Photodriven Photocatalyst/Metal-Free Direct C-C/C-N Bond Formation: Synthesis of Indoles via EDA Complexes

Article abstract of DOI:10.1021/acs.joc.9b01689

The photodriven direct C-C/C-N bond formation initiated by electron donor-acceptor (EDA) complexes for the synthesis of indoles has been accomplished via [3+2] annulations of secondary arylamines with alkynes using IC₄F₉ as oxidants in the absence of any photocatalysts and metals. This green transformation exhibits the advantages of operational simplicity, good functional tolerances, and mild reaction conditions. The in situ generated EDA complexes derived from arylamines with alkynes were characterized by UV-vis absorption spectrometry and NMR titration experiments.

Full text of DOI:10.1021/acs.joc.9b01689

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Note
Photo-Driven Photocatalyst-/Metal-Free Direct C-C/C-N
Bond Formation: Synthesis of Indoles via EDA Complexes
Wei Guo, Kailiang Tao, Zhen Xie, Liuhuan Cai, Mingming Zhao, Wen
Tan, Gongping Liu, Weijie Mei, Ling Deng, XiaoLin Fan, and Lvyin Zheng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01689 • Publication Date (Web): 18 Sep 2019
Downloaded from pubs.acs.org on September 18, 2019
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Photo-Driven Photocatalyst-/Metal-Free Direct C-C/C-N
Bond Formation: Synthesis of Indoles via EDA Complexes
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†
†
Wei Guo,* Kailiang Tao, Zhen Xie, Liuhuan Cai, Mingming Zhao, Wen Tan,
Gongping Liu, Weijie Mei, Ling Deng, Xiaolin Fan,* Lvyin Zheng*
Key Laboratory of Organo-pharmaceutical Chemistry of Jiangxi Province, Gannan Normal
University, Ganzhou 341000, China
Fax: (+86) 0797-8393536; *E-mail: guoweigw@126.com; fanxl2008@gnnu.edu.cn;
zhenglvyin@126.com
R2
R2
R2
COOR3
COOR3
NH
N
NH
hv
R1
+
R1
COOR3
R1
IC4F9
Et3N
3
H
R OOC
3
COOR3
R OOC
in-situ formed EDA complexes
CH3CN, air, r.t.
photocatalyst free
metal free
direct C-C/C-N bond formation
mild conditions
ABSTRACT:
The photo-driven direct C-C/C-N bond formation initiated by electron donor-acceptor
(EDA) complexes for the synthesis of indoles has been accomplished via [3 + 2]
annulations of secondary arylamines with alkynes using IC F as oxidants in the
4
9
absent of any photocatalysts and metals. This green transformation exhibits the
advantages of operational simplicity, good functional tolerances and mild reaction
conditions. The in-situ generated EDA complexes derived from arylamines with
alkynes were characterized by UV−vis absorption spectrometry and NMR titration
experiments.
Electron donor-acceptor (EDA) complexes have known wide applications for the
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construction of useful organic products by photochemical transformations in recent
years.1 Generally, typical EDA complexes derived from electron-rich and
electron-deficient substrates undergo photochemical reaction via the photo-induced
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2
electron transfer process without the addition of external photocatalysts. Moreover,
the appearance of color change from EDA complex is visible, which can also be
3
detected by optical absorption spectrum, exhibiting an obvious red shift. Driven by
light irradiation, the electron transfer within EDA complex plays an important role in
accelerating the generation of active radical species, which further facilitates the
4
subsequent transformation. Despite the prevalence of photocatalyzed transformations,
photochemical methodologies based on the formation of EDA complexes for the new
applications are still highly desirable.
Indoles are often regarded as the most important structural scaffolds in natural and
synthetic N-heterocycles, which are also considered as the privileged structures
exiting in pharmaceuticals, agrochemicals and advanced functional materials.5
Advances for the efficient construction of indole core skeletons have been receiving
6
continuing attentions in the recent years. Generally, great endeavors on the synthesis
of indoles mainly are focus on the C-C/C-N bond formations from two or three
starting materials by exploring various transition metals (e.g., Mn, Co, Ni, Cu, Ag, Au,
7
Ru, Pd, Rh, Ir) as catalysts (Scheme 1a). In recent years, photocatalyzed organic
reactions have emerged as very powerful weapons in the ambitions of acquiring fine
8
chemicals because of the advantage of sustainable and environmentally benign. For
examples, Hwang’s group successfully developed an excellent copper catalyzed
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three-component coupling strategy for the synthesis of indoles from arylamines,
terminal alkynes, and quinines under visible-light irradiation (Scheme 1b).9
Subsequently, Rueping’s group also succeeded in the photoredox catalyzed
cyclization of acetanilides with alkynes for constructing of indoles using Rh(III)/Ag(I)
as co-catalysts, Ru(III) as photocatalyst (Scheme 1c).10 Although remarkable
achievements in the field of transition metal catalyzed synthesis of indoles have been
accomplished, eliminating the metallic residues is an extremely impending issue.
Recently, we have explored visible-light-promoted coupling annulations for the
synthesis of 2-iminothiazolidin-4-ones via in situ formed EDA complexes without the
need of any external metals and photocatalysts, in which the EDA complexes from
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0
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1
electron donors and acceptors promote the reaction process. We further envision that
the preparation of indoles may be performed through investigating the appropriate
electron-rich/electron-deficient substrates. In this context, we herein advance the
photo-induced direct C-C/C-N bond formation concept for the construction of indoles
from the [3 + 2] annulations of secondary arylamines with but-2-ynedioates in the
absent of any photoredox catalysts and metals, in which the in situ generated EDA
complexes derived from secondary arylamines and alkynes could be involved in the
reaction (Scheme 1d).
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(
I) Previous works: metal catalyzed reactions
(a) traditional metal catalyzed reactions
H
N
R
R2
R
N
external oxidants
R1 metal catalyst
high temperature
Pd, Cu, Ru, Rh, etc.
+
R1
X
R2
pre-functionalization
X = H, Cl, Br, I
(b) Hwang et al. 2015
OH
CuCl (5 mol%)
visible light, r.t.
+
R
+
O
O
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NH2
HN
R
(
c) Rueping et al. 2019
[
RhCp*Cl2]2 (2 mol%)
AgSbF6 (8 mol%)
Ac
NHAc
+
R
[Ru(dtbbpy) bpy](PF ) (1 mol%)
N
R
2
6 2
20 oC, 12 h
PhCl (1 mL), 11 W CFL
1
H
R
R
(II) This work: photocatalyst-/metal-free photoinduced reactions
(d) Guo et al.
R2
R2
R2
COOR3
NH
COOR3
NH
N
hv (10 W, 365 nm)
R1
+
R1
R1
COOR3
IC4F9 (1.5 equiv)
Et3N (1.0 equiv)
CH3CN, air, 23 o
H
R OOC
3
R3OOC
in-situ formed EDA complexes
COOR3
C
photocatalyst free
metal free
direct C-C/C-N bond formation
mild conditions
Scheme 1. Synthesis of Indoles from Arylamines and Alkynes
Table 1. Screening of Reaction Conditionsa
COOC H
2
5
NH
H
N
hv (10 W, 365 nm)
IC F (1.5 equiv)
+
COOC H
2
5
4
9
C H OOC
2
Et N (1.0 equiv)
5
3
COOC H
2
5
o
1
a
2a
CH CN, air, 23 C
3
3a
Entry
Variation of the initial conditions
3a, Yield (%)b
1
2
3
4
none
70
55
30
59
with Rose Bengal (1 mol %)
with Eosin B (1 mol %)
with Eosin Y (1 mol %)
5
6
7
8
9
with Ir(ppy) (1 mol %)
49
52
trace
0
3
with RuCl (bpy) (1 mol %)
2
3
no Et N
3
no IC4F9
no light
0
1
0
NaOH instead of Et N
50
54
8
3
11
K CO instead of Et N
2
3
3
1
1
2
3
DABCO instead of Et N
3
DBU instead of Et N
44
57
<5
56
3
14
TMEDA instead of Et N
3
1
1
5
6
IBr or ICl or KI or I or KI/I instead of IC F
2
2
4
9
DMF instead of CH CN
3
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DMSO instead of CH CN
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CH Cl instead of CH CN
31
2
2
3
19
H O or NMP instead of CH CN
2
trace
3
2
0
465 nm or 520 nm LEDs light sources instead of 365 <45
nm
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under N2
under O2
23
65
2
2
aReaction conditions: Unless otherwise stated, the reaction of N-methylaniline 1a
(
0.10 mmol), diethyl but-2-ynedioate 2a (0.10 mmol), IC F (0.15 mmol) and Et N
4 9 3
o
(
0.10 mmol) was carried out at 23 C in CH CN (1 mL) under 10 W UV (365 nm)
3
b
LED irradiation for 12 h in the open air. Isolated yields based on 1a.
To verify our hypothesis, N-methylaniline (1a) was selected as the model electron
donor to react with diethyl but-2-ynedioate (2a) as electron acceptor, and IC F as
4
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initiator for investigating the feasibility of the designed transformation (Table 1).
Initially, the reaction was performed in CH CN under the light irradiation of 365 nm
3
UV LEDs at room temperature by using Et N as the base. To our delight, the target
3
product 3a was obtained in 70% isolated yield (Table 1, entry 1). Then, several
organic and inorganic photocatalysts such as Rose Bengal, Eosin B, Eosin Y, Ir(ppy)3
and RuCl (bpy) were explored, however, none of them could give higher yields
2
3
(Table 1, entries 2-6). Furthermore, control experiments showed that Et N, IC F , and
3
4 9
light sources are all critical for the construction of indoles (Table 1, entries 7-9).
