Gold(I)-catalyzed polycyclizations of polyenyne-type anilines based on hydroamination and consecutive hydroarylation cascade

Article abstract of DOI:10.1021/jo2018119

A hydroamination-double hydroarylation cascade using aniline derivatives bearing a trienyne moiety as the substrate was efficiently promoted by a gold(I) catalyst to produce benzo[a]naphtho[2,1-c]carbazole derivatives in good yields. This reaction is applicable to various substituted trienyne-type anilines, including 2,3-diethynylthiophene derivatives. The reaction of anilines bearing a tetraenyne and pentaenyne moiety allows direct construction of highly fused carbazoles by tetra- and pentacyclization, respectively, through hydroamination and consecutive hydroarylation without producing any theoretical waste products from the substrates.

Full text of DOI:10.1021/jo2018119

Article
pubs.acs.org/joc
Gold(I)-Catalyzed Polycyclizations of Polyenyne-Type Anilines Based
on Hydroamination and Consecutive Hydroarylation Cascade
Kimio Hirano, Yusuke Inaba, Kiyosei Takasu, Shinya Oishi, Yoshiji Takemoto, Nobutaka Fujii,
and Hiroaki Ohno*
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
S
* Supporting Information
ABSTRACT: A hydroamination−double hydroarylation cas-
cade using aniline derivatives bearing a trienyne moiety as the
substrate was efficiently promoted by a gold(I) catalyst to
produce benzo[a]naphtho[2,1-c]carbazole derivatives in good
yields. This reaction is applicable to various substituted
trienyne-type anilines, including 2,3-diethynylthiophene de-
rivatives. The reaction of anilines bearing a tetraenyne and
pentaenyne moiety allows direct construction of highly fused
carbazoles by tetra- and pentacyclization, respectively, through hydroamination and consecutive hydroarylation without
producing any theoretical waste products from the substrates.
platinum-catalyzed naphthalene formation from 2,3-diethynylben-
zenes via nucleophilic addition of methoxide onto activated alkyne,
which was followed by 6-endo-dig cyclization to construct a single
benzene ring.5,6 In contrast, catalytic consecutive hydroarylation to
form multiple benzene rings has not been reported.
INTRODUCTION
■
Polyene cyclization based on biogenetic conversion of
squalenes into polycyclic triterpenoids enables direct con-
struction of complex polycyclic molecules in a single operation
(Scheme 1, eq 1).1 Recent progress in this area including
We expected that consecutive hydroarylation (Scheme 1, eq 3)
would be a promising approach to polyenyne-type cyclization.
Recently, we found that highly alkynophilic gold salts promote
a 5-endo-dig-hydroamination/6-endo-dig hydroarylation7,8 cascade
of anilines-derived diynes 1 (n = 0) to give aryl-annulated[a]-
carbazoles 2 (n = 0) (Scheme 2),9−12 which constitute an
Scheme 1. Cascade Cyclization of Polyene and Polyenyne
Derivatives
Scheme 2. Synthetic Strategy Based on Hydroamination and
Consecutive Hydroarylation
catalytic enantio-controlled polyene cyclization2 has made this
transformation a more powerful tool in organic synthesis.
However, consecutive cyclization of polyenynes to form highly
fused aromatic compounds (eq 2) is unknown as far as we are
aware. This is partly because of the digonal bonding of the sp-
hybridized carbons of enynes in the ground state, which
restricts them from being in an appropriate orientation for
polycyclization. A related reaction, anionic Bergman cyclization
of enediynes, was reported for construction of a fused benzene
ring.3,4 Recently, Liu and co-workers reported ruthenium- or
Received: September 2, 2011
Published: September 27, 2011
© 2011 American Chemical Society
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important class of compounds for their diverse biological
activities.13 Based on this chemistry, introduction of another
alkyne moiety to the substrates might allow the second
hydroarylation leading to benzo[a]naphtho[2,1-c]carbazoles 3
(n = 1). Although hydroarylation of the carbazole benzene ring
onto alkyne is unprecedented, we anticipated the nitrogen atom
at the para-position would accelerate this transformation. If the
third and further hydroarylation successfully proceeded from 3,
polycyclization products such as 4 would be obtained. In these
cases, hydroarylation with a simple naphthalene ring of 3/4 as
well as activation of the appropriate alkyne in each step among
several alkynes are challenging issues in this strategy. Here we
report our study on the synthesis of highly fused carbazoles
based on gold-catalyzed 5-endo-dig hydroamination and
consecutive 6-endo-dig hydroarylation cascade using poly-
enyne-type anilines (n = 1−3).
Scheme 4. Preparation of Tetra- and Pentaenyne-Type
Substrates 12 and 14
RESULTS AND DISCUSSION
■
Synthesis of Polyenyne-Type Anilines. The requisite
trienyne-type substrates 9 for construction of benzo[a]-
naphtho[2,1-c]carbazoles 3 (n = 1) were prepared in a
straightforward manner as shown in Scheme 3. Sonogashira
Scheme 3. Preparation of Trienyne-Type Substrates 9
reaction with dienyne-type halide 10, TBAF treatment, and
coupling with iodobenzene gave 12 in good overall yield.
Pentaenyne-type aniline 14 was synthesized by a 1 + 2 + 2
approach, which repeated the coupling−deprotection sequence
starting from ethynylaniline 5 with dienyne-type halide 10,
followed by arylation at the terminal alkyne of 13. This afforded
the desired pentaenyne-type substrate 14 in good yield. The
required polyenyne-type anilines with the desired number of
enyne units could be prepared using the protected dienyne
synthon 10 in an short synthesis starting from either mono- or
dienyne-type aniline (5 or 7).
Tricyclization through Hydroarylation with Carbazole
Ring. Following synthesis of the polyenyne substrates, the
gold-catalyzed tricyclization through the second hydroarylation
with carbazole benzene ring was investigated (Table 1).
Treatment of trienyne-type aniline 9a with 5 mol % of
Ph3PAuCl/AgOTf in MeCN at 80 °C produced the double
cyclization product 16a in only 28% yield (entry 1). A
considerable amount of the starting material was recovered
(53%). Fortunately, increased loading (20 mol %) of the
catalyst resulted in formation of the desired tricyclization
product, benzo[a]naphtho[2,1-c]carbazole derivative 15a, in
49% yield (entry 2). Among the several silver salts tested for
activation of the gold complex (entries 2−8), tetrafluoroborate
was the most promising, producing 15a in 77% yield (entry 8).
However, decreasing the loading of the catalyst to 5 mol % was
not successful (entry 9). The relatively lower electron density
of the benzene ring of the carbazole intermediate compared
with the indole 3 position would be problematic. In contrast,
use of the gold−phosphine catalyst JohnPhosAuCl (Figure 1)
in the presence of AgBF4 exhibited improved turnover to give
15a in 68% yield with a 5 mol % catalyst loading (entry 11).
coupling of 2-ethynylaniline 514 with protected 1-bromo-2-
ethynylbenzene 615 followed by cleavage of the trimethylsilyl
group with tetra-n-butylammonium fluoride (TBAF) afforded
dienyne-type aniline 7 in 73% yield. A further coupling reaction
with 1-bromo-2-ethynylbenzenes 8, which have an alkyl
substituent at the alkyne terminus, gave the trienyne-type
anilines 9a−c. By comparison, the second coupling−depro-
tection sequence of dienyne-type aniline 7 with 1-bromo-2-
ethynylbenzene 6 led to the corresponding terminal alkyne 9d,
which was converted to aryl-substituted substrates 9e−i in
good yields by coupling with a series of aryl iodides. Other
trienyne-type anilines were also prepared in a similar manner
(see the Experimental Section).
Tetraenyne-type aniline 12 was easily prepared by a 2 + 2
approach with dienyne-type aniline 7 (Scheme 4). A cross-coupling
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Table 1. Optimization of Reaction Conditions for Tricyclization
yield (%)
entry
catalyst
loading (mol %)
time (h)
15a
16a
recovery (%)
53
1
Ph3PAuCl/AgOTf
Ph3PAuCl/AgOTf
Ph3PAuCl/AgNTf2
Ph3PAuCl/AgSbF6
Ph3PAuCl/AgOTs
Ph3PAuCl/AgPF6
Ph3PAuCl/AgClO4
Ph3PAuCl/AgBF4
Ph3PAuCl/AgBF4
JohnPhosAuCl/AgBF4
JohnPhosAuCl/AgBF4
JohnPhosAuCl/AgBF4
5
20
20
20
20
20
20
20
5
2
28
2
1
49
55
72
60
58
55
77
3
4
4
2.5
1
5
6
1
7
3
8
1.5
4
9
29
43
10
11
20
5
0.5
4.5
0.5
65
68
73
a
12
5
a
AcOH was used as the solvent.
a
Table 2. Reaction of Various Trienyne-Type Substrates
Figure 1. Screened gold−phosphine catalysts.
Acetic acid (AcOH) was the solvent of choice for the tricyclization
to afford 15a with a slightly improved yield (73%) within 30 min
(entry 12), presumably due to the promoted proto-deauration.
Using the optimized conditions described in entry 12 (5 mol %
JohnPhosAuCl/AgBF4 in AcOH, Table 1), the tricyclization
was extended to other types of substrates (Table 2).
Replacement of the n-propyl group with a cyclohexyl group
at the alkyne terminus (as R1) was tolerated (entries 1 and 2).
However, the sterically hindered tert-butyl group completely
interrupted the third cyclization to give the double cyclization
product 16c in 72% yield (entry 3). The reaction of terminal
alkyne derivative 9d was also unsuccessful and gave a complex
mixture of unidentified products (entry 4). By contrast, all the
aryl-substituted trienyne-type substrates 9e−i produced the
desired tricyclization products in 47−77% yields (entries 5−9).
Relatively low yields of the reaction using 9h and 9i bearing a
4-methyl- or 4-methoxyphenyl group (entries 8 and 9) can be
attributed to the predominant coordination of the electron-rich
aryl substituted alkyne to the gold complex, which somewhat
hinders the first and/or second cyclization step. The
substitution effect at the aniline part was also investigated
(entries 10−13). The reaction of 9j and 9k bearing a methyl
and chloro substitution at the para-position of the amino group
(as R2) gave the corresponding tricyclization products 15j (66%
yield) and 15k (68% yield), respectively. As anticipated, a
cyano group at the same position significantly decreased the
reactivity to afford the tricyclization product 15l in only 14%
yield with a complex mixture of unidentified products (entry 12).
entry subst
R1
R2
R3
time (h) yield (%)
1
9a
9b
9c
9d
9e
9f
n-Pr
c-Hex
t-Bu
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
0.5
24
73
70
2
H
b
3
H
24
3
−
−
c
4
H
5
C6H4(4-CN)
C6H4(4-Cl)
Ph
H
0.5
77
68
63
60
47
66
68
14
52
6
H
1
7
9g
9h
9i
H
0.5
0.75
1
8
C6H4(4-Me)
C6H4(4-OMe)
n-Pr
H
9
H
10
11
12
13
9j
Me
Cl
CN
H
0.5
0.5
1
9k
9l
n-Pr
n-Pr
9m
n-Pr
0.5
a
All reactions were carried out using JohnPhosAuCl (5 mol %) and
b
AgBF4 (5 mol %) in AcOH at 80 °C. Double cyclization product 16c
was obtained in 72% yield. A mixture of unidentified products was
obtained.
c
This was presumably because of the decreased nucleophilicity
at the reaction site(s) as well as the activation/coordination
ability of gold catalysts for the nitrile functionality.16
Tricyclization of 3-chloro-substituted aniline derivative 9m
resulted in 15m in 52% yield (entry 13).
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As shown in Scheme 5, exposure of the plausible inter-
mediate 16a to the optimized reaction conditions afforded 15a
Table 3. Optimization of Reaction Conditions for
Tetracyclization
Scheme 5. Reaction of the Intermediate 16a
in 90% yield, the same product formed by tricyclization of 9a.
Combined with the reaction using insufficient loading of the
catalyst to produce 16a with recovered starting material (Table 1,
entries 1 and 9), this result strongly supports the reaction
pathway occurs through hydroamination and stepwise hydro-
arylation/proto-deauration (Scheme 2).
yield (%)
Next, the reaction of thiophene derivatives 17 and 18 was
investigated (Scheme 6). The reactivity of trienyne-type aniline
entry Au(I) catalyst loading (mol %) solvent time (h) 21
22
1
2
3
4
5
6
7
8
9
JohnPhosAuCl
JohnPhosAuCl
JohnPhosAuCl
JohnPhosAuCl
JohnPhosAuCl
XPhosAuCl
5
20
20
10
5
AcOH
AcOH
EtOH
EtOH
EtOH
EtOH
EtOH
AcOH
EtOH
24
3
38
55
78
12
Scheme 6. Reaction of Thiophene Derivatives
3
a
a
a
29
24
1
58
61
10
5
86
65
61
86
a
XPhosAuCl
24
14
3
22
XPhosAuCl
5
XPhosAuCl
7.5
a
1
Determined by H NMR.
hindered catalyst XPhosAuCl (Figure 1) was then tested in the reac-
tion. Treatment of 12 with XPhosAuCl/AgBF4 (10 or 7.5 mol %)
in EtOH showed clean conversion within 1−3 h to give 21 in 86%
yield (entries 6 and 9).17 This result suggests that the
5-position of benzo[a]naphtho[2,1-c]carbazole derivatives of the
same type as 22 has sufficient reactivity for the gold(I)-catalyzed
intramolecular hydroarylation of alkynes.
Finally, pentacyclization of 14 through hydroamination and
quadruple hydroarylation cascade (Scheme 7) was investigated.
Scheme 7. Application to Pentacyclization
17 bearing a thiophene ring at the distal position from the
aniline moiety was relatively low, and the tricyclization product
19 was obtained in a moderate yield (45%). By contrast, aniline
18 bearing a thiophene ring at the central position of the
molecule produced the corresponding fused thiophene 20 in
79% yield under the standard reaction conditions.
