Stereoselective synthesis of cis- and trans-3,4-dihydro-3,4,8- trihydroxynaphthalen-1(2H)-one

Article abstract of DOI:10.1002/hlca.200800380

A short and efficient protocol for the stereoselective synthesis of racemic trans- and cis-3,4-dihydro-3,4,8-trihydroxynaphthalen-1(2H)-one (1 and 2, resp.), is described, comprising nine and eight steps starting from commercial juglone (=5-hydroxynaphtha

Full text of DOI:10.1002/hlca.200800380

Helvetica Chimica Acta – Vol. 92 (2009)
903
Stereoselective Synthesis of cis- and trans-3,4-Dihydro-3,4,8-
trihydroxynaphthalen-1(2H)-one
by Emmanuel Couche´*1), Abdellatif Fkyerat, and Raffaele Tabacchi
´
ˆ
Laboratoire de Chimie Organique Analytique, Institut de Chimie, Universite de Neuchatel, Avenue de
ˆ
Bellevaux 51, Case postale 158, CH-2009 Neuchatel
A short and efficient protocol for the stereoselective synthesis of racemic trans- and cis-3,4-dihydro-
3,4,8-trihydroxynaphthalen-1(2H)-one (1 and 2, resp.), is described, comprising nine and eight steps
starting from commercial juglone (¼ 5-hydroxynaphthalene-1,4-dione; 12) (Scheme 4). Furthermore, an
attempt to obtain 1 and 2 via phthalide annulation as the key step (Schemes 2 and 3) and a regioselective
oxidation of the intermediate 1,2,3,4-tetrahydronaphthalene-1,2,4,5-tetrols 27 and 28 with activated
MnO2 were carried out (Scheme 4).
Introduction. – In our investigation on phytotoxic substances produced by
Ceratocystis fimbriata sp. coffea, a fungus found in the canker of the coffea tree, we
have reported the isolation and structure elucidation by spectroscopic methods of
trans- and cis-3,4-dihydro-3,4,8-trihydroxynaphthalen-1(2H)-one (1 and 2, resp.) [1].
These natural polyhydroxylated a-tetralones (¼ 3,4-dihydronaphthalen-1(2H)-ones)
are known as metabolites implicated in the branched pathway of fungal DHN-melanin
biosynthesis [2 – 6]. Until now, only the natural (ꢀ)-trans-isomer has been isolated from
six different fungal microorganisms [1][7 – 11]. In addition, the natural cis-isomer
known also exclusively as the (ꢀ)-enantiomer has also been isolated from the
mutagenic microorganism [12]. The control of the configuration of these natural
products is achieved by a NADPH-dependent dehydrogenase, belonging to class B, i.e.,
transferring the pro-S hydrogen from C(4) of the nicotinamide ring to the Si face of the
naphthalenol substrate [4].
Our studies on the phytotoxicity of natural samples have shown that the metabolite
1 does not seem to develop necrosis in the cells of the coffea tree [13]. Furthermore,
Borgschulte and co-workers have reported that 1 is toxic in contact with the leaves of
1
)
Present address: Axoglia Therapeutics S.A., 162a, Av. de la Faꢂencerie L-1511 Luxembourg (phone:
þ 3524666446288; fax: þ 3524666446371; e-mail: ecouche@axoglia.com).
ꢀ 2009 Verlag Helvetica Chimica Acta AG, Zꢁrich

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the poplar tree [8]. At the same time, Bꢀrki et al. [14] have established that the trans-
and cis-4-hydroxyscytalones (3 and 4, resp.) generate a partial toxicity in the leaves of
the plane tree. The numerous contradictions encountered in various reports concerning
the beneficial or the potential toxic effect of polyhydroxylated a-tetralone derivatives
in contact with different vegetable species encouraged us to reexamine the biological
activity of these compounds. In relation to this reexamination, we have now developed
a stereoselective synthesis of 1 and 2.
To synthesis the a-tetralones 1 and 2, we decided to use the same protocol as in the
synthesis of 3,4-dihydro-2,4,8-trihydroxynaphthalen-1(2H)-one [15]. This protocol
involved the ring opening of a phthalide (¼ isobenzofuran-1(3H)-one). However, here,
two alternatives could be considered. The first one involves the homologation of 7-
(benzyloxy)phthalide in the presence of a Michael acceptor substituted by an alkoxy
group in position 3 (Pathway A in Scheme 1). The second alternative is the ring opening
of 4-(benzyloxy)phthalide with benzyl acrylate, followed by the introduction of the
required additional OH group (Pathway B) or by direct decarboxylation and
Scheme 1

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subsequent oxidation (Pathway C). Pathway A could permit, via the direct formation of
adduct 5, followed by decarboxylation, a rapid access to 1 and 2.
Results and Discussion. – The homologation reaction according to Pathway A was
realized with 5,7-dimethoxyphthalide (6) and methyl 3-methoxy acrylate (¼ methyl 3-
methoxyprop-2-enoate). However, several attempts under different conditions never
yielded the desired compound but only the polysubstituted naphthalene-2-carboxylate
7 and the phthalide derivative 8 (Scheme 2).
Scheme 2. Ring Opening of 5,7-Dimethoxyphthalide (6) with Methyl 3-Methoxyacrylate (Pathway A)
a) 6 (1.0 equiv.), lithium diisopropylamide (LDA; 2.0 equiv.), MeOCH¼CHCO2Me (1.5 equiv.), THF,
ꢀ 408; 35% (18% of 7 and 17% of 8).
Analogously to the ring opening of 7-(benzyloxy)phthalide [15], 4-(benzyloxy)-
phthalide (9) underwent homologation in the presence of benzyl acrylate (Pathway B
or C) (Scheme 3). Unlike the 7-(benzyloxy)phthalide ring opening, the addition of the
first drops of lithium diisopropylamide (LDA) to 9 gave a strongly dark-colored
mixture. It is likely that the relocation of the benzylic anion at the aromatic moiety
produces a strong bathochromic effect. In contrast to 7-(benzyloxy)phthalide, one
equiv. of LDA was enough to convert all 4-(benzyloxy)phthalide (9) into the b-keto
ester 10 (Scheme 3). A 1H-NMR experiment in CDCl3 with intermediate 10 established
that the ratio between the keto forms and the enol form was 6% of the cis-isomer, 72%
of enol, and 22% of the trans-isomer. The attribution of the cis- and trans-isomers and
the enol form is based on the following 1H-NMR signals: d(H) 2.54 (ddd, J ¼ 3.5, 4.4,
14.2, 1HꢀC(3)), 4.21 (dd, J ¼ 4.3, 12.6, HꢀC(2)), and 5.41 (t, J ¼ 3.5, HꢀC(4)) for the
trans-isomer, d(H) 3.66 (dd, J ¼ 4.3, 12.6, HꢀC(2)) for the cis-isomer, and d(H) 2.69
(dd, J ¼ 5.4, 17.3, HaxꢀC(3)) and 3.19 (dd, J ¼ 2.6, 17.3, HeqꢀC(3)) for the enol form.
Furthermore, the huge amount of the enol form was easily deduced from the OH signal
at d(H) 12.42. Soon, we will report the results of some phthalide annulations depending
on different substitutions at the aromatic moiety; the choice of the attribution of
1H-NMR signals to the cis- and trans-isomers or the enol form will then be discussed. In
contrast to the hydrogenolysis of benzyl (benzyloxy)-1,2,3,4-tetrahydro-4-hydroxy-1-
oxonaphthalene-2-carboxylate in THF, which gave isosclerone (¼ 3,4-dihydro-4,8-
dihydroxynaphthalen-1(2H)-one in 41% yield [15], the study of the direct decarbox-
ylation of 10 under the same conditions afforded, after purification, sclerone (¼ 3,4-
dihydro-4,5-dihydroxynaphthalen-1(2H)-one; 11) in a poor yield (< 5%). Subsequent-
ly to this result, the study of Pathway C has been given up.

