FeCl3?6H2O-catalyzed alkenylation of indoles with aldehydes

Article abstract of DOI:10.1021/jo301416s

FeCl₃?6H₂O-catalyzed efficient C3-alkenylation of indoles was realized through the condensation of aldehydes and indole derivatives in the presence of 2 equiv of ethanol at ambient temperature, forming 3- vinylindoles in up to 93% yields. Ethanol promoted formation of the desired products. An obvious solvent effect was observed, and bisindoles were identified as the reaction intermediates.

Full text of DOI:10.1021/jo301416s

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Note
FeCl3-6H2O-Catalyzed Alkenylation of Indoles with Aldehydes
Qin Yang, Liandi Wang, Tenglong Guo, and Zhengkun Yu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo301416s • Publication Date (Web): 25 Aug 2012
Downloaded from http://pubs.acs.org on August 26, 2012
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Submitted to J. Org. Chem. for consideration as a note (revised: jo-2012-01416s)
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FeCl3·6H2O-Catalyzed Alkenylation of Indoles with Aldehydes
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Qin Yang,a Liandi Wang,a Tenglong Guoa and Zhengkun Yu*,a,b
aDalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian,
Liaoning 116023, China; bState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China
E-mail: zkyu@dicp.ac.cn
RECEIVED DATE (will be automatically inserted after manuscript is accepted).
_____________________________________________________________________
Ar
2.5 mol %
FeCl3⋅6H2O
CHO
+
EtOH (2.2 equiv)
CH2Cl2, rt, 3 h
R2
N
R1
R2
Ar
N
R1
R3
R3
Abstract: FeCl3ꢀ6H2Oꢁcatalyzed efficient C3ꢁalkenylation of indoles was realized
through the condensation of aldehydes and indole derivatives in the presence of two
equivalents of ethanol at ambient temperature, forming 3ꢁvinylindoles in up to 93%
yields. Ethanol promoted formation of the desired products. An obvious solvent effect
was observed, and bisindoles were identified as the reaction intermediates.
_____________________________________________________________________
Indole is an important subunit of many bioactive compounds and natural products,
and indole derivatives have become more and more attractive for the construction of
agriculturally and pharmaceutically useful molecules.1 Functionalized indoles2 such
as vinylindoles can be considered as diene equivalents for the synthesis of
polyfunctional indole derivatives.3 FriedelꢁCrafts alkylation4 and arylation5 of indoles
have been extensively explored, but their alkenylation has been received much less
attention. Although vinylindoles can be obtained by functional groupꢁdirected organic
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synthesis,6 alkenylation protocols are expected to produce more versatile vinylindoles.
Direct alkenylation of the C2ꢁposition of indoles bearing a readily removable
Nꢁpyrimidyl group with alkynes was realized by using a cobalt complex catalyst,7a
and 3ꢁcyanoindoles reacted with internal alkynes to form 2ꢁvinylindoles under nickel
catalysis.7b Iron(III)ꢁcatalyzed hydroarylation of propynoic acids with indoles
afforded the corresponding vinylindoles.7c Palladiumꢁcatalyzed intramolecular
addition of indolyl CꢁH to alkynes gave fused alkenylated indoles.7d Direct oxidative
alkenylation of indoles by an alkene has been demonstrated an applicable potential to
access vinylindoles.8 Intramolecular alkenylation was also performed for the same
purpose.9 Both Brønsted10a and Lewis10b acids catalyzed the direct couplings of
indoles with 1,3ꢁdicarbonyls to form 3ꢁalkenylated indoles or 2ꢁvinylindoles.11 Under
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microwave irradiation at 140 C, treatment of indoles with aldehydes (3 equiv) in the
presence of trifluoroacetic acid (3 equiv) formed 3ꢁvinylindoles in 18ꢁ76% yields.12
In view of practical application, iron catalysis is potentially attractive in organic
synthesis.13 Iron compounds have been known to promote the alkenylation of
arenes.14 Recently, we disclosed efficient FeCl3ꢁ and FeCl3⋅6H2Oꢁmediated
intramolecular cyclization of alkynyl acetals and intermolecular reactions of alkynes
and aldehyde acetals.15 In these cases, acetals exhibited much higher reactivity than
their mother aldehydes. Keeping this finding in hand, we envisioned that FeCl3⋅xH2O
might also promote the reactions of heteroarene CꢁH bond with aldehyde acetals.
Herein, we report FeCl3⋅6H2Oꢁcatalyzed alkenylation of indoles with the in-situ
generated acetals, i.e., aldehydes in the presence of ethanol.
Initially, the reaction of 1,2ꢁdimethylindole (1a) with phenylacetaldehyde (2a)
was carried out in the presence of FeCl3⋅xH2O (Table 1). The reaction was completed
in toluene within 24 h in the presence of 5 mol % FeCl3⋅6H2O as catalyst, affording
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the desired product 3ꢁvinylindole (3a) in 80% yield (Table 1, entry 1), and in pꢁxylene
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a similar result was obtained (entry 3). Shortening the reaction time to 3 h led to a
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Table 1. Screening of conditions for the reaction of
1,2-dimethylindole (1a) with phenylacetaldehyde (2a)a
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Ph
CHO
conditions
(1)
+
N
Ph
N
1a
2a
3a
catalyst
(mol %)
additive
(equiv)
time yieldb
temp
entry
1
solvent
(h)
(%)
(°C)
toluene
toluene
25
24
80
FeCl3⋅6H2O (5)
2
3
25
25
25
25
25
25
25
40
0
3
24
3
3
3
3
3
3
3
3
3
3
3
3
3
44
70
tracec
trace
trace
85
FeCl3⋅6H2O (5)
FeCl3⋅6H2O (2.5)
FeCl3⋅6H2O (2.5)
FeCl3⋅6H2O (5)
FeCl3⋅6H2O (5)
FeCl3⋅6H2O (5)
FeCl3 (5)
pꢁxylene
pꢁxylene
CH3CN
EtOH
4
5
6
7
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
8
79
9
FeCl3⋅6H2O (5)
FeCl3⋅6H2O (5)
FeCl3⋅6H2O (10)
80
10
11
58
25
25
25
25
25
25
79
12 FeCl3⋅6H2O (2.5)
87
13
EtOH (0.2)
EtOH (2.2)
EtOH (2.2)
H2O (2.2)
88
FeCl3⋅6H2O (2.5)
FeCl3⋅6H2O (2.5)
14
91
15 FeCl3⋅6H2O (1.0)
71
traced
16
FeCl3⋅6H2O (2.5)
a
Conditions: 1,2ꢁdimethylindole (1a), 0.5 mmol; phenylacetaldehyde (2a), 0.55
b
c
mmol; solvent, 3 mL. Average yield of two or three experiments. The major
product was bisindole 4c (93%). d The major product was bisindole 4c (79%)
lower yield (44%) for 3a in toluene (entry 2), and resulted in bisindole 4c (93%)
instead of 3a as the major product in p-xylene (entry 4). In CH3CN and EtOH, the
reaction was nearly prohibited (entries 5 and 6). Under the same conditions in CH2Cl2,
the reaction efficiently proceeded to give 3a in 85% yield (entry 7), while 3a was only
obtained in 79% yield with 5 mol % anhydrous FeCl3 as catalyst (entry 8).
