Synthesis of 1,3-disubstituted naphtho[2,3-c]pyran-5,10-diones

Article abstract of DOI:10.1016/S0040-4020(01)00307-6

Two convenient and simple methods for the synthesis of 1,3-disubstituted naphtho[2,3-c]pyran-5,10-diones, which involve the introduction of acylmethyl groups onto 2-(1-hydroxyethyl)-1,4-naphthoquinones and subsequent base- and acid-induced ring closure, were developed.

Full text of DOI:10.1016/S0040-4020(01)00307-6

TETRAHEDRON
Pergamon
Tetrahedron 57 +2001) 4213±4219
Synthesis of 1,3-disubstituted naphtho[2,3-c]pyran-5,10-diones
Tuyen Nguyen Van, Bart Kesteleyn and Norbert De Kimpep
Department of Organic Chemistry, Faculty of Agricultural and Applied Biological Sciences, Ghent University,
Coupure links 653 B 9000 Ghent, Belgium
Received 12 December 2000; revised 22 February 2001; accepted 8March 2001
AbstractÐTwo convenient and simple methods for the synthesis of 1,3-disubstituted naphtho[2,3-c]pyran-5,10-diones, which involve the
introduction of acylmethyl groups onto 2-+1-hydroxyethyl)-1,4-naphthoquinones and subsequent base- and acid-induced ring closure, were
developed. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
longin 1, dehydroherbarin 2a and the pigments 2b, 2c,
were found to possess interesting antimicrobial, anti-
parasitic and phytotoxic activities.6±8 In addition, several
1,3-disubstituted-3,4-dehydropyranonaphthoquinones have
been reported to possess signi®cant antineoplastic
activity. Compound 3 +3543R1), a metabolite produced by
Streptomycin tanashiensis K3543, was recently identi®ed as
a very active neoplasm inhibitor.9 The synthetic C+3)-
carbonyl substituted pyranonaphthoquinones 4 have been
found as very effective antitumor chemotherapeutics.10
Naphtho[2,3-c]pyran-5,10-diones are an important class of
compounds due to their broad range of biological
activities.1±4 Their useful biological activities have made
these compounds attractive synthetic objectives. The
development of new synthetic strategies for the synthesis
of pyranonaphthoquinones is still very popular in synthetic
organic chemistry.4,5
In fact, several methods11±13 have been developed for the
synthesis of 3,4-dehydropyranonaphthoquinones but their
use is generally limited. An interesting method has been
developed for the synthesis of 3-aryl substituted pentalongin
derivatives in a one-pot procedure from phenacylpyridinium
ylides and 2-+phenoxymethyl)-1,4-naphthoquinone.14a,b
However, this procedure is not applicable for the synthesis
of 1,3-disubstituted pentalongin derivatives. Concerning the
synthesis of 1,3-disubstituted pentalongin derivatives, only
two procedures have been described so far. The ®rst pro-
cedure concerned a tandem conjugate addition-cyclization
sequence between 2-+1-hydroxyalkyl)-1,4-naphthoquinone
and enamines and imines.15b The second procedure involved
a dif®cult multi-step conversion, including oxidation with
DDQ and Diels Alder cyclocondensation.10
We report herein two simple and convenient one-pot
syntheses of a series of 1,3-disubstituted naphtho[2,3-
c]pyran-5,10-diones via introduction of acylmethyl groups
onto 2-+1-hydroxyethyl)-1,4-naphthoquinone by using acyl-
methylpyridinium ylides and
cyclization.
a ®nal intramolecular
A particular group of naturally occurring 3,4-dehydropyra-
nonaphthoquinones, which include examples such as penta-
2. Results and discussion
Keywords: 1,3-disubstituted naphtho[2,3-c]pyran-5,10-diones; 1,4-naphtho-
quinones; acylmethylation.
Corresponding author; e-mail: norbert.dekimpe@rug.ac.be
The starting material 10, i.e. 1,4-dimethoxy-2-+1-hydroxy-
ethyl)naphthalene, is a suitable substrate for the synthesis of
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020+01)00307-6

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T. Nguyen Van et al. / Tetrahedron 57 ,2001) 4213±4219
Scheme 1.
1,3-disubstituted naphtho[2,3-c]pyran-5,10-diones. The
synthesis of compound 10 is shown in Scheme 1. Naphtho-
quinone 5 was smoothly reduced by treatment with tin+II)
chloride and concentrated hydrogen chloride in methanol
under re¯ux for 3 hours to afford 4-methoxy-1-naphthol 6
in 90% yield. 4-Methoxy-1-naphthol 6 was acetylated with
acetic anhydride in pyridine at room temperature for
12 hours to give the corresponding acetate 7 in 97%
yield.13 This compound 7 underwent Fries rearrangement13
with BF3´Et2O at 1208C for ®ve minutes to afford the
Scheme 2.

