I2-promoted direct one-pot synthesis of 2,2-bisindolyl-1- arylethanones from multiform substrates arylethenes, 2-hydroxy-aromatic ketones, and carbinols

Article abstract of DOI:10.1016/j.tet.2013.06.054

An I₂-promoted domino protocol was developed to construct 2,2-bisindolyl-1-arylethanones from multiform substrates arylethenes, 2-hydroxy-aromatic ketones, and carbinols via three distinct pathways. Through a logical coupled oxidation/Friedel-Crafts alkylation domino process, a variety of 2,2-bisindolyl-1-arylethanones were synthesized in one-pot.

Full text of DOI:10.1016/j.tet.2013.06.054

Tetrahedron xxx (2013) 1e7
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I2-promoted direct one-pot synthesis of 2,2-bisindolyl-1-
arylethanones from multiform substrates arylethenes, 2-hydroxy-
aromatic ketones, and carbinols
*
Feng-Cheng Jia, Yan-Ping Zhu, Mei-Cai Liu, Mi Lian, Qing-He Gao, Qun Cai, An-Xin Wu
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An I2-promoted domino protocol was developed to construct 2,2-bisindolyl-1-arylethanones from
multiform substrates arylethenes, 2-hydroxy-aromatic ketones, and carbinols via three distinct path-
ways. Through a logical coupled oxidation/FriedeleCrafts alkylation domino process, a variety of 2,2-
bisindolyl-1-arylethanones were synthesized in one-pot.
Received 29 March 2013
Received in revised form 5 June 2013
Accepted 13 June 2013
Available online xxx
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
I2-promoted
One-pot
FriedeleCrafts alkylation
Bisindoles
1. Introduction
Due to the diverse activities of BIMs, many synthetic approaches
have been reported for the synthesis of bis(indolyl)methanes. The
Indole is a fundamental subunit of many bioactive compounds
and natural products.1 Among the indole derivatives, bis(indolyl)
methanes (BIMs), which were widely isolated from various ter-
restrial and marine natural sources,2 are well known to possess
various biological activities, pharmacological activities, such as
antimicrobial and antifungal,3a antibacterial,3b analgesic and anti-
inflammatory activities.3c Notably, cancer chemotherapy with
BIMs has recently been reviewed.4 For instance, bis(5-
methoxyindol-3-yl) methane was found to considerably inhibit
the growth of cancer cell lines (Fig. 1).5
most common methods involve FriedeleCrafts alkylation of indoles
with aldehydes/ketones, and many kinds of catalysts was adopted
to promote these reactions, such as Lewis acid,6 protoic acid,7a ionic
liguid,7b,c and other catalysts.7d In addition, alcohols, amines, im-
ines, alkynes, alkenes,8 and other substrates9 were also regarded as
effective modules to construct bis(indolyl)methanes block. Re-
cently, Wang and co-workers proposed a graceful Rhenium-
catalyzed site-switchable addition of indoles to terminal alkynes
for the synthesis of bisindolylalkane derivatives.10 Lee’s group de-
veloped an excellent Au(I)-catalyzed synthetic method to construct
diverse bisindoles from 3,3-disubstituted cyclopropenes.11 Our
group also presented a new method for direct synthesis of 2,2-
bisindolyl-1-arylethanones from aryl methyl ketones and indoles
via sp3 CeH diarylation.12 In this protocol,
a-ketoaldehyde proved
to be a key intermediate. On the basis of previous reports, we found
that a wide range of terminal aryl alkenes could easily be trans-
formed to
a
-iodo acetophenone in the presence of I2/IBX in
-iodo acetophenone was easily converted to a-
DMSO,13 and
a
ketoaldehyde in the media of DMSO via Kornblum oxidation.14
Herein, we attempt to directly construct various 2,2-bisindolyl-1-
arylethanones from arylethenes and indoles via the cascade
integration of iodination/oxidation/FriedeleCrafts alkylation
(Scheme 1).
Fig. 1. Chemical structures of bioactive bisindole derivatives.
* Corresponding author. Tel./fax: þ86 027 6786 7773; e-mail address: chwuax@
mail.ccnu.edu.cn (A.-X. Wu).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.06.054
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2
F.-C. Jia et al. / Tetrahedron xxx (2013) 1e7
experimental optimizations toward the dosage of I2 (Table 1, entries
sp C–H
17e19), we finally found that 1a (0.5 mmol) reacted with I2/IBX
(0.75 mmol/0.5 mmol) in DMSO at 80 ꢀC for 3 h, which was fol-
lowed by the addition of 2a (1.0 mmol) at room temperature for
another 5 h, the desired product (3aa) was afforded in 66% yield
(Table 1, entry 18).
With the optimal conditions in hand, the scope of the trans-
formation was investigated in the media of I2/IBX, and the results
were summarized in Table 2. As illustrated in Table 2, arylethenes
bearing electron-donating or -withdrawing groups, such as Me,
OMe, t-Bu, F, Cl, Br, and CN, could perform smoothly with N-
methylindole 2a to afford the desired products 3aae3ma in mod-
erate to good yields (54e75%). Furthermore, 2-naphthyl ethene
(1n) and biphenyl ethane (1o) also reacted with N-methylindole 2a
to obtain the desired products 3na and 3oa in 61% and 68% yields,
respectively. The results demonstrated that neither the electronic
nature nor steric hindrance of the arylethenes had considerable
influence on the reaction efficiency. Furthermore, the target com-
pound 3fa was determined by X-ray crystallographic analysis
(Fig. 2).
Scheme 1. Protocols for synthesis of 2,2-biaryl-1-arylethanones.
2. Results and discussion
Initially, the reaction of styrene (1a) with N-methylindole (2a)
was chosen as a model reaction for optimization of the conditions.