FeCl3⋅6H2O behaved more efficiently than FeCl3 as catalyst presumably due to the
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coordination of water molecules to the iron atom to stabilize the metal center during
the catalytic reaction. Variation of temperature to 40 and 0 oC deteriorated the reaction
(entries 9 and 10). Increasing the catalyst loading to 10 mol % did not improve the
formation of 3a, whereas lowering FeCl3⋅6H2O loading to 2.5 mol % increased the
yield of 3a to 87% (entries 7, 11 and 12). Furthermore, addition of ethanol facilitated
formation of the desired product and 3a was isolated in 91% yield in the presence of
two equivalents of ethanol (entries 13 and 14), which is presumably attributed to the
in-situ formation of the more reactive species, i.e., phenylacetaldehyde diethyl acetal
(2a′). However, further lowering the catalyst loading to 1 mol % led to 3a in 71%
yield (entry 15). By replacing ethanol with water, the reaction only generated a trace
amount of 3a as well as bisindole 4c (79%) as the major product (entry 16). The sepaꢁ
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Ph
2.5 mol %
OEt
OEt
FeCl3⋅6H2O
25 oC, 2 h
(2)
+
N
N
Ph
2a' (1.1 equiv)
in CH2Cl2:
in p-xylene:
3a
1a (0.5 mmol)
70%
64%
rate reaction of 1a with 2a′ in CH2Cl2 and pꢁxylene afforded 3a in 70% and 64%
yields over a period of 2 hours, respectively (eq 2), suggesting that the reaction
proceeded faster in CH2Cl2 than in pꢁxylene. Monitoring by means of TLC analysis
revealed that the reaction in CH2Cl2 was finished within 2 h and accompanied by
unidentified side reactions, while the reaction in p-xylene was slower and 3a could be
obtained in 85% yield by extending the reaction time to 3 h, showing an obvious
solvent effect (Table 1 and eq 2). It is noteworthy that diethyl acetal 2a′ is not very
stable and difficult to be isolated in high purity. Although 2a′ reacted with 1a more
efficiently in pꢁxylene due to the undesired reactions occurring in CH2Cl2 (eq 2),
CH2Cl2 was still chosen as the reaction medium because the reaction of 2a and 1a
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proceeded much faster in CH2Cl2 than in pꢁxylene (entries 3, 4 and 14). In all the
cases, compound 3a was obtained in the exclusive (E)ꢁconfiguration.
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Table 2. Alkenylation of indoles (1) with phenylacetaldehyde (2a)a
Ph
2.5 mol %
FeCl3⋅6H2O
CHO
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(3)
+
EtOH (2.2 equiv)
CH2Cl2
R2
N
R1
R2
Ph
N
R1
R3
R3
1
2a
3
3a, 91%
3b, 81%
3c, 80%
3d, 75%
3e, 88%
3f, 77%
3g, 81%b
3h, 91%
3i, 73%b
3j, 43%
3o, 66%
3k, 66%b
3l, 80%b
3m, 92%
3n, 93%
3p, 69%b
3q, 69%
3r, 79%c
3s, 74%b
3t, 62%
3u, 7%b,d
a
o
Conditions: indole (1), 0.5 mmol; aldehyde (2a), 0.55 mmol; EtOH, 1.1 mmol; CH2Cl2, 3 mL; 25 C, 3
h. b Using 5 mol % FeCl3⋅6H2O. c 10 h. d 36 h, E
> 20:1.
:Z
Next, the substrate scope was explored under the optimized conditions (Table 2).
With 2ꢁsubstituted N-unprotected indoles as substrates, the desired products 3b-l were
obtained in 43ꢁ91% yields, and treatment of Nꢁalkylꢁ2ꢁsubstituted indoles with 2a
produced 3n-t in 66ꢁ93% yields. Substituent effects of the Nꢁ, 2ꢁ and 5ꢁsubstituents on
the reaction efficiency were observed (Table 2). Based on the proposed mechanism
(Scheme 1), when the 2ꢁposition of an indole substrate is substituentꢁfree,
nucleophilic attack of the 2ꢁC of such an indole at species B in path a or species A′ in
path b can not result in relatively stable intermediates of type C or B′, leading to the
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2ꢁalkenylation product in a poor yield. Thus, with a 1,3ꢁdisubstituted indole as
substrate, 3u was only obtained in 7% yield over a period of 36 h. Unexpectedly, the
reaction of 2ꢁmethylꢁ5ꢁnitroindole with 2a afforded compound 4a in 91% yield (eq 4),
9
2a (1.1 equiv)
2.5 mol %
2
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R
2
Ph
R
2
R
FeCl ⋅6H O
3
2
(4)
1
EtOH (2.2 equiv)
N
R
o
H
N
CH Cl , 25
C
N
1
2
2
1
R
R
H
H
1
1
2
4a (R = Me, R = NO , 10 h), 91%
2
1
2
4b (R = R = H, 3 h), 43%
revealing a remarkable electronic effect of 5ꢁNO2 group. Bisindole 4a was gradually
formed as an insoluble solid in CH2Cl2 during the reaction, but it could not undergo
further reaction with 2a to form the desired product. The reaction of simple indole
with 2a also produced the product of type 4, i.e., 4b (43%), giving no desired product
under the same conditions due to the substituent effect as discussed above (eq 4).
