Cu-Catalyzed Dimerization of Indole Derived Oxime Acetate for Synthesis of Biimidazo[1,2- a]indoles

Article abstract of DOI:10.1021/acs.joc.1c00010

A copper-mediated cyclization and dimerization of indole derived oxime acetate was developed to generate a series of biimidazo[1,2-a]indole scaffolds with two contiguous stereogenic quaternary carbons in one step.

Full text of DOI:10.1021/acs.joc.1c00010

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Article
Cu-Catalyzed Dimerization of Indole Derived Oxime Acetate for
Synthesis of Biimidazo[1,2‑a]indoles
Tao Xie,§ Qi-Bang Sui,§ Lu-Zhe Qin,§ Xiaoan Wen, Hongbin Sun, Qing-Long Xu,* and Le Zhen*
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ABSTRACT: A copper-mediated cyclization and dimerization of
indole derived oxime acetate was developed to generate a series of
biimidazo[1,2-a]indole scaffolds with two contiguous stereogenic
quaternary carbons in one step.
dimeric indoline alkaloids by several research groups.6 Second,
the homodimerization of tryptamine and tryptophol derivatives
was developed in the presence of copper catalyst,7 oxidant,8
and other catalysts9 for the construction of these dimeric
indoline alkaloids. Even though there are several methods to
achieve the cyclization/homodimerization reaction, there are
only linkages at the C3 position of the indole core to generate
the radical species. Therefore, the development of novel
methods toward dimeric indoline skeletons was still desirable
and challenging.
In the past 10 years, O-acyl oximes as versatile intermediates
were employed in chemical transformation for the synthesis of
different heterocycles.10 The N−O bond in the oxime acetate
is much more active than the normal N−O bond; there are
many studies on the synthesis of nitrogen-containing hetero-
cycles by breaking the N−O bond of O-acyl oximes, most of
which are synthesized in the presence of transition metals,
including Pd,11 Rh,12 Ru,13 Fe,14 Co,15 Cu,16 etc. In addition,
microwave,17 UV,18 and visible light catalyses19 have also been
reported. We chose copper as catalyst to initiate N−O bond
breaking, participating in the radical cyclization reaction. In our
previous work, we developed copper-catalyzed dearomatization
reaction of indole from 2-methylindole derived oxime acetates,
providing access to structurally novel spiro[indoline-3,2′-
pyrrolidine] derivatives.20 Then, the oxime acetates connected
with the N1 position of the indole core was synthesized,
Herein, we report the copper-catalyzed nitrogen radical
generation, followed by an intramolecular radical cyclization
and homodimerization reaction, affording the novel biimidazo-
[1,2-a]indoles scaffold directly (Scheme 1).
INTRODUCTION
■
The dimeric structures are widespread in a number of natural
alkaloids, possessing attractive biological activities, especially
indole skeletons, such as (+)-chimonanthine, (+)-folicanthine,
and (−)-calycanthine.1 These dimeric indoline derivatives
always containing vicinal stereogenic quaternary carbon
centers, especially at C3a and C3a′ positions of the indole
core, have attracted considerable attention for the community
of synthetic chemists in the past few years.2 Great progress has
been made to realize the synthesis of dimeric indoline
derivatives.3 Among these reported methods, the straightfor-
ward strategy is the selective radical-mediated C−C bond
connection at the C3 position of two similar indoline
precursors (Scheme 1). Two strategies were widely developed
to the synthesis of indole-based dimeric alkaloids. First, the
homocoupling reaction using 3-brominated indoline deriva-
tives for the synthesis of dimeric indoline derivatives was
realized by different transition metal catalysts, including Co4
and Ni,5 that have been applied to the synthesis of naturally
Scheme 1. Straightforward Strategies to Realize
Homodimerization Reaction
Received: January 3, 2021
Published: March 29, 2021
https://doi.org/10.1021/acs.joc.1c00010
© 2021 American Chemical Society
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a
Table 1. Optimization of Reaction Conditions
a
b
c
Reaction condition: 1a (0.2 mmol), [Cu] (20 mol %), solvent (2.0 mL), 105 °C, 2.5 h under argon condition. Isolated yield. Reacted at 80 °C,
5 h.
lower temperature reduced reaction yield and increased
reaction time (entry 14, Table 1). Finally, the optimum
conditions were identified to be Cu(acac)2 (20 mol %) in
toluene at 105 °C under argon condition.
RESULTS AND DISCUSSION
■
In our initial study, (E)-2-(3-methyl-1H-indol-1-yl)-1-phenyl-
ethan-1-one O-acetyl oxime (1a) (see the synthetic route in
the Supporting Information for details) was chosen as the
model substrate to investigate copper-catalyzed radical-
mediated cyclization/dimerization reaction at 105 °C in
toluene under argon condition, using Cu(eh)2 as initial
catalyst. Just as we expect, the desired indoline derived dimeric
product (dl-2a and meso-2a) was obtained in 35% and 20%
yield (entry 1, Table 1), respectively, and the structures of
these dimeric products were confirmed by X-ray single crystal
diffraction (thermal ellipsoids are set at 30% probability; see in
the Supporting Information for details).21 Encouraged by these
results, we explored the optimal conditions of the catalyst,
solvent, and reaction temperature. As depicted in Table 1,
Cu(acac)2 had a better yield compared with other copper
catalysts (entry 3, Table 1). Sequential screening of solvents
found that p-xylene was obtained in the highest total yield
(66%) (entry 10, Table 1). Given its high boiling point and
considerable yield of toluene, we chose toluene as the optimal
solvent for the subsequent reaction optimization. We also
investigated the influence of reaction temperature. We found a
With the optimal conditions established, we explored the
generality of our copper-catalyzed radical-mediated cycliza-
tion/dimerization protocol. As illustrated in Table 2,
substituents on the benzene ring of the indole core such as
methyl, methoxy, fluoro, chloro, and bromo were all well-
tolerated, and the corresponding products were obtained in
good isolated yields (2e−2m, 40−65% total yields). But 4-
OMe replaced substrate (1g) only afforded meso-product 2g in
28% yield; this may be due to the large methoxy group
hindrance at the C4 position in the benzene ring of the indole
core, so the dl-configuration product was not easily formed,
while the meso-configuration product was not affected. An
ethyl group at the C3 position of the substrate 1b also worked
well to afford desired product dl-2b and meso-2b in good yield.
Nevertheless, the isopropyl group (1c) and isobutyl group
(1d) at the C3 position only afforded meso-product in 47% and
dl-product in 51% yield, respectively. As with the 4-OMe
substrate (1g) above, we hypothesized that the 3-substituent
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a
Table 2. Substrate Scope
b
entry
1
R1, R2, R3
Me, H, Ph
Et, H, Ph
iPr, H, Ph
product
yield (%)
dl-2 yield (%)
meso-2 yield (%)
1
2
3
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
1r
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
2r
64
60
47
51
65
59
28
64
61
40
45
52
53
63
62
65
58
56
62
59
45
59
64
64
58
34
37
30
23
47
4
iBu, H, Ph
51
33
33
5
6
7
8
Me, 5-Me, Ph
Me, 6-Me, Ph
Me, 4-MeO, Ph
Me, 5-MeO, Ph
Me, 7-MeO, Ph
Me, 4-F, Ph
Me, 6-Cl, Ph
Me, 6-Br, Ph
Me, 7-Br, Ph
Me, H, 4-MeC6H4
Me, H, 3-MeOC6H4
Me, H, 4-MeOC6H4
Me, H, 2-FC6H4
Me, H, 3-FC6H4
Me, H, 4-FC6H4
Me, H, 2,4-F2C6H3
Me, H, 2-ClC6H4
Me, H, 3-ClC6H4
Me, H, 4-ClC6H4
Me, H, 3,4-Cl2C6H3
Me, H, 4-BrC6H4
32
26
28
31
31
22
20
22
15
29
32
27
28
26
30
24
23
30
31
28
28
33
30
18
25
30
38
34
30
38
30
30
32
35
22
29
33
36
30
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
1s
1t
2s
2t
1u
1v
1w
1x
1y
2u
2v
2w
2x
2y
a
b
Reaction condition: 1a (0.6 mmol), Cu(acac)2 (20 mol %), toluene (6.0 mL), 105 °C, 2.5 h under argon condition. Isolated yield.
hindrance of the isopropyl group was so large that the products
of the meso-configuration were easier to form. However, it is
not clear why the C3-position substituent of isobutyl produces
dl-product instead of meso-product. Next, the substitution
pattern on the aromatic ring adjacent to the oxime moiety was
varied (1n−1y), and it gave our desired products in good
yields (45−65% total yields). These yields had not changed
much; only the C2 position substitution of 2-OMe and 2-Cl
has a lower yield (total yield 44% and 45%). We also
preferentially think in terms of steric hindrance; the C2
substitution pattern maybe influences the activity of the free
radical because of its hindrance. Taken together, this protocol
provides a new approach to biimidazo[1,2-a]indole derivatives
via radical-mediated cyclization/dimerization reaction in the
presence of copper catalyst.
Scheme 2. Proposed Mechanism
After carrying out a series of substrate expansions, we further
investigated the practicality of the reaction. We used the gram-
scale substrate of 1a (4 mmol, 1.22 g) with Cu(acac)2 (0.8
mmol, 211 mg) and dry toluene (40 mL), which afforded the
comparable yield of dl-2a (30%, 292 mg) and meso-2a (31%,
307 mg), and confirmed the convenience of the protocol in
this study.
On the basis of the above results and the literature reports, a
plausible catalytic pathway is proposed in Scheme 2. Initially,
the copper catalyst reductively cleaves the N−O bond of acyl
oxime 1a to form iminyl radical A. Subsequently, an
intramolecular 5-exo-trig cyclization of iminyl radical A gives
C-centered radical B, which is dimerized to produce product
C. Finally, a double bond is formed by oxidizing the
intermedate C to produce the product 2a. To understand
the mechanism of the reaction, we added radical scavengers to
the reaction and found that, when TEMPO (1.0 equiv) was
added, the reaction could still proceed but the product was
obtained in a much lower yield (30%). Meanwhile, when the
substrate 3 derived from tetrahydrocarbazole was conducted
under the optimal reaction conditions (Scheme 3), the dimeric
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EtOAc = 50:1) to afford the corresponding 3-methyl-1H-indole (S3,
70% yield for two steps).
Scheme 3. Reaction of the Substrate 3 Derived from
Tetrahydrocarbazole
3-Methyl-1H-indole (S3) (2.0 equiv) and KOH (3.0 equiv) were
added to a two-neck bottle under argon. DMSO (1.0 M) was added
by syringe, and the mixture was stirred at room temperature for 2 h. A
solution of Int-1 (1.0 equiv) in DMSO was added by syringe slowly to
the mixture. The mixture was stirred overnight at room temperature.
Upon completion of the reaction as indicated by TLC analysis, the
mixture was diluted with water and extracted with EtOAc. The
combined organic layer was washed with brine, dried over anhydrous
Na2SO4, and concentrated under the reduced pressure. The residue
was directly purified by flash column chromatography on silica gel
(petroleum ether/EtOAc = 20:1) to afford the desired products S4
(47% yield).
4 Å molecular sieves were added to a solution of S4 (1.0 equiv) in
EtOH (1.5 M). The mixture was stirred to remove water at room
temperature for 2 h; then NH2OH·HCl (6.0 equiv) was added. The
reaction mixture was stirred overnight at room temperature. After the
completion of the reaction indicated by TLC, the reaction mixture
was filtered and the residue was washed with EtOAc. The filtrate was
concentrated under the reduced pressure and was purified by flash
column chromatography on silica gel (petroleum ether/EtOAc =
15:1) to afford the desired product S5 (67% yield).
AcCl (1.2 equiv) and Et3N (1.2 equiv) were added to a solution of
S5 (1.0 equiv) in DCM (0.5 M) at 0 °C for 0.5 h. After completion,
the reaction mixture was directly purified by flash column
chromatography on silica (petroleum ether/EtOAc = 10:1) gel to
afford the substrate 1 (88% yield).
