Ruthenium-catalyzed direct C3 alkylation of indoles with α,β-unsaturated ketones

Article abstract of DOI:10.1039/c4ob02124j

In this paper, a simple and highly efficient ruthenium-catalyzed direct C3 alkylation of indoles with various α,β-unsaturated ketones without chelation assistance has been developed. This novel C-H activation methodology exhibits a broad substrate scope s

Full text of DOI:10.1039/c4ob02124j

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DOI: 10.1039/C4OB02124J
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ARTICLE TYPE
Ruthenium-Catalyzed Direct C3 Alkylation of Indoles with α,β-
Unsaturated Ketones
Shuai-Shuai Li,a,b,c Hui Lin,c Xiao-Mei Zhanga and Lin Dong*c
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
5
DOI: 10.1039/b000000x
especially without directing groups still remains huge
In this paper, a simple and highly efficient ruthenium-
catalyzed direct C3 alkylation of indoles with various α,β-
unsaturated ketones without the chelation assistance has been
developed. This novel C-H activation methodology exhibits a
broad substrate scope such as different substituted indoles,
pyrroles, and other azoles. Further synthetic applications of
the alkylation products can lead to more attractive 3,4-fused
tricyclic indoles.
challenges.14 Herein, we report an efficient Ruꢀcatalyzed direct
C3 alkylation of indoles with α,βꢀunsaturated ketones via CꢀH
30 activation without the chelation assistance, which can also
tolerate air (Scheme 1, approach 2).
The indole unit is widely utilized in the synthesis of a large
number of pharmaceuticals and biologically active compounds.1
Therefore, functionalization of the indole structure has received a
great deal of attention over the past several decades.2–10 For
10 example, a variety of alkylation of indoles with electron deficient
olefins has been reported since 1955.9 Many groups made
significant contributions on C–H arylation reactions.3 Very
recently, Pdꢀcatalyzed direct C2 or C3 alkenylations of indoles
were developed (Scheme 1, approach 1).4ꢀ6 Despite these great
Scheme 1 Transitionꢀmetalꢀcatalyzed CꢀH activation of indoles with α,βꢀ
unsaturated ketones
15 advances, however, the development of new approaches via 35 Results and Discussion
transitionꢀmetalꢀcatalyzed C–H activation to afford the indole
derivatives is still highly desirable.
Firstly, we investigated the potential reaction of Nꢀmethyl indole
1a with chalcone 2a to form C3 alkylation of indole product 3aa
(Table 1). [Cp*RhCl2]2 and [Ir(cod)Cl2]2 were previously studied
as catalysts, however, only a trace amount of product 3aa or a
40 complex mixture of unidentified products could be observed
(entries 1 and 2). Fortunately, RuCOCl(PPh3)2 can catalyze the
alkylation reaction and gave 3aa in 59% yield (entry 3).
Surprisingly, AgSbF6 alone as catalyst also worked well even at
room temperature (entries 4ꢀ7). To our delight, the yield
45 increased significantly when RuCl2(PPh3)3 was applied as
catalyst, and the yield was still excellent even after reducing the
catalyst loading (entries 8 and 9). Among the test of the solvents,
DCM produced the best satisfactory result and the desired
product 3aa could be obtained in 96% yield (entries 10ꢀ14). The
50 same yield could be afforded when the loading of RuCl2(PPh3)3
was decreased to 3 mol % (entry 15), while the reactivity was
worse under only 1 mol % loading (entry 16). However, the
reaction yields were significantly diminished when less AgSbF6
was used (entries 17 and 18).
More recently, the lessꢀexpensive ruthenium catalyst has been
exploited in the chelationꢀassisted oxidative coupling reactions.11
20 In particular, in 1993 Murai published a pioneering work on the
Ruꢀcatalyzed orthoꢀC–H bond alkylation of aromatic ketones
with olefins via a chelation assisted strategy.12 Very recently,
Chatani reported Ruꢀcatalyzed orthoꢀC–H bond alkylation of
aromatic amides with α,βꢀunsaturated ketones but need bidentateꢀ
25 chelation assistance.13 However, to the best of our knowledge,
Ruꢀcatalyzed CꢀH activation with α,βꢀunsaturated acceptors
a S.ꢀS. Li, Prof. Dr. X.ꢀM. Zhang
Key Laboratory for Asymmetric Synthesis and Chiraltechnology of
Sichuan Province,
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences,
Chengdu 610041, China
b S.ꢀS. Li
Graduate School of the Chinese Academy of Sciences,
Beijing 100049, China
c S.ꢀS. Li, H. Lin, Prof. Dr. L. Dong
Key Laboratory of DrugꢀTargeting and Drug Delivery System of the
Education Ministry, West China School of Pharmacy, and State Key
Laboratory of Biotherapy, West China Hospital, Sichuan University,
Chengdu 610041, China
Eꢀmail: dongl@scu.edu.cn
†Electronic Supplementary Information (ESI) available: See
DOI: 10.1039/b000000x/
55
Under the optimized conditions, the scope and limitation of
α,βꢀunsaturated ketones were explored (Table 2). Gratifying, a
variety of α,βꢀunsaturated ketones reacted smoothly under this
catalytic system. Initially, a series of substituted chalcones were
employed to react with indole 1a. The results showed that
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Table 1 Optimization of the reaction conditions a
40 Table 2 The scope of α,βꢀunsaturated ketones a
5
Entry
1[c]
Catalyst
/[equiv]
[Cp*RhCl2]2/0.05
Additive
/[equiv]
Cu(OAc)2/1, DCE
AgSbF6/0.4
Cu(OAc)2/1, DCE
AgSbF6/0.4
CuCl/1.9,
AgSbF6/0.4
ꢀ
Solvent
T
Yield
[h] [%][b]
9
9
6
Trace
Mess
59
2[c]
[Ir(cod)Cl2]2/0.05
3[c]
RuCOCl(PPh3)2/0.1
DCE
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
AgSbF6/0.4
AgSbF6/0.09
AgSbF6/0.09
AgSbF6/0.06
DCE
DCE
DCM
DCM
DCE
DCE
DMF
THF
toluene
CH3CN
DCM
4
70
Trace
45
22
96
96
50
90
91
74
96
96
72
88
50
ꢀ
ꢀ
ꢀ
18
18
18
4
4
24
5
7
8
4
4
RuCl2(PPh3)3/0.1
RuCl2(PPh3)3/0.05
RuCl2(PPh3)3/0.05
RuCl2(PPh3)3/0.05
RuCl2(PPh3)3/0.05
RuCl2(PPh3)3/0.05
RuCl2(PPh3)3/0.05
RuCl2(PPh3)3/0.03
RuCl2(PPh3)3/0.01
RuCl2(PPh3)3/0.03
RuCl2(PPh3)3/0.03
AgSbF6/0.4
AgSbF6/0.2
AgSbF6/0.2
AgSbF6/0.2
AgSbF6/0.2
AgSbF6/0.2
AgSbF6/0.2
AgSbF6/0.2 DCM
AgSbF6/0.2 DCM
AgSbF6/0.09 DCM
AgSbF6/0.06 DCM
4
15
18
a
Reaction conditions unless otherwise specified: 0.05 mmol of 1a, 0.058
b
c
mmol of 2a, 1 mL of solvent, 25 °C, under air. Isolated yield. Ar
10 atmosphere, 110 °C.
a Reaction conditions unless otherwise specified: 0.120 mmol of 1a, 0.132
mmol of 2, 3 mol % of RuCl2(PPh3)3, 20 mol % AgSbF6, 2 mL of DCM,
25 °C, under air, isolated yield.
benzene ring bearing either electronꢀdonating or ꢀwithdrawing
groups all proceeded well to give the corresponding products
3abꢀ3ag with good to excellent yields. To push the limitation of
15 this approach, phenyl was replaced by other functional groups,
which did proceed but led to lower reactivity (products 3ahꢀ3aj).
In addition, wherein R2 was naphthalene or furan, products 3ak
and 3al were obtained in excellent yields. However, the methyl
group just provided 3am in 55% yield. Similarly, (1E,4E)ꢀ1,5ꢀ
20 diphenylpentaꢀ1,4ꢀdienꢀ3ꢀone 2n and (E)ꢀ1,4ꢀdiaryꢀ2ꢀbutenꢀ1,4ꢀ
diones 2o were also tolerated in the reaction, the desired products
could be prepared in 70% and 98% yield, respectively. To our
delight, terminal olefin pentꢀ1ꢀenꢀ3ꢀone 2p and dialkyl
substituted chalcone (E)ꢀpentꢀ3ꢀenꢀ2ꢀone 2q also performed well
25 with indole 1a, giving the corresponding alkylated products 3ap
and 3aq in 75% and 71% yield, respectively. It is worth
mentioned that cyclic α,βꢀunsaturated ketones were also efficient
to this method. Under the standard reaction conditions, 4ꢀ
methoxyꢀ4ꢀmethylcyclohexaꢀ2,5ꢀdienone 2r underwent the
30 reaction with indole 1a to give 3ꢀarylated product 3ar. Notable is
that the efficiency of cyclohexenone is lower than
cyclopentenone (3as, 3at), likely owing to geometrical
constraints or strain.9d
45
product 3ha in 70% yield. Notably, this new protocol is also
appropriate for sterically hindered 2ꢀphenly indole 1i, which
provided 3ia in 73% yield.
50 Table 3 The scope of indoles a
O
Ph
Ph
O
RuCl2(PPh3)3 (3 mol %)
AgSbF6 (20 mol %)
R5
R3
N
R4
+
R5
Ph
Ph
R3
DCM, r.t.
under air
N
R4
1
2a
3
(R3 = H, R4 = CH3, R5 = 4-Br), 70%
3ba
3ca
O
Ph
(R3 = H, R4 = CH3, R5 = 4-Me), 79%
Ph
3da (R3 = H, R4 = CH3, R5 = 5-MeO), 96%
3ea (R3 = H, R4 =CH3, R5 = 5-Br), 80%
3fa (R3 = H, R4 = CH3, R5 = 6-MeO), 86%
3ga (R3 = H, R4 = CH3, R5 = 7-MeO), 91%
4
7
5
R5
R3
N
6
R4
(R3 = H, R4 = Ph, R5 = H), 70%
3ha
(R3 = Ph, R4 = CH3, R5 = H), 73%
3ia
As shown in Table 3, the scope of indoles in the Cꢀ3 alkylation
35 reactions was further studied. Various substituents on indole ring
exhibited good reactivity (3baꢀ3ga), even for the bromine
substituents 1b and 1e. Moreover, Nꢀphenyl substituted indoles
could achieve this alkylation reaction and gave the corresponding
a
Reaction conditions unless otherwise specified: 0.120 mmol of 1, 0.132
mmol of 2a, 3 mol % of RuCl2(PPh3)3, 20 mol % AgSbF6, 2 mL of DCM,
25 °C, under air, isolated yield.