Substituted arylacetaldehydes can not be easily prepared in high purity that crude
arylacetaldehydes16 were directly used for the synthesis of alkenylated indoles. Such a
twoꢁstep procedure was developed to give the desired products 6a and 6b in 69ꢁ78%
yields (eq 5), which extended the substrate scope. 2ꢁSubstituted phenylacetaldehyde
(5c) also reacted with 1a to form the desired product 6c in moderate to good yields
2.5 mol % Pd(MeCN)2Cl2
H2O (1.1 equiv)
CHO
BQ (1.15 equiv)
tBuOH, 85 oC, 1 h
R
R
0.8 mmol
5a (R = Me)
5b (R = Br)
(5)
R
1a (0.5 mmol)
2.5 mol % FeCl3⋅6H2O
EtOH (2.2 equiv)
CH2Cl2, 25 oC, 3 h
N
6a (R = Me), 78%
6b (R = Br), 69%
Ph
CH
CH
5 mol % FeCl ⋅6H O
3
3
2
1a
+
(6)
3
EtOH (2.2 equiv)
Ph
CHO
N
o
CH Cl , 25
C
2
2
6c
5c
with EtOH (4 h):
without EtOH (10 h):
41%
78% (E/Z = 7:1)
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(eq 6). It should be noted that in the presence of EtOH the reaction proceeded to
completion within 4 h to give 6c (41%) as well as a considerable amount of
unidentified byꢁproducts, while in the absence of EtOH the reaction initially generated
bisindole 4c as the major product within the first 4 h which was then gradually
transformed to 6c (78%) over a period of 10 h. The diethyl acetal intermediate
generated in situ from the interaction of sterically hindered aldehyde 5c and ethanol
may be susceptible to the reaction condition to undergo side reactions and form
undesired products. These results suggest the possible role of ethanol during the
reaction of 1 with 2: (1) as an additive to form the more reactive diethyl acetal interꢁ
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Ph
CHO
5 mol % FeCl ⋅6H O
3
2
1a
+
(7)
EtOH (2.2 equiv)
o
Ph
N
CH Cl , 40 C, 10 h
2
2
5d
6d, 13%
mediate in situ and thus accelerate the reaction; (2) as a medium to help dissolving the
bisindole intermediate to promote the reaction; (3) The in-situ generated diethyl acetal
species may undergo side reactions to form undesired products under the reaction
conditions. However, both 3ꢁphenylpropionaldehyde (5d) and butyraldehyde (5e)
only exhibited a poor reactivity. By means of 5 mol % catalyst at 40 °C, the reaction
of 5d with 1a formed the alkenylation product 6d in 13% yield (eq 7).
Ph
2.5 mol % FeCl3⋅6H2O
EtOH (2.2 equiv)
CH2Cl2, 25 oC, 3 h
N
R1
N
R1
R2 R2
(8)
Ph
4c (R1 = Me, R2 = Me)
4d (R1 = H, R2 = Me)
4e (R1 = H, R2 = Ph )
+
N
R1
R2
N
R1
R2
R1 = Me, R2 = Me
R1 = H, R2 = Me
R1 = H, R2 = Ph
1a, 28%
1b, 30%
1c, 97%
3a, 33%
3b, 22%
3e, 92%
Bisindoles 4c and 4d were separately synthesized as the reaction intermediates by
quenching the corresponding reactions of 1 and 2 in CH2Cl2 at 10 minutes with
saturated aqueous NaHCO3, and 4e was prepared by carrying out the reaction in
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pꢁxylene for 3 h. Monitoring the reaction of 1a and 2a by 1H NMR and TLC analysis
revealed that the reaction initially formed bisindole 4c which was then gradually
transformed to vinylindole 3a. However, these bisindoles (4c-e) could not tolerate the
reaction conditions in CH2Cl2, decomposing into the corresponding free indoles 1aꢁc
and vinylindoles 3a, 3b and 3e, respectively, as the reaction proceeded (eq 8).
Furthermore, in the presence of a phenylacetaldehyde substrate such as 2a, bisindole
4d was efficiently transformed to the alkenylation product 3b (eq 9), further
suggesting that bisindole of type 4 is the reaction intermediate in the catalytic cycle.
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Ph
2.5 mol % FeCl3⋅6H2O
CHO
(9)
4d
+
EtOH (2.2 equiv)
Ph
2a (1 equiv)
N
CH2Cl2, 25 oC, 3 h
H
3b, 79%
A plausible mechanism is proposed in Scheme 1. In the presence of ethanol (path a),
the Lewis acid iron catalyst promotes in-situ generation of phenylacetaldehyde diethyl
acetal (2a′)17 which then interacts with FeCl3 to form oxocarbenium cation B and
anion A.15c Species B reacts with indole 1 to form iminium cation C which is
considered as a relatively stable intermediate in the catalytic cycle due to the
substituent effect from the 2ꢁposition of the indole backbone. C is tautomerized to D
which loses EtOH to form E. Species E reacts with 1 to produce bisindole sepecies
F/4 which interact with anion A to afford the desired product 3 and 1, and regenerate
the catalyst.12 The released 1 can be used in the next catalytic cycle through a
convergent way. It is also possible for E to interact with A to form 3. Without ethanol
as additive (path b), Lewis acid FeCl3 activates the aldehyde substrate (2a) through
coordination of the carbonyl oxygen to the iron(III) center to form adduct A′, i.e., the
activated form of 2a. Species A′ reacts with indole 1 to generate inonic intermediate
B′ which can be further transformed to adduct C′. Dehydration of C′ affords product 3
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and regenerates the catalyst. Adduct C′ may also interact with 1 to form bisindole 4
5
6
7
8
which reacts with A′ to afford 3 and regenerate the catalyst. It is noteworthy that one
equivalent of BHT (butylated hydroxytoluene) was added as a radical scavenger to the
reaction of 1a and 2a, leading to 3a in 71% yield, which excludes a radical pathway.4f
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Ph
path a
Ph
CHO
2a
+ 1 + EtOH
[Fe]
EtOH
OEt
R'
N
R
3
Ph
2a'
OEt
FeCl3
A
(EtO)FeCl3
Ph
H
A
OEt
N
R
N
Ph
R' R'
-H+
B
R
Ph
+H+
F
N
R
R'
+1 -1
1
N
R
N
R
R' R'
Ph
EtO
Ph
4
N
R
R'
N
R
R'
E
C
-EtOH
-FeCl3
HOEt
+ A
Ph
EtOH
3
N
R
R'
D
path b
Ph
+ H2O
N
R
R'
Ph
CHO
2a
3
FeCl3
3 + H2O
A'
FeCl3
Ph
FeCl3
O
4
Ph
HO
A'
H
FeCl3·xH2O
N
R
R'
N
R
R'
1
C'
Cl3Fe
O
Ph
N
R
R'
B'
Scheme 1. Proposed mechanism.
