Efficient one-pot synthesis of benzopyranobenzopyrans and naphthopyranobenzopyrans by domino aldol-type reaction/hetero Diels-Alder reaction of resorcinols and naphthols

Article abstract of DOI:10.1016/j.tet.2008.10.101

The efficient one-pot synthetic approaches for benzopyranobenzopyrans and naphthopyranobenzopyrans are described. The key strategies involve ethylenediamine diacetate-catalyzed cyclization by domino aldol-type reaction/hetero Diels-Alder reaction of resorcinols and naphthols to benzaldehydes with O-allyl ether groups. These reactions provide a rapid route for the synthesis of novel types of polyheterocycles with stereochemically defined quaternary carbon centers.

Full text of DOI:10.1016/j.tet.2008.10.101

Tetrahedron 65 (2009) 101–108
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient one-pot synthesis of benzopyranobenzopyrans and
naphthopyranobenzopyrans by domino aldol-type reaction/
hetero Diels–Alder reaction of resorcinols and naphthols
,
a
b
Yong Rok Lee a , Yun Mi Kim , Sung Hong Kim
*
a School of Chemical Engineering and Technology, Yeungnam University, Gyeongsan 712-749, Republic of Korea
b Analysis Research Division, Daegu Center, Korea Basic Science Institute, Daegu 702-701, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 July 2008
Received in revised form 31 October 2008
Accepted 31 October 2008
Available online 5 November 2008
The efficient one-pot synthetic approaches for benzopyranobenzopyrans and naphthopyranobenzopyr-
ans are described. The key strategies involve ethylenediamine diacetate-catalyzed cyclization by domino
aldol-type reaction/hetero Diels–Alder reaction of resorcinols and naphthols to benzaldehydes with
O-allyl ether groups. These reactions provide a rapid route for the synthesis of novel types of poly-
heterocycles with stereochemically defined quaternary carbon centers.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Benzopyranobenzopyrans
Naphthopyranobenzopyrans
Aldol-type reaction
Hetero Diels–Alder reaction
Resorcinols
Naphthols
1. Introduction
numerous applications, such as light sensitive sunglasses,7 molec-
ular electronics,8 optical memories,9 and biological photo-
The hetero Diels–Alder reaction is a powerful synthetic tool for
constructing heterocyclic compounds and natural products.1
Among these, combination of hetero Diels–Alder reaction with
other reactions in a domino fashion has been widely used for the
formation of multiple bonds. A number of examples using this
strategy have been reported in the last decade.2 As the pioneering
work, Tietze extensively described the domino Knoevenagel/hetero
Diels–Alder reaction of 1,3-dicarbonyls to benzaldehydes with
O-allyl ether groups for the synthesis of tetracycles with a pyran
ring, as shown in Scheme 1.3 These strategies allow for the facile
synthesis of polycycles from 1,3-dicarbonyls. However, no exam-
ples on combination of aldol-type reaction with hetero Diels–Alder
reaction starting from commercially available resorcinols and
naphthols have been reported.
switches,10 which were reported. This wide range of interesting
activities and properties has prompted studies into the de-
velopment of a convenient and efficient methodology for synthe-
sizing polyheterocycles with benzopyran and naphthopyran
moieties.
Recently, Brønsted acids and bases have demonstrated their
potential to serve as active catalysts for a variety of synthetically
useful reactions in organic chemistry.11 In particular, we have de-
veloped a new and useful methodology for preparing a variety of
benzopyrans using ethylenediamine diacetate (EDDA) as effective
Brønsted acid and base catalysts.12 These reactions involve a for-
mal [3þ3]-cycloaddition through a 6
p-electrocyclization. This
methodology provides a rapid route for the synthesis of benzo-
pyran derivatives and biologically active natural products.13 Very
Molecules with the benzopyran and naphthopyran moieties are
widely found in nature.4,5 These compounds exhibit a range of bi-
ological and pharmacological properties including antioxidant,
anticancer, anti-inflammatory, antiviral, antibacterial, and anti-HIV
activities.6 They were also the subject of many studies and
O
O
O
O
O
catalyst
+
O
O
O
O
O
* Corresponding author. Tel.: þ82 53 810 2529; fax: þ82 53 810 4631.
E-mail address: yrlee@yu.ac.kr (Y.R. Lee).
Scheme 1. Domino Knoevenagel/hetero Diels–Alder reaction.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.10.101

102
Y.R. Lee et al. / Tetrahedron 65 (2009) 101–108
recently, we have also developed a new and efficient synthetic
approach for biologically interesting tetrahydroquinoline ana-
logues from 1,3-dicarbonyls to amoinobenzaldehydes through
domino Knoevenagel/hetero Diels–Alder reactions.14 As a part of an
ongoing study into the synthetic efficacy of these two metho-
dologies, this study examined the reactions of resorcinols and
naphthols to benzaldehydes with O-allyl ether groups. We report
herein an efficient one-pot synthesis of a variety of benzopyr-
anobenzopyrans and naphthopyranobenzopyrans with sub-
stituents on the pyranyl rings using domino aldol-type reaction/
hetero Diels–Alder reaction.
of coupling constant of 1H NMR and by direct comparison with
reported data.15,16 The signal of benzylic methine on the pyr-
anyl ring in 6 appears as a doublet (J¼4.3 Hz) at
d 4.47. In the
cis-fused cycloadducts of these types of other known tetra-
cycles, the signals of benzylic methine showed as a doublet
with coupling constant J¼4–6 Hz, whereas those of trans-fused
adducts appeared as a doublet with coupling constant J¼9–
11 Hz.15,16
The stereospecificity of compound 6 may be explained by
the endo-transition structure as shown in Scheme 3. Reaction
of 5 with benzaldehyde 2 in the presence of EDDA/TEA first
gives intermediate 7 as an aldol-type product. Such a process
was already suggested by Shigemasa to give aldol-type prod-
ucts through a CaCl2/KOH-mediated reaction of resorcinol to
aldehydes.17 TEA likely increases the activity of dehydration of
the intermediate 7 to form quinone methide 8a and 8b.18
However, in the final step of cycloaddition, the endo-transition
structure (8b) must have been more favorable than the exo-
transition structure (8a) due to an sp2-geminal effect according
to the phenomenon of 1,3-allylic strain.19 This explanation has
been already proved by Tietze’s work, who reported the syn-
thesis of tetracycles using intramolecular hetero Diels–Alder
cycloaddition of benzylidene-1,3-dicarbonyl compounds and
O-allyl ether of salicylic aldehydes.16,20 The regiospecificity of
the sole product 6 may be due to hydrogen bond between the
hydroxy group and carbonyl group. Therefore, cyclization of
compound 6 is likely to occur on the position without forma-
tion of a hydrogen bond. The further structure in relation to
cis-stereochemistry and regiochemistry of 6 were confirmed by
X-ray single crystal analysis as shown in Figure 1.