55 Table 4 Reaction of indole and α,βꢀunsaturated ketones a
2
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To our satisfactory, aliphatic enones were also tolerated,
furnishing the corresponding products in good yields (5ap, 5aq,
5as and 5at). Moreover, even the indole with 2ꢀmethyl group
30 could be tolerated in the reaction and formed 5ba in 76% yield.
Surprisingly, azole 4c was also compatible in this system.
R1
R2
RuCl2(PPh3)3 (3 mol %)
AgSbF6 (20 mol %)
O
R3
O
R3
X
R1
R2
+
N
H
X
N
DCM, r.t.
under air
H
X=C, N
X=C, N
2
4
5
O
3
H
4
O
R2
R
2
5aa (R = H), 90%
Ph
Pd(OAc)2, PPh3,
R1
Ph
O
5ab (R = 2-Cl), 93%
5ac (R = 3-Cl), 90%
5ad (R = 4-Cl), 88%
5ae (R = 4-Br), 90%
5af (R = 4-MeO), 63%
5ag (R = 4-CF3), 70%
Br
S
1) NaBH4, MeOH
Ph
Ph
Ph
O
2) CuI, KI,TMEDA,
K2CO3, dioxane
140 °C
CH3
N
O
DIEA, DMF, 110 °C
O
N
N
N
H
CH3
8c
N
H
CH3
N
H
R1 = Ph, R2 = Styryl
O
3
+
8a
80% conversion
Ph
R1 = H, R2 = Et
5ah 87%
5ai 40%
Ph
H
Ph
Ph
Ph
Ph
O
Ph
O
1) NaBH4, MeOH
Ph
O
O
2) CuI, KI,TMEDA,
K2CO3, dioxane
140 °C
O
N
CH3
N
H
N
N
H
N
H
8d
CH3
8b
72% conversion
R1 = Ph, R2 = Ph
86% yield
(2 : 1)
5an 60%
5ak 80%
5al 73%
Ph
O
Scheme 3 Synthetic applications of 3
O
O
Ph
35
O
N
N
N
To additionally explore the scope of our approach, Nꢀmethyl
pyrrole 6 was applied (Scheme 2). Interestingly, both C2 and C3
alkylation products were obtained under standard conditions. In
addition, monoalkylated and dialkylated products were also
40 formed. The 2,5ꢀdialkylated pyrrole was isolated in 33% yield as
an essentially 1:1 mixture of diastereoisomers 7c,d.
Further conversion of the alkylation product 3 into useful 3,4ꢀ
fused tricyclic indoles was investigated, which are considered as
attractive synthetic targets because of their biological activities
45 and synthetic challenges (Scheme 3).15 As our previous
speculated, the alkylation products 3 were converted to the
corresponding alcohol intermediates by reduction, which then
underwent Cuꢀcatalyzed Ullmannꢀtype cyclization reactions to
produce sevenꢀmembered Oꢀarylated rings 8a and 8b in good
50 conversion yields over two steps. Furthermore, an efficient
method to obtain the tricyclic ketones 8c and 8d which are
bridged with eightꢀmembered ring was developed through
intramolecular Heck reaction.
H
H
H
5aq 76%
5ap 91%
5ao 99%
O
N
O
O
Ph
Ph
Ph
O
Ph
N
N
N
H
N
H
H
H
5ba 76%
5ca 30%
5as 40%
5at 51%
a
Reaction conditions unless otherwise specified: 0.120 mmol of 4, 0.132
mmol of 2, 3 mol % of RuCl2(PPh3)3, 20 mol % AgSbF6, 2 mL of DCM,
25 °C, under air. Yields are reported for the isolated products.
5
Encouraged by these results, we decided to examine the
applicability of the alkylation reaction of unprotected indoles
(Table 4). Halide at the orthoꢀ, metaꢀ, or paraꢀposition were
compatible in this alkylation reaction, producing 5abꢀ5ae in
satisfactory yields. In addition it seemed that there is no strong
10 influence on the electronic characteristics at the para position of
phenyl (5af, 5ag). In contrast, NꢀH indoles also reacted smoothly
with substituted chalcones but affording relatively lower
reactivity than Nꢀprotected indoles (5ah, 5ai, 5ak, 5al and 5an).
Notably, (E)ꢀ1,4ꢀdiaryꢀ2ꢀbutenꢀ1,4ꢀdiones 2o gave the best result.
15
55
60
65
O
Ph
Ph
Ph
O
+
N
Ph
N
CH3
CH3
20
4
standard
conditions
O
7a
33%
7b 6%
+
(3)
N
Ph
Ph
CH3
6
Ph
Ph
O
2a
+
+
O
N
Ph
Ph
N
Ph
Ph
CH3
CH3
Ph
Ph
O
O
7c
7d
17%
16%
70 Scheme 4 Deuteriumꢀlabeling experiments
25 Scheme 2 Reaction of NꢀCH3 pyrrole 6 with 2a
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Deuteriumꢀlabeling experiments were carried out to study the
General Procedure for Synthesis of 3-alkyl indole derivatives:
mechanism of this alkylation reaction (Scheme 4). When 1a was 50 Nꢀ methyl indole 1a (6.6 mg, 0.05 mmol), chalcone 2a (12.1 mg,
conducted in D2O under the specified conditions, no deuterium
was observed at C3 of indoles (eqs 4, 5). In contrast, when 1a
was stirred under RuCl2(PPh3)3 in the absence of α,βꢀunsaturated
ketones, the content of deuterium on Cꢀ3 was 40% (eq 6).16 All of
0.058 mmol), RuCl2(PPh3)3 (1.4 mg, 3 mol %) and AgSbF6 (3.44
mg, 20 mol %) were stirred in DCM (1.0 mL) at room
temperature for 4 h. After completion, the reaction mixture was
purified by flash chromatography eluting with ethyl acetate and
5
these data imply that the CꢀH activation was happened on the first 55 petroleum ether (1:50) to give the product 3aa as a white solid
step under the catalysis of RuCl2(PPh3)3, and on the other hand, it
is possible that AgSbF6 might be acting as a Lewis acid to
10 promote this reaction.
(16.3 mg, 96%).
3-(1-methyl-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3aa).
4h, 96% yield; 1H NMR (400 MHz, CDCl3): δ 7.96 (d, J = 7.6 Hz,
2H), 7.58ꢀ7.54 (m, 1H), 7.49ꢀ7.43 (m, 3H), 7.40ꢀ7.39 (m, 2H),
Depend on the evidence that we obtained and previous report,
a plausible process is proposed (Scheme 5). The ruthenium 60 7.31ꢀ7.27 (m, 3H), 7.23ꢀ7.17 (m, 2H), 7.06ꢀ7.03 (m, 1H), 6.87 (s,
catalyst first replaces the C(3)ꢀH of indole to generate complex I,
which presumably be stabilized by carbonyl and adjacent π
15 system. Then intermediate I undergoes conjugate addition to
form ruthenium species II. Finally, protonation forms the
alkylation product 3aa.
1H), 5.10 (t, J = 7.2 Hz, 1H), 3.81 (ddd, J = 6.4, 20.4, 24.4 Hz,
2H), 3.73 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 198.4,
144.4, 137.3, 137.1, 132.9, 128.5, 128.4, 128.0, 127.8, 126.9,
126.2, 121.6, 119.5, 118.8, 117.7, 109.2, 45.3, 38.0, 32.6 ppm.
65 ESI HRMS: calcd. for C24H21NO+Na 362.1521, found 362.1515.
3-(2-Chloro-phenyl)-3-(1-methyl-1H-indol-3-yl)-1-phenyl-
propan-1-one (3ab). 8 h, 91% yield; 1H NMR (400 MHz,
CDCl3): δ 7.97 (d, J = 7.6 Hz, 2H), 7.55ꢀ7.52 (m, 1H), 7.44ꢀ7.41
(m, 3H), 7.39ꢀ7.37 (m, 1H), 7.25ꢀ7.23 (m, 2H), 7.18ꢀ7.15 (m, 1H),
70 7.11ꢀ7.09 (m, 2H), 7.02ꢀ6.98 (m, 1H), 6.85 (s, 1H), 5.53 (t, J =
7.2 Hz, 1H), 3.73 (ddd, J = 8.4, 20.8, 44.4 Hz, 2H), 3.70 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3): δ 198.0, 141.7, 137.2, 136.8,
133.5, 133.0, 129.7, 128.9, 128.6, 128.1, 127.5, 127.0, 126.9,
126.6, 121.7, 119.5, 118.9, 116.1, 109.2, 44.3, 34.7, 32.7 ppm.
75 ESI HRMS: calcd. for C24H20ClNO+Na 396.1131 found
C24H2035ClNNaO 396.1133, C24H2037ClNNaO 398.1105.
20
3-[1-(3-Chloro-phenyl)-3-phenyl-but-3-enyl]-1-methyl-1H-
1
indole (3ac). 10 h, 80% yield; H NMR (400 MHz, CDCl3): δ
25 Scheme 5 Proposed catalytic cycle
7.96 (d, J = 7.6 Hz, 2H), 7.58ꢀ7.54 (m, 1H), 7.47ꢀ7.44 (m, 3H),
80 7.36 (s, 1H), 7.29ꢀ7.25 (m, 2H), 7.24ꢀ7.14 (m, 3H), 7.07ꢀ7.04 (m,
1H), 6.87 (s, 1H), 5.07 (t, J = 7.2 Hz, 1H), 3.78 (ddd, J = 6.8 , 20,
33.6 Hz, 2H), 3.73 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ
197.9, 146.6, 137.3, 136.9, 134.1, 133.1, 129.6, 128.6, 128.0,
127.9, 126.7, 126.4, 126.1, 121.8, 119.3, 118.9, 117.0, 109.2,
85 44.9, 37.7, 32.7 ppm. ESI HRMS: calcd. for C24H20ClNO+Na
396.1131 found C24H2035ClNNaO 396.1142, C24H2037ClNNaO
398.1096.
