3-alkenylation or 3-alkylation of indole with propargylic alcohols: Construction of 3,4-dihydrocyclopenta[ b ]indole and 1,4-dihydrocyclopenta[ b ]indole in the presence of different catalysts

Article abstract of DOI:10.1021/jo300339a

3-Alkenylation or 3-alkylation of indole with propargylic alcohols could be efficiently controlled by the catalyst. In the presence of triflic acid, 3-alkenylation of indole occurred and a 3,4-dihydrocyclopenta[b]indole skeleton was effectively constructed in moderate to excellent yields via a cascade process. In the presence of Cu(OTf)_2, 3-alkylation of indole resulted in the formation of 3-propargylic indole, which could be further converted into 2-iodo-1,4-dihydrocyclopenta[b]indoles in the presence of N-iodosuccinimide and boron trifluoride etherate. Possible mechanisms related to the 3-alkenylation or 3-alkylation of indole and their extension to the formation of 3,4-dihydrocyclopenta[b]indoles or 1,4-dihydrocyclopenta[b]indoles are postulated and discussed.

Full text of DOI:10.1021/jo300339a

Article
pubs.acs.org/joc
3-Alkenylation or 3-Alkylation of Indole with Propargylic Alcohols:
Construction of 3,4-Dihydrocyclopenta[b]indole and 1,4-
Dihydrocyclopenta[b]indole in the Presence of Different Catalysts
Li Zhang, Yuanxun Zhu, Guangwei Yin, Ping Lu,* and Yanguang Wang*
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China
S
* Supporting Information
ABSTRACT: 3-Alkenylation or 3-alkylation of indole with propargylic alcohols could be efficiently controlled by the catalyst. In
the presence of triflic acid, 3-alkenylation of indole occurred and a 3,4-dihydrocyclopenta[b]indole skeleton was effectively
constructed in moderate to excellent yields via a cascade process. In the presence of Cu(OTf)2, 3-alkylation of indole resulted in
the formation of 3-propargylic indole, which could be further converted into 2-iodo-1,4-dihydrocyclopenta[b]indoles in the
presence of N-iodosuccinimide and boron trifluoride etherate. Possible mechanisms related to the 3-alkenylation or 3-alkylation
of indole and their extension to the formation of 3,4-dihydrocyclopenta[b]indoles or 1,4-dihydrocyclopenta[b]indoles are
postulated and discussed.
INTRODUCTION
RESULTS AND DISCUSSION
■
■
3,4-Dihydrocyclopenta[b]indole and 1,4-dihydrocyclopenta[b]-
indole are key substructures and can be extended to,
respectively, indeno[2,1-b]indole skeleton and indeno[1,2-
b]indole via Diels−Alder cycloaddition reaction (Scheme 1).
Indeno[2,1-b]indole is of particularly importance as it was
mapped in a route to cyanobacterial alkaloid (Fischerindole I),
while indeno[1,2-b]indole was mapped into KSP inhibitor
(Terpendole E).1,2
Total synthesis of Fischerindole I as well as Terpendole E is
attractive because they display a broad range of bioactivities and
is also challenging due to its structural complexity and the
dense functionalities.3 Baran et al.4−6 and Gademann et al.7 had
successfully done the pioneer work in synthesizing these
bioactive compounds with a spectacular protecting-group-free
strategy. In the literature, the C ring is normally constructed by
Friedel−Crafts alkylation on the 2-position of indole,8 by Pd-
catalyzed carbopalladation−annulation of indole,9 by biradical
cyclization of allenyl azide,10,11 and by photostimulated reaction
of 2-iodoaniline with the enolate anion of 2-indanone.12
Rhodium-catalyzed13 or silver-catalyzed14 3-alkylation of indole
followed by sequential cyclization could also fuse the C ring
efficiently.
As a part of our ongoing research of the chemistry of
propargylic alcohol under acid condition,15−18 we tried the
reaction between N-methylindole (1a) and propargylic alcohol
(2a), which was prepared from fluorenone and phenyl-
acetylene, in refluxing dichloromethane (DCM) for 12 h in
the presence of triflic acid (TfOH) (Scheme 2). As we
expected, 3a was isolated in a yield of 66%, and the structure of
3a was established by X-ray analysis of its single crystal (Figure
1).
In order to have a better conversion, we optimized the
reaction conditions, and results are summarized in Table 1.
When ytterbium triflate was used as the catalyst, 3-alkylated
indole (4a) was formed instead of the 3-alkenylated indole
(3a). HPLC area % of 4a was determined to be 53% (Table 1,
entry 1). Two peaks at 13C NMR spectrum (91.46 and 81.34
ppm) were ascribed to two sp hybridized carbons of 4a. Copper
triflate afforded 4a in 63% HPLC area. No desired product (3a)
was observed (Table 1, entry 2). When silver triflate was used,
Special Issue: Robert Ireland Memorial Issue
Received: February 21, 2012
© XXXX American Chemical Society
A
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Scheme 1. Structures of 3,4-Dihydrocyclopenta[b]indole and 1,4-Dihydrocyclopenta[b]indole
Scheme 2. Formation of Cyclopenta[b]indoles from Propargylic Alcohols and Indoles
Figure 1. Crystal structures of 3a (left) and 3c (right).
3a could be detected except for the formation of 4a (Table 1,
entry 3). To our delight, when the catalyst was changed into
FeCl3, AlCl3, SnCl4, BF3·Et2O, and TfOH, the peak area of 3a
was significantly increased (Table 1, entries 4−8). By increasing
the reaction temperature to 83 °C by using dichloroethane
(DCE) as the solvent, the HPLC area % of 3a approached 91%
(Table 1, entry 9). When other halogenated alkanes such as
chloroform and carbon tetrachloride were used as solvent, the
reaction lost its selectivity (Table 1, entries 10 and 11). The
reaction could also be conducted in acetonitrile, but with
relatively lower HPLC area % (Table 1, entry 12).
With the optimized reaction condition in hand (Table 1,
entry 9), we test the substrate diversity for the selective
formation of 3. When we altered 1a to N-methyl-5-nitroindole
(1b), 3b was quantitatively prepared (Table 2, entry 2). When
2b, a benzophenone derived propargylic alcohol, reacted with
the substituted indoles (1a−1f), corresponding products (3c−
3h) were obtained in yields between 22% and 86% (Table 2,
entries 3−8). Here it is noteworthy that indoles with electron-
withdrawing groups attached at the 5 position benefitted the
reaction and gave satisfactorily isolated yields (Table 1, entries
4, 7, and 8). As a comparison, methyl substituted indole (1c)
afforded corresponding 3e in 28% yield only. In this case, a
direct 3-alkylated indole (4b) was formed and isolated in 9%
yield. When we modified the phenylacetylene part of the
propargylic alcohol, the best yield was seen for 2e among cases
of 2c, 2d, and 2e (Table 2, entries 9−11). In this case, R5 of 2e
is the p-fluorophenyl, with the nature of an electron-
withdrawing group. Acetophenone derived alcohol (2f) did
react with 1a, but too many products were indicated by TLC
(Table 2, entry 12) and the desired product could not be
isolated. However, the reaction between 2f and 1b afforded 3l
in yield of 96% (Table 2, entry 13). Benzaldehyde derived
alcohol (2g) gave the 3-alkylated indole (4c) in yield of 61%,
while the 3-alkenylated indole derivative was not detected
(Table 2, entry 14). Acetone derived alcohol (2h) reacted with
1b or 1e smoothly and produced 3m and 3n in yields of 56%
and 57%, respectively (Table 2, entries 16 and 17). However,
too many spots were observed by TLC when 2h reacted with
1a or 1f (Table 2, entries 15 and 18). Yield was improved when
1b reacted with pentafluorosubstituted propargylic alcohol (2i)
(Table 2, entry 19). Reactions between 1b and 2j, 1b and 2k,
and 1b and 2l afforded the corresponding cyclized products 3p,
3q, and 3r, respectively (Table 2, entries 20−22). Reaction of
B
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a
Table 1. Optimization of Reaction Conditions
b
c
entry
acid
solvent
CH2Cl2
3a
4a
1
Yb(OTf)3 (20 mol %)
2
53
63
39
4
2
Cu(OTf)2 (20 mol %)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
ClCH2CH2Cl
CHCl3
0
3
3
AgOTf (20 mol %)
FeCl3
4
59
82
63
85
83
91
47
21
59
5
AlCl3
0
6
SnCl4
3
7
BF3·Et2O
TfOH
2
8
0
9
TfOH
4
10
11
12
TfOH
42
55
0
TfOH
CCl4
TfOH
CH3CN
a
1a (0.25 mmol), 2a (0.25 mmol), acid (0.25 mmol, otherwise indicated in parentheses), and 3 mL of solvent were mixed at room temperature and
b
c
refluxed for 12 h. HPLC peak area percentage of 3a. C18 column was used for HPLC analysis. HPLC peak area percentage of 4a.
a
Table 2. Synthesis of Various 3-Alkenylated Indoles (3)
b
b
entry
1 (R1, R2)
2 (R3/R4/R5)
3 (%) + 4 (%)
1
1a (H, Me)
2a
2a
3a (74)
3b (93)
3c (58)
3d (86)
2
1b (NO2, Me)
3
1a
2b (Ph/Ph/Ph)
4
1b
2b
5
1c (Me, Me)
2b
3e (28) + 4b (9)
3f (22)
3g (79)
3h (74)
3i (52)
3j (49)
3k (75)
c
6
1d (OMe, Me)
2b
7
1e (CN, Me)
2b
8
1f (Br, Me)
2b
9
1a
2c (Ph/Ph/p-Me-Ph)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
1a
2d (Ph/Ph/p-OMe-Ph)
1a
2e (Ph/Ph/p-F-Ph)
1a
2f (Ph/Me/Ph)
1b
2f
3l (96)
4c (61)
c
1b
2g (Ph/H/Ph)
1a
2h (Me/Me/Ph)
1b
2h
3m (56)
3n (57)
c
1e
2h
1f
2h
1b
2i (Me/Me/C6F5)
2j (Me/Et/Ph)
2k (-(CH2)4-/Ph)
2l (-(CH2)5-/Ph)
2m (Ph/Ph/n-C5H11)
2b
3o (74)
3p (38)
3q (47)
3r (61)
3s (41)
c
1b
1b
1b
1b
1g (H, H)
1h (H, Ts)
1i (H, PO(OEt)2)
2b
c
2b
c
a
b
c
1 (0.5 mmol), 2 (0.5 mmol), TfOH (0.5 mmol), and 5 mL of DCE were mixed at room temperature and refluxed for 12 h. Isolated yield. No
isolable products.