T. Nguyen Van et al. / Tetrahedron 57 ,2001) 4213±4219
4215
Scheme 3.
2-acetyl-4-methoxy-1-naphthol 8 in 96% yield. 2-Acetyl-4-
methoxy-1-naphthol 8 was treated with an excess of
dimethyl sulfate and potassium carbonate in dry acetone
under re¯ux16 to afford the corresponding 2-acetyl-1,4-
dimethoxynaphthalene 9 in 98% yield, which underwent
smooth reduction with sodium borohydride16 in methanol
to form the alcohol 10 in 86% yield.
The second procedure for the synthesis of 3,4-dehydro-
naphtho[2,3-c]pyran-5,10-diones 14 is outlined in Scheme
3. The intramolecular condensation of compounds 12 into
compounds 15 was performed in toluene, which allowed the
complete dehydration by treatment with 0.02 equiv. of
p-toluenesulfonic acid over a period of 10±20 minutes,
affording compounds 14 in excellent yields of 90±97%.
Oxidative demethylation16 of alcohol 10 with 2 equivalents
of cerium+IV) ammonium nitrate in aqueous acetonitrile at
room temperature gave the corresponding quinone 11 in
87% yield. The introduction of an acylmethyl group onto
quinone 11 was accomplished by using N-acylmethyl-
pyridinium salts and triethylamine in acetonitrile under
nitrogen at 508C for 2ndash;4 hours.14a±d Several substituted
phenacylmethyl units were introduced, including methyl-,
chloro-, ¯uoro- and methoxysubstituted derivatives. The
®nal intramolecular cyclization of compounds 12 was
performed with 1 equivalent of triethylamine in acetonitrile
under re¯ux for 2 hours.14a,b Unfortunately, in our hands this
procedure was not successful. In this case, the hydroxyl
group of compound 12 is a weak leaving group, compared
to bromo or aryloxy groups in the case of the reported
procedure.14a,b However, the intramolecular cyclization of
compounds 12 has been modi®ed successfully by using 1
equivalent of triethylamine in toluene under re¯ux for two
hours +Scheme 2). Under these condition the corresponding
3,4-dehydronaphtho[2,3-c]pyran-5,10-diones 14 were
obtained in acceptable yields +61±66%). Also the title
compounds 14 with two aliphatic substituents at the 1-
and 3-position became easily accessible in 64±68% yield
+compounds 14g, h).
In conclusion, two convenient and simple methods for the
synthesis of 1,3-disubstituted naphtho[2,3-c]pyran-5,10-
diones from 2-+1-hydroxyethyl)-1,4-naphthoquinone 10
are described. By means of the ®rst method, the novel
quinones 14a±g were obtained in 61±68% yield, while by
the second method, the quinones 14a±d were obtained in
90±97% yield.
3. Experimental
Melting points were determined on a Buchi 535 apparatus.
1H NMR spectra +270 MHz) and 13C NMR spectra
+67 MHz) were recorded with a Jeol JNM-EX 270 NMR
spectrometer. IR spectra were measured with a Perkin
Elmer Model 983 spectrophotometer. Mass spectra were
recorded with a Varian- MAT 112 mass spectrometer
+70 eV).
3.1. Compound data
3.1.1. 4-Methoxy-1-naphthol6. To a solution of 15.8g
+0.1 mol) of 1,4-naphthoquinone 5 in MeOH +200 mL)
was added dropwise a solution of 66.5 g +0.35 mol) SnCl2
in 12 M HCl +70 mL) at room temperature over a period of
20 minutes. The solution was then re¯uxed for 3 hours and
cooled to room temperature. Then MeOH was removed to
1/5 of the starting volume and the residue was poured in
cold water to give a precipitate, which was ®ltered and
dissolved in CH2Cl2. The organic solution was dried
+MgSO4), and the solvent was removed in vacuo to give
13.4 g of compound 6 +77% yield, white solid, mp 126±
The mechanism of the cyclization reaction of compounds 12
is outlined in Scheme 2.14a,b In order to con®rm the mechan-
ism of the reaction, attempts were made to isolate the inter-
mediates 12. Unfortunately, the reaction products were
obtained as a mixture of compound 12 and 15 in a 1:4
ratio. In other words, compounds 12 were not stable and
easily underwent the intramolecular addition to give
compounds 15. Crystallization allowed the isolation of the
pure compounds 15b,c. These results initiated us to develop
a new method for the synthesis of 1,3-disubstituted-3,4-
dehydronaphtho[2,3-c]pyran-5,10-diones 14.