Conclusion
In summary, we have developed a new approach for direct C3
alkylation of indoles with α,βꢀunsaturated ketones via rutheniumꢀ
catalyzed CꢀH activation without the chelation assistance. Our
30 methodology exhibits
mechanistic investigations and application to more types of
heteroaromatic compounds are being conducted in our laboratory.
a
broad substrate scope. Further
3-(4-Chloro-phenyl)-3-(1-methyl-1H-indol-3-yl)-1-phenyl-
propan-1-one (3ad). 8 h, 95% yield; 1H NMR (400 MHz,
90 CDCl3): δ 7.92 (d, J = 7.2 Hz, 2H), 7.56ꢀ7.52 (m, 1H), 7.45ꢀ7.39
(m, 3H), 7.29ꢀ7.24 (m, 3H), 7.21ꢀ7.17 (m, 3H), 7.04ꢀ7.00 (m, 1H),
6.82 (s, 1H), 5.03 (t, J = 7.2 Hz, 1H), 3.74 (ddd, J = 6.4, 20, 29.6
Hz, 2H), 3.73 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 198.2,
142.9, 137.3, 136.9, 133.1, 131.8, 129.1, 128.6, 128.5, 128.0,
95 126.7, 126.1, 121.8, 119.1, 119.0, 117.3, 109.3, 45.0, 37.4, 32.7
ppm. ESI HRMS: calcd. for C24H20ClNO+Na 396.1131 found
C24H2035ClNNaO 396.1140, C24H2037ClNNaO 398.1090.
3-(4-Bromo-phenyl)-3-(1-methyl-1H-indol-3-yl)-1-phenyl-
propan-1-one (3ae). 10 h, 96% yield; 1H NMR (400 MHz,
100 CDCl3): δ 7.92 (d, J = 7.6 Hz, 2H), 7.55ꢀ7.51 (m, 1H), 7.44ꢀ7.39
(m, 3H), 7.36ꢀ7.34 (m, 2H), 7.26ꢀ7.16 (m, 4H), 7.03ꢀ7.00 (m, 1H),
6.81 (s, 1H), 5.01 (t, J = 7.2 Hz, 1H), 3.75 (ddd, J = 10.8, 22.2,
31.8 Hz, 2H), 3.70 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ
198.1, 143.4, 137.3, 136.9, 133.1, 131.4, 129.6, 128.6, 128.0,
105 126.7, 126.1, 121.8, 119.9, 119.4, 118.9, 117.2, 109.3, 44.9, 37.4,
Acknowledgments
We are grateful for the financial support from the NSFC
35 (21202106), Sichuan University “985 projectꢀScience and
technology innovation platform for novel drug development”.
Experimental
General remarks
NMR data were obtained for 1H at 300 MHz or 400 MHz, and for
40 13C at 75 MHz or 100 MHz. Chemical shifts were reported in
ppm from tetramethylsilane with the solvent resonance as the
internal standard in CDCl3 or DMSOꢀd6 solution. ESI HRMS was
recorded on a Waters SYNAPT G2 and Water XEVO G2 QꢀToF.
UV detection was monitored at 220 nm. TLC was performed on
45 glassꢀbacked silica plates. Column chromatography was
performed on silica gel (200ꢀ300 mesh), eluting with ethyl acetate
and petroleum ether. CH2Cl2, CHCl2CHCl2 were distilled over
CaH2.
4
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DOI: 10.1039/C4OB02124J
32.7 ppm. ESI HRMS: calcd. for C24H20BrNO+Na 440.0626,
found C24H2079BrNNaO 440.0615, C24H2081BrNNaO 442.0593.
3-(4-Methoxy-phenyl)-3-(1-methyl-1H-indol-3-yl)-1-phenyl-
propan-1-one (3af). 10 h, 95% yield; 1H NMR (400 MHz,
CDCl3): δ 7.92 (d, J = 7.6 Hz, 2H), 7.53ꢀ7.50 (m, 1H), 7.44ꢀ7.39
(m, 3H), 7.27ꢀ7.23 (m, 3H), 7.18ꢀ7.15 (m, 1H), 7.02ꢀ6.98 (m, 1H),
3H) ppm; 13C NMR (100 MHz, DMSO): δ 198.3, 145.4, 136.9,
60 135.2, 134.3, 132.4, 130.3, 129.8, 128.8, 128.4, 128.3, 128.0,
127.8, 127.1, 126.9, 126.5, 126.1, 123.8, 121.4, 119.2, 118.6,
117.7, 109.8, 44.5, 37.7, 32.5 ppm. ESI HRMS: calcd. for
C28H23NO+Na 412.1677, found 412.1667.
5
1-Furan-2-yl-3-(1-methyl-1H-indol-3-yl)-3-phenyl-propan-1-
1
6.81ꢀ6.77 (m, 3H), 5.00 (t, J = 7.2 Hz, 1H), 3.75 (ddd, J = 6.8, 65 one (3al). 10 h, 96% yield; H NMR (400 MHz, CDCl3): δ 7.52
25.2, 33.2 Hz, 2H), 3.73 (s, 3H), 3.68 (s, 3H) ppm; 13C NMR
(s, 1H), 7.45ꢀ7.43 (m, 1H), 7.36ꢀ7.34 (m, 2H), 7.26ꢀ7.23 (m, 3H),
7.18ꢀ7.12 (m, 2H), 7.11ꢀ7.10 (m, 1H), 7.02ꢀ6.98 (m, 1H), 6.87 (s,
1H), 6.46ꢀ6.45 (m, 1H), 5.03 (t, J = 7.6 Hz, 1H), 3.70 (s, 3H),
3.63 (ddd, J = 7.6, 19.6, 28.4 Hz, 2H) ppm; 13C NMR (100 MHz,
70 CDCl3): δ 187.6, 152.9, 146.2, 144.1, 137.2, 128.3, 127.8, 126.9,
126.2, 121.6, 119.6, 118.8, 117.4, 117.0, 112.2, 109.1, 45.0, 38.1,
32.6 ppm. ESI HRMS: calcd. for C22H19NO2+Na 352.1313,
found 352.1307.
(100 MHz, CDCl3): δ 198.6, 157.8, 137.3, 137.0, 136.4, 132.9,
10 128.7, 128.5, 128.0, 126.9, 126.1, 121.6, 119.6, 118.7, 118.1,
113.7, 109.1, 55.1, 45.4, 37.3, 32.6 ppm. ESI HRMS: calcd. for
C25H23NO2+Na 392.1626, found 392.1627.
3-(1-Methyl-1H-indol-3-yl)-1-phenyl-3-(4-trifluoromethyl-
phenyl)-propan-1-one (3ag). 12 h, 98% yield; 1H NMR (400
15 MHz, CDCl3): δ 7.93 (d, J = 7.6 Hz, 2H), 7.56ꢀ7.40 (m, 8H),
7.28ꢀ7.26 (m, 1H), 7.23ꢀ7.18 (m, 1H), 7.05ꢀ7.01 (m, 1H), 6.84 (s,
4-(1-Methyl-1H-indol-3-yl)-4-phenyl-butan-2-one (3am). 8 h,
1
1H), 5.12 (t, J = 7.2 Hz, 1H), 3.79 (ddd, J = 6.4, 20.4, 26 Hz, 2H), 75 55% yield; H NMR (400 MHz, CDCl3): δ 7.48ꢀ7.46 (m, 1H),
3.72 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): 198.0, 148.5,
137.3, 136.8, 133.2, 128.6, 128.1, 128.0, 126.7, 126.2, 125.4,
20 125.3, 125.3, 121.2, 119.3, 119.0, 116.9, 109.3, 44.8, 37.8, 32.7
ppm. ESI HRMS: calcd. for C25H20F3NO+Na 430.1395, found
430.1401.
3-(1-Methyl-1H-indol-3-yl)-3-naphthalen-1-yl-1-phenyl-
propan-1-one (3ah). 10 h, 77% yield; 1H NMR (400 MHz,
25 CDCl3): δ 8.30 (d, J = 8.8 Hz, 1H), 7.94 (d, J = 7.6 Hz, 2H), 7.85ꢀ
7.35 (m, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.54ꢀ7.38 (m, 8H), 7.35ꢀ
7.36ꢀ7.34 (m, 2H), 7.32ꢀ7.26 (m, 3H), 7.23ꢀ7.18 (m, 2H), 7.07ꢀ
7.03 (m, 1H), 6.86 (s, 1H), 4.86 (t, J = 7.6 Hz, 1H), 3.74 (s, 3H),
3.23 (ddd, J = 7.2, 19.6, 32 Hz, 2H), 2.10 (s, 3H) ppm; 13C NMR
(100 MHz, CDCl3): δ 207.6, 144.1, 137.2, 128.4, 127.6, 126.8,
80 126.3, 126.1, 121.7, 119.4, 118.8, 117.2, 109.2, 50.4, 38.3, 32.6,
30.3 ppm. ESI HRMS: calcd. for C19H19NO+Na 300.1364, found
300.1360.
5-(1-Methyl-1H-indol-3-yl)-1,5-diphenyl-pent-1-en-3-one
1
(3an). 8 h, 70% yield; H NMR (400 MHz, CDCl3): δ 7.56 (s,
7.31 (m, 1H), 7.24ꢀ7.21 (m, 1H), 7.19ꢀ7.15 (m, 1H), 6.99 (t, J = 85 1H), 7.52ꢀ7.48 (m, 3H), 7.42ꢀ7.40 (m, 5H), 7.33ꢀ7.28 (m, 3H),
7.2 Hz, 1H), 5.94 (t, J = 6.8 Hz, 1H), 3.88 (ddd, J = 7.6, 21.4,
61.8 Hz, 2H), 3.62 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ
30 198.3, 140.0, 137.3, 137.0, 134.0, 133.0, 131.4, 128.8, 128.5,
128.0, 127.0, 126.9, 126.1, 125.4, 125.3, 124.2, 123.6, 121.6,
726ꢀ7.19 (m, 2H), 7.09ꢀ7.05 (m, 1H), 6.91 (s, 1H), 6.76ꢀ6.72 (m,
1H), 5.02 (t, J = 7.2 Hz, 1H), 3.74 (s, 3H), 3.50 (ddd, J = 6.8,
19.2, 37.2 Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3): δ 198.6,
144.2, 142.6, 137.2, 134.4, 130.4, 128.8, 128.4, 128.2, 127.7,
119.5, 118.8, 117.5, 109.2, 44.9, 33.0, 32.6 ppm. ESI HRMS: 90 126.9, 126.2, 126.1, 121.6, 119.6, 118.8, 117.5, 109.2, 47.5, 38.4,
calcd. for C28H23NO+Na 412.1677, found 412.1675.
32.6 ppm. ESI HRMS: calcd. for C26H23NO+Na 388.1677, found
388.1676.