Among various bases tested, Et N was the most effective one (Table 1, entries 10-14).
3
In order to study the role of iodine, other iodine compounds were investigated and
found to be inferior to IC F , showing that •C F radicals are playing a key role in the
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4 9
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process. (Table 1, entry 15). The solvent investigations revealed that CH CN gave the
3
highest yield (Table 1, entries 16-19). Other light sources were also performed in
these reactions, however, the yields of 3a were not further improved (Table 1, entry
20). The results revealed that UVA light is playing a key role to generate the •C4F9
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c, 2a
and iodine radicals with the assistance of Et N.
When the reaction was carried out
3
under N , only 23% yield of 3a was obtained (Table 1, entry 21). However, when the
2
reaction was performed under O , 3a was obtained in 65% yield, indicating that O is
2
2
important for the reaction (Table 1, entry 21). As a result, the optimal reaction
conditions were established as described in entry 1 of Table 1. Finally, a gram-scale
reaction was successfully achieved under the optimal conditions, and the isolated
yield of 3a was 56% (see Experimental Section).
Scheme 2. Interactions between 1a and 2a. (a) UV−vis absorption spectra of 1a, 2a,
and the mixture of 1a + 2a in CH CN from 320 to 550 nm, respectively ([1a] = 0.5 M,
3
[2a] = 0.5 M). (b) Job’s plot of the EDA complexes for ratio between 1a and 2a with
UV/vis absorption spectrometry. (c), (d) NMR titration experiments between 1a and
2a.
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In order to further explore the formation of electron donor-acceptor (EDA)
complexes from 1a and 2a, we investigated the UV−vis absorption spectroscopic
properties of 1a, 2a, and the mixture of these two components in CH CN, respectively.
3
1
1
1
1
1
1
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2
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0
Obviously, a yellow color appeared when colorless 1a was mixed with colorless 2a,
which could ascribe to the generation of charge-transfer (CT) band (Scheme 2a).12
Moreover, the UV−vis absorption spectrometry displays the new absorption bands in
the 420 nm-550 nm region, which can be attributed to the presence of a new
electronic transition from the amine to the alkyne within the [amine-alkyne]
1
3
complex. Furthermore, the Job’s plot of the complex was explored by the UV−vis
absorption spectrometry (details in the Supporting Information). The maximal
absorption was observed when the ratio of 1a/2a in CH CN is 1:1, which can be
3
inferred that the charge-transfer complex is generated from 1a and 2a via a
14
single-electron transfer (SET) process (Scheme 2b). We further performed the NMR
titration experiments to investigate the interactions of 1a and 2a (details in the
Supporting Information).15 The results revealed that the increasing amount of
acceptors (2a) could withdraw higher electron from 1a, leading to the down-field shift
1
for the H NMR signal of methyl group of 1a (Scheme 2, c). As for 2a, the chemical
shifts of ethyl group moved to the higher field with the increase of amount of donators
(1a) (Scheme 2, d). Considering the above results, the EDA complex is derived from
N-methylanilines (using as the electron donators) and diethyl but-2-ynedioates (using
as the electron acceptors).
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Table 2. Scope of Secondary Arylamines and But-2-ynedioatesa
R2
COOR3
IC4F9 (1.5 eq)
Et3N (1 eq)
H
N
N
R2
R1
+
COOR3
1
2 h, hv (10 W, 365 nm)
COOR3 CH CN (1 mL), 23 oC, air
COOR3
3
1
2
3
3
a, R1 = H, 70%
R1
N
N
3b, R1 = F, 62%
3c, R1 = Cl, 78%
0
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0
N
COOEt
COOEt
COOEt
R1
3d, R1 = Br, 56%
R1
COOEt
COOEt
COOEt
3
e, R1 = CH3, 44%
1
3
3
ga, R1 = F, 40%
ha, R1 = Cl, 25%
3ia, R1 = Br, 35%
ja, R1 = CH3, 38%
3gb
3hb
, R = F, 43%
f, R1 = OCH3, 63%
3
1
, R = Cl, 23%
3ib, R1 = Br, 30%
, R1 = CH3, 35%
3
ka, R = CH3, R' = Cl, 23%
3
3jb
N
3la, R = CH3, R' = Br, 27%
COOEt 3ma, R = CH3, R' = CN, trace EtOOC
3na, R = Cl, R' = CH3, 30%
EtOOC
COOEt
COOEt
R
R'
COOEt
3oa, R = Br, R' = CH3, 30%
3pa, R = CH3, R' = CH3, 34%
N
N
3qa, R = OCH3, R' = OCH3, 33%
3r, 50%
3s, 28%
3kb, R = CH3, R' = Cl, 20%
3
lb, R = CH3, R' = Br, 24%
R'
N
N
O
O
N
3mb, R = CH3, R' = CN, 52%
COOEt
COOEt
COOEt
COOEt
3
nb, R = Cl, R' = CH3, 27%
3ob, R = Br, R' = CH3, 26%
pb, R = CH3, R' = CH3, 32%
R
N
COOEt
COOEt
3u, 36%
3
3t, 65%
3qb, R = OCH3, R' = OCH3, 35%
R2
R'
N
N
N
N
COOEt
COOEt
COOCH3
COOEt
COOEt
R
COOEt
COOCH3
COOEt
3y, 38%
3
3
v, R2 = CH2CH3, 57%
w, R2 = CH(CH3)2, 25%
3xa, R = CH , R' = H, 30%
3z
, 57%
3
3xb, R = H, R' = CH , 33%
3
a
Reaction conditions: 1 (0.10 mmol), 2 (0.10 mmol), IC F (0.15 mmol) and Et N
4
9
3
o
(0.10 mmol) in CH CN (1 mL) at 23 C under 10 W UV (365 nm) LED irradiation for
3
b
1
2 h in the open air. Isolated yields based on 1.
With the optimized reaction conditions in hand, we then turned our attention to the
exploration of the generality and limitation for the [3 + 2] annulations (Table 2). We
were pleased to find that the para-substituted N-methylanilines bearing
electron-donating and electron-withdrawing groups were reacted smoothly with 2a,
giving the corresponding products (3a-3f) in moderate to good yields. It is notable
that meta-substituted N-methylanilines are useful substrates in this protocol, providing
two different substituted target materials (3ga-3jb). These transformations afford
diversity-oriented practical applications in organic and medicinal chemistry. To our
delight, N-methylaniline substrates that include disubstituted groups at meta-/para-
positions remain viable in this transformation, delivering the desired products with
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two different configurations (3ka-3qb). Moreover, cyclic substrates are also tolerated
and afford the respective 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolines (3r, 3s).
Gratifyingly, hetercyclic-amines can be utilized in this new annulations protocol to
afford the corresponding products (3t, 3u) in moderate yields. Additionally,
N-ethylaniline, N-isopropylaniline and N-allylaniline proceed smoothly to give the
desired products 3v-3y. Satisfactorily, the methyl but-2-ynedioate (2b) also worked
well to accomplish the photo-driven C-C/C-N bond formation transformation, giving
the desired product 3z in 57% yield.
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1
1
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1
1
1
1
1
1
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2
2
2
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Scheme 3. Control Experiments
COOEt
H
N
N
Standard conditions
COOEt
(a)
+
COOEt
COOEt
1a
2a
3a
(
1) TEMPO (4 equiv), 3a, 9%
(
2) DPE (4 equiv), 3a, 17%
(3) BHT (4 equiv), 3a, 14%
COOEt
H
N
N
Et3N (1 eq)
CH3CN (1 mL), air, 23 oC,
COOEt
+
(b)
I
COOEt
COOEt
12 h, hv (10 W, 365 nm)
4
2a
3a, 0%
COOEt
H
N
Et3N (1 eq)
N
COOEt
COOEt
+
(c)
12 h, hv (10 W, 365 nm)
CH3CN (1 mL), 23 oC, air
COOEt
1a
2a
A, 66 %
IC4F9 (1.5 eq)
Et3N (1 eq)
N
COOEt
COOEt
N
(d)
COOEt
1
2 h, hv (10 W, 365 nm)
CH3CN (1 mL), 23 oC, air
COOEt
a, 35 %
A
3
To gain more details about the reaction mechanism, we conducted some control
experiments (Scheme 3). When four equivalents of radical inhibitors such as TEMPO,
DPE and BHT were added in the reaction systems, the yields of 3a were reduced from
70% to 9%, 17% and 14%, respectively, indicating radical reaction pathways involved
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in this transformation (Scheme 3a).16 When 1a was replaced with
2
-iodo-N-methylaniline (4) under the standard conditions, no desired product 3a was
obtained (Scheme 3b). However, when the reaction was performed in the absence of
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IC F , compound A was obtained in 66% yield (Scheme 3c). Furthermore, when
4
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compound A was performed under the standard conditions, 3a was obtained in 35%
isolated yield (Scheme 3d). This result implied that compound A might a possible
intermediate.
Based on the above experiments, a proposed mechanism for the novel photo-driven
annulations is outlined in Scheme 4. At first, the in situ generated EDA complex (I)
from N-methylaniline 1a and diethyl but-2-ynedioate 2a delivers the radical ion pair
(
II) via the light-induced single-electron transfer (SET) process.17 Coupling of the
radical ion pair (II) generates intermediate A.17,18 Then, addition of iodine radical to
intermediate A affords the radical intermediate B, which is further converted into
intermediate C through SET process under the condition of air/O atmosphere.
