A practical procedure for multisubstituted β-naphthols and their derivatives

Article abstract of DOI:10.1016/S0040-4020(03)01066-4

A number of multisubstituted β-naphthols were efficiently prepared by intramolecular aldol condensation of readily available substituted benzyaldehydes, whose substituents were introduced easily by a selective alkylation on the benzylic position of the su

Full text of DOI:10.1016/S0040-4020(03)01066-4

Tetrahedron 59 (2003) 6621–6625
A practical procedure for multisubstituted b-naphthols
and their derivatives
*
Wan-Guo Wei and Zhu-Jun Yao
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, People’s Republic of China
Received 15 April 2003; revised 30 May 2003; accepted 23 June 2003
Abstract—A number of multisubstituted b-naphthols were efficiently prepared by intramolecular aldol condensation of readily available
substituted benzyaldehydes, whose substituents were introduced easily by a selective alkylation on the benzylic position of the substrates.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
be very useful in the synthesis of many naturally occurring
products. For example, naphthol 9a could be modified and
applied in the synthesis of quinonoid compounds, which
acted as potential intermediates in the synthesis of
biologically important naphthoquinones5 and heterocycles6
(Fig. 1).
The multisubstituted naphthalenes and naphthols have
attracted much attention on account of their usefulness as
bioactive agents, where the substitution patterns may play
an important role in the biological activities,1 as well as their
potential as intermediates in structural and synthetic
chemistry.2 The most important step in the synthetic
pathways to construct these molecules is the introduction
of suitable substitution groups into the naphthalene
skeleton, which is often not easily achieved by those
conventional electrophilic aromatic substitutions, especially
owing to the problems associated with regiochemical
control. The various substitutions of naphthalene-based
complex structure are usually introduced at the stage of
starting material.3 Therefore, the development of efficient
synthetic strategies and methods is a very important issue
today in the synthesis of multisubstituted naphthalenes and
naphthols.
2. Results and discussion
The presented procedure was started from aldehyde 1,
which could be easily prepared by a known method.7
Dithioacetal 4 was synthesized by condensation of benzyl
chloride 2 with lithium salt of 1,3-dithane 3. At this stage,
the dithiane and dimethylacetal protecting groups allowed 4
to expose to severe basic reaction conditions, such as
metallation in the 4-position of the benzene ring to introduce
In the course of our synthetic study toward the natural
product chlorofusin,4 we found that the key intermediate 8a
was very susceptible to cyclization in the presence of base to
furnish b-naphthol 9a. It gave us an idea to check the
generality of this transformation and its potential appli-
cations in the synthesis of multisubstituted naphthalene-
based structures. Herein we describe our recent results on
the synthetic investigation of highly substituted b-naphthols
utilizing the above mentioned aldol condensation of
benzyaldehydes. The newly developed synthetic procedure
for a-substituted b-naphthols allows to establish diverse
substituents easily in the a-position. These naphthols would
Keywords: b-naphthols; benzyaldehyde; benzylic position.
*
Figure 1. Examples of naturally occurring naphthoquinones and their
multisubstituted naphthol-based synthetic intermediates.
Corresponding author. Tel.: þ86-21-6416-3300; fax: þ86-21-6416-6128;
e-mail: yaoz@pub.sioc.ac.cn
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)01066-4

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W.-G. Wei, Z.-J. Yao / Tetrahedron 59 (2003) 6621–6625
of them made the reaction more complicated. Finally, an
intramolecular aldol condensation of 8(a–f) with sodium
hydroxide, and dehydration in situ provided the correspond-
ing a-substituted b-naphthols 9(a–f) in moderate to good
yields (Scheme 2 and Table 1).
As an application, the multisubstituted naphthols could
be easily converted to the corresponding naphthoquinones
by various oxidative conditions. Thus, 9a (it was
slightly unstable when exposed to air) could be converted
into o-naphthoquinone 10 in 62% yield by treatment with
Fremy’s salt8 in THF (Scheme 3).
Scheme 3.
3. Conclusion
In summary, we have developed an efficient way to the
synthetically important intermediate 7, which allows us to
introduce a variety of substitutents on the benzylic position
by a convenient alkylation reaction. A subsequent intra-
molecular aldol condensation of intermediates 8(a–f) leads
to a-substituted b-naphthols that contain a variety of
substituents at its a-position.
