Copper-catalyzed aerobic oxidative dicarbonylation of indoles utilizing α-carbonyl aldehydes

Article abstract of DOI:10.1016/j.tet.2015.07.004

An efficient and practical protocol for copper-catalyzed aerobic oxidative dicarbonylation of indoles using α-carbonyl aldehydes to construct C-3 indole-substituted 1,2-diketones is developed. Various C-3 indole-substituted 1,2-diketones were observed in good to excellent yields under mild reaction conditions. This transformation used air as an ideal oxidant and produced water as the only by-product.

Full text of DOI:10.1016/j.tet.2015.07.004

Accepted Manuscript
Copper-Catalyzed Aerobic Oxidative Dicarbonylation of Indoles Utilizing α-Carbonyl
Aldehydes
Jin-Ming Yang, Zhong-Jian Cai, Qing-Dong Wang, Dong Fang, Shun-Jun Ji
PII:
S0040-4020(15)01010-8
10.1016/j.tet.2015.07.004
TET 26949
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 13 April 2015
Revised Date: 29 June 2015
Accepted Date: 1 July 2015
Please cite this article as: Yang J-M, Cai Z-J, Wang Q-D, Fang D, Ji S-J, Copper-Catalyzed Aerobic
Oxidative Dicarbonylation of Indoles Utilizing α-Carbonyl Aldehydes, Tetrahedron (2015), doi: 10.1016/
j.tet.2015.07.004.
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Copper-Catalyzed Aerobic Oxidative
Leave this area blank for abstract info.
Dicarbonylation of Indoles Utilizing
Carbonyl Aldehydes
α-
a,
b
a
a
b,
Jin-Ming Yang, * Zhong-Jian Cai, Qing-Dong Wang, Dong Fang, and Shun-Jun Ji *
a
School of Pharmacy, Yancheng Teachers University, Yancheng 224051, P. R. China
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry , Chemical Engineering and
b
Materials Science, SoochowUniversity, Suzhou 215123, P. R. China

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Copper-Catalyzed Aerobic Oxidative Dicarbonylation of Indoles Utilizing
Carbonyl Aldehydes
α-
a,*
b
a
a
b,
Jin-Ming Yang, Zhong-Jian Cai, Qing-Dong Wang, Dong Fang, and Shun-Jun Ji *
a
School of Pharmacy, Yancheng Teachers University, Yancheng 224051, P. R. China
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry , Chemical Engineering and Materials Science, SoochowUniversity, Suzhou
b
2
15123, P. R. China
ARTICLE INFO
ABSTRACT
Article history:
Received
An efficient and practical protocol for copper-catalyzed aerobic oxidative dicarbonylation of
indoles using -carbonyl aldehydes to construct C-3 indole-substituted 1,2-diketones is
α
Received in revised form
Accepted
Available online
developed. Various C-3 indole-substituted 1,2-diketones were observed in good to excellent
yields under mild reaction conditions. This transformation used air as an ideal oxidant and
produced water as the only by-product.
Keywords:
2
015 Elsevier Ltd. All rights reserved.
Copper-catalyzed
Aerobic oxidative dicarbonylation
Indoles
1
,2-diketones
1
. Introduction
catalyzed aerobic oxidative esterification reaction of 1,3-diones
to construct -ketoesters by C-C bond cleavage and oxidative C-
H bond functionalization (Scheme 1, eq. 3). Moreover, they
explored a more efficient and practical strategy for construction
α
9
Indole skeleton is widespread in bioactive synthetic and
1
natural products, and occupies a privileged position in
medicinally relevant compounds, hence the direct indole
functionalization reactions are deemed important. Heteroaryl
1
blocks in organic synthesis, which are ideal for the preparation of4
heterocyclic compounds possessing pharmacological properties.
Therefore, exploring new methods for the direct dicarbonylation
2
of
α
-ketoesters through Cu-catalyzed aerobic oxidative
carbonyl aldehydes with alcohols
Scheme 1, eq. 4). This transformation used air as an ideal
3
dehydrogenative coupling of
(
α
-
10
,2-diketones are a class of versatile and powerful building
oxidant and produced water as the only by-product. In light of
our sustained efforts to perfrom Cu-catalyzed aerobic oxidative
11
cross-coupling, we try to explore the possibility of direct dicar-
5
of nonactivated indoles will be much meaningful.
In 2004, Li developed a strategy for constructing functional
molecules by only using two different C-H bonds under oxidative
conditions, which was termed cross-dehydrogenative coupling
6
(
CDC). Over the past decade, copper catalyzed aerobic oxidative
cross dehydrogenative coupling (CDC) has gained impressive
progress, which is regarded as an efficient tool in synthetic
7
methodology. In 2010, Li and co-workers described a novel
copper-catalyzed intramolecular C-H oxidation/acylation
protocol for constructing substituted indoline-2,3-diones with
8
good functional groups tolerance (Scheme 1, eq. 1), as such
reaction only used two C-H bonds under oxidative conditions.
Recently, they reported a novel intermolecular reaction of
amino carbonyls with indoles, which could selectively furnish 2-
1H-indol-3-yl)-2-imino-carbonyls and 2-(1H-indol-3-yl)-2-
oxocar-bonyls via copper catalyzed C-H oxidative/cross-coupling
α-
(
5e
(
Scheme 1, eq. 2). More recently, Jiao’s group reported a Cu-
∗
Corresponding author. Fax: +86-512-65880307; E-mail:
chemyjm@163.com; shunjun@suda.edu.cn
Scheme 1 Copper-catalyzed cross-dehydrogenative coupling.

2
Tetrahedron
bonylation of non-activated indoles using
α
-
c
A
arb
C
on
C
yl
E
a
P
ld
T
eh
E
yd
D
es MA62
NU
%
y
S
ie
C
ld,RIre
P
spectively. However, N-benzoyl indole1d with
T
under mild conditions (Scheme 1, eq. 5). Recently, Wu and co-
workers established a molecular iodine mediated direct oxidative
cross-coupling of indoles with methyl ketones for the
dicarbonylation of indoles. Meanwhile, Vishwakarma, Ahmed
and co-workers developed a novel aminocatalytic cross-coupling
approach to construt C-3 indole-substituted 1,2-diketones via
electron-withdrawing moieties could not transform to the
corresponding product for the decreased electron density. All 4-
methyl-, 5-methyl-, 6-methyl- or 7-methyl-substituted indole
substrates could proceed smoothly to furnish the desired products in
moderate to good yield (3e-3h). Notably, 3i could be isolated in 91%
yield when 5-methoxy-indole was subjected to the reaction with 2a.
Particularly, the reactions of 2-substitued indole such as 2-methyl- or
5f
5g
iminium ions.
2
-phenyl-indole with 2a gave the dicarbonylation products 3k and 3l
2
. Results and discussion
in 83% and 75% yield, respectively, which was hard to be obtained
by other reported methods. However, the reaction of indole with
strong electron-withdrawing substituent group failed to give the
desired product due to the decreased electron density.
Our study was initiated by treating 1-methyl-1H-indole 1a with
phenylglyoxal monohydrate 2a in the presence of pyridine (0.5 equiv)
o
and CuBr (0.1 equiv) at 90 C for 6 hours. To our delight, 1-(1-
methyl-1H-indol-3-yl)-2-phenylethane-1,2-dione 3a was formed in
2% LC-yield (75% isolated yield). Then, we screened different
Table 2
8
catalysts, solvents, reaction temperature, as well as additives (details
see Supporting Information). As presented in Table 1, a range of
copper salts, such as CuCl, CuI, Cu O, CuCl , CuBr and
a
The reaction of various indoles with α-carbonyl aldehyde
2
2
2
O
.
CuBr (10 mol %)
Py (50 mol %)
O
Cu(OAc) H O could promote the reaction smoothly and afford the
O
2
2
R1
+
.H2O
O
desired product in 75% to 81% LC-yields (Table 1, entries 2-7). We
then proceed on to screen the effect of different bases, whereby,
good yields were achieved when using either organic bases (Table 1,
entries 8-12) or inorganic bases (Table 1, entries 12-14). However,
the yields obtained were all lower than using pyridine. When the
reaction were carried out in other different solvents (Table 1, entries
N
R
toluene (2 mL)
90 o
C
R1
N
R
3
1
2a
O
O
O
O
O
O
O
O
1
5-18) such as CH CN and 1,4-dioxane, lower yields were obtained.
N
N
Bn
N
N
3
O
Only trace amount of 3a was detected when DCE and DMSO were
Ph
3d, 0%
3
a, 75%
3b, 65%
3c, 62%
examined instead of toluene.
Table 1
O
N
O
O
O
a
Screening of reaction conditions.
O
O
O
O
N
N
N
3e, 74%
3f, 78%
3g, 80%
3h, 89%
O
N
O
O
O
O
O
O
O
O
Br
b
Entry
Cat.
0.1 equiv)
Base
Solvent
(2 mL)
Yield
(LC-MS)
Ph
N
N
N
(
（
0.5 equiv）
c
3i, 91%
3j, 53%
3k, 83%
3l, 75%
1
2
3
4
5
6
7
8
9
CuBr
CuCl
CuI
Pyridine
Pyridine
Pyridine
Pyridine
Pyridine
Pyridine
Pyridine
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
82 (75)
81
81
75
76
76
75
67
79
72
78
75
73
75
36
20
Trace
Trace
Cu
CuCl
CuBr
2
O
O
O
CN
2
O
O
O2N
2
.
N
N
Cu(OAc)
2
H
2
O
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
Et
3
N
3
m, 0%
3n, 0%
DABCO
Pyrrolidine
Piperidine
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
a
Reaction conditions: 1 (0.5 mmol), 2a (0.5 mmol), CuBr (0.05 mmol),
Pyridine (0.25 mmol), toluene (2 mL) at 90 °C, 6 h.
Et
Na
2
NH
CO
2
3
Next, various -carbonyl aldehydes were applied to the reaction
α
NaHCO
3
with 1a under the optimal reaction conditions and the results were
listed in Table 3. The para-position substituted with methyl,
methoxy, isopropyl or t-butyl gave the desired products 4a-d in
Pyridine
Pyridine
Pyridine
Pyridine
CH
3
CN
1,4-dioxane
DCE
DMSO
moderate yields (70% to 75% yields). Moreover, halo-substituted α-
a
Reaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), cat. (0.05 mmol),
carbonyl aldehydes were also tolerant in this transformation,
affording halo-substituted products (4e-i) in moderate to good yields.
The structure of 4g was also further confirmed by X-ray
b
Pyridine (0.25 mmol), solvent (2 mL) at 90 °C. The yields were determined
c
by LC analysis using biphenyl as the internal standard. Isolated yields.
12
crystallography (Details see supporting information). Substituents
at the meta and ortho position of the aromatic ring reduced the yields
for the steric effect. It is noteworthy that naphthyl substituted and
With the optimized conditions in hand, the substrate scope was
o
explored at 90 C for 6 h under atmospheric air using 10 mol% of
CuBr as the promoter, pyridine as the base, and toluene (2 mL) as the
solvent. As presented in Table 2, A range of indoles could be
converted to the corresponding indoleyl 1,2-diketones smoothly. The
dicarbonylation of indoles with different N-protective groups could
react smoothly to afford the desired products 3b and 3c in 65% and
heteroaryl substituted
generating 4j, 4k and 4l in 68%, 75% and 82% yield, respectively.
Meanwhile, -carbonyl aldehydes carbonyl aldehydes with electron-
deficient groups (trifluoromethyl group) also worked well to afford
m in 77% yield. However, strong electron-withdrawing substituted
α-carbonyl aldehydes survived well,
α
4