2
Elimination of a proton from intermediate C gives intermediate D,19 which is then
fragmented to give intermediate E. The intermediate E is further oxidized by C F I to
4
9
produce intermediate F, C F radical and iodine anion. Subsequently, C F was
4
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8 18
obtained through radical coupling process in 62% GC yield. Finally, the desired
product 3a is obtained from intermediate F through the elimination of a proton.16,20
Scheme 4. Possible Reaction Mechanism
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hv
IC4F9
I
C4F9
+
Et N
3
COOEt
NH
NH
+
NH
COOEt
COOEt
hv
+
-
SET
COOEt
EtOOC
EtOOC
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
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4
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9
0
1a
2a
EDA complex
I
II
N
N
O2
O2-
N
I
-H+
COOEt
+
CH OOEt
2
COOEt
I
I
SET
COOEt
CH OOEt
2
CH OOEt
2
A
B
C
detected by GC-MS
IC4F
9
N
N
-
I
N
Et N
N
COOEt
I
3
+
COOEt
COOEt
COOEt
COOEt
I
H+
COOEt
COOEt
D
C4F9 I-
COOEt
3a
E
F
detected by GC-MS
C8F
18
detected by GC-MS
2% GC yield
6
In conclusion, we have exhibited the utility of in situ formed EDA complexes
for the preparation of indoles via direct C-C/C-N bond formation under the
irradiation of light. Compared with previously reported method, this
photo-driven [3 + 2] annulation does not require any photocatalysts and metals.
Furthermore, this protocol features operational simplicity, good functional
tolerances and mild reaction conditions, and allows for the construction of a
diverse collection of valuable indole products. Mechanistic experiments have
provided obvious evidence supporting for the generation of a donor-acceptor
complex while facilitating the photo-driven reaction process. We anticipate that
this EDA complexes concept will prove powerful for pursuing new green
photo-induced organic transformations in the near future.
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EXPERIMENTAL SECTION
General Information. Melting points were tested using a melting point instrument
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and are uncorrected. IR spectra were obtained with an infrared spectrometer on either
1
potassium bromide pellets or liquid films between two potassium bromide pellets. H
and 13CNMR spectra were performed on a 400 MHz NMR spectrometer. GC−MS
data were obtained using electron ionization. HRMS data were collected from a
high-resolution mass spectrometer (LCMS-IT-TOF). The reaction was carried out on
the photoreaction instrument (WP-TEC-1020L, WATTCAS, China) using a
condenser system. The distance from the light source to the irradiation vessel is 5 mm.
TLC was used on commercially available 100−400 mesh silica gel plates (GF254).
The starting materials including 1a, 1b, 1c, 1d, 1e, 1f, 1g, 1h, 1i, 1j, 1r, 1s, 1u, 1v, 1w,
1
x, 1y, 2a and 2b were purchased from a commercial way. Other materials (1k, 1l,
1m, 1n, 1o, 1p, 1q and 1t) were synthesized by our lab. Unless otherwise noted, all
purchased chemicals were used without further purification.
General Procedure for Synthesis of N-methylanilines.
A solution of dimethyl sulfates (0.252 g, 2 mmol) and anilines (0.186 g, 2 mmol) in
1
0 mL H O was stirred of 1 h under ice bath. After completion of the reaction
2
monitored by TLC, 30% sodium hydroxide solution (10 mL) was added. The mixture
was extracted by ethyl acetate (3  15 mL), and then washed with water (2  10 mL).
The combined organic phase was dried over MgSO , filtered, and then concentrated in
4
vacuum. The residue was purified by flash chromatography on silica gel to give the
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desired products (using the mixture of petroleum ether and ethyl acetate (5:1) as
eluent).
3
-chloro-N,4-dimethylaniline (1k): yellow liquid, 55% yield (169 mg); IR (KBr,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
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3
3
4
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4
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5
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5
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5
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2
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7
8
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0
1
2
3
4
5
6
7
8
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0
1
2
3
4
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7
8
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0
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2
3
4
5
6
7
8
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2
3
4
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7
8
9
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−
1
1
cm ) 2923, 2811, 1616, 1512, 1442, 1315, 1254, 1159, 1038, 997, 805, 694; H
NMR (400 MHz, CDCl , ppm) δ 7.00−6.98 (d, J = 8 Hz, 1H), 6.60 (s, 1H), 6.43−6.41
3
1
3
1
(dd, J = 8 Hz, 1H), 2.78 (s, 3H), 2.24 (s, 3H); C{ H} NMR (100 MHz, CDCl , ppm)
3
δ 148.5, 134.8, 131.2, 124.0, 112.6, 111.4, 30.8, 18.9; Ms (EI, 70 eV): m/z = 154, 125,
+
1
20, 91, 77; HRMS (ESI) calcd for C H ClN [M + H] m/z 156.0575; found m/z
8
11
156.0578.
3
-bromo-N,4-dimethylaniline (1l): yellow liquid, 58% yield (231 mg); IR (KBr,
−
1
1
cm ) 2922, 2815, 1611,1509, 1445, 1313, 1252, 1162, 1026, 983, 838, 805,688; H
NMR (400 MHz, CDCl , ppm) δ 7.01−6.99 (d, J = 8 Hz, 1H), 6.80−6.79 (d, J = 4 Hz,
3
13
1
1
H), 6.48−6.46 (dd, J = 8 Hz, 1H), 2.79 (s, 3H), 2.27 (s, 3H); C{ H} NMR (100
MHz, CDCl , ppm) δ 148.5, 131.0, 125.8, 125.4, 115.7, 112.0, 30.8, 21.6; Ms (EI, 70
3
+
eV): m/z = 199, 184, 120, 91, 71; HRMS (ESI) calcd for C H BrN [M + H] m/z
8
11
200.0069; found m/z 200.0067.
-methyl-5-(methylamino)benzonitrile (1m): yellow solid, 52% yield (151 mg);
2
o
−1
mp 47-49 C. IR (KBr, cm ) 2922, 2813, 2219, 1613, 1520, 1470, 1332, 1268, 1172,
1
1067, 824; H NMR (400 MHz, CDCl , ppm) δ 7.08−7.06 (d, J = 8 Hz, 1H), 6.75 (s,
3
1
3
1
1
H), 6.73−6.71 (dd, J = 8 Hz, 1H), 2.81 (s, 3H), 2.40 (s, 3H); C{ H} NMR (100
MHz, CDCl , ppm) δ 147.4, 130.9, 129.8, 118.8, 117.5, 114.5, 112.9, 30.6, 19.2; Ms
3
+
(
EI, 70 eV): m/z = 145, 116, 89, 77; HRMS (ESI) calcd for C H N H [M + H] m/z
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147.0917; found m/z 147.0915.
-chloro-N,3-dimethylaniline (1n): yellow liquid, 54% yield (166 mg); IR (KBr,
4
−1
1
cm ) 2924, 2858, 1604, 1501, 1323, 1254, 1185, 1044, 840, 801, 688; H NMR (400
0
1
2
3
4
5
6
7
8
9
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1
2
3
4
5
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8
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MHz, CDCl , ppm) δ 7.15−7.13 (d, J = 8 Hz, 1H), 6.49 (s, 1H), 6.42−6.40 (dd, J = 8
3
1
3
1
Hz, 1H), 2.83 (s, 3H), 2.33 (s, 3H); C{ H} NMR (100 MHz, CDCl , ppm) δ 148.0,
3
136.4, 129.4, 122.3, 114.6, 111.2, 30.8, 20.3; Ms (EI): m/z = 154, 125, 118, 91, 77;
+
HRMS (EI, 70 eV) calcd for C H ClN [M + H] m/z 156.0575; found m/z 156.0581.
8
11
4
-bromo-N,3-dimethylaniline (1o): yellow liquid, 47% yield (187 mg); IR (KBr,
−
1
1
cm ) 2922, 2819, 1600, 1501, 1392, 1322, 1255, 1157, 1021, 845, 801, 688; H
NMR (400 MHz, CDCl , ppm) δ 7.28−7.26 (d, J = 8 Hz, 1H), 6.48−6.47 (d, J = 4 Hz,
3
1
3
1
1H), 6.32−6.30 (dd, J = 8 Hz, 1H), 2.79 (s, 3H), 2.31 (s, 3H); C{ H} NMR (100
MHz, CDCl , ppm) δ 148.6, 138.2, 132.6, 114.7, 111.6, 111.6, 30.8, 23.1; Ms (EI, 70
3
+
eV): m/z = 199, 184, 119, 91, 77; HRMS (ESI) calcd for C H BrN [M + H] m/z
8
11
200.0069; found m/z 200.0076.
2
1
−1
N,3,4-trimethylaniline (1p): yellow liquid, 56% yield (150 mg); IR (KBr, cm )
1
2923, 2810, 1617, 1513, 1446, 1320, 1263, 1153, 1075, 1002, 847, 804; H NMR
(
400 MHz, CDCl , ppm) δ 6.95−6.93 (d, J = 8 Hz, 1H), 6.44−6.43 (d, J = 4 Hz, 1H),
3
13
1
6
.39−6.37 (dd, J = 8 Hz, 1H), 2.79 (s, 3H), 2.20 (s, 3H), 2.15 (s, 3H); C{ H} NMR
(100 MHz, CDCl , ppm) δ 147.7, 137.3, 130.3, 125.3, 114.4, 110.0, 31.2, 20.1, 18.7;
3
Ms (EI, 70 eV): m/z = 134, 120, 91, 77.