First, we screened a series of oxidants for the reaction, such as
TBHP, DMP, BTI, m-CPBA, HTIB, DDQ, PhI(OAc)2, and H2O2. Un-
fortunately, these oxidants failed to obtain the desired product 3aa
(Table 1, entries 1e8). To our delight, the reaction led to the desired
product (3aa) in a very low yield of 6% using IBX as oxidant (Table 1,
entry 9). Moreover, several different additives (NIS, KI, and TBAI)
was not found to promote the reaction (Table 1, entries 10e12). In
addition, the reaction could not perform without I2 (Table 1, entry
13). Elevation or decrease of the reaction temperature could not
improve the reaction yields (Table 1, entries 14e16). After several
Table 2
Reaction scope of arylethenesa
Entry
1 (Ar)
3
Yieldsb (%)
1
2
3
4
5
6
7
8
1a (C6H5)
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
3ja
3ka
3la
3ma
3na
3oa
66
62
61
64
54
67
58
63
62
70
74
75
70
61
68
1b (3-MeeC6H4)
1c (4-MeeC6H4)
1d (2,4-Me2eC6H3)
1e (2,4,6-Me3eC6H2)
1f (4-t-BueC6H4)
1g (4-MeOeC6H4)
1h (3-FeC6H4)
Table 1
Optimization of the reaction conditions
9
1i (4-FeC6H4)
10
11
12
13
14
15
1j (4-CleC6H4)
1k (3-BreC6H4)
1l (4-BreC6H4)
1m (4-CNeC6H4)
1n (2-Naphthyl)
1o (4-PheC6H4)
Entry
Additive (equiv)
Oxidant (equiv)
Temp (ꢀC)
Yieldc (%)
1a
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (1.0)
NIS (1.0)
KI (1.0)
TBAI (1.0)
d
TBHP (1.0)
DMP (1.0)
BTI (1.0)
m-CPBA (1.0)
HTIB (1.0)
DDQ (1.0)
PhI(OAc)2 (1.0)
H2O2 (1.0)
IBX (1.0)
IBX (1.0)
IBX (1.0)
IBX (1.0)
IBX (1.0)
IBX (1.0)
IBX (1.0)
IBX (1.0)
IBX (1.0)
IBX (1.0)
IBX (1.0)
80
80
80
80
80
80
80
80
80
80
80
80
80
80
60
100
80
80
80
nr
nr
nr
nr
nr
nr
nr
nr
6
nr
nr
nr
nr
62
42
58
64
66
45
a
2a
Reaction conditions: 1 (0.5 mmol), I2 (0.75 mmol), and IBX (0.5 mmol) were
heated in 3 mL DMSO at 80 ꢀC for 2e4 h, and then 2a (1.0 mmol) was added for
another 5e8 h.
3a
4a
b
5a
Isolated yields.
6a
7a
8a
9a
10a
11a
12a
13a
14b
15b
16b
17b
18b
19b
I2 (1.0)
I2 (1.0)
I2 (1.0)
I2 (2.0)
I2 (1.5)
I2 (0.5)
a
Reaction conditions: 1a (0.5 mmol), 2a (1.0 mmol), additive (0.5 mmol), oxidant
(0.5 mmol) were heated at 80 ꢀC in 3 mL DMSO for 3 h.
b
Reaction conditions: 1a (0.5 mmol), I2, and oxidant (0.5 mmol) were heated at
80 ꢀC for 3 h and then 2a (1.0 mmol) was added at room temperature for another 5 h.
c
Isolated yield. IBX¼o-iodoxy-benzoic acid, TBHP¼tert-butyl hydroperoxide,
DMP¼1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one,
BTI¼[bis-(tri-
fluoroacetoxy)iodo]benzene, m-CPBA¼3-chloroperbenzoic acid, HTIB¼[hydro(-
tosyloxy)iodo]benzene, DDQ¼2,3-dichloro-5,6-dicyano-1,4-benzoquinone. nr¼no
reaction.
Fig. 2. X-ray crystal structure of compound 3fa.
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F.-C. Jia et al. / Tetrahedron xxx (2013) 1e7
3
Subsequently, a series of indole derivatives and arylethenes
were examined. The electronic and steric nature of arylethenes had
little influence on the reaction efficiency, and all the corresponding
products were obtained in 55%e72% yields (Table 3, entries 1e6).
Then we turned our attention to the indole derivatives (2ce2h). The
substrates (2c and 2d) bearing electron-rich substituents could
perform smoothly to give the corresponding products in generally
good yields (Table 3, 3ac and 3ad). However, the electron-
withdrawing groups, such as 6-Br and 6-NO2, were shown to
largely decrease the reactivity, affording the desired products 3ae
and 3af in relatively low yields (Table 3). Meanwhile, the N-ally-
lindole 2g and N-benzylindole 2h also gave their corresponding
products 3ag and 3ah in 26% and 37% yields, respectively.
To our delight, 1-arylethanols 5 were also found compatible for
the transformation in the presence of IBX and I2 in DMSO. The re-
sults are summarized in Table 5. Here, 1-arylethanols 5 were
treated with IBX (1.0 equiv) and I2 (1.5 equiv) in DMSO at 80e90 ꢀC,
and then 2.0 equiv of N-methylindole 2a was added to the mixture
at room temperature. 1-Phenylethanol and 1-(4-bromophenyl)
ethanol (5a and 5c) could smoothly afford the expected products in
76% and 78% yields (Table 5, 3aa and 3la), respectively. However,
when the substrates 5b and 5d were used, the desired products
(3pa and 3qa) were only obtained in relatively low yields, possibly
due to the strong steric hindrance involved.
Table 5
Scope of 1-arylethanolsa
Table 3
Reaction scope of arylethenes and indole derivativesa
Entry
5 (Ar)
3
Yieldsb (%)
1
2
3
4
5a (C6H5)
3aa
3pa
3la
76
45
78
42
5b (2-MeOeC6H4)
5c (4-BreC6H4)
5d (6-MeOenaphthyl)
Entry
1 (Ar)
2
3
Yieldsb
(%)
3qa
a
Reaction conditions: 5 (0.5 mmol), IBX (0.5 mmol), and I2 (0.75 mmol) were
heated in 3 mL DMSO at 80e90 ꢀC for 3e5 h, and then 2a (1.0 mmol) was added at
room temperature for another 5e10 h.
1
2
3
4
5
6
7
8
1a (C6H5)
2b (R1¼H, R2¼H)
3ab
3gb
3kb
3mb
3nb
3ob
3ac
3ad
3ae
3af
60
55
62
72
60
70
71
75
45
Trace
26
37
1g (4-MeOeC6H5)
1k (3-BreC6H4)
1m (4-CNeC6H4)
1n (2-Naphthyl)
1o (4-PheC4H4)
1a (C6H5)
b
Isolated yields.
To gain insight into the mechanism, a series of control experi-
2c (R1¼H, R2¼6-Me)
2d (R1¼H, R2¼2-Me)
2e (R1¼H, R2¼6-Br)
2f (R1¼H, R2¼6-NO2)
2g (R1¼allyl, R2¼H)
2h (R1¼benzyl, R2¼H)
ments were also performed (Scheme 2). Styrene (1a) was converted
into a-iodo acetophenone (A) in 79% yield using the I2/IBX system
9
(Scheme 2a).13 Furthermore, phenacyl iodine (A) could be con-
verted into phenylglyoxal (B) or hydrated hemiacetal (C) in
a quantitative conversion in DMSO at 80 ꢀC (Scheme 2a).14 In ad-
dition, phenacyl iodine (A) could react with N-methylindole 2a and
I2 to obtain the product (3aa) in 87% yield (Scheme 2b). The re-
action of hydrated hemiacetal (C) with 2a also proceeded smoothly
in excellent yield (>95%) (Scheme 2c). These results clearly dem-
onstrated that phenacyl iodine (A) and phenylglyoxal (B) may be
key intermediates in the transformation. However, when hydrated
hemiacetal (C) was tested in the absence of I2, 3aa was obtained in
only 30% yield after 10 h (Scheme 2d). This results indicated that
10
11
12
3ag
3ah
a
Reaction conditions: 1 (0.5 mmol), I2(0.75 mmol), and IBX (0.5 mmol) were
heated in 3 mL DMSO at 80e90 ꢀC for 2e4 h, and then 2 (1.0 mmol) was added for
another 5e10 h.
b
Isolated yields.