1a
2a
3a, 61%
CuBr (10 mol %)
Py (50 mol %)
Ar
O
O
O
+
.H2O
O
(8)
N
tol. (2 mL)
9
0 o
C
N
3
1
a
2a
3a, 0%
α
-carbonyl aldehydes carbonyl aldehyde led to t
A
he
C
de
C
si
E
red
P
p
TED
ct MANUSCRIPT
ro
du
4
n in trace yield.
Scheme 2 Some control experiments.
We then carried out some control reactions so as to understand
the mechanim of this transformation (Scheme 2). No desired product
a was formed when the reaction was proceeded in the absence of
1
0
Based on our above results and the reported works, a plausible
reaction mechanism for the Cu-catalyzed dicarbonylation reaction is
presented in Scheme 3. Indole 1a react with 2,2-dihydroxy-1-
phenylethanone 2a′ generated from 2-oxo-2-phenylacetaldehyde
hydrate to give the benzoin intermediate 5 via a copper catalyzed
3
CuBr (Scheme 2, eq. 6). The reaction also proceeded and gave the
desired product in 61% isolated yield under the modified conditions
without pyridine (Scheme 2, eq. 7). These experiments indicate that
copper salt is essential for the reaction and pyridine is as an additive
to increase the yield. Furthermore, the reaction in the atmosphere of
Ar was also investigated, which failed to give 3a (Scheme 2, eq. 8).
This result indicated that air is an important oxidant for the reaction
to work.
13
Friedel-Crafts type reaction and followed by a copper-catalyzed
aerobic oxidation of the benzoin intermediate 5 to deliver the final
14
product 3a.
Table 3
a
The reaction of indole with various ɑ-carbonyl aldehydes
Scheme 3 A plausible mechanism.
3
. Conclusion
In conclusion, we have developed a Cu-catalyzed aerobic
oxidative dicarbonylation of indoles and α-carbonyl aldehydes under
mild conditions. The reaction can serve as an efficient and practical
protocol for the synthesis of various indole-substituted 1,2-diketones
in moderate to excellent yield with a broad substrate scopes. This
transformation used air as an ideal oxidant and produce water as the
only by-product, which is environmentally friendly. Further
investigations to understand the mechanism of this reaction and their
applications in other organic reactions are ongoing in our laboratory.
4
4
. Experimental Section
.1. General
Melting points were recorded on an Electrothermal digital
melting point apparatus and were uncorrected. IR spectra were
1
recorded on a Varian FT-1000 spectrophotometer. H NMR and
1
3
1
C NMR spectra were recorded on a BRUKER 400 MHz ( H
13
NMR) and 100 MHz ( C NMR) spectrumeter using CDCl or
3
DMSO-d6 as solvent and TMS as internal standard. High
resolution mass spectra were obtained using BRUKER
micrOTOF-Q III instrument with ESI source.
4
.2. Typical procedure for the construction of 3a:
The substrate 1-methyl-1H-indole (1a, 0.5 mmol, 0.0655 g),
a
Reaction conditions: 1a (0.5 mmol), 2 (0.5 mmol), CuBr (0.05 mmol),
phenylglyoxal monohydrate (2a, 0.5 mmol, 0.0760 g), CuBr
0.05 mmol, 0.0072 g, 10 mol%), and Pyridine (0.25 mmol,
.0198 g) were added to a 10 mL Schlenk tube, followed by
Pyridine (0.25 mmol), toluene (2 mL) at 90 °C, 6 h.
(
0
addition of Toluene (2.0 mL). The mixture was stirred at 90 ℃ as
monitored by TLC. The solution was then quenched by H O and
2
extracted with EtOAc, the combined organic layers were dried
over Na SO , filtered, and evaporated under vaccum. The residue
2
4
was purified by column chromatography on silica gel (eluent:
light petroleum ether : ethyl acetate, V : V = 5 : 1) to afford the
desired product 1-(1-methyl-1H-indol-3-yl)-2-phenylethane-1,2-
dione 3a.
4
.2.1.
1-(1-methyl-1H-indol-3-yl)-2-phenylethane-1,2-dione
o
(3a): Yellow Solid, mp: 92-93 C; IR (neat, ν, cm-1): 1674, 1618,
-
1
1
1
1
1
523, 1446cm ; H NMR (400 MHz, CDCl ) 8.53 – 8.43 (m,
H), 8.09 (d, J = 7.5 Hz, 2H), 7.77 (s, 1H), 7.61 (t, J = 7.4 Hz,
H), 7.48 (t, J = 7.7 Hz, 2H), 7.40 – 7.33 (m, 3H), 3.77 (s, 3H);
3