2. Results and discussion
As starting materials, benzaldehydes 2–4 with O-allyl ether
groups were prepared from salicylaldehyde (1) in one step, as
shown in Scheme 2. Treatment of salicylaldehyde (1) with prenyl
bromide in the presence of K2CO3 in DMF at room temperature for
12 h afforded benzaldehyde 2 in 99% yield. A reaction of 1 with
geranyl bromide gave benzaldehyde 3 in 99% yield, whereas
treatment with trans,trans-farnesyl bromide afforded compound 4
in 98% yield.
O
O
R
Br
H
H
K2CO3
DMF
R
O
OH
1
2 R=H, 99%
3 R=prenyl, 99%
4 R=geranyl, 98%
In order to extend the utility of this methodology, further re-
actions of several types of resorcinols to benzaldehydes 2–4 were
carried out in the presence of ethylenediamine diacetate
(20 mol %)/TEA (2 mL) in refluxing xylene. The results are sum-
marized in Table 2. First, reactions of orcinol (9) and olivetol (10)
were examined. Reaction of orcinol (9) with 2.0 equiv of benzal-
dehyde 2 in refluxing xylene for 18 h afforded adduct 16 in 56%
yield, whereas that of olivetol (10) gave product 17 in 52% yield
(entries 1 and 2). Similarly, reactions of resorcinols with ester
group on benzene ring were successful. Reactions of methyl 2,4-
dihydroxybenzoate (11) and ethyl 2,4-dihydroxybenzoate (12) in
refluxing xylene for 18 h afforded the desired products 18 and 19
in 57 and 62% yields, respectively (entries 3 and 4). Similarly,
treatment of ethyl 2,4-dihydroxy-6-methylbenzoate (13) in
refluxing xylene for 18 h afforded product 20 in 60% yield (entry
5). In other resorcinols with carbonyl group on the benzene ring,
such as 2,4-dihydroxypropiophenone (14) and 2,4-dihydroxy-
benzophenone (15), cycloaddition reactions were also successful.
Treatment of 14 with benzaldehyde 2 in refluxing xylene for 12 h
afforded product 21 in 63% yield, whereas reaction of 15 gave
adduct 22 in 71% yield (entries 6 and 7). We also studied the
reactions of compound 15 with benzaldehydes 3 and 4 with long
chains under the optimized reaction conditions. In these cases,
a longer reaction time (24 h) was required and products 23 and
24 were obtained in 64% and 60% yields, respectively, as sole
products (entries 8 and 9). As shown in Scheme 4, stereospecific
construction of quaternary carbon centers on compounds 23 and
24 may also be explained through the endo-transition state of
structures 25 and 26. The stereochemical assignment of com-
pounds 23 and 24 was also confirmed by comparison with X-ray
structure of the compound 36, which was obtained by other
domino hetero Diels–Alder reaction.21 These reactions provided
a rapid route for the synthesis of a variety of benzopyrano-
benzopyrans with substituents on the benzopyranyl ring.
Scheme 2. Preparation of benzaldehydes 2–4 with O-allyl ether.
To give benzopyranobenzopyrans, reaction of 2,4-dihydroxy-
acetophenone (5) with 2.0 equiv of benzaldehyde 2 under several
conditions was first attempted (Table 1). Both indium(III) chlo-
ride (20 mol %) and ytterbium(III) triflate (20 mol %) as Lewis acid
catalysts in refluxing acetonitrile gave no adducts. With pyridine
as a reactant and solvent at 140 ꢀC for 24 h, no products were
obtained. However, with triethylamine (excess) or ethylenedi-
amine diacetate (20 mol %) as a catalyst, adduct 6 was obtained
as a sole compound. The best yield (64%) was obtained in
the presence of EDDA (20 mol %)/TEA (2 mL) as co-catalyst in
refluxing xylene for 24 h.
Compound 6 was easily separated by column chromatogra-
phy and the cis-stereochemistry of 6 is confirmed on the basis
Table 1
Reaction of 2,4-dihydroxyacetophenone (5) with benzaldehyde 2 under several
conditions
O
H
O
OH
OH
O
O
H
O
H
2
2 equiv
OH
O
6
5
Conditions
Yield (%)
InCl3 (20 mol %)
Yb (OTf)3 (20 mol %)
Pyridine (excess)
TEA (excess)
EDDA (20 mol %)
EDDA (20 mol %)
EDDA (20 mol %)
Acetonitrile, reflux, 12 h
Acetonitrile, reflux, 12 h
140 ꢀC, 24 h
Xylene, reflux, 24 h
Chloroform, reflux, 24 h
Benzene, reflux, 24 h
Xylene, reflux, 24 h
Xylene, reflux, 24 h
0
0
0
20
27
33
51
64
On the basis of these successful results, we examined additional
reactions between naphthols 27–29 and benzaldehydes 2–4 to
EDDA (20 mol %)/TEA (2 ml)

Y.R. Lee et al. / Tetrahedron 65 (2009) 101–108
103
O
OH
H
O
OH
O
O
O
O
EDDA
TEA
-H2O
TEA
O
O
OH
OH
OH
+
O
5
O
O
O
8a
8b
7
exo
endo
H
hetero Diels-Alder
aldol
X
O
2
O
OH
O
H
O
OH
O
H
H
H
O
6a
O
6
Scheme 3. Possible explanation of the stereochemistry and regiochemistry of compound 6.
4. Experimental section
4.1. 2-(3-Methylbut-2-enyloxy)benzaldehyde (2)
To a solution of 1 (1.807 g, 14.8 mmol) in DMF (20 mL) was
added sodium hydride (1.776 g, 60%, 44.4 mmol) at 0 ꢀC. After
20 min, prenyl bromide (2.426 g, 16.3 mmol) in DMF (3 mL) was
added dropwise. The reaction mixture was stirred at room tem-
perature for 12 h and water (30 mL) was added slowly at 0 ꢀC. The
reaction mixture was extracted with ethyl acetate (30 mLꢁ3),
washed with water (30 mL) and saturated NH4Cl solution (30 mL),
dried over MgSO4, and evaporated. The residue was purified by
column chromatography on silica gel (hexane/ethyl acetate, 20:1)
to give 2 (2.787 g, 99%) as an oil: 1H NMR (300 MHz, CDCl3)
d 10.54
(1H, s), 7.80 (1H, dd, J¼7.6, 1.7 Hz), 7.70 (1H, ddd, J¼8.0, 7.6, 1.7 Hz),
7.00–6.95 (2H, m), 5.50–5.45 (1H, m), 4.64 (2H, d, J¼6.6 Hz), 1.78
(3H, s), 1.73 (3H, s); 13C NMR (75 MHz, CDCl3)
d 189.9, 161.3, 138.6,
135.7, 128.2, 125.1, 120.5, 118.9, 112.9, 65.4, 25.7, 18.2; IR (neat)
2976, 2861, 1688, 1599, 1481, 1458, 1383, 1287, 1236, 1190, 1161,
1101, 1044, 993, 758 cmꢂ1; m/z (EI) 190 (Mþ, 4), 148 (6), 147 (6),
123 (8), 122 (100), 121 (46), 120 (7), 69 (97), 68 (13), 65 (13), 53
(6); HRMS m/z (Mþ) calcd for C12H14O2: 190.0994. Found:
190.0992.