In conclusion, efficient FeCl3⋅6H2Oꢁcatalyzed C3ꢁalkenylation of 2ꢁsubstituted
indoles has been successfully realized by using phenylacetaldehydes as alkenylating
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reagents in the presence of ethanol. Formation of diethyl acetal of the aldehyde
substrate and/or adduct of aldehyde with the catalyst is proposed to initiate the
catalytic cycle and the reaction proceeds via the bisindole intermediate. The present
protocol provides a convenient route to vinylindole derivatives under mild conditions.
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Experimental Section
General considerations. H and 13C{1H} NMR spectra were recorded on a 400
1
and 100 MHz FTꢁNMR spectrometer, and all chemical shift values refer to δTMS
=
0.00 ppm or CDCl3 (δ(1H), 7.26 ppm; δ(13C), 77.16 ppm). The HRMS analysis was
obtained on a GCꢁTOF mass spectrometer. FeCl3⋅6H2O and FeCl3 (>99.0%) were
purchased from the 5th Shengyang Reagent Factory, China. All the other chemical
reagents were purchased from commercial sources and used as received unless
otherwise
indicated.
Nꢁsubstituted
indoles,
i.e.,
1,2ꢁdimethylindole,
1ꢁethylꢁ2ꢁmethylindole, 1ꢁbenzylꢁ2ꢁ methylindole, and 1ꢁmethylꢁ2ꢁphenylindole,18
1ꢁallylꢁ2ꢁmethylꢁindole,19 1ꢁallylꢁ2ꢁphenylꢁ1Hꢁindole,20 2ꢁcyclohexylindole and
2ꢁpentylindole,21 1ꢁmethylꢁ2ꢁ cyclohexylindole,22 and 1,3ꢁdimethylindole23 were
prepared as reported.
A typical procedure for FeCl3·6H2O-catalyzed alkenylation of indoles 1 with
aldehyde 2a − synthesis of 3a: To a 25ꢁmL round bottom flask, were successively
added FeCl3⋅6H2O (3.4 mg, 0.0125 mmol), CH2Cl2 (3 mL), EtOH (51.0 mg, 1.1
mmol), phenylacetaldehyde (2a) (66.0 mg, 0.55 mmol) and 1,2ꢁdimethylindole (1a)
(72.5 mg, 0.5 mmol). The mixture was stirred at ambient temperature for 3 h. All the
volatiles were removed under reduced pressure, and the resultant residue was purified
by silica gel column chromatography (eluent: petroleum ether (60ꢁ90 °C)/CH2Cl2 =
8:1, v/v) to afford the target product 3a24 (112.0 mg, 91%). M.p.: 130ꢁ132 C. H
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NMR (400 MHz, CDCl3): δ 8.01 (d, J = 6.9 Hz, 1 H), 7.55 (d, J = 7.5 Hz, 2 H),
7.40ꢁ7.31 (m, 4 H), 7.27ꢁ7.21 (m, 3 H), 7.13 (d, J = 16.4 Hz, 1 H), 3.70 and 2.54 (s
each, 3:3 H).
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(E)-2-Methyl-3-styryl-1H-indole ((E)-3b):6c 95 mg, yield 81%. Yellow solid.
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M.p.: 187ꢁ188 C. 1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 6.9 Hz, 1 H), 7.83 (s, 1
H), 7.64 (d, J = 7.5 Hz, 2 H), 7.47 (t, J = 7.5 Hz, 2 H), 7.39 and 7.21 (d each, J = 16.4
Hz, 1:1 H), 7.34ꢁ7.27 (m, 4 H), 2.55 (s, 3 H).
(E)-2-Cyclohexyl-3-styryl-1H-indole ((E)-3c): 121 mg, yield 80%. White solid.
M.p.: 64ꢁ66 oC. H NMR (400 MHz, CDCl3) δ 8.04 (br, 2 H), 7.60 (d, J = 6.8 Hz, 2
1
H), 7.45ꢁ7.37 (m, 4 H), 7.26 (m, 3 H), 7.20 (d, J = 16.4 Hz, 1 H), 3.15 (m, 1 H), 2.04
(m, 2 H), 1.94 (m, 2 H), 1.87 (d, J = 13.9 Hz, 1 H), 1.52 (m, 4 H), 1.35 (m, 1 H).
13C{1H} NMR (100 MHz, CDCl3) δ 143.8, 139.2, 135.6, 126.55, 109.5, 128.7, 126.51,
125.8, 125.4, 121.8, 121.7, 120.5, 120.2, 110.9, 36.0, 33.1, 26.7, 26.1. HRMS (EI)
Calcd for C22H23N: 301.1830; Found: 301.1842.
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(E)-2-Pentyl-3-styryl-1H-indole ((E)-3d): 108 mg, yield 75%. Yellow oil. H
NMR (400 MHz, CDCl3) δ 8.06 (d, J = 6.9 Hz, 1 H), 7.90 (s, 1 H), 7.60 (d, J = 7.7 Hz,
2 H), 7.43 (t, 2 H), 7.34 (m, 2 H), 7.29ꢁ7.24 (m, 3 H), 7.20 (d, J = 16.4 Hz, 1 H), 2.89
(t, J = 7.7 Hz, 2 H), 1.74 (m, 2 H), 1.42 (m, 4 H), 0.96 (t, 3 H). 13C{1H} NMR (100
MHz, CDCl3) δ 139.5, 139.2, 135.7, 126.6, 110.7, 128.7, 126.5, 125.8, 125.3, 121.9,
121.8, 120.5, 120.1, 110.8, 31.6, 29.6, 26.6, 22.6, 14.1. HRMS (EI) Calcd for
C21H23N: 289.1830; Found: 289.1823.
(E)-2-Phenyl-3-styryl-1H-indole ((E)-3e): 130 mg, yield 88%. White solid.
M.p.: 90ꢁ91 oC. 1H NMR (400 MHz, CDCl3) δ 8.20 (m, 1 H), 8.12 (s, 1 H), 7.62 (m, 2
H), 7.59ꢁ7.54 (m, 4 H), 7.51ꢁ7.30 (m, 9 H). 13C{1H} NMR (100 MHz, CDCl3) δ 138.9,
137.5, 136.5, 132.5, 126.9, 111.9, 129.0, 128.9, 128.7, 128.3, 127.5, 126.7, 126.0,
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123.0, 122.4, 120.91, 120.89, 111.3. HRMS (EI) Calcd for C22H17N: 295.1361; Found:
295.1366.