To further expand the scope of the substrates, 2-
hydroxyaromatic ketones, such as 4ae4d were also investigated.
To our delight, 2-hydroxy-aromatic ketones could easily be trans-
formed to arylglyoxals in the presence of IBX in DMSO, which then
reacted with N-methylindole (2a) in the presence of I2 to afford the
corresponding products in one-pot. The desired products were
afforded in moderate to good yields (55e72%, Table 4, entries 1e4).
Table 4
Scope of 2-hydroxy-aromatic ketonesa
Entry
4 (Ar)
3
Yieldsb (%)
1
2
3
4
4a (C6H5)
3aa
3ca
3ia
3la
60
55
62
72
4b (4-MeeC6H4)
4c (4-FeC6H4)
4d (4-BreC6H4)
a
Reaction conditions: 4 (0.5 mmol) and IBX (0.5 mmol) were heated in 3 mL
DMSO at 80 ꢀC for 3e5 h, and then 2a (1 mmol) and I2 (0.75 mmol) were added at
room temperature for another 5e10 h.
b
Isolated yields.
Scheme 2. Controlled experiment to prove the mechanism.
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4
F.-C. Jia et al. / Tetrahedron xxx (2013) 1e7
iodine also played an important role in the FriedeleCrafts alkyl-
ation process.
On the basis of the results described above and previous re-
ports,12,15 a possible mechanism of the present reaction was pro-
posed using styrene (1a) and N-methylindole (2a) as an example
(Scheme 3). Initially, the substrate 1a was converted into the in-
150 MHz NMR spectrometers and resonances (d) are given in ppm.
HRMS were obtained on a 7.0 TFTMS equipped with ESI. The X-ray
crystal structure determinations of 3fa was obtained on a Bruker
SMART APEX CCD system. Melting points were determined using
XT-4 apparatus and not corrected.
termediate
a-iodo acetophenone (A) in the presence of I2. Sub-
sequently, intermediate
A
was conveniently converted to
4.2. General procedure for synthesis of 3 (3aa as an example)
phenylglyoxal (B) in the media of DMSO via Kornblum oxidation.14
Carbinol 5a was oxidized by IBX to afford acetophenone 5a0, which
was followed by iodination and Kornblum oxidation to give phe-
nylglyoxal (B). In addition, 2-hydroxy-1-phenylethanone 4a was
easily oxidized to phenylglyoxal (B) by oxidant IBX.16 Then, the
aldehyde group of phenylglyoxal (B) was activated by excess or
regenerated Lewis acid I2.7a,17 N-Methy-lindole 2a could attack the
activated aldehyde group of phenylglyoxal (B) to give the 3-
alkylidene-3H-indolium cation D. Finally, another N-methyl-
indole 2a could further trap the cation D to give the desired
product 3aa.
A sealed tube was charged with styrene (1a) (52 mg, 0.5 mmol),
IBX (140 mg, 0.5 mmol), and iodine (189.5 mg, 0.75 mmol) at room
temperature, and dried solvent DMSO (3 mL) was then added. The
resulting mixture was stirred at 80e85 ꢀC for 2 h, after disap-
pearance of the reactant (monitored by TLC), then added N-meth-
ylindole 2a (134 mg, 1.0 mmol) at room temperature for another
5 h. After the reaction completed, then added 50 mL water to the
mixture, extracted with EtOAc three times (3ꢂ50 mL). The extract
was washed with 10% Na2S2O3 solution, dried over anhydrous
Na2SO4, and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel (petroleum ether/
EtOAc¼10:1) to afford the desired product 3aa as a brown solid
(66% yield).
4.3. Characterization data
4.3.1. 2,2-Bis(1-methyl-1H-indol-3-yl)-1-phenylethanone (3aa).12
Yield 66%; brown solid, mp 79e81 ꢀC; IR (KBr): 1684, 1614, 1595,
1540, 1471, 1371, 1330, 1198, 1013 cmꢁ1; 1H NMR (600 MHz, CDCl3):
d
(ppm)¼8.10 (d, J¼7.2 Hz, 2H), 7.56 (d, J¼7.8 Hz, 2H), 7.49 (t,
J¼7.2 Hz, 1H), 7.39 (t, J¼7.6 Hz, 2H), 7.28 (s, 1H), 7.21 (s, 1H), 7.20 (d,
J¼7.8 Hz, 2H), 7.07 (t, J¼7.2 Hz, 2H), 6.87 (s, 2H), 6.52 (s, 1H), 3.66 (s,
6H); 13C NMR (150 MHz, CDCl3):
d
(ppm)¼198.6, 137.2, 137.0, 132.8,
128.7, 128.5, 127.0, 121.7, 119.1, 119.0, 112.8, 109.3, 41.7, 32.7; HRMS
(ESI): m/z [MþNa]þ calcd for C26H22N2ONa: 401.1624; found:
401.1624.
Scheme 3. The plausible mechanism of the present reaction.
4.3.2. 2,2-Bis(1-methyl-1H-indol-3-yl)-1-(m-tolyl)ethanone (3ba).
Yield 62%; yellow solid, mp 178e181 ꢀC; IR (KBr): 1687, 1613, 1584,
3. Conclusion
1471, 1266, 1174, 1155, 1131, 1118, 1013 cmꢁ1 1H NMR (600 MHz,
;
CDCl3):
d
(ppm)¼8.05 (t, J¼8.4 Hz, 2H), 7.70 (d, J¼7.8 Hz, 2H), 7.41
In summary, we have developed an efficient I2-promoted
domino oxidative dual-(het)arylation process to construct 2,2-
bisindolyl-1-arylethanones from multiform substrates aryle-
thenes, 2-hydroxy-aryl ketones, and 1-arylethanols. In the trans-
formation, two mechanism-different reactions (oxidation and
subsequent FriedeleCrafts alkylation) were assembled in a single
reactor. Applications of this methodology for the construction of
other heterocycles are currently being investigated in our
laboratory.
(d, J¼7.2 Hz, 1H), 7.37 (d, J¼7.8 Hz, 3H), 7.32 (t, J¼7.2 Hz, 2H), 7.19 (t,
J¼7.2 Hz, 2H), 6.99 (s, 2H), 6.66 (s, 1H), 3.73 (s, 6H), 2.46 (s, 3H); 13
C
NMR (100 MHz, CDCl3):
d
(ppm)¼198.8, 138.3, 137.1, 136.8, 133.6,
129.1, 128.5, 128.4, 126.9, 125.9, 121.6, 119.0, 118.9, 112.7, 109.3, 41.5,
32.7, 21.4; HRMS (ESI): m/z [MþNa]þ calcd for C27H24N2ONa:
415.1781; found: 415.1780.