413
Tetrahedron
C NMR (100 MHz, CDCl ) δ 193.34, 187.2
A
0,
C
13
C
9.
E
15
P
, 1
T
37
E
.25, MA13
D
NU
3.79
S
, 1
C
33
R
.0
I
3
P
, 129.82, 128.26, 126.98, 126.55, 123.21, 121.52,
T
3
1
1
33.85, 132.98, 129.82, 128.29, 125.84, 123.75, 123.01, 122.11,
12.33, 109.62, 33.28; HRMS (ESI) m/z: Found: 286.0838.
120.19, 111.82, 37.52, 18.98; HRMS (ESI) m/z: Found:
+
300.0992. Calcd for C H NO : (M+Na) 300.0995.
18
15
2
+
Calcd for C H NO : (M+Na) 286.0838.
17
13
2
4
.2.8. 1-(5-methoxy-1-methyl-1H-indol-3-yl)-2-phenyle-thane-
o
4
.2.2.
1-(1-benzyl-1H-indol-3-yl)-2-phenylethane-1,2-dione
1,2-dione (3i): Yellow Solid, mp: 147-148 C; IR (neat, ν, cm-1):
o
-1 1
(3b): Yellow Solid, mp: 79-80 C; IR (neat, ν, cm-1): 1667, 1616,
1672, 1616, 1580, 1449cm ; H NMR (400 MHz, CDCl ) δ 8.15
(d, J = 7.4 Hz, 2H), 8.02 (d, J = 1.8 Hz, 1H), 7.77 (s, 1H), 7.67 (t,
J = 7.4 Hz, 1H), 7.54 (t, J = 7.7 Hz, 2H), 7.30 (d, J = 8.9 Hz, 1H),
7.04 (dd, J = 8.9, 2.3 Hz, 1H), 3.98 (s, 3H), 3.82 (s, 3H);
NMR (100 MHz, CDCl ) δ 193.34, 187.04, 156.66, 138.94,
3
-
1 1
1
595, 1577, 1517cm ; H NMR (400 MHz, CDCl ) δ 8.38 (d, J
3
=
7
7.8 Hz, 1H), 7.98 (d, J = 7.3 Hz, 2H), 7.78 (s, 1H), 7.48 (t, J =
.4 Hz, 1H), 7.34 (t, J = 7.7 Hz, 2H), 7.24 (ddd, J = 8.0, 6.0, 2.2
Hz, 1H), 7.16 (dd, J = 9.9, 4.0 Hz, 5H), 7.02 – 6.98 (m, 2H), 5.16
1
3
C
3
13
(s, 2H); C NMR (100 MHz, CDCl ) δ 193.12, 187.25, 138.53,
133.79, 133.04, 132.12, 129.81, 128.26, 126.82, 114.05, 112.07,
3
1
1
36.79, 134.72, 133.88, 132.97, 129.91, 128.62, 128.31, 127.89,
26.57, 126.19, 123.89, 123.14, 122.29, 112.85, 110.29, 50.68;
110.44, 103.46, 55.37, 33.46; HRMS (ESI) m/z: Found:
+
316.0948. Calcd for C H NO : (M+Na) 316.0944.
18
15
3
HRMS (ESI) m/z: Found: 362.1150. Calcd for C H NO :
23
17
2
+
4.2.9. 1-(5-bromo-1-methyl-1H-indol-3-yl)-2-phenyle-thane-
o
(M+Na) 362.1151.
1
,2-dione (3j): Yellow Solid, mp: 192-193 C; IR (neat, ν, cm-1):
-1 1
4
.2.3. 1-(1-allyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (3c):
1659, 1636, 1595, 1579, 1450cm ; H NMR (400 MHz, DMSO-
d6) δδ 8.38 (s, 1H), 8.31 (s, 1H), 7.98 (d, J = 7.5 Hz, 2H), 7.76 (t,
J = 7.4 Hz, 1H), 7.62 (dd, J = 15.4, 8.1 Hz, 3H), 7.54 (dd, J = 8.7,
o
Yellow Solid, mp: 66-67 C; IR (neat, ν, cm-1): 1670, 1611,
1
-
1 1
577, 1521, 1450cm ; H NMR (400 MHz, CDCl ) δ 8.39 (d, J
3
13
=
9.6 Hz, 1H), 8.06 – 7.97 (m, 2H), 7.74 (s, 1H), 7.51 (t, J = 6.8
1.4 Hz, 1H), 3.88 (s, 3H); C NMR (100 MHz, DMSO-d ) δ
6
Hz, 1H), 7.38 (t, J = 7.7 Hz, 2H), 7.30 – 7.22 (m, 3H), 5.86 (ddd,
J = 15.9, 10.7, 5.6 Hz, 1H), 5.13 (dd, J = 39.8, 13.7 Hz, 2H), 4.62
193.55, 187.78, 142.10, 136.53, 134.84, 132.67, 129.78, 129.16,
127.12, 126.45, 123.39, 116.10, 113.55, 110.75, 33.63; HRMS
13
+
(
d, J = 5.6 Hz, 2H); C NMR (100 MHz, CDCl ) δ 193.20,
(ESI) m/z: Found: 363.9946. Calcd for C H BrNO : (M+Na)
3
17 12
2
1
1
1
87.25, 138.13, 136.65, 133.86, 132.96, 130.97, 129.96, 129.86,
29.62, 128.29, 127.96, 126.05, 123.75, 123.06, 122.25, 118.81,
363.9944.
4
.2.10.
1-(1,2-dimethyl-1H-indol-3-yl)-2-phenylethane-1,2-
o
12.67, 110.08, 49.25, 0.60; HRMS (ESI) m/z: Found: 312.0995;
+
dione (3k): Yellow Solid, mp: 147-148 C; IR (neat, ν, cm-1):
Calcd for C H NO : (M+Na) 312.0995.
-1 1
19
15
2
1
670, 1597, 1578, 1510, 1415cm ; H NMR (400 MHz, CDCl )
3
4
.2.4.
1-(1,4-dimethyl-1H-indol-3-yl)-2-phenylethane-1,2-
δ 8.13 (d, J = 7.4 Hz, 2H), 7.98 (d, J = 7.4 Hz, 1H), 7.70 (t, J =
o
dione (3e): Yellow Solid, mp: 102-103 C; IR (neat, ν, cm-1):
1
7.4 Hz, 1H), 7.57 (t, J = 7.7 Hz, 2H), 7.39 – 7.27 (m, 3H), 3.73 (s,
-
1
1
13
669, 1632, 1575, 1495, 1451cm ; H NMR (400 MHz, CDCl )
3H), 2.70 (s, 3H); C NMR (100 MHz, CDCl ) δ 195.01, 189.57,
3
3
δ 8.11 (d, J = 7.3 Hz, 2H), 7.75 (s, 1H), 7.67 (t, J = 7.4 Hz, 1H),
147.18, 136.57, 133.97, 132.88, 129.56, 128.52, 125.63, 122.59,
7
2
1
1
.54 (t, J = 7.7 Hz, 2H), 7.38 – 7.30 (m, 1H), 7.22 (t, J = 7.5 Hz,
122.56, 120.30, 110.07, 109.21, 29.33, 12.27; HRMS (ESI) m/z:
13
+
H), 3.81 (s, 3H), 3.08 (s, 3H); C NMR (100 MHz, CDCl ) δ
Found: 300.0993. Calcd for C H NO : (M+Na) 300.0995.
3
18 15
2
94.56, 187.38, 141.03, 138.31, 133.78, 133.48, 133.16, 129.69,
28.33, 124.81, 124.65, 124.08, 113.64, 107.00, 33.41, 22.79;
4
1
.2.11. 1-(1-methyl-2-phenyl-1H-indol-3-yl)-2-phenylethane-
o
,2-dione (3l): Yellow Solid, mp: 119-120 C; IR (neat, ν, cm-1):
HRMS (ESI) m/z: Found: 300.0991. Calcd for C H NO :
-1 1
18
15
2
+
1673, 1610, 1577, 1464, 1435cm ; H NMR (400 MHz, CDCl )
3
(M+Na) 300.0995.
δ 8.62 (d, J = 4.5 Hz, 1H), 7.65 (d, J = 7.6 Hz, 2H), 7.54 (t, J =
4
.2.5.
1-(1,5-dimethyl-1H-indol-3-yl)-2-phenylethane-1,2-
7.3 Hz, 1H), 7.47 (s, 3H), 7.34 (dd, J = 13.6, 6.3 Hz, 3H), 7.25 –
o
13
dione (3f): Yellow Solid, mp: 87-88 C; IR (neat, ν, cm-1): 1661,
7.08 (m, 4H), 3.57 (s, 3H); C NMR (100 MHz, CDCl ) δ
3
-
1
1
1
1
7
1
1
1
632, 1595, 1448cm ; H NMR (400 MHz, CDCl ) δ 8.20 (s,
H), 8.03 – 7.98 (m, 2H), 7.65 (s, 1H), 7.53 (t, J = 7.4 Hz, 1H),
.40 (t, J = 7.7 Hz, 2H), 7.18 – 7.16 (m, 1H), 7.11 (d, J = 9.7 Hz,
H), 3.70 (s, 3H), 2.44 (s, 3H); C NMR (100 MHz, CDCl ) δ
93.37, 187.14, 139.09, 135.64, 133.78, 133.04, 132.87, 129.83,
28.24, 126.10, 125.24, 121.95, 111.98, 109.20, 33.32, 21.07;
193.37, 190.65, 149.38, 136.72, 133.18, 133.07, 130.58, 129.29,
128.86, 128.54, 127.78, 127.50, 126.03, 123.71, 123.23, 122.19,
112.08, 109.53, 30.54; HRMS (ESI) m/z: Found: 362.1155.
3
13
+
Calcd for C H NO : (M+Na) 362.1151.
3
23 17
2
4
.2.12.
1-(1-methyl-1H-indol-3-yl)-2-(p-tolyl)ethane-1,2-
o
dione (4a): Yellow Solid, mp: 95-96 C; IR (neat, ν, cm-1): 1672,
1613, 1605, 1577, 1463cm ; H NMR (400 MHz, CDCl
HRMS (ESI) m/z: Found: 300.0996. Calcd for C H NO :
-1 1
18
15
2
+
) δ 8.50
3
(M+Na) 300.0995.
–
8.42 (m, 1H), 8.00 (d, J = 8.2 Hz, 2H), 7.77 (s, 1H), 7.40 – 7.35
13
4
.2.6.
1-(1,6-dimethyl-1H-indol-3-yl)-2-phenylethane-1,2-
(m, 3H), 7.28 (d, J = 8.0 Hz, 2H), 3.80 (s, 3H), 2.42 (s, 3H); C
o
dione (3g): Yellow Solid, mp: 120-121 C; IR (neat, ν, cm-1):
1
NMR (100 MHz, CDCl ) δ 193.09, 187.49, 145.01, 139.03,
3
-
1
1
668, 1612, 1594, 1573, 1503, 1450cm ; H NMR (400 MHz,
137.23, 130.50, 129.95, 129.01, 125.87, 123.68, 122.95, 122.17,
CDCl ) δ 8.33 (d, J = 8.1 Hz, 1H), 8.09 (d, J = 7.3 Hz, 2H), 7.71
112.42, 109.53, 33.27, 21.41; HRMS (ESI) m/z: Found:
3
+
(
s, 1H), 7.61 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.21 (d,
300.0992. Calcd for C H NO : (M+Na) 300.0995.
18
15
2
13
J = 8.1 Hz, 1H), 7.15 (s, 1H), 3.75 (s, 3H), 2.52 (s, 3H);
C
4
.2.13.
1-(4-methoxyphenyl)-2-(1-methyl-1H-indol-3-
o
NMR (100 MHz, CDCl ) δ 193.40, 187.12, 138.78, 137.68,
3
yl)ethane-1,2-dione (4b): Yellow Solid, mp: 116-117 C; IR
1
1
3
33.86, 133.79, 133.04, 129.81, 128.26, 124.65, 123.56, 121.74,
-1 1
(
neat, ν, cm-1): 1661, 1599, 1573, 1460cm ; H NMR (400 MHz,
CDCl ) δ 8.46 (d, J = 4.5 Hz, 1H), 8.08 (d, J = 8.6 Hz, 2H), 7.78
s, 1H), 7.36 (s, 3H), 6.95 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H), 3.79
12.34, 109.60, 33.20, 21.42; HRMS (ESI) m/z: Found:
+
3
00.0990. Calcd for C H NO : (M+Na) 300.0995.
18
15
2
(
13
4
.2.7.
1-(1,7-dimethyl-1H-indol-3-yl)-2-phenylethane-1,2-
(s, 3H); C NMR (100 MHz, CDCl ) δ 192.05, 187.71, 164.08,
3
o
dione (3h): Yellow Solid, mp: 129-130 C; IR (neat, ν, cm-1):
1
139.05, 137.21, 132.27, 125.95, 125.90, 123.63, 122.91, 122.14,
-
1 1
665, 1620, 1596, 1450cm ; H NMR (400 MHz, CDCl ) δ 8.41
113.59, 112.46, 109.52, 55.12, 33.25; HRMS (ESI) m/z: Found:
3
+
(
d, J = 7.9 Hz, 1H), 8.14 (d, J = 7.4 Hz, 2H), 7.72 (s, 1H), 7.67 (t,
J = 7.4 Hz, 1H), 7.54 (t, J = 7.7 Hz, 2H), 7.29 (dd, J = 12.8, 5.3
316.0947. Calcd for C H NO : (M+Na) 316.0944.
18
15
3
13
4.2.14.
1-(4-isopropylphenyl)-2-(1-methyl-1H-indol-3-
o
Hz, 1H), 7.11 (d, J = 7.2 Hz, 1H), 4.06 (s, 3H), 2.77 (s, 3H);
C
yl)ethane-1,2-dione (4c): Yellow Solid, mp: 116-117 C; IR
NMR (100 MHz, CDCl ) δ 193.33, 187.08, 140.70, 135.94,
3

