 7a was formed via a tryptaldehyde-like
intermediate. BiCl3 can catalyze the Friedel–Crafts
alkylation of an indole derivative and 2a, thus, we
mainly aimed to identify the actual catalyst in the
benzoannulation reaction between this intermediate
and 6a. Scheme 5 shows that BiCl3 and HBr can both
catalyze the reaction between tryptaldehyde 4b and
6a producing 7a in 70% and 93% yields, respectively
(equation (a)). However, a remarkable difference was
observed when an acetal of 4b was used. While the
reaction of 4b′ and 6a proceeded well via HBr as a
catalyst, most of 4b′ remained unchanged with the
BiCl3 catalyst (equation (b)). These results imply that
HBr played a key role in the deacetalization reaction
of 4b′.
reaction mixture of
a
BiCl3-catalyzed three-
component reaction of 1b, 2a, and 6a. These results
imply that proposing 8a or 8a′ as the reaction
intermediate might be inappropriate. The reaction
should likely proceed via a mechanism involving
tryptaldehyde and its acetal as intermediates.
Therefore, this reaction is also mechanistically an
example of byproduct HBr-participated relay
catalysis. In the beginning of the reaction, Friedel–
Crafts alkylation of 1b and 2a occurred via the BiCl3
catalyst through the formation of an intermediate (V)
(Scheme 7). This generated 4b′ as the reaction
product and HBr as the byproduct. The HBr catalyzed
deacetalization of 4b′, affording 4b. Finally, 7a was
generated through benzoannulation of 4b and 6a.
Catalysis of HBr played a key role in the last two
steps of the reaction. To obtain an indirect proof of
the catalytic effect of HBr, one equivalent of γ-
butyrolactone was added to the reaction system. In
this case, the yield of 7a dropped to 42% (Table 3,
entry 10). The 4-bromobutyric acid can be detected
by GC-MS analysis. This result verified that partial
removal of hydrogen bromide has a detrimental effect
on the reaction.
Table 3. Three-component reaction of 1b, 2a, and 6a.[a]
Entry
1
Catalyst
Yield (%)
—
0
2
BiCl3
92
3
HBr (AcOH sol. 40 wt%)
5
4
PTSA
12
5
FeCl3
8
6
BiCl3 (10 mol%)
BiCl3
65
7[b]
8[c]
9[d]
56
47 (8)[e]
BiCl3
BiCl3
69
10[f]
BiCl3
42
[a]
Scheme 5. Reaction of 4b-type tryptaldehydes with 6a.
1b: 0.3 mmol, 2a: 0.6 mmol, 6a: 0.6 mmol, MeCN: 1.0
ml, 80 °C 2 h.
[b] Ratio of 1b/2a/6a: 1/1/1.
[c] 50 °C.
[d] 1 h.
[e] yield of tryptaldehyde ethylene acetal 4b′.
[f] γ-Butyrolactone (0.3 mmol) was added.
The 1,3-dicarbonyl compound 6a is also an active
nucleophile, and its reaction with 2a will produce a
substituted 1,3-dicarbonyl compound 8a′ (Scheme 6).
The deacetalization product of this compound
theoretically forms a cyclic dihydrofuran 8a.[27]
Although these compounds were barely detected in
the reaction mixture, we also investigated the
possibility of synthesizing 7a via the benzoannulation
reaction of 1b and 8a or 8a′. As shown in Scheme 6,
Scheme 6. Benzoannulation of 8a or 8a′ with 1b.
5
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10.1002/adsc.201800669
Advanced Synthesis & Catalysis
Scheme 7. Plausible mechanism of the three-component reaction of indole, -bromoacetaldehydes, and 6a.
ketoester is also amenable to this three-component
reaction affording the desired product 7l in 50% yield.
However, the reaction of the indole, 2a, and
acetylacetone proceeded sluggishly producing
compound 7k in 37% yield. The scope of the reaction
with respect to the indole component was next
investigated and found to be excellent. Indoles with
different substituents smoothly reacted with 2a and
6a. Both electron-rich (7n, 7o and 7s) and moderately
electron-poor (7q and 7r) indoles readily participated
in the reaction. However, the target compound cannot
be formed when 6-nitro-1H-indole was used, perhaps
due to the poor nucleophilicity. Notably, the similar
substituted carbazoles have been synthesized with a
Lewis acid-catalyzed benzoannulation protocol via 2-
butoxy-2,3-dihydrofurans
and
indoles
as
substrates.[10e] However, a two-step method has to be
used to synthesize 2-butoxy-2,3-dihydrofurans; this
method also involves the use of Ru complex as
catalyst.[28] The present three-component reaction was
established based on relay catalysis of BiCl3 and
byproduct HBr. This offered a cost-effective route for
accessing carbazole products.
Scheme 8. Scope of three-component reactions of indoles,
2a, and 1,3-dicarbonyl compounds.
Conclusion
Then, we probed the scope of reaction with respect
to both 1,3-dicarbonyl and indole components.
Scheme 8 suggests that various -ketoesters with an
electron-donating -acyl readily participated in this
three-component reaction. This led to the expected
carbazoles in generally good yields (7b–e, 7j).
However, the expected carbazoles cannot be formed
when the -ketoesters with electron-withdrawing -
acyl were used, i.e., ethyl trifluoroacetoacetate or
ethyl benzoylacetate. Ether, double and triple bonds,
and thiophene functionalities can all be delivered into
the product molecules without structural damage (7f–
i, 7m). An acid-liable cyclopropyl-containing -
Straightforward methods for the synthesis of
benzo[]carbazoles and carbazoles from indoles and
-bromoacetaldehyde acetal were developed via the
BiCl3 catalyst. The reaction mechanism involved a
byproduct HBr-participated relay catalysis in which
the BiCl3 catalyst promoted a Friedel–Crafts
alkylation reaction while eliminating the HBr
byproduct. Intriguingly, the resulting HBr played the
role of catalyst in the following steps, and generated
benzo[]carbazole and carbazole products. To the
best of our knowledge, this study is the first to
present this unique system of catalysis, although
6
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10.1002/adsc.201800669
Advanced Synthesis & Catalysis
with 1,2-dichloroethane (10.0 mL) and washed with brine
(2 × 30.0 mL). The acquired organic phase was then dried
over anhydrous Na2SO4. After removing the volatile
solvent, the product 4b′ was obtained by isolation with
silica column chromatography (0.4 g, yield = 99%, eluting
solvent: pertroleum ether/ethyl acetate = 50/1 (v/v)).
similar concomitant waste acid-participated relay
catalysis might already exist in some organic
reactions. This method could be useful for developing
other synthetic methodologies via byproducts
generated in the upstream steps; we are actively
working in this direction.