(E)-2-(3-Methyl-1H-indol-1-yl)-1-phenylethan-1-one O-Acetyl
Oxime (1a). Eluent: petroleum ether/ethyl acetate: 10/1; white
solid; mp 80−82 °C; 1H NMR (300 MHz, DMSO-d6) δ 7.65 (d, J =
6.7 Hz, 2H), 7.49−7.24 (m, 5H), 7.12 (appt, J = 7.8 Hz, 1H), 7.06 (s,
1H), 6.99 (appt, J = 7.2 Hz, 1H), 5.63 (s, 2H), 2.26 (s, 3H), 2.15 (s,
3H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 168.5, 162.8, 136.7,
132.7, 131.2, 128.9, 128.7, 127.0, 126.7, 122.0, 119.2, 119.1, 110.5,
109.8, 41.8, 20.0, 9.8. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C19H18N2O2Na 329.1260; Found 329.1265.
(E)-2-(3-Ethyl-1H-indol-1-yl)-1-phenylethan-1-one O-Acetyl
Oxime (1b). Eluent: petroleum ether/ethyl acetate: 10/1; white
solid; mp 54−56 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.64 (d, J =
7.6 Hz, 2H), 7.45 (d, J = 7.9 Hz, 1H), 7.42−7.29 (m, 4H), 7.12 (appt,
J = 7.7 Hz, 1H), 7.07 (s, 1H), 6.99 (appt, J = 7.5 Hz, 1H), 5.64 (s,
2H), 2.60 (q, J = 7.7 Hz, 2H), 2.26 (s, 3H), 1.16 (t, J = 7.5 Hz, 3H).
13C{1H} NMR (126 MHz, DMSO-d6) δ 168.4, 162.9, 136.8, 132.7,
131.1, 128.9, 128.0, 127.9, 125.7, 122.0, 119.2, 117.6, 109.8, 42.0,
20.0, 18.1, 15.0. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C20H20N2O2Na 343.1417; Found 343.1420.
(E)-2-(3-Isopropyl-1H-indol-1-yl)-1-phenylethan-1-one O-Acetyl
Oxime (1c). Eluent: petroleum ether/ethyl acetate: 10/1; white
solid; mp 75−78 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.61 (d, J =
7.4 Hz, 2H), 7.49 (d, J = 7.9 Hz, 1H), 7.40 (appt, J = 7.4 Hz, 1H),
7.36−7.30 (m, 3H), 7.11 (appt, J = 7.6 Hz, 1H), 7.06 (s, 1H), 6.98
(appt, J = 7.4 Hz, 1H), 5.65 (s, 2H), 3.08−2.98 (m, 1H), 2.27 (s,
3H), 1.21 (d, J = 6.9 Hz, 6H). 13C{1H} NMR (126 MHz, DMSO-d6)
δ 168.4, 163.0, 136.9, 132.7, 131.0, 128.8, 128.0, 127.2, 124.7, 121.9,
119.5, 119.2, 109.9, 42.3, 25.2, 23.7, 20.0. HRMS (ESI-TOF) m/z:
[M + Na]+ Calcd for C21H22N2O2Na 357.1573; Found 357.1576.
(E)-2-(3-Isobutyl-1H-indol-1-yl)-1-phenylethan-1-one O-Acetyl
Oxime (1d). Eluent: petroleum ether/ethyl acetate: 10/1; white
solid; mp 99−101 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.58 (d, J =
7.3 Hz, 2H), 7.42 (d, J = 7.8 Hz, 1H), 7.38 (appt, J = 7.4 Hz, 1H),
7.35−7.27 (m, 3H), 7.11 (appt, J = 7.6 Hz, 1H), 7.07 (s, 1H), 6.97
(appt, J = 7.4 Hz, 1H), 5.68 (s, 2H), 2.45 (d, J = 6.9 Hz, 2H), 2.28 (s,
3H), 1.82−1.72 (m, 1H), 0.78 (d, J = 6.6 Hz, 6H). 13C{1H} NMR
(126 MHz, DMSO-d6) δ 168.5, 163.2, 136.5, 132.6, 130.9, 128.8,
128.5, 128.0, 127.2, 121.8, 119.3, 119.2, 114.4, 109.8, 42.2, 34.1, 29.1,
22.8, 20.0. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C22H24N2O2Na 371.1730; Found 371.1734.
product was not obtained, affording the tertiary alcohol 4 in
26% yield as the major product, and the structure of product 4
was confirmed by X-ray single crystal diffraction (see in the
Supporting Information for details).21
CONCLUSION
■
In summary, we have developed a concise way to achieve
radical-mediate cyclization/homodimerization reaction in the
presence of a commercially available copper catalyst. With this
method, a number of novel biimidazo[1,2-a]indole derivative
were produced in good yields. Further applications and
mechanistic studies of these radical-mediated cyclization/
dimerization reactions are currently undergoing in our
laboratory.
EXPERIMENTAL SECTION
■
1
General Information. H and 13C NMR spectra were recorded
on an ACF* 300Q spectrometer. Low- and high-resolution mass
spectra (LRMS and HRMS) were recorded in electron impact mode.
The mass analyzer type used for the HRMS measurements was TOF.
Reactions were monitored by TLC on silica gel 60 F254 plates.
Column chromatography was carried out on silica gel (200−300
mesh).
Data for 1H NMR are recorded as follows: chemical shift (δ, ppm),
multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet or
unresolved, br s = broad singlet, coupling constant(s) in Hz,
integration). Data for 13C NMR are reported in terms of chemical
shift (δ, ppm).
General Procedure for the Synthesis of Substrates 1 and 3
(see the Synthetic Route in the Supporting Information for
Details). Ethylmagnesium bromide (1.2 equiv) was added dropwise
to a solution of phenylacetylene (1.3 equiv) in THF (1.0 M) in a two-
neck bottle under argon condition at 0 °C. The mixture was stirred at
0 °C for 1 h, and then 2-bromoacetophenone (1.0 equiv) was added
dropwise. The mixture was stirred at 0 °C for another 0.5 h. After the
reaction was completed (monitored by TLC), the mixture was
quenched with saturated NH4Cl and extracted with EtOAc. The
combined organic phases were dried over Na2SO4 and concentrated
in vacuo. The crude product Int-1 was used for the next reaction.
A round-bottomed flask was charged with S1 (1.0 equiv) and DMF
(5.0 equiv). The reaction mixture was stirred at 0 °C, and POCl3 (1.2
equiv) was added dropwise in 5 min. The mixture was heated to 40
°C for 2 h, then 2 M NaOH was added slowly, and the mixture was
heated to 90 °C for another 1 h. After the reaction was completed
(monitored by TLC), the mixture was diluted with water and
extracted with EtOAc. The combined organic layer was dried over
anhydrous Na2SO4, which was concentrated under the reduced
pressure. The corresponding compound S2 was used in the next step
without further purification.
In a dry round-bottom flask, LiAlH4 (2.0 equiv) in THF (0.5 M)
was cooled at 0 °C. A solution of crude S2 (1.0 equiv) in THF was
added dropwise in 10 min. The mixture was stirred overnight at room
temperature. After the reaction was completed (monitored by TLC),
H2O was added slowly, followed by 15% NaOH (aq.) and H2O. The
mixture was stirred for 15 min; then MgSO4 was added and stirred for
another 15 min. The solid was removed by filtration and washed with
EtOAc. The filtrate was evaporated under reduced pressure and
purified by flash chromatography on silica gel (petroleum ether/
(E)-2-(3,5-Dimethyl-1H-indol-1-yl)-1-phenylethan-1-one O-Ace-
tyl Oxime (1e). Eluent: petroleum ether/ethyl acetate: 10/1; white
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solid; mp 100−102 °C. 1H NMR (500 MHz, DMSO-d6) δ 7.64 (d, J
= 7.3 Hz, 2H), 7.45−7.38 (m, 1H), 7.36−7.30 (m, 2H), 7.24 (d, J =
8.3 Hz, 1H), 7.18 (s, 1H), 7.00 (s, 1H), 6.94 (d, J = 8.5 Hz, 1H), 5.59
(s, 2H), 2.34 (s, 3H), 2.27 (s, 3H), 2.11 (s, 3H). 13C{1H} NMR (126
MHz, DMSO-d6) δ 168.5, 162.8, 135.1, 132.7, 131.1, 128.9, 128.0,
127.7, 126.7, 123.5, 118.8, 109.9, 109.5, 41.8, 21.5, 20.0, 9.8. HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for C20H20N2O2Na 343.1417;
Found 343.1420.
(E)-2-(3,6-Dimethyl-1H-indol-1-yl)-1-phenylethan-1-one O-Ace-
tyl Oxime (1f). Eluent: petroleum ether/ethyl acetate: 10/1; white
solid; mp 103−105 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.66 (d, J
= 7.6 Hz, 2H), 7.45−7.38 (m, 1H), 7.36−7.32 (m, 2H), 7.29 (d, J =
8.0 Hz, 1H), 7.17 (s, 1H), 6.93 (s, 1H), 6.83 (d, J = 8.0 Hz, 1H), 5.56
(s, 2H), 2.38 (s, 3H), 2.26 (s, 3H), 2.11 (s, 3H). 13C{1H} NMR (126
MHz, DMSO-d6) δ 168.5, 162.7, 137.1, 132.8, 131.2, 131.1, 129.0,
128.0, 126.7, 125.9, 120.9, 118.9, 110.4, 109.7, 41.6, 22.0, 20.0, 9.8.
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C20H20N2O2Na
343.1417; Found 343.1419.
solid; mp 130−132 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.70−7.65
(m, 3H), 7.41 (appt, J = 7.3 Hz, 1H), 7.39−7.34 (m, 3H), 7.12 (dd, J
= 8.3, 1.7 Hz, 1H), 7.04 (s, 1H), 5.63 (s, 2H), 2.25 (s, 3H), 2.12 (s,
3H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 168.3, 162.4, 137.5,
132.7, 131.3, 129.0, 128.0, 127.7, 127.4, 122.1, 120.9, 115.0, 112.9,
111.1, 41.9, 20.0, 9.6. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C19H17BrN2O2Na 407.0371; Found 407.0372.
(E)-2-(7-Bromo-3-methyl-1H-indol-1-yl)-1-phenylethan-1-one O-
Acetyl Oxime (1m). Eluent: petroleum ether/ethyl acetate: 10/1;
1
white solid; mp 140−142 °C; H NMR (500 MHz, DMSO-d6) δ
7.45−7.35 (m, 3H), 7.29 (appt, J = 7.2 Hz, 1H), 7.27−7.19 (m, 4H),
6.86 (appt, J = 8.0 Hz, 1H), 5.96 (s, 2H), 2.16 (s, 3H), 2.14 (s,
3H).13C{1H} NMR (126 MHz, DMSO-d6) δ 167.9, 164.9, 132.5,
132.0, 131.6, 130.0, 129.8, 128.0, 127.7, 126.4, 120.23 118.5, 110.4,
102.6, 45.7, 19.4, 9.1. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C19H17BrN2O2Na 407.0371; Found 407.0368.
(E)-2-(3-Methyl-1H-indol-1-yl)-1-(p-tolyl)ethan-1-one O-Acetyl
Oxime (1n). Eluent: petroleum ether/ethyl acetate: 10/1; white
solid; mp 102−104 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.58 (d, J
= 8.1 Hz, 2H), 7.41 (d, J = 7.8 Hz, 1H), 7.37 (d, J = 8.2 Hz, 1H), 7.15
(d, J = 7.9 Hz, 2H), 7.12 (appt, J = 7.6 Hz, 1H), 7.06 (s, 1H), 6.99
(appt, J = 7.6 Hz, 1H), 5.60 (s, 2H), 2.25 (s, 6H), 2.15 (s, 3H).
13C{1H} NMR (126 MHz, DMSO-d6) δ 168.5, 162.5, 141.1, 136.6,
129.8, 129.6, 128.7, 127.9, 126.6, 122.0, 119.2, 119.1, 110.4, 109.8,
41.6, 21.3, 20.0, 9.8. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C20H20N2O2Na 343.1417; Found 343.1421.