3-(1-Methyl-1H-indol-3-yl)-1-phenyl-3-thiophen-2-yl-propan-
35 1-one (3ai). 18 h, 60% yield; 1H NMR (400 MHz, CDCl3): δ 7.96
(d, J = 7.6 Hz, 2H), 7.59ꢀ7.54 (m, 2H), 7.47ꢀ7.43 (m, 2H), 7.31ꢀ
2-(1-Methyl-1H-indol-3-yl)-1,4-diphenyl-butane-1,4-dione
1
(3ao). 6 h, 98% yield; H NMR (400 MHz, CDCl3): δ 8.07ꢀ8.05
7.21 (m, 2H), 7.12ꢀ7.07 (m, 2H), 6.96ꢀ6.95 (m, 2H), 6.91ꢀ6.89 (m, 95 (m, 2H), 7.98ꢀ7.96 (m, 2H), 7.78ꢀ7.76 (m, 1H), 7.54ꢀ7.50 (m, 1H),
1H), 5.39 (t, J = 7.2 Hz, 1H), 3.86 (ddd, J = 7.6, 17.6, 21.2 Hz,
2H), 3.73 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 197.9,
40 148.9, 137.2, 136.9, 133.0, 128.5, 128.0, 126.5, 126.4, 126.3,
124.1, 123.3, 121.7, 119.5, 118.9, 117.4, 109.3, 46.2, 33.3, 32.7
746ꢀ7.39 (m, 3H), 7.37ꢀ7.33 (m, 2H), 7.28ꢀ7.22 (m, 2H), 7.18ꢀ
7.15 (m, 1H), 6.88 (s, 1H), 5.59 (dd, J = 3.6, 10.4 Hz, 1H), 4.24
(dd, J = 10.4, 18.4 Hz, 1H), 3.42 (dd, J = 3.2, 18 Hz, 1H), 3.66 (s,
3H) ppm; 13C NMR (100 MHz, CDCl3): δ 199.1, 198.6, 137.1,
ppm. ESI HRMS: calcd. For C22H19NOS+Na 368.1085, found 100 136.5, 136.4, 133.1, 132.6, 128.7, 128.5, 128.4, 128.1, 127.4,
368.1093.
126.4, 122.0, 119.5, 118.7, 111.4, 109.5, 43.1, 39.4, 32.7 ppm.
ESI HRMS: calcd. for C25H21NO2+Na 390.1470, found 390.1465.
1-(1-Methyl-1H-indol-3-yl)-pentan-3-one (3ap). 8 h, 75% yield;
1H NMR (400 MHz, CDCl3): δ 7.57 (d, J = 8.0 Hz, 1H), 7.28ꢀ
3-(1-Methyl-1H-indol-3-yl)-1-phenyl-butan-1-one (3aj). 10 h,
45 60% yield; H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 7.2 Hz,
2H), 7.67ꢀ7.65 (m, 1H), 7.55ꢀ7.51 (m, 1H), 7.45ꢀ7.41 (m, 2H),
1
7.29ꢀ7.27 (m, 1H), 7.24ꢀ7.20 (m, 1H), 7.12ꢀ7.08 (m, 1H), 6.88 (s, 105 7.19 (m, 2H), 7.12ꢀ7.08 (m, 1H), 6.82 (s, 1H), 3.70 (s, 3H), 3.03
1H), 3.81 (m, 1H), 3.73 (s, 3H), 3.34 (ddd, J = 5.2, 18.8, 89.4 Hz,
2H), 1.43 (d, J = 6.8 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3):
50 δ 199.7, 137.3, 137.2, 132.9, 128.5, 128.1, 126.6, 125.0, 121.5,
120.0, 119.3, 118.6, 109.3, 46.6, 32.6, 29.7, 27.0, 21.1 ppm. ESI
HRMS: calcd. for C19H19NO+Na 300.1364, found 300.1366.
3-(1-Methyl-1H-indol-3-yl)-1-naphthalen-2-yl-3-phenyl-
(t, J = 7.6 Hz, 2H), 2.79 (t, J = 7.6 Hz, 2H), 2.39 (q, J = 7.2 Hz,
2H), 1.03 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3):
δ 211.3, 136.9, 127.5, 126.3, 121.5, 118.7, 118.6, 113.7, 109.1,
42.9, 35.9, 32.5, 19.2, 7.7 ppm. ESI HRMS: calcd. for
110 C14H17NO+Na 238.1208, found 238.1210.
4-(1-Methyl-1H-indol-3-yl)-pentan-2-one (3aq). 8 h, 71% yield;
1H NMR (400 MHz, CDCl3): δ 7.64ꢀ7.62 (m, 1H), 7.29ꢀ7.27 (m,
1H), 7.24ꢀ7.20 (m, 1H), 7.12ꢀ7.09 (m, 1H), 6.82 (s, 1H), 3.72 (s,
3H), 3.65ꢀ3.60 (m, 1H), 2.81 (ddd, J = 6.0, 19, 86.6 Hz, 2H), 2.09
propan-1-one (3ak). 12 h, 96% yield; 1H NMR (400 MHz,
55 DMSO): δ 8.79 (s, 1H), 8.13 (d, J = 7.6 Hz, 1H), 7.97ꢀ7.95 (m,
3H), 7.68ꢀ7.60 (m, 2H), 7.49ꢀ7.43 (m, 3H), 7.35ꢀ7.33 (m, 2H),
7.25ꢀ7.21 (m, 2H), 7.11ꢀ7.08 (m, 2H), 6.96ꢀ6.92 (m, 1H), 4.94 (t, 115 (s, 3H), 1.37 (d, J = 6.8 Hz, 3H) ppm; 13C NMR (100 MHz,
J = 7.2 Hz, 1H), 4.01 (ddd, J = 7.2, 20.8, 32.8 Hz, 2H), 3.71 (s,
CDCl3): δ 208.6, 137.1, 126.5, 124.9, 121.5, 119.4, 119.1, 118.6,
This journal is © The Royal Society of Chemistry [year]
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DOI: 10.1039/C4OB02124J
109.3, 51.6, 32.5, 30.3, 26.9, 21.4 ppm. ESI HRMS: calcd. for
C14H17NO+Na 238.1208, found 238.1205.
3-(5-Bromo-1-methyl-1H-indol-3-yl)-1,3-diphenyl-propan-1-
60 one (3ea). 8 h, 80% yield; 1H NMR (400 MHz, CDCl3): δ 7.91 (d,
J = 7.6 Hz, 2H), 7.54ꢀ7.50 (m, 2H), 7.43ꢀ7.39 (m, 2H), 7.33ꢀ7.31
(m, 2H), 7.27ꢀ7.22 (m, 2H), 7.20ꢀ7.16 (m, 2H), 7.08ꢀ7.05 (m, 1H),
6.83 (s, 1H), 4.98 (t, J = 7.6 Hz, 1H), 3.72 (ddd, J = 7.2, 20.4,
27.6 Hz, 2H), 3.63 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ
4-Methyl-3-(1-methyl-1H-indol-3-yl)-phenol (3ar). 12 h, 42%
1
yield; H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.0 Hz, 1H),
5
7.52ꢀ7.50 (m, 1H), 7.43ꢀ7.38 (m, 1H), 7.32ꢀ7.26 (m, 2H), 7.16 (s,
1H), 7.05ꢀ7.04 (m, 1H), 6.89ꢀ6.86 (m, 1H), 5.23 (s, 1H), 3.93 (s,
3H), 2.20 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 153.3, 65 198.1, 143.9, 136.9, 135.9, 133.0, 128.5, 128.4, 128.0, 127.6,
136.6, 135.6, 131.3, 128.6, 127.6, 127.3, 121.7, 120.2, 119.4,
117.4, 115.6, 113.4, 109.3, 32.8, 19.8 ppm. ESI HRMS: calcd. for
127.3, 126.4, 124.4, 121.9, 117.3, 112.2, 110.7, 45.2, 37.8, 32.8
ppm. ESI HRMS: calcd. for C24H20BrNO+Na 440.0626 found
C24H2079BrNNaO 440.0626, C24H2081BrNNaO 442.0608.
10 C16H15NO+Na 260.1051, found 260.1048.
3-(1H-Indol-3-yl)-cyclohexanone (3as). 4 h, 33% yield; 1H
3-(6-Methoxy-1-methyl-1H-indol-3-yl)-1,3-diphenyl-propan-
1
NMR (400 MHz, CDCl3): δ 7.63 (d, J = 7.6 Hz, 1H), 7.32ꢀ7.30 70 1-one (3fa). 8 h, 86% yield; H NMR (400 MHz, CDCl3): δ 7.92
(m, 1H), 7.27ꢀ7.23 (m, 1H), 7.14ꢀ7.11 (m, 1H), 6.84 (s, 1H), 3.76
(s, 3H), 3.49ꢀ3.44 (m, 1H), 2.82ꢀ2.81 (m, 1H), 2.66ꢀ2.60 (m, 1H),
15 2.50ꢀ2.37 (m, 2H), 2.27ꢀ2.24 (m, 1H), 2.09ꢀ2.02 (m, 1H), 1.99ꢀ
1.93 (m, 1H), 1.88ꢀ1.82 (m, 1H) ppm; 13C NMR (100 MHz,
(d, J = 7.2 Hz, 2H), 7.53ꢀ7.49 (m, 1H), 7.42ꢀ7.38 (m, 2H), 7.35ꢀ
7.33 (m, 2H), 7.28ꢀ7.22 (m, 3H), 7.16ꢀ7.12 (m, 1H), 6.71ꢀ6.65 (m,
3H), 5.00 (t, J = 7.2 Hz, 1H), 3.82 (s, 3H), 3.74 (ddd, J = 6.8,
20.2, 27.4 Hz, 2H), 3.62 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3): δ 211.8, 170.6, 137.0, 126.4, 125.2, 121.7, 119.0, 118.8, 75 CDCl3): δ 198.5, 156.3, 144.4, 138.0, 137.0, 132.9, 128.5, 128.4,
118.1, 109.3, 48.1, 41.5, 35.8, 32.6, 31.8, 24.8 ppm. ESI HRMS:
calcd. for C15H17NO+Na 250.1208, found 250.1196.
128.0, 127.7, 126.2, 125.0, 121.4, 120.2, 117.7, 108.6, 92.73,
55.60, 45.3, 38.1, 32.6 ppm. ESI HRMS: calcd. for
C25H23NO2+Na 392.1626 found 392.1621.
20 3-(1-methyl-1H-indol-3-yl)cyclopentanone (3at).
