One-pot access to indolo[2,3- b]quinolines by electrophile-triggered cross-amination/friedel-crafts alkylation of indoles with 1-(2-tosylaminophenyl) ketones

Article abstract of DOI:10.1021/jo202035p

Activation of C2 and C3 of indoles by molecular iodine (I₂) and base followed by in situ reaction with 1-(2-tosylaminophenyl)ketones or 2-tosylaminobenzaldehyde can afford highly substituted indolo(2,3-b)quinolines in moderate to excellent yields (up to 99%). The reaction provides a metal-free selective difunctionalization of indoles. The synthetic potential of the protocol has been illustrated by the synthesis of neocryptolepine and its 11-methyl analogue.

Full text of DOI:10.1021/jo202035p

Article
pubs.acs.org/joc
One-Pot Access to Indolo[2,3-b]quinolines by Electrophile-Triggered
Cross-Amination/Friedel−Crafts Alkylation of Indoles with 1-(2-
Tosylaminophenyl)ketones
Shaukat Ali,† Ying-Xiu Li,† Saeed Anwar,‡ Fang Yang,† Zi-Sheng Chen,† and Yong-Min Liang*,†
†State Key Laboratory of Applied Organic Chemistry, Lanzhou University, and State Key Laboratory of Solid Lubrication,
Lanzhou Institute of Chemical Physics, Chinese Academy of Science, Lanzhou 730000, P.R. China
‡Department of Chemistry, Abdul Wali Khan University, Mardan 23200, Pakistan
S
* Supporting Information
ABSTRACT: Activation of C2 and C3 of indoles by mole-
cular iodine (I2) and base followed by in situ reaction with
1-(2-tosylaminophenyl)ketones or 2-tosylaminobenzaldehyde
can afford highly substituted indolo(2,3-b)quinolines in moderate
to excellent yields (up to 99%). The reaction provides a metal-
free selective difunctionalization of indoles. The synthetic
potential of the protocol has been illustrated by the synthesis
of neocryptolepine and its 11-methyl analogue.
keto group (see Schemes 1 and 3) . In this way a new
sequential reaction could be developed to affect selective
difunctionalization of indoles. Herein, we report a metal-free
cascade coupling of indoles with 1-(2-tosylaminophenyl)-
ketones affording indolo[2,3-b]quinolines and its application
to the synthesis of neocryptolepine and 11-methylneocrypto-
lepine natural products.
INTRODUCTION
■
Indoloquinolines have been well established to be useful as
antibacterial, antifungal, antimalarial, anticancer, antiplatelet,
aggregation, analgesic, antihypertensive agents as well as
exhibiting several other activities.1 It is believed that they act
as DNA intercalating agents2 and topoisomerase II inhibitors,3
and thereby one structure can exhibit an array of activities. The
interesting biological activities of indoloquinolines (Figure 1)
has stimulated the interest of synthetic chemists in developing
new synthetic pathways to these polyheteroaromatic ring
systems.4−9 However, most of these syntheses suffer from
lack of substrate generality, use of metal catalysts, and/or
involve two or more steps with exhaustive isolation/purification
efforts resulting in low overall yields and hence of little interest
to the pharmaceutical industry. Very recently, Seidel’s group
reported an excellent methodology for neocryptolepines and
analogues.10,11 This reaction is extremely efficient for preparing
a variety of substituted neocryptolepines. It is, however, not
possible to synthesize 11-substituted neocryptolepines and 6H-
indolo(2,3-b)quinolines by Seidel’s method. In our laboratory,
we were interested in exploring a more general method for a
one-pot/cascade synthesis of indoloquinolines from readily
available substrates. We have previously described a metal-free
cascade synthesis of functionalized quinolines.12 In pursuit of a
protocol for preparing functionalized quinolines with diverse
pharmacological properties, we envisioned that the readily
available indoles can be activated by iodonium to undergo
cross-amination with 1-(2-tosylaminophenyl)ketones at posi-
tion-2. Elimination of HI promoted by a suitable base would
then leave position 3 again prone to electrophilic attack by the
RESULTS AND DISCUSSION
■
Our study began with the coupling reaction of an equal amount
of N-methylindole 1a with 2-(tosylamino)benzophenone 2a in
the presence of 2.0 equiv of iodine (I2) and 2.0 equiv of K2CO3
in acetonitrile at room temperature. After 6 h, an examination
of the reaction mixture revealed 25% of the expected
indolo[2,3-b]quinolines 3a, 60% of the cross-aminated product
4 and 15% recovery of the starting materials. This initial
investigation showed that the cross-amination step was going
well but the cyclization via Friedel−Crafts alkylation did not
occur smoothly. Changing the amount of iodine or base was
not successful. When the nature of the base was changed,
Cs2CO3 was found to be best (Table 1, entry 2), but the
cyclization step was only 30% complete along with 62% of the
cross-aminated product 4 and 8% starting materials. In order to
promote the cyclization step a number of Lewis and Bronsted
acids were screened. Of them only AlCl3, HCl and AlCl3/TfOH
were found to promote the cyclization step (Table 1 entries
9, 10, and 13). Of course, we were interested to produce a
Received: October 6, 2011
Published: December 2, 2011
© 2011 American Chemical Society
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Figure 1. Selected indoloquinoline natural products.
at 90 °C, a complete disappearance of starting materials
was observed, and the highest yield of 3a (88%) was obtained
Scheme 1. Design of a One-Pot Access to Indolo(2,3-
b)quinolines
(Table 1 entry 15).
With the standard reaction conditions in hand, we then
explored the scope and generality of the method. We first
examined the use of different protecting groups for the indolic
N-atom. A variety of protecting groups such as alkyl, benzyl,
and allyl groups was well tolerated (Scheme 2, products 3a−
3c). However, in the case of a tosyl group and N-unsubstituted
indoles we observed no reaction. We then examined the effect
of substituents in the indole moiety of indolo[2,3-b]quinolines
(Scheme 2, products 3d−3i). In general, we found that the
presence of substituents with different electronic and steric
properties in various positions did not have a significant effect
on the formation of the indoloquinolines; all provided good to
excellent yields. Similarly, the change of substituents in the
2-(tosylamino)phenyl ketones upon the efficiency of indolo-
[2,3-b]quinolines formation (Scheme 2, products 3j and 3k)
revealed no effect on the formation of the indoloquinolines.