(E)-1-(3-Methoxyphenyl)-2-(3-methyl-1H-indol-1-yl)ethan-1-one
O-Acetyl Oxime (1o). Eluent: petroleum ether/ethyl acetate: 10/1;
white solid; mp 90−92 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.50−
7.38 (m, 2H), 7.31−7.21 (m, 2H), 7.19−7.11 (m, 2H), 7.07 (s, 1H),
7.02 (appt, J = 7.2 Hz, 1H), 6.97 (d, J = 6.8 Hz, 1H), 5.64 (s, 2H),
3.67 (s, 3H), 2.28 (s, 3H), 2.18 (s, 3H). 13C{1H} NMR (126 MHz,
DMSO-d6) δ 168.5, 162.7, 159.4, 136.7, 134.0, 130.1, 128.7, 126.6,
122.0, 120.4, 119.2, 119.1, 117.0, 113.2, 110.6, 109.8, 55.6, 41.9, 20.0,
9.8. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C20H20N2O3Na
359.1366; Found 359.1372.
(E)-1-(4-Methoxyphenyl)-2-(3-methyl-1H-indol-1-yl)ethan-1-one
O-Acetyl Oxime (1p). Eluent: petroleum ether/ethyl acetate: 10/1;
white solid; mp 116−119 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.66
(d, J = 8.4 Hz, 2H), 7.43 (d, J = 7.8 Hz, 1H), 7.39 (d, J = 8.2 Hz, 1H),
7.13 (appt, J = 7.7 Hz, 1H), 7.06 (s, 1H), 7.00 (appt, J = 7.6 Hz, 1H),
6.91 (d, J = 8.4 Hz, 2H), 5.59 (s, 2H), 3.72 (s, 3H), 2.24 (s, 3H), 2.16
(s, 3H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 168.5, 161.9, 161.7,
136.6, 129.6, 128.7, 126.5, 124.8, 122.0, 119.2, 119.1, 114.5, 110.5,
109.8, 55.7, 41.4, 20.0, 9.8. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for C20H20N2O3Na 359.1366; Found 359.1365.
(E)-2-(4-Methoxy-3-methyl-1H-indol-1-yl)-1-phenylethan-1-one
O-Acetyl Oxime (1g). Eluent: petroleum ether/ethyl acetate: 10/1;
1
white solid; mp 85−87 °C; H NMR (500 MHz, DMSO-d6) δ 7.64
(d, J = 7.5 Hz, 2H), 7.45−7.40 (m, 1H), 7.38−7.32 (m, 2H), 7.01
(appt, J = 8.0 Hz, 1H), 6.94 (d, J = 8.2 Hz, 1H), 6.90 (s, 1H), 6.44 (d,
J = 7.7 Hz, 1H), 5.58 (s, 2H), 3.78 (s, 3H), 2.28 (s, 3H), 2.27 (s,
3H).13C{1H} NMR (126 MHz, DMSO-d6) δ 168.5, 162.8, 155.0,
138.4, 132.6, 131.1, 128.9, 128.0, 125.4, 123.1, 118.1, 110.7, 103.2,
99.9, 55.5, 42.0, 20.0, 12.5. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for C20H20N2O3Na 359.1366; Found 359.1370.
(E)-2-(5-Methoxy-3-methyl-1H-indol-1-yl)-1-phenylethan-1-one
O-Acetyl Oxime (1h). Eluent: petroleum ether/ethyl acetate: 10/1;
1
white solid; mp 85−87 °C; H NMR (500 MHz, DMSO-d6) δ 7.63
(d, J = 7.3 Hz, 2H), 7.42−7.38 (m, 1H), 7.36−7.32 (m, 2H), 7.25 (d,
J = 8.8 Hz, 1H), 7.01 (s, 1H), 6.88 (d, J = 2.4 Hz, 1H), 6.75 (dd, J =
8.9, 2.4 Hz, 1H), 5.59 (s, 2H), 3.73 (s, 3H), 2.27 (s, 3H), 2.11 (s,
3H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 168.5, 162.8, 153.8,
132.7, 131.8, 131.1, 129.1, 128.9, 128.0, 127.3, 111.9, 110.5, 110.1,
101.1, 55.8, 41.9, 20.0, 9.9. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for C20H20N2O3Na 359.1366; Found 359.1370.
(E)-2-(7-Methoxy-3-methyl-1H-indol-1-yl)-1-phenylethan-1-one
O-Acetyl Oxime (1i). Eluent: petroleum ether/ethyl acetate: 10/1;
1
white solid; mp 97−99 °C; H NMR (500 MHz, DMSO-d6) δ 7.46
(d, J = 6.9 Hz, 2H), 7.34−7.28 (m, 1H), 7.26−7.22 (m, 2H), 7.02 (s,
1H), 6.93 (d, J = 7.9 Hz, 1H), 6.83 (appt, J = 7.8 Hz, 1H), 6.57 (d, J =
7.7 Hz, 1H), 5.77 (s, 2H), 3.77 (s, 3H), 2.20 (s, 3H), 2.11 (s, 3H).
13C{1H} NMR (126 MHz, DMSO-d6) δ 168.5, 164.9, 147.2, 133.0,
130.9, 130.4, 128.5, 127.9, 126.1, 119.9, 111.9, 110.4, 103.1, 55.5,
45.7, 19.9, 9.9. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C20H20N2O3Na 359.1366; Found 359.1368.
(E)-1-(2-Fluorophenyl)-2-(3-methyl-1H-indol-1-yl)ethan-1-one
O-Acetyl Oxime (1q). Eluent: petroleum ether/ethyl acetate: 10/1;
white solid; mp 72−74 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.44−
7.28 (m, 3H), 7.25 (d, J = 8.1 Hz, 1H), 7.17−7.01 (m, 3H), 7.01−
6.92 (m, 2H), 5.59 (s, 2H), 2.27 (s, 3H), 2.13 (s, 3H). 13C{1H} NMR
(E)-2-(4-Fluoro-3-methyl-1H-indol-1-yl)-1-phenylethan-1-one O-
Acetyl Oxime (1j). Eluent: petroleum ether/ethyl acetate: 10/1; white
solid; mp 86−88 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.63 (d, J =
7.6 Hz, 2H), 7.45−7.40 (m, 1H), 7.38−7.32 (m, 2H), 7.18 (d, J = 8.2
Hz, 1H), 7.07 (s, 2H), 6.74−6.67 (m, 1H), 5.64 (s, 2H), 2.25 (s, 6H).
13C{1H} NMR (126 MHz, DMSO-d6) δ 168.39, 162.54, 157.08 (d,
1
(126 MHz, DMSO-d6) δ 168.2, 161.2, 160.0 (d, JC‑F = 249.0 Hz),
3
136.7, 132.7 (d, JC‑F = 8.4 Hz), 130.8 (d, J = 2.5 Hz), 128.7, 126.9,
124.7 (d, 4JC‑F = 3.3 Hz), 121.9, 120.6 (d, 3JC‑F = 14.3 Hz), 119.2 (d,
2JC‑F = 22.7 Hz), 116.1 (d, 2JC‑F = 21.1 Hz), 110.4, 109.6, 44.0 (d, J =
1JC‑F = 244.4 Hz), 139.54 (d, 3JC‑F = 11.9 Hz), 132.53, 131.18, 128.95,
127.96, 127.28, 122.71 (d, 3JC‑F = 7.9 Hz), 116.82 (d, 2JC‑F = 19.6 Hz),
108.74, 106.55 (d, 4JC‑F = 3.4 Hz), 104.40 (d, 2JC‑F = 19.0 Hz), 42.21,
20.00, 11.55. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C19H17FN2O2Na 347.1166; Found 347.1170.
1.9 Hz), 19.9, 9.7. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C19H17FN2O2Na 347.1166; Found 347.1170.
(E)-1-(3-Fluorophenyl)-2-(3-methyl-1H-indol-1-yl)ethan-1-one
O-Acetyl Oxime (1r). Eluent: petroleum ether/ethyl acetate: 10/1;
white solid; mp 86−88 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.51−
7.44 (m, 2H), 7.41 (d, J = 7.5 Hz, 1H), 7.39−7.34 (m, 2H), 7.28−
7.20 (m, 1H), 7.15−7.10 (m, 1H), 7.08 (s, 1H), 6.99 (appt, J = 7.4
Hz, 1H), 5.64 (s, 2H), 2.27 (s, 3H), 2.15 (s, 3H). 13C{1H} NMR
(E)-2-(6-Chloro-3-methyl-1H-indol-1-yl)-1-phenylethan-1-one O-
Acetyl Oxime (1k). Eluent: petroleum ether/ethyl acetate: 10/1;
white solid; mp 110−112 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.67
(d, J = 7.4 Hz, 2H), 7.53 (s, 1H), 7.45−7.38 (m, 2H), 7.38−7.32 (m,
2H), 7.06 (s, 1H), 7.00 (d, J = 8.5 Hz, 1H), 5.64 (s, 2H), 2.25 (s,
3H), 2.13 (s, 3H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 168.3,
162.5, 137.1, 132.6, 131.3, 129.0, 128.0, 127.5, 127.4, 126.9, 120.5,
119.5, 111.1, 109.9, 41.9, 20.0, 9.6. HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C19H17ClN2O2Na 363.0871; Found 363.0875.
(E)-2-(6-Bromo-3-methyl-1H-indol-1-yl)-1-phenylethan-1-one O-
Acetyl Oxime (1l). Eluent: petroleum ether/ethyl acetate: 10/1. white
1
(126 MHz, DMSO-d6) δ 168.4, 162.2 (d, JC‑F = 244.6 Hz), 161.8,
3
3
136.6, 135.0 (d, JC‑F = 8.1 Hz), 131.1 (d, JC‑F = 8.3 Hz), 128.7,
4
3
126.6, 124.3 (d, JC‑F = 2.8 Hz), 122.1, 119.2 (d, JC‑F = 12.9 Hz),
2
2
118.0 (d, JC‑F = 20.9 Hz), 114.8 (d, JC‑F = 23.5 Hz), 110.7, 109.7,
41.9, 20.0, 9.8. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C19H17FN2O2Na 347.1166; Found 347.1170.
5522
https://doi.org/10.1021/acs.joc.1c00010
J. Org. Chem. 2021, 86, 5518−5529

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(E)-1-(4-Fluorophenyl)-2-(3-methyl-1H-indol-1-yl)ethan-1-one
O-Acetyl Oxime (1s). Eluent: petroleum ether/ethyl acetate: 10/1;
white solid; 89−92 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.70 (dd, J
= 8.9, 5.5 Hz, 2H), 7.41 (d, J = 7.9 Hz, 1H), 7.35 (d, J = 8.2 Hz, 1H),
7.18 (appt, J = 8.8 Hz, 2H), 7.13 (appt, J = 6.5 Hz, 1H), 7.07 (s, 1H),
6.99 (appt, J = 7.5 Hz, 1H), 5.63 (s, 2H), 2.27 (s, 3H), 2.15 (s, 3H).
13C{1H} NMR (126 MHz, DMSO-d6) δ 168.4, 163.9 (d, 1JC‑F = 249.0
132.0, 130.0, 128.8, 126.6, 124.8, 122.1, 119.3, 119.2, 110.6, 109.7,
41.8, 20.0, 9.8. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C19H17BrN2O2Na 407.0366; Found 407.0373.
(E)-1-Phenyl-2-(1,2,3,4-tetrahydro-9H-carbazol-9-yl)ethan-1-one
O-Acetyl Oxime (3). Eluent: petroleum ether/ethyl acetate: 10/1;
1
white solid; mp 136−138 °C; H NMR (500 MHz, DMSO-d6) δ
7.47−7.39 (m, 3H), 7.35 (appt, J = 7.2 Hz, 1H), 7.33−7.22 (m, 3H),
7.08 (appt, J = 7.5 Hz, 1H), 6.96 (appt, J = 7.3 Hz, 1H), 5.59 (s, 2H),
2.62−2.52 (m, 4H), 2.20 (s, 3H), 1.83−1.73 (m, 2H), 1.73−1.62 (m,
2H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 168.3, 164.1, 136.8,
135.9, 132.9, 130.8, 128.7, 127.9, 127.4, 121.1, 119.2, 117.9, 109.7,
109.5, 23.2, 23.0, 22.1, 21.0, 19.9. HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C22H22N2O2Na 369.1573; Found 369.1578.
