Rhodium-Catalyzed Cascade Annulative Coupling of 3,5-Diarylisoxazoles with Alkynes

Article abstract of DOI:10.1055/s-0037-1610376

A rhodium-catalyzed cascade annulative coupling of 3,5-diarylisoxazoles with three equivalents of an alkyne proceeds smoothly in the presence of a Cu(II) oxidant, where the sequential construction of isoquinoline and naphtho[1,8- bc ]pyran frameworks connected by a biaryl linkage is achieved by a single operation. Most of the obtained polycyclic compounds exhibit visible fluorescence in both the solution and the solid state. The hexaphenylated isoquinoline-naphthopyran conjugate (R = Ph) as a representative product shows a green emission which can be turned off by making an isoquinolinium salt with an acid. The emission is also reversibly turned on by treatment with a base.

Full text of DOI:10.1055/s-0037-1610376

SYNTHESIS
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Georg Thieme Verlag Stuttgart · New York
2018, 50, A–M
paper
A
en
T. Noguchi et al.
Paper
Synthesis
Rhodium-Catalyzed Cascade Annulative Coupling of 3,5-Diaryl-
isoxazoles with Alkynes
Teppei Noguchia
R
Yuji Nishii*b
R
Masahiro Miura*a
0
0
0
0
0-
0
0
1
8-
2
8
8
6-
4
3
9
Ar
R
N
O
N
Rh(III) catalyst
Ar
R
R
+
a Department of Applied Chemistry, Graduate School of Engineering,
Osaka University, Suita, Osaka 565-0871, Japan
O
R
R
Cu(II) salt
Ar
3 equiv
up to 88% yield
miura@chem.eng.osaka-u.ac.jp
R
b Frontier Research Base for Global Young Researchers, Graduate School
of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
y_nishii@chem.eng.osaka-u.ac.jp
Ar
Published as part of the 50 Years SYNTHESIS – Golden Anniversary Issue
Received: 07.08.2018
Accepted after revision: 28.08.2018
Published online: 19.09.2018
two equivalents of alkynes under various catalytic condi-
tions including rhodium catalysis have been utilized as
straightforward methods for the synthesis of benzo-fused
arenes [Scheme 1 (a)].2,4,5 These annulative cyclization reac-
tions are potentially useful in exploring novel functional
molecules since highly elaborate aromatics can be obtained
from readily available starting materials.6
DOI: 10.1055/s-0037-1610376; Art ID: st-2018-e0533-op
License terms:
Abstract A rhodium-catalyzed cascade annulative coupling of 3,5-di-
arylisoxazoles with three equivalents of an alkyne proceeds smoothly in
the presence of a Cu(II) oxidant, where the sequential construction of
isoquinoline and naphtho[1,8-bc]pyran frameworks connected by a bi-
aryl linkage is achieved by a single operation. Most of the obtained
polycyclic compounds exhibit visible fluorescence in both the solution
and the solid state. The hexaphenylated isoquinoline-naphthopyran
conjugate (R = Ph) as a representative product shows a green emission
which can be turned off by making an isoquinolinium salt with an acid.
The emission is also reversibly turned on by treatment with a base.
(a) Annulative coupling with 2 equiv of alkynes:
DG
R
DG
R
R
Rh catalyst
oxidant
H
H
+
R
R
(2 equiv)
R
(b) Annulative coupling of isoxazoles involving N–O bond cleavage:
R
Key words C–H activation, annulative coupling, isoquinoline, rhodi-
um catalyst, polyaromatic compounds
R
O
H
N
R1
Rh catalyst
w/o oxidant
N
+
R
R
R1
OH
R2
Polycyclic aromatic and heteroaromatic compounds
have attracted much research interest owing to their sub-
stantial and increasing importance as functional organic
materials involving light-emitting devices, solar cells, and
semiconductors.1 Accordingly, the development of new syn-
thetic methods for such fused-aromatic systems is in high
demand.
Transition-metal-catalyzed direct annulative coupling
reactions of directing group substituted aromatic sub-
strates with alkynes have been extensively studied in the
last few decades because of their high efficiency and opera-
tional simplicity.2,3 In particular, the reactions of this type
are powerful synthetic tools for constructing various ben-
zo-fused heteroaromatic molecules through the annulation
accompanied by the incorporation of a heteroatom-con-
taining directing group. Under certain circumstances,
alkynes may also be multiply annulated onto the aromatic
substrates to lead to higher -extended carbocyclic systems.
For example, the dehydrogenative coupling reactions with
1 equiv
R2
R
(c) This work: cascade annulative coupling of isoxazoles:
R
R1
N
H
H
O
N
Rh catalyst
oxidant
R
R
O
R
R
R
+
R1
R2
R
3 equiv
H
H
R2
Scheme 1 Rh-catalyzed annulative coupling reactions
Recently, we have developed the synthesis of 1-substi-
tuted isoquinolines7 through coupling using aryl-substitut-
ed isoxazoles as the starting substrates as a new repertoire
of the rhodium-catalyzed direct transformation chemistry,
where the N–O bond of the ring system acts as the internal
oxidant [Scheme 1 (b)].8 In the course of our continuous in-
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

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T. Noguchi et al.
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Synthesis
vestigation into the annulative coupling with alkynes, we
have found that 3,5-diarylisoxazoles can undergo cascade
oxidative annulation to give rise to the corresponding iso-
quinoline-conjugated naphtho[1,8-bc]pyran frameworks
with the incorporation of three equivalents of alkyne
[Scheme 1 (c)]. The naphtho[1,8-bc]pyran skeleton is in-
volved in various natural and synthetic compounds,9 and
their synthesis through the catalytic oxidative annulation
on 1-naphthols and related substrates has been achieved by
our group3c and the groups of Ackermann,10 Wang,3h,11 and
Li.12 In this publication, the scope of this novel catalytic
transformation using the isoxazoles and alkynes as the
building blocks and the optical properties of the obtained
biaryl-type coupling products are described.
As an initial attempt, we examined the reaction of 3,5-
diphenylisoxazole (1a) with excess diphenylacetylene (2a,
3.6 equiv) in the presence of [Cp*Rh(MeCN)3][SbF6]2
(Cp* = pentamethylcyclopentadienyl) (4.0 mol%) as catalyst
and Cu(OAc)2 (4.0 equiv) as oxidant at 100 °C for 18 hours
(Table 1, entry 1), and the corresponding 1:3 coupling prod-
uct 3aa was obtained in 66% NMR yield. Acetate salts of
Ag(I) and Mn(III) were not suitable as the oxidants for the
present reaction (entries 2 and 3). A number of solvents
were then tested (entries 4–7) and the highest yield was
achieved using 1,4-dioxane (86%, entry 6). Interestingly, re-
ducing the amount of 2a to 3.1 equivalents resulted in a
product yield of 94% (83% after purification) within 9 hours
(entry 8). No reaction took place in the absence of any Rh
catalyst (entry 9). Throughout the optimization study, a 1:2
coupling product 4aa was sometimes detected in small
quantities (<5% yield). This implies that the annulative cou-
pling on the naphthol moiety of 4aa is the last step of the
catalytic sequence that leads to 3aa (see discussion below).
With the reaction conditions of entry 8 in Table 1, we
examined the substrate scope of alkynes (Scheme 2). Good
to excellent yields were achieved with variously substituted
diphenylacetylenes 2 with the exception of 2d and 2g. The
lower product yields with 2d and 2g are probably because
of their weaker coordinating properties due to the steric
bulkiness and the electron-deficient nature, respectively. Of
note is that the C–Br linkage in 2h remained intact during
the reaction. An aliphatic alkyne, oct-4-yne (2i) was also
applicable to furnish the corresponding product in 63%
yield. No productive results were obtained with silyl- or
carbonyl-substituted alkynes (not shown).
Table 1 Optimization Studies for the Coupling of 1a and 2aa
Ph
Ph
O
N
Ph
O
Ph
[Cp*Rh(MeCN)3][SbF6]2
(4.0 mol%)
N
N
1a
Ph
Ph
Ph
Ph
Ph
Ph
OH
oxidant (4.0 equiv)
+
+
solvent
Ph
Ph
100 °C, 18 h
2a
3aa
4aa
Entry
2a (equiv)
Oxidant
Solvent
Yieldb (%)
3aa
66
4aa
n.d.
n.d.
4
1
2
3
4
5
6
7
8c
3.6
3.6
3.6
3.6
3.6
3.6
3.6
3.1
Cu(OAc)2
AgOAc
PhCF3
PhCF3
PhCF3
DCE
n.d.
8
Mn(OAc)3·2H2O
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
62
3
o-xylene
1,4-dioxane
DMF
34
5
86
n.d.
n.d.
n.d.
n.d.
1,4-dioxane
94
(83)d
9e
3.1
Cu(OAc)2
1,4-dioxane
n.d.
n.d.
a Reaction conditions: 1a (0.2 mmol), 2a (0.62 or 0.72 mmol), oxidant (0.8 mmol), [Cp*Rh(MeCN)3][SbF6]2 (4.0 mol%), solvent (4.0 mL).
b Determined by NMR analysis; n.d. = not detected.
c Reaction time: 9 h.
d Isolated yield.
e Without the Rh catalyst.
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ployed, the corresponding 1:2 coupling products 4oa and
4pa were formed selectively. This is apparently due to the
fact that no Csp2–H bond for the third annulation is avail-
able in the products (Scheme 4).