3,4-dimethoxy-N-methylaniline (1q): yellow liquid, 58% yield (194 mg); IR (KBr,
−
1
cm ) 2934, 2830, 1617, 1516, 1463, 1297, 1233, 1160, 1128, 1024, 918, 826, 762,
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632; H NMR (400 MHz, CDCl , ppm) δ 6.77−6.75 (d, J = 8 Hz, 1H), 6.24 (s, 1H),
3
1
3
1
6
.16−6.14 (dd, J = 8 Hz, 1H), 3.83 (s, 3H), 3.80 (s, 3H), 2.80 (s, 3H); C{ H} NMR
(
100 MHz, CDCl , ppm) δ 150.1, 144.4, 141.5, 113.4, 103.1, 98.6, 56.8, 55.7, 31.5;
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
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4
4
4
4
4
4
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5
5
5
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5
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Ms (EI, 70 eV): m/z = 167, 152, 124, 109, 94; HRMS (ESI) calcd for C H NO [M +
9
14
2
+
H] m/z 168.1019; found m/z 168.1027.
N-methylbenzo[d][1,3]dioxol-5-amine (1t):21 yellow liquid, 53% yield (160 mg);
−
1
IR (KBr, cm ) 2883, 2810, 1634, 1504, 1445, 1356, 1296, 1205, 1145, 1038, 937,
1
8
12, 791; H NMR (400 MHz, CDCl , ppm) δ 6.68−6.66 (d, J = 8 Hz, 1H), 6.24 (s,
3
1
3
1
1H), 6.05−6.03 (dd, J = 8 Hz, 1H), 5.84 (s, 2H), 2.77 (s, 3H); C{ H} NMR (100
MHz, CDCl , ppm) δ 148.4, 145.2, 139.6, 108.6, 103.8, 100.6, 95.6, 31.6; Ms (EI, 70
3
eV): m/z = 151, 136, 122, 93, 78.
General Procedure for the Synthesis of Indoles.
A solution of N-methylanilines (0.10 mmol), diethyl but-2-ynedioates (17 mg, 0.10
mmol), perfluorobutyl iodides (51.8 mg, 0.15 mmol), and Et N (10 mg, 0.10 mmol,
3
o
1
.0 equiv) was stirred at 23 C in CH CN (1.0 mL) under 10 W UV (365 nm) LED
3
irradiation for 12 h in the open air. After completion of the reaction monitored by
TLC, the solution was concentrated in vacuum. The residue was then purified by flash
chromatography on silica gel to afford the desired products 3 (using the mixture of
petroleum ether and ethyl acetate (5:1) as eluent).
For the gram scale synthesis of 3a: N-methylanilines 1a (3.0 mmol, 0.321 g),
diethyl but-2-ynedioates 2a (3.0 mmol, 0.510 g), perfluorobutyl iodides (4.5 mmol,
1.552 g), Et N (0.303 g, 3 mmol, 1.0 equiv) and CH CN (4.0 mL) were added
3
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subsequently into a 25 mL dry quartz flask. The mixture was irradiated by a 10 W 365
o
nm LEDs performed on the photoreaction instrument for 12 h at 23 C in the open air.
The photoreaction was monitored by TLC. Subsequently, water (10 mL) was added,
and the resulting mixture was extracted with ethyl acetate. The collected organic
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phase was dried over MgSO , filtered, and then concentrated under reduced pressure.
4
The crude product was purified by silica gel flash chromatography using the mixture
of petroleum ether/ethyl acetate (PE/EA = 5/1) as eluent to afford the target
compound 3a (0.463 g, yield of 56%).
2
2
Diethyl 1-methyl-1H-indole-2,3-dicarboxylate(3a): yellow liquid, 70% yield (19
−
1
mg); IR (KBr, cm ) 3055, 2982, 2816, 1704, 1613, 1532, 1469, 1411, 1336, 1246,
1
1157, 1106, 1035, 922, 860, 787, 753, 620; H NMR (400 MHz, CDCl , ppm) δ
3
8
8
.15−8.13 (d, J = 8 Hz, 1H), 7.37−7.35 (m, 2H), 7.33−7.27 (m, 1H), 4.51−4.46 (q, J =
Hz, 2H), 4.41−4.36 (q, J = 8 Hz, 2H), 3.82 (s, 3H), 1.45−1.42 (t, J = 8 Hz, 3H),
1
3
1
1.41−1.39 (t, J = 8 Hz, 3H); C{ H} NMR (100 MHz, CDCl , ppm) δ 164.2, 162.9,
3
1
36.8, 135.0, 125.4, 124.3, 122.5, 122.3, 110.1, 108.0, 62.3, 60.2, 31.3, 14.4, 14.1;
MS (EI, 70 eV): m/z = 275, 243, 216, 185, 159, 129, 102, 77.
Diethyl 5-fluoro-1-methyl-1H-indole-2,3-dicarboxylate (3b): red solid, 62% yield
o
−1
(
18 mg); mp 78-80 C. IR (KBr, cm ) 2983, 2870, 1705, 1625, 1530, 1481, 1412,
1
1380, 1303, 1240, 1174, 1104, 1031, 949, 865, 799, 694; H NMR (400 MHz, CDCl ,
3
ppm) δ 7.81−7.78 (dd, J = 8 Hz, 1H), 7.31−7.28 (m, 1H), 7.13−7.08 (m, 1H),
4.52−4.46 (q, J = 8 Hz, 2H), 4.41−4.35 (q, J = 8 Hz, 2H), 3.82 (s, 3H), 1.45−1.42 (t, J
1
3
1
=
8 Hz, 3H), 1.42−1.39 (t, J = 8 Hz, 3H); C{ H} NMR (100 MHz, CDCl , ppm) δ
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163.7, 162.5, 159.5 (d, J = 240.0 Hz) , 136.5, 133.3, 126.1 (d, J = 10.0 Hz), 113.3 (d,
J = 30.0 Hz), 111.1 (d, J = 10.0 Hz), 107.8, 107.5 (d, J = 30.0 Hz), 62.5, 60.3, 31.6,
1
4.4, 14.1; MS (EI, 70 eV): m/z = 293, 248, 220, 175, 148; HRMS (ESI) calcd for
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
C H FNO Na [M + Na] m/z 316.0956, found m/z 316.0959.
1
5
16
4
Diethyl 5-chloro-1-methyl-1H-indole-2,3-dicarboxylate (3c): yellow liquid, 78%
−
1
yield (21 mg); IR (KBr, cm ) 2981, 1736, 1603, 1531, 1493, 1410, 1374, 1206, 1097,
1
1
8
029, 936, 858, 817, 769, 713, 647, 618; H NMR (400 MHz, CDCl , ppm) δ
3
.13−8.12 (m, 1H), 7.31−7.30 (m, 2H), 4.52−4.47 (q, J = 8 Hz, 2H), 4.41−4.36 (q, J =
8 Hz, 2H), 3.82 (s, 3H), 1.46−1.43 (t, J = 8 Hz, 3H), 1.42−1.39 (t, J = 8 Hz, 3H);
1
3
1
C{ H} NMR (100 MHz, CDCl , ppm) δ 163.6, 162.5, 136.2, 135.1, 128.5, 126.3,
3
124.8, 121.9, 111.2, 107.5, 62.5, 60.4, 31.6, 14.4, 14.0; MS (EI, 70 eV): m/z = 309,
+
2
64, 236, 209, 191; HRMS (ESI) calcd for C H ClNO [M + H] m/z 310.0841;
1
5
17
4
found m/z 310.0844.
Diethyl 5-bromo-1-methyl-1H-indole-2,3-dicarboxylate (3d): yellow liquid, 56%
−
1
yield (20 mg); IR (KBr, cm ) 2981, 1710, 1597, 1526, 1476, 1409, 1383, 1229, 1098,
1
1023, 861, 788, 753, 618; H NMR (400 MHz, CDCl , ppm) δ 8.29−8.28 (d, J = 4 Hz,
3
1
H), 7.46−7.43 (dd, J = 8 Hz, 1H), 7.25−7.23 (m, 1H), 4.52−4.46 (q, J = 8 Hz, 2H),
.41−4.36 (q, J = 8 Hz, 2H), 3.81 (s, 3H), 1.45−1.43 (t, J = 4 Hz, 3H), 1.42−1.39 (t, J
4
1
3
1
= 8 Hz, 3H); C{ H} NMR (100 MHz, CDCl , ppm) δ 163.6, 162.4, 136.0, 135.4,
3
1
27.4, 126.9, 125.0, 116.2, 111.6, 107.4, 62.5, 60.4, 31.5, 14.4, 14.1; MS (EI, 70 eV):
+
m/z = 353, 309, 280, 253,237, 209; HRMS (ESI) calcd for C H BrNO [M + H]
1
5
17
4
m/z 354.0335; found m/z 354.0341.
