Access to 3-arylindoles through a tandem one-pot protocol involving dearomatization, a regioselective michael addition reaction, and rearomatization

Article abstract of DOI:10.1002/ejoc.201400079

A facile, general and rapid protocol for the introduction of oxygenated aryls at the 3-position of indoles is described. This approach consists of a tandem dearomatization, a regioselective Michael addition reaction, and rearomatization in a one-pot three-step sequence to obtain 3-arylindoles in good yields. A non-metal mediated detour method for installing oxygenated aryls at the 3-position of indoles is described. Copyright

Full text of DOI:10.1002/ejoc.201400079

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FULL PAPER
DOI: 10.1002/ejoc.201400079
Access to 3-Arylindoles through a Tandem One-Pot Protocol Involving
Dearomatization, a Regioselective Michael Addition Reaction, and
Rearomatization
Santhosh Kumar Chittimalla,*[a] Chennakesavulu Bandi,[a] Sireesha Putturu,[a][‡]
Rajesh Kuppusamy,[a][‡] Kevin Christopher Boellaard,[b] David Chu Aan Tan,[b] and
Demi Ming Jie Lum[b]
Keywords: Synthetic methods / Domino reactions / Michael addition / Nitrogen heterocycles / Quinones
A facile, general and rapid protocol for the introduction of
oxygenated aryls at the 3-position of indoles is described.
This approach consists of a tandem dearomatization, a re-
gioselective Michael addition reaction, and rearomatization
in a one-pot three-step sequence to obtain 3-arylindoles in
good yields.
our attention. However, the study was limited to 2-meth-
oxyphenols bearing an electron-withdrawing substituent
(–CO2CH3, –COCH3 or –CN) at the 4-position. Conse-
quently, on the basis of the above observation and in con-
tinuation of our research work focused on the chemistry of
MOBs,[9,10] we re-visited this remarkable reaction method-
ology to exploit the potential of MOBs as an aryl source
for the synthesis of oxygenated aryl-substituted indoles. To
the best of our knowledge, reaction of indoles with MOBs
that do not bear electron-withdrawing substitutions is not
known. In this report we disclose our efforts to develop
conditions for a tandem one-pot protocol consisting of de-
aromatization, a regioselective Michael addition reaction
and rearomatization to access 3-arylindoles starting from
commercially/easily available 2-methoxyphenols and in-
doles.
Introduction
Indole, a “privileged scaffold” in medicinal chemistry is
a common core in numerous natural and synthetic products
possessing a remarkable spectrum of biological activity.[1]
Owing to the incredible range of pharmacological proper-
ties, several useful approaches to the construction of this
core structure have been developed and documented in the
literature.[2] During one of our projects, we needed 3-arylin-
doles in which the aryl group had to be a highly oxygenated
system. 3-Arylindoles are known to possess numerous bio-
logical properties.[3] A literature survey indicated various
general procedures for the synthesis of 3-arylindoles from
non-indole precursors including Fischer’s indole synthe-
sis,[4] and metal-catalyzed reactions.[5] In addition, there is
growing research interest in the development of new and
efficient methodologies for the direct and regioselective
arylation of indole at the 3-position with the aid of metal
catalysis.[6] In addition, p-benzoquinones and p-benzoquin-
ol ethers were employed in the synthesis of requisite 3-
arylindoles in metal free procedures.[7] In this context, more
than a decade ago, the unique ability of masked o-benzo-
quinones (MOBs) on reaction with indoles to furnish [4+2]
cycloaddition reaction products or 3-arylindole under ap-
propriate conditions was reported.[8] These results attracted
Results and Discussion
We began the study by investigating the aforementioned
tandem one-pot reaction with creosol (2-methoxy-4-meth-
ylphenol, 1) and indole (a; Table 1). At the outset, a meth-
anolic solution of 1 was treated with diacetoxyiodobenzene
(DAIB) at room temperature for 15 min. To this reaction
[a] Medicinal Chemistry Department, AMRI Singapore Research mixture indole (a) was added and stirring was continued.
After 16 h only Diels–Alder dimer 1D[11] was isolated
Centre,
61 Science Park Road, #05-01 The Galen, Science Park III,
(Table 1, Entry 1). However, when the reaction temperature
was increased to 70 °C, a 1:1.5 mixture of 3-arylindole 1a
and dimer 1D were produced (Table 1, Entry 2). The struc-
Singapore 117525
E-mail: santhosh.chittimalla@amriglobal.com
chemcsk@gmail.com
http://www.amriglobal.com/
1
ture of compound 1a was confirmed based on H NMR
[b] School of Chemical & Life Sciences, Singapore Polytechnic,
500 Dover Road, Singapore 139651
and 13C NMR spectroscopy, DEPT, and HRMS analyses.
In the 1H NMR spectra of compound 1a, peaks at δ =
7.05 ppm (s, Ha) and 6.85 ppm (s, Hb) correspond to pro-
[‡] These authors contributed equally to this work
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201400079.
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Table 1. Optimization of the reaction conditions for the synthesis of 3-arylindoles.
Entry
Catalyst
Temperature
Time
Product 1a:1D
1[a]
2[c]
3[e]
4[f]
–
–
r.t.
70 °C
r.t.
70 °C
70 °C
70 °C
70 °C
16 h
16 h
16 h
4 h
16 h
16 h
16 h
only 1D (85%)[b]
1.0:1.5[d]
1.5:1[d]
HClO4/SiO2 (5 mol-%)
HClO4/SiO2 (5 mol-%)
CH3SO3H (25 mol-%)
pTSA (25 mol-%)
HClO4/SiO2 (1 mol-%)
only 1a (86%)[b]
4:1[d]
5[g,h]
6[i]
3:1[d]
7[j]
9:1[d]
[a] 1 (1.0 equiv.), PhI(OAc)2 (1.2 equiv.), MeOH, room temp., 15 min followed by addition of indole (a, 1.3 equiv.). [b] Yield of isolated
product. [c] Same reaction conditions as for Entry 1, after the addition of indole (a), the reaction mixture was dipped in a 70 °C pre-
heated oil bath for 16 h. [d] Product ratio is obtained from 1H NMR spectroscopic data integration of the crude reaction mixture. [e] Same
reaction conditions as for Entry 1, and along with indole (a), 5 mol-% of catalyst HClO4/SiO2 was added. [f] Same reaction conditions
as for Entry 3, the reaction mixture was dipped in a 70 °C pre-heated oil bath for 4 h. [g] Same reaction conditions as for Entry 4, 25 mol-
% CH3SO3H was used as the catalyst. [h] 20–30% of uncharacterizable product was also obtained. [i] Same reaction conditions as for
Entry 4, 25 mol-% p-toluenesulfonic acid (pTSA) was used as the catalyst. [j] Same reaction conditions as for Entry 4, 1 mol-% of HClO4/
SiO2 was used as the catalyst.
tons of the aryl system indicating the assigned structure. oxyphenol).[8] Although we could not isolate any intermedi-
The proton at 2-position of indole in compound 1a ap- ates from the reaction mixture, a conceivable mechanism
peared at δ = 7.13 ppm (d, J = 2.4 Hz, Hc) as a doublet for the tandem one-pot protocol leading to 3-arylindole de-
owing to the coupling with adjacent indole “-NH-”. In the rivative is depicted in Figure 1. Accordingly, 2-meth-
1
deuterium exchange H NMR experiment “Hc” appeared oxyphenol 1 is initially oxidized by DAIB in the presence
as a singlet owing to decoupling with indole “-NH-”.[12] It of methanol to give MOB of 1. At this stage, indole (a) is
is noteworthy that the regioselectivity of the obtained prod- added to the reaction mixture, which then participates in
uct (in which indole is attached at the 5-position to 2-meth- the Michael addition reaction step with MOB followed by
oxyphenol) is completely different from the literature pre- spontaneous aromatization of the intermediate providing
cedent (in which indole is attached at 3-position to 2-meth- observed 3-arylindole 1a.
Figure 1. A plausible mechanism for the formation of 3-arylindole 1a.
2
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Access to 3-Arylindoles through a Tandem One-Pot Protocol
It was predicted that the ratio of 3-arylindole 1a over sumed to be the result of the incompatibility of indoles un-
dimer 1D could be enhanced if the rate of the Michael ad- der the acidic environment and elevated temperatures that
dition reaction step is improved. Interestingly, acetic acid led to unidentified impurities and isolation problems.
liberated during the MOB generation step was not enough Therefore, subsequent reactions were carried out at room
to improve the Michael addition reaction. Thus, catalysts temperature. Gratifyingly, this proved to be the case and
for the above tandem reaction leading to product 1a were products 2a and 2b were obtained in 81% and 78% yield,
screened. Motivated by our previous work with silica-sup- respectively (Scheme 2). As a result, 5 mol-% HClO4/SiO2
ported perchloric acid (HClO4/SiO2),[13] we first decided to and room temperature were adopted as the new general
investigate the above tandem sequence in the presence of conditions. Under these reaction conditions, 3-arylindoles
this inexpensive catalyst system. As shown in Table 1, initial 3a–3b, 4a–4b and 5a–5b were produced in satisfactory
optimization studies revealed that efficient 3-arylation of in- yields (Scheme 3). It should be noted that in the case of 2-
dole occurred in the presence of 5 mol-% of HClO4/SiO2 at methoxyphenols 3 and 4, about 10% of dimers 3D and 4D
70 °C (Table 1, Entry 4). Interestingly, 25 mol-% of were also isolated (Figure 2). Interestingly, the reaction of
CH3SO3H or pTSA was not as effective as 1 mol-% of 2-methoxyphenol 6 with indoles a or b under the tandem
HClO4/SiO2 (Table 1, Entries 3–7). Nevertheless, in all the reaction conditions either at room temperature or elevated
catalyzed reaction procedures the product to dimer ratio temperature (70 °C) did not yield any desired product. The
was improved.
only isolated product in these cases was MOB of 6 (Fig-
With the established conditions in hand, we evaluated ure 2). This result can be attributed to the presence of the
the reaction of creosol (1) with several differently substi- bulky tert-butyl group near the reaction center causing se-
tuted indoles b–f. To our delight, as delineated in Scheme 1, vere steric hindrance.
the tandem procedure was successful with all the indole
substrates used to give corresponding 3-arylated indoles 1b–
1f in good yields.