R
R
O
N
[Cp*Rh(MeCN)3][SbF6]2
(4.0 mol%)
Cu(OAc)2 (4.0 equiv)
O
N
R
R
R
R
+
R
R
Ph
Ph
1,4-dioxane
100 °C, 12 h
Ph
R2
O
Ph
O
N
R1
1a
Ar
2
3ax
n-Pr
N
[Cp*Rh(MeCN)3][SbF6]2
(4.0 mol%)
Cu(OAc)2 (4.0 equiv)
R1
1
Ph
Ph
Ph
Ph
Ar = 4-MeC6H4
Ar = 3-MeC6H4
Ar = 2-MeC6H4
79% (3ab)
85% (3ac)
29% (3ad)a
+
n-Pr
Ar
O
1,4-dioxane
100 °C, 12 h
Ph
Ph
N
N
2a
R2
3
n-Pr
n-Pr
O
n-Pr
n-Pr
Ar
Ar
Ar
Ar = 4-t-BuC6H4 76% (3ae)
Ar = 4-OMeC6H4 75% (3af)
Ar = 4-CF3C6H4 46% (3ag)
Ph
Ph
Ar
Ph
Ph
Ar = 4-BrC6H4
69% (3ah)
R = Me
75% (3ba)
N
N
63% (3ai)
A = t-Bu 76% (3ca)a
A = OMe 80% (3da)
A = CF3 84% (3ea)
Scheme 2 Substrate scope for alkynes. a Reaction at 120 °C.
Ph
Ph
O
Ph
Ph
Ph
Ph
O
Ph
Ph
We then carried out the reactions of various 3,5-diaryl-
isoxazoles 1b–n with diphenylacetylene (2a) (Scheme 3). A
variety of substituents can be installed onto the naph-
tho[1,8-bc]pyran subunit by using isoxazoles 1b–g with dif-
ferent substituents on the 5-aryl group. It is noteworthy
that the reaction of 1g resulted in the selective formation of
3ga in which the methyl group is placed at the C4 position
of the ring system. This peculiar regioselectivity seems to
be achieved as the second annulation takes place at the ste-
rically more accessible site (see discussion below). Addi-
tionally, the catalytic system can be utilized for the con-
struction of a thienochromene framework to give 3ha as a
single isomer albeit with a low yield. The structures of 3ga
and 3ha were unambiguously determined by X-ray crystal-
lography.13 Apparently, functionality on the 3-aryl group of
the isoxazoles falls into the isoquinoline subunit. Thus, the
1:3 coupling products 3ia–ma were obtained in high yields
with use of isoxazoles 1i–m having a substituent on the 3-
aryl group. No significant drop of the product yield was ob-
served even in the presence of an ortho-methyl substituent
(3ma). A thienopyridine moiety was also constructed albeit
with low yield (3na). When isoxazoles 1o and 1p were em-
A = Br
67% (3fa)
Me
3ba–fa
R
30% (3ga)
Ph
Ph
Ph
O
R
Ph
O
N
N
R = Me 84% (3ia)
A = OMe 78% (3ja)
A = CF3 56% (3ka)
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
S
23% (3ha)a
3ia–ka
Ph
Ph
Ph
Ph
Ph
Ph
N
N
N
S
Me
Me
Ph
Ph
O
Ph
Ph
O
Ph
O
Ph
Ph
Ph
Ph
Ph
Ph
Ph
28% (3na)a
88% (3la)
88% (3ma)
Scheme 3 Substrate scope for isoxazoles. a Reaction at 130 °C for 24 h.
Ph
Ph
Ph
[Cp*Rh(MeCN)3][SbF6]2
(4.0 mol%)
Ph
[Cp*Rh(MeCN)3][SbF6]2
Me
N
(4.0 mol%)
O
S
N
N
O
Cu(OAc)2 (2.0 equiv)
Cu(OAc)2 (2.0 equiv)
N
Ph
Ph
OH
Me
Ph
Ph
+
+
Ph
Ph
Ph
Ph
OH
S
1,4-dioxane
130 °C, 24 h
Ph
1,4-dioxane
100 °C, 12 h
Ph
1o
2a
(2.1 equiv)
1p
2a
(2.1 equiv)
4oa: 50%
4pa: 73%
Scheme 4 Annulative coupling with two equivalents of alkynes
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2Cu(I)
1a
[Cp*RhX]+
HX
2Cu(II)
A
Cp*Rh
3ax
Cp* Rh
O
N
Ph
R
R
Rh(III)
3rd annulation
R
R
OH
2Cu(I)
Cp*
Rh
R
B
R
2Cu(II)
R
N
O
R
2nd annulation
R
Ph
Rh(I)
R
R
Cp*
R
C-N formation
N-O cleavage
R
N
O
Rh
R
R
R
N
O
N
Ph
RhCp*
Ph
D
C
Scheme 5 Proposed reaction mechanism
A proposed catalytic cycle for the reaction of 1a with 2
is illustrated in Scheme 5. The reaction is initiated by coor-
dination-assisted C–H bond activation to form a five-mem-
bered rhodacycle complex A. Then, alkyne insertion and
subsequent formal SN-type reaction8g,14 onto the nearby N–
O bond gives a Rh alkoxide species C, which is in equilibri-
um with a carbon-enolate complex D. From this stage, oxi-
dative annulation undergoes with incorporating the second
alkyne molecule to construct the naphthol moiety.
the 1:1 coupling product, to the optimal reaction condi-
tions; however, no C–C bond forming reaction was trig-
gered (Scheme 6, upper). Finally, another oxidative cou-
pling proceeded with the third alkyne molecule to furnish
the 1:3 coupling products 3. This step was confirmed sepa-
rately by the reaction of 4aa with 2a affording the product
3aa in a high yield (Scheme 6, lower). In total, four C–C
bonds, one C–N bond, and one C–O bond are formed in a
one-shot manner.
According to the following control experiment, it is as-
sumed that the catalytic Rh species may be liberated only
after the second annulative coupling. We adopted -(2-pyr-
idyl)acetophenone (5), which is structurally analogous to
It has been reported that a series of naphtho[1,8-
bc]pyran derivatives exhibit relatively strong fluorescence
even in their solid state.3c,9c Consequently, we investigated
the optical properties of the present coupling products
O
N
N
[Cp*Rh(MeCN)3][SbF6]2
(4.0 mol%)
Cu(OAc)2 (4.0 equiv)
N
Ph
5
Ph
Ph
OH
Ph
Ph
O
Ph
Ph
or
+
1,4-dioxane
100 °C, 12 h
Ph
Ph
2a
(2.1 equiv)
Not detected
Ph
Ph
Ph
Ph
O
[Cp*Rh(MeCN)3][SbF6]2
(4.0 mol%)
Cu(OAc)2 (2.0 equiv)
N
N
+
Ph
Ph
Ph
OH
Ph
Ph
Ph
Ph
1,4-dioxane
100 °C, 18 h
2a
(1.1 equiv)
Ph
4aa
3aa: 84%
Scheme 6 Control experiments
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(Figure 1). When excited at 342 nm, 3aa emitted a green
fluorescence with a broad spectral width ranging from 450
nm to 600 nm in chloroform solution [Figure 1 (b)]. No ob-
vious bathochromic shift was observed in the solid state
measurement and the quantum efficiency was comparable:
0.15 for the CHCl3 solution and 0.11 for the powder [Figure
1 (d) and Table S1].
Substituents on the naphthopyran or isoquinoline motif
did not largely affect the luminescence property, and the
tested molecules (3ae, 3af, 3ag, 3ca, 3da, 3ea, and 3ja) re-
corded similar fluorescence spectra within 20 nm shift of
the peak top. In contrast, the compound 3ai which is de-
rived from an aliphatic alkyne showed blue-green emission
with the peak top at around 470 nm (Figure 2).
Interestingly, 3aa showed a characteristic spectral
change in response to the formation of an isoquinolinium
salt. We first prepared a hydrochloric salt of 3aa (3aa·HCl)
and measured its spectra. The color changed from light yel-
low to deep orange with expansion of the absorption edge
up to 600 nm [Figure 1 (a) and (c)]. On the other hand, the
emission intensity was considerably decreased in the solu-
tion and eventually quenched in the solid state [Figure 1
(d)]. This difference between the solution and the solid is
due to the fact that the salt can partly dissociate into free
3aa and HCl in chloroform. Indeed, more obvious spectral
change was observed when excess HCl (1.0 mol/L in Et2O)
was added [Figure 1 (a) and (b)] to the solution. The revers-
ibility of this event is realized by the sequential addition of
HCl and Et3N. We also synthesized an N-methylated iso-
quinolinium salt 3aa·MeOTf as a reference, and as expected,
similar spectra to those of 3aa in the presence of the excess
HCl were obtained in the solution since the dissociation of
the CH3–N bond is not possible in this case.
Additionally, we looked into the potential axial chirality
of the coupling products. As a representative example, com-
pound 3ag can be separated into a pair of enantiomers in a
chiral HPLC analysis (see the Supporting Information). Fur-
ther studies on their chiroptical properties are underway in
our group.
In summary, we have developed a rhodium-catalyzed
cascade annulative coupling reaction of 3,5-diarylisoxaz-
oles with alkynes. In this catalytic system, three equivalents
of alkynes are consolidated and isoquinoline-conjugated
naphtho[1,8-bc]pyran frameworks are efficiently con-
structed by a single manipulation. The starting isoxazole
derivatives are readily available and can be stored without
any special treatments. The coupling products exhibit fluo-
rescence in both the solution and solid state, and addition-
ally, its turn-off/on is reversibly achievable by treatment
with an acid and a base.
Figure 1 (a) UV-vis absorption and (b) fluorescence spectra of 3aa (black), 3aa·HCl (orange), 3aa·HCl + 10 equiv of HCl (blue), and 3aa·MeOTf (gray)
in CHCl3 solution (5.0 × 10–5 mol/L); the fluorescence spectra of 3aa·HCl + 10 equiv of HCl and 3aa·MeOTf overlap close to the baseline. (c) UV-vis
absorption and (d) fluorescence spectra of 3aa (black), 3aa·HCl (orange), and 3aa·MeOTf (gray) in solid state.
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Figure 2 Normalized fluorescence spectra of 3ae (blue), 3af (orange), 3ag (gray), 3ai (red), 3ca (yellow), 3da (purple), 3ea (navy), and 3ja (green) at
room temperature. (a) Spectra in CHCl3 solution (left, 5.0 × 10–6 mol/L). (b) Spectra in solid state (right).