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5
5
5
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6
Diethyl 1,5-dimethyl-1H-indole-2,3-dicarboxylate (3e): yellow liquid, 44% yield
−
1
(
13 mg); IR (KBr, cm ) 2981, 2934, 2864, 1703, 1529, 1485, 1411, 1378, 1223, 1152,
1
1
107, 1035, 946, 859, 791, 700; H NMR (400 MHz, CDCl , ppm) δ 7.92−7.92 (m,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
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0
1
2
3
4
5
6
7
8
9
0
1H), 7.24 (s, 1H), 7.19−7.17 (m, 1H), 4.50−4.45 (q, J = 8 Hz, 2H), 4.41−4.36 (q, J = 8
Hz, 2H), 3.81 (s, 3H), 2.48 (s, 3H), 1.45−1.42 (t, J = 8 Hz, 3H), 1.41−1.39 (t, J = 8 Hz,
3H); 13C{ H} NMR (100 MHz, CDCl , ppm) δ 164.3, 162.9, 135.3, 134.7, 132.1,
1
3
1
26.1, 125.7, 121.8, 109.7, 107.6, 62.2, 60.1, 31.4, 21.6, 14.4, 14.1; MS (EI, 70 eV):
+
m/z = 289, 244, 216, 189, 171, 145; HRMS (ESI) calcd for C H NO [M + H] m/z
1
6
20
4
290.1387; found m/z 290.1390.
Diethyl 5-methoxy-1-methyl-1H-indole-2,3-dicarboxylate (3f): yellow liquid, 63%
−
1
yield (19 mg); IR (KBr, cm ) 2924, 2853, 1719, 1701, 1623, 1524, 1459, 1382, 1251,
1
6
1
7
196, 1103, 1040, 951, 848, 806, 779; H NMR (400 MHz, d -DMSO, ppm) δ
.58−7.56 (d, J = 8 Hz, 1H), 7.46−7.45 (d, J = 4 Hz, 1H), 7.04−7.01 (dd, J = 8 Hz,
1H), 4.44−4.38 (q, J = 8 Hz, 2H), 4.29−4.24 (q, J = 8 Hz, 2H), 3.81 (s, 3H), 3.79 (s,
1
3
1
3
H), 1.37−1.33 (t, J = 8 Hz, 3H), 1.33−1.29 (t, J = 8 Hz, 3H); C{ H} NMR (100
MHz, CDCl , ppm) δ 164.3, 162.8, 156.2, 134.9, 131.9, 126.3, 115.4, 111.0, 107.3,
3
1
02.9, 62.2, 60.1, 55.7, 31.5, 14.4, 14.1; MS (EI, 70 eV): m/z = 305, 290, 260, 232,
+
2
18, 187; HRMS (ESI) calcd for C H NO [M + H] m/z 306.1336; found m/z
1
6
20
5
306.1331.
Diethyl 4-fluoro-1-methyl-1H-indole-2,3-dicarboxylate (3ga): yellow liquid, 40%
−
1
yield (12 mg); IR (KBr, cm ) 2928, 2867, 1719, 1625, 1576, 1528, 1462, 1378, 1217,
1
1
154, 1107, 1063, 733, 646, 624; H NMR (400 MHz, CDCl , ppm) δ 7.32−7.28 (m,
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1H), 7.17−7.15 (d, J = 8 Hz, 1H), 6.91−6.86 (m, 1H), 4.44−4.38 (m, 4H), 3.97 (s, 3H),
1
3
1
1
.42−1.38 (t, J = 8 Hz, 6H); C{ H} NMR (100 MHz, CDCl , ppm) δ 164.9, 161.3,
3
1
56.7 (d, J = 251.0 Hz), 139.9 (d, J = 10.0 Hz), 129.3, 125.7 (d, J = 8.0 Hz), 113.7 (d,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
J = 21.0 Hz), 111.5 (d, J = 3.0 Hz), 107.1 (d, J = 20.0 Hz), 106.3 (d, J = 4.0 Hz), 61.8,
6
1.3, 32.1, 14.1, 14.0; MS (EI, 70 eV): m/z = 293, 247, 220, 176, 148; HRMS (ESI)
+
calcd for C H FNO Na [M + Na] m/z 316.0956; found m/z 316.0948.
1
5
16
4
Diethyl 6-fluoro-1-methyl-1H-indole-2,3-dicarboxylate (3gb): yellow liquid, 43%
−1
yield (13 mg); IR (KBr, cm ) 2928, 2858, 1708, 1622, 1536, 1468, 1382, 1252, 1221,
1
1177, 1092, 1032, 938, 828, 734, 613; H NMR (400 MHz, CDCl , ppm) δ 8.08−8.05
3
(m, 1H), 7.07−7.02 (m, 2H), 4.50−4.45 (q, J = 8 Hz, 2H), 4.41−4.35 (q, J = 8 Hz, 2H),
1
3
1
3.79 (s, 3H), 1.45−1.42 (t, J = 8 Hz, 3H), 1.41−1.38 (t, J = 8 Hz, 3H); C{ H} NMR
(
100 MHz, CDCl , ppm) δ 163.9, 162.5, 161.0 (d, J = 241.0 Hz), 137.1 (d, J = 12.0
3
Hz), 135.2 (d, J = 3.0 Hz), 123.7 (d, J = 10.0 Hz), 121.8, 111.7, 111.5, 108.5, 96.5 (d,
J = 26.0 Hz), 62.3, 60.4, 31.5, 14.4, 14.0; MS (EI, 70 eV): m/z = 293, 248, 220, 176,
+
1
48; HRMS (ESI) calcd for C H FNO [M + H] m/z 294.1136; found m/z
1
5
17
4
294.1140.
Diethyl 4-chloro-1-methyl-1H-indole-2,3-dicarboxylate (3ha): yellow solid, 25%
o
−1
yield (8 mg); mp 92-94 C; IR (KBr, cm ) 2922, 2847, 1718, 1634, 1527, 1461, 1410,
1
1371, 1248, 1222, 1189, 1123, 1029, 938, 831, 777, 735; H NMR (400 MHz,
d6-DMSO, ppm) δ 7.69−7.67 (m, 1H), 7.41−7.37 (m, 1H), 7.29−7.27 (m, 1H),
4.35−4.30 (m, 4H), 4.02 (s, 3H), 1.33−1.28 (m, 6H); 13C{ H} NMR (100 MHz,
d6-DMSO, ppm) δ 165.5, 160.5, 139.0, 127.1, 126.5, 125.8, 122.4, 121.0, 114.9,
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5
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6
111.2, 61.9, 61.6, 32.7, 14.3, 14.2; MS (EI, 70 eV): m/z = 309, 264, 236, 209, 191,
+
1
3
64; HRMS (ESI) calcd for C H ClNO Na [M + Na] m/z 332.0660; found m/z
1
5
16
4
32.0656.
Diethyl 6-chloro-1-methyl-1H-indole-2,3-dicarboxylate (3hb): yellow liquid, 23%
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
−
1
yield (7 mg); IR (KBr, cm ) 2969, 2927, 2856, 1729, 1608, 1542, 1476, 1419, 1380,
1
1321, 1268, 1221, 1188, 1130, 1029, 991, 879, 837, 776, 731, 649; H NMR (400
6
MHz, d -DMSO, ppm) δ 8.00−7.97 (d, J = 12 Hz, 1H), 7.85−7.84 (d, J = 4 Hz, 1H),
7
.34−7.31 (dd, J = 8 Hz, 1H), 4.45−4.40 (q, J = 8 Hz, 2H), 4.31−4.26 (q, J = 8 Hz,
1
3
1
2H), 3.82 (s, 3H), 1.37−1.33 (t, J = 8 Hz, 3H), 1.32−1.29 (t, J = 8 Hz, 3H); C{ H}
NMR (100 MHz, CDCl , ppm) δ 163.7, 162.4, 137.2, 135.5, 130.5, 124.0, 123.5,
3
123.4, 110.2, 108.3, 62.4, 60.4, 31.5, 14.4, 14.1; MS (EI, 70 eV): m/z = 309, 264, 236,
+
2
09, 192, 164; HRMS (ESI) calcd for C H ClNO Na [M + Na] m/z 332.0660;
1
5
16
4
found m/z 332.0664.
Diethyl 4-bromo-1-methyl-1H-indole-2,3-dicarboxylate (3ia): yellow solid, 35%
o
−1
yield (12 mg); mp 109-111 C; IR (KBr, cm ) 2924, 2856, 1704, 1604, 1527, 1461,
1
1389, 1246, 1211, 1110, 1033, 910, 826, 730; H NMR (400 MHz, CDCl , ppm) δ
3
7
.39−7.34 (m, 2H), 7.23−7.19 (t, J = 8 Hz, 1H), 4.47−4.42 (q, J = 8 Hz, 2H),
.41−4.36 (q, J = 8 Hz, 2H), 4.05 (s, 3H), 1.45−1.42 (t, J = 8 Hz, 3H), 1.41−1.37 (t, J
4
1
3
1
= 8 Hz, 3H); C{ H} NMR (100 MHz, CDCl , ppm) δ 166.2, 160.7, 138.9, 126.2,
3
1
26.1, 125.5, 123.1, 116.9, 115.3, 109.7, 61.8, 61.5, 32.2, 14.1, 14.0; MS (EI, 70 eV):
+
m/z = 353, 310, 280, 253, 236, 209; HRMS (ESI) calcd for C H BrNO [M + H]
1
5
17
4
m/z 354.0335; found m/z 354.0341.