The Procedure for Synthesis of 5a
The reaction was conducted in 10 mL of V-type flask
equipped with triangle magnetic stirring. Compound 1a
(2.0 mmol), 2e (1.0 mmol, prepared from -
bromoacetaldehyde dimethyl acetal) and PTSA (5 mol%)
in MeOH (4.0 mL). The mixture was then stirred at room
temperature for 0.5 h. After the reaction, the mixture was
diluted with ethyl acetate (15 mL) and washed with brine
(20 mL). The acquired organic phase was then dried over
anhydrous Na2SO4. After removing the volatile solvent, the
product 5a was obtained by isolation with silica column
Experimental Section
General Procedure for synthesis of 3a
In a typical reaction, 1a (0.3 mmol) and 2a (0.6 mmol)
were mixed with BiCl3 (30 mol%) in MeCN (1.0 mL). The
mixture was then stirred at 80 °C for 3 h. After the reaction,
the mixture was cooled to room temperature, and the
product 3a was obtained by isolation with preparative TLC
(56.0 mg, yield = 86%, eluting solvent: pertroleum
ether/ethyl acetate = 20/1 (v/v)). Synthesis of the other
compounds including carbazoles was performed by an
analogous procedure.
chromatography (441.0 mg, yield
= 90%, elutent:
pertroleum ether/ethyl acetate = 5/1 (v/v)).
The Procedure for Synthesis of 7a-s
In a typical reaction, 1b (0.3 mmol), 2a (0.6 mmol) and 6a
The Procedure for Synthesis of 3a in large scale
(0.6 mmol) were mixed with BiCl3 (15 mol%) in MeCN
°
(1.0 mL). The mixture was then stirred at 80 C for 2 h.
The reaction was conducted in a 50.0 mL of bottomed
flask equipped with magnetic stirring and a condenser.
Compound 1a (10.0 mmol) and 2a (20.0 mmol) were
mixed with BiCl3 (3.3 mmol, 30 mol%) in MeCN (30.0
After the reaction, the mixture was cooled to room
temperature, and the product 7a was obtained by isolation
with preparative TLC (69.8 mg, yield = 92%, eluting
solvent: pertroleum ether/ethyl acetate = 10/1 (v/v)).
Synthesis of the other compounds was performed by an
analogous procedure.
°
mL). The mixture was then stirred at 80 C for 3 h. After
the reaction, the mixture was cooled to room temperature
and diluted with ethyl acetate (50.0 mL) and washed with
brine (2 × 50.0 mL). The acquired organic phase was then
dried over anhydrous Na2SO4. After removing the volatile
solvent, the product 3a was obtained by isolation with
silica column chromatography (1.8 g, yield = 83%, eluting
solvent: pertroleum ether/ethyl acetate = 20/1 (v/v)).
The Procedure for Synthesis of 8a
The reaction was conducted in 50.0 mL of bottomed flask
equipped with round magnetic stirring. In a typical reaction,
ethyl
3-oxobutanoate
(10.0
mmol)
and
-
chloroacetaldehyde (wt 40%, 11.0 mmol) were mixed with
NaOH (10.0 mmol) in MeCN (30.0 mL). The mixture was
then stirred at room temperature for 10 min. After the
reaction, the mixture was diluted with ethyl acetate (60.0
mL) and washed with brine (2 × 50.0 mL). The acquired
organic phase was then dried over anhydrous Na2SO4.
After removing the volatile solvent, the product 8a was
obtained by isolation with silica column chromatography
(1.55 g, yield = 90%, eluting solvent: pertroleum
ether/ethyl acetate = 20/1 (v/v)).
The Procedure for Synthesis of 4a
The reaction was conducted in a 50.0 mL of bottomed
flask equipped with magnetic stirring. Compound 1a (10.0
mmol) and 2a (20.0 mmol) were mixed with catalyst (3.0
mmol, 10 mol%) in MeCN (30.0 mL). The mixture was
then stirred at 50 °C for 6 h. After the reaction, the mixture
was cooled to room temperature and diluted with ethyl
acetate (50.0 mL) and washed with brine (2 × 50.0 mL).
The acquired organic phase was then dried over anhydrous
Na2SO4. After removing the volatile solvent, the product
4a was obtained by isolation with silica column
chromatography (0.3 g, yield = 12%, eluting solvent:
pertroleum ether/ethyl acetate = 10/1 (v/v)).
The Procedure for Synthesis of 8a′
The reaction was conducted in 50.0 mL of bottomed flask
equipped with round magnetic stirring. Ethyl 3-
oxobutanoate (10.0 mmol) was added to a mixture of 1.09
g (8.0 mmol) of calcined potassium carbonate in 30.0 mL
of DMSO. The mixture was stirred for 10 h at 80 °C. After
the reaction, the mixture was cooled to room temperature
and then water (80.0 mL) was added. The aqueous phase
was extracted with ethyl acetate (2 × 50.0 mL). The
acquired organic phase was then dried over anhydrous
Na2SO4. After removing the volatile solvent, the product
8a′ was obtained by isolation with silica column
chromatography (1.14 g, yield = 53%, eluting solvent:
pertroleum ether/ethyl acetate = 10/1 (v/v)).
The Procedure for Synthesis of 4b
A solution of tryptophol (5.0 mmol) in DMSO (10.0 mL)
was added IBX (5.5 mmol, 1.1 equiv). The resulting
suspension was stirred at 40 °C for 2 h. After the reaction,
the mixture was cooled to room temperature, and filtered
through a cotton plug. Then the filtrate washed with brine
(30.0 mL) and diluted with ethyl acetate (2 × 20.0 mL).
The acquired organic phase was then dried over anhydrous
Na2SO4. After removing the volatile solvent, the product
4b was obtained by isolation with silica column
chromatography (0.6 g, yield = 78%, eluting solvent:
pertroleum ether/ethyl acetate = 10/1 (v/v)).
Spectroscopic data of compounds
11H-benzo[]carbazole (3a):[14] 56.0 mg, 86%; white
solid, mp: 223–224 oC; 1H (400 Hz, CDCl3, 25 oC, TMS): δ
= 7.31–7.35 (m, 1H), 7.44–7.48 (m, 1H), 7.53–7.62 (m,
3H), 7.68 (d, J = 8.8 Hz, 1H), 8.03 (d, J = 7.6 Hz, 1H),
8.11–8.17 (m, 3H), 8.78 ppm (s, 1H); 13C (100 Hz, CDCl3,
25 oC, TMS): δ = 111.2, 118.6, 119.5, 120.0, 120.1, 120.4,
120.6, 121.2, 124.3, 125.0, 125.4, 125.7, 129.2, 132.6,
135.0, 138.6 ppm.