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(E)-2-(4-Fluorophenyl)-3-styryl-1H-indole ((E)-3f): 121 mg, yield 77%. White
solid. M.p.: 104ꢁ107 oC. 1H NMR (400 MHz, acetoneꢁd6) δ 10.69 (s, 1 H), 8.16 (d, J =
7.4 Hz, 1 H), 7.75 (m, 2 H), 7.56 (d, J = 7.5 Hz, 2 H), 7.52 (d, J = 7.5 Hz, 1 H), 7.46
(d, J = 16.5 Hz, 1 H), 7.33 (m, 5 H), 7.23 (m, 3 H). 13C{1H} NMR (100 MHz,
acetoneꢁd6) δ 163.4 (d, J = 244.9 Hz), 139.7, 137.8, 137.7, 127.5, 111.9, 129.9 (d, J =
3.2 Hz), 131.8 (d, J = 8.6 Hz), 116.5 (d, J = 21.6 Hz), 129.4, 126.5, 127.4, 127.3,
123.4, 123.1, 121.4, 121.2, 112.4. HRMS (EI) Calcd for C22H16FN: 313.1267; Found:
313.1277.
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(E)-2-(4-Chlorophenyl)-3-styryl-1H-indole ((E)-3g): 134 mg, yield 81%. White
solid. M.p.: 129ꢁ130 oC. 1H NMR (400 MHz, CDCl3) δ 8.12 (m, 2 H), 7.54ꢁ7.48 (m, 6
H), 7.40 (t, 3 H), 7.34ꢁ7.26 (m, 5 H). 13C{1H} NMR (100 MHz, CDCl3) δ 138.6,
136.5, 136.0, 134.3, 131.0, 126.9, 112.4, 130.0, 129.3, 128.8, 128.1, 127.0, 126.0,
123.3, 121.8, 121.1, 121.0, 111.4. HRMS (EI) Calcd for C22H16ClN: 329.0971; Found:
329.0970.
(E)-2-(Naphthalen-2-yl)-3-styryl-1H-indole ((E)-3h): 157 mg, yield 91%. White
solid. M.p.: 85ꢁ88 oC. 1H NMR (400 MHz, CDCl3) δ 8.19 (m, 2 H), 8.03 (s, 1 H),
7.96ꢁ7.89 (m, 3 H), 7.72 (d, J = 8.4 Hz, 1 H), 7.59ꢁ7.48 (m, 5 H), 7.41ꢁ7.26 (m, 6 H),
7.28 (t, 1 H). 13C{1H} NMR (100 MHz, CDCl3) δ 138.9, 137.5, 136.7, 133.5, 132.9,
130.0, 127.0, 112.3, 128.8, 128.7, 128.3, 128.0, 127.9, 127.7, 126.84, 126.78, 126.7,
126.5, 126.0, 123.1, 122.3, 121.0, 120.9, 111.4. HRMS (EI) Calcd for C26H19N:
345.1517; Found: 345.1528.
(E)-2,5-Dimethyl-3-styryl-1H-indole ((E)-3i): 91 mg, yield 73%. White solid.
M.p.: 165ꢁ167 oC. 1H NMR (400 MHz, CDCl3) δ 7.79 (s, 1 H), 7.71 (br, 1 H), 7.59 (d,
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J = 7.4 Hz, 2 H), 7.41 and 7.26 (t each, 2:1 H), 7.32 (d, J = 16.4 Hz, 1 H), 7.18ꢁ7.11
(m, 2 H), 7.05 (d, J = 8.1 Hz, 1 H), 2.55 and 2.49 (s each, 3:3 H). 13C{1H} NMR (100
MHz, CDCl3) δ 139.2, 134.9, 133.9, 129.8, 126.9, 110.7, 128.7, 126.5, 125.8, 125.0,
123.3, 122.0, 119.6, 110.3, 21.8, 12.5. HRMS (EI) Calcd for C18H17N: 247.1361;
Found: 247.1363.
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(E)-5-Methoxy-2-methyl-3-styryl-1H-indole ((E)-3j): 57 mg, yield 43%. White
solid. M.p.: 115ꢁ117 oC. 1H NMR (400 MHz, CDCl3) δ 7.84 (br, 1 H), 7.54 (d, J = 7.5
Hz, 2 H), 7.44 (s, 1 H), 7.38 and 7.23 (t each, 2:1 H), 7.29 (d, J = 16.4 Hz, 1), 7.04 (d,
J = 16.4 Hz, 1 H), 7.19 (d, J = 8.7 Hz, 1 H), 6.85 (dd, J = 8.7 and 2.3 Hz, 1 H), 3.92
and 2.51 (s each, 3:3 H). 13C{1H} NMR (100 MHz, CDCl3) δ 154.8, 139.1, 135.5,
130.7, 127.3, 111.0, 128.6, 126.5, 125.8, 125.1, 121.9, 111.2, 110.9, 102.9, 56.2, 12.7.
HRMS (EI) Calcd for C18H17NO: 263.1310; Found: 263.1320.
(E)-5-Fluoro-2-methyl-3-styryl-1H-indole ((E)-3k): 82 mg, yield 66%. White
solid. M.p.: 126ꢁ129 oC. 1H NMR (400 MHz, CDCl3) δ 7.78 (br, 1 H), 7.66 (d, J = 8.6
Hz, 1 H), 7.57 (d, J = 7.7 Hz, 2 H), 7.42 (t, 2 H), 7.30ꢁ7.25 (m, 2 H), 7.16 (dd, J = 8.7
and 4.5 Hz, 1 H), 7.05 (d, J = 16.5 Hz, 1 H), 6.96 (dt, J = 9.0 and 2.2 Hz, 1 H), 2.48 (s,
3 H). 13C{1H} NMR (100 MHz, CDCl3) δ 158.5, 138.8, 136.5, 132.0, 127.0, 111.3,
128.8, 125.8, 126.7, 125.4, 121.3, 111.1, 109.7 (d, J = 25.8 Hz), 105.1 (d, J = 24.1
Hz), 12.5. HRMS (EI) Calcd for C17H14NF: 251.1110; Found: 251.1119.
(E)-5-Chloro-2-methyl-3-styryl-1H-indole ((E)-3l): 107 mg, yield 80%. White
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solid. M.p.: 128ꢁ130 oC. H NMR (400 MHz, CDCl3) δ 7.99 (s, 1 H), 7.93 (br, 1 H),
7.63 (d, J = 7.4 Hz, 2 H), 7.47 (t, 2 H), 7.35ꢁ7.28 (m, 2 H), 7.23 (m, 2 H), 7.11 (d, J =
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16.5 Hz, 1 H), 2.55 (s, 3 H). C{1H} NMR (100 MHz,CDCl3) δ 138.7, 136.0, 133.9,
127.7, 126.1, 110.9, 128.8, 126.8, 125.9, 125.8, 121.9, 121.0, 119.3, 111.6, 12.5.
