Synthesis of benzo[g]chrysenes

Article abstract of DOI:10.1016/j.tet.2012.10.054

A facile synthetic route toward diversified benzo[g]chrysenes 2 starting with commercially available isovanillin (1a) or 3-hydroxybenzaldehyde (1b) in modest total yields is described via the transformations of Claisen rearrangement of 3, Grignard additio

Full text of DOI:10.1016/j.tet.2012.10.054

Tetrahedron 69 (2013) 129e136
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Synthesis of benzo[g]chrysenes
*
Meng-Yang Chang , Ming-Hao Wu
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 August 2012
Received in revised form 11 October 2012
Accepted 18 October 2012
Available online 25 October 2012
A facile synthetic route toward diversified benzo[g]chrysenes 2 starting with commercially available
isovanillin (1a) or 3-hydroxybenzaldehyde (1b) in modest total yields is described via the trans-
formations of Claisen rearrangement of 3, Grignard addition of 4, DBU-promoted cyclodehydration of 5,
and photolytic Scholl oxidative annulation of 6. Skeleton 3 is prepared via O-allylation of 1 with trans-
cinnamyl bromide.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Benzo[g]chrysenes
Claisen rearrangement
Grignard addition
Cyclodehydration
Photolytic Scholl oxidative annulation
1. Introduction
EtO C
2
Reformatsky reaction /
OMe
O
Friedel-Crafts acylation
O
(Jerina and Lehr)
The skeleton of benzo[g]chrysene (BgC) consists of one penta-
cyclic aromatic hydrocarbon (PAH).1,2 It is produced by the com-
bustion of fossil fuels and organic materials, and has been
employed as a substrate in investigations of the mechanisms un-
derlying the carcinogenicity of PAHs.3 Despite the importance of
BgC as a cancer carcinogen, it is not readily yielded through syn-
thesis. Common synthetic routes for making the skeleton of BgC
include the double Grignard addition and aromatization (Harvey),4
Wittig olefination and photolysis (Hecht),5 Reformatsky reaction
and FriedeleCrafts acylation (Lehr),6 Suzuki cross-coupling re-
action and acid-mediated ring-closure (Kumar),7 and other ap-
proaches,8 as shown in Scheme 1.
O
ZnBr
PPh
3
H
OMe
2C-involvement /
cyclodehydration
(Harvey)
11
10
Wittig olefination /
photolysis (Hecht)
12
13
9
8
CHO
7
6
14
1
Br
5
(HO) B
2
2
4
O
O
MgBr
3
benzo[g]chrysene
2 x
Since palladium complex mediated SuzukieMiyaura cross-
coupling of an organoboron compound with a broad range of pol-
yhalogenated substituents is useful for stereospecific carbon-
ecarbon bond formation, most of the related literature on synthetic
PAHs is focused on cross-coupling annulation. There have been
extensive studies on the process for preparing functionalized PAHs,
such as dibenzochrysenes,9 benzo[a]pyrenes,10 and other struc-
tures.11 However, as yet, there have been very few efficient syn-
theses of BgC skeletons bearing appropriate functional groups of
different position. In continuation of our investigation with the
Suzuki coupling / 2C-involvement /
acid-mediated ring-closure (Kumar)
double Grignard addition /
aromatization (Harvey)
Scheme 1. Synthetic routes of benzo[g]chrysene (BgC).
benzene rings) is employed to construct 2 with 12,13-dimethoxy
groups, via a series of simple and efficient functional group trans-
formations of Claisen rearrangement, Grignard addition, base-
promoted cyclodehydration and photolytic Scholl annulation
(Scheme 2).
application of 1a and 1b,12
a novel synthetic sequence of
A/D/E/B/C approach (from one benzene ring to five fused
2. Results and discussion
The starting materials, compounds 4aee, with the 2-cinnamyl
group, were acquired from commercially available isovanillin (1a)
and 3-hydroxybenzaldehyde (1b) with an A-ring motif, in moderate
* Corresponding author. Tel.: þ886 7 3121101x2220; fax: þ886 7 3125339; e-mail
addresses: mychang@kmu.edu.tw, mychang624@yahoo.com.tw (M.-Y. Chang).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.10.054

130
M.-Y. Chang, M.-H. Wu / Tetrahedron 69 (2013) 129e136
D ring: Claisen
rearrangement
R1
R1
R2
MgBr
1)
R1
HO
Y
A
B ring: DBU-promoted
cyclodehydration
2) PCC, CH2Cl2
R2
R1
R2
CHO
MgBr
O
O
H
A
B
E
Y = H; 2-Me; 2-OMe;
1
Y
4-OMe; 4-F; 3,4-OCH2O
4a~4e
C
D
Br
5a~5o
3) DBU,
toluene
E ring: Grignard
addition
deprotonation then
cyclodehydration
Y
E
Y
R1 = R2 = OMe (yield of three-step)
D
6a, Y = H (72%)
2
6b, Y = 2-Me (79%)
6c, Y = 4-OMe (52%)
6d, Y = 2-OMe (60%)
6e, Y = 4-F (69%)
R1 = OMe, R2 = OBn
C-ring: photolytic
Scholl annulation
6j, Y = H (70%)
R1
6k, Y = 4-OMe (62%)
B
6l, Y = 3,4-OCH2O (58%)
Scheme 2. Retrosynthetic route of 2 from 1a,b.
R2
6f, Y = 3,4-OCH2O (50%) R1 = H, R2 = OMe
R1 = OMe, R2 = O-n-Bu
6g, Y = H (78%)
6m, Y = H (70%)
6n, Y = 4-OMe (61%)
Y
overall three-step yields according to the reported procedures in
the standard sequence of O-allylation, Claisen rearrangement and
O-alkylation as shown in Scheme 3.12
6h, Y = 4-OMe (60%)
R1 = OMe, R2 = OAllyl
6i, Y = 3,4-OCH2O (52%) 6o, Y = 3,4-OCH2O (66%)
6a~6o
Scheme 4. Three-step synthesis of 6 (B-ring).
Br
R1
R1
O
X
1) K2CO3,
cyclodehydration reaction of skeleton 5 with DBU produced a bet-
ter homogeneous reaction reactivity and experimental operation
than the reported protocol in the synthesis of skeleton 6. How is the
cyclodehydration reaction of skeleton 5 produced? Skeleton 6 with
a 1,2-diaryl group should first be generated as a conjugated carb-
anion from the deprotonation of the resulting 5 with benzoyl and
the 2-cinnamyl group. After the subsequent intramolecular ring-
closure and dehydration, the carbon framework of naphthalene is
produced. By monitoring the reaction with TLC, brilliant blue col-
ored naphthalene 6 with 1,2-diaryl group was easily observed in
TLC plates after short wavelength UV irradiation. The three-step
synthetic process for the formation of the naphthalene skeleton
can be monitored by TLC until the reaction is completed. The for-
mation of the cycloadduct 6 was confirmed through spectral
analysis. For example, the 1H NMR spectrum of 6a exhibited two
HO
CHO
CHO
X = H, OMe
1a, R1 = OMe
3a, R1 = OMe, X = H
3b, R1 = X = H
1b, R1 = H
X
3c, R1 = X = OMe
2) decalin, reflux
3) K2CO3, MeI,
n-BuBr, BnBr or allylBr
(yield of three-step)
for 3a or 3b
R1
4a, R1 = R2 = OMe (48%)
4b, R1 = OMe, R2 = O-n-Bu (53%)
4c, R1 = OMe, R2 = OBn (50%)
4d, R1 = H, R2 = OMe (42%)
R2
O
H
4e, R1 = OMe, R2 = OAllyl (40%)
Scheme 3. Three-step synthesis of 4.
O-Allylation of two phenols, 1a or 1b, with trans-cinnamyl
bromide (D ring, X¼H, OMe) afforded ether product 3a, 3b or 3c in
the presence of K2CO3 in THF at reflux for 8 h. To change the re-
action solvent from THF to acetone, the allylation reaction of 1a or
1b provided a similar yield of cinnamyl ether product. However,
chalcone was isolated as the major product during the aldol con-
densation of 1b. Under the general double Claisen rearrangement
condition (in refluxing decalin, 8 h) and O-alkylation condition (in
refluxing THF, 8 h), 4aee were provided as the sole isomers from
1a,b, with the acceptable yields of three-steps via O-allylation,
Claisen rearrangement, and O-alkylation. Furthermore, Wittig ole-
fination of 4a with Ph3P]CHCO2Et produced (E,E)-isomer 4f. The
structure of 4f was determined by single-crystal X-ray crystallog-
raphy. The stereochemistry of 4aee could also be demonstrated to
be the E-configuration.13 By controlling the heating time of cin-
namyl ether, a product with one rearrangement and its double-
rearranged isomer were isolated in different ratios under the
abovementioned boiling conditions. Unfortunately, attempts at
successfully completing the Claisen rearrangement of 3c were un-
successful. Furthermore, 6 was provided in moderate yields from
three-steps of the Grignard methylation of 4aee with six aryl-
magnesium bromides (E-ring, Y¼H; 2-Me; 2-OMe; 4-OMe; 4-F; 3,4-
OCH2O) and oxidation of the resulting alcohols with PCC, followed
singlets at
d
7.25 and 7.01 for the protons of the A ring. The protons
7.79 and 7.47 (d,
of the B ring appeared as two doublets at
d
J¼8.4 Hz). The structure of 6a was confirmed by HRMS, which
showed a peak at m/z 341.1550 [Mþþ1]. Furthermore, the skeleton
of 6a was determined by single-crystal X-ray crystallography.13
Structure 6a was shown in Fig. 1. Next, Scholl oxidation of 6 was
further studied for contracting the C-ring of 2. Scholl oxidation
generates a new carbonecarbon bond between two functionalized
aryl vertices.9i,15,16
by DBU-promoted intramolecular cyclodehydration of
Scheme 4).