The Procedure for Synthesis of 4b′
The reaction was conducted in 10.0 mL of V-type flask
equipped with triangle magnetic stirring. Compound 4b
(2.0 mmol), ethylene glycol (4.0 mmol), and PTSA (20
mol%) were mixed in 1,2-dichloroethane (4.0 mL). The
mixture was then stirred at 30 °C for 2 h. After the reaction,
the mixture was cooled to room temperature, and diluted
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800669
Advanced Synthesis & Catalysis
8-Methyl-11H-benzo[]carbazole (3b):[29] 58.9 mg, 85%;
1289, 1189, 1159, 1056, 1015, 965, 914, 855, 808, 782,
743, 682, 599, 557, 510, 439 cm-1; HRMS (EI): m/z: calcd
for C19H17NNaO: 298.1202 [M + Na] +; found: 298.1206.
N-(Prop-2-yn-1-yl)-11H-benzo[]carbazole (3j): 56.6
mg, 74%; white solid, mp: 165–166 oC; 1H (400 Hz,
DMSO-d6, 25 oC): δ = 3.42 (s,1H), 5.75 (d, J = 2.0 Hz, 2H),
7.31–7.35 (m,1H), 7.51–7.54 (m, 1H), 7.58–7.61 (m, 1H),
7.68–7.72 (m, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.87 (d, J =
8.4 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 8.24–8.30 (m, 2H),
8.80 ppm (d, J = 8.4 Hz, 1H); 13C NMR (100 Hz, DMSO-
d6, 25 oC): δ = 35.6, 75.7, 79.8, 109.8, 118.9, 119.2, 119.7,
120.1, 120.9, 121.7, 122.5, 124.9, 125.1, 125.6, 129.1,
133.1, 133.8, 139.7 ppm; IR: v = 3363, 3275, 3049, 2922,
2851, 2115, 1920, 1885, 1800, 1743, 1657, 1592, 1557,
1525, 1466, 1446, 1406, 1381, 1326, 1248, 1253, 1193,
1127, 1037, 924, 1088, 1037, 977, 924, 852, 806, 742, 729,
683, 648, 554, 506, 431 cm-1; HRMS (EI): m/z: calcd for
C19H13NNa: 278.0940 [M + Na] +; found: 278.0945.
o
white solid, mp: 258–259 C; 1H (400 Hz, DMSO-d6, 25
oC): δ = 2.50 (s, 3H), 7.23 (d, J = 8.0 Hz, 1H), 7.52–7.55
(m, 2H), 7.59–7.64 (m, 2H), 7.95 (s, 1H), 8.17 (d, J = 8.0
Hz, 1H), 8.16 (d, J = 8.8 Hz, 1H), 8.48 (d, J = 8.0 Hz, 1H),
o
12.08 (s, 1H); 13C NMR (100 Hz, DMSO-d6, 25 C): δ =
21.2, 111.1, 117.0, 118.9, 119.4, 119.5, 121.3, 121.8, 123.4,
125.1, 125.4, 126.0, 127.8, 128.5, 131.8, 135.4, 137.0.
8-Methoxy-11H-benzo[]carbazole (3c):[30] 66.7 mg,
90%; white solid, mp: 205–206 oC; 1H (400 Hz, DMSO-d6,
o
25 C): δ = 3.88 (s, 3H), 7.05 (dd, J = 2.4, 8.8 Hz, 1H),
7.51–7.64 (m, 4H), 7.73 (d, J = 2.0 Hz, 1H), 8.01 (d, J =
8.0 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 8.48 (d, J = 8.0 Hz,
1H), 12.03 ppm (s, 1H); 13C NMR (100 Hz, DMSO-d6, 25
oC): δ = 55.6, 102.1, 112.0, 114.1, 117.3, 118.6, 119.7,
121.4, 121.7, 123.6, 125.1, 125.3, 128.5, 131.9, 133.6,
135.8, 153.5 ppm.
8-Fluoro-11H-benzo[]carbazole (3d):[31] 56.4 mg, 80%;
o
1
dark brown solid, 214–215 C; H (400 Hz, DMSO-d6, 25
oC): δ = 7.23–7.28 (m, 1H), 7.55–7.66 (m, 4H), 7.99–8.05
(m, 2H), 8.20 (d, J = 8.4 Hz, 1H); 8.50 (d, J = 8.0 Hz, 1H),
3-Methyl-11H-benzo[]carbazole (3k):[34] 57.5 mg, 83%;
o
1
white solid, mp: 195–196 C; H (400 Hz, DMSO-d6, 25
oC): δ = 2,58 (s, 3H), 7.23–7.32 (m, 1H), 7.41–7.45 (m,
2H), 7.56–7.60 (m, 2H), 7.80 (s, 1H), 8.03 (d, J = 8.4 Hz,
1H), 8.10–8.13 (m, 2H), 8.75 ppm (s, 1H); 13C NMR (100
Hz, DMSO-d6, 25 oC): δ = 21.4, 111.0, 118.1, 119.7, 120.0,
120.1, 120.3, 122.1, 124.4, 124.6, 124.7, 125.4, 128.1,
132.2, 132.4, 134.9, 138.5 ppm.
o
12.30 ppm (s, 1H); 13C (100 Hz, DMSO-d6, 25 C): δ =
105.1 (JC-F = 24.0 Hz), 112.2 (JC-F = 3.0 Hz), 112.4 (JC-F
12.0 Hz), 117.2, 119.2, 119.7, 121.3, 121.9, 123.6 (JC-F
=
=
10.0 Hz), 125.6 (JC-F = 12.0 Hz), 128.6, 132.1, 135.2,
136.5, 155.7, 158.0 ppm; 19F (377 Hz, DMSO-d6, 25 oC): δ
= –124.3 (sextet, J = 3.8 Hz, 1F) ppm.
3-Methoxy-11H-benzo[]carbazole (3l):[34] 57.8 mg,
78%; white solid, mp: 243–244 oC; 1H (400 Hz, DMSO-d6,
8-Chloro-11H-benzo[]carbazole (3e):[32] 58.7 mg, 78%;
o
o
white solid, mp: 208–209 C; 1H (400 Hz, DMSO-d6, 25
25 C): δ = 3.91 (s, 3H), 7.18–7.22 (m, 1H), 7.30 (dd, J =
oC): δ = 7.41 (dd, J = 2.0, 7.2 Hz, 1H), 7.56–7.59 (m, 1H),
7.64–7.68 (m, 3H), 8.05 (d, J = 8.0 Hz, 1H), 8.23–8.29 (m,
2H), 8.51 (d, J = 8.0 Hz, 1H), 12.40 ppm (s, 1H); 13C NMR
(100 Hz, DMSO-d6, 25 oC): δ = 112.8, 116.6, 119.3, 119.6,
119.7, 121.2, 121.9, 123.6, 124.3, 124.5, 125.6, 125.7,
128.6, 132.2, 136.1, 137.1 ppm.
2.4, 8.8 Hz, 1H), 7.35–7.39 (m, 1H), 7.48 (d, J = 2.0 Hz,
1H), 7.54–7.61 (m, 2H), 8.11–8.16 ppm (m, 2H), 8.42 (d, J
= 9.2 Hz, 1H), 12.08 (s, 1H); 13C NMR (100 Hz, DMSO-d6,
o
25 C): δ = 55.2, 107.9, 111.2, 115.9, 116.1, 117.0, 118.4,
119.0, 119.4, 120.0, 123.3, 123.4, 124.0, 133.5, 135.6,
138.6, 157.0 ppm.
