Three different dimerizations of 2-bromo-3-methyl-1,4-naphthoquinones

Article abstract of DOI:10.1021/jo300696m

Three types of dimeric naphthoquinones, which possess structurally diverse skeletons, can be prepared in one step from 2-bromo-3-methyl-1,4- naphthoquinones. 2,2′-Dimeric naphthoquinones were prepared by a one-pot Stille-type reaction via vinylstannanes. Oxepines are formed by unexpected domino reactions via 1,4-dihydroxynaphthalene species. Epoxides are formed by a Michael/Darzens reaction via the o-quinone methides.

Full text of DOI:10.1021/jo300696m

Article
pubs.acs.org/joc
Three Different Dimerizations of 2-Bromo-3-methyl-1,
4-naphthoquinones
Shuhei Azuma,† Kazuyuki Nishio,† Konomi Kubo,† Takahiro Sasamori,‡ Norihiro Tokitoh,‡
Kouji Kuramochi,*,† and Kazunori Tsubaki*,†
†Graduate School for Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamo Hangi-cho, Sakyo-ku,
Kyoto 606-8522, Japan
‡Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan
S
* Supporting Information
ABSTRACT: Three types of dimeric naphthoquinones, which possess
structurally diverse skeletons, can be prepared in one step from 2-bromo-3-
methyl-1,4-naphthoquinones. 2,2′-Dimeric naphthoquinones were pre-
pared by a one-pot Stille-type reaction via vinylstannanes. Oxepines are
formed by unexpected domino reactions via 1,4-dihydroxynaphthalene
species. Epoxides are formed by a Michael/Darzens reaction via the
o-quinone methides.
a
INTRODUCTION
Table 1. Stille-Type Homocoupling Reaction of 1a
■
Naphthoquinones are known to dimerize in various ways,
depending on their structure and the particular set of
conditions.1,2 However, the products of the dimerizations are
difficult to predict or control, and only a few methods for
efficient and selective synthesis of dimeric naphthoquinones
have been reported.1c Moreover, little is known of the
dimerization reactions of brominated naphthoquinones. We
were interested in direct homocoupling of 2-bromo-1,4-
naphthoquinones to synthesize symmetrical 2,2′-dimeric
3
naphthoquinones such as bivitamin K3 and biplumbagin.4
This synthetic approach clearly has advantages in terms of
redox economy over traditional oxidative coupling of 4-alkoxy-
1-naphthols.2b In addition, 2-bromo-3-methyl-1,4-naphthoqui-
nones (1) can serve as a potential starting material for
generating structurally diverse naphthoquinone dimers because
they contain numerous reactive groups, allowing for a variety of
dimerizations. In this paper, we describe novel and selective
dimerizations of 1.
yield (%)
b
c
b
entry
Pd catalyst
temp (°C)
2a
3a
4a
1
2
Pd(dppf)Cl2
Pd(PPh3)4
80
80
70
54
13
20
d
3
Pd(PPh3)2Cl2
100
64
a
Unless otherwise indicated, the reactions were carried out in the
presence of Pd catalyst (0.2 equiv), (Me3Sn)2 (1.1 equiv), and CuI
(1.0 equiv). Yields of the isolated product. Yields estimated by H
b
c
1
RESULTS AND DISCUSSION
■
d
After a systematic survey5 of homocoupling of 1a,6 we found
that a Stille-type reaction was effective (Table 1). Treatment of
1a with hexamethylditin (1.1 equiv) and CuI (1.0 equiv) in the
presence of [1,1′-bis(diphenylphosphino)ferrocene]palladium
dichloride (Pd(dppf)Cl2) (0.2 equiv) in dioxane gave the
desired 2a3,7 in 70% yield (entry 1). In this reaction, 2,3-
dimethyl-1,4-naphthoquinone (3a)8 was also obtained in 13%
yield. The use of Pd(PPh3)4 decreased the yield of 2a and
NMR using 2,5-dimethylfuran as internal standard. Used 0.1 equiv of
Pd(PPh3)2Cl2 without CuI.
increased the yield of 3a (entry 2). The use of Pd(PPh3)2Cl2
(0.1 equiv) as a catalyst, in the absence of CuI, gave 4a, a
Received: April 7, 2012
Published: April 24, 2012
© 2012 American Chemical Society
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a
a
Table 2. Formation of Homodimers 2 from 1
Table 3. Formation of Oxepines 5a from 1a
b
entry
Pd catalyst/ligand
yield (%)
1
2
Pd(dppf)Cl2/−
Pd2(dba)3/( )-BINAP
36
47
96
c
3
Pd2(dba)3/( )-BINAP
a
Unless otherwise indicated, the reactions were carried out in the
b
entry
substrate 1
product 2
yield (%)
presence of Pd catalyst (0.1 equiv), (Me3Sn)2 (1.1 equiv), and CuI
b
1
2
3
4
5
1b
1c
1d
1e
1f
2b
58
65
(1.0 equiv) with or without ( )-BINAP (0.1 equiv). Yields of the
c
2c
isolated product. With 1.0 equiv of Na2CO3.
2d and 2d′
2d: 41, 2d′: 40
2e
2f
72
12
was slightly improved when tris(dibenzylideneacetone)-
dipalladium (Pd2(dba)3) (0.05 equiv) and ( )-2,2′-bis-
(diphenylphosphino)-1,1′-binaphthyl (BINAP) (0.1 equiv)
were used as the catalyst and ligand, respectively (entry 2).
We found that the addition of Na2CO3 significantly improved
the yield of 5a (entry 3). Although the use of CuBr instead of
CuI gave 5a in 87% yield, the use of CuBr2 gave 5a in only 13%
yield, suggesting that Cu(I) activated 1a to give oxepine for-
mation. The reaction was quenched with acetic anhydride
(Ac2O) before completion to give acetylated oxepine 6 and 1,4-
diacetylnaphthalene 7 in 11% and 10% yields, respectively,
along with recovered starting material 1a (50%) (Scheme 2).
Isolation of compound 7 indicates that 1,4-dihydroxynaph-
thalene species are intermediates in oxepine formation.
a
The reactions were carried out in the presence of Pd(dppf)Cl2
(0.2 equiv), (Me3Sn)2 (1.1 equiv), and CuI (1.0 equiv). Yields of the
isolated product.
b
Scheme 1. Crossover Reaction between Vinyl Bromide 1c
and Vinylstannane 4a for Mechanistic Studies on the
Formation of 2,2′-Dimeric Naphthoquinones
We next examined the effects of the reagents used on the
oxepine formation (Table 4). The reaction in the absence of
hexamethylditin afforded a complex mixture (entry 1). Although
the reaction proceeded in the absence of CuI or ( )-BINAP,
there was a decrease in yield (entries 2 and 3). Interestingly, the
oxepine 5a was obtained in 82% yield when the reaction was
conducted without Pd2(dba)3 (entry 4). These results suggested
that ( )-BINAP might coordinate with copper ion.14
Using optimized conditions, the influence of additional func-
tional groups on oxepine formation was examined (Table 5).
Although the reaction can tolerate a methyl group in the
benzene ring, oxepine 5b or 5c were only obtained in moderate
yield (entry 1 and 2, respectively). The reaction of 1d resulted
in a poor yield of 5d. Unfortunately, the reaction of 1e or 1f led
to decomposition of the substrate.
To rationalize the unexpected formation of 5a, a mixture of
vinyl bromide 1c and vinylstannane 4a was subjected to the
same reaction, producing 3a and 5c in 19% and 55% yields,
respectively (Scheme 3). This result indicates that the oxepines
are not derived from vinylstannanes but from vinyl bromides.