Figure 1. X-ray structure of compound 6.
afford naphthopyranobenzopyrans as shown in Table 3. Reaction of
1-naphthol (27) with benzaldehyde 2 using 20 mol % of ethyl-
enediamine diacetate/TEA (2 ml) in refluxing xylene for 12 h gave
product 30 (94%) (entry 1), whereas reactions with aldehydes 3 and
4 provided adducts 31 and 32 in 83 and 70% yields, respectively, as
sole products (entries 2 and 3). The stereochemistry of quaternary
carbon centers having a long chain on compounds 31 and 32 was
determined in a similar manner as shown in Scheme 4. With other
naphthols containing substituents, cycloaddition reactions were
also successful. Reaction of 4-methoxy-1-naphthol (28) with
benzaldehyde 2 in the presence of 20 mol % of ethylenediamine
diacetate/TEA (2 mL) in refluxing xylene for 18 h gave product 33
(68%), whereas with 4-chloro-1-naphthol (29) adduct 34 was
produced in 73% yield. These reactions also provided a rapid entry
to the synthesis of naphthopyranobenzopyrans with substituents
on the benzochromene ring.
4.2. (E)-2-(3,7-Dimethylocta-2,6-dienyloxy)benzaldehyde (3)
To a solution of 1 (0.904 g, 7.4 mmol) in DMF (20 mL) was
added sodium hydride (0.888 g, 60%, 22.2 mmol) at 0 ꢀC. After
20 min, geranyl bromide (1.770 g, 8.2 mmol) in DMF (3 mL) was
added dropwise. The reaction mixture was stirred at room tem-
perature for 12 h and water (30 mL) was added slowly at 0 ꢀC. The
mixture was extracted with ethyl acetate (30 mLꢁ3), washed with
water (30 mL) and saturated NH4Cl solution (30 mL), dried over
MgSO4, and evaporated. The residue was purified by column
chromatography on silica gel (hexane/ethyl acetate, 20:1) to give 3
(1.893 g, 99%) as an oil: 1H NMR (300 MHz, CDCl3)
d 10.48 (1H, s),
7.80 (1H, dd, J¼7.5, 1.7 Hz), 7.49 (1H, ddd, J¼8.0, 7.5, 1.7 Hz), 7.00–
6.94 (2H, m), 5.49–5.44 (1H, m), 5.14–5.11 (1H, m), 4.63 (2H, d,
J¼6.4 Hz), 1.72 (3H, s), 2.16–2.00 (4H, m), 1.64 (3H, s), 1.57 (3H, s);
3. Conclusion
We have demonstrated a new and efficient methodology
for biologically interesting benzopyranobenzopyrans and naph-
thopyranobenzopyrans by domino aldol-type/hetero Diels–Alder
reactions from commercially available resorcinols and naphthols.
These reactions provide a rapid route for the synthesis of novel
types of polycycles with stereochemically defined quaternary
carbon centers.
13C NMR (75 MHz, CDCl3)
d 189.9, 161.3, 141.8, 135.8, 135.7, 131.9,
128.2, 123.6, 120.5, 118.8, 113.0, 65.5, 39.4, 26.2, 25.6, 17.6, 16.7; IR
(neat) 2969, 2920, 2859, 1690, 1599, 1481, 1456, 1383, 1287, 1236,
1190, 1161, 1103, 992, 833, 758 cmꢂ1; m/z (EI) 258 (Mþ, 2), 137 (26),
136 (15), 122 (31), 121 (21), 95 (13), 93 (18), 81 (49), 69 (100), 68
(13), 67 (13); HRMS m/z (Mþ) calcd for C17H22O2: 258.1620. Found:
258.1623.

104
Y.R. Lee et al. / Tetrahedron 65 (2009) 101–108
Table 2
Reactions of resorcinols with benzaldehydes 2–4a
Entry
Resorcinol
Benzaldehyde
Time (h)
Product
Yield (%)
OH
OH
H
O
H
1
2
18
56
OH
O
9
16
OH
OH
H
O
2
2
18
52
H
R1
OH
R1=n-C5H11
R1
O
10
17
O
OH
O
OH
H
O
H
MeO
EtO
3
2
18
18
57
MeO
OH
OH
O
11
18
O
OH
O
OH
H
O
4
2
62
EtO
EtO
H
O
12
19
O
O
OH
O
O
OH
H
O
H
EtO
5
6
7
8
2
2
2
3
18
12
12
24
60
63
71
64
OH
OH
OH
OH
O
O
13
20
OH
OH
H
O
H
14
21
O
OH
OH
O
OH
O
H
H
O
15
22
O
O
O
OH
O
H
H
O
15
23
OH
O
OH
O
H
H
9
4
24
60
OH
O
15
24
a
Resorcinols (1.0 mmol) and benzaldehydes 2–4 (2.0 mmol) under EDDA (20 mol %)/TEA (2 mL) in refluxing xylene.

Y.R. Lee et al. / Tetrahedron 65 (2009) 101–108
105
water (30 mL) and saturated NH4Cl solution (30 mL), dried over
MgSO4, and evaporated. The residue was purified by column
chromatography on silica gel (hexane/ethyl acetate, 20:1) to give 4
H
O
OH
O
H
O
O
O
H
(2.368 g, 98%) as an oil: 1H NMR (300 MHz, CDCl3)
d 10.48 (1H, s),
7.80 (1H, dd, J¼7.5, 1.7 Hz), 7.49 (1H, ddd, J¼8.0, 7.5, 1.7 Hz), 7.01–
6.94 (2H, m), 5.50–5.46 (1H, m), 5.11–5.04 (1H, m), 4.64 (2H, d,
J¼6.4 Hz), 2.18–1.91 (8H, m), 1.73 (3H, s), 1.65 (3H, s), 1.58 (3H, s);
O
R
O
R
endo
hetero Diels-Alder
13C NMR (75 MHz, CDCl3)
d 189.9, 161.3, 141.8, 135.7, 135.5, 131.2,
23 R= CH3
24 R=CH2CH2CH(CH3)2
128.2, 125.1, 124.2, 123.5, 120.5, 118.8, 112.9, 65.5, 39.6, 39.4, 26.6,
26.1, 25.6, 17.6, 16.7, 16.0; IR (neat) 2967, 2922, 2857, 1690, 1599,
25 R= CH3
26 R=CH2CH2CH(CH3)2
1481, 1456, 1383, 1287, 1236, 1190, 1161, 1103, 992, 833, 758 cmꢂ1
;
m/z (EI) 326 (Mþ, 2), 207 (7), 189 (6), 161 (9), 149 (10), 137 (34), 122
(30), 121 (24), 93 (33), 81 (95), 69 (100), 55 (20); HRMS m/z (Mþ)
calcd for C22H30O2: 326.2246. Found: 326.2244.