5 (see
In the isolation of pure 5c,d, 5f, 5h,i, 5k,l and 5n,o (Y¼electron-
donating oxygenated group), we found that some unknown by-
products were slowly generated during the purification pro-
cedure. Because 5c,d, 5f, 5h,i, 5k,5l, and 5n,o could not be sepa-
rated as pure products by column chromatography; crude 5 was
further reacted with DBU to construct the B-ring of 6 in toluene at
reflux for 1 h. According to the literature method,14 the useful
transformation from benzoyl benzene 5 to naphthalene 6 required
simultaneous high-pressure irradiation (400 W mercury lamp)
in t-BuOK-promoted cyclodehydration. In our case, the
Fig. 1. X-ray structure of 6a.
A number of processes are available for the Scholl reaction of o-
terphenyl. The following combination of Lewis acid (or oxidant)
and reaction solvent has been reported in the literature: FeCl3 in
CH2Cl2,16a MoCl5 in CH2Cl2,16b CuCl2/AlCl3 in CS2,16c Tl(O2CCF3)3 in
CF3CO2H,16d PhI(O2CCF3)/BF3$OEt2 in CH2Cl2,16e MsOH/DDQ in
CH2Cl2,9i and I2/photolysis in benzene.16f These concise methodol-
ogies might result in high yields and present trace impurities or

M.-Y. Chang, M.-H. Wu / Tetrahedron 69 (2013) 129e136
131
byproducts. Of these methods, the photolytic Scholl oxidative an-
Table 2 (continued)
nulation provides a more convenient operation and higher yields,
as shown in Table 1. After screening seven Scholl conditions, we
found that a metal-mediated coupling reaction of model substrate
6a provided a lower yield (entries 1e3). Adjusting the DDQ as the
oxidant, the isolated yields were not noticeably enhanced (entry 4),
and 6a was recovered in 48% yield.
Entry
Reactants 6
Products 2/yieldaec (%)
MeO
MeO
MeO
MeO
3
F
F
6e
6f
2e / 40
MeO
MeO
MeO
MeO
Table 1
Synthesis of 2a (C-ring)
4
5
6
MeO
MeO
MeO
Scholl oxidative
photocyclization
O
O
O
O
2f / 66
2g / 75
MeO
C
condition
MeO
O
MeO
O
6a
2a
6g
,b
Entry
Reagents (equiv), solvent (mL), time (h)
Yielda
MeO
O
MeO
O
1
2
3
4
5
6
7
8
FeCl3 (2), CH2Cl2 (10), 1
MoCl5 (2), CH2Cl2 (10), 1
CuCl2 (2), CH2Cl2 (10), 1
MsOH (2), DDQ (2), CH2Cl2 (10), 1
I2 (1), benzene (15), 40
I2 (1), EtOAc (15), 40
I2 (1), 1,2-epoxybutane (10), EtOAc (15), 40
I2 (2), 1,2-epoxybutane (30), EtOAc (15), 80
21%
27%
38%
48%
59%c
60%c
71%c
80%c
OMe
OMe
2h / 58
6h
MeO
O
MeO
O
7
8
a
The reactions were run on a 0.2 mmol scale with 6a at rt.
b
c
The product 2a was >95% pure as determined by 1H NMR analysis.
O
O
O
ꢀ
O
6i
6j
2i / 55
2j / 70
The photolytic reaction was irradiated with 2540 A.
MeO
BnO
MeO
BnO
ꢀ
When photolytic irradiation (2540 A) was employed to the
Scholl condition in benzene, the afforded yield of 2a was improved
to 59%, and 6a was recovered in 30% yield (entry 5). When the
10 equiv of 1,2-epoxybutane was added, and the solvent was
changed from benzene to EtOAc, 2a was obtained in 71% yield and
10% of 6a was recovered. When the equivalent of the reagent was
increased and the reaction time extended, the acceptable 80% yield
of 2a was produced, and 6a was isolated in nearly 6% yield. From the
above results, we believe that the optimal reaction condition of
photolytic Scholl oxidative annulation of 6 for preparing 2 should
be iodine (2.0 equiv) and 1,2-epoxybutane (30.0 equiv) in EtOAc
(15 mL) at rt for 80 h. Furthermore, twelve 2a, 2c, 2eel, and 2n,o
were obtained as a single isomer with the 20e80% yield via the
above experimental condition (see Table 2). However, 6b with the
MeO
BnO
MeO
BnO
9
OMe
OMe
6k
2k / 62
MeO
BnO
MeO
BnO
10
O
O
O
O
6l
6n
6o
2l / 59
MeO
MeO
11
12
OMe
OMe
2n / 20
2o / 60
Table 2
MeO
O
MeO
O
Photolytic Scholl annulation of 2
R1
R1
R2
O
I2,
R2
O
O
O
O
EtOAc, hv
Y
Y
a
For the best one-pot reaction conditions: the reactions were run on a 0.2 mmol
6
2
scale with skeleton 6 at rt.
b
The skeleton 2 were >95% pure as determined by 1H NMR analysis.
The photolytic reaction was irradiated with 2540 A.
Entry
1
Reactants 6
Products 2/yieldaec (%)
c
ꢀ
MeO
MeO
MeO
MeO
2-methoxy group (Y¼OMe), or 6d with the methyl group (Y¼Me),
could not be converted to 2b or 2d under photolytic annulation due
to the steric hindrance of the Ygroup on the 2-position of the E ring.
Only the starting material, 6b or 6d, was recovered. From the dis-
tribution of product yields, we found that the yield of 2e with
electron-withdrawing groups (Y¼F) had a 40% yield. 6e was re-
covered with a 39% yield. For the formed yield of 2c, 2f, 2h,i, 2k,l or
2o with different electron-donating oxygenated groups, the better
yield was produced by 2f. When no substituent was at the E ring
6a
6c
2a / 80
MeO
MeO
MeO
MeO
2
OMe
OMe
2c / 62

132
M.-Y. Chang, M.-H. Wu / Tetrahedron 69 (2013) 129e136
(Y¼H), 2a, 2g or 2j provided the best yield under the photolytic
Scholl oxidative annulation conditions. However, when R1 was
hydrogen, 6m was recovered, and no 2m was isolated. Only 20%
yield of 2n was obtained under the reaction condition. We believe
that the methoxy group on the C-12 position affected the Scholl
reaction. The structures of 2f, 2i, and 2k were determined using
single-crystal X-ray analysis.13 Structures 2f, 2i, and 2k were shown
in Figs. 2e4.
4. Experimental section
4.1. General
THF was distilled prior to use. All other reagents and solvents
were obtained from commercial sources and used without further
purification. Reactions were routinely carried out under an atmo-
sphere of dry nitrogen with magnetic stirring. Products in organic
solvents were dried with anhydrous magnesium sulfate before
concentration in vacuo. Melting points were determined with
a SMP3 melting apparatus. 1H and 13C NMR spectra were recorded
on a Varian INOVA-400 spectrometer operating at 400 and at
100 MHz, respectively. Chemical shifts (d) are reported in parts per
million (ppm) and the coupling constants (J) are given in Hertz.
High resolution mass spectra (HRMS) were measured with a mass
spectrometer Finnigan/Thermo Quest MAT 95XL. X-ray crystal
structures were obtained with an Enraf-Nonius FR-590 diffrac-
tometer (CAD4, Kappa CCD). Elemental analyses were carried out
with Heraeus Vario III-NCSH, Heraeus CHNeOS-Rapid Analyzer or
Elementar Vario EL III.
4.2. A representative synthetic procedure of skeleton 4 is as
follows
Fig. 2. X-ray structure of 2f.
K2CO3 (2.7 g, 20.0 mmol) was added to a stirred solution of iso-
vanillin (1a, 1.52 g, 10.0 mmol) or 3-hydroxybenzaldehyde (1b,
1.22 g, 10.0 mmol) in THF (100 mL) at rt. The reaction mixture was
stirred at rt for 10 min. trans-Cinnamyl bromide (2.4 g, 12.0 mmol)
was added to the reaction mixture at rt. The reaction mixture was
stirred at reflux for 8 h. The reaction was traced by TLC until 1a or 1b
was consumed. The reaction mixture was cooled to rt, concentrated,
and extracted with EtOAc (3ꢀ60 mL). The combined organic layers
were washed with brine, dried, filtered, and evaporated to afford
crudeproduct underreducedpressure. Withoutfurtherpurification,
decalin (8 mL) was added to a solution of skeleton 3. The reaction
mixture was stirred at reflux for 8 h. The reaction was traced by TLC
until the resulting product was consumed. The reaction mixture was
cooled to rt. Decalin was evaporated to afford crude product under
reduced pressure. Without further purification, K2CO3 (550 mg,
4.0 mmol) was added to a solution of the resulting product in THF
(100 mL) at rt. The reaction mixture was stirred at rt for 10 min.