Hz), 162.0, 136.6, 130.4 (d, 3JC‑F = 8.8 Hz), 129.1 (d, 4JC‑F = 3.0 Hz),
3
2
128.7, 126.6, 122.1, 119.2 (d, JC‑F = 11.7 Hz), 116.0 (d, JC‑F = 21.9
Hz), 110.6, 109.7, 41.9, 20.0, 9.8. HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C19H17FN2O2Na 347.1166; Found 347.1168.
(E)-1-(2,4-Difluorophenyl)-2-(3-methyl-1H-indol-1-yl)ethan-1-
one O-Acetyl Oxime (1t). Eluent: petroleum ether/ethyl acetate: 10/
1
1; white solid; mp 68−70 °C; H NMR (500 MHz, DMSO-d6) δ
General Procedure for the Synthesis of Product 2. In a flame-
dried Schlenk bottle, a mixture of 1 (0.6 mmol) and Cu(acac)2 (0.12
mmol) in dry toluene (6.0 mL) was added. The reaction mixture was
heated at 105 °C for 2.5 h under argon condition. After completion,
the mixture was evaporated under reduced pressure and the residue
was purified by flash column chromatography on silica gel (petroleum
ether/EtOAc = 15:1 to 6:1) to afford the products dl-2, meso-2.
9,9′-Dimethyl-2,2′-diphenyl-9H,9′H-9,9′-biimidazo[1,2-a]indole
(dl-2a). Eluent: petroleum ether/ethyl acetate: 15/1 to 10/1; 34%
yield (25.9 mg, 0.3 mmol substrate); white solid; mp 266−268 °C; 1H
NMR (300 MHz, DMSO-d6) δ 8.28 (s, 2H), 7.98 (d, J = 7.2 Hz, 4H),
7.47 (appt, J = 7.6 Hz, 4H), 7.31 (appt, J = 7.4 Hz, 2H), 7.24 (d, J =
7.6 Hz, 2H), 7.10 (appt, J = 7.3 Hz, 2H), 6.78 (appt, J = 7.3 Hz, 2H),
5.91 (d, J = 7.5 Hz, 2H), 2.11 (s, 6H). 13C{1H} NMR (126 MHz,
DMSO-d6) δ 158.0, 145.7, 140.5, 137.2, 135.1, 129.0, 128.7, 127.2,
125.3, 124.9, 123.2, 111.1, 107.7, 50.0, 19.4. HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C34H27N4 491.2230; Found 491.2236.
9,9′-Dimethyl-2,2′-diphenyl-9H,9′H-9,9′-biimidazo[1,2-a]indole
(meso-2a). Eluent: petroleum ether/ethyl acetate: 10/1 to 6/1; 30%
yield (21.6 mg, 0.3 mmol substrate); light yellow solid; mp 237−239
°C; 1H NMR (500 MHz, DMSO-d6) δ 7.89 (d, J = 5.1 Hz, 2H), 7.74
(d, J = 7.4 Hz, 4H), 7.40−7.29 (m, 8H), 7.23−7.18 (m, 2H), 7.06 (s,
4H), 1.95 (s, 3H), 1.94 (s, 3H). 13C{1H} NMR (126 MHz, DMSO-
d6) δ 157.4, 144.9, 139.5, 137.7, 135.0, 128.7, 128.3, 126.4, 124.9,
124.7, 123.9, 110.7, 106.6, 49.5, 19.3. HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C34H27N4 491.2230; Found 491.2234.
7.43−7.35 (m, 2H), 7.25 (d, J = 8.2 Hz, 1H), 7.19 (appt, J = 10.0 Hz,
1H), 7.10 (appt, J = 7.7 Hz, 1H), 7.04−6.91 (m, 3H), 5.58 (s, 2H),
2.28 (s, 3H), 2.13 (s, 3H). 13C{1H} NMR (126 MHz, DMSO-d6) δ
168.1, 163.5 (dd, 1JC‑F = 250.0 Hz, 3JC‑F = 12.3 Hz), 160.5, 160.3 (dd,
3
2
1JC‑F = 251.8 Hz, JC‑F = 12.9 Hz), 136.7, 132.3 (dd, JC‑F = 10.2 Hz,
4JC‑F = 3.7 Hz), 128.7, 126.8, 122.0, 119.2 (d, 2JC‑F = 25.8 Hz), 117.2
(dd, 3JC‑F = 14.6 Hz, 3JC‑F = 3.8 Hz), 112.1 (dd, 2JC‑F = 21.7 Hz, 4JC‑F
=
2
3.7 Hz), 110.5, 109.6, 104.8 (appt, JC‑F = 26.0 Hz), 43.9, 19.9, 9.7.
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C19H16F2N2O2Na
365.1078; Found 365.1082.
(E)-1-(2-Chlorophenyl)-2-(3-methyl-1H-indol-1-yl)ethan-1-one
O-Acetyl Oxime (1u). Eluent: petroleum ether/ethyl acetate: 10/1;
white solid; mp 89−91 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.42−
7.35 (m, 2H), 7.33−7.26 (m, 2H), 7.18−7.04 (m, 3H), 7.03−6.91
(m, 2H), 5.59 (s, 2H), 2.30 (s, 3H), 2.12 (s, 3H). 13C{1H} NMR
(126 MHz, DMSO-d6) δ 168.2, 163.5, 136.8, 132.1, 131.8, 131.7,
130.9, 129.7, 128.7, 127.1, 127.0, 121.9, 119.2, 119.0, 110.4, 109.8,
44.2, 19.9, 9.7. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C19H17ClN2O2Na 363.0871; Found 363.0873.
(E)-1-(3-Chlorophenyl)-2-(3-methyl-1H-indol-1-yl)ethan-1-one
O-Acetyl Oxime (1v). Eluent: petroleum ether/ethyl acetate: 10/1;
white solid; mp 111−113 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.58
(s, 1H), 7.48 (d, J = 6.3 Hz, 1H), 7.37−7.29 (m, 2H), 7.26 (appt, J =
8.2 Hz, 2H), 7.04 (appt, J = 7.6 Hz, 1H), 6.99 (s, 1H), 6.91 (appt, J =
7.4 Hz, 1H), 5.56 (s, 2H), 2.19 (s, 3H), 2.06 (s, 3H). 13C{1H} NMR
(126 MHz, DMSO-d6) δ 168.4, 161.9, 136.6, 134.7, 133.6, 130.9,
130.8, 128.7, 127.6, 126.7, 126.6, 122.1, 119.3, 119.2, 110.7, 109.7,
41.9, 20.0, 9.8. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C19H17ClN2O2Na 363.0871; Found 363.0875.
(E)-1-(4-Chlorophenyl)-2-(3-methyl-1H-indol-1-yl)ethan-1-one
O-Acetyl Oxime (1w). Eluent: petroleum ether/ethyl acetate: 10/1;
white solid; mp 130−132 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.62
(d, J = 8.6 Hz, 2H), 7.43 (d, J = 7.8 Hz, 1H), 7.38 (d, J = 8.6 Hz, 2H),
7.34 (d, J = 8.3 Hz, 1H), 7.13 (appt, J = 7.5 Hz, 1H), 7.05−6.97 (m,
2H), 5.57 (s, 2H), 2.24 (s, 3H), 2.18 (s, 3H). 13C{1H} NMR (126
MHz, DMSO-d6) δ 168.1, 162.0, 137.0, 136.0, 131.9, 129.7, 129.0,
128.9, 126.5, 122.1, 119.3, 119.1, 111.0, 109.7, 42.3, 19.7, 9.5. HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for C19H17ClN2O2Na 363.0871;
Found 363.0872.
9,9′-Diethyl-2,2′-diphenyl-9H,9′H-9,9′-biimidazo[1,2-a]indole
(dl-2b). Eluent: petroleum ether/ethyl acetate: 15/1 to 10/1; 37%
1
yield (60.6 mg); light yellow solid; mp 250−251 °C; H NMR (500
MHz, DMSO-d6) δ 8.13 (s, 2H), 7.98 (d, J = 7.4 Hz, 4H), 7.46 (appt,
J = 7.6 Hz, 4H), 7.31 (appt, J = 7.5 Hz, 2H), 7.21 (d, J = 7.6 Hz, 2H),
7.09 (appt, J = 7.7 Hz, 2H), 6.77 (appt, J = 7.6 Hz, 2H), 5.93 (d, J =
7.6 Hz, 2H), 3.28−3.18 (m, 2H), 2.85−2.73 (m, 2H), 0.30 (t, J = 7.3
Hz, 6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 156.7, 145.8, 138.3,
138.2, 135.1, 129.0, 128.6, 127.2, 125.3, 124.8, 123.4, 110.9, 107.6,
55.8, 24.7, 9.0. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C36H31N4 519.2549; Found 519.2548.
9,9′-Diethyl-2,2′-diphenyl-9H,9′H-9,9′-biimidazo[1,2-a]indole
(meso-2b). Eluent: petroleum ether/ethyl acetate: 10/1 to 6/1; 23%
1
yield (37.8 mg); white solid; mp 214−217 °C; H NMR (500 MHz,
DMSO-d6) δ 7.97 (s, 2H), 7.74 (d, J = 7.5 Hz, 4H), 7.42−7.29 (m,
8H), 7.22 (appt, J = 7.2 Hz, 2H), 7.14−6.91 (m, 4H), 3.06−2.94 (m,
2H), 2.48−2.38 (m, 2H), 0.24 (t, J = 7.2 Hz, 6H). 13C{1H} NMR
(126 MHz, DMSO-d6) δ 156.1, 145.0, 139.1, 137.5, 135.2, 129.2,
129.0, 126.9, 124.9, 124.4, 111.1, 107.3, 55.6, 25.0, 9.2. HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C36H31N4 519.2549; Found
519.2549.
9,9′-Diisopropyl-2,2′-diphenyl-9H,9′H-9,9′-biimidazo[1,2-a]-
indole (meso-2c). Eluent: petroleum ether/ethyl acetate: 30/1 to 15/
1; 47% yield (77.0 mg); light yellow solid; mp 118−120 °C; 1H NMR
(300 MHz, DMSO-d6) δ 8.24 (s, 2H), 7.85 (d, J = 7.1 Hz, 4H), 7.58
(d, J = 7.1 Hz, 4H), 7.50−7.34 (m, 6H), 7.33−7.10 (m, 4H), 4.04 (s,
2H), 1.21 (d, J = 6.1 Hz, 6H), 0.64 (d, J = 4.9 Hz, 6H).13C{1H} NMR
(126 MHz, DMSO-d6) δ 155.7, 145.3, 138.7, 137.2, 135.1, 129.1,
128.6, 127.0, 126.1, 125.1, 124.9, 111.4, 107.8, 46.4, 31.0, 20.4, 17.9.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C38H35N4 547.2856;
Found 547.2857.
(E)-1-(3,4-Dichlorophenyl)-2-(3-methyl-1H-indol-1-yl)ethan-1-
one O-Acetyl Oxime (1x). Eluent: petroleum ether/ethyl acetate: 10/
1; white solid; mp 78−80 °C; 1H NMR (500 MHz, DMSO-d6) δ 7.86
(s, 1H), 7.64−7.56 (m, 2H), 7.43 (d, J = 7.8 Hz, 1H), 7.35 (d, J = 8.2
Hz, 1H), 7.14 (appt, J = 7.6 Hz, 1H), 7.10 (s, 1H), 7.01 (appt, J = 7.4
Hz, 1H), 5.66 (s, 2H), 2.29 (s, 3H), 2.17 (s, 3H). 13C{1H} NMR
(126 MHz, DMSO-d6) δ 168.3, 161.2, 136.6, 133.9, 133.2, 131.7,
131.2, 129.8, 128.8, 128.2, 126.6, 122.2, 119.4, 119.2, 110.8, 109.7,
41.9, 19.9, 9.8. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C19H16Cl2N2O2Na 397.0481; Found 397.0484.
