Selective synthesis of benzyl enol ethers of β-dicarbonyl compounds in basic condition and the application towards synthesis of naphthoquinones

Article abstract of DOI:10.3987/COM-13-S(S)66

Selective synthesis of benzyl enol ether of β-tetronic acids and β-dicarbonyl compounds in basic condition was examined. Benzylation of α-methyl-β-tetronic acid with benzyl tosylate in the presence of potassium carbonate gave the corresponding benzyl enol ether exclusively. The reaction of β-tetronic acid and cyclic 1,3-diketones gave the O-benzyl adducts preferentially than the C,O-dibenzylated ones. Diels-Alder reaction of furan derived the benzyl enol ether of α-methyl-β-tetronic acid and benzyne furnished the functionalized napthoquinone derivatives.

Full text of DOI:10.3987/COM-13-S(S)66

HETEROCYCLES, Vol. 88, No. 1, 2014
817
HETEROCYCLES, Vol. 88, No. 1, 2014, pp. 817 - 825. © 2014 The Japan Institute of Heterocyclic Chemistry
Received, 29th June, 2013, Accepted, 24th July, 2013, Published online, 1st August, 2013
DOI: 10.3987/COM-13-S(S)66
SELECTIVE SYNTHESIS OF BENZYL ENOL ETHERS OF
-DICARBONYL COMPOUNDS IN BASIC CONDITION AND THE
APPLICATION TOWARDS SYNTHESIS OF NAPHTHOQUINONES†
Kazuaki Katakawa, Dai Yonenaga, Tomoyo Terada, Naoya Aida, Airi
Sakamoto, Keishi Hoshino, and Takuya Kumamoto*
Department of Organic Synthetic Chemistry, Research Institute of Pharmaceutical
Sciences, Musashino University, 1-1-20, Shinmachi, Nishitokyo-city, Tokyo
202-8585, Japan. e-mail: t_kum632@musashino-u.ac.jp
Abstract – Selective synthesis of benzyl enol ether of -tetronic acids and
-dicarbonyl compounds in basic condition was examined. Benzylation of
-methyl--tetronic acid with benzyl tosylate in the presence of potassium
carbonate gave the corresponding benzyl enol ether exclusively. The reaction of
-tetronic acid and cyclic 1,3-diketones gave the O-benzyl adducts preferentially
than the C,O-dibenzylated ones. Diels-Alder reaction of furan derived the
benzyl enol ether of -methyl--tetronic acid and benzyne furnished the
functionalized napthoquinone derivatives.
Enol ethers of -tetronic acids (4-O-alkyl -tetronates) 1 are versatile building blocks in natural product
synthesis and medicinal chemistry (Figure 1).1 Synthesis of these compounds is normally achieved by
treating -tetronic acids 2 and alcohols in the presence of acid catalyst.2 Mitsunobu reaction condition3
and alkylation in basic condition4 are another candidates and can be applicable to acid-sensitive substrates.
The drawback of these conditions is the selectivity of C- / O-alkylation, in which C-alkylated 3 (or
C,O-dialkylated 4) -dicarbonyl compounds can be generated in this reaction system. For example,
CsF-mediated O-selective alkylation of tetronic acid was achieved in high selectivity with alkyl halides
with low reactivity such as ethyl iodide, however, low selectivity was observed when more reactive alkyl
halide such as benzyl bromide was utilized.4b As a part of our projects of synthetic studies of natural
products including naphthoquinones such as teretifoliones B (5
),5 we have planned construction of oxygen-
†This article is dedicated to Professor Victor Snieckus on the occasion of his 77th birthday.

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HETEROCYCLES, Vol. 88, No. 1, 2014
functionalized naphthoquinones via Diels-Alder reaction (DAR) of furans from enol ethers of -tetronic
acids and benzyne.6 In this report, we wish to report the selective synthesis of benzyl enol ethers of
-tetronic acids and some -diketones in basic condition and the application of the benzyl enol ether to
naphthoquinone synthesis via DAR with benzyne.