We found that oxepine 5a was obtained by treatment of 1a with
t-BuOK in THF (Scheme 4A). Furthermore, irradiation of a
solution of 1a and hexamethylditin in DMF with a white
fluorescent lamp afforded 5a in 39% yield (Scheme 4B). The
photodimerization of 1a did not occur in the absence of
hexamethylditin, indicating that a photoinduced electron
transfer from hexamethylditin to an excited state of naphtho-
quinone 1a is involved in the photodimerization.15 Irradiation
of 1a and hexamethylditin in the presence of Ac2O gave 1,4-
diacetylnaphthalene 7 in 48% yield (Scheme 4C). This result
suggests that 1,4-dihydroxynaphthalene species are intermedi-
ates in photoinduced oxepine formation.
plausible intermediate of the homocoupling, in 64% yield
(entry 3).
Using optimal conditions (Table 1, entry 1), various 2-
bromo-3-methyl-1,4-naphthoquinones (1) were subjected to
the homodimerization reaction (Table 2). The dimerization of
1b or 1c, which have a methyl group in the benzene ring, gave
the desired dimer 2b or 2c in moderate yields (entries 1 and 2).
The reaction of the acetyloxy derivative 1d afforded 2d and
the mono-deacetylated product 2d′ in 41% and 40% yields,
respectively (entry 3). The dimerization of the methoxy
derivative 1e9 gave 2e10 in 72% yield (entry 4). Because of the
instability of 5-hydroxy-3-bromo-2-methyl-1,4-naphthoqui-
none (1f)11 under the reaction conditions, the yield of 2f12
was low (entry 5).
To analyze the mechanism of the homodimerization
reaction, the crossover reaction between 1c and 4a was per-
formed to afford the heterodimer 2g, homodimer 2a, and
recovered 1c in 57%, 39%, and 33%, respectively (Scheme 1).
This result suggests that compound 2 was formed by both Stille
coupling between 1 and 4 and oxidative dimerization13 of
stannanes 4.
During the course of our investigations of Stille-type homo-
coupling, we found a novel dimerization of 1a (Table 3). When
the reaction was carried out using Pd(dppf)Cl2 (0.1 equiv) in
DMF, the oxepine 5a was obtained in 36% yield as the sole
product (entry 1). The structure of 5a was confirmed by X-ray
crystallography (see the Supporting Information). The yield
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Scheme 2. Trapping Experiments with Acetic Anhydride in Oxepine Formation
a
Table 4. Effects of Reagents on Formation of Oxepine 5a
Scheme 4. Formation of 5a by Treatment of 1a with t-BuOK
in THF (A) and Irradiation of 1a and Hexamethylditin in the
Presence (B) or Absence (C) of Acetic Anhydride
b
entry Pd2(dba)3 ( )-BINAP (Me3Sn)2 CuI Na2CO3 yield (%)
c
1
2
3
4
+
+
+
−
+
+
−
+
−
+
+
+
+
−
+
+
+
+
+
+
−
27
43
82
a
The plus sign indicates the presence of the reagent, and the minus
b
sign indicates the absence of the reagent or product. Yields of the
isolated product. Complex mixture.
c
Table 5. Formation of Oxepines from 2-Bromo-3-methyl-
a,b
1,4-napthoquinones
with generation of the excited triplet state (1a*) of
bromonaphthoquinone 1a (Scheme 5B).15 Reaction of 1a*
with hexamethylditin would give a semiquinone radical anion C
and a radical cation of hexamethylditin, which could produce a
1,4-bis(trimethylstannoxy)naphthoquinone D.15b Elimination of
trimethyltin hydride from D, followed by dimerization of the
resulting o-quinone methides E, would give a stannyl ether F. The
conversion of D into E might involve homolytic cleavage of the
Sn−O bond, followed by hydrogen abstraction from the methyl
group by the resulting trimethyltin radical. Hydrolysis of F would
afford 5a. Oxepine formation from hexamethylditin, CuI,
( )-BINAP, and Na2CO3 in DMF would start with formation
of an adduct of 1 with CuI (Scheme 5C).16 The resulting
complex 1·CuI would react with hexamethylditin to give 1,4-
dihydroxynaphthalene species G. The intermediate G could then
generate the o-quinone methide H. Formation of an ethylene
bridge, followed by intramolecular seven-membered ether ring
formation, would afford 5. A palladium catalyst might activate 1
by coordination17 or might accelerate the final intramolecular
ether formation.18 Formation of a Pd enolate at the carbonyl
group adjacent to the methyl group, followed
by β-hydride elimination, might provide the quinone methide
E or H.19
b
entry
substrate 1
product 5
yield (%)
1
2
3
1b
1c
1d
5b: R1 = Me, R2 = R3 = H
5c: R1 = R3 = H, R2 = Me
5d: R1 = R2 = H, R3 = OAc
51
47
26
a
The reactions were carried out in the presence of Pd2(dba)3
(0.05 equiv), ( )-BINAP (0.1 equiv), (Me3Sn)2 (1.1 equiv), and
b
CuI (1.0 equiv). Yields of the isolated product.
Scheme 3. Crossover Reaction Study of Oxepine Formation
for Mechanistic Analysis
We found another novel dimerization of 1a in the course of
our investigations of oxepine formation (Table 6). Treatment
of 1a with Na2CO3 in DMF gave an epoxide dimer 8a in 52%
yield (entry 1). The structure of 8a was unambiguously deter-
mined by X-ray crystallography; an anti relationship between
the methyl group and the epoxide was indicated (see the
Supporting Information). The use of K2CO3 or Rb2CO3 as a
base slightly improves the yield of 8a (entries 2 and 3). The
yield was improved to 85% by using Cs2CO3 (entry 4).
The formation of epoxide dimers 8 from various 2-bromo-
3-methyl-1,4-naphthoquinones was examined (Table 7). The
Our proposed mechanism for the oxepine formation is
shown in Scheme 5. Oxepine formation by t-BuOK in THF
starts with the formation of the o-quinone methide derivative A
(Scheme 5A). The o-quinone methide attacks the enone moiety
of another o-quinone methide to give the hydroquinone dianion
B.1c Finally 1,4-addition of the hydroquinone anion to the
β-bromo enone, followed by elimination of a bromide anion,
affords the oxepine 5a. Photoinduced oxepine formation starts
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Scheme 5. Proposed Mechanism for Formation of Oxepine 5a from 1a by Treatment with t-BuOK in THF (A), Formation
of 5a by Irradiation of 1a and (Me3Sn)2 (B), and Formation of 5 by Treatment with (Me3Sn)2, CuI, ( )-BINAP, and Na2CO3
in DMF (C)
epoxides 8b and 8c were obtained in good yields from 1b and 1c,
respectively (entry 1 and 2). However, the yield decreased when
compound 1d or 1e was the substrate (entry 3 and 4). Compound
1f decomposed under the basic conditions used in this reaction.
The mechanism for the formation of epoxide dimer 8 is
shown in Scheme 6. Treatment of 1 with Cs2CO3 establishes
an equilibrium between 1 and the o-quinone methide I. The
o-quinone methide I attacks the enone of 1, and the resulting
enolate undergoes an intramolecular Darzens reaction to yield
the epoxide dimer 8.20
structurally diverse skeletons can be constructed from 1 in a single
step. Stille-type homocoupling is a convenient method for the
preparation of 2,2′-dimeric naphthoquinones 2. The unprecedented
formation of oxepines 5 and epoxides 8 can be rationalized by
unique domino reactions. The resulting highly functionalized
oxepines and epoxides can serve as useful building blocks for the
construction of combinatorial libraries. Exploration of synthetic
uses of these reactions, as well as biological evaluations of the core
skeletons, are in progress.