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Diethyl 6-bromo-1-methyl-1H-indole-2,3-dicarboxylate (3ib): yellow solid, 30%
o
−1
yield (11 mg); mp 101-103 C; IR (KBr, cm ) 2976, 2927, 1717, 1594, 1528, 1459,
1
1
411, 1383, 1223, 1187, 1111, 1028, 876, 773, 734; H NMR (400 MHz, CDCl , ppm)
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
δ 8.00−7.98 (d, J = 8 Hz, 1H), 7.54−7.53 (d, J = 4 Hz, 1H), 7.40−7.37 (dd, J = 8 Hz,
H), 4.51−4.46 (q, J = 8 Hz, 2H), 4.40−4.35 (q, J = 8 Hz, 2H), 3.80 (s, 3H),
1
1
3
1
1.45−1.38 (m, 6H); C{ H} NMR (100 MHz, CDCl , ppm) δ 163.7, 162.4, 137.5,
3
1
7
35.4, 125.9, 124.2, 123.7, 118.0, 113.2, 108.2, 62.5, 60.4, 31.5, 14.4, 14.0; MS (EI,
0 eV): m/z = 353, 328, 280, 253, 236, 209; HRMS (ESI) calcd for C H BrNO [M
1
5
17
4
+
+ H] m/z 354.0335; found m/z 354.0337.
Diethyl 1,4-dimethyl-1H-indole-2,3-dicarboxylate (3ja): yellow liquid, 38% yield
−
1
(11 mg); IR (KBr, cm ) 2987, 2928, 2855, 1712, 1605, 1527, 1466, 1409, 1372, 1243,
1
6
1
208, 1157, 1053, 946, 859, 775, 745, 601; H NMR (400 MHz, d -DMSO, ppm) δ
7
.49−7.46 (d, J = 12 Hz, 1H), 7.31−7.27 (t, J = 8 Hz, 1H), 7.00−6.98 (d, J = 8 Hz,
1
3
1
1H), 4.35−4.28 (m, 4H), 3.96 (s, 3H), 2.45 (s, 3H), 1.33−1.28 (m, 6H); C{ H} NMR
6
(
100 MHz, d -DMSO, ppm) δ 166.7, 161.2, 138.1, 131.4, 127.3, 125.8, 123.2, 122.8,
114.7, 109.6, 61.7, 61.4, 32.2, 19.5, 14.4, 14.3; MS (EI, 70 eV): m/z = 289, 243, 216,
+
1
87, 171, 143; HRMS (ESI) calcd for C H NO [M + H] m/z 290.1387; found m/z
1
6
20
4
2
90.1393.
Diethyl 1,6-dimethyl-1H-indole-2,3-dicarboxylate (3jb): yellow liquid, 35% yield
−
1
(
10 mg); IR (KBr, cm ) 2980, 2929, 2856, 1711, 1528, 1466, 1409, 1383, 1244, 1211,
1
1155, 1101, 1053, 864, 812, 778, 746; H NMR (400 MHz, CDCl , ppm) δ 8.00−7.98
3
(
d, J = 8 Hz, 1H), 7.15 (s, 1H), 7.13−7.11 (d, J = 8 Hz, 1H), 4.50−4.44 (q, J = 8 Hz,
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2H), 4.40−4.35 (q, J = 8 Hz, 2H), 3.81 (s, 3H), 2.51 (s, 3H), 1.45−1.42 (t, J = 8 Hz,
1
3
1
3
1
H), 1.41−1.38 (t, J = 8 Hz, 3H); C{ H} NMR (100 MHz, CDCl , ppm) δ 164.3,
3
62.9, 137.3, 134.5, 134.1, 124.5, 123.3, 122.0, 109.9, 108.3, 62.2, 60.2, 31.3, 22.0,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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1
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3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
14.4, 14.1; MS (EI, 70 eV): m/z = 289, 244, 216, 187, 171, 143; HRMS (ESI) calcd
+
for C H NO [M + H] m/z 290.1387; found m/z 290.1389.
1
6
20
4
Diethyl 4-chloro-1,5-dimethyl-1H-indole-2,3-dicarboxylate (3ka): yellow solid,
o
−1
2
3% yield (7 mg); mp 102-104 C; IR (KBr, cm ) 2924, 2858, 1717, 1631, 1526,
1
1
459, 1382, 1228, 1198, 1123, 1022, 868, 789, 699, 620; H NMR (400 MHz, CDCl ,
3
ppm) δ 7.21−7.19 (d, J = 8 Hz, 1H), 7.17−7.15 (d, J = 8 Hz, 1H), 4.46−4.41 (q, J = 8
Hz, 2H), 4.40−4.34 (q, J = 8 Hz, 2H), 4.00 (s, 3H), 2.43 (s, 3H), 1.44−1.40 (t, J = 8
1
3
1
Hz, 3H), 1.40−1.36 (t, J = 8 Hz, 3H); C{ H} NMR (100 MHz, CDCl , ppm) δ 166.7,
3
1
1
60.8, 137.6, 128.6, 128.5, 125.9, 125.6, 122.1, 115.6, 108.6, 100.0, 61.7, 61.3, 32.0,
9.4, 14.1, 14.0; MS (EI, 70 eV): m/z = 323, 278, 250, 223, 205; HRMS (ESI) calcd
+
for C H ClNO [M + H] m/z 324.0997; found m/z 324.0990.
1
6
19
4
Diethyl 6-chloro-1,5-dimethyl-1H-indole-2,3-dicarboxylate (3kb): yellow liquid,
−
1
20% yield (7 mg); IR (KBr, cm ) 2982, 2870, 1736, 1615, 1578, 1532, 1472, 1409,
1
1
305, 1254, 1114, 1042, 952, 862, 791, 702, 610; H NMR (400 MHz, CDCl , ppm) δ
3
7
.98 (s, 1H), 7.38 (s, 1H), 4.50−4.45 (q, J = 8 Hz, 2H), 4.40−4.35 (q, J = 8 Hz, 2H),
1
3
1
3.78 (s, 3H), 2.49 (s, 3H), 1.45−1.38 (m, 6H); C{ H} NMR (100 MHz, CDCl , ppm)
3
δ 163.9, 162.5, 135.8, 135.2, 131.3, 130.4, 124.3, 123.4, 110.4, 107.6, 62.4, 60.3, 31.5,
20.5, 14.4, 14.0; MS (EI, 70 eV): m/z = 323, 278, 250, 223, 205; HRMS (ESI) calcd
+
for C H ClNO [M + H] m/z 324.0997; found m/z 324.1003.
1
6
19
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Diethyl 4-bromo-1,5-dimethyl-1H-indole-2,3-dicarboxylate (3la): yellow solid,
o
−1
2
7% yield (10 mg); mp 120-122 C; IR (KBr, cm ) 2974, 2940, 1714, 1631, 1534,
1
1
412, 1381, 1227, 1196, 1116, 1055, 885, 785, 696; H NMR (400 MHz, CDCl , ppm)
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
δ 7.24 (s, 1H), 7.24 (s, 1H), 4.47−4.42 (q, J = 8 Hz, 2H), 4.40−4.35 (q, J = 8 Hz, 2H),
4
.03 (s, 3H), 2.48 (s, 3H), 1.45−1.41 (t, J = 8 Hz, 3H), 1.40−1.37 (t, J = 8 Hz, 3H);
1
3
1
C{ H} NMR (100 MHz, CDCl , ppm) δ 166.7, 160.8, 137.4, 131.1, 128.3, 125.7,
3
1
23.7, 116.8, 116.5, 109.4, 61.8, 61.4, 32.1, 22.5, 14.1, 14.0; MS (EI, 70 eV): m/z =
+
3
67, 322, 294, 251, 223, 83; HRMS (ESI) calcd for C H BrNO [M + H] m/z
1
6
19
4
368.0492; found m/z 368.0498.
Diethyl 6-bromo-1,5-dimethyl-1H-indole-2,3-dicarboxylate (3lb): yellow liquid,
−
1
24% yield (9 mg); IR (KBr, cm ) 2922, 2847, 1705, 1632, 1531, 1467, 1408, 1382,
1
1
251, 1223, 1112, 1039, 904, 792, 703, 618; H NMR (400 MHz, CDCl , ppm) δ 7.98
3
(
s, 1H), 7.57 (s, 1H), 4.50−4.45 (q, J = 8 Hz, 2H), 4.40−4.35 (q, J = 8 Hz, 2H), 3.77 (s,
1
3
1
3H), 2.51 (s, 3H), 1.45−1.38 (m, 6H); C{ H} NMR (100 MHz, CDCl , ppm) δ 163.8,
3
1
62.5, 136.1, 135.2, 131.8, 124.9, 123.2, 121.3, 113.7, 107.5, 62.4, 60.3, 31.5, 23.3,
14.4, 14.1; MS (EI, 70 eV): m/z = 367, 322, 294, 251, 223, 183; HRMS (ESI) calcd
+
for C H BrNO [M + H] m/z 368.0492; found m/z 368.0494.
1
6
19
4
Diethyl 6-cyano-1,5-dimethyl-1H-indole-2,3-dicarboxylate (3mb): yellow solid,
o
−1
52% yield (16 mg); mp 86-88 C; IR (KBr, cm ) 2926, 2855, 1738, 1708, 1627, 1530,
1
1
476, 1381, 1298, 1249, 1180, 1101, 1022, 861, 787, 697; H NMR (400 MHz,
CDCl , ppm) δ 8.07 (s, 1H), 7.86 (s, 1H), 4.53−4.48 (q, J = 8 Hz, 2H), 4.40−4.36 (q, J
3
1
3
1
=
8 Hz, 2H), 3.83 (s, 3H), 2.65 (s, 3H), 1.46−1.39 (m, 6H); C{ H} NMR (100 MHz,
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CDCl , ppm) δ 163.3, 162.1, 138.4, 134.4, 134.2, 128.8, 123.4, 118.9, 115.2, 108.4,
3
1
07.5, 62.7, 60.5, 31.6, 20.6, 14.4, 14.0; MS (EI, 70 eV): m/z = 314, 269, 241, 214,
+
1
96, 168; HRMS (ESI) calcd for C H N O [M + H] m/z 315.1339; found m/z
1
7
19
2
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
315.1339.
