Synthesis of Functionalized Indoles via Palladium-Catalyzed Aerobic Cycloisomerization of o-Allylanilines Using Organic Redox Cocatalyst

Article abstract of DOI:10.1021/acs.joc.8b01999

A scalable and practical synthesis of functionalized indoles via Pd-^tBuONO cocatalyzed aerobic cycloisomerization of o-allylanilines is reported. Using molecular oxygen as a terminal oxidant, a series of substituted indoles were prepared in moderate to good yields. The avoidance of hazardous oxidants, heavy-metal cocatalysts, and high boiling point solvents such as DMF and DMSO enables this method to be applied in pharmaceutical synthesis. A practical gram-scale synthesis of indomethacin demonstrates its application potential.

Full text of DOI:10.1021/acs.joc.8b01999

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Note
Synthesis of Functionalized Indoles via Palladium-Catalyzed Aerobic
Cycloisomerization of o-Allylanilines Using Organic Redox Cocatalyst
Xiao-Shan Ning, Mei-Mei Wang, Jian-Ping Qu, and Yan-Biao Kang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01999 • Publication Date (Web): 08 Oct 2018
Downloaded from http://pubs.acs.org on October 8, 2018
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The Journal of Organic Chemistry
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Synthesis of Functionalized Indoles via Palladium-Catalyzed Aerobic
Cycloisomerization of o-Allylanilines Using Organic Redox Cocata-
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lyst
†
‡
Xiao-Shan Ning,†‡ Mei-Mei Wang,‡ Jian-Ping Qu,* and Yan-Biao Kang*
†Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Jiangsu National Synergetic Innovation Center for
Advanced Materials, Nanjing Tech University, Nanjing 211816, China
‡Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
t
ABSTRACT: A scalable and practical synthesis of functionalized indoles via Pd- BuONO cocatalyzed aerobic cycloisomerization of o-allylani-
lines is reported. Using molecular oxygen as a terminal oxidant, a series of substituted indoles were prepared in moderate to good yields. The
avoidance of hazardous oxidants, heavy metal-cocatalysts as well as high boiling point solvents like DMF and DMSO enables this method to be
applied in the pharmaceutical synthesis. A practical gram-scale synthesis of indomethacin demonstrates its application potential.
Substituted indoles are among the most studied heterocycles be-
cause numerous biologically active molecules as well as medicinal
agents are based on the indole skeleton (Figure 1).1 The synthesis of
this class of compounds thus attracts tremendous research interests.
Starting with the seminal studies by Fischer et. al.,2 a large number of
methods toward the synthesis of substituted indoles have been de-
veloped.3-5 On the other hand, molecular oxygen is undoubtedly a
clean terminal oxidant whereas the hazardous transition metal redox
cocatalysts normally cannot be avoided in such aerobic processes.
Several modifications to avoid the hazardous oxidants in indole syn-
thesis have been developed recently.6-7
On the basis of our previous work on Pd-tBuONO cocatalyzed aer-
obic oxygenations of alkenes,8 we have recently developed a general
synthetically practical approach from 2-vinylanilines through regi-
oselective C-H amination.9 It provides an efficient method for ac-
cessing substituted indoles bearing C2, C4-C7 functional groups in
one step. This method is aslo practical in pharmaceutical synthesis
as it employs molecular O2 as the sole terminal oxidant avoiding the
use of hazardous oxidants, metal cocatalysts (Scheme 1A). During
our further investigation, we found that using the same Pd-tBuONO
system9 cycloisomerization of o-allylanilines underwent smoothly
(Scheme 1B) as well. And this could also afford functionalized in-
doles in a practical manner. Here we report this in details.
Scheme 1. Pd-tBuONO-Catalyzed Aerobic C-H amination of o-
Vinylanilines (A) and Cycloisomerization of o-Allylanilines (B)
Figure 1. Representative molecules based on indole skeleton.
Hegedus indole synthesis, an intramolecular oxidative N-heterocy-
clization of o-alkenyl anilines or o-allylanilines, has evolved as an ef-
ficient method to construct indole skeleton.3a,4,5 Traditionally, stoi-
chiometric or catalytic palladium salts have been used in the pres-
ence of oxidants such as Cu(OAc)2, AgOAc, PhI(OAc)2, benzoqui-
none, etc. Using molecular oxygen as the terminal oxidant to replace
the hazardous oxidant is an attractive choice. Several examples have
been reported but with limited success.4d,7
The reaction conditions have been investigated in previous work.9
The optimized reaction conditions for 2-vinyl anilines were applied
directly into the cyclization of 2-allyl anilines. The scope of substi-
tuted indoles were investigated using Pd(PhCN)2Cl2 as catalyst,
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tBuONO ascocatalyst andtBuOH assolvent inthepresence of 1 atm
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gram scale synthesis of indomethacin 6, a nonsteroidal anti-inflam-
matory drug which is commonly used as a prescription medication
to reduce fever, pain, stiffness, and swelling from inflammation, to
demonstrate the application potential in pharmaceutical synthesis.
By using present method, 1.63 grams of indomethacin 6 was synthe-
sized via a Pd-tBuONO cocatalyzed aerobic cycloisomerization of o-
allylanilines 1d through 5 steps in overall 46% of yield.
O2 atmosphere at 70 oC (Scheme 2). Various N-protecting groups are
applicable (Ms, Ns, Ts, Cbz, CO2Me). Indoles with different N-protect-
ing groups were investigated. Indoles bearing N-Ms (2a), N-Ts (2b), N-
Ns (2c), N-CO2Me (2d), and N-Cbz (2e) were achieved in 64-85%
yields. Either 2-methyl or 2-ethyl indoles could be readily obtained (2f,
2k). C2,C3-dimethyl indole is also avaible by this method (2h-2j). Ben-
zyl 5-chloro-2-methyl-1H-indole-1-carboxylate (2l) and methyl 2-me-
thyl-1H-benzo[g]indole-1-carboxylate (2m) were all synthesized in
good yields. Methyl 1,2,3,4-tetrahydro-9H-carbazole-9-carboxylate
(2n) could be obtained in 78% yield, while methyl 9H-carbazole-9-car-
boxylate (2o) could be obtained in 70% yield after treatment with DDQ
when the amination was completed.