EXPERIMENTAL SECTION
■
CONCLUSION
■
General Information. All nonaqueous reactions were carried out
using distilled solvents under a N2 atmosphere in dried glassware,
unless otherwise noted. Analytical TLC was performed on glass plates
We have developed three novel dimerization reactions of 2-bromo-
3-methyl-1,4-naphthoquinones (1). Moreover, we have shown that
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a
used for spin multiplicity: s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet, and br = broad. IR spectra were recorded on a
FT-IR spectrometer and are reported in wavenumbers (cm−1). High-
resolution mass spectra (HRMS) were obtained on a magnetic sector
mass spectrometer using electron impact ionization (EI) or a TOF
mass spectrometer using electrospray ionization (ESI).
Table 6. Optimization of Formation of Epoxide Dimer 8a
2-Bromo-3,6-dimethyl-1,4-naphthoquinone (1b). Br2 (0.10 mL,
1.94 mmol) was added to a solution of 2,7-dimethylnaphthoquinone21
(186 mg, 1.00 mmol) in AcOH (10 mL) at rt. The mixture was stirred at
rt for 12 h. The reaction was quenched by the addition of water, and the
solid was removed by filtration. The solid was dissolved in CHCl3. The
resulting solution was washed with water (×2) and brine, dried
over Na2SO4, and concentrated. The residue was dissolved in pyridine
(5 mL), and the mixture was stirred at 0 °C for 20 min. The reaction was
quenched by the addition of 1 M HCl aqueous solution, and the mixture
was diluted with EtOAc. After the layers were separated, the aqueous
layer was extracted with EtOAc ( × 2). The combined organic layer was
washed with water (×2) and brine, dried over Na2SO4, and concentrated.
The residue was purified by flash column chromatography (toluene/
hexane = 2/3 to 2/1) to give 1b (219 mg, 83%) as a yellow solid: mp =
111−112 °C; IR (KBr) νmax = 3188, 3059, 2922, 1672, 1595, 1298, 1277,
b
entry
base
time (min)
yield (%)
c,d
1
2
3
4
Na2CO3
K2CO3
180
60
52
68
66
85
Rb2CO3
Cs2CO3
45
30
a
b
The reactions were carried out using 1.5 equiv of base. Yields of the
isolated product. The reaction was carried out at 0 °C for 90 min and
c
d
at rt for 90 min. 17% of 1a was recovered.
Table 7. Formation of Epoxides from 2-Bromo-3-methyl-1,4-
a,b
naphthoquinones
1
1022, 872, 847, 785, 717 cm−1; H NMR (CDCl3, 270 MHz) δ = 8.04
(d, J = 8.0 Hz, 1H), 7.91 (s, 1H), 7.52 (d, J = 8.0 Hz, 1H), 2.50 (s, 3H),
2.38 (s, 3H); 13C NMR (CDCl3, 67.8 MHz) δ = 182.0, 177.0, 148.0,
145.2, 139.0, 134.4, 131.3, 128.8, 127.6, 127.3, 21.9, 17.9; HRMS (EI)
calcd for C12H979BrO2 ([M]+) 263.9786, found 263.9786.
3-Bromo-2,6-dimethyl-1,4-naphthoquinone (1c). Br2 (1.50 mL,
29.1 mmol) was added to a solution of 2,6-dimethylnaphthoquinone21
(2.79 g, 15.0 mmol) in AcOH (100 mL) at rt. The mixture was stirred
at rt for 13 h. The reaction was quenched by the addition of water, and
the solid was removed by filtration. The solid was dissolved in CHCl3.
The resulting solution was washed with water (×2) and brine, dried
over Na2SO4, and concentrated. The residue was dissolved in pyridine
(10 mL), and the mixture was stirred at 0 °C for 30 min and at rt for
15 min. The reaction was quenched by the addition of 1 M HCl
aqueous solution, and the mixture was diluted with EtOAc. After the
layers were separated, the aqueous layer was extracted with EtOAc
(×2). The combined organic layer was washed with water (×2) and
brine, dried over Na2SO4, and concentrated. The residue was purified
by flash column chromatography (toluene/hexane = 2/3 to 2/1) to
give 1c (2.21 g, 56%) as a yellow solid: mp = 115−116 °C; IR (KBr)
νmax = 3062, 2922, 1674, 1655, 1294, 1026, 910, 843, 781, 717 cm−1;
1H NMR (CDCl3, 270 MHz) δ = 7.95 (d, J = 7.8 Hz, 1H), 7.89 (s,
b
entry
substrate 1
product 8
yield (%)
1
2
3
4
1b
1c
1d
1e
8b: R1 = Me, R2 = R3 = H
8c: R1 = R3 = H, R2 = Me
8d: R1 = R2 = H, R3 = OAc
8e: R1 = R2 = H, R3 = OMe
71
68
24
23
a
b
The reactions were carried out using 1.5 equiv of Cs2CO3. Yields of
the isolated product.
Scheme 6. Proposed Mechanism for Formation of Epoxides
8 from 1
1H), 7.51 (d, J = 7.8 Hz, 1H), 2.49 (s, 3H), 2.36 (s, 3H); 13C NMR
(CDCl3, 67.8 MHz) δ = 181.4, 177.4, 148.2, 144.9, 138.5, 134.6, 130.8,
129.0, 127.6, 127.0, 21.8, 17.8; HRMS (EI) calcd for C12H981BrO2
([M]+) 265.9766, found 265.9765.
5-Acetyloxy-3-bromo-2-methyl-1,4-naphthoquinone (1d).
Ac2O (12 mL) was added to a solution of 1f11 (400 mg, 1.50 mmol)
in pyridine (6 mL) at 0 °C. The mixture was stirred at rt for 1 h. The
reaction was quenched by the addition of 1 M HCl aqueous solution,
and the mixture was diluted with EtOAc. The suspension was filtered
through Celite. After the layers were separated, the aqueous layer was
extracted with EtOAc (×2). The combined organic layer was washed
with water (×2) and brine, dried over Na2SO4, and concentrated. The
residue was purified by flash column chromatography (EtOAc/hexane =
1/8) to give 1d (421 mg, 91%) as a yellow solid: mp = 153−155 °C; IR
(KBr) νmax = 3095, 2925, 1768, 1672, 1604, 1587, 1444, 1304, 1250,
1188, 1022, 920, 879, 792, 754 cm−1; 1H NMR (CDCl3, 270 MHz) δ =
8.10 (dd, J = 7.9 Hz, 1.4 Hz, 1H), 7.77 (dd, J = 7.9 Hz, 7.9 Hz, 1H), 7.39
(dd, J = 7.9 Hz, 1.4 Hz, 1H), 2.49 (s, 3H), 2.39 (s, 3H); 13C NMR
(CDCl3, 67.8 MHz) δ = 181.0, 175.6, 169.2, 149.9, 147.4, 139.9, 134.9,
133.1, 129.6, 125.5, 122.5, 21.2, 17.8; HRMS (EI) calcd for C13H979BrO4
([M]+) 307.9684, found 307.9674.