5
-
1 1
(
neat, ν, cm-1): 1666, 1631, 1600, 1465cm ; H
A
N
C
M
C
R
E
(4
P
0
T
0 M
E
H
D
z,MA12
N
3.
U
68
S
, 1
C
22
R
.9
I
8
P
,
T
122.24, 111.53, 109.51, 33.38; HRMS (ESI)
+
CDCl ) δ 8.53 (s, 1H), 8.08 (s, 2H), 7.83 (s, 1H), 7.42 (s, 5H),
m/z: Found: 320.0454. Calcd for C H ClO : (M+Na) 320.0449.
3
17 12
2
1
3
3
.86 (s, 3H), 3.03 (s, 1H), 1.33 (s, 6H); C NMR (100 MHz,
4
.2.21.
1-(1-methyl-1H-indol-3-yl)-2-(naphthalen-1-
o
yl)ethane-1,2-dione (4j): Yellow Solid, mp: 102-103 C; IR
neat, ν, cm-1): 1649, 1638, 1525, 1469cm ; H NMR (400
MHz, CDCl ) δ 8.64 (s, 1H), 8.54 (d, J = 6.4 Hz, 1H), 8.17 (dd, J
8.6, 1.4 Hz, 1H), 7.93 (dd, J = 8.4, 3.0 Hz, 2H), 7.88 (d, J = 8.2
CDCl ) δ 193.12, 187.53, 155.65, 139.04, 137.23, 130.85, 130.12,
26.45, 125.88, 123.68, 122.94, 122.18, 112.43, 109.53, 33.98,
3.27, 23.13; HRMS (ESI) m/z: Found: 328.1305. Calcd for
3
1
3
-1
1
(
+
3
C H NO : (M+Na) 328.1308.
20
19
2
=
4
.2.15.
1-(4-(tert-butyl)phenyl)-2-(1-methyl-1H-indol-3-
Hz, 1H), 7.83 (s, 1H), 7.62 (t, J = 7.1 Hz, 1H), 7.54 (t, J = 7.2
Hz, 1H), 7.44 – 7.37 (m, 3H), 3.80 (s, 3H); C NMR (100 MHz,
o
13
yl)ethane-1,2-dione (4d): Yellow Solid, mp: 180-181 C; IR
neat, ν, cm-1): 1669, 1628, 1600, 1522, 1463cm ; H NMR
-
1
1
(
CDCl ) δ 193.40, 187.33, 139.18, 137.28, 135.70, 133.23,
3
(
400 MHz, CDCl ) δ 8.37 (d, J = 4.7 Hz, 1H), 7.93 (d, J = 8.1 Hz,
131.96, 130.25, 129.51, 128.71, 128.30, 127.38, 126.45, 125.93,
3
2
3
1
1
H), 7.67 (s, 1H), 7.40 (d, J = 8.1 Hz, 2H), 7.26 (s, 3H), 3.69 (s,
123.92, 123.77, 123.06, 122.24, 112.54, 109.58, 33.30; HRMS
13
+
H), 1.24 (s, 10H); C NMR (100 MHz, CDCl ) δ 193.11,
(ESI) m/z: Found: 336.0993. Calcd for C H NO : (M+Na)
3
21 15
2
87.49, 157.84, 139.04, 137.23, 130.42, 129.81, 125.89, 125.30,
23.68, 122.94, 122.19, 112.43, 109.53, 34.84, 33.27, 30.56;
336.0995.
4
.2.22.
1-(1-methyl-1H-indol-3-yl)-2-(naphthalen-2-
o
HRMS (ESI) m/z: Found: 342.1463. Calcd for C H NO :
21
21
2
+
yl)ethane-1,2-dione (4k): Yellow Solid, mp: 106-107 C; IR
neat, ν, cm-1): 1637, 1595, 1524, 1468cm ; H NMR (400
(M+Na) 342.1465.
-1 1
(
4
.2.16.
1-(4-fluorophenyl)-2-(1-methyl-1H-indol-3-
MHz, CDCl ) δ 8.00 (s, 1H), δ 8.64 (s, 1H), 8.54 (d, J = 6.8 Hz,
3
o
yl)ethane-1,2-dione (4e): Yellow Solid, mp: 112-113 C; IR
neat, ν, cm-1): 1665, 1611, 1593, 1504cm ; H NMR (400 MHz,
CDCl ) δ 8.46 (s, 1H), 8.14 (s, 2H), 7.82 (s, 1H), 7.38 (s, 3H),
.15 (t, J = 8.0 Hz, 2H), 3.82 (s, 3H); C NMR (100 MHz,
1H), 8.16 (d, J = 8.5 Hz, 1H), 7.97 – 7.90 (m, 2H), 7.88 (d, J =
8.1 Hz, 1H), 7.83 (s, 1H), 7.62 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.4
-
1 1
(
1
3
Hz, 1H), 7.41 (dd, J = 9.5, 2.6 Hz, 3H), 3.80 (s, 3H); C NMR
3
13
7
(100 MHz, CDCl ) δ 193.40, 187.33, 139.18, 137.28, 135.69,
3
CDCl ) δ 191.50, 186.55, 166 (d, J = 255.4), 139.20, 137.24,
133.22, 131.95, 130.25, 129.51, 128.71, 128.30, 127.38, 126.46,
125.93, 123.92, 123.77, 123.06, 122.24, 112.54, 109.58, 33.30;
HRMS (ESI) m/z: Found: 336.0999. Calcd for C H NO :
3
1
1
32.7 (d, J = 9.6), 129.4 (d, J = 2.6) 125.89, 123.81, 123.09,
22.14, 115.5 (d, J = 21.9), 112.26, 109.59, 33.32; HRMS (ESI)
2
1
15
2
+
+
m/z: Found: 304.0747. Calcd for C H FNO : (M+Na)
(M+Na) 336.0995.
17
12
2
3
04.0744.
4
.2.23. 1-(1-methyl-1H-indol-3-yl)-2-(thiophen-2-yl)ethane-
o
4
.2.17.
1-(4-chlorophenyl)-2-(1-methyl-1H-indol-3-
1,2-dione (4l): Yellow Solid, mp: 93-94 C; IR (neat, ν, cm-1):
1642, 1610, 1578, 1520, 1463cm ; H NMR (400 MHz, CDCl )
δ 8.36 (dd, J = 6.0, 1.6 Hz, 1H), 7.97 (d, J = 5.8 Hz, 2H), 7.69 –
o
-1 1
yl)ethane-1,2-dione (4f): Yellow Solid, mp: 157-158 C; IR
3
-
1 1
(neat, ν, cm-1): 1670, 1618, 1583, 1459cm ; H NMR (400 MHz,
CDCl ) δ 8.48 – 8.42 (m, 1H), 8.08 – 8.01 (m, 2H), 7.81 (s, 1H),
7.61 (m, 1H), 7.24 (ddd, J = 10.6, 7.7, 4.3 Hz, 3H), 7.07 – 7.00
3
13
13
7
.49 – 7.42 (m, 2H), 7.42 – 7.35 (m, 3H), 3.81 (s, 3H).;
C
(m, 1H), 3.66 (s, 3H); C NMR (100 MHz, CDCl ) δ 184.11,
3
NMR (100 MHz, CDCl ) δ 191.78, 186.24, 140.36, 139.24,
184.11, 139.92, 138.87, 137.00, 136.25, 136.24, 127.94, 126.41,
3
1
1
37.24, 131.38, 131.22, 128.61, 125.89, 123.84, 123.13, 122.15,
123.67, 123.02, 122.14, 111.52, 109.61, 33.30; HRMS (ESI) m/z:
+
12.21, 109.61, 33.34; HRMS (ESI) m/z: Found: 320.0441.
Found: 292.0401. Calcd for C H NO S: (M+Na) 292.0403.
15
11
2
+
Calcd for C H ClO : (M+Na) 320.0449.
17
12
2
4
.2.24. 1-(1-methyl-1H-indol-3-yl)-2-(4-(trifluoromethyl)-
o
4
.2.18.
1-(4-bromophenyl)-2-(1-methyl-1H-indol-3-
phenyl)ethane-1,2-dione (4m): Yellow Solid, mp: 153-154 C;
IR (neat, ν, cm-1): 1680, 1614, 1579, 1491cm ; H NMR (400
o
-1 1
yl)ethane-1,2-dione (4g): Yellow Solid, mp: 165-166 C; IR
-
1 1
(neat, ν, cm-1): 1662, 1624, 1583, 1467cm ; H NMR (400 MHz,
MHz, CDCl ) δ 8.46 (d, J = 4.0 Hz, 1H), 8.22 (d, J = 8.1 Hz,
3
CDCl ) δ 8.51 – 8.41 (m, 1H), 7.96 (d, J = 8.5 Hz, 2H), 7.81 (s,
2H), 7.86 (s, 1H), 7.75 (d, J = 8.2 Hz, 2H), 7.41 (d, J = 10.0 Hz,
3
13
1
H), 7.62 (d, J = 8.5 Hz, 2H), 7.39 (dd, J = 6.7, 3.3 Hz, 3H), 3.81
3H), 3.84 (s, 3H); C NMR (100 MHz, CDCl ) δ 191.70,
3
13
(s, 3H); C NMR (100 MHz, CDCl ) δ 191.97, 186.16, 139.24,
185.53, 139.34, 137.27, 135.85, 134.7 (q, J = 32.5), 130.17,
125.91, 125.2 (q, J = 3.7), 123.95, 123.24, 123.0 (q, J = 271.3),
122.17, 112.13, 109.64, 33.36; HRMS (ESI) m/z: Found:
3
1
1
3
37.24, 131.79, 131.60, 131.28, 129.25, 125.89, 123.85, 123.14,
22.16, 112.21, 109.60, 33.35; HRMS (ESI) m/z: Found:
+
+
63.9931. Calcd for C H BrNO : (M+Na) 363.9944.
354.0712. Calcd for C H F NO : (M+Na) 354.0712.
17
12
2
18 12
3
2
4
.2.19.
1-(3-fluorophenyl)-2-(1-methyl-1H-indol-3-
o
Acknowledgements
yl)ethane-1,2-dione (4h): Yellow Solid, mp: 121-122 C; IR
neat, ν, cm-1): 1672, 1619, 1523cm ; H NMR (400 MHz,
-
1
1
(
We gratefully acknowledge the Natural Science Foundation of
China (no. 21172162, 21372174), the Ph.D. Programs
Foundation of Ministry of Education of China (2013201130004),
Nature Science Foundation of Jiangsu Province (BK20141257)
Nature Science Foundation of YanCheng Teachers University
CDCl ) δ 8.52 (s, 1H), 7.94 (d, J = 6.8 Hz, 1H), 7.87 (s, 2H), 7.51
3
(
d, J = 5.5 Hz, 1H), 7.44 (s, 3H), 7.38 (d, J = 6.8 Hz, 1H), 3.88
13
(s, 3H); C NMR (100 MHz, CDCl ) δ 191.72, 186.02, 162.3 (d,
3
J = 247), 139.22, 137.26, 135.0 (d, J = 6.5), 130.0 (d, J = 7.5),
1
2
25.9 (d, J = 2.8), 125.85, 123.87, 123.15, 122.18, 120.8 (d, J =
(14YCKL001) PAPD, and Soochow University for financial
1.3), 116.1 (d, J = 22.5), 112.19, 109.60, 33.34; HRMS (ESI)
+
support.
m/z: Found: 304.0745. Calcd for C H FNO : (M+Na)
17
12
2
3
04.0744.
References
4
.2.20.
1-(2-chlorophenyl)-2-(1-methyl-1H-indol-3-
o
yl)ethane-1,2-dione (4i): Yellow Solid, mp: 163-164 C; IR
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-
1
1
(neat, ν, cm-1): 1687, 1611, 1588, 1518cm ; H NMR (400
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3
1
3
13
H); C NMR (100 MHz, CDCl ) δ 193.52, 184.44, 139.10,
3
37.14, 134.85, 132.88, 132.76, 131.37, 129.88, 126.52, 126.36,