Scheme 1. Reagents and conditions: (i) CH(OMe)3, p-TsOH, MeOH, 508C,
87%; (ii) n-BuLi, THF, 278 to 2208C, 3, 42%; (iii) n-BuLi, THF, MeI,
278 to 2108C, 75%; (iv) Acetone, p-TsOH (cat), 94%; (v) Hg(OAc)2,
CH3CN/H2O, 83%.
an alkyl group, affording alkylated product 5. The
subsequent facile removal of the acetal (with p-TsOH)
and dithiane (with Hg(OAc)2) both in high yields makes this
synthetic route to precursor 7 very simple and efficient
(Scheme 1).
4. Experimental
4.1. General
With the intermediate 7 in hand, a selective alkylation on
the benzylic position with various alkyl halides was
performed by using n-Bu4NOH as the base, affording
8(b–f) in desirable yields. Other bases, such as tetrapropyl-
ammonium hydroxide, had also been investigated, but most
1H NMR spectra were recorded on a Varian 300 MHz
spectrometer for solution in CDCl3 with TMS as internal
standards. IR spectra were recorded on an FT-IR instrument.
MPs were obtained with a Yanagimoto micro melting point
apparatus and are uncorrected. Mass spectra were recorded
with a HP-5989 instrument and HRMS were measured by a
Finnigan MAþ mass spectrometer. Flash column chromato-
graphy was performed on silica gel (10–40 mm) using a
mixture of petroleum ether and ethyl acetate as the eluent.
4.1.1. 1-Chloromethyl-2-dimethoxymethyl-3,5-
dimethoxybenzene (2). To a solution of 17 (195 mg,
1 mmol) and p-TsOH (8 mg, cat) in anhydrous methanol
(5 mL) was added CH(OMe)3 (0.6 mL, 5.5 mmol). After
being stirred at 458C for 2 h, Et3N (1 mL) was added and
most of the solvent was removed under reduced pressure.
The residue was partitioned between water and ethyl ether.
The organic phase was separated and washed with brine,
dried over Na2SO4 and evaporated. The crude white solid
product was dried and used directly without further
Scheme 2. Reagents and conditions: (i) RX, CH2Cl2, n-Bu4NOH (10%),
408C; (ii) MeOH, aq NaOH, rt.
Table 1. The results of alkylation of 7 and intramolecular aldol
condensation of 8
Entry
Alkyl halide (RX)
Yield (%)a
Product 8
Product 9
1
2
3
4
5
6
R¼H (7¼8a)
MeI
EtI
Allyl bromide
BnBr
PMBBr
9a/86
9b/77
9c/72
9d/40
9e/67
9f/65
1
purification (206 mg, 87%). H NMR (300 MHz, CDCl3):
d 6.70 (d, J¼2.4 Hz, 1H), 6.40 (d, J¼2.4 Hz, 1H), 5.72 (s, 1H),
8b/74
8c/78
8d/87
8e/85
8f/92
4.96 (s, 2H), 3.82 (s, 3H), 3.80 (s, 3H), 3.40 (s, 6H) ppm.
4.1.2. tert-Butyl-(3-[1,3]dithian-2-ylpropoxy)dimethylsi-
lane (3). To a solution of 3-[1,3]dithian-2-ylpropan-1-ol9
a
Isolated yields.

W.-G. Wei, Z.-J. Yao / Tetrahedron 59 (2003) 6621–6625
6623
(40.72 g, 228 mmol), imidazole (25 g, 365 mmol) in DMF
(50 mL) was added dropwise a solution of TBSCl (45 g,
297 mmol) in DMF (80 mL). The reaction mixture was
stirred at 08C for 1 h and then at room temperature for
another 1 h. The reaction was quenched by aqueous NH4Cl
solution (150 mL), extracted with EtOAc (3£150 mL). The
combined organic phases were washed with brine, dried
over Na2SO4, concentrated and purified by chromatography
brine, dried over Na2SO4, evaporated and purified by
chromatography to give 6 as a colorless oil (61 mg, 95%).
1H NMR (300 MHz, CDCl3): d 10.40 (s, 1H), 6.80 (s, 1H),
3.85 (s, 3H), 3.78 (s, 3H), 3.70 (s, 2H), 3.60 (t, J¼6.0 Hz,
2H), 2.90–2.70 (m, 4H), 2.16 (s, 3H), 1.95–1.70 (m, 6H),
0.80 (s, 9H), 0.09 (s, 6H) ppm. EIMS (m/z): 469 (M215)þ.