The structure of product 3j was also confirmed by single-crystal
X-ray crystallography (see the Supporting Information for
details). Afterward, we examined the influence of R4 in the
starting ketones 2 on the outcome of the reaction and yields of
metal-free protocol, and thus, the use of HCl for further
screening was continued. By using excess of HCl as additive, a
70% yield of 3a was obtained with no cross-aminated product
4 but again conversion was not complete (Table 1 entry 10).
Turning to stoichiometry of the reaction revealed that by
using 1.5 equiv of indole 1a with respect to ketone 2a 3a was
furnished in 83% yield (Table 1 entry 14), but there were still
some traces of substrates. When the reaction was carried out
Table 1. Optimization of Reaction Conditions
a
b
entry
base
solvent
additive (equiv)
temp (°C)
yield (%) 3a/4
1
K2CO3
CH3CN
CH3CN
CH3CN
CH3OH
DMF
rt
rt
25/60
30/62
7/10
2
Cs2CO3
K3PO4
3
rt
4
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
rt
6/40
5
rt
traces
10/30
32/63
6/45
6
DCM
rt
7
CH3CN
CH3OH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
90
70
rt
8
9
AlCl3 (2)
65/−
70/−
33/62
37/62
60/−
c
10
11
12
13
14
15
HCl
rt
TfOH (0.1)
rt
HSbF6 (0.1)
rt
AlCl3 (0.5)/ TfOH (0.1)
rt
c
d
HCl
rt
83/−
88/−
c
d
HCl
90
90
90
e
c
16
HCl
86/−
84/−
f
c
17
HCl
a
All reactions were run under the following conditions, unless otherwise indicated: 0.2 M 1a, 0.2 M 2a, 0.4 M I2, and 0.4 M base in wet solvent.
b
Additive was added to the reaction mixture at room temperature after 9 h and further stirred at room temperature for 6 h. Based on isolation of
products after column chromatography. 250 μL (25 equiv) of 12 M HCl was used as additive. 0.3 M 1a, 0.6 M I2 and 0.6 M base was used. 0.61 M
I2 was used. 0.59 M I2 was used.
c
d
e
f
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a,b,c
Scheme 2. Scope of Metal-Free Cross-Amination/Alkylation Cascade of Indoles with 1-(2-Tosylaminophenyl)ketones
a
All reactions were run under the following conditions, unless otherwise indicated: 0.3 M 1, 0.2 M 2, 0.6 M I2, and 0.6 M base in wet solvent for 9 h
at 90 °C and then 250 μL of 12 M HCl was added at room temperature and further stirred at room temperature for 6 h. The equiv of iodine and
b
c
Cs2CO3 corresponds to 1. The yields are based on isolation of products after column chromatography. After adding HCl the reaction was stirred
for 12 h.
the various 11-substituted indolo[2,3-b]quinolines (Scheme 2,
products 3l−3m and 3o−3q). With an electron-withdrawing
group such as 4-ClC6H5, we observed only 5% of the
corresponding indolo[2,3-b]quinoline. However, 4-BrC6H5
gave 90% yield of the corresponding indolo[2,3-b]quinoline
(Scheme 2, product 3q), although Cl and Br differ only slightly
in electronegativity. With a more electron-rich but rather bulky
group such as 4-MeOC6H5, the reaction time was increased to
21 h, and only 32% yield of the product was obtained. Also,
when 3,4-Me2C6H4 was used, only traces of product was
generated. These findings show that the yields of products 3
are evidently susceptible to subtle changes in the nature of the
C-11 substituent (or, correctly, R4 in 2).
Knowing the importance of neocryptolepines as antimalarial
and antitumor agents, we also investigated the reaction of 2-
tosylaminobenzaldehyde 2f with N-methyl and N-benzyl
indoles 1a and 1b under initially optimized conditions. The
corresponding indolo[2,3-b]quinolines 3r and 3s were obtained
in moderate yields of 32% and 40% along with dialkylated
products (or more properly 11-indolylindolo[2,3-b]quinolines)
5a and 5b in 63% and 52% yields, respectively. The dialkylated
products were suppressed, and the yields of the desired
products were improved by carrying out the reactions at room
temperature with 3 equiv of the indole derivative (see Table 2).
The mechanism of this reaction involves electrophilic
addition of iodonium to the 3-position of indole 1 to give
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Table 2. Cross-Amination/Alkylation of N-Methyl Indole (1a) and N-Benzyl Indole (1b) with 2-Tosylaminobenzaldehyde
a,b
(2f)
yield (%)
entry
R
1 (mmol)
2f(mmol)
temp. (°C)
3
5
1
2
3
4
5
6
Me
Bn
1a (0.3)
1b (0.3)
1a (0.2)
1a (0.4)
1a (0.6)
1b (0.6)
0.2
0.2
0.2
0.2
0.2
0.2
90
90
90
90
rt
3r (32)
3s (40)
3r (20)
3r (55)
3r (71)
3s (78)
5a (63)
5b (52)
5a (73)
5a (15)
−
Me
Me
Me
Bn
rt
−
a
All reactions were run for 9 h, and then 250 μL of 12 M HCl was added at room temperature and further stirred at room temperature for 6 h. The
b
equiv of iodine and Cs2CO3 corresponds to 1. The yields are based on isolation of products after column chromatography.
Scheme 3. Proposed Mechanism
cation A, which undergoes 2-amination with 2 to afford B. The
intermediate B eliminates a molecule of HI in the presence of
base to give 4. Alkylation and subsequent detosylation of 4 in
the prescence of HCl gives 3. The formation of 11-
indolylindolo[2,3-b]quinolines 5 can be explained as follows.
When the intermediate carbocation C has a H-atom on the 11-
position (R4 = H), due to less steric hindrance and more
reactivity it is attacked by a second molecule of 1 to give D.
Finally, D gains full aromaticity via oxidation by molecular
iodine (I2) or air13,14 to give 5 (see Scheme 3).
The application of the new annulation strategy to the
synthesis of the neocryptolepine, a linear 5-N-methyl-5H-
indolo[2,3-b]quinoline alkaloid isolated from the West African
shrub Cryptolepis sanguinolenta which has been reported to
exhibit strong antiplasmodial activity,15 illustrates the utility of
this methodology. 11-Methylneocryptolepine which has been
found to display strong antimicrobial and cytotoxic activities in
vitro and significant antitumor properties in vivo16 can also be
prepared by using our protocol. Products 3s and 3n were
prepared on 10 mmol scale. To our delight; the reactions
proceeded without change in reaction yields. Debenzylation17
with AlCl3 in refluxing benzene and then regioselective
methylation18 of quinoline N-atom with Me2SO4 afforded
neocryptolepine 7a and 11-methylneocryptolepine 7b in overall
68% and 64% yields, respectively (Scheme 4).