O
RO
R'
HO
R'
O
RO
R
HO
R'
O
O
O
O
O
O
O
O
O
R'
R
3
1
2
4
5
O
teretifolione B (R' = H),
methylteretifolione B (R' = Me)
(R' = H or alkyl)
Figure 1. Structures of -tetronic acid derivatives 1-4 and teretifoliones B (5)
At first, benzylation of -methyl--tetronic acid (6)7 was examined. Treatment of 6 and benzyl bromide
in the presence of potassium carbonate as a base in N,N-dimethylformamide (DMF)4c gave a complex
mixture including desired 7, which was isolated in 22% after purification (Table 1, run 1). Utilization of
cesium carbonate instead of potassium carbonate gave similar result (run 2). Reactions with cesium
fluoride4a and benzyl bromide or chloride afforded a mixture of 7 and undesired C-benzylated product 8
Table 1. Benzylation of -methyl--tetronic acid (6) in basic conidition
HO
BnO
O
BnX
O
O
O +
O
O
O
Bn
Me
base
DMF
rt, 18-24 h
Me
Me
6
7
8
run
1
X in BnX (eq)
Br (1.0)
base (eq)
7 : 8a
Isolated 7 (%)
K2CO3 (2.0)
Cs2CO3 (2.0)
CsF (2.0)
many spots
many spots
1 : 2
22
28
-
2
Br (1.0)
3
Br (1.0)
4
Cl (1.0)
CsF (2.0)
1 : 1
-
5
OTs (1.0)
OTs (1.0)
OTs (1.0)
OTs (1.5)
CsF (2.0)
3 : 1
1 : 0b
1 : 0b
1 : 0b
48
68
60
86
6
Cs2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (3.0)
7
8
a Estimated from integration of 1H-NMR of the crude products. b 8 was not observed in 1H-NMR of the
crude products.

HETEROCYCLES, Vol. 88, No. 1, 2014
819
in low selectivity (runs 3 and 4). Benzyl tosylate (BnOTs, 9), prepared from benzyl alcohol and tosyl
chloride in solvent-free condition8 was applied to this reaction and the ratio of 7 and 8 was improved to
3 : 1. 7 was isolated in 48% yield (run 5). Reaction with cesium and potassium carbonates gave 7
exclusively. 8 was not observed in 1H-NMR of crude product (runs 6 and 7). Reaction with increased
amounts of both reagents benzyl tosylate and potassium carbonate gave 7 in 86% as isolated yield (run 8).
Benzylation of other -dicarbonyl compounds was examined. Benzylation of -tetronic acid (10a) gave
the corresponding O-benzylated product 11a exclusively with small amount of C,O-dibenzylated one 12a,
generated through the reaction of initial C-benzylation followed by O-benzylation. Generation of
C,C-dibenzylated product 13 was not observed (Table 2, run 1). BnOTs (9) prepared in solution phase
with modified reported procedure9 gave similar result (run 2). Reaction of cyclopentane-1,3-dione (10b)
gave a mixture of O-benzylated 11b and C,O-dibenzylated products 12b in the same ratio as 10a (run 3),
however, the selectivity was decreased to 5 : 1 in the case of cyclohexane-1,3-dione (10c) (run 4). Trial
for the benzylation of Merdrum’s acid (14) gave only C,C-dibenzylated product (data not shown).10
Table 2. Benzylation of -dicarbonyl compounds 10 with BnOTs (9)a
HO
BnO
BnO
O
HO
O
O
BnOTs (9)
a: X = O
b: X = CH2
c: X = CH2CH2
X
X
X
Bn
Bn
X
K2CO3
DMF
rt, 18 h
O
Bn
O
O
O
O
10
11
12
13
14
run
1
2c
substrate
10a
11 : 12b
15 : 1
15 : 1
15 : 1
5 : 1
Isolated 11 (%)
72
77
59
52
10a
3
10b
4
10c
a 9 (1.5 eq) and K2CO3 (3.0 eq) was used otherwise noted. b Estimated from integration of 1H-NMR of
the crude products. c 9 (2.0 eq) prepared in solution phase was used.