Scheme 1. Creosol (1) as aryl source in the synthesis of 3-arylin-
doles.
In an effort to extend the scope of this methodology, 2-
methoxyphenols bearing sterically different substitutions
were chosen to be installed at the 3-position of selected in-
Scheme 2. Effect of sterically different substitutions in the synthesis
of 3-arylindoles.
doles a and b. Thus, when 2-methoxyphenol 2 was subjected
to the optimized tandem reaction conditions with indole
The tandem protocol success with 4-substituted 2-meth-
(a), we noticed that purification of the desired product from oxyphenols in Scheme 1 and Scheme 2, led us to examine
the reaction mixture was tedious. This difficulty was pre- the substrate scope with a selected set of 3-substituted 2-
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in Figure 1. Similarly, 3-bromo-2-methoxyphenol (8) and
indole a participated in the tandem reaction procedure pro-
viding 3-arylindole 8a in 70% yield. However, compound 8
with indole b provided 3-arylindole 8b in only 30% yield
along with the Michael addition reaction product MA-I in
30% isolated yield (Scheme 3 and Scheme 4). Interestingly,
this is the only case in which the intermediate Michael ad-
dition product was isolated. On the other hand, when the
reaction time was increased to 8 h, product 8b could be iso-
lated in 73% yield with no trace of Michael addition reac-
tion product (Scheme 4). Subsequently, to verify our ration-
ale shown in Figure 1, in a separate experiment, a meth-
anolic solution of compound MA-I was heated to 70 °C in
the presence of 5 mol-% HClO4/SiO2 catalyst for 2 h. To
our satisfaction, 30% of 8b was produced as expected along
with 35% of recovered Michael adduct MA-I (Scheme 4).
In contrast to 2-methoxyphenols 7 and 8, when the tandem
procedure was applied to 3-methyl-2-methoxyphenol (9)
and indoles a and b, a 1:1 mixture of products 9a:9aЈ and
3:1 mixture of products 9b:9bЈ were isolated (Scheme 3, Fig-
ure 2). Nevertheless, the present tandem protocol was appli-
cable to 2-methoxyphenols bearing different substitution
patterns.
Scheme 3. Various 2-methoxyphenols as aryl source in the synthesis
of 3-arylindoles.
Scheme 4. Tandem protocol applied to 2-methoxyphenol 8 and in-
dole b.
Next we chose two new indoles, N-ethylindole (g) and 2-
methylindole (h) for the tandem protocol with 2-meth-
oxyphenols 1 and 7–9.[15] 2-Methylindole (h) was chosen to
verify if the substitution at 2-position of indole would affect
the reaction course; and N-ethylindole (g) will provide in-
formation on whether free “-NH” is necessary for the reac-
tion to proceed. Initially, 2-methoxyphenols 1 and 7–9 were
Figure 2. Structures of dimers 3D/4D, MOB of phenol 6 and re-
gioisomers 9aЈ 9bЈ and 9gЈ.
methoxyphenols 7–9. At the outset, 2,3-dimethoxyphenol subjected to the tandem protocol with N-ethylindole (g).
(7) was treated with DAIB in methanol for 30 min. To this Products 1g (83%), 7g (85%), and 8g (68%) were obtained
reaction mixture was separately added indoles a, b, c or f in moderate to good yields (Scheme 5). However product
along with 5 mol-% HClO4/SiO2 catalyst. The reaction ves- 9g was obtained in only 30% yield along with its re-
sel was then dipped in a 70 °C pre-heated oil bath.[14] After gioisomer 9gЈ (Scheme 5, Figure 2). This outcome was in
the completion of reaction and chromatographic purifica- line with the previous results obtained with 2-methoxy-3-
tion, 3-arylindoles 7a (92%), 7b (73%), 7c (83%) and 7f methylphenol (9). Subsequently, 2-methylindole was used in
(83%) were produced in good yields (Scheme 3). For exam- the tandem protocol with 2-methoxyphenols 1 and 7–9;
1
ple, in the H NMR spectra of compound 7a, appearance interestingly, products 7h–9h were only formed. The major
of aryl protons at δ = 6.90 (d, J = 2.1 Hz, 1 H, Ha), 6.79 product in the tandem reaction involving 1 and indole h
(d, J = 2.1 Hz, 1 H, Hb) ppm with meta coupling indicated was MOB dimer 1D (Scheme 5) with only traces of desired
1
the assigned regioselectivity. Thus, the products obtained product 1h according to the H NMR spectroscopic data
were in accordance with the postulated mechanism shown of the crude reaction mixture.
4
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Access to 3-Arylindoles through a Tandem One-Pot Protocol
Figure 3. Diagnostic 2D NOESY cross peaks.
Scheme 5. Tandem protocol applied to 2-methoxyphenol 1, 7–9
and indoles g and h.
The structures of all of the products were assigned on
1
the basis of H NMR and 13C NMR spectroscopy, DEPT
and HRMS analyses. In addition, 2D NOESY experiments
on a selected set of compounds further confirmed the pro-
posed structural assignment (Figure 3).
Figure 4. Possible products in the reaction between MOBs and in-
dole, and factors affecting the observed results.
Several conclusions can be drawn from the results ob-
tained and are shown in Figure 4. [I] In the majority of the reactions on several occasions.[16] However, in this study no
cases, the Michael addition reaction of indole to in-situ- Diels–Alder adduct (Figure 4, Path b; MOB acting as diene
generated MOB occurred at the 3-position as opposed to and indole as dienophile) was observed under the reaction
the 5-position reported in the literature.[8] The difference in conditions employed. Consequently, from the literature pre-
regioselectivity in the previous work can be attributed to cedent[8] and observed experimental results, it can be in-
the presence of electron-withdrawing groups (–CO2CH3, ferred that MOB should have a strong electron-withdrawing
–COCH3 or –CN) at the 4-position of MOB that directed substituent to participate in an inverse electron demand
the Michael addition reaction to the 5-position (Figure 3, Diels–Alder reaction with indole to furnish the Diels–Alder
Path a). In this work both electronic and steric factors con- adduct following Path b. [III] Recently it was reported that
tributed to the Michael addition reaction at the 3-position 4-alkyl-substituted MOBs under acid catalysis provide p-
and thus the observed regioselectivity. [II] Indole was re- quinol ethers through Figure 4, Path c,[17] however, in our
ported to take part in inverse electron demand Diels–Alder study no such products were observed. [IV] The failure of
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General Procedure for the Synthesis of 3-Arylindoles: To a solution
of 2-methoxyphenol (1.0 mmol) in methanol (4 mL) was added
DAIB (1.2 mmol) and the resulting mixture was stirred for 15–
30 min at room temperature (generation of MOB). After this time,
indole (1.2 mmol) and HClO4/SiO2 (0.05 mmol, 100 mg) were
added at ambient temperature and the reaction vessel was dipped
in a 70 °C pre-heated oil bath or left stirring at room temperature
until the reaction was complete. The reaction mixture was concen-
trated and the residue was purified by column chromatography on
silica gel by using a mixture of ethyl acetate and hexanes as eluent
2-methylindole to provide the desired product with 4-substi-
tuted MOBs can be attributed to steric hindrance between
both the methyl groups as indicated in Figure 4. [V-a] 5-
Methoxy- and 5-bromo- substituted MOBs on reaction
with indoles provided only one kind of product owing to
the reaction of indole at the 3-position of MOBs; however,
5-methyl-substituted MOB provided two isomers owing to
the reaction of indole at both the 3- and 4-positions, respec-
tively. The difference can be attributed to the electronic fac-
tors, in which the Br and OMe substituents decrease the to obtain 3-arylindoles.
5-(1H-Indol-3-yl)-2-methoxy-4-methylphenol (1a): 1H NMR
(400 MHz, CDCl3): δ = 8.19 (br. s, 1 H), 7.56 (d, J = 8.0 Hz, 1 H),
electrophilicity at the 4-position owing to the mesomeric
effect, whereas an Me group could not affect such a de-
crease in the electrophilicity at the 4-position leading to the 7.42 (d, J = 8.0 Hz, 1 H), 7.27–7.23 (m, 1 H), 7.18–7.16 (m, 1 H),
7.13 (d, J = 2.4 Hz, 1 H), 7.05 (s, 1 H), 6.85 (s, 1 H), 5.55 (s, 1 H),
3.95 (s, 3 H), 2.27 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 145.3 (C), 143.1 (C), 135.8 (C), 128.4 (C), 127.2 (C), 127.1 (C),
122.7 (CH), 122.0 (CH), 120.1 (CH), 119.8 (CH), 117.1 (C), 116.9
(CH), 112.8 (CH), 111.1 (CH), 55.9 (CH3), 20.2 (CH3) ppm.