Scheme 4. Explanation for construction of stereochemically defined quaternary car-
bon centers on compounds 23 and 24.
4.3. (E),(E)-2-(3,7,11-Trimethyldodeca-2,6,10-
trienyloxy)benzaldehyde (4)
4.4. General procedure for the synthesis of benzopyrano-
benzopyrans and naphthopyranobenzopyrans
To a solution of 1 (0.904 g, 7.4 mmol) in DMF (20 mL) was added
sodium hydride (0.888 g, 60%, 22.2 mmol) at 0 ꢀC. After 20 min,
trans,trans-farnesyl bromide (2.325 g, 8.2 mmol) in DMF (3 mL) was
added dropwise. The reaction mixture was stirred at room tem-
perature for 12 h and water (30 mL) was added slowly at 0 ꢀC. The
mixture was extracted with ethyl acetate (30 mLꢁ3), washed with
Ethylenediamine diacetate (36 mg, 0.2 mmol) and TEA (2 mL)
were added to a solution of resorcinol or naphthol (1.0 mmol) and
benzaldehyde (2.0 mmol) in xylene (10 mL) at room temperature.
The reaction mixture was stirred in refluxing xylene for 12–24 h.
The removal of the solvent under reduced pressure left an oily
Table 3
Reactions of naphthols with benzaldehydes 2–4a
Entry
1
Naphthols
Benzaldehyde
Time (h)
Product
Yield (%)
H
O
OH
O
O
2
12
94
H
27
30
H
OH
O
2
3
24
83
H
27
31
OH
H
O
O
3
4
24
70
H
27
32
H
H
OH
O
O
O
4
2
18
68
OMe
OMe
33
28
H
H
OH
O
5
2
18
73
Cl
Cl
29
34
a
Naphthols (1.0 mmol) and benzaldehydes 2–4 (2.0 mmol) under EDDA (20 mol %)/TEA (2 mL) in refluxing xylene.

106
Y.R. Lee et al. / Tetrahedron 65 (2009) 101–108
residue, which was then purified by column chromatography on
silica gel to give the product.
d
11.62 (1H, s), 7.70 (1H, d, J¼8.9 Hz), 7.25 (1H, d, J¼7.7 Hz), 7.07 (1H,
d, J¼7.7, 7.4 Hz), 6.80 (1H, dd, J¼8.0, 7.4 Hz), 6.72 (1H, d, J¼8.0 Hz),
6.38 (1H, d, J¼8.9 Hz), 4.53–4.46 (3H, m), 3.92 (3H, s), 2.24–2.18
4.4.1. 1-(1-Hydroxy-6,6-dimethyl-6a,12b-dihydro-6H,7H-5,8-
dioxabenzo[c]phenanthren-2-yl)ethanone (6)
A reaction of 2,4-dihydroxyacetophenone (5) (0.152 g,1.0 mmol)
with benzaldehyde 2 (0.380 g, 2.0 mmol) in refluxing xylene
(10 mL) for 24 h and purification by column chromatography on
(1H, m), 1.53 (3H, s), 1.07 (3H, s); 13C NMR (75 MHz, CDCl3)
d 170.9,
161.9, 159.4, 154.0, 129.7, 129.2, 127.6, 122.5, 120.7, 115.9, 110.5,
109.5, 104.3, 78.2, 65.7, 52.0, 38.6, 29.3, 28.9, 23.8; IR (KBr)
2980, 1664, 1622, 1584, 1489, 1439, 1345, 1267, 1217, 1134, 1061,
997, 889, 791, 752 cmꢂ1; m/z (EI) 340 (Mþ, 92), 309 (26), 308
(100), 293 (11), 281 (11), 280 (48), 239 (17), 224 (10), 223 (59),
159 (20); HRMS m/z (Mþ) calcd for C20H20O5: 340.1311. Found:
340.1313.
silica gel (hexane/ethyl acetate, 10:1) afforded compound
6
(0.208 g, 64%) as a solid: mp 152–153 ꢀC; 1H NMR (300 MHz, CDCl3)
d
13.47 (1H, s), 7.59 (1H, d, J¼8.9 Hz), 7.23 (1H, d, J¼8.0 Hz), 7.06
(1H, dd, J¼8.0, 7.5 Hz), 6.80 (1H, dd, J¼7.8, 7.5 Hz), 6.70 (1H, d,
J¼7.8 Hz), 6.37 (1H, d, J¼8.9 Hz), 4.50 (2H, dd, J¼12.0, 4.2 Hz), 4.47
(1H, d, J¼4.3 Hz), 2.58 (3H, s), 2.24–2.18 (1H, m), 1.53 (3H, s), 1.08
4.4.5. 1-Hydroxy-6,6-dimethyl-6a,12b-dihydro-6H,7H-5,8-
dioxabenzo[c]phenanthrene-2-carboxylic acid ethyl ester (19)
(3H, s); 13C NMR (75 MHz, CDCl3)
d
202.6, 163.5, 160.0, 153.9, 130.9,
A reaction of ethyl 2,4-dihydroxybenzoate (12) (0.182 g,
129.2, 127.6, 122.3, 120.7, 115.8, 112.9, 110.7, 109.3, 78.6, 65.5, 38.5,
29.0, 28.8, 26.1, 23.8; IR (KBr) 2969, 1618, 1487, 1449, 1412, 1373,
1323, 1267, 1127, 1084, 1059, 893, 828, 804, 758 cmꢂ1; m/z (EI) 324
(Mþ, 100), 325 (21), 324 (100), 309 (16), 282 (11), 281 (50), 268 (9),
255 (13), 240 (11), 239 (67), 159 (13), 69 (8); HRMS m/z (Mþ) calcd
for C20H20O4: 324.1362. Found: 324.1363.