IR (liquid film, cm21): 2954, 2931, 2857, 1682, 1598,
1568, 1464, 1383, 1292, 1257, 1129, 837, 777. Anal. calcd
for C24H40O4S2Si: C, 59.46; H, 8.32. Found: C, 59.50; H,
8.63.
1
to afford product as a colorless oil (64.2 g, 96%). H NMR
(300 MHz, CDCl3): d 4.00 (t, J¼6.6 Hz, 1H), 3.60
(t, J¼6.0 Hz, 2H), 2.82–2.78 (m, 4H), 2.10–1.60 (m, 6H),
0.82 (s, 9H), 0.00 (s, 6H) ppm. IR (neat, cm21): 2953, 2858,
1256, 1105, 837, 776. EIMS (m/z): 291 (M21)þ.
4.1.6. 6-[5-(tert-Butyldimethylsilyloxy)-2-oxopentyl]-2,4-
dimethoxy-3-methylbenzaldehyde (7). To a solution of 6
(218 mg, 0.45 mmol) in CH3CN (8 mL) and H2O (2 mL)
was added Hg(OAc)2 (359 mg, 1.13 mmol). After a while,
the resulting solution became homogenous and a white
slurry appeared. After being stirred at room temperature for
1 h, the mixture was filtered through celite and washed with
CH2Cl2. The organic layer was separated and washed with
brine, dried over Na2SO4, filtered and evaporated. The
residue was purified by column chromatography to give 7 as
a yellow oil (147 mg, 83%). 1H NMR (CDCl3, 300 MHz): d
10.20 (s, 1H), 6.40 (s, 1H), 4.00 (s, 2H), 3.80 (s, 3H), 3.75
(s, 3H), 3.60 (t, J¼6.0 Hz, 2H), 2.65 (t, J¼7.5 Hz, 2H), 2.10
(s, 3H), 1.80–1.70 (m, 2H), 0.85 (s, 9H), 0.00 (s, 6H) ppm.
IR (liquid film, cm21): 2955, 2931, 1720, 1677, 1600, 1569,
1465, 1131, 837. EIMS (m/z): 337 (M–57)þ. Anal. calcd for
C21H34O5Si: C, 63.92; H, 8.68. Found: C, 64.29; H, 8.88.
4.1.3. tert-Butyl-{3-[2-(2-dimethoxymethyl-3,5-
dimethoxybenzyl)-[1,3]dithian-2-yl]propoxy}dimethyl-
silane (4). A solution of the dithiane 3 (3.81 g, 13.05 mmol)
in THF (20 mL) at 2788C was treated with 1.6 M n-BuLi in
hexane (10 mL, 16.0 mmol). The resulting reaction solution
was stirred at 2408C for 3 h and then at 2308C for 1.5 h. To
the solution cooled at 2788C was added benzyl chloride 2
(2.83 g, 10.9 mmol) in THF (25 mL) slowly and the reaction
mixture was warmed to room temperature overnight. The
reaction was quenched with brine and the aqueous phase
was extracted with ethyl acetate. The combined organic
extracts were dried over Na2SO4 and evaporated, the residue
was purified by chromatography to afford the crude product
4 as a yellow oil (2.33 g, 42%). 1H NMR (300 MHz,
CDCl3): d 7.18 (d, J¼2.4 Hz, 1H), 6.38 (d, J¼2.4 Hz, 1H),
5.72 (s, 1H), 3.80 (s, 3H), 3.78 (s, 3H), 3.60 (s, 2H), 3.58
(t, J¼6.3 Hz, 2H), 3.40 (s, 6H), 2.94–2.90 (m, 4H), 2.00–
1.60 (m, 6H), 0.90 (s, 9H), 0.01 (s, 6H) ppm. EIMS (m/z):
485 (M231)þ.
4.2. General procedure for the preparation of 8(b–f)
A solution of 7 (0.3 mmol) in CH2Cl2 (10 mL) was treated
with tetrabutylammonium hydroxide (10% in H2O) and RX
(2.0 equiv.) at 408C and the reaction process was monitored
by TLC. Upon completion, saturated NH4Cl aqueous
solution was added. The mixture was extracted with
EtOAc (3£15 mL). The combined organic extracts were
washed with brine, dried over Na2SO4, filtered and
evaporated. The residue was purified by column chromato-
graphy to afford 8(b–f).