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Scheme 3. Gram-Scale Synthesis of Indomethacin
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Scheme 2. Reaction Scopea
The reaction mechanism is proposed in Scheme 4 on the bases of
previous report.9 The isomerization transforms allyl aniline to pro-
penyl aniline isomer C, which passes through a Wacker process to
produce the final indoles. The pathway from C to 2 has been dis-
cussed with experimental evidence.9
Scheme 4. Proposed Mechanism
a Reaction conditions: 1 (0.25 mmol), tBuOH (2 mL), isolatedyields.
b Treated by DDQ (2.0 equiv) after amination. c Under Hegedus condi-
tions: Pd(PhCN)2Cl2 (10 mol%), benzoquinone (2 equiv), LiCl (10
equiv), THF, 75 oC, 24 h.
To evaluate the effectiveness and practical utility of this reaction in
organic synthesis, a gram scale preparation of 2d from 1d using the
standard condition wasperformed giving thedesiredproduct in63%
isolated yield (Scheme 3). Compound 2d was then applied in the
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The Journal of Organic Chemistry
(s, 3 H), 3.84 (s, 3 H), 2.58 (s, 3 H). 13C{1H} NMR (100 MHz, CDCl3)
In conclusion, we have developed a general and practical synthesis
of functionalized indoles via a Pd-tBuONO cocatalyzed aerobic cy-
cloisomerization of o-allylanilines. Using molecular oxygen as termi-
nal oxidant, a series of substituted indoles were prepared in moder-
ate to good yields under mild conditions. The non-involvement of
hazardous oxidants, heavy metal cocatalysts as well as high boiling
point solvents such as DMF and DMSO facilitates the application of
this method in pharmaceutical synthesis. A gram scale synthesis of
indomethacin was performed to demonstrate its application poten-
tial.
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138.8, 131.3, 130.7, 116.5, 111.9, 108.8, 102.8, 55.9, 53.6,
17.1. For gram scale reaction in Scheme 3, Pd(PhCN)2Cl2 (287.7 mg,
0.75 mmol) was weigheddirectly intoa500 mL roundbottomand dried
under high vacuum for 15 min, purged oxygen 3 times. Under an atmos-
phere of oxygen (1 atm, ballon), tBuOH (80 mL) and tBuONO (206.2
mg, 2 mmol) were added and stirred methyl (2-allyl-4-methoxy-
phenyl)carbamate (1d) (2.21 g, 10 mmol) was then added and the re-
sulting reaction mixture was heated at 70 °C until the starting material
disappeared and cooled to room temperature, filtered through a thin sil-
ica gel pad and washed with EtOAc. The filtrate was concentrated and
theresidue waspurifiedbychromatographyon silicagel(PE/ Et2O 50/ 1
to PE/ EA 10/ 1) to afford the corresponding product 2d as a white solid
(1.39 g, 63%).
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EXPERIMENTAL SECTION
General Information. Solvents were pre-dried over activated MS 4Å
and heated to reflux over sodium (for toluene and THF) or calcium
hydride (for CH2Cl2) under a nitrogen atmosphere and collected by
Benzyl 5-methoxy-2-methyl-1H-indole-1-carboxylate (2e). This com-
pound was prepared according to the general procedure and purified by
flash column chromatography (PE/ Et2O = 100/ 1); yellow oil (24 h,
1
distillation. H NMR (400 MHz) and 13C{1H} NMR (100 MHz)
47.6 mg, 64%). 1H NMR (400 MHz, CDCl3
J = 9.2 Hz, 1 H),
spectra were recorded on a Bruker spectrometer. Chemical shifts are re-
1
13
0; CDCl3, 1
7.46 (d, J = 6.8 Hz, 2 H), 7.41-7.34 (m, 3 H), 6.89 (d, J = 2.8 Hz, 1 H),
6.80 (dd, J = 9.0, 2.2 Hz, 1 H), 6.24 (s, 1 H), 5.42 (s, 2 H), 3.81 (s, 3 H),
2.55 (s, 3 H). 13C{1H} NMR (100 MHz, CDCl3
135.5, 131.4, 130.8, 129.1, 129.0, 128.9, 116.7, 111.9, 108.9, 102.9, 68.8,
55.9, 17.3. HRMS (ESI-TOF) m/ z: [M+Na]+ Calcd for C18H17NO3Na
318.1106; found 318.1102.
2-Methyl-1-tosyl-1H-indole (2f).12 This compound was prepared ac-
cording to the general procedure and purified by flash column chroma-
tography (PE/ Et2O = 200/ 1); colorless oil (12 h, 50.5 mg, 71%). 1H
77.36).
General procedure for Pd-tBuONO Cocatalyzed Aerobic Cycloi-
somerization of o-Allylanilines. Pd(PhCN)2Cl2 (7.2 mg, 0.019
mmol) was weighed directly into a 25 mL Schlenk tube and dried under
high vacuum for 15 min, purged oxygen 3 times. Under an atmosphere
of oxygen (1 atm, ballon), tBuOH (2 mL) and tBuONO (5.2 mg, 0.05
mmol) were added and stirred. 2-allylaniline (0.25 mmol) was then
added and the resulting reaction mixture was heated at 70 °C until the
starting material disappeared (monitored by TLC) and cooled to room
temperature, filtered through a thin silica gel pad and washed with
EtOAc. The filtrate was concentrated and the residue was purified by
chromatography on silica gel to afford the corresponding products.
5-Methoxy-2-methyl-1-(methylsulfonyl)-1H-indole (2a). This com-
pound was This compound was prepared according to the general pro-
cedure and purified by flash column chromatography (PE/ Et2O =
40/ 1); colorless oil (6 h, 50.8 mg, 85%). 1H NMR (400 MHz, CDCl3
7.85 (d, J = 8.8 Hz, 1 H), 6.94 (d, J = 2.4 Hz, 1 H), 6.86 (dd, J = 9.2, 2.4
Hz, 1 H), 6.36 (s, 1 H), 3.84 (s, 3 H), 2.98 (s, 3 H), 2.55 (s, 3 H).
13C{1H} NMR (100 MHz, CDCl3
NMR (400 MHz, CDCl3
J = 8.0 Hz, 1 H), 7.66 (d, J = 8.4 Hz,
2 H), 7.39 (d, J = 7.2 Hz, 1 H), 7.23-7.19 (m, 4 H), 6.34 (s, 1 H), 2.60
(s, 3 H), 2.34 (s, 3 H). 13C{1H}NMR(100 MHz, CDCl3
137.3, 136.6, 130.2, 130.0, 126.6, 124.0, 123.7, 120.3, 114.8, 109.9, 21.8,
16.1.