1.0 mmol) with benzaldehyde 2 (0.380 g, 2.0 mmol) in refluxing
xylene (10 mL) for 18 h and purification by column chromatogra-
phy on silica gel (hexane/ethyl acetate, 20:1) afforded compound 19
(0.220 g, 62%) as a solid: mp 134–135 ꢀC; 1H NMR (300 MHz, CDCl3)
d
11.60 (1H, s), 7.64 (1H, d, J¼8.9 Hz), 7.17 (1H, d, J¼7.8 Hz), 6.99 (1H,
d, J¼7.8, 7.4 Hz), 6.72 (1H, dd, J¼8.0, 7.4 Hz), 6.63 (1H, d, J¼8.0 Hz),
6.29 (1H, d, J¼8.9 Hz), 4.46–4.28 (5H, m), 2.32–2.20 (1H, m), 1.44
(3H, s), 1.33 (3H, t, J¼7.2 Hz), 0.99 (3H, s); 13C NMR (75 MHz, CDCl3)
4.4.2. 3,6,6-Trimethyl-6a,12b-dihydro-6H,7H-5,8-
dioxabenzo[c]phenanthren-1-ol (16)
d 170.6, 162.0, 159.3, 154.0, 129.7, 129.2, 127.6, 122.5, 120.7, 115.9,
A reaction of orcinol (9) (0.124 g,1.0 mmol) with benzaldehyde 2
(0.380 g, 2.0 mmol) in refluxing xylene (10 mL) for 18 h and puri-
fication by column chromatography on silica gel (hexane/ethyl ac-
etate, 10:1) afforded compound 16 (0.166 g, 56%) as a solid: mp
110.4, 109.3, 104.6, 78.2, 65.7, 61.0, 38.7, 29.3, 28.9, 23.8, 14.3; IR
(KBr) 2980, 1661, 1584, 1489, 1373, 1265, 1136, 1061, 1020, 910, 793,
752 cmꢂ1; HRMS m/z (Mþ) calcd for C21H22O5: 354.1467. Found:
354.1469.
140–141 ꢀC; 1H NMR (300 MHz, CDCl3)
d 12.01 (1H, s), 7.30 (1H, d,
J¼7.8 Hz), 7.11 (1H, d, J¼7.8, 7.4 Hz), 6.84 (1H, dd, J¼8.0, 7.4 Hz), 6.76
(1H, d, J¼8.0 Hz), 6.29 (1H, s), 6.24 (1H, s), 4.47 (1H, dd, J¼11.8,
4.6 Hz), 4.35 (1H, dd, J¼11.8, 4.6 Hz), 4.33 (1H, d, J¼4.6 Hz), 2.27–
2.20 (1H, m), 2.22 (3H, s), 1.46 (3H, s), 1.09 (3H, s); 13C NMR
4.4.6. 1-Hydroxy-3,6,6-trimethyl-6a,12b-dihydro-6H,7H-5,8-
dioxabenzo[c]phenanthrene-2-carboxylic acid ethyl ester (20)
A
reaction of ethyl 2,4-dihydroxy-6-methylbenzoate (13)
(0.196 g, 1.0 mmol) with benzaldehyde 2 (0.380 g, 2.0 mmol) in
refluxing xylene (10 mL) for 18 h and purification by column
chromatography on silica gel (hexane/ethyl acetate, 20:1) afforded
compound 20 (0.221 g, 60%) as a solid: mp 126–127 ꢀC; 1H NMR
(75 MHz, CDCl3)
d 154.9, 154.4, 153.9, 139.0, 129.3, 128.1, 123.3,
120.9, 116.4, 110.6, 108.3, 106.8, 76.2, 65.8, 39.2, 30.2, 28.5, 24.0,
21.1; IR (KBr) 3428, 3036, 2982, 2942, 1618, 1584, 1489, 1450,
1240, 1175, 1132, 1080, 1049, 995, 885, 853, 816, 748 cmꢂ1; m/z (EI)
296 (Mþ, 60), 281 (7), 253 (17), 227 (20), 212 (15), 211 (100),
159 (13); HRMS m/z (Mþ) calcd for C19H20O3: 296.1412. Found:
296.1411.
(300 MHz, CDCl3)
d
12.55 (1H, s), 7.27 (1H, d, J¼7.7 Hz), 7.06 (1H, d,
J¼7.7, 7.4 Hz), 6.80 (1H, dd, J¼8.0, 7.4 Hz), 6.71 (1H, d, J¼8.0 Hz),
6.24 (1H, s), 4.53–4.39 (5H, m), 2.51 (3H, s), 2.23–2.16 (1H, m), 1.52
(3H, s), 1.43 (3H, t, J¼7.1 Hz), 1.06 (3H, s); 13C NMR (75 MHz, CDCl3)
d
172.3, 163.7, 157.7, 154.0, 141.6, 129.3, 127.5, 122.8, 120.7, 115.8,
4.4.3. 6,6-Dimethyl-3-pentyl-6a,12b-dihydro-6H,7H-5,8-
dioxabenzo[c]phenanthren-1-ol (17)
112.5, 108.5, 104.4, 78.1, 65.7, 61.2, 38.9, 29.3, 28.9, 24.2, 23.8, 14.3;
IR (KBr) 3038, 2980, 2936, 1644, 1397, 1489, 1453, 1397, 1368, 1323,
1269, 1246, 1136, 1090, 1009, 806, 752 cmꢂ1; m/z (EI) 368 (Mþ, 55),
323 (27), 322 (100), 295 (14), 294 (66), 293 (10), 279 (15), 253 (12),
237 (34); HRMS m/z (Mþ) calcd for C22H24O5: 368.1624. Found:
368.1621.
A reaction of olivetol (10) (0.180 g, 1.0 mmol) with benzaldehyde
2 (0.380 g, 2.0 mmol) in refluxing xylene (10 mL) for 18 h and pu-
rification by column chromatography on silica gel (hexane/ethyl
acetate, 20:1) afforded compound 17 (0.183 g, 52%) as a solid: mp
113–114 ꢀC; 1H NMR (300 MHz, CDCl3)
d 12.51 (1H, s), 7.31 (1H, d,
J¼7.8 Hz), 7.10 (1H, d, J¼7.8, 7.4 Hz), 6.84 (1H, dd, J¼8.0, 7.4 Hz), 6.75
(1H, d, J¼8.0), 6.29 (1H, s), 6.25 (1H, s), 4.48 (1H, dd, J¼11.8, 4.6 Hz),
4.35 (1H, dd, J¼11.8, 4.6 Hz), 4.33 (1H, d, J¼4.6 Hz), 2.46 (2H, t,
J¼7.5 Hz), 2.26–2.21 (1H, m), 1.62–1.52 (3H, m), 1.46 (3H, s), 1.37–
1.29 (3H, m), 1.09 (3H, s), 0.87 (3H, t, J¼6.6 Hz); 13C NMR (75 MHz,
4.4.7. 1-(1-Hydroxy-6,6-dimethyl-6a,12b-dihydro-6H,7H-5,8-
dioxabenzo[c]phenanthren-2-yl)propane-1-one (21)
A
reaction of 2,4-dihydroxypropiophenone (14) (0.166 g,
1.0 mmol) with benzaldehyde 2 (0.380 g, 2.0 mmol) in refluxing
xylene (10 mL) for 12 h and purification by column chromato-
graphy on silica gel (hexane/ethyl acetate, 20:1) afforded com-
pound 21 (0.213 g, 63%) as a solid: mp 124–125 ꢀC; 1H NMR
CDCl3)
d 154.8, 154.4, 153.8, 144.0, 129.1, 128.0, 123.3, 120.8, 116.3,
109.8, 107.6, 107.0, 76.2, 65.8, 39.2, 35.6, 31.5, 30.6, 30.2, 28.5, 24.0,
22.5, 14.0; IR (KBr) 3368, 2930, 1624, 1487, 1452, 1429, 1348, 1246,
1171, 1136, 1078, 1043, 889, 790, 754 cmꢂ1; HRMS m/z (Mþ) calcd
for C23H28O3: 352.2038. Found: 352.2034.