HRMS (ESI+): calcd. for C16H15NNaO2 [M + Na] 276.0995; found
276.0991.
5-[5-(Benzyloxy)-1H-indol-3-yl]-2-methoxy-4-methylphenol (1b): 1H
NMR (400 MHz, CDCl3): δ = 8.07 (br. s, 1 H), 7.45–7.42 (m, 2
H), 7.38–7.32 (m, 2 H), 7.32–7.25 (m, 2 H), 7.06 (d, J = 2.4 Hz, 2
H), 7.03 (d, J = 2.4 Hz, 1 H), 6.97 (s, 1 H), 6.95 (dd, J = 2.4,
8.8 Hz, 1 H), 6.80 (s, 1 H), 5.49 (s, 1 H), 5.03 (s, 2 H), 3.91 (s, 3
H), 2.20 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.5
(C), 145.3 (C), 143.2 (C), 137.6 (C), 131.1 (C), 128.43 (CH ϫ2),
128.40 (C), 127.7 (CH), 127.6 (CH ϫ2), 127.58 (C), 127.2 (C),
123.5 (CH), 117.0 (C), 116.8 (CH), 113.2 (CH), 112.8 (CH), 111.8
(CH), 103.3 (CH), 70.9 (CH2), 56.0 (CH3), 20.2 (CH3) ppm.
HRMS (ESI+): calcd. for C23H22NO3 [M + H] 360.1594; found
360.1596.
other possible isomers 9aЈ, 9bЈ, and 9gЈ. [V-b] The reaction
between 2-methylindole and 5-methyl-substituted MOB
gave 85% of isomer 9h, probably owing to the steric hin-
drance between both the methyl groups as indicated in Fig-
ure 4.
Next we investigated application of the tandem protocol
of 2-methoxyphenols 10–12. To our surprise, the tandem
reaction at room temperature or 70 °C furnished only di-
mers 10D–12D (Figure 5). Presumably, after the oxidation
step, the competing MOB dimerization is preferred over the
Michael addition reaction in these cases.
5-(5-Bromo-1H-indol-3-yl)-2-methoxy-4-methylphenol (1c): 1H
NMR (400 MHz, CDCl3): δ = 8.26 (br. s, 1 H), 7.61 (s, 1 H), 7.22–
7.30 (m, 2 H), 7.11 (d, J = 2.0 Hz, 1 H), 6.93 (s, 1 H), 6.81 (s, 1
H), 5.52 (s, 1 H), 3.92 (s, 3 H), 2.20 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 145.5 (C), 143.2 (C), 134.4 (C), 129.0 (C),
128.4 (C), 126.3 (C), 124.9 (CH), 123.8 (CH), 122.5 (CH), 116.9
(CH), 116.8 (C), 113.2 (C), 112.8 (CH), 112.5 (CH), 56.0 (CH3),
29.6 (C), 20.1 (CH3) ppm. HRMS (ESI+): calcd. for
C16H14BrNNaO2 [M + Na] 354.0100; found 354.0115.
Figure 5. 2-Methoxyphenols 10–12 and dimers 10D–12D.
Conclusions
In conclusion, the ability of unactivated MOBs to un-
dergo a tandem one-pot three-step reaction facilitates a use-
ful, direct and efficient approach for the preparation of 3-
arylindoles. This strategy is amenable for the introduction
of diverse oxygenated aryls at C-3 of the indole and gen-
erally the yields are good. However, a few 2-methoxyphen-
ols did not provide expected results under the reaction con-
ditions and investigations are in progress to obtain 3-aryl-
indoles from such 2-methoxyphenols.
5-(5-Chloro-1H-indol-3-yl)-2-methoxy-4-methylphenol (1d): 1H
NMR (300 MHz, CDCl3): δ = 8.24 (br. s, 1 H), 7.48 (app. s, 1 H),
7.32 (app. d, J = 8.7 Hz, 1 H), 7.19–7.14 (m, 2 H), 6.96 (s, 1 H),
6.83 (s, 1 H), 5.53 (s, 1 H), 3.94 (s, 3 H), 2.23 (s, 3 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 145.5 (C), 143.2 (C), 134.2 (C), 128.43
(C), 128.39 (C), 126.4 (C), 125.7 (C), 124.0 (CH), 122.4 (CH), 119.5
(CH), 117.0 (C), 116.8 (CH), 112.8 (CH), 112.1 (CH), 56.0 (CH3),
20.2 (CH3) ppm. HRMS (ESI+): calcd. for C16H15ClNO2 [M + H]
288.0786; found 288.0798.
5-(6-Chloro-1H-indol-3-yl)-2-methoxy-4-methylphenol (1e): 1H
NMR (300 MHz, CDCl3): δ = 8.18 (br. s, 1 H), 7.42–7.40 (m, 2
H), 7.12–7.08 (m, 2 H), 6.97 (s, 1 H), 6.82 (s, 1 H), 5.50 (s, 1 H),
3.94 (s, 3 H), 2.22 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
145.5 (C), 143.2 (C), 136.2 (C), 128.4 (C), 128.0 (C), 126.5 (C),
125.9 (C), 123.2 (CH), 121.0 (CH), 120.6 (CH), 117.4 (C), 116.8
(CH), 112.8 (CH), 111.0 (CH), 56.0 (CH3), 20.1 (CH3) ppm.
HRMS (ESI+): calcd. for C16H15ClNO2 [M + H] 288.0786; found
288.0787.
Experimental Section
Preparation of HClO4/SiO2 Catalyst System: To a suspension of
SiO2 (230–400 mesh, 50 g) in CH2Cl2 (150 mL) at room tempera-
ture was added 70% aqueous HClO4 (3.60 g, 2.2 mL, 25.0 mmol).
After stirring for 30 min, the mixture was concentrated and the
residue was heated to 60 °C under vacuum for 2 h to furnish per-
chloric acid adsorbed on silica gel (HClO4/SiO2, 0.05 mmol/
100 mg) as a free flowing powder.
2-Methoxy-4-methyl-5-(7-methyl-1H-indol-3-yl)phenol (1f): 1H
NMR (300 MHz, CDCl3): δ = 8.11 (br. s, 1 H), 7.42–7.31 (m, 1
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H), 7.15 (d, J = 2.4 Hz, 1 H), 7.09–6.97 (m, 3 H), 6.82 (s, 1 H),
2-Methoxy-4-propylphenol (4):[19] A solution of 4-allyl-2-meth-
5.47 (s, 1 H), 3.94 (s, 3 H), 2.54 (s, 3 H), 2.25 (s, 3 H) ppm. 13C oxyphenol (1.0 g, 6.1 mmol) in ethanol (50 mL) and 10% Pd/C
NMR (100 MHz, CDCl3): δ = 145.3 (C), 143.2 (C), 135.4 (C), 128.4
(200 mg) was stirred at room temperature under a hydrogen atmo-
(C), 127.4 (C), 126.8 (C), 122.6 (CH), 122.4 (CH), 120.2 (CH), sphere by using a hydrogen filled balloon for 16 h. The reaction
120.0 (C), 117.9 (CH), 117.7 (C), 116.9 (CH), 112.8 (CH), 56.0
(CH3), 20.3 (CH3), 16.6 (CH3) ppm. HRMS (ESI+): calcd. for
C17H18NO2 [M + H] 268.1332; found 268.1325.
mixture was filtered through a pad of Celite and the filtrate was
evaporated to provide 2-methoxy-4-propylphenol (0.94 g, 93%
yield). 1H NMR (400 MHz, CDCl3): δ = 6.81–6.85 (m, 1 H), 6.65–
6.71 (m, 2 H), 5.47 (br. s, 1 H), 3.88 (s, 3 H), 2.52 (dd, J = 7.2,
7.6 Hz, 2 H), 1.56–1.67 (m, 2 H), 0.94 (t, J = 7.6 Hz, 3 H) ppm.
5-(1H-Indol-3-yl)-2-methoxy-4-propylphenol (4a): 1H NMR
(300 MHz, CDCl3): δ = 8.14 (br. s, 1 H), 7.48 (d, J = 8.1 Hz, 1 H),
7.41 (d, J = 8.1 Hz, 1 H), 7.21 (t, J = 7.2 Hz, 1 H), 7.07–7.15 (m,
2 H), 6.95 (s, 1 H), 6.83 (s, 1 H), 5.45 (s, 1 H), 3.94 (s, 3 H), 2.48–
2.58 (m, 2 H), 1.41–1.51 (m, 2 H), 0.78 (t, J = 7.5 Hz, 3 H) ppm.