Methyl iodide (300 mg, 2.1 mmol), n-butyl bromide (290 mg,
2.1 mmol) or benzyl bromide (362 mg, 2.1 mmol) was added to the
reaction mixture at rt. The reaction mixture was stirred at reflux for
8 h(the reactionwas traced byTLC). Thereaction mixturewas cooled
to rt, concentrated, and extracted with EtOAc (3ꢀ60 mL). The com-
bined organic layers were washed with brine, dried, filtered, and
evaporated to afford crude product under reduced pressure. Purifi-
cation on silica gel (hexanes/EtOAc¼8/1e4/1) afforded 4aee.
Fig. 3. X-ray structure of 2i.
4.2.1. 4,5-Dimethoxy-2-(3-phenylallyl)benzaldehyde (4a). Compo-
und 4a is a known compound and the analytical data are consistent
with those in the Ref. 12b,c.
Fig. 4. X-ray structure of 2k.
4.2.2. 5-Butoxy-4-methoxy-2-(3-phenylallyl)benzaldehyde
(4b). Yield¼53% (1.72 g); colorless oil; HRMS (ESI, Mþþ1) calcd for
C21H25O3 325.1804, found 325.1811; 1H NMR (400 MHz, CDCl3):
3. Conclusion
d
10.20 (s, 1H), 7.39 (s, 1H), 7.32e7.24 (m, 4H), 7.20e7.16 (m, 1H),
In summary, we have successfully presented a novel synthetic
A/D/E/B/C ring formation through a sequence approach for
the preparation of substituted benzo[g]chrysenes 2 via a ser-
ies of simple and efficient functional group transformations of
Claisen rearrangement, Grignard addition, base-promoted cyclo-
dehydration, and photolytic Scholl annulation. This synthesis be-
gins with simple starting materials and reagents, and provides
a potential methodology for chemical biology research.
6.75 (s, 1H), 6.14e6.31 (m, 2H), 4.06 (t, J¼6.4 Hz, 2H), 3.92 (s, 3H),
3.89 (d, J¼4.8 Hz, 2H), 1.87e1.80 (m, 2H), 1.54e1.45 (m, 2H), 0.97 (t,
J¼7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 189.98, 154.25, 147.41,
137.39, 137.01, 131.33, 128.88, 128.45 (2ꢀ), 127.25, 126.77, 126.07
(2ꢀ), 113.15, 112.73, 68.75, 56.06, 34.84, 31.03, 19.11, 13.78.
4.2.3. 5-Benzyloxy-2-(3-phenylallyl)-4-methoxybenzaldehyde
(4c). Yield¼50% (1.79 g); mp¼103e105 ꢁC (recrystallized from

M.-Y. Chang, M.-H. Wu / Tetrahedron 69 (2013) 129e136
133
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C24H23O3
5 in toluene (5 mL) at rt. The reaction mixture was stirred at reflux
for 1 h. The reaction mixture was cooled to rt, concentrated, and
extracted with EtOAc (3ꢀ30 mL). The combined organic layers were
washed with brine, dried, filtered, and evaporated to afford crude
products under reduced pressure. Purification on silica gel (hex-
anes/EtOAc¼10/1e6/1) afforded skeleton 6.
359.1647, found 359.1450; 1H NMR (400 MHz, CDCl3):
d 7.48e7.45
(m, 1H), 7.46 (s, 1H), 7.40e7.20 (m, 10H), 6.79 (s, 1H), 6.39e6.36 (m,
2H), 5.19 (s, 2H), 3.95 (s, 3H), 3.92e3.90 (m, 2H); 13C NMR
(100 MHz, CDCl3):
d 189.97, 154.52, 147.02, 137.98, 137.05, 137.05,
136.46, 131.46, 128.80, 128.61 (2ꢀ), 128.52, 128.08, 127.52, 127.33
(2ꢀ), 126.14, 114.05, 113.36, 114.05, 113.36, 71.00, 56.15, 34.98.
4.3.1. 6,7-Dimethoxy-1,2-diphenylnaphthalene
(6a). Yield¼72%
4.2.4. 5-Methoxy-2-(3-phenylallyl)benzaldehyde (4d). Yield¼42%
(245 mg); mp¼182e183 ꢁC (recrystallized from hexanes and EtOAc);
(1.06 g); colorless oil; 1H NMR (200 MHz, CDCl3):
d 10.29 (s, 1H),
HRMS (ESI, Mþþ1) calcd for C24H21O2 341.1542, found 341.1550; 1H
7.47 (s, 1H), 7.46e7.13 (m, 7H), 6.37e6.34 (m, 2H), 3.87 (s, 3H), 3.84
(d, J¼4.8 Hz, 2H).
NMR (400 MHz, CDCl3):
d
7.79 (d, J¼8.4 Hz,1H), 7.47 (d, J¼8.4 Hz,1H),
7.35e7.13 (m, 11H), 7.01 (s, 1H), 4.05 (s, 3H), 3.76 (s, 3H); 13C NMR
(100 MHz, CDCl3): 149.46, 149.24, 142.21, 139.35, 136.80, 136.29,
d
4.2.5. 5-Allyloxy-4-methoxy-2-(3-phenylallyl)benzaldehyde
(4e). Yield¼40% (1.23 g); colorless oil; HRMS (ESI, Mþþ1) calcd for
C20H21O3 309.1491, found 309.1496; 1H NMR (400 MHz, CDCl3):
131.21 (2ꢀ),130.05(2ꢀ),128.67 (2ꢀ),128.21 (2ꢀ),127.83 (2ꢀ),127.44
(2ꢀ),126.64,125.87,106.20,105.62, 55.82, 55.50. Single-crystal X-ray
diagram: crystal of compound 6a was grown by slow diffusion of
EtOAc into a solution of compound 6a in CH2Cl2 to yield colorless
prisms. The compound crystallizes in the monoclinic crystal system,
d
10.21 (s,1H), 7.41 (s,1H), 7.33e7.26 (m, 4H), 7.22e7.18 (m,1H), 6.78
(s,1H), 6.43e6.33 (m, 2H), 6.14e6.05 (m,1H), 5.44 (dq, J¼1.6,17.2 Hz,
ꢀ
ꢀ
1H), 5.32 (dq, J¼1.6, 10.8 Hz, 1H), 4.66 (dd, J¼1.6, 5.2 Hz, 2H), 3.95 (s,
space group P 1 21/c 1, a¼6.9648 (13) A, b¼27.326 (5) A, c¼9.7577
3H), 3.91 (d, J¼4.4 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d
189.95,
(17) A, V¼1782.8 (6) A , Z¼4, Dcalcd¼1.268 g/cm3, F(000)¼720, 2
q
3
ꢀ
ꢀ
154.30, 146.82, 137.81, 137.04, 132.66, 131.46, 128.82, 128.52 (2ꢀ),
range 1.49e26.89ꢁ, R indices (all data) R1¼0.0723, wR2¼0.1350.
127.33,126.78,126.13 (2ꢀ),118.53,113.42,113.23, 69.84, 56.12, 34.94.
4.3.2. 6,7-Dimethoxy-2-phenyl-1-o-tolylnaphthalene (6b). Yield¼79%
(280 mg); mp¼146e148 ꢁC (recrystallized from hexanes and EtOAc);
HRMS (ESI, Mþþ1) calcd for C25H23O2 355.1698, found 355.1703; 1H
4.2.6. 3-[4,5-Dimethoxy-2-(3-phenylallyl)phenyl]acrylic acid ethyl
ester (4f). Ph3P]CHCO2Et (420 mg, 1.2 mmol) was added to 4a
(280 mg, 1.0 mmol) in CH2Cl2 (10 mL) at rt. The reaction mixture
was stirred at reflux for 1 h. The solvent was concentrated under
reduced pressure. The residue was extracted with EtOAc
(3ꢀ30 mL). The combined organic layers were washed with brine,
dried, filtered, and evaporated to afford crude product under re-
duced pressure. Purification on silica gel (hexanes/EtOAc¼6/1e4/1)
afforded 4f (331 mg, 94%) as a colorless solid. Mp¼116e117 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
NMR (400 MHz, CDCl3):
d
7.79 (d, J¼8.4 Hz,1H), 7.47 (d, J¼8.4 Hz,1H),
7.24e7.13 (m, 10H), 6.71 (s, 1H), 4.04 (s, 3H), 3.71 (s, 3H), 1.91 (s, 3H);
13C NMR (100 MHz, CDCl3):
d
149.58, 149.27, 142.10, 138.71, 136.92,
136.66, 135.58, 131.43, 129.73, 129.59 (2ꢀ), 128.55, 128.25, 128.11,
127.43 (2ꢀ), 127.22, 126.61, 126.04, 125.89, 125.27, 106.28, 105.34,
55.84, 55.53.