CONCLUSION
■
In short, we have described a useful annulation strategy of
readily available indoles to indolo(2,3-b)quinolines. The
reaction is metal-free and can produce substituted indolo(2,3-
b)quinolines in a one-pot manner. Our simple approach to
indolo(2,3-b)quinolines complements existing routes and
allows access to some novel C-11-substituted derivatives.
Synthesis of neocryptolepine and its various analogues can be
carried out in overall moderate yields.
EXPERIMENTAL SECTION
General Methods Used for Preparing Starting Materials 1a−
1i and 2a−2i. Starting materials 1a−1i were prepared by
methylation, benzylation, or allylation of the corresponding indoles
■
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Scheme 4. Synthesis of Neocryptolepine and 11-Methylneocryptolepine
according to the literature procedure.19 Starting materials 2a−2i were
prepared by tosylation of the corresponding 2-aminobenzoketones or
2-aminobenzaldehyde according to the literature procedure.20,21 2-
Aminobenzaldehyde was prepared by reduction of 2-nitrobenzalde-
hyde according to the literature procedure22 and used immediately.
The respective characterization data of all the starting materials match
those reported in the literature.
General Procedure A. Preparation of Indolo(2,3-b)quinolines
(3a−3s) and (5a−5b). Iodine (152.4 mg, 2.0 equiv) was added to a
solution of 1a (0.3 mmol, 39.3 mg), 2a (0.2 mmol, 70.2 mg) and
Cs2CO3 (195.6 mg, 2.0 equiv) in acetonitrile (1.0 mL). The resulting
mixture was stirred for 9 h at 90 °C. Then the reaction mixture was
cooled to room temperature, and 250 μL (25 equiv) of 12 M HCl was
added, and the mixture further stirred at room temperature for 6 h.
The reaction was then quenched by adding saturated aq solution of
Na2S2O3 and extracted with ethyl acetate (3 × 15 mL). The combined
organic phases were washed with aq NaHCO3 and brine, and dried
over anhyd. Na2SO4. After removal of solvent the crude product was
purified by column chromatography with silica gel using a mixture of
petroleum ether (bp 40−80 °C) and ethyl acetate (20: 1) to give 54.5
mg of 3a (88%).
J = 5.2 Hz), 7.51−7.54 (2H, m), 7.41−7.45 (1H, m), 7.32−7.37 (2H,
m), 7.05 (1H, d, J = 7.6 Hz), 6.96 (1H, t, J = 7.6 Hz), 6.06−6.15 (1H,
m), 5.17 (4H, q, J = 5.2 Hz) ; 13C NMR (CDCl3, 100 MHz): δ 151.8,
146.7, 142.3, 142.2, 136.6, 132.7, 129.3, 128.9, 128.6, 128.4, 127.7,
127.6, 123.0, 122.8, 120.7, 119.7, 116.8, 115.8, 109.2, 43.6, 31.9, 22.6;
IR (neat) ν: 3393, 3059, 2923, 1594, 1473, 1403, 1357, 1324, 1259,
1215, 1180, 1154, 1120, 1068, 1027, 765, 742, 701, 663, 613 cm−1;
HRMS (ESI) calcd for C24H19N2 (M+ + H): 335.1543, found:
335.1545.
6,10-Dimethyl-11-phenyl-6H-indolo[2,3-b]quinoline (3d): yield
86%; light green solid; mp 184−186 °C; 1H NMR (CDCl3, 400
MHz): δ 8.11 (1H, d, J = 8.0 Hz), 7.64−7.68 (1H, m), 7.49−7.55 (6H,
m), 7.37 (1H, t, 7.6 Hz), 7.23−7.28 (2H, m), 6.84 (1H, d, J = 7.2 Hz),
4.02 (3H, s), 1.7 (3H, s) ; 13C NMR (CDCl3, 100 MHz): δ 152.2,
145.8, 143.7, 142.5, 139.7, 135.5, 131.2, 128.6, 128.2, 127.8, 127.7,
127.2, 127.1, 124.2, 123.3, 122.4, 119.5, 117.3, 105.9, 27.7, 22.1; IR
(neat) ν: 3395, 3053, 2925, 1579, 1464, 1446, 1383, 1307, 1248, 1155,
1108, 1066, 1026, 961, 754, 702 cm−1; HRMS (ESI) calcd for
C23H19N2 (M+ + H): 323.1543, found: 323.1546.
6,9-Dimethyl-11-phenyl-6H-indolo[2,3-b]quinoline (3e): yield
1
99%; yellow solid; mp 108−110 °C; H NMR (CDCl3, 400 MHz):
In case of indolo(2,3-b)quinolines 3r and 3s the amount of indole
1b was 0.6 mmol, 124.3 mg, and the reaction was conducted at room
temperature. The rest of procedure remains the same.
δ 8.16 (1H, d, J = 8.4 Hz), 7.67−7.73 (2H, m), 7.50−7.52 (2H, m),
7.31−7.35 (1H, m), 7.27 (2H, t, J = 1.2 Hz), 7.24 (1H, d, J = 4.8 Hz),
6.83 (1H, s), 3.99 (3H, s), 2.27 (3H, s) ; 13C NMR (CDCl3, 100
MHz): δ 152.5, 146.6, 142.2, 141.0, 136.6, 130.8, 128.9, 128.6, 128.4,
128.3, 127.4, 126.3, 123.6, 123.2, 123.2, 122.6, 120.6, 115.9, 108.1,
27.7, 21.3; IR (neat) ν: 3398, 3060, 2922, 2851, 1634, 1596, 1567,
1484, 1447, 1385, 1332, 1295, 1252, 1164, 1119, 1068, 1020, 761, 703
cm−1; HRMS (ESI) calcd for C23H19N2 (M+ + H): 323.1543, found:
323.1550.