4.3.3. 2,2-Bis(1-methyl-1H-indol-3-yl)-1-p-tolylethanone (3ca).12
Yield 61%; brown solid; mp 137e139 ꢀC; IR (KBr): 1675, 1605, 1547,
1471, 1371, 1330, 1181, 1012, 975, 740, 689 cmꢁ1; 1H NMR (400 MHz,
4. Experimental
4.1. General
CDCl3):
d
(ppm)¼8.05 (d, J¼7.6 Hz, 2H), 7.58 (d, J¼8.0 Hz, 2H), 7.29
(d, J¼8.0 Hz, 2H), 7.22 (t, J¼7.6 Hz, 4H), 7.09 (t, J¼7.6 Hz, 2H), 6.88 (s,
2H), 6.53 (s, 1H), 3.66 (s, 6H), 2.36 (s, 3H); 13C NMR (100 MHz,
CDCl3):
d
(ppm)¼198.2, 143.6, 137.1, 134.2, 129.2, 128.9, 128.5, 126.9,
All substrates and reagents were commercially available and
used without further purification. TLC analysis was performed us-
ing pre-coated glass plates. Column chromatography was per-
formed using silica gel (200e300 mesh). IR spectra were recorded
on a PerkineElmer PE-983 infrared spectrometer as KBr pellets
121.6, 119.0, 118.9, 112.8, 109.3, 41.4, 32.7, 21.6; HRMS (ESI): m/z
[MþNa]þ calcd for C27H24N2ONa: 415.1781; found: 415.1782.
4.3.4. 1-(2,4-Dimethylphenyl)-2,2-bis(1-methyl-1H-indol-3-yl)etha-
none (3da). Yield 64%; red solid; mp 63e66 ꢀC; IR (KBr): 1682,1611,
with absorption in cmꢁ1
.
1H spectra were recorded in CDCl3 or
) are
1470, 1401, 1329, 1197, 1153, 1132, 1012 cmꢁ1 1H NMR (600 MHz,
;
DMSO on 400/600 MHz NMR spectrometers and resonances (
d
CDCl3):
d
(ppm)¼7.80 (d, J¼7.2 Hz, 1H), 7.53 (d, J¼7.2 Hz, 2H), 7.27
given in parts per million relative to tetramethylsilane. Data are
reported as follows: chemical shift, multiplicity (s¼singlet,
d¼doublet, t¼triplet, m¼multiplet), coupling constants (Hertz) and
integration. 13C spectra were recorded in CDCl3 or DMSO on 100/
(d, J¼7.2 Hz, 1H), 7.20 (s, 3H), 7.06 (t, J¼6.0 Hz, 2H), 7.03 (s, 1H), 6.97
(d, J¼6.6 Hz, 1H), 6.91 (s, 2H), 6.36 (s, 1H), 3.67(s, 6H), 2.42 (s, 3H),
2.30 (s,3H); 13C NMR (100 MHz, CDCl3):
d
(ppm)¼202.0,141.7,139.2,
137.1, 135.1, 132.8, 129.1, 128.4, 127.0, 126.2, 121.6, 119.0, 113.1, 109.3,
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F.-C. Jia et al. / Tetrahedron xxx (2013) 1e7
5
44.2, 32.7, 21.4, 21.3; HRMS (ESI): m/z [MþNa]þ calcd for
1473, 1425, 1373, 1330, 1226, 1209, 1196, 1012 cmꢁ1
(600 MHz, CDCl3):
;
1H NMR
C
28H26N2ONa: 429.1937; found: 429.1945.
d
(ppm)¼8.24 (s, 1H), 8.00 (d, J¼7.8 Hz, 1H), 7.59
(d, J¼7.8 Hz, 1H), 7.54 (d, J¼7.8 Hz, 2H), 7.27 (d, J¼8.4 Hz, 2H),
7.28e7.20 (m, 3H), 7.08 (t, J¼7.8 Hz, 2H), 6.85 (s, 2H), 6.43(s, 1H),
4.3.5. 1-Mesityl-2,2-bis(1-methyl-1H-indol-3-yl)ethanone
Yield 54%; yellow solid; mp 94e97 ꢀC; IR (KBr): 1696, 1611, 1469,
1400, 1329, 1150, 1132, 1014, cmꢁ1 1H NMR (600 MHz, CDCl3):
(ppm)¼7.33 (d, J¼7.2 Hz, 4H), 7.24 (s, 1H), 7.22 (s, 1H), 7.15 (t,
J¼7.2 Hz, 2H), 6.95 (t, J¼7.8 Hz, 2H), 6.75 (s, 2H), 5.97 (s, 1H), 3.73 (s,
6H), 2.26 (s, 3H), 1.87 (s, 6H); 13C NMR (100 MHz, CDCl3):
(3ea).-
3.66 (s, 6H); 13C NMR (100 MHz, CDCl3):
d
(ppm)¼197.1,138.6,137.2,
;
135.6, 131.6, 130.1, 128.5, 127.3, 126.8, 122.9, 121.8, 119.2, 118.9, 112.2,
109.4, 41.9, 32.8; HRMS (ESI): m/z [MþNa]þ calcd for
d
C26H21BrN2ONa: 479.0730; found: 479.0732.
d
(ppm)¼
207.4, 139.7, 138.6,136.8, 134.1, 128.5, 128.4, 127.2, 121.4, 119.2, 118.8,
4.3.12. 1-(4-Bromophenyl)-2,2-bis(1-methyl-1H-indol-3-yl)ethanone
(3la).12 Yield 75%; brown solid; mp 168e170 ꢀC; IR (KBr): 1681,
1583, 1535, 1474, 1423, 1372, 1330, 1196, 1176, 1070, 1009 cmꢁ1; 1H
111.8, 109.1, 47.4, 32.8, 21.1, 19.4; HRMS (ESI): m/z [MþH]þ calcd for
C
29H29N2O: 421.2274; found: 421.2275.
NMR (400 MHz, CDCl3):
d
(ppm)¼7.95 (d, J¼8.4 Hz, 2H), 7.52 (t,
4.3.6. 1-(4-(tert-Butyl)phenyl)-2,2-bis(1-methyl-1H-indol-3-yl)etha-
none (3fa). Yield 67%;red solid;mp 247e250 ꢀC; IR (KBr): 1684,1602,
1472, 1365, 1346, 1270, 1231, 1189, 1110, 1010 cmꢁ1; 1H NMR (600 MHz,
J¼8.4 Hz, 4H), 7.29 (d, J¼8.4 Hz, 2H), 7.22 (t, J¼8.0 Hz, 2H), 7.08 (t,
J¼7.6 Hz, 2H), 6.85 (s, 2H), 6.43 (s, 1H), 3.67 (s, 6H); 13C NMR
(100 MHz, CDCl3):
d
(ppm)¼197.5, 137.2, 135.5, 131.8, 130.3, 128.5,
CDCl3):
d
(ppm)¼8.06 (d, J¼8.4 Hz, 2H), 7.57 (d, J¼7.8 Hz, 2H), 7.41 (d,
127.9, 126.8, 121.8, 119.2, 118.8, 112.3, 109.4, 41.8, 32.8; HRMS (ESI):
J¼8.4 Hz, 2H), 7.27 (d, J¼7.8 Hz, 2H), 7.22e7.19 (m, 2H), 7.07 (t,
m/z [MþNa]þ calcd for C26H21BrN2ONa: 479.0729; found: 479.0727.