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Scheme 3. Ring Opening of 4-(Benzyloxy)phthalide (9) (Pathway C)
a) 9 (1.0 equiv.), LDA (1.0 equiv.), THF, ꢀ 408. b) H2C¼CHCO2Bn (1.5 equiv.), ꢀ 108, 1 h 30 min; 37%
overall).
Like in the total synthesis of the 2,4,8-trihydroxy-a-tetralones [15], the metal
enolate of 10 could be oxidized by treatment with an N-sulfonyloxaziridine and then
could undergo a decarboxylation step (Pathway B) or follow the reverse procedure
(Pathway C). However, the risk of epimerization at C(2) with exclusive formation of
the cis-diastereoisomer during the hydrogenolysis in Pathway B did not encourage us to
follow this method [15].
Consequently, 11 was prepared in two steps by reduction of juglone (¼ 5-
hydroxynaphthalene-1,4-dione; 12) [16][17] (Scheme 4). To control the stereoselec-
tivity during the subsequent reduction of the C¼O group, we decided to use the di(tert-
butyl)silylene protective group; thus, 11 was treated with di(tert-butyl)dichlorosilane at
808 in MeCN in the presence of Et3N to give 13 in 83% yield. The reaction was
completed in 48 h. With di(tert-butyl)silylene ditriflate ((CF3SO3)2SitBu2) at room
temperature, the reaction occurred in 3.5 h but gave a lower yield (51%). The benzylic
O-atom at C(4) of compound 13 is in the equatorial conformation (naphthalene atom
numbering). In the total synthesis of the 2,4,8-trihydroxy-a-tetralones [15], a keto
group was transformed to a silyl enol ether by treatment with 3 equiv. of tBuMe2SiOTf
in the presence of Et3N. Similarly, the sclerone derivative 13 gave silyl enol ether 14 in
excellent yield with 1 equiv. of tBuMe2SiOTf in the presence of 1.5 equiv. of Et3N in 1,2-
dichloroethane at room temperature after 20 min.
Intermediate 14 was subjected to oxidation with 3-chloroperbenzoic acid (m-
CPBA) or with a catalytic amount of OsO4. When the oxidation of 14 was carried out
with m-CPBA, the formation of compounds 15 and 16 in favor of the derivative 15 (de
10%) was observed (Scheme 5). During this oxidation, only the product 15 resulted
t
from a rearrangement of the BuMe2Si group. This rearrangement allowed the easy
separation of 15 and 16 by column chromatography. Thus, when the O-atom attack of
m-CPBA on the C¼C of the silyl enol ether moiety of 14 takes place syn to the tBu2SiO
group at C(4), the epoxide-ring opening leads to a pseudo-equatorial conformation of
t
the BuMe2SiO group at C(2) naphthalene atom numbering as for 13. During this

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Scheme 4. Total Synthesis of trans- and cis-3,4-Dihydro-3,4,8-trihydroxynaphthalen-1(2H)-ones (1 and 2,
resp.)
a) SnCl2, 2 H2O, 4m HCl, reflux, 1 h; 75%. b) NaBH4 (0.6 equiv.), EtOH/H2O 99 :1, r.t., 10 min; 43%. c)
t
tBu2SiCl2 (1.1 equiv.), Et3N (5.0 equiv.), HOBt (0.1 equiv.), MeCN, 808, 48 h; 83%. d) BuMe2SiOTf
(1.0 equiv.), Et3N (1.5 equiv.), 1,2-dichloroethane, r.t., 20 min; 92%. e) OsO4 (2%), pyridine (cat.),
K3[Fe(CN)6] (3.0 equiv.), K2CO3 (3.0 equiv.), MeSO2NH2 (1.0 equiv.), tBuOH/H2O 1:1, 08, 20 h; 56%.
f) NaBH4 (1.0 equiv.), EtOH/H2O 99 :1, r.t., 10 min; 82% (67% of 18 and 15% of 19). g) HF · pyridine
complex (3.0 equiv.) in HF, THF/pyridine 97:3, r.t., 25 min; 96%. h) Activated MnO2 (9.0 equiv.),
MeCl/MeOH 5 :1, r.t., 24 h; 53%. i) Buffer soln. pH 10/THF 1:1, r.t., 3.5 h; 53%. j) NaBH4 (1.0 equiv.),
EtOH/H2O 99 :1, r.t., 10 min; 76%. k) HF · pyridine complex (3.0 equiv.) in HF, THF/pyridine 97:3, r.t.,
2.5 h; 57%. l) Activated MnO2 (9.0 equiv.), CHCl3/MeOH 5 :1, r.t., 24 h; 55%. m) HF · pyridine complex
(3.0 equiv.) in HF, THF/pyridine 97:3, r.t., 25 min; 52%.
concerted process in which the cleavage of the SiꢀO bond would be simultaneous with
the epoxide-ring opening, the OH group formed at C(2) is able to meet the tBuMe2Si
group and gives 15 (Fig. 1,a). On the other hand, when the attack of the O-atom of m-
t
CPBA takes place anti to the Bu2SiO group at C(4), the OH group formed at C(2),
t
which is pushed in a pseudo-axial position, cannot meet the BuMe2Si group during
epoxide-ring opening (Fig. 1,b).

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Scheme 5. Oxidaton of Silyl Enol Ether 14 with m-CPBA to give Racemic 21 and 22
a) m-CPBA (1.0 equiv.), Cl(CH2)2Cl, ꢀ 158, then r.t. 1.5 h; 63% (35% of 15 and 28% of 16). b) NaBH4
(1.0 equiv.), EtOH/H2O 10 :1, 10 min, r.t.; 71% (21/22 92 :8).
Fig. 1. Epoxide-ring opening to 15 and 16 (the ! represent the movement of each group formed during
t
ring opening): a) The OH group formed at C(2) is able to meet the BuMe2Si group and triggers off the
tBuMe2Si rearrangement. b) The OH group formed at C(2) and the tBuMe2Si group move away preventing
tBuMe2Si rearrangement (arbitrary atom numbering)

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909
On oxidation with catalytic amounts of OsO4, silyl enol ether 14 gave exclusively
the trans compound 16 (Scheme 4). In this reaction, the control of the temperature is
important to avoid formation of 17 in the basic medium. However, the ring opening of
the dioxasilin of 16 in basic medium (!17) is very useful for the control of the
stereoselectivity in the subsequent reduction step. An X-ray study of intermediate 17
showed that OHꢀC(2) is in equatorial position, while the (hydroxysilyl)oxy group at
C(4) is axial (Fig. 2), a conformation due to an intramolecular H-bond between the H-
atom of the phenolic OH group and the O-atom of the hydroxysilyl group.
Furthermore, the crystal packing of 17 (Fig. 3) shows that symmetry-related molecules
are linked by H-bonding involving three OH groups (O(2), O(4), and O(5)); this forms
a polymer extending in the b direction. On the other hand, in compound 16, OHꢀC(2)
is pseudo-axial, while the silyloxy moiety at C(4) is pseudo-equatorial. This difference
of conformation between 16 and 17 was decisive during the reduction step which was
Fig. 2. View of the molecular structure of compound 17. Thermal ellipsoids drawn at the 30% probability
level; arbitrary atom numbering.

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Fig. 3. Packing Structure of 17
only studied with NaBH4 in aqueous EtOH solution. Thus, reduction of 16 gave a
mixture of the diastereoisomeric cis- and trans-1,2-diol 18 and 19, respectively (cis/trans
79 :21), which was separated by chromatography (silica gel), whereas reduction of 17
afforded trans-1,2-diol 20 with 100% diastereoisomer excess (Scheme 4). To improve
the diastereoisomer excess of the cis-1,2-diol (!de 84%), compound 15 was reduced to
cis-1,2-diol 21 (Scheme 5).
The last steps of the total synthesis of the targets 1 and 2 were planned to consist of a
series of protection and deprotection reactions followed by a regioselective oxidation
of the benzylic alcohol moiety. Thus, the protection of the 1,2-diol moiety of 18 and 19
by acetylation with Ac2O in the presence of catalytic amounts of N,N-dimethylpyridin-
4-amine (DMAP) in CH2Cl2 yielded the diacetyl derivatives 23 and 24 (Scheme 6).
Subsequent deprotection of the silylene group with HF · pyridine complex provided 25
and 26. Unfortunately, the oxidation of the benzylic alcohol moiety of 25 and 26 by
different methods (Dess – Martin, tetrapropylammonium perruthenate (TPAP),
MnO2) failed to afford the desired products and resulted in the decomposition of
starting material. Finally, the targets 1 and 2 were obtained by direct deprotection of the