Polycyclization through Hydroarylation with the
Naphthalene Ring. Tetracyclization of the tetraenyne-type
aniline 12 (Table 3) through hydroarylation with the newly
formed simple naphthalene ring was investigated next. To our
delight, the reaction of 12 under the optimized conditions for
tricyclization in AcOH produced the desired benzo[a]-
chryseno[5,6-c]carbazole derivative 21 in 38% yield. Formation
of diastereomers based on the rotational barrier of the fused
ring system was not observed. Increasing the catalyst loading to
20 mol % somewhat improved the yield (55%, entry 2). Changing
the reaction solvent to ethanol (EtOH) led to a better result (78%
yield, entry 3). However, decreasing the catalyst loading was not
successful in this case and produced the tricyclization intermediate
22 as the major product (entries 4 and 5). The sterically more
In this case, the fourth hydroarylation with the naphthalene
moiety of the benzo[a]chryseno[5,6-c]carbazoles like 21
(Table 3) was tested. Reaction of 14 with XPhosAuCl/AgBF4
(20 mol %) in EtOH for 21 h produced a highly fused
carbazole 23 having a benzo[a]naphtho[1′,2′:11,12]chryseno-
[5,6-c]carbazole skeleton in 68% yield. Interestingly, this was
produced as a 2:1 mixture of stereoisomers, the isomeric ratio
of which was increased to 3:1 when the isolated isomeric
mixture of 23 (2:1) was heated under reflux in xylene for 10 h
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Figure 2. Crystal structure (benzene molecules as the solvent were omitted for clarity) and UV/vis spectra of 24.
a pad of Celite. The filtrate was concentrated under reduced pressure, and
the residue was purified by column chromatography over silica gel with
hexane to afford 8b (0.40 g, 76% yield): colorless oil containing
homodimer of ethynylcyclohexane (ca. 10%). IR (neat): 2228 (CC)
in the absence of any reagents and catalysts. Fortunately,
tosylation of 23 followed by recrystallization led to isolation of
the major isomer. X-ray analysis of the tosylate major isomer 24
has shown that this compound has an unprecedented
polynaphthalene helix structure (Figure 2). UV/vis spectra of
24 (λmax = 263, 331, 395 nm, CHCl3) is in good coincidence
with those of related polyaromatic hydrocarbon and carbazole
structures.18 From these observations, gold-catalyzed polycyc-
lization of enyne-type substrates shows significant potential for
construction of highly fused aromatic ring systems.
1
cm−1. H NMR (500 MHz, CDCl3) δ: 1.35−1.47 (m, 4H), 1.60−1.64
(m, 2H), 1.77−1.84 (m, 2H), 1.87−1.90 (m, 2H), 2.65−2.70 (m, 1H),
7.10 (ddd, J = 7.7, 7.7, 1.7 Hz, 1H), 7.21 (ddd, J = 7.7, 7.7, 1.1 Hz, 1H),
7.42 (dd, J = 7.7, 1.7 Hz, 1H), 7.55 (d, J = 7.7 Hz, 1H). 13C NMR (125
MHz, CDCl3) δ: 24.6, 26.0 (2C), 29.7, 32.4 (2C), 79.5, 99.5, 125.6, 126.1,
126.8, 128.5, 132.2, 133.2. HRMS (FAB) calcd for C14H15Br [M+]
262.0352; found: 262.0349.
1-Bromo-2-(3,3-dimethylbut-1-yn-1-yl)benzene (8c). By a proce-
dure identical to that described for the preparation of 8b, 1-bromo-2-
iodobenzene (0.51 mL, 4.0 mmol) was converted into 8c (0.32 g, 33%
yield) using 3,3-dimethylbut-1-yne (1.4 mL, 12 mmol): colorless oil.
CONCLUSION
■
A gold-catalyzed cascade cyclization of polyenyne-type anilines
for atom-economical synthesis of highly fused carbazoles was
developed. The reaction of trienyne-type anilines produced
benzo[a]naphtho[2,1-c]carbazoles through hydroarylation with
the carbazole benzene ring. The gold catalysts promote the
third and fourth hydroarylation with simple naphthalene rings
to afford benzene-fused chryseno[5,6-c]- and naphtho-
[1′,2′:11,12]chryseno[5,6-c]carbazoles, respectively. This is the
first example of consecutive hydroarylation cascade, the
polyenyne version of biogenetic polyene cyclization, in which
the newly formed benzene ring(s) participates in the next
cyclization to form multiple benzene rings. Synthesis and
evaluation of the absorption properties of other fused aromatic
ring systems are now underway.
1
IR (neat): 2243 (CC) cm−1. H NMR (400 MHz, CDCl3) δ: 1.35
(s, 9H), 7.09 (dd, J = 7.7, 7.7 Hz, 1H), 7.21 (dd, J = 7.7, 7.7 Hz, 1H), 7.41
(d, J = 7.7 Hz, 1H), 7.55 (d, J = 7.7 Hz, 1H). 13C NMR (125 MHz,
CDCl3) δ: 28.2, 30.8 (3C), 78.0, 103.6, 125.7, 126.0, 126.8, 128.5, 132.2,
133.0. HRMS (FAB) calcd for C12H14Br [MH+] 237.0279; found:
237.0271.
2-[(2-{[2-(Pent-1-yn-1-yl)phenyl]ethynyl}phenyl)ethynyl]aniline
(9a). To a solution of 8a (1.1 g, 5.2 mmol) in THF (10 mL) were
successively added diisopropylamine (3.6 mL, 26 mmol), CuI (0.059
g, 0.31 mmol), PdCl2(PhCN)2 (0.12 g, 0.31 mmol), P(t-Bu)3 (0.15
mL, 0.62 mmol), and 7 (1.3 g, 6.0 mmol) at room temperature under
argon. The mixture was stirred at room temperature for 10 h. The
mixture was filtered through a pad of Celite. The filtrate was
concentrated under reduced pressure, and the residue was purified by
column chromatography over silica gel with hexane−EtOAc (10:1) to
afford 9a (1.4 g, 77% yield) as an orange oil. IR (neat): 3480 (NH),
3380 (NH), 2210 (CC) cm−1. 1H NMR (500 MHz, CDCl3) δ: 0.96
(t, J = 7.2 Hz, 3H), 1.54−1.57 (m, 2H), 2.36 (t, J = 7.2 Hz, 2H), 4.40
(br s, 2H), 6.65 (d, J = 8.0 Hz, 1H), 6.67 (dd, J = 8.6, 8.6 Hz, 1H),
7.11 (dd, J = 7.7, 7.7 Hz, 1H), 7.23−7.34 (m, 4H), 7.38 (d, J = 7.4 Hz,
1H), 7.44 (d, J = 6.9 Hz, 1H), 7.53−7.59 (m, 3H). 13C NMR (125
MHz, CDCl3) δ: 13.5, 21.6, 22.1, 79.4, 90.5, 92.1 (2C), 93.7, 95.4,
107.5, 114.0, 117.4, 125.1, 125.3, 125.8, 126.7, 127.2, 127.6, 128.1,
128.2, 129.9, 131.4, 131.86, 131.93, 132.2, 132.3, 148.4. HRMS (FAB)
calcd for C27H21N [M+] 359.1674; found: 359.1669.
2-[(2-{[2-(Cyclohexylethynyl)phenyl]ethynyl}phenyl)ethynyl]-
aniline (9b). By a procedure identical to that described for the
preparation of 9a, 7 (0.27 g, 1.23 mmol) was converted into 9b (0.29 g,
74% yield) using 8b (0.26 g, 0.99 mmol): pale brown solid; mp 129−
131 °C. IR (neat): 3479 (NH), 3379 (NH), 2211 (CC) cm−1.
1H NMR (500 MHz, CDCl3) δ: 1.24−1.26 (m, 3H), 1.45−1.50 (m, 3H),
1.68−1.72 (m, 2H), 1.74−1.78 (m, 2H), 2.58−2.62 (m, 1H), 4.39 (br s,
2H), 6.64 (d, J = 8.0 Hz, 1H), 6.67 (dd, J = 7.7, 7.7 Hz, 1H), 7.11 (dd,
J = 7.7, 7.7 Hz, 1H), 7.25−7.31 (m, 4H), 7.37 (d, J = 8.0 Hz, 1H), 7.44
EXPERIMENTAL SECTION
■
General Methods. 1H NMR spectra were recorded at 400 or 500
MHz. 13C NMR spectra were recorded at 100 or 125 MHz. Internal
references were used for CDCl3 in 1H and 13C NMR spectra. Data are
presented as follows: chemical shift (in ppm on the δ scale relative to
δTMS = 0), multiplicity (s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet, br = broad), coupling constant (J/Hz) and
number of protons. Melting points were measured by a hot stage melting
point apparatus and are uncorrected. For column chromatography, silica
gel (45−75 μm) and amino silica gel (100−200 mesh) were employed.
The compounds 5,14 6,15 7,9b 1-bromo-2-(cyclohexylethynyl)benzene
(8a),19 and S320 were synthesized according to the literature procedures.
Other reagents are commercially available, which were used without
further purification.
1-Bromo-2-(cyclohexylethynyl)benzene (8b). A mixture of
1-bromo-2-iodobenzene (0.26 mL, 2.0 mmol), CuI (9.5 mg, 0.05 mmol),
PdCl2(PPh3)2 (35 mg, 0.05 mmol), Et3N (1.4 mL, 10 mmol), and
ethynylcyclohexane (0.77 mL, 6.0 mmol) in THF (4 mL) was stirred at
room temperature for 2 h under argon. The mixture was filtered through
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(d, J = 7.4 Hz, 1H), 7.53−7.60 (m, 3H). 13C NMR (125 MHz, CDCl3)
δ: 24.6, 25.9 (2C), 29.7, 32.5 (2C), 79.3, 90.6, 92.1, 92.1, 93.7, 99.6, 107.5,
114.0, 117.4, 125.2, 125.3, 125.9, 126.8, 127.2, 127.6, 128.1, 128.2, 129.9,
131.3, 131.8, 131.9, 132.2 (2C), 148.4. Anal. Calcd for C30H25N: C, 90.19;
H, 6.31; N, 3.51. Found: C, 90.07; H, 6.31; N, 3.53.
2-[(2-{[2-(Phenylethynyl)phenyl]ethynyl}phenyl)ethynyl]aniline
(9g). By a procedure identical to that described for the preparation of
9e, 9d (0.16 g, 0.50 mmol) was converted into 9g (0.18 g, 94% yield)
using iodobenzene (54 μL, 0.48 mmol): brown oil. IR (neat): 3481
(NH), 3382 (NH), 2251 (CC), 2212 (CC) cm−1. 1H NMR (500
MHz, CDCl3) δ: 4.41 (br s, 2H), 6.63 (d, J = 8.0 Hz, 1H), 6.65 (dd,
J = 6.6, 6.6 Hz, 1H), 7.09 (dd, J = 7.7, 7.7 Hz, 1H), 7.24−7.35
(m, 8H), 7.50 (dd, J = 7.2, 2.0 Hz, 2H), 7.58 (d, J = 8.0 Hz, 2H), 7.60
(dd, J = 9.2, 9.2 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ: 88.1, 90.6,
91.9, 92.8, 93.6, 94.0, 107.5, 114.0, 117.5, 123.1, 125.0, 125.5, 125.8,
126.0, 127.7, 128.0, 128.2 (2C), 128.3 (2C), 128.4, 129.9, 131.5, 131.7
(2C), 131.8, 132.0, 132.3, 132.3, 148.3. HRMS (FAB) calcd for
C30H19N [M+] 393.1517; found: 393.1525.
2-[(2-{[2-(3,3-Dimethylbut-1-yn-1-yl)phenyl]ethynyl}phenyl)-
ethynyl]aniline (9c). By a procedure identical to that described for
the preparation of 9a, 7 (0.20 g, 0.92 mmol) was converted into 9c
(0.099 g, 35% yield) using 8c (0.18 g, 0.76 mmol): orange oil. IR
1
(neat): 3478 (NH), 3384 (NH), 2210 (CC) cm−1. H NMR (400
MHz, CDCl3) δ: 1.18 (s, 9H), 4.30 (br s, 2H), 6.53 (d, J = 8.3 Hz,
1H), 6.57 (dd, J = 8.5, 8.5 Hz, 1H), 7.00 (dd, J = 7.3, 7.3 Hz, 1H),
7.15−7.19 (m, 4H), 7.28 (d, J = 6.8 Hz, 1H), 7.34 (d, J = 7.1 Hz, 1H),
7.46−7.49 (m, 3H). 13C NMR (100 MHz, CDCl3) δ: 28.1, 30.9 (3C),
77.2, 77.8, 90.6, 92.00, 92.03, 93.7, 103.6, 107.4, 113.9, 117.4, 125.1,
125.3, 125.8, 126.6, 127.2, 127.6, 128.11, 128.14, 129.9, 131.3, 131.6,
131.9, 132.1, 148.3. HRMS (FAB) calcd for C28H23N [M+] 374.1909;
found: 374.1902.
2-[(2-{[2-(p-Tolylethynyl)phenyl]ethynyl}phenyl)ethynyl]aniline
(9h). By a procedure identical to that described for the preparation of
9e, 9d (0.19 g, 0.61 mmol) was converted into 9h (0.20 g, 83% yield)
using p-iodotoluene (0.13 g, 0.58 mmol): pale brown crystals; mp
100−102 °C. IR (neat): 3483 (NH), 3378 (NH), 2212 (CC) cm−1
.