(300 MHz, CDCl3)
d
13.59 (1H, s), 7.64 (1H, d, J¼8.9 Hz), 7.25 (1H,
d, J¼7.8 Hz), 7.07 (1H, d, J¼7.8, 7.4 Hz), 6.80 (1H, dd, J¼8.0,
7.4 Hz), 6.71 (1H, d, J¼8.0 Hz), 6.38 (1H, d, J¼8.9 Hz), 4.54–4.48
(3H, m), 2.99 (2H, q, 7.2 Hz), 2.25–2.20 (1H, m), 1.54 (3H, s), 1.27
4.4.4. 1-Hydroxy-6,6-dimethyl-6a,12b-dihydro-6H,7H-5,8-
(3H, t, J¼7.5 Hz), 1.09 (3H, s); 13C NMR (75 MHz, CDCl3)
d 205.5,
dioxabenzo[c]phenanthrene-2-carboxylic acid methyl ester (18)
A reaction of methyl 2,4-dihydroxybenzoate (11) (0.168 g,
1.0 mmol) with benzaldehyde 2 (0.380 g, 2.0 mmol) in refluxing
xylene (10 mL) for 18 h and purification by column chromatogra-
phy on silica gel (hexane/ethyl acetate, 20:1) afforded compound 18
(0.194 g, 57%) as a solid: mp 123–124 ꢀC; 1H NMR (300 MHz, CDCl3)
163.6, 159.8, 154.0, 130.1, 129.2, 127.7, 122.4, 120.8, 115.9, 112.4,
110.8, 109.2, 78.6, 65.6, 38.6, 31.1, 29.1, 28.9, 23.8, 8.7; IR (KBr)
2980, 1620, 1489, 1416, 1323, 1258, 1123, 1071, 910, 891, 797,
754 cmꢂ1; m/z (EI) 338 (Mþ, 100), 310 (13), 309 (64), 295 (33),
253 (45), 241 (25), 159 (9), 69 (10); HRMS m/z (Mþ) calcd for
C21H22O4: 338.1518. Found: 338.1520.

Y.R. Lee et al. / Tetrahedron 65 (2009) 101–108
107
4.4.8. 1-(1-Hydroxy-6,6-dimethyl-6a,12b-dihydro-6H,7H-5,8-
mp 108–109 ꢀC; 1H NMR (300 MHz, CDCl3)
d
8.30–8.28 (1H, m),
dioxabenzo[c]phenanthren-2-yl)phenylmethanone (22)
7.78–7.73 (1H, m), 7.54–7.45 (4H, m), 7.35 (1H, d, J¼8.6 Hz), 7.26
(1H, dd, J¼8.0, 7.4 Hz), 7.07 (1H, dd, J¼7.6, 7.4 Hz), 6.90 (1H, d,
J¼8.0 Hz), 4.53 (1H, d, J¼11.8 Hz), 4.33 (1H, d, J¼4.6 Hz), 3.96 (1H,
dd, J¼11.8, 11.1 Hz), 2.37–2.30 (1H, m), 1.69 (3H, s), 1.52 (3H, s); 13C
A
reaction of 2,4-dihydroxybenzophenone (15) (0.214 g,
1.0 mmol) with benzaldehyde 2 (0.380 g, 2.0 mmol) in refluxing
xylene (10 mL) for 12 h and purification by column chromatogra-
phy on silica gel (hexane/ethyl acetate,15:1) afforded compound 22
(0.274 g, 71%) as a solid: mp 65–66 ꢀC; 1H NMR (300 MHz, CDCl3)
NMR (75 MHz, CDCl3) d 154.0, 146.4, 133.4,132.4, 128.4, 127.3, 126.3,
126.0, 125.4, 125.1, 122.4, 122.0, 119.7, 119.6, 116.8, 114.8, 74.7, 63.5,
37.1, 33.5, 26.4, 26.2; IR (KBr) 3057, 2980, 2926, 1583, 1491, 1454,
1387, 1329, 1302, 1238, 1148, 1093, 1057, 1042, 1026, 965, 939, 909,
870, 814, 791, 758 cmꢂ1; HRMS m/z (Mþ) calcd for C22H20O2:
316.1463. Found: 316.1465.
d
13.46 (1H, s), 7.65 (2H, d, J¼8.9 Hz), 7.55–7.44 (4H, m), 7.33 (1H, d,
J¼7.8 Hz), 7.08 (1H, d, J¼7.8, 7.4 Hz), 6.83 (1H, dd, J¼8.0, 7.4 Hz),
6.72 (1H, d, J¼8.0 Hz), 6.33 (1H, d, J¼8.9 Hz), 4.63–4.49 (3H, m),
2.28–2.20 (1H, m), 1.54 (3H, s), 1.10 (3H, s); 13C NMR (75 MHz,
CDCl3)
d 200.2, 164.8, 160.3, 154.0, 138.3, 133.9, 131.4, 129.3, 128.9,
128.3, 127.8, 122.3, 120.8, 115.9, 112.2, 111.0, 109.2, 78.8, 65.6, 38.6,
29.2, 28.9, 23.9; IR (KBr) 2980, 1615, 1487, 1348, 1269, 1138, 1071,
885, 756 cmꢂ1; HRMS m/z (Mþ) calcd for C25H22O4: 386.1518.
Found: 386.1522.