Diethyl 5-chloro-1,4-dimethyl-1H-indole-2,3-dicarboxylate (3na): yellow liquid,
−
1
30% yield (10 mg); IR (KBr, cm ) 2924, 2855, 1716, 1640, 1526, 1458, 1410, 1383,
1
1
7
247, 1209, 1108, 1049, 1012, 906, 782, 700; H NMR (400 MHz, CDCl , ppm) δ
3
.36−7.34 (d, J = 8 Hz, 1H), 7.17−7.15 (d, J = 8 Hz, 1H), 4.45−4.35 (m, 4H), 4.01 (s,
1
3
1
3H), 2.55 (s, 3H), 1.43−1.40 (t, J = 8 Hz, 3H), 1.39−1.37 (t, J = 8 Hz, 3H); C{ H}
NMR (100 MHz, CDCl , ppm) δ 167.3, 161.0, 136.7, 129.2, 127.3, 126.9, 124.0,
3
116.0, 109.1, 100.0, 61.6, 61.4, 31.9, 15.8, 14.1, 14.1; MS (EI, 70 eV): m/z = 323, 277,
+
2
50, 223, 221, 192; HRMS (ESI) calcd for C H ClNO [M + H] m/z 324.0997;
1
6
19
4
found m/z 324.1000.
Diethyl 5-chloro-1,6-dimethyl-1H-indole-2,3-dicarboxylate (3nb): yellow liquid,
−
1
2
7% yield (9 mg); IR (KBr, cm ) 2925, 2855, 1704, 1656, 1529, 1464, 1381, 1218,
1
1181, 1102, 1043, 941, 869, 782, 734, 700; H NMR (400 MHz, CDCl , ppm) δ 8.10
3
(s, 1H), 7.21 (s, 1H), 4.50−4.45 (q, J = 8 Hz, 2H), 4.41−4.35 (q, J = 8 Hz, 2H), 3.79 (s,
13
1
3
H), 2.51 (s, 3H), 1.45−1.39 (m, 6H); C{ H} NMR (100 MHz, CDCl , ppm) δ 163.7,
3
162.6, 135.7, 135.3, 132.5, 129.6, 124.6, 122.2, 111.5, 107.6, 62.4, 60.3, 31.5, 21.1,
1
4.5, 14.1; MS (EI, 70 eV): m/z = 323, 278, 250, 223, 205; HRMS (ESI) calcd for
+
C H ClNO Na [M + Na] m/z 346.0817; found m/z 346.0820.
1
6
18
4
Diethyl 5-bromo-1,4-dimethyl-1H-indole-2,3-dicarboxylate (3oa): yellow liquid,
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−
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30% yield (11 mg); IR (KBr, cm ) 2921, 2845, 1715, 1632, 1520, 1466, 1410, 1383,
1
1
7
245, 1209, 1110, 1047, 1012, 886, 771, 678; H NMR (400 MHz, CDCl , ppm) δ
3
.52−7.50 (d, J = 8 Hz, 1H), 7.11−7.09 (d, J = 8 Hz, 1H), 4.45−4.35 (m, 4H), 4.01 (s,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
1
3H), 2.59 (s, 3H), 1.43−1.40 (t, J = 8 Hz, 3H), 1.40−1.37 (t, J = 8 Hz, 3H); C{ H}
NMR (100 MHz, CDCl , ppm) δ 167.4, 160.9, 137.1, 131.2, 129.8, 126.4, 124.1,
3
117.7, 116.1, 109.5, 61.7, 61.4, 32.0, 18.9, 14.1, 14.1; MS (EI, 70 eV): m/z = 367, 323,
+
2
94, 251, 238, 214; HRMS (ESI) calcd for C H BrNO [M + H] m/z 368.0492;
1
6
19
4
found m/z 368.0492.
Diethyl 5-bromo-1,6-dimethyl-1H-indole-2,3-dicarboxylate (3ob): yellow liquid,
−
1
2
6% yield (10 mg); IR (KBr, cm ) 2919, 2847, 1705, 1627, 1529, 1463, 1375, 1216,
1
1102, 1041, 907, 793, 737; H NMR (400 MHz, CDCl , ppm) δ 8.30 (s, 1H), 7.22 (s,
3
1
3
H), 4.50−4.45 (q, J = 8 Hz, 2H), 4.41−4.35 (q, J = 8 Hz, 2H), 3.79 (s, 3H), 2.54 (s,
H), 1.45−1.39 (m, 6H); 13C{ H} NMR (100 MHz, CDCl , ppm) δ 163.7, 162.6,
1
3
136.2, 135.2, 133.8, 125.5, 125.0, 119.6, 111.4, 107.3, 62.4, 60.4, 31.5, 23.9, 14.4,
1
4.1; MS (EI, 70 eV): m/z = 367, 323, 294, 251, 238, 214; HRMS (ESI) calcd for
+
C H BrNO [M + H] m/z 368.0492; found m/z 368.0488.
1
6
19
4
Diethyl 1,4,5-trimethyl-1H-indole-2,3-dicarboxylate (3pa): red solid, 34% yield
o
−1
(
10 mg); mp 82-84 C; IR (KBr, cm ) 2977, 2924, 2858, 1710, 1653, 1531, 1457,
1
1380, 1210, 1101, 1052, 906, 865, 798, 734; H NMR (400 MHz, CDCl , ppm) δ
3
7
.19−7.17 (d, J = 8 Hz, 1H), 7.12−7.10 (d, J = 8 Hz, 1H), 4.44−4.39 (q, J = 8 Hz, 2H),
4.39−4.34 (q, J = 8 Hz, 2H), 3.99 (s, 3H), 2.41 (s, 3H), 2.36 (s, 3H), 1.43−1.40 (t, J =
1
3
1
8
Hz, 3H), 1.39−1.36 (t, J = 8 Hz, 3H); C{ H} NMR (100 MHz, CDCl , ppm) δ
3
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168.3, 161.3, 137.3, 129.2, 128.8, 128.7, 125.4, 123.6, 115.8, 107.5, 61.4, 61.1, 31.7,
1
9.6, 15.1, 14.2, 14.1; MS (EI, 70 eV): m/z = 303, 257, 228, 201, 185, 172; HRMS
+
(
ESI) calcd for C H NO [M + H] m/z 304.1543; found m/z 304.1547.
1
7
22
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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6
7
8
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8
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0
Diethyl 1,5,6-trimethyl-1H-indole-2,3-dicarboxylate (3pb): yellow liquid, 32%
−
1
yield (10 mg); IR (KBr, cm ) 2928, 2855, 1709, 1582, 1526, 1460, 1408, 1372, 1229,
1
1153, 1096, 1024, 872, 795, 761; H NMR (400 MHz, CDCl , ppm) δ 7.86 (s, 1H),
3
7
.13 (s, 1H), 4.49−4.43 (q, J = 8 Hz, 2H), 4.40−4.35 (q, J = 8 Hz, 2H), 3.80 (s, 3H),
2
.40 (s, 3H), 2.38 (s, 3H), 1.44−1.42 (t, J = 8 Hz, 3H), 1.40−1.38 (t, J = 8 Hz, 3H);
1
3
1
C{ H} NMR (100 MHz, CDCl , ppm) δ 164.4, 163.0, 135.9, 133.9, 133.6, 131.6,
3
1
23.8, 122.1, 110.2, 107.9, 62.0, 60.1, 31.3, 20.7, 20.2, 14.4, 14.1; MS (EI, 70 eV):
+
m/z = 303, 258, 230, 203, 185, 157; HRMS (ESI) calcd for C H NO [M + H] m/z
1
7
22
4
3
04.1543; found m/z 304.1548.
Diethyl 4,5-dimethoxy-1-methyl-1H-indole-2,3-dicarboxylate (3qa): yellow liquid,
−
1
33% yield (11 mg); IR (KBr, cm ) 2928, 2853, 1710, 1622, 1572, 1506, 1464, 1410,
1
1
376, 1311, 1224, 1107, 1026, 966, 865, 784, 688; H NMR (400 MHz, CDCl , ppm)
3
δ 7.14−7.12 (d, J = 8 Hz, 1H), 7.05−7.03 (d, J = 8 Hz, 1H), 4.45−4.40 (q, J = 8 Hz,
H), 4.39−4.34 (q, J = 8 Hz, 2H), 3.98 (s, 3H), 3.93 (s, 3H), 3.90 (s, 3H), 1.44−1.40 (t,
2
13
1
J = 8 Hz, 3H), 1.39−1.36 (t, J = 8 Hz, 3H); C{ H} NMR (100 MHz, CDCl , ppm) δ
3
167.0, 161.0, 146.1, 142.4, 135.3, 125.8, 119.5, 116.3, 114.3, 105.6, 61.4, 61.2, 61.1,
5
8.2, 31.9, 14.2, 14.0; MS (EI, 70 eV): m/z = 335, 320, 290, 262, 246, 218; HRMS
+
(ESI) calcd for C H NO Na [M + Na] m/z 358.1261; found m/z 358.1258.