N-Methyl-11H-benzo[]carbazole (3f):[29] 50.6 mg, 73%;
10H-Thieno[2,3-]carbazole (3m):[35] 54.2 mg, 81%;
o
1
o
1
white solid, mp: 173–174 C; H (400 Hz, CDCl3, 25 C,
TMS): δ = 4.29 (s, 3H), 7.37–7.40 (m, 2H), 7.51–7.63 (m,
4H), 7.70 (d, J = 8.4 Hz, 1H), 8.09 (d, J = 7.6 Hz, 1H),
8.19–8.21 (m, 2H), 8.67 ppm (d, J = 8.0 Hz, 1H); 13C NMR
black solid, mp: 91–92 oC; H (400 Hz, DMSO-d6, 25 oC):
δ = 7.29 (t, J = 7.6 Hz, 1H), 7.42–7.44 (m, 2H), 7.51 (d, J
= 5.6 Hz, 2H), 7.70 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 8.0 Hz,
1H), 8.11 (d, J = 8.0 Hz, 1H), 8.35 ppm (s, 1H); 13C NMR
(100 Hz, DMSO-d6, 25 oC): δ = 111.1, 116.0, 117.4, 119.4,
120.2, 120.3, 122.6, 124.1, 124.3, 125.4, 125.7, 134.2,
139.1, 139.3 ppm.
o
(100 Hz, CDCl3, 25 C, TMS): δ = 33.9, 109.0, 119.0,
119.2, 119.5, 119.7, 120.5, 122.1, 122.8, 123.0, 124.6,
124.7, 125.2, 129.5, 133.7, 135.5, 140.7ppm.
N-Ethyl-11H-benzo[]carbazole (3g):[33] 41.3 mg, 75%;
2-(2-Phenyl-1H-indol-3-yl)acetaldehyde (4a):[24c] 0.3 g,
12%; plight green liquid; 1H (400 Hz, CDCl3, 25 oC,
TMS): δ = 3.86 (d, J = 1.6 Hz, 2H), 7.13–7.16 (m, 1H),
7.20–7.24 (m, 1H), 7.34–7.38 (m, 2H), 7.42–7.47 (m, 4H),
7.52 (d, J = 8.0 Hz, 1H), 8.33 (s, 1H), 9.73 ppm (t, J = 2.4
Hz, 1H); 13C NMR (100 Hz, CDCl3, 25 oC, TMS): δ = 40.2,
o
1
o
white solid, mp: 157–158 C; H (400 Hz, CDCl3, 25 C,
TMS): δ = 1.71 (t, J = 7.2 Hz, 3H), 4.85 (q, J = 7.2 Hz,
2H), 7.43–7.46 (m, 1H), 7.60–7.66 (m, 3H), 7.69–7.73 (m,
1H), 7.77 (d, J = 8.4 Hz, 1H), 8.15 (d, J = 8.0 Hz, 1H),
8.27–8.29 (m, 2H), 8.59 ppm (d, J = 8.4 Hz, 1H); 13C NMR
(100 Hz, CDCl3, 25 oC, TMS): δ = 15.1, 40.5, 108.9, 119.2, 103.1, 111.2, 118.8, 120.4, 122.9, 128.2, 128.4, 129.2,
119.3, 119.6, 119.7, 120.6, 121.9, 122.3, 123.2, 124.6,
124.8, 125.5, 129.7, 133.7, 134.4, 140.0 ppm.
132.2, 136.0, 136.9, 200.2 ppm.
2-(1H-Indol-3-yl)acetaldehyde (4b):[36] 0.6 g, 78%;
1
o
Ethyl 2-(11H-benzo[]carbazol-11-yl)acetate (3h): 63.6
mg, 70%; white solid, mp: 124–125 oC; 1H (400 Hz,
DMSO-d6, 25 oC): δ = 1.20 (t, J = 7.2 Hz, 3H), 4.20 (q, J =
7.2 Hz, 2H), 5.82 (s, 2H), 7.32 (t, J = 7.6 Hz, 1H), 7.47–
7.51 (m, 1H), 7.54–7.64 (m, 2H), 7.75 (d, J = 8.4 Hz, 1H),
7.83 (d, J = 8.4 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 8.25 (d,
J = 7.6 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.37 ppm (d, J =
brown liquid; H (400 Hz, CDCl3, 25 C, TMS): δ = 3.80
(d, J = 1.2 Hz, 2H), 7.13–7.17 (m, 2H), 7.20–7.25 9m, 1H),
7.38 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 8.22 (s,
1H), 9.76 ppm (t, J = 2.4 Hz, 1H); 13C NMR (100 Hz,
CDCl3, 25 oC, TMS): δ = 40.5, 106.2, 111.5, 118.6, 120.1,
122.7, 123.6, 127.5, 136.4, 199.8 ppm.
3-((1,3-Dioxolan-2-yl)methyl)-1H-indole (4b'):[37] 0.4 g,
o
1
o
8.8 Hz, 1H); 13C NMR (100 Hz, DMSO-d6, 25 C): δ =
99%; brown liquid; H (400 Hz, CDCl3, 25 C, TMS): δ =
3.11 (d, J = 4.8 Hz, 2H), 3.78–3.86 (m, 2H), 3.88–3.99 (m,
2H), 5.13–5.16 (m, 1H), 6.97 (d, J = 1.2, Hz, 1H), 7.08–
7.19 (m, 2H), 7.23 (d, J = 7.6 Hz, 1H), 7.65 (d, J = 7.6 Hz,
14.1, 47.7, 61.2, 109.8, 118.9, 119.2, 119.6, 120.0, 120.8,
121.3, 121.8, 122.5, 124.8, 125.0, 125.6, 129.4, 133.1,
134.3, 140.5, 169.3 ppm; IR: v = 3363, 3114, 3047, 2978,
2923, 2851, 1938, 1869, 1796, 1743, 1558, 1526, 1469,
1444, 1409, 1390, 1333, 1288, 1210, 1163, 1130, 1095,
1051, 1018, 988, 913, 861, 801, 735, 630, 553, 509, 436
cm-1; HRMS (EI): m/z: calcd for C20H17NNaO2: 326.1151
[M + Na] +; found: 326.1156.
o
1H), 8.03 ppm (s, 1H); 13C NMR (100 Hz, CDCl3, 25 C,
TMS): δ = 30.6, 65.0, 104.5, 110.3, 111.2, 119.1, 119.4,
122.0, 123.1, 127.8, 136.2 ppm.