General Procedure for Stille-Type Homocoupling Reaction
(Tables 1 and 2). A Pd catalyst (0.2 or 0.1 equiv) was added to a
solution of 1 (1.0 equiv) and hexamethylditin (1.1 equiv) in the
presence or absence of CuI (1.0 equiv) in degassed dioxane at rt. The
mixture was stirred at the indicated temperature (80 or 100 °C) under
a N2 atmosphere until no further TLC changes were observed. The
coated with silica gel. Flash chromatography was carried out on silica
gel (230−400 mesh). NMR spectra were recorded on a 270 or
600 MHz spectrometer. Chemical shifts are expressed as δ (ppm)
relative to Me4Si or the residual solvent resonance, and coupling
constants (J) are expressed in hertz. The following abbreviations are
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reaction was quenched by the addition of water, and the mixture was
diluted with EtOAc. The mixture was filtered through Celite. After the
layers were separated, the aqueous layer was extracted with EtOAc
(×2). The combined organic layer was washed with water (×2) and
brine, dried over Na2SO4, and concentrated. The residue was purified
by column chromatography (EtOAc/hexane). The structures of 2a,7
7.71 (dd, J = 8.1 Hz, 1.4 Hz, 1H), 7.65 (dd, J = 8.1 Hz, 8.1 Hz, 1H),
7.40 (dd, J = 8.1 Hz, 1.4 Hz, 1H), 7.28 (dd, J = 8.1 Hz, 1.4 Hz, 1H),
2.37 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H); 13C NMR (CDCl3, 67.8
MHz) δ = 187.3, 183.45, 183.39, 180.9, 169.1, 161.3, 149.5, 147.2,
144.9, 140.6, 140.2, 136.3, 134.7, 133.6, 131.9, 129.7, 125.1, 124.3,
123.2, 119.4, 114.7, 21.2, 14.5, 14.3; HRMS (EI) calcd for C24H16O7
([M]+) 416.0896, found 416.0894.
8
2e,10 2f,12 and 3a were confirmed by comparison of the H NMR
1
data with reported data.
8,8′-Dimethoxy-3,3′-dimethyl[2,2′-binaphthalene]-1,1′,4,4′-
tetrone (2e). Following the general procedure, the homocoupling
reaction of 1e (33.7 mg, 120 μmol) using hexamethylditin (43.2 mg,
132 μmol) and CuI (22.9 mg, 120 μmol) in the presence of Pd(dppf)Cl2
(17.6 mg, 24 μmol) for 13.5 h gave the crude product. The crude
product was purified by silica gel column chromatography (EtOAc/
hexane = 1/5 to 1/1) to give 2e (17.4 mg, 72%) as a yellow solid: mp =
3,3′-Dimethyl[2,2′-binaphthalene]-1,1′,4,4′-tetrone (2a).
Following the general procedure, the homocoupling reaction of 1a
(30.1 mg, 120 μmol) using hexamethylditin (43.2 mg, 132 μmol) and
CuI (22.9 mg, 120 μmol) in the presence of Pd(dppf)Cl2 (17.6 mg,
24 μmol) for 7 h gave the crude product. The crude product was
purified by silica gel column chromatography (EtOAc/hexane = 1/15
to 1/5) to give 3a (14.3 mg, 70%) as a yellow solid: mp = 249−250 °C
273−275 °C (lit.10 261−263 °C); H NMR (CDCl3, 270 MHz) δ =
1
7
1
(lit. mp = 249−251 °C); H NMR (CDCl3, 270 MHz) δ = 8.20−
8.16 (m, 2H), 8.12−8.07 (m, 2H), 7.82−7.72 (m, 4H), 2.07 (s, 6H);
13C NMR (CDCl3, 67.8 MHz) δ =184.3 (2C), 182.4 (2C), 145.6
7.81 (dd, J = 8.0 Hz, 1.1 Hz, 2H), 7.69 (dd, J = 8.0 Hz, 2H), 7.28 (dd,
J = 8.0, 1.1 Hz, 2H), 3.95 (s, 6H), 2.01 (s, 6H); 13C NMR (CDCl3, 67.8
MHz): δ = 184.6 (2C), 181.8 (2C), 159.6 (2C), 142.8 (2C), 142.7 (2C),
134.8 (2C), 134.1 (2C), 119.6 (2C), 119.2 (2C), 117.6 (2C), 56.4 (2C),
13.9 (2C).
(2C), 140.4 (2C), 133.84 (2C), 133.77 (2C), 131.8 (2C), 131.8(2C),
126.6 (2C), 126.5 (2C), 14.5 (2C).
3,3′,6,6′-Tetramethyl[2,2′-binaphthalene]-1,1′,4,4′-tetrone
(2b). Following the general procedure, the homocoupling reaction of
1b (31.8 mg, 120 μmol) using hexamethylditin (43.2 mg, 132 μmol)
and CuI (22.9 mg, 120 μmol) in the presence of Pd(dppf)Cl2 (17.6 mg,
24 μmol) for 7 h gave the crude product. The crude product was purified
by silica gel column chromatography (EtOAc/hexane = 1/15 to 1/5) to
give 2b (12.8 mg, 58%) as a yellow solid: mp = 203−204 °C; IR (KBr)
νmax = 3197, 3057, 2958, 2924, 2860, 1664, 1599, 1377, 1344, 1290,
8,8′-Dihydroxy-3,3′-dimethyl[2,2′-binaphthalene]-1,1′,4,4′-
tetrone (2f). Following the general procedure, the homocoupling
reaction of 1f (32.0 mg, 120 μmol) using hexamethylditin (43.2 mg,
132 μmol) and CuI (22.9 mg, 120 μmol) in the presence of
Pd(dppf)Cl2 (17.6 mg, 24 μmol) for 7 h gave the crude product. The
crude product was purified by silica gel column chromatography
(EtOAc/hexane = 1/15 to 1/5) to give 2f (2.6 mg, 12%) as a yellow
solid: mp = 212−213 °C (lit.12 mp = 212−214 °C); 1H NMR (CDCl3,
270 MHz) δ = 11.8 (s, 2H), 7.73 (t, J = 8.0 Hz, 2H), 7.66 (dd, J = 8.0
Hz, 1.4 Hz, 2H), 7.29 (dd, J = 8.0 Hz, 1.4 Hz, 2H), 2.08 (s, 6H); 13C
NMR (CDCl3, 67.8 MHz) δ = 187.4 (2C), 183.3 (2C), 161.4 (2C),
147.4 (2C), 139.5 (2C), 136.5 (2C), 131.8 (2C), 124.4 (2C), 119.5
(2C), 114.6 (2C), 14.6 (2C).
1
1151, 1022, 849, 714 cm−1; H NMR (CDCl3, 270 MHz) δ = 7.98 (d,
J = 7.9 Hz, 2H), 7.96 (s, 2H), 7.55 (d, J = 7.9 Hz, 2H), 2.53 (s, 6H), 2.04
(s, 6H); 13C NMR (CDCl3, 67.8 MHz) δ = 184.6 (2C), 182.3 (2C),
145.3 (2C), 144.9 (2C), 140.5 (2C), 134.4 (2C), 131.9 (2C), 129.6
(2C), 126.83 (2C), 126.76 (2C), 22.0 (2C), 14.4 (2C); HRMS (EI)
calcd for C24H18O4 ([M]+) 370.1205, found 370.1204.
2-Methyl-3-(trimethylstannyl)-1,4-naphthoquinone (4a).