All manipulations were performed under N2 using standard Schlenk
techniques unless otherwise noted. DMF and 1,4-dioxane were dried
and deoxygenated by a Glass Counter Solvent Dispending System
(Nikko Hansen & Co., Ltd.). PhCF3, DCE, and o-xylene were distilled
from CaH2 and stored with molecular sieves 4Å. CH2Cl2 was degassed
with N2 bubbling and dried with molecular sieves 4Å. THF (stabilizer
free) was purchased from Wako Pure Chemical Industries as dehy-
drated solvent and used without purification. Silica gel column chro-
matography was performed using Wakosil® C-200 (64–210 m) or
Kanto Chemical 60N (40–100m). 3,5-Diphenylisoxazole (1a) was
synthesized according to the literature procedure.15 The other isoxaz-
oles were synthesized by the copper-catalyzed cycloaddition of ox-
ime chlorides with terminal alkynes according to the literature proce-
dure.16 Alkynes 2b–h,17 rhodium complexes,3b,18 and -(2-pyridyl)-
acetophenone (5)19 were synthesized according to the literature. All
other reagents were commercially available and used without further
purification.
3,5-Diphenylisoxazole (1a)20d
White solid; yield: 281 mg (64%).
1H NMR (400 MHz, CDCl3):  = 6.84 (s, 1 H), 7.43–7.52 (m, 6 H), 7.83–
7.89 (m, 4 H).
13C NMR (100 MHz, CDCl3):  = 97.5, 125.9, 126.8, 127.5, 129.0, 129.0,
129.2, 130.1, 130.3, 163.0, 170.4.
3-Phenyl-5-(p-tolyl)isoxazole (1b)20d
White solid; yield: 98 mg (42%).
1H NMR (400 MHz, CDCl3):  = 2.42 (s, 3 H), 6.78 (s, 1 H), 7.29–7.31
(m, 2 H), 7.45–7.50 (m, 3 H), 7.73–7.75 (m, 2 H), 7.86–7.88 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 21.5, 96.9, 124.8, 125.8, 126.8, 128.9,
129.3, 129.7, 129.9, 140.5, 162.9, 170.6.
5-(4-tert-Butylphenyl)-3-phenylisoxazole (1c)
NMR spectra were measured at 400 MHz (1H NMR), at 100 MHz (13
C
Purified by column chromatography (hexane/EtOAc 15:1); white sol-
id; yield (2.0-mmol scale): 276 mg (50%); mp 95–97 °C.
1H NMR (400 MHz, CDCl3):  = 1.36 (s, 9 H), 6.79 (s, 1 H), 7.46–7.52
(m, 5 H), 7.76–7.79 (m, 2 H), 7.86–7.88 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 31.2, 34.9, 97.0, 124.8, 125.7, 126.0,
126.8, 128.9, 129.3, 130.0, 153.7, 162.9, 170.6.
HRMS (APCI): m/z [M + H]+ calcd for C19H20NO: 278.1539; found:
278.1538.
NMR), and at 376 MHz (19F NMR) in 5 mm NMR tubes. 1H NMR chem-
ical shifts were reported relative to the resonance of TMS ( = 0.00) or
the residual solvent signals at  = 7.26 for CDCl3. 13C NMR chemical
shifts were reported relative to the residual solvent signals at  = 77.2
for CDCl3. Melting points were measured with Mettler Toledo MP90.
HRMS were recorded by APCI-TOF. GC analyses were carried out with
Shimadzu GC8APF equipped with a silicon OV-17 column (2.6
mm × 1.5 m). GC-MS spectra were recorded on Shimadzu GCMS-
QP2010 SE with a CBP-1 column (0.5 mm × 25 m). Preparative gel
permeation chromatography (GPC) was conducted with Showa Denko
H-2001/H-2002 (eluent: CHCl3) or YMC T2000 (eluent: EtOAc) col-
umn. Absorption and fluorescence spectra were recorded on JASCO V-
750 and JASCO FP8500 spectrometers. Quantum efficiency was deter-
mined using an integration sphere system.
5-(4-Methoxyphenyl)-3-phenylisoxazole (1d)20e
White solid; yield: 122 mg (48%).
1H NMR (400 MHz, CDCl3):  = 3.88 (s, 3 H), 6.71 (s, 1 H), 6.99–7.01
(m, 2 H), 7.45–7.51 (m, 3 H), 7.77–7.80 (m, 2 H), 7.84–7.88 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 55.4, 96.1, 114.4, 120.4, 126.8, 127.5,
128.9, 129.3, 129.9, 161.2, 163.0, 170.4.
Isoxazole Derivatives 1;15,16,20 General Procedure
Oxime chloride (1.0 mmol) and terminal alkyne (1.0 mmol) were dis-
solved in H2O/t-BuOH (1:1, 6.0 mL) under an N2 atmosphere. To the
solution, sodium ascorbate (0.1 mmol, 1.0 mol/L in water), Cu-
SO4·5H2O (0.02 mmol in 0.10 mL of water), and NaHCO3 (4.33 mmol,
4.33 equiv) were added at r.t. The mixture was stirred overnight and
then it was poured into EtOAc; the aqueous layer was extracted with
EtOAc. The combined organic layers were washed with brine, dried
(Na2SO4), and concentrated in vacuo. Unless otherwise noted, the res-
idue was subjected to column chromatography (silica gel, hex-
ane/EtOAc 9:1), and further purification was conducted by recrystal-
lization (hexane layered over EtOAc solution).
3-Phenyl-5-[4-(trifluoromethyl)phenyl]isoxazole (1e)20c
White solid; yield: 130 mg (45%).
1H NMR (400 MHz, CDCl3):  = 6.94 (s, 1 H), 7.48–7.52 (m, 3 H), 7.76
(d, J = 8.2 Hz, 2 H), 7.87–7.89 (m, 2 H), 7.96–7.98 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 98.9, 123.7 (q, J = 271.0 Hz), 126.1 (q,
J = 3.8 Hz), 126.8, 128.8, 128.8, 129.0, 130.3, 130.6, 131.9 (q, J = 32.7
Hz), 163.2, 168.8.
19F NMR (376 MHz, CDCl3):  = –62.9.
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

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Synthesis
5-(4-Bromophenyl)-3-phenylisoxazole (1f)20d
13C NMR (100 MHz, CDCl3):  = 21.4, 97.6, 124.0, 125.9, 127.4, 127.5,
128.8, 129.0 (2 C), 130.2, 130.8, 138.7, 163.1, 170.3.
White solid; yield: 112 mg (37%).
1H NMR (400 MHz, CDCl3):  = 6.84 (s, 1 H), 7.48–7.49 (m, 3 H), 7.62–
7.64 (m, 2 H), 7.70–7.72 (m, 2 H), 7.85–7.87 (m, 2 H).
5-Phenyl-3-(o-tolyl)isoxazole (1m)20a
Purified by column chromatography and GPC (EtOAc); yellow oil;
yield (2.5-mmol scale): 258 mg (44%).
1H NMR (400 MHz, CDCl3):  = 2.53 (s, 3 H), 6.70 (s, 1 H), 7.27–7.38
13C NMR (100 MHz, CDCl3):  = 97.9, 124.6, 126.4, 126.8, 127.3, 128.9,
129.0, 130.1, 132.3, 163.1, 169.3.
(m, 3 H), 7.43–7.51 (m, 3 H), 7.55–7.57 (m, 1 H), 7.83–7.86 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 21.1, 100.2, 125.9, 126.0, 127.5, 128.9,
129.0, 129.5, 129.5, 130.2, 131.1, 136.9, 163.7, 169.6.
3-Phenyl-5-(m-tolyl)isoxazole (1g)20c
Purified by column chromatography and GPC (EtOAc); white solid;
yield: 80 mg (34%).
1H NMR (400 MHz, CDCl3):  = 2.43 (s, 3 H), 6.81 (m, 1 H), 7.25–7.27
(m, 1 H), 7.35–7.39 (m, 1 H), 7.45–7.50 (m, 3 H), 7.63–7.66 (m, 2 H),
7.86–7.88 (m, 2 H).
5-Phenyl-3-(thiophen-2-yl)isoxazole (1n)20g
White solid; yield (3.0-mmol scale): 141 mg (21%).
1H NMR (400 MHz, CDCl3):  = 6.76 (s, 1 H), 7.13–7.15 (m, 1 H), 7.43–
13C NMR (100 MHz, CDCl3):  = 21.5, 97.4, 123.0, 126.4, 126.8, 127.4,
7.53 (m, 5 H), 7.81–7.83 (m, 2 H).
128.9, 129.2, 130.0, 131.0, 138.8, 163.0, 170.6.
13C NMR (100 MHz, CDCl3):  = 97.5, 125.9, 127.2, 127.4, 127.7, 127.7,
3-Phenyl-5-(thiophen-3-yl)isoxazole (1h)
129.0, 130.4, 130.9, 158.2, 170.4.
White solid; yield (2.0-mmol scale): 116 mg (25%); mp 120–122 °C.
1H NMR (400 MHz, CDCl3):  = 6.69 (s, 1 H), 7.43–7.50 (m, 5 H), 7.83–
3-Phenyl-5-(thiophen-2-yl)isoxazole (1o)20c
Purified by column chromatography (hexane/EtOAc 10:1); white sol-
id; yield: 97 mg (43%).
1H NMR (400 MHz, CDCl3):  = 6.69 (s, 1 H), 7.13–7.15 (m, 1 H), 7.45–
7.87 (m, 3 H).
13C NMR (100 MHz, CDCl3):  = 97.3, 124.3, 125.4, 126.8, 127.1, 128.9
(2 C), 129.1, 130.0, 162.9, 166.6.
7.47 (m, 4 H), 7.55–7.56 (m, 1 H), 7.83–7.86 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 97.3, 126.9, 127.1, 128.0, 128.1, 128.7,
HRMS (APCI): m/z [M + H]+ calcd for C13H10NOS: 228.0478; found:
228.0467.
128.9, 129.3, 130.1, 163.0, 164.4.
5-Phenyl-3-(p-tolyl)isoxazole (1i)20d
3-Phenyl-5-(o-tolyl)isoxazole (1p)20c
White solid; yield (3.0-mmol scale): 188 mg (27%).
Purified by column chromatography and GPC (CHCl3); yellow oil;
yield: 93 mg (39%).