4.3.3. 6,7-Dimethoxy-1-(4-methoxyphenyl)-2-phenylnaphthalene
(6c). Yield¼52% (192 mg); colorless gum; HRMS (ESI, Mþþ1) calcd
for C25H23O3 371.1647, found 371.1655; 1H NMR (400 MHz, CDCl3):
for C22H25O4 353.1753, found 353.1759; 1H NMR (400 MHz):
d 7.99
(d, J¼15.6 Hz, 1H), 7.34e7.27 (m, 4H), 7.21e7.18 (m, 1H), 7.10 (s, 1H),
6.74 (s, 1H), 6.34e6.26 (m, 3H), 4.25 (q, J¼7.2 Hz, 2H), 3.91 (s, 3H),
3.90 (s, 3H), 3.65 (d, J¼5.2 Hz, 2H), 1.33 (t, J¼7.2 Hz, 3H); 13C NMR
d
7.75 (d, J¼8.4 Hz, 1H), 7.43 (d, J¼8.4 Hz, 1H), 7.21e7.10 (m, 8H), 7.02
(s, 1H), 6.86e6.83 (m, 2H), 4.04 (s, 3H), 3.82 (s, 3H), 3.76 (s, 3H); 13C
NMR (100 MHz, CDCl3): 158.21, 149.45, 149.26, 142.45, 137.04,
(100 MHz):
d
167.18, 150.94, 147.82, 141.55, 137.26, 133.34, 131.25,
d
128.69, 128.47 (2ꢀ), 127.19, 126.15 (2ꢀ), 125.38, 117.15, 112.83,
108.82, 60.37, 55.94 (2ꢀ), 36.13,14.33. Single-crystal X-ray diagram:
crystal of compound 4f was grown by slow diffusion of EtOAc into
a solution of compound 4f in CH2Cl2 to yield colorless prism. The
compound crystallizes in the triclinic crystal system, space group
135.98, 133.70, 132.30 (2ꢀ), 131.56, 130.17, 130.11 (2ꢀ), 127.55 (2ꢀ),
126.74,125.83,125.73,113.34 (2ꢀ),106.24,105.71, 55.88, 55.62, 55.12;
Anal. Calcd for C25H22O3: C, 81.06; H, 5.99. Found: C, 81.45; H, 6.30.
4.3.4. 6,7-Dimethoxy-1-(2-methoxyphenyl)-2-phenylnaphthalene
(6d). Yield¼60% (222 mg); colorless gum; HRMS (ESI, Mþþ1) calcd
for C25H23O3 371.1647, found 371.1651; 1H NMR (400 MHz, CDCl3):
ꢀ
ꢀ
ꢀ
Pꢂ1, a¼8.8858 (6) A, b¼10.6870 (7) A, c¼11.4669 (7) A, V¼919.34
3
(10) A , Z¼2, Dcalcd¼1.273 g/cm3, F(000)¼376,
2
q
range
ꢀ
2.08e26.43ꢁ, R indices (all data) R1¼0.0511, wR2¼0.1451.
d
7.77 (d, J¼8.0 Hz, 1H), 7.45 (d, J¼8.4 Hz, 1H), 7.30e7.25 (m, 2H),
7.19 (s, 1H), 7.18e7.11 (m, 4H), 7.08 (dd, J¼1.6, 7.6 Hz, 1H), 6.91 (dt,
J¼1.2, 7.6 Hz, 1H), 6.86 (s, 1H), 6.85 (d, J¼7.6 Hz, 1H), 4.03 (s, 3H),
4.3. A representative synthetic procedure of skeleton 6 is as
follows
3.73 (s, 3H), 3.52 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 157.44,
149.48, 149.23, 142.62, 137.52, 133.75, 132.60, 132.60, 130.20, 129.44
(2ꢀ), 128.70, 128.49, 127.27 (2ꢀ), 126.43, 125.98, 125.95, 120.31,
110.73, 106.33, 105.53, 55.87, 55.56, 55.23; Anal. Calcd for C25H22O3:
C, 81.06; H, 5.99. Found: C, 81.25; H, 6.32.
A solution of different Grignard reagent (1.0 M in THF, 1.5 mL,
1.5 mmol) was added to a stirred solution of the skeleton 4
(1.0 mmol) in THF (10 mL) at ice bath. The reaction mixture was
stirred at rt for 5 h. Water (5 mL) was added to the reaction mixture
and the mixture was filtered through a short plug of Celite. The
filtrate was concentrated under reduced pressure. The residue was
extracted with EtOAc (3ꢀ50 mL). The combined organic layers were
washed with brine, dried, filtered, and evaporated to afford differ-
ent crude product under reduced pressure. Without further puri-
fication, a solution of the resulting secondary alcohol in CH2Cl2
(10 mL) was added to a mixture of pyridinium chlorochromate
(430 mg, 2.0 mmol) and Celite (500 mg) in CH2Cl2 (20 mL). After
being stirred at rt for 3 h, the mixture was filtered through a short
silica gel column. The filtrate was dried, filtered, and evaporated to
yield crude compound. Without further purification, DBU (300 mg,
2.0 mmol) was added to a stirred solution of the resulting skeleton
4.3.5. 1-(4-Fluorophenyl)-6,7-dimethoxy-2-phenylnaphthalene
(6e). Yield¼69% (246 mg); mp¼66e68 ꢁC (recrystallized from hex-
anes and EtOAc); HRMS (ESI, Mþþ1) calcd for C24H20FO2 359.1447,
found 359.1452; 1H NMR (400 MHz, CDCl3):
d
7.78 (d, J¼8.4 Hz, 1H),
7.44 (d, J¼8.4 Hz, 1H), 7.22e7.11 (m, 8H), 7.04e6.99 (m, 2H), 6.93 (s,
1H), 4.04 (s, 3H), 3.77 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
161.65 (d,
J¼244.1 Hz), 149.63, 149.33, 142.05, 137.13, 135.29 (d, J¼3.8 Hz),
135.15, 132.81, 132.72, 130.04 (2ꢀ), 128.71, 128.26, 127.60 (2ꢀ),
126.62, 126.08, 125.04, 115.02, 114.81, 106.31, 105.31, 55.87, 55.56.
4.3.6. 1-(3,4-Methylenedioxyphenyl)-6,7-dimethoxy-2-
phenylnaphthalene (6f). Yield¼50% (192 mg); colorless gum; HRMS

134
M.-Y. Chang, M.-H. Wu / Tetrahedron 69 (2013) 129e136
(ESI, Mþþ1) calcd for C25H21O4 385.1440, found 385.1449; 1H NMR
127.69, 127.52 (2ꢀ), 127.41 (2ꢀ), 126.77, 125.81, 125.64, 113.36 (2ꢀ),
(400 MHz, CDCl3):
d
7.75 (d, J¼8.4 Hz, 1H), 7.42 (d, J¼8.4 Hz, 1H),
108.44, 106.44, 70.42, 55.95, 55.15.
7.24e7.14 (m, 6H), 7.03 (s, 1H), 6.77 (dd, J¼0.8, 7.6 Hz, 1H),
6.69e6.66 (m, 2H), 5.99 (d, J¼1.2 Hz,1H), 5.95 (d, J¼1.2 Hz,1H), 4.04
4.3.12. 7-Benzyloxy-6-methoxy-1-(3,4-methylenedioxyphenyl)-2-
phenylnaphthalene (6l). Yield¼58% (267 mg); mp¼168e170 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C31H25O4 461.1753, found 461.1750; 1H NMR (400 MHz, CDCl3):
(s, 3H), 3.80 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 149.53, 149.29,
147.25, 146.19, 142.30, 137.04, 135.79, 133.06, 129.95 (2ꢀ), 128.71,
128.49, 127.59 (2ꢀ), 126.69, 125.97, 125.87, 124.73, 111.67, 107.91,
106.25, 105.60, 100.84, 55.87, 55.68.
d
7.74 (d, J¼8.4 Hz,1H), 7.40 (d, J¼8.4 Hz,1H), 7.33e7.14 (m,11H), 7.04
(s, 1H), 6.73 (d, J¼8.0 Hz, 1H), 6.56 (d, J¼1.6 Hz, 1H), 6.52 (dd, J¼1.6,
8.0 Hz, 1H), 6.03 (d, J¼1.2 Hz, 1H), 5.97 (d, J¼1.6 Hz, 1H), 5.12 (s, 2H),
4.3.7. 7-Butoxy-6-methoxy-1,2-diphenylnaphthalene (6g). Yield¼78%
(297 mg); mp¼127e128 ꢁC (recrystallized from hexanes and EtOAc);
HRMS (ESI, Mþþ1) calcd for C27H27O2 383.2011, found 383.2014; 1H
4.05 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 149.70, 148.20, 147.13,
146.09, 142.24, 136.84, 136.61, 135.74, 132.97, 129.93 (2ꢀ), 128.72,
128.41 (2ꢀ), 128.33, 127.75, 127.57 (2ꢀ), 127.41 (2ꢀ), 126.70, 125.94,
125.78, 124.64, 111.65, 108.39, 107.94, 106.43, 100.80, 70.50, 55.91.