13C NMR (400 MHz, CDCl3): δ = 145.5 (C), 143.1 (C), 135.8 (C),
133.6 (C), 127.7 (C), 126.8 (C), 122.4 (CH), 122.1 (CH), 120.0
(CH), 119.8 (CH), 117.3 (CH), 117.1 (C), 111.6 (CH), 111.0 (CH),
56.0 (CH3), 35.2 (CH2), 24.9 (CH2), 13.9 (CH3) ppm. HRMS
(ESI+): calcd. for C18H20NO2 [M + H] 282.1489; found 282.1488.
5-[5-(Benzyloxy)-1H-indol-3-yl]-2-methoxy-4-propylphenol (4b): 1H
NMR (300 MHz, CDCl3): δ = 8.04 (br. s, 1 H), 7.39–7.41 (m, 2
H), 7.25–7.39 (m, 4 H), 7.08 (d, J = 2.7 Hz, 1 H), 7.02–6.94 (m, 2
H), 6.93 (s, 1 H), 6.82 (s, 1 H), 5.46 (s, 1 H), 5.02 (s, 2 H), 3.94 (s,
3 H), 2.45–2.55 (m, 2 H), 1.43–1.54 (m, 2 H), 0.77 (t, J = 7.2 Hz,
3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.6 (C), 145.5 (C),
143.2 (C), 137.7 (C), 133.7 (C), 131.1 (C), 128.4 (CH ϫ2), 128.1
(C), 127.7 (CH), 127.6 (CH ϫ2), 126.8 (C), 123.3 (CH), 117.2
(CH), 117.0 (C), 113.2 (CH), 111.7 (CH), 111.6 (CH), 103.1 (CH),
70.9 (CH2), 56.0 (CH3), 35.2 (CH2), 24.9 (CH2), 14.0 (CH3) ppm.
HRMS (ESI+): calcd. for C25H26ClNO3 [M + H] 388.1907; found
388.1913.
4-Isopropyl-2-methoxyphenol (5):[20] A solution of 1-(4-hydroxy-3-
methoxyphenyl)ethanone (3.0 g, 18.1 mmol) in dry tetrahydrofuran
(30 mL) at 0 °C was added methylmagnesiumbromide (13.3 mL,
39.8 mmol, 3.0 m in diethyl ether). The reaction mixture was al-
lowed to stir for 3 h at room temperature. Aqueous 1 n HCl was
added to the reaction and it was extracted with ethyl acetate. Or-
ganic extracts were collected and dried with sodium sulfate, filtered
and concentrated to give a residue. The obtained residue was dis-
solved in ethanol (40 mL) and 10% wet Pd/C (500 mg) was added
to it and subjected to hydrogenation on a Parr shaker at 45 psi for
8 h. The reaction mixture was filtered through a pad of Celite fol-
lowed by solvent evaporation to provide a residue that was purified
by column chromatography with silica gel by using a mixture of
ethyl acetate and hexanes as eluent to give 4-isopropyl-2-meth-
oxyphenol (5, 2.2 g, 73% for two steps). 1H NMR (400 MHz,
CDCl3): δ = 6.84 (d, J = 8.8 Hz, 1 H), 6.69–6.74 (m, 2 H), 5.44 (s,
1 H), 3.89 (s, 3 H), 2.78–2.90 (m, 1 H), 1.22 (d, J = 6.8 Hz, 6
H) ppm.
4-Bromo-5-(1H-indol-3-yl)-2-methoxyphenol (2a): 1H NMR
(300 MHz, CDCl3): δ = 8.23 (br. s, 1 H), 7.60 (d, J = 7.8 Hz, 1 H),
7.41 (d, J = 7.8 Hz, 1 H), 7.34 (d, J = 2.4 Hz, 1 H), 7.24–7.13 (m,
3 H), 7.12 (s, 1 H), 5.56 (s, 1 H), 3.93 (s, 3 H) ppm. 13C NMR
(300 MHz, CDCl3): δ = 145.9 (C), 144.8 (C), 135.6 (C), 128.8 (C),
126.7 (C), 123.8 (CH), 122.2 (CH), 120.1 (CH), 120.0 (CH), 117.7
(CH), 116.5 (C), 115.5 (CH), 113.0 (C), 111.2 (CH), 56.3
(CH3) ppm. HRMS (ESI+): calcd. for C15H12BrNNaO2 [M + Na]
339.9944; found 339.9943.
5-[5-(Benzyloxy)-1H-indol-3-yl]-4-bromo-2-methoxyphenol (2b): 1H
NMR (300 MHz, CDCl3): δ = 8.12 (br. s, 1 H), 7.46–7.44 (m, 2
H), 7.39–7.28 (m, 5 H), 7.16 (s, 1 H), 7.13 (d, J = 2.4 Hz, 1 H),
7.07 (s, 1 H), 6.95 (dd, J = 2.4, 8.7 Hz, 1 H), 5.58 (s, 1 H), 5.05 (s,
2 H), 3.91 (s, 3 H) ppm. 13C NMR (300 MHz, CDCl3): δ = 153.6
(C), 145.9 (C), 144.8 (C), 137.6 (C), 131.0 (C), 128.8 (C), 128.5 (CH
ϫ2), 127.73 (CH ϫ2), 127.71 (CH), 127.0 (C), 124.6 (CH), 117.6
(CH), 116.3 (C), 115.5 (CH), 113.3 (CH), 112.9 (C), 111.9 (CH),
103.5 (CH), 71.0 (CH2), 56.3 (CH3) ppm. HRMS (ESI+): calcd. for
C22H18BrNNaO3 [M + Na] 446.0362; found 446.0367.
4-Ethyl-2-methoxyphenol (3):[18] A solution of 1-(4-hydroxy-3-meth-
oxyphenyl)ethanone (2.0 g, 12.0 mmol) in glacial acetic acid
(50 mL) was heated to 70 °C with stirring. To this solution was
added zinc dust (7.8 g, 120 mmol) portion-wise for 15 min. The re-
sulting heterogeneous mixture was then heated to reflux and stirred
for 6 h. The reaction mixture was filtered through a pad of Celite
followed by solvent evaporation. The residue was basified with sat-
urated aqueous sodium hydrogen carbonate solution. The resulting
aqueous layer was then extracted with ethyl acetate (5ϫ 30 mL),
dried with sodium sulfate, filtered and concentrated under vacuum
to afford 4-ethyl-2-methoxyphenol (3, 1.65 g, 90% yield) as a yel-
low oil. 1H NMR (400 MHz, CDCl3): δ = 6.81–6.86 (m, 1 H), 6.66–
6.73 (m, 2 H), 5.45 (br. s, 1 H), 3.89 (s, 3 H), 2.59 (q, J = 10.0 Hz,
2 H), 1.22 (t, J = 10.0 Hz, 3 H) ppm.
4-Ethyl-5-(1H-indol-3-yl)-2-methoxyphenol
(3a):
1H
NMR
(400 MHz, CDCl3): δ = 8.16 (br. s, 1 H), 7.48 (dd, J = 0.8, 8.0 Hz,
1 H), 7.39–7.44 (m, 1 H), 7.19–7.24 (m, 1 H), 7.09–7.15 (m, 2 H),
6.96 (s, 1 H), 6.85 (s, 1 H), 5.47 (s, 1 H), 3.95 (s, 3 H), 2.58 (q, J =
7.6 Hz, 2 H), 1.07 (t, J = 7.6 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 145.7 (C), 143.1 (C), 135.8 (C), 135.2 (C), 127.7 (C),
126.5 (C), 122.5 (CH), 122.1 (CH), 120.0 (CH), 119.8 (CH), 117.3
(CH), 117.0 (C), 111.0 (CH), 111.0 (CH), 56.0 (CH3), 26.2 (CH2),
16.2 (CH3) ppm. HRMS (ESI+): calcd. for C17H17NNaO2 [M +
Na] 290.1151; found 290.1160.
5-(1H-Indol-3-yl)-4-isopropyl-2-methoxyphenol (5a): 1H NMR
(300 MHz, CDCl3): δ = 8.14 (br. s, 1 H), 7.47 (d, J = 8.1 Hz, 1 H),
7.39 (d, J = 8.1 Hz, 1 H), 7.25–7.17 (m, 1 H), 7.14–7.06 (m, 2 H),
6.91 (s, 1 H), 6.89 (s, 1 H), 5.49 (s, 1 H), 3.95 (s, 3 H), 3.17–3.08 (m,
1 H), 1.12 (d, J = 6.9 Hz, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 146.0 (C), 143.0 (C), 140.2 (C), 135.8 (C), 128.0 (C), 125.9 (C),
122.6 (CH), 122.0 (CH), 119.8 (CH), 119.7 (CH), 117.2 (CH), 117.0
(C), 111.0 (CH), 107.8 (CH), 56.0 (CH3), 29.5 (CH), 24.6 (CH3
ϫ2) ppm. HRMS (ESI+): calcd. for C18H20NO2 [M + H] 282.1489;
found 282.1485.