1H NMR (400 MHz, CDCl3):  = 2.57 (s, 3 H), 6.72 (s, 1 H), 7.30–7.39
(m, 3 H), 7.46–7.51 (m, 3 H), 7.75–7.78 (m, 1 H), 7.87–7.90 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 21.5, 100.6, 126.3, 126.8, 127.1, 128.6,
1H NMR (400 MHz, CDCl3):  = 2.42 (s, 3H), 6.81 (s, 1 H), 7.28–7.30 (m,
2 H), 7.43–7.52 (m, 3 H), 7.75–7.78 (m, 2 H), 7.82–7.85 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 21.5, 97.4, 125.8, 126.3, 126.7, 127.6,
129.0, 129.6 (2 C), 130.2, 162.9, 170.2.
128.9, 129.3, 130.0, 130.1, 131.4, 136.3, 162.6, 170.6.
3-(4-Methoxyphenyl)-5-phenylisoxazole (1j)20e
White solid; yield (3.0-mmol scale): 150 mg (20%).
1H NMR (400 MHz, CDCl3):  = 3.87 (s, 3 H), 6.78 (s, 1 H), 6.99–7.01
(m, 2 H), 7.43–7.51 (m, 3 H), 7.79–7.85 (m, 4 H).
13C NMR (100 MHz, CDCl3):  = 55.4, 97.3, 114.3, 121.7, 125.8, 127.6,
Rh-Catalyzed Annulative Coupling (Scheme 2 and Scheme 3); Gen-
eral Procedure
A glass tube equipped with a magnetic stir bar was charged with isox-
azole
1
(0.2 mmol), alkyne
2
(0.62 mmol, 3.1 equiv),
128.2, 129.0, 130.2, 161.0, 162.6, 170.2.
[Cp*Rh(MeCN)3](SbF6)2 (0.008 mmol, 4.0 mol%), and Cu(OAc)2 (0.8
mmol, 4.0 equiv). The tube was evacuated and backfilled with N2 (3 ×)
followed by addition of 1,4-dioxane (4.0 mL) via syringe. The resulting
mixture was heated at 100 °C for 12 h. After cooling to r.t., the mix-
ture was poured into water and extracted with EtOAc (3 ×). The com-
bined organic extracts were washed with brine, dried (Na2SO4), and
concentrated under reduced pressure. The residue was subjected to
column chromatography (silica gel) to afford the corresponding prod-
uct. Further purification was performed by GPC if required.
5-Phenyl-3-[4-(trifluoromethyl)phenyl]isoxazole (1k)20f
White solid; yield: 59 mg (20%).
1H NMR (400 MHz, CDCl3):  = 6.87 (s, 1 H), 7.48–7.54 (m, 3 H), 7.75
(d, J = 8.1 Hz, 2 H), 7.85–7.87 (m, 2 H), 7.99–8.01 (m, 2 H).
13C NMR (100 MHz, CDCl3):  = 97.4, 123.9 (q, J = 270.7 Hz), 125.9,
126.0 (q, J = 3.7 Hz), 126.0, 127.2, 129.1, 130.5, 131.4 (q, J = 32.4 Hz),
132.6, 161.9, 171.1.
Note: the coupling products 3 exhibit broadened and split peaks in
NMR spectra owing to the presence of rotamers, and the following
data are reported as appeared in the spectra.
19F NMR (376 MHz, CDCl3):  = –62.8.
5-Phenyl-3-(m-tolyl)isoxazole (1l)20b
Purified by column chromatography and GPC (CHCl3); white solid;
yield (3.0-mmol scale): 344 mg (49%).
3,4-Diphenyl-1-(2,3,7,8-tetraphenylbenzo[de]chromen-9-yl)iso-
quinoline (3aa)
1H NMR (400 MHz, CDCl3):  = 2.44 (s, 3 H), 6.83 (s, 1 H), 7.29–7.30
(m, 1 H), 7.30–7.34 (m, 1 H), 7.45–7.52 (m, 3 H), 7.65–7.67 (m, 1 H),
7.70–7.71 (m, 1 H), 7.84–7.86 (m, 2 H).
Purified by column chromatography (hexane/EtOAc 5:1); yellow sol-
id; yield: 125 mg (83%); mp 167–169 °C.
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Synthesis
1H NMR (400 MHz, CDCl3):  = 6.54 (dd, J = 1.0, 7.1 Hz, 1 H), 6.70–6.72
(m, 4 H), 6.80–6.89 (m, 4 H), 6.97–7.03 (m, 2 H), 7.11 (s, 5 H), 7.13–
7.33 (m, 12 H), 7.34–7.40 (m, 5 H), 7.48–7.53 (m, 2 H), 7.55–7.58 (m, 1
H), 8.16–8.17 (m, 1 H).
132.5, 133.6, 133.9, 135.6, 135.7, 136.1, 136.1, 136.8, 137.2, 137.6,
137.9, 138.8, 138.9, 139.2, 139.6, 140.8, 141.0, 148.4, 149.6, 149.7,
157.1.
HRMS (APCI): m/z [M + H]+ calcd for C63H50NO: 836.3887; found:
13C NMR (100 MHz, CDCl3):  = 116.4, 117.4, 118.7, 121.9, 123.1,
125.7, 126.4, 126.5, 126.7, 127.1, 127.2, 127.3, 127.4, 127.5, 127.7,
127.8, 127.9, 128.0, 128.0, 128.2, 128.4, 128.5, 129.3, 129.4, 129.7,
130.0, 130.3, 130.9, 131.0, 131.2, 131.4, 131.5, 131.6, 131.8, 132.3,
133.7, 133.9, 135.6, 136.1, 137.5, 139.1, 139.7, 140.7, 141.1, 148.7,
149.7, 149.9, 156.9.
836.3878.
1-(2,3,7,8-Tetra-o-tolylbenzo[de]chromen-9-yl)-3,4-di-o-tolyliso-
quinoline (3ad)
Purified by column chromatography (hexane/EtOAc 10:1) and GPC;
yellow solid; yield: 48 mg (29%); crystals suitable for X-ray measure-
ment are obtained from MeOH solution layered with hexane; mp
187–189 °C.
HRMS (APCI): m/z [M + H]+ calcd for C57H38NO: 752.2948; found:
752.2946.
1H NMR (400 MHz, CDCl3):  = 1.44–2.42 (m, 18 H), 6.30–6.42 (m, 1
H), 6.57–6.70 (m, 1 H), 6.70–7.16 (m, 15 H), 7.16–7.21 (m, 10 H),
7.35–7.50 (m, 2 H), 7.99–8.12 (m, 1 H).
2-(3,4-Diphenylisoquinolin-1-yl)-3,4-diphenylnaphthalen-1-ol
(4aa)
Purified by column chromatography (hexane/EtOAc 10:1) and GPC;
yellow solid; crystals suitable for X-ray measurement were obtained
by pentane vapor diffusion into the EtOAc solution; mp 258–260 °C.
1H NMR (400 MHz, CDCl3):  = 6.55–6.70 (m, 3 H), 6.76–6.85 (m, 1 H),
6.90–6.92 (m, 2 H), 7.01–7.02 (m, 1 H), 7.07–7.10 (m, 3 H), 7.15–7.23
(m, 5 H), 7.26–7.47 (m, 8 H), 7.50–7.56 (m, 2 H), 7.78 (d, J = 8.1 Hz, 1
H), 8.48–8.50 (m, 1 H), 9.20 (br, 1 H).
13C NMR (100 MHz, CDCl3):  = 118.6, 123.0, 124.8, 125.2, 125.3,
125.5, 126.3, 126.3, 126.4, 126.5, 126.6, 127.1, 127.2, 127.4, 127.5,
127.8, 127.9, 128.5, 130.2, 130.2, 131.1, 131.2, 131.4, 131.7, 132.1,
133.8, 136.5, 137.1, 138.6, 139.4, 139.8, 140.2, 148.8, 150.7, 157.9.
13C NMR (100 MHz, CDCl3):  = 19.2, 19.2, 19.3, 19.4, 19.4, 19.6, 19.7,
19.7, 19.8, 19.9, 19.9, 20.1, 20.1, 20.2, 20.3, 20.6, 20.6, 20.9, 20.9, 21.3,
115.7, 115.8, 115.9, 117.1, 117.6, 117.8, 118.0, 118.6, 119.1, 119.2,
122.0, 122.1, 122.7, 122.8, 122.9, 123.4, 124.3, 124.5, 124.6, 124.9,
125.2, 125.3, 125.5, 125.8, 125.9, 126.1, 126.2, 126.3, 126.4, 126.8,
126.9, 126.9, 127.0, 127.0, 127.1, 127.4, 127.6, 127.7, 127.8, 127.8,
128.2, 128.3, 128.4, 128.7, 128.8, 129.2, 129.5, 129.5, 129.6, 129.6,
129.7, 129.7, 129.8, 129.9, 130.1, 130.2, 130.4, 130.7, 130.7, 130.9,
131.0, 131.3, 131.5, 131.8, 132.0, 132.1, 132.7, 132.9, 133.0, 133.2,
133.3, 133.5, 133.6, 133.7, 134.2, 134.7, 134.8, 135.6, 135.6, 136.1,
136.2, 136.4, 136.6, 136.7, 136.9, 136.9, 136.9, 137.1, 137.2, 137.3,
137.4, 137.5, 137.6, 137.8, 138.0, 138.1, 138.6, 140.0, 140.4, 140.5,
140.8, 149.7, 150.0, 151.0, 151.2, 151.3, 155.9.
HRMS (APCI): m/z [M + H]+ calcd for C43H30NO: 576.2322; found:
576.2321.
HRMS (APCI): m/z [M + H]+ calcd for C63H50NO: 836.3887; found:
836.3882.
1-(2,3,7,8-Tetra-p-tolylbenzo[de]chromen-9-yl)-3,4-di-p-tolyliso-
quinoline (3ab)
3,4-Bis(4-tert-butylphenyl)-1-[2,3,7,8-tetrakis(4-tert-butylphe-
nyl)benzo[de]chromen-9-yl]isoquinoline (3ae)
Purified by column chromatography (hexane/EtOAc 5:1) and GPC;
yellow solid; yield: 132 mg (79%); mp 180–182 °C.