6
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8
.
.
Tang, B.-X.; Song, R.-J.; Wu, C.-Y.; Liu, Y.; Zhou, M.-B.; Wei, W.-T.;
Deng, G.-B.; Yin, D.-L.; Li, J.-H. J. Am. Chem. Soc., 2010, 132, 8900.
Zhang, C.; Feng P.; Jiao, N. J. Am. Chem. Soc., 2013, 135, 15257.
9
1
1
0. Zhang, C.; Jiao, N. Org. Chem. Front., 2014, 1, 109.
1. (a) Cai, Z.-J.; Wang, S.-Y.; Ji, S.-J. Org. Lett. 2012, 14, 6068. (b) Cai,
Z.-J.; Wang, S.-Y.; Ji, S.-J. Adv. Synth. Catal. 2013, 355, 2686.
1
1
1
2. Compounds 3g was determined by X-ray crystallography. See the
Supporting Information for full details. CCDC 1041632 (3g) contain the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data
3. (a) Gathergood, N.; Zhuang, W.; Jørgensen, K. A. J. Am. Chem. Soc.
000, 122, 12517. (b) Bigi, F.; Casiraghi, G.; Casnati, G.; Sartori, G.;
_
request/cif.
2
Fava, G. G.; Belicchi, M. F. J. Org. Chem. 1985, 50, 5018. (c) Erker, G.;
van der Zeijden, A. A. H. Angew. Chem., Int. Ed. 1990, 29, 512. (d)
Poulsen, T. B.; Jørgensen, K. A. Chem. Rev. 2008, 108, 2903.
4. (a) Clarke, H. T.; Dreger, E. E. Org. Synth. 1926, 6, 6. (b) Bordner, C.
A. U.S. Patent 2,377,749, June 5, 1945. (c) Gampp, H.; Haspra, D.;
Spieler, W.; Zuberbühler, A. D. Helv. Chim. Acta 1984, 67, 1019. (d)
Singh, G.; Mahajan, D. S. Oxid. Commun. 2005, 28, 555. (e) Allen, S.
E.; Walvoord, R. R.; Padilla-Salinas, R.; Kozlowski, M. C. Chem. Rev.
2
013, 113, 6234.

ACCEPTED MANUSCRIPT
Supporting Information for
Copper-Catalyzed Aerobic Oxidative Dicarbonylation of Indoles
Utilizing -Carbonyl Aldehydes
Jin-Ming Yang,a,* Zhong-Jian Cai, Qing-Dong Wang, Dong Fang, and Shun-Jun Ji *
b
a
a
b,
a
b
School of Pharmacy, Yancheng Teachers University, Yancheng 224051, P. R. China
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry , Chemical Engineering and Materials Science,
SoochowUniversity, Suzhou 215123, P. R. China
E-mail: chemyjm@163.com; shunjun@suda.edu.cn
Table of Contents
Experimental Section ------------------------------------------------------------------S2
Optimization of The Reaction Conditions ---------------------------------------- S3-S4
Characterization Data of Compounds ----------------------------------------
S4-S12
1
13
Copies of H and C NMR Spectra for Compounds ----------------------
S13-S36
S1

ACCEPTED MANUSCRIPT
Experimental Section
General
Melting points were recorded on an Electrothermal digital melting point apparatus and were
1
13
uncorrected. IR spectra were recorded on a Varian FT-1000 spectrophotometer. H NMR and C
1
13
NMR spectra were recorded on a BRUKER 400 MHz ( H NMR) and 100 MHz ( C NMR)
spectrumeter using CDCl or DMSO-d as solvent and TMS as internal standard. High resolution
3
6
mass spectra were obtained using BRUKER micrOTOF-Q III instrument with ESI source.
Typical procedure for the construction of 3a:
The substrate 1-methyl-1H-indole (1a, 0.5 mmol, 0.0655 g), phenylglyoxal monohydrate (2a, 0.5
mmol, 0.0760 g), CuBr (0.05 mmol, 0.0072 g, 10 mol%), and Pyridine (0.25 mmol, 0.0198 g)
were added to a 10 mL Schlenk tube, followed by addition of Toluene (2.0 mL). The mixture was
stirred at 90 ℃ as monitored by TLC. The solution was then quenched by H
2
O and extracted
with EtOAc, the combined organic layers were dried over Na SO , filtered, and evaporated under
2
4
vaccum. The residue was purified by column chromatography on silica gel (eluent: light
petroleum ether : ethyl acetate, V : V = 5 : 1) to afford the desired product
1
-(1-methyl-1H-indol-3-yl)-2-phenylethane-1,2-dione 3a.
S2

ACCEPTED MANUSCRIPT
Table S1: The reactions of 1a and 2a catalyzed by different catalysts .
cat.
base
temp
yield
entry
solvent (mL)
(
equiv)
(equiv)
Py (0.5)
Py (0.5)
Py (0.5)
Py (0.5)
Py (0.5)
Py (0.5)
(℃) (LC-MS)
1
2
3
4
5
6
7
8
CuBr (0.1)
CuCl (0.1)
CuI (0.1)
Tol. (2)
Tol. (2)
Tol. (2)
Tol. (2)
Tol. (2)
Tol. (2)
Tol. (2)
Tol. (2)
90
90
90
90
90
90
90
90
82
81
81
75
76
76
75
75
Cu O (0.1)
2
CuCl (0.1)
2
CuBr (0.1)
2
Cu(OAc)
2
.H
O (0.1)
2
O (0.1) Py (0.5)
CuSO
4
.H
2
Py (0.5)
a
b
Reaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), cat. (0.05 mmol), Pyridine (0.25 mmol), solvent (2 mL) at 90 °C , 6 h. The yields were
determined by LC analysis using biphenyl as the internal standard.
Table S2: The reactions of 1a and 2a catalyzed by different solvents .
cat.
base
temp
yield
entry
solvent (mL)
(
equiv)
(equiv)
(℃) (LC-MS)
1
2
3
4
5
6
7
CuBr (0.1) Py (0.5)
CuBr (0.1) Py (0.5)
CuBr (0.1) Py (0.5)
CuBr (0.1) Py (0.5)
CuBr (0.1) Py (0.5)
Tol. (2)
90
80
80
90
90
90
80
82
36
CH CN (2)
3
CH NO (2)
38
3
2
DMSO (2)
DCE (2)
Trace
Trace
20
CuBr (0.1) Py (0.5) 1,4-dioxane (2)
CuBr (0.1) Py (0.5) EtOH (2)
Trace
a
b
Reaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), cat. (0.05 mmol), Pyridine (0.25 mmol), solvent (2 mL) at 90 °C , 6 h. The yields were
determined by LC analysis using biphenyl as the internal standard.
Table S3: The reactions of 1a and 2a catalyzed by different base .
cat.
base
temp
yield
entry
solvent (mL)
(
equiv)
(equiv)
Py (0.5)
(℃) (LC-MS)
1
2
3
4
5
6
7
8
CuBr (0.1)
CuBr (0.1)
CuBr (0.1)
Tol. (2)
Tol. (2)
Tol. (2)
Tol. (2)
Tol. (2)
Tol. (2)
Tol. (2)
Tol. (2)
90
90
90
90
90
90
90
90
82
67
79
72
78
75
73
75
Et N (0.5)
3
DABCO (0.5)
CuBr (0.1) Pyrrolidine (0.5)
CuBr (0.1) Piperidine (0.5)
Et NH (0.5)
CuBr (0.1)
CuBr (0.1)
CuBr (0.1)
2
Na CO (0.5)
2
3
NaHCO (0.5)
3
a
b
Reaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), cat. (0.05 mmol), base (0.25 mmol), tol. (2 mL) at 90 °C , 6 h. The yields were determined
by LC analysis using biphenyl as the internal standard.
S3