(E)-1-(4-Bromophenyl)-2-(3-methyl-1H-indol-1-yl)ethan-1-one
O-Acetyl Oxime (1y). Eluent: petroleum ether/ethyl acetate: 10/1;
light yellow solid; mp 126−129 °C; 1H NMR (500 MHz, DMSO-d6)
δ 7.59 (d, J = 8.3 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 7.8
Hz, 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.13 (appt, J = 7.7 Hz, 1H), 7.07
(s, 1H), 7.00 (appt, J = 7.5 Hz, 1H), 5.63 (s, 2H), 2.27 (s, 3H), 2.16
(s, 3H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 168.3, 162.1, 136.6,
5523
https://doi.org/10.1021/acs.joc.1c00010
J. Org. Chem. 2021, 86, 5518−5529

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
9,9′-Diisobutyl-2,2′-diphenyl-9H,9′H-9,9′-biimidazo[1,2-a]indole
(dl-2d). Eluent: petroleum ether/ethyl acetate: 30/1 to 15/1; 51%
yield (74.0 mg, 0.5 mmol substrate); light yellow solid; mp 218−220
°C; 1H NMR (500 MHz, DMSO-d6) δ 8.11 (s, 2H), 7.99 (d, J = 7.3
Hz, 4H), 7.48 (appt, J = 7.7 Hz, 4H), 7.32 (appt, J = 7.4 Hz, 2H),
7.18 (d, J = 7.7 Hz, 2H), 7.08 (appt, J = 7.6 Hz, 2H), 6.75 (appt, J =
7.5 Hz, 2H), 5.90 (d, J = 7.6 Hz, 2H), 3.42 (dd, J = 13.8, 4.4 Hz, 2H),
2.61 (dd, J = 13.9, 7.9 Hz, 2H), 1.04−0.92 (m, 2H), 0.67 (d, J = 6.7
Hz, 6H), 0.40 (d, J = 6.6 Hz, 6H). 13C{1H} NMR (126 MHz,
DMSO-d6) δ 157.3, 145.7, 138.2, 138.1, 135.3, 129.1, 128.7, 127.2,
125.4, 124.5, 124.1, 110.9, 107.6, 55.2, 25.5, 24.8, 22.8. HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C40H39N4 575.3169; Found
575.3173.
125.2, 114.4, 111.7, 109.9, 107.7, 55.8, 50.2, 19.5. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C36H31N4O2 551.2442; Found 551.2448.
7,7′-Dimethoxy-9,9′-dimethyl-2,2′-diphenyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (meso-2h). Eluent: petroleum ether/ethyl
acetate: 10/1 to 6/1; 31% yield (50.4 mg); white solid; mp 242−244
°C; 1H NMR (500 MHz, DMSO-d6) δ 7.85 (s, 2H), 7.74 (d, J = 7.7
Hz, 4H), 7.34 (appt, J = 7.6 Hz, 4H), 7.29 (d, J = 8.4 Hz, 2H), 7.20
(appt, J = 7.4 Hz, 2H), 6.90 (dd, J = 8.5, 2.3 Hz, 2H), 6.84 (s, 2H),
3.72 (s, 6H), 1.87 (s, 6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ
157.6, 157.1, 144.9, 141.4, 135.6, 132.0, 128.8, 126.7, 125.0, 114.4,
112.8, 111.6, 107.0, 56.3, 50.2, 19.9. HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C36H31N4O2 551.2442; Found 551.2448.
5,5′-Dimethoxy-9,9′-dimethyl-2,2′-diphenyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (dl-2i). Eluent: petroleum ether/ethyl ac-
etate: 15/1 to 10/1; 30% yield (50.2 mg); white solid; mp 263−264
°C; 1H NMR (500 MHz, DMSO-d6) δ 7.99 (d, J = 6.9 Hz, 4H), 7.93
(s, 2H), 7.44 (t, J = 7.7 Hz, 4H), 7.29 (appt, J = 7.5 Hz, 2H), 6.83 (d,
J = 8.3 Hz, 2H), 6.75 (appt, J = 8.0 Hz, 2H), 5.61 (d, J = 7.6 Hz, 2H),
3.83 (s, 6H), 2.12 (s, 6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ
157.4, 145.9, 145.2, 142.0, 135.2, 129.0, 127.1, 126.0, 126.0, 125.3,
115.5, 112.9, 109.7, 56.8, 50.3, 19.7. HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C36H31N4O2 551.2442; Found 551.2449.
5,5′-Dimethoxy-9,9′-dimethyl-2,2′-diphenyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (meso-2i). Eluent: petroleum ether/ethyl
acetate: 10/1 to 6/1; 31% yield (50.4 mg); white solid; mp 230−233
°C; 1H NMR (500 MHz, DMSO-d6) δ 7.75 (d, J = 7.6 Hz, 4H), 7.69
(s, 2H), 7.34 (appt, J = 7.7 Hz, 4H), 7.19 (appt, J = 7.4 Hz, 2H),
7.09−7.00 (m, 4H), 6.68 (s, 2H), 3.86 (s, 6H), 1.93 (s, 6H). 13C{1H}
NMR (126 MHz, DMSO-d6) δ 157.3, 146.2, 144.8, 141.2, 135.5,
128.7, 127.2, 126.6, 125.3, 125.1, 117.7, 113.5, 109.2, 57.0, 50.3, 19.7.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C36H31N4O2 551.2442;
Found 551.2445.
8,8′-Difluoro-9,9′-dimethyl-2,2′-diphenyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (dl-2j). Eluent: petroleum ether/ethyl ac-
etate: 15/1 to 10/1; 18% yield (29.1 mg); white solid; mp 220−222
°C; 1H NMR (500 MHz, DMSO-d6) δ 7.90 (s, 2H), 7.73 (d, J = 8.9
Hz, 4H), 7.40−7.31 (m, 6H), 7.26−7.19 (m, 2H), 7.18 (d, J = 7.7 Hz,
2H), 6.89−6.81 (m, 2H), 2.13 (s, 6H). 13C{1H} NMR (126 MHz,
DMSO-d6) δ 159.60 (d, J = 248.7 Hz), 157.13, 145.71, 139.88 (d, J =
9.3 Hz), 135.13, 131.66 (d, J = 8.9 Hz), 128.81, 127.00, 125.17,
112.66 (d, J = 23.1 Hz), 107.68 (d, J = 3.1 Hz), 107.28, 51.94 (d, J =
2.8 Hz), 18.10 (d, J = 4.8 Hz). HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C34H25F2N4 527.2042; Found 527.2048.
7,7′,9,9′-Tetramethyl-2,2′-diphenyl-9H,9′H-9,9′-biimidazo[1,2-
a]indole (dl-2e). Eluent: petroleum ether/ethyl acetate: 15/1 to 10/
1
1; 33% yield (51 mg); white solid; mp 267−269 °C; H NMR (500
MHz, DMSO-d6) δ 8.05 (s, 2H), 7.97 (d, J = 7.5 Hz, 4H), 7.46 (appt,
J = 7.6 Hz, 4H), 7.30 (appt, J = 7.4 Hz, 2H), 7.05 (d, J = 7.7 Hz, 2H),
6.88 (d, J = 7.7 Hz, 2H), 5.75 (s, 2H), 2.11 (s, 6H), 1.96 (s, 6H).
13C{1H} NMR (126 MHz, DMSO-d6) δ 157.9, 145.5, 140.5, 135.3,
135.0, 134.0, 129.0, 128.6, 127.1, 125.3, 124.3, 110.4, 107.4, 50.3,
21.1, 19.0. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C36H31N4
519.2543; Found 519.2551.
7,7′,9,9′-Tetramethyl-2,2′-diphenyl-9H,9′H-9,9′-biimidazo[1,2-
a]indole (meso-2e). Eluent: petroleum ether/ethyl acetate: 10/1 to
6/1; 32% yield (50 mg); white solid; mp 260−262 °C; 1H NMR (500
MHz, DMSO-d6) δ 7.84 (s, 2H), 7.76 (d, J = 7.6 Hz, 4H), 7.36 (appt,
J = 7.7 Hz, 4H), 7.23 (appt, J = 6.7 Hz, 4H), 7.16 (d, J = 8.0 Hz, 2H),
6.99 (s, 2H), 2.30 (s, 6H), 1.87 (s, 6H). 13C{1H} NMR (126 MHz,
DMSO-d6) δ 157.8, 145.1, 140.0, 136.0, 135.5, 133.6, 129.2, 128.8,
126.7, 126.5, 125.0, 110.6, 107.0, 50.0, 21.4, 19.7. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C36H31N4 519.2543; Found 519.2547.
6,6′,9,9′-Tetramethyl-2,2′-diphenyl-9H,9′H-9,9′-biimidazo[1,2-
a]indole (dl-2f). Eluent: petroleum ether/ethyl acetate: 15/1 to 10/1;
1
33% yield (50.7 mg); light yellow solid; mp 260−261 °C; H NMR
(500 MHz, DMSO-d6) δ 8.24 (s, 2H), 7.97 (d, J = 7.6 Hz, 4H), 7.48
(appt, J = 7.6 Hz, 4H), 7.31 (appt, J = 7.3 Hz, 2H), 7.11 (s, 2H), 6.60
(d, J = 7.8 Hz, 2H), 5.82 (d, J = 7.8 Hz, 2H), 2.16 (s, 6H), 2.08 (s,
6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 158.1, 145.1, 138.4,
137.6, 137.1, 134.9, 129.2, 127.3, 125.6, 125.1, 122.8, 111.9, 107.9,
49.4, 21.4, 19.8. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C36H31N4 519.2543; Found 519.2543.
6,6′,9,9′-Tetramethyl-2,2′-diphenyl-9H,9′H-9,9′-biimidazo[1,2-
8,8′-Difluoro-9,9′-dimethyl-2,2′-diphenyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (meso-2j). Eluent: petroleum ether/ethyl
acetate: 10/1 to 6/1; 22% yield (35 mg); light yellow solid; mp 227−
228 °C; 1H NMR (500 MHz, DMSO-d6) δ 8.04 (s, 2H), 7.83 (d, J =
7.7 Hz, 4H), 7.41 (appt, J = 7.6 Hz, 4H), 7.30−7.22 (m, 4H), 7.18 (d,
J = 7.7 Hz, 2H), 6.74−6.68 (m, 2H), 2.17 (s, 6H). 13C{1H} NMR
a]indole (meso-2f). Eluent: petroleum ether/ethyl acetate: 10/1 to
1
6/1; 26% yield (40.8 mg); light yellow solid; mp 248−250 °C; H
NMR (500 MHz, DMSO-d6) δ 7.83 (s, 2H), 7.70 (d, J = 7.3 Hz, 4H),
7.31 (appt, J = 7.4 Hz, 4H), 7.24−7.12 (m, 4H), 6.96 (s, 2H), 6.91−
6.82 (m, 2H), 2.29 (s, 6H), 1.85 (s, 6H). 13C{1H} NMR (126 MHz,
DMSO-d6) δ 158.3, 145.2, 138.9, 138.2, 137.3, 135.5, 128.8, 126.7,
125.1, 125.1, 125.0, 111.8, 106.9, 49.6, 21.4, 20.0. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C36H31N4 519.2543; Found 519.2545.
8,8′-Dimethoxy-9,9′-dimethyl-2,2′-diphenyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (meso-2g). Eluent: petroleum ether/ethyl
acetate: 10/1 to 6/1; 28% yield (46.4 mg); white solid; mp 227−228
°C; 1H NMR (500 MHz, DMSO-d6) δ 8.01 (s, 2H), 7.93 (d, J = 7.3
Hz, 4H), 7.44 (appt, J = 7.7 Hz, 4H), 7.27 (appt, J = 7.4 Hz, 2H),
7.10 (appt, J = 8.0 Hz, 2H), 6.93 (d, J = 7.6 Hz, 2H), 6.44 (d, J = 8.4
Hz, 2H), 3.29 (s, 6H), 2.12 (s, 6H). 13C{1H} NMR (126 MHz,
DMSO-d6) δ 159.7, 156.9, 145.5, 138.7, 135.7, 130.0, 128.9, 127.1,
126.8, 125.3, 108.1, 107.2, 103.6, 56.5, 50.3, 19.7. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C36H31N4O2 551.2442; Found 551.2450.