1H NMR (500 MHz, CDCl3) δ: 2.33 (s, 3H), 4.41 (br s, 2H), 6.63 (d,
2-({2-[(2-Ethynylphenyl)ethynyl]phenyl}ethynyl)aniline (9d). To
a solution of 6 (0.19 g, 0.76 mmol) in THF (5 mL) were successively
added diisopropylamine (0.53 mL, 3.8 mmol), CuI (8.7 mg, 0.045
mmol), PdCl2(PhCN)2 (17 mg, 0.045 mmol), P(t-Bu)3 (22 μL, 0.091
mmol), and 7 (0.20 g, 0.91 mmol) at room temperature under argon.
The mixture was stirred at 60 °C for 16 h. The mixture was filtered
through a pad of Celite. The filtrate was concentrated under reduced
pressure. To the residue were added THF (5 mL) and TBAF (1 M
solution in THF; 0.91 mL, 0.91 mmol) at 0 °C. The mixture was
stirred at 0 °C for 0.5 h and quenched by addition of saturated
aqueous NH4Cl and brine, dried over Na2SO4, filtrated, and
concentrated in vacuo. The residue was purified by column
chromatography on silica gel with hexane−EtOAc (10:1) to afford
9d (0.17 g, 69% yield in two steps): brown oil. IR (neat): 3480 (NH),
J = 8.0 Hz, 1H), 6.65 (dd, J = 7.4, 7.4 Hz, 1H), 7.07−7.10 (m, 3H),
7.24−7.40 (m, 7H), 7.55−7.62 (m, 4H). 13C NMR (125 MHz, CDCl3)
δ: 21.5, 87.5, 90.6, 91.9, 92.7, 93.6, 94.3, 107.5, 114.0, 117.5, 120.0, 124.99,
125.04, 125.4, 125.8, 126.2, 127.7, 127.8, 128.3, 129.0 (2C), 129.9, 131.4,
131.6 (2C), 131.7, 132.0, 132.2, 132.3, 138.6, 148.3. Anal. Calcd for
C31H21N: C, 91.37; H, 5.19; N, 3.44. Found: C, 91.15; H, 5.19; N, 3.44.
2-{[2-({2-[(4-Methoxyphenyl)ethynyl]phenyl}ethynyl)phenyl]-
ethynyl}aniline (9i). By a procedure identical to that described for the
preparation of 9e, 9d (0.21 g, 0.65 mmol) was converted into 9i (0.22 g,
83% yield) using p-iodoanisole (0.15 g, 0.62 mmol): orange oil. IR
1
(neat): 3472 (NH), 3379 (NH), 2212 (CC) cm−1. H NMR (500
MHz, CDCl3) δ: 3.79 (s, 3H), 4.42 (br s, 2H), 6.63 (d, J = 8.0 Hz,
1H), 6.65 (dd, J = 7.2, 7.2 Hz, 1H), 6.79 (d, J = 8.6 Hz, 2H), 7.09 (dd,
J = 7.2, 7.2 Hz, 1H), 7.27−7.36 (m, 5H), 7.43 (d, J = 8.6 Hz, 2H),
7.57−7.60 (m, 4H). 13C NMR (125 MHz, CDCl3) δ: 55.3, 86.9, 90.6,
92.0, 92.6, 93.6, 94.2, 107.5, 113.9 (2C), 114.0, 115.2, 117.5, 125.1,
125.2, 125.8, 126.3, 127.6, 127.7, 128.26, 128.29, 129.9, 131.5, 131.6,
132.0, 132.2, 132.3, 133.2 (2C), 148.4, 159.7. HRMS (FAB) calcd for
C31H21NO [M+] 423.1623; found: 423.1622.
1
3377 (NH), 3295 (CCH), 2250 (CC), 2210 (CC) cm−1. H
NMR (400 MHz, CDCl3) δ: 3.25 (s, 1H), 4.39 (br s, 2H), 6.67 (d, J =
8.3 Hz), 6.69 (dd, J = 7.6, 7.6 Hz), 7.13 (dd, J = 7.7, 7.7 Hz, 1H),
7.29−7.40 (m, 5H), 7.56−7.61 (m, 4H). 13C NMR (125 MHz,
CDCl3) δ: 81.6, 82.0, 90.5, 91.4, 92.7, 93.6, 107.6, 114.1, 117.6, 124.7,
124.9, 125.8, 126.0, 127.7, 128.2, 128.4, 128.5, 129.9, 131.5, 132.0,
132.3, 132.5, 132.6, 148.3. HRMS (FAB) calcd for C24H16N [MH+]
318.1277; found: 318.1283.
4-{[2-({2-[(2-Aminophenyl)ethynyl]phenyl}ethynyl)phenyl]-
ethynyl}benzonitrile (9e). A mixture of 9d (0.16 g, 0.49 mmol), CuI
(2.3 mg, 0.012 mmol), PdCl2(PPh3)2 (8.4 mg, 0.012 mmol), Et3N
(0.33 mL, 2.4 mmol), and p-iodobenzonitrile (0.11 g, 0.47 mmol) in
THF (1.0 mL) was stirred at room temperature for 1 h under argon.
The mixture was filtered through a pad of Celite. The filtrate was
concentrated under reduced pressure, and the residue was purified by
column chromatography over silica gel with hexane−EtOAc (5:1) to
afford 9e (0.16 g, 83% yield) as a pale yellow solid: mp 166−167 °C.
1
IR (neat): 3460 (NH), 3364 (NH), 2221 (CC). H NMR (500
MHz, CDCl3) δ: 4.35 (br s, 2H), 6.60 (d, J = 8.0 Hz, 1H), 6.62 (dd,
J = 7.4, 7.4 Hz, 1H), 7.07 (dd, J = 7.7, 7.7 Hz, 1H), 7.30−7.37 (m, 5H),
7.50 (s, 4H), 7.57−7.64 (m, 4H). 13C NMR (125 MHz, CDCl3) δ: 90.7,
91.4, 92.2, 92.3, 93.1, 93.5, 107.4, 111.4, 114.0, 117.5, 118.5, 124.7, 124.9,
125.8, 127.7, 127.8, 128.4, 128.5, 128.8, 129.9, 131.6, 131.8 (2C), 132.0
(2C), 132.1 (3C), 132.2, 132.4, 148.2. Anal. Calcd for C31H18N2: C,
88.97; H, 4.34; N, 6.69. Found: C, 88.69; H, 4.33; N, 6.59.
2-{[2-({2-[(4-Chlorophenyl)ethynyl]phenyl}ethynyl)phenyl]-
ethynyl}aniline (9f). By a procedure identical to that described for the
preparation of 9e, 9d (0.16 g, 0.51 mmol) was converted into 9f (0.20
g, 95% yield) using p-chloroiodobenzene (0.12 g, 0.49 mmol): white
solid; mp 104−106 °C. IR (neat): 3475 (NH), 3378 (NH), 2210
1
(CC) cm−1. H NMR (500 MHz, CDCl3) δ: 4.38 (br s, 2H), 6.62
(d, J = 8.6 Hz, 1H), 6.64 (dd, J = 8.0, 8.0 Hz, 1H), 7.08 (dd, J = 6.9,
6.9 Hz, 1H), 7.22 (d, J = 8.6 Hz, 2H), 7.28−7.36 (m, 5H), 7.39 (d, J =
8.6 Hz, 2H), 7.56−7.60 (m, 4H). 13C NMR (125 MHz, CDCl3) δ: 89.0,
90.7, 91.6, 91.7, 92.9, 93.6, 107.5, 114.0, 117.5, 121.5, 124.9, 125.5, 125.6,
125.8, 127.7, 128.2, 128.3, 128.4, 128.6 (2C), 129.9, 131.5, 131.8, 132.0,
132.2, 132.3, 132.9 (2C), 134.4, 148.3. Anal. Calcd for C30H18ClN: C,
84.20; H, 4.24; N, 3.27. Found: C, 84.24; H, 4.24; N, 3.22.
1-Ethynyl-2-(pent-1-yn-1-yl)benzene (S1). To a solution of 6 (1.9 g,
7.7 mmol) in THF (15 mL) were successively added diisopropyl-
amine (5.4 mL, 38 mmol), CuI (44 mg, 0.23 mmol), PdCl2(PhCN)2
(88 mg, 0.23 mmol), P(t-Bu)3 (0.11 mL, 0.46 mmol), and pent-1-yne
(1.1 mL, 11 mmol) at room temperature under argon. The mixture
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was stirred at room temperature for 24 h. The mixture was filtered
through a pad of Celite. The filtrate was concentrated under reduced
pressure. The residue was dissolved in THF (15 mL), and TBAF (1 M
solution in THF; 9.2 mL, 9.2 mmol) was added to the mixture at 0 °C.
The mixture was stirred at 0 °C for 0.5 h and quenched by addition of
saturated aqueous NH4Cl and brine, dried over Na2SO4, filtrated, and
concentrated in vacuo. The residue was purified by column
chromatography over silica gel with hexane−EtOAc (100:1) to afford
7.46 (d, J = 7.4 Hz, 1H), 7.51 (d, J = 6.9 Hz, 1H), 7.58−7.60 (m, 2H),
7.65 (s, 1H). 13C NMR (125 MHz, CDCl3) δ: 13.4, 21.5, 22.0, 79.3,
87.8, 91.8, 92.2, 95.2, 95.7, 99.7, 107.8, 113.7, 119.4, 124.8, 124.9,
125.3, 126.7, 127.3, 128.3, 128.4, 128.5, 131.5, 132.0, 132.1, 132.3,
133.3, 136.0, 151.4. Anal. Calcd for C28H20N2: C, 87.47; H, 5.24; N,
7.29. Found: C, 87.56; H, 5.46; N, 7.29.
5-Chloro-2-[(2-{[2-(pent-1-yn-1-yl)phenyl]ethynyl}phenyl)-
ethynyl]aniline (9m). By a procedure identical to that described for
the preparation of 9a, 5-chloro-2-iodoaniline (0.16 g, 0.62 mmol) was
converted into 9m (0.20 g, 84% yield) using S2 (0.20 g, 0.74 mmol):
pale yellow oil. IR (neat): 3481 (NH), 3383 (NH), 2250 (CC),
1
S1 quantitatively as an orange oil. IR (neat): 2251 (CC) cm−1. H
NMR (500 MHz, CDCl3) δ: 1.08 (t, J = 6.9 Hz, 3H), 1.64−1.67 (m,
2H), 2.45 (t, J = 6.9 Hz, 2H), 3.27 (s, 1H), 7.19−7.27 (m, 2H), 7.40
(d, J = 7.4 Hz, 1H), 7.47 (d, J = 7.4 Hz, 1H). 13C NMR (125 MHz,
CDCl3) δ: 13.5, 21.6, 22.1, 79.2, 80.4, 82.4, 94.9, 124.4, 127.1 (2C),
128.4, 131.9, 132.4. HRMS (FAB) calcd for C13H12 [MH+] 169.1017;
found: 169.1016.
1
2204 (CC) cm−1. H NMR (400 MHz, CDCl3) δ: 0.96 (t, J = 7.3
Hz, 3H), 1.51−1.60 (m, 2H), 2.36 (t, J = 7.1 Hz, 2H), 4.47 (br s, 2H),
6.63−6.65 (m, 2H), 7.23−7.35 (m, 5H), 7.44−7.46 (m, 1H), 7.49−
7.61 (m, 3H). 13C NMR (125 MHz, CDCl3) δ: 13.5, 21.5, 22.1, 79.4,
89.5, 92.0, 92.1, 94.4, 95.5, 106.0, 113.7, 117.6, 125.1 (2C), 125.5,
126.7, 127.2, 127.8, 128.2, 128.3, 131.3, 131.9, 132.1, 132.3, 132.8,
135.5, 149.2. HRMS (FAB) calcd for C27H20ClN [M+] 393.1284;
found: 393.1288.
1-Ethynyl-2-{[2-(pent-1-yn-1-yl)phenyl]ethynyl}benzene (S2). To
a solution of 6 (1.0 g, 4.0 mmol) in THF (10 mL) were successively
added diisopropylamine (2.8 mL, 20 mmol), CuI (23 mg, 0.12 mmol),
PdCl2(PhCN)2 (46 mg, 0.12 mmol), P(t-Bu)3 (0.058 mL, 0.24 mmol),
and S1 (0.70 g, 4.2 mmol) at room temperature under argon. The
mixture was stirred at room temperature for 18 h. The mixture was
filtered through a pad of Celite. The filtrate was concentrated under
reduced pressure. The residue was dissolved in THF (10 mL), and
TBAF (1 M solution in THF; 4.2 mL, 4.2 mmol) was added to the
mixture at 0 °C. The mixture was stirred at 0 °C for 1 h and quenched
by addition of saturated aqueous NH4Cl and brine, dried over Na2SO4,
filtrated, and concentrated in vacuo. The residue was purified by
column chromatography over silica gel with hexane−EtOAc (100:1)
to afford S2 (0.94 g, 88% yield in two steps) as an orange oil. IR
({2-[(2-Bromophenyl)ethynyl]phenyl}ethynyl)trimethylsilane
(S4). A mixture of S3 (2.9 g, 9.7 mmol), CuI (46 mg, 0.24 mmol),
PdCl2(PPh3)2 (0.17 g, 0.24 mmol), Et3N (6.8 mL, 49 mmol), and
1-bromo-2-ethynylbenzene (2.1 g, 12 mmol) in THF (20 mL) was
stirred at room temperature for 1 h under argon. The mixture was filtered
through a pad of Celite. The filtrate was concentrated under reduced
pressure, and the residue was purified by column chromatography over
silica gel with hexane−EtOAc (100:1) to afford S4 (3.41 g, quant) as a
colorless oil. IR (neat): 2156 (CC) cm−1. 1H NMR (400 MHz,
CDCl3) δ: 0.26 (s, 9H), 7.18 (ddd, J = 7.7, 7.7, 1.5 Hz, 1H), 7.27−7.32
(m, 3H), 7.50−7.52 (m, 1H), 7.56−7.63 (m, 3H). 13C NMR (100 MHz,
CDCl3) δ: 0.0 (3C), 91.7, 92.5, 98.8, 103.4, 125.4, 125.51, 125.54, 125.6,
126.9, 128.18, 128.21, 129.5, 132.1, 132.4, 132.5, 133.6. HRMS (FAB)
calcd for C19H17BrSi [M+] 352.0283; found: 352.0290.