NMR (400 MHz, CDCl3):
d
7.77 (d, J¼8.4 Hz,1H), 7.44 (d, J¼8.4 Hz,1H),
7.33e7.24 (m, 4H), 7.22e7.18 (m, 7H), 6.98 (s,1H), 4.02 (s, 3H), 3.88 (t,
J¼6.8 Hz, 2H), 1.80e1.73 (m, 2H), 1.46e1.37 (m, 2H), 0.92 (t, J¼7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3):
d
149.68, 148.95, 142.31, 139.45,
4.3.13. 7-Methoxy-1,2-diphenylnaphthalene (6m). Yield¼70% (216
mg); mp¼141e143 ꢁC (recrystallized from hexanes and EtOAc);
HRMS (ESI, Mþþ1) calcd for C23H19O 311.1436, found 311.1440; 1H
136.70, 136.23, 131.11 (2ꢀ), 130.11 (2ꢀ), 128.61, 128.29, 127.82 (2ꢀ),
127.47 (2ꢀ),126.61,126.54,125.89,125.85,106.90,106.38, 68.19, 55.91,
30.72, 19.12, 13.80.
NMR (400 MHz, CDCl3):
d
7.83 (dd, J¼8.4, 11.2 Hz, 2H), 7.43 (d,
J¼8.4 Hz,1H), 7.31e7.11 (m, 11H), 6.97 (d, J¼2.4 Hz,1H), 3.69 (s, 3H);
4.3.8. 7-Butoxy-6-methoxy-1-(4-methoxyphenyl)-2-phenylnaphtha-
lene (6h). Yield¼60% (247 mg); colorless gum; HRMS (ESI,
Mþþ1) calcd for C28H29O3 413.2117, found 413.2122; 1H NMR
13C NMR (100 MHz, CDCl3):
d
157.89, 142.18, 139.21, 138.88, 136.51,
133.82, 131.33 (2ꢀ), 130.06 (2ꢀ), 129.38, 127.87, 127.52 (2ꢀ), 127.24,
127.15, 126.67, 126.11, 126.08, 118.05 (2ꢀ), 105.48, 55.09.
(400 MHz, CDCl3):
d
7.75 (d, J¼8.4 Hz, 1H), 7.43 (d, J¼8.4 Hz, 1H),
7.22e7.10 (m, 8H), 7.02 (s, 1H), 6.85 (d, J¼8.8 Hz, 2H), 4.02 (s,
3H), 3.91 (t, J¼6.8 Hz, 2H), 3.82 (s, 3H), 1.82e1.75 (m, 2H),
1.49e1.40 (m, 2H), 0.94 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz,
4.3.14. 7-Methoxy-1-(4-methoxyphenyl)-2-phenylnaphthalene
(6n). Yield¼61% (207 mg); mp¼132e134 ꢁC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C24H21O2
CDCl3):
d
158.20, 149.65, 148.92, 142.50, 136.88, 135.85, 132.31
341.1542, found 341.1546; 1H NMR (400 MHz, CDCl3):
d 7.83 (dd,
(2ꢀ), 131.65, 130.11 (2ꢀ), 128.65, 128.61, 127.52 (2ꢀ), 126.59,
125.79, 125.69, 113.30 (2ꢀ), 106.94, 106.39, 68.21, 55.90, 55.12,
30.78, 19.16, 13.83.
J¼7.6, 8.8 Hz, 2H), 7.48 (d, J¼8.8 Hz, 1H), 7.43 (d, J¼8.4 Hz, 1H),
7.22e7.09 (m, 6H), 7.02 (d, J¼2.4 Hz, 1H), 6.96 (d, J¼8.8 Hz, 1H), 6.84
(d, J¼8.8 Hz, 2H), 3.82 (s, 3H), 3.72 (s, 3H); 13C NMR (100 MHz,
CDCl3):
d
158.25, 157.87, 142.38, 139.06, 134.19, 133.49, 132.36 (2ꢀ),
4.3.9. 7-Butoxy-6-methoxy-1-(3,4-methylenedioxyphenyl)-2-
phenylnaphthalene (6i). Yield¼52% (222 mg); colorless gum;
HRMS (ESI, Mþþ1) calcd for C28H27O4 427.1909, found 427.1910;
130.07 (2ꢀ), 129.38, 127.72, 127.58 (2ꢀ), 127.08, 126.12, 126.01,
118.03, 114.16, 113.37 (2ꢀ), 105.51, 55.34, 55.14.
1H NMR (400 MHz, CDCl3):
d
7.74 (d, J¼8.4 Hz, 1H), 7.41 (d,
4.3.15. 7-Alloxy-6-methoxy-1-(3,4-methylenedioxyphenyl)-2-
phenylnaphthalene (6o). Yield¼66% (271 mg); mp¼156e157 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C27H23O4 411.1596, found 411.1599; 1H NMR (400 MHz, CDCl3):
J¼8.4 Hz, 1H), 7.24e7.14 (m, 6H), 7.03 (s, 1H), 6.77 (d, J¼7.6 Hz,
1H), 6.69e6.66 (m, 2H), 5.97 (d, J¼1.2 Hz, 1H), 5.95 (d, J¼1.2 Hz,
1H), 4.02 (s, 3H), 3.94 (t, J¼6.8 Hz, 2H), 1.84e1.77 (m, 2H),
1.51e1.41 (m, 2H), 0.95 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz,
d
7.74 (d, J¼8.4 Hz,1H), 7.41 (d, J¼8.0 Hz,1H), 7.23e7.14 (m, 6H), 7.05
CDCl3):
d
149.70, 148.99, 147.22, 146.16, 142.36, 136.89, 135.68,
(s, 1H), 6.76 (d, J¼8.0 Hz, 1H), 6.67 (d, J¼1.2 Hz, 1H), 6.64 (dd, J¼1.2,
8.0 Hz, 1H), 6.06e5.94 (m, 1H), 5.99 (d, J¼1.2 Hz, 1H), 5.95 (d,
J¼1.2 Hz,1H), 5.31e5.26 (m, 2H), 4.53 (d, J¼5.6 Hz, 2H), 4.03 (s, 3H);
133.16, 129.96 (2ꢀ), 128.61, 128.53, 127.59 (2ꢀ), 126.55, 125.94,
125.83, 124.74, 111.71, 107.88, 106.84, 106.39, 100.83, 68.27, 55.91,
30.78, 19.17, 13.82.
13C NMR (100 MHz, CDCl3):
d 149.57, 148.36, 147.19, 146.17, 142.30,
136.95, 135.78, 133.10, 133.05, 129.97 (2ꢀ), 128.74, 128.40, 127.61
(2ꢀ), 126.74, 125.98, 125.85, 124.76, 118.62, 111.76, 107.91, 107.57,
106.40, 100.85, 69.58, 55.91.
4.3.10. 7-Benzyloxy-6-methoxy-1,2-diphenylnaphthalene
(6j). Yield¼70% (290 mg); mp¼134e135 ꢁC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C30H25O2
417.1855, found 417.1859; 1H NMR (400 MHz, CDCl3):
d
7.74
4.4. A representative synthetic procedure of skeleton 2 is as
follows
(d, J¼8.4 Hz, 1H), 7.41 (d, J¼8.4 Hz, 1H), 7.27e7.24 (m, 8H), 7.20
(s, 1H), 7.15e7.10 (m, 5H), 7.06e7.04 (m, 2H), 6.98 (s, 1H), 5.04
(s, 2H), 4.04 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
149.69, 148.15,
Skeleton 6 (0.2 mmol) and I2 (100 mg, 0.4 mmol) was dissolved
142.21, 139.30, 136.67, 136.56, 136.29, 131.20 (2ꢀ), 130.08 (2ꢀ),
128.72, 128.43 (2ꢀ), 128.08, 127.88 (2ꢀ), 127.68, 127.45 (2ꢀ),
127.43 (2ꢀ), 126.70, 126.48, 125.90, 125.81, 108.37, 106.43, 70.35,
55.93.
in EtOAc (15 mL) at rt. Then, 1,2-epoxybytane (440 mg, 6.0 mmol)
was added to the reaction mixture and the reaction mixture was
ꢀ
irradiated under a nitrogen atmosphere with a lamp (
l¼2540 A),
using a Pyrex glass filter at rt for 80 h. The solvent was evaporated
to afford crude product. Purification on silica gel (hexanes/
EtOAc¼4/1e2/1) afforded skeleton 2.