1H NMR (400 MHz, CDCl3):  = 2.06 (s, 3 H), 2.15 (s, 3 H), 2.25 (s, 3 H),
2.31 (s, 3 H), 2.39 (s, 6 H), 6.42–6.60 (m, 4 H), 6.61–6.82 (m, 4 H),
6.84–6.96 (m, 2 H), 7.02–7.21 (m, 16 H), 7.43–7.50 (m, 2 H), 7.56 (d,
J = 7.7 Hz, 1 H), 8.09–8.12 (m, 1 H).
13C NMR (100 MHz, CDCl3):  = 21.0, 21.2, 21.2, 21.3, 21.4, 21.4, 116.0,
116.7, 118.8, 121.7, 122.9, 125.7, 126.2, 127.2, 127.3, 127.6, 127.9,
128.0, 128.1, 128.4, 128.6, 128. 7, 129.0, 129.1, 129.5, 130.0, 130.2,
130.7, 130.8, 131.0, 131.0, 131.2, 131.40, 131.4, 132.7, 132.8, 134.0,
134.8, 134.8, 135.6, 136.3, 136.3, 136.8, 137.2, 137.9, 138.4, 140.6,
148.5, 149.6, 149.8, 157.0.
Purified by column chromatography (hexane/EtOAc 20:1) and GPC;
yellow solid; yield: 165 mg (76%); mp 205–207 °C.
1H NMR (400 MHz, CDCl3):  = 1.08 (s, 9 H), 1.17 (s, 9 H), 1.21 (s, 9 H),
1.27 (s, 9 H), 1.34 (s, 9 H), 1.36 (s, 9 H), 6.50–6.52 (m, 1 H), 6.58 (d,
J = 8.6 Hz, 2 H), 6.80–6.82 (m, 3 H), 6.95 (d, J = 8.5 Hz, 2 H), 7.04–7.07
(m, 3 H), 7.10–7.24 (m, 9 H), 7.28–7.32 (m, 3 H), 7.41 (m, 3 H), 7.46–
7.54 (m, 2 H), 7.62–7.64 (m, 1 H), 8.18–8.20 (m, 1 H).
13C NMR (100 MHz, CDCl3):  = 31.1, 31.2, 31.3, 31.4, 31.4, 31.5, 34.1,
34.3, 34.4, 34.6, 34.7, 116.0, 116.8, 118.9, 121.7, 122.9, 123.1, 124.0,
124.1, 124.5, 124.5, 125.8, 126.1, 126.2, 127.4, 127.7, 1278.0, 128.2,
129.0, 129.4, 129.9, 130.4, 130.7, 130.8, 130.9, 131.0, 131.1, 131.1,
131.3, 132.8, 133.8, 134.7, 136.3, 136.3, 137.0, 138.4, 141.0, 148.0,
148.4, 148.9, 149.1, 149.7, 149.8, 149.9, 150.8, 157.0.
HRMS (APCI): m/z [M + H]+ calcd for C63H50NO: 836.3887; found:
836.3884.
HRMS (APCI): m/z [M + H]+ calcd for C81H86NO: 1088.6704; found:
1088.6674.
1-(2,3,7,8-Tetra-m-tolylbenzo[de]chromen-9-yl)-3,4-di-m-tolyli-
soquinoline (3ac)
Purified by column chromatography (hexane/EtOAc 10:1); yellow sol-
id; yield: 142 mg (85%); mp 150–152 °C.
1H NMR (400 MHz, CDCl3):  = 1.66–2.44 (m, 18 H), 6.40–6.76 (m, 8
H), 6.80–7.18 (m, 15 H), 7.20–7.40 (m, 3 H), 7.54–7.59 (m, 3 H), 8.19
(br, 1 H).
13C NMR (100 MHz, CDCl3):  = 21.3, 21.3, 21.4, 21.4, 21.5, 116.2,
117.4, 118.6, 121.7, 123.1, 125.9, 125.9, 126.3, 126.4, 126.9, 127.0,
127.4, 127.6, 127.7, 128.1, 128.2, 128.3, 128.4, 128.6, 128.7, 129.0,
129.1, 129.3, 129.6, 131.1, 131.2, 131.6, 131.7, 132.1, 132.2, 132.3,
3,4-Bis(4-methoxyphenyl)-1-[2,3,7,8-tetrakis(4-methoxyphe-
nyl)benzo[de]chromen-9-yl]isoquinoline (3af)
Purified by column chromatography (hexane/EtOAc 2:1) and GPC;
yellow solid; yield: 139 mg (75%); mp 187–189 °C.
1H NMR (400 MHz, CDCl3):  = 3.57 (d, J = 5.8 Hz, 3 H), 3.64 (d, J = 5.8
Hz, 3 H), 3.73 (d, J = 5.8 Hz, 3 H), 3.78 (d, J = 5.8 Hz, 3 H), 3.83–3.84 (m,
6 H), 6.25 (br, 1 H), 6.33–6.37 (m, 2 H), 6.46–6.55 (m, 2 H), 6.55–6.65
(m, 2 H), 6.65–6.72 (m, 2 H), 6.77–6.84 (m, 3 H), 6.84–7.00 (m, 4 H),
7.00–7.20 (m, 9 H), 7.26–7.34 (m, 1 H), 7.42–7.51 (m, 2 H), 7.57–7.60
(m, 1 H), 8.06–8.09 (m, 1 H).
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

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Synthesis
13C NMR (100 MHz, CDCl3):  = 55.0, 55.1, 55.2, 55.3, 112.1, 112.6,
112.9, 113.4, 113.6, 113.8, 114.8, 115.6, 115.8, 118.9, 121.7, 122.6,
125.7, 126.2, 126.4, 127.2, 127.5, 128.1, 128.5, 129.6, 130.0, 130.6,
131.6, 131.7, 132.0, 132.2, 132.3, 132.4, 132.5, 132.6, 132.9, 133.9,
134.2, 136.5, 140.4, 148.5, 149.6, 149.6, 157.0, 157.3, 157.9, 158.4,
158.6, 158.9, 159.0.
13C NMR (100 MHz, CDCl3):  = 13.3, 14.2, 14.4, 14.7, 14.8, 19.6, 21.2,
23.5, 23.8, 24.3, 24.4, 28.4, 29.8, 30.7, 31.6, 33.2, 37.4, 111.2, 111.6,
118.6, 119.4, 121.5, 123.1, 125.2, 126.7, 127.1, 127.4, 127.6, 128.0,
129.3, 131.5, 133.3, 135.6, 138.4, 148.3, 151.7, 152.4, 156.2.
HRMS (APCI): m/z [M + H]+ calcd for C39H50NO: 548.3887; found:
548.3867.
HRMS (APCI): m/z [M + H]+ calcd for C63H50NO7: 932.3582; found:
932.3563.
1-(5-Methyl-2,3,7,8-tetraphenylbenzo[de]chromen-9-yl)-3,4-di-
phenylisoquinoline (3ba)
1-{2,3,7,8-Tetrakis[4-(trifluoromethyl)phenyl]ben-
zo[de]chromen-9-yl}-3,4-bis[4-(trifluoromethyl)phenyl]isoquin-
oline (3ag)
Purified by column chromatography (hexane/EtOAc 3:1); yellow sol-
id; yield: 114 mg (75%); mp 159–161 °C.
1H NMR (400 MHz, CDCl3):  = 2.19 (s, 3 H), 6.39 (s, 1 H), 6.68–6.70
(m, 4 H), 6.79–6.88 (m, 4 H), 6.99–7.02 (m, 3 H), 7.10 (s, 5 H), 7.16–
7.21 (m, 4 H), 7.23 (m, 2 H), 7.247.30 (m, 4 H), 7.33–7.42 (m, 5 H),
7.48–7.52 (m, 2 H), 7.55–7.57 (m, 1 H), 8.16–8.18 (m, 1 H).
13C NMR (100 MHz, CDCl3):  = 22.4, 117.3, 117.9, 118.3, 120.2, 122.2,
125.6, 125.7, 126.3, 126.5, 126.7, 127.1, 127.2, 127.4, 127.4, 127.6,
127.7, 127.8, 128.0, 128.4, 128.6, 129.3, 129.3, 129.7, 130.0, 130.3,
130.4, 130.9, 131.1, 131.2, 131.5, 131.6, 131.7, 131.8, 132.2, 133.8,
134.2, 135.7, 136.0, 137.6, 138.2, 139.3, 139.9, 140.8, 141.2, 148.8,
149.7, 149.9, 157.1.
Purified by column chromatography (hexane/EtOAc 5:1); yellow sol-
id; yield: 107 mg (46%); mp 341–343 °C.
1H NMR (400 MHz, CDCl3):  = 6.58–6.60 (m, 1 H), 6.72 (d, J = 8.2 Hz, 2
H), 6.78 (d, J = 7.8 Hz, 1 H), 6.97–7.04 (m, 4 H), 7.11–7.13 (m, 2 H),
7.18–7.22 (m, 2 H), 7.28–7.42 (m, 6 H), 7.47–7.62 (m, 6 H), 7.67–7.76
(m, 5 H), 8.28–8.30 (m, 1 H).
13C NMR (100 MHz, CDCl3):  = 117.6, 118.0, 118.3, 121.9, 122.2,
122.5, 122.7, 123.7, 124.5, 124.6, 124.7, 124.7, 124.9, 125.3, 125.4,
125.8, 125.9, 126.5, 126.8, 127.2, 127.5, 127.9, 128.4, 128.6, 129.0,
129.2, 129.3, 129.6, 129.8, 129.9, 130.2, 130.4, 130.5, 130.6, 130.9,
131.1, 131.4, 131.5, 131.6, 131.7, 132.1, 133.7, 135.6, 136.3, 138.5,
139.6, 140.3, 142.0, 142.9, 143.6, 147.9, 148.7, 149.8, 156.7.
HRMS (APCI): m/z [M + H]+ calcd for C58H40NO: 766.3104; found:
766.3101.