4.4.12. 6-Methyl-6-(4-methylpent-3-enyl)-6a,7-dihydro-6H,12bH-
5,8-dioxabenzo[c]chrysene (31)
A reaction of 1-naphthol (27) (0.144 g, 1.0 mmol) with benzal-
dehyde 3 (0.517 g, 2.0 mmol) in refluxing xylene (10 mL) for 24 h
and purification by column chromatography on silica gel (hexane/
ethyl acetate, 30:1) afforded compound 31 (0.319 g, 83%) as an oil:
4.4.9. [1-Hydroxy-6-methyl-6-(4-methylpent-3-enyl)-6a,12b-
dihydro-6H,7H-5,8-dioxabenzo[c]phenanthren-2-yl]-
phenylmethanone (23)
1H NMR (300 MHz, CDCl3)
d 8.59–8.47 (1H, m), 7.99–7.97 (1H, m),
7.76–7.69 (4H, m), 7.57 (1H, d, J¼9.0 Hz), 7.48 (1H, dd, J¼8.0, 7.4 Hz),
7.29 (1H, dd, J¼7.6, 7.4 Hz), 7.13 (1H, d, J¼8.0 Hz), 5.34–5.30 (1H, m),
4.53 (1H, dd, J¼11.8, 1.8 Hz), 4.55 (1H, d, J¼4.0 Hz), 4.23 (1H, dd,
J¼11.8, 11.4 Hz), 2.72–2.63 (1H, m), 2.48–2.36 (2H, m), 2.13–2.02
A
reaction of 2,4-dihydroxybenzophenone (15) (0.214 g,
1.0 mmol) with benzaldehyde 3 (0.517 g, 2.0 mmol) in refluxing
xylene (10 mL) for 24 h and purification by column chromatography
on silica gel (hexane/ethyl acetate, 15:1) afforded compound 23
(2H, m), 1.88 (6H, s), 1.80 (3H, s); 13C NMR (75 MHz, CDCl3)
d 154.1,
(0.291 g, 64%) as an oil: 1H NMR (300 MHz, CDCl3)
d
13.47 (1H, s),
146.3, 133.4, 132.4, 132.0, 128.4, 127.3, 126.2, 126.0, 125.4, 125.1,
123.5, 122.4, 122.0, 119.7, 119.6, 116.8, 115.1, 76.9, 63.7, 38.2, 35.4,
33.3, 25.6, 22.8, 22.7, 22.1, 17.5; IR (neat) 2918, 1584, 1491, 1454,
1386, 1327, 1262, 1240, 1099, 1057, 964, 812, 758 cmꢂ1; m/z (EI) 384
(Mþ, 23), 300 (22), 299 (94), 248 (18), 247 (15), 232 (19), 231 (100),
69 (22); HRMS m/z (Mþ) calcd for C27H28O2: 384.2089. Found:
384.2086.
7.66 (2H, d, J¼8.9 Hz), 7.56–7.45 (4H, m), 7.35 (1H, d, J¼7.8 Hz), 7.09
(1H, d, J¼7.8, 7.4 Hz), 6.85 (1H, dd, J¼8.0, 7.4 Hz), 6.74 (1H, d,
J¼8.0 Hz), 6.36 (1H, d, J¼8.9 Hz), 5.16–5.12 (1H, m), 4.60 (1H, d,
J¼5.4 Hz), 4.52 (1H, dd, J¼12.0, 3.9 Hz), 4.44 (1H, d, J¼12.0 Hz), 2.40–
2.32 (1H, m), 2.20–2.08 (2H, m), 1.86–1.80 (2H, m), 1.69 (3H, s), 1.61
(3H, s), 1.11 (3H, s); 13C NMR (75 MHz, CDCl3)
d 200.1, 164.8, 160.5,
154.1,138.4,133.9,132.2,131.4,129.3,129.9,129.8,128.3,128.2,127.7,
123.6, 122.7, 120.8, 115.9, 112.1, 110.9, 109.2, 80.2, 65.4, 40.6, 35.7,
29.1, 25.7, 22.7, 21.6,17.7; IR (neat) 2924,1613,1487,1449,1412,1381,
1346, 1269, 1155, 1111, 1069, 999, 909, 816, 733 cmꢂ1; m/z (EI) 454
(Mþ, 7), 371 (11), 370 (26), 369 (100), 301 (21), 105 (22), 77 (9), 69
(14); HRMS m/z (Mþ) calcd for C30H30O4:454.2144. Found: 454.2145.
4.4.13. (E)-6-(4,8-Dimethylnona-3,7-dienyl)-6-methyl-6a,7-
dihydro-6H,12bH-5,8-dioxabenzo[c]chrysene (32)
A reaction of 1-naphthol (27) (0.144 g, 1.0 mmol) with benzal-
dehyde 4 (0.653 g, 2.0 mmol) in refluxing xylene (10 mL) for 24 h
and purification by column chromatography on silica gel (hexane/
ethyl acetate, 30:1) afforded compound 32 (0.317 g, 70%) as an oil:
4.4.10. (E)-[6-(4,8-Dimethylnona-3,7-dienyl)-1-hydroxy-6-methyl-
6a,12b-dihydro-6H,7H-5,8-dioxabenzo[c]phenanthren-2-yl]-
phenylmethanone (24)
1H NMR (300 MHz, CDCl3)
d 8.23–8.19 (1H, m), 7.72–7.68 (1H, m),
7.49–7.39 (4H, m), 7.28 (1H, d, J¼8.9 Hz), 7.20 (1H, dd, J¼8.0, 7.4 Hz),
7.00 (1H, dd, J¼7.6, 7.4 Hz), 6.83 (1H, d, J¼8.0 Hz), 5.06–5.00 (2H,
m), 4.53–4.48 (1H, m), 4.27 (1H, d, J¼4.0 Hz), 3.95 (1H, dd, J¼11.8,
11.1 Hz), 2.45–2.39 (1H, m), 2.22–2.09 (2H, m), 2.00–195 (2H, m),
1.91–1.77 (4H, m), 1.63 (3H, s), 1.61 (3H, s), 1.53 (3H, s), 1.51 (3H, s);
A
reaction of 2,4-dihydroxybenzophenone (15) (0.214 g,
1.0 mmol) with benzaldehyde 4 (0.653 g, 2.0 mmol) in refluxing
xylene (10 mL) for 24 h and purification by column chromatography
on silica gel (hexane/ethyl acetate, 15:1) afforded compound 24
13C NMR (75 MHz, CDCl3)
d 154.1, 146.3, 135.7, 133.4, 132.3, 131.3,
(0.314 g, 60%) as an oil: 1H NMR (300 MHz, CDCl3)
d
13.51 (1H, s),
128.4, 127.2, 126.2, 126.0, 125.4, 125.1, 124.2, 123.3, 122.4, 122.0,
119.7, 119.6, 116.8, 115.0, 76.9, 63.6, 39.6, 38.2, 35.4, 33.3, 26.6, 25.6,
22.8, 22.0, 17.6, 15.9; IR (neat) 2922, 1584, 1491, 1454, 1385, 1240,
1101, 1055, 965, 812, 758 cmꢂ1; HRMS m/z (Mþ) calcd for C32H36O2:
452.2715. Found: 452.2713.
7.69 (2H, d, J¼8.9 Hz), 7.59–7.47 (4H, m), 7.38 (1H, d, J¼7.8 Hz), 7.11
(1H, d, J¼7.8, 7.4 Hz), 6.86 (1H, dd, J¼8.0, 7.4 Hz), 6.76 (1H, d,
J¼8.0 Hz), 6.40 (1H, d, J¼8.9 Hz), 5.21–5.16 (1H, m), 5.14–5.09 (1H,
m), 4.63 (1H, d, J¼5.0 Hz), 4.53 (1H, dd, J¼12.0, 4.0 Hz), 4.45 (1H, dd,
J¼12.0, 3.6 Hz), 2.42–2.34 (1H, m), 2.24–1.96 (6H, m),1.90–1.84 (2H,
m), 1.70 (3H, s), 1.64 (3H, s), 1.62 (3H, s), 1.14 (3H, s); 13C NMR
4.4.14. 14-Methoxy-6,6-dimethyl-6a,7-dihydro-6H,12bH-5,8-
dioxabenzo[c]chrysene (33)
(75 MHz, CDCl3) d 200.1, 164.8, 160.5, 154.1, 138.3, 135.8,133.8,131.4,
131.3,129.2,128.8,128.7,128.2,128.1,127.7,124.2,123.4,122.6,120.7,
115.9, 112.1, 110.9, 109.2, 80.2, 65.4, 40.5, 39.6, 35.6, 29.1, 26.6, 25.7,
22.6, 21.5, 17.7, 16.0; IR (neat) 2922, 1613, 1487, 1449, 1412, 1381,
1346, 1269, 1154, 1109, 1067, 999, 903, 754 cmꢂ1; m/z (EI) 522 (Mþ,
7), 371 (12), 370 (26), 369 (100), 301 (18), 105 (19), 81 (16), 69 (41);
HRMS m/z (Mþ) calcd for C35H38O4: 522.2770. Found: 522.2774.