ACCEPTED MANUSCRIPT
Table S6: The reactions of 1a and 2a with different time.
cat.
base
Time
temp
yield
entry
solvent (mL)
(
equiv)
(equiv)
(h)
4
(℃) (LC-MS)
1
2
3
4
5
CuBr (0.1) Py (0.5)
CuBr (0.1) Py (0.5)
CuBr (0.1) Py (0.5)
CuBr (0.1) Py (0.5)
CuBr (0.1) Py (0.5)
Tol. (2)
Tol. (2)
Tol. (2)
Tol. (2)
Tol. (2)
90
90
90
90
90
74
74
82
76
5
6
7
8
76
a
b
Reaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), cat. (0.05 mmol), base (0.25 mmol), tol. (2 mL) at 90 °C. The yields were determined by LC
analysis using biphenyl as the internal standard.
S4

ACCEPTED MANUSCRIPT
Characterization Data of Compounds:
1
-(1-methyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (3a)
o
Yellow Solid, mp: 92-93 C;
-1
IR (neat, ν, cm-1): 1674, 1618, 1523, 1446cm ;
1H NMR (400 MHz, CDCl
) 8.53 – 8.43 (m, 1H), 8.09 (d, J = 7.5 Hz, 2H),
.77 (s, 1H), 7.61 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.40 – 7.33 (m,
3
7
3
H), 3.77 (s, 3H);
1
3
C NMR (100 MHz, CDCl ) δ 193.34, 187.20, 139.15, 137.25, 133.85,
3
1
32.98, 129.82, 128.29, 125.84, 123.75, 123.01, 122.11, 112.33, 109.62,
3
3.28;
+
HRMS (ESI) m/z: Found: 286.0838. Calcd for C17
H13NO
2
: (M+Na) 286.0838.
1
-(1-benzyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (3b)
o
Yellow Solid, mp: 79-80 C;
IR (neat, ν, cm-1): 1667, 1616, 1595, 1577, 1517cm ;
1H NMR (400 MHz, CDCl
) δ 8.38 (d, J = 7.8 Hz, 1H), 7.98 (d, J = 7.3 Hz,
H), 7.78 (s, 1H), 7.48 (t, J = 7.4 Hz, 1H), 7.34 (t, J = 7.7 Hz, 2H), 7.24 (ddd,
J = 8.0, 6.0, 2.2 Hz, 1H), 7.16 (dd, J = 9.9, 4.0 Hz, 5H), 7.02 – 6.98 (m, 2H),
-1
3
2
5
.16 (s, 2H);
1
3
C NMR (100 MHz, CDCl ) δ 193.12, 187.25, 138.53, 136.79, 134.72,
3
1
1
33.88, 132.97, 129.91, 128.62, 128.31, 127.89, 126.57, 126.19, 123.89, 123.14, 122.29, 112.85,
10.29, 50.68;
+
HRMS (ESI) m/z: Found: 362.1150. Calcd for C23
H17NO
2
: (M+Na) 362.1151.
1
-(1-allyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (3c)
o
Yellow Solid, mp: 66-67 C;
IR (neat, ν, cm-1): 1670, 1611, 1577, 1521, 1450cm ;
1H NMR (400 MHz, CDCl
) δ 8.39 (d, J = 9.6 Hz, 1H), 8.06 – 7.97 (m, 2H),
.74 (s, 1H), 7.51 (t, J = 6.8 Hz, 1H), 7.38 (t, J = 7.7 Hz, 2H), 7.30 – 7.22 (m,
-1
3
7
3
4
H), 5.86 (ddd, J = 15.9, 10.7, 5.6 Hz, 1H), 5.13 (dd, J = 39.8, 13.7 Hz, 2H),
.62 (d, J = 5.6 Hz, 2H);
1
3
C NMR (100 MHz, CDCl ) δ 193.20, 187.25, 138.13, 136.65, 133.86,
3
1
1
32.96, 130.97, 129.96, 129.86, 129.62, 128.29, 127.96, 126.05, 123.75,
23.06, 122.25, 118.81, 112.67, 110.08, 49.25, 0.60;
+
HRMS (ESI) m/z: Found: 312.0995; Calcd for C19
H15NO
2
: (M+Na) 312.0995.
S5

ACCEPTED MANUSCRIPT
1
-(1,4-dimethyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (3e)
o
Yellow Solid, mp: 102-103 C;
-1
IR (neat, ν, cm-1): 1669, 1632, 1575, 1495, 1451cm ;
1H NMR (400 MHz, CDCl
) δ 8.11 (d, J = 7.3 Hz, 2H), 7.75 (s, 1H), 7.67 (t,
3
J = 7.4 Hz, 1H), 7.54 (t, J = 7.7 Hz, 2H), 7.38 – 7.30 (m, 1H), 7.22 (t, J = 7.5
Hz, 2H), 3.81 (s, 3H), 3.08 (s, 3H);
13C NMR (100 MHz, CDCl
1
) δ 194.56, 187.38, 141.03, 138.31, 133.78,
33.48, 133.16, 129.69, 128.33, 124.81, 124.65, 124.08, 113.64, 107.00,
3
3
3.41, 22.79;
+
HRMS (ESI) m/z: Found: 300.0991. Calcd for C18
H15NO
2
: (M+Na) 300.0995.
1
-(1,5-dimethyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (3f)
o
Yellow Solid, mp: 87-88 C;
IR (neat, ν, cm-1): 1661, 1632, 1595, 1448cm ;
1H NMR (400 MHz, CDCl
) δ 8.20 (s, 1H), 8.03 – 7.98 (m, 2H), 7.65 (s,
H), 7.53 (t, J = 7.4 Hz, 1H), 7.40 (t, J = 7.7 Hz, 2H), 7.18 – 7.16 (m, 1H),
.11 (d, J = 9.7 Hz, 1H), 3.70 (s, 3H), 2.44 (s, 3H);
-1
3
1
7
1
3C NMR (100 MHz, CDCl
3
) δ 193.37, 187.14, 139.09, 135.64, 133.78,
1
33.04, 132.87, 129.83, 128.24, 126.10, 125.24, 121.95, 111.98, 109.20,
3
3.32, 21.07;
+
HRMS (ESI) m/z: Found: 300.0996. Calcd for C18
H
15NO : (M+Na) 300.0995.
2
1
-(1,6-dimethyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (3g)
o
Yellow Solid, mp: 120-121 C;
-1
IR (neat, ν, cm-1): 1668, 1612, 1594, 1573, 1503, 1450cm ;
1H NMR (400 MHz, CDCl
) δ 8.33 (d, J = 8.1 Hz, 1H), 8.09 (d, J = 7.3 Hz,
H), 7.71 (s, 1H), 7.61 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.21 (d,
J = 8.1 Hz, 1H), 7.15 (s, 1H), 3.75 (s, 3H), 2.52 (s, 3H);
3
2
13C NMR (100 MHz, CDCl
) δ 193.40, 187.12, 138.78, 137.68, 133.86,
3
1
33.79, 133.04, 129.81, 128.26, 124.65, 123.56, 121.74, 112.34, 109.60,
3
3.20, 21.42;
+
HRMS (ESI) m/z: Found: 300.0990. Calcd for C18
H
15NO : (M+Na) 300.0995.
2
1
-(1,7-dimethyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (3h)
o
Yellow Solid, mp: 129-130 C;
-1
IR (neat, ν, cm-1): 1665, 1620, 1596, 1450cm ;
1H NMR (400 MHz, CDCl
) δ 8.41 (d, J = 7.9 Hz, 1H), 8.14 (d, J = 7.4 Hz,
H), 7.72 (s, 1H), 7.67 (t, J = 7.4 Hz, 1H), 7.54 (t, J = 7.7 Hz, 2H), 7.29 (dd, J
3
2
=
12.8, 5.3 Hz, 1H), 7.11 (d, J = 7.2 Hz, 1H), 4.06 (s, 3H), 2.77 (s, 3H);
) δ 193.33, 187.08, 140.70, 135.94, 133.79,
1
3C NMR (100 MHz, CDCl
3
S6