5-[5-(Benzyloxy)-1H-indol-3-yl]-4-ethyl-2-methoxyphenol (3b): 1H
NMR (300 MHz, CDCl3): δ = 8.06 (br. s, 1 H), 7.40–7.47 (m, 2
H), 7.26–7.29 (m, 4 H), 7.09 (d, J = 2.1 Hz, 1 H), 6.94–7.03 (m, 2
H), 6.93 (s, 1 H), 6.84 (s, 1 H), 5.47 (s, 1 H), 5.02 (s, 2 H), 3.94 (s,
3 H), 2.55 (q, J = 7.5 Hz, 2 H), 1.05 (t, J = 7.5 Hz, 3 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 153.6 (C), 145.7 (C), 143.2 (C), 137.6
(C), 135.2 (C), 131.1 (C), 128.4 (CH ϫ2), 128.0 (C), 127.7 (CH),
127.6 (CH ϫ2), 126.6 (C), 123.3 (CH), 117.2 (CH), 116.9 (C), 113.2
(CH), 111.8 (CH), 111.0 (CH), 103.2 (CH), 70.9 (CH2), 56.0 (CH3), 5-[5-(Benzyloxy)-1H-indol-3-yl]-4-isopropyl-2-methoxyphenol (5b):
26.2 (CH2), 16.2 (CH3) ppm. HRMS (ESI+): calcd. for C24H24NO3 1H NMR (400 MHz, CDCl3): δ = 8.07 (br. s, 1 H), 7.45–7.42 (m,
[M + H] 374.1751; found 374.1756.
2 H), 7.38–7.27 (m, 4 H), 7.08 (d, J = 2.4 Hz, 1 H), 7.00–6.99 (m,
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O40079
/KAP1
Date: 26-02-14 19:24:41
Pages: 12
S. K. Chittimalla et al.
FULL PAPER
1 H), 6.96 (app. dd, J = 2.4, 8.8 Hz, 1 H), 6.89 (app. d, J = 2.0 Hz,
5-(1-Ethyl-1H-indol-3-yl)-2,3-dimethoxyphenol (7g): 1H NMR
(300 MHz, CDCl3): δ = 7.92 (d, J = 7.8 Hz, 1 H), 7.38 (app. d, J
1 H), 5.48 (s, 1 H), 5.02 (s, 2 H), 3.96 (s, 3 H), 3.15–3.08 (m, 1 H),
1.07 (d, J = 6.8 Hz, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = = 8.1 Hz, 1 H), 7.22–7.28 (m, 2 H), 7.12–7.21 (m, 1 H), 6.89 (d, J
153.6 (C), 146.0 (C), 143.0 (C), 140.2 (C), 137.6 (C), 131.0 (C),
128.4 (CH ϫ2), 128.3 (C), 127.7 (CH), 127.6 (CH ϫ2), 125.9 (C),
123.4 (CH), 117.1 (CH), 116.9 (C), 113.3 (CH), 111.8 (CH), 107.8
= 1.8 Hz, 1 H), 6.77 (d, J = 1.8 Hz, 1 H), 5.79 (s, 1 H), 4.20 (q, J
= 7.2 Hz, 2 H), 3.94 (s, 3 H), 3.93 (s, 3 H), 1.50 (t, J = 7.2 Hz, 3
H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 152.5 (C), 149.5 (C),
(CH), 102.7 (CH), 70.8 (CH2), 56.0 (CH3), 29.5 (CH), 24.6 (CH3 136.4 (C), 133.9 (C), 131.9 (C), 126.1 (C), 124.7 (CH), 121.8 (CH),
ϫ2) ppm. HRMS (ESI+): calcd. for C25H25NNaO3 [M + Na]
410.1727; found 410.1722.
119.9 (CH), 119.8 (CH), 116.5 (C), 109.6 (CH), 106.9 (CH), 103.5
(CH), 61.0 (CH3), 55.9 (CH3), 40.9 (CH2), 15.4 (CH3) ppm. HRMS
(ESI+): calcd. for C18H20NO3 [M + H] 298.1438; found 298.1449.
4-tert-Butyl-2-methoxyphenol (6): A two-step literature protocol
utilizing 4-tert-butylphenol as starting material was employed for
the synthesis of 4-tert-butyl-2-methoxyphenol.[21] 1H NMR
(400 MHz, CDCl3): δ = 6.80–6.95 (m, 3 H), 5.53 (br. s, 1 H), 3.88
(s, 3 H), 1.30 (9 H) ppm.
2,3-Dimethoxy-5-(2-methyl-1H-indol-3-yl)phenol (7h): 1H NMR
(300 MHz, CDCl3): δ = 7.95 (br. s, 1 H), 7.67 (d, J = 7.5 Hz, 1 H),
7.29–7.39 (m, 1 H), 7.06–7.21 (m, 2 H), 6.72 (d, J = 2.1 Hz, 1 H),
6.64 (d, J = 2.1 Hz, 1 H), 5.80 (s, 1 H), 3.96 (s, 3 H), 3.89 (s, 3 H),
2.51 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 152.3 (C),
149.2 (C), 135.1 (C), 133.7 (C), 131.6 (C), 131.4 (C), 127.7 (C),
121.4 (CH), 119.9 (CH), 118.7 (CH), 114.1 (C), 110.3 (CH), 109.0
(CH), 105.6 (CH), 61.0 (CH3), 55.9 (CH3), 12.4 (CH3) ppm.
HRMS (ESI+): calcd. for C17H17NNaO3 [M + Na] 306.1101; found
306.1108.
4-tert-Butyl-6,6-dimethoxycyclohexa-2,4-dienone (MOB of 6): 1H
NMR (400 MHz, CDCl3): δ = 7.01 (dd, J = 2.4, 10.0 Hz, 1 H),
6.08 (d, J = 2.4 Hz, 1 H), 6.01 (d, J = 10.0 Hz, 1 H), 3.36 (s, 6 H),
1.16 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 195.5 (C),
145.8 (C), 140.5 (CH), 126.3 (CH), 125.5 (CH), 91.6 (C), 50.0 (2ϫ
CH3), 34.4 (C), 28.4 (3ϫ CH3) ppm. HRMS (ESI+): calcd. for [M
+ Na] 233.1148; found 233.1154.
3-Bromo-2-methoxyphenol (8):[22] A four-step protocol was utilized
for the synthesis of aforementioned 3-bromo-2-methoxyphenol
starting from 1,2-dihydroxybenzene. A solution of 1,2-dihydroxy-
benzene (5.0 g, 45.5 mmol) in acetone (150 mL) was treated with
K2CO3 (9.4 g, 68.3 mmol) and stirred for 20 min. To mixture this
was added MOMCl (3.85 g, 3.6 mL, 47.8 mmol) and stirred for 8 h
at room temperature. The reaction mixture was filtered through a
pad of Celite and the solvents were evaporated followed by aqueous
NH4Cl and ethyl acetate extraction. The organic extracts were col-
lected and concentrated to give a residue that was purified by col-
umn chromatography to give mono-MOM-protected catechol[23]
(3.9 g, 56%). 1H NMR (300 MHz, CDCl3): δ = 7.08 (d, J = 8.1 Hz,
1 H), 6.91–6.99 (m, 2 H), 6.77–6.87 (m, 1 H), 5.96 (br. s, 1 H), 5.19
(s, 2 H), 3.52 (s, 3 H) ppm.
5-(1H-Indol-3-yl)-2,3-dimethoxyphenol (7a): 1H NMR (300 MHz,
CDCl3): δ = 8.22 (br. s, 1 H), 7.93 (d, J = 7.8 Hz, 1 H), 7.42 (app.
d, J = 7.8 Hz, 1 H), 7.33 (d, J = 2.4 Hz, 1 H), 7.14–7.29 (m, 2 H),
6.90 (d, J = 2.1 Hz, 1 H), 6.79 (d, J = 2.1 Hz, 1 H), 5.80 (s, 1 H),
3.95 (s, 3 H), 3.93 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 152.5 (C), 149.5 (C), 136.6 (C), 134.1 (C), 131.8 (C), 125.6 (C),
122.4 (CH), 121.7 (CH), 120.3 (CH), 119.7 (CH), 118.1 (C), 111.4
(CH), 107.1 (CH), 103.7 (CH), 61.1 (CH3), 55.9 (CH3) ppm.
HRMS (ESI+): calcd. for C16H16NO3 [M + H] 270.1125; found
270.1122.
5-[5-(Benzyloxy)-1H-indol-3-yl]-2,3-dimethoxyphenol
(7b):
1H
NMR (400 MHz, CDCl3): δ = 8.12 (br. s, 1 H), 7.42–7.49 (m, 3
H), 7.35–7.41 (m, 2 H), 7.27–7.33 (m, 3 H), 6.99 (dd, J = 2.4,
8.8 Hz, 1 H), 6.85 (d, J = 2.0 Hz, 1 H), 6.70 (d, J = 2.0 Hz, 1 H),
5.80 (s, 1 H), 5.12 (s, 2 H), 3.94 (s, 3 H), 3.86 (s, 3 H) ppm. 13C
NMR (100 MHz, CDC13 + CD3OD): δ = 153.4 (C), 152.7 (C),
150.0 (C), 137.4 (C), 134.1 (C), 132.0 (C), 128.4 (CH ϫ2), 127.6
(CH), 127.4 (CH ϫ2), 125.7 (C), 122.7 (CH), 117.2 (C), 112.9
(CH), 112.1 (CH), 107.3 (CH), 104.4 (C), 103.2 (CH), 103.1 (CH),
71.0 (CH2), 60.8 (CH3), 55.7 (CH3) ppm. HRMS (ESI+): calcd. for
C23H21NNaO4 [M + Na] 398.1363; found 398.1368.