Benzyl enol ether of -methyl--tetronic acid 7 was applied to naphthoquinone synthesis (Scheme 1).
Furanone 7 was converted to furan 15,11 which were reacted with benzyne (17) in situ prepared from iodo
triflate 1412 and n-butyllitium to give epoxynaphthalene 19, which has decomposed in the course of
aqueous workup to give benzyloxynaphthoquinone 2013 in 32% yield from 7. DAR of furan 16 and
benzyne (17) in the same manner gave naphthol 22 through epoxynaphthalene 21 in 46% isolated yield.
Treatment of crude 22 with tetrabutylammonium fluoride (TBAF) gave 20 in 43% from 16. Oxidation
of crude 22 with aqueous iron (III) chloride in methanol14 gave 20 and hydroxynaphthoquinone 2315 in
37% and 12% yields, respectively.

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HETEROCYCLES, Vol. 88, No. 1, 2014
BnO
Me
BnO
Me
OH
(c)
BnO
Me
(a) or (b)
O
O
O
BnO
Me
O
(from 16)
OR1
OR1
15: R1 = TMS
16: R1 = TIPS
7
19: R1 = TMS
21: R1 = TIPS
OTIPS
22
17
(d)
(from 15)
TfO
O
R2O
Me
I
(e) or (f)
20: R2 = Bn
23: R2 = H
18
O
Scheme 1. Synthesis of napthoquinones 20 and 23. Conditions: (a) 1) n-BuLi, THF, -78 - -40 °C; 2)
TMSCl, -40 - 0 °C, (b) TIPSOTf, Et3N, CH2Cl2, 0 °C, 1 h (62%), (c) n-BuLi, -78 C, 45 min, (d) workup
(20: 32%); (e) TBAF, THF, 1 h, rt (20: 43%), (f) aq FeCl3, methanol, rt, 1.5 h (20: 37%, 23: 12%).
In summary, synthesis of benzyl enol ether of -tetronic acids with O-selective benzylation in basic
condition was achieved by utilization of benzyl tosylate and potassium carbonate. Other -dicarbonyl
compounds were also O-benzylated selectively in this condition except Merdrum’s acid. Application of
the enol ether of -tetronic acid to DAR with bezyne gave desired functionalized naphthoquinones in
moderate yield. Further research to improve the yield of DAR and synthetic studies towards
naphthoquinone natural products with modified benzynes are now in progress.
EXPERIMENTAL
Melting points were determined on a Yanagimoto micro melting point hot-stage instrument and are
uncorrected. IR spectra were recorded on a JASCO FT/IR-4100 spectrophotometer with Attenuated
Total Reflectance Unit ATR PRO450-S. 1H- (400 MHz) and 13C-NMR (100 MHz) spectra were
recorded with JEOL JNM ECX 400 spectrometer with deuterated chloroform as a solvent and
tetramethylsilane as an internal reference. EIMS was recorded on a JEOL GC-Mate II. Anhydrous
CH2Cl2, DMF were purchased and THF was used as received as a gift from Wako Chemicals. TMSCl
was used after distillation from CaH2.
Benzyl tosylate (9)
(Synthesis in solvent-free condition) A mixture of tosyl chloride (2.8 g, 15 mmol) and K2CO3 (9.2 g, 67
mmol) was ground in mortar under N2 atmosphere. Benzyl alcohol (2.8 g, 15 mmol) was added
portionwise and the mixture was ground for further 1 h. Et2O (100 mL) was added and the mixture was
filtered through a pad of Celite®. The filtrate was washed with ice-water (1 x 10 mL) and brine (1 x 10
mL) and dried over Na2SO4 in refrigerator. The solvent was evaporated in vacuo and the residue was

HETEROCYCLES, Vol. 88, No. 1, 2014
821
washed with hexane - Et2O (1 : 4) to give 9 (2.1 g, 54%) as colorless needles.
mp 57-58 °C. IR no characteristic absorption. 1H-NMR  (ppm) 2.44 (3H, s, CH3), 5.06 (2H, s, CH2),
7.23-7.30 (2H, m, Ar-H), 7.30-7.34 (5H, m, Ar-H), 7.80 (2H, d, J = 8.2 Hz, Ar-H).