ACCEPTED MANUSCRIPT
1
33.03, 129.82, 128.26, 126.98, 126.55, 123.21, 121.52, 120.19, 111.82, 37.52, 18.98;
+
HRMS (ESI) m/z: Found: 300.0992. Calcd for C18
H15NO
2
: (M+Na) 300.0995.
1
-(5-methoxy-1-methyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (3i)
o
Yellow Solid, mp: 147-148 C;
IR (neat, ν, cm-1): 1672, 1616, 1580, 1449cm ;
1H NMR (400 MHz, CDCl
) δ 8.15 (d, J = 7.4 Hz, 2H), 8.02 (d, J = 1.8
Hz, 1H), 7.77 (s, 1H), 7.67 (t, J = 7.4 Hz, 1H), 7.54 (t, J = 7.7 Hz, 2H),
.30 (d, J = 8.9 Hz, 1H), 7.04 (dd, J = 8.9, 2.3 Hz, 1H), 3.98 (s, 3H), 3.82
-1
3
7
(
s, 3H);
1
3C NMR (100 MHz, CDCl
3
) δ 193.34, 187.04, 156.66, 138.94, 133.79,
1
33.04, 132.12, 129.81, 128.26, 126.82, 114.05, 112.07, 110.44, 103.46, 55.37, 33.46;
+
HRMS (ESI) m/z: Found: 316.0948. Calcd for C18
H15NO
3
: (M+Na) 316.0944.
1
-(5-bromo-1-methyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (3j)
o
Yellow Solid, mp: 192-193 C;
IR (neat, ν, cm-1): 1659, 1636, 1595, 1579, 1450cm ;
1H NMR (400 MHz, DMSO-d
) δδ 8.38 (s, 1H), 8.31 (s, 1H), 7.98 (d, J =
.5 Hz, 2H), 7.76 (t, J = 7.4 Hz, 1H), 7.62 (dd, J = 15.4, 8.1 Hz, 3H), 7.54
dd, J = 8.7, 1.4 Hz, 1H), 3.88 (s, 3H);
-1
6
7
(
1
3C NMR (100 MHz, DMSO-d
) δ 193.55, 187.78, 142.10, 136.53,
6
1
34.84, 132.67, 129.78, 129.16, 127.12, 126.45, 123.39, 116.10, 113.55,
1
10.75, 33.63;
+
HRMS (ESI) m/z: Found: 363.9946. Calcd for C17
H
12BrNO : (M+Na) 363.9944.
2
1
-(1,2-dimethyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (3k)
o
Yellow Solid, mp: 147-148 C;
-1
IR (neat, ν, cm-1): 1670, 1597, 1578, 1510, 1415cm ;
1H NMR (400 MHz, CDCl
) δ 8.13 (d, J = 7.4 Hz, 2H), 7.98 (d, J = 7.4 Hz,
H), 7.70 (t, J = 7.4 Hz, 1H), 7.57 (t, J = 7.7 Hz, 2H), 7.39 – 7.27 (m, 3H),
3
1
3
.73 (s, 3H), 2.70 (s, 3H);
C NMR (100 MHz, CDCl ) δ 195.01, 189.57, 147.18, 136.57, 133.97,
1
3
3
1
32.88, 129.56, 128.52, 125.63, 122.59, 122.56, 120.30, 110.07, 109.21,
2
9.33, 12.27;
+
HRMS (ESI) m/z: Found: 300.0993. Calcd for C18
H15NO
2
: (M+Na) 300.0995.
S7

ACCEPTED MANUSCRIPT
1
-(1-methyl-2-phenyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (3l)
o
Yellow Solid, mp: 119-120 C;
-1
IR (neat, ν, cm-1): 1673, 1610, 1577, 1464, 1435cm ;
1H NMR (400 MHz, CDCl
) δ 8.62 (d, J = 4.5 Hz, 1H), 7.65 (d, J = 7.6 Hz,
H), 7.54 (t, J = 7.3 Hz, 1H), 7.47 (s, 3H), 7.34 (dd, J = 13.6, 6.3 Hz, 3H),
.25 – 7.08 (m, 4H), 3.57 (s, 3H);
3
2
7
1
3C NMR (100 MHz, CDCl
3
) δ 193.37, 190.65, 149.38, 136.72, 133.18,
1
33.07, 130.58, 129.29, 128.86, 128.54, 127.78, 127.50, 126.03, 123.71,
1
23.23, 122.19, 112.08, 109.53, 30.54;
+
HRMS (ESI) m/z: Found: 362.1155. Calcd for C23
H17NO
2
: (M+Na) 362.1151.
1
-(1-methyl-1H-indol-3-yl)-2-(p-tolyl)ethane-1,2-dione (4a)
o
Yellow Solid, mp: 95-96 C;
IR (neat, ν, cm-1): 1672, 1613, 1605, 1577, 1463cm ;
1H NMR (400 MHz, CDCl
) δ 8.50 – 8.42 (m, 1H), 8.00 (d, J = 8.2 Hz, 2H),
.77 (s, 1H), 7.40 – 7.35 (m, 3H), 7.28 (d, J = 8.0 Hz, 2H), 3.80 (s, 3H), 2.42
-1
3
7
(
s, 3H);
1
3C NMR (100 MHz, CDCl
3
) δ 193.09, 187.49, 145.01, 139.03, 137.23,
1
3
30.50, 129.95, 129.01, 125.87, 123.68, 122.95, 122.17, 112.42, 109.53,
3.27, 21.41;
+
HRMS (ESI) m/z: Found: 300.0992. Calcd for C18
H
15NO : (M+Na) 300.0995.
2
1
-(4-methoxyphenyl)-2-(1-methyl-1H-indol-3-yl)ethane-1,2-dione (4b)
o
Yellow Solid, mp: 116-117 C;
IR (neat, ν, cm-1): 1661, 1599, 1573, 1460cm ;
1H NMR (400 MHz, CDCl
) δ 8.46 (d, J = 4.5 Hz, 1H), 8.08 (d, J = 8.6 Hz,
H), 7.78 (s, 1H), 7.36 (s, 3H), 6.95 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H), 3.79 (s,
-1
3
2
3
H);
1
3
C NMR (100 MHz, CDCl ) δ 192.05, 187.71, 164.08, 139.05, 137.21,
3
1
5
32.27, 125.95, 125.90, 123.63, 122.91, 122.14, 113.59, 112.46, 109.52,
5.12, 33.25;
+
HRMS (ESI) m/z: Found: 316.0947. Calcd for C18
H15NO
3
: (M+Na) 316.0944.
S8