Characterization Data of Products (3a−3s) and (5a−5b). 6-
Methyl-11-phenyl-6H-indolo[2,3-b]quinoline (3a): yield 88%; light-
1
green solid; mp 152−154 °C; H NMR (CDCl3, 400 MHz): δ 8.17
(1H, d, J = 8.4 Hz), 7.68−7.74 (2H, m), 7.61−7.66 (3H, m), 7.52−
7.53 (2H, m), 7.45−7.51 (1H, m), 7.32−7.38 (2H, m), 7.05 (1H, d,
J = 7.6 Hz), 6.96−7.00 (1H, m), 4.02 (3H, s) ; 13C NMR (CDCl3, 100
MHz): δ 152.4, 146.8, 142.9, 142.3, 136.6, 129.8, 129.3, 128.9, 128.4,
127.7, 127.2, 126.3, 123.7, 123.0, 122.7, 120.5, 119.6, 115.9, 108.3,
27.7; IR (neat) ν: 3399, 3056, 2925, 2862, 1598, 1480, 1392, 1319,
1252, 1122, 1024, 746, 703 cm−1 ; HRMS (ESI) calcd for C22H17N2
(M+ + H): 309.1386, found: 309.1388.
6,8-Dimethyl-11-phenyl-6H-indolo[2,3-b]quinoline (3f): yield
83%; light-yellow solid; mp 136−140 °C; 1H NMR (CDCl3, 400
MHz): δ 8.15 (1H, d, J = 8.4 Hz), 7.69 (2H, q, J = 8.4 Hz), 7.61−7.68
(2H, m), 7.50 (2H, q, J = 2.0 Hz), 7.31−7.40 (2H, m), 6.92(1H, d, J =
8.0 Hz), 6.79 (1H, d, J = 8.0 Hz), 3.98 (3H, s), 2.5 (3H, s) ; 13C NMR
(CDCl3, 100 MHz): δ 152.6, 146.5, 143.3, 142.2, 141.4, 140.9, 138.3,
136.7, 129.8, 128.9, 127.2, 126.2, 124.9, 123.7, 122.6, 120.9, 118.1,
116.0, 108.8, 27.6, 22.2; IR (neat) ν: 3399, 3059, 2923, 2854, 1597,
1466, 1423, 1391, 1307, 1251, 1161, 1114, 1067, 1027, 765,703 cm−1;
HRMS (ESI) calcd for C23H19N2 (M+ + H): 323.1543, found:
323.1547
6,7-Dimethyl-11-phenyl-6H-indolo[2,3-b]quinoline (3g): yield
97%; light-green solid; mp 196−200 °C; 1H NMR (CDCl3, 400
MHz): δ 8.14 (1H, d, J = 8.4 Hz), 7.67 (2H, t, J = 4.0 Hz), 7.60 (3H,
d, J = 6.8 Hz), 7.47 (2H, d, J = 8.0 Hz), 7.30 (1H, t, J = 7.2 Hz), 7.15
(1H, d, J = 6.8 Hz), 6.81 (2H, m), 4.32 (3H, s), 2.85 (3H, s); 13C
NMR (CDCl3, 100 MHz): δ 152.8, 146.6, 141.9, 136.7, 130.9, 129.3,
128.5, 127.5, 126.3, 124.8, 123.9, 122.6, 121.2, 121.0, 120.4, 119.6,
118.2, 115.7, 102.2, 29.3, 22.6; IR (neat) ν: 3400, 3046, 2923, 2854,
1607, 1580, 1492, 1459, 1389, 1297, 1222, 1163, 1131, 1080, 1025,
6-Benzyl-11-phenyl-6H-indolo[2,3-b]quinoline (3b): yield 90%;
1
light-yellow solid; mp 148−150 °C; H NMR (CDCl3, 400 MHz):
δ 8.16 (1H, d, J = 8.4 Hz), 7.73 (1H, d, J = 8.0 Hz), 7.67−7.71 (1H,
m), 7.61−7.64 (3H, m), 7.53 (2H, dd, J = 2.0, 7.6 Hz), 7.33−7.37
(4H, m), 7.24−7.28 (3H, t, J = 6.4 Hz), 7.21−7.23 (1H, t, J = 4.0 Hz),
7.05 (1H, d, J = 7.6 Hz), 6.93- 6.97 (1H, t, J = 7.6 Hz), 5.79 (2H, s) ;
13C NMR (CDCl3, 100 MHz): δ 152.2, 146.8, 142.3, 142.1, 137.3,
136.6, 129.3, 128.9, 128.6, 128.5, 127.8, 127.6, 127.3, 127.2, 126.4,
126.3, 124.0, 123.0, 122.8, 120.8, 119.8, 115.8, 109.3, 44.9; IR (neat) ν:
3664, 3394, 3070, 2922, 1595, 1464, 1404, 1320, 1120, 1068, 1025,
865, 751, 702, 614 cm−1; HRMS (ESI) calcd for C28H21N2 (M+ + H):
385.1699, found: 385.1697.
6-Allyl-11-phenyl-6H-indolo[2,3-b]quinoline (3c): yield 81%;
1
light-green solid; mp 100−102 °C; H NMR (CDCl3, 400 MHz):
δ 8.15 (1H, d, J = 8.8 Hz), 7.67−7.74 (2H, m), 7.62−7.64 (3H, q,
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771, 745, 704, 403 cm−1; HRMS (ESI) calcd for C23H19N2 (M+ + H):
323.1543, found: 323.1548
109.6, 109.4, 44.7, 15.1; IR (neat) ν: 3395, 3060, 2923, 2854, 1722,
1621, 1602, 1577, 1471, 1404, 1379, 1321, 1286, 1263, 1213, 1153,
1122, 1072, 745, 702, 462 cm−1; HRMS (ESI) calcd for C23H19N2
(M+ + H): 323.1543, found: 323.1539.
9-Bromo-6-methyl-11-phenyl-6H-indolo[2,3-b]quinoline (3h): yield
85%; light-green solid; mp 180−184 °C; 1H NMR (CDCl3, 400 MHz): δ
8.13 (1H, d, J = 8.4 Hz), 7.67−7.72 (2H, m), 7.62−7.65 (3H, m), 7.50
(1H, dd, J = 2.0, 8.8 Hz), 7.45−7.47(2H, m), 7.31−7.35 (1H, m), 7.16
(1H, d, J = 8.4 Hz), 7.09 (1H, s), 3.94 (3H, s) ; 13C NMR (CDCl3,
100 MHz): δ 152.1, 147.0, 142.9, 141.4, 135.8, 130.2, 129.2, 129.1, 129.0,
128.8, 127.6, 126.4, 125.5, 123.6, 123.0, 122.1, 114.8, 112.2, 109.7, 27.7;
IR (neat) ν: 3397, 3062, 2922, 2840, 1626, 1585, 1477, 1442, 1383, 1330,
1278, 1122, 1069, 1027, 765, 767, 711, 613, 402 cm−1; HRMS (ESI)
calcd for C22H16N2Br (M+ + H): 387.0491, found: 387.0497.