(Synthesis in solution phase) To a solution of benzyl alcohol (0.1 mL, 1.00 mmol), Et3N (0.22 mL, 1.58
mmol), DMAP (30 mg, 0.25 mmol) in CH2Cl2 (5 mL), a solution of tosyl chloride (286 mg, 1.50 mmol)
in CH2Cl2 (5 mL) was added at 0 °C. After stirring at 0 °C for 30 min, the reaction mixture was washed
with H2O (1 x 10 mL), saturated aqueous NaHCO3 (2 x 10 mL), and brine (1 x 2 mL) and dried over
Na2SO4. The solvent was evaporated in vacuo to give 9 (294 mg, 78%) as a colorless oil.
4-Benzyloxy-3-methyl-5H-furan-2-one (7)
Under N2 atmosphere, DMF (1.8 mL) was added to a mixture of 6 (101 mg, 0.88 mmol), 9 (345 mg, 1.31
mmol), prepared in solvent-free condition, and K2CO3 (365 mg, 2.64 mmol) at rt and the reaction mixture
was stirred at rt for 24 h. H2O (1.0 mL) was added and the whole was extracted with AcOEt (3 x 10
mL). The combined organic layer was washed with saturated aqueous NH4Cl, H2O, saturated aqueous
NaHCO3, and brine (each 1 x 1 mL), and dried over Na2SO4. The solvent was evaporated in vacuo to
give a yellow oil, which was purified by column chromatography (CC) (SiO2, hexane – AcOEt 4 : 1) to
give 7 as pale yellow solids (154 mg, 86%).
mp 111-112 °C (from hexane – AcOEt = 1 : 1). IR max (cm-1) 1727, 1650. 1H-NMR  (ppm) 1.86 (3H,
t, J = 1.5 Hz, CH3), 4.63 (2H, q, J = 1.5 Hz, CH2), 5.22 (2H, s, CH2), 7.34-7.45 (5H, m, Ar-H).
13C-NMR  (ppm) 7.4, 66.0, 72.3, 99.6, 127.3, 129.0, 135.0, 171.2, 175.2 (one C missing). HR-EIMS
m/z 204.0773 (Calcd for C12H12O3: 204.0787).
3-Benzyl-3-methylfuran-2,4-dione (8)
A colorless oil. IR max (cm-1) 1749. 1H-NMR  (ppm) 1.43 (3H, s, CH3), 3.04 (1H, d, J = 13.1 Hz,
CH2), 3.13 (1H, d, J = 13.1 Hz, CH2), 3.64 (1H, d, J = 17.2 Hz, CH2), 4.36 (1H, d, J = 17.2 Hz, CH2),
7.10-7.13 (2H, m, Ar-H), 7.23-7.30 (3H, m, Ar-H). 13C-NMR  (ppm) 19.9, 43.0, 51.0, 72.7, 127.9,
128.9, 129.4, 134.3, 176.9, 210.6. HR-EIMS m/z 204.0809 (Calcd for C12H12O3: 204.0787).
4-Benzyloxy-5H-furan-2-one (11a)
Colorless powder. mp 110-111 °C (from hexane – AcOEt = 1 : 1) (lit2a 103-104 °C). IR max (cm-1)
1739, 1615. 1H-NMR  (ppm) 4.68 (2H, d, J = 1.1 Hz, CH2), 5.08 (2H, s, CH2), 5.19 (1H, t, J = 1.1 Hz,
CH), 7.36-7.43 (5H, m, Ar-H).