C
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Table 3. Synthesis of 3-Alkylated Indoles (4) and 2-Iodo-1,4-dihydrocyclopenta[b]indoles (5)
Article
a
b
c
c
entry
1 (R1, R2)
2 (R3/R4/R5)
4 (%)
5 (%)
1
1a (H, Me)
2a
2a
2a
2a
2a
2a
4a (68)
5a (46)
5b (31)
5c (54)
5d (38)
5e (36)
5f (43)
5g (26)
5h (45)
d
2
1b (NO2, Me)
4d (84)
3
1c (Me, Me)
4e (73)
4f (58)
4g (93)
4
1d (OMe, Me)
5
1e (CN, Me)
d
6
1f (Br, Me)
4h (86)
7
1a
1a
1a
1a
1a
1b
2b (Ph/Ph/Ph)
4i (65)
4j (60)
e
8
2c (Ph/Ph/p-Me-Ph)
2d (Ph/Ph/ p-OMe-Ph)
2e (Ph/Ph/ p-F-Ph)
2f (Ph/Me/Ph)
9
10
11
12
4k (34)
4l (84)
4m (37)
5i (39)
e
f
2n
5j (16)
a
b
1 (1 mmol), 2 (1 mmol), Cu(OTf)2 (0.1 mmol), and 10 mL of DCM were mixed at room temperature and reacted. 4 (0.5 mmol), NIS (0.5
c
d
mmol), BF3·Et2O (0.5 mmol), and 10 mL of DCM were mixed at room temperature and reacted. Isolated yield. Refluxing needed and tracked by
TLC. No isolable product. Structure of 2n is shown in Scheme 8.
e
f
Scheme 3. Possible Mechanism for Formation of 3, 4, and 5
1b with n-heptyne derived alcohol (2m) gave 3s in a yield of
41% (Table 2, entry 23). Finally we examined the substituent
on the nitrogen of indole. No unsubstitution (1g) or
substitution by sulfonyl (1h) or phosphoryl (1i) made the
reaction complicated and resulted in a mixture that could not
be purified by column chromatography (Table 2, entries 24−
26).
As we mentioned in Table 1, 3-alkylated indole (4a) could be
formed and isolated in the presence of catalysts such as
Yb(OTf)3, Cu(OTf)2, AgOTf, and TfOH as well. The most
suitable catalyst for the formation of 4a was found to be
Cu(OTf)2 (Table 1, entry 2). We thereby tested the substrate
diversity for the formation of 4 in the presence of Cu(OTf)2,
and the results are summarized in Table 3. Because of the large
difference of the reaction activity resulted from the various
substituted groups, reaction time and reaction temperature
were varied and determined by TLC tracking. Similarly, the
nature of the substituted group on the 5-position of the indole
played a key role in the formation of 4. With electron-
withdrawing groups such as nitro, nitrile, and bromo, 1b, 1e,
and 1f afforded 4d, 4g, and 4h in yields of 84%, 93%, and 86%,
respectively (Table 3, entries 2, 5, and 6). Those with electron-
donating groups, 1c and 1d, produced 4e and 4f in relatively
lower yields (Table 3, entries 3 and 4). Substitute effect on the
propargylic alcohols 2 was not apparent. When 2d was used,
the desired 3-alkylated product 4 could not be isolated,
although the starting materials were completely consumed after
a certain period (Table 3, entry 9). Acetophenone derived
propargylic alcohol 2f provided 4l in 84% yield (Table 3, entry
11), while the reaction between 1b and 2n provided 4m in 37%
yield (Table 3, entry 12). With the 3-alkylated indoles 4a−4m
in hand, we tried to cyclize them into 2-iodo-1,4-
D
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dihydrocyclopenta[b]indoles (5). The workable method was
using the NIS as the electrophile in the presence of boron
trifluoride etherate in DCM as solvent as shown in Table 3. In
this way, 5a−5h were constructed from 4a and 4d−4j,
accordingly, in yields between 26% and 54%. 4l failed to afford
an isolable product (Table 3, entries 11), while 4k and 4m gave
the corresponding 5i and 5j in yields of 39% and 16%,
respectively (Table 3, entries 10, and12). Structure of 5j was
established by X-ray analysis of its single crystal (see Supporting
Information).
Figure 2. Optimized structures of 4a (left) and 4i (right), calculated
with Gaussian 03 on the B3LYP Levels.
On the basis of the investigation of the reaction condition
and the substrate diversity, we postulated a possible mechanism
for this transformation (Scheme 3). Propargylic alcohol was
dehydrated under acidic condition and generated propargylic
carbocation A, which could be directly trapped by indole (1) to
form 3-alkylated indoles 4 in some cases. Via Meyer−Schuster
rearrangement,19,20 A was converted into allenylic carbocation
B, which subsequently reacted with indole (1) to derive 3-
allenylated indole C. Compound C undergoes protonation
under the acidic conditions to form allylic carbocation D, which
readily undergoes intramolecular cyclization to provide
intermediate E. After deprotonation of E, compound 3, with
the 3,4-dihydrocyclopenta[b]indole skeleton, was constructed
in moderate to excellent yields.
Structures of 1,3-dihydrobenzo[cd]indole and 1,5-
dihydrobenzo[cd]indole could be derived into naphtho[3,2,1-
cd]indole and naphtha[1,2,3-cd]indole via Diels−Alder reac-
tion. The former compound is the key substructure of ergot
analogues that are anagestic and cell-protective agents,21−24
while the later one was the core of bioactive hapalindole G and
its relatives.25−28 Therefore, we sought to construct 1,3-
dihydrobenzo[cd]indole and 1,5-dihydrobenzo[cd]indole skel-
etons.
By analyzing the NMR spectra of 3 and 4 (Scheme 4), we
observed the “fluorene effect”. Chemical shifts of Ha in fluorene
Scheme 4. Comparative Analysis of Chemical Shifts of Ha
and Ca in 3 and 4
A methyl group was first used to occupy 2-position of indole,
such as 1j, to force the cyclization occurring on the C-4 of
indole ring (Scheme 5) in the presence of the triflic acid.
However, instead of obtaining the expected 3-alkenylated
product with the 1,5-dihydrobenzo[cd]indole skeleton, we
isolated 6 in 71% yield. Structure of 6 was established by its
single crystal analysis (see Supporting Information). By
postulating the possible mechanism for the formation of 6,
we found that the 3-alkenylation did occur at the beginning,
and a key intermediate J was formed. After the subsequent
protonation, K was formed. The problem arises because of the
acidity of the allylic proton (Ha) of K. As a result, after the
sequential deprotonation, 6π-electron electrocyclic ring closure
(6π-ERC), protonation, and finally β-elimination, 6 was
obtained.
Then we move our attention to other propargylic alcohols,
such as 2a, a fluorene derived propargylic alcohol. A possible
depronation from K to L could be avoided. Reaction between
1j and 2a afforded 7a (Scheme 6), structure of 7a was
established by the X-ray analysis of its single crystal (see
Supporting Information). Meyer−Schuster rearrangement
occurs, and 3-alkenylation happens on the 3-position of indole.
K′ was formed similar to the formation of K. However, the
sequential cyclization occurred on the phenyl ring of 2a instead
of the C-4 of indole. A similar situation was observed for the
reaction between 2a and 1k, which had the phenyl group
derived 3a and 3b were 5.92 and 6.02 ppm, respectively. It was
highly shielded by the plane of fluorene in comparison with
those of analogues 3c, 3e−3f, and 3h−3k, which varied from
6.35 to 6.43 ppm. The shielding effect of the fluorene could be
clearly seen from the comparative images of the single crystal
structures of 3a and 3c (Figure 1). On the other hand, chemical
shifts of Ha in fluorene derived 4a and 4d−4h fell within 7.20−
7.29 ppm, which was deshielded by the fluorene plane (Figure
2). In comparison, chemical shifts of Ha for 4b and 4i−4k were
observed in a range of 6.17−6.23 ppm. Chemical shifts of Ca’s
in 3 and 4 depended upon the relative electron densities of Ca.
Electron densities of 3a and 3c were calculated to be 0.1763
and 0.1789, while the electron densities of 4a and 4i were
calculated to be 0.2911 and 0.2934, respectively. It is noticeable
that the higher the electron density of the Ca, the lower the
value of its chemical shift.
E
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Scheme 5. Possible Mechanism for the Formation of 6
Scheme 6. Formation of 7
Scheme 7. Formation of 4n and 4o
occupied on the 2-position of indole and the methoxy group
occupied on the 5-position of the indole to enrich the electron
density of the indole. Still, 7b was isolated in 65% yield.