19F NMR (376 MHz, CDCl3):  = –62.54, –62.56, –62.61, –62.65, –62.69,
–69.92.
HRMS (APCI): m/z [M + H]+ calcd for C63H32F18NO: 1160.2191; found:
1160.2174.
1-(5-tert-Butyl-2,3,7,8-tetraphenylbenzo[de]chromen-9-yl)-3,4-
diphenylisoquinoline (3ca)
Purified by column chromatography (hexane/EtOAc 4:1); yellow sol-
id; yield: 122 mg (76%); mp 238–240 °C.
1H NMR (400 MHz, CDCl3):  = 1.11 (s, 9 H), 6.65–6.71 (m, 5 H), 6.80–
6.89 (m, 4 H), 6.99–7.03 (m, 2 H), 7.07–7.12 (m, 5 H), 7.16–7.32 (m, 10
H), 7.32–7.43 (m, 5 H), 7.46–7.53 (m, 2 H), 7.55–7.58 (m, 1 H), 8.15–
8.17 (m, 1 H).
13C NMR (100 MHz, CDCl3):  = 30.9, 35.1, 115.2, 117.6, 118.0, 118.4,
120.1, 125.6, 125.7, 126.3, 126.4, 126.7, 127.1, 127.2, 127.3, 127.4,
127.6, 127.8, 127.8, 127.9, 128.4, 128.6, 129.2, 129.3, 129.7, 130.1,
130.3, 130.9, 131.1, 131.2, 131.4, 131.6, 131.6, 131.9, 133.9, 135.7,
136.0, 137.6, 139.3, 139.9, 140.7, 141.1, 148.5, 149.6, 149.8, 151.0,
157.1.
3,4-Bis(4-bromophenyl)-1-[2,3,7,8-tetrakis(4-bromophenyl)ben-
zo[de]chromen-9-yl]isoquinoline (3ah)
Purified by column chromatography (hexane/EtOAc 10:1); yellow sol-
id; yield: 170 mg (69%); mp 203–205 °C.
1H NMR (400 MHz, CDCl3):  = 6.42–6.50 (m, 2 H), 6.50–6.56 (m, 2 H),
6.82–6.92 (m, 4 H), 6.96–7.00 (m, 3 H), 7.07–7.08 (m, 3 H), 7.13–7.24
(m, 5 H), 7.27–7.30 (m, 2 H), 7.38–7.41 (m, 1 H), 7.41–7.45 (m, 2 H),
7.51–7.60 (m, 6 H), 8.13 (m, 1 H).
13C NMR (100 MHz, CDCl3):  = 116.9, 116.9, 118.3, 120.4, 121.1,
121.6, 121.7, 121.9, 122.2, 122.8, 123.3, 125.8, 127.2, 127.3, 128.6,
128.8, 129.9, 130.1, 130.4, 130.7, 130.9, 131.2, 131.5, 131.5, 131.7,
132.0, 132.34, 132.7, 132.7, 132.9, 132.9, 133.0, 133.0, 133.3, 133.7,
133.9, 135.7, 135.7, 137.4, 138.2, 139.4, 139.4, 148.0, 148.8, 149.6,
156.7.
HRMS (APCI): m/z [M + H]+ calcd for C61H46NO: 808.3574; found:
808.3583.
1-(5-Methoxy-2,3,7,8-tetraphenylbenzo[de]chromen-9-yl)-3,4-di-
phenylisoquinoline (3da)
HRMS (APCI): m/z [M + H]+ calcd for C57H32Br6NO: 1225.7529; found:
1225.7500.
Purified by column chromatography (hexane/EtOAc 5:1); yellow sol-
id; yield: 126 mg (80%); mp 155–157 °C.
1H NMR (400 MHz, CDCl3):  = 3.59 (s, 3 H), 6.23 (d, J = 2.2 Hz, 1 H),
6.56 (d, J = 2.2 Hz, 1 H), 6.68–6.73 (m, 4 H), 6.80–6.89 (m, 4 H), 6.98–
7.05 (m, 3 H), 7.10 (s, 5 H), 7.18–7.23 (m, 6 H), 7.27–7.40 (m, 7 H),
7.46–7.52 (m, 2 H), 7.55–7.56 (m, 1 H), 8.15–8.18 (m, 1 H).
13C NMR (100 MHz, CDCl3):  = 54.9, 101.9, 108.4, 117.0, 117.5, 125.7,
125.7, 126.4, 126.4, 126.7, 127.1, 127.2, 127.4, 127.4, 127.6, 127.7,
127.8, 128.0, 128.0, 128.1, 128.4, 128.6, 129.3, 129.7, 130.0, 130.1,
130.3, 130.8, 131.0, 131.2, 131.3, 131.5, 131.8, 133.6, 134.2, 135.4,
135.6, 136.0, 137.5, 139.4, 139.9, 141.1, 141.3, 149.2, 149.6, 149.8,
157.0, 159.7.
3,4-Dipropyl-1-(2,3,7,8-tetrapropylbenzo[de]chromen-9-yl)iso-
quinoline (3ai)
Purified by column chromatography (hexane/EtOAc 40:1); yellow oil;
yield: 69 mg (63%).
1H NMR (400 MHz, CDCl3):  = 0.43 (t, J = 7.3 Hz, 3 H), 0.61 (t, J = 7.3
Hz, 3 H), 0.76–0.87 (m, 2 H), 0.94 (t, J = 7.3 Hz, 3 H), 1.01 (t, J = 7.3 Hz,
3 H), 1.08–1.13 (m, 6 H), 1.21–1.27 (m, 1 H), 1.47–1.54 (m, 3 H), 1.65–
1.87 (m, 6 H), 1.95 (t, J = 7.2 Hz, 2 H), 2.12–2.19 (m, 1 H), 2.28–2.32
(m, 2 H), 2.59–2.66 (m, 1 H), 2.89–2.91 (m, 2 H), 2.92–3.14 (m, 4 H),
6.75 (d, J = 7.2 Hz, 1 H), 7.29–7.35 (m, 2 H), 7.49 (d, J = 8.7 Hz, 1 H),
7.56–7.65 (m, 2 H), 8.02 (d, J = 8.6 Hz, 1 H).
HRMS (APCI): m/z [M + H]+ calcd for C58H40NO2: 782.3054; found:
782.3045.
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

J
T. Noguchi et al.
Paper
Synthesis
3,4-Diphenyl-1-[2,3,7,8-tetraphenyl-5-(trifluoromethyl)ben-
zo[de]chromen-9-yl]isoquinoline (3ea)
13C NMR (100 MHz, CDCl3):  = 111.2, 115.9, 119.7, 125.8, 126.0,
126.5, 126.7, 126.8, 127.0, 127.1, 127.3, 127.3, 127.4, 127.6, 127.8,
128.2, 128.3, 128.4, 128.9, 129.1, 129.6, 129.7, 129.8, 130.1, 130.1,
131.20, 131.5, 133.6, 135.9, 136.0, 137.5, 139.3, 139.5, 140.3, 140.0,
142.1, 148.5, 149.7, 149.9, 155.9.
HRMS (APCI): m/z [M + H]+ calcd for C55H36NOS: 758.2512; found:
758.2511.
Purified by column chromatography (hexane/EtOAc 4:1); yellow sol-
id; yield: 138 mg (84%); mp 160–162 °C.
1H NMR (400 MHz, CDCl3):  = 6.67–6.71 (m, 5 H), 6.82–6.89 (m, 4 H),
6.98–7.07 (m, 2 H), 7.09–7.13 (m, 5 H), 7.15–7.25 (m, 6 H), 7.27–7.35
(m, 3 H), 7.37–7.44 (m, 5 H), 7.50–7.55 (m, 3 H), 7.57–7.60 (m, 1 H),
8.09–8.12 (m, 1 H).
6-Methyl-3,4-diphenyl-1-(2,3,7,8-tetraphenylbenzo[de]chromen-
9-yl)isoquinoline (3ia)
13C NMR (100 MHz, CDCl3):  = 111.4, 117.0, 120.4, 120.4, 120.9,
122.8, 122.9, 125.5, 125.9, 126.1, 126.7, 126.9, 127.0, 127.1, 127.2,
127.2, 127.4, 127.5, 127.9, 128.2, 128.2, 128.4, 128.5, 128.6, 129.6,
129.6, 129.8, 129.9, 130.0, 130.2, 130.3, 130.7, 130.9, 131.2, 131.2,
131.4, 131.5, 131.6, 132.3, 133.0, 133.2, 134.0, 134.7, 136.1, 137.4,
138.1, 139.1, 141.0, 142.1, 149.5, 149.9, 150.0, 156.2.
Purified by column chromatography (hexane/EtOAc 4:1); yellow sol-
id; yield: 129 mg (84%); mp 157–159 °C.
1H NMR (400 MHz, CDCl3):  = 2.39 (s, 3 H), 6.53–6.55 (m, 1 H), 6.70–
6.73 (m, 4 H), 6.81–6.88 (m, 4 H), 6.99–7.05 (m, 2 H), 7.07–7.11 (m, 5
H), 7.13–7.32 (m, 12 H), 7.33–7.43 (m, 6 H), 8.04–8.06 (m, 1 H).
19F NMR (376 MHz, CDCl3):  = –63.03.
13C NMR (100 MHz, CDCl3):  = 22.2, 116.3, 117.4, 118.9, 121.9, 123.1,
124.6, 125.7, 125.8, 126.4, 126.6, 127.0, 127.2, 127.4, 127.4, 127.7,
127.8, 127.9, 128.0, 128.1, 128.2, 128.4, 128.6, 128.8, 129.0, 129.3,
129.4, 130.0, 130.1, 130.3, 130.9, 131.0, 131.1, 131.2, 131.4, 131.6,
131.8, 132.4, 133.7, 133.8, 135.7, 136.3, 137.7, 139.2, 139.7, 140.0,
140.7, 141.3, 148.6, 149.7, 150.1, 156.6.
HRMS (APCI): m/z [M + H]+ calcd for C58H37F3NO: 820.2822; found:
820.2848.