4.3.11. 7-Benzyloxy-6-methoxy-1-(4-methoxyphenyl)-2-
phenylnaphthalene (6k). Yield¼62% (277 mg); mp¼144e145 ꢁC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C31H27O3 447.1960, found 447.1966; 1H NMR (400 MHz, CDCl3):
4.4.1. 12,13-Dimethoxybenzo[g]chrysene (2a). Yield¼80% (54 mg);
mp¼183e185 ꢁC (recrystallized from hexanes and EtOAc); HRMS
(ESI, Mþþ1) calcd for C24H19O2 339.1385, found 339.1388; 1H NMR
d
7.73 (d, J¼8.4 Hz, 1H), 7.41 (d, J¼8.4 Hz, 1H), 7.30e7.26 (m, 5H),
7.20 (s, 1H), 7.19e7.10 (m, 5H), 7.01 (s, 1H), 6.95 (d, J¼8.8 Hz, 2H),
(400 MHz, CDCl3):
d
8.96 (d, J¼7.6 Hz, 1H), 8.73 (d, J¼8.0 Hz, 2H),
6.79 (d, J¼8.8 Hz, 2H), 5.07 (s, 2H), 4.04 (s, 3H), 3.84 (s, 3H); 13C
8.69 (dd, J¼2.0, 7.6 Hz, 1H), 8.63 (dd, J¼2.0, 7.6 Hz, 1H), 8.50 (d,
J¼8.8 Hz, 1H), 8.40 (s, 1H), 7.89 (d, J¼8.8 Hz, 1H), 7.72e7.60 (m, 3H),
7.33 (s, 1H), 4.09 (s, 3H), 4.06 (s, 3H); 13C NMR (100 MHz, CDCl3):
NMR (100 MHz, CDCl3):
d
158.12,149.66, 148.16,142.41,136.85 (2ꢀ),
136.65,135.95,132.22 (2ꢀ),131.48,130.92 (2ꢀ),128.78,128.42 (2ꢀ),

M.-Y. Chang, M.-H. Wu / Tetrahedron 69 (2013) 129e136
135
d
149.22, 149.00, 130.89, 130.09, 129.71, 129.55, 129.42, 128.34,
129.42, 129.19, 127.40, 126.67, 126.51, 125.89, 125.53, 125.15, 123.98,
123.56, 123.08, 119.09, 114.52, 110.04, 107.36, 105.87, 68.79, 55.93,
55.50, 31.21, 19.31, 13.94.
127.32, 127.18, 126.77, 126.52, 126.47, 126.45, 125.83, 125.42, 123.70,
123.48, 123.05, 119.18, 108.66, 107.18, 56.02, 55.91.
4.4.2. 3,12,13-Trimethoxybenzo[g]chrysene (2c). Yield¼62% (47
mg); colorless gum; HRMS (ESI, Mþþ1) calcd for C25H21O3 369.1491,
4.4.7. 13-Butoxy-2,3-methylenedioxy-12-methoxybenzo[g]chrysene
(2i). Yield¼55% (47 mg); mp¼164e166 ꢁC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C28H25O4
found 369.1496; 1H NMR (400 MHz, CDCl3):
d
8.87 (d, J¼9.2 Hz, 1H),
8.62 (ddd, J¼1.6, 5.6, 7.2 Hz, 2H), 8.48 (d, J¼8.8 Hz, 1H), 8.33 (s, 1H),
8.12 (d, J¼2.8 Hz, 1H), 7.83 (d, J¼8.4 Hz, 1H), 7.69 (dt, J¼1.6, 6.8 Hz,
1H), 7.66 (dt, J¼1.6, 6.8 Hz, 1H), 7.31 (s, 1H), 7.25 (dd, J¼2.8, 8.8 Hz,
1H), 4.09 (s, 3H), 4.07 (s, 3H), 4.06 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 158.19,149.08,149.97,132.52,130.45,129.91,129.47,129.21,
127.42, 126.73, 126.57, 125.95, 125.52, 125.13, 123.92, 123.56, 123.10,
119.22, 114.48, 108.66, 107.17, 105.96, 56.01, 55.90, 55.50.
425.1753, found 425.1754; 1H NMR (400 MHz, CDCl3):
d 8.61e8.59
(m, 1H), 8.48e8.46 (m, 1H), 8.46 (d, J¼8.8 Hz, 1H), 8.34 (s, 1H), 8.29
(s, 1H), 8.07 (s, 1H), 7.81 (d, J¼8.8 Hz, 1H), 7.65e7.62 (m, 2H), 7.29 (s,
1H), 6.14 (s, 2H), 6.21 (t, J¼6.8 Hz, 2H), 4.07 (s, 3H), 1.99e1.92 (m,
2H), 1.62e1.53 (m, 2H), 1.03 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d 149.36, 148.49, 147.47, 147.20, 129.49, 129.41, 129.27,
126.98, 126.56 (2ꢀ), 126.45, 126.33, 125.72, 125.48, 125.21, 123.49,
122.84, 119.09, 109.82, 107.44, 106.89, 102.48, 101.45, 68.84, 55.94,
31.22, 19.30, 13.89. Single-crystal X-ray diagram: crystal of com-
pound 2i was grown by slow diffusion of EtOAc into a solution of
compound 2i in CH2Cl2 to yield colorless prisms. The compound
crystallizes in the monoclinic crystal system, space group P 1 21/c 1,
4.4.3. 3-Fluoro-12,13-dimethoxybenzo[g]chrysene (2e). Yield¼40%
(28 mg); mp¼178e180 ꢁC (recrystallized from hexanes and EtOAc);
HRMS (ESI, Mþþ1) calcd for C24H18FO2 357.1291, found 357.1296;
1H NMR (400 MHz, CDCl3):
d
8.92 (dd, J¼5.6, 9.2 Hz, 1H), 8.62 (dd,
3
ꢀ
ꢀ
ꢀ
ꢀ
J¼1.6, 8.0 Hz, 1H), 8.54 (dd, J¼1.6, 8.0 Hz, 1H), 8.47 (d, J¼9.2 Hz, 1H),
8.32 (dd, J¼2.4, 10.8 Hz, 1H), 8.27 (s, 1H), 7.86 (d, J¼8.4 Hz, 1H),
7.73e7.65 (m, 2H), 7.35 (ddd, J¼2.8, 8.0, 9.2 Hz,1H), 7.31 (s, 1H), 4.09
a¼6.3608 (6) A, b¼27.461 (3) A, c¼23.465 (2) A, V¼4090.4 (7) A ,
Z¼8, Dcalcd¼1.379 g/cm3, F(000)¼1792, 2
q
range 1.14e26.41ꢁ, R in-
dices (all data) R1¼0.1411, wR2¼0.1410.
(s, 3H), 4.05 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 161.33 (d,
J¼244.9 Hz), 149.34, 149.10, 132.90 (d, J¼8.3 Hz), 130.86, 130.46,
130.43, 130.37, 129.49, 128.78, 127.92, 126.85, 126.64, 126.30, 126.15,
123.56, 123.24, 119.14, 114.07 (d, J¼22.7 Hz), 109.02 (d, J¼22.0 Hz),
108.37, 107.23, 56.00, 55.19.
4.4.8. 13-Benzyloxy-12-methoxybenzo[g]chrysene (2j). Yield¼70%
(58 mg); colorless gum; HRMS (ESI, Mþþ1) calcd for C30H23O2
415.1698, found 415.1702; 1H NMR (400 MHz, CDCl3):
d 8.67 (dt,
J¼2.4, 8.8 Hz, 2H), 8.61 (d, J¼8.8 Hz, 1H), 8.48 (d, J¼8.8 Hz, 1H), 8.36
(d, J¼8.0 Hz, 1H), 8.27 (s, 1H), 7.87 (d, J¼8.8 Hz, 1H), 7.69e7.54 (m,
5H), 7.48e7.31 (m, 5H), 5.37 (s, 2H), 4.12 (s, 3H); 13C NMR (100 MHz,
4.4.4. 2,3-Methylenedioxy-12,13-dimethoxybenzo[g]chrysene
(2f). Yield¼66% (50 mg); mp¼220e222 ꢁC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C25H19O4 383.1283,
CDCl3):
d 149.43, 147.85, 137.04, 130.72, 130.02, 129.58, 129.50,
128.76 (2ꢀ), 128.25, 128.14, 127.87, 127.25, 127.08, 126.95 (2ꢀ),
126.73, 126.39, 126.28, 126.11, 125.81, 125.18, 123.48, 123.45, 123.01,
119.28, 111.28, 107.47, 70.47, 55.97.
found 383.1284; 1H NMR (400 MHz, CDCl3):
d 8.61e8.59 (m, 1H),
8.48e8.46(m,1H), 8.46 (d, J¼8.8Hz,1H), 8.36 (s,1H), 8.30(s,1H), 8.07
(s, 1H), 7.81 (d, J¼8.8 Hz, 1H), 7.66e7.61 (m, 2H), 7.30 (s, 1H), 6.13 (s,
2H), 4.08 (s, 3H), 4.06 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
148.94,
4.4.9. 13-Benzyloxy-3,12-dimethoxybenzo[g]chrysene (2k). Yield¼62%
(52 mg); HRMS (ESI, Mþþ1) calcd for C31H25O3 445.1804, found
148.91, 147.48 (2ꢀ), 147.19, 129.49, 129.37, 129.32, 127.02, 126.61,
126.48, 126.40, 125.71, 125.42, 125.17, 123.48, 122.85, 119.22, 108.43,
107.26, 106.78, 102.52, 101.45, 56.07, 55.90. Single-crystal X-ray dia-
gram: crystal of compound 2f was grown by slow diffusion of EtOAc
into a solution of compound 2f in CH2Cl2 to yield colorless prisms.