1
126.58C, CH2Cl2). H NMR +CDCl3) d: 8.20±8.23 +1H,
m, H-8), 8.09±8.13 +1H, m, H-5), 7.48±7.52 +2H, m, H-7
and H-6), 6.71 +1H, d, Jˆ8.1 Hz, H-2), 6.62 +1H, d,
Jˆ8.1 Hz, H-3), 3.94 +3H, s, OMe). 13C NMR +CDCl3) d:

4216
T. Nguyen Van et al. / Tetrahedron 57 ,2001) 4213±4219
149.7 +C-1), 145.0 +C-4), 125.9 +C-7), 125.7 +C-2), 125.3
+Cquat), 122.3 +Cquat), 122.0 +C-6), 121.3 +C-3), 107.9
+C-5), 103.4 +C-8), 55.8 +OMe). IR +KBr): 3416 +OH),
1635, 1597, 1456, 1359, 1266, 1093, 1022 cm21. MS, m/z
+%): 174 +M1, 100), 160 +28), 131 +48), 103 +38), 77 +41).
Anal. Calcd. C11H10O2: C 75.84%, H 5.79%; found: C
75.71%, H 5.70%.
a silica gel column +hexane/ethyl acetate, 10/1) to give
13.6 g of compound 9 in 98% yield as a colorless oil. H
1
NMR +CDCl3) d: 8.19±8.25 +1H, m, H-5), 8.15±8.19 +1H,
m, H-8), 7.56±7.63 +2H, m, H-6 and H-7), 6.68 +1H, s, H-2),
4.01 +3H, s, OMe), 3.96 +3H, s, OMe), 2.82 +3H, s, Me). 13C
NMR +CDCl3) d: 199.7 +CyO), 151.8+C-4), 153.4 +C-1),
129.0 +C-3), 128.7 +Cquat), 127.7 +C-7), 127.2 +Cquat),
127.1 +C-6), 123.2 +C-5), 122.5 +C-8), 102.1 +C-2), 63.8
+3H, s, OMe), 55.7 +OMe), 30.9 +Me). IR +NaCl): 1661
+CyO), 1595, 1453, 1368, 1225, 1103 cm21. MS, m/z
+%): 230 +M1, 100), 215 +85), 188 +34), 187 +40). Anal.
Calcd. C14H14O3: C 73.03%, H 6.13%; found: C 72.76%,
H 5.94%.
3.1.2. 1-Acetoxy-4-methoxynaphthalene 7. A mixture of
10.0 g +0.057 mol) of 4-methoxy-1-naphthol 6, Ac2O
+20 mL) and pyridine +30 mL) was stirred at room tempera-
ture for 24 hours.13 The reaction mixture was poured in cold
water and extracted twice with EtOAc. The extract was
washed with 2M HCl, water and dried +MgSO4). Then the
solvent was evaporated in vacuo to give 12 g of product 7
3.1.5. 3-,1-Hydroxyethyl)-1,4-dimethoxynaphthalene 10.
To a solution of 5.0 g +21.74 mmol) of 3-acetyl-1,4-
dimethylnaphthalene 9 in dry MeOH +50 mL) was added
2.41g +65.25 mmol) of sodium borohydride.16 The mixture
was stirred for one hour at room temperature, then quenched
with saturated aqueous ammonium chloride and extracted
with ethyl acetate. The extract was washed with brine,
water, dried +MgSO4), and the solvent was evaporated in
vacuo to give 4.8g of the crude product which was puri®ed
by chromatography on a silica gel column +hexane / ethyl
acetate, 10 / 1) to give 4.3 g of compound 10 +86% yield,
white solid, mp 100±1028C, hexane), +Lit.17 101±1038C).
1H NMR +CDCl3) d: 8.20 +1H, d, Jˆ8.4 Hz, H-8), 7.98 +1H,
d, Jˆ8.4 Hz, H-5), 7.45±7.51 +2H, m, H-7 and H-6), 6.86
+1H, s, H-3), 5.00±5.03 +1H, m, CH±OH), 3.96 +3H, s,
OMe), 3.87 +3H, s, OMe), 1.55 +3H, d, Jˆ6.7 Hz, Me).
13C NMR +CDCl3) d: 152.4 +C-1), 145.4 +C-4), 133.2
+C-2), 128.3 +Cquat), 126.6 +C-6), 126.0 +Cquat), 125.3
+C-7), 122.4 +C-8), 121.8 +C-5), 100.9 +C-3), 64.6 +CH±
OH), 63.9 +3H, s, OMe), 62.7 +OMe), 24.3 +Me). IR
+KBr): 3354 +OH), 2949, 1626, 1596, 1509, 1458, 1361,
1263, 1083 cm21. MS, m/z +%): 232 +M1, 21), 86 +32), 84
+50), 51 +57), 49 +100).