3,3'-(2-Bromoethane-1,1-diyl)bis(2-phenyl-1H-indole)
o
1
(5a): 441.0 mg, 90%; white solid, mp: 178–179 C; H
(400 Hz, CDCl3, 25 oC, TMS): δ = 4.46 (d, J = 8.0 Hz, 2H),
5.12 (t, J = 8.4 Hz, 1H), 6.95–6.99 (m, 2H), 7.12–7.15 (m,
2H), 7.22–7.25 (m, 6 H), 7.30–7.33 (m, 6H), 7.59 (d, J =
8.0 Hz, 2H), 8.06 ppm (s, 2H); 13C NMR (100 Hz, CDCl3,
N-(2-Methoxyethyl)-11H-benzo[]carbazole (3i): 61.1
mg, 74%; brown liquid; 1H (400 Hz, DMSO-d6, 25 oC): δ =
3.18 (s, 3H), 3.90 (t, J = 5.6 Hz, 2H), 5.03 (t, J = 5.6 Hz,
2H), 7.28 (t, J = 7.6Hz, 1H), 7.45-7.48 (m, 1H), 7.54–7.58
(m, 1H), 7.63–7.68 (m, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.76
(d, J = 8.0 Hz, 1H ), 8.09 (d, J = 8.0 Hz, 1H), 8.21 (d, J =
7.6 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.63 ppm (d, J = 8.8
o
25 C, TMS): δ = 38.5, 65.2, 110.9, 112.5, 120.0, 120.9,
122.0, 128.0, 128.2, 128.5, 129.0, 133.4, 136.0, 136.5 ppm;
IR: v = 3552, 3396, 3289, 3056, 2966, 2925, 2854, 1886,
1663, 1605, 1549, 1487, 1452, 1425, 1367, 1335, 1309,
1261, 1243, 1184, 1158, 1047, 1018, 964, 922, 881, 845,
744, 700, 665, 609, 564, 537, 501, 436 cm-1; HRMS (EI):
m/z: calcd for C30H23BrN2Na: 513.0937 [M + Na] +; found:
513.0935.
o
Hz, 1H); 13C NMR (100 Hz, DMSO-d6, 25 C): δ = 45.2,
59.5, 71.1, 110.3, 118.8, 119.2, 119.4, 119.6, 120.5, 121.8,
122.1, 122.3, 124.7, 124.8, 125.6, 129.3, 133.1, 133.9,
140.8 ppm; IR: v = 3362, 3053, 2924, 2890, 2815, 1888,
1747, 1660, 1615, 1558, 1528, 1468, 1407, 1383, 1331,
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800669
Advanced Synthesis & Catalysis
Ethyl 1-methyl-9H-carbazole-2-carboxylate (7a):[10e]
117.4, 120.0, 121.2, 122.2, 123.1, 123.3, 125.1, 125.9,
127.1, 139.3, 140.5, 167.3 ppm; IR: v = 3381, 3309, 2955,
2925, 2854, 1717, 1624, 1573, 1500, 1460, 1376, 1328,
1287, 1252, 1215, 1193, 1144, 1050, 1016, 971, 823, 751,
675, 494 cm-1; HRMS (EI): m/z: calcd for C17H13NNaO2:
286.0838 [M + Na] +; found: 286.0834.
o
1
69.8 mg, 92%; white solid, mp: 111–113 C; H (400 Hz,
o
CDCl3, 25 C, TMS): δ = 1.44 (t, J = 7.6 Hz, 3H), 2.82 (s,
3H), 4.41 (q, J = 7.6 Hz, 2H), 7.24–7.27 (m, 1H), 7.44–
7.50 (m, 2H), 7.83 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 8.0 Hz,
1H), 8.09 (d, J = 7.6 Hz, 1H), 8.25 ppm (s, 1H); 13C NMR
o
(100 Hz, CDCl3, 25 C, TMS): δ = 14.6, 15.0, 60.9, 111.1,
2-(Methacryloyloxy)ethyl
1-methyl-9H-carbazole-2-
1
117.4, 120.0, 121.2, 122.0, 122.7, 123.3, 125.6, 126.7,
127.0, 139.5, 140.6, 168.5 ppm.
carboxylate (7i): 56.6 mg, 56%; colourless oil; H (400
o
Hz, CDCl3, 25 C, TMS): δ = 1.98 (s, 3H), 2.84 (s, 3H),
Methyl 1-methyl-9H-carbazole-2-carboxylate (7b):[10e]
4.53–4.55 (m, 2H), 4.60–4.62 (m, 2H), 5.61 (s, 1H), 6.18
(s, 1H), 7.26–7.29 (m, 1H), 7.46–7.51 (m, 2H), 7.84 (d, J =
8.4 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 8.09 (d, J = 7.6 Hz,
1
o
58.1 mg, 81%; colourless oil; H (400 Hz, CDCl3, 25 C,
TMS): δ = 2.80 (s, 3H), 3.94 (s, 3H), 7.22–7.26 (m, 1H),
7.43–7.47 (m, 2H), 7.82 (d, J = 8.4 Hz, 1H), 7.91 (d, J =
8.4 Hz, 1H), 8.07 (d, J = 7.6 Hz, 1H), 8.28 ppm (s, 1H);
o
1H), 8.20 ppm (s, 1H); 13C NMR (100 Hz, CDCl3, 25 C,
TMS): δ = 15.0, 18.3, 62.5, 62.7, 111.1, 117.4, 120.0,
121.2, 122.1, 122.9, 123.1, 125.7, 125.8, 126.1, 127.0,
135.8, 139.6, 140.6, 167.2, 168.1 ppm; IR: v = 3391, 2955,
2922, 2851, 1705, 1622, 1497, 1454, 1417, 1378, 1342,
1284, 1254, 1179, 1146, 1057, 1023, 938, 890, 846, 811,
o
13C NMR (100 Hz, CDCl3, 25 C, TMS): δ = 15.0, 52.0,
111.1, 117.4, 120.0, 121.2, 122.0, 122.9, 123.2, 125.7,
126.2, 127.0, 139.5, 140.6, 169.0 ppm.
Methyl
1-isopropyl-9H-carbazole-2-carboxylate
(7c):[10e] 28.1 mg, 35%; light yellow oil; 1H (400 Hz,
787, 745, 730, 642, 594, 531, 451, 435 cm-1; HRMS (EI):
CDCl3, 25 oC, TMS): δ = 1.55 (s, 3H), 1.57 (s, 3H), 3.95 (s, m/z: calcd for C8H12O2Na: 360.1206 [M + Na] ; found:
+
3H), 4.01–4.07 (m, 1H), 7.23 (s, 1H), 7.45–7.57 9m, 3H),
7.94 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 8.24
360.1204.