The compound crystallizes in the orthorhombic crystal system, space
445.1806; 1H NMR (400 MHz, CDCl3):
d
8.59 (dt, J¼1.2, 8.8 Hz, 2H),
8.46 (d, J¼8.8 Hz, 1H), 8.23 (d, J¼9.2 Hz, 1H), 8.18 (s, 1H), 8.07 (d,
J¼2.4 Hz, 1H), 7.81 (d, J¼8.8 Hz, 1H), 7.69e7.62 (m, 2H), 7.55 (d,
J¼7.2 Hz, 2H), 7.47 (t, J¼7.2 Hz, 2H), 7.41e7.37 (m, 1H), 7.34 (s, 1H),
6.93 (dd, J¼2.4, 8.8 Hz, 1H), 5.37 (s, 2H), 4.12 (s, 3H), 4.05 (s, 3H); 13C
ꢀ
ꢀ
ꢀ
group P n a 21, a¼26.3820 (19) A, b¼3.7786 (3) A, c¼17.0118 (4) A,
NMR (100 MHz, CDCl3): d 157.97, 149.39, 147.65, 137.12, 132.33, 130.37,
V¼1695.9 (2) A , Z¼4, Dcalcd¼1.498 g/cm3, F(000)¼800, 2
q
range
129.82, 129.63, 129.21, 128.77 (2ꢀ), 127.83, 127.35, 126.90 (2ꢀ),
126.63, 126.52, 125.85, 125.45, 124.86, 123.73, 123.83, 123.05, 119.33,
114.73, 111.32, 107.44, 105.76, 70.43, 55.97, 55.43. Single-crystal X-ray
diagram: crystal of compound 2k was grown by slow diffusion of
EtOAc into a solution of compound 2k in CH2Cl2 to yield colorless
prisms. The compound crystallizes in the monoclinic crystal system,
3
ꢀ
1.95e26.41ꢁ, R indices (all data) R1¼0.0316, wR2¼0.0744.
4.4.5. 13-Butoxy-12-methoxybenzo[g]chrysene (2g). Yield¼75% (53
mg); mp¼120e122 ꢁC (recrystallized from hexanes and EtOAc);
HRMS (ESI, Mþþ1) calcd for C27H25O2 381.1855, found 381.1856; 1H
ꢀ
ꢀ
NMR (400 MHz, CDCl3):
d
8.94 (dd, J¼0.8, 8.0 Hz,1H), 8.73 (dd, J¼1.6,
space group P 1 21/n 1, a¼12.2066 (3) A, b¼8.1982 (2) A, c¼23.0377
3
ꢀ ꢀ
7.2 Hz, 1H), 8.69 (dd, J¼2.0, 7.2 Hz, 1H), 8.63 (dd, J¼2.0, 7.2 Hz, 1H),
8.50 (d, J¼8.8Hz,1H), 8.38(s,1H), 7.88(d, J¼8.8 Hz,1H), 7.72e7.60 (m,
4H), 7.32 (s,1H), 4.21 (t, J¼6.8 Hz, 2H), 4.07 (s, 3H),1.99e1.92 (m, 2H),
1.62e1.53 (m, 2H), 1.02 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
(6) A, V¼2269.34 (10) A , Z¼4, Dcalcd¼1.301 g/cm3, F(000)¼936, 2
q
range 1.80e26.39ꢁ, R indices (all data) R1¼0.0573, wR2¼0.1204.
4.4.10. 13-Benzyloxy-2,3-methylenedioxy-12-methoxybenzo[g]chrys-
ene (2l). Yield¼59% (54 mg); mp¼178e180 ꢁC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C31H23O4
d
149.42,148.75,130.87,130.12,129.74,129.55,129.36,128.79,128.43,
127.30, 127.11, 126.73, 126.46, 126.43, 125.80, 125.44, 123.66, 123.48,
123.05, 119.04, 109.97, 107.34, 68.77, 55.95, 31.19, 19.30, 13.93.
459.1596, found 459.1608; 1H NMR (400 MHz, CDCl3):
d 8.59e8.57
(m, 1H), 8.46e8.44 (m, 2H), 8.31 (s, 1H), 8.12 (s, 1H), 8.05 (s, 1H),
7.80 (d, J¼8.8 Hz, 1H), 7.64e7.59 (m, 2H), 7.57e7.55 (m, 2H),
7.42e7.38 (m, 2H), 7.33e7.30 (m, 2H), 6.14 (s, 2H), 5.34 (s, 2H), 4.09
4.4.6. 13-Butoxy-3,12-dimethoxybenzo[g]chrysene (2h). Yield¼58%
(48 mg); mp¼116e118 ꢁC (recrystallized from hexanes and EtOAc);
HRMS (ESI, Mþþ1) calcd for C28H27O3 411.1960, found 411.1969; 1H
(s, 3H); 13C NMR (100 MHz, CDCl3):
d 149.47, 147.97, 147.45, 147.16
NMR (400 MHz, CDCl3):
d
8.85 (d, J¼9.2 Hz, 1H), 8.62 (ddd, J¼1.6,
(2ꢀ),136.83,129.61,129.47,129.33,128.72 (2ꢀ),128.03,127.45 (2ꢀ),
126.95, 126.58, 126.43, 126.32, 125.70, 125.36, 125.06, 123.47,
122.82, 119.34, 111.13, 107.60, 106.89, 102.44, 101.39, 71.09, 55.94.
5.2, 7.2 Hz, 2H), 8.47 (d, J¼9.2 Hz, 1H), 8.31 (s, 1H), 8.12 (d, J¼2.8 Hz,
1H), 7.82 (d, J¼8.4 Hz, 1H), 7.71e7.63 (m, 2H), 7.31 (s, 1H), 7.25 (dd,
J¼2.8, 9.2 Hz, 1H), 4.20 (t, J¼6.8 Hz, 2H), 4.08 (s, 3H), 4.07 (s, 3H),
1.99e1.92 (m, 2H),1.63e1.53 (m, 2H),1.03 (t, J¼7.2 Hz, 3H); 13C NMR
4.4.11. 3,13-Dimethoxybenzo[g]chrysene (2n). Yield¼20% (13 mg);
colorless gum; HRMS (ESI, Mþþ1) calcd for C24H19O2 339.1385,
(100 MHz, CDCl3):
d 158.16, 149.42, 148.63, 132.48, 130.49, 130.01,

136
M.-Y. Chang, M.-H. Wu / Tetrahedron 69 (2013) 129e136
Tetrahedron 1999, 55, 625; (d) Kiselyov, A. S.; Lee, H.; Harvey, R. G. J. Org. Chem.
found 339.1391; 1H NMR (400 MHz, CDCl3):
d
8.93 (d, J¼9.2 Hz, 1H),
1995, 60, 6123 and cited references therein; (e) Wu, A.; Xu, D.; Lu, D.; Penning,
T. M.; Blair, I. A.; Harvey, R. G. Tetrahedron 2012, 68, 7217.
8.64 (dt, J¼2.4, 7.6 Hz, 2H), 8.46 (d, J¼9.2 Hz, 1H), 8.34 (d, J¼2.0 Hz,
1H), 8.13 (d, J¼2.4 Hz, 1H), 7.91 (t, J¼8.8 Hz, 1H), 7.72e7.68 (m, 3H),
7.26 (dd, J¼2.4, 8.8 Hz, 2H), 4.08 (s, 3H), 3.99 (s, 3H); 13C NMR
5. (a) Krzeminski, J.; Lin, J.-M.; Amin, S.; Hecht, S. S. Chem. Res. Toxicol. 1994, 7, 125;
(b) Luch, A.; Glatt, H.; Platt, K. L.; Oesch, F.; Seidal, A. Carcinogenesis 1994, 15,
2507; (c) Sayer, J. M.; Yagi, H.; Croisy-Delcey, M.; Jerina, D. M. J. Am. Chem. Soc.
1981, 103, 4970.
(100 MHz, CDCl3):
d 158.16, 157.95, 132.43, 132.38, 131.15, 130.85,
130.26, 130.04, 129.60, 129.55, 127.40, 126.92, 126.49, 123.98,
123.90, 123.11, 118.59, 116.94, 114.62, 114.22, 108.96, 105.87,
55.50 (2ꢀ).
6. (a) Bushman, D. R.; Grossman, S. J.; Jerina, D. M.; Lehr, R. E. J. Org. Chem. 1989,
54, 3533; (b) Utermoehlen, C. M.; Singh, M.; Lehr, R. E. J. Org. Chem. 1987, 52,
5574.
7. (a) Kumar, S. J. Org. Chem. 1997, 62, 8535; (b) Kumar, S. Synthesis 2001, 841.
8. Laali, K. K.; Okazaki, T. J. Org. Chem. 2001, 66, 780.
4.4.12. 13-Alloxy-2,3-methylenedioxy-12-methoxybenzo[g]chrysene
(2o). Yield¼60% (49 mg); mp¼134e136 ꢁC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C27H21O4
9. (a) Shimizu, M.; Nagao, I.; Tomioka, Y.; Hiyama, T. Angew. Chem., Int. Ed. 2008,
47, 8096; (b) Shimizu, M.; Nagao, I.; Kadowaki, T.; Hiyama, T. Tetrahedron 2011,
67, 8014; (c) Navale, T. S.; Zhai, L.; Lindeman, S. V.; Rathore, R. Chem. Commun.