J¼7.8 Hz, 2H), 6.87 (s, 2H), 6.52 (s, 1H), 3.67 (s, 6H), 1.30 (s, 9H); 13
C
NMR (100 MHz, CDCl3):
d
(ppm)¼198.1, 156.4, 137.2, 134.3, 128.7, 128.5,
4.3.13. 4-(2,2-Bis(1-methyl-1H-indol-3-yl)acetyl)benzonitrile
127.1,125.5,121.6,119.1,119.0,113.0,109.3, 41.5, 35.0, 32.7, 31.0; HRMS
(3ma). Yield 70%; yellow solid; mp 225e228 ꢀC; IR (KBr): 2229,
(ESI): m/z [MþH]þ calcd for C30H31N2O: 435.2431; found: 435.2433.
1685, 1473, 1373, 1330, 1230, 1198, 1013 cmꢁ1 1H NMR (600 MHz,
;
CDCl3):
d
(ppm)¼8.12 (d, J¼7.2 Hz, 2H), 7.63 (d, J¼7.8 Hz, 2H), 7.52
4.3.7. 1-(4-Methoxyphenyl)-2,2-bis(1-methyl-1H-indol-3-yl)etha-
none (3ga).12 Yield 58%; brown solid; mp 137e139 ꢀC; IR (KBr): 1669,
1600,1574,1465,1329,1262,1225,1174,1013, 978, 740 cmꢁ1; 1H NMR
(d, J¼7.8 Hz, 2H), 7.29 (d, J¼7.8 Hz, 2H), 7.23 (t, J¼7.8 Hz, 2H), 7.09 (t,
7.2 Hz, 2H), 6.85 (s, 2H), 6.43 (s, 1H), 3.67 (s, 6H); 13C NMR
(100 MHz, CDCl3):
d
(ppm)¼196.9, 139.9, 137.2, 132.3, 129.0, 126.7,
(400 MHz, CDCl3):
d
(ppm)¼8.13 (d, J¼8.8 Hz, 2H), 7.58 (d, J¼7.6 Hz,
121.9, 119.3, 118.7, 118.0, 115.7, 111.7, 109.5, 42.3, 32.7; HRMS (ESI):
2H), 7.30 (d, J¼8.4 Hz, 2H), 7.22 (d, J¼7.6 Hz, 2H), 7.09 (t, J¼8.4 Hz, 2H),
m/z [MþNa]þ calcd for C27H21N3ONa: 426.1577; found: 426.1580.
6.91 (s,1H), 6.89 (s, 3H), 6.51 (s,1H), 3.82 (s, 3H), 3.68 (s, 6H); 13C NMR
(100 MHz, CDCl3):
d
(ppm)¼197.2, 163.2, 137.1, 131.0, 129.6, 128.4,
4.3.14. 2,2-Bis(1-methyl-1H-indol-3-yl)-1-(naphthalen-2-yl)etha-
none (3na).12 Yield 61%; brownsolid; mp 107e110 ꢀC; IR (KBr): 1674,
1624, 1593, 1536, 1470, 1424, 1372, 1330, 1214, 1180, 1155, 1127, 1067,
127.0,121.6,119.0,118.9,113.7,112.9,109.3,55.3,41.2,32.7;HRMS(ESI):
m/z [MþNa]þ calcd for C27H24N2O2Na: 431.1730; found: 431.1732.
1013 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
(ppm)¼8.69 (s, 1H), 8.14 (d,
4.3.8. 1-(3-Fluorophenyl)-2,2-bis(1-methyl-1H-indol-3-yl)ethanone
(3ha). Yield 63%; red solid; mp 150e153 ꢀC; IR (KBr): 1683, 1608,
J¼7.2 Hz, 1H), 7.88 (d, J¼8.0 Hz, 1H), 7.82 (d, J¼8.8 Hz, 2H), 7.61 (d,
J¼8.0 Hz, 2H), 7.53 (t, J¼7.2 Hz, 1H), 7.47 (t, J¼7.2 Hz, 1H), 7.28 (d,
J¼8.4 Hz, 2H), 7.21 (t, J¼8.8 Hz, 2H), 7.08 (t, J¼7.2 Hz, 2H), 6.91 (s, 2H),
1477, 1448, 1426, 1373, 1330, 1269, 1210, 1196, 1131, 1013 cmꢁ1 1H
;
NMR (600 MHz, CDCl3):
d
(ppm)¼7.84 (s, 1H), 7.59 (d, J¼7.8 Hz, 2H),
6.69 (s, 1H), 3.66 (s, 6H); 13C NMR (100 MHz, CDCl3):
d
(ppm)¼198.6,
7.39 (d, J¼4.8 Hz, 1H), 7.25 (d, J¼7.8 Hz, 2H), 7.19 (d, J¼7.8 Hz, 2H),
7.11 (d, J¼7.8 Hz, 1H), 7.06 (d, J¼7.2 Hz, 3H), 6.90 (s, 2H), 6.43 (s, 1H),
137.2, 135.4, 134.2,132.5,130.2,129.7, 128.5,128.4,128.3,127.6, 127.0,
126.6,124.7,121.7,119.1,119.0,112.8,109.4, 41.8, 32.8;HRMS (ESI):m/z
[MþNa]þ calcd for C30H24N2ONa: 451.1781; found: 451.1779.
3.65 (s, 6H); 13C NMR (100 MHz, CDCl3):
d
(ppm)¼197.2, 159.9,
137.2, 134.0, 133.9, 131.4, 128.5, 127.2, 124.4, 121.6, 119.2, 119.1, 116.7,
116.5, 112.1, 109.3, 45.7, 32.7; HRMS (ESI): m/z [MþNa]þ calcd for
C
26H21FN2ONa: 419.1530; found: 419.1532.