1-(5-Bromo-2,3,7,8-tetraphenylbenzo[de]chromen-9-yl)-3,4-di-
phenylisoquinoline (3fa)
Purified by column chromatography (hexane/EtOAc 4:1) and GPC;
yellow solid; yield: 110 mg (67%); mp 172–174 °C.
1H NMR (400 MHz, CDCl3):  = 6.61 (m, 1 H), 6.68–6.70 (m, 4 H), 6.80–
6.89 (m, 4 H), 6.98–7.05 (m, 2 H), 7.10 (s, 5 H), 7.12–7.31 (m, 9 H),
7.32–7.43 (m, 6 H), 7.49–7.53 (m, 2 H), 7.55–7.58 (m, 1 H), 8.10–8.13
(m, 1 H).
HRMS (APCI): m/z [M + H]+ calcd for C58H40NO: 766.3104; found:
766.3104.
6-Methoxy-3,4-diphenyl-1-(2,3,7,8-tetraphenylben-
zo[de]chromen-9-yl)isoquinoline (3ja)
Purified by column chromatography (hexane/EtOAc 4:1); yellow sol-
id; yield: 122 mg (78%); mp 157–159 °C.
1H NMR (400 MHz, CDCl3):  = 3.68 (s, 3 H), 6.52–6.54 (m, 1 H), 6.71–
6.85 (m, 6 H), 6.87–6.91 (m, 3 H), 6.97–7.05 (m, 2 H), 7.09–7.16 (m, 8
H), 7.17–7.32 (m, 9 H), 7.34–7.41 (m, 5 H), 8.02–8.04 (m, 1 H).
13C NMR (100 MHz, CDCl3):  = 116.5, 119.2, 119.3, 120.4, 123.6,
124.9, 125.8, 125.9, 126.6, 126.7, 126.8, 128.0, 128.2, 128.4, 128.6,
129.5, 129.5, 129.6, 129.8, 130.2, 130.5, 130.7, 130.9, 131.1, 131.3,
131.5, 133.3, 134.5, 134.8, 135.0, 136.1, 137.4, 138.4, 139.3, 141.0,
141.9, 149.7, 149.9, 149.9, 156.5.
13C NMR (100 MHz, CDCl3):  = 55.2, 103.9, 116.3, 117.4, 118.8, 121.9,
123.0, 123.2, 125.7, 126.4, 126.5, 126.6, 127.0, 127.2, 127.4, 127.7,
127.8, 127.9, 128.0, 128.0, 128.2, 128.5, 128.6, 128.8, 129.2, 129.4,
129.4, 130.1, 130.2, 130.9, 131.0, 131.2, 131.3, 131.4, 131.6, 131.7,
132.3, 133.7, 133.8, 135.7, 133.7, 133.8, 135.7, 137.8, 138.1, 139.2,
139.7, 140.6, 141.4, 148.6, 149.7, 150.6, 156.1, 160.4.
HRMS (APCI): m/z [M + H]+ calcd for C57H37BrNO: 832.2037; found:
832.1912.
1-(4-Methyl-2,3,7,8-tetraphenylbenzo[de]chromen-9-yl)-3,4-di-
phenylisoquinoline (3ga)
Purified by column chromatography (hexane/EtOAc 5:1); yellow sol-
id; yield: 47 mg (30%); crystals suitable for X-ray measurement were
obtained from CH2Cl2 solution layered with pentane; mp 157–159 °C.
HRMS (APCI): m/z [M + H]+ calcd for C58H40NO2: 782.3054; found:
782.3053.
1H NMR (400 MHz, CDCl3):  = 1.62 (s, 3 H), 6.65–6.71 (m, 4 H), 6.79–
6.86 (m, 4 H), 6.95–7.01 (m, 5 H), 7.05–7.11 (m, 4 H), 7.15–7.41 (m, 14
H), 7.48–7.54 (m, 3 H), 8.15–8.17 (m, 1 H).
13C NMR (100 MHz, CDCl3):  = 22.6, 117.7, 118.7, 123.1, 123.5, 125.6,
125.7, 126.2, 126.3, 126.4, 126.5, 126.6, 127.0, 127.0, 127.2, 127.3,
127.4, 127.6, 127.7, 127.8, 127.9, 128.3, 128.8, 129.2, 129.6, 130.0,
130.3, 130.9, 131.2, 131.5, 131.5, 131.7, 132.0, 132.9, 134.4, 135.9,
137.6, 138.5, 139.3, 139.6, 139.7, 141.1, 149.6, 149.7, 150.2, 157.2.
3,4-Diphenyl-1-(2,3,7,8-tetraphenylbenzo[de]chromen-9-yl)-6-
(trifluoromethyl)isoquinoline (3ka)
Purified by column chromatography (hexane/EtOAc 4:1); yellow sol-
id; yield: 83 mg (56%); mp 188–190 °C.
1H NMR (400 MHz, CDCl3):  = 6.57–6.58 (m, 1 H), 6.68–6.70 (m, 4 H),
6.83–6.90 (m, 4 H), 7.00–7.02 (m, 2 H), 7.09–7.14 (m, 5 H), 7.16–7.26
(m, 10 H), 7.32–7.44 (m, 6 H), 7.68 (d, J = 8.8 Hz, 1 H), 7.89 (s, 1 H),
8.32 (d, J = 8.7 Hz, 1 H).
HRMS (APCI): m/z [M + H]+ calcd for C58H40NO: 766.3104; found:
13C NMR (100 MHz, CDCl3):  = 116.6, 117.6, 117.9, 121.8, 122.1,
123.2, 123.6, 123.6, 125.2, 125.9, 126.5, 127.1, 127.3, 127.5, 127.7,
127.8, 128.0, 128.0, 128.1, 128.2, 128.4, 128.5, 128.7, 129.0, 129.3,
130.0, 130.2, 130.9, 131.0, 131.1, 131.3, 131.3, 131.3, 131.5, 131.5,
131.8, 132.3, 133.6, 134.1, 135.3, 135.4, 136.3, 138.9, 139.5, 140.5,
148.7, 149.9, 151.4, 157.2.
19F NMR (376 MHz, CDCl3):  = –62.78.
HRMS (APCI): m/z [M + H]+ calcd for C58H37F3NO: 820.2822; found:
766.3120.
3,4-Diphenyl-1-(2,3,6,7-tetraphenylthieno[4,3,2-de]chromen-8-
yl)isoquinoline (3ha)
Purified by column chromatography (hexane/EtOAc 4:1); yellow sol-
id; yield: 35 mg (23%); crystals suitable for X-ray measurement were
obtained from CH2Cl2 solution layered with pentane; mp 164–166 °C.
1H NMR (400 MHz, CDCl3):  = 6.39 (m, 1 H), 6.72 (m, 2 H), 6.86–6.94
(m, 6 H), 6.99–7.11 (m, 7 H), 7.16–7.35 (m, 12 H), 7.39–7.42 (m, 2 H),
7.51–7.55 (m, 2 H), 7.56–7.60 (m, 1 H), 8.17–8.19 (m, 1 H).
820.2815.
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

K
T. Noguchi et al.
Paper
Synthesis
7-Methyl-3,4-diphenyl-1-(2,3,7,8-tetraphenylbenzo[de]chromen-
9-yl)isoquinoline (3la)
1H NMR (400 MHz, CDCl3):  = 6.49–6.57 (m, 2 H), 6.66–6.78 (m, 1 H),
6.79–7.10 (m, 8 H), 7.11–7.18 (m, 5 H), 7.29–7.47 (m, 8 H), 7.71 (d,
J = 8.4 Hz, 1 H), 9.90 (br, 1 H) °C.
13C NMR (100 MHz, CDCl3):  = 119.5, 124.7, 125.1, 125.5, 126.1,
126.3, 126.5, 126.9, 127.3, 127.3, 127.4, 127.5, 127.78, 128.1, 128.5,
129.3, 130.0, 130.1, 130.3, 130.9, 131.3, 132.3, 136.3, 137.0, 138.3,
139.1, 134.0, 140.0, 141.1, 148.6, 149.3, 157.8.
Purified by column chromatography (hexane/EtOAc 4:1); yellow sol-
id; yield: 135 mg (88%); mp 158–160 °C.
1H NMR (400 MHz, CDCl3):  = 2.47 (s, 3 H), 6.55 (d, J = 7.1 Hz, 1 H),
6.69–6.76 (m, 4 H), 6.79–6.83 (m, 1 H), 6.84–6.90 (m, 3 H), 6.95–7.04
(m, 3 H), 7.11–7.12 (m, 5 H), 7.14–7.31 (m, 10 H), 7.33–7.41 (m, 6 H),
7.44–7.46 (m, 1 H), 7.88 (s, 1 H).
HRMS (APCI): m/z [M + H]+ calcd for C41H28NOS: 582.1886; found:
13C NMR (100 MHz, CDCl3):  = 21.8, 116.3, 117.4, 119.0, 121.9, 123.1,
125.6, 125.7, 126.2, 126.4, 126.5, 126.6, 127.0, 127.3, 127.4, 127.4,
127.7, 127.8, 127.9, 128.0, 128.1, 128.2, 128.3, 128.5, 129.3, 129.4,
130.1, 130.3, 130.9, 131.0, 131.1, 131.2, 131.4, 131.5, 131.6, 131.9,
132.5, 133.8, 133.8, 134.3, 135.7, 136.3, 137.7, 139.2, 139.8, 140.8,
141.3, 148.7, 149.2, 149.8, 156.1.
582.1897.
2-(3,4-Diphenylisoquinolin-1-yl)-8-methyl-3,4-diphenylnaphtha-
len-1-ol (4pa)
Purified by column chromatography (hexane/EtOAc 10:1) and GPC;
yellow solid; yield: 86 mg (73%); crystals suitable for X-ray measure-
ment were obtained by hexane vapor diffusion into EtOAc solution;
mp 170–172 °C.
HRMS (APCI): m/z [M + H]+ calcd for C58H40NO: 766.3104; found:
766.3102.