To a solution of tert-butylamine (2.8 g, 4.1 mL, 39 mmol) in tolu-
ene (35 mL) at –30 °C was added bromine (3.1 g, 1.0 mL,
19.5 mmol) dropwise and stirred for 30 min. The reaction mixture
was further cooled to –60 °C to which a solution of mono-MOM-
protected catechol (3.0 g, 19.5 mmol) in dichloromethane (–5 mL)
was added. The reaction was brought to room temperature over a
period of 4–5 h then treated with 10% sodium thiosulfate, washed
with brine and extracted with ethyl acetate. The organic extracts
were dried with sodium sulfate, filtered and concentrated to give a
residue. 1H NMR (300 MHz, CDCl3) (peaks assigned from 1H
NMR spectroscopic data obtained for the crude residue): δ = 7.16
(dd, J = 1.5, 8.1 Hz, 1 H), 7.04 (dd, J = 1.5, 8.1 Hz, 1 H), 6.72
(app. t, J = 8.1 Hz, 1 H), 5.21 (s, 2 H), 3.52 (s, 3 H) ppm. The
obtained residue was dissolved in dimethylformamide (DMF,
40 mL) and was treated with K2CO3 (5.5 g, 40 mmol) and methyl
iodide (4.16 g, 1.8 mL, 29.3 mmol). The reaction mixture was
stirred at room temperature for 8 h and after usual workup pro-
5-(5-Bromo-1H-indol-3-yl)-2,3-dimethoxyphenol (7c): 1H NMR
(400 MHz, CDCl3): δ = 8.29 (br. s, 1 H), 8.02 (d, J = 1.6 Hz, 1 H),
7.22–7.37 (m, 3 H), 6.85 (d, J = 1.6 Hz, 1 H), 6.70 (d, J = 1.6 Hz,
1 H), 5.86 (s, 1 H), 3.95 (s, 3 H), 3.93 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 152.6 (C), 149.6 (C), 135.2 (C), 134.3 (C),
130.9 (C), 127.4 (C), 125.3 (CH), 122.7 (CH), 122.3 (CH), 117.9
(C), 113.7 (C), 112.8 (CH), 107.2 (CH), 103.8 (CH), 61.1 (CH3),
56.0 (CH3) ppm. HRMS (ESI+): calcd. for C16H14BrNNaO3 [M +
Na] 370.0049; found 370.0063.
vided a crude residue. 1H NMR (300 MHz, CDCl3) (peaks assigned
2,3-Dimethoxy-5-(7-methyl-1H-indol-3-yl)phenol (7f): 1H NMR from H NMR spectroscopic data obtained for the crude residue):
1
(400 MHz, CDCl3): δ = 8.18 (br. s, 1 H), 7.82 (d, J = 8.0 Hz, 1 H),
7.30 (d, J = 2.4 Hz, 1 H), 7.14 (app. t, J = 7.2 Hz, 1 H), 7.07 (d, J
δ = 7.19 (dd, J = 1.5, 8.1 Hz, 1 H), 7.09 (dd, J = 1.5, 8.1 Hz, 1 H),
6.90 (app. t, J = 8.1 Hz, 1 H), 5.21 (s, 2 H), 3.88 (s, 3 H), 3.51 (s,
= 7.2 Hz, 1 H), 6.93 (d, J = 1.6 Hz, 1 H), 6.82 (d, J = 1.6 Hz, 1 3 H) ppm. The obtained crude product was treated with 4 n HCl
H), 5.91 (br. s, 1 H), 3.97 (s, 3 H), 3.94 (s, 3 H), 2.52 (s, 3 H) ppm.
13C NMR (CDCl3, 100 MHz): δ = 152.5 (C), 149.5 (C), 136.1 (C),
134.0 (C), 131.9 (C), 125.2 (C), 122.9 (CH), 121.5 (CH), 120.5
in dioxane (15 mL) and stirred for 5 h. The solvents were evapo-
rated and the obtained residue was purified by column chromatog-
raphy with silica gel by using a mixture of ethyl acetate and hexanes
(CH), 120.48 (C), 118.5 (C), 117.5 (CH), 107.1 (CH), 103.7 (CH), as eluent to give 3-bromo-2-methoxyphenol (8, 1.9 g, 49% over 3
61.0 (CH3), 55.9 (CH3), 16.5 (CH3) ppm. HRMS (ESI+): calcd. for steps). 1H NMR (400 MHz, CDCl3): δ = 7.06 (dd, J = 1.6, 8.0 Hz,
C17H17NNaO3 [M + Na] 306.1101; found 306.1108.
1 H), 6.83–6.97 (m, 2 H), 6.30 (s, 1 H), 3.88 (s, 3 H) ppm.
8
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O40079
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Date: 26-02-14 19:24:41
Pages: 12
Access to 3-Arylindoles through a Tandem One-Pot Protocol
3-Bromo-5-(1H-indol-3-yl)-2-methoxyphenol (8a): 1H NMR The reaction mixture was subjected to hydrogenation at 45 psi at
(400 MHz, CDCl3): δ = 8.18 (br. s, 1 H), 7.88 (d, J = 7.6 Hz, 1 H),
7.38–7.40 (m, 2 H), 7.10–7.28 (m, 4 H), 5.92 (br. s, 1 H), 3.92 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 149.9 (C), 142.6 (C),
136.5 (C), 133.8 (C), 125.3 (C), 123.2 (CH), 122.5 (CH), 122.1
room temperature on a Parr shaker. After 8 h, the reaction mixture
was filtered through a pad of Celite and the filtrate was concen-
trated. The residue was purified by column chromatography by
using ethyl acetate/hexanes as eluents to provide 2-methoxy-3-
1
(CH), 120.5 (CH), 119.5 (CH), 116.3 (C), 116.1 (C), 113.8 (CH), methylphenol (0.82 g, 91% yield) as an off-white solid. H NMR
111.5 (CH), 61.2 (CH3) ppm. HRMS (ESI+): calcd. for (400 MHz, CDCl3): δ = 6.91 (t, J = 8.0 Hz, 1 H), 6.79 (d, J =
C15H12BrNNaO2 [M + Na] 339.9944; found 339.9942.
8.0 Hz, 1 H), 6.69 (d, J = 8.0 Hz, 1 H), 5.60 (br. s, 1 H), 3.79 (s, 3
H), 2.30 (s, 3 H) ppm.
5-(1H-Indol-3-yl)-2-methoxy-3-methylphenol (9a): 1H NMR
5-[5-(Benzyloxy)-1H-indol-3-yl]-3-bromo-2-methoxyphenol (8b): 1H
NMR (400 MHz, CDCl3): δ = 8.14 (br. s, 1 H), 7.47–7.51 (m, 2
H), 7.37–7.43 (m, 3 H), 7.28–7.35 (m, 4 H), 7.16 (d, J = 2.0 Hz, 1 (400 MHz, CDCl3): δ = 8.16 (br. s, 1 H), 7.92 (d, J = 8.0 Hz, 1 H),
H), 6.99 (dd, J = 2.4, 8.8 Hz, 1 H), 5.72 (s, 1 H), 5.13 (s, 2 H), 3.96
7.37 (app. d, J = 8.0 Hz, 1 H), 7.26 (d, J = 2.8 Hz, 1 H), 7.15–7.25
(m, 2 H), 7.11 (d, J = 2.0 Hz, 1 H), 7.01 (d, J = 2.0 Hz, 1 H), 5.71
(s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.9 (C), 150.0
(C), 142.6 (C), 137.5 (C), 133.9 (C), 131.8 (C), 128.6 (CH ϫ2), (br. s, 1 H), 3.83 (s, 3 H), 2.36 (s, 3 H) ppm. 13C NMR (100 MHz,
127.8 (CH), 127.7 (CH ϫ2), 125.7 (C), 123.1 (CH), 122.9 (CH),
116.3 (C), 116.0 (C), 113.6 (CH), 113.4 (CH), 112.1 (CH), 103.2
(CH), 71.0 (CH2), 61.2 (CH3) ppm. HRMS (EI+): calcd. for
C22H18BrNNaO3 [M + Na] 446.0362; found 446.0350.
CDCl3): δ = 148.9 (C), 143.9 (C), 136.6 (C), 132.1 (C), 130.9 (C),
125.7 (C), 122.3 (CH), 121.6 (CH), 121.6 (CH), 120.2 (CH), 119.8
(CH), 117.8 (C), 112.1 (CH), 111.3 (CH), 60.8 (CH3), 16.0
(CH3) ppm. HRMS (ESI+): calcd. for C16H15NNaO2 [M + Na]
276.0995; found 276.1004.