Afterward, 3-alkenylation on the 3-position of the indole ring
did occur in the presence of triflic acid, but the subsequent
intramolecular Friedel−Crafts alkylation on the C-4 of indole
ring was not successful.
compound 8 was constructed with the skeleton of 1,3-
dihydrobenzo[cd]indole (Scheme 8). Structure of 8 was
Scheme 8. Formation of 8
Then we tried the sequence of 3-alkylation and subsequent
cyclization to construct 1,3-dihydrobenzo[cd]indole. In the
presence of Cu(OTf)2, 4n and 4o were isolated in yields of
70% and 57%, respectively (Scheme 7). Structure of 4n was
established by X-ray analysis of its single crystal (see Supporting
Information). Unfortunately, the target molecules were not
constructed from either 4n or 4o even though various
electrophiles were tested, such as NIS, iodine, and iodine
chloride.
established by X-ray analysis of its single crystal (see Supporting
Information). Enlightened by this result, we tested the reactions
between 2n and 1j or 1l, which resulted in complete
consumption of the starting materials, but none of the desired
product was isolated.
Fortunately, when 1k reacted with 2n, in which the steric
hindrance raised by the phenyl group was eliminated,
F
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Scheme 9. Gram Scale Reactions of the 3-Alkenylation and 3-Alkylation of Indole
143.1, 142.3, 141.5, 136.7, 129.1, 128.9, 128.5, 128.2, 128.1, 127.6,
124.4, 121.9, 121.0, 120.74, 120.66, 120.2, 120.0, 110.2, 62.4, 30.0; MS
(ESI) (m/z) 396.2 (M + H+); HRMS (EI) (m/z) calcd for C30H21N
395.1674, found 395.1680.
Larger scale reactions were carried between 1b (880 mg, 5
mmol) and 2a (1.41 g, 5 mmol) (Scheme 9). Thus, 3b (1.9 g,
86%) was obtained in 1 h at room temperature in the presence
of equivalent TfOH, while 4d (1.4 g, 63%) was obtained in 3 h
at refluxing temperature by decreasing the catalyst loading to 5
mol % Cu(OTf)2.
4-Methyl-7-nitro-1-phenyl-4H-spiro[cyclopenta[b]indole-
3,9′-fluorene] (3b). Yellow solid; 205 mg, 93% yield; mp 174.5−
1
175.2 °C ; H NMR (500 MHz, CDCl3) δ 8.79 (d, J = 2.1 Hz, 1H),
8.06 (dd, J = 9.1, 2.2 Hz, 1H), 7.86 (t, J = 7.5 Hz, 4H), 7.55 (t, J = 7.6
Hz, 2H), 7.43 (dd, J = 14.0, 6.9 Hz, 3H), 7.29−7.17 (m, 3H), 7.09 (d,
J = 7.6 Hz, 2H), 6.02 (s, 1H), 3.01 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 154.0, 143.9, 143.7, 142.3, 142.1, 141.6, 135.7, 130.7, 129.3,
128.9, 128.7, 128.3, 127.4, 124.2, 123.2, 120.9, 120.8, 116.9, 116.3,
110.0, 62.5, 30.4; MS (ESI) (m/z) 441.4 (M + H+); HRMS (EI) (m/
z) calcd for C30H20N2O2 440.1525, found 440.1528.
CONCLUSION
■
In conclusion, we selectively synthesized 3,4-
dihydrocyclopenta[b]indoles and 1,4-dihydrocyclopenta[b]-
indoles from indoles and propargylic alcohols by the choice
of the catalysts. 3-Alkenylation of indole with propargylic
alcohols could be realized by the triflic acid, while 3-alkylation
of indole could be accomplished by Cu(OTf)2. We also
attempted to construct 1,3-dihydrobenzo[cd]indole as well as
1,5-dihydrobenzo[cd]indole skeletons. Fortunately, one 1,3-
dihydrobenzo[cd]indole was furnished by fine-tuning the
electron density of the indole ring and altering the structure
of the propargylic alcohol.
4-Methyl-1,3,3-triphenyl-3,4-dihydrocyclopenta[b]indole
1
(3c). White solid; 115 mg, 58% yield; mp 184.7−186.9 °C; H NMR
(500 MHz, CDCl3) δ 7.84 (d, J = 7.4 Hz, 2H), 7.81 (d, J = 7.8 Hz,
1H), 7.44 (t, J = 7.6 Hz, 2H), 7.37−7.28 (m, 6H), 7.28−7.21 (m, 6H),
7.20−7.11 (m, 2H), 6.44 (s, 1H), 3.53 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 155.1, 141.5, 141.2, 140.1, 136.5, 136.2, 128.82, 128.78,
128.6, 128.1, 127.7, 127.3, 122.0, 120.9, 120.4, 120.3, 119.1, 110.2,
62.3, 31.6; MS (ESI) (m/z) 398.2 (M + H+); HRMS (EI) (m/z) calcd
for C30H23N 397.1830, found 397.1837.
EXPERIMENTAL SECTION
General Methods. H NMR spectra were recorded at 400 or 500
4-Methyl-7-nitro-1,3,3-triphenyl-3,4-dihydrocyclopenta[b]-
indole (3d). Yellow solid; 190 mg, 86% yield; mp 231.4−234.3 °C ;
1H NMR (500 MHz, CDCl3) δ 8.73 (s, 1H), 8.11 (d, J = 8.8 Hz, 1H),
7.81 (d, J = 7.3 Hz, 2H), 7.52 (t, J = 7.3 Hz, 2H), 7.42 (t, J = 7.1 Hz,
1H), 7.38−7.21 (m, 11H), 6.53 (s, 1H), 3.63 (s, 3H); 13C NMR (125
MHz, CDCl3) δ 157.9, 144.0, 142.2, 140.3, 139.1, 137.6, 135.6, 129.2,
129.0, 128.6, 128.4, 127.9, 127.4, 121.5, 120.9, 117.2, 116.4, 110.1,
62.7, 32.1; MS (ESI) (m/z) 443.2 (M + H+); HRMS (EI) (m/z) calcd
for C30H22N2O2 442.1681, found 442.1689.
■
1
MHz using TMS as an internal standard and 13C NMR spectra at 100
or 125 MHz using CDCl3 as an internal standard. The following
abbreviations are used to describe peak patterns where appropriate: b,
broad; s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet.
Coupling constants are reported in hertz. High resolution mass spectra
(HRMS) were performed on an electron ionization time-of-flight (EI-
TOF) mass spectrometer. Reactions were controlled using TLC on
silica. HPLC analyses were performed on a HPLC system equipped
with C18 columns, detected at 273 nm. Flow phase was acetonitrile/
water (95/5), and flow rate was 1.0 mL/min. Melting points were
measured with a micro melting point apparatus.
4,7-Diethyl-1,3,3-triphenyl-3,4-dihydrocyclopenta[b]indole
1
(3e). White solid; 58 mg, 28% yield; mp 171.7−173.1 °C; H NMR
(500 MHz, CDCl3) δ 7.82 (d, J = 7.4 Hz, 2H), 7.58 (s, 1H), 7.43 (t, J
= 7.3 Hz, 2H), 7.35−7.10 (m, 12H), 7.00 (d, J = 8.1 Hz, 1H), 6.40 (s,
1H), 3.47 (s, 3H), 2.44 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
155.2, 141.3, 140.2, 139.9, 136.6, 136.0, 129.5, 128.8, 128.7, 128.6,
128.0, 127.7, 127.3, 122.4, 122.1, 120.1, 118.5, 109.9, 62.1, 31.6, 22.0;
The N-methyl-indoles and propargylic alcohols were prepared
according to the published methods.29 Other materials were purchased
from common commercial sources and used without additional
purification.
General Procedure for the Preparation of 3, 6, and 7. To a
solution of indole 1 (0.5 mmol) and propargylic alcohol 2 (0.5 mmol)
in dichloromethane (5 mL) was added a solution of triflic acid (75 mg,
0.5 mmol) in dichloromethane (3 mL) dropwise over 2 min, and the
solution was stirred for 10 min at room temperature. After being
stirred at reflux temperature for 6 h, the mixture was evaporated under
vacuum. The product was isolated by silica gel column chromatog-
raphy with a hexane/dichloromethane mixture.
+
MS (ESI) (m/z) 411.3 (M ); HRMS (EI) (m/z) calcd for C31H25N
411.1987, found 411.1985.
7-Methoxy-4-methyl-1,3,3-triphenyl-3,4-dihydrocyclopenta-
[b]indole (3f). White solid; 47 mg, 22% yield; mp 189.7−190.4 °C;
1H NMR (500 MHz, CDCl3) δ 7.83 (d, J = 7.2 Hz, 2H), 7.45 (t, J =
7.6 Hz, 2H), 7.41−7.17 (m, 13H), 6.86 (dd, J = 8.9, 2.4 Hz, 1H), 6.40
(s, 1H), 3.83 (s, 3H), 3.52 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
155.7, 154.6, 141.1, 140.2, 136.9, 136.6, 135.8, 128.83, 128.77, 128.6,
128.1, 127.6, 127.3, 122.1, 118.5, 110.9, 110.3, 103.1, 62.2, 56.4, 31.7;
MS (ESI) (m/z) 428.2 (M + H+); HRMS (EI) (m/z) calcd for
C31H25NO 427.1936, found 427.1932.