4
h, 66%
1
yield; H NMR (400 MHz, CDCl3): δ 7.57 (d, J = 8.0 Hz, 1H),
3-(7-Methoxy-1-methyl-1H-indol-3-yl)-1,3-diphenyl-propan-
7.28ꢀ7.26 (m, 1H), 7.22ꢀ7.19 (m, 1H), 7.10ꢀ7.06 (m, 1H), 6.78 (s, 80 1-one (3ga). 8 h, 91% yield; 1H NMR (400 MHz, CDCl3): δ 7.86
1H), 3.70 (s, 3H), 3.66ꢀ3.64 (m, 1H), 2.73ꢀ2.66 (m, 1H), 2.49ꢀ
2.44 (m, 1H), 2.43ꢀ2.34 (m, 2H), 2.31ꢀ2.22 (m, 1H), 2.12ꢀ2.04 (m,
25 1H) ppm; 13C NMR (75 MHz, DMSO): δ 218.3, 136.9, 126.8,
125.6, 121.2, 118.9, 118.4, 116.5, 109.7, 44.9, 37.9, 33.1, 32.3,
(d, J = 7.2 Hz, 2H), 7.49ꢀ7.45 (m, 2H), 7.37ꢀ7.34 (m, 4H), 7.24ꢀ
7.19 (m, 3H), 7.14ꢀ7.07 (m, 2H), 7.00ꢀ6.96 (m, 1H), 5.12 (t, J =
7.2 Hz, 1H), 3.93 (ddd, J = 7.6, 17.2, 20 Hz, 2H), 3.58 (s, 3H),
2.41 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 199.0, 144.4,
29.7 ppm. ESI HRMS: calcd. For C14H15NO+Na 236.1051, found 85 137.1, 136.8, 133.6, 132.8, 128.4, 128.2, 128.0, 127.5, 126.4,
236.1042.
125.8, 120.2, 119.1, 118.7, 112.9, 108.7, 43.7, 37.0, 29.4, 10.5
ppm. ESI HRMS: calcd. for C25H23NO2+Na 392.1626 found
392.1619.
3-(4-Bromo-1-methyl-1H-indol-3-yl)-1,3-diphenyl-propan-1-
30 one (3ba). 10 h, 70% yield; H NMR (400 MHz, CDCl3): δ 7.96
1
(d, J = 7.6 Hz, 2H), 7.56ꢀ7.53 (m, 1H), 7.46ꢀ7.42 (m, 2H), 7.39ꢀ
7.37 (m, 2H), 7.32ꢀ7.25 (m, 3H), 7.22ꢀ7.20 (m, 2H), 7.05ꢀ7.00 (m, 90 20 h, 60% yield; H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 7.6
1,3-diphenyl-3-(1-phenyl-1H-indol-3-yl)propan-1-one (3ha).
1
1H), 6.74 (s, 1H), 5.82 (t, J = 7.2 Hz, 1H), 3.82 (ddd, J = 5.6,
20.4, 27.2 Hz, 2H), 3.67 (s, 3H) ppm; 13C NMR (100 MHz,
35 CDCl3): δ 197.9, 144.3, 138.5, 137.0, 132.9, 128.5, 128.3, 128.1,
128.0, 126.1, 124.8, 123.8, 122.4, 118.8, 114.3, 108.5, 46.7, 36.9,
Hz, 2H), 7.58ꢀ7.54 (m, 3H), 7.53ꢀ7.44 (m, 8H), 7.37ꢀ7.30 (m,
3H), 7.26ꢀ7.20 (m, 3H), 7.13ꢀ7.09 (m, 1H), 5.18 (t, J = 7.2 Hz,
1H), 3.86 (ddd, J = 6.4, 20.4, 22.8 Hz, 2H) ppm; 13C NMR (100
MHz, CDCl3): δ 198.3, 143.9, 139.7, 137.0, 136.3, 132.9, 129.5,
32.9 ppm. ESI HRMS: calcd. for C24H20BrNO+Na 440.0626, 95 128.5, 128.4, 128.0, 127.8, 126.4, 126.2, 125.2, 124.1, 122.6,
found C24H2079BrNNaO 440.0620, C24H2081BrNNaO 442.0612.
3-(1,4-Dimethyl-1H-indol-3-yl)-1,3-diphenyl-propan-1-one
40 (3ca). 8 h, 79% yield; 1H NMR (400 MHz, CDCl3): δ 7.97 (d, J =
8.0 Hz, 2H), 7.59ꢀ7.55 (m, 1H), 7.48ꢀ7.45 (m, 2H), 7.31ꢀ7.25 (m,
120.3, 120.0, 119.8, 110.5, 45.1, 38.0 ppm. ESI HRMS: calcd. for
C29H23NO+Na 424.1677, found 424.1674.
3-(1-Methyl-2-phenyl-1H-indol-3-yl)-1,3-diphenyl-propan-1-
1
one (3ia). 14 h, 73% yield; H NMR (400 MHz, CDCl3): δ 7.86
4H), 7.19ꢀ7.14 (m, 1H), 7.12ꢀ7.08 (m, 2H), 6.86 (s, 1H), 6.79 (d, 100 (d, J = 7.6Hz, 2H), 7.72 (d, J = 7.6 Hz, 1H), 7.54ꢀ7.48 (m, 4H),
J = 6.4 Hz, 1H), 5.45 (t, J = 7.2 Hz, 1H), 3.74 (ddd, J = 6.8, 24.6,
33 Hz, 2H), 3.72 (s, 3H), 2.57 (s, 3H) ppm; 13C NMR (100 MHz,
45 CDCl3): δ 198.2, 145.4, 137.6, 137.1, 133.0, 131.2, 128.6, 128.4,
128.0, 127.9, 126.5, 126.1, 125.8, 121.7, 120.8, 118.1, 107.0,
7.41ꢀ7.36 (m, 7H), 7.30ꢀ7.25 (m, 3H), 7.20ꢀ7.14 (m, 2H), 5.07 (t,
J = 7.2 Hz, 1H), 3.92 (ddd, J = 7.2, 15.6, 20.4 Hz, 2H), 3.56 (s,
3H) ppm; 13C NMR (100 MHz, CDCl3): δ 198.4, 144.6, 138.3,
137.3, 136.8, 132.7, 131.8, 130.8, 128.3, 128.2, 128.0, 127.5,
47.1, 38.6, 32.8, 20.7 ppm. ESI HRMS: calcd. for C25H23NO+Na 105 126.4, 125.7, 121.4, 120.1, 119.2, 114.6, 109.5, 44.2, 37.5, 30.6
376.1677, found 376.1680.
ppm. ESI HRMS: calcd. for C30H25NO+Na 438.1834 found
438.1833.
3-(5-Methoxy-1-methyl-1H-indol-3-yl)-1,3-diphenyl-propan-
50 1-one (3da). 8 h, 96% yield; 1H NMR (400 MHz, CDCl3): δ 7.97
(d, J = 7.6 Hz, 2H), 7.58ꢀ7.54 (m, 1H), 7.47ꢀ7.43 (m, 2H), 7.41ꢀ
3-(1H-Indol-3-yl)-1,3-diphenyl-propan-1-one (5aa). 12 h, 90%
1
yield; H NMR (400 MHz, DMSO): δ 10.9 (s, 1H), 8.03 (d, J =
7.39 (m, 2H), 7.31ꢀ7.26 (m, 2H), 7.21ꢀ7.15 (m, 2H), 6.89ꢀ6.83 (m, 110 7.2 Hz, 2H), 7.63ꢀ7.61 (m, 1H), 7.54ꢀ7.50 (m, 2H), 7.46ꢀ7.42 (m,
3H), 5.05 (t, J = 7.2 Hz, 1H), 3.81 (ddd, J = 6.8, 20.2, 29.2 Hz,
2H), 3.77 (s, 3H), 3.69 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3):
55 δ 198.5, 153.5, 144.3, 137.0, 132.9, 132.6, 128.5, 128.4, 128.0,
127.7, 127.2, 126.7, 126.2, 117.2, 111.7, 109.9, 101.4, 55.8, 45.2,
3H), 7.38ꢀ7.33 (m, 2H), 7.26ꢀ7.22 (m, 2H), 7.13ꢀ7.12 (m, 1H),
7.06ꢀ7.03 (m, 1H), 6.93ꢀ6.90 (m, 1H), 4.90 (t, J = 6.4 Hz, 1H),
3.90 (ddd, J = 6.8, 20, 40.8 Hz, 2H) ppm; 13C NMR (100 MHz,
DMSO): δ 214.7, 198.6, 145.5, 137.1, 136.6, 133.3, 128.9, 128.3,
37.9, 32.8 ppm. ESI HRMS: calcd. for C25H23NO2+Na 392.1626, 115 128.0, 126.6, 126.0, 122.1, 121.2, 118.9, 118.5, 118.2, 111.6,
found 392.1633.
6
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DOI: 10.1039/C4OB02124J
44.5, 37.9 ppm. ESI HRMS: calcd. for C23H19NO+Na 348.1364,
found 348.1365.
3H), 7.62ꢀ7.58 (m, 2H), 7.54ꢀ7.50 (m, 2H), 7.48ꢀ7.43 (m, 2H),
60 7.34ꢀ7.32 (m, 1H), 7.06ꢀ7.03 (m, 1H), 6.94ꢀ6.90 (m, 1H), 4.99 (s,
1H), 3.97 (ddd, J = 6.8, 21.2, 24.4 Hz, 2H) ppm; 13C NMR (100
MHz, DMSO): δ 198.3, 150.4, 136.9, 136.5, 133.4, 128.9, 128.8,
128.3, 126.4, 125.2, 125.2, 122.4, 121.3, 118.7, 118.7, 117.4,
111.6, 44.0, 37.6 ppm. ESI HRMS: calcd. for C24H18F3NO+Na
3-(2-Chloro-phenyl)-3-(1H-indol-3-yl)-1-phenyl-propan-1-one
1
(5ab). 12 h, 93% yield; H NMR (400 MHz, DMSO): δ 10.93 (s,
5
1H), 8.03 (d, J = 7.2 Hz, 2H), 7.65ꢀ7.62 (m, 1H), 7.54ꢀ7.50 (m,
2H), 7.46ꢀ7.42 (m, 3H), 7.34ꢀ7.30 (m, 2H), 7.23ꢀ7.15 (m, 2H),
7.07ꢀ7.03 (m, 1H), 6.94ꢀ6.91 (m, 1H), 5.38 (t, J = 7.2 Hz, 1H), 65 416.1238, found 416.1240.
4.02 (dd, J = 7.2, 16.8 Hz, 1H), 3.72 (dd, J = 6.4, 17.6 Hz, 1H)
3-(1H-Indol-3-yl)-3-naphthalen-1-yl-1-phenyl-propan-1-one
ppm; 13C NMR (100 MHz, DMSO): δ 203.1, 147.4, 141.8, 141.4,
(5ah). 12 h, 87% yield; 1H NMR (400 MHz, CDCl3): δ 8.35ꢀ8.33
(m, 1H), 7.97ꢀ7.95 (m, 2H), 7.90ꢀ7.87 (m, 2H), 7.75ꢀ7.73 (m, 1H),
7.58ꢀ7.54 (m, 1H), 7.50ꢀ7.44 (m, 5H), 7.42ꢀ7.33 (m, 2H), 7.29ꢀ
10 138.3, 137.7, 134.5, 134.4, 133.8, 133.2, 132.7, 132.3, 131.5,
127.8, 127.7, 126.3, 123.6, 121.8, 116.6, 48.8, 39.9 ppm. ESI
HRMS: calcd. for C23H18ClNO+Na 382.0975, found 70 7.26 (m, 1H), 7.17ꢀ7.14 (m, 1H), 7.04ꢀ7.00 (m, 1H), 6.77ꢀ6.76 (m,
C23H1835ClNNaO 382.0960, C23H1837ClNNaO 384.0944.