Following the general procedure, the reaction of 1a (50.0 mg, 119
μmol) with hexamethylditin (71.1 mg, 217 μmol) in the presence of
Pd(PPh3)2Cl2 (14.0 mg, 12 μmol) for 1 h gave the crude product. The
crude product was purified by silica gel column chromatography
(EtOAc/hexane = 1/15) to give 4a (43.0 mg, 64%) as a yellow solid:
mp = 69−70 °C; IR (KBr) νmax = 3070, 2981, 2912, 1657, 1635, 1591,
3,3′,7,7′-Tetramethyl[2,2′-binaphthalene]-1,1′,4,4′-tetrone
(2c). Following the general procedure, the homocoupling reaction of
1c (95.4 mg, 360 μmol) using hexamethylditin (130 mg, 396 μmol)
and CuI (68.6 mg, 360 μmol) in the presence of Pd(dppf)Cl2 (52.7 mg,
72 μmol) for 7 h gave the crude product. The crude product was purified
by silica gel column chromatography (EtOAc/hexane = 1/15 to 1/5) to
give 2c (43.4 mg, 65%) as a yellow solid: mp = 256−258 °C; IR (KBr)
νmax = 3199, 3059, 3010, 2960, 2925, 1662, 1599, 1375, 1327, 1292,
1169, 958, 843, 714 cm−1; 1H NMR (CDCl3, 270 MHz) δ = 8.06 (d, J =
7.8 Hz, 2H), 7.88 (s, 2H), 7.56 (d, J = 7.8 Hz, 2H), 2.50 (s, 6H), 2.04 (s,
6H); 13C NMR (CDCl3, 67.8 MHz) δ = 184.1 (2C), 182.7 (2C), 145.6
(2C), 144.9 (2C), 140.3 (2C), 134.5 (2C), 131.8 (2C), 129.8 (2C),
126.9 (2C), 126.7 (2C), 22.0 (2C), 14.4 (2C); HRMS (EI) calcd for
C24H18O4 ([M]+) 370.1205, found 370.1207.
1
1284, 1180, 1093, 951, 781, 698, 528 cm−1; H NMR (CDCl3, 270
MHz) δ = 8.09−8.04 (m, 1H), 8.04−7.98 (m, 1H), 7.72−7.66 (m, 2H),
2.28 (s, 3H), 0.39 (s, 9H); 13C NMR (CDCl3, 67.8 MHz) δ = 188.8,
183.2, 157.5, 156.7, 133.13, 133.09, 132.8, 132.2, 126.4, 126.3, 18.3,
−6.03 (3C); HRMS (EI) calcd for C14H16O2120Sn ([M]+) 336.0175,
found 336.0178.
Crossover Reaction between 1c and 4a (Scheme 1). Pd-
(dppf)Cl2 (8.8 mg, 12.0 μmol) was added to a solution of 1c (15.9 mg,
60.0 μmol), 4a (20.1 mg, 60.0 μmol), and CuI (11.4 mg, 59.9 μmol) in
degassed dioxane at rt. The mixture was stirred at 80 °C under a N2
atmosphere for 2.5 h. The reaction was quenched by the addition of
water, and the mixture was diluted with EtOAc. The mixture was
filtered through Celite. After the layers were separated, the aqueous
layer was extracted with EtOAc (×2). The combined organic layer was
washed with water (×2) and brine, dried over Na2SO4, and con-
centrated. The crude product was purified using silica-gel column
chromatography (EtOAc/hexane = 1/10) to give an inseparable mixture
of 2g and 2a (16.2 mg), and recovered 1c (5.3 mg, 33%). Yields of 2g
and 2a were estimated by 1H NMR using 2,5-dimethylfuran as an
internal standard.
3,3′,7-Trimethyl[2,2′-binaphthalene]-1,1′,4,4′-tetrone (2g):
mp = 224−226 °C; IR (KBr) vmax = 3062, 3057, 2925, 1662, 1597,
1375, 1329, 1286, 958 cm−1; 1H NMR (CDCl3, 270 MHz) δ = 8.20−8.15
(m, 1H), 8.12−8.09 (m, 1H), 8.06 (d, J = 7.6 Hz, 1H), 7.88 (brs, 1H),
7.80−7.72 (m, 2H), 7.56 (brd, J = 7.6 Hz, 1H), 2.50 (s, 3H), 2.08−2.03 (m,
6H); 13C NMR (CDCl3, 67.8 MHz) δ = 184.3, 184.1, 182.7, 182.4, 145.6,
144.9, 140.5, 140.2, 134.5, 133.8 (2C), 133.7, 132.0, 131.8, 131.7, 129.8,
126.9, 126.7, 126.6, 126.5, 22.0, 14.4 (2C); HRMS (ESI) calcd for
C23H16O4Na ([M + Na]+) 379.0940, found 379.0958.
8,8′-Diacetyloxy-3,3′-dimethyl[2,2′-binaphthalene]-1,1′,4,4′-
tetrone (2d). Following the general procedure, the homocoupling
reaction of 1d (37.1 mg, 120 μmol) using hexamethylditin (43.2 mg,
132 μmol) and CuI (22.9 mg, 120 μmol) in the presence of Pd-
(dppf)Cl2 (17.1 mg, 24 μmol) for 10 h gave the crude product. The
crude product was purified by silica gel column chromatography
(EtOAc/hexane = 1/12) to give 2d (11.3 mg, 41%) as an orange solid
and 2d′ (10.0 mg, 40%) as a yellow solid. 2d: mp = 230−231 °C dec;
IR (KBr) νmax = 3076, 3049, 2962, 2925, 1763, 1664, 1647, 1628,
1
1614, 1593, 1458, 1369, 1288, 1257, 1200, 1024, 744 cm−1; H NMR
(CDCl3, 270 MHz) δ = 8.12 (dd, J = 7.8 Hz, 1.4 Hz, 2H), 7.77 (dd,
J = 7.8 Hz, 7.8 Hz, 2H), 7.38 (dd, J = 7.8 Hz, 1.4 Hz, 2H), 2.36 (s,
6H), 2.00 (s, 6H); 13C NMR (CDCl3, 67.8 MHz) δ = 183.6 (2C),
180.8 (2C), 169.1 (2C), 149.4 (2C), 144.7 (2C), 141.3 (2C), 134.6
(2C), 133.6 (2C), 129.5 (2C), 125.0 (2C), 123.3 (2C), 21.2 (2C),
14.2 (2C); HRMS (EI) calcd for C26H18O8 ([M]+) 458.1002, found
458.1001.
8-Acetyloxy-8′-hydroxy-3,3′-dimethyl[2,2′-binaphthalene]-
1,1′,4,4′-tetrone (2d′): mp = 226−228 °C dec; IR (KBr) νmax
=
3440, 3080, 3022, 1770, 1664, 1593, 1369, 1325, 1267, 1190, 1022,
1
875 750, 732 cm−1; H NMR (CDCl3, 270 MHz) δ = 11.82 (s, 1H),
8.14 (dd, J = 8.1 Hz, 1.4 Hz, 1H), 7.79 (dd, J = 8.1 Hz, 8.1 Hz, 1H),
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General Procedure for the Formation of Oxepine Dimers 5.
( )-BINAP (0.1 equiv) was added to a solution of 1 (1.0 equiv),
hexamethylditin (1.1 equiv), CuI (1.0 equiv), and Na2CO3 (1.0 equiv)
in degassed DMF, followed by addition of Pd2(dba)3 (0.05 equiv), at
rt. The mixture was stirred at rt under a N2 atmosphere until no
further TLC changes were observed. The reaction was quenched by
the addition of water, and the mixture was diluted with EtOAc. The
mixture was filtered through Celite. After the layers were separated, the
aqueous layer was extracted with EtOAc (×2). The combined organic
layer was washed with water (×2) and brine, dried over Na2SO4, and
concentrated. The residue was purified by column chromatography
(EtOAc/hexane).