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silylene group of 18 and 20 with HF · pyridine complex in dry THF/pyridine via the
tetrols 27 and 28, respectively, regioselectively oxidized at room temperature with
activated MnO2 for 20 h in MeOH/CHCl3 1:5 (Scheme 4).
Scheme 6. Acetylation of Compounds 18 and 19 to Give Racemic 25 and 26
a) Ac2O (10.0 equiv.), DMAP (0.3 equiv.), CH2Cl2; 70 – 93%. b) HF · pyridine complex (3.0 equiv.) in
HF, THF/pyridine 97:3, r.t., 30 min; 64 – 78%.
Conclusions. – The stereoselective total synthesis of trans- and cis-3,4-dihydro-3,4,8-
trihydroxynaphthalen-1(2H)-ones (1 and 2, resp.) was elaborated in nine and eight
steps, respectively, from juglone (12). The stereoselectivity was controlled by the
presence of the protective di(tert-butyl)silylene group. As described earlier in the
asymmetric synthesis of 3,4-dihydro-2,4,8-trihydroxy-naphthalen-1(2H)-one [15], the
asymmetric Sharpless dihydroxylation of silyl enol ether 14 permitted to achieve easily
the enantioselective synthesis of 1 or 2.
Currently, the total synthesis of racemic vermelone (¼ 3,4-dihydro-3,8-dihydrox-
ynaphthalen-1(2H)-one) is described in eleven steps from 3-oxopentanedioic acid
diethyl ester, and the asymmetric synthesis of (ꢀ)-(3R)-vermelone in five steps from
the natural product (þ)-(3R)-scytalone (¼(3R)-3,4-dihydro-3,6,8-trihydroxynaphtha-
len-1(2H)-one) [5][6][18][19]. Intermediate 16 could be used to synthesize vermelone
in only three steps by catalytic hydrogenolysis under pressure (5 bar) in acetone,
followed by deprotection of the di(tert-butyl)silylene group and regioselective
oxidation with MnO2.
The authors would like to thank Prof. Helen Stoeckli-Evans for carrying out the X-ray structure
analysis of compound 17 and Dr. Claude Saturnin for recording 400-MHz NMR spectra. Financial
ˆ
support was provided by the Swiss National Science Foundation and the Canton of Neuchatel.
Experimental Part
General. Activated MnO2 was purchased from Fluka (ref. 63548). Solvents and reagents were
distilled by standard procedures prior to use, and air-sensitive compounds were handled under either N2
or Ar. Reactions were monitored by TLC. TLC: Macherey-Nagel silica gel 60 F254 plates; visualization by
UV light and/or spraying with 5% (v/v) H2SO4/EtOH followed by heating. Column chromatography
(CC): Macherey-Nagel silica gel 60. M.p.: Bꢀchi-B510 apparatus. IR Spectra: Perkin-Elmer FT-IR-1720-
X spectrometer; n˜ in cmꢀ1. 1H- and 13C-NMR Spectra: Bruker AMX-400 spectrometer; chemicals shifts d
in ppm rel. to the residual H-atom resonances of the solvent used, J in Hz. MS: Finnigan LCQ apparatus;
in m/z. Microanalyses were performed in the Mikroelementaranalytisches Laboratorium, ETH-Zꢁrich.

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Methyl 1,4-Dihydroxy-6,8-dimethoxynaphthalene-2-carboxylate (7) and Methyl 3-(4,6-Dimethoxy-3-
oxoisobenzofuran-1(3H)-ylidene)propanoate (8). To 5,7-dimethoxyphthalide (200 mg, 1.03 mmol; 6)
[20] in freshly distilled THF (40 ml) at ꢀ 408 under Ar, commercial 2m LDA (1.03 ml, 2.06 mmol) was
added dropwise with a syringe (! light-orange soln.) After 5 min stirring, methyl 3-methoxyacrylate
(152 ml, 1.54 mmol) [21] in dry THF (3 ml) was slowly added by syringe while maintaining the temp. at ꢀ
408. Then, the burgundy mixture was allowed to warm to r.t. within 2 h and quenched by the addition of
1m HCl (40 ml). The aq. layer was extracted with AcOEt (3 ꢁ 20 ml), the combined org. extract washed
with H2O (2 ꢁ 10 ml) and brine (20 ml) and dried (MgSO4), the solvent evaporated, and the residue
purified by CC (SiO2, AcOEt/hexane 2 :3): 50.2 mg (18%) of 7 and 49.3 mg (17%) of 8.
Data of 7: Pale yellow solid. Rf (AcOEt/hexane 2 :3) 0.31. IR (KBr): 3400, 1655, 1631, 1611, 1261,
1220. 1H-NMR (400 MHz, CDCl3): 4.03 (s, MeO); 4.04 (s, MeO); 4.06 (s, MeO); 6.71 (d, J ¼ 2.4,
HꢀC(5)); 7.27 (d, J ¼ 2.4, HꢀC(7)); 7.30 (s, HꢀC(3)); 8.65 (s, OH); 11.99 (s, OH). 13C-NMR (100 MHz,
CDCl3): 51.78; 55.05; 55.75; 94.05 (C(7)); 99.13 (C(5)); 103.11; 106.42 (C(3)); 112.21; 133.58; 143.55;
156.98; 160.78; 161.20; 171.44 (C(9)). EI-MS (70 eV): 278 (Mþ), 218, 116, 91, 58.
Data of 8: White solid. M.p. 167 – 1708 (hexane/AcOEt). Rf (AcOEt/hexane 2 :3) 0.22. IR (KBr):
1
1784, 1733, 1617, 1600. H-NMR (400 MHz, CDCl3): 3.51 (d, J ¼ 7.3, CH2(2)); 3.74 (s, MeO); 3.92 (s,
MeO); 3.96 (s, MeO); 5.74 (t, J ¼ 7.3, HꢀC(3)); 6.45 (d, J ¼ 2.8, HꢀC(5’)); 6.68 (d, J ¼ 2.8, HꢀC(7’)).
13C-NMR (100 MHz, CDCl3): 30.91 (C(2)); 52.09; 55.98; 56.05; 95.20 (C(5’)); 99.59 (C(3)); 100.30
(C(7’)); 105.58; 143.19; 146.80; 159.26; 164.27; 167.03; 171.18 (C(1)). EI-MS (70 eV): 278 (Mþ), 219, 191,
161. Anal. calc. for C14H14O6 (278.3): C 60.43, H 5.07; found: C 60.24, H 4.95.
4-(Benzyloxy)isobenzofuran-1(3H)-one ( ¼ 4-(Benzyloxy)phthalide; 9). To 4-hydroxyphthalide
(3 g, 20 mmol) [22] and K2CO3 (8.3 g, 60 mmol) in DMF (50 ml) at 08 under Ar, BnBr (3.8 g, 22 mmol)
in dry DMF (10 ml) was added dropwise. The mixture was stirred at r.t. for 48 h and then quenched by
addition of H2O (50 ml) at 58. The aq. layer was extracted with Et2O (3 ꢁ 100 ml), the combined org.
extract washed with brine (20 ml) and dried (MgSO4), the solvent evaporated, and the residue purified
by CC (SiO2, AcOEt/hexane 1:1): 3.5 g (72%) of 9. White solid. M.p. 110 – 1118 (hexane/AcOEt). IR
1
(KBr): 1760, 1610, 1498, 1281. H-NMR (400 MHz, CDCl3): 5.20 (s, CH2(3)); 5.31 (s, PhCH2); 7.18 (d,
J ¼ 7.8, HꢀC(5)); 7.36 – 7.48 (m, 6 H); 7.53 (t, J ¼ 8.0, HꢀC(6)). 13C-NMR (100 MHz, CDCl3): 68.63
(PhCH2); 70.84 (C(3)); 116.53 (C(5)); 118.03; 127.84; 127.94; 128.87; 129.20; 131.21; 135.75; 136.25;
153.79 (C(4)); 171.55 (C(1)). Anal. calc. for C15H12O3 (240.3): C 74.99, H 5.03; found: C 74.80, H 5.04.
Benzyl 5-(Benzyloxy)-1,2,3,4-tetrahydro-4-hydroxy-1-oxonaphthalene-2-carboxylate (10). To 9
(500 mg, 2.08 mmol) in freshly distilled THF (100 ml) at ꢀ 408 under Ar, 2m LDA (1.04 ml, 2.08 mmol)
was added dropwise with a syringe (!dark soln.). After 5 min stirring, benzyl acrylate (439 mg,
2.70 mmol) in dry THF (5 ml) was slowly added by syringe while maintaining the temp. at ꢀ 408 (! pale
yellow soln.). Then, the mixture was allowed to warm to ꢀ 108 within 1 h 30 min and quenched by the
addition of 1m HCl (20 ml) followed by H2O (80 ml). The aq. layer was extracted with AcOEt (3 ꢁ
70 ml), the combined org. extract washed with brine (25 ml) and dried (MgSO4), the solvent evaporated
and the residue purified by CC (SiO2, AcOEt/hexane 3 :7): 308 mg (37%) of 10. Pale yellow oil. Rf
1
(AcOEt/hexane 3 :7) 0.36. H-NMR (400 MHz, CDCl3): enol-10: 2.69 (dd, J ¼ 5.4, 17.3, 1 H, CH2(3));
3.19 (dd, J ¼ 2.6, 17.3, 1 H, CH2(3)); 5.29 – 5.31 (m, 2 PhCH2O, HꢀC(4)); 7.11 (dd, J ¼ 0.9, 8.3, HꢀC(6));
7.31 – 7.48 (m, 12 H); 7.60 (d, J ¼ 7.8, HꢀC(8)); 12.42 (s, OH); trans-10: 2.54 (ddd, J ¼ 3.5, 4.4, 14.2, 1 H,
CH2(3)); 2.65 – 2.72 (m, 1 H, CH2(3)); 4.21 (dd, J ¼ 4.3, 12.6, HꢀC(2)); 5.19 (s, PhCH2O); 5.29 – 5.31 (m,
PhCH2O); 5.41 (t, J ¼ 3.5, HꢀC(4)); 7.23 (dd, J ¼ 1.0, 8.2, HꢀC(6)); 7.31 – 7.48 (m, 11 H); 7.67 (dd, J ¼
0.9, 8.0, HꢀC(8)); cis-10: 3.66 (dd, J ¼ 4.3, 12.6, HꢀC(2)). 13C-NMR (100 MHz, CDCl3): enol-10: 29.28
(C(3)); 59.89 (C(4)); 66.78; 71.04; 94.37 (C(2)); 115.53; 117.98; 127.76; 128.18; 128.51; 128.62; 128.72;
129.05; 129.16; 129.31; 130.43; 136.24; 136.99; 155.85 (C(5)); 164.13 (C(1)); 173.03 (C(11)); trans-10:
32.95 (C(3)); 49.89 (C(2)); 60.94 (C(4)); 67.39; 71.16; 119.95; 127.38; 127.86; 127.96; 128.67; 128.89;
128.94; 129.00; 129.38; 132.28; 136.16; 136.46; 156.41 (C(5)); 170.67 (C(11)); 193.75 (C(1)). ESI-MS
(neg.): 401 ([M ꢀ H]ꢀ).
(4RS)-3,4-Dihydro-4,5-dihydroxynaphthalen-1(2H)-one (¼ Sclerone; 11). To b-hydrojuglone (¼2,3-
dihydro-5-hydroxynaphthalene-1,4-dione [16] (1.45 g, 8.24 mmol) in EtOH (180 ml) at 08, NaBH4
(187 mg, 0.494 mmol) in H2O (1.8 ml) was added. The mixture was stirred for 10 min and then quenched
with H2O (100 ml). After addition of 1m HCl until pH 7 was reached, EtOH was evaporated and the aq.