Benzyl 1-methyl-9H-carbazole-2-carboxylate (7j):[39]
75.6 mg, 80%; yellow solid, mp: 145–146 oC; 1H (400 Hz,
DMSO-d6, 25 oC): δ = 2.81 (s, 3H), 5.37 (s, 2H), 7.18–7.24
(m, 1H), 7.31–7.38 (m, 1H), 7.41–7.52 (m, 5H), 7.57 (d, J
= 8.0 Hz, 1H), 7.71 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 8.4 Hz,
1H), 8.15 (d, J = 8.0 H,z 1H), 11.48 ppm (s, 1H); 13C NMR
ppm (s, 1H); 13C NMR (100 Hz, CDCl3, 25 C, TMS): δ =
o
22.0, 29.2, 52.4, 58.6, 99.9, 107.3, 111.1, 117.9, 119.9,
120.1, 121.3, 122.7, 127.1, 131.2, 137.3, 160.0, 169.4 ppm.
Methyl 1-ethyl-9H-carbazole-2-carboxylate (7d): 58.4
1
mg, 77%; light yellow liquid; H (400 Hz, DMSO-d6, 25
oC): δ = 1.28 (t, J = 7.2 Hz, 3H), 3.26 (q, J = 7.2 Hz, 2H),
3.87 (s, 3H), 6.55 (s, 2H), 7.17–7.21 (m, 1H), 7.43–7.47
(m, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H),
8.03 (d, J = 8.4 Hz, 1H), 8.15 (d, J = 8.0 Hz, 1H), 11.50
(100 Hz, DMSO-d6, 25 C): δ = 15.0, 66.0, 111.4, 117.3,
o
119.0, 120.6, 121.0, 122.0, 123.0, 124.7, 125.4, 127.0,
128.0, 128.1, 128.5, 136.4, 140.0, 140.9, 167.4 ppm.
1-(1-Methyl-9H-carbazol-2-yl)ethanone (7k):[10e] 24.8
ppm (s, 1H); 13C NMR (100 Hz, DMSO-d6, 25 C): δ =
mg, 37%; yellow oil; H (400 Hz, DMSO-d6, 25 C): δ =
2.70 (d, J = 0.8 Hz, 3H), 2.78 (s, 3H), 7.25–7.28 (m, 1H),
7.45–7.51 (m, 2H), 7.63 (d, J = 8.0 Hz, 1H), 7.95 (d, J =
8.0 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 8.25 ppm (s, 1H);
13C NMR (100 Hz, DMSO-d6, 25 oC): δ = 15.0, 30.2, 111.1,
117.4, 120.1, 121.0, 121.3, 123.3, 127.2, 132.4, 134.8,
139.8, 140.7, 141.5, 202.1 ppm.
o
1
o
14.9, 21.7, 51.8, 111.4, 117.5, 119.0, 120.6, 120.9, 122.0,
124.8, 125.1, 126.6, 128.9, 138.6, 140.9, 168.0 ppm; IR: v
= 3374, 3060, 2953, 2926, 2854, 1714, 1624, 1573, 1500,
1459, 1430, 1377, 1342, 1326, 1288, 1263, 1214, 1196,
1147, 1075, 1055, 1013, 891, 825, 799, 608, 499, 432 cm-1;
HRMS (EI): m/z: calcd for C16H15O2NNa: 276.0995 [M +
Na] +; found: 276.0998.
Methyl
1-cyclopropyl-9H-carbazole-2-carboxylate
Ethyl 1-propyl-9H-carbazole-2-carboxylate (7e):[10e]
(7l):[10e] 39.8 mg, 50%; light yellow oil; 1H (400 Hz,
64.3 mg, 76%; light yellow oil; 1H (400 Hz, CDCl3, 25 oC,
CDCl3, 25 oC, TMS): δ = 0.63–0.67 (m, 2H), 1,12–1,17 (m,
TMS): δ = 1.09 (t, J = 7.6 Hz, 3H), 1.44 (t, J = 7.2 Hz, 3H), 2H), 2.31–2.38 (m, 1H), 3.97 (s, 3H), 7.17–7.31 (m, 1H),
1.75–1.84 (m, 2H), 3.22–3.26 (m, 2H), 4.01 (q, J = 7.2 Hz,
2H), 7.23–7.27 (m, 1H), 7.44–7.50 (m, 2H), 7.81 (d, J =
8.4 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 7.6 Hz,
7.44–7.54 (m, 2H), 7.60 (d, J = 8.0 Hz, 1H), 7.95 (d, J =
8.0 Hz, 1H), 8.07 (d, J = 7.6 Hz, 1H), 8.53 ppm (s, 1H);
o
13C NMR (100 Hz, CDCl3, 25 C, TMS): δ = 6.7, 10.8,
o
1H), 8.26 ppm (s, 1H); 13C NMR (100 Hz, CDCl3, 25 C,
52.1, 110.9, 118.2, 119.7, 120.8, 121.0, 123.0, 125.3, 125.4,
126.8, 129.7, 140.0, 140.1, 169.5 ppm.
TMS): δ = 14.4, 14.6, 23.6, 31.1, 60.8, 110.9, 117.5, 119.8,
121.0, 122.1, 123.2, 125.7, 126.4, 126.8, 127.4, 139.0,
140.4, 168.4 ppm.
2-(Thiophen-3-yl)ethyl
1-methyl-9H-carbazole-2-
1
carboxylate (7m): 80.4 mg, 80%; colourless liquid; H
(400 Hz, CDCl3, 25 oC, TMS): δ = 2.80 (s, 3H), 3.34 (t, J =
7.2 Hz, 2H), 4.58 (t, J = 7.2 Hz, 2H), 6.95–6.98 (m, 2H),
7.18–7.28 (m, 2H), 7.44–7.48 (m, 2H), 7.85 (d, J = 8.0 Hz,
1H), 7.93 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 7.6 Hz, 1H),
8.18 ppm (s, 1H); 13C NMR (100 Hz, CDCl3, 25 oC, TMS):
2-Methoxyethyl 1-methyl-9H-carbazole-2-carboxylate
o
1
(7f):[10e] 62.8 mg, 74%; white solid, mp: 156–157 C; H
o
(400 Hz, DMSO-d6, 25 C): δ = 2.79 (s, 1H), 3.33 (s, 1H),
3.68–3.70 (m, 2H), 4.40–4.42 (m, 2H), 7.18–7.22 (m, 1H),
7.46 (t, J = 7.6 Hz, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.65 (d, J
= 8.4 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H), 8.16 (d, J = 7.6 Hz, δ = 15.0, 29.7, 65.2, 111.1, 117.4, 120.1, 121.3, 122.2,
1H), 11.47 ppm (s, 1H); 13C NMR (100 Hz, DMSO-d6, 25
oC): δ = 14.9, 58.1, 63.4, 69.9, 111.4, 117.3, 119.1, 120.6,
121.0, 122.0, 122.7, 124.6, 125.7, 126.7, 139.5, 140.9,
167.6 ppm.