7,7′-Dimethoxy-9,9′-dimethyl-2,2′-diphenyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (dl-2h). Eluent: petroleum ether/ethyl
acetate: 15/1 to 10/1; 33% yield (54.5 mg); white solid; mp 255−
257 °C; 1H NMR (500 MHz, DMSO-d6) δ 8.07 (s, 2H), 7.95 (d, J =
7.6 Hz, 4H), 7.45 (appt, J = 7.6 Hz, 4H), 7.29 (appt, J = 7.4 Hz, 2H),
7.16 (d, J = 8.4 Hz, 2H), 6.65 (dd, J = 8.4, 2.5 Hz, 2H), 5.65 (d, J =
2.5 Hz, 2H), 2.97 (s, 6H), 2.13 (s, 6H). 13C{1H} NMR (126 MHz,
DMSO-d6) δ 157.6, 157.3, 145.3, 141.9, 135.3, 130.9, 129.0, 127.1,
1
(126 MHz, DMSO-d6) δ 158.9 (d, JC‑F = 249.8 Hz), 157.5, 146.2,
3
3
139.7 (d, JC‑F = 9.6 Hz), 135.1, 131.4 (d, JC‑F = 8.7 Hz), 128.9,
2
127.1, 125.3, 112.5 (d, JC‑F = 22.5 Hz), 107.9, 107.5, 50.6, 18.6.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C34H25F2N4 527.2042;
Found 527.2048.
6,6′-Dichloro-9,9′-dimethyl-2,2′-diphenyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (dl-2k). Eluent: petroleum ether/ethyl
acetate: 15/1 to 10/1; 25% yield (42.1 mg); yellow solid; mp 254−
256 °C; 1H NMR (500 MHz, DMSO-d6) δ 8.17 (s, 2H), 7.96 (d, J =
7.6 Hz, 4H), 7.52−7.45 (m, 6H), 7.34 (appt, J = 7.4 Hz, 2H), 6.88 (d,
J = 8.1 Hz, 2H), 5.97 (d, J = 8.1 Hz, 2H), 2.14 (s, 6H). 13C{1H}
NMR (126 MHz, DMSO-d6) δ 158.1, 146.1, 139.1, 138.4, 134.8,
133.5, 129.1, 127.6, 125.5, 124.8, 124.5, 111.9, 108.2, 49.9, 19.1.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C34H25Cl2N4 559.1451;
Found 559.1451.
6,6′-Dichloro-9,9′-dimethyl-2,2′-diphenyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (meso-2k). Eluent: petroleum ether/ethyl
acetate: 10/1 to 6/1; 20% yield (33.1 mg); light yellow solid; mp
1
262−263 °C; H NMR (500 MHz, DMSO-d6) δ 7.93 (s, 2H), 7.70
(d, J = 7.7 Hz, 4H), 7.52 (s, 2H), 7.35 (appt, J = 7.6 Hz, 4H), 7.24−
7.20 (m, 2H), 7.14 (s, 4H), 1.88 (s, 6H). 13C{1H} NMR (126 MHz,
5524
https://doi.org/10.1021/acs.joc.1c00010
J. Org. Chem. 2021, 86, 5518−5529

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
DMSO-d6) δ 157.7, 145.2, 139.1, 138.3, 134.8, 133.7, 129.1, 127.2,
124.9, 124.4, 111.9, 107.6, 49.5, 19.3. HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C34H25Cl2N4 559.1451; Found 559.1452.
130.1, 128.7, 124.9, 123.2, 118.0, 113.3, 111.1, 111.1, 108.0, 55.8,
50.0, 19.4. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C36H31N4O2
551.2442; Found 551.2443.
2,2′-Bis(3-methoxyphenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
[1,2-a]indole (meso-2o). Eluent: petroleum ether/ethyl acetate: 10/1
to 6/1; 32% yield (52.6 mg); light yellow solid; mp 214−216 °C; 1H
NMR (500 MHz, DMSO-d6) δ 7.99 (s, 2H), 7.50−7.30 (m, 12H),
7.06 (s, 2H), 6.76 (d, J = 6.6 Hz, 2H), 3.74 (s, 6H), 1.97 (s, 6H).
13C{1H} NMR (126 MHz, DMSO-d6) δ 160.0, 157.4, 144.7, 139.6,
6,6′-Dibromo-9,9′-dimethyl-2,2′-diphenyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (dl-2l). Eluent: petroleum ether/ethyl ac-
etate: 15/1 to 10/1; 30% yield (59.2 mg); white solid; mp 250−252
°C; 1H NMR (500 MHz, DMSO-d6) δ 8.17 (s, 2H), 7.94 (d, J = 7.4
Hz, 4H), 7.59 (s, 2H), 7.47 (appt, J = 7.5 Hz, 4H), 7.33 (appt, J = 7.4
Hz, 2H), 7.01 (d, J = 8.1 Hz, 2H), 5.89 (d, J = 8.0 Hz, 2H), 2.11 (s,
6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 157.9, 146.0, 139.5,
138.5, 134.7, 129.1, 127.7, 127.5, 125.4, 124.8, 121.4, 114.7, 108.1,
49.9, 19.0. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C34H25Br2N4
647.0440; Found 647.0446.
6,6′-Dibromo-9,9′-dimethyl-2,2′-diphenyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (meso-2l). Eluent: petroleum ether/ethyl
acetate: 10/1 to 6/1; 22% yield (43.4 mg); white solid; mp 243−245
°C; 1H NMR (500 MHz, DMSO-d6) δ 7.96 (s, 2H), 7.73 (d, J = 7.7
Hz, 4H), 7.69 (s, 2H), 7.37 (t, J = 7.9 Hz, 4H), 7.30 (d, J = 9.9 Hz,
2H), 7.25 (appt, J = 8.9 Hz, 2H), 7.13 (d, J = 8.1 Hz, 2H), 1.89 (s,
6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 157.8, 145.7, 139.4,
139.0, 135.1, 128.9, 127.2, 127.2, 127.1, 125.2, 121.9, 114.7, 107.5,
49.8, 19.5. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C34H25Br2N4
647.0440; Found 647.0444.
5,5′-Dibromo-9,9′-dimethyl-2,2′-diphenyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (dl-2m). Eluent: petroleum ether/ethyl
acetate: 15/1 to 10/1; 38% yield (61.5 mg, 0.5 mmol substrate);
light yellow solid; mp 221−223 °C; 1H NMR (300 MHz, DMSO-d6)
δ 8.43 (s, 2H), 8.06 (d, J = 7.1 Hz, 4H), 7.48 (appt, J = 7.6 Hz, 4H),
7.41−7.28 (m, 4H), 6.80 (appt, J = 7.9 Hz, 2H), 5.88 (d, J = 7.6 Hz,
2H), 2.14 (s, 6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 157.9,
145.5, 142.5, 136.1, 134.5, 132.7, 129.1, 127.6, 126.4, 125.6, 122.4,
109.1, 104.1, 50.5, 19.0. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C34H2581Br2N4 649.0426; Found 649.0419.
137.9, 136.6, 130.0, 129.3, 124.5, 117.1, 113.0, 111.3, 109.7, 107.5,
55.3, 49.7, 19.4. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C36H31N4O2 551.2442; Found 551.2452.
2,2′-Bis(4-methoxyphenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
[1,2-a]indole (dl-2p). Eluent: petroleum ether/ethyl acetate: 15/1 to
1
10/1; 38% yield (62.6 mg); white solid; mp 205−207 °C; H NMR
(300 MHz, DMSO-d6) δ 8.14 (s, 2H), 7.94−7.84 (m, 4H), 7.20 (d, J
= 7.7 Hz, 2H), 7.13−6.98 (m, 6H), 6.76 (appt, J = 7.6 Hz, 2H), 5.90
(d, J = 7.6 Hz, 2H), 3.82 (s, 6H), 2.09 (s, 6H). 13C{1H} NMR (126
MHz, DMSO-d6) δ 158.9, 157.5, 145.3, 140.2, 137.1, 128.7, 127.6,
126.4, 124.8, 123.0, 114.6, 111.0, 106.7, 55.6, 49.7, 19.4. HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C36H31N4O2 551.2442; Found
551.2450.
2,2′-Bis(4-methoxyphenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
[1,2-a]indole (meso-2p). Eluent: petroleum ether/ethyl acetate: 10/1
to 6/1; 27% yield (44.6 mg); light yellow solid; mp 205−207 °C; 1H
NMR (300 MHz, DMSO-d6) δ 7.85 (s, 2H), 7.74−7.48 (m, 4H),
7.44−7.22 (m, 4H), 7.17−6.37 (m, 8H), 3.78 (s, 6H), 1.94 (s, 6H).
13C{1H} NMR (126 MHz, DMSO-d6) δ 158.6, 157.4, 144.9, 139.6,
138.1, 129.2, 128.0, 126.2, 124.3, 114.4, 111.1, 106.0, 55.6, 49.6, 19.6.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C36H31N4O2 551.2442;
Found 551.2451.
2,2′-Bis(2-fluorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
[1,2-a]indole (dl-2q). Eluent: petroleum ether/ethyl acetate: 15/1 to
1
5,5′-Dibromo-9,9′-dimethyl-2,2′-diphenyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (meso-2m). Eluent: petroleum ether/ethyl
acetate: 10/1 to 6/1; 15% yield (24 mg, 0.5 mmol); light yellow solid;
10/1; 30% yield (48 mg); white solid; mp 246−248 °C; H NMR
(500 MHz, DMSO-d6) δ 8.40−8.28 (m, 2H), 8.08 (d, J = 3.6 Hz,
2H), 7.43−7.27 (m, 8H), 7.10 (appt, J = 7.7 Hz, 2H), 6.79 (appt, J =
7.6 Hz, 2H), 5.99 (d, J = 7.7 Hz, 2H), 2.16 (s, 6H). 13C{1H} NMR
1
mp 235−237 °C; H NMR (500 MHz, DMSO-d6) δ 8.09 (s, 2H),
1
7.79 (d, J = 7.2 Hz, 4H), 7.54 (d, J = 7.0 Hz, 2H), 7.38 (t, J = 7.2 Hz,
4H), 7.26 (t, J = 7.0 Hz, 2H), 7.06 (d, J = 7.1 Hz, 4H), 2.00 (s, 6H).
13C{1H} NMR (126 MHz, DMSO-d6) δ 157.8, 145.1, 141.9, 140.5,
(126 MHz, DMSO-d6) δ 159.6 (d, JC‑F = 247.6 Hz), 157.6, 140.4,
4
3
138.9, 137.1, 128.7, 128.6 (d, JC‑F = 3.6 Hz), 125.1 (d, JC‑F = 12.4
3
2
Hz), 123.1, 122.7 (d, JC‑F= 12.9 Hz), 116.1 (d, JC‑F = 21.7 Hz),
111.5, 111.2 (d, 2JC‑F = 12.5 Hz), 50.0, 19.4. HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C34H25F2N4 527.2042; Found 527.2049.
2,2′-Bis(2-fluorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
[1,2-a]indole (meso-2q). Eluent: petroleum ether/ethyl acetate: 10/1
138.9, 137.0, 134.8, 133.1, 128.8, 127.2, 125.9, 125.4, 124.4, 108.5,
104.4, 50.4, 19.2. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C34H2581Br2N4 649.0426; Found 649.0419.
9,9′-Dimethyl-2,2′-di-p-tolyl-9H,9′H-9,9′-biimidazo[1,2-a]indole
1
to 6/1; 28% yield (45 mg); white solid; mp 225−227 °C; H NMR
(dl-2n). Eluent: petroleum ether/ethyl acetate: 15/1 to 10/1; 34%
1
(500 MHz, DMSO-d6) δ 8.01 (appt, J = 7.2 Hz, 2H), 7.79 (d, J = 3.4
Hz, 2H), 7.45 (d, J = 7.7 Hz, 2H), 7.32 (appt, J = 7.0 Hz, 2H), 7.28−
7.16 (m, 6H), 7.12−7.00 (m, 4H), 1.98 (s, 6H). 13C{1H} NMR (126
yield (52.4 mg); white solid; mp 249−251 °C; H NMR (500 MHz,
DMSO-d6) δ 8.16 (s, 2H), 7.87 (d, J = 7.7 Hz, 4H), 7.27 (d, J = 7.8
Hz, 4H), 7.21 (d, J = 7.8 Hz, 2H), 7.08 (appt, J = 7.7 Hz, 2H), 6.75
(appt, J = 7.7 Hz, 2H), 5.92 (d, J = 7.6 Hz, 2H), 2.36 (s, 6H), 2.10 (s,
6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 157.9, 145.9, 140.5,
137.3, 136.5, 132.4, 129.6, 128.6, 125.3, 124.8, 123.2, 111.0, 107.1,
50.0, 21.2, 19.4. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C36H31N4 519.2543; Found 519.2552.