Helvetica Chimica Acta – Vol. 92 (2009)
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layer extracted with AcOEt (3 ꢁ 200 ml). Then the combined org. extract was washed with brine
(150 ml) and dried (MgSO4), the solvent evaporated, and the residue purified by CC (SiO2, AcOEt/
hexane 1:1): 632 mg (43%) of 11. White solid. Rf (AcOEt/hexane 1:1) 0.21. 1H-NMR (400 MHz,
CDCl3): 1.72 (br., OH); 2.23 (m, 1 H, CH2(3)); 2.53 – 2.61 (m, 1 H, CH2(2), 1 H, CH2(3)); 2.84 (dt, J ¼
5.0, 16.2, 1 H, CH2(2)); 5.37 (dd, J ¼ 4.9, 9.9, HꢀC(4)); 7.13 (dd, J ¼ 1.3, 8.1, HꢀC(6)); 7.32 (dt, J ¼ 0.6,
8.0, HꢀC(7)); 7.60 (dd, J ¼ 1.2, 7.8, HꢀC(8)); 8.46 (br., OH). 13C-NMR (100 MHz, CDCl3): 32.38
(C(3)); 36.01 (C(2)); 68.44 (C(4)); 119.17 (C(4a)); 122.27 (C(7)); 128.53 (C(5)); 129.50 (C(6)); 132.22
(C(8a)); 155.93 (C(5)); 196.77 (C(1)). ESI-MS (pos.): 179 ([M þ H]þ).
(4RS)-4,5-{[Bis(1,1-dimethylethyl)silylene]dioxy}-3,4-dihydronaphthalen-1(2H)-one (¼(3aRS)-2,2-
Bis(1,1-dimethylethyl)-4,5-dihydronaphtho[1,8-de]-1,3,2-dioxasilin-6(3aH)-one; 13). To 11 (480 mg,
2.69 mmol) in dry MeCN (15 ml), HOBt ((¼1-hydroxy-1H-benzotriazole; 37 mg, 0.27 mmol), Et3N
t
(1.88 ml, 13.5 mmol; freshly distilled from CaH2) and Bu2SiCl2 (626 ml, 2.96 mmol) were added. The
mixture was stirred at 808 for 48 h. Then, the soln. was cooled to r.t. and poured into ice (25 g). The aq.
layer was further extracted with Et2O (3 ꢁ 30 ml), the combined org. extract washed with sat. NaHCO3
soln. (25 ml) and brine (25 ml) and dried (MgSO4), the solvent evaporated, and the brown oily residue
purified by CC (silica gel, AcOEt/hexane 1:9): 709 mg (83%) of 13. Pale yellow solid. Recrystallization
from hexane gave a white solid. M.p. 1158 (hexane). Rf (AcOEt/hexane 1:9) 0.65. IR (KBr): 2926, 2857,
1689, 1594, 1467, 1284, 1263, 829. 1H-NMR (400 MHz, CDCl3): 0.97 (s, Me3C); 1.17 (s, Me3C); 2.07 – 2.16
(m, 1 H, CH2(3)); 2.50 – 2.63 (m, 1 H, CH2(2), 1 H, CH2(3)); 2.77 – 2.84 (m, 1 H, CH2(2)); 5.30 (dd, J ¼
4.9, 11.2, HꢀC(4)); 7.16 (dd, J ¼ 1.3, 8.0, HꢀC(6)); 7.31 (t, J ¼ 8.0, HꢀC(7)); 7.65 (dd, J ¼ 1.3, 7.8,
HꢀC(8)). 13C-NMR (100 MHz, CDCl3): 21.56; 21.92; 27.32; 27.35; 33.17 (C(3)); 37.23 (C(2)); 69.65
(C(4)); 120.35 (C(8)); 124.92 (C(6)); 129.33 (C(7)); 132.02; 133.16; 154.17 (C(5)); 197.29 (C(1)). ESI-MS
(pos.): 319 ([M þ H]þ). Anal. calc. for C18H26O3Si (318.5): C 67.88, H 8.23; found: C 68.04, H 8.17.
(1RS)-1,8-{[Bis(1,1-dimethylethyl)silylene]dioxy}-4-{[(1,1-dimethylethyl)dimethylsilyl]oxy}-1,2-di-
hydronaphthalene (¼(3aRS)-2,2-Bis(1,1-dimethylethyl)-6-{[1,1-dimethylethyl)dimethylsilyl]oxy]-3a,4-
dihydronaphtho[1,8-de]-1,3,2-dioxasilin; 14). To 13 (709 mg, 2.23 mmol) in 1,2-dichloroethane (20 ml)
at r.t. under Ar, Et3N (467 ml, 3.35 mmol; freshly distilled from KOH) was added by syringe. Then, at r.t.,
tBuMe2SiOTf (512 ml, 2.23 mmol) was added dropwise by syringe. The mixture was stirred for 25 min,
then SiO2 (5 g) was directly added to the soln. The solvent was evaporated and the residue purified by CC
(SiO2, AcOEt/hexane 2 :98): 886 mg (92%) of 14. Colorless oil. Rf (AcOEt/hexane 2 :98): 0.72. IR
1
(KBr): 2933, 2891, 2860, 1579, 1471, 1353, 1261. H-NMR (400 MHz, CDCl3): 0.21 (s, MeSi); 0.24 (s,
MeSi); 1.02 (s, Me3C); 1.05 (s, Me3C); 1.11 (s, Me3C); 2.43 – 2.59 (m, CH2(2)); 5.06 (dd, J ¼ 2.5, 6.8,
HꢀC(3)); 5.31 (dd, J ¼ 7.5, 14.0, HꢀC(1)); 6.84 (dd, J ¼ 1.2, 8.0, HꢀC(7)); 7.08 (dd, J ¼ 1.2, 7.7,
HꢀC(5)); 7.16 (t, J ¼ 7.8, HꢀC(6)). 13C-NMR (100 MHz, CDCl3): ꢀ 4.17; ꢀ 4.08; 18.68; 21.80; 26.24;
27.23; 27.30; 32.35 (C(2)); 70.39 (C(1)); 101.81 (C(3)); 115.70 (C(5)); 119.47 (C(7)); 124.19; 128.54
(C(6)); 133.75; 148.04 (C(4)); 152.92 (C(8)). ESI-MS (pos.): 433 ([M þ H]þ).
(2RS,4SR)-4,5-{[Bis(1,1-dimethylethyl)silylene]dioxy}-2-{[(1,1-dimethylethyl)dimethylsilyl]oxy}-
3,4-dihydronaphthalen-1(2H)-one (¼(3aRS,5SR)-2,2-Bis(1,1-dimethylethyl)-5-{[(1,1-dimethylethyl)silyl]-
oxy}-4,5-dihydronaphtho[1,8-de]-1,3,2-dioxasilin-6(3aH)-one; 15). To 14 (158 mg, 0.366 mmol) in 1,2-
dichloroethane (7 ml) at ꢀ 158 under Ar, 70% m-CPBA (90 mg, 0.366 mmol) in 1,2-dichloroethane
(2 ml) was added dropwise by syringe. The mixture was stirred at r.t. for 90 min. Then, the solvent was
evaporated and the residue purified by CC (SiO2, AcOEt/hexane 5 :95): 57 mg (35%) of 15 and 34 mg
(28%) of 16. 15: Colorless oil. Rf (AcOEt/hexane 5 :95) 0.65. IR (KBr): 2934, 2861, 1699, 1595, 1468,
1281, 1263. 1H-NMR (400 MHz, CDCl3): 0.05 (s, MeSi); 0.18 (s, MeSi); 0.85 (s, Me3C); 0.96 (s, Me3C);
1.19 (s, Me3C); 2.12 (ddd, J ¼ 2.2, 10.2, 12.5, 1 H, CH2(3)); 2.69 (dt, J ¼ 4.1, 12.5, 1 H, CH2(3)); 4.35 (dd,
J ¼ 2.1, 3.8, HꢀC(2)); 5.58 (dd, J ¼ 4.9, 10.2, HꢀC(4)); 7.17 (dd, J ¼ 1.2, 8.0, HꢀC(6)); 7.33 (t, J ¼ 8.0,
HꢀC(7)); 7.64 (dd, J ¼ 1.2, 7.8, HꢀC(8)). 13C-NMR (100 MHz, CDCl3): ꢀ 4.78; ꢀ 4.44; 18.52; 21.56;
25.99; 27.36; 41.47 (C(3)); 65.66 (C(4)); 72.84 (C(2)); 121.10 (C(8)); 124.80 (C(6)); 129.38 (C(7)); 130.16;
133.18; 154.11 (C(5)); 194.59 (C(1)). ESI-MS (pos.): 471 ([M þ Na]þ).
(2RS,4RS)-4,5-{[Bis(1,1-dimethylethyl)silylene]dioxy}-3,4-dihydro-2-hydroxynaphthalen-1(2H)-one
(¼(3aRS,5RS)-2,2-Bis(1,1-dimethylethyl)-4,5-dihydro-5-hydroxynaphtho[1,8-de]-1,3,2-dioxasilin-6(3aH)-
one; 16). To a soln. of K2CO3 (276 mg, 2.00 mmol), K3[Fe(CN)6] (418 mg, 2.00 mmol), and pyridine (2 ml,
0.013 mmol) in H2O (3.7 ml), tBuOH (1 ml) and 2.5% OsO4 soln. in tBuOH (140 ml, 0.013 mmol) were