5-[5-(Benzyloxy)-1H-indol-3-yl]-3-bromo-2,2-dimethoxycyclohex-
3-enone (MA-I): 1H NMR (400 MHz, CDCl3): δ = 8.03 (br. s, 1 4-(1H-Indol-3-yl)-2-methoxy-3-methylphenol (9aЈ): 1H NMR
H), 7.51–7.44 (m, 2 H), 7.43–7.36 (m, 2 H), 7.35–7.25 (m, 2 H),
7.11 (d, J = 2.4 Hz, 1 H), 6.98 (d, J = 2.4 Hz, 1 H), 6.96 (app. d,
J = 2.4 Hz, 1 H), 6.80 (d, J = 3.6 Hz, 1 H), 5.11 (s, 2 H), 4.13–4.02
(400 MHz, CDCl3): δ = 8.20 (br. s, 1 H), 7.46 (d, J = 8.0 Hz, 1 H),
7.41 (app. d, J = 8.0 Hz, 1 H), 7.19–7.26 (m, 2 H), 7.10–7.16 (m, 2
H), 7.08 (d, J = 8.0 Hz, 1 H), 6.88 (d, J = 8.0 Hz, 1 H), 3.85 (s, 3
(m, 1 H), 3.40 (s, 3 H), 3.39 (s, 3 H), 3.13–3.02 (m, 2 H) ppm. 13C H), 2.23 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.7
NMR (100 MHz, CDCl3): δ = 200.5 (C), 153.4 (C), 140.5 (CH),
137.4 (C), 131.8 (C), 128.5 (CH ϫ2), 127.9 (CH), 127.6 (CH ϫ2),
125.9 (C), 122.8 (C), 121.8 (CH), 115.6 (C), 113.6 (CH), 112.3
(CH), 102.0 (CH), 96.9 (C), 71.0 (CH2), 52.1 (CH3), 51.9 (CH3),
(C), 145.7 (C), 135.8 (C), 130.2 (C), 127.7 (C), 127.4 (C), 127.2
(CH), 122.7 (CH), 122.1 (CH), 120.0 (CH), 119.8 (CH), 117.2 (C),
112.5 (CH), 111.2 (CH), 60.6 (CH3), 13.9 (CH3) ppm. HRMS
(ESI+): calcd. for C16H15NNaO2 [M + Na] 276.0995; found
43.4 (CH2), 36.1 (CH) ppm. HRMS (ESI+): calcd. for 276.0992.
C23H22BrNNaO4 [M + Na] 478.0624; found 478.0613.
5-[5-(Benzyloxy)-1H-indol-3-yl]-2-methoxy-3-methylphenol (9b): 1H
1
3-Bromo-5-(1-ethyl-1H-indol-3-yl)-2-methoxyphenol (8g): H NMR
NMR (400 MHz, CDCl3): δ = 8.08 (br. s, 1 H), 7.42–7.52 (m, 3
H), 7.35–7.41 (m, 2 H), 7.22–7.34 (m, 3 H), 7.05 (d, J = 1.6 Hz, 1
H), 6.97 (dd, J = 2.4, 8.8 Hz, 1 H), 6.93 (d, J = 1.6 Hz, 1 H), 5.68
(s, 1 H), 5.11 (s, 2 H), 3.84 (s, 3 H), 2.35 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 153.7 (C), 148.9 (C), 143.8 (C), 137.7 (C),
132.1 (C), 131.9 (C), 130.9 (C), 128.5 (CH ϫ2), 127.8 (CH), 127.6
(400 MHz, CDCl3): δ = 7.89 (d, J = 7.6 Hz, 1 H), 7.32–7.39 (m, 2
H), 7.21–7.29 (m, 3 H), 7.12–7.20 (m, 1 H), 5.87 (br. s, 1 H), 4.14
(q, J = 7.2 Hz, 2 H), 3.92 (s, 3 H), 1.45 (t, J = 7.2 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 149.9 (C), 142.3 (C), 136.4 (C),
134.0 (C), 125.9 (C), 125.0 (CH), 123.0 (CH), 122.0 (CH), 120.1
(CH), 119.7 (CH), 115.9 (C), 114.8 (C), 113.6 (CH), 109.6 (CH), (CH ϫ2), 126.1 (C), 122.5 (CH), 121.4 (CH), 117.7 (C), 113.2
61.2 (CH3), 41.0 (CH2), 15.3 (CH3) ppm. HRMS (ESI+): calcd. for (CH), 112.0 (CH ϫ2), 103.6 (CH), 71.1 (CH2), 60.8 (CH3), 16.0
C17H16BrNNaO2 [M + Na] 368.0257; found 363.0259.
3-Bromo-2-methoxy-5-(2-methyl-1H-indol-3-yl)phenol (8h): 1H
(CH3) ppm. HRMS (ESI+): calcd. for C23H21NNaO3 [M + Na]
382.1414; found 382.1412.
NMR (400 MHz, CDCl3): δ = 7.86 (br. s, 1 H), 7.63 (d, J = 7.6 Hz, 4-[5-(Benzyloxy)-1H-indol-3-yl]-2-methoxy-3-methylphenol
(9bЈ):
1 H), 7.17–7.26 (m, 2 H), 7.07–7.16 (m, 2 H), 7.03 (d, J = 1.6 Hz, 1H NMR (400 MHz, CDCl3): δ = 8.12 (br. s, 1 H), 7.41–7.49 (m,
1 H), 5.95 (br. s, 1 H), 3.93 (s, 3 H), 2.39 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 149.7 (C), 142.4 (C), 135.0 (C), 133.7 (C),
131.8 (C), 127.4 (C), 125.2 (CH), 121.6 (CH), 120.1 (CH), 118.4
(CH), 115.8 (CH), 115.7 (C), 112.5 (C), 110.4 (CH), 61.1 (CH3),
12.4 (CH3) ppm. HRMS (ESI+): calcd. for C16H14BrNNaO2 [M +
Na] 354.0100; found 354.0107.
2-Methoxy-3-methylphenol (9):[18] To a solution of 2,3-dihydroxy-
benzaldehyde (2.0 g, 14.5 mmol) in DMF (25 mL) was added
K2CO3 (2.2 g, 15.9 mmol). After stirring the mixture for 30 min,
methyliodide (0.99 mL, 15.9 mmol) was added dropwise and the
reaction was continued for 16 h. The reaction was quenched with
water and extracted with ethyl acetate (4ϫ 30 mL). The organic
layers were dried with sodium sulfate and concentrated under vac-
uum. The residue was purified by column chromatography to af-
ford 3-hydroxy-2-methoxybenzaldehyde (1.3 g, 60% yield).[24] 1H
NMR (300 MHz, CDCl3): δ = 10.27 (s, 1 H), 7.38 (dd, J = 1.8,
7.8 Hz, 1 H), 7.24 (dd, J = 1.8, 7.8 Hz, 1 H), 7.16 (app. t, J =
2 H), 7.28–7.40 (m, 4 H), 7.10 (d, J = 2.4 Hz, 1 H), 7.06 (d, J =
8.4 Hz, 1 H), 6.95–7.02 (m, 2 H), 6.89 (d, J = 8.4 Hz, 1 H), 5.71
(br. s, 1 H), 5.06 (s, 2 H), 3.86 (s, 3 H), 2.19 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 153.5 (C), 147.7 (C), 145.7 (C), 137.6
(C), 131.1 (C), 130.2 (C), 128.4 (2 X CH), 127.75 (C), 127.7 (CH),
127.5 (2 X CH), 127.1 (CH), 123.5 (CH), 117.0 (C), 113.2 (CH),
112.5 (CH), 111.9 (CH), 103.4 (CH), 70.9 (CH2), 60.7 (CH3), 13.9
(CH3) ppm. HRMS (ESI+): calcd. for C23H22NO3 [M + H]
360.1594; found 360.1605.
5-(1-Ethyl-1H-indol-3-yl)-2-methoxy-3-methylphenol (9g): 1H NMR
(400 MHz, CDCl3): δ = 7.91–7.95 (m, 1 H), 7.35–7.38 (m, 1 H),
7.22–7.27 (m, 2 H), 7.16 (ddd, J = 1.2, 7.2, 8.0 Hz, 1 H), 7.11 (d,
J = 2.0 Hz, 1 H), 7.00 (dd, J = 0.4, 2.0 Hz, 1 H), 5.67 (br. s, 1 H),
4.19 (q, J = 7.6 Hz, 2 H), 3.84 (s, 3 H), 2.36 (s, 3 H), 1.49 (t, J =
7.6 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.9 (C),
143.6 (C), 136.4 (C), 132.3 (C), 130.9 (C), 126.2 (C), 124.6 (CH),
121.7 (CH), 121.4 (CH), 120.0 (CH), 119.7 (CH), 116.3 (C), 111.9
7.8 Hz, 1 H), 5.85 (br. s, 1 H), 3.98 (s, 3 H) ppm. A mixture of 3- (CH), 109.5 (CH), 60.7 (CH3), 40.9 (CH2), 16.0 (CH3), 15.4
hydroxy-2-methoxybenzaldehyde (1.0 g, 6.6 mmol) and 10% Pd/C
(150 mg) in ethanol (25 mL) was taken in a pressure reaction vessel.