1
+97% yield, white solid, mp 53±548C, hexane). H NMR
+CDCl3) d: 8.25±8.27 +1H, m, H-8), 7.75±7.78 +1H, m,
H-5), 7.38±7.45 +2H, m, H-7 and H-6), 7.05 +1H, d,
Jˆ8.6 Hz, H-2), 6.58 +1H, d, Jˆ8.6 Hz, H-3), 3.78 +3H, s,
OMe), 2.28+3H, s, Me). 13C NMR +CDCl3) d: 169.6 +CyO),
153.2 +C-1), 139.7 +C-2), 127.2 +Cquat), 126.6 +C-6), 125.9
+Cquat), 125.4 +C-7), 122.1 +C-5), 120.6 +C-8), 117.5 +C-2),
102.6 +C-3), 55.2 +OMe), 20.5 +Me). IR +KBr): 1751 +CyO),
1624, 1594, 1579, 1458, 1264, 1087, 883, 766 cm21. MS,
m/z +%): 216 +M1, 11), 174 +77), 159 +63), 131 +10), 105
+10), 91 +12), 77 +15), 43 +100). Anal. Calcd. C13H12O3: C
72.21%, H 5.59%; found: C 72.34%, H 5.69%.
3.1.3. 2-Acetyl-4-methoxy-1-naphthol 8. A ¯ask, contain-
ing 10 g +0.046 mol) of 1-acetoxy-4-methoxynaphthalene 7,
was heated to 1208C and then BF3.Et2O +5 mL) was added
by a syringe.13 After 5 min, the mixture was treated
cautiously with cold water +20 mL). The reaction mixture
was extracted twice with EtOAc. The extract was washed
with NaHCO3, dried +MgSO4), and the solvent was evapo-
rated in vacuo to give 12.2 g of compound 8, which was
puri®ed by ¯ash chromatography to obtain 9.6 g of pure
product 8 +96% yield, white solid, mp 115±1168C, hexane).
1H NMR +CDCl3) d: 13.65 +1H, s, Ar-OH), 8.42 +1H, d,
Jˆ8.4 Hz, H-8), 8.17 +1H, d, Jˆ8.4 Hz, H-5), 7.28±7.69
+2H, m, H-7 and H-6), 6.74 +1H, s, H-3), 3.95 +3H, s,
OMe), 2.64 +3H, s, Me). 13C NMR +CDCl3) d: 203.6
+CyO), 153.3 +C-4), 147.3 +C-1), 130.2 +C-3), 129.6
+C-7), 126.5 +C-6), 125.9 +Cquat), 124.3 +C-8), 121.8
+C-5), 111.9 +Cquat), 100.7 +C-2), 55.6 +OMe), 26.9 +Me).
IR +KBr): 3414 +OH), 1626 +CyO), 1590, 1573, 1453, 1392,
1237, 1109, 1022 cm21. MS, m/z +%): 216 +M1, 18), 202
+42), 187 +23), 160 +30), 159 +29), 129 +29), 94 +46), 43
+100). Anal. Calcd. C13H12O3: C 72.21%, H 5.59%; found:
C 72.29%, H 5.68%.
3.1.6. 3-,1-Hydroxyethyl)-1,4-naphthoquinone 11. To a
solution of 4.0 g +1.7 mmol) of 3-+1-hydroxyethyl)-1,4-
dimethoxynaphthalene 10 in a mixture of water +40 mL)
and acetonitrile +40 mL), was added 18g +0.034 mol) of
ceric ammonium nitrate.16 The mixture was stirred for
15 min, then poured in water and extracted with ether.
The extract was washed with water, brine, dried +MgSO4),
and the solvent was evaporated in vacuo to give 3.02 g of
compound 11 in 87% yield, as yellow powder, 87±888C
1
+hexane), +Lit.17 88±898C). H NMR +CDCl3) d: 8.06±
8.11 +2H, m, H-5 and H-8), 7.73±7.78 +2H, m, H-6 and
H-7), 7.01 +1H, s, H-3), 5.0-5.03 +1H, m, CH±OH), 1.52
+3H, d, Jˆ6.2Hz, Me). 13C NMR +CDCl3) d: 185.6 +CyO),
185.3 +CyO), 152.7 +Cquat), 134.1 +C-6), 133.9 +C-7),
132.9 +C-8), 132.3 +Cquat), 131.9 +Cquat), 126.5 +C-5),
126.2 +C-3), 63.3 +CH±OH), 22.6 +Me). IR +KBr): 3414
+OH), 1657 +CyO), 1617 +CyO), 1592, 1288, 1247, 1155,
1018cm 21. MS, m/z +%): 202 +M1, 96), 187 +64), 160
+100), 159 +97).