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Helvetica Chimica Acta – Vol. 92 (2009)
added, followed by MeSO2NH2 (63 mg, 0.66 mmol). Then, the mixture was cooled to 08, 14 (288 mg,
t
0.66 mmol) diluted in BuOH (2.7 ml) was added, and the mixture was stirred overnight at 08. After
quenching with Na2SO3 (500 mg), the mixture was stirred for 1 h at r.t., and then H2O (10 ml) was added.
The aq. layer was extracted with of AcOEt (3 ꢁ 25 ml), the combined org. extract washed with brine
(20 ml) and dried (MgSO4), the solvent evaporated, and the residue purified by CC (SiO2, AcOEt/
hexane 1:4): 126 mg (56%) of 16. White solid. M.p. 1248 (hexane). Rf (AcOEt/hexane 2 :8) 0.25. IR
(KBr): 3474, 2962, 2935, 2860, 1686, 1594, 1467, 1296, 1263. 1H-NMR (400 MHz, CDCl3): 0.94 (s, Me3C);
1.19 (s, Me3C); 2.43 (ddd, J ¼ 5.7, 7.0, 12.7, 1 H, CH2(3)); 2.61 (ddd, J ¼ 4.7, 7.0, 12.7, 1 H, CH2(3)); 4.49
(dd, J ¼ 4.7, 7.0, HꢀC(2)); 5.46 (t, J ¼ 6.3, HꢀC(4)); 7.21 (dd, J ¼ 1.1, 8.0, HꢀC(6)); 7.36 (t, J ¼ 8.0,
HꢀC(7)); 7.58 (dd, J ¼ 1.1, 7.7, HꢀC(8)). 13C-NMR (100 MHz, CDCl3) 21.65; 21.95; 27.39; 27.45; 37.74
(C(3)); 65.09 (C(4)); 70.45 (C(2)); 120.39 (C(8)); 125.27 (C(6)); 129.74; 129.93 (C(7)); 132.37; 154.83
(C(5)); 197.43 (C(1)). ESI-MS (pos.): 357 ([M þ Na]þ). Anal. calc. for C18H26O4Si (334.5): C 64.64, H
7.83; found: C 64.66, H 7.69.
(2RS,4RS)-4-{[Bis(1,1-dimethylethyl)hydroxysilyl]oxy}-3,4-dihydro-2,5-dihydroxynaphthalen-1(2H)-
one (17). A soln. of 16 (62 mg, 0.186 mmol) in buffer soln. pH 10/THF 1:1 (10 ml) was stirred at r.t. for
90 min and then neutralized with 2m HCl (! pH 7). The aq. layer was extracted with AcOEt (3 ꢁ 20 ml),
the combined org. extract washed with brine (20 ml) and dried (MgSO4), the solvent evaporated, and the
residue purified by CC (SiO2, AcOEt/hexane 1:4): 35 mg (53%) of 17. White solid. Rf (AcOEt/hexane
2 :8) 0.15. IR (KBr): 3435, 2935, 2860, 1694, 1062. 1H-NMR (400 MHz, CDCl3): 0.85 (s, Me); 1.07 (s, Me,
Me3C); 1.16 (s, Me); 2.23 (dt, J ¼ 2.8, 13.0, 1 H, CH2(3)); 2.83 (ddd, J ¼ 3.3, 5.2, 13.0, 1 H, CH2(3)); 5.07
(dd, J ¼ 5.1, 12.7, HꢀC(2)); 5.52 (t, J ¼ 2.9, HꢀC(4)); 7.21 (dd, J ¼ 1.1, 7.7, HꢀC(6)); 7.38 (t, J ¼ 8.0,
HꢀC(7)); 7.71 (dd, J ¼ 1.1, 7.7, HꢀC(8)). 13C-NMR (100 MHz, CDCl3): 20.19; 20.51; 27.10; 27.63; 27,67;
40.39 (C(3)); 63.27 (C(4)); 69.21 (C(2)); 120.65 (C(8)); 124.80 (C(6)); 130.46; 130.62 (C(7)); 130.69;
154.29 (C(5)); 200.18 (C(1)). ESI-MS (neg.): 351 ([M ꢀ H]ꢀ).
X-Ray Crystal Structure of 17. X-Ray crystal data for C18H28O5Si (Mr 352.51): Orthorhombic space
group Pbca, Dc ¼ 1.229 g · cmꢀ3, Z ¼ 8; a ¼ 11.640, b ¼ 14.381, c ¼ 22.761 ꢃ, a ¼ b ¼ g ¼ 908, V ¼
3809.8 ꢃ3; MoKa radiation, l ¼ 0.71073 ꢃ, 2.42 < q < 25.898; number of reflections measured 27881,
number of independent reflections 3666, number of observed reflections 3056 (I > 2s(I)), T 153 K.
Suitable crystals of 17 were grown from benzene as pale yellow blocks. Intensity data were collected at
153 K with a Stoe-Image-Plate-Diffraction system [23] and MoKa graphite-monochromated radiation.
Image-plate distance 70 mm, f oscillation scans 0 – 1988, step Df ¼ 1.08, 2q range 3.27 – 52.18, dmax
–
dmin ¼ 12.45 – 0.81 ꢃ. The structure was solved by direct methods with the program SHELXS-97 [24]. The
refinement and all further calculations were carried out with SHELXL-97 [25]. The H-atoms were
located from Fourier difference maps and refined isotropically. The non-H-atoms were refined
anisotropically by means of weighted full-matrix least-squares on F2. All-data refinement of 319
parameters based on F2 converged at R(F) ¼ 0.0431 and wR(F2) ¼ 0.0955. The molecular structure and
crystallographic numbering scheme are illustrated in the PLATON drawing [26] (Fig. 2) CCDC-602497
contains the supplementary crystallographic data. These data can be obtained free of charge via http://
www.ccdc.cam.ac.uk/data_request.cif.
(1RS,2SR,4SR)- and (1RS,2RS,4RS)-4,5-{[Bis(1,1-dimethylethyl)silylene]dioxy}-1,2,3,4-tetrahydro-
naphthalene-1,2-diol (¼(3aRS,5RS,6SR)- and (3aRS,5RS,6RS)-2,2-Bis(1,1-dimethylethyl)-3a,4,5,6-tetra-
hydronaphtho[1,8-de]-1,3,2-dioxasilin-5,6-diol, resp.; 18 and 19). To a soln. of 16 (277 mg, 0.829 mmol) in
EtOH (20 ml) at r.t., NaBH4 (32 mg, 0.829 mmol) in H2O (4 ml) was added. The mixture was stirred for
10 min and then H2O (20 ml) was added. After neutralization of the soln. (! pH 7) with 1m HCl, EtOH
was evaporated and the aq. layer extracted with AcOEt (3 ꢁ 40 ml). The combined org. extract was
washed with brine (20 ml) and dried (MgSO4), the solvent evaporated, and the residue purified by CC
(SiO2, AcOEt/hexane 3 :7): 186 mg (67%) of 18 and 43 mg (15%) of 19.
Data of 18: White solid. M.p. 1208 (hexane/AcOEt). Rf (AcOEt/hexane 3 :7) 0.30. IR (KBr): 3390,
2934, 2860, 1602, 1584, 1473, 1455, 1266, 968. 1H-NMR (400 MHz, CDCl3): 0.94 (s, Me3C); 1.15 (s, Me3C);
1.81 (ddd, J ¼ 1.8, 10.2, 12.0, 1 H, CH2(3)); 2.59 (dt, J ¼ 5.6, 12.0, 1 H, CH2(3)); 3.00 (br., OH); 4.17 – 4.20
(m, HꢀC(2)); 4.64 (d, J ¼ 3.4, HꢀC(1)); 5.34 (dd, J ¼ 5.9, 10.2, HꢀC(4)); 6.85 (d, J ¼ 7.9, HꢀC(6)); 7.10
(d, J ¼ 7.7, H ꢀC(8)), 7.22 (t, J ¼ 7.8, HꢀC(7)). 13C-NMR (100 MHz, CDCl3): 21.71; 21.87; 27.51; 27.59;