1
(neat): 2226 (CC) cm−1. H NMR (400 MHz, CDCl3) δ: 1.05 (t,
J = 7.4 Hz, 3H), 1.63−1.70 (m, 2H), 2.46 (t, J = 7.4 Hz, 2H), 3.33 (s,
1H), 7.24−7.35 (m, 4H), 7.43−7.44 (m, 1H), 7.53−7.55 (m, 3H). 13
C
NMR (125 MHz, CDCl3) δ: 13.6, 21.7, 22.2, 79.5, 81.1, 82.2, 91.0,
92.6, 94.8, 124.5, 125.5, 126.49, 126.53, 127.2, 127.9, 128.1, 128.4,
131.9, 132.0, 132.2, 132.6. HRMS (FAB) calcd for C21H16 [M+]
268.1252; found: 268.1248.
4-Methyl-2-[(2-{[2-(pent-1-yn-1-yl)phenyl]ethynyl}phenyl)-
ethynyl]aniline (9j). By a procedure identical to that described for the
preparation of 9a, 2-iodo-4-methylaniline (0.14 g, 0.62 mmol) was
converted into 9j (0.20 g, 88% yield) using S2 (0.20 g, 0.74 mmol):
pale brown oil. IR (neat): 3465 (NH), 3378 (NH), 2197 (CC)
cm−1. 1H NMR (500 MHz, CDCl3) δ: 0.97 (t, J = 7.2 Hz, 3H), 1.53−
1.60 (m, 2H), 2.20 (s, 3H), 2.37 (t, J = 6.9 Hz, 2H), 4.26 (br s, 2H),
6.57 (d, J = 8.6 Hz, 1H), 6.93 (d, J = 8.6 Hz, 1H), 7.20−7.33 (m, 5H),
7.44 (d, J = 6.9 Hz, 1H), 7.55−7.57 (m, 3H). 13C NMR (125 MHz,
CDCl3) δ: 13.5, 20.2, 21.6, 22.1, 79.4, 90.8, 92.1 (2C), 93.4, 95.4,
107.6, 114.2, 125.2, 125.3, 125.9, 126.65, 126.72, 127.2, 127.5, 128.1,
128.2, 130.8, 131.3, 131.9, 132.1, 132.2 (2C), 146.1. HRMS (FAB)
calcd for C28H24N [MH]+ 374.1909; found: 374.1910.
4-Chloro-2-[(2-{[2-(pent-1-yn-1-yl)phenyl]ethynyl}phenyl)-
ethynyl]aniline (9k). By a procedure identical to that described for
the preparation of 9a, 4-chloro-2-iodoaniline (0.16 g, 0.69 mmol) was
converted into 9k (0.20 g, 74% yield) using S2 (0.19 g, 0.73 mmol):
yellow oil. IR (neat): 3482 (NH), 3381 (NH), 2204 (CC) cm−1. 1H
NMR (500 MHz, CDCl3) δ: 0.96 (t, J = 7.4 Hz, 3H), 1.54−1.57 (m,
2H), 2.36 (t, J = 7.2 Hz, 2H), 4.40 (br s, 2H), 6.56 (d, J = 8.6 Hz, 1H),
7.05 (dd, J = 8.6, 2.3 Hz, 1H), 7.27−7.31 (m, 5H), 7.45 (d, J = 8.0 Hz,
1H), 7.52−7.60 (m, 3H). 13C NMR (125 MHz, CDCl3) δ: 13.5, 21.6,
22.1, 79.4, 89.1, 91.9, 92.2, 94.6, 95.5, 108.8, 115.1, 121.7, 125.1, 125.3,
126.7, 127.3 (2C), 128.0, 128.2, 128.3, 129.8, 131.0, 131.4, 131.9,
132.2, 132.3, 147.0. HRMS (FAB) calcd for C27H21ClN [MH+]
394.1363; found: 394.1358.
({2-[(2-Iodophenyl)ethynyl]phenyl}ethynyl)trimethylsilane (10).
To a stirred solution of S4 (4.8 g, 14 mmol) in anhydrous Et2O (70
mL) was added dropwise a solution of n-BuLi (1.6 M in hexane; 9.8
mL, 16 mmol) at −78 °C under argon. The reaction mixture was
stirred at −78 °C for 1 h, and a solution of I2 (4.8 g, 19 mmol) in
anhydrous Et2O (80 mL) was added dropwise to the mixture. The
reaction mixture was stirred at −78 °C for 3 h, then warmed to room
temperature, and stirred overnight. The mixture was quenched by the
addition of 5% aqueous Na2S2O3, washed with H2O (3×), dried over
Na2SO4, filtrated, and concentrated in vacuo. The residue was purified
by column chromatography over silica gel with hexane−EtOAc
(100:1) to afford 10 (5.1 g, 94% yield) as a colorless oil. IR (neat):
1
2159 (CC) cm−1. H NMR (400 MHz, CDCl3) δ: 0.26 (s, 9H),
7.01 (ddd, J = 7.7, 7.7, 1.7 Hz, 1H), 7.30−7.32 (m, 3H), 7.52−7.59
(m, 3H), 7.88 (d, J = 8.0 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ:
0.0 (3C), 91.7, 95.1, 98.8, 100.7, 103.4, 125.4, 125.6, 127.7, 128.2,
129.4, 129.9, 131.7, 132.1, 132.4, 132.8, 138.7. HRMS (FAB) calcd for
C19H18ISi [MH+] 401.0222; found: 401.0229.
2-{[2-({2-[(2-Ethynylphenyl)ethynyl]phenyl}ethynyl)phenyl]-
ethynyl}aniline (11). A mixture of 10 (1.0 g, 2.6 mmol), CuI (12 mg,
0.064 mmol), PdCl2(PPh3)2 (45 mg, 0.064 mmol), Et3N (1.8 mL,
13 mmol), and 7 (0.58 g, 2.7 mmol) in THF (5.0 mL) was stirred at
room temperature for 3 h under argon. The mixture was filtered
through a pad of Celite. The filtrate was concentrated under reduced
pressure, and the residue was purified by column chromatography over
silica gel with hexane−EtOAc (5:1) to afford 2-[(2-{[2-({2-[(trimethyl-
silyl)ethynyl]phenyl}ethynyl)phenyl]ethynyl}phenyl)ethynyl]aniline (S5)
(0.95 g, 77% yield) as a brown amorphous solid.
4-Amino-3-[(2-{[2-(pent-1-yn-1-yl)phenyl]ethynyl}phenyl)-
ethynyl]benzonitrile (9l). By a procedure identical to that described
for the preparation of 9a, 4-amino-3-iodobenzonitrile (0.16 g, 0.66
mmol) was converted into 9l (0.25 g, 99% yield) using S2 (0.21 g,
0.79 mmol): pale brown solid; mp 137−138 °C. IR (neat): 3476
(NH), 3364 (NH), 2220 (CC) cm−1. 1H NMR (500 MHz, CDCl3)
δ: 0.95 (t, J = 7.4 Hz, 3H), 1.52−1.55 (m, 2H), 2.35 (t, J = 6.9 Hz,
2H), 4.92 (br s, 2H), 6.62 (d, J = 8.6 Hz, 1H), 7.27−7.36 (m, 5H),
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Compound S5: IR (neat): 3485 (NH), 3382 (NH), 2252 (CC),
ethynyl}phenyl)ethynyl]phenyl}ethynyl)aniline (S6) (2.7 g, 83%
yield) as a pale brown amorphous solid.
1
2211 (CC), 2158 (CC) cm−1. H NMR (500 MHz, CDCl3) δ:
0.23 (s, 9H), 4.43 (br s, 2H), 6.64 (d, J = 8.0 Hz, 1H), 6.65 (dd, J =
8.0, 8.0 Hz, 1H), 7.09 (dd, J = 7.7, 7.7 Hz, 1H), 7.17−7.35 (m, 7H),
7.46−7.48 (m, 2H), 7.56−7.63 (m, 4H). 13C NMR (125 MHz,
CDCl3) δ: 0.0 (3C), 90.6, 91.9, 92.0, 92.7, 93.0, 93.7, 98.7, 103.5,
107.5, 114.1 (2C), 117.5, 125.1, 125.5, 125.8, 125.9, 126.0, 127.7,
128.0, 128.20 (2C), 128.22, 128.3, 129.9, 131.5, 132.0, 132.1, 132.15,
132.18, 132.3, 132.6, 148.4. HRMS (FAB) calcd for C35H28NSi [MH+]
490.1991; found: 490.1991.
To a solution of S5 (0.94 g, 1.9 mmol) in THF (4.0 mL) was added
TBAF (1 M solution in THF; 2.3 mL, 2.3 mmol) at 0 °C. The mixture
was stirred at 0 °C for 2.5 h and quenched by addition of saturated
aqueous NH4Cl and brine, dried over Na2SO4, filtrated, and
concentrated in vacuo. The residue was purified by column
chromatography over silica gel with hexane−EtOAc (5:1) to afford
11 (0.79 g, 98% yield) as a brown oil.
Compound S6: IR (neat): 3484 (NH), 3384 (NH), 2210 (CC),
1
2158 (CC) cm−1. H NMR (500 MHz, CDCl3) δ: 0.23 (s, 9H),
4.43 (br s, 2H), 6.63 (d, J = 7.4 Hz, 1H), 6.65 (dd, J = 6.9, 6.9 Hz,
1H), 7.09 (dd, J = 7.4, 7.4 Hz, 1H), 7.20−7.35 (m, 9H), 7.50−7.59
(m, 8H). 13C NMR (125 MHz, CDCl3) δ: 0.0 (3C), 90.6, 91.9, 92.18,
92.24, 92.3, 92.8, 93.0, 93.7, 98.6, 103.5, 107.6, 114.1, 117.5, 125.0,
125.4, 125.5, 125.6, 125.7, 125.8, 126.0, 126.1, 127.7, 128.0, 128.06,
128.09, 128.18 (2C), 128.24, 128.3, 129.9, 131.4, 131.9, 132.0, 132.1,
132.2 (2C), 132.4, 132.4, 132.5, 148.3. HRMS (FAB) calcd for
C43H32NSi [MH+] 590.2304; found: 590.2297.
To a solution of S6 (2.7 g, 4.5 mmol) in THF (10 mL) was added
TBAF (1 M solution in THF; 5.4 mL, 5.4 mmol) at 0 °C. The mixture
was stirred at 0 °C for 0.5 h and quenched by addition of saturated
aqueous NH4Cl and brine, dried over Na2SO4, filtrated, and
concentrated in vacuo. The residue was purified by column
chromatography over silica gel with hexane−EtOAc (5:1) to afford
13 (2.3 g, 97% yield) as a brown amorphous solid.
Compound 11: IR (neat): 3480 (NH), 3380 (NH), 3293 (C
CH), 2248 (CC), 2210 (CC) cm−1
.
1H NMR (500 MHz,
CDCl3) δ: 3.18 (s, 1H), 4.41 (br s, 2H), 6.62 (d, J = 8.0 Hz, 1H), 6.64
(dd, J = 6.3, 6.3 Hz, 1H), 7.08 (dd, J = 7.7, 7.7 Hz, 1H), 7.25−7.33
(m, 7H), 7.47−7.51 (m, 2H), 7.58−7.62 (m, 4H). 13C NMR (125
MHz, CDCl3) δ: 81.4, 82.0, 90.7, 91.8, 92.0, 92.2, 92.8, 93.6, 107.4,
114.0, 117.5, 124.4, 125.0, 125.3, 125.7, 125.8, 126.1, 127.6, 128.0,
128.2, 128.26, 128.29, 128.4, 129.9, 131.4, 131.9, 132.2, 132.40,
132.42, 132.5, 132.6, 148.3. HRMS (FAB) calcd for C32H20N [MH+]
418.1596; found: 418.1588.
Compound 13: IR (neat): 3476 (NH), 3381 (NH), 2252 (CC),
1
2210 (CC) cm−1. H NMR (400 MHz, CDCl3) δ: 3.19 (s, 1H),
4.43 (br s, 2H), 6.62−6.67 (m, 2H), 7.09 (dd, J = 7.8, 7.8 Hz, 1H),
7.22−7.27 (m, 6H), 7.32−7.36 (m, 3H), 7.47−7.64 (m, 8H). 13C
NMR (125 MHz, CDCl3) δ: 81.3, 82.1, 90.5, 91.8, 91.9, 92.16, 92.22,
92.7, 93.0, 93.7, 107.5, 114.0, 117.5, 124.4, 124.9, 125.47, 125.51,
125.6, 125.7, 126.0, 126.3, 127.6, 128.0, 128.08, 128.13 (2C), 128.2
(2C), 128.4, 129.8, 131.3, 131.9, 132.2, 132.27, 132.28, 132.32, 132.4,
132.5 (2C), 148.3. HRMS (FAB) calcd for C40H24N [MH+] 518.1909;
found: 518.1904.