1H NMR (400 MHz, CDCl3):  = 3.04 (s, 3 H), 6.58–6.65 (m, 2 H), 6.73–
6.78 (m, 2 H), 6.84 (d, J = 7.7 Hz, 2 H), 7.03–7.10 (m, 2 H), 7.17–7.23
(m, 4 H), 7.24–7.30 (m, 2 H), 7.30–7.42 (m, 8 H), 7.43–7.46 (m, 1 H),
7.48–7.50 (m, 1 H), 7.59–7.61 (m, 1 H), 7.84–7.86 (m, 1 H), 8.76 (br, 1
H).
13C NMR (100 MHz, CDCl3):  = 25.4, 118.8, 124.0, 125.2, 125.3, 125.5,
126.2, 126.3, 126.5, 126., 127.1, 127.3, 127.4, 127.7, 127.9, 128.1,
128.5, 130.2, 130.3, 130.4, 131.2, 131.5, 131.6, 132.3, 135.6, 136.3,
136.7, 137.1, 138.3, 140.0, 140.1, 140.3, 148.8, 153.2, 158.2.
8-Methyl-3,4-diphenyl-1-(2,3,7,8-tetraphenylbenzo[de]chromen-
9-yl)isoquinoline (3ma)
Purified by column chromatography (hexane/EtOAc 4:1); yellow sol-
id; yield: 135 mg (88%); crystals suitable for X-ray measurement were
obtained by slow evaporation of hexane solution; mp 157–159 °C.
1H NMR (400 MHz, CDCl3):  = 2.59 (s, 3 H), 6.53 (dd, J = 1.0, 7.0 Hz, 1
H), 6.67 (s, 1 H), 6.76–6.81 (m, 4 H), 6.86–6.95 (m, 4 H), 7.01–7.06 (m,
2 H), 7.10–7.20 (m, 11 H), 7.22–7.31 (m, 6 H), 7.33–7.38 (m, 5 H),
7.42–7.45 (m, 1 H).
HRMS (APCI): m/z [M + H]+ calcd for C44H32NO: 590.2478; found:
13C NMR (100 MHz, CDCl3):  = 23.8, 116.3, 117.4, 122.0, 123.1, 123.4,
124.7, 125.6, 126.4, 126.7, 127.0, 127.3, 127.4, 127.6, 127.7, 127.7,
127.8, 128.0, 128.1, 128.3, 128.6, 129.0, 129.1, 129.5, 129.7, 129.8,
130.1, 130.9, 131.0, 131.2, 131.4, 131.5, 131.6, 132.4, 133.7, 133.8,
135.5, 135.6, 137.6, 138.1, 139.2, 139.4, 139.8, 141.1, 148.7, 148.8,
148.8, 155.2.
590.2494.
3,4-Diphenyl-1-(2,3,7,8-tetraphenylbenzo[de]chromen-9-yl)iso-
quinoline Hydrochloride (3aa·HCl)
To a solution of 3aa (0.1 mmol) in CH2Cl2 (1.0 mL) was added HCl
solution (1 mol/L in Et2O, 1.0 mL) at r.t. After stirring for 1 h, volatiles
were removed under reduced pressure to give isoquinolinium salt
3aa·HCl as a red solid; yield: 74 mg (93%); mp 187–189 °C.
HRMS (APCI): m/z [M + H]+ calcd for C58H40NO: 766.3104; found:
766.3105.
1H NMR (400 MHz, CDCl3):  = 6.58–6.59 (m, 1 H), 6.67–6.90 (m, 8 H),
4,5-Diphenyl-7-(2,3,7,8-tetraphenylbenzo[de]chromen-9-yl)thie-
no[2,3-c]pyridine (3na)
7.01–7.08 (m, 3 H), 7.08–7.42 (m, 22 H), 7.61 (br, 3 H), 8.26 (br, 1 H).
13C NMR (100 MHz, CDCl3):  = 116.7, 117.7, 121.8, 123.3, 126.0,
126.5, 126.6, 127.3, 127.5, 127.8, 127.8, 127.9, 128.1, 128.2, 128.5,
128.7, 129.2, 129.4, 129.9, 130.1, 130.6, 130.8, 131.0, 131.1, 131.2,
131.3, 131.8, 132.1, 132.4, 133.7, 134.4, 135.4, 138.9, 139.4, 140.4,
148.8, 150.1.
HRMS (APCI): m/z [M – Cl]+ calcd for C57H38NO: 752.2948; found:
752.2925.
Purified by column chromatography (hexane/EtOAc 4:1); yellow sol-
id; yield: 43 mg (28%); mp 172–174 °C.
1H NMR (400 MHz, CDCl3):  = 6.55 (dd, J = 1.4, 6.7 Hz, 1 H), 6.76–6.77
(m, 1 H), 6.82–6.84 (m, 1 H), 6.86–6.95 (m, 5 H), 7.00–7.08 (m, 2 H),
7.10–7.20 (m, 11 H), 7.22–7.24 (m, 8 H), 7.33–7.45 (m, 4 H), 7.54 (d,
J = 5.5 Hz, 1 H).
13C NMR (100 MHz, CDCl3):  = 116.4, 117.5, 118.9, 121.9, 123.1,
123.5, 125.9, 126.4, 126.8, 127.1, 127.3, 127.5, 127.7, 127.9, 127.9,
128.1, 128.2, 128.4, 128.5, 128.7, 129.3, 130.4, 130.6, 131.0, 131.1,
131.4, 131.5, 131.5, 132.5, 133.7, 134.0, 135.6, 136.6, 138.2, 139.1,
139.4, 140.1, 140.6, 145.6, 148.7, 149.8, 150.1, 150.9.
HRMS (APCI): m/z [M + H]+ calcd for C55H36NOS: 758.2512; found:
758.2511.
2-Methyl-3,4-diphenyl-1-(2,3,7,8-tetraphenylbenzo[de]chromen-
9-yl)isoquinolinium Triflate (3aa·MeOTf)
To a solution of 3aa (0.1 mmol) in CH2Cl2 (1.0 mL) was added MeOTf
solution (0.10 mmol in 0.5 mL of CH2Cl2) at r.t. After stirring for 1 h,
volatiles were removed under reduced pressure to give isoquinolini-
um salt 3aa·MeOTf as a red solid; yield: 78 mg (85%); mp 181–183 °C.
1H NMR (400 MHz, CDCl3):  = 3.98 (s, 3 H), 6.49–6.56 (m, 2 H), 6.71–
6.85 (m, 5 H), 6.92–7.10 (m, 6 H), 6.94–7.24 (m, 8 H), 7.28–7.42 (m, 10
H), 7.42–7.54 (m, 2 H), 7.70–7.72 (m, 1 H), 8.10–8.14 (m, 2 H), 8.50–
8.52 (m, 1 H).
13C NMR (100 MHz, CDCl3):  = 46.6, 108.3, 118.8, 118.9, 119.3, 121.4,
122.5, 124.1, 127.3, 127.4, 127.7, 127.9, 128.3, 128.37, 128.40, 128.5,
128.8, 129.0, 129.1, 129.2, 129.2, 129.3, 129.3, 129.6, 129.86, 129.91,
6-(3,4-Diphenylisoquinolin-1-yl)-4,5-diphenylbenzo[b]thiophen-
7-ol (4oa)
Purified by column chromatography (hexane/EtOAc 5:1) and GPC;
yellow solid; yield: 54 mg (50%); crystals suitable for X-ray measure-
ment were obtained by slow evaporation of CHCl3 solution; mp 152–
154 °C.
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

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T. Noguchi et al.
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Synthesis
130.1, 130.4, 130.5, 130.86, 130.94, 131.1, 131.3, 132.1, 132.3, 132.5,
132.7, 133.4, 134.0, 136.0, 136.8, 137.2, 137.29, 137.4, 137.8, 138.9,
145.3, 150.0, 157.8.
HRMS (APCI): m/z [M – MeOTf + H]+ calcd for C57H38NO: 752.2948;
X.; Yu, X.; Ji, D.; Yamamoto, Y.; Almansour, A. I.; Arumugam, N.;
Kumar, R. S.; Bao, M. Org. Lett. 2016, 18, 4246. (i) Castro, L. C. M.;
Obata, A.; Aihara, Y.; Chatani, N. Chem. Eur. J. 2016, 22, 1362.
(j) Annamalai, P.; Chen, W.-Y.; Raju, S.; Hsu, K.-C.; Upadhyay, N.
S.; Cheng, C.-H.; Chuang, S.-C. Adv. Synth. Catal. 2016, 358, 3642.
(k) Fukuzumi, K.; Unoh, Y.; Nishii, Y.; Satoh, T.; Hirano, K.;
Miura, M. J. Org. Chem. 2016, 81, 2474. (l) Wang, L.; Yu, Y.; Yang,
M.; Kuai, C.; Cai, D.; Yu, J.; Cuia, X. Adv. Synth. Catal. 2017, 359,
3818. (m) Feng, R.; Gao, Y.; Liu, Z.; Zhang, Y. Synlett 2017, 28,
2147.
found: 752.2935.
Funding Information
This work was supported by JSPS KAKENHI JP 17H06092 (Grant-in-
(6) For recent examples, see: (a) Jayakumar, J.; Parthasarathy, K.;
Chen, Y.-H.; Lee, T.-H.; Chuang, S.-C.; Cheng, C.-H. Angew. Chem.
Int. Ed. 2014, 53, 9889. (b) Ge, Q.; Hu, Y.; Li, B.; Wang, B. Org.
Lett. 2016, 18, 2483. (c) Ge, Q.; Lia, B.; Wang, B. Org. Biomol.
Chem. 2016, 14, 1814. (d) Feng, B.; Wan, D.; Yan, L.; Kadam, V.
D.; You, J.; Gao, G. RSC Adv. 2016, 6, 66407. (e) Han, Y. R.; Shim,
S.-H.; Kim, D.-S.; Jun, C.-H. Org. Lett. 2017, 19, 2941. (f) Yin, J.;
Zhou, F.; Zhu, L.; Yang, M.; Lan, Y.; You, J. Chem. Sci. 2018, 9,
5488. (g) Shankar, M.; Ghosh, K.; Mukherjee, K.; Rit, R. K.;
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M