HRMS (EI) Calcd for C17H14NCl: 267.0815; Found: 267.0822.
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(E)-6-Phenyl-7-styryl-5H-[1,3]dioxolo[4,5-f]indole ((E)-3m): 156mg, yield 92%.
White solid. M.p.: 149ꢁ150 oC. 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1 H), 7.63ꢁ7.54
(m, 7 H), 7.50ꢁ7.40 (m, 4 H), 7.34 (t, 1 H), 7.23 (d, J = 16.5 Hz, 1 H), 6.90 (s, 1 H),
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131.5, 120.8, 112.2, 129.0, 128.7, 128.5, 127.8, 127.0, 126.7, 125.9, 122.4, 100.9,
99.6, 92.2. HRMS (EI) Calcd for C23H17NO2: 339.1259; Found: 339.1267.
(E)-1-Ethyl-2-methyl-3-styryl-1H-indole ((E)-3n): 121 mg, yield 93%. White
solid. M.p.: 105ꢁ107 oC. 1H NMR (400 MHz, CDCl3) δ 8.12 (br, 1 H), 7.66, 7.48ꢁ7.43,
7.34, and 7.26ꢁ7.20 (m each, 2:4:3:1 H), 4.24 (q, 2 H), 2.63 (s, 3 H), 1.46 (t, 3 H).
13C{1H} NMR (CDCl3, 100 MHz) δ 139.4, 136.2, 135.8, 126.1, 110.6, 128.7, 126.4,
125.7, 124.9, 122.2, 121.5, 120.2, 120.0, 109.1, 38.0, 15.3, 10.6. HRMS (EI) Calcd
for C19H19N: 261.1517; Found: 261.1525.
(E)-1-Benzyl-2-methyl-3-styryl-1H-indole ((E)-3o): 107 mg, yield 66%. White
solid. M.p.: 123ꢁ125 oC. 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 7.6 Hz, 1 H), 7.60
(d, J = 7.4 Hz, 2 H), 7.42 and 7.32ꢁ7.25 (m each, 3:8 H), 7.03 (d, J = 7.0 Hz, 2 H),
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5.35 (s, 2 H), 2.50 (s, 3 H). C{1H} NMR (100 MHz, CDCl3) δ 139.2, 137.4, 137.2,
136.4, 126.1, 111.1, 128.9, 128.7, 127.5, 126.5, 126.0, 125.8, 125.4, 122.0, 121.8,
120.5, 120.0, 109.5, 46.7, 10.9. HRMS (EI) Calcd for C24H21N: 323.1674; Found:
323.1678.
(E)-1-Allyl-2-methyl-3-styryl-1H-indole ((E)-3p): 95 mg, yield 69%. White
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solid. M.p.: 76ꢁ78 oC. H NMR (400 MHz, CDCl3) δ 8.09 (br, 1 H), 7.62 (d, J = 7.2
Hz, 2 H), 7.42 and 7.27 (m each, 3:4 H), 7.21 (d, J = 16.4 Hz, 1 H), 5.97 (m, 1 H),
5.19 (d, J = 10.2 Hz, 1 H), 4.90 (d, J = 17.1 Hz, 1 H), 4.71 (t, 2 H), 2.53 (s, 3 H).
13C{1H} NMR (100 MHz, CDCl3) δ 139.2, 136.8, 136.3, 126.0, 110.8, 132.9, 128.7,
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126.4, 125.7, 125.1, 122.1, 121.6, 120.4, 119.9, 116.5, 109.4, 45.4, 10.6. HRMS (EI)
Calcd for C20H19N: 273.1517; Found: 273.1520.
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(E)-1-Methyl-2-phenyl-3-styryl-1H-indole ((E)-3q): 107 mg, yield 69%. White
solid. M.p.: 142ꢁ144 oC.1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.1 Hz, 1 H), 7.48,
7.35, and 7.19 (m each, 7:5:3 H), 3.62 (s, 3 H). 13C{1H} NMR (100 MHz, CDCl3) δ
141.0, 139.1, 138.0, 131.4, 125.7, 112.1, 131.2, 128.64, 128.59, 126.4, 125.8, 122.8,
122.6, 120.8, 109.9, 31.1. HRMS (EI) Calcd for C23H19N: 309.1517; Found:
309.1518.
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(E)-1-Ethyl-2-phenyl-3-styryl-1H-indole ((E)-3r): 127mg, yield 79%. White
solid. M.p.: 113ꢁ115 oC. 1H NMR (400 MHz, CDCl3) δ 8.35 (m, 1 H), 7.65, 7.57, 7.47,
and 7.30 (m each, 5:3:4:2 H), 7.38 (d, J = 16.5 Hz, 1 H), 4.21 (q, 2 H), 1.39 (t, 3 H).
13C{1H} NMR (100 MHz, CDCl3) δ 140.5, 139.1, 136.7, 131.6, 126.0, 112.3, 131.0,
128.64, 128.59, 128.58, 126.3, 125.7, 125.5, 122.8, 122.4, 120.8, 120.7, 110.6, 38.8,
15.3. HRMS (EI) Calcd for C24H21N: 323.1674; Found: 323.1676.
(E)-1-Allyl-2-phenyl-3-styryl-1H-indole ((E)-3s): 125 mg, yield 74%. Yellow
oil. 1H NMR (400 MHz, CDCl3) δ 8.17 (br, 1 H), 7.48, 7.41, 7.29, and 7.15 (m each,
5:2:5:3 H), 5.89 (m, 1 H), 5.15 (d, J = 10.3 Hz, 1 H), 4.94 (d, J = 17.1 Hz, 1 H), 4.59
(br, 2 H). 13C{1H} NMR (100 MHz, CDCl3) δ 140.9, 139.1, 137.4, 131.3, 112.4,
133.5, 131.0, 128.7, 128.6, 128.5, 126.4, 125.9, 125.8, 122.8, 122.6, 120.9, 120.8,
116.7, 110.7, 46.6. HRMS (EI) Calcd for C25H21N: 335.1674; Found: 335.1678.
(E)-2-Cyclohexyl-1-methyl-3-styryl-1H-indole ((E)-3t): 97 mg, yield 62%.