4-Methyl-1-phenyl-4H-spiro[cyclopenta[b]indole-3,9′-fluo-
1
rene] (3a). White solid; 146 mg, 74% yield; mp 211.7−214.2 °C; H
NMR (400 MHz, CDCl3) δ 7.90 (d, J = 7.3 Hz, 2H), 7.86 (dd, J = 5.8,
2.9 Hz, 1H), 7.82 (d, J = 7.6 Hz, 2H), 7.49 (t, J = 7.6 Hz, 2H), 7.38 (t,
J = 7.4 Hz, 3H), 7.24−7.13 (m, 5H), 7.10 (d, J = 7.5 Hz, 2H), 5.92 (s,
1H), 2.95 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 150.7, 144.7,
4-Methyl-1,3,3-triphenyl-3,4-dihydrocyclopenta[b]indole-7-
carbonitrile (3g). White solid; 167 mg, 79% yield; mp 241.7−243.8
°C; 1H NMR (500 MHz, CDCl3) δ 8.11 (s, 1H), 7.76 (d, J = 7.2 Hz,
2H), 7.48 (t, J = 7.6 Hz, 2H), 7.38 (ddd, J = 22.0, 11.5, 4.9 Hz, 3H),
G
dx.doi.org/10.1021/jo300339a | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
7.31−7.23 (m, 10H), 6.50 (s, 1H), 3.58 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 157.1, 142.8, 140.3, 139.2, 137.4, 135.7, 129.1, 129.0, 128.5,
128.4, 127.7, 127.4, 125.6, 123.8, 121.5, 121.2, 120.1, 111.1, 103.2,
62.6, 31.9; MS (ESI) (m/z) 423.3 (M + H+); HRMS (EI) (m/z) calcd
for C31H22N2 422.1783, found 422.1786.
7-Bromo-4-methyl-1,3,3-triphenyl-3,4-dihydrocyclopenta-
[b]indole (3h). White solid; 176 mg, 74% yield; mp 218.7−219.1 °C;
1H NMR (500 MHz, CDCl3) δ 7.88 (d, J = 1.6 Hz, 1H), 7.77 (d, J =
3,3,4-Trimethyl-7-nitro-1-(perfluorophenyl)-3,4-
dihydrocyclopenta[b]indole (3o). Yellow solid; 151 mg, 74% yield;
mp 188.7−189.5 °C; H NMR (500 MHz, CDCl3) δ 8.92 (d, J = 2.0
Hz, 2H), 8.14 (dd, J = 9.1, 2.1 Hz, 1H), 7.32 (d, J = 9.1 Hz, 1H), 7.16
(s, 1H), 3.83 (s, 3H), 1.85 (s, 6H); 13C NMR (125 MHz, CDCl3)
δ147.7 (d, JCF = 245.5 Hz), 141.5 (d, JCF = 256.0 Hz), 141.4, 140.8,
137.9 (d, JCF = 251.4 Hz), 128.3, 125.1, 123.0, 118.2, 117.8, 109.7,
109.2, 100.5, 65.8, 33.5, 32.0, 30.5; MS (ESI) (m/z) 409.1 (M + H+);
HRMS (EI) (m/z) calcd for C20H13F5N2O2 [M+] 408.0897 (m/z),
found 408.0893.
1
7.4 Hz, 2H), 7.45 (t, J = 7.6 Hz, 2H), 7.35 (t, J = 7.4 Hz, 1H), 7.32−
7.20 (m, 11H), 7.15 (d, J = 8.7 Hz, 1H), 6.43 (s, 1H), 3.51 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 156.1, 140.8, 140.2, 139.7, 136.5,
3 - E t h y l - 3 , 4 - d i m e t h y l - 7 - n i t r o - 1 - p h e n y l - 3 , 4 -
dihydrocyclopenta[b]indole (3p). Yellow solid; 63 mg, 38% yield;
136.1, 129.0, 128.9, 128.5, 128.3, 127.5, 123.7, 123.3, 122.7, 118.7,
113.8, 111.6, 62.3, 31.7; MS (ESI) (m/z) 476.1 (M + H+); HRMS
(EI) (m/z) calcd for C30H22BrN 475.0936, found 475.0945.
4-Methyl-3,3-diphenyl-1-(p-tolyl)-3,4-dihydrocyclopenta[b]-
indole (3i). White solid; 107 mg, 52% yield; mp 203.5−204.0 °C; 1H
NMR (500 MHz, CDCl3) δ 7.81 (d, J = 7.7 Hz, 1H), 7.74 (d, J = 7.7
Hz, 2H), 7.39−7.11 (m, 15H), 6.40 (s, 1H), 3.53 (s, 3H), 2.39 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 155.1, 141.5, 141.1, 140.2,
137.8, 135.6, 133.6, 129.5, 128.7, 128.6, 127.6, 127.3, 122.0, 120.8,
120.4, 120.2, 119.2, 110.2, 62.2, 31.6, 21.7; MS (ESI) (m/z) 412.2 (M
+ H+); HRMS (EI) (m/z) calcd for C31H25N 411.1987, found
411.1982.
1
mp 156.1−158.3 °C; H NMR (500 MHz, CDCl3) δ 8.64 (d, J = 2.1
Hz, 1H), 8.05 (dd, J = 9.1, 2.2 Hz, 1H), 7.80−7.70 (m, 2H), 7.51 (t, J
= 7.7 Hz, 2H), 7.40 (t, J = 7.4 Hz, 1H), 7.32 (d, J = 9.1 Hz, 1H), 6.00
(s, 1H), 3.93 (s, 3H), 2.04 (dt, J = 13.9, 6.5 Hz, 2H), 1.56 (s, 3H), 0.72
(t, J = 7.4 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 157.8, 143.8,
141.8, 140.4, 136.2, 135.4, 129.1, 128.2, 127.2, 121.7, 120.8, 116.7,
115.8, 109.6, 50.5, 31.6, 29.7, 21.2, 10.0; MS (ESI) (m/z) 333.1 (M +
H+); HRMS (EI) (m/z) calcd for C21H20N2O2 332.1525, found
332.1519.
4-Methyl-7-nitro-1-phenyl-4H-spiro[cyclopenta[b]indole-
3,1′-cyclopentane] (3q). Yellow solid; 81 mg, 47% yield; mp 190.2−
1
191.3 °C; H NMR (500 MHz, CDCl3) δ 8.62 (d, J = 2.1 Hz, 1H),
1-(4-Methoxyphenyl)-4-methyl-3,3-diphenyl-3,4-
8.04 (dd, J = 9.1, 2.2 Hz, 1H), 7.74 (d, J = 7.1 Hz, 2H), 7.50 (t, J = 7.7
Hz, 2H), 7.39 (t, J = 7.4 Hz, 1H), 7.31 (d, J = 9.1 Hz, 1H), 6.26 (s,
1H), 3.93 (s, 3H), 2.40−2.23 (m, 2H), 2.14−1.91 (m, 6H); 13C NMR
(125 MHz, CDCl3) δ 156.8, 144.0, 141.9, 138.5, 136.3, 135.7, 129.1,
128.1, 127.2, 121.4, 120.8, 116.6, 115.8, 109.6, 55.7, 33.0, 31.6, 26.7;
MS (ESI) (m/z) 345.1 (M + H+); HRMS (EI) (m/z) calcd for
C22H20N2O2 344.1525, found 344.1532.
dihydrocyclopenta[b]indole (3j). White solid; 105 mg, 49% yield;
1
mp 204.8−206.0 °C; H NMR (500 MHz, CDCl3) δ 7.81 (d, J = 7.7
Hz, 1H), 7.77 (d, J = 8.3 Hz, 2H), 7.30 (t, J = 6.9 Hz, 5H), 7.27−7.11
(m, 8H), 6.98 (d, J = 8.3 Hz, 2H), 6.35 (s, 1H), 3.82 (s, 3H), 3.52 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 159.7, 155.1, 141.5, 140.7,
140.3, 134.8, 129.1, 128.8, 128.7, 128.6, 127.3, 122.0, 120.8, 120.3,
120.2, 119.3, 114.2, 110.2, 62.1, 55.7, 31.6; MS (ESI) (m/z) 428.2 (M
+ H+); HRMS (EI) (m/z) calcd for C31H25NO 427.1936, found
427.1939.
4′-Methyl-7′-nitro-1′-phenyl-4′H-spiro[cyclohexane-1,3′-
cyclopenta[b]indole] (3r). Yellow solid; 109 mg, 61% yield; mp
1
223.3−225.7 °C; H NMR (500 MHz, CDCl3) δ 8.62 (d, J = 1.9 Hz,
1-(4-Fluorophenyl)-4-methyl-3,3-diphenyl-3,4-
1H), 8.02 (dd, J = 9.1, 2.0 Hz, 1H), 7.75 (d, J = 7.3 Hz, 2H), 7.50 (t, J
= 7.6 Hz, 2H), 7.39 (t, J = 7.4 Hz, 1H), 7.29 (d, J = 9.1 Hz, 1H), 6.59
(s, 1H), 3.96 (s, 3H), 2.15 (td, J = 12.9, 3.0 Hz, 2H), 1.93 (t, J = 13.6
Hz, 3H), 1.81−1.63 (m, 4H), 1.60 (d, J = 12.8 Hz, 1H), 1.50−1.35
(m, 1H); 13C NMR (125 MHz, CDCl3) δ 159.1, 143.8, 141.8, 139.9,
136.5, 132.2, 129.1, 128.2, 127.2, 120.9, 120.7, 116.7, 115.9, 109.6,
50.5, 32.2, 31.7, 26.1, 25.0; MS (ESI) (m/z) 359.3 (M + H+); HRMS
(EI) (m/z) calcd for C23H22N2O2 358.1681, found 358.1685.