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HETEROCYCLES, Vol. 88, No. 1, 2014
3-Benzyl-4-benzyloxy-5H-furan-2-one (12a)
A colorless oil. IR max (cm-1) 1745, 1666. 1H-NMR  (ppm) 3.62 (2H, s, CH2), 4.68 (2H, s, CH2),
5.13 (2H, s, CH2), 7.19-7.28 (8H, m, Ar-H), 7.37-7.40 (2H, m, Ar-H). 13C-NMR  (ppm) 28.1, 65.7,
72.2, 103.8, 126.4, 127.1, 128.4, 128.5, 129.0 (overlapped), 134.8, 139.0, 172.2, 174.4. HR-EIMS m/z
280.1093 (Calcd for C18H16O3: 280.1100).
3-Benzyloxycyclopent-2-en-1-one (11b)
Colorless solids. mp 47.5-49.5 °C. IR max (cm-1) 1702, 1677. 1H-NMR  (ppm) 2.45-2.48 (2H, m,
CH2), 2.66-2.69 (2H, m, CH2), 5.03 (2H, s, CH2), 5.41 (1H, t, J = 1.1 Hz, CH), 7.37-7.43 (5H, m, Ar-H).
13C-NMR  (ppm) 28.6, 34.0, 73.6, 105.5, 127.9, 128.76, 128.78, 134.5, 189.7, 205.8. HR-EIMS m/z
188.0841 (Calcd for C12H12O2: 188.0837).
2-Benzyl-3-benzyloxycyclopent-2-en-1-one (12b)
A colorless oil. IR max (cm-1) 1687, 1628. 1H-NMR  (ppm) 2.44-2.47 (2H, m, CH2), 2.68 (2H, t, J =
4.9 Hz, CH2), 3.51 (2H, s, CH2), 5.21 (2H, s, CH2), 7.14-7.18 (1H, m, Ar-H), 7.20-7.28 (6H, m, Ar-H),
7.32-7.38 (3H, m, Ar-H). 13C-NMR  (ppm) 25.1, 27.4, 33.6, 70.9, 120.8, 125.8, 126.9, 128.2, 128.5,
128.7, 128.8, 135.8, 140.1, 184.1, 204.1. HR-EIMS m/z 278.1313 (Calcd for C19H18O2: 278.1307).
3-Benzyloxycyclohex-2-en-1-one (11c)
Colorless solids. mp 64-65 °C (lit16 67 °C). IR max (cm-1) 1648, 1602. 1H-NMR  (ppm) 2.01 (2H,
quint., J = 6.5 Hz, CH2), 2.37 (2H, t, J = 6.6 Hz, CH2), 2.48 (2H, t, J = 6.3 Hz, CH2), 4.89 (2H, s, CH2),
5.49 (1H, s, CH), 7.34-7.42 (5H, m, Ar-H). 13C-NMR  (ppm) 21.2, 29.0, 36.7, 70.4, 103.4, 127.8,
128.5, 128.7, 135.0, 177.5, 199.7. HR-EIMS m/z 202.0997 (Calcd for C13H14O2: 202.0994).
2-Benzyl-3-benzyloxycyclohex-2-en-1-one (12c)
A colorless oil. IR max (cm-1) 1639, 1606. 1H-NMR  (ppm) 1.97 (2H, quint., J = 6.5 Hz, CH2), 2.37
(2H, t, J = 6.8 Hz, CH2), 2.60 (2H, t, J = 6.3 Hz, CH2), 3.67 (2H, s, CH2), 5.01 (2H, s, CH2), 6.95-7.14
(1H, m, Ar-H), 7.16-7.24 (6H, m, Ar-H), 7.30-7.38 (3H, m, Ar-H). 13C-NMR  (ppm) 20.9, 25.6, 27.9,
36.4, 69.5, 119.8, 125.3, 127.0, 127.9, 128.2, 128.7, 128.8, 136.2, 141.6, 171.6, 197.9. HR-EIMS m/z
292.1439 (Calcd for C20H20O2: 292.1463).