4.3.15. 1-(Biphenyl-4-yl)-2,2-bis(1-methyl-1H-indol-3-yl)ethanone
(3oa).12 Yield 68%; brown solid; mp 191e193 ꢀC; IR (KBr): 1680,
1602, 1556, 1537, 1473, 1423, 1371, 1330, 1221, 1183, 1156, 1131, 1118,
4.3.9. 1-(4-Fluorophenyl)-2,2-bis(1-methyl-1H-indol-3-yl)ethanone
1009 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
(ppm)¼8.19 (d, J¼8.4 Hz,
(3ia). Yield 62%; red solid; mp 184e186 ꢀC; IR (KBr): 1679, 1596,
1505, 1483, 1465, 1372, 1330, 1224, 1197, 1157, 1031, 1012 cmꢁ1 1H
;
2H), 7.62 (d, J¼8.8 Hz, 3H), 7.57 (d, J¼7.2 Hz, 3H), 7.43 (t, J¼7.6 Hz,
2H), 7.36 (t, J¼7.2 Hz, 1H), 7.29 (d, J¼8.0 Hz, 2H), 7.22 (d, J¼7.6 Hz,
NMR (600 MHz, CDCl3):
d
(ppm)¼8.12 (t, J¼6.6 Hz, 2H), 7.54 (d,
2H), 7.09 (t, J¼7.6 Hz, 2H), 6.89 (s, 2H), 6.56 (s, 1H), 3.69 (s, 6H); 13
C
J¼7.8 Hz, 2H), 7.28 (d, J¼7.8 Hz, 2H), 7.21 (t, J¼7.2 Hz, 2H), 7.09e7.04
(m, 4H), 6.86 (s, 2H), 6.46 (s, 1H), 3.67 (s, 6H); 13C NMR (100 MHz,
NMR (100 MHz, CDCl3):
d
(ppm)¼198.1, 145.4, 139.9, 137.2, 135.5,
CDCl3):
d
(ppm)¼197.0, 166.7, 137.2, 133.4, 131.4, 131.3, 128.4, 126.9,
129.4, 128.9, 128.5, 128.1, 127.2, 127.0, 121.7, 119.1, 119.0, 112.7, 109.4,
41.7, 32.8; HRMS (ESI): m/z [MþNa]þ calcd for C32H26N2ONa:
477.1937; found: 477.1941.
121.7, 119.2, 118.8, 115.7, 112.5, 109.4, 41.7, 32.8; HRMS (ESI): m/z
[MþH]þ calcd for C26H22FN2O: 397.1711; found: 397.1713.
4.3.16. 2,2-Di(1H-indol-3-yl)-1-phenylethanone (3ab).12 Yield 60%;
brown solid; mp 135e138 ꢀC; IR (KBr): 3397, 3381, 3057, 1736, 1679,
1618, 1595, 1458, 1419, 1340, 1220, 1201, 1091, 1002 cmꢁ1; 1H NMR
4.3.10. 1-(4-Chlorophenyl)-2,2-bis(1-methyl-1H-indol-3-yl)ethanone
(3ja).12 Yield 70%; white solid; mp 150e153 ꢀC; IR (KBr): 1680,
1588, 1545, 1466, 1423, 1400, 1371, 1329, 1265, 1232, 1198, 1089,
1011, 981, 811, 746 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
(ppm)¼8.06
(600 MHz, DMSO-d6):
d
(ppm)¼10.94 (s, 1H), 8.18 (d, J¼7.2 Hz, 2H),
(d, J¼8.4 Hz, 2H), 7.56 (d, J¼8.0 Hz, 2H), 7.39 (d, J¼8.4 Hz, 2H), 7.32
(d, J¼8.4 Hz, 2H), 7.24 (d, J¼7.6 Hz, 2H), 7.11 (t, J¼14.8 Hz, 2H), 6.87
(s, 2H), 6.46 (s, 1H), 3.70 (s, 6H); 13C NMR (100 MHz, CDCl3):
7.58 (d, J¼7.8 Hz, 2H), 7.55 (d, J¼7.2 Hz, 2H), 7.47 (t, J¼7.2 Hz, 2H),
7.36 (t, J¼8.4 Hz, 2H), 7.20 (s, 2H), 7.07 (t, J¼7.2 Hz, 2H), 6.965 (t,
J¼7.2 Hz, 2H), 6.67 (s, 1H); 13C NMR (150 MHz, DMSO-d6):
(ppm)¼
d
d
(ppm)¼197.3, 139.2, 137.2, 135.1, 130.2, 128.9, 128.5, 126.8, 121.8,
198.0, 136.6, 136.2, 132.9, 128.7, 128.6, 126.5, 124.3, 121.1, 119.0,
119.2, 118.8, 112.3, 109.4, 41.8, 32.8; HRMS (ESI): m/z [MþNa]þ calcd
118.6, 112.9, 111.5, 41.6; HRMS (ESI): m/z [MþNa]þ calcd for
for C26H21ClN2ONa: 435.1235; found: 435.1232.
C24H18N2ONa: 373.1311; found: 373.1321.
4.3.11. 1-(3-Bromophenyl)-2,2-bis(1-methyl-1H-indol-3-yl)ethanone
(3ka). Yield 74%; brown solid; mp 200e203 ꢀC; IR (KBr): 1688,
4.3.17. 2,2-Di(1H-indol-3-yl)-1-(4-methoxyphenyl)ethanone
(3gb).12 Yield 55%; brown solid; mp 220e222 ꢀC; IR (KBr): 3408,
Please cite this article in press as: Jia, F.-C.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.06.054

6
F.-C. Jia et al. / Tetrahedron xxx (2013) 1e7
3376, 3044, 2965, 2929, 1665, 1595, 1507, 1456, 1417, 1338, 1264, 1226,
1163, 1118, 1091, 1004 cmꢁ1; 1H NMR (400 MHz, DMSO-d6):
10.91 (s, 2H), 8.17 (d, J¼8.8 Hz, 2H), 7.57 (d, J¼8.0 Hz, 2H), 7.35 (d,
J¼8.0 Hz, 2H), 7.17 (t, J¼7.6 Hz, 2H), 7.05 (t, J¼7.6 Hz, 2H), 7.00e6.92
(m, 4H), 6.61 (s, 1H), 3.79 (s, 3H); 13C NMR (100 MHz, DMSO-d6):
3376, 1674, 1579, 1459, 1427, 1300, 1221, 1008 cmꢁ1
(400 MHz, DMSO-d6):
;
1H NMR
(ppm)¼10.84 (s, 2H), 8.04 (d, J¼7.6 Hz, 2H),
d
(ppm)¼
d
7.51 (t, J¼7.2 Hz, 1H), 7.41 (t, J¼7.6 Hz, 2H), 7.22 (d, J¼8.0 Hz, 2H),
7.16 (d, J¼8.0 Hz, 2H), 6.92 (t, J¼7.2 Hz, 2H), 6.78 (t, J¼7.6 Hz, 2H),
6.44 (s, 1H), 2.13 (s, 6H); 13C NMR (100 MHz, DMSO-d6):
d
(ppm)¼
d
(ppm)¼196.4, 162.9, 136.3, 130.9, 129.3, 126.5, 124.3, 120.9, 119.0,
198.6, 137.0, 135.0, 132.8, 132.7, 128.6, 128.2, 119.7, 118.2, 118.1, 110.4,
107.7, 42.1, 11.9; HRMS (ESI): m/z [MþNa]þ calcd for C26H22N2ONa:
401.1624; found: 401.1620.
118.4,113.9,113.3,111.5, 55.4, 41.2; HRMS (ESI): m/z [MþNa]þ calcd for
C
25H20N2O2Na: 403.1417; found: 403.1401.