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White solid. M.p.: 117ꢁ120 C. H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 7.5 Hz, 1
H), 7.70 (m, 3 H), 7.55 (t, 2 H), 7.40 (m, 4 H), 7.26 (d, J = 16.3 Hz, 1 H), 3.91 (s, 3
H), 3.23 (m, 1 H), 2.10, 2.01, 1.64ꢁ1.46 (m each, 6:1:3 H). 13C{1H} NMR (100 MHz,
CDCl3) δ 143.9, 139.2, 137.4, 126.2, 110.1, 128.7, 126.5, 126.2, 125.8, 122.7, 121.6,
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120.2, 120.1, 109.2, 37.2, 32.1, 27.3, 26.2, 30.7. HRMS (EI) Calcd for C23H25N:
315.1987; Found: 315.1990.
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(E)-1,3-Dimethyl-2-styryl-1H-indole ((E)-3u): E/Z = 30:1. 8 mg, yield 7%.
White solid. M.p.: 79ꢁ82 oC. 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.6 Hz, 1 H),
7.68 (d, J = 7.3 Hz, 2 H), 7.53 (t, 2 H), 7.38 (m, 4 H), 7.28 (m, 1 H), 7.08 (d, J = 16.4
Hz, 1 H), 3.90 (s, 3 H), 2.63 (s, 3 H). 13C{1H} NMR (100 MHz, CDCl3) δ 137.7,
137.6, 134.3, 128.7, 110.2, 132.2, 128.9, 127.8, 126.4, 122.3, 119.2, 118.9, 117.9,
109.0, 30.7, 10.4. HRMS (EI) Calcd for C18H17N: 247.1361; Found: 247.1370.
3,3'-(2-Phenylethane-1,1-diyl)bis(2-methyl-5-nitro-1H-indole) (4a): 150 mg,
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yield 91%. Yellow solid. M.P.: 265ꢁ268 C. 1H NMR (400 MHz, acetoneꢁd6) δ 10.59
(s, 2 H), 8.47 (s, 2 H), 7.90 and 7.39 (d each, J = 8.9 Hz, 2:2 H), 7.16 (m, 3 H), 7.04
(d, J = 7.4 Hz, 2 H), 4.85 (t, 1 H), 3.81 (d, J = 7.9 Hz, 2 H), 2.35 (s, 6 H). 13C{1H}
NMR (100 MHz, acetoneꢁd6) δ 141.9, 141.7, 139.8, 136.7, 128.2, 116.2, 130.0, 128.8,
126.8, 116.6, 116.3, 111.4, 41.4, 38.0, 12.6. HRMS (EI) Calcd for C19H15N4O4
[MꢁC7H7]+: 363.1093; Found: 363.1087.
3,3'-(2-Phenylethane-1,1-diyl)bis(1H-indole) (4b):25 36 mg, yield 43%.
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Colorless oil. H NMR (400 MHz, CDCl3) δ 7.85 (s, 2 H), 7.58 (d, J = 7.9 Hz, 2 H),
7.32 (d, J = 8.1 Hz, 2 H), 7.14 (m, 7 H), 7.03 (t, 2 H), 6.94 (s, 2 H), 4.81 (t, 1 H), 3.55
(d, J = 7.4 Hz, 2 H).
3,3'-(2-Phenylethane-1,1-diyl)bis(1,2-dimethyl-1H-indole) (4c): Compound 1a
(363 mg, 2.5 mmol) was added to a stirred solution of FeCl3⋅6H2O (17 mg, 0.0625
mmol), EtOH (255 mg, 5.5 mmol), and 2a (330 mg, 2.75 mmol) in CH2Cl2 (15 mL),
and stirring was continued for 10 min. To the resultant mixture was added 15 mL
saturated aqueous NaHCO3 and extraction was performed with CH2Cl2 (3×15 mL).
The combined organic phase was washed with brine (10 mL), dried over anhydrous
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Na2SO4, evaporated all the volatiles under reduced pressure. Purification of the
resulting residue by flash silica gel column chromatography (petroleum ether (60ꢁ90
oC)/CH2Cl2 = 10:1, v/v) afforded 4c as a white solid (363 mg, 37%). M.p.: 268ꢁ270 oC.
1H NMR (400 MHz, acetoneꢁd6) δ 7.72, 7.20, 7.08, 6.98, 6.88 (m each, 2:2:3:2:4 H),
4.63 and 3.76 (m each, 1:2 H), 3.50 and 2.05 (s each, 6:6 H). 13C{1H} NMR (100
MHz, acetoneꢁd6) δ 142.9, 137.7, 133.9, 128.1, 114.3, 129.9, 128.5, 126.4, 120.6,
120.3, 119.1, 109.5, 42.1, 39.4, 29.5, 10.5. HRMS (EI) Calcd for C21H21N2 [MꢁC7H7]+:
301.1704; Found: 301.1690.
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3,3'-(2-Phenylethane-1,1-diyl)bis(2-methyl-1H-indole) (4d): In
a
fashion
similar to the preparation of 4c, bisindole 4d was obtained from the reaction of 1b and
o
2a as a yellow solid (402 mg, 44%). M.p.: >264 C, sublimated. 1H NMR (400 MHz,
acetoneꢁd6) δ 9.67 (s, 2 H), 7.62 (d, J = 7.9 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2 H), 7.11 (m,
3 H), 6.96ꢁ6.91 (m, 4 H), 6.84 (t, 2 H), 4.63 (t, 1 H), 3.75 (d, J = 7.8 Hz, 2 H), 2.15 (s,
6 H). 13C{1H} NMR (100 MHz, acetoneꢁd6) δ 142.1, 135.8, 131.3, 128.3, 113.5, 129.1,
127.6, 125.4, 119.7, 119.1, 118.2, 110.2, 40.9, 37.8, 11.5. HRMS (EI) Calcd for
C19H17N2 [MꢁC7H7]+: 273.1391; Found: 273.1380.
3,3'-(2-Phenylethane-1,1-diyl)bis(2-phenyl-1H-indole) ((E)-4e)： The mixture
of 2ꢁphenylꢁ1Hꢁ indole (483 mg, 2.5 mmol), FeCl3⋅6H2O (17 mg, 0.0625 mmol) and
2a (330 mg, 2.75 mmol) in pꢁxylene (15 mL) was stirred at room temperature for 3 h.