9-Methoxy-6-methyl-11-phenyl-6H-indolo[2,3-b]quinoline (3i): yield
11-(4-Bromophenyl)-6-methyl-6H-indolo[2,3-b]quinoline (3o): yield
90%; light-green solid; mp 156−160 °C; 1H NMR (CDCl3, 400
MHz): δ 8.16 (1H, d, J = 8.4 Hz), 7.77 (2H, d, J = 8.4 Hz), 7.66−7.70
(2H, m), 7.47−7.52 (1H, m), 7.37 (4H, q, J = 8.4 Hz), 7.10 (1H, d, J =
7.6 Hz), 7.01−7.05 (1H, m), 4.00 (3H, s) ; 13C NMR (CDCl3, 100
MHz): δ 152.2, 146.7, 142.9, 140.7, 135.5, 132.2, 132.5, 131.1, 129.6,
128.7, 127.7, 127.2, 125.9, 123.3, 122.8, 120.2, 119.8, 115.8, 108.5,
27.6; IR (neat) ν: 3732, 3393, 2922, 2857, 1591, 1455, 1429, 1387,
1156, 1107, 1065, 1025, 826, 767, 717, 582 cm−1; HRMS (ESI) calcd
for C22H16N2Br (M+ + H): 387.0491, found: 387.0486.
1
86%; yellow solid; mp 152−154 °C; H NMR (CDCl3, 400 MHz): δ
8.14 (1H, d, J = 8.4 Hz), 7.66−7.74 (2H, m), 7.59−7.64 (3H, m),
7.50−7.52 (2H, m), 7.30−7.34 (1H, m), 7.22 (1H, d, J = 8.4 Hz), 7.05
(1H, dd, J = 2.4, 8.8 Hz), 6.54 (1H, s), 3.96 (3H, s), 3.57 (3H, s) ; 13C
NMR (CDCl3, 100 MHz): δ 153.6, 152.6, 146.8, 142.2, 137.5, 136.4,
130.8, 129.4, 128.6, 128.4, 128.2, 127.5, 126.3, 123.3, 122.5, 120.8,
115.9, 108.8, 107.0, 55.5, 27.7; IR (neat) ν: 3393, 3058, 2923, 2854,
1594, 1483, 1386, 1331, 1289, 1263, 1223, 1118, 1067, 1029, 801, 769,
703, 653, 614, 402 cm−1; HRMS (ESI) calcd for C23H19ON2 (M+ + H):
339.1492, found: 339.1498.
6-Methyl-11-(p-tolyl)-6H-indolo[2,3-b]quinoline (3p): yield 86%;
1
light-green solid; mp 119−121 °C; H NMR (CDCl3, 400 MHz): δ
8.16−8.18 (1H, m), 7.75 (1H, dd, J = 0.8, 8.4 Hz), 7.67−7.71 (1H,
m), 7.32−7.50 (7H, m), 7.13 (1H, d, J = 8.0 Hz), 6.98−7.02 (1H, m),
4.01 (3H, s), 2.56 (3H, s) ; 13C NMR (CDCl3, 100 MHz): δ 152.4,
146.8, 142.9, 142.5, 138.2, 133.4, 129.6, 129.2, 128.6, 127.6, 127.5,
126.4, 123.9, 123.0, 122.6, 120.7, 119.6, 116.0, 108.3, 27.6, 21.5; IR
(neat) ν: 3403, 3057, 2923, 2862, 1592, 1479, 1429, 1392, 1322, 1251,
1160, 1119, 1068, 1027, 818, 755, 634 cm−1; HRMS (ESI) calcd for
C23H19N2 (M+ + H): 323.1543, found: 323.1547.
2-Chloro-6-methyl-11-phenyl-6H-indolo[2,3-b]quinoline (3j): yield
1
80%; light-green solid; mp 260−263 °C; H NMR (CDCl3, 400 MHz):
11-(4-Methoxyphenyl)-6-methyl-6H-indolo[2,3-b]quinoline
1
(3q): yield 32%; yellow solid; mp 90−92 °C; H NMR (CDCl3, 400
δ 8.07 (1H, d, J = 9.2 Hz), 7.59−7.67 (5H, m), 7.36 (1H, d, J = 8.4
Hz), 6.98−7.05 (2H, m) 3.99 (3H, s) ; 13C NMR (CDCl3, 100 MHz):
δ 152.4, 145.1, 143.0, 141.3, 135.9, 129.4, 129.3, 129.2, 129.1, 128.7,
128.2, 128.1, 124.9, 124.3, 123.2, 120.2, 119.9, 116.5, 108.5, 27.6; IR
(neat) ν: 3400, 3047, 2918, 2849, 2279, 1595, 1466, 1443, 1387, 1340,
1308, 1118, 1070, 1025, 812, 772, 735, 708, 403 cm−1; HRMS (ESI)
calcd for C22H16N2Cl (M+ + H): 343.0997, found: 343.1003.
MHz): δ 7.68 (1H, d, J = 8.0 Hz), 7.64 (1H, d, J = 7.6 Hz), 7.35 (2H,
t, J = 8.4 Hz), 7.28−7.32 (3H, m), 7.20−7.24 (2H, m), 7.17−7.19
(2H, m), 7.11−7.15 (1H, m), 6.61 (1H, brs), 3.86 (3H, s), 3.74 (3H, s) ;
13C NMR (CDCl3, 100 MHz): δ 142.0, 137.9, 136.9, 135.0, 130.1, 128.3,
127.6, 122.3, 120.9, 120.3, 120.1, 119.9, 119.5, 116.1, 115.9, 109.4, 109.3,
107.3, 101.3, 22.6, 14.1; IR (neat) ν: 3733, 3402, 3049, 2923, 2855, 1583,
1461, 1382, 1320, 1243, 1071, 1023, 743, 667, 571 cm−1; HRMS (ESI)
calcd for C23H19ON2 (M+ + H): 339.1492, found: 339.1497.