4.1.4. tert-Butyl-{3-[2-(2-dimethoxymethyl-3,5-
dimethoxy-4-methylbenzyl)-[1,3]dithian-2-yl]propoxy}-
dimethylsilane (5). A solution of crude 4 (16.57 g,
32.0 mmol) in THF (100 mL) at 2788C was treated with
1.6 M n-BuLi (34.0 mL, 54.6 mmol). The mixture was
stirred at 2208C for 5 h and then at 2108C for 0.5 h. MeI
(6.0 mL, 96 mmol) was added dropwise, and the mixture
was stirred at room temperature overnight. The reaction was
quenched with aqueous brine and extracted with acetyl
acetate. The combined extracts were dried over Na2SO4,
filtered and evaporated. The residue was purified by column
chromatography and recrystallized from hexane and ethyl
acetate to give 5 as a white solid (12.8 g, 75%). Mp: 81–
4.2.1. 6-[5-(tert-Butyldimethylsilyloxy)-1-methyl-2-oxo-
pentyl]-2,4-dimethoxy-3-methylbenzaldehyde (8b). 1H
NMR (CDCl3, 300 MHz): d 10.40 (s, 1H), 6.48 (s, 1H),
5.15 (q, J¼7.2 Hz, 1H), 3.80 (s, 3H), 3.75 (s, 3H), 3.55
(t, J¼6.0 Hz, 2H), 2.50 (t, J¼7.2 Hz, 2H), 2.10 (s, 3H),
1.75–1.65 (m, 2H), 1.35 (d, J¼7.2 Hz, 3H), 0.80 (s, 9H),
0.00 (s, 6H) ppm. IR (liquid film, cm21): 2955, 2932, 1714,
1680, 1597, 1567, 1464, 1131, 837. EIMS (m/z): 351 (M–
57)þ. HRMS calcd for C22H36O5SiNa (MþNa)þ calcd:
431.2230, found: 431.2224.
1
828C. H NMR (300 MHz, CDCl3): d 7.18 (s, 1H), 5.58
(s, 1H), 3.80 (s, 3H), 3.68 (s, 3H), 3.60 (s, 2H), 3.58
(t, J¼6.3 Hz, 2H), 3.40 (s, 6H), 3.00–2.80 (m, 4H), 2.12
(s, 3H), 2.08–1.62 (m, 6H), 0.87 (s, 9H), 0.00 (s, 6H) ppm.
IR (KBr, cm21): 2925, 2884, 1606, 1577, 1446, 1124, 1067,
848, 774. ESIMS (m/z): 553 (MþNa)þ. Anal. calcd for
C26H46O5S2Si: C, 58.83; H, 8.73. Found: C, 58.87; H, 8.60.
4.2.2. 6-[5-(tert-Butyldimethylsilyloxy)-1-ethyl-2-oxo-
pentyl]-2,4-dimethoxy-3-methylbenzaldehyde (8c). 1H
NMR (CDCl3, 300 MHz): d 10.50 (s, 1H), 6.50 (s, 1H),
5.25 (t, J¼7.2 Hz, 1H), 3.85 (s, 3H), 3.80 (s, 3H), 3.55
(t, J¼6.3 Hz, 2H), 2.50 (t, J¼7.2 Hz, 2H), 2.20 (s, 3H),
2.15–2.00 (m, 1H), 1.75–1.60 (m, 3H), 0.75 (s, 9H), 0.90–
0.70 (q, 3H, superimposed on 0.75), 0.00 (s, 6H) ppm. IR
(liquid film, cm21): 2957, 2932, 1712, 1682, 1597, 1567,
1464, 1129, 837. EIMS (m/z): 365 (M–57)þ. HRMS calcd
for C23H38O5SiNa (MþNa)þ calcd: 445.2386, found:
445.2381.