2-({2-[(2-{[2-(Phenylethynyl)phenyl]ethynyl}phenyl)ethynyl]-
phenyl}ethynyl)aniline (12). A mixture of 11 (0.78 g, 1.9 mmol), CuI
(8.5 mg, 0.045 mmol), PdCl2(PPh3)2 (31 mg, 0.045 mmol), Et3N (1.2
mL, 8.9 mmol), and iodobenzene (0.20 mL, 1.8 mmol) in THF (4.0
mL) was stirred at room temperature for 2 h under argon. The mixture
was filtered through a pad of Celite. The filtrate was concentrated
under reduced pressure, and the residue was purified by column
chromatography over silica gel with hexane−EtOAc (5:1) to afford 12
(0.83 g, 94% yield) as a brown amorphous solid. IR (neat): 3475
(NH), 3379 (NH), 2211 (CC) cm−1. 1H NMR (500 MHz, CDCl3)
δ: 4.42 (s, 2H), 6.61 (d, J = 8.6 Hz, 1H), 6.64 (dd, J = 8.6, 8.6 Hz,
1H), 7.08 (dd, J = 7.7, 7.7 Hz, 1H), 7.19−7.34 (m, 10H), 7.51−7.61
(m, 8H). 13C NMR (125 MHz, CDCl3) δ: 88.3, 90.5, 91.8, 92.1, 92.7,
93.0, 93.7 (2C), 107.5, 114.0, 117.5, 123.2, 125.0, 125.4, 125.6, 125.68,
125.71, 126.0, 127.6, 127.9, 128.12, 128.14, 128.18, 128.25 (3C),
128.3, 129.8, 131.3, 131.6 (2C), 131.7, 131.9, 132.1, 132.2, 132.3,
132.5, 148.3. HRMS (FAB) calcd for C38H24N [MH+] 494.1909;
found: 494.1915.
Synthesis of 2-({2-[(2-Ethynylphenyl)ethynyl]phenyl}ethynyl)-
aniline (9d) from 5. A mixture of 10 (1.6 g, 4.0 mmol), CuI (19
mg, 0.10 mmol), PdCl2(PPh3)2 (0.070 g, 0.10 mmol), Et3N (2.8 mL,
20 mmol), and 5 (0.56 g, 4.8 mmol) in THF (10 mL) was stirred at
room temperature for 3 h under argon. The mixture was filtered
through a pad of Celite. The filtrate was concentrated under reduced
pressure, and the residue was purified by column chromatography over
silica gel with hexane−EtOAc (10:1) to afford 2-[(2-[(2-[(trimethylsilyl)-
ethynyl]phenyl)ethynyl]phenyl)ethynyl]aniline (1.2 g, 79% yield) as a
brown oil. To a solution of this compound (1.2 g, 3.2 mmol) in THF
(6 mL) was added TBAF (1 M solution in THF; 3.8 mL, 3.8 mmol) at
0 °C. The mixture was stirred at 0 °C for 0.5 h and quenched by addition
of saturated aqueous NH4Cl and brine, dried over Na2SO4, filtrated, and
concentrated in vacuo. The residue was purified by column
chromatography over silica gel with hexane−EtOAc (5:1) to afford 9d
(1.0 g, 77% yield in two steps) as a brown oil.
2-{[2-({2-[(2-{[2-(Phenylethynyl)phenyl]ethynyl}phenyl)ethynyl]-
phenyl}ethynyl)phenyl]ethynyl}aniline (14). A mixture of 13 (0.31 g,
0.60 mmol), CuI (2.7 mg, 0.014 mmol), PdCl2(PPh3)2 (10 mg, 0.014
mmol), Et3N (0.40 mL, 2.8 mmol), and iodobenzene (0.064 mL, 0.57
mmol) in THF (1.2 mL) was stirred at room temperature for 6 h
under argon. The mixture was filtered through a pad of Celite. The
filtrate was concentrated under reduced pressure, and the residue was
purified by column chromatography over silica gel with hexane−
EtOAc (5:1) to afford 14 (0.29 g, 99% yield) as a brown amorphous
solid. IR (neat): 3479 (NH), 3380 (NH), 2252 (CC), 2212 (CC)
1
cm−1. H NMR (500 MHz, CDCl3) δ: 4.40 (s, 2H), 6.62 (d, J = 8.6
Hz, 1H), 6.64 (dd, J = 7.4, 7.4 Hz, 1H), 7.08 (dd, J = 7.7, 7.7 Hz, 1H),
7.20−7.28 (m, 11H), 7.33 (d, J = 6.3 Hz, 1H), 7.50−7.58 (m, 10H).
13C NMR (125 MHz, CDCl3) δ: 88.4, 90.5, 91.9, 92.2, 92.3, 92.4, 92.7,
92.9, 93.6, 93.7, 107.6, 114.0, 117.5, 123.3, 125.0, 125.4, 125.55, 125.65,
125.66, 125.7, 125.9, 127.6, 127.9, 128.02, 128.05, 128.07, 128.09, 128.13,
128.15, 128.22 (2C), 128.3, 129.8, 131.3, 131.7 (2C), 131.7, 131.9, 132.0,
132.1, 132.21, 132.24, 132.3, 132.47, 132.48, 148.3. HRMS (FAB) calcd
for C46H28N [MH+] 594.2222; found: 594.2227.
2-[(2-{[2-({2-[(2-Ethynylphenyl)ethynyl]phenyl}ethynyl)phenyl]-
ethynyl}phenyl)ethynyl]aniline (13). A mixture of 10 (2.2 g, 5.5
mmol), CuI (26 mg, 0.14 mmol), PdCl2(PPh3)2 (97 mg, 0.14 mmol),
Et3N (3.8 mL, 28 mmol), and 9d (2.1 g, 6.6 mmol) in THF (10 mL)
was stirred at room temperature for 5.5 h under argon. The mixture
was filtered through a pad of Celite. The filtrate was concentrated
under reduced pressure, and the residue was purified by column
chromatography over silica gel with hexane−EtOAc (7:1) to afford 2-
({2-[(2-{[2-({2-[(trimethylsilyl)ethynyl]phenyl}ethynyl)phenyl]-
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Article
3-Bromo-2-(pent-1-yn-1-yl)thiophene (S7). To a solution of 2,3-
dibromothiophene (0.52 mL, 4.6 mmol) in Et3N (6 mL) were
successively added CuI (54 mg, 0.28 mmol), PdCl2(PPh3)2 (0.10 g,
0.15 mmol), and pent-1-yne (0.52 mL, 5.5 mmol) at room
temperature under argon. The mixture was stirred at 80 °C for
18 h. The mixture was filtered through a pad of Celite. The filtrate was
concentrated under reduced pressure, and the residue was purified by
column chromatography over silica gel with hexane−EtOAc (400:1)
to afford S7 (0.56 g, 53% yield) as an orange oil. IR (neat): 2250
2.4 mmol), and 1-bromo-2-iodobenzene (0.062 mL, 0.49 mmol) in
THF (1.0 mL) was stirred at room temperature for 2 h under argon.
The mixture was filtered through a pad of Celite. The filtrate was
concentrated under reduced pressure, and the residue was purified by
column chromatography over silica gel with hexane−EtOAc (5:1) to
afford 2-[(2-[(2-bromophenyl)ethynyl]thiophen-3-yl)ethynyl]aniline
(0.15 g, 81% yield) as an orange oil. To a solution of this compound
(0.14 g, 0.38 mmol) in piperidine (1 mL) were successively added CuI
(7.3 mg, 0.038 mmol), PdCl2(PPh3)2 (27 mg, 0.038 mmol), and pent-
1-yne (0.11 mL, 1.1 mmol) at room temperature under argon. The
mixture was stirred at 80 °C for 13 h and quenched by the addition of
saturated aqueous NH4Cl at room temperature. The aqueous mixture
was extracted with EtOAc, and the layers were separated. The organic
layer was washed with brine, dried over Na2SO4, filtrated, and
concentrated in vacuo. The residue was purified by column
chromatography over silica gel with hexane−EtOAc (10:1) to afford
18 (0.10 g, 59% yield in two steps) as an orange oil. IR (neat): 3482
(NH), 3379 (NH), 2198 (CC) cm−1. 1H NMR (500 MHz, CDCl3)
δ: 1.00 (t, J = 7.2 Hz, 3H), 1.56−1.64 (m, 2H), 2.38 (t, J = 6.9 Hz,
2H), 4.40 (s, 2H), 6.68 (d, J = 6.6 Hz, 1H), 6.69 (dd, J = 6.6, 6.6 Hz,
1H), 7.10−7.14 (m, 2H), 7.21−7.29 (m, 3H), 7.36 (d, J = 8.0 Hz,
1H), 7.43 (d, J = 6.6 Hz, 1H), 7.52 (d, J = 6.6 Hz, 1H). 13C NMR
(125 MHz, CDCl3) δ: 13.6, 21.6, 22.1, 79.3, 85.5, 89.5, 90.4, 95.7,
96.3, 107.5, 114.1, 117.6, 125.0, 125.5, 126.4, 126.7, 126.9, 127.3,
128.4, 129.0, 129.9, 131.7, 131.8, 132.0, 148.2. HRMS (FAB) calcd for
C25H20NS [MH+] 366.1316; found: 366.1316.
General Procedure for Synthesis of Fused Carbazoles by
Tricyclization: Synthesis of 6-Propyl-11H-benzo[a]naphtho[2,1-c]-
carbazole (15a) (Table 1, Entry 12) and 6-[2-(Pent-1-ynyl)phenyl]-
11H-benzo[a]carbazole (16a) (Table 1, Entry 1). To a stirred
solution of aniline 9a (70 mg, 0.19 mmol) in AcOH (0.57 mL) under
argon was added a suspension of JohnPhosAuCl (5.1 mg, 9.7 μmol, 5
mol %) and AgBF4 (1.9 mg, 9.7 μmol, 5 mol %) in AcOH (0.4 mL) at
room temperature. The mixture was stirred at 80 °C for 0.5 h. The
reaction mixture was diluted with EtOAc, washed with saturated
aqueous NH4Cl and brine, dried over Na2SO4, filtrated, and
concentrated in vacuo. The residue was purified by column
chromatography over amino silica gel with hexane/Et2O (1:1) to
afford 15a (51 mg, 73% yield). On the other hand, the reaction of 9a
(47 mg, 0.13 mmol) with Ph3PAuCl (3.3 mg, 6.6 μmol, 5 mol %)/
AgOTf (1.7 mg, 6.6 μmol, 5 mol %) in MeCN (0.7 mL) for 2 h gave
16a (13 mg, 28% yield).
1
(CC) cm−1. H NMR (400 MHz, CDCl3) δ: 1.07 (t, J = 7.3 Hz,
3H), 1.64−1.67 (m, 2H), 2.45 (t, J = 7.0 Hz, 2H), 6.92 (d, J = 5.4 Hz,
1H), 7.10 (d, J = 5.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 13.5,
21.8, 21.9, 72.4, 98.8, 114.9, 121.7, 125.7, 129.8. HRMS (FAB) calcd
for C9H9BrS [M+] 227.9608; found: 227.9606.
2-[(2-{[2-(Pent-1-yn-1-yl)thiophen-3-yl]ethynyl}phenyl)ethynyl]-
aniline (17). To a solution of S7 (0.55 g, 2.4 mmol) in THF (5 mL)
were successively added diisopropylamine (1.7 mL, 12 mmol), CuI
(27 mg, 0.14 mmol), PdCl2(PhCN)2 (0.55 g, 0.14 mmol), P(t-Bu)3
(0.070 mL, 0.29 mmol), and 7 (0.54 g, 2.5 mmol) at room
temperature under argon. The mixture was stirred at room
temperature for 15 h. The mixture was filtered through a pad of
Celite. The filtrate was concentrated under reduced pressure, and the
residue was purified by column chromatography over silica gel with
hexane−EtOAc (10:1) to afford 17 (0.77 g, 88% yield) as a brown oil.
1
IR (neat): 3421 (NH), 3377 (NH), 2209 (CC) cm−1. H NMR
(500 MHz, CDCl3) δ: 0.98 (t, J = 7.4 Hz, 3H), 1.53−1.56 (m, 2H),
2.34 (t, J = 7.2 Hz, 2H), 4.43 (br s, 2H), 6.68 (d, J = 7.4 Hz, 1H), 6.68
(dd, J = 7.4, 7.4 Hz, 1H), 7.06−7.14 (m, 3H), 7.27−7.34 (m, 2H),
7.38 (d, J = 8.0 Hz, 1H), 7.56 (dd, J = 6.6, 6.6 Hz, 2H). 13C NMR
(125 MHz, CDCl3) δ: 13.5, 21.8, 21.9, 73.0, 87.6, 90.6, 91.8, 93.7,
99.8, 107.6, 114.1, 117.5, 124.7, 125.0, 125.3, 125.8, 127.6, 127.8,
128.2, 129.6, 129.9, 131.3, 131.9, 132.3, 148.4. HRMS (FAB) calcd for
C25H19NS [M]+ 365.1238; found: 365.1236.
[(3-Bromothiophen-2-yl)ethynyl]trimethylsilane (S8). To a sol-
ution of 2,3-dibromothiophene (0.52 mL, 4.6 mmol) in Et3N (6 mL)
were successively added CuI (54 mg, 0.28 mmol), PdCl2(PPh3)2 (0.10
g, 0.15 mmol), and TMS−acetylene (0.76 mL, 5.5 mmol) at room
temperature under argon. The mixture was stirred at 80 °C for 16 h.
The mixture was filtered through a pad of Celite. The filtrate was
concentrated under reduced pressure, and the residue was purified by
column chromatography over silica gel with hexane−EtOAc (400:1)
to afford S8 (0.67 g, 57% yield) as an orange oil. IR (neat): 2149
(CC) cm−1. 1H NMR (400 MHz, CDCl3) δ: 0.27 (s, 9H), 6.93 (dd,
J = 5.4, 0.5 Hz, 1H), 7.17 (dd, J = 5.4, 0.5 Hz, 1H). 13C NMR (100
MHz, CDCl3) δ: 0.0 (3C), 95.7, 103.7, 116.9, 121.0, 127.2, 130.2;
HRMS (FAB) calcd for C9H11BrSSi [M+] 257.9534; found: 257.9534.