3.1.4. 2-Acetyl-1,4-dimethoxynaphthalene 9. A mixture of
14.0 g +49.2 mmol) of 2-acetyl-4-methoxy-1-naphthol 8,
17.6 g +123.4 mmol) of dimethyl sulfate and 15.48g
+123.48mmol) of potassium carbonate in dry acetone
+200 mL) was stirred vigorously and re¯uxed for 24
hours.16 The mixture was cooled to room temperature, and
®ltered to remove potassium carbonate. The ®ltrate was
evaporated in vacuo and the residue was poured in water
and extracted twice with ethyl acetate. The combined
extracts were washed with water, dried +MgSO4) and the
solvent was evaporated in vacuo to give 15.0 g of crude
product. The product was puri®ed by chromatography on
3.1.7. 2-,1-Hydroxyethyl)-3-,acylmethyl)-1,4-naphtho-
quinone 12. To a solution of 0.01 mol of 2-+1-hydroxy-
ethyl)-1,4-naphthoquinone 11 and 0.01 mol of pyridinium
ylide14a±d in acetonitrile +40 mL), under N2 at 508C,
was added dropwise a solution of 0.01 mol of Et3N in

T. Nguyen Van et al. / Tetrahedron 57 ,2001) 4213±4219
4217
acetonitrile +10 mL). The mixture was stirred for 2±4 hours
at room temperature. The solvent was evaporated in vacuo
and the residue was quenched with water and extracted with
CH2Cl2. The extract was washed with 1 M HCl, water and
dried +MgSO4). The solvent was evaporated in vacuo to give
the crude intermediate reaction products 12 and 15 in a 1:4
ratio. These products were treated with 0.01 mol of triethyl-
amine in toluene +10 mL), and the mixture was re¯uxed for
2 hours. The mixture was poured in water and extracted with
EtOAc. The extract was washed with 2 M HCl, water and
dried +MgSO4). The solvent was evaporated in vacuo to give
the crude product, which was puri®ed by ¯ash chromato-
graphy on silica gel +hexane/ethyl acetate, 9/1) to give the
pure 2,3-disubstituted naphthoquinones 14 +®rst procedure).
+C-3), 65.7 +C-1), 34.4 +C-4), 21.1 +Me), 20.5 +Me). IR
+KBr): 3440 +OH), 1662 +CyO), 1644 +CyO), 1592, 1515,
1457, 1405, 1296, 1044 cm21. MS, m/z +%): 334 +M1, 16),
317 +100), 284 +12), 204 +83), 203 +13), 125 +90). Anal.
Calcd. C21H18O4: C 75.43%, H 5.43%; found: C 75.56%,
H 5.47%.
3.1.10. 3-,4-Chlorophenyl)-1-methyl-1H-naphtho[2,3-c]-
pyrane-5,10-dione 14a. Compound 14a was synthesized
according to the ®rst and the second procedure in 63%
and 95% yield, respectively; red powder, mp 142±1438C
1
+hexane). H NMR +CDCl3) d: 1.46 +3H, d, Jˆ6.7 Hz,
Me), 5.85±5.87 +1H, m, H-1), 6.63 +1H, s, H-4), 7.37 +2H,
dd, Jˆ8.6 Hz, and Jˆ2.0 Hz, H-30, H-50), 7.67±7.69 +2H,
m, H-7 and H-8), 7.72 +2H, dd, Jˆ8.6 Hz, and Jˆ2.0 Hz,
H-20 and H-60), 8.04±8.11 +2H, m, H-6 and H-9). 13C NMR
+CDCl3) d: 182.5 +CyO), 181.7 +CyO), 157.7 +C-3), 136.7
+Cquat), 135.9 +Cquat), 133.9 +C-8), 133.2 +C-7), 132.6
+Cquat), 131.8+Cquat), 131.7 +Cquat), 128.8+C-3 0, C-50),
128.1 +Cquat), 127.4 +C-20, C-60), 126.4 +C-6), 125.9 +C-9),
92.7 +C-4), 69.9 +C-1), 17.9 +Me). IR +KBr): 1667 +CyO),
To 1 mmol of the mixture of the intermediates 12 and 15,
dissolved in toluene +15 mL), was added 0.02 mmol of
p-TsOH. The reaction mixture was re¯uxed for 10 min.