Helvetica Chimica Acta – Vol. 92 (2009)
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37.12 (C(3)); 66.27 (C(4)); 69.42 (C(2)); 70.30 (C(1)); 118.47 (C(6)); 120.37 (C(8)); 127.19; 129.51
(C(7)); 136.73; 154.41 (C(5)). ESI-MS (pos.): 359 ([M þ Na]þ).
Data of 19: White solid. Rf (AcOEt/hexane 3 :7) 0.23. 1H-NMR (400 MHz, CDCl3 þ D2O): 0.91 (s,
Me3C); 1.15 (s, Me3C); 2.25 (t, J ¼ 5.9, CH2(3)); 3.98 (q, J ¼ 5.9, HꢀC(2)); 4.44 (d, J ¼ 6.0, HꢀC(1)); 5.23
(t, J ¼ 6.7, HꢀC(4)); 6.89 (dd, J ¼ 0.5, 7.9, HꢀC(6)); 7.07 (d, J ¼ 7.7, H ꢀC(8)); 7.24 (t, J ¼ 7.9, HꢀC(7)).
13C-NMR (100 MHz, CDCl3): 21.65; 21.92; 27.49; 27.52; 35.66 (C(3)); 66.31 (C(4)); 70.75 (C(2)); 72.96
(C(1)); 118.94 (C(6)); 120.27 (C(8)); 126.59; 129.72 (C(7)); 136.75; 154.58 (C(5)). ESI-MS (pos.): 359
([M þ Na]þ).
(1RS,2RS,4RS)-4-{[Bis(1,1-dimethylethyl)hydroxysilyl]oxy}-1,2,3,4-tetrahydronaphthalene-1,2,5-tri-
ol (20). As described for 18/19, with 17 (41 mg, 0.116 mmol) in EtOH (3 ml) and NaBH4 soln. (600 ml, c ¼
9.3 g lꢀ1, 0.14 mmol) in H2O: 32 mg (76%) of 20. White solid. Rf (AcOEt/hexane 1:1) 0.22. IR (KBr):
1
3412, 2932, 2858, 1589, 1471, 1053. H-NMR (400 MHz, CD3COCD3 þ D2O): 0.84 (s, Me); 0.99 (s, Me,
Me3C); 1.06 (s, Me); 1.83 (ddd, J ¼ 3.2, 11.8, 13.1, 1 H, CH2(3)); 2.37 (dt, J ¼ 3.4, 13.1, 1 H, CH2(3)); 4.23
(ddd, J ¼ 3.3, 8.4, 11.7, HꢀC(2)); 4.34 (d, J ¼ 8.5, HꢀC(1)); 5.34 (t, J ¼ 3.2, HꢀC(4)); 6.76 (ddd, J ¼ 0.7,
1.2, 7.5, HꢀC(6)); 7.12 – 7.17 (m, HꢀC(7), HꢀC(8)). 13C-NMR (100 MHz, CD3COCD3): 20.10; 20.45;
20.99; 27.11; 27.38; 27.51; 39.44 (C(3)); 64.75 (C(4)); 68.82 (C(2)); 75.80 (C(1)); 115.33 (C(6)); 119.61;
124.83; 129.30; 140.09; 154.75 (C(5)). ESI-MS (neg.): 353 ([M ꢀ H]ꢀ).
(1RS,2SR,4RS)- and (1RS,2RS,4SR)-4,5-{[Bis(1,1-dimethylethyl)silylene]dioxy}-2-{[(1,1-dimethyl-
ethyl)dimethylsilyl]oxy}-1,2,3,4-tetrahydronaphthalen-1-ol (¼(3aRS,5SR,6SR)- and (3aRS,5SR,6SR)-
2,2-Bis(1,1-dimethylethyl)-5-{[(1,1-dimethylethyl)dimethylsilyl]oxy}-3a,4,5,6-tetrahydronaphtho[1,8-de]-
1,3,2-dioxasilin-6-ol; 21 and 22, resp.). As described for 18/19, with 15 (23 mg, 0.0513 mmol) in EtOH
(1 ml) and NaBH4 soln. (100 ml, c ¼ 19.5 g lꢀ1, 0.0513 mmol) in H2O: 17 mg (71%) of 21/22 (ratio 92 :8).
Colorless oil mixture.
Data of 21: Colorless oil. Hexane/AcOEt. Rf (AcOEt/hexane 3 :7) 0.36. 1H-NMR (400 MHz,
CDCl3): 0.16 (s, Me); 0.19 (s, Me); 0.88 (s, Me3C); 0.95 (s, Me3C); 1.15 (s, Me3C); 1.85 (ddd, J ¼ 1.6, 10.3,
13.5, 1 H, CH2(3)); 2.45 (d, J ¼ 10.8, OH); 2.53 (dt, J ¼ 5.6, 13.5, 1 H, CH2(3)); 4.36 (ddd, J ¼ 1.6, 3.8, 5.5,
HꢀC(2)); 4.61 (dd, J ¼ 3.8, 10.8, HꢀC(1)); 5.34 (dd, J ¼ 5.6, 10.3, HꢀC(4)); 6.84 (d, J ¼ 7.9, HꢀC(6));
7.20 – 7.26 (m, HꢀC(7), HꢀC(8)). 13C-NMR (100 MHz, CDCl3): ꢀ 4.83; ꢀ 4.49; 14.54; 18.50; 21.65;
26.14; 27.46; 27.51; 38.51 (C(3)); 66.49 (C(4)); 70.20 (C(1)); 70.65 (C(2)); 118.01 (C(6)); 121.00; 127.02;
129.21; 137.99; 153.89 (C(5)). ESI-MS (neg.): 450 ([M ꢀ H]ꢀ).
Data of 22: Colorless oil. Hexane/AcOEt. Rf (AcOEt/hexane 3 :7) 0.36. 1H-NMR (400 MHz,
CDCl3): 0.23 (s, Me); 0.26 (s, Me); 0.94 (s, Me3C); 1.00 (s, Me3C); 1.15 (s, Me3C); 1.81 – 1.89 (m, 1 H,
CH2(3)); 2.70 (dt, J ¼ 5.6, 13.5, 1 H, CH2(3)); 4.20 – 4.24 (m, HꢀC(2)); 4.80 (d, J ¼ 5.6, HꢀC(1)); 5.40
(dd, J ¼ 5.6, 10.3, HꢀC(4)); 6.84 (d, J ¼ 7.9, HꢀC(6)); 6.99 (d, J ¼ 7.8, HꢀC(8)); 7.21 – 7.24 (m, HꢀC(7)).
13C-NMR (100 MHz, CDCl3): ꢀ 4.28; ꢀ 3.84; 21.68; 21.87; 21.97; 26.23; 27.51; 27.61; 36.77 (C(3)); 66.37
(C(4)); 69.77 (C(2)); 71.51 (C(1)); 118.21 (C(6)); 120.50 (C(8)); 127.27; 129.13 (C(7)); 136.84; 154.35
(C(5)). ESI-MS (neg.): 450 ([M ꢀ H]ꢀ).
(1RS,2SR,4SR)-4,5-{[Bis(1,1-dimethylethyl)silylene]dioxy}-1,2,3,4-tetrahydronaphthalene-1,2-diyl
Diacetate (¼(3aRS,5RS,6SR)-2,2-Bis(1,1-dimethylethyl)-3a,4,5,6-tetrahydronaphtho[1,8-de]-1,3,2-dioxa-
silin-5,6-diol Diacetate; 23). To a soln. of 18 (92 mg, 0.274 mmol) in dry CH2Cl2 (5 ml) at r.t. under Ar,
DMAP (10 mg, 0.0822 mmol) and then dry Ac2O (259 ml, 0.274 mmol) were added by syringe. The
mixture was stirred for 48 h and then quenched with H2O (5 ml). The aq. layer was extracted with CH2Cl2
(3 ꢁ 10 ml), the combined org. extract washed with brine (20 ml) and dried (MgSO4), the solvent
evaporated, and the residue purified by CC (SiO2, AcOEt/hexane 3 :7): 107 mg (93%) of 23. White
solid. M.p. 116 – 1178 (hexane/AcOEt). Rf (AcOEt/hexane 3 :7) 0.44. IR (KBr): 2934, 2858, 1749, 1586,
1268, 1249. 1H-NMR (400 MHz, CDCl3): 0.92 (s, Me3C); 1.17 (s, Me3C); 2.05 (s, MeCOO); 2.03 – 2.10 (m,
1 H, CH2(3)); 2.14 (s, MeCOO); 2.62 (dt, J ¼ 6.3, 12.8, 1 H, CH2(3)); 5.31 (dd, J ¼ 6.4, 8.9, HꢀC(4)); 5.61
(ddd, J ¼ 2.8, 6.2, 8.9, HꢀC(2)); 6.10 (d, J ¼ 3.5, HꢀC(1)); 6.84 (d, J ¼ 7.7, H ꢀC(6)); 6.91 (d, J ¼ 8.0,
HꢀC(8)); 7.23 (t, J ¼ 8.0, HꢀC(7)). 13C-NMR (100 MHz, CDCl3): 21.36; 21.43; 21.71; 21.90; 27.46; 27.54;
34.58 (C(3)); 66.37 (C(4)); 68.96 (C(2)); 70.05 (C(1)); 119.16 (C(8)); 120.05 (C(6)); 127.29 (C(7));
129.59; 132.64; 154.73 (C(5)); 170.95; 171.05. ESI-MS (pos.): 443 ([M þ Na]þ). Anal. calc. for C22H32O6Si
(420.6): C 62.83, H 7.67; found: C 62.85, H 7.55.