2-[(2-Ethynylthiophen-3-yl)ethynyl]aniline (S9). To a solution of
S8 (1.2 g, 4.8 mmol) in THF (12 mL) were successively added
diisopropylamine (3.3 mL, 24 mmol), CuI (55 mg, 0.29 mmol),
PdCl2(PhCN)2 (0.11 g, 0.29 mmol), P(t-Bu)3 (0.14 mL, 0.57 mmol),
and 5 (0.67 g, 5.7 mmol) at room temperature under argon. The
mixture was stirred at 60 °C for 16 h. The mixture was filtered through
a pad of Celite. The filtrate was concentrated under reduced pressure.
The residue was dissolved in THF (10 mL), and TBAF (1 M solution
in THF; 5.7 mL, 5.7 mmol) was added to the mixture at 0 °C. The
mixture was stirred at 0 °C for 0.5 h and quenched by addition of
saturated aqueous NH4Cl and brine, dried over Na2SO4, filtrated, and
concentrated in vacuo. The residue was purified by column
chromatography over silica gel with hexane−EtOAc (5:1) to afford
S9 (0.43 g, 40% yield in two steps) as a brown oil. IR (neat): 3376
Compound 15a: a brown amorphous solid. IR (neat): 3422 (NH)
cm−1. 1H NMR (500 MHz, CDCl3) δ: 1.01 (t, J = 7.2 Hz, 3H), 1.88−
1.96 (m, 2H), 3.43 (t, J = 8.0 Hz, 2H), 7.20 (dd, J = 7.2, 7.2 Hz, 1H),
7.38 (dd, J = 7.7, 7.7 Hz, 1H), 7.51−7.61 (m, 5H), 7.76 (s, 1H), 7.92
(d, J = 8.0 Hz, 1H), 8.13 (d, J = 6.9 Hz, 1H), 8.41 (d, J = 8.6 Hz, 1H),
8.60 (d, J = 8.0 Hz, 1H), 8.88 (br s, 1H), 8.97 (d, J = 8.0 Hz, 1H). 13
C
NMR (125 MHz, CDCl3) δ: 14.3, 24.7, 39.6, 111.2, 113.9, 119.5,
120.8, 122.1, 123.2, 123.6, 124.2, 125.0, 125.2, 125.4, 125.7, 126.1,
126.4, 126.5, 127.8, 128.38, 128.43, 129.1, 130.3, 131.9, 134.8, 137.6,
138.7. HRMS (FAB) calcd for C27H21N [M+] 359.1674; found:
359.1665.
Compound 16a: a brown amorphous solid. IR (neat): 3440 (NH),
1
2252 (CC) cm−1. H NMR (400 MHz, CDCl3) δ: 0.32 (t, J = 7.6
Hz, 3H), 0.83−0.92 (m, 2H), 1.85 (t, J = 6.6 Hz, 2H), 7.02 (dd, J =
7.8, 7.8 Hz, 1H), 7.19 (d, J = 6.9 Hz, 1H), 7.34 (dd, J = 7.8, 7.8 Hz,
1H), 7.42−7.47 (m, 2H), 7.52−7.57 (m, 4H), 7.59−7.66 (m, 2H),
8.00 (d, J = 8.2 Hz, 1H), 8.18 (d, J = 8.2 Hz, 1H), 8.86 (br s, 1H). 13
C
NMR (125 MHz, CDCl3) δ: 12.6, 21.1, 21.4, 79.9, 93.6, 110.6, 117.5,
119.6, 120.26, 120.30, 121.2, 122.0, 124.0, 124.1, 124.4, 125.27,
125.32, 127.4, 127.5, 128.9, 130.0, 132.0, 132.2, 134.9, 135.2, 138.6,
143.2. HRMS (FAB) calcd for C27H21N [M+] 359.1674; found:
359.1676.
1
(NH), 3299 (NH), 3015 (CCH), 2199 (CC) cm−1. H NMR
(400 MHz, CDCl3) δ: 3.62 (s, 1H), 4.41 (br s, 2H), 6.69−6.73 (m,
2H), 7.07 (d, J = 5.0 Hz, 1H), 7.15 (dd, J = 7.8, 7.8 Hz, 1H), 7.21 (d,
J = 5.5 Hz, 1H), 7.36 (dd, J = 7.8, 1.4 Hz, 1H). 13C NMR (100 MHz,
CDCl3) δ: 76.6, 85.2, 88.9, 90.4, 107.3, 114.3, 117.8, 124.0, 126.6,
128.3, 129.0, 130.0, 131.8, 148.0. HRMS (FAB) calcd for C14H9NS
[M+] 223.0456; found: 223.0464.
6-Cyclohexyl-11H-benzo[a]naphtho[2,1-c]carbazole (15b) (Table
2, Entry 2). By a procedure similar to that described for the
preparation of 15a, 9b (52 mg, 0.13 mmol) was converted into 15b
(36 mg, 70% yield) as a pale brown amorphous solid by treatment
with JohnPhosAuCl (3.5 mg, 6.5 μmol) and AgBF4 (1.3 mg, 6.5 μmol)
2-[(2-{[2-(Pent-1-yn-1-yl)phenyl]ethynyl}thiophen-3-yl)ethynyl]-
aniline (18). A mixture of S9 (0.11 g, 0.51 mmol), CuI (2.3 mg,
0.012 mmol), PdCl2(PPh3)2 (8.5 mg, 0.012 mmol), Et3N (0.34 mL,
in AcOH (0.81 mL) at 80 °C for 24 h. IR (neat): 3422 (NH) cm−1
.
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The Journal of Organic Chemistry
Article
1H NMR (500 MHz, CDCl3) δ: 1.41−1.45 (m, 3H), 1.79−1.91 (m,
6-(p-Tolyl)-11H-benzo[a]naphtho[2,1-c]carbazole (15h) (Table 2,
Entry 8). By a procedure similar to that described for the preparation
of 15a, 9h (49 mg, 0.12 mmol) was converted into 15h (29 mg, 60%
yield) as a pale brown solid by treatment with JohnPhosAuCl (3.3 mg,
6.0 μmol) and AgBF4 (1.2 mg, 6.0 μmol) in AcOH (0.75 mL) at 80 °C
5H), 2.09−2.12 (m, 2H), 3.72−3.75 (m, 1H), 7.22 (dd, J = 7.4, 7.4
Hz, 1H), 7.39 (dd, J = 7.4, 7.4 Hz, 1H), 7.51 (dd, J = 7.7, 7.7 Hz, 1H),
7.56−7.61 (m, 4H), 7.83 (s, 1H), 7.94 (d, J = 8.0 Hz, 1H), 8.16 (d, J =
7.4 Hz, 1H), 8.39 (d, J = 8.6 Hz, 1H), 8.43 (d, J = 8.0 Hz, 1H), 8.96
(d, J = 8.0 Hz, 1H), 9.01 (s, 1H). 13C NMR (125 MHz, CDCl3) δ:
26.4, 27.3 (2C), 36.4 (2C), 42.9, 111.2, 113.8, 119.5, 120.9, 122.2,
122.7, 123.1, 123.6, 124.2, 124.8, 125.2, 125.5, 125.6, 126.4, 126.6,
127.4, 128.2, 128.8, 128.9, 129.9, 131.9, 134.6, 138.7, 143.4. HRMS
(FAB) calcd for C30H25N [M+] 399.1987; found: 399.1993.
1
for 0.75 h: mp 241−243 °C. IR (neat): 3428 (NH) cm−1. H NMR
(500 MHz, CDCl3) δ: 2.44 (s, 3H), 7.12 (dd, J = 7.4, 7.4 Hz, 1H),
7.22−7.27 (m, 3H), 7.38 (d, J = 7.4 Hz, 2H), 7.43 (dd, J = 7.7, 7.7 Hz,
1H), 7.46 (dd, J = 7.4, 7.4 Hz, 1H), 7.60 (m, 3H), 7.75 (s, 1H), 7.88
(d, J = 8.6 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 8.11 (d, J = 7.4 Hz, 1H),
8.48 (d, J = 8.0 Hz, 1H), 9.03 (s, 1H), 9.06 (d, J = 8.0 Hz, 1H). 13C
NMR (125 MHz, CDCl3) δ: 21.2, 111.3, 113.5, 119.5, 120.5, 122.3,
123.2, 124.1, 124.3, 124.3, 125.4, 125.6, 126.8, 127.1, 127.2, 128.3,
128.6, 129.4 (2C), 129.5 (2C), 129.7, 130.0, 130.19, 130.20, 131.9,
135.4, 136.5, 138.5, 138.7, 142.6. HRMS (FAB) calcd for C31H21N
[M+] 407.1674; found: 407.1671.
6-[2-(3,3-Dimethylbut-1-yn-1-yl)phenyl]-11H-benzo[a]carbazole
(16c) (Table 2, Entry 3). By a procedure similar to that described for
the preparation of 15a, 9c (47 mg, 0.13 mmol) was converted into
biscyclization product 16c (33 mg, 72% yield) as a pale yellow
amorphous solid by treatment with JohnPhosAuCl (3.4 mg, 6.3 μmol)
and AgBF4 (1.2 mg, 6.3 μmol) in AcOH (0.78 mL) at 80 °C for 24 h.
1
IR (neat): 3430 (NH), 2250 (CC) cm−1. H NMR (500 MHz,
6-(4-Methoxyphenyl)-11H-benzo[a]naphtho[2,1-c]carbazole
(15i) (Table 2, Entry 9). By a procedure similar to that described for
the preparation of 15a, 9i (58 mg, 0.14 mmol) was converted into 15i
(27 mg, 47% yield) as white crystals by treatment with JohnPhosAuCl
(3.7 mg, 6.9 μmol) and AgBF4 (1.4 mg, 6.9 μmol) in AcOH (0.86 mL)
CDCl3) δ: 0.56 (s, 9H), 7.03 (dd, J = 7.7, 7.7 Hz, 1H), 7.28 (d, J = 8.0
Hz, 1H), 7.32 (dd, J = 7.7, 7.7 Hz, 1H), 7.42−7.44 (m, 2H), 7.51−
7.61 (m, 6H), 7.98 (d, J = 8.0 Hz, 1H), 8.14 (d, J = 8.0 Hz, 1H), 8.87
(s, 1H). 13C NMR (125 MHz, CDCl3) δ: 27.4, 30.0 (3C), 78.4, 102.0,
110.5, 117.6, 119.6, 120.2, 120.3, 121.2, 122.3, 124.1, 124.3, 124.4,
125.25, 125.31, 127.4, 127.5, 128.9, 129.8, 131.6, 132.0, 134.7, 135.3,
138.5, 143.5. HRMS (FAB) calcd for C28H23N [M+] 373.1830; found:
373.1833.
1
at 80 °C for 1 h: mp 293−295 °C. IR (neat): 3419 (NH) cm−1. H
NMR (500 MHz, CDCl3) δ: 3.89 (s, 3H), 6.97 (d, J = 8.6 Hz, 2H),
7.15 (dd, J = 7.7, 7.7 Hz, 1H), 7.27 (dd, J = 8.0 Hz, 1H), 7.41−7.46
(m, 3H), 7.51 (dd, J = 7.4, 7.4 Hz, 1H), 7.57−7.68 (m, 3H), 7.75 (s,
1H), 7.90 (d, J = 9.2 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 8.15 (d, J = 8.0
Hz, 1H), 8.49 (d, J = 8.0 Hz, 1H), 9.02 (s, 1H), 9.07 (d, J = 8.6 Hz,
1H). 13C NMR (125 MHz, CDCl3) δ: 55.3, 111.3, 113.5, 114.3 (2C),
119.5, 120.5, 122.3, 123.2, 124.2, 124.2, 124.3, 124.4, 125.3, 125.6,
126.8, 126.9, 127.2, 128.3, 128.5, 129.7, 129.8, 130.2, 130.6 (2C),
131.9, 135.4, 138.0, 138.2, 138.7, 158.8. HRMS (FAB) calcd for
C31H21NO [M+] 423.1623; found: 423.1630.
4-(11H-Benzo[a]naphtho[2,1-c]carbazol-6-yl)benzonitrile (15e)
(Table 2, Entry 5). By a procedure similar to that described for the
preparation of 15a, 9e (51 mg, 0.12 mmol) was converted into 15e
(39 mg, 77% yield) as a yellow solid by treatment with JohnPhosAuCl
(3.3 mg, 6.1 μmol) and AgBF4 (1.2 mg, 6.1 μmol) in AcOH (0.76 mL)
at 80 °C for 0.5 h: mp 199−200 °C. IR (neat): 3353 (NH), 2227
1
(CN) cm−1. H NMR (500 MHz, CDCl3) δ: 7.16 (dd, J = 8.0, 8.0
14-Methyl-6-propyl-11H-benzo[a]naphtho[2,1-c]carbazole (15j)
(Table 2, Entry 10). By a procedure similar to that described for
the preparation of 15a, 9j (57 mg, 0.15 mmol) was converted into 15j
(37 mg, 66% yield) as a pale brown amorphous solid by treatment
with JohnPhosAuCl (4.1 mg, 7.6 μmol) and AgBF4 (1.5 mg, 7.6 μmol)
Hz, 1H), 7.29 (dd, J = 7.7, 7.7 Hz, 1H), 7.47 (dd, J = 7.4, 7.4 Hz, 1H),
7.54 (dd, J = 7.4, 7.4 Hz, 1H), 7.60−7.73 (m, 9H), 8.01 (d, J = 8.6 Hz,
1H), 8.19 (d, J = 7.4 Hz, 1H), 8.48 (d, J = 8.0 Hz, 1H), 9.09 (s, 1H),
9.10 (d, J = 7.4 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ: 110.4,
111.5, 113.4, 119.1, 119.7, 120.8, 122.4, 122.8, 123.1, 124.5 (2C),
125.05, 125.09, 125.9, 127.1, 127.4, 127.5, 128.3, 128.8, 129.2, 129.8,
130.1, 130.2 (2C), 131.5, 132.5 (2C), 135.4, 136.4, 138.7, 150.1.