4.1.5. 6-{2-[3-(tert-Butyldimethylsilyloxy)propyl]-
[1,3]dithian-2-ylmethyl}-2,4-dimethoxy-3-methylbenzal-
dehyde (6). A solution of 5 (83 mg, 0.16 mmol) in acetone
(2 mL) was treated with p-TsOH (cat) at room temperature
for 5 min. The reaction was quenched with aqueous Na2CO3
solution and the organic solvent was removed under reduced
pressure. The resulting mixture was extracted with ethyl
acetate. The combined extracts were washed with water and

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W.-G. Wei, Z.-J. Yao / Tetrahedron 59 (2003) 6621–6625
4.2.3. 6-[1-Allyl-5-(tert-butyldimethylsilyloxy)-2-oxopen-
1
tyl]-2,4-dimethoxy-3-methylbenzaldehyde (8d). H NMR
(s, 3H), 0.85 (s, 9H), 0.00 (s, 6H) ppm. IR (KBr, cm21):
3260 (br), 2955, 2933, 1635, 1580, 1497, 1465, 1259, 1112,
826, 779. EIMS (m/z): 390 (M)þ. Anal. calcd for
C22H34O4Si: C, 67.65; H, 8.77. Found: C, 67.57; H, 8.86.
(CDCl3, 300 MHz): d 10.40 (s, 1H), 6.50 (s, 1H), 5.75–5.60
(m, 1H), 4.40 (t, J¼7.2 Hz, 1H), 5.00–4.85 (m, 2H), 3.80
(s, 3H), 3.75 (s, 3H), 3.50 (t, J¼6.0 Hz, 2H), 2.80–2.70
(m, 1H), 2.50 (t, J¼7.5 Hz, 2H), 2.40–2.30 (m, 1H), 2.10 (s,
3H), 1.75–1.65 (m, 2H), 0.75 (s, 9H), 20.05 (s, 6H) ppm. IR
(liquid film, cm21): 2955, 2931, 1714, 1681, 1597, 1567,
1464, 1129, 837, 777. EIMS (m/z): 377 (M–57)þ. Anal. calcd
for C24H38O5Si: C, 66.32; H, 8.81. Found: C, 66.20; H, 8.53.
4.3.3. 3-[2-(tert-Butyldimethylsilyloxy)ethyl]-1-ethyl-5,7-
dime thoxy-6-methylnaphthalen-2-ol (9c). 1H NMR
(CDCl3, 300 MHz): d 8.30 (s, 1H), 7.60 (s, 1H), 7.00
(s, 1H), 4.00 (t, J¼5.1 Hz, 2H), 3.95 (s, 3H), 3.85 (s, 3H),
3.10–3.00 (m, 4H), 2.30 (s, 3H), 1.25 (t, J¼4.5 Hz, 3H),
0.90 (s, 9H), 0.10 (s, 6H) ppm. IR (liquid film, cm21): 3280
(br), 2956, 2932, 1633, 1580, 1465, 1387, 1253, 1115, 827.
EIMS (m/z): 404 (M)þ. HRMS calcd for C23H36O4SiNa
(MþNa)þ calcd: 427.2281, found: 427.2275.
4.2.4. 6-[1-Benzyl-5-(tert-butyldimethylsilyloxy)-2-oxo-
pentyl]-2,4-dimethoxy-3-methylbenzaldehyde (8e). 1H
NMR (CDCl3, 300 MHz): d 10.30 (s, 1H), 7.20–7.10
(m, 5H), 6.55 (s, 1H), 5.70 (t, J¼7.2 Hz, 1H), 3.80 (s, 3H),
3.75 (s, 3H), 3.45 (t, J¼6.3 Hz, 2H), 3.30 (dd, J¼8.1 Hz,
13.2 Hz, 1H), 2.70 (dd, J¼6.3 Hz, 13.2 Hz, 1H), 2.50–2.25
(m, 2H), 2.10 (s, 3H), 1.65–1.55 (m, 2H), 0.80 (S, 9H),
20.10 (s, 6H) ppm. IR (liquid film, cm21): 2955, 2931,
1714, 1679, 1596, 1567, 1464, 1129, 837, 777. EIMS (m/z):
427 (M–57)þ. Anal. calcd for C28H40O5Si: C, 69.38; H,
8.32. Found: C, 69.05; H, 8.77.
4.3.4. 1-Allyl-3-[2-(tert-butyldimethylsilyloxy)ethyl]-5,7-
dimethoxy-6-methylnaphthalen-2-ol (9d). White solid,
Mp: 75–788C. 1H NMR (CDCl3, 300 MHz): d 8.40
(s, 1H), 7.60 (s, 1H), 6.95 (s, 1H), 6.10–5.95 (m, 1H),
5.10–5.00 (m, 2H), 4.00 (t, J¼5.1 Hz, 2H), 3.90 (s, 3H),
3.85 (s, 3H), 3.80 (d, J¼0.6 Hz, 2H), 3.08 (t, J¼5.1 Hz, 2H),
2.25 (s, 3H), 0.90 (s, 9H), 0.08 (s, 6H) ppm. IR (KBr, cm21):
3268 (br), 2954, 2932, 1635, 1579, 1465, 1387, 1259, 1116,
826, 734. EIMS (m/z): 416 (M)þ.