4 - M e t h y l - 7 - n i t r o - 1 - p e n t y l - 3 , 3 - d i p h e n y l - 3 , 4 -
dihydrocyclopenta[b]indole (3s). Yellow oil; 89 mg, 41% yield; 1H
NMR (500 MHz, CDCl3) δ 8.69 (s, 1H), 8.09 (d, J = 8.6 Hz, 1H),
7.29 (dd, J = 28.7, 6.7 Hz, 11H), 5.80 (s, 1H), 3.82 (s, 2H), 3.34 (s,
3H), 2.15 (d, J = 6.9 Hz, 2H), 1.50−1.35 (m, 4H), 0.91 (dd, J = 14.7,
7.8 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 156.0, 145.6, 145.3,
142.1, 133.6, 128.9, 128.3, 127.1, 122.9, 121.1, 117.7, 117.6, 117.2,
109.8, 57.0, 56.8, 32.3, 31.7, 29.4, 22.8, 14.4; MS (ESI) (m/z) 437 (M
+ H+); HRMS (EI) (m/z) calcd for C29H28N2O2 436.2151, found
436.2133.
dihydrocyclopenta[b]indole (3k). White solid; 156 mg, 75% yield;
1
mp 202.2−204.0 °C; H NMR (500 MHz, CDCl3) δ 7.83−7.76 (m,
2H), 7.74 (d, J = 7.7 Hz, 1H), 7.30 (d, J = 7.3 Hz, 5H), 7.28−7.21 (m,
6H), 7.16 (ddd, J = 20.6, 16.1, 7.9 Hz, 4H), 6.38 (s, 1H), 3.53 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 162.9 (d, JCF = 246.7 Hz), 155.1,
141.5, 140.2, 140.0, 135.9, 132.7 (d, JCF = 2.1 Hz), 129.3 (d, JCF = 7.9
Hz), 128.8, 128.6, 127.4, 121.8, 121.0, 120.4, 120.1, 118.9, 115.7 (d,
JCF = 21.4 Hz), 110.3, 62.3, 31.6; MS (ESI) (m/z) 416.2 (M + H+);
HRMS (EI) (m/z) calcd for C30H22FN 415.1736, found 415.1734.
3,4-Diethyl-7-nitro-1,3-diphenyl-3,4-dihydrocyclopenta[b]-
indole (3l). Yellow solid; 182 mg, 96% yield; mp 170.9−171.6 °C; 1H
NMR (500 MHz, CDCl3) δ 8.70 (d, J = 2.1 Hz, 1H), 8.06 (dd, J = 9.1,
2.2 Hz, 1H), 7.84−7.74 (m, 2H), 7.49 (t, J = 7.6 Hz, 2H), 7.38 (t, J =
7.4 Hz, 1H), 7.34−7.22 (m, 6H), 6.22 (s, 1H), 3.62 (s, 3H), 1.95 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 159.6, 143.7, 142.0, 139.4,
139.3, 138.4, 135.8, 129.2, 129.2, 128.4, 127.5, 127.3, 126.3, 121.2,
120.8, 117.0, 116.2, 109.9, 52.4, 31.5, 19.6; MS (ESI) (m/z) 381.1 (M
+ H+); HRMS (EI) (m/z) calcd for C25H20N2O2 380.1525, found
380.1528.
3,3,4-Trimethyl-7-nitro-1-phenyl-3,4-dihydrocyclopenta[b]-
indole (3m). Yellow solid; 89 mg, 56% yield; mp 169.0−171.2 °C; 1H
NMR (500 MHz, CDCl3) δ 8.63 (d, J = 2.1 Hz, 1H), 8.04 (dd, J = 9.1,
2.1 Hz, 1H), 7.74 (d, J = 7.4 Hz, 2H), 7.50 (t, J = 7.6 Hz, 2H), 7.39 (t,
J = 7.4 Hz, 1H), 7.31 (d, J = 9.1 Hz, 1H), 6.04 (s, 1H), 3.95 (s, 3H),
1.57 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 158.9, 143.7, 141.8,
138.9, 137.7, 136.2, 129.1, 128.2, 127.2, 120.8, 120.5, 116.8, 115.9,
109.7, 45.8, 31.6, 22.4; MS (ESI) (m/z) 391.1 (M + H+); HRMS (EI)
(m/z) calcd for C20H18N2O2 318.1368, found 318.1371.
General Procedure for the Preparation of 4. To a solution of
indole 1 (1 mmol) and propargylic alcohol 2 (1 mmol) in
dichloromethane (5 mL) was added Cu(OTf)2 (72 mg, 20 mol %).
After being stirred at reflux temperature for 6 h, the mixture was
evaporated under vacuum. The product was isolated by silica gel
column chromatography with a hexane/dichloromethane mixture.
1-Methyl-3-(9-(phenylethynyl)-9H-fluoren-9-yl)-1H-indole
1
(4a). White solid; 269 mg, 68% yield; mp 182.5−183.0 °C; H NMR
(500 MHz, CDCl3) δ 7.78 (d, J = 7.6 Hz, 2H), 7.57 (d, J = 7.6 Hz,
2H), 7.46−7.40 (m, 2H), 7.39−7.33 (m, 2H), 7.29 (s, 1H), 7.27−7.20
(m, 5H), 7.17 (d, J = 8.2 Hz, 1H), 7.10−7.04 (m, 1H), 6.90 (d, J = 8.0
Hz, 1H), 6.80 (t, J = 7.5 Hz, 1H), 3.66 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 149.8, 139.9, 138.1, 132.1, 128.5, 128.3, 128.2, 128.1, 125.5,
123.8, 121.8, 120.38, 120.35, 119.3, 116.0, 109.6, 91.6, 81.4, 49.6, 33.0;
MS (ESI) (m/z) 396.2 (M + H+); HRMS (EI) (m/z) calcd for
C30H21N 395. 1674, found 395. 1667.
3,3,4-Trimethyl-1-phenyl-3,4-dihydrocyclopenta[b]indole-7-
carbonitrile (3n). White solid; 85 mg, 57% yield; mp 159.6−161.0
°C; 1H NMR (500 MHz, CDCl3) δ 8.02 (s, 1H), 7.70 (d, J = 7.4 Hz,
2H), 7.48 (t, J = 7.5 Hz, 2H), 7.44−7.30 (m, 3H), 6.01 (s, 1H), 3.93
(s, 3H), 1.56 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 158.0, 142.5,
139.0, 137.4, 136.3, 129.0, 128.1, 127.2, 125.1, 123.2, 121.4, 119.0,
110.7, 102.7, 45.6, 31.4, 22.4; MS (ESI) (m/z) 299.1 (M + H+);
HRMS (EI) (m/z) calcd for C21H18N2 298.1470, found 298.1470.
1,5-Dimethyl-3-(1,1,3-triphenylprop-2-yn-1-yl)-1H-indole
1
(4b). White solid; 37 mg, 9% yield; mp 185.7−185.9 °C; H NMR
(500 MHz, CDCl3) δ 7.51−7.42 (m, 6H), 7.38 (s, 1H), 7.34−7.22 (m,
H
dx.doi.org/10.1021/jo300339a | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
9H), 7.17 (d, J = 8.3 Hz, 1H), 7.03 (d, J = 8.4 Hz, 1H), 6.17 (s, 1H),
3.62 (s, 3H), 2.34 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 145.5,
136.6, 132.0, 129.5, 129.0, 128.5, 128.3, 128.1, 127.2, 127.0, 124.3,
123.7, 121.9, 119.4, 109.2, 95.1, 84.8, 50.4, 33.1, 21.9; MS (ESI) (m/z)
412.2 (M + H+); HRMS (EI) (m/z) calcd for C31H25N 411.1987,
found 411.1993.
3-(1,3-Diphenylprop-2-yn-1-yl)-1-methyl-5-nitro-1H-indole
(4c). Yellow solid; 223 mg, 61% yield; mp 155.3−156.1 °C; 1H NMR
(500 MHz, CDCl3) δ 8.66 (d, J = 1.9 Hz, 1H), 8.07 (dd, J = 9.1, 2.0
Hz, 1H), 7.53 (d, J = 7.4 Hz, 2H), 7.48 (dd, J = 6.5, 2.9 Hz, 2H), 7.35
(t, J = 7.6 Hz, 2H), 7.32−7.20 (m, 5H), 7.06 (s, 1H), 5.45 (s, 1H),
3.74 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 141.6, 140.8, 140.5,
132.0, 130.6, 129.1, 128.6, 128.4, 128.1, 127.6, 126.0, 123.5, 118.8,
117.8, 117.4, 109.7, 89.8, 84.3, 35.5, 33.5; MS (ESI) (m/z) 367.1 (M +
H+); HRMS (EI) (m/z) calcd for C24H18N2O2 366.1368, found
366.1370.
1-Methyl-5-nitro-3-(9-(phenylethynyl)-9H-fluoren-9-yl)-1H-
indole (4d). Yellow solid; 370 mg, 84% yield; mp 213.4−214.6 °C;
1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 7.97−7.90 (m, 1H), 7.82
(d, J = 7.6 Hz, 2H), 7.57 (d, J = 7.5 Hz, 2H), 7.51−7.44 (m, 2H), 7.40
(t, J = 7.5 Hz, 2H), 7.33−7.22 (m, 6H), 7.11 (d, J = 9.1 Hz, 1H), 3.67
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 149.0, 141.5, 140.7, 139.7,
132.1, 130.7, 128.8, 128.61, 128.55, 125.3, 124.9, 123.3, 120.7, 119.5,
117.8, 117.5, 109.6, 90.4, 82.3, 49.3, 33.4; MS (ESI) (m/z) 441.2 (M +
H+); HRMS (EI) (m/z) calcd for C30H20N2O2 440.1525, found
440.1528.