2-Bromo-6-methyl-11-phenyl-6H-indolo[2,3-b]quinoline (3k): yield
1
82%; yellow solid; mp 248−251 °C; H NMR (CDCl3, 400 MHz): δ
8.01 (1H, d, J = 9.2 Hz), 7.83 (1H, s), 7.72 (1H, dd, 2, 8.8 Hz), 7.64
(3H, t, J = 5.6 Hz), 7.37 (1H, d, J = 8 Hz) 6.98−7.04 (2H, m), 3.99
(3H, s) ; 13C NMR (CDCl3, 100 MHz): δ 152.4, 145.3, 143.0, 141.3,
135.8, 131.8, 129.3, 129.1, 128.8, 128.5, 128.3, 128.2, 128.1, 127.2,
120.2, 119.9, 116.5, 116.1, 108.5, 27.7; IR (neat) ν: 3794, 3664, 3407,
3053, 2921, 2851, 1060, 1463, 1443, 1385, 1309, 1220, 1158, 1110,
1066, 1023, 771, 738, 705 cm−1; HRMS (ESI) calcd for C22H16N2Br
(M+ + H): 387.0491, found: 387.0497.
6-Methyl-6H-indolo[2,3-b]quinoline (3r): yield 71%; light-green
1
solid; mp 42−45 °C; H NMR (CDCl3, 400 MHz): δ 8.67 (1H, s),
8.11 (2H, q, J = 4.4 Hz), 7.9 (1H, d, J = 8 Hz), 7.69 (1H, t, J = 7.6
Hz), 7.55 (1H, t, J = 7.6 Hz), 7.42 (1H, t, J = 7.6 Hz), 7.38 (1H, d, J =
8.0 Hz), 7.27 (1H, t, J = 7.2 Hz), 3.97 (3H, s); 13C NMR (CDCl3, 100
MHz): δ 152.7, 146.7, 142.8, 128.8, 128.5, 128.0, 127.4, 127.3, 124.1,
122.8, 121.4, 120.4, 119.9, 118.2, 108.7, 27.7; IR (neat) ν: 3401, 3054,
2924, 2856, 1606, 1573, 1481, 1431, 1395, 1362, 1321, 1254, 1148,
1118, 779, 743 cm−1; HRMS (ESI) calcd for C16H13N2 (M+ + H):
233.1073, found: 233.1075.
6,11-Dimethyl-6H-indolo[2,3-b]quinoline (3l): yield 83%; yellow
solid; mp 96−98 °C; 1H NMR (CDCl3, 400 MHz): δ 8.27 (1H, d, J =
8 Hz), 8.23 (1H, dd, J = 0.8, 8.4 Hz)), 8.12 (1H, d, J = 8.8 Hz), 7.69−
7.73 (1H, m), 7.55−7.60 (1H, m), 7.46−7.50 (1H, m) 7.41 (1H, d, J =
8 Hz), 7.30−7.34 (1H, m), 3.98 (3H, s), 3.19 (3H, s) ; 13C NMR
(CDCl3, 100 MHz): δ 152.4, 146.7, 145.0, 142.7, 128.5, 128.1, 127.3,
123.6, 123.3, 122.9, 122.6, 120.7, 119.9, 115.3, 108.5, 27.6, 15.1; IR
(neat) ν: 3399, 3060, 2852, 2245, 1685, 1626, 1602, 1578, 1472, 1430,
1390, 1319, 1285, 1245, 1120, 1089, 1065, 1025, 747, 403 cm−1;
HRMS (ESI) calcd for C17H15N2 (M+ + H): 247.1230, found:
247.1236.
6-Benzyl-6H-indolo[2,3-b]quinoline (3s): yield 78%; white solid;
1
mp 160−163 °C; H NMR (CDCl3, 400 MHz): δ 8.74 (1H, s), 8.12
(2H, t, J = 8.4 Hz), 8.00 (1H, d, J = 7.2 Hz), 7.68−7.73 (1H, m),
7.44−7.48 (2H, m), 7.22−7.36 (H, m), 5.76 (2H, s) ; 13C NMR
(CDCl3, 100 MHz): δ 142.06, 137.3, 136.7, 128.6, 128.0, 127.7, 127.0,
126.9, 125.1, 123.3, 122.6, 122.5, 121.1, 120.8, 120.3, 119.6, 117.1,
110.1, 109.1, 50.4; IR (neat) ν: 3390, 2918, 1604, 1570, 1470, 1408,
1382, 1262, 1205, 1146, 1066, 1024, 737, 702 cm−1 ; HRMS (ESI)
calcd for C22H17N2 (M+ + H): 309.1386, found: 309.1388.
11-Ethyl-6-methyl-6H-indolo[2,3-b]quinoline (3m): yield 85%;
yellow solid; mp 126−130 °C; 1H NMR (CDCl3, 400 MHz): δ
8.19−8.25 (2H, m), 8.13 (1H, d, J = 8.4 Hz), 7.68−7.73 (1H, m),
7.54−7.59 (1H, m), 7.45−7.49 (1H, m), 7.40 (1H, d, J = 8 Hz), 7.29−
7.33 (1H, m), 3.97 (3H, s), 3.63 (2H, q, J = 7.6 Hz), 1.51 (3H, t, J =
7.6 Hz) ; 13C NMR (CDCl3, 100 MHz): δ 152.4, 146.7, 145.0, 142.7,
128.5, 128.1, 127.3, 123.6, 123.3, 122.9, 122.6, 120.7, 119.9, 115.3,
108.5, 27.6, 22.1, 13.6; IR (neat) ν: 3664, 3398, 3060, 2963, 2923,
2851, 1626, 1601, 1567, 1473, 1428, 1393, 1319, 1275, 1245, 1121,
1057, 1024, 748, 402 cm−1; HRMS (ESI) calcd for C18H17N2 (M+ +
H): 261.1386, found: 261.1380.