4.3.18. 1-(3-Bromophenyl)-2,2-di(1H-indol-3-yl)ethanone
(3kb). Yield 62%; white solid; mp 255e258 ꢀC; IR (KBr): 3404, 3375,
3061, 2858, 1685, 1561, 1458, 1414, 1340, 1269, 1218, 1197, 1090,
4.3.24. 2,2-Bis(6-bromo-1H-indol-3-yl)-1-phenylethanone
(3ae).12 Yield 45%; brown solid; mp 68e70 ꢀC; IR (KBr): 3339,
2954, 2925, 2856, 1714, 1676, 1612, 1595, 1450, 1401, 1332, 1286,
1013 cmꢁ1
;
1H NMR (400 MHz, DMSO-d6):
d
(ppm)¼10.94 (s, 2H),
1213, 1047, 1023 cmꢁ1
;
1H NMR (400 MHz, DMSO-d6):
d
(ppm)¼
8.26 (s, 1H), 8.17 (d, J¼8.0 Hz, 1H), 7.75 (d, J¼7.6 Hz, 1H), 7.57 (d,
J¼7.6 Hz, 2H), 7.43 (t, J¼8.0 Hz,1H), 7.34 (d, J¼8.0 Hz, 2H), 7.12 (s, 2H),
7.06 (t, J¼7.6 Hz, 2H), 6.95 (t, J¼7.4 Hz, 2H), 6.66 (s, 1H); 13C NMR
11.13 (s, 2H), 8.18 (t, J¼7.2 Hz, 2H), 7.47e7.58 (m, 7H), 7.25 (d,
J¼8.0 Hz, 2H), 7.12 (d, J¼7.6 Hz, 2H), 7.70 (d, J¼11.2 Hz, 1H); 13C
NMR (100 MHz, DMSO-d6):
d
(ppm)¼197.6, 137.2, 136.3, 133.0,
(100 MHz, DMSO-d6):
d
(ppm)¼196.7, 138.6, 136.3,135.6,131.0, 130.9,
128.6, 128.5, 125.5, 121.4, 120.8, 114.1, 113.9, 113.1, 79.1, 41.3; HRMS
(ESI): m/z [MþNa]þ calcd for C24H16Br2N2ONa: 528.9522; found:
530.9509.
127.6, 126.5, 124.6, 122.2, 121.1, 119.1, 118.6, 112.5, 111.6, 41.8; HRMS
(ESI): m/z [MþH]þ calcd for C24H18BrN2O: 429.0597; found: 429.0591.
4.3.19. 4-(2,2-Di(1H-indol-3-yl)acetyl)benzonitrile (3mb). Yield
72%; yellow solid; mp 119e123 ꢀC; IR (KBr): 3401, 3124, 2361, 2339,
2231, 1728, 1686, 1457, 1402, 1339, 1244, 1214, 1097, 1045 cmꢁ1; 1H
4.3.25. 2,2-Bis(1-allyl-1H-indol-3-yl)-1-phenylethanone
(3ag).12 Yield 26%; brown solid; mp 163e165 ꢀC; IR (KBr): 1686,
1467, 1443, 1334, 1216, 1188 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
NMR (600 MHz, CDCl3):
d
(ppm)¼8.02 (d, 8.4 Hz, 2H), 7.99 (s, 2H),
d
(ppm)¼8.09 (d, J¼8.0 Hz, 2H), 7.57 (d, J¼8.0 Hz, 2H), 7.49 (t,
7.49 (d, J¼7.2 Hz, 2H), 7.45 (d, J¼7.8 Hz, 2H), 7.17 (d, J¼7.8 Hz, 2H), 7.11
J¼7.2 Hz, 1H), 7.39 (t, J¼7.6 Hz, 2H), 7.28 (d, J¼8.0 Hz, 2H), 7.22 (s,
1H), 7.20 (s, 1H), 7.17 (d, J¼8.4 Hz, 1H), 7.06 (t, J¼7.2 Hz, 2H), 6.93
(s, 1H), 6.51 (s, 1H), 5.96e5.88 (m, 2H), 5.11 (d, J¼10.0 Hz, 2H),
5.03 (s, 1H), 4.99 (s, 1H), 4.62 (d, J¼5.2 Hz, 4H); 13C NMR
(t, J¼7.4 Hz, 2H), 7.03 (t, J¼7.4 Hz, 2H), 6.60 (s, 2H), 6.34 (s, 1H); 13
C
NMR (100 MHz, CDCl3):
d
(ppm)¼197.6, 139.5, 136.3, 132.3, 128.9,
126.1, 124.2, 122.2, 119.7, 118.5, 117.9, 115.6, 112.6, 111.6, 42.6; HRMS
(ESI): m/z [MþH]þ calcd for C25H18N3O: 376.1444; found: 376.1444.
(100 MHz, CDCl3):
d
(ppm)¼198.5, 137.0, 136.7, 133.4, 132.7, 128.7,
128.5, 127.6, 127.3, 121.7, 119.3, 119.1, 117.1, 113.1, 109.8, 48.8, 41.9;
HRMS (ESI): m/z [MþNa]þ calcd for C30H26N2ONa: 453.1937;
found: 453.1942.
4.3.20. 2,2-Di(1H-indol-3-yl)-1-(naphthalen-2-yl)ethanone
(3nb).12 Yield 60%; brown solid; mp 205e208 ꢀC; IR (KBr): 3505,
3408, 3397, 3054, 2963, 2868, 1672, 1621, 1591, 1454, 1416, 1355,
1336, 1306, 1263, 1216, 1170, 1092, 1025, 1010 cmꢁ1
;
1H NMR
4.3.26. 2,2-Bis(1-benzyl-1H-indol-3-yl)-1-phenylethanone
(400 MHz, DMSO-d6):
d
(ppm)¼10.94 (s, 2H), 9.00 (s, 1H), 8.13 (d,
(3ah).12 Yield 37%; brown solid; mp 188e190 ꢀC; IR (KBr): 1685,
J¼8.8 Hz, 1H), 8.10 (d, J¼8.0 Hz, 1H), 7.96 (d, J¼8.0 Hz, 1H), 7.93 (s,
1H), 7.65e7.59 (m, 4H), 7.34 (d, J¼8.0 Hz, 2H), 7.25 (s, 2H), 7.05 (t,
J¼7.6 Hz, 2H), 6.95 (t, J¼7.6 Hz, 2H), 6.86 (s, 1H); 13C NMR (100 MHz,
1607, 1493, 1466, 1448, 1374, 1359, 1335, 1197, 1172 cmꢁ1 1H NMR
;
(400 MHz, CDCl3):
d
(ppm)¼8.09 (d, J¼7.6 Hz, 2H), 7.59 (d, J¼8.0 Hz,
2H), 7.46 (t, J¼7.6 Hz, 1H), 7.36 (t, J¼7.6 Hz, 2H), 7.19e7.16 (m, 7H),
7.11 (t, J¼7.2 Hz, 3H), 7.04 (d, J¼7.2 Hz, 3H), 6.98 (s, 2H), 6.96 (t,
J¼7.2 Hz, 3H), 6.53 (s, 1H), 5.16 (s, 4H); 13C NMR (100 MHz, CDCl3):
DMSO-d6):
d
(ppm)¼197.9, 136.3, 134.8, 133.8, 132.2, 130.0, 129.6,
128.5, 128.2, 127.5, 126.8, 126.5, 124.5, 124.4, 121.0, 119.0, 118.5,
113.0,111.5, 40.1; HRMS (ESI): m/z [MþNa]þ calcd for C28H20N2ONa:
423.1468; found: 423.1476.
d
(ppm)¼198.3, 137.5, 137.0, 136.9, 132.7, 128.7, 128.6, 128.5, 128.1,
127.4,127.36,126.5,121.9,119.4,119.3,113.3,109.9, 49.9, 42.2; HRMS
(ESI): m/z [MþNa]þ calcd for C38H30N2ONa: 553.2250; found:
553.2292.