1H), 5.97 (t, J = 6.8 Hz, 1H), 3.89 (ddd, J = 8.0, 21.2, 77.2 Hz,
2H) ppm; 13C NMR (100 MHz, CDCl3): δ 198.5, 139.9, 137.0,
136.6 ,134.0, 133.1, 131.4, 128.8, 128.6, 128.0, 127.0, 126.6,
126.1, 125.5, 125.3, 124.3, 123.6, 122.2, 122.0, 119.4, 119.3,
3-(3-Chloro-phenyl)-3-(1H-indol-3-yl)-1-phenyl-propan-1-one
1
15 (5ac). 12 h, 90% yield; H NMR (400 MHz, CDCl3): δ 8.08 (s,
1H), 7.95 (d, J = 7.6 Hz, 2H), 7.58ꢀ7.55 (m, 1H), 7.47ꢀ7.43 (m,
3H), 7.35ꢀ7.30 (m, 2H), 7.28ꢀ7.26 (m, 1H), 7.21ꢀ7.14 (m, 3H), 75 118.9, 111.1, 44.6, 33.2 ppm. ESI HRMS: calcd. for
7.08ꢀ7.04 (m, 1H), 6.95ꢀ6.94 (m, 1H), 5.07 (t, J = 7.2 Hz, 1H),
3.77 (ddd, J = 6.4, 20.4, 44.4 Hz, 2H) ppm; 13C NMR (100 MHz,
20 CDCl3): δ 198.2, 146.4, 136.8, 136.5, 134.1, 133.2, 129.6, 128.6,
128.0, 127.9, 126.5, 126.3, 126.1, 122.2, 121.4, 119.5, 119.2,
C27H21NO+Na 398.1521, found 398.1530.
3-(1H-indol-3-yl)-1-phenyl-3-(thiophen-2-yl)propan-1-one
1
(5ai). 48 h, 40% yield; H NMR (400 MHz, DMSO): δ 10.92 (s,
1H), 8.02 (d, J = 7.2Hz, 2H), 7.64ꢀ7.60 (m, 1H), 7.51 (t, J = 7.2
118.4, 111.2, 44.8, 37.8 ppm. ESI HRMS: calcd. for 80 Hz, 3H), 7.35ꢀ7.33 (m, 2H), 7.23ꢀ7.22 (m, 1H), 7.08ꢀ7.04 (m,
C23H18ClNO+Na 382.0975, found C23H1835ClNNaO 382.0967,
C23H1837ClNNaO 384.0947.
1H), 7.00ꢀ6.99 (m, 1H), 6.95 (t, J = 7.2 Hz, 1H), 6.88ꢀ6.86 (m,
1H), 5.20 (t, J = 7.2 Hz, 1H), 3.92 (d, J = 7.2 Hz, 2H) ppm; 13C
NMR (100 MHz, DMSO): δ 198.2, 149.9, 136.9, 136.6, 133.4,
128.9, 128.3, 126.7, 126.3, 124.1, 123.8, 122.4, 121.3, 118.9,
25 3-(4-chlorophenyl)-3-(1H-indol-3-yl)-1-phenylpropan-1-one
1
(5ad). 12 h, 87% yield; H NMR (400 MHz, DMSO): δ 10.91 (s,
1H), 8.02 (d, J = 7.6 Hz, 2H), 7.63ꢀ7.60 (m, 1H), 7.52ꢀ7.48 (m, 85 118.7, 117.9, 111.7, 45.4, 32.9 ppm. ESI HRMS: calcd. for
2H), 7.44ꢀ7.42 (m, 3H), 7.38 (s, 1H), 7.33ꢀ7.31 (m, 1H), 7.28ꢀ
7.26 (m, 2H), 7.04 (t, J = 7.2 Hz, 1H), 6.90 (t, J = 7.6 Hz, 1H),
30 4.89 (t, J = 7.2 Hz, 1H), 3.89 (ddd, J = 6.8, 20.8, 35.2 Hz, 2H)
ppm; 13C NMR (100 MHz, DMSO): δ 198.4, 144.5, 137.0, 136.6,
C21H17NOS+Na 354.0929, found 354.0930.
3-(1H-Indol-3-yl)-1-naphthalen-2-yl-3-phenyl-propan-1-one
1
(5ak). 11 h, 80% yield; H NMR (400 MHz, DMSO): δ 10.89 (s,
1H), 8.81 (s, 1H), 8.14 (d, J = 8.0 Hz, 1H), 7.98ꢀ7.07 (m, 3H),
133.4, 130.5, 129.9, 128.9, 128.3, 128.2, 126.4, 122.2, 121.3, 90 7.68ꢀ7.60 (m, 2H), 7.47ꢀ7.45 (m, 3H), 7.39 (m, 1H), 7.34ꢀ7.32 (m,
118.8, 118.6, 117.8, 111.6, 44.2, 37.2 ppm. ESI HRMS: calcd. for
C23H18ClNO+Na 382.0975, found C23H1835ClNNaO 382.0967,
35 C23H1837ClNNaO 384.0940.
1H), 7.24 (t, J = 7.2 Hz, 2H), 7.11 (t, J = 7.2Hz, 1H), 7.06ꢀ7.02
(m, 1H), 6.93ꢀ6.89 (m, 1H), 4.97 (t, J = 7.2Hz, 1H), 4.02 (ddd, J
= 7.2, 20.8, 66.8 Hz, 2H) ppm; 13C NMR (100 MHz, DMSO): δ
198.5, 145.5, 136.6, 135.2, 134.4, 132.4, 130.3, 129.8, 128.8,
3-(4-Bromo-phenyl)-3-(1H-indol-3-yl)-1-phenyl-propan-1-one
1
(5ae). 14 h, 90% yield; H NMR (400 MHz, DMSO): δ 10.91 (s, 95 128.4, 128.3, 128.0, 127.8, 127.1, 126.6, 126.0, 123.8, 122.1,
1H), 8.02ꢀ8.00 (m, 2H), 7.63ꢀ7.60 (m, 1H), 7.52ꢀ7.48 (m, 2H),
7.43ꢀ7.31 (m, 7H), 7.03 (t, J = 7.2 Hz, 1H), 6.90 (t, J = 7.2Hz,
40 1H), 4.87 (t, J = 5.6 Hz, 1H), 3.88 (ddd, J = 6.4, 20.4, 33.6 Hz,
2H) ppm; 13C NMR (100 MHz, DMSO): δ 198.4, 145.0, 137.0,
121.2, 118.9, 118.5, 118.2, 111.6, 44.4, 38.0 ppm. ESI HRMS:
calcd. for C27H21NO+Na 398.1521, found 398.1511.
1-Furan-2-yl-3-(1H-indol-3-yl)-3-phenyl-propan-1-one (5al).
1
16 h, 73% yield; H NMR (400 MHz, DMSO): δ 10.88 (s, 1H),
136.6, 133.4, 131.1, 130.3, 128.9, 128.3, 126.4, 122.2, 121.3, 100 7.95 (s, 1H), 7.60ꢀ7.59 (m, 1H), 7.43ꢀ7.38 (m, 3H), 7.33ꢀ7.30 (m,
119.0, 118.8, 118.6, 117.8, 111.6, 44.2, 37.2 ppm. ESI HRMS:
calcd. for C23H18BrNO+Na 426.0469, found C23H1879BrNNaO
45 426.0483, C23H1881BrNNaO 428.3361.
2H), 7.24ꢀ7.20 (m, 2H), 7.12ꢀ7.08 (m, 1H), 7.04ꢀ7.00 (m, 1H),
6.91ꢀ6.88 (m, 1H), 6.69ꢀ6.68 (m, 1H), 4.85 (s, 1H), 3.64 (ddd, J =
6.4, 19.6, 60 Hz, 2H) ppm; 13C NMR (100 MHz, DMSO): δ
186.9, 152.4, 148.1, 148.0, 145.1, 136.5, 128.4, 127.9, 126.5,
3-(1H-indol-3-yl)-3-(4-methoxyphenyl)-1-phenylpropan-1-one
1
(5af). 26 h, 63% yield; H NMR (400 MHz, CDCl3): δ 8.00 (s, 105 126.1, 122.1, 122.1, 121.3, 119.3, 118.9, 118.6, 117.8, 112.7,
1H), 7.91 (d, J = 7.6 Hz, 2H), 7.51ꢀ7.49 (m, 1H), 7.42ꢀ7.48 (m,
3H), 7.27ꢀ7.22 (m, 3H), 7.13ꢀ7.09 (m, 1H), 7.01ꢀ6.98 (m, 1H),
50 6.90 (s, 1H), 6.77 (d, J = 8.4 Hz, 2H), 5.00 (t, J = 7.2 Hz, 1H),
3.71 (ddd, J = 6.4, 20, 30 Hz, 2H), 3.70 (s, 3H) ppm; 13C NMR
112.7, 111.6, 44.2, 38.0 ppm. ESI HRMS: calcd. for
C21H17NO2+Na 338.1157, found 338.1157.
5-(1H-Indol-3-yl)-1,5-diphenyl-pent-1-en-3-one (5an). 12 h,
1
62% yield; H NMR (400 MHz, DMSO): δ 10.88 (s, 1H), 7.69ꢀ
(100 MHz, CDCl3): δ 198.8, 157.8, 137.0, 136.6, 136.3, 133.0, 110 7.67 (m ,2H), 7.63 (s, 1H), 7.43ꢀ7.38 (m, 6H), 7.33ꢀ7.30 (m, 2H),
128.7, 128.5, 128.0, 126.5, 122.0, 121.3, 119.5, 119.4, 119.2,
113.7, 111.1, 55.1, 45.3, 37.4 ppm. ESI HRMS: calcd. for
55 C24H21NO2+Na 378.1470, found 378.1466.
7.25ꢀ7.22 (m, 2H), 7.13ꢀ7.09 (m, 1H), 7.05ꢀ7.01 (m, 1H), 6.96 (s,
1H), 6.92ꢀ6.88 (m, 1H), 4.84 (t, J = 7.6 Hz, 1H), 3.52 (ddd, J =
7.6, 20, 66.4 Hz, 2H) ppm; 13C NMR (100 MHz, DMSO): δ
198.7, 145.4, 142.4, 136.6, 134.7, 130.6, 129.1, 128.6, 128.3,
3-(1H-indol-3-yl)-1-phenyl-3-(4-(trifluoromethyl)phenyl)
propan-1-one (5ag). 26 h, 70% yield; 1H NMR (400 MHz, 115 127.9, 126.9, 126.6, 126.0, 122.1, 121.2, 118.9, 118.4, 118.0,
DMSO): δ 10.96 (s, 1H), 8.04 (d, J = 7.6 Hz, 2H), 7.67ꢀ7.65 (m,
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DOI: 10.1039/C4OB02124J
111.6, 46.5, 38.0 ppm. ESI HRMS: calcd. for C25H21NO+Na
374.1521, found 374.1514.