7.5 Hz, 1H), 6.23 (s, 1H), 3.61 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 145.3, 138.2, 132.0, 129.4, 129.2, 128.5, 128.3, 128.1, 127.04, 126.96,
124.2, 122.3, 122.0, 120.1, 119.3, 109.5, 95.0, 84.9, 50.3, 33.0; MS
(ESI) (m/z) 398.2 (M + H+); HRMS (EI) (m/z) calcd for C30H23N,
found 397.1829.
3-(1,1-Diphenyl-3-(p-tolyl)prop-2-yn-1-yl)-1-methyl-1H-in-
1
dole (4j). White solid; 247 mg, 60% yield; mp 211.1−211.9 °C; H
NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 7.8
Hz, 4H), 7.34 (dd, J = 8.0, 1.7 Hz, 2H), 7.31−7.17 (m, 8H), 7.05 (d, J
= 7.3 Hz, 2H), 7.01−6.94 (t, 1H), 6.23 (d, J = 1.9 Hz, 1H), 3.61 (s,
3H), 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 145.4, 138.2,
138.1, 131.9, 129.4, 129.2, 129.0, 128.3, 127.0, 122.3, 122.0, 121.1,
120.2, 119.3, 109.5, 94.2, 85.0, 50.3, 33.0, 21.8; MS (ESI) (m/z) 412.2
(M + H+); HRMS (EI) (m/z) calcd for C31H25N 411.1987, found
411.1987.
3-(3-(4-Fluorophenyl)-1,1-diphenylprop-2-yn-1-yl)-1-meth-
yl-1H-indole (4k). White solid; 141 mg, 34% yield; mp 192.5−193.6
1
°C; H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 8.1 Hz, 1H), 7.50−
7.44 (m, 4H), 7.44−7.37 (m, 2H), 7.33−7.21 (m, 7H), 7.21−7.15 (m,
1H), 7.03−6.97 (m, 1H), 6.93 (td, J = 8.6, 1.7 Hz, 2H), 6.22 (d, J = 1.7
Hz, 1H), 3.62 (d, J = 1.7 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
162.6 (d, JCF = 248.6 Hz), 145.2, 138.2, 133.8 (d, JCF = 8.3 Hz), 129.4,
128.9, 128.3, 127.1, 126.9, 122.2, 122.1, 120.22, 120.20 (d, JCF = 3.4
Hz), 119.4, 115.7 (d, JCF = 22.0 Hz), 109.6, 94.6, 83.8, 50.3, 33.0; MS
(ESI) (m/z) 416.2 (M + H+); HRMS (EI) (m/z) calcd for C30H22FN
415.1736, found 415.1738.
1,5-Diethyl-3-(9-(phenylethynyl)-9H-fluoren-9-yl)-1H-indole
3-(2,4-Diphenylbut-3-yn-2-yl)-1-methyl-1H-indole (4l). White
1
(4e). White solid; 299 mg, 73% yield; mp 170.1−171.0 °C; H NMR
1
solid; 281 mg, 84% yield; mp 180.8−181.7 °C; H NMR (400 MHz,
(400 MHz, CDCl3) δ 7.81−7.73 (m, 2H), 7.58 (dd, J = 7.5, 2.9 Hz,
2H), 7.46−7.39 (m, 2H), 7.39−7.30 (m, 2H), 7.23 (ddd, J = 6.6, 6.2,
2.0 Hz, 5H), 7.16 (d, J = 2.6 Hz, 1H), 7.06 (dd, J = 8.3, 1.9 Hz, 1H),
6.90 (d, J = 8.2 Hz, 1H), 6.79 (s, 1H), 3.62 (d, J = 0.8 Hz, 3H), 2.20
(d, J = 2.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 149.9, 139.8,
136.6, 132.1, 128.5, 128.33, 128.28, 128.2, 128.0, 125.9, 125.5, 123.9,
123.5, 120.3, 120.2, 115.4, 109.3, 91.8, 81.4, 49.7, 33.0, 21.9; MS (ESI)
(m/z) 410.2 (M + H+); HRMS (EI) (m/z) calcd for C31H23N
409.1830, found 409.1828.
CDCl3) δ 7.64−7.57 (m, 1H), 7.50 (d, J = 8.0 Hz, 2H), 7.47−7.43 (m,
1H), 7.43 (d, J = 2.0 Hz, 2H), 7.34−7.22 (m, 5H), 7.23−7.19 (m,
1H), 7.19−7.13 (m, 1H), 7.00 (s, 1H), 6.99−6.93 (m, 1H), 3.74 (s,
3H), 2.10 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 146.6, 138.1,
132.0, 128.5, 128.0, 127.0, 126.8, 126.6, 126.5, 124.2, 121.9, 121.6,
120.5, 119.2, 109.5, 95.5, 83.3, 40.2, 33.1, 31.4; MS (ESI) (m/z) 336.2
(M + H+); HRMS (EI) (m/z) calcd for C25H21N 335.1674, found
335.1675.
3-(9-Ethynyl-9H-fluoren-9-yl)-1-methyl-5-nitro-1H-indole
(4m). Yellow solid; 135 mg, 37% yield; mp 203.6−204.1 °C; 1H NMR
(400 MHz, CDCl3) δ 7.94 (dd, J = 9.1, 2.0 Hz, 1H), 7.84 (d, J = 7.6
Hz, 2H), 7.72 (d, J = 1.7 Hz, 1H), 7.48 (d, J = 7.6 Hz, 2H), 7.42 (t, J =
7.5 Hz, 3H), 7.27 (t, J = 7.5 Hz, 2H), 7.16 (d, J = 9.1 Hz, 1H), 3.76 (s,
3H), 2.44 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 148.4, 141.5,
140.8, 139.8, 131.1, 129.0, 128.7, 125.1, 124.5, 120.8, 118.7, 117.6,
109.6, 85.2, 70.3, 48.5, 33.6; MS (ESI) (m/z) 365.1 (M + H+); HRMS
(EI) (m/z) calcd for C24H16N2O2 364.1212, found 364.1211.
1-Ethyl-2-phenyl-3-(9-(phenylethynyl)-9H-fluoren-9-yl)-1H-
indole (4n). White solid; 340 mg, 70% yield; mp 159.8−161.0 °C; 1H
NMR (400 MHz, CDCl3) δ 7.73−7.47 (m, 4H), 7.45−6.64 (m, 18H),
3.91−3.69 (m, 2H), 1.25−1.04 (m, 3H); 13C NMR (100 MHz,
CDCl3) δ 151.1, 139.7, 138.0, 135.6, 132.4, 132.1, 131.4, 128.2, 128.1,
128.0, 127.9, 127.7, 125.7, 124.0, 121.7, 121.5, 120.1, 119.6, 111.1,
109.7, 92.4, 82.4, 50.2, 38.4, 15.6; MS (ESI) (m/z) 486.2 (M + H+);
HRMS (EI) (m/z) calcd for C37H27N 485.2143, found 485.2141.
5-Methoxy-1-methyl-2-phenyl-3-(9-(phenylethynyl)-9H-flu-
oren-9-yl)-1H-indole (4o). White solid; 286 mg, 57% yield; mp
5-Methoxy-1-methyl-3-(9-(phenylethynyl)-9H-fluoren-9-yl)-
1H-indole (4f). White solid; 247 mg, 58% yield; mp 172.3−173.1 °C;
1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.5 Hz, 2H), 7.58 (d, J =
7.6 Hz, 2H), 7.48−7.42 (m, 2H), 7.38 (td, J = 7.5, 1.0 Hz, 2H), 7.31−
7.24 (m, 6H), 7.08 (d, J = 8.9 Hz, 1H), 6.73 (dd, J = 8.9, 2.4 Hz, 1H),
6.30 (d, J = 2.3 Hz, 1H), 3.70 (s, 3H), 3.48 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 153.7, 149.8, 139.9, 133.4, 132.2, 128.54, 128.48,
128.4, 128.3, 125.8, 125.6, 123.9, 120.2, 115.4, 112.1, 110.3, 102.1,
91.5, 81.5, 55.7, 49.6, 33.3; MS (ESI) (m/z) 426.2 (M + H+); HRMS
(EI) (m/z) calcd for C31H23NO 425.1780, found 425.1781.
1-Methyl-3-(9-(phenylethynyl)-9H-fluoren-9-yl)-1H-indole-
5-carbonitrile (4g). Pale solid; 391 mg, 93% yield; mp 205.8−206.5
°C; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.6 Hz, 2H), 7.50 (dd,
J = 6.8, 4.9 Hz, 2H), 7.47−7.33 (m, 5H), 7.23 (ddd, J = 18.1, 12.8, 4.9
Hz, 6H), 7.15−7.06 (m, 2H), 3.64 (d, J = 3.5 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 148.9, 139.6, 139.4, 132.0, 130.3, 128.7, 128.53,
128.48, 128.4, 125.7, 125.2, 125.0, 124.7, 123.2, 121.0, 120.6, 117.5,
110.5, 102.2, 90.6, 81.9, 49.2, 33.1; MS (ESI) (m/z) 421.2 (M + H+);
HRMS (EI) (m/z) calcd for C31H20N2 420.1626, found 420.1627.