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Helvetica Chimica Acta – Vol. 92 (2009)
(1RS,2RS,4RS)-4,5-{[Bis(1,1-dimethylethyl)silylene]dioxy}-1,2,3,4-tetrahydronaphthalene-1,2-diyl
Diacetate (¼(3aRS,5RS,6RS)-2,2-Bis(1,1-dimethylethyl)-3a,4,5,6-tetrahydronaphtho[1,8-de]-1,3,2-dioxa-
silin-5,6-diol Diacetate; 24). As described for 23, with 19 (14 mg, 0.0417 mmol) in dry CH2Cl2 (2 ml),
DMAP (1.5 mg, 0.0125 mmol), and Ac2O (39 ml, 0.417 mmol): 12 mg (70%) of 24. White solid. Rf
(AcOEt/hexane 3 :7) 0.44. IR (KBr): 2963, 2934, 2860, 1747, 1602, 1584, 1474, 1368, 1247, 1227. 1H-NMR
(400 MHz, CDCl3): 0.96 (s, Me3C); 1.16 (s, Me3C); 2.05 (s, MeCOO); 2.11 (s, MeCOO); 2.12 – 2.18 (m,
1 H, CH2(3)); 2.51 (ddt, J ¼ 1.2, 4.3, 13.9, 1 H, CH2(3)); 5.18 (dd, J ¼ 5.9, 10.6, HꢀC(4)); 5.23 (ddd, J ¼
2.8, 5.8, 7.0, HꢀC(2)); 5.87 (d, J ¼ 2.7, HꢀC(1)); 6.93 – 6.95 (m, HꢀC(6), HꢀC(7)); 7.22 (dt, J ¼ 0.6, 8.0,
HꢀC(8)). 13C-NMR (100 MHz, CDCl3) 21.45; 21.60; 21.64; 21.92; 27.42; 27.50; 32.51 (C(3)); 65.97
(C(4)); 68.80 (C(1)); 70.44 (C(2)); 119.71; 123.02; 127.95; 129.58 (C(7)); 132.34; 154.44 (C(5)); 170.25;
170.34. ESI-MS (pos.): 443 ([M þ Na]þ).
(1RS,2SR,4SR)-1,2,3,4-Tetrahydro-4,5-dihydroxynaphthalene-1,2-diyl Diacetate (¼(1RS,2SR,6SR)-
1,2,3,4-Tetrahydronaphthalene-1,2,4,5-tetrol 1,2-Diacetate; 25). To a soln. of 23 (90 mg, 0.214 mmol) in
dry THF (5 ml) in a plastic flask at r.t., and dry pyridine (323 ml, 2.97 mmol) and then 70% HF/pyridine
(161 mg, 4.27 mmol) were added by syringe. The mixture was stirred for 30 min, then AcOEt (15 ml) was
added. The mixture was washed with brine (10 ml) and dried (MgSO4), the solvent evaporated, and the
residue purified by CC (SiO2, AcOEt/hexane 1:1): 47 mg (78%) of 25. White solid. M.p. 1418 (hexane/
AcOEt). Rf (AcOEt/hexane 1:1) 0.22. IR (KBr): 3481, 3242, 1734, 1719, 1595, 1471, 1368, 1260, 1229.
1H-NMR (400 MHz, CD3COCD3): 1.99 (s, MeCOO); 2.04 (s, MeCOO); 2.06 – 2.10 (m, 1 H, CH2(3));
2.45 (ddd, J ¼ 5.1, 10.8, 13.4, 1 H, CH2(3)); 3.84 (br., OH); 5.26 (t, J ¼ 4.7, HꢀC(4)); 5.53 (dt, J ¼ 3.3, 10.8,
HꢀC(2)); 6.13 (d, J ¼ 3.4, HꢀC(1)); 6.78 (d, J ¼ 7.7, H ꢀC(6)); 6.88 (dd, J ¼ 1.1, 8.0, HꢀC(8)); 7.19 (t, J ¼
7.8, HꢀC(7)). 13C-NMR (100 MHz, CD3COCD3) 20.44; 20.46; 32.48 (C(3)); 63.58 (C(4)); 67.91 (C(2));
69.07 (C(1)); 116.10 (C(8)); 120.83 (C(6)); 125.33; 129.64 (C(7)); 134.15; 156.27 (C(5)); 170.11; 170.27.
ESI-MS (neg.): 279 ([M ꢀ H]ꢀ). Anal. calc. for C14H16O6 (280.3): C 60.00, H 5.75; found: C 60.14, H 5.91.
(1RS,2RS,4RS)-2-Acetoxy-4,5-dihydroxy-1,2,3,4-tetrahydronaphthalene-1,2-diyl
Diacetate
(¼(1RS,2RS,3RS)-1,2,3,4-Tetrahydronaphthalene-1,2,4,5-tetrol 1,2-Diacetate; 26). As described for 25,
with 24 (15 mg, 0.0286 mmol) in dry THF (2 ml), dry pyridine (76 ml, 0.698 mmol), and 70% HF/pyridine
(25 mg, 0.662 mmol): 5 mg (64%) of 26. White solid. Rf (AcOEt/hexane 1:1) 0.24. 1H-NMR (400 MHz,
CD3COCD3): 2.01 (s, MeCOO); 2.10 (s, MeCOO); 2.26 – 2.29 (m, CH2(3)); 4.74 (br., OH); 5.19 – 5.22
(m, HꢀC(4)); 5.37 – 5.42 (m, HꢀC(2)); 5.92 (d, J ¼ 6.4, HꢀC(1)); 6.75 (d, J ¼ 7.7, H ꢀC(6)); 6.83 (dd, J ¼
1.1, 8.1, HꢀC(8)); 7.18 (t, J ¼ 7.8, HꢀC(7)); 8.86 (br., OH). 13C-NMR (100 MHz, CD3COCD3): 20.43;
20.49; 33.79 (C(3)); 63.77 (C(4)); 69.58 (C(2)); 71.11 (C(1)); 115.75 (C(8)); 119.94 (C(6)); 125.23; 129.48
(C(7)); 134.53; 156.46 (C(5)); 169.77; 170.25. ESI-MS (neg.): 279 ([M ꢀ H]ꢀ).
(1RS,2SR,4SR)-1,2,3,4-Tetrahydronaphthalene-1,2,4,5-tetrol (27). To a soln. of 18 (103 mg,
0.307 mmol) in dry THF (10 ml) in a plastic flask at r.t., dry pyridine (465 ml, 4.27 mmol) and then
70% HF/pyridine (231 mg, 6.11 mmol) were added by syringe. The mixture was stirred for 30 min and
then AcOEt (15 ml) was added. The mixture was poured over SiO2 (1.5 g), the solvent evaporated, and
the residue purified by CC (SiO2, AcOEt): 58 mg (96%) of 27. White solid. Rf (AcOEt) 0.24. 1H-NMR
(400 MHz, CD3OD): 1.95 (ddt, J ¼ 1.0, 3.5, 13.4, 1 H, CH2(3)); 2.30 (ddd, J ¼ 4.8, 11.1, 13.4, 1 H, CH2(3));
4.24 (dt, J ¼ 3.3, 11.1, HꢀC(2)); 4.61 (d, J ¼ 3.5, HꢀC(1)); 5.20 (t, J ¼ 4.2, HꢀC(4)); 6.78 (dd, J ¼ 1.1, 8.0,
HꢀC(8)); 6.91 (dd, J ¼ 0.6, 7.6, HꢀC(6)); 7.17 (t, J ¼ 7.8, HꢀC(7)). 13C-NMR (100 MHz, CD3OD): 34.26
(C(3)); 63.91 (C(4)); 66.67 (C(2)); 70.09 (C(1)); 114.74 (C(8)); 121.16 (C(6)); 124.21; 129.16 (C(7));
138.58; 156.08 (C(5)). ESI-MS (neg.): 195 ([M ꢀ H]ꢀ).
(1RS,2RS,4RS)-1,2,3,4-Tetrahydronaphthalene-1,2,4,5-tetrol (28). As described for 27, with 19
(20 mg, 0.0594 mmol) in dry THF (5 ml) dry pyridine (90 ml, 0.828 mmol), and 70% HF/pyridine
(45 mg, 1.19 mmol): 6 mg (52%) of 28. White solid. As described for 27, with 20 (14 mg, 0.0395 mmol) in
dry THF (1.4 ml), dry pyridine (63 ml, 0.578 mmol), and 70% HF/pyridine (32 mg, 8.48 mmol) but for 2 h
30 min: 4.4 mg (57%) of 28. White solid. Rf (AcOEt) 0.15. 1H-NMR (400 MHz, CD3OD): 1.92 (ddd, J ¼
4.5, 11.0, 13.5, 1 H, CH2(3)); 2.22 (dt, J ¼ 3.6, 13.5, 1 H, CH2(3)); 4.05 (ddd, J ¼ 3.3, 7.8, 11.0, HꢀC(2));
4.33 (d, J ¼ 7.7, H ꢀC(1)); 5.15 (t, J ¼ 4.1, HꢀC(4)); 6.73 (ddd, J ¼ 0.7, 1.1, 7.9, HꢀC(8)); 7.06 (dt, J ¼ 0.9,
7.8, HꢀC(6)); 7.16 (t, J ¼ 7.9, HꢀC(7)). 13C-NMR (100 MHz, CD3OD): 37.25 (C(3)); 63.48 (C(4)); 68.96
(C(2)); 74.44 (C(1)); 113.90 (C(8)); 118.63 (C(6)); 124.04; 129.10 (C(7)); 139.71; 155.82 (C(5)). ESI-MS
(neg.): 195 ([M ꢀ H]ꢀ).