A reaction of 4-methoxy-1-naphthol (28) (0.174 g, 1.0 mmol)
with benzaldehyde 2 (0.380 g, 2.0 mmol) in refluxing xylene
(10 mL) for 18 h and purification by column chromatography on
silica gel (hexane/ethyl acetate, 10:1) afforded compound 33
(0.236 g, 68%) as a solid: mp 154–155 ꢀC; 1H NMR (300 MHz, CDCl3)
d
8.22–8.12 (2H, m), 7.55–7.43 (3H, m), 7.22 (1H, dd, J¼8.0, 7.6 Hz),
7.03 (1H, dd, J¼7.6, 7.4 Hz), 6.87 (1H, d, J¼8.0 Hz), 6.83 (1H, s), 4.54–
4.48 (1H, m), 4.26 (1H, d, J¼3.8 Hz), 3.95 (1H, dd, J¼11.2, 8.2 Hz),
3.84 (3H, s), 2.33–2.26 (1H, m), 1.62 (3H, s), 1.47 (3H, s); 13C NMR
4.4.11. 6,6-Dimethyl-6a,7-dihydro-6H,12bH-5,8-dioxabenzo[c]-
chrysene (30)
A reaction of 1-naphthol (27) (0.144 g, 1.0 mmol) with benzal-
dehyde 2 (0.380 g, 2.0 mmol) in refluxing xylene (10 mL) for 12 h
and purification by column chromatography on silica gel (hexane/
ethyl acetate, 30:1) afforded compound 30 (0.297 g, 94%) as a solid:
(75 MHz, CDCl3) d 170.9,154.1,148.9,140.0,131.9,128.3, 126.2, 125.7,
125.4, 122.5, 121.7, 121.5, 119.6, 116.8, 113.9, 103.8, 74.2, 63.7, 55.3,
37.2, 33.8, 26.2, 26.0; IR (KBr) 3067, 2976, 1632, 1586, 1491, 1460,
1383, 1329, 1308, 1267, 1236, 1152, 1126, 1099, 1042, 1026, 962, 932,

108
Y.R. Lee et al. / Tetrahedron 65 (2009) 101–108
756 cmꢂ1; HRMS m/z (Mþ) calcd for C23H22O3: 346.1569. Found:
346.1568.
5. (a) Costa, S. M. O.; Lemos, T. L. G.; Pessoa, O. D. L.; Pessoa, C.; Montenegro, R.;
Braz-Filho, R. J. Nat. Prod. 2001, 64, 792; (b) Singh, R.; Geetanjali; Chauhan,
S. M. S. Chem. Biodivers. 2004, 1, 1241.
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4.4.15. 14-Chloro-6,6-dimethyl-6a,7-dihydro-6H,12bH-5,8-
dioxabenzo[c]chrysene (34)
A reaction of 4-chloro-1-naphthol (29) (0.179 g, 1.0 mmol) with
benzaldehyde 2 (0.380 g, 2.0 mmol) in refluxing xylene (10 mL) for
18 h and purification by column chromatography on silica gel
(hexane/ethyl acetate, 40:1) afforded compound 34 (0.256 g, 73%)
as a solid: mp 155–156 ꢀC; 1H NMR (300 MHz, CDCl3)
d 8.25 (1H, d,
J¼8.0 Hz), 8.11 (1H, d, J¼7.6 Hz), 7.60–7.44 (4H, m), 7.23 (1H, dd,
J¼8.0, 7.6 Hz), 7.04 (1H, dd, J¼7.6, 7.4 Hz), 6.85 (1H, d, J¼8.0 Hz),
4.52–4.46 (1H, m), 4.25 (1H, d, J¼4.5 Hz), 3.87 (1H, dd, J¼11.4,
11.3 Hz), 2.34–2.25 (1H, m), 1.68 (3H, s), 1.47 (3H, s); 13C NMR
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(75 MHz, CDCl3) d 153.9, 145.6, 132.1, 130.3, 128.6, 127.1, 126.5, 126.1,
125.8, 124.0, 122.8, 122.4, 121.7, 120.0, 116.9, 115.4, 77.2, 75.1, 63.3,
36.8, 33.3, 26.2, 26.0; IR (KBr) 3073, 2982, 1586, 1493, 1454, 1375,
1327, 1300, 1263, 1229, 1146, 1107, 1042, 914, 760, 737 cmꢂ1; HRMS
m/z (Mþ) calcd for C22H19ClO2: 350.1074. Found: 350.1073.
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Acknowledgements
This work was supported by grant No. RTI04-01-04 from the
Regional Technology Innovation Program of the Ministry of
Knowledge Economy (MKE).
14. Lee, Y. R.; Hung, T. V. Tetrahedron 2008, 64, 7338.
15. Shanmugasundaram, M.; Manikandan, S.; Raghunathan, R. Tetrahedron 2002,
58, 997.
16. Tietze, L. F.; Geissler, H.; Fennen, J.; Brumby, T.; Brand, S.; Schulz, G. J. Org. Chem.
1994, 59, 182.
17. Saimoto, H.; Yoshida, K.; Murakami, T.; Morimoto, M.; Sashiwa, H.; Shigemasa,
Y. J. Org. Chem. 1996, 61, 6768.
Supplementary data
18. Lumb, J.-P.; Trauner, D. Org. Lett. 2005, 26, 5865.
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2008.10.101.
19. (a) Hoffmann, R. W. Chem. Rev. 1989, 89, 1841; (b) Tietze, L. F.; Beifuss, U.;
}
Ruther, M.; Ruhlmann, A.; Antel, J.; Sheldrick, G. M. Angew. Chem., Int. Ed. Engl.
1988, 27, 1186.
20. Tietze, L. F.; Brumby, T.; Pretor, M.; Remberg, G. J. Org. Chem. 1988, 53, 810.
21. Reaction of 4-hydroxy-1-methyl-2-quinolone (35) with 3 in the presence of
EDDA/TEA gave product 36 (59%) as a sole compound.
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O
H
OHC
OH
N
O
N
O
3
H
O
EDDA/TEA
xylene
O
35
59%
36
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