6-Methyl-11-(1-methyl-1H-indol-3-yl)-6H-indolo[2,3-b]quinoline
1
(5a): yield 73%; yellow solid; mp 230−233 °C; H NMR (CDCl3,
400 MHz): δ 8.18 (1H, d, J = 8.4 Hz), 7.99 (1H, dd, J = 1.2, 8.4 Hz),
7.67−7.71 (1H, m), 7.52 (1H, d, J = 8.4 Hz), 7.42−7.46 (1H, m),
7.29−7.38 (5H, m), 7.16 (2H, t, J = 8.8 Hz), 7.03 (1H, t, J = 7.2 Hz),
6.88−6.92 (1H, m), 4.04 (3H, s), 4.01 (3H, s) ; 13C NMR (CDCl3,
100 MHz): δ 152.7, 146.8, 142.8, 137.1, 135.9, 128.6, 127.6, 127.5,
127.4, 126.9, 124.9, 123.4, 122.4, 122.3, 120.9, 120.7, 120.0, 119.4,
117.1, 110.1, 109.9, 109.6, 108.1, 33.2, 27.7; IR (neat) ν: 3413, 3058,
2923, 2856, 1586, 1556, 1468, 1430, 1390, 1321, 1246, 1214, 1157,
1118, 1073, 1023, 752, 666 cm−1; HRMS (ESI) calcd for C25H20N3
(M+ + H): 362.1652, found: 362.1658.
6-Benzyl-11-(1-benzyl-1H-indol-3-yl)-6H-indolo[2,3-b]quinoline
(5b): yield 52%; light-green solid; mp 110−112 °C; 1H NMR (CDCl3,
400 MHz): δ 8.18 (1H, d, J = 8.4 Hz), 7.99 (1H, d, J = 8.4 Hz), 7.67
(1H, t, J = 7.2 Hz), 7.51 (1H, d, J = 8.4 Hz), 7.43 (1H, s), 7.20−7.37
(16H, m), 7.04 (1H, t, J = 7.6 Hz), 6.81 (1H, t, J = 7.6 Hz), 5.74 (2H,
6-Benzyl-11-methyl-6H-indolo[2,3-b]quinoline (3n): yield 81%;
1
light-green solid; mp 144−147 °C; H NMR (CDCl3, 400 MHz): δ
8.10 (1H, dd, J = 0.8, 8.4 Hz), 7.67−7.71 (1H, m), 7.41−7.49 (2H,
m), 7.20−7.30 (3H, m), 5.71 (2H, s), 3.18 (3H, s) ; 13C NMR
(CDCl3, 100 MHz): δ 152.1, 146.6, 144.1, 141.9, 138.9, 137.0, 128.2,
127.1, 126.4, 124.3, 123.5, 122.6, 121.6, 120.1, 119.9, 118.9, 116.2,
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Article
q, J = 16 Hz), 5.43 (2H, q, J = 16 Hz); 13C NMR (CDCl3, 100 MHz):
δ 152.4, 146.9, 142.0, 137.4, 137.4, 137.3, 136.7, 128.9, 128.6, 128.0,
127.9, 127.8, 127.7, 127.4, 127.2, 127.0, 126.9, 125.1, 123.3, 122.6,
122.5, 121.1, 120.8, 120.3, 119.6, 117.1, 110.7, 110.1, 109.1, 50.4, 44.9;
IR (neat) ν: 3394, 3058, 2922, 2857, 1598, 1542, 1461, 1393, 1320,
1254, 1158, 1067, 1023, 916, 752, 663, 602 cm−1; HRMS (ESI) calcd
for C37H28N3 (M+ + H): 514.2278, found: 514.2280.
material is available free of charge via the Internet at http://
pubs.acs.org
AUTHOR INFORMATION
■
Corresponding Author
*liangym@lzu.edu.cn
General Procedure for Preparing 6H-Indolo[2,3-b]-
quinolines, 6a and 6b. Anhydrous AlCl3 (754.3 mg, 5.65 equiv)
was added to a solution of 3s (1 mmol, 308 mg) in dry benzene (10.0
mL) and then refluxed for 9 h. On completion, 30 mL of 0.15 M HCl was
added and extracted with ethyl acetate. The combined organic phases
were washed with aq NaHCO3 and brine and were dried over anhyd.
Na2SO4. After removal of solvent the crude product was purified by
column chromatography with silica gel using a mixture of petroleum ether
(bp 40−80 °C) and ethyl acetate (4:1) to give 217 mg of 6a (99%).
Characterization Data of Products (6a−6b). 6H-Indolo[2,3-
ACKNOWLEDGMENTS
■
We thank the NSF (NSF-21072080, NSF-20732002) for
financial support. We acknowledge National Basic Research
Program of China (973 program), 2010CB833203, and also the
support by the 111 Project.
REFERENCES
■
1
b]quinoline (6a): yield 99%; light-yellow solid; mp 276−280 °C; H
(1) Yang, S. W.; Abdel-Kader, M.; Malone, S.; Werkhoven, M. C. M.; Jan,
H. W.; Bursuker, I.; Neddermann, K.; Fairchild, C.; Raventos-Suarez, C.;
Menendez, A. T.; Lane, K.; Kingston, D. G. I. J. Nat. Prod. 1999, 62, 976.
(2) Molina, A.; Vaquero, J. J.; Garcia-Navio, J. L.; Alvarez-Builla, J.;
Pascula-Terasa, B.; Gago, F.; Rodrigo, M. M.; Ballestros, M. J. Org.
Chem. 1996, 61, 5587−5599.
(3) Guittat, L.; Alberti, P.; Rosu, F.; Van Miert, S.; Thetiot, E.;
Pieters, L.; Gabelica, V.; Pauw, D. E.; Ottaviani, A.; Riou, J. F.; Mergny,
J. L. Biochimie 2003, 85, 535.
(4) (a) Molina, P.; Alajarin, M.; Vidal, A. J. Chem. Soc., Chem.
Commun. 1990, 1277. (b) Molina, P.; Alajarin, M.; Vidal, A.; Sanchez-
Andrada, P. J. Org. Chem. 1992, 57, 929.
(5) Shi, C.; Zhang, Q.; Wang, K. K. J. Org. Chem. 1999, 64, 925.
(6) (a) Saito, T.; Ohmori, H.; Furuno, E.; Motoki, S. J. Chem. Soc.,
Chem. Commun. 1992, 22. (b) Saito, T.; Ohmori, H.; Ohkubo, T.;
Motoki, S. J. Chem. Soc., Chem. Commun. 1993, 1802.
(7) Zhang, Q.; Shi, C.; Zhang, H.-R.; Wang, K. K. J. Org. Chem. 2000,
65, 7977.