2,5-Dimethyl-1-tosyl-1H-indole (2g). This compound was prepared ac-
cording to the general procedure and purified by flash column chroma-
tography (PE/ Et2O =200/ 1); yellowoil (18 h, 46.2 mg, 62%). 1H NMR
(400 MHz, CDCl3 8.02 (d, J = 8.4 Hz, 1 H), 7.63 (d, J = 8.0 Hz, 2 H),
7.17 (d, J = 6.4 Hz, 3 H), 7.06 (d, J = 8.4 Hz, 1 H), 6.25 (s, 1 H), 2.57 (s,
3 H), 2.38 (s, 3 H), 2.31 (s, 3 H). 13C{1H} NMR (100 MHz, CDCl3
144.9, 137.7, 136.7, 135.5, 133.3, 130.2, 130.1, 126.6, 125.4, 120.3,
114.5, 109.8, 21.8, 21.5, 16.1. HRMS (ESI-TOF) m/ z: [M+Na]+ Calcd
for C17H17NO2SNa 322.0872; found 322.0876.
112.6, 109.9, 103.2, 56.0, 40.7, 15.9. HRMS (ESI-TOF) m/ z: [M+Na]+
Calcd for C11H13NO3SNa 262.0514; found 262.0512.
5-Methoxy-2-methyl-1-tosyl-1H-indole(2b).10 Thiscompoundwaspre-
pared according to the general procedure and purified by flash column
chromatography (PE/ Et2O = 200/ 1); colorless oil (24 h, 61.2 mg,
2,3-Dimethyl-1-tosyl-1H-indole (2h).11 This compound was prepared
according to the general procedure and purified by flash column chro-
matography (PE/ Et2O = 50/ 1); colorless oil (10 h, 59.1 mg, 79%). 1H
78%). 1H NMR (400 MHz, CDCl3
J = 10.0 Hz, 1 H), 7.62
(d, J = 8.4 Hz, 2 H), 7.18 (d, J = 8.0 Hz, 2 H), 6.87-6.84 (m, 2 H), 6.26
(s, 1 H), 3.80 (s, 3 H), 2.57 (d, J = 0.4 Hz, 3 H), 2.33 (s, 3 H). 13C{1H}
NMR (100 MHz, CDCl3
NMR (400 MHz, CDCl3
J = 8.0 Hz, 1 H), 7.62 (d, J = 8.0 Hz,
2 H), 7.36 (d, J = 7.6 Hz, 1 H), 7.28-7.21 (m, 2 H), 7.17 (d, J = 8.0 Hz,
2 H), 2.51 (s, 3 H), 2.32 (s, 3 H), 2.12 (s, 3 H). 13C{1H} NMR (100
130.1, 126.6, 115.7, 112.5, 110.1, 103.0, 55.9, 21.9, 16.1.
MHz, CDCl3
, 130.1, 126.6, 124.2,
5-Methoxy-2-methyl-1-((4-nitrophenyl)sulfonyl)-1H-indole (2c). This
compound was prepared according to the general procedure and puri-
fied by flash column chromatography (PE/ Et2O = 40/ 1); yellow oil (17
123.5, 118.6, 116.3, 114.9, 21.9, 13.1, 9.2.
2,3-Dimethyl-1-(methylsulfonyl)-1H-indole (2i).11 This compound was
prepared according to the general procedure and purified by flash col-
umn chromatography (PE/ Et2O = 100/ 1), yellow oil (12 h, 35.8 mg,
h, 58.1 mg, 67%). 1H NMR (400 MHz, CDCl3
-8.21 (m, 2 H),
7.98 (d, J = 8.8 Hz, 1 H), 7.89-7.86 (m, 2 H),6.88-6.86 (m, 2 H), 6.32
(s, 1 H), 3.80 (s, 3 H), 2.57 (s, 3 H). 13C{1H} NMR (100 MHz, CDCl3)
64%). 1H NMR (400 MHz, CDCl3
0-7.97 (m, 1 H), 7.46-7.44 (m,
1 H), 7.29-7.25 (m, 2 H), 2.95 (s, 3 H), 2.51 (s, 3 H), 2.20 (s, 3 H).
13C{1H} NMR (100 MHz, CDCl3
118.8, 116.3, 114.4, 40.5, 12.9, 9.2.
2,3-Dimethyl-1-((4-nitrophenyl)sulfonyl)-1H-indole (2j). This com-
pound was prepared according to the general procedure and purified by
flash column chromatography (PE/ Et2O = 100/ 1); yellow solid, mp
168-170 oC (12 h, 62.1 mg, 75%). 1H NMR (400 MHz, CDCl3
(d, J = 9.2 Hz, 2 H), 8.13 (d, J = 7.6 Hz, 1 H), 7.88 (d, J = 9.2 Hz, 2 H),
111.6, 103.5, 55.9, 16.2. HRMS (ESI-TOF) m/ z: [M+Na]+ Calcd for
C16H14N2O5SNa 369.0521; found 369.0514.
Methyl 5-methoxy-2-methyl-1H-indole-1-carboxylate (2d).9 This com-
pound was prepared according to the general procedure and purified by
flash column chromatography (PE/ Et2O = 50/ 1); white solid, mp 69-
70 oC (12 h, 39.1 mg, 71%). 1H NMR (400 MHz, CDCl3
J =
9.2 Hz, 1 H), 6.91 (s, 1 H), 6.84 (d, J = 9.2 Hz, 1 H), 6.27 (s, 1 H), 4.02
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7.37 (d, J = 7.2 Hz, 1 H), 7.32-7.25 (m, 2 H), 2.53 (s, 3 H), 2.13 (s, 3 H).
13C{1H} NMR (100 MHz, CDCl3
4, 132.3, 131.9,
127.9, 124.9, 124.8, 124.4, 119.1, 118.1, 114.8, 13.2, 9.3. HRMS (ESI-
TOF) m/ z: [M+Na]+ Calcd for C16H14N2O4SNa 353.0572; found
353.0574.
2-Ethyl-1-tosyl-1H-indole (2k).12 This compound was prepared ac-
cording to the general procedure and purified by flash column chroma-
tography (PE/ Et2O = 200/ 1); yellow solid (24 h, 41.5 mg, 55%). 1H
mg, 76%). 1H NMR (400 MHz, CDCl3
(d, J = 9.2 Hz, 1 H), 8.12 (dd, J = 9.2, 2.3 Hz, 1 H), 6.48 (br, 1 H), 4.10
(s, 3 H), 2.64 (s, 3 H). 13C NMR (100 MHz, CDCl3
141.2, 139.7, 129.5, 118.7, 115.8, 115.7, 108.9, 54.2, 16.9. HRMS (ESI)
calcd for C11H11N2O4 [M+H]+ 235.0719, found 235.0715.