2-Benzyloxy-3-methylnaphthalene-1,4-dione (20)
To a solution of 7 (50 mg, 0.24 mmol) in THF (1.5 mL), n-BuLi (1.36 M in hexane, 0.18 mL, 0.25

HETEROCYCLES, Vol. 88, No. 1, 2014
823
mmoL) was added at -78 °C and the reaction mixture was stirred at -40 °C for 35 min. TMSCl (31 L,
0.24 mmol) was added and the reaction mixture was stirred at -40 °C for 10 min and at 0 °C for 1 h. A
solution of 18 (86 mg, 0.24 mmol) in THF (1.5 mL) and n-BuLi (1.36 M in hexane, 0.18 mL, 0.25 mmol)
were added successively at -78 °C and the reaction mixture was stirred at -78 °C for 45 min. H2O (1
mL) was added and the whole was extracted with AcOEt (3 x 5 mL). The combined organic layer was
washed with brine (1 x mL), dried over Na2SO4, and evaporated in vacuo. The residue was purified by
CC (SiO2, hexane – AcOEt = 100 : 0 to 85 : 15) to give 20 as a brown oil (25 mg, 37%).
(lit13a mp 40-42 °C) IR max (cm-1) 1667, 1651, 1614, 1594. 1H-NMR  (ppm) 2.04 (3H, s, CH3), 5.42
(2H, s, CH2), 7.31-7.39 (3H, m, Ar-H), 7.41-7.45 (2H, m, Ar-H), 7.67-7.72 (2H, m, Ar-H), 8.05-8.08 (2H,
m, Ar-H). 13C-NMR  (ppm) 9.7, 75.1, 126.2, 128.3, 128.5, 128.6, 131.5, 132.0, 133.1, 133.3, 133.7,
136.7, 156.8, 181.4, 185.7 (one C missing). HR-EIMS m/z 278.0946 (Calcd for C18H14O3: 278.0943).
4-Benzyloxy-3-methyl-2-triisopropyloxyfuran (16)
According the reported procedure,17 to a solution of 7 (120 mg, 0.59 mmol) and Et3N (0.11 mL, 0.79
mmol) in CH2Cl2 (0.6 mL), TIPSOTf (0.17 mL, 0.63 mmol) was added at 0 °C and the whole was stirred
at 0 °C for 1 h. The mixture was diluted with hexane (anhydrous, 3.0 mL), washed with ice-cooled
aqueous half saturated NaHCO3 (2 x 1.2 mL) and ice-cooled brine (1 x 1.2 mL), and dried over MgSO4.
The solvent was evaporated in vacuo and the residue was suspended in hexane (anhydrous, 1.2 mL) then
filtered. The filtrate was concentrated in vacuo to give 16 as colorless solids (177 mg) as a mixture of
16, TIPSOH and 7 in 1 : 0.57 : 0.13 (74% w/w purity, 62% yield as 16).
Colorless solids. 1H-NMR  (ppm) 1.08 (18H, d, J = 7.1 Hz, 6 x CH3), 1.19-1.28 (3H, m, 3 x CH), 1.80
(3H, s, CH3), 4.82 (2H, s, CH2), 6.45 (1H, s, CH), 7.29–7.42 (5H, m, Ar-H). 13C-NMR  (ppm) 5.6,
12.3, 17.5, 71.7, 86.4, 111.7, 127.4, 127.9, 128.4, 137.1, 149.5, 151.5. HR-EIMS m/z 360.2146 (Calcd
for C21H32O3Si: 360.2121).
2-Benzyloxy-3-methyl-4-triisopropylsilyloxynaphthalen-1-ol (22)
To a solution of 16 (149 mg, 74%, 0.31 mmol) and 18 (121 mg, 0.34 mmol) in THF (5 mL), n-BuLi (1.09
N in hexane, 0.63 mL, 0.69 mmol) was added at -78 °C for 15 min. H2O (5 mL) was added and the
whole was extracted with AcOEt (3 x 10 mL). The combined organic layer was washed with H2O (1 x 3
mL) and brine (1 x 3 mL) and dried over Na2SO4. The solvent was evaporated in vacuo and the residue
was purified by CC (SiO2, hexane – AcOEt = 95 : 5 – 91 : 9) to give 22 as a pale yellow oil (82 mg).