6-Bromo-5-hydroxy-7,8-dihydrodinaphth[1,2-b:2′,3′-f ]-
oxepine-9,14-dione (5a). Following the general procedure, the
reaction of 1a (30.1 mg, 120 μmol) using hexamethylditin (43.2 mg,
132 μmol), CuI (22.9 mg, 120 μmol), and Na2CO3 (12.7 mg, 120 μmol)
in the presence of Pd2(dba)3 (5.5 mg, 6.00 μmol) and ( )-BINAP for
1 h gave the crude product. The crude product was purified by silica gel
column chromatography (EtOAc/hexane = 1/10) to give 5a (24.3 mg,
96%) as an orange solid: mp = 166−168 °C; IR (KBr) νmax = 3500,
3450, 3240, 3064, 2987, 2923, 1662, 1619, 1585, 1390, 1292, 1257, 1196,
1153, 958, 904, 769 cm−1; 1H NMR (CDCl3, 270 MHz) δ = 8.61 (brd,
J = 8.2 Hz, 1H), 8.21−8.16 (m, 2H), 8.08−8.04 (m, 1H), 7.75−7.70 (m,
2H), 7.65−7.59 (m, 1H), 7.54−7.45 (m, 1H), 6.04 (s, 1H), 3.54 (m,
2H), 3.00 (m, 2H); 13C NMR (CDCl3, 67.8 MHz) δ = 185.1, 179.8,
155.2, 146.1, 145.5, 133.8, 133.4, 131.6, 130.6, 130.0, 128.4, 127.7, 126.8,
126.34, 126.29, 126.2, 122.6, 122.04, 122.01, 104.6, 28.2, 25.7; HRMS
(ESI) calcd for C22H1379BrO4Na ([M + Na]+) 442.9889, found
442.9868.
6.00 μmol) and ( )-BINAP for 2 h gave the crude product. The crude
product was purified by silica gel column chromatography (EtOAc/
hexane = 1/2 to 1/1) to give 5d (8.4 mg, 26%) as an orange solid: mp
= 137−138 °C dec; IR (KBr) νmax = 2929, 1766, 1674, 1657, 1624,
1
1595, 1371, 1201, 1066, 951, 893, 760 cm−1; H NMR (CDCl3, 270
MHz) δ = 8.54 (dd, J = 8.4 Hz, 1.1 Hz, 1H), 8.03 (dd, J = 8.1 Hz, 1.4
Hz, 1H), 7.72 (dd, J = 8.1 Hz, 8.1 Hz, 1H), 7.57 (dd, J = 8.4 Hz, 7.6
Hz, 1H), 7.36 (dd, J = 8.1, 1.4 Hz, 1H), 7.16 (dd, J = 8.1 Hz, 1.1 Hz,
1H), 6.65 (s, 1H), 3.51 (m, 2H), 2.95 (m, 2H), 2.56 (s, 3H), 2.40 (s,
3H); 13C NMR (CDCl3, 67.8 MHz) δ = 184.3, 178.0, 169.5, 169.2,
155.1, 149.6, 145.42, 145.36, 145.2, 134.9, 133.3, 129.8, 129.3, 129.0,
128.9, 127.5, 124.8, 122.1, 120.8, 120.3, 116.3, 107.3, 28.4, 25.6, 21.3
(2C); HRMS (EI) calcd for C26H1781BrO8 ([M]+) 538.0091, found
538.0084.
Trapping Experiments with Acetic Anhydride in Oxepine
Formation (Scheme 2). ( )-BINAP (7.5 mg, 12.0 μmol) was added
to a solution of 1a (30.1 mg, 120 μmol), hexamethylditin (43.2 mg,
132 μmol), 22.9 mg, 120 μmol), and Na2CO3 (12.7 mg, 120 μmol) in
degassed DMF, followed by addition of Pd2(dba)3 (5.5 mg, 6.00 μmol),
at rt. The mixture was stirred at rt under a N2 atmosphere for 0.5 h. Then
Ac2O (113 μL, 1.20 mmol) was added to the reaction mixture. After
being stirred for an additional 2 h, the reaction was quenched by the
addition of water, and the mixture was diluted with EtOAc. The mixture
was filtered through Celite. After the layers were separated, the aqueous
layer was extracted with EtOAc (×2). The combined organic layer was
washed with water (×2) and brine, dried over Na2SO4, and concentrated.
The residue was purified by column chromatography (EtOAc/hexane
=1/10) to give 6 (2.7 mg, 10%) as a yellow solid and 7 (4.4 mg, 11%) as
a white solid.
6-Bromo-5-hydroxy-2,11-dimethyl-7,8-dihydrodinaphth-
[1,2-b:2′,3′-f ]oxepine-9,14-dione (5b). Following the general
procedure, the reaction of 1b (95.4 mg, 360 μmol) using hexa-
methylditin (130 mg, 396 μmol), CuI (68.6 mg, 360 μmol), and
Na2CO3 (38.2 mg, 360 μmol) in the presence of Pd2(dba)3 (16.5 mg,
18.0 μmol) and ( )-BINAP for 4 h gave the crude product. The crude
product was purified by silica gel column chromatography (EtOAc/
hexane = 1/10) to give 5b (41.3 mg, 51%) as a yellow solid: mp =
208−210 °C dec; IR (KBr) νmax = 3506, 3199, 3057, 3026, 2981, 2933,
2920, 2891, 2860, 1668, 1649, 1620, 1601, 1419, 1300, 1282, 1259,
5-Acetyloxy-6-bromo-7,8-dihydrodinaphth[1,2-b:2′,3′-f ]-
oxepine-9,14-dione (6): mp = 242−244 °C; IR (KBr) νmax = 3068,
2983, 2931, 1772, 1672, 1660, 1622, 1591, 1362, 1294, 1259, 1190,
1072, 958, 903, 766, 719 cm−1; 1H NMR (CDCl3, 270 MHz) δ = 8.73
(brd, J = 7.3 Hz, 1H), 8.24−8.23 (m, 1H), 8.22−8.21 (m, 1H), 7.75−
7.74 (m, 1H), 7.73−7.72 (m, 1H), 7.71−7.70 (m, 1H), 3.61 (m, 2H),
3.02 (m, 2H), 2.52 (s, 3H); 13C NMR (CDCl3, 67.8 MHz) δ = 185.0,
179.8, 168.1, 154.8, 150.0, 142.1, 134.0, 133.5, 131.6, 130.64, 130.61,
129.3, 127.7, 127.6, 126.9, 126.6, 126.4, 126.3, 122.8, 120.9, 114.7,
28.1, 25.5, 20.8; HRMS (FAB+) calcd for C24H1679BrO5 ([M + H]+)
465.0183, found 463.0176.
1
1207, 1084, 968, 933, 879, 809, 737 cm−1; H NMR (CDCl3, 270
MHz) δ = 8.35 (brs, 1H), 8.07 (d, J = 8.1 Hz, 1H), 8.05 (d, J = 8.1 Hz,
1H), 7.83 (brs, 1H), 7.51 (brd, J = 8.1 Hz, 1H), 7.33 (brd, J = 8.1 Hz,
1H), 5.98 (s, 1H), 3.50 (m, 2H), 2.96 (m, 2H), 2.57 (s, 3H), 2.48 (s,
3H); 13C NMR (DMSO, 67.8 MHz) δ = 184.5, 179.1, 154.4, 147.3,
144.8, 144.0, 136.5, 134.1, 131.0, 129.4, 129.4, 128.0, 127.9, 126.3,
126.0, 125.8, 122.3, 122.0, 120.5, 105.0, 27.7, 25.3, 21.8, 21.4; HRMS
(EI) calcd for C24H1781BrO4 ([M]+) 450.0293, found 450.0290.