5-Methoxy-2-methyl-indole(3).9 Toasolution of 2d (1.39 g, 6.3mmol)
in MeOH (30 mL) was added 3N KOH (3.20 mL), and the mixture was
refluxed for 1 h. After completed, the reaction mixture was cooled to
room temperature, the mixture was concentrated under reduced pres-
sure and the residue was added H2O (10 mL), the organic compounds
were extracted with ethyl acetate, then the combined organic phase was
washed with brine, dried over Na2SO4, filtered, and concentrated by ro-
tary evaporation. The corresponding product 3 was obtained without
further purification, yellow oil (1.02 g, quant). 1H NMR (400 MHz,
J = 2.2 Hz, 1 H), 8.18
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NMR (400 MHz, CDCl3
J = 8.4 Hz, 1 H), 7.62 (d, J = 8.4 Hz,
2 H), 7.41 (d, J = 8.0 Hz, 1 H), 7.27-7.16 (m, 4 H), 6.38 (s, 1 H), 3.02
(qd, J = 7.6, 0.8 Hz, 2 H), 2.32 (s, 3 H), 1.33 (t, J = 7.6 Hz, 3 H). 13C{1H}
NMR (100 MHz, CDCl3
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124.1, 123.7, 120.4, 115.0, 108.0, 22.6, 21.9, 13.2.
Benzyl 5-chloro-2-methyl-1H-indole-1-carboxylate (2l). This com-
pound was prepared according to the general procedure and purified by
flash column chromatography (PE/ Et2O = 200/ 1); yellow solid (16 h,
CDCl3
J = 8.8 Hz, 1 H), 6.99 (s, 1 H), 6.76
(d, J = 8.4 Hz, 1 H), 6.14 (s, 1 H), 3.83 (s, 3 H), 2.40 (s, 3 H). 13C{1H}
NMR (100 MHz, CDCl3
57.0 mg, 76%). 1H NMR (400 MHz, CDCl3
J = 8.8 Hz, 1 H),
102.2, 100.6, 56.2, 14.1.
7.47 (d, J = 7.6 Hz, 2 H), 7.43-7.37 (m, 4 H), 7.14 (d, J = 8.8 Hz, 1 H),
6.25 (s, 1 H), 5.44 (s, 2 H), 2.56 (s, 3 H). 13C{1H} NMR (100 MHz,
CDCl3
119.5, 116.9, 108.3, 69.2, 17.3. HRMS (ESI-TOF) m/ z: [M+Na]+
Calcd for C17H14ClNO2Na 322.0611; found 322.0606.
Ethyl 2-(5-methoxy-2-methyl-indol-3-yl)acetate (4).9 To a solution of 3
(1.02 g, 6.3 mmol) in dry THF (60 mL) was added a solution of nBuLi
in hexane (1.6 M, 7.56 mmol, 4.73 mL) dropwise at 0 °C. The reaction
mixture was stirred at 0 °C for 30 min, and to the mixture was added
ZnCl2 (0.86 g, 6.3 mmol) at room temperature. The mixture was con-
tinuously stirred for 30 min, then a solution of ethyl bromoacetate (1.26
g, 7.56 mmol) in THF (20 mL) was added, and the mixture was stirred
for further 24 h. The reaction was quenched with saturated aqueous
NH4Cl, the organic layer was separated and the aqueous layer was ex-
tracted with ethyl acetate, then the combined organic phase was washed
withbrine, driedoverNa2SO4, filtered, andconcentratedby rotary evap-
oration. The mixture was purified by column chromatography on silica
gel (PE/ EA 20/ 1 to 5/ 1) to afford the corresponding product 4 as a
Methyl 2-methyl-1H-benzo[g]indole-1-carboxylate (2m). This com-
pound was prepared according to the general procedure and purified by
flashcolumn chromatography (PE/ Et2O =100/ 1);white solid, mp129-
130 oC (24 h, 32.9 mg, 55%). 1H NMR (400 MHz, CDCl3
J
= 8.4 Hz, 1 H), 7.90 (d, J = 8.0 Hz, 1 H), 7.63 (d, J = 8.4 Hz, 1 H), 7.54
(d, J = 8.4 Hz, 1 H), 7.48 (t, J = 8.4 Hz, 1 H), 7.40 (t, J = 7.0 Hz, 1 H),
6.43 (s, 1 H), 4.08 (s, 3 H), 2.58 (s, 3 H). 13C{1H} NMR (100 MHz,
CDCl3
123.3, 122.7, 119.7, 108.2, 54.4, 15.9. HRMS (ESI-TOF) m/ z:
[M+Na]+ Calcd for C15H13NO2Na 262.0844; found 262.0837.
Methyl 1,2,3,4-tetrahydro-9H-carbazole-9-carboxylate (2n). This com-
pound was prepared according to the general procedure and purified by
flash column chromatography (PE/ Et2O = 200/ 1); yellow oil (2 h, 44.6
brown oil (1.32 g, 85%). 1H NMR (400 MHz, CDCl3
(br s, 1 H),
7.13 (d, J = 8.8 Hz, 1 H), 7.00 (d, J = 2.4 Hz, 1 H), 6.77 (dd, J = 8.8, 2.4
Hz, 1 H), 4.13 (q, J = 7.2 Hz, 2 H), 3.85 (s, 3 H), 3.64 (s, 2 H), 2.37 (s,
3 H), 1.24 (t, J = 7.2 Hz, 3 H). 13C{1H} NMR (100 MHz, CDCl3
172.5, 154.4, 133.8, 130.5, 129.3, 111.3, 104.8, 100.7, 61.0, 56.2, 30.9.
14.6, 12.1.
2-(5-Methoxy-2-methyl-indol-3-yl)acetic acid (5).9 To a 100 mL round
bottom were added 4 (1.32 g, 5.3 mmol) and 1 M NaOH (30 mL) at
100 °C, then the mixture was stirred for 6 h. After completed, the reac-
tion mixture was cooled to room temperature, addition of 12 N HCl re-
sulted in precipitation of the product which was filtered off and washed
with water, and dried under infrared drying lamps for 1 h to afford the
corresponding product 5 asabrown solid, mp161-162oC(1.06g, 91%).
1H NMR (400 MHz, DMSO-d6
mg, 78%). 1H NMR (400 MHz, CDCl3
J = 7.2, 1.6 Hz, 1 H),
7.40-7.38 (m, 1 H), 7.27-7.20 (m, 2 H), 4.01 (s, 3 H), 3.01-2.98 (m, 2
H), 2.66-2.62 (m, 2 H), 1.92-1.80 (m, 4 H). 13C{1H} NMR (100 MHz,
CDCl3
25.8, 23.8, 22.5, 21.4. HRMS (ESI-TOF) m/ z: [M+Na]+ Calcd for
C14H15NO2Na 252.1000; found 252.0991.