After crystallization at -35 °C, an aliquot (62 mg) was washed with hexane to give 22 as colorless solids
(46 mg, 46%).

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HETEROCYCLES, Vol. 88, No. 1, 2014
mp 82-85 °C. IR max (cm-1) 3372. 1H-NMR  (ppm) 1.12 (18H, d, J = 7.8 Hz, 6 x CH3), 1.40 (3H,
sept., J = 7.6 Hz, 3 x CH), 2.44 (3H, s, CH3), 4.91 (2H, s, CH2), 5.52 (1H, s, OH), 7.37-7.47 (7H, m,
Ar-H), 7.98-8.02 (1H, m, Ar-H), 8.04-8.08 (1H, m, Ar). 13C-NMR  (ppm) 11.8, 14.2, 18.1, 75.8, 118.0,
121.6, 122.2, 122.9, 124.6, 124.7, 125.6, 128.2, 128.6, 128.9, 136.9, 138.1, 139.8, 143.9. HR-EIMS m/z
436.2440 (Calcd for C27H36O3Si: 436.2434).
Synthesis of naphthoquinones 20 and 23 from napthol 22.
(with TBAF) To a solution of crude 22 (182 mg, prepared from 7 (147 mg, 74%, 0.30 mmol) and 18 (120
mg, 0.34 mmol)) in THF (6.5 mL), TBAF (1 M solution in THF, 0.34 mL, 0.34 mmol) was added at rt
and the reaction mixture was stirred at rt for 15 min. AcOEt (30 mL) was added and the whole was
washed with saturated aqueous NH4Cl (1 x 3 mL) and dried over Na2SO4. The solvent was evaporated
in vacuo and the residue was purified by CC (SiO2, hexane – AcOEt = 95 : 5 to 50 : 50, CH2Cl2 – hexane
= 1 : 1) to give 20 as a pale brown oil (36 mg, 43%).
(with aq. FeCl3) To a solution of crude 22 (177 mg, prepared from 7 (146 mg, 81%, 0.33 mmol) and 18
(120 mg, 0.34 mmol)) in MeOH (6.8 mL), aqueous FeCl3 (219 mg, 1.35 mmol in 1.9 mL) was added at rt
and the reaction mixture was stirred at rt for 1.5 h. H2O (12 mL) was added and the mixture was
extracted with CH2Cl2 (2 x 40 mL, 1 x 20 mL). The combined organic layer was washed with H2O (1 x
8 mL) and brine (1 x 8 mL) and dried over Na2SO4. The solvent was evaporated in vacuo and the
residue was purified by CC (SiO2, hexane – AcOEt = 95 : 5, CH2Cl2 – hexane = 1 : 1) to give 20 as a
brown oil (34 mg, 37%) and 23 as pale yellow solids (8 mg, 12%).
2-Hydroxy-3-methylnaphthalene-1,4-dione (23)
mp 167-169 °C (lit15 172-173 °C). IR max (cm-1) 3328, 1653. 1H-NMR  (ppm) 2.11 (3H, s, CH3),
7.69 (1H, td, J = 7.6 Hz, 1.4 Hz, Ar-H), 7.76 (1H, td, J = 7.5 Hz, 1.5 Hz, Ar-H), 8.09 (1H, dd, J = 7.6 Hz,
1.1 Hz, Ar-H), 8.13 (1H, dd, J = 7.7 Hz, 1.0 Hz, Ar-H). EIMS m/z 188 (M+, 100%), 160 (69%), 132
(76%), 131 (79%), 105 (65%), 77 (65%).
ACKNOWLEDGEMENTS
This work was partially supported by The Uehara Memorial Foundation and a Grant from Musashino
Joshi-Gakuin.
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