ACCEPTED MANUSCRIPT
1
-(4-isopropylphenyl)-2-(1-methyl-1H-indol-3-yl)ethane-1,2-dione (4c)
o
Yellow Solid, mp: 116-117 C;
-1
IR (neat, ν, cm-1): 1666, 1631, 1600, 1465cm ;
1H NMR (400 MHz, CDCl
) δ 8.53 (s, 1H), 8.08 (s, 2H), 7.83 (s, 1H), 7.42
s, 5H), 3.86 (s, 3H), 3.03 (s, 1H), 1.33 (s, 6H);
3C NMR (100 MHz, CDCl
) δ 193.12, 187.53, 155.65, 139.04, 137.23,
30.85, 130.12, 126.45, 125.88, 123.68, 122.94, 122.18, 112.43, 109.53,
3.98, 33.27, 23.13;
3
(
1
3
1
3
HRMS (ESI) m/z: Found: 328.1305. Calcd for C20
28.1308.
H
19NO
: (M+Na)+
2
3
1
-(4-(tert-butyl)phenyl)-2-(1-methyl-1H-indol-3-yl)ethane-1,2-dione (4d)
o
Yellow Solid, mp: 180-181 C;
-1
IR (neat, ν, cm-1): 1669, 1628, 1600, 1522, 1463cm ;
1H NMR (400 MHz, CDCl
) δ 8.37 (d, J = 4.7 Hz, 1H), 7.93 (d, J = 8.1 Hz,
H), 7.67 (s, 1H), 7.40 (d, J = 8.1 Hz, 2H), 7.26 (s, 3H), 3.69 (s, 3H), 1.24 (s,
3
2
1
0H);
1
3
C NMR (100 MHz, CDCl ) δ 193.11, 187.49, 157.84, 139.04, 137.23,
3
1
3
30.42, 129.81, 125.89, 125.30, 123.68, 122.94, 122.19, 112.43, 109.53,
4.84, 33.27, 30.56;
HRMS (ESI) m/z: Found: 342.1463. Calcd for C21
H
21NO
: (M+Na)+
2
342.1465.
1
-(4-fluorophenyl)-2-(1-methyl-1H-indol-3-yl)ethane-1,2-dione (4e)
o
Yellow Solid, mp: 112-113 C;
-1
IR (neat, ν, cm-1): 1665, 1611, 1593, 1504cm ;
1H NMR (400 MHz, CDCl
) δ 8.46 (s, 1H), 8.14 (s, 2H), 7.82 (s, 1H), 7.38 (s,
H), 7.15 (t, J = 8.0 Hz, 2H), 3.82 (s, 3H);
) δ 191.50, 186.55, 166 (d, J = 255.4), 139.20,
3
3
1
3C NMR (100 MHz, CDCl
3
1
1
37.24, 132.7 (d, J = 9.6), 129.4 (d, J = 2.6) 125.89, 123.81, 123.09, 122.14,
15.5 (d, J = 21.9), 112.26, 109.59, 33.32;
HRMS (ESI) m/z: Found: 304.0747. Calcd for C17
H
12FNO
: (M+Na)+
2
3
04.0744.
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1
-(4-chlorophenyl)-2-(1-methyl-1H-indol-3-yl)ethane-1,2-dione (4f)
o
Yellow Solid, mp: 157-158 C;
-1
IR (neat, ν, cm-1): 1670, 1618, 1583, 1459cm ;
1H NMR (400 MHz, CDCl
) δ 8.48 – 8.42 (m, 1H), 8.08 – 8.01 (m, 2H), 7.81
s, 1H), 7.49 – 7.42 (m, 2H), 7.42 – 7.35 (m, 3H), 3.81 (s, 3H).;
3C NMR (100 MHz, CDCl
) δ 191.78, 186.24, 140.36, 139.24, 137.24,
31.38, 131.22, 128.61, 125.89, 123.84, 123.13, 122.15, 112.21, 109.61,
3.34;
3
(
1
3
1
3
HRMS (ESI) m/z: Found: 320.0441. Calcd for C17
H
12ClO
: (M+Na)+
2
320.0449.
1
-(4-bromophenyl)-2-(1-methyl-1H-indol-3-yl)ethane-1,2-dione (4g)
o
Yellow Solid, mp: 165-166 C;
-1
IR (neat, ν, cm-1): 1662, 1624, 1583, 1467cm ;
1H NMR (400 MHz, CDCl
) δ 8.51 – 8.41 (m, 1H), 7.96 (d, J = 8.5 Hz, 2H),
.81 (s, 1H), 7.62 (d, J = 8.5 Hz, 2H), 7.39 (dd, J = 6.7, 3.3 Hz, 3H), 3.81 (s,
3
7
3
H);
1
3
C NMR (100 MHz, CDCl ) δ 191.97, 186.16, 139.24, 137.24, 131.79,
3
1
3
31.60, 131.28, 129.25, 125.89, 123.85, 123.14, 122.16, 112.21, 109.60,
3.35;
+
HRMS (ESI) m/z: Found: 363.9931. Calcd for C17
H
12BrNO
2
: (M+Na) 363.9944.
1
-(3-fluorophenyl)-2-(1-methyl-1H-indol-3-yl)ethane-1,2-dione (4h)
o
Yellow Solid, mp: 121-122 C;
IR (neat, ν, cm-1): 1672, 1619, 1523cm ;
1H NMR (400 MHz, CDCl
) δ 8.52 (s, 1H), 7.94 (d, J = 6.8 Hz, 1H), 7.87 (s,
H), 7.51 (d, J = 5.5 Hz, 1H), 7.44 (s, 3H), 7.38 (d, J = 6.8 Hz, 1H), 3.88 (s,
-1
3
2
3
H);
1
3
C NMR (100 MHz, CDCl ) δ 191.72, 186.02, 162.3 (d, J = 247), 139.22,
3
1
1
37.26, 135.0 (d, J = 6.5), 130.0 (d, J = 7.5), 125.9 (d, J = 2.8), 125.85,
23.87, 123.15, 122.18, 120.8 (d, J = 21.3), 116.1 (d, J = 22.5), 112.19,
1
09.60, 33.34;
+
HRMS (ESI) m/z: Found: 304.0745. Calcd for C17
H12FNO
2
: (M+Na) 304.0744.
1
-(2-chlorophenyl)-2-(1-methyl-1H-indol-3-yl)ethane-1,2-dione (4i)
o
Yellow Solid, mp: 163-164 C;
IR (neat, ν, cm-1): 1687, 1611, 1588, 1518cm ;
1H NMR (400 MHz, CDCl
) δ 8.47 – 8.39 (m, 1H), 8.04 (s, 1H), 7.78 (d, J
6.8 Hz, 1H), 7.48 (d, J = 7.0 Hz, 1H), 7.44 – 7.36 (m, 5H), 3.88 (s, 3H);
-1
3
=
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13C NMR (100 MHz, CDCl
) δ 193.52, 184.44, 139.10, 137.14, 134.85, 132.88, 132.76, 131.37,
3
1
29.88, 126.52, 126.36, 123.68, 122.98, 122.24, 111.53, 109.51, 33.38;
+
HRMS (ESI) m/z: Found: 320.0454. Calcd for C17
2
H12ClO : (M+Na) 320.0449.
1
-(1-methyl-1H-indol-3-yl)-2-(naphthalen-1-yl)ethane-1,2-dione (4j)
o
Yellow Solid, mp: 102-103 C;
IR (neat, ν, cm-1): 1649, 1638, 1525, 1469cm ;
1H NMR (400 MHz, CDCl
) δ 8.64 (s, 1H), 8.54 (d, J = 6.4 Hz, 1H),
.17 (dd, J = 8.6, 1.4 Hz, 1H), 7.93 (dd, J = 8.4, 3.0 Hz, 2H), 7.88 (d, J =
-1
3
8
8
.2 Hz, 1H), 7.83 (s, 1H), 7.62 (t, J = 7.1 Hz, 1H), 7.54 (t, J = 7.2 Hz,
H), 7.44 – 7.37 (m, 3H), 3.80 (s, 3H);
1
1
3C NMR (100 MHz, CDCl
) δ 193.40, 187.33, 139.18, 137.28, 135.70,
3
1
1
33.23, 131.96, 130.25, 129.51, 128.71, 128.30, 127.38, 126.45, 125.93, 123.92, 123.77, 123.06,
22.24, 112.54, 109.58, 33.30;
+
HRMS (ESI) m/z: Found: 336.0993. Calcd for C21
H15NO
2
: (M+Na) 336.0995.
1
-(1-methyl-1H-indol-3-yl)-2-(naphthalen-2-yl)ethane-1,2-dione (4k)
o
Yellow Solid, mp: 106-107 C;
IR (neat, ν, cm-1): 1637, 1595, 1524, 1468cm ;
1H NMR (400 MHz, CDCl
) δ 8.00 (s, 1H), δ 8.64 (s, 1H), 8.54 (d, J =
.8 Hz, 1H), 8.16 (d, J = 8.5 Hz, 1H), 7.97 – 7.90 (m, 2H), 7.88 (d, J = 8.1
Hz, 1H), 7.83 (s, 1H), 7.62 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.4 Hz, 1H),
-1
3
6
7
.41 (dd, J = 9.5, 2.6 Hz, 3H), 3.80 (s, 3H);
1
3C NMR (100 MHz, CDCl
3
) δ 193.40, 187.33, 139.18, 137.28, 135.69,
1
33.22, 131.95, 130.25, 129.51, 128.71, 128.30, 127.38, 126.46, 125.93,
1
23.92, 123.77, 123.06, 122.24, 112.54, 109.58, 33.30;
+
HRMS (ESI) m/z: Found: 336.0999. Calcd for C21
H15NO
2
: (M+Na) 336.0995.
1
-(1-methyl-1H-indol-3-yl)-2-(thiophen-2-yl)ethane-1,2-dione (4l)
o
Yellow Solid, mp: 93-94 C;
IR (neat, ν, cm-1): 1642, 1610, 1578, 1520, 1463cm ;
1H NMR (400 MHz, CDCl
) δ 8.36 (dd, J = 6.0, 1.6 Hz, 1H), 7.97 (d, J = 5.8
Hz, 2H), 7.69 – 7.61 (m, 1H), 7.24 (ddd, J = 10.6, 7.7, 4.3 Hz, 3H), 7.07 –
-1
3
7
.00 (m, 1H), 3.66 (s, 3H);
C NMR (100 MHz, CDCl ) δ 184.11, 184.11, 139.92, 138.87, 137.00,
1
3
3
1
36.25, 136.24, 127.94, 126.41, 123.67, 123.02, 122.14, 111.52, 109.61,
3
3.30;
+
HRMS (ESI) m/z: Found: 292.0401. Calcd for C15
H11NO
2
S: (M+Na) 292.0403.
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1
-(1-methyl-1H-indol-3-yl)-2-(4-(trifluoromethyl)phenyl)ethane-1,2-dione (4m)
o
Yellow Solid, mp: 153-154 C;
-1
IR (neat, ν, cm-1): 1680, 1614, 1579, 1491cm ;
1H NMR (400 MHz, CDCl
) δ 8.46 (d, J = 4.0 Hz, 1H), 8.22 (d, J = 8.1 Hz,
H), 7.86 (s, 1H), 7.75 (d, J = 8.2 Hz, 2H), 7.41 (d, J = 10.0 Hz, 3H), 3.84 (s,
3
2
3
H);
1
3
C NMR (100 MHz, CDCl ) δ 191.70, 185.53, 139.34, 137.27, 135.85,
3
1
34.7 (q, J = 32.5), 130.17, 125.91, 125.2 (q, J = 3.7), 123.95, 123.24, 123.0
(
q, J = 271.3), 122.17, 112.13, 109.64, 33.36;
+
HRMS (ESI) m/z: Found: 354.0712. Calcd for C18
H
12
F
3
NO : (M+Na) 354.0712.
2
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1
13
Copies of H and C NMR Spectra for Compounds
1H NMR Spectrum of Compound 3a
13C NMR Spectrum of Compound 3a
S13

ACCEPTED MANUSCRIPT
1H NMR Spectrum of Compound 3b
13C NMR Spectrum of Compound 3b
S14

ACCEPTED MANUSCRIPT
1H NMR Spectrum of Compound 3c
13C NMR Spectrum of Compound 3c
S15

ACCEPTED MANUSCRIPT
1H NMR Spectrum of Compound 3e
13C NMR Spectrum of Compound 3e
S16

ACCEPTED MANUSCRIPT
1H NMR Spectrum of Compound 3f
13C NMR Spectrum of Compound 3f
S17

ACCEPTED MANUSCRIPT
1H NMR Spectrum of Compound 3g
13C NMR Spectrum of Compound 3g
S18

ACCEPTED MANUSCRIPT
1H NMR Spectrum of Compound 3h
13C NMR Spectrum of Compound 3h
S19

ACCEPTED MANUSCRIPT
1H NMR Spectrum of Compound 3i
13C NMR Spectrum of Compound 3i
S20

ACCEPTED MANUSCRIPT
1H NMR Spectrum of Compound 3j
13C NMR Spectrum of Compound 3j
S21

ACCEPTED MANUSCRIPT
1H NMR Spectrum of Compound 3k
13C NMR Spectrum of Compound 3k
S22