Methyl 9H-carbazole-9-carboxylate (2o). This compound was pre-
pared according to the general procedure and treated with DDQ (2.0
equiv), purified by flash column chromatography (PE/ Et2O = 200/ 1);
brown solid, mp 72-73 oC (4 h, 39.2 mg, 70%). 1H NMR (400 MHz,
CDCl3
J = 8.4 Hz, 2 H), 7.96 (d, J = 7.6 Hz, 2 H), 7.46 (t, J =
7.14 (d, J = 8.4 Hz, 1 H), 6.90 (d, J = 2.0 Hz, 1 H), 6.64 (dd, J = 8.8, 2.4
Hz, 1 H), 3.74 (s, 3 H), 3.53 (s, 2 H), 2.30 (s, 3 H). 13C{1H} NMR (100
MHz, DMSO-d6
7.6 Hz, 2 H), 7.35 (t, J = 7.6 Hz, 2 H), 4.12 (s, 3 H). 13C{1H} NMR (100
MHz, CDCl3
HRMS (ESI-TOF) m/ z: [M+Na]+ Calcd for C14H11NO2Na 248.0687;
found 248.0679.
104.0, 100.2, 55.4, 30.1, 11.5.
Indomethacin (6).9 To a solution of 5 (1.06 g, 4.8 mmol) in dry THF
(40 mL) was added a solution of tBuOK (1.08 g, 9.6 mmol) in THF (40
mL) dropwise at -78 °C, and the mixture was stirred for 1 h. To the mix-
ture was added a solution of 4-chlorobenzoyl chloride (1.01 g, 5.76
mmol) in THF (5 mL), and the whole mixture was allowed up to room
temperature for 16 h. Addition of 12 N HCl resulted in precipitation of
the product which was filtered off and washed with water, and dried un-
der infrared drying lamps for 1 h to afford 6 as a yellow solid, mp 155-
Methyl 5-cyano-2-methyl-1H-indole-1-carboxylate (2p). Prepared ac-
cording to the general procedure, purified by flash column chromatog-
raphy (PE/ Et2O = 40/ 1), as a white solid, mp: 138-139 oC (24 h, 42.4
mg, 79%). 1H NMR (400 MHz, CDCl3
J = 8.7 Hz, 1 H), 7.75
(s, 1 H), 7.49 (dd, J = 8.7, 1.6 Hz, 1 H), 6.40 (s, 1 H), 4.08 (s, 3 H), 2.63
(s, 3 H), 13C NMR (100 MHz, CDCl3
126.7, 124.3, 120.0, 116.4, 108.1, 106.4, 54.1, 16.9. HRMS (ESI) calcd
for C12H11N2O2 [M+H]+ 215.0821, found 215.0820.
Methyl 2-methyl-5-nitro-1H-indole-1-carboxylate (2q). Prepared ac-
cording to the general procedure, purified by flash column chromatog-
raphy (PE/ Et2O = 20/ 1), as a yellow solid, mp: 147-148 oC (12 h, 44.5
157oC (1.63 g, 95%). 1H NMR (400 MHz, CDCl3
J = 8.0 Hz,
2 H), 7.46 (d, J = 8.4 Hz, 2 H), 6.94 (d, J = 1.6 Hz, 1 H), 6.85 (d, J = 8.8
Hz, 1 H), 6.67 (dd, J = 8.8, 1.6 Hz, 1 H), 3.82 (s, 3 H), 3.69 (s, 2 H), 2.38
(s, 3 H). 13C NMR (100 MHz, CDCl3
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The Journal of Organic Chemistry
136.4, 133.9, 131.3, 130.9, 130.6, 129.3, 115.2, 111.9, 111.8, 101.3, 55.9,
30.1, 13.5.
(100 MHz, CDCl3) 157.0, 154.6, 136.4, 135.8, 132.8, 128.7, 128.6,
128.3, 125.1, 116.7, 115.6, 112.2, 67.0, 55.5, 36.5. HRMS (ESI-TOF)
m/ z: [M+Na]+ Calcd for C18H19NO3Na 320.1263; found 320.1260.
N-(2-allylphenyl)-4-methylbenzenesulfonamide (1f).14 This compound
was prepared according to the general procedure 1 with 2-allylaniline
(0.79 g, 5.9 mmol), CH2Cl2 (30 mL), pyridine (1.40 g, 17.7mmol), tosyl
chloride (1.21 g, 7.1 mmol) at 0 °C; column chromatography with
PE/ EA (10/ 1), yellow oil, 1.44 g, 85%. 1H NMR (400 MHz, CDCl3
7.60 (d, J = 8.0 Hz, 2 H), 7.40 (d, J = 8.0 Hz, 1 H), 7.23-7.18 (m, 3 H),
7.11 (t, J = 7.2 Hz, 1 H), 7.07 (d, J = 7.2 Hz, 1 H), 6.55 (br s, 1 H), 5.83-
5.73 (m, 1 H), 5.11 (d, J = 10.0 Hz, 1 H), 4.94 (d, J = 17.2 Hz, 1 H), 3.02
(d, J = 5.6 Hz, 2 H), 2.39 (s, 3 H).
1
2
3
4
5
6
7
8
General Procedure 1 for the Preparation of 2-allyl anilines. To a
solution of 2-allyl anilines (1.0 equiv) in CH2Cl2 (15 mL) were added
pyridine (1.4 equiv) and RCl (MsCl, TsCl, Ns, Cbz, MeOCOCl, etc)
(1.2equiv) at 0°C. Afterbeingstirredat 25 °Cforovernight, thereaction
mixture was poured into water and then the product was extracted with
CH2Cl2 (3 times), dried over Na2SO4, filtered, and concentrated by ro-
tary evaporation. Thecrude mixture waspurifiedbycolumn chromatog-
raphy on silica gel to afford the corresponding product 1.