7.30ꢀ7.25 (m, 1H), 6.23 (s, 1H), 5.2 (dd, J = 5.2, 8.4 Hz, 1H),
60 4.49 (q, J = 8.8 Hz, 1H) 3.64 (dd, J = 4.8, 17.6 Hz, 1H) ppm; 13
C
2-(1H-Indol-3-yl)-1,4-diphenyl-butane-1,4-dione (5ao). 12 h,
99% yield; 1H NMR (400 MHz, CDCl3): δ 8.27 (s, 1H), 8.04ꢀ8.02
(m, 2H), 7.95ꢀ7.93 (m, 2H), 7.77ꢀ7.75 (m, 1H), 7.53ꢀ7.49 (m, 1H),
7.43ꢀ7.37 (m, 3H), 7.32ꢀ7.27 (m, 3H), 7.22ꢀ7.14 (m, 2H), 6.92 (s,
NMR (100 MHz, CDCl3): δ 196.6, 140.7, 139.2, 136.4, 133.3,
129.7, 128.8, 128.6, 128.2, 127.9, 126.6, 105.5, 60.7, 44.1 ppm.
ESI HRMS: calcd. for C18H16N2O+Na 299.1160, found 299.1154.
3-(1-methyl-1H-pyrrol-2-yl)-1,3-diphenylpropan-1-one (7a). 8
5
1H), 5.58 (dd, J = 3.2, 10.4 Hz, 1H), 4.24 (dd, J = 10.4, 18.4 Hz, 65 h, 33% yield; 1H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 7.2 Hz,
1H) 3.40 (dd, J = 3.6, 18.4 Hz, 1H) ppm; 13C NMR (100 MHz,
CDCl3): δ 199.2, 198.8, 136.4, 136.4, 133.2, 132.7, 128.7, 128.5,
2H), 7.57ꢀ7.55 (m, 1H), 7.46ꢀ7.42 (m, 2H), 7.28ꢀ7.17 (m, 5H),
6.54 (s, 1H), 6.08 (s, 2H), 4.81 (t, J = 7.2 Hz, 1H), 3.80 (dd, J =
7.2, 17.2 Hz, 1H), 3.50 (dd, J = 7.2, 17.2 Hz, 1H), 3.38 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3): δ 197.8, 143.2, 137.0, 134.3,
70 133.0, 128.6, 128.5, 128.0, 127.9, 126.4, 121.9, 106.3, 105.6,
45.5, 38.2, 33.9 ppm. ESI HRMS: calcd. for C20H19NO+Na
312.1364, found 312.1365.
10 128.4, 128.1, 125.9, 122.8, 122.4, 119.9, 118.6, 112.9, 111.5,
42.8, 39.6 ppm. ESI HRMS: calcd. for C24H19NO2+Na 376.1313,
found 376.1311.
1-(1H-Indol-3-yl)-pentan-3-one (5ap). 12 h, 91% yield; 1H
NMR (400 MHz, DMSO): δ 10.77 (s, 1H), 7.53ꢀ7.51 (m, 1H),
15 7.35ꢀ7.33 (m, 1H), 7.09ꢀ7.05 (m, 2H), 6.99ꢀ6.96 (m, 1H), 2.90 (t,
J = 7.2Hz, 2H), 2.80 (t, J = 7.2 Hz, 2H), 2.45 (q, J = 7.2 Hz, 2H),
3-(1-methyl-1H-pyrrol-3-yl)-1,3-diphenylpropan-1-one (7b). 8
1
h, 6% yield; H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 7.6 Hz,
0.93 (s, 3H) ppm; 13C NMR (100 MHz, DMSO): δ 210.9, 136.5, 75 2H), 7.55ꢀ7.51 (m, 1H), 7.45ꢀ7.41 (m, 2H), 7.32ꢀ7.30 (m, 3H),
127.2, 122.4, 121.2, 118.5, 118.4, 113.8, 111.5, 42.4, 35.2, 19.3,
7.8 ppm. ESI HRMS: calcd. for C13H15NO+Na 224.1051, found
20 224.1044.
7.28ꢀ7.26 (m, 1H), 7.18ꢀ7.14 (m, 1H), 6.48 (s, 1H), 6.32 (s, 1H),
5.97 (s, 1H), 4.69 (t, J = 7.2 Hz, 1H), 3.62 (ddd, J = 7.2, 20.3,
34.4 Hz, 2H), 2.56 (s, 3H) ppm. ESI HRMS: calcd. for
C20H19NO+Na 312.1364, found 312.1364.
4-(1H-Indol-3-yl)-pentan-2-one (5aq). 12 h, 76% yield; 1H
NMR (400 MHz, CDCl3): δ 8.05 (s, 1H), 7.64 (d, J = 8.0 Hz, 1H), 80 (3R,3'S)-3,3'-(1-methyl-1H-pyrrole-2,5-diyl)bis(1,3-
7.33ꢀ7.32 (m, 1H), 7.20ꢀ7.16 (m, 1H), 7.13ꢀ7.09 (m, 1H), 6.93 (s,
1H), 3.66ꢀ3.60 (m, 1H), 2.81 (ddd, J = 6.0, 18.8, 86.4 Hz, 2H),
25 2.08 (s, 3H), 1.37 (d, J = 6.8 Hz, 3H) ppm; 13C NMR (100 MHz,
CDCl3): δ 208.8, 136.4, 126.2, 121.9, 120.8, 120.1, 119.1, 119.0,
diphenylpropan-1-one) (7c). 8 h, 16% yield; 1H NMR (400
MHz, CDCl3): δ 7.90 (d, J = 7.2 Hz, 4H), 7.55ꢀ7.52 (m, 2H),
7.44ꢀ7.41 (m, 4H), 7.27ꢀ7.23 (m, 4H), 7.18ꢀ7.14 (m, 6H), 6.04 (s,
2H), 4.71 (t, J = 7.2 Hz, 2H), 3.61 (ddd, J = 6.4, 20.4, 91.6 Hz,
111.3, 51.4, 30.4, 26.9, 21.2 ppm. ESI HRMS: calcd. for 85 4H), 3.05 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 197.9,
C13H15NO+Na 224.1051, found 224.1042.
143.3, 137.1, 134.4, 132.9, 128.5, 128.4, 127.9, 127.8, 126.4,
104.2, 45.4, 38.6, 30.6 ppm. ESI HRMS: calcd. for
C35H31NO2+Na 520.2252, found 520.2250.
3-(1H-Indol-3-yl)-cyclohexanone (5as). 16 h, 41% yield; 1H
30 NMR (400 MHz, CDCl3): δ 8.18 (s, 1H), 7.66 (d, J = 8.0 Hz, 1H),
7.39 (d, J = 8.0 Hz, 1H), 7.27ꢀ7.22 (m, 1H), 7.18ꢀ7.14 (m, 1H),
(3R,3'R)-3,3'-(1-methyl-1H-pyrrole-2,5-diyl)bis(1,3-
6.98 (s, 1H), 3.51ꢀ3.44 (m, 1H), 2.86ꢀ2.81 (m, 1H), 2.69ꢀ2.63 (m, 90 diphenylpropan-1-one) (7d). 8 h, 17% yield; 1H NMR (400
1H), 2.53ꢀ2.39 (m, 2H), 2.31ꢀ2.27 (m, 1H), 2.11ꢀ1.95 (m, 2H),
1.91ꢀ1.81 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 212.0,
35 136.4, 126.0, 122.1, 120.3, 119.5, 119.3, 118.9, 111.3, 48.0, 41.5,
35.9, 31.6, 24.8 ppm. ESI HRMS: calcd. for C14H15NO+Na
236.1051, found 236.1043.
MHz, CDCl3): δ 7.92ꢀ7.90 (m, 4H), 7.55ꢀ7.52 (m, 2H), 7.44ꢀ7.41
(m, 4H), 7.26ꢀ7.15 (m, 4H), 7.11ꢀ7.09 (m, 6H), 6.00 (s, 2H), 4.75
(t, J = 7.2 Hz, 2H), 3.75 (dd, J = 7.2, 17.2 Hz, 2H), 3.43 (dd, J =
7.2, 17.2 Hz, 2H), 2.99 (s, 3H) ppm; 13C NMR (75 MHz, DMSO):
95 δ 197.8, 143.7, 136.7, 134.2, 133.2, 128.7, 128.2, 128.0, 127.7,
126.1, 104.2, 44.6, 37.9, 30.2 ppm. ESI HRMS: calcd. for
C35H31NO2+Na 520.2252, found 520.2258.
3-(1H-Indol-3-yl)-cyclopentanone (5at). 16 h, 51% yield; 1H
NMR (400 MHz, CDCl3): δ 8.15 (s, 1H), 7.64ꢀ7.62 (m, 1H),
40 7.38ꢀ7.36 (m, 1H), 7.24ꢀ7.20 (m, 1H), 7.16ꢀ7.20 (m, 1H), 6.96ꢀ
6.95 (m, 1H), 3.75ꢀ3.67 (m, 1H), 2.79ꢀ2.72 (m, 1H), 2.56ꢀ2.50 (m,
1H), 2.50ꢀ2.41 (m, 2H), 2.40ꢀ2.27 (m, 1H), 2.17ꢀ2.08 (m, 1H)
ppm; 13C NMR (100 MHz, CDCl3): δ 219.6, 136.6, 126.5, 122.2,
119.9, 119.4, 119.0, 118.4, 111.3, 45.2, 38.1, 33.6, 29.8 ppm. ESI
45 HRMS: calcd. for C13H13NO+Na 222.0895, found 222.0892.
3-(2-Methyl-1H-indol-3-yl)-1,3-diphenyl-propan-1-one (5ba).