4.3.21. 1-([1,10-Biphenyl]-4-yl)-2,2-di(1H-indol-3-yl)ethanone
(3ob). Yield 70%; red solid; mp 116e119 ꢀC; IR (KBr): 3407, 3054,
1673, 1557, 1456, 1339, 1217, 1186, 1096 cmꢁ1
;
1H NMR (600 MHz,
4.3.27. 1-(2-Methoxyphenyl)-2,2-bis(1-methyl-1H-indol-3-yl)etha-
CDCl3):
d
(ppm)¼8.13 (d, J¼8.4 Hz, 2H), 7.96 (s, 2H), 7.55 (s, 1H), 7.54
none (3pa). Yield 45%; red solid; mp 173e176 ꢀC; IR (KBr): 1677,
(s, 1H), 7.53 (s, 2H), 7.52 (s, 2H), 7.41 (t, J¼7.2 Hz, 2H), 7.36 (d,
J¼7.2 Hz, 1H), 7.18 (d, J¼7.8 Hz, 2H), 7.11 (t, J¼7.2 Hz, 2H), 7.04 (t,
J¼7.2 Hz, 2H), 6.61 (s, 2H), 6.47 (s, 1H); 13C NMR (100 MHz, CDCl3):
1594, 1482, 1431, 1331, 1283, 1239, 1192, 1159, 1015 cmꢁ1 1H NMR
;
(600 MHz, CDCl3):
d
(ppm)¼7.59 (d, J¼7.8 Hz, 3H), 7.35 (t, J¼7.2 Hz,
1H), 7.24 (d, J¼7.8 Hz, 2H), 7.18 (t, J¼7.8 Hz, 2H), 7.05 (t, J¼7.2 Hz,
d
(ppm)¼198.6, 145.5, 139.7, 136.4, 135.3, 129.4, 128.9, 128.1, 127.2,
2H), 6.88 (s, 4H), 6.62 (s, 1H), 3.80 (s, 3H), 3.64 (s, 6H); 13C NMR
126.5, 124.2, 122.0, 119.5, 118.8, 113.7, 111.5, 42.1; HRMS (ESI): m/z
[MþNa]þ calcd for C30H22N2ONa: 449.1624; found: 449.1622.
(100 MHz, CDCl3):
d
(ppm)¼201.5, 157.9, 137.1, 132.8, 131.0, 128.9,
128.3, 127.4, 121.3, 120.5, 119.3, 118.8, 113.1, 111.4, 109.1, 55.5, 45.4,
32.6; HRMS (ESI): m/z [MþNa]þ calcd for C27H24N2O2Na: 431.1730;
found: 431.1733.
4.3.22. 2,2-Bis(6-methyl-1H-indol-3-yl)-1-phenylethanone
(3ac).12 Yield 71%; brown solid; mp 207e210 ꢀC; IR (KBr): 3430,
3396, 3397, 1667, 1628, 1595, 1454, 1338, 1340, 1247, 1218,
4.3.28. 1-(6-Methoxynaphthalen-2-yl)-2,2-bis(1-methyl-1H-indol-3-
yl)ethanone (3qa). Yield 42%; brown solid; mp 239e243 ꢀC; IR
(KBr): 1679, 1616, 1473, 1349, 1331, 1273, 1252, 1230, 1175, 1154,
1101 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
(ppm)¼7.95 (d, J¼8.0 Hz,
2H), 7.80 (s, 2H), 7.25 (s, 2H), 7.07 (q, J¼7.6 Hz, 4H), 6.97 (s, 2H), 6.81
(s, 2H), 6.59 (d, J¼8.0 Hz, 2H), 2.28 (s, 6H); 13C NMR (100 MHz,
1061 cmꢁ1
;
1H NMR (600 MHz, CDCl3):
d
(ppm)¼8.57 (s, 1H), 8.17
CDCl3):
d
(ppm)¼198.6, 138.3, 136.9, 131.6, 131.2, 130.5, 127.4, 125.1,
(d, J¼9.0 Hz, 1H), 8.11 (d, J¼9.0 Hz, 1H), 7.85 (d, J¼9.0 Hz, 1H), 7.60
(d, J¼7.8 Hz, 2H), 7.29 (d, J¼8.4 Hz, 2H), 7.23 (s,1H), 7.21 (d, J¼7.8 Hz,
2H), 7.16 (d, J¼9.0 Hz, 1H), 7.09 (t, J¼7.2 Hz, 2H), 6.90 (s, 2H), 6.65 (s,
123.6, 121.3, 120.9, 118.3, 110.9, 55.9, 21.5; HRMS (ESI): m/z [MþH]þ
calcd for C26H21N2O: 377.1648; found: 377.1643.
1H), 3.99 (s, 3H), 3.68 (s, 6H); 13C NMR (100 MHz, CDCl3):
d
(ppm)¼
4.3.23. 2,2-Bis(2-methyl-1H-indol-3-yl)-1-phenylethanone
197.9,158.4,137.9,137.2,132.6,132.3,131.6,130.5,128.7, 128.5,127.0,
126.9, 121.7, 119.2, 119.0, 113.0, 112.7, 109.4, 87.0, 57.0, 41.8, 32.8;
(3ad).12 Yield 75%; brown solid; mp 202e204 ꢀC; IR (KBr): 3406,
Please cite this article in press as: Jia, F.-C.; et al., Tetrahedron (2013), http://dx.doi.org/10.1016/j.tet.2013.06.054

F.-C. Jia et al. / Tetrahedron xxx (2013) 1e7
7
HRMS (ESI): m/z [MþH]þ calcd for C31H27N2O2: 459.2067; found:
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Acknowledgements
We thank the National Natural Science Foundation of China
(Grant 21032001 and 21272085). We also thank Dr. Chuanqi Zhou,
Hebei University, for analytical support.
Supplementary data
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1H NMR, 13C NMR, and HRMS spectra for all compounds, X-ray
crystal structures of compounds 3fa is available. Supplementary
data related to this article can be found at http://dx.doi.org/10.1016/
j.tet.2013.06.054.
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