N-(2-allyl-4-methoxyphenyl)methanesulfonamide (1a).13 This com-
pound was prepared according to the general procedure 1 with 2-allyl-
4-methoxyaniline (2.3 mmol), MsCl (2.8 mmol), pyridine (2.8 mmol),
and CH2Cl2 (20 mL); column chromatography with PE/ EA (5/ 1),
white solid, mp 94.5-95 oC, 0.50 g, 90%. 1H NMR (400 MHz, CDCl3
7.37 (d, J = 8.4 Hz, 1 H), 6.80 (d, J = 8.0 Hz, 2 H), 6.18 (br s, 1 H), 5.99-
5.89 (m, 1 H), 5.17 (d, J = 9.6 Hz, 1 H), 5.07 (d, J = 17.2 Hz, 1 H), 3.80
(s, 3 H), 3.44 (d, J = 6.0 Hz, 2 H), 2.98 (s, 3 H). 13C{1H} NMR (100
MHz, CDCl3
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N-(2-allyl-4-methylphenyl)-4-methylbenzenesulfonamide (1g). This
compound was prepared according to the general procedure 1 with 2-
allyl-4-methylaniline (3.0 mmol), TsCl (3.6 mmol), pyridine (3.6
mmol), CH2Cl2 (20 mL);column chromatographywith PE/ EA(10/ 1),
yellow oil, 0.86 g, 95%. 1H NMR (400 MHz, CDCl3
J = 8.4
Hz, 2 H), 7.23 (t, J = 8.4 Hz, 3 H), 7.00 (dd, J = 8.0, 1.2 Hz, 1 H), 6.88
(s, 1 H), 6.45 (br s, 1 H), 5.81-5.71 (m, 1 H), 5.09 (dd, J = 10.0, 1.2 Hz,
1 H), 4.92 (dd, J = 17.2, 1.6 Hz, 1 H), 2.95 (d, J = 6.0 Hz, 2 H), 2.39 (s,
3 H), 2.27 (s, 3 H). 13C{1H} NMR (100 MHz, CDCl3
112.7, 55.6, 39.9, 36.6.
N-(2-allyl-4-methoxyphenyl)-4-methylbenzenesulfonamide (1b).14 This
compound was prepared according to the general procedure 1 with 2-
allyl-4-methoxyaniline (3.6 mmol), tosyl chloride (4.3 mmol), pyridine
(4.3 mmol), CH2Cl2 (20 mL); column chromatography with PE/ EA
136.5, 135.9, 132.7, 132.3, 131.2, 129.7, 128.4, 127.2, 125.4, 116.9, 36.2,
21.7, 21.0.
HRMS (ESI-TOF) m/ z: [M+Na]+ Calcd for
C17H19NO2SNa 324.1029; found 324.1032.
(5/ 1), yellow oil, 0.93 g, 82%. 1H NMR (400 MHz, CDCl3
J
N-(2-(but-3-en-2-yl)phenyl)-4-methylbenzenesulfonamide (1h). This
compound was prepared according to the general procedure 1 with 2-
(but-3-en-2-yl)aniline (2.0 mmol), tosyl chloride (2.4 mmol), pyridine
(2.4 mmol), CH2Cl2 (30 mL); column chromatography with PE/ EA
(10/ 1), yellow oil, 0.55 g, 91%. 1H NMR (400 MHz, CDCl3 7.60 (d,
J = 8.0 Hz, 2 H), 7.37-7.35 (m, 1 H), 7.23 (d, J = 8.0 Hz, 2 H), 7.18-7.14
(m, 3 H), 6.54 (br s, 1 H), 5.77-5.69 (m, 1 H), 5.06 (d, J = 10.0 Hz, 1
H), 4.92 (d, J = 17.6 Hz, 1 H), 3.25-3.19 (m, 1 H), 2.39 (s, 3 H), 1.14 (d,
J = 7.2 Hz, 3 H). 13C{1H} NMR (100 MHz, CDCl3 143.9, 141.9,
137.5, 136.8, 134.3, 129.7, 127.5, 127.4, 127.3, 126.6, 125.0, 114.7, 37.8,
21.7, 19.3. HRMS (ESI-TOF) m/ z: [M+Na]+ Calcd for
C17H19NO2SNa 324.1034; found 324.1029.
N-(2-(but-3-en-2-yl)phenyl)methanesulfonamide (1i). This compound
was prepared according to the general procedure 1 with 2-(but-3-en-2-
yl)aniline (2.5 mmol), MsCl (3.0 mmol), pyridine (3.0 mmol), CH2Cl2
(20 mL); column chromatography with PE/ EA (5/ 1), yellow oil, 0.44
g, 78%. 1H NMR (400 MHz, CDCl3) 7.49 (d, J = 7.6 Hz, 1 H), 7.30-
7.21 (m, 3 H), 6.50 (br s, 1 H), 5.99-5.91 (m, 1 H), 5.16 (dd, J = 10.4,
0.8 Hz, 1 H), 5.06 (d, J = 1.2 Hz, 1 H), 3.68 (s, 1 H), 3.02 (s, 3 H), 1.42
(d, J = 6.8 Hz, 3 H). 13C{1H} NMR (100 MHz, CDCl3 141.9, 136.7,
134.5, 128.1, 127.7, 126.5, 123.4, 115.0, 40.2, 38.3, 19.6. HRMS (ESI-
TOF) m/ z: [M+Na]+ Calcd for C11H15NO2SNa 248.0721; found
248.0717.
= 8.0 Hz, 2 H), 7.24-7.21 (m, 3 H), 6.72 (dd, J = 8.8, 2.0 Hz, 1 H), 6.62
(s, 1 H), 6.24 (br s, 1 H), 5.79-5.69 (m, 1 H), 5.09 (d, J = 10.0 Hz, 1 H),
4.92 (d, J = 16.8 Hz, 1 H), 3.77 (s, 3 H), 2.92 (d, J = 6.4 Hz, 2 H), 2.41
(s, 3H). 13C{1H}NMR (100 MHz, CDCl3
135.7, 129.7, 128.4, 127.4, 127.3, 117.0, 115.9, 112.5, 55.5, 36.3, 21.7.
N-(2-allyl-4-methoxyphenyl)-4-nitrobenzenesulfonamide (1c). This
compound was prepared according to the general procedure 1 with 2-
allyl-4-methoxyaniline (2.3 mmol), NsCl (2.8 mmol), pyridine (2.8
mmol), CH2Cl2 (20mL);column chromatographywith PE/ EA(20/ 1),
amorphous solid, 0.55 g, 68%. 1H NMR (400 MHz, CDCl3 8.30 (d, J
= 8.8 Hz, 2 H), 7.87 (d, J = 8.8 Hz, 2 H), 7.18 (d, J = 8.8 Hz, 1 H), 6.74
(dd, J = 9.0, 2.6 Hz, 1 H), 6.66 (d, J = 2.0 Hz, 1 H), 6.48 (br s, 1 H), 5.80-
5.71 (m, 1 H), 5.10 (d, J = 10.0 Hz, 1 H), 4.92 (d, J = 17.2 Hz, 1 H), 3.78
(s, 3 H), 2.96 (d, J = 6.0 Hz, 2 H). 13C{1H} NMR (100 MHz, CDCl3
159.0, 150.3, 145.5, 136.6, 135.4, 128.5 (twopeaks), 126.1, 124.3, 117.2,
116.1, 112.8, 55.5, 36.3. HRMS (ESI-TOF) m/ z: [M+Na]+ Calcd for
C16H16N2O5SNa 371.0672; found 371.0675.