The mixture was poured in water and extracted with
EtOAc. The extract was washed with water and dried
+MgSO4). The solvent was evaporated in vacuo to give the
crude product, which was puri®ed by ¯ash chromatography
on silica gel +hexane/ethyl acetate, 9/1) to give the
pure 2,3-disubstituted naphthoquinones 14a±d +second
procedure).
1642 +CyO), 1589, 1543, 1481, 1334, 1265, 1006 cm21
.
MS, m/z +%): 338/336 +M1, 1), 286 +13), 105 +11), 99
+23), 89 +24), 71 +30), 43 +100). Anal. Calcd. C20H13O3Cl:
C 71.33%, H 3.89%; found: C 70.93%, H 3.77%.
3.1.8.
3-,4-Fluorophenyl)-3-hydroxy-1-methyl-3,4-di-
3.1.11. 3-,4-Fluorophenyl)-1-methyl-1H-naphtho[2,3-c]-
pyrane-5,10-dione 14b. Compound 14b was synthesized
according to the ®rst and the second procedure in 62%
and 90% yield, respectively; red powder, mp 154±1558C
hydro-1H-naphtho[2,3-c]pyran-5,10-dione 15b. The
crude reaction mixture of compound 12b and 15b was
recrystallized in hexane to give the pure compound 15b as
1
1
a red powder, mp 128±1298C +hexane). H NMR +CDCl3)
+hexane). H NMR +CDCl3) d: 1.47 +3H, d, Jˆ6.5 Hz,
d: 1.68+3H, d, Jˆ6.6 Hz, Me), 2.37 +1H, s, CH3), 2.53 +1H,
dd, J1ˆ16.5 Hz, J2ˆ2.6 Hz, ABY system, H-4a), 3.23 +1H,
dd, J1ˆ16.5 Hz, J2ˆ2.0 Hz, ABY system, H-4b), 5.15±5.19
+1H, m, H-1), 7.09 +2H, dd, Jˆ7.9 Hz and Jˆ8.5 Hz, H-30,
H-50), 7.64 +2H, dd, Jˆ7.9 Hz and Jˆ8.5 Hz, H-20 and
H-60), 7.71±7.78 +2H, m, H-7 and H-8), 8.06±8.12 +2H,
m, H-6 and H-9); 13C NMR +CDCl3) d: 183.7 +CyO),
Me), 5.85±5.92 +1H, m, H-1), 6.62 +1H, s, H-4), 7.10 +2H,
dd, Jˆ8.4 Hz, and Jˆ8.6 Hz, H-30, H-50), 7.66±7.73 +2H,
m, H-7 and H-8), 7.80 +2H, dd, Jˆ8.4 Hz, and Jˆ8.6 Hz, H-
20 and H-60), 8.06±8.13 +2H, m, H-6 and H-9). 13C NMR
+CDCl3) d, 182.7 +CyO), 181.8 +CyO), 164.2 +d,
1JCFˆ247.9, CF), 158.0 +C-3), 136.2 +Cquat), 133.9 +C-7),
133.1 +C-8), 132.7 +Cquat), 131.7 +Cquat), 129.7 +Cquat),
129.6 +Cquat), 128.4 +C-9), 128.3 +C-6), 127.7 +Cquat),
126.4 +C-60), 125.9 +C-20), 115.8+C-3 0), 115.5 +C-50),
91.9 +C-4), 69.9 +C-1), 17.9 +Me). IR +KBr): 1655 +CyO),
1
183.4 +CyO), 162.7 +d, JCFˆ247.9, CF), 144.9 +Cquat),
140.3 +Cquat), 139.2 +Cquat), 133.8+C-7), 133.6 +C-8),
132.9 +Cquat), 131.2 +Cquat), 127.0 +C-30), 126.9 +C-50,
C-5), 126.3 +C-9), 115.4 +C-20), 115.0 +C-60), 94.9 +C-3),
65.8+C-1), 34.5 +C-4), 20.4 +Me). IR +KBr): 3452 +OH),
1666 +CyO), 1637 +CyO), 1595, 1509, 1452, 1406, 1336,
1185, 1078 cm21. MS, m/z +%): 338+M 1, 40), 320 +60), 208
+33), 127 +39), 100 +10), 93 +100). Anal. Calcd. C20H15O4F:
C 71.00%, H 4.47%; found: C 71.06%, H 4.67%.
1640 +CyO), 1586, 1533, 1495, 1331, 1297, 1156 cm21
.
MS, m/z +%): 320 +M1, 2), 304 +18), 99 +26), 89 +36), 57
+44), 43 +100). Anal. Calcd. C20H13O3F: C 74.99%, H
4.09%; found: C 75.03%, H 3.93%.