123.1, 123.3, 124.2, 125.8, 126.2, 127.1, 127.2, 139.5,
140.3, 140.6, 168.2 ppm; IR: v = 3372, 3060, 2956, 2925,
2854, 1710, 1624, 1574, 1499, 1458, 1422, 1379, 1327,
1285, 1213, 1194, 1148, 1048, 1014, 971, 891, 850, 824,
788, 752, 734, 697, 576, 497, 435 cm-1; HRMS (EI): m/z:
Allyl 1-methyl-9H-carbazole-2-carboxylate (7g): 60.4
1
+
mg, 76%; light brown liquid; H (400 Hz, DMSO-d6, 25
calcd for C20H17NO2NaS: 358.0872 [M + Na] ; found:
oC): δ = 2.80 (s, 3H) 4.82 (d, J = 5.2 Hz, 2H), 5.29–5.32
(m, 1H), 5.41–5.46 (m, 1H), 6.05–6.15 (m, 1H), 7.20 (t, J
358.0876.
Ethyl 1,9-dimethyl-9H-carbazole-2-carboxylate (7n):[40]
o
1
= 7.2 Hz, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.4 Hz, 56.1 mg, 70%; white solid, mp: 112–113 C; H (400 Hz,
1H), 8.04 (d, J = 8.4Hz, 1H), 8.16 (d, J = 8.0 Hz, 1H),
11.48 ppm (s, 1H);13C NMR (100 Hz, DMSO-d6, 25 oC): δ
= 15.0, 64.9, 111.4, 117.4, 117.9, 119.1, 120.5, 121.0,
122.0, 122.9, 124.7, 125.5, 126.7, 132.9, 139.5, 140.9,
167.2 ppm; IR: v = 3363, 3060, 2955, 2925, 2853, 1711,
1625, 1576, 1501, 1459, 1422, 1378, 1360, 1327, 1286,
1257, 1214, 1194, 1147, 1094, 1048, 1026, 930, 819, 753,
708, 499, 440 cm-1; HRMS (EI): m/z: calcd for
C17H15O2NNa: 288.0995 [M + Na] +; found: 288.0990.
DMSO-d6, 25 oC): δ = 1.35 (t, J = 7.2 Hz, 3H), 2.95 (s, 3H),
4.16 (s, 3H), 4.33 (q, J = 7.2 Hz, 2H), 7.21–7.25 (m,1 H),
7.48–7.65 (m, 2H), 7.64 (d, J = 8.0 Hz, 1H), 8.06 (d, J =
8.0 Hz, 1H), 8.17 ppm (d, J = 8.0 Hz, 1H); 13C NMR (100
o
Hz, DSMO-d6, 25 C): δ = 14.2, 16.3, 33.2, 60.7, 109.7,
117.5, 119.3, 120.2, 120.6, 121.3, 121.9, 125.0, 126.8,
129.5, 139.7, 142.7, 168.5 ppm.
Methyl 5-fluoro-1-methyl-9H-carbazole-2-carboxylate
o
1
(7o):[10e] 55.5 mg, 72%; white solid, mp: 175–176 C; H
o
Prop-2-yn-1-yl
1-methyl-9H-carbazole-2-carboxylate
(400 Hz, CDCl3, 25 C, TMS): δ = 2.84 (s, 3H), 3.97 (s,
1
(7h): 63.1 mg, 80%; light brown oil; H (400 Hz, CDCl3,
3H), 6.91–6.96 (m, 1H), 7.26–7.28 (m, 1H), 7.37–7.42 (m,
1H), 7.86 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 8.4 Hz, 1H),
8.33 ppm (s, 1H); 13C NMR (100 Hz, CDCl3, 25 oC, TMS):
δ = 15.0, 52.2, 105.5, 105.7, 106.8 (JC-F = 3.7 Hz), 111.8,
112.0, 111.8 (JC-F = 3.1 Hz), 122.5, 123.0, 126.4, 127.6,
o
25 C, TMS): δ = 2.53 (t, J = 2.0 Hz, 1H), 2.86 (s, 3H),
4.96 (d, J = 2.0 Hz, 2H), 7.26–7.30 (m, 1H), 7.46–7.54 (m,
2H), 7.89 (d, J = 8.4 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H),
8.10 (d, J = 8.0 Hz, 1H), 8.21 ppm (s, 1H); 13C NMR (100
Hz, CDCl3, 25 oC, TMS): δ = 15.0, 52.2, 74.9, 78.1, 111.0,
9
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800669
Advanced Synthesis & Catalysis
127.7, 138.9,142.4 (JC-F = 10.1 Hz), 157.6, 160.1, 168.7
1H), 7.59 ppm (d, J = 2.0 Hz, 1H); 13C NMR (100 Hz,
DMSO-d6, 25 oC): δ = 13.8, 14.6, 60.2, 110.8, 113.5, 141.9,
159.0, 163.6 ppm.
o
ppm; 19F (377Hz, CDCl3, 25 C, TMS): δ = -118.5 ppm.
Methyl 5-chloro-1-methyl-9H-carbazole-2-carboxylate
(7p): 50.0 mg, 61%; white solid, mp: 156–157 oC; 1H (400
o
Hz, DMSO-d6, 25 C): δ = 2.77 (s, 3H), 3.86 (s, 3H), 7.19
(dd, J = 0.8, 8.4 Hz, 1H), 7.54 (d, J = 0.6 Hz, 1H), 7.66 (d,
J = 8.4 Hz, 1H), 8.00 (d, J = 8.0 Hz, 1H), 8.14 (d, J = 7.6
Hz, 1H), 11.61 ppm (s, 1H); 13C NMR (100 Hz, DMSO-d6,
Acknowledgements
o
25 C, TMS): δ = 14.9, 51.8, 110.9, 117.4, 120.9, 122.4,
The authors thank the National Natural Science Foundation of
China (21761132014) and the Fundamental Research Funds for
the Central Universities of China (2016YXZD033) for the
financial support. The Cooperative Innovation Center of Hubei
Province is also acknowledged.
121.0, 123.0, 124.0, 126.1, 131.1, 128.6, 139.8, 141.4,
167.9 ppm; IR: v = 3368, 2953, 2854, 1716, 1698, 1625,
1575, 1500, 1459, 1411, 1378, 1339, 1287, 1259, 1230,
1202, 1149, 1095, 1055, 977, 871, 824, 802, 749, 646, 590,
433 cm-1; HRMS (EI): m/z: calcd for C15H12ClNaO2:
296.0449 [M + Na] +; found: 296.0445.