Methyl (2-allyl-4-methoxyphenyl)carbamate (1d). This compound was
prepared according to the general procedure 1with 2-allyl-4-methoxy-
aniline (3.0 mmol), methyl chloroformate (3.6 mmol), pyridine (3.6
mmol), CH2Cl2 (20 mL); column chromatography with PE/ EA (1/ 1),
yellow solid, mp 65-66 oC, 0.53 g, 79%. 1H NMR (400 MHz, CDCl3
7.53 (br s, 1 H), 6.78 (dd, J = 8.8, 2.0 Hz, 1 H), 6.72 (s, 1 H), 6.41 (br s,
1 H), 5.97-5.88 (m, 1 H), 5.13 (d, J = 10.0 Hz, 1 H), 5.05 (d, J = 17.2 Hz,
1 H), 3.78 (s, 3 H), 3.74 (s, 3 H), 3.32 (d, J = 6.0 Hz, 2 H). 13C{1H}
NMR (100 MHz, CDCl3
N-(2-(but-3-en-2-yl)phenyl)-4-nitrobenzenesulfonamide (1j). This
compound was prepared according to the general procedure 1 with 2-
(but-3-en-2-yl)aniline (2.5 mmol), NsCl (3.0 mmol), pyridine (3.0
mmol), CH2Cl2 (20 mL);column chromatographywith PE/ EA(10/ 1),
amorphous yellow solid, 0.74 g, 88%. 1H NMR (400 MHz, CDCl3
8.30 (d, J = 8.8 Hz, 2 H), 7.92 (d, J = 8.8 Hz, 2 H), 7.34-7.31 (m, 1 H),
7.26-7.17 (m, 3 H), 6.75 (br s, 1 H), 5.79-5.71 (m, 1 H), 5.08 (d, J = 10.4
Hz, 1 H), 4.93 (d, J = 17.2 Hz, 1 H), 3.29-3.22 (m, 1 H), 1.17 (d, J = 7.2
116.7, 115.6, 112.3, 55.5, 52.4, 36.7. HRMS (ESI-TOF) m/ z: [M+Na]+
Calcd for C12H15NO3Na 244.0950; found 244.0948.
Benzyl (2-allyl-4-methoxyphenyl)carbamate (1e). This compound was
prepared according to the general procedure 1 with 2-allyl-4-methoxy-
aniline (2.5 mmol), CbzCl (3.0 mmol), pyridine (3.5 mmol), CH2Cl2
(10 mL); column chromatography with PE/ EA (10/ 1), white solid, mp
80-81 oC, 0.64 g, 86%. 1H NMR (400 MHz, CDCl3) 7.56 (s, 1 H),
7.38-7.35 (m, 5 H), 6.78 (d, J = 8.8 Hz, 1 H), 6.72 (s, 1 H), 6.44 (br s, 1
H), 5.96-5.86 (m, 1 H), 5.18 (s, 2 H), 5.11 (d, J = 10.0 Hz, 1 H), 5.01 (d,
J = 17.2 Hz, 1 H), 3.77 (s, 3 H), 3.31 (d, J = 6.0 Hz, 2 H). 13C{1H} NMR
Hz, 3 H). 13C{1H} NMR (100 MHz, CDCl3
150.2, 145.4, 141.7,
138.2, 133.1, 128.6, 128.0, 127.6 (two peaks), 125.2, 124.4, 114.9, 37.9,
19.5. HRMS (ESI-TOF) m/ z: [M+Na]+ Calcd for C16H16N2O4SNa
355.0728; found 355.0727.
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Benzyl (2-allyl-4-chlorophenyl)carbamate (1l). This compound was
SUPPORTING INFORMATION
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prepared according to the general procedure 1 with 2-allyl-4-chloroan-
iline (1.1 mmol), CbzCl (1..3 mmol), pyridine (1.5 mmol), CH2Cl2 (20
mL); column chromatography with PE/ EA (10/ 1), white solid, mp 90-
91 oC, 0.30 g, 94%. 1H NMR (400 MHz, CDCl3 7.75 (s, 1 H), 7.38-
7.33 (m, 5 H), 7.20 (dd, J = 8.8, 2.4 Hz), 7.12 (d, J = 2.4 Hz, 1 H), 6.63
(br s, 1 H), 5.94-5.84 (m, 1 H), 5.18-5.14 (m, 3 H), 5.03 (dd, J = 17.2,
1.6 Hz, 1 H), 3.29 (d, J = 6.0 Hz, 2 H). 13C{1H} NMR (100 MHz,
CDCl3 153.8, 136.0, 134.9, 134.7, 131.1, 129.9, 129.5, 128.7, 128.4
(two peaks), 127.5, 123.4, 117.5, 67.2, 36.1. HRMS (ESI-TOF) m/ z:
[M+Na]+ Calcd for C17H16ClNO2Na 324.0767; found 324.0760.
Methyl (2-allylnaphthalen-1-yl)carbamate (1m). This compound was
prepared according to the general procedure 1 with 2-allylnaphthalen-
1-amine (4 mmol), methyl chloroformate (4.8 mmol), pyridine (5.6
mmol), CH2Cl2 (20mL); column chromatographywith PE/ EA(10/ 1),
yellow solid, mp 120-123 oC, 0.70 g, 72%. 1H NMR (400 MHz, CDCl3)
7.93-7.92 (m, 1 H), 7.80 (d, J = 8.0 Hz, 1 H), 7.74 (d, J = 8.0 Hz, 1 H),
7.51-7.42 (m, 2 H), 7.34 (d, J = 8.4 Hz, 1 H), 6.55 (br s, 1 H), 5.96-5.94
(m, 1 H), 5.09-5.02 (m, 2 H), 3.80 (s, 3 H), 3.53 (d, J = 6.0 Hz, 2 H).
13C{1H} NMR (100 MHz, CDCl3 155.8, 136.3, 134.8, 133.2, 131.3,
130.0, 128.2, 128.0, 127.9, 126.8, 125.7, 122.8, 116.2, 52.8, 36.7. HRMS
(ESI-TOF) m/ z: [M+Na]+ Calcd for C15H15NO2Na 264.1000; found
264.0995.