All the volatiles were evaporated under reduced pressure and the resultant residue was
purified by silica gel column chromatography (eluent: petroleum ether
(60ꢁ90 °C)/ethyl acetate = 2:1, v/v) to afford 4e as a white solid (311 mg, 51%). M.p:
241ꢁ245 oC. 1H NMR (400 MHz, acetoneꢁd6) δ 10.10 (br, 2 H), 7.71 and 7.36 (d each,
J = 8.1 Hz, 2:2 H), 7.25ꢁ7.22 (m, 10 H), 7.04 (t, 2 H), 7.01ꢁ6.93 (m, 3 H), 6.91ꢁ6.79
(m, 4 H), 5.26 (t, 1 H), 3.73 (d, J = 7.9 Hz, 2 H). 13C{1H} NMR (100 MHz,
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acetoneꢁd6) δ 142.3, 137.4, 136.5, 135.1, 129.3, 115.8, 129.9, 129.7, 129.0, 128.5,
128.2, 126.4, 122.2, 121.9, 119.5, 111.9, 37.7. HRMS (EI) Calcd for C29H21N2
[MꢁC7H7]+: 397.1704; Found:397.1703.
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(E)-1,2-Dimethyl-3-(4-methylstyryl)-1H-indole ((E)-6a): Preheatedꢁtoꢁ85 C
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tBuOH (5 mL) was added to a mixture of Pd(MeCN)2Cl2 (5.2 mg, 0.02 mg) and
pꢁbenzoquinone (100 mg, 0.92 mmol). Water (16 ꢂL, 0.88 mmol) and 1ꢁmethylꢁ4ꢁ
vinylbenzene (95 mg, 0.8 mmol) were then added with stirring. After being stirred at
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85 C for 60 min the mixture was allowed to cool to room temperature. The resulting
mixture was filtered through a short path of celite, eluting with ethyl acetate. All the
volatiles were removed under reduced pressure to give crude 2ꢁpꢁtolylacetaldehyde16
and its solution in 3 mL CH2Cl2 was added to the mixture of FeCl3⋅6H2O (3.4 mg,
0.0125 mmol), EtOH (51.0 mg, 1.1 mmol) and 1a (72.5 mg, 0.5 mmol), and was
stirred at ambient temperature for 3 h. All the volatiles were removed under reduced
pressure, and the resultant mixture was purified by silica gel column chromatography
(eluent: petroleum ether (60ꢁ90 °C)/CH2Cl2 = 8:1, v/v) to afford 6a as a white solid
(102 mg, 78%). M.p.: 117ꢁ118 oC. 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 7.5 Hz,
1 H), 7.48 (d, J = 7.8 Hz, 2 H), 7.34ꢁ7.24 (m, 4 H), 7.21 (d, J = 7.9 Hz, 2 H), 7.13 (d,
J = 16.4 Hz, 1 H), 3.68, 2.53, and 2.41 (s each, 3:3:3 H). 13C{1H} NMR (100 MHz,
CDCl3) δ 137.3, 136.5, 136.3, 136.1, 125.9, 110.6, 129.4, 125.6, 125.0, 121.4, 121.2,
120.2, 119.9, 109.0, 29.7, 21.3, 10.8. HRMS (EI) Calcd for C19H19N: 261.1517;
Found: 261.1514.
(E)-3-(4-Bromostyryl)-1,2-dimethyl-1H-indole ((E)-6b): In a fashion similar to
the preparation of 6a, 6b was obtained as a yellow solid (113 mg, yield 69%). M.p.:
o
168ꢁ170 C. 1H NMR (400 MHz, CDCl3) δ 8.01ꢁ7.98 (m, 1 H), 7.48 (d, J = 8.4 Hz, 2
H), 7.40 (d, J = 8.4 Hz, 2 H), 7.34ꢁ7.22 (m, 4 H), 7.05 (d, J = 16.3 Hz, 1 H), 3.67 and
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2.51 (s each, 3:3 H). 13C{1H} NMR (100 MHz, CDCl3) δ 138.3, 137.4, 137.0, 125.8,
119.7, 110.3, 131.7, 127.1, 123.4, 122.9, 121.6, 120.4, 119.8, 109.2), 29.8, 10.8.
HRMS (EI) Calcd for C18H16BrN: 325.0466; Found: 325.0463.
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(E)-1,2-Dimethyl-3-(2-phenylprop-1-enyl)-1H-indole ((E/Z)-6c)：E/Z = 7:1,
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101 mg, yield 78%. White solid. M.p.: 98ꢁ100 oC. H NMR (400 MHz, CDCl3) δ for
(E/Z)ꢁ6c: 7.69 (d, J = 7.2 Hz, 2 H), 7.56 (d, J = 7.7 Hz, 1 H), 7.46 (t, 2 H), 7.35, 7.26
and 7.19 (m each, 2:1:1 H), 7.03 (s, 1 H); for (E)ꢁ6c: 3.75, 2.42, and 2.20 (s each,
3:3:3 H); for (Z)ꢁ6c: 3.59, 2.40, and 1.95 (s each, 3:3:3 H). 13C{1H} NMR (100 MHz,
CDCl3) δ for (E/Z)ꢁ6c: 143.5, 136.8, 136.7, 134.4, 119.2, 110.7; for (E)ꢁ6c: 128.4,
126.9, 125.9, 120.9, 120.0, 119.4, 119.3, 108.8, 29.7, 18.1, 11.7; for (Z)ꢁ6c: 128.2,
127.3, 126.2, 120.6, 119.2, 119.0, 108.4, 29.6, 25.6, 11.1. HRMS (EI) Calcd for
C19H19N: 261.1517; Found: 261.1532.
(E)-1,2-Dimethyl-3-(3-phenylprop-1-enyl)-1H-indole ((E)-6d): 17 mg, yield
1
13%. Yellow oil. H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 7.9 Hz, 1 H), 7.32 and
7.24 (m each, 4:2 H), 7.17 (d, J = 7.2 Hz, 1 H), and 7.12 (t, 1 H), 6.67 (d, J = 15.8 Hz,
1 H), 6.30 (dt, J = 15.8 and 6.9 Hz, 1 H), 3.66 and 2.45 (s each, 3:3 H), 3.64 (d, J =
6.7 Hz, 2 H). 13C{1H} NMR (100 MHz, CDCl3) δ 141.5, 137.2, 135.0, 126.1, 110.2,
128.7, 128.5, 126.0, 125.8, 124.0, 121.2, 119.8, 119.6, 108.8, 40.5, 29.6, 10.7. HRMS
(EI) Calcd for C19H19N: 261.1517; Found: 261.1526.
Acknowledgements. We are grateful to the National Basic Research Program of
China (2009CB825300) and the National Natural Science Foundation of China
(21272232) for support of this research.
Supporting Information Available: Copies of NMR spectra. This material is
available free of charge via the Internet at http://pubs.acs.org.
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