HRMS (FAB) calcd for C31H19N2 [MH+] 419.1548; found: 419.1549.
6-(4-Chlorophenyl)-11H-benzo[a]naphtho[2,1-c]carbazole (15f)
(Table 2, Entry 6). By a procedure similar to that described for the
preparation of 15a, 9f (51 mg, 0.12 mmol) was converted into 15f (35
mg, 68% yield) as brown crystals by treatment with JohnPhosAuCl
(3.3 mg, 6.0 μmol) and AgBF4 (1.2 mg, 6.0 μmol) in AcOH (0.75 mL)
in AcOH (0.76 mL) at 80 °C for 0.5 h. IR (neat): 3426 (NH) cm−1
.
1H NMR (500 MHz, CDCl3) δ: 0.99 (t, J = 7.4 Hz, 3H), 1.88−1.91
(m, 2H), 2.46 (s, 3H), 3.40 (t, J = 7.7 Hz, 2H), 7.17 (dd, J = 6.3, 6.3
Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.50−7.53 (m, 3H), 7.58 (dd, J =
7.4, 7.4 Hz, 1H), 7.73 (s, 1H), 7.90 (d, J = 8.0, 8.0 Hz, 1H), 8.03 (dd,
J = 7.2, 2.0 Hz, 1H), 8.19 (s, 1H), 8.56 (dd, J = 7.7, 2.0 Hz, 1H), 8.77
(s, 1H), 8.95 (d, J = 8.0 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ:
14.3, 21.8, 24.7, 39.5, 110.8, 113.6, 120.8, 122.1, 123.1, 123.4, 124.9,
124.9, 125.5, 125.58, 125.63, 126.0, 126.3, 126.5, 127.7, 128.3, 128.5,
128.6, 129.2, 130.2, 131.8, 135.0, 137.0, 137.6. HRMS (FAB) calcd for
C28H23N [M+] 373.1830; found: 373.1832.
1
at 80 °C for 1 h: mp 172−174 °C. IR (neat): 3427 (NH) cm−1. H
NMR (500 MHz, CDCl3) δ: 7.18 (dd, J = 7.7 Hz, 1H), 7.28 (dd, J =
7.7, 7.7 Hz, 1H), 7.42−7.45 (m, 5H), 7.53 (dd, J = 7.4, 7.4 Hz, 1H),
7.63−7.66 (m, 3H), 7.73 (s, 1H), 7.81 (d, J = 8.6 Hz, 1H), 8.00 (d, J =
8.0 Hz, 1H), 8.17 (d, J = 8.0 Hz, 1H), 8.48 (d, J = 8.0 Hz, 1H), 9.04 (s,
1H), 9.08 (d, J = 8.6 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ: 111.3,
113.5, 119.6, 120.6, 122.3, 123.1, 123.6, 124.4, 124.5, 124.6, 125.2,
125.8, 126.9, 127.2, 127.3, 128.3, 128.7, 129.0 (2C), 129.7, 129.86,
129.88, 130.8 (2C), 131.7, 132.9, 135.4, 137.2, 138.7, 143.9. HRMS
(FAB) calcd for C30H18ClN [M+] 427.1128; found: 427.1135.
14-Chloro-6-propyl-11H-benzo[a]naphtho[2,1-c]carbazole (15k)
(Table 2, Entry 11). By a procedure similar to that described for the
preparation of 15a, 9k (51 mg, 0.13 mmol) was converted into 15k
(35 mg, 68% yield) as a pale brown solid by treatment with
JohnPhosAuCl (3.5 mg, 6.5 μmol) and AgBF4 (1.3 mg, 6.5 μmol) in
AcOH (0.65 mL) at 80 °C for 0.5 h: mp 191−192 °C. IR (neat): 3438
(NH) cm−1. 1H NMR (500 MHz, CDCl3) δ: 1.01 (t, J = 7.4 Hz, 3H),
1.89−1.92 (m, 2H), 3.39 (t, J = 8.0 Hz, 2H), 7.28 (dd, J = 8.6, 2.3 Hz,
1H), 7.39 (d, J = 8.6 Hz, 1H), 7.53−7.62 (m, 4H), 7.75 (s, 1H), 7.91
(d, J = 8.0 Hz, 1H), 8.04 (d, J = 6.9 Hz, 1H), 8.35 (s, 1H), 8.54 (d, J =
9.2 Hz, 1H), 8.81 (d, J = 8.0 Hz, 1H), 8.89 (s, 1H). 13C NMR (125
MHz, CDCl3) δ: 14.3, 24.7, 39.4, 112.0, 113.3, 120.8, 121.8, 122.6,
123.9, 124.2, 124.9, 125.4 (2C), 125.8, 126.3, 126.4, 126.6, 126.7,
127.5, 128.0, 128.4, 128.7, 130.5, 131.9, 135.6, 136.9, 137.5. HRMS
(FAB) calcd for C27H20ClN [M+] 393.1284; found: 393.1292.
6-Propyl-11H-benzo[a]naphtho[2,1-c]carbazole-14-carbonitrile
(15l) (Table 2, Entry 12). By a procedure similar to that described for
the preparation of 15a, 9l (52 mg, 0.13 mmol) was converted into 15l
(7.4 mg, 14% yield) as a brown amorphous solid by treatment with
JohnPhosAuCl (3.6 mg, 6.7 μmol) and AgBF4 (1.3 mg, 6.7 μmol) in
AcOH (0.65 mL) at 80 °C for 1 h: mp 267−269 °C. IR (neat): 3301
6-Phenyl-11H-benzo[a]naphtho[2,1-c]carbazole (15g) (Table 2,
Entry 7). By a procedure similar to that described for the preparation
of 15a, 9g (51 mg, 0.13 mmol) was converted into 15g (32 mg, 63%
yield) as a brown amorphous solid by treatment with JohnPhosAuCl
(3.5 mg, 6.4 μmol) and AgBF4 (1.3 mg, 6.4 μmol) in AcOH (0.64 mL)
at 80 °C for 0.5 h. IR (neat): 3423 (NH) cm−1. 1H NMR (400 MHz,
CDCl3) δ: 7.11 (dd, J = 7.8, 7.8 Hz, 1H), 7.27 (dd, J = 7.8, 7.8 Hz,
1H), 7.37−7.52 (m, 7H), 7.58−7.67 (m, 3H), 7.77 (s, 1H), 7.82 (d,
J = 8.7 Hz, 1H), 8.00 (d, J = 8.2 Hz, 1H), 8.13 (d, J = 8.2 Hz, 1H),
8.49 (d, J = 8.2 Hz, 1H), 9.06 (br s, 1H), 9.08 (d, J = 8.2 Hz, 1H). 13
C
NMR (100 MHz, CDCl3) δ: 111.3, 113.6, 119.6, 120.4, 122.3, 123.2,
123.9, 124.3, 124.38, 124.42, 125.4, 125.7, 126.8, 126.9, 127.2, 127.3,
128.3, 128.6, 128.8 (2C), 129.6 (2C), 129.7, 130.0, 130.1, 131.8, 135.4,
138.5, 138.7, 145.4. HRMS (FAB) calcd for C30H19N [M+] 393.1517;
found: 393.1520.
1
(NH), 2222 (CN) cm−1. H NMR (500 MHz, DMSO-d6) δ: 0.96
9077
dx.doi.org/10.1021/jo2018119|J. Org. Chem. 2011, 76, 9068−9080

The Journal of Organic Chemistry
Article
(t, J = 7.4 Hz, 3H), 1.83−1.86 (m, 2H), 3.44 (t, J = 8.0 Hz, 2H), 7.64−
7.71 (m, 2H), 7.73−7.83 (m, 3H), 7.88 (d, J = 8.6 Hz, 1H), 7.91 (s,
1H), 8.06 (d, J = 8.0 Hz, 1H), 8.61 (s, 1H), 8.66 (t, J = 8.6 Hz, 2H),
8.77 (d, J = 8.0 Hz, 1H). 13C NMR (125 MHz, DMSO-d6) δ: 14.0,
24.0, 38.8, 100.7, 111.9, 113.1, 120.5, 121.9, 122.6, 123.9, 124.1, 125.2,
125.6, 126.1, 126.2, 126.37, 126.43, 126.6, 126.7, 126.9, 127.1, 127.7,
127.8, 129.9, 131.4, 136.5, 137.2, 140.9. HRMS (FAB) calcd for
C28H20N2 [M+] 384.1621; found: 384.1621.
J = 7.7, 7.7 Hz, 1H), 7.31 (dd, J = 7.7, 7.7 Hz, 1H), 7.40−7.57 (m,
9H), 7.71 (d, J = 8.0 Hz, 1H), 7.79 (d, J = 8.6 Hz, 1H), 7.91 (s, 1H),
7.91 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 8.6 Hz, 1H), 8.08 (d, J = 8.6 Hz,
1H), 8.19 (d, J = 8.0 Hz, 1H), 8.57 (d, J = 8.0 Hz, 1H), 9.08 (br s,
1H), 9.09 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 111.4,
113.0, 119.9, 120.6, 120.7, 122.6, 123.2, 124.5, 124.6 (2C), 124.6,
125.0, 125.1, 125.7, 125.9, 126.1, 126.8, 127.2, 127.3, 127.9, 128.3,
128.8, 128.9, 129.2, 129.4, 129.7, 130.00, 130.04, 130.3, 130.7, 130.8,
131.2, 131.3, 132.3, 135.7, 137.5, 138.7, 145.1. HRMS (FAB) calcd for
C38H23N [M+] 493.1830; found 493.1821.
13-Chloro-6-propyl-11H-benzo[a]naphtho[2,1-c]carbazole
(15m) (Table 2, Entry 13). By a procedure similar to that described
for the preparation of 15a, 9m (50 mg, 0.13 mmol) was converted into
15m (26 mg, 52% yield) as a brown amorphous solid by treatment
with JohnPhosAuCl (3.5 mg, 6.4 μmol) and AgBF4 (1.3 mg, 6.4 μmol)
Compound 22: pale brown amorphous solid. IR (neat): 3426
1
(NH), 2336 (CC) cm−1. H NMR (400 MHz, CDCl3) δ: 6.14 (d,
J = 6.9 Hz, 2H), 6.33 (dd, J = 7.8, 7.8 Hz, 2H), 6.76 (dd, J = 7.8,
7.8 Hz, 1H), 7.12 (dd, J = 7.8, 7.8 Hz, 1H), 7.30 (dd, J = 7.8, 7.8 Hz,
1H), 7.39−7.67 (m, 8H), 7.82 (s, 1H), 7.84 (dd, J = 8.7, 2.7 Hz, 2H),
7.98−8.04 (m, 2H), 8.54 (d, J = 8.2 Hz, 1H), 8.85 (s, 1H), 9.12 (dd,
J = 4.1, 4.1 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 88.7, 92.4,
111.3, 113.9, 119.7, 120.5, 121.9, 122.4, 123.1, 123.2, 124.3, 124.6,
124.8, 125.2, 125.6, 125.7, 126.7, 127.18 (2C), 127.21 (2C), 127.3,
127.4, 128.1, 128.5, 128.79, 128.81, 129.1, 129.7, 130.7 (2C), 130.8,
131.8, 132.6, 135.6, 137.0, 138.8, 147.7. HRMS (FAB) calcd for
C38H23N [M+] 493.1830; found 493.1824.
in AcOH (0.80 mL) at 80 °C for 0.5 h. IR (neat): 3427 (NH) cm−1
.
1H NMR (400 MHz, CDCl3) δ: 1.02 (t, J = 7.3 Hz, 3H), 1.90−1.94
(m, 2H), 3.40 (t, J = 8.0 Hz, 2H), 7.12 (dd, J = 8.7, 1.8 Hz, 1H), 7.47−
7.60 (m, 5H), 7.76 (s, 1H), 7.91 (d, J = 7.8 Hz, 1H), 8.06 (d, J = 7.8
Hz, 1H), 8.25 (d, J = 8.7 Hz, 1H), 8.56 (d, J = 8.2 Hz, 1H), 8.81 (d,
J = 8.2 Hz, 1H), 8.88 (br s, 1H). 13C NMR (100 MHz, CDCl3)
δ: 14.3, 24.7, 39.5, 111.0, 113.5, 119.9, 120.8, 121.8, 123.7, 123.9,
125.2, 125.4, 125.8 (2C), 126.3, 126.5, 126.6, 127.6, 128.0, 128.4,
128.6, 129.7, 130.3, 131.8, 135.1, 137.6, 139.1. HRMS (FAB) calcd for
C27H20ClN [M+] 393.1284; found: 393.1277.