1
MHz, DMSO-d6) δ 159.4 (d, JC‑F = 247.3 Hz), 157.4, 139.8, 138.5,
4
3
138.1, 129.2, 128.4 (d, JC‑F = 4.4 Hz), 128.1 (d, JC‑F = 8.2 Hz),
125.2, 124.7 (d, JC‑F = 2.8 Hz), 124.6, 122.9 (d, JC‑F = 13.1 Hz),
115.9 (d, JC‑F = 21.6 Hz), 111.6, 110.6 (d, JC‑F = 13.4 Hz), 49.9,
19.5. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C34H25F2N4
527.2042; Found 527.2053.
4
3
2
2
9,9′-Dimethyl-2,2′-di-p-tolyl-9H,9′H-9,9′-biimidazo[1,2-a]indole
(meso-2n). Eluent: petroleum ether/ethyl acetate: 10/1 to 6/1; 29%
2,2′-Bis(3-fluorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
1
[1,2-a]indole (dl-2r). Eluent: petroleum ether/ethyl acetate: 15/1 to
yield (45.0 mg); light yellow solid; mp 234−236 °C; H NMR (300
1
10/1; 30% yield (47.3 mg); light yellow solid; mp 253−255 °C; H
MHz, DMSO-d6) δ 7.91 (s, 2H), 7.76−7.48 (m, 4H), 7.42−7.24 (m,
4H), 7.17 (d, J = 7.7 Hz, 4H), 7.10−6.46 (m, 4H), 2.31 (s, 6H), 1.95
(s, 6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 157.7, 145.5, 139.9,
138.2, 136.0, 132.7, 129.4, 129.1, 125.3, 125.1, 124.3, 111.1, 106.4,
49.9, 21.1, 19.7. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C36H31N4 519.2543; Found 519.2551.
NMR (300 MHz, DMSO-d6) δ 8.37 (s, 2H), 7.81 (d, J = 7.9 Hz, 2H),
7.77−7.70 (m, 2H), 7.56−7.46 (m, 2H), 7.22 (d, J = 7.7 Hz, 2H),
7.17−7.05 (m, 4H), 6.79 (appt, J = 7.6 Hz, 2H), 5.90 (d, J = 7.6 Hz,
2H), 2.10 (s, 6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 163.4 (d,
1JC‑F = 243.0 Hz), 158.1, 144.5, 140.5, 137.7 (d, 3JC‑F = 7.5 Hz), 137.1,
131.1 (d, 3JC‑F = 8.0 Hz), 128.8, 125.2, 123.2, 121.3, 113.8 (d, 2JC‑F
=
2,2′-Bis(3-methoxyphenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
21.5 Hz), 111.8 (d, 2JC‑F = 22.6 Hz), 111.2, 108.8, 50.1, 19.4. HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C34H25F2N4 527.2042; Found
527.2044.
[1,2-a]indole (dl-2o). Eluent: petroleum ether/ethyl acetate: 15/1 to
1
10/1; 30% yield (50 mg); light yellow solid; mp 241−243 °C; H
NMR (500 MHz, DMSO-d6) δ 8.15 (s, 2H), 7.60−7.51 (m, 4H),
7.37 (appt, J = 7.7 Hz, 2H), 7.21 (d, J = 7.6 Hz, 2H), 7.09 (appt, J =
7.6 Hz, 2H), 6.89 (d, J = 7.9 Hz, 2H), 6.77 (appt, J = 7.5 Hz, 2H),
5.98 (d, J = 7.5 Hz, 2H), 3.88 (s, 6H), 2.13 (s, 6H). 13C{1H} NMR
(126 MHz, DMSO-d6) δ 160.5, 157.9, 145.5, 140.5, 137.2, 136.5,
2,2′-Bis(3-fluorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
[1,2-a]indole (meso-2r). Eluent: petroleum ether/ethyl acetate: 10/1
to 6/1; 26% yield (41.6 mg); white solid; mp 227−230 °C; 1H NMR
(500 MHz, DMSO-d6) δ 7.97 (s, 2H), 7.56 (d, J = 7.7 Hz, 2H), 7.48
5525
https://doi.org/10.1021/acs.joc.1c00010
J. Org. Chem. 2021, 86, 5518−5529

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Article
(d, J = 10.3 Hz, 2H), 7.38 (dd, J = 14.1, 8.0 Hz, 2H), 7.35−7.30 (m,
4H), 7.12−6.96 (m, 6H), 1.97 (s, 6H). 13C{1H} NMR (126 MHz,
(appt, J = 7.1 Hz, 2H), 7.16−6.97 (m, 4H), 2.00 (s, 6H). 13C{1H}
NMR (126 MHz, DMSO-d6) δ 157.0, 141.2, 139.9, 138.1, 133.4,
130.4, 130.3, 129.2, 128.0, 127.3, 125.2, 124.7, 111.7, 111.0, 49.9,
19.5. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C34H25Cl2N4
559.1451; Found 559.1452.
1
DMSO-d6) δ 163.2 (d, JC‑F = 242.8 Hz), 157.9, 144.1, 139.8, 137.9
3
3
(d, JC‑F = 8.5 Hz), 130.7 (d, JC‑F = 8.5 Hz), 129.2, 125.3, 124.6,
120.9 (d, 4JC‑F = 2.4 Hz), 113.3 (d, 2JC‑F = 21.3 Hz), 111.5, 111.3 (d,
2JC‑F = 6.2 Hz), 108.0, 49.9, 19.5. HRMS (ESI-TOF) m/z: [M + H]+
2,2′-Bis(3-chlorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
[1,2-a]indole (dl-2v). Eluent: petroleum ether/ethyl acetate: 15/1 to
Calcd for C34H25F2N4 527.2042; Found 527.2049.
1
10/1; 29% yield (48.2 mg); white solid; mp 261−263 °C; H NMR
2,2′-Bis(4-fluorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
(300 MHz, DMSO-d6) δ 8.41 (s, 2H), 8.01 (s, 2H), 7.93 (d, J = 7.7
Hz, 2H), 7.50 (appt, J = 7.8 Hz, 2H), 7.37 (d, J = 7.7 Hz, 2H), 7.22
(d, J = 7.6 Hz, 2H), 7.12 (appt, J = 7.6 Hz, 2H), 6.81 (appt, J = 7.6
Hz, 2H), 5.90 (d, J = 7.7 Hz, 2H), 2.11 (s, 6H). 13C{1H} NMR (126
MHz, DMSO-d6) δ 158.1, 144.1, 140.4, 137.3, 137.0, 134.2, 130.9,
128.8, 126.9, 125.2, 124.9, 123.7, 123.2, 111.2, 108.8, 50.1, 19.4.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C34H25Cl2N4 559.1451;
Found 559.1461.
[1,2-a]indole (dl-2s). Eluent: petroleum ether/ethyl acetate: 15/1 to
1
10/1; 32% yield (50 mg); white solid; mp 270−272 °C; H NMR
(300 MHz, DMSO-d6) δ 8.27 (s, 2H), 8.00 (dd, J = 8.6, 5.7 Hz, 4H),
7.30 (appt, J = 8.9 Hz, 4H), 7.23 (d, J = 7.8 Hz, 2H), 7.10 (appt, J =
7.7 Hz, 2H), 6.79 (appt, J = 7.6 Hz, 2H), 5.90 (d, J = 7.6 Hz, 2H),
2.10 (s, 6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 161.9 (d, 1JC‑F
= 244.0 Hz), 158.1, 144.8, 140.5, 137.2, 131.7, 128.7, 127.2 (d, 3JC‑F
7.8 Hz), 125.0, 123.2, 115.9 (d, JC‑F = 21.3 Hz), 111.1, 107.6, 50.1,
19.4. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C34H25F2N4
527.2042; Found 527.2051.
=
2
2,2′-Bis(3-chlorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
[1,2-a]indole (meso-2v). Eluent: petroleum ether/ethyl acetate: 10/1
to 6/1; 30% yield (50.3 mg); white solid; mp 210−212 °C; 1H NMR
(300 MHz, DMSO-d6) δ 8.10 (s, 2H), 7.75 (s, 2H), 7.71−7.57 (m,
2H), 7.46−7.20 (m, 8H), 7.18−6.77 (m, 2H), 1.98 (s, 6H). 13C{1H}
NMR (126 MHz, DMSO-d6) δ 157.7, 143.3, 139.5, 137.7, 137.3,
133.9, 130.9, 129.4, 126.6, 124.8, 124.5, 123.2, 111.4, 108.3, 49.8,
19.2. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C34H25Cl2N4
559.1451; Found 559.1460.
2,2′-Bis(4-fluorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
[1,2-a]indole (meso-2s). Eluent: petroleum ether/ethyl acetate: 10/1
to 6/1; 30% yield (47.1 mg); white soild; mp 220−222 °C; 1H NMR
(300 MHz, DMSO-d6) δ 7.97 (s, 2H), 7.85−7.62 (m, 4H), 7.41−7.28
(m, 4H), 7.19 (appt, J = 8.7 Hz, 4H), 7.12−6.88 (m, 4H), 1.95 (s,
1
6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 161.5 (d, JC‑F= 243.2
3
Hz), 157.6, 144.0, 139.5, 137.9, 131.7, 129.3, 126.6 (d, JC‑F = 7.9
Hz), 124.6, 115.8 (d, 2JC‑F = 21.6 Hz), 111.3, 107.1, 49.6, 19.5. HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C34H25F2N4 527.2042; Found
527.2046.
2,2′-Bis(4-chlorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
[1,2-a]indole (dl-2w). Eluent: petroleum ether/ethyl acetate: 15/1 to
1
10/1; 33% yield (54.6 mg); white solid; mp 258−260 °C; H NMR
(300 MHz, DMSO-d6) δ 8.34 (s, 2H), 7.99 (d, J = 8.4 Hz, 4H), 7.53
(d, J = 8.5 Hz, 4H), 7.23 (d, J = 7.7 Hz, 2H), 7.11 (appt, J = 7.7 Hz,
2H), 6.79 (appt, J = 7.6 Hz, 2H), 5.89 (d, J = 7.6 Hz, 2H), 2.10 (s,
6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 158.1, 144.5, 140.4,
137.0, 134.0, 131.8, 129.1, 128.7, 126.9, 125.1, 123.1, 111.2, 108.2,
50.0, 19.4. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C34H25Cl2N4
559.1451; Found 559.1458.
2,2′-Bis(2,4-difluorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (dl-2t). Eluent: petroleum ether/ethyl ac-
etate: 15/1 to 10/1; 35% yield (54.7 mg); white solid; mp 234−236
1
°C; H NMR (500 MHz, DMSO-d6) δ 8.32 (dd, J = 8.8 Hz, 2H),
8.04 (d, J = 3.6 Hz, 2H), 7.33 (d, J = 7.8 Hz, 2H), 7.29−7.23 (m,
2H), 7.23−7.17 (m, 2H), 7.09 (appt, J = 7.4 Hz, 2H), 6.78 (appt, J =
7.6 Hz, 2H), 5.97 (d, J = 7.6 Hz, 2H), 2.14 (s, 6H). 13C{1H} NMR
1
3
(126 MHz, DMSO-d6) δ 161.5 (dd, JC‑F = 247.0 Hz, JC‑F = 12.0
2,2′-Bis(4-chlorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
Hz), 159.6 (dd, 1JC‑F = 250.7 Hz, 3JC‑F = 12.0 Hz), 157.6, 140.4, 138.2,
[1,2-a]indole (meso-2w). Eluent: petroleum ether/ethyl acetate: 10/
1
3
3
1 to 6/1; 31% yield (52.6 mg); white solid; mp 235−238 °C; H
137.1, 129.6 (dd, JC‑F = 9.0 Hz, JC‑F = 5.8 Hz), 128.7, 125.2, 123.1,
119.4 (dd, 2JC‑F = 13.2 Hz, 4JC‑F = 3.1 Hz), 112.2 (dd, 2JC‑F = 21.1 Hz,
NMR (500 MHz, DMSO-d6) δ 7.90 (s, 2H), 7.73 (d, J = 8.5 Hz, 4H),
7.38 (d, J = 8.5 Hz, 4H), 7.32 (d, J = 3.5 Hz, 4H), 7.06 (dd, J = 8.6,
4.3 Hz, 4H), 1.95 (s, 6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ
158.0, 144.1, 139.8, 138.0, 134.3, 131.4, 129.2, 128.9, 126.6, 125.3,
124.6, 111.3, 107.5, 49.9, 19.5. HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C34H25Cl2N4 559.1451; Found 559.1460.