(CH3) ppm. HRMS (ESI+): calcd. for C18H20NO2 [M + H]
282.1489; found 282.1484.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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Job/Unit: O40079
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Date: 26-02-14 19:24:41
Pages: 12
S. K. Chittimalla et al.
FULL PAPER
4-(1-Ethyl-1H-indol-3-yl)-2-methoxy-3-methylphenol
(9gЈ):
1H 1.6, 10.0 Hz, 1 H), 5.92 (ddd, J = 1.6, 6.4, 8.0 Hz, 1 H), 3.45 (s, 3
NMR (400 MHz, CDCl3): δ = 7.46 (app. d, J = 8.0 Hz, 1 H), 7.37 H), 3.41 (s, 3 H), 3.35–3.40 (m, 1 H), 3.27–3.31 (m, 1 H), 3.24 (s,
(app. d, J = 8.0 Hz, 1 H), 7.20–7.27 (m, 1 H), 7.06–7.13 (m, 2 H),
7.05 (s, 1 H), 6.87 (d, J = 8.0 Hz, 1 H), 5.71 (br. s, 1 H), 4.20 (q, J
= 7.2 Hz, 2 H), 3.85 (s, 3 H), 2.25 (s, 3 H), 1.50 (t, J = 7.2 Hz, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.5 (C), 145.7 (C),
135.7 (C), 130.0 (C), 127.89 (C), 127.87 (C), 127.2 (CH), 125.7
(CH), 121.5 (CH), 120.2 (CH), 119.3 (CH), 115.7 (C), 112.5 (CH),
109.3 (CH), 60.6 (CH3), 40.9 (CH2), 15.5 (CH3), 14.0 (CH3) ppm.
HRMS (ESI+): calcd. for C18H19NNaO2 [M + Na] 304.1308; found
304.1321.
3 H), 3.21–3.23 (m, 1 H), 3.11–3.14 (m, 1 H), 3.08 (s, 3 H) ppm.
Dimer 11D:[25] 1H NMR (400 MHz, CDCl3): δ = 6.27 (d, J =
3.2 Hz, 1 H), 6.19 (t, J = 7.2 Hz, 1 H), 5.53 (d, J = 8.0 Hz, 1 H),
3.46 (s, 3 H), 3.39 (s, 3 H), 3.26 (d, J = 8.4 Hz, 1 H), 3.22 (s, 3 H),
3.09 (d, J = 6.8 Hz, 1 H), 3.04 (s, 3 H), 2.86–2.94 (m, 1 H), 1.85
(s, 3 H), 1.33 (s, 3 H) ppm.
Dimer 12D:[25] 1H NMR (400 MHz, CDCl3): δ = 5.91 (s, 1 H), 5.81
(d, J = 6.8 Hz, 1 H), 3.42 (s, 3 H), 3.38 (s, 3 H), 3.22 (s, 3 H), 3.12–
3.20 (m, 3 H), 3.04 (s, 3 H), 3.00 (app. d, J = 6.8 Hz, 1 H), 1.95 (s,
3 H), 1.60 (s, 3 H) ppm.
2-Methoxy-3-methyl-5-(2-methyl-1H-indol-3-yl)phenol (9h): 1H
NMR (400 MHz, CDCl3): δ = 7.89 (br. s, 1 H), 7.73 (d, J = 7.6 Hz,
1 H), 7.30 (app. d, J = 7.6 Hz, 1 H), 7.12–7.23 (m, 2 H), 7.01 (d, J
= 2.0 Hz, 1 H), 6.91 (d, J = 2.0 Hz, 1 H), 5.85 (s, 1 H), 3.90 (s, 3
H), 2.47 (s, 3 H), 2.42 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 148.6 (C), 143.5 (C), 135.1 (C), 131.9 (C), 131.3 (C), 130.6 (C),
127.7 (C), 123.5 (CH), 121.3 (CH), 119.8 (CH), 118.8 (CH), 114.0
(CH), 113.8 (C), 110.3 (CH), 60.6 (CH3), 15.9 (CH3), 12.4
(CH3) ppm. HRMS (ESI+): calcd. for C17H18NO2 [M + H]
268.1332; found 268.1328.
Supporting Information (see footnote on the first page of this arti-
1
cle): Copies of the H NMR and 13C NMR spectra.
Acknowledgments
The authors sincerely thank Dr. Anjan Chakrabarti and Dr. Take-
shi Yura for their encouragement. K. C. B, D. C. A. T. and
D. M. J. L. thank AMRI Singapore for a short internship opportu-
nity. Sincere gratitude goes to Ms. Ng Su Ling and Dr. Wee Xi Kai
of Singapore Polytechnic for technical support. Thanks are also
due to School of Chemical and Life Sciences, Singapore Polytech-
nic for partial financial support (CLS-13A087) to conduct this re-
search work.
2-Methoxy-6-methylphenol (11):[25] A mixture of 2-hydroxy-3-meth-
oxybenzaldehyde (2.0 g, 13.2 mmol) and 10% Pd/C (300 mg) in
ethanol (50 mL) was taken in a pressure reaction vessel. The reac-
tion mixture was subjected to hydrogenation at 40 psi at room tem-
perature on a Parr shaker. After 8 h, the reaction mixture was fil-
tered through a pad of Celite and the filtrate was evaporated. The
residue was purified by column chromatography by using ethyl
acetate/hexanes as eluents to provide 2-methoxy-6-methylphenol
(1.45 g, 82% yield) as an off-white low-melting solid. 1H NMR
(400 MHz, CDCl3): δ = 6.70–6.80 (m, 3 H), 5.71 (s, 1 H), 3.89 (s,
3 H), 2.28 (s, 3 H) ppm.
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Dimer 1D:[26] 1H NMR (400 MHz, CDCl3): δ = 6.14 (d, J =
10.0 Hz, 1 H), 5.94 (d, J = 10.0 Hz, 1 H), 5.48–5.53 (m, 1 H), 3.41
(s, 3 H), 3.39 (s, 3 H), 3.31 (s, 3 H), 3.07 (s, 3 H), 2.83–2.89 (m, 2
H), 2.77 (d, J = 6.4 Hz, 1 H), 1.75 (d, J = 1.6 Hz, 3 H), 1.36 (s, 3
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1
Dimer 3D: H NMR (400 MHz, CDCl3): δ = 6.28 (d, J = 10.4 Hz,
1 H), 5.98 (d, J = 10.4 Hz, 1 H), 5.39–5.46 (m, 1 H), 3.39 (s, 3 H),
3.38 (s, 3 H), 3.30 (s, 3 H), 3.04 (s, 3 H), 2.96 (d, J = 6.8 Hz, 1 H),
2.87 (t, J = 2.0 Hz, 1 H), 2.82 (d, J = 2.0 Hz, 1 H), 2.05–2.13 (m,
2 H), 1.71–1.84 (m, 1 H), 1.60–1.70 (m, 1 H), 1.02 (t, J = 7.6 Hz,
3 H), 0.92 (d, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 202.1 (C), 193.2 (C), 150.4 (CH), 149.2 (C), 127.5 (CH), 119.3
(CH), 98.3 (C), 94.7 (C), 57.8 (CH), 50.3 (CH3), 50.2 (CH3), 49.9
(CH3), 48.8 (CH3), 48.5 (C), 45.6 (CH), 44.9 (CH), 32.8 (CH2),
27.5 (CH2), 10.0 (CH3), 9.3 (CH3) ppm. HRMS (ESI+): calcd. for
C20H28NaO6 [M + Na] 387.1778; found 387.1792.
1
Dimer 4D: H NMR (400 MHz, CDCl3): δ = 6.30 (d, J = 10.4 Hz,
1 H), 5.97 (d, J = 10.4 Hz, 1 H), 5.40–5.45 (m, 1 H), 3.40 (s, 3 H),
3.39 (s, 3 H), 3.32 (s, 3 H), 3.05 (s, 3 H), 2.94 (d, J = 6.4 Hz, 1 H),
2.82–2.88 (m, 2 H), 1.98–2.06 (m, 2 H), 1.48–1.75 (m, 3 H), 1.24–
1.48 (m, 3 H), 0.92 (t, J = 6.8 Hz, 3 H), 0.89 (t, J = 7.2 Hz, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 202.1 (C), 193.1 (C),
151.0 (CH), 147.9 (C), 127.2 (CH), 119.9 (CH), 98.3 (C), 94.7 (C),
58.3 (CH), 50.4 (CH3), 50.1 (CH3), 49.9 (CH3), 48.7 (CH3), 48.2
(C), 45.6 (CH), 45.0 (CH), 42.6 (CH2), 36.7 (CH2), 19.0 (CH2),
18.1 (CH2), 14.7 (CH3), 13.7 (CH3) ppm. HRMS (ESI+): calcd. for
C22H32NaO6 [M + Na] 415.2097, 415.2091; found 415.2100.
Dimer 10D:[25] 1H NMR (400 MHz, CDCl3): δ = 6.42 (dd, J = 4.0,
10.0 Hz, 1 H), 6.27 (ddd, J = 1.2, 7.6, 8.8 Hz, 1 H), 6.05 (dd, J =
10
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O40079
/KAP1
Date: 26-02-14 19:24:41
Pages: 12
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Received: January 16, 2014
Published Online: ᭿
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11

Job/Unit: O40079
/KAP1
Date: 26-02-14 19:24:41
Pages: 12
S. K. Chittimalla et al.
FULL PAPER
Heterocycles
S. K. Chittimalla,* C. Bandi, S. Putturu,
R. Kuppusamy, K. C. Boellaard,
D. C. A. Tan, D. M. J. Lum ............ 1–12
Access to 3-Arylindoles through a Tandem
One-Pot Protocol Involving Dearomatiz-
ation, a Regioselective Michael Addition
Reaction, and Rearomatization
A non-metal mediated detour method for installing oxygenated aryls at the 3-position of
indoles is described.
Keywords: Synthetic methods / Domino re-
actions
/ Michael addition / Nitrogen
heterocycles / Quinones
12
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0