Methyl (1',2',3',4'-tetrahydro-[1,1'-biphenyl]-2-yl)carbamate (1n). This
compound was prepared according to the general procedure 1 with
1',2',3',4'-tetrahydro-[1,1'-biphenyl]-2-amine (0.35 g, 2.0 mmol),
CH2Cl2 (20 mL), pyridine (0.22 g, 2.8 mmol), chloroformate (0.23 g,
2.4 mmol) at 0 °C, column chromatography with PE/ EA (10/ 1), yellow
oil, 0.46 g, 99%. 1H NMR (400 MHz, CDCl3 7.79 (br s, 1 H), 7.25-
7.20 (m, 1 H), 7.18 (dd, J = 7.6, 1.6 Hz, 1 H), 7.07 (t, J = 7.2 Hz, 1 H),
6.86 (br s, 1 H), 6.03-5.99 (m, 1 H), 5.70 (dd, J = 10.0, 2.0 Hz, 1 H),
3.77 (s, 3 H), 3.52-3.49 (m, 1 H), 2.13-2.12 (m, 2 H), 1.97-1.95 (m, 1
H), 1.81-1.75 (m, 1 H), 1.69-1.58 (m, 2 H). 13C{1H} NMR (100 MHz,
CDCl3 154.7, 135.4, 130.0, 129.5, 129.3, 127.2, 124.5, 122.5, 52.5,
38.9, 29.9, 24.9, 21.5. HRMS (ESI-TOF) m/ z: [M+Na]+ Calcd for
C14H17NO2Na 254.1157; found 254.1150.
This material is available free of charge via the Internet at
http:/ / pubs.acs.org.
NMR Spectra (PDF).
AUTHOR INFORMATION
Corresponding Author
ybkang@ustc.edu.cn
ias_jpqu@njtech.edu.cn
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ORCID
Yan-Biao Kang: 0000-0002-7537-4627
Jian-Ping Qu: 0000-0002-5002-5594
Notes
ACKNOWLEDGMENT
We thank the National Natural Science Foundation of China
(21602001, 21672196, 21404096, U1463202), and the Fundamental
Research Funds for the Central Universities of China
(WK2060190086) for financial support.
REFERENCES
(1) (a) Sundberg, R. J. Indoles; 2nd ed.; Academic Press: London, 1996.
(b) Kawasaki, T.; Higuchi, K. Simple Indole Alkaloids and Those with a
NonrearrangedMonoterpenoidUnit. Nat. Prod. Rep. 2005, 22, 761-793.(c)
Kochanowska-Karamyan, A. J.; Hamann, M. T. Marine Indole Alkaloids:
PotentialNewDrugLeadsfortheControlofDepressionandAnxiety. Chem.
Rev. 2010, 110, 4489-4497. (d) Kaushik, N. K.; Kaushik, N.; Attri, P.; Ku-
mar,N.; Kim, C. H.; Verma, A. K.; Choi, E. H. Biomedical Importance of In-
doles. Molecules 2013, 18, 6620-6662.
(2) (a) Fischer, E.; Jourdan, F. Ueber die Hydrazine der Brenztrau-
bensäure. Ber. Dtsch. Chem. Ges. 1883, 16, 2241-2245. (b) Robinson, B. The
Fischer Indole Synthesis. Chem. Rev. 1963, 63, 373-401.
(3) Selected reviews on synthesis of substituted indoles: (a) Hegedus, L.
S. Transition Metals in the Synthesis and Functionalization of Indoles [New
Synthesis Methods (72)]. Angew. Chem., Int. Ed. 1988, 27, 1113-1226. (b)
Humphrey, G. R.; Kuethe, J. T. Practical Methodologies for the Synthesis of
Indoles. Chem. Rev. 2006, 106, 2875-2911. (c) Taber, D. F.; Tirunahari, P.
K. Indole Synthesis: a Review and Proposed Classification. Tetrahedron
2011, 67, 7195-7210. (d) Cacchi, S.; Fabrizi, G. Update 1 of: Synthesis and
Functionalization of Indoles Through Palladium-Catalyzed Reactions.
Chem. Rev. 2011, 111, PR215-PR283. (e) Vicente, R. Recent Advances in
Indole Syntheses: New Routesfor a Classic Target. Org. Biomol. Chem. 2011,
Methyl (2-allyl-4-cyanophenyl)carbamate (1p). This compound was
prepared according to the general procedure 1 with 2-allyl-4-cyanocy-
aniline (5.8 mmol), methyl chloroformate (7.0 mmol), pyridine (7.0
mmol), CH2Cl2 (40mL);column chromatographywith PE/ EA(15/ 1),
white solid, mp 116-117 oC, 1.1 g, 88%. 1H NMR (400 MHz, CDCl3
8.12 (d, J = 6.7 Hz, 1 H), 7.55 7.53 (m, 1 H), 7.44 (s, 1 H), 6.93 (br, 1
H), 5.97 5.87 (m, 1 H), 5.26 (d, J = 10.1 Hz, 1 H), 5.12 (d, J = 17.2 Hz,
1 H), 3.80 3.78(m, 3 H), 3.39 (d, J=5.8 Hz, 2 H), 13CNMR(100MHz,
CDCl3
9
(f) Kochanowska-Karamyan, A. J.; Hamann, M. T. Marine
Indole Alkaloids: Potential New Drug Leads for the Control of Depression
andAnxiety. Chem. Rev. 2010, 110 IndolesinMul-
106.6, 52.8, 36.1. HRMS (ESI) calcd for C12H13N2O2 [M+H]+
217.0977, found 217.0980.
Methyl (2-allyl-4-nitrophenyl)carbamate (1q). This compound was
prepared according to the general procedure 1 with 2-allyl-4-nitroan-
iline (2.1 mmol), methyl chloroformate (2.5 mmol), pyridine (2.5
mmol), CH2Cl2 (14mL);column chromatographywith PE/ EA(15/ 1),
white solid, mp 105-106 oC, 0.45 g, 90%. 1H NMR (400 MHz, CDCl3)
J = 9.1 Hz, 1 H), 8.15 8.13 (m, 1 H), 8.07 (s, 1 H), 7.02 (br,
1 H), 6.01 5.91 (m, 1 H), 5.29 (d, J = 10.2 Hz, 1 H), 5.16 (d, J = 17.2
Hz, 1 H), 3.81 (s, 3 H), 3.46 (d, J = 6.0 Hz, 2 H), 13C NMR (100 MHz,
CDCl3
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