Helvetica Chimica Acta – Vol. 92 (2009)
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cis-(3RS,4SR)-3,4-Dihydro-3,4,8-trihydroxynaphthalen-1(2H)-one (2). Under stirring, 27 (31 mg,
0.158 mmol) was dissolved in MeOH (1.7 ml), and then CHCl3 (8.6 ml) was added. At r.t., activated
MnO2 (151 mg, ca. 1.56 mmol; Fluka ref. 63548) was added by spatula. The mixture was stirred overnight
and then filtered over SiO2. The SiO2 was washed with AcOEt and then the solvent evaporated: 16.3 mg
(53%) of 2. Pale yellow solid. Rf (AcOEt) 0.33. 1H-NMR (400 MHz, CD3OD): 2.88 (dd, J ¼ 3.9, 17.4, 1 H,
CH2(2)); 2.99 (dd, J ¼ 7.2, 17.4, 1 H, CH2(2)); 4.30 (ddd, J ¼ 2.8, 3.9, 6.9, HꢀC(3)); 4.86 (d, J ¼ 2.8,
HꢀC(4)); 6.88 (ddd, J ¼ 0.5, 1.0, 8.4, HꢀC(5)); 7.12 (dt, J ¼ 1.0, 7.5, HꢀC(7)); 7.54 (dd, J ¼ 7.5, 8.4,
HꢀC(6)). 13C-NMR (100 MHz, CD3OD): 42.90 (C(2)); 69.45 (C(3)); 70.29 (C(4)); 115.65 (C(9)); 116.82
(C(5)); 119.02 (C(7)); 136.93 (C(6)); 144.65 (C(10)); 162.22 (C(5)); 203.72 (C(1)). ESI-MS (neg.): 193
([M ꢀ H]ꢀ).
trans-(3RS,4RS)-3,4-Dihydro-3,4,8-trihydroxynaphthalen-1(2H)-one (1). As described for 2, with 28
(6 mg, 0.0306 mmol), MeOH (0.3 ml), CHCl3 (1.7 ml), and activated MnO2 (30 mg, ca. 0.3 mmol):
3.3 mg (55%) of 1. Pale yellow solid. Rf (AcOEt) 0.33. 1H-NMR (400 MHz, CD3OD): 2.72 (dd, J ¼ 8.0,
17.2, 1 H, CH2(2)); 3.11 (dd, J ¼ 4.0, 17.2, 1 H, CH2(2)); 4.05 – 4.11 (m, HꢀC(3)); 4.63 (d, J ¼ 7.0,
HꢀC(4)); 6.88 (dd, J ¼ 0.6, 8.6, HꢀC(5)); 7.14 (dt, J ¼ 0.6, 7.4, HꢀC(7)); 7.56 (dd, J ¼ 7.4, 8.4, HꢀC(6)).
ESI-MS (neg.): 193 ([M ꢀ H]ꢀ).
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Received October 16, 2008