Methyl 6-cyano-9H-carbazole-2-carboxylate (7q): 32.5
1
o
mg, 43%; colourless oil; H (400 Hz, DMSO-d6, 25 C): δ
= 2.79 (s, 3H), 3.88 (s, 3H), 7.67–7.74 (m, 2H), 7.81–7.83
(m, 1H), 8.16 (d, J = 8.0 Hz, 1H), 8.78 (s, 1H), 12.08 ppm
References
(s, 1H); 13C NMR (100 Hz, DMSO-d6, 25 C): δ = 15.4,
o
[1] a) R. A. Sheldon, Chem. Soc. Rev. 2012, 41, 1437–
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52.5, 101.3, 113.0, 118.6, 122.1, 122.7, 123.8, 124.3, 125.4,
127.1, 130.0, 130.1, 140.6, 143.2, 168.3 ppm; IR: v = 3337,
2954, 2924, 2853, 2213, 1746, 1718, 1622, 1580, 1498,
1462, 1433, 1337, 1307, 1289, 1261, 1214, 1199, 1147,
1129, 1092, 1055, 878, 823, 783, 740, 665, 612, 586, 535,
518, 485, 423 cm-1; HRMS (EI): m/z: calcd for
C16H12N2NaO2: 273.0634 [M + Na] +; found: 273.0635.
Methyl 6-bromo-1-methyl-9H-carbazole-2-carboxylate
(7r): 43.7 mg, 46%; white solid, mp: 172–173 oC; 1H (400
Hz, DMSO-d6, 25 oC): δ = 2.77 (s, 3H), 3.87 (s, 3H), 7.50–
7.52 (m, 1H), 7.56–7.59 (m, 1H), 7.65 (d, J = 8.4 Hz, 1H),
8.08 (d, J = 8.4 Hz, 1H), 8.42 (s, 1H), 11.65 ppm (s, 1H);
13C NMR (100 Hz, DMSO-d6, 25 oC): δ = 14.9, 51.9, 111.1,
113.4, 117.8, 120.8, 123.0,123.5, 124.0, 126.4, 129.1,
139.5, 139.9, 168.0 ppm; IR: v = 3444, 3225, 3191, 3102,
3064, 2995, 2951, 2915, 2853, 2673, 2253, 2126, 1711,
1622, 1571, 1501, 1454, 1436, 1409, 1382, 1337, 1298,
1266, 1202, 1152, 1056, 1008, 930, 881, 820, 787, 756,
735, 699, 627, 514, 483, 427 cm-1; HRMS (EI): m/z: calcd
for C15H12BrNaO2: 339.9944 [M + Na] +; found: 339.99470
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1832–1844.
Methyl
6-methoxy-1-methyl-9H-carbazole-2-
carboxylate (7s): 71.1 mg, 88%; white solid, mp: 158–159
oC; 1H (400 Hz, DMSO-d6, 25 oC): δ = 2.82 (s, 3H), 3.93 (s,
3H), 3.95 (s, 3H), 7.12 (dd, J = 2.4, 8.8 Hz, 1H), 7.40 (d, J
= 8.8 Hz, 1H), 7.54 (d, J = 2.0 Hz, 1H), 7.80 (d, J = 8.4 Hz,
1H), 7.89 (d, J = 8.4 Hz, 1H), 8.06 ppm (s, 1H); 13C NMR
[5] X.-P. Zeng, J. Zhou, Waste-mediated reactions, J. Zhou
(Ed), Multicatalyst System in Asymmetric Catalysis,
633–670, 2015, John Wiley & Sons, Inc.
o
(100 Hz, DMSO-d6, 25 C): δ = 15.0, 52.0, 56.2, 103.5,
111.9, 116.8, 117.3, 121.7, 123.1, 123.7, 125.6, 126.2,
135.5, 140.2, 154.3, 168.9 ppm; IR: v = 3411, 2951, 2922,
2851, 1890, 1848, 1604, 1581, 1495, 1460, 1434, 1376,
1341, 1286, 1241, 1202, 1177, 1145, 1073, 1051, 1024,
974, 878, 846, 825, 802, 783, 747, 666, 610, 588, 519 cm-1;
HRMS (EI): m/z: calcd for C16H15NNaO3: 292.0944 [M +
Na] +; found: 292.0949.
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Ethyl 5-hydroxy-2-methyl-4,5-dihydrofuran-3-
1
carboxylate (8a): 1.55 g, 90%; clourless liquid; H (400
Hz, CDCl3, 25 oC, TMS): δ = 1.27 (t, J = 7.2 Hz, 3H), 2.20
(s, 3H), 2.84 (d, J = 2.0 Hz, 1H), 4.114.23 (m, 2H), 4.24–
4.30 (m, 1H), 4.34–4.48 (m, 1H), 5.17–5.19 ppm (m, 1H);
o
13C NMR (100 Hz, CDCl3, 25 C, TMS): δ = 14.4, 14.5,
59.9, 73.0, 77.6, 107.0, 165.8, 172.0 ppm; IR: v = 3363,
3192, 2957, 2925, 2853, 1706, 1660, 1636, 1465, 1410,
1379, 1336, 1222, 1141, 1083, 1026, 985, 922, 861, 800,
722, 634 cm-1; HRMS (EI): m/z: calcd for C8H12O2Na:
195.0628 [M + Na] +; found: 195.0624.
Ethyl
2-((1,3-dioxolan-2-yl)methyl)-3-oxobutanoate
1
(8a'): 1.14 g, 53%; colourless liquid; H (400 Hz, CDCl3,
o
25 C, TMS): δ = 1.26 (t, J = 7.2 Hz, 3H), 2.25 (s, 3H),
2.29–2.31 (m, 2H), 3.68 (t, J = 7.2 Hz, 1H), 3.81–3.87 (m,
2H), 3.88–3.94 (m, 2H), 4.18 (q, J = 7.2 Hz, 2H), 4.95
ppm (t, J = 7.6 Hz, 1H); 13C NMR (100 Hz, CDCl3, 25 oC,
TMS): δ = 14.0, 29.0, 31.7, 54.2, 61.5, 65.0, 65.1, 102.0,
169.5, 202.4 ppm; IR: v = 3425, 2982, 2829, 2755, 2658,
2255, 1742, 1717, 1644, 1473, 1430, 1393, 1362, 1300,
1268, 1182, 1142, 1095, 1025, 947, 866, 734, 703, 648,
511 cm-1; HRMS (EI): m/z: calcd for C10H16O5Na:
239.0890 [M + Na] +; found: 239.0894.
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Ethyl 2-methylfuran-3-carboxylate (9a):[38] yellow oil;
1H (400 Hz, DMSO-d6, 25 oC): δ = 1.28 (t, J = 7.2 Hz, 3H),
2.54 (s, 3H), 4.22 (q, J = 7.2 Hz, 2H), 6.66 (d, J = 2.0 Hz,
10
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800669
Advanced Synthesis & Catalysis
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FULL PAPER
Relay Catalysis of Bismuth Trichloride and
Byproduct Hydrogen Bromide Enables
Synthesis
of
Carbazole
and
Benzo[]carbazoles from Indoles and -
Bromoacetaldehyde Acetals
Adv. Synth. Catal. Year, Volume, Page – Page
Fengtian Wu, Wenbo Huang, Yiliqi, Jian Yang,
and Yanlong Gu*
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