5-Bromo-1-methyl-3-(9-(phenylethynyl)-9H-fluoren-9-yl)-
1H-indole (4h). White solid; 407 mg, 86% yield; mp 182.7−183.8 °C;
1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 7.6 Hz, 2H), 7.56 (d, J =
7.6 Hz, 2H), 7.43 (dd, J = 6.5, 2.8 Hz, 2H), 7.38 (t, J = 7.5 Hz, 2H),
7.29−7.21 (m, 5H), 7.17 (t, J = 3.7 Hz, 3H), 7.01 (d, J = 8.6 Hz, 1H),
3.60 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 149.4, 139.8, 136.7,
132.1, 128.9, 128.54, 128.52, 128.4, 127.3, 125.4, 124.8, 123.6, 123.0,
120.5, 115.9, 112.8, 111.2, 91.1, 81.8, 49.4, 33.2; MS (ESI) (m/z)
474.1 (M + H+); HRMS (EI) (m/z) calcd for C30H20BrN 473.0779,
found 473.0782.
1
179.2−180.8 °C; H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 7.5 Hz,
4H), 7.31−6.95 (m, 15H), 6.84 (d, J = 8.0 Hz, 2H), 3.59 (s, 3H), 3.25
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 154.0, 150.9, 139.7, 132.2,
132.1, 131.3, 128.3, 128.1, 127.93, 127.89, 127.7, 125.7, 123.9, 120.0,
112.3, 110.7, 110.2, 102.9, 92.3, 82.5, 56.0, 50.1, 30.7; MS (ESI) (m/z)
502.2 (M + H+); HRMS (EI) (m/z) calcd for C37H27NO[M+] (m/z)
501.2093, found 501.2097.
General Procedure for the Preparation of 5. To a solution of 4
(0.5 mmol) and 1-iodopyrrolidine-2,5-dione (NIS) (113 mg, 0.5
mmol) in dichloromethane (5 mL) was added a solution of BF3·Et2O
(72 mg, 0.5 mmol) in dichloromethane (3 mL) dropwise over 3 min.
After being stirred at room temperature for 2 h, the mixture was
evaporated under vacuum. The product was isolated by silica gel
column chromatography with a hexane/dichloromethane mixture.
1-Methyl-3-(1,1,3-triphenylprop-2-yn-1-yl)-1H-indole (4i).
White solid; 258 mg, 65% yield; mp 183.2−184.6 °C; 1H NMR
(400 MHz, CDCl3) δ 7.55 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 7.1 Hz,
4H), 7.44 (dd, J = 6.6, 2.9 Hz, 2H), 7.33−7.17 (m, 11H), 6.99 (t, J =
I
dx.doi.org/10.1021/jo300339a | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1
2-Iodo-4-methyl-3-phenyl-4H-spiro[cyclopenta[b]indole-
1,9′-fluorene] (5a). White solid; 120 mg, 46% yield; mp 210−5−
mp 204.6−205.6 °C; H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.0
Hz, 2H), 7.46 (d, J = 7.9 Hz, 1H), 7.38 (dd, J = 6.6, 3.1 Hz, 4H),
7.34−7.24 (m, 9H), 7.19−7.13 (m, 1H), 7.12−7.02 (m, 1H), 3.49 (s,
3H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 154.4, 146.0,
140.6, 138.4, 138.3, 133.6, 129.5, 129.3, 129.2, 128.7, 127.9, 121.3,
120.9, 120.5, 120.1, 119.8, 110.1, 102.4, 66.1, 31.4, 21.8; MS (ESI) (m/
z) 538.1(M + H+); HRMS (EI) (m/z) calcd for C31H24IN 537.0953,
found 537.0951.
1
211.3 °C; H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 7.5 Hz, 2H),
7.85 (d, J = 7.6 Hz, 2H), 7.54 (t, J = 7.1 Hz, 3H), 7.45 (t, J = 7.6 Hz,
3H), 7.28−7.08 (m, 6H), 7.05 (d, J = 7.6 Hz, 2H), 2.97 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 149.9, 147.8, 143.0, 142.6, 140.7, 136.1,
129.3, 129.0, 128.7, 128.6, 128.4, 124.4, 121.9, 121.2, 121.0, 120.8,
120.4, 119.5, 110.2, 92.5, 67.7, 30.1; MS (ESI) (m/z) 522.1 (M + H+);
HRMS (EI) (m/z) calcd for C30H20IN 521.0640, found 521.0641.
2-Iodo-4-methyl-7-nitro-3-phenyl-4H-spiro[cyclopenta[b]-
indole-1,9′-fluorene] (5b). White solid; 88 mg, 31% yield; mp
245.2−246.7 °C; 1H NMR (400 MHz, CDCl3) δ 8.47 (d, J = 2.1 Hz,
1H), 8.05 (dd, J = 9.1, 2.2 Hz, 1H), 7.89 (t, J = 7.1 Hz, 4H), 7.60 (t, J
= 7.6 Hz, 2H), 7.53 (d, J = 7.6 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 7.27
(t, J = 7.5 Hz, 2H), 7.21 (d, J = 9.1 Hz, 1H), 7.05 (d, J = 7.5 Hz, 2H),
3.02 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 153.1, 146.7, 143.2,
143.0, 142.3, 141.5, 135.3, 129.5, 129.3, 129.1, 128.7, 124.3, 124.0,
121.0, 120.0, 116.7, 116.5, 110.1, 95.3, 68.1, 30.6; MS (ESI) (m/z)
567.0 (M + H+); HRMS (EI) (m/z) calcd for C30H19IN2O2 566.0491,
found 566.0487.
2-Iodo-4,7-dimethyl-3-phenyl-4H-spiro[cyclopenta[b]-
indole-1,9′-fluorene] (5c). White solid; 144 mg, 54% yield; mp
225.4−226.8 °C; 1H NMR (400 MHz, CDCl3) δ 7.93−7.88 (m, 2H),
7.83 (d, J = 7.6 Hz, 2H), 7.55 (t, J = 7.5 Hz, 2H), 7.50−7.40 (m, 3H),
7.31 (s, 1H), 7.26−7.20 (m, 2H), 7.05 (dd, J = 10.3, 8.1 Hz, 3H), 6.97
(dd, J = 8.4, 1.2 Hz, 1H), 2.93 (s, 3H), 2.40 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 149.9, 147.9, 142.9, 142.8, 139.1, 136.3, 129.8, 129.4,
129.0, 128.64, 128.61, 128.4, 124.4, 122.7, 121.3, 121.2, 120.7, 119.1,
109.9, 92.2, 67.7, 30.1, 21.9; MS (ESI) (m/z) 536.1 (M + H+); HRMS
(EI) (m/z) calcd for C31H22IN 535.0797, found 535.0800.
3-(4-Fluorophenyl)-2-iodo-4-methyl-1,1-diphenyl-1,4-
dihydrocyclopenta[b]indole (5i). White solid; 105 mg, 39% yield;
mp 207.1−208.6 °C; 1H NMR (400 MHz, CDCl3) δ 7.76 (dd, J = 8.5,
5.6 Hz, 2H), 7.42−7.24 (m, 12H), 7.23−7.13 (m, 3H), 7.09 (t, J = 7.5
Hz, 1H), 3.50 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.9 (d, JCF
=
247.6 Hz), 154.5, 145.2, 140.6, 138.1, 132.5 (d, JCF = 3.2 Hz), 131.3
(d, JCF = 8.1 Hz), 129.5, 128.8, 128.0, 121.5, 120.7, 120.6, 119. 8,
119.5, 115.6 (d, JCF = 21.5 Hz), 110.3, 103.0, 66.2, 31.4; MS (ESI) (m/
z) 541.1 (M + H+); HRMS (EI) (m/z) calcd for C30H21FIN 541.0703,
found 541.0706.
2-Iodo-4-methyl-7-nitro-4H-spiro[cyclopenta[b]indole-1,9′-
1
fluorene] (5j). White solid; 39 mg, 16% yield; mp 192−194 °C; H
NMR (500 MHz, CDCl3) δ 7.98 (dd, J = 9.0, 2.1 Hz, 1H), 7.89 (d, J =
7.6 Hz, 2H), 7.57 (d, J = 2.1 Hz, 1H), 7.44 (t, J = 7.4 Hz, 2H), 7.38 (s,
1H), 7.34 (d, J = 9.1 Hz, 1H), 7.18 (t, J = 7.4 Hz, 2H), 6.81 (d, J = 7.5
Hz, 2H), 3.97 (s, 3H); 13C NMR (125 MHz, DMSO) δ 152.2, 143.4,
143.1, 142.8, 142.1, 131.4, 128.9, 128.1, 124.2, 123.4, 121.8, 120.9,
116.2, 113.8, 111. 6, 110.4, 68.7, 31.9; MS (ESI) (m/z) 491.0(M +
H+); HRMS (EI) (m/z) calcd for C24H15IN2O2 490.0178, found
490.0177.
N,6′-Diethyl-4′-phenyl-[1,1′:2′,1″-terphenyl]-2-amine (6).
1
White solid; 124 mg, 71% yield; mp 175−178 °C; H NMR (500
2-Iodo-7-methoxy-4-methyl-3-phenyl-4H-spiro[cyclopenta-
[b]indole-1,9′-fluorene] (5d). White solid; 105 mg, 38% yield; mp
221.3−222.1 °C; 1H NMR (400 MHz, CDCl3) δ 7.94−7.88 (m, 2H),
7.84 (d, J = 7.6 Hz, 2H), 7.54 (dd, J = 10.3, 4.6 Hz, 2H), 7.48−7.42
(m, 3H), 7.25−7.21 (m, 2H), 7.06 (t, J = 7.8 Hz, 3H), 7.02 (d, J = 2.4
Hz, 1H), 6.81 (dd, J = 8.9, 2.5 Hz, 1H), 3.78 (s, 3H), 2.93 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 154.8, 150.4, 147.7, 142.9, 142.8, 136.1,
129.3, 129.0, 128.7, 128.6, 128.4, 124.4, 121.4, 121.3, 120.8, 110.8,
110.6, 102.2, 92.0, 67.7, 56.3, 30.2; MS (ESI) (m/z) 552.1 (M + H+);
HRMS (EI) (m/z) calcd for C31H22INO 551.0746, found 551.0746.