6-Bromo-5-hydroxy-3,12-dimethyl-7,8-dihydrodinaphth-
[1,2-b:2′,3′-f ]oxepine-9,14-dione (5c). Following the general
procedure, the reaction of 1c (31.8 mg, 120 μmol) using hexa-
methylditin (43.2 mg, 132 μmol), CuI (22.9 mg, 120 μmol), and
Na2CO3 (12.7 mg, 120 μmol) in the presence of Pd2(dba)3 (5.5 mg,
6.00 mmol) and ( )-BINAP for 2 h gave the crude product. The
crude product was purified by silica gel column chromatography
(EtOAc/hexane = 1/10) to give 5c (12.6 mg, 47%) as a yellow solid:
mp = 213−215 °C dec; IR (KBr) νmax = 3452, 3199, 3062, 2921, 1674,
1,4-Diacetyloxy-2-bromo-3-methylnaphthalene (7): mp =
214−216 °C; IR (KBr) νmax = 3074, 2979, 2931, 1757, 1593, 1429,
1360, 1207, 1163, 1074, 1012, 962, 900, 760 cm−1; 1H NMR (CDCl3,
270 MHz) δ = 7.76−7.73 (m, 2H), 7.51−7.49 (m, 2H), 2.49 (s, 3H),
2.47 (s, 3H), 2.40 (s, 3H); 13C NMR (CDCl3, 67.8 MHz) δ = 168.4,
168.0, 142.6, 142.3, 127.3, 127.2, 126.9, 126.5, 126.4, 121.4, 121.3,
117.0, 20.8, 20.6, 17.4; HRMS (EI) calcd for C15H1381BrO4 ([M]+)
337.9978, found 337.9978.
Crossover Reaction Study of Oxepine Formation (Scheme 3).
( )-BINAP (7.5 mg, 12.0 μmol) was added to a solution of 4a
(20.1 mg, 60.0 μmol), 1c (15.9 mg, 60.0 μmol), hexamethylditin
(27 μL, 130 μmol), CuI (22.8 mg, 120 μmol), and Na2CO3 (12.7 mg,
120 μmol) in degassed DMF (2 mL), followed by addition of
Pd2(dba)3 (5.5 mg, 6.00 μmol), at rt. The mixture was stirred under a
N2 atmosphere for 1.5 h. The reaction was quenched by the addition
of water, and the mixture was diluted with EtOAc. The mixture was
filtered through Celite. After the layers were separated, the aqueous
layer was extracted with EtOAc (×2). The combined organic layer was
washed with water (×2) and brine, dried over Na2SO4, and concen-
trated. The residue was purified by column chromatography (EtOAc/
hexane = 1/10 to 1/4) to give 3a (2.1 mg, 19%) and 5c (7.4 mg, 55%).
Reaction of 1a with t-BuOK (Scheme 4A). To a solution of
1a (50.0 mg, 199 μmol) and in DMF was added t-BuOK (37.0 mg,
330 μmol) at −78 °C. The mixture was stirred at the same
temperature for 15 min under N2 atmosphere. The reaction was
quenched by the addition of 1 M HCl aqueous solution, and the
mixture was diluted with EtOAc. After the aqueous layer was extracted
with EtOAc (×2), the combined organic layer was washed with water
(×2) and brine, dried over Na2SO4, and concentrated. The residue was
1
1655, 1595, 1295, 1205, 1163, 1026, 910, 842, 781, 717 cm−1; H
NMR (CDCl3, 270 MHz) δ = 8.47 (d, J = 8.4 Hz, 1H), 7.96−7.90 (m,
3H), 7.48 (ddd, J = 7.8 Hz, 1.8 Hz, 0.8 Hz, 1H), 7.42 (dd, J = 8.6 Hz,
1.8 Hz, 1H), 5.97 (1H, s), 3.52−3.45 (m, 2H), 2.99−2.92 (m, 2H),
2.52 (s, 3H), 2.49 (s, 3H); 13C NMR (CDCl3, 67.8 MHz) δ = 185.1,
180.3, 155.2, 145.7, 145.6, 144.5, 136.3, 134.6, 130.5, 130.0, 129.9,
129.4, 127.4, 126.7, 126.4, 125.1, 122.8, 122.0, 121.0, 104.7, 28.1, 25.9,
21.94, 21.88; HRMS (EI) calcd for C24H1781BrO4 ([M]+) 450.0293,
found 450.0290.
4,13-Diacetyloxy-6-bromo-5-hydroxy-7,8-dihydrodinaphth-
[1,2-b:2′,3′-f ]oxepine-9,14-dione (5d). Following the general
procedure, the reaction of 1d (37.1 mg, 120 μmol) using hexa-
methylditin (43.2 mg, 132 μmol), CuI (22.9 mg, 120 μmol), and
Na2CO3 (12.7 mg, 120 μmol) in the presence of Pd2(dba)3 (5.5 mg,
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purified by column chromatography (EtOAc/hexane = 1/5) to give 3a
(12.3 mg, 29%).
128.5, 128.4, 127.6, 127.3, 126.2, 78.5, 68.2, 55.7, 36.7, 22.0, 21.9, 21.5;
HRMS (ESI) calcd for C24H1779BrO4Na ([M + Na]+) 471.0202, found
471.0204.
Photoreaction of 1a with Hexamethylditin (Scheme 4B). A
solution of 1a (50.2 mg, 200 μmol) and hexamethylditin (131 mg,
400 μmol) in DMF (3 mL) was irradiated with a white fluorescent
lamp for 28 h. The mixture was diluted with EtOAc. The organic layer
was washed with water (×2) and brine, dried over Na2SO4, and
concentrated. The residue was purified by column chromatography
(EtOAc/hexane = 1/5) to give 5a (16.3 mg, 39%).
Photoreaction of 1a with Hexamethylditin in the Presence
of Acetic Anhydride (Scheme 4C). A solution of 1a (50.3 mg,
200 μmol), hexamethylditin (133 mg, 405 μmol), and Ac2O (94 μL,
994 μmol) in DMF (3 mL) was irradiated with a white fluorescent
lamp for 29 h. The mixture was diluted with EtOAc. The organic layer
was washed with water (×2) and brine, dried over Na2SO4, and
concentrated. The residue was purified by column chromatography
(EtOAc/hexane = 1/5) to give 7 (32.1 mg, 48%).
General Procedure for the Formation of Epoxide Dimers 8
(Tables 6 and 7). Base (1.5 equiv) was added to a solution of 1
(1.0 equiv) in DMF at 0 °C. The mixture was stirred at rt under N2
atmosphere until no further change in TLC was observed. The
reaction was quenched by the addition of water, and the mixture was
diluted with EtOAc. The mixture was filtered through Celite. The
layers were separated, the aqueous layer was extracted with EtOAc
(×2). The combined organic layer was washed with water (×2) and
brine, dried over Na2SO4, and concentrated. The residue was purified
by column chromatography (EtOAc/hexane).
(7aR*,13aR*,13bS*)-6-Bromo-13a,13b-epoxy-7a-methyl-7H-
dibenzo[b,g]fluorene-5,8,13-trione (8a). Following the general
procedure, the reaction of 1a (50.0 mg, 199 μmol) with Cs2CO3 (98.0 mg,
301 μmol) for 0.5 h gave the crude product. The crude product was
purified by silica gel column chromatography (EtOAc/hexane = 1/5) to
give 8a (35.7 mg, 85%) as a yellow solid: mp = 182−184 °C; IR (KBr)
νmax = 3064, 2968, 2915, 2854, 1707, 1664, 1267, 1257, 1196, 1093, 991,
850, 769, 739, 700 cm−1; 1H NMR (CDCl3, 270 MHz) δ = 8.34−8.28 (m,
1H), 8.26−8.16 (m, 2H), 7.95−7.83 (m, 2H), 7.72−7.57 (m, 3H), 3.32
(d, J = 16.7 Hz, 1H), 2.30 (d, J = 16.7 Hz, 1H), 1.42 (s, 3H); 13C NMR
(CDCl3, 67.8 MHz) δ = 196.3, 187.9, 176.5, 155.4, 135.8, 135.6, 134.5,
133.8, 132.5, 132.4, 131.5, 129.9, 128.3, 128.2, 127.6, 127.1, 126.2, 78.3,
68.1, 55.8, 36.6, 21.9; HRMS (ESI) calcd for C22H1381BrO4Na ([M +
Na]+) 444.9868, found 444.9871.