1
7
21
6
Diethyl 5,6-dimethoxy-1-methyl-1H-indole-2,3-dicarboxylate (3qb): yellow solid,
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o
−1
35% yield (12 mg); mp 113-115 C; IR (KBr, cm ) 2927, 2856, 1730, 1699, 1533,
1
1
486, 1309, 1238, 1165, 1101, 1015, 951, 856, 783; H NMR (400 MHz, CDCl , ppm)
3
δ 7.55 (s, 1H), 6.77 (s, 1H), 4.47−4.42 (q, J = 8 Hz, 2H), 4.40−4.35 (q, J = 8 Hz, 2H),
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3.97 (s, 3H), 3.97 (s, 3H), 3.83 (s, 3H), 1.44−1.42 (t, J = 8 Hz, 3H), 1.40−1.38 (t, J =
1
8
Hz, 3H); 13C{ H} NMR (100 MHz, CDCl , ppm) δ 164.5, 162.7, 149.1, 147.3,
3
131.9, 131.7, 118.8, 108.6, 102.8, 92.5, 61.9, 60.2, 56.2, 56.2, 31.7, 14.4, 14.1; MS
(
EI, 70 eV): m/z = 335, 320, 290, 262, 246, 218; HRMS (ESI) calcd for C H NO
17 22 6
+
[
M + H] m/z 336.1442; found m/z 336.1448.
Diethyl 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1,2-dicarboxylate (3r): yellow
−
1
liquid, 50% yield (15 mg); IR (KBr, cm ) 2980, 2895, 1745, 1701, 1571, 1494, 1378,
1
1218, 1151, 1047, 1021, 938, 861, 794, 754, 671; H NMR (400 MHz, CDCl , ppm) δ
3
7
.86−7.84 (d, J = 8 Hz, 1H), 7.20−7.16 (t, J = 8 Hz, 1H), 7.06 −7.04 (d, J = 8 Hz, 1H),
.49−4.44 (q, J = 8 Hz, 2H), 4.42−4.36 (q, J = 8 Hz, 2H), 4.30−4.28 (t, J = 4 Hz, 2H),
4
1
3
1
3.01−2.98 (t, J = 8 Hz, 2H), 2.27−2.22 (m, 2H), 1.44−1.39 (m, 6H); C{ H} NMR
(
100 MHz, CDCl , ppm) δ 164.5, 162.4, 134.1, 132.1, 124.0, 122.8, 122.8, 121.5,
3
119.8, 109.0, 62.0, 60.2, 43.9, 24.5, 22.7, 14.5, 14.1; MS (EI, 70 eV): m/z = 301, 255,
+
2
28, 200, 183, 155; HRMS (ESI) calcd for C H NO [M + H] m/z 302.1387; found
1
7
20
4
m/z 302.1389.
Diethyl
8-methyl-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1,2-dicarboxylate
−
1
(
3s): yellow liquid, 28% yield (9 mg); IR (KBr, cm ) 2925, 2854, 1705, 1644, 1515,
1
1429, 1379, 1277, 1222, 1121, 1024, 862, 761, 694; H NMR (400 MHz, CDCl , ppm)
3
δ 7.63 (s, 1H), 6.89 (s, 1H), 4.48−4.42 (q, J = 8 Hz, 2H), 4.41−4.36 (q, J = 8 Hz, 2H),
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4.29−4.26 (t, J = 8 Hz, 2H), 2.96−2.93 (t, J = 8 Hz, 2H), 2.45 (s, 3H), 2.25−2.19 (m,
1
2
1
H), 1.44−1.39 (m, 6H); 13C{ H} NMR (100 MHz, CDCl , ppm) δ 164.6, 162.4,
3
32.6, 132.4, 131.7, 123.4, 122.5, 119.0, 108.5, 61.9, 60.1, 43.9, 24.4, 22.9, 21.9, 14.5,
0
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
14.1; MS (EI, 70 eV): m/z = 315, 269, 242, 214, 197, 169; HRMS (ESI) calcd for
+
C H NO Na [M + Na] m/z 338.1363; found m/z 338.1369.
1
8
21
4
Diethyl 5-methyl-5H-[1,3]dioxolo[4,5-f]indole-6,7-dicarboxylate (3t): yellow
−
1
liquid, 65% yield (21 mg); IR (KBr, cm ) 2927, 2856, 1701, 1523, 1473, 1407, 1309,
1
1
231, 1182, 1081, 1037, 941, 859, 782, 721; H NMR (400 MHz, CDCl , ppm) δ 7.47
3
(s, 1H), 6.78 (s, 1H), 6.00 (s, 2H), 4.47−4.41 (q, J = 8 Hz, 2H), 4.39−4.34 (q, J = 8 Hz,
1
3
1
2
H), 3.78 (s, 3H), 1.43−1.37 (m, 6H); C{ H} NMR (100 MHz, CDCl , ppm) δ 164.3,
3
162.5, 147.1, 145.3, 132.6, 132.2, 119.9, 109.4, 101.2, 100.4, 90.5, 62.0, 60.3, 31.8,
1
4.4, 14.1; MS (EI, 70 eV): m/z = 319, 274, 246, 219, 172; HRMS (ESI) calcd for
+
C H NO Na [M + Na] m/z 342.0948; found m/z 342.0956.
1
6
17
6
Diethyl 1-methyl-1H-pyrrolo[3,2-b]pyridine-2,3-dicarboxylate (3u): yellow liquid,
−
1
3
6% yield (10 mg); IR (KBr, cm ) 2974, 2922, 2852, 1735, 1631, 1523, 1460, 1383,
1
1301, 1093, 1049, 877, 718, 620; H NMR (400 MHz, CDCl , ppm) δ 8.86 (s, 1H),
3
8
.45−8.44 (d, J = 4 Hz, 1H), 8.02−8.01 (d, J = 4 Hz, 1H), 4.55−4.50 (q, J = 8 Hz, 2H),
13
1
4
.42−4.37 (q, J = 8 Hz, 2H), 3.93 (s, 3H), 1.47−1.40 (m, 6H); C{ H} NMR (100
MHz, CDCl , ppm) δ 163.1, 162.1, 141.4, 138.4, 133.8, 130.5, 116.3, 107.1, 100.0,
3
6
2.8, 60.5, 31.7, 14.4, 14.0; MS (EI, 70 eV): m/z = 276, 231, 203, 176, 158; HRMS
+
(ESI) calcd for C H N O [M + H] m/z 277.1183; found m/z 277.1184.
1
4
17
2
4
Diethyl 1-ethyl-1H-indole-2,3-dicarboxylate (3v): yellow liquid, 57% yield (17
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1
2
3
4
5
6
7
8
9
−
1
mg); IR (KBr, cm ) 3065, 2982, 2875, 1754, 1702, 1534, 1427, 1377, 1345, 1259,
1
1
204, 1157, 1107, 1037, 949, 856, 788, 753, 628; H NMR (400 MHz, CDCl , ppm) δ
3
8
.16−8.14 (m, 1H), 7.40−7.38 (m, 1H), 7.36−7.32 (m, 1H), 7.31−7.27 (m, 1H),
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4.51−4.46 (q, J = 8 Hz, 2H), 4.41−4.36 (q, J = 8 Hz, 2H), 4.30−4.25 (q, J = 8 Hz, 2H),
1
3
1
1
.45−1.39 (m, 9H); C{ H} NMR (100 MHz, CDCl , ppm) δ 164.2, 163.0, 135.6,
3
134.7, 125.6, 124.2, 122.5, 122.5, 110.2, 107.7, 62.3, 60.2, 40.2, 15.5, 14.5, 14.1; MS
(
EI, 70 eV): m/z = 289, 244, 214, 170, 143, 114; HRMS (ESI) calcd for C H NO
16 20 4
+
[
M + H] m/z 290.1387; found m/z 290.1391.
Diethyl 1-isopropyl-1H-indole-2,3-dicarboxylate (3w): yellow liquid, 25% yield (8
−
1
mg); IR (KBr, cm ) 2979, 2927, 2854, 1735, 1703, 1533, 1426, 1373, 1349, 1203,
1
1107, 1077, 1019, 864, 790, 753; H NMR (400 MHz, CDCl , ppm) δ 8.21−8.18 (m,
3
1
H), 7.54−7.52 (m, 1H), 7.32−7.27 (m, 2H), 4.73−4.66 (m, 1H), 4.52−4.46 (q, J = 8
Hz, 2H), 4.40−4.34 (q, J = 8 Hz, 2H), 1.67 (s, 3H), 1.65 (s, 3H), 1.45−1.38 (m, 6H);
1
3
1
C{ H} NMR (100 MHz, CDCl , ppm) δ 166.6, 164.1, 164.0, 136.0, 134.7, 126.2,
3
1
23.5, 122.6, 122.2, 111.9, 62.4, 60.0, 50.2, 21.6, 14.4, 14.0; MS (EI, 70 eV): m/z =
+
303, 258, 228, 211, 188, 170; HRMS (ESI) calcd for C H NO [M + H] m/z
1
7
22
4
3
04.1543; found m/z 304.1543.
Diethyl 1-ethyl-4-methyl-1H-indole-2,3-dicarboxylate (3xa): yellow liquid, 30%
−
1
yield (9 mg); IR (KBr, cm ) 2980, 2923, 2870, 1713, 1616, 1528, 1467, 1374, 1278,
1
6
1
205, 1158, 1057, 941, 862, 776, 747, 610; H NMR (400 MHz, d -DMSO, ppm) δ
7.52−7.50 (d, J = 8 Hz, 1H), 7.30−7.27 (m, 1H), 7.00−6.98 (d, J = 8 Hz, 1H),
.53−4.48 (q, J = 8 Hz, 2H), 4.36−4.28 (m, 4H), 2.44 (s, 3H), 1.33−1.28 (m, 9H);
4
2
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