4.2.5. 6-[5-(tert-Butyldimethylsilyloxy)-1-(4-methoxy-
benzyl)-2-oxopentyl]-2,4-dimethoxy-3-methylbenzalde-
1
hyde (8f). H NMR (CDCl3, 300 MHz): d 10.40 (s, 1H),
4.3.5. 1-Benzyl-3-[2-(tert-butyldimethylsilyloxy)ethyl]-
5,7-dimethoxy-6-methylnaphthalen-2-ol (9e). 1H NMR
(CDCl3, 300 MHz): d 8.45 (s, 1H), 7.60 (s, 1H), 7.25–7.00
(m, 5H), 6.85 (s, 1H), 4.40 (s, 2H), 3.95 (t, J¼4.8 Hz, 2H),
3.80 (s, 3H), 3.70 (s, 3H), 3.05 (t, J¼5.1 Hz, 2H), 2.20
(s, 3H), 0.80 (s, 9H), 0.00 (s, 6H) ppm. IR (liquid film,
cm21): 3259 (br), 2953, 2931, 1633, 1579, 1460, 1388,
1257, 1110, 836. EIMS (m/z): 466 (M)þ. Anal. calcd for
C28H38O4Si: C, 72.06; H, 8.21. Found: C, 72.48; H, 8.46.
7.10 (d, J¼8.7 Hz, 2H), 6.80 (d, J¼5.4 Hz, 1H), 6.60 (s, 3H),
5.65 (t, J¼5.4 Hz, 1H), 3.95 (s, 3H), 3.80 (s, 3H), 3.75
(s, 3H), 3.50 (t, J¼6.3 Hz, 2H), 3.40 (dd, J¼8.1 Hz,
14.1 Hz, 1H), 2.85 (dd, J¼6.6, 14.1 Hz, 1H), 2.55–2.30
(m, 2H), 2.20 (s, 3H), 1.75–1.60 (m, 2H), 0.80 (s, 9H), 0.00
(s, 6H) ppm. IR (liquid film, cm21): 2955, 2931, 1713, 1679,
1596, 1566, 1464, 1149, 1128, 836, 777. EIMS (m/z): 514
(M)þ. Anal. calcd for C29H42O6Si: C, 67.67; H, 8.22.
Found: C, 67.77; H, 8.48.
4.3.6. 3-[2-(tert-Butyldimethylsilyloxy)ethyl]-5,7-
dimethoxy1-(4-methoxybenzyl)-6-methylnaphthalen-2-
ol (9f). H NMR (CDCl3, 300 MHz): d 8.45 (s, 1H), 7.70
4.3. General procedure for the preparation of 9(a–f)
1
To a solution of 8 (0.2 mmol) in CH3OH (5 mL) was added
aqueous NaOH solution (6N, 0.1 mL). The reaction mixture
was stirred at room temperature for 15 min. Most of the
solvent was removed under reduced pressure and the residue
was diluted with ethyl acetate, washed with aqueous NH4Cl
solution. The organic phase was dried over Na2SO4 and
evaporated. The residue was purified by column chromato-
graphy to give 9(a–f).
(s, 1H), 7.20 (d, J¼8.4 Hz, 2H), 6.95 (s, 1H), 6.75 (d,
J¼8.4 Hz, 2H), 4.40 (s, 2H), 4.00 (t, J¼5.0 Hz, 2H), 3.90
(s, 3H), 3.80 (s, 3H), 3.75 (s, 3H), 3.10 (t, J¼5.1 Hz, 2H),
0.90 (s, 9H), 0.05 (s, 6H) ppm. IR (liquid film, cm21): 3258
(br), 2953, 2933, 1633, 1581, 1511, 1465, 1387, 1248, 1141,
1110, 839, 784. EIMS (m/z): 496 (M)þ. Anal. calcd for
C29H40O5Si: C, 70.12; H, 8.12. Found: C, 69.94; H, 8.38.