6-Phenyl-15H-benzo[a]naphtho[1′,2′:11,12]chryseno[5,6-c]-
carbazole (23) (Scheme 7). To a stirred solution of aniline 14
(0.34 g, 0.57 mmol) in ethanol (2.5 mL) under argon was added a
suspension of XPhosAuCl (81 mg, 0.11 mmol, 20 mol %) and AgBF4
(23 mg, 0.11 mmol, 20 mol %) in ethanol (1.5 mL) at room
temperature. The mixture was stirred at 80 °C for 21 h. The reaction
mixture was diluted with EtOAc, washed with saturated aqueous
NH4Cl and brine, dried over Na2SO4, filtrated, and concentrated in
vacuo. The residue was purified by column chromatography on silica
gel with hexane/EtOAc (5:1) to afford 23 (ca. 2:1 isomeric mixture,
0.23 g, 68% yield) as a yellow solid: mp >300 °C. IR (neat): 3441
5-Propyl-10H-benzo[a]thieno[3′,2′:3,4]benzo[1,2-c]carbazole
(19) (Scheme 6). By a procedure similar to that described for the
preparation of 15a, 17 (65 mg, 0.18 mmol) was converted into 19 (29
mg, 45% yield) as a brown amorphous solid by treatment with
JohnPhosAuCl (4.8 mg, 8.8 μmol) and AgBF4 (1.8 mg, 8.8 μmol) in
1
AcOH (1.1 mL) at 80 °C for 1 h. IR (neat): 3429 (NH) cm−1. H
NMR (500 MHz, CDCl3) δ: 1.01 (t, J = 7.2 Hz, 3H), 1.91−1.93 (m,
2H), 3.43 (t, J = 8.0 Hz, 2H), 7.25 (dd, J = 7.7, 7.7 Hz, 1H), 7.37 (dd,
J = 7.7, 7.7 Hz, 1H), 7.47 (d, J = 5.7 Hz, 1H), 7.51−7.57 (m, 3H), 7.91
(s, 1H), 8.05 (d, J = 6.3 Hz, 1H), 8.33 (d, J = 5.7 Hz, 1H), 8.44 (d, J =
8.0 Hz, 1H), 8.59 (d, J = 7.4 Hz, 1H), 8.88 (s, 1H). 13C NMR (125
MHz, CDCl3) δ: 14.3, 24.9, 39.7, 111.2, 113.5, 119.6, 120.1, 120.7,
122.0, 122.8, 122.9, 124.0, 125.03, 125.04, 125.2, 125.5, 126.7, 126.8,
128.4, 130.8, 132.8, 134.4, 136.7, 138.6, 138.7. HRMS (FAB) calcd for
C25H19NS [M+] 365.1238; found: 365.1245.
1
(NH) cm−1. H NMR (500 MHz, CDCl3) δ: (for both isomers) 6.89
(dd, J = 7.4, 7.4 Hz, 0.7H), 6.95 (dd, J = 7.4, 7.4 Hz, 0.3H), 7.03−7.06
(m, 1H), 7.23−7.42 (m, 4.7H), 7.45−7.58 (m, 5.6H), 7.63−7.79 (m,
3.3H), 7.89 (d, J = 8.0 Hz, 0.7H), 8.00−8.07 (m, 4.3H), 8.15 (dd, J =
7.7, 7.7 Hz, 0.7H), 8.22 (d, J = 8.0 Hz, 0.3H), 8.25 (d, J = 8.0 Hz,
0.7H), 8.74−8.80 (m, 2.7H), 9.10−9.13 (m, 2H). 13C NMR (100
MHz, CDCl3) δ: [all the signals (<1.0C) for both isomers] 111.3,
111.5, 113.0, 113.7, 119.5, 120.1, 120.5, 120.7, 120.9, 121.0, 122.0,
122.6, 123.0, 123.5, 123.9, 124.0, 124.1, 124.2, 124.3, 124.6, 124.77,
124.79, 124.9, 125.25, 125.33, 125.35 (ca. 1C), 125.42, 125.8, 125.9,
126.1, 126.3, 126.46, 126.52, 126.7, 126.78, 126.83, 126.9, 127.36,
127.38, 127.42, 127.7, 127.8, 127.9, 127.99, 128.03, 128.1, 128.18,
128.20, 128.22, 128.25, 128.27, 128.39, 128.44, 128.5, 128.67, 128.72,
128.9, 129.0, 129.1, 129.3, 129.39, 129.43, 129.60, 129.62, 129.7,
129.9, 130.0, 130.6, 130.77, 130.79, 130.9, 131.0, 131.3, 131.37,
131.43, 131.6, 131.8, 132.1, 132.7, 133.3, 133.8, 135.5, 136.2, 136.4,
137.0, 137.6, 138.7, 139.3, 143.98, 144.03, 144.8. HRMS (FAB) calcd
for C46H27N [M+] 593.2143; found 593.2134.
Propyl-10H-naphtho[2,1-c]thieno[3,2-a]carbazole (20) (Scheme
6). By a procedure similar to that described for the preparation of 15a,
18 (45 mg, 0.12 mmol) was converted into 20 (36 mg, 79% yield) as
brown crystals by treatment with JohnPhosAuCl (3.4 mg, 6.2 μmol)
and AgBF4 (1.2 mg, 6.2 μmol) in AcOH (0.77 mL) at 80 °C for 1 h:
1
mp 158−160 °C. IR (neat): 3429 (NH) cm−1. H NMR (400 MHz,
CDCl3) δ: 1.19 (t, J = 7.3 Hz, 3H), 1.91−1.95 (m, 2H), 3.50 (t, J = 7.8
Hz, 2H), 7.23 (dd, J = 7.8, 7.8 Hz, 1H), 7.42 (dd, J = 7.3, 7.3 Hz, 1H),
7.54 (dd, J = 7.6, 7.6 Hz, 1H), 7.58−7.63 (m, 2H), 7.68 (d, J = 5.5 Hz,
1H), 7.72 (s, 1H), 7.74 (d, J = 5.5 Hz, 1H), 7.93 (d, J = 7.8 Hz, 1H),
8.54 (d, J = 8.2 Hz, 1H), 8.73 (br s, 1H), 9.17 (d, J = 8.2 Hz, 1H). 13
C
NMR (100 MHz, CDCl3) δ: 14.3, 24.3, 38.9, 111.1, 114.4, 118.8,
119.1, 123.3, 123.5, 123.9, 124.4, 125.1, 125.6, 126.0, 126.47, 126.54,
126.7, 127.4, 128.57, 128.61, 131.7, 134.5, 135.3, 136.5, 138.6. Anal.
Calcd for C25H19NS: C, 82.15; H, 5.24; N, 3.83. Found: C, 82.04; H,
5.37; N, 3.82.
6-Phenyl-15-tosyl-15H-benzo[a]naphtho[1′,2′:11,12]chryseno-
[5,6-c]carbazole (24) (Scheme 7). To a solution of 23 (0.23 g, 0.38
mmol) in DMF (1.0 mL) was added NaH (60% dispersion in mineral
oil; 0.046 g, 1.2 mmol) at 0 °C. After being stirred at the same
temperature for 20 min, TsCl (0.22 mg, 1.2 mmol) was added to the
mixture and the stirring was continued for 23 h at room temperature.
The reaction mixture was diluted with EtOAc, washed with saturated
aqueous NH4Cl and brine, dried over Na2SO4, filtrated, and
concentrated in vacuo. The residue was purified by column
chromatography over silica gel with hexane/EtOAc (5:1) to afford
24 (ca. 5:1 isomeric mixture, 0.15 g, 53% yield) as a yellow solid,
which was recrystallized from chloroform/hexane to give the single
isomer of 24 as a yellow solid: mp >300 °C. IR (neat): 1370 (SO),
1-Phenyl-11H-benzo[a]chryseno[5,6-c]carbazole (21) (Table 3,
Entry 9) and 6-[2-(Phenylethynyl)phenyl]-11H-benzo[a]naphtho-
[2,1-c]carbazole (22) (Table 3, Entry 5). To a stirred solution of
aniline 12 (57 mg, 0.11 mmol) in ethanol (0.52 mL) under argon was
added a suspension of XPhosAuCl (6.2 mg, 8.6 μmol, 7.5 mol %) and
AgBF4 (1.7 mg, 8.6 μmol, 7.5 mol %) in ethanol (0.2 mL) at room
temperature. The mixture was stirred at 80 °C for 3 h. The reaction
mixture was diluted with EtOAc, washed with saturated aqueous
NH4Cl and brine, dried over Na2SO4, filtrated, and concentrated in
vacuo. The residue was purified by column chromatography over
amino silica gel with hexane/Et2O (1:1) to afford 21 (49 mg, 86%
yield). On the other hand, the reaction of 12 (73 mg, 0.15 mmol) with
JohnPhosAuCl (3.9 mg, 7.4 μmol, 5 mol %)/AgBF4 (1.4 mg, 7.4 μmol,
5 mol %) in EtOH (0.93 mL) for 24 h gave 22 (45 mg, 61% yield).
Compound 21: yellow solid; mp >300 °C. IR (neat): 3427 (NH)
1
1175 (SO) cm−1. H NMR (500 MHz, CDCl3) δ: 2.12 (s, 3H),
6.86 (d, J = 8.6 Hz, 2H), 6.96 (dd, J = 7.7, 7.7 Hz, 1H), 7.17−7.41 (m,
10H), 7.47−7.49 (m, 2H), 7.54 (dd, J = 7.4, 7.4 Hz, 1H), 7.70 (dd,
J = 7.7, 7.7 Hz, 3H), 7.99−8.05 (m, 5H), 8.16 (d, J = 8.6 Hz, 1H),
8.22 (d, J = 8.0 Hz, 1H), 8.41 (d, J = 8.6 Hz, 1H), 8.63 (d, J = 8.6 Hz,
1H), 8.66 (d, J = 8.6 Hz, 1H), 9.01 (d, J = 8.6 Hz, 1H). 13C NMR
1
cm−1. H NMR (500 MHz, CDCl3) δ: 7.09−7.17 (m, 2H), 7.25 (dd,
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(125 MHz, CDCl3) δ: 21.3, 120.1, 123.0, 124.0, 124.1, 124.9, 124.99,
125.02, 125.3, 125.5, 125.6, 125.8, 126.3, 126.62, 126.64, 126.7, 126.8,
126.9, 127.0, 127.7 (4C), 127.8, 128.25, 128.30, 128.35, 128.38 (4C),
128.45, 128.47, 128.54, 128.8, 129.2, 129.8, 130.0, 130.1, 130.3,
130.46, 130.51, 130.6, 131.7, 132.4 (2C), 132.7, 133.4, 137.6, 140.2,
142.6, 144.5, 144.6. HRMS (FAB) calcd for C53H33NO2S [M+]
747.2232; found 747.2231.
(b) Suzuki, I.; Wakayama, M.; Shigenaga, A.; Nemoto, H.; Shibuya, M.
Tetrahedron Lett. 2000, 41, 10019−10023, (see also refs 10b and c).
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(6) For palladium-catalyzed biscyclization of unconjugated ene-
diynes, see: (a) Trost, B. M.; Lee, D. C. J. Am. Chem. Soc. 1988, 110,
7255−7258. For palladium-catalyzed tricyclization of unconjugated
enediynes, see: (b) Trost, B. M.; Shi, Y. J. Am. Chem. Soc. 1993, 115,
12491−12509.
ASSOCIATED CONTENT
■
S
* Supporting Information
(7) For pioneering works on gold-catalyzed hydroarylation, see:
1
ORTEP diagram of 24, H and 13C NMR spectra of all new
(a) Furstner, A.; Mamane, V. J. Org. Chem. 2002, 67, 6264−6267.
̈
compounds, and a crystallographic information file (CIF) for
24. This material is available free of charge via the Internet at
http://pubs.acs.org.
(b) Reetz, M. T.; Sommer, K. Eur. J. Org. Chem. 2003, 3485−3496.
(c) Shi, Z.; He, C. J. Org. Chem. 2004, 69, 3669−3671. (d) Mamane,
V.; Hannen, P.; Furstner, A. Chem.Eur. J. 2004, 10, 4556−4575.
̈
(e) Li, Z.; Shi, Z.; He, C. J. Organomet. Chem. 2005, 690, 5049−5054.
(f) Nevado, C.; Echavarren, A. M. Chem.Eur. J. 2005, 11, 3155−
3164. (g) Hashmi, A. S. K.; Blanco, M. C. Eur. J. Org. Chem. 2006,
4340−4342.
AUTHOR INFORMATION
■
Corresponding Author
(8) For reviews including gold-catalyzed hydroarylation, see:
(a) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180−3211. (b) Gorin,
*E-mail: hohno@pharm.kyoto-u.ac.jp.
́
́
D. J.; Toste, F. D. Nature 2007, 446, 395−403. (c) Jimenez-Nunez, E.;
̃
ACKNOWLEDGMENTS
■
Echavarren, A. M. Chem. Commun. 2007, 333−346. (d) Jimen
́
ez-
This work was supported by a Grant-in-Aid for Scientific
Research on Innovative Areas “Integrated Organic Synthesis”
(H.O. and K.T.) and the Targeted Proteins Research Program
from the Ministry of Education, Culture, Sports, Science and
Technology of Japan, as well as the Program for Promotion of
Fundamental Studies in Health Sciences of the National
Institute of Biomedical Innovation (NIBIO). We thank Dr. Koji
Tsukamoto (School of Pharmacy, Hyogo University of Health
Sciences) for instruction of X-ray analysis and valuable
discussions.
Nunez, E.; Echavarren, A. M. Chem. Rev. 2008, 108, 3326−3350.
̌
́
(e) Shen, H. C. Tetrahedron 2008, 64, 3885−3903. (f) Skouta, R.; Li,
C.-J. Tetrahedron 2008, 64, 4917−4938. (g) Bandini, M. Chem. Soc.
Rev. 2011, 40, 1358−1367.
(9) (a) Hirano, K.; Inaba, Y.; Watanabe, T.; Oishi, S.; Fujii, N.;
Ohno, H. Adv. Synth. Catal. 2010, 352, 368−372. (b) Hirano, K.;
Inaba, Y.; Takahashi, N.; Shimano, M.; Oishi, S.; Fujii, N.; Ohno, H.
J. Org. Chem. 2011, 76, 1212−1227.
(10) For related Bergman- or Myers−Saito-type reactions involving
hydroarylation, see: (a) Nath, M.; Pink, M.; Zaleski, J. M. J. Am. Chem.
Soc. 2005, 127, 478−479. (b) Poloukhtine, A.; Popik, V. V. J. Am.
Chem. Soc. 2007, 129, 12062−12063. (c) Poloukhtine, A.; Rassadin,
V.; Kuzmin, A.; Popik, V. V. J. Org. Chem. 2010, 75, 5953−5962.
(11) For gold-catalyzed electrophilic activation of alkynes toward
intramolecular nucleophilic attack at the C-3 position of indoles, see:
(a) Ferrer, C.; Echavarren, A. M. Angew. Chem., Int. Ed. 2006, 45,
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