3.1.12. 1-Methyl-3-,4-methylphenyl)-1H-naphtho[2,3-c]-
pyrane-5,10-dione 14c. Compound 14c was synthesized
according to the ®rst and the second procedure in 65%
and 97% yield, respectively; red powder, mp 122±1268C
3.1.9. 3-Hydroxy-3-,4-methylphenyl)-1-methyl-3,4-di-
hydro-1H-naphtho[2,3-c]pyran-5,10-dione 15c. The
crude reaction mixture of compound 12c and 15c was
recrystallized in hexane to give the pure compound 15c as
1
+hexane). H NMR +CDCl3) d: 1.47 +3H, d, Jˆ6.7 Hz,
Me), 2.40 +Ar-Me), 5.86±5.93 +1H, m, H-1), 6.65 +1H, s,
H-4), 7.24 +2H, d, Jˆ9.4 Hz, H-30, H-50), 7.68±7.75 +4H, m,
H-7, H-8, H-20 and H-60), 8.06±8.13 +2H, m, H-6 and H-9).
13C NMR +CDCl3) d: 183.0 +CyO), 181.7 +CyO), 159.4
+C-3), 141.3 +Cquat), 136.5 +Cquat), 133.9 +C-8), 133.0
+C-7), 132.8+Cquat), 131.8+Cquat), 130.7 +Cquat), 129.4
+C-30, C-50), 127.4 +Cquat), 126.4 +C-9), 126.3 +C-20, C-60),
125.9 +C-6), 91.7 +C-4), 69.8+C-1), 21.5 +Ar- Me), 17.8
+Me). IR +KBr): 1667 +CyO), 1639 +CyO), 1538, 1333,
1300, 814 cm21. MS, m/z +%): 316 +M1, 1), 301 +9), 286
+20), 103 +20), 99 +24), 71 +50), 43 +100). Anal. Calcd.
C21H16O3: C 79.73%, H 5.10%; found: C 79.86%, H 5.19%.
1
a red powder, mp 136±1388C +hexane). H NMR +CDCl3)
d: 1.67 +3H, d, Jˆ6.9 Hz, Me), 2.37 +1H, s, CH3), 2.55 +1H,
dd, J1ˆ18.6 Hz, J2ˆ2.3 Hz, ABX system, H-4a), 3.21 +1H,
dd, J1ˆ18.6 Hz, J2ˆ3.5 Hz, ABX system, H-4b), 5.10±5.18
+1H, m, H-1), 7.26 +2H, d, Jˆ7.9 Hz, H-20, H-60), 7.62 +2H,
d, Jˆ7.9 Hz, H-30 and H-50), 7.68±7.75 +2H, m, H-7 and
H-8), 8.05±8.16 +2H, m, H-6 and H-9); 13C NMR +CDCl3)
d: 183.8 +CyO), 183.5 +CyO), 145.1 +Cquat), 141.5
+Cquat), 139.6 +Cquat), 133.9 +Cquat), 133.7 +C-7), 133.5
+C-8), 132.3 +Cquat), 131.8 +Cquat), 129.4 +C-30), 129.1
+C-50, C-5), 128.5 +C-9), 126.2 +C-20), 124.8+C-6 ), 95.1
0

4218
T. Nguyen Van et al. / Tetrahedron 57 ,2001) 4213±4219
3.1.13. 1-Methyl-3-,4-methoxyphenyl)-1H-naphtho[2,3-
c]-pyrane-5,10-dione 14d. Compound 14d was synthesized
according to the ®rst and the second procedure in 61% and
92% yield, respectively; red powder, mp 152±1538C
H-5, H-9). 13C NMR +CDCl3) d: 183.1 +CyO), 181.9
+CyO), 172.6 +C-3), 136.4 +Cquat), 133.7 +C-8), 132.9
+C-7), 132.6 +Cquat), 131.8+Cquat), 126.7 +Cquat), 126.3
+C-9), 125.7 +C-5), 89.6 +C-4), 69.1 +C-1), 27.3 +Me3), 17.4
+C1-Me). IR +KBr): 1666 +CyO), 1650 +CyO), 1580, 1557,
1500, 1357, 1331, 1299, 1265 cm21. MS, m/z +%): 282 +M1,
1), 225 +10), 102 +13), 187 +9), 163 +13), 160 +14), 149 +25),
129 +22), 94 +52), 57 +67), 55 +50), 43 +100). Anal. Calcd.
C18H18O3: C 76.57%, H 6.43%; found: C 76.24%, H
6.21%.