2009, 2857; (d) Yamaguchi, S.; Swager, T. M. J. Am. Chem. Soc. 2001, 123, 12087;
(e) Li, C.-W.; Wang, C.-I.; Liao, H.-Y.; Chaudhuri, R.; Liu, R.-S. J. Org. Chem. 2007,
72, 9203; (f) Sharma, A. K.; Kumar, S.; Amin, S. J. Org. Chem. 2004, 69, 3979; (g)
Chaudhuri, R.; Hsu, M.-Y.; Li, C.-W.; Wang, C.-I.; Chen, C.-J.; Lai, C.-K.; Chen, L.-Y.;
Liu, S.-H.; Wu, C.-C.; Liu, R.-S. Org. Lett. 2008, 10, 3053; (h) Schultz, A.; Laschat,
S.; Diele, S.; Nimtz, M. Eur. J. Org. Chem. 2003, 2829; (i) Navale, T. S.; Thakur, K.;
Rathore, R. Org. Lett. 2011, 13, 1634.
10. (a) Harvey, R. G.; Lim, K.; Dai, Q. J. Org. Chem. 2004, 69, 1372; (b) Schlude, H.
Chem. Ber. 1971, 104, 3995; (c) Johnson, W. S. Org. React. 1944, 2, 114; (d) Zhang,
F.-J.; Cortez, C.; Harvey, R. G. J. Org. Chem. 2000, 65, 3952.
11. (a) Wang, Z.; Dotz, F.; Enkelmann, V.; Mullen, K. Angew. Chem., Int. Ed. 2005, 44,
1247; (b) Yue, W.; Lv, A.; Gao, J.; Jiang, W.; Hao, L.; Li, C.; Li, Y.; Polander, L. E.;
Barlow, S.; Hu, W.; Di Motta, S.; Negri, F.; Marder, S. R.; Wang, Z. J. Am. Chem. Soc.
2012, 134, 5770; (c) Chen, T.-A.; Liu, R.-S. Org. Lett. 2011, 13, 4644; (d) Chen, J.-D.;
Lu, H.-Y.; Chen, C.-F. Chem.dEur. J. 2010, 16, 11843.
409.1440, found 409.1436; 1H NMR (400 MHz, CDCl3):
d 8.59e8.56
(m, 1H), 8.47e8.44 (m, 1H), 8.44 (d, J¼8.8 Hz, 1H), 8.25 (s, 1H), 8.24
(s, 1H), 8.05 (s, 1H), 7.79 (d, J¼8.8 Hz, 1H), 7.64e7.60 (m, 2H), 7.29
(s, 1H), 6.25e6.16 (m, 1H), 6.12 (s, 2H), 5.56 (dq, J¼1.2, 17.2 Hz, 1H),
5.46 (dq, J¼1.2, 10.4 Hz, 1H), 4.81 (dt, J¼1.6, 5.6 Hz, 2H), 4.08 (s, 3H);
13C NMR (100 MHz, CDCl3):
d 149.17, 147.72, 147.44, 147.16, 133.46
(2ꢀ), 129.48, 129.37, 129.33, 126.91, 126.55, 126.42, 126.33, 125.67,
125.32, 124.98, 123.46, 122.82, 119.24, 118.64, 110.38, 107.39, 107.09,
102.41, 101.42, 69.78, 55.89.
Acknowledgements
12. (a) Chang, M.-Y.; Lee, N.-C. Synlett 2012, 867; (b) Chang, M.-Y.; Wu, M.-H.; Lee,
N.-C.; Lee, M.-F. Tetrahedron Lett. 2012, 53, 2125; (c) Chang, M.-Y.; Wu, M.-H.
Tetrahedron Lett. 2012, 53, 3173; (d) Chang, M.-Y.; Wu, M.-H.; Lee, T.-W. Tetra-
hedron 2012, 68, 6224; (e) Chang, M.-Y.; Wu, M.-H.; Chen, Y.-L. Tetrahedron Lett.
2012, 53, 4156; (f) Chang, M.-Y.; Tai, H.-Y.; Chen, Y.-L.; Hsu, R.-T. Tetrahedron
2012, 68, 7941; (g) Chang, M.-Y.; Wu, M.-H.; Tai, H.-Y. Org. Lett. 2012, 14, 3936;
(h) Chang, M.-Y.; Wu, M.-H. Tetrahedron 2012, 68, 9616; (i) Chang, M.-Y.; Chan,
C.-K.; Lin, S.-Y.; Hsu, R.-T. Tetrahedron 2012, 68, 10272.
13. CCDC 894231 (4f), 892761 (6a), 892794 (2f), 896140 (2i), and 896671 (2k)
contain the supplementary crystallographic data for this paper. This data can be
obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from
the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: 44-1223-336033; e-
mail: deposit@ccdc.cam.ac.uk).
14. (a) De Koning, C. B.; Michael, J. P.; Rousseau, A. L. Tetrahedron Lett. 1997, 38, 893;
(b) De Koning, C. B.; Michael, J. P.; Rousseau, A. L. J. Chem. Soc., Perkin Trans. 1
2000, 787; (c) De Koning, C. B.; Manzini, S. S.; Michael, J. P.; Mmutlane, E. M.;
Tshabidi, T. R.; Van Otterlo, W. A. L. Tetrahedron 2005, 61, 555; (d) Sibi, M. P.;
Dankwardt, J. W.; Snieckus, V. J. Org. Chem. 1986, 51, 271; (e) Pearson, D. E.;
Buehler, C. A. Chem. Rev. 1974, 74, 45; (f) Rao, B. B.; Wei, J.-R.; Lin, C.-H. Org. Lett.
2012, 14, 3640.
The authors would like to thank the National Science Council of
the Republic of China for its financial support.
Supplementary data
Scanned photocopies of 1H and 13C NMR spectral data and
crystallographic data of 4f, 6a, 2f, 2i, and 2k (CIF) were supported.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2012.10.054.
References and notes
1. (a) Harvey, R. G. Polycyclic Aromatic Hydrocarbons; Wiley-VCH: New York, NY,
1997; (b) Harvey, R. G. Polycyclic Aromatic Hydrocarbons: Chemistry and Carci-
nogenicity; Cambridge University: Cambridge, UK, 1991; (c) Bax, A.; Ferretti, J.
A.; Nashed, N.; Jerina, D. M. J. Org. Chem. 1985, 50, 3029; (d) Jogenson, K.
Molecules 2010, 15, 4334.
15. (a) Berresheim, A. J.; Muller, M.; Muller, K. Chem. Rev. 1999, 99, 1747; (b) Kumar,
S. Liq. Cryst. 2005, 32, 1089.
16. (a) Boden, N.; Bushby, R. J.; Headdock, G.; Lozman, O. R.; Wood, A. Liq. Cryst.
2001, 28, 139; (b) King, B. T.; Kroulik, J.; Robertson, C. R.; Rempala, P.; Hilton, C.
L.; Korinek, J. D.; Gortari, L. M. J. Org. Chem. 2007, 72, 2279; (c) Simpson, C. D.;
Mattersteig, G.; Martin, K.; Gherghel, L.; Bauer, R. E.; Rader, H. J.; Mullen, K. J.
Am. Chem. Soc. 2004, 126, 3139; (d) McKillop, A.; Turrell, A. G.; Young, D. W.;
Taylor, E. C. J. Am. Chem. Soc. 1980, 102, 6504; (e) Churruca, F.; SanMartin, R.;
Carril, M.; Urtiaga, M. K.; Solans, X.; Tellitu, I.; Dominguez, E. J. Org. Chem. 2005,
70, 3178; (f) Zhang, X.; Jiang, X.; Zhang, K.; Mao, L.; Luo, J.; Chi, C.; Chan, H. S. O.;
Wu, J. J. Org. Chem. 2010, 75, 8069.
2. (a) Harvey, R. G. Polycyclic Aromatic Hydrocarbons: Chemistry and Carcinogene-
sis; Cambridge University: Cambridge, 1991; (b) Harvey, R. G.; Geacintov, N. E.
Acc. Chem. Res. 1988, 21, 66.
3. For the reviews on PAHs, see: (a) Weil, T.; Vosch, T.; Hofkens, J.; Peneva, K.;
€
€
Mullen, K. Angew. Chem., Int. Ed. 2010, 49, 9068; (b) Wu, J.; Pisula, W.; Mullen, K.
Chem. Rev. 2007, 107, 718; (c) Anthony, J. E. Chem. Rev. 2006, 106, 5028; (d)
Karitzky, A. R.; Li, J.; Xie, L. Tetrahedron 1999, 55, 8263.
4. (a) Sukumaran, K. B.; Harvey, R. G. J. Org. Chem. 1981, 46, 2740; (b) Tang, X.-Q.;
Harvey, R. G. Tetrahedron Lett. 1995, 36, 6037; (c) Zhang, J.-T.; Harvey, R. G.