2-Iodo-4-methyl-3-phenyl-4H-spiro[cyclopenta[b]indole-
1,9′-fluorene]-7-carbonitrile (5e). White solid; 98 mg, 36% yield;
MHz, CDCl3) δ 7.66 (d, J = 7.5 Hz, 2H), 7.54 (s, 2H), 7.43 (t, J = 7.6
Hz, 2H), 7.33 (t, J = 7.3 Hz, 1H), 7.22−7.06 (m, 6H), 6.79 (d, J = 6.5
Hz, 1H), 6.58 (t, J = 7.3 Hz, 1H), 6.54 (d, J = 8.1 Hz, 1H), 3.48 (s,
1H), 2.67 (s, 3H), 2.18 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
147.1, 143.3, 141.8, 141.0, 140.8, 138.8, 136.1, 130.7, 129.3, 129.1,
128.6, 128.4, 127.8, 127.7, 127.4, 127.1, 126.9, 125.6, 117.0, 109.9,
31.0, 20.9; MS (ESI) (m/z) 350.2 (M + H+); HRMS (EI) (m/z) calcd
for C26H23N 349.1830, found 349.1835.
1,2-Diethyl-3-(spiro[fluorene-9,1′-inden]-3′-yl)-1H-indole-
1
(7a). White solid; 41 mg, 20% yield; mp 191.8−192.4 °C; H NMR
(500 MHz, CDCl3) δ 7.82 (d, J = 7.6 Hz, 2H), 7.64 (d, J = 7.8 Hz,
1H), 7.35 (dd, J = 17.0, 8.0 Hz, 4H), 7.21 (dt, J = 12.0, 7.0 Hz, 4H),
7.12 (t, J = 7.4 Hz, 1H), 7.07 (d, J = 7.4 Hz, 2H), 7.02 (t, J = 7.4 Hz,
1H), 6.70 (d, J = 7.4 Hz, 1H), 6.19 (s, 1H), 3.75 (s, 3H), 2.51 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 149.3, 146.2, 145.9, 142.4, 139.9,
1
mp 226.8−227.6 °C; H NMR (400 MHz, CDCl3) δ 7.91−7.83 (m,
5H), 7.59 (t, J = 7.4 Hz, 2H), 7.52 (d, J = 7.3 Hz, 1H), 7.49 (t, J = 7.6
Hz, 2H), 7.38 (dd, J = 8.5, 1.4 Hz, 1H), 7.31−7.21 (m, 3H), 7.04 (d, J
= 7.6 Hz, 2H), 3.00 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 152.2,
146.8, 143.0, 142.0, 141.6, 135.4, 129.4, 129.2, 129.03, 129.01, 128.6,
124.9, 124.3, 124.1, 122.6, 121.0, 121.0, 120.6, 111.0, 103.5, 94.8, 67.9,
30.4. MS (ESI) (m/z) 547.1 (M + H+); HRMS (EI) (m/z) calcd for
C31H19IN2 546.0593, found 546.0590.
137.7, 137.2, 135.0, 128.01, 127.95, 127.6, 127.2, 126.3, 124.1, 122.9,
121.8, 121.4, 120.5, 120.0, 119.8, 109.1, 107.7, 67.9, 30.1, 12.0; MS
(ESI) (m/z) 410.2 (M + H+); HRMS (EI) (m/z) calcd for C31H23N
409.1830, found 409.1833.
7-Bromo-2-iodo-4-methyl-3-phenyl-4H-spiro[cyclopenta[b]-
indole-1,9′-fluorene] (5f). White solid; 129 mg, 43% yield; mp
221.8−222.5 °C; 1H NMR (400 MHz, CDCl3) δ 7.88−7.81 (m, 4H),
7.63 (d, J = 1.8 Hz, 1H), 7.60−7.52 (m, 2H), 7.50−7.42 (m, 3H), 7.24
(qd, J = 7.7, 1.5 Hz, 3H), 7.06−7.00 (m, 3H), 2.93 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 151.0, 147.3, 143.0, 142.3, 139.4, 135.8, 129.2,
128.9, 128.8, 128.5, 124.4, 124.0, 122.4, 122.0, 121.4, 120.9, 113.9,
111.6, 93.3, 67.8, 30.2; MS (ESI) (m/z) 600.0 (M + H+); HRMS (EI)
(m/z) calcd for C30H19BrIN 598.9746, found 598.9742.
5-Methoxy-1-methyl-2-phenyl-3-(spiro[fluorene-9,1′-
inden]-3′-yl)-1H-indole(7b). White solid; 163 mg, 65% yield; mp
1
196.3−197.5 °C; H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.5 Hz,
2H), 7.47 (d, J = 7.1 Hz, 2H), 7.39−7.26 (m, 6H), 7.17 (d, J = 2.3 Hz,
1H), 7.13 (t, J = 7.7 Hz, 3H), 7.08 (d, J = 7.3 Hz, 1H), 6.99 (dd, J =
8.8, 2.4 Hz, 1H), 6.92 (dd, J = 11.7, 7.7 Hz, 3H), 6.61 (d, J = 7.4 Hz,
1H), 6.03 (s, 1H), 3.82 (s, 3H), 3.72 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 154.8, 149.0, 146.1, 145.7, 142.3, 139.9, 139.6, 138.6, 133.2,
132.3, 131.0, 128.6, 128.4, 128.2, 127.9, 127.8, 127.1, 126.0, 124.1,
122.6, 121.6, 120.3, 112.5, 110.8, 108.9, 102.7, 67.7, 56.4, 31.7; MS
(ESI) (m/z) 502.2 (M + H+); HRMS (EI) (m/z) calcd for C37H27NO
501.2093, found 501.2090.
2-Iodo-4-methyl-1,3,3-triphenyl-3,4-dihydrocyclopenta[b]-
1
indole (5g). Pale solid; 63 mg, 24% yield; mp 194.8−195.6 °C; H
NMR (500 MHz, CDCl3) δ 7.78 (d, J = 7.3 Hz, 2H), 7.49 (t, J = 7.5
Hz, 2H), 7.43 (t, J = 7.1 Hz, 2H), 7.39 (dd, J = 6.1, 3.2 Hz, 4H), 7.34−
7.28 (m, 6H), 7.25 (d, J = 8.2 Hz, 1H), 7.15 (dd, J = 8.8, 6.3 Hz, 1H),
7.07 (t, J = 7.5 Hz, 1H), 3.48 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
154.4, 146.1, 140.6, 138.2, 136.5, 129.5, 129.4, 128.8, 128.6, 128.5,
128.0, 121.4, 120.8, 120.5, 119.9, 119.7, 110.2, 102.8, 66.2, 31.4; MS
(ESI) (m/z) 523.1 (M +); HRMS (EI) (m/z) calcd for C30H22IN
523.0797, found 523.0795.
Procedure for the Preparation of 8. To a solution of indole 1k
(119 mg, 0.5 mmol), propargylic alcohol 2n (103 mg, 0.5 mmol), and
1-iodopyrrolidine-2,5-dione (NIS) (113 mg, 0.5 mmol) in dichloro-
methane (5 mL) was added a solution of BF3·Et2O (72 mg, 0.5 mmol)
in dichloromethane (3 mL) dropwise over 3 min. After being stirred at
room temperature for 2 h, the mixture was evaporated under vacuum.
The product was isolated by silica gel column chromatography with a
hexane/dichloromethane mixture.
2-Iodo-4-methyl-1, 1-diphenyl-3-( p -t olyl)-1, 4-
dihydrocyclopenta[b]indole (5h). White solid; 121 mg, 45% yield;
J
dx.doi.org/10.1021/jo300339a | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
4-Iodo-6-methoxy-1-methyl-2-phenyl-1H-spiro[benzo[cd]-
indole-3,9′-fluorene] (8). White solid; 55 mg, 20% yield; mp 212.1−
213.0 °C; 1H NMR (400 MHz, CDCl3) δ 7.93 (s, 1H), 7.29 (d, J = 7.3
Hz, 2H), 7.27−7.14 (m, 6H), 7.12 (d, J = 8.8 Hz, 1H), 7.00 (t, J = 7.5
Hz, 1H), 6.86 (d, J = 8.8 Hz, 1H), 6.80 (t, J = 7.6 Hz, 2H), 6.12 (d, J =
7.9 Hz, 2H), 3.96 (s, 3H), 3.30 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 154.6, 148.1, 140.3, 138.6, 133.8, 130.8, 130.2, 129.6, 128.0, 127.8,
127.7, 127.4, 125.8, 124.8, 119.6, 113.8, 110.9, 110.4, 109.4, 108.2,
61.2, 57.9, 30.9; MS (ESI) (m/z) 552.1 (M + H+); HRMS (EI) (m/z)
calcd for C31H22INO 551.0746, found 551.0735.
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ASSOCIATED CONTENT
■
S
* Supporting Information
HPLC reports of reaction conditions, copies of H and 13C
1
NMR spectra, and crystallographic information in CIF format
for compounds 3a, 3c, 4n, 5j, 6, 7a, and 8. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Corresponding Author E-mail: pinglu@zju.edu.cn; orgwyg@
zju.edu.cn
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China
(Grants 21032005 and 20872128) for financial support.
■
REFERENCES
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