(7aR*,13aR*,13bS*)-4,12-Diacetyloxy-6-bromo-13a,13b-
epoxy-7a-methyl-7H-dibenzo[b,g]fluorene-5,8,13-trione (8d).
Following the general procedure, the reaction of 1d (61.8 mg,
200 μmol) with Cs2CO3 (97.7 mg, 300 μmol) for 1 h gave the crude pro-
duct. The crude product was purified by silica gel column chromatography
(EtOAc/hexane =1/2 to 1/1) to give 8d (13.0 mg, 24%) as a yellow solid:
mp = 152−153 °C; IR (KBr) νmax = 3072, 3016, 2964, 2929, 2854, 1766,
1
1710, 1672, 1194, 1026, 928, 879, 835 746 cm−1; H NMR (CDCl3,
270 MHz) δ = 8.18 (d, J = 7.8 Hz, 1H), 7.89 (t, J = 8.1 Hz, 1H), 7.64 (t,
J = 7.8 Hz, 1H), 7.48 (d, J = 8.1 Hz, 1 H), 7.36 (d, J = 8.1 Hz, 1 H), 7.22
(d, J = 7.8 Hz, 1 H), 3.28 (d, J = 16.7 Hz, 1 H), 2.91 (d, J = 16.7 Hz, 1 H),
2.48 (s, 3 H), 2.41 (s, 3 H), 1.42 (s, 3H); 13C NMR (CDCl3, 67.8 MHz)
δ = 195.3, 185.5, 174.9, 169.7, 169.1, 153.8, 150.7, 149.6, 136.2, 135.3,
133.7, 133.3, 129.9, 127.9, 126.9, 126.6, 125.7, 125.5, 124.3, 79.2, 67.5,
55.8, 36.8, 21.29, 21.27, 21.1; HRMS (ESI) calcd for C26H1781BrO8Na
([M + Na]+) 560.9978, found 560.9986.
(7aR*,13aR*,13bS*)-6-Bromo-13a,13b-epoxy-4,12-dime-
thoxy-7a-methyl-7H-dibenzo[b,g]fluorene-5,8,13-trione (8e).
Following the general procedure, the reaction of 1e (28.1 mg, 100 μmol)
with Cs2CO3 (48.9 mg, 150 μmol) for 4 h gave the crude product. The
crude product was purified by silica gel column chromatography (EtOAc/
hexane =1/2 to 1/1) to give 8e (5.5 mg, 23%) as a yellow solid: mp = 163−
164 °C dec; IR (KBr) νmax = 3087, 3012, 2972, 2941, 2842, 1701, 1662,
1581, 1432, 1392, 1277, 1277, 1213, 1186, 1049, 999, 811, 775 754 cm−1;
1H NMR (CDCl3, 270 MHz) δ = 7.85 (dd, J = 7.8 Hz, 1.4 Hz, 1H), 7.79
(dd, J = 7.8 Hz, 7.8 Hz, 1H), 7.59 (dd, J = 7.8 Hz, 7.8 Hz, 1H), 7.37 (dd,
J = 7.8 Hz, 1.4 Hz, 1H), 7.11 (d, J = 7.8 Hz, 1H), 7.06 (d, J = 7.8 Hz, 1H),
4.05 (s, 3H), 3.99 (s, 3H), 3.24 (d, J = 16.9 Hz, 1H), 2.88 (d, J = 16.9 Hz,
1H), 1.41 (s, 3H); 13C NMR (CDCl3, 150 MHz) δ= 196.6, 185.8, 175.5,
161.0, 159.8, 152.1, 136.1, 135.9, 134.2, 133.7, 127.7, 124.7, 121.4, 120.6,
119.8, 118.1, 113.5, 80.2, 68.0, 56.6, 56.4, 55.7, 36.7, 21.1; HRMS (ESI)
calcd for C24H1781BrO6Na ([M + Na]+) 505.0080, found 505.0074.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra for all new compounds, ORTEP
drawings and X-ray crystallographic data for 5a and 8a (CIF).
This material is available free of charge via the Internet at
http://pubs.acs.org.
(7aR*,13aR*,13bS*)-6-Bromo-13a,13b-epoxy-2,7a,10-tri-
methyl-7H-dibenzo[b,g]fluorene-5,8,13-trione (8b). Following
the general procedure, the reaction of 1b (53.0 mg, 200 μmol) with
Cs2CO3 (97.7 mg, 300 μmol) for 1 h gave the crude product. The
crude product was purified by silica gel column chromatography
(EtOAc/hexane = 1/5) to give 8b (32.0 mg, 71%) as a yellow solid:
mp = 215 °C dec; IR (KBr) νmax = 2968, 2925, 1704, 1664, 1601,
AUTHOR INFORMATION
Corresponding Author
■
*(K.K.) Tel and Fax: +81-75-703-5603. E-mail: kuramoch@kpu.ac.
jp. (K.T.) Tel and Fax: +81-75-703-5902. E-mail: tsubaki@
kpu.ac.jp.
1
1282, 1261, 1147, 1026, 899, 829, 769, 750 cm−1; H NMR (CDCl3,
270 MHz) δ = 8.19 (d, J = 8.1 Hz, 1H), 8.10 (d, J = 8.1 Hz, 1H), 8.01
(s, 1H), 7.66 (d, J = 8.1 Hz, 1H), 7.44 (s, 1H), 7.40 (d, J = 8.1 Hz,
1H), 3.29 (d, J = 16.7 Hz, 1H), 2.94 (d, J = 16.7 Hz, 1H), 2.57 (s, 3H),
2.49 (s, 3H), 1.39 (s, 3H); 13C NMR (CDCl3, 67.8 MHz) δ = 196.8,
187.6, 176.5, 155.2, 147.2, 143.6, 135.2, 133.7, 131.5, 130.9, 130.2,
128.6, 128.2, 128.0, 127.3, 126.2, 78.4, 68.1, 55.8, 36.6, 22.12, 22.06,
22.0; HRMS (ESI) calcd for C24H1781BrO4Na ([M + Na]+) 473.0181,
found 473.0188.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Challenging
Exploratory Research (23659013). We are grateful to Prof.
Takeo Kawabata (Kyoto University) and Prof. Fumio
Sugawara, Dr. Toshifumi Takeuchi, and Dr. Shinji Kamisuki
(Tokyo University of Science) for assistance with NMR and
HRMS measurements.
(7aR*,13aR*,13bS*)-6-Bromo-13a,13b-epoxy-3,7a,11-tri-
methyl-7H-dibenzo[b,g]fluorene-5,8,13-trione (8c). Following
the general procedure, the reaction of 1c (53.0 mg, 200 μmol) with
Cs2CO3 (98.0 mg, 301 μmol) for 1 h gave the crude product. The
crude product was purified by silica gel column chromatography
(EtOAc/hexane = 1/5) to give 8c (30.7 mg, 68%) as a yellow solid:
mp = 218−219 °C dec; IR (KBr) νmax = 2972, 2924, 2854, 1707, 1666,
REFERENCES
■
1
1599, 1267, 1163, 991, 904, 829, 746 cm−1; H NMR (CDCl3, 270
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