NMR (DMSO-d6, 400 MHz): δ 11.68 (1H, s), 9.04 (1H, s), 8.25 (1H,
d, J = 7.6 Hz), 8.09 (1H, dd, J = 0.8, 8.0 Hz), 7.96 (1H, d, J = 8.4 Hz),
7.69−7.73 (1H, m), 7.45−7.55 (3H, m), 7.24−7.28 (1H, m) ; 13C
NMR (DMSO-d6, 100 MHz): δ 152.8, 146.3, 141.4, 128.6, 128.1,
127.4, 126.9, 123.6, 122.6, 121.7, 120.2, 119.6, 117.8, 111.5, 110.8; IR
(neat) ν: 3400, 3131, 2922, 2852, 1609, 1457, 1379, 1261, 1230, 1157,
1071, 1014, 947, 781, 731, 692, 472 cm−1 ; HRMS (ESI) calcd for
C15H11N2 (M+ + H): 219.0917, found: 219.0913.
11-Methyl-6H-indolo[2,3-b]quinoline (6b): yield 99%; light-yellow
1
solid; mp 260−262 °C; H NMR (DMSO-d6, 400 MHz): δ 11.67
(1H, s), 8.31−8.34 (2H, m), 7.94 (1H, dd, J = 0.8, 8.4 Hz), 7.69−7.73
(1H, m), 7.47−7.54 (3H, m), 7.25−7.29 (1H, m) ; 13C NMR
(DMSO-d6, 100 MHz): δ 152.2, 146.0, 141.3, 138.7, 128.4, 127.4,
127.3, 124.3, 123.6, 123.4, 122.4, 121.0, 119.6, 115.9, 110.7, 14.8; IR
(neat) ν: 3781, 3691, 3401, 3159, 3086, 2922, 2856, 1668, 1602, 1453,
1385, 1240, 1062, 1025, 738, 594, 403 cm−1; HRMS (ESI) calcd for
C16H13N2 (M+ + H): 233.1073, found: 233.1078.
General Procedure for Preparing Neocryptolepine (7a) and
11-Methylneocryptolepine (7b). Dimethyl sulfate (150.7 mg, 1.2
equiv) was added to a solution of 6a (0.9954 mmol, 217 mg) in dry
acetonitrile (5 mL) under argon and then refluxed for 12 h. On
completion, the reaction was quenched with aq solution of K2CO3 and
extracted with ethyl acetate. The combined organic phases were
washed with aq K2CO3 and brine and dried over anhyd. Na2SO4. After
removal of solvent the crude product was purified by column
chromatography with silica gel using mixture of petroleum ether (bp
40−80 °C) and ethyl acetate (20: 1) to give 204 mg of 7a (88%).
Characterization Data of Products (7a and 7b). 5-Methyl-
5H-indolo[2,3-b]quinoline (7a): yield 88%; red solid; mp 101−103
°C; 1H NMR (CDCl3, 400 MHz): δ 8.71 (1H, s), 8.12 (2H, t, J = 6.8
Hz), 7.99 (1H, d, J = 8.0 Hz), 7.69 (1H, m), 7.56−7.60 (1H, m),
7.41−7.47 (2H, m), 7.29 (1H, t, J = 7.6 Hz), 3.99 (3H, s) ; 13C NMR
(CDCl3, 100 MHz): δ 146.8, 142.8, 128.8, 128.5, 128.0, 127.5, 127.3,
124.1, 122.8, 121.4, 120.4, 119.9, 118.2, 118.0, 108.7, 27.7; IR (neat) ν:
3396, 3054, 2924, 2853, 1724, 1637, 1606, 1574, 1491, 1474, 1430,
1396, 1360, 1321, 1255, 1118, 1019, 787, 744, 600, 476 cm−1; HRMS
(ESI) calcd for C16H13N2 (M+ + H): 233.1073, found: 233.1066.
5,11-Dimethyl-5H-indolo[2,3-b]quinoline (7b): yield 81%; pale-
(8) (a) Molina, P.; Fresneda, P. M.; Delgado, S. Synthesis 1999, 326.
(b) Fresneda, P. M.; Molina, P.; Delgado, S. Tetrahedron Lett. 1999,
40, 7275. (c) Alajarin, M.; Molina, P.; Vidal, A. J. Nat. Prod. 1997, 60,
747.
(9) Timari, G.; Soos, T.; Hajos, G. Synlett 1997, 1067.
(10) Vecchione, M. K.; Sun, A. X.; Seidel, D. Chem. Sci. 2011,
DOI: 10.1039/c1sc00506e.
(11) During our study of this annulation approach of indoles to
indolo(2,3-b)quinolines, a similar approach10 to neocryptolepine and
analogues has been developed by Seidel’s group using free indoles and
secondary aminobenzaldehydes as coupling partners. However,
Siedel’s approach is limited to the use of secondary amino-
benzaldehydes and the inertness of aminobenzophenones indicates
the lack of substrate generality. Moreover, when Siedel’s approach was
applied to our model substrates, we did not obtain the expected
product (see scheme below for inertness of aminobenzophenones to
Seidel’s approach).
1
yellow solid; mp 222−224 °C; H NMR (CDCl3, 400 MHz): δ 8.28
(1H, d, J = 8.0 Hz), 8.23 (1H, d, J = 8.4 Hz), 7.69 (1H, t, J = 7.2 Hz),
7.56 (1H, t, J = 7.6 Hz), 7.46 (1H, t, J = 8.0 Hz), 7.42 (1H, d, J = 8.0
Hz), 7.30 (1H, t, J = 7.6 Hz), 3.08 (3H, s), 3.20 (3H, s) ; 13C NMR
(CDCl3, 100 MHz): δ 142.7, 130.2, 130.0, 128.5, 128.0, 127.9, 127.3,
124.1, 124.0, 123.5, 122.5, 121.4, 119.8, 108.5, 62.1, 31.9, 14.1; IR
(neat) ν: 3407, 2922, 2852, 1742, 1632, 1603, 1460, 1383, 1215, 1155,
1090, 1067, 1025, 758, 667 cm−1 ; HRMS (ESI) calcd for C17H15N2
(M+ + H): 247.1230, found: 247.1234.
ASSOCIATED CONTENT
* Supporting Information
Experimental details, analytical data for all new compounds,
■
(12) Ali, S.; Zhu, H. T.; Xia, X. F.; Ji, K. G.; Yang, Y. F.; Song, X. R.;
Liang., Y. M. Org. Lett. 2011, 13, 2598−2601.
(13) Forrest, T. P.; Dauphinee, G. A.; Deraniyagala, S. A. Can.
J. Chem. 1985, 63, 412.
S
and X-ray crystallography data of 3j in CIF format. This
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The Journal of Organic Chemistry
Article
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