1
+hexane). H NMR +CDCl3) d: 1.46 +3H, d, Jˆ6.7 Hz,
Me), 3.85 +OMe), 5.85±5.88 +1H, m, H-1), 6.57 +1H, s,
H-4), 6.94 +2H, d, Jˆ9.2 Hz, H-30, H-50), 7.26±7.69 +2H,
m, H-7 and H-8), 7.75 +2H, d, Jˆ9.2 Hz, H-20 and H-60),
8.05±8.08 +2H, m, H-6 and H-9). 13C NMR +CDCl3) d:
183.0 +CyO), 181.6 +CyO), 161.9 +C-40), 159.3 +C-3),
136.6 +Cquat), 133.9 +C-8), 132.9 +C-7), 132.9 +Cquat),
131.8+Cquat), 12.81 +C-3 0, C-50), 126.8+Cquat), 126.4
3.1.17. 1-Methyl-3-methyl-1H-naphtho[2,3-c]-pyrane-5,10-
dione 14h. Compound 14h was synthesized according to the
®rst procedure in 68% yield; red powder, mp 83±848C
0
+C-9), 126.0 +Cquat), 125.8+C-6), 114.0 +C-6 , C-20), 90.8
+C-4), 69.8+C-1), 55.4 +OMe), 17.8+Me). IR +KBr): 1662
+CyO), 1639 +CyO), 1591, 1538, 1500, 1333, 1300, 1268,
1256, 1175 cm21. MS, m/z +%): 332 +M1, 1), 316 +7), 103
+13), 89 +75), 85 +17), 71 +33), 57 +43), 43 +100). Anal.
Calcd. C21H16O4: C 75.89%, H 4.85%; found: C 75.62%,
H 4.68%.
1
+hexane) +lit15a 74±758C). H NMR +CDCl3) d: 1.41 +3H,
d, Jˆ6.7 Hz, C1-Me), 2.02 +3H, s, Me), 5.69±5.71 +H, m,
H-1), 5.89 +1H, s, H-4), 7.26±7.72 +2H, m, H-7 and H-8),
8.03±8.09 +2H, m, H-6 and H-9). 13C NMR +CDCl3) d:
182.9 +CyO), 182.0 +CyO), 162.7 +C3), 136.1 +Cquat),
133.9 +C-8), 133.0 +C-7), 132.6 +Cquat), 131.7 +Cquat),
126.5 +Cquat), 126.3 +C-9), 125.8+C-6), 93.2 +C-4), 69.7
+C-1), 21.0 +C3-Me), 18.1 +C1-Me). IR +KBr): 1669 +CyO),
3.1.14. 3-,2,4-Dimethoxyphenyl)-1-methyl-1H-naphtho-
[2,3-c]-pyrane-5,10-dione 14e. Compound 14e was synthe-
sized according to the ®rst procedure in 67% yield; red
1654 +CyO), 1583, 1560, 1364, 1330, 1297, 1098 cm21
MS, m/z +%): 240 +M1, 34), 225 +100), 197 +19), 168+9),
141 +11), 115 +13), 105 +13), 43 +41).
.
1
powder, mp 143±1448C. H NMR +CDCl3) d: 1.47 +3H, d,
Jˆ6.7 Hz, Me), 3.82 +3H, s, OMe), 3.94 +3H, s, OMe),
5.81±5.88 +1H, m, H-1), 6.90 +1H, s, H-4), 6.93 +1H, d,
Jˆ6.2 Hz, H-30), 7.10 +1H, s, H-60), 7.32 +1H, d,
Jˆ6.7 Hz, H-50), 7.64±7.74 +2H, m, H-7 and H-8), 8.05±
8.11 +2H, m, H-6, H-9). 13C NMR +CDCl3) d: 183.0 +CyO),
Acknowledgements
0
181.9 +CyO), 155.9 +C-3), 153.3 +C-20), 152.8+C-5 ), 136.4
The authors are indebted to the Janssen Research Founda-
tion for ®nancial support.
+Cquat), 133.8+C-)8, 133.0 +C-7), 132.8+Cquat), 131.9
+Cquat), 127.8+Cquat), 126.4 +C-9), 125.8+C-6), 123.0
+Cquat), 116.8+C-6 0), 113.9 +C-30), 112.6 +C-50), 98.0
+C-4), 69.3 +C-1), 56.1 +OMe), 55.8+OMe), 17.6 +Me). IR
+KBr): 1662 +CyO), 1640 +CyO), 1592, 1547, 1333, 1295,
1267, 1177cm21. MS, m/z +%): 362 +M1, 1), 174 +34), 163
+13), 159 +29), 97 +29), 7 +56), 57 +100). Anal. Calcd.
C22H18O5: C 72.92%, H 5.01%; found: C 72.56%, H 4.89%.
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