Notes and references
100
105
110
115
1
(a) R. J. Sundberg, The Chemistry of Indoles, Academic Press, New
York, 1970; (b) E. C. Taylor, J. E. Saxton, The Chemistry of
Heterocyclic Compounds, ed. WileyꢀInterscience, New York, 1983 &
1994, vol. 25; (c) T. Kawasaki, K. Higuchi, Nat. Prod. Rep., 2005,
22, 761; (d) G. R. Humphrey, J. T. Kuethe, Chem. Rev., 2006, 106,
2875; (e) Nurullah Saracoglu, Top. Heterocycl. Chem., 2007, 11
(Bioactive Heterocycles V), 145; (f) M. Bandini, A. Eichholzer,
Angew. Chem., Int. Ed., 2009, 48, 9608.
1
16 h, 76% yield; H NMR (400 MHz, CDCl3): δ 7.86 (d, J = 7.2
Hz, 2H), 7.75 (s, 1H), 7.50ꢀ7.46 (m, 2H), 7.38ꢀ7.34 (m, 4H),
7.25ꢀ7.18 (m, 3H), 7.15ꢀ7.11 (m, 1H), 7.06ꢀ7.03 (m, 1H), 7.00ꢀ
50 6.96 (m, 1H), 5.08 (t, J = 6.8 Hz, 1H), 3.92 (ddd, J = 7.6, 24.8, 26
Hz, 2H), 2.36 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 199.1,
144.2, 137.1, 135.4, 132.9, 131.7, 128.4, 128.2, 128.0, 127.5,
127.4, 125.8, 120.6, 119.1, 119.1, 113.5, 110.4, 43.5, 36.7, 12.1
ppm. ESI HRMS: calcd. for C24H21NO+Na 362.1521, found
55 362.1508.
2
3
(a) E. M. Beck, M. J. Gaunt, Top. Curr. Chem., 2010, 292, 85; (b) M.
Zeng, S.ꢀL. You, Synlett, 2010, 1289; (c) Q. Kang, Z.ꢀA. Zhao, S.ꢀL.
You, J. Am. Chem. Soc., 2007, 129, 1484.
For selected examples, see: (a) L. Joucla, L. Djakovitch, Adv. Synth.
Catal., 2009, 351, 673; (b) D. R. Stuart, K. Fagnou, Science, 2007,
316, 1172; (c) W. Lu, C. Jia, T. Kitamura, Y. Fujiwara, Org. Lett.,
2000, 2, 2927; (d) D. R. Stuart, E. Villemure, K. Fagnou, J. Am.
Chem. Soc., 2007, 129, 12072; (e) T. A. Dwight, N. R. Rue, D.
Charyk, R. Josselyn, B. DeBoef, Org. Lett., 2007, 9, 3137; (f) B. S.
Lane, D. Sames, Org. Lett., 2004, 6, 2897; (g) B. B. Touré, B. S.
Lane, D. Same, Org. Lett., 2006, 8, 1979; (h) N. R. Deprez, D.
1,3-Diphenyl-3-(1H-pyrazol-4-yl)-propan-1-one (5ca). 10 h,
1
30% yield; H NMR (400 MHz, CDCl3): δ 7.97 (d, J = 7.6 Hz,
2H), 7.57ꢀ7.49 (m, 3H), 7.45ꢀ7.42 (m, 2H), 7.33ꢀ7.32 (m, 4H),
8
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DOI: 10.1039/C4OB02124J
Kalyani, A. Krause, M. S. Sanford, J. Am. Chem. Soc., 2006, 128,
16 For more details, see the Supporting Information.
4972; (i) X. Wang, D. V. Gribkov, D. Sames, J. Org. Chem., 2007,
72, 1476; (j) N. Lebrasseur, I. Larrosa, J. Am. Chem. Soc., 2008, 130,
2926; (k) J. Zhao, Y. Zhang, K. Cheng, J. Org. Chem., 2008, 73,
7428; (l) S.ꢀD. Yang, C.ꢀL. Sun, Z. Fang, B.ꢀJ. Li, Y.ꢀZ. Li, Z.ꢀJ. Shi,
Angew. Chem. Int. Ed., 2008, 47, 1473; (m) X. Wang, B. S. Lane, D.
Sames, J. Am. Chem. Soc., 2005, 127, 4996; (n) R. J. Phipps, N. P.
Grimster, M. J. Gaunt, J. Am. Chem. Soc., 2008, 130, 8172; (o) B. S.
Lane, M. A. Brown, D. Sames, J. Am. Chem. Soc., 2005, 127, 8050;
(p) L. Djakovitch, V. Dufaud, R. Zaidi, Adv. Synth. Catal., 2006, 348,
715; (q) T. Tsuchimoto, M. Iwabuchi, Y. Nagase, K. Oki, H.
Takahashi, Angew. Chem. Int. Ed., 2011, 50, 1375; (r) C. Bressy, D.
Alberico, M. Lautens, J. Am. Chem. Soc., 2005, 127, 13148.
5
10
15
20
25
30
35
4
5
(
a) Y. Yokoyama, T. Matsumoto, Y. Murakami, J. Org. Chem., 1995,
60, 1486; (b) C. Jia, W. Lu, T. Kitamura, Y. Fujiwara, Org. Lett.,
1999, 1, 2097; (c) A. Maehara, H. Tsurugi, T. Satoh, M. Miura, Org.
Lett., 2008, 10, 1159; (d) T. Itahara, K. Kawasaki, F. Ouseto,
Synthesis, 1984, 236; (e) L. Djakovitch, P. Rouge, J. Mol. Catal. A:
Chem., 2007, 273, 230.
(a) E. Capito, J. M. Brown, A. Ricci, Chem. Commun., 2005, 1854;
(b) A. GarcíaꢀRubia, R. G. Arrayás, J. C. Carretero, Angew. Chem.,
Int. Ed., 2009, 48, 6511; (c) A. GarcíaꢀRubia, B. Urones, R. G.
Arrayás, J. C. Carretero, Chem. Eur. J., 2010, 16, 9676.
N. P. Grimster, C. Gauntlett, C. R. A. Godfrey, M. J. Gaunt, Angew.
Chem., Int. Ed., 2005, 44, 3125.
Y. Nakao, K. S. Kanyiva, S. Oda, T. Hiyama, J. Am. Chem. Soc.,
2006, 128, 8146.
For the intramolecular a lkenylation, see: (a) G. Abbiati, E. M.
Beccalli, G. Broggini, C. Zoni, J. Org. Chem., 2003, 68, 7625; (b) A.
Kong, X. Han, X. Lu, Org. Lett., 2006, 8, 1339; (c) J. A. Schiffner, A.
B. Machotta, M. Oestreich, Synlett, 2008, 2271.
(a) W. E. Noland, G. M. Christensen, G. L. Sauer, G. G. S. Dutto, J.
Am. Chem. Soc., 1955, 77, 456; (b) J. Szmuszkovicz, J. Am. Chem.
Soc., 1957, 79, 2819; (c) J. F. Austin, D. W. C. MacMillan, J. Am.
Chem. Soc., 2004, 124, 1172; (d) J. Moran, T. Suen, A. M.
Beauchemin J. Org. Chem., 2006, 71, 676; (e) K. B. Jensen, J.
Thorhauge, R. G. Hazell, K. A. Jørgensen, Angew. Chem., Int. Ed.,
2001, 40, 160; (f) W.ꢀT. Wang, X.ꢀM. Feng, Chem. Eur. J., 2010, 16,
1664.
6
7
8
9
40 10 For some reviews, see: (a) C. Jia, T. Kitamura, Y. Fujiwara, Acc.
Chem. Res., 2001, 34, 633; (b) S. Beccalli, G. Broggini, M. Martinelli,
S. Sottocornola, Chem. Rev., 2007, 107, 5318; (c) L. Ackermann, R.
Vicente, A. R. Kapdi, Angew. Chem., Int. Ed., 2009, 48, 9792; (d) X.
Chen, K. M. Engle, D.ꢀH. Wang, J.ꢀQ. Yu, Angew. Chem., Int. Ed.,
45
50
55
60
65
70
2009, 48, 5094; (e) B.ꢀJ. Li, S.ꢀD. Yang, Z.ꢀJ. Shi, Synlett, 2008, 949;
(f) P. Thansandote, M. Lautens, Chem.Eur. J., 2009, 15, 5874; (g) T.
Kitamura, Eur. J. Org. Chem., 2009, 1111; (h) R. Giri, B.ꢀF. Shi, K.
M. Engle, N. Maugel, J.ꢀQ. Yu, Chem. Soc. Rev., 2009, 38, 3242; (i)
O. Daugulis, H.ꢀQ. Do, D. Shabashov, Acc. Chem. Res., 2009, 42,
1074; (j) R. Jazzar, J. Hitce, A. Renaudat, J. SofackꢀKreutzer, O.
Baudoin, Chem. Eur. J., 2010, 16, 2654; (k) T. W. Lyons, M. S.
Sanford, Chem. Rev., 2010, 110, 1147; (l) D. A. Colby, R. G.
Bergman, J. A. Ellman, Chem. Rev., 2010, 110, 624; (m) E. M. Beck,
M. J. Gaunt, Top. Curr. Chem., 2010, 292, 106; (n) C.ꢀL. Sun, B.ꢀJ.
Li , Z.ꢀJ. Shi, Chem. Rev., 2011, 111, 1293.
11 (a) L. Ackermann, A. V. Lygin, N. Hofmann, Angew. Chem., Int.
Ed., 2011, 50, 6379; (b) B. Li, H. Feng, S. Xu, B. Wang, Chem. Eur.
J., 2011, 17, 12573; (c) L. Ackermann, A. V. Lygin, N. Hofmann,
Org. Lett., 2011, 13, 3278; (d) L. Ackermann, L. Wang, A. V. Lygin,
Chem. Sci., 2012, 3, 177; (e) R. K. Chinnagolla, M. Jeganmohan, Eur.
J. Org. Chem., 2012, 417; (f) V. S. Thirunavukkarasu, M. Donati, L.
Ackermann, Org.Lett., 2012, 14, 3416; (g) K. Parthasarathy, N.
Senthilkumar, J. Jayakumar, C.ꢀH. Cheng, Org. Lett., 2012, 14, 3478;
(h) B. Li, H. Feng, N. Wang, J. Ma, H. Song, S. Xu, B. Wang, Chem.
Eur. J., 2012, 18, 12873.
12 S. Murai, F. Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani, M.
Sonoda, N. Chatani, Nature, 1993, 366, 529.
13 G. Rouquet, N. Chatani, Chem. Sci., 2013, 4, 2201.
14 F. Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani, M. Sonoda, N.
Chatani, S. Murai, Bull. Chem. Soc. Jpn., 1995, 68, 62.
15 D. Shan, Y. Gao, Y. Jia, Angew. Chem. Int. Ed., 2013, 52, 4902.
This journal is © The Royal Society of Chemistry [year]
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