4.3.7. 3-[2-(tert-Butyldimethylsilyloxy)ethyl]-5,7-
dimethoxy-6-methyl-[1,2]naphthoquinone (10). To an
aqueous solution of Fremy’s salt (90 mg, 0.34 mmol) in
0.4N K2HPO4 (2.0 mL) was added a solution of phenol 9a
(42 mg, 0.11 mmol) in THF (3.0 mL). The resulting mixture
was stirred at room temperature for 2 days (monitored by
TLC, additional Fremy’s salt was added if necessary). The
mixture was extracted with ethyl acetate and the combined
organic extracts were washed with brine, dried over
Na2SO4, filtered, evaporated and purified by chromato-
graphy to afford 10 as a reddish oil (17 mg, 62%) with
4.3.1. 3-[2-(tert-Butyldimethylsilyloxy)-ethyl]-5,7-
dimethoxy-6-methylnaphthalen-2-ol (9a). 1H NMR
(CDCl3, 300 MHz): d 8.45 (s, 1H), 7.70 (s, 1H), 7.20
(s, 1H), 6.75 (s, 1H), 4.00 (t, J¼5.1 Hz, 2H), 3.90 (s, 3H),
3.85 (s, 3H), 3.05 (t, J¼5.1 Hz, 2H), 2.30 (s, 3H), 0.90
(s, 9H), 0.10 (s, 6H) ppm. IR (liquid film, cm21): 3277 (br),
2954, 2932, 1641, 1576, 1464, 1396, 1256, 1144, 1110,
838, 782. EIMS (m/z): 376 (M)þ, 319 (M–57)þ. Anal.
calcd for C21H32O4Si: C, 66.98; H, 8.56. Found: C, 66.79;
H, 8.37.
1
material recovered (9a, 10 mg, 24%). H NMR (CDCl3,
4.3.2. 3-[2-(tert-Butyldimethylsilyloxy)ethyl]-5,7-
dimethoxy-1,6-dimethylnaphthalen-2-ol (9b). Mp: 115–
300 MHz): d 7.60 (s, 1H), 7.38 (s, 1H), 3.92 (s, 3H), 3.80
(s, 3H), 3.80 (t, J¼6.0 Hz, 2H), 2.62 (t, J¼6.0 Hz, 2H), 2.20
(s, 3H), 0.90 (s, 9H), 0.05 (s, 6H) ppm. IR (liquid film,
cm21): 2956, 2920, 1663, 1584, 1465, 1319, 1258, 1143,
1101, 836, 778. ESIMS (m/z): 391 (Mþ1)þ. HRMS calcd
1
1178C. H NMR (CDCl3, 300 MHz): d 8.30 (s, 1H), 7.50
(s, 1H), 6.85 (s, 1H), 3.95 (t, J¼4.8 Hz, 2H), 3.90 (s, 3H),
3.80 (s, 3H), 3.00 (t, J¼5.4 Hz, 2H), 2.45 (s, 3H), 2.20

W.-G. Wei, Z.-J. Yao / Tetrahedron 59 (2003) 6621–6625
6625
for C21H30O5SiNa (MþNa)þ calcd: 413.1760, found:
Litrico, A.; Semones, M. A.; Xu, S. L. J. Org. Chem. 1993, 58,
6429–6437. (b) Terao, Y.; Satoh, T.; Miura, M.; Nomura, M.
Tetrahedron 2000, 56, 1315–1320.
413.1770.
3. (a) Ghera, E.; Ben-David, Y. J. Org. Chem. 1985, 50,
3355–3359. (b) De Koning, C. B.; Rousseau, A. L.; Van
Otterlo, W. A. L. Tetrahedron 2003, 59, 7–36.
Acknowledgements
The Major State Basic Research and Development Program
of China (Grant No. G2000077500), the Chinese Academy
of Sciences, and the Shanghai Municipal Commission of
Science and Technology are acknowledged for financial
supports.
4. Duncan, S. J.; Gru¨schow, S.; William, D. H.; McNicholas, C.;
Purewal, R.; Hajek, M.; Gerlitz, M.; Martin, S.; Wrigley, S. K.;
Moore, M. J. Am. Chem. Soc. 2001, 123, 554–560.
5. (a) Merlic, C. A.; Aldrich, C. C. J. Am. Chem. Soc. 2000, 122,
3224–3225. (b) Hauser, F. M.; Sengupta, D.; Corlett, S. A.
J. Org. Chem. 1994, 59, 1967–1969.
´ ´ ´
6. Martınez, A.; Estevez, J. C.; Estevez, R. J.; Castedo, L.
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