4JC‑F = 2.7 Hz), 111.5, 110.8 (d, 3JC‑F = 13.1 Hz), 104.5 (appt, 2JC‑F
=
26.1 Hz), 50.0, 19.4. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C34H23F4N4 563.1853; Found 563.1862.
2,2′-Bis(2,4-difluorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (meso-2t). Eluent: petroleum ether/ethyl
acetate: 10/1 to 6/1; 24% yield (37.8 mg); white solid; mp 227−230
2,2′-Bis(3,4-dichlorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (dl-2x). Eluent: petroleum ether/ethyl
acetate: 15/1 to 10/1; 36% yield (45.3 mg); white solid; mp 270−
1
°C; H NMR (500 MHz, DMSO-d6) δ 8.05−7.96 (m, 2H), 7.81 (s,
2H), 7.47 (d, J = 7.6 Hz, 2H), 7.34 (appt, J = 7.7 Hz, 2H), 7.23 (appt,
2H), 7.14−6.96 (m, 6H), 1.99 (s, 6H). 13C{1H} NMR (126 MHz,
DMSO-d6) δ 161.4 (dd, 1JC‑F = 246.5 Hz, 3JC‑F = 12.0 Hz), 159.4 (dd,
1
271 °C; H NMR (500 MHz, DMSO-d6) δ 8.32 (s, 2H), 8.17 (s,
2H), 7.95 (d, J = 7.9 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.21 (d, J =
7.8 Hz, 2H), 7.12 (appt, J = 7.8 Hz, 2H), 6.81 (appt, J = 7.3 Hz, 2H),
5.98 (d, J = 7.8 Hz, 2H), 2.13 (s, 6H). 13C{1H} NMR (126 MHz,
DMSO-d6) δ 158.2, 143.2, 140.4, 136.9, 135.9, 132.2, 131.4, 129.6,
128.9, 126.8, 125.3, 123.2, 111.3, 109.3, 50.1, 19.4. HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C34H2335Cl4N4 627.0677; Found
627.0627.
3
1JC‑F = 249.4 Hz, JC‑F = 12.0 Hz), 157.5, 139.8, 138.1, 137.8, 129.4
(dd, 3JC‑F = 8.2 Hz, 3JC‑F = 7.5 Hz), 129.3, 125.3, 124.7, 119.7 (d, 3JC‑F
2
2
= 13.0 Hz), 111.9 (d, JC‑F = 21.0 Hz), 111.7, 110.2 (d, JC‑F = 13.0
Hz), 104.4 (appt, 3JC‑F = 26.2 Hz), 50.0, 19.5. HRMS (ESI-TOF) m/
z: [M + H]+ Calcd for C34H23F4N4 563.1853; Found 563.1860.
2,2′-Bis(2-chlorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
[1,2-a]indole (dl-2u). Eluent: petroleum ether/ethyl acetate: 15/1 to
10/1; 22% yield (61.2 mg, 1.0 mmol substrate); white solid; mp 263−
265 °C; 1H NMR (500 MHz, DMSO-d6) δ 8.30 (d, J = 9.5 Hz, 4H),
7.58 (d, J = 7.9 Hz, 2H), 7.49 (appt, J = 7.4 Hz, 2H), 7.36 (d, J = 7.3
Hz, 4H), 7.11 (appt, J = 7.6 Hz, 2H), 6.80 (appt, J = 7.6 Hz, 2H),
6.04 (d, J = 7.5 Hz, 2H), 2.16 (s, 6H). 13C{1H} NMR (126 MHz,
DMSO-d6) δ 157.2, 141.7, 140.4, 137.1, 133.3, 130.8, 130.7, 128.7,
128.6, 127.6, 125.1, 123.2, 111.6, 111.5, 50.1, 19.3. HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C34H25Cl2N4 559.1451; Found
559.1450.
2,2′-Bis(3,4-dichlorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-
biimidazo[1,2-a]indole (meso-2x). Eluent: petroleum ether/ethyl
acetate: 10/1 to 6/1; 28% yield (35.5 mg); white solid; mp 225−227
1
°C; H NMR (500 MHz, DMSO-d6) δ 8.01 (s, 2H), 7.92 (s, 2H),
7.68 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 7.38−7.29 (m,
4H), 7.09 (appt, J = 7.2 Hz, 2H), 7.06−6.92 (m, 2H), 1.99 (s, 6H).
13C{1H} NMR (126 MHz, DMSO-d6) δ 158.1, 142.8, 139.7, 137.9,
136.1, 132.0, 131.1, 129.3, 129.1, 126.6, 125.3, 124.8, 111.4, 108.5,
50.1, 19.3. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C34H2335Cl4N4 627.0677; Found 627.0644.
2,2′-Bis(4-bromophenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
2,2′-Bis(2-chlorophenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
[1,2-a]indole (meso-2u). Eluent: petroleum ether/ethyl acetate: 10/1
to 6/1; 23% yield (65.5 mg, 1.0 mmol substrate); white solid; mp
251−258 °C; 1H NMR (500 MHz, DMSO-d6) δ 8.10 (d, J = 6.7 Hz,
4H), 7.47 (appt, J = 7.3 Hz, 4H), 7.34 (appt, J = 7.3 Hz, 4H), 7.25
[1,2-a]indole (dl-2y). Eluent: petroleum ether/ethyl acetate: 15/1 to
1
10/1; 30% yield (58.1 mg); white solid; mp 262−264 °C; H NMR
(500 MHz, DMSO-d6) δ 8.35 (s, 2H), 7.92 (d, J = 8.4 Hz, 4H), 7.66
(d, J = 8.4 Hz, 4H), 7.23 (d, J = 7.7 Hz, 2H), 7.10 (appt, J = 7.6 Hz,
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J. Org. Chem. 2021, 86, 5518−5529

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
2H), 6.78 (appt, J = 7.6 Hz, 2H), 5.88 (d, J = 7.6 Hz, 2H), 2.09 (s,
6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 157.8, 144.1, 140.1,
136.8, 134.1, 132.1, 128.9, 127.1, 125.2, 122.9, 120.1, 111.3, 108.6,
49.7, 19.3. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C34H25Br2N4
647.0440; Found 647.0444.
2,2′-Bis(4-bromophenyl)-9,9′-dimethyl-9H,9′H-9,9′-biimidazo-
[1,2-a]indole (meso-2y). Eluent: petroleum ether/ethyl acetate: 10/1
to 6/1; 28% yield (55.2 mg); light yellow solid; mp 244−245 °C; 1H
NMR (300 MHz, DMSO-d6) δ 8.04 (s, 2H), 7.77−7.60 (m, 4H),
7.55 (d, J = 8.1 Hz, 4H), 7.43−7.24 (m, 4H), 7.21−6.53 (m, 4H),
1.96 (s, 6H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 158.0, 144.2,
139.9, 138.1, 134.7, 131.8, 129.3, 127.0, 125.3, 124.6, 119.7, 111.3,
107.6, 50.0, 19.6. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C34H25Br2N4 647.0440; Found 647.0440.
2-Phenyl-4,5,6,7-tetrahydro-1H,7aH-imidazo[2,1-k]carbazol-7a-
ol (4). Eluent: petroleum ether/ethyl acetate: 15/1 to 10/1; 26% yield
(47.3 mg); white solid; mp 128−131 °C; 1H NMR (500 MHz,
DMSO-d6) δ 7.86−7.79 (m, 2H), 7.52−7.47 (m, 1H), 7.44 (appt, J =
7.2 Hz, 2H), 7.16−7.08 (m, 2H), 6.94 (d, J = 7.8 Hz, 1H), 6.88 (appt,
J = 7.1 Hz, 1H), 4.81 (s, 1H), 4.74 (d, J = 16.4 Hz, 1H), 4.47 (d, J =
16.3 Hz, 1H), 2.14−2.05 (m, 1H), 1.82−1.73 (m, 1H), 1.72−1.65
(m, 1H), 1.65−1.55 (m, 2H), 1.47−1.33 (m, 3H). 13C{1H} NMR
(126 MHz, DMSO-d6) δ 167.3, 151.6, 138.6, 132.7, 131.6, 129.0,
128.5, 122.5, 122.0, 114.1, 105.0, 78.1, 61.5, 38.9, 28.7, 22.2, 20.2.
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C20H20N2ONa
327.1468; Found 327.1469.
Lu-Zhe Qin − Jiangsu Key Laboratory of Drug Discovery for
Metabolic Diseases and State Key Laboratory of Natural
Medicines, Center of Drug Discovery, China Pharmaceutical
University, Nanjing 210009, China
Xiaoan Wen − Jiangsu Key Laboratory of Drug Discovery for
Metabolic Diseases and State Key Laboratory of Natural
Medicines, Center of Drug Discovery, China Pharmaceutical
University, Nanjing 210009, China; orcid.org/0000-
0001-7852-1154
Hongbin Sun − Jiangsu Key Laboratory of Drug Discovery for
Metabolic Diseases and State Key Laboratory of Natural
Medicines, Center of Drug Discovery, China Pharmaceutical
University, Nanjing 210009, China; orcid.org/0000-
0002-3452-7674
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00010
Author Contributions
§These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the National Natural Science
Foundation of China (grants 21971256, 21977118, and
81773584) is gratefully acknowledged. This project was also
supported by the National Science & Technology Major
Project “Key New Drug Creation and Manufacturing
Program”, China (2019ZX09301-151), the Jiangsu Provincial
Key Research and Development Project (BE2018710), the
“Double First-Class” University project (CPU2018GY01,
CPU2018GY35, CPU2018GY45), and the Program for
Jiangsu Province Innovative Research Team.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00010.
Copies of NMR spectra for all reported compounds and
X-ray crystal structures and analysis data of compounds
dl-2a, meso-2a, and 4 (PDF)
Accession Codes
CCDC 2053628, 2053629, and 2053636 contain the
supplementary crystallographic data for this paper. These
data can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, or by emailing data_request@ccdc.cam.ac.
uk, or by contacting The Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
1223 336033.
REFERENCES
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Corresponding Authors
Qing-Long Xu − Jiangsu Key Laboratory of Drug Discovery
for Metabolic Diseases and State Key Laboratory of Natural
Medicines, Center of Drug Discovery, China Pharmaceutical
University, Nanjing 210009, China; orcid.org/0000-
0003-4450-6866; Email: qlxu@cpu.edu.cn
Le Zhen − Key Laboratory of Drug Metabolism and
Pharmacokinetics, China Pharmaceutical University, Nanjing
210009, China; orcid.org/0000-0002-1854-0764;
Email: i_m_zhenle@163.com
Authors
Tao Xie − Jiangsu Key Laboratory of Drug Discovery for
Metabolic Diseases and State Key Laboratory of Natural
Medicines, Center of Drug Discovery, China Pharmaceutical
University, Nanjing 210009, China
Qi-Bang Sui − Jiangsu Key Laboratory of Drug Discovery for
Metabolic Diseases and State Key Laboratory of Natural
Medicines, Center of Drug Discovery, China Pharmaceutical
University, Nanjing 210009, China
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(21) CCDC-2053628, CCDC-2053629, and CCDC-2053636
contain the supplementary crystallographic data for the products dl-
2a, meso-2a, and 4. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre.
5529
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