Stereoisomerization of α-hydroxy-β-sulfenyl-α,β- dimethyl naphthoquinones controlled by nonbonded sulfur-oxygen interactions

Article abstract of DOI:10.1016/j.tet.2013.01.033

The anti α-hydroxy-β-sulfenyl-α,β-dimethyl naphthoquinones isomerize in basic media into syn/anti mixtures of isomers, giving the syn isomer as the major product. Conversely, anti α-hydroxy-β-alkoxy-α,β-dimethyl naphthoquinones isomerize to furnish the an

Full text of DOI:10.1016/j.tet.2013.01.033

Tetrahedron 69 (2013) 2098e2101
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stereoisomerization of a-hydroxy-b-sulfenyl-a,b-dimethyl
naphthoquinones controlled by nonbonded sulfureoxygen
interactions
*
*
ꢀ
ꢀ
Antonio Latorre, Santiago Rodríguez , Amit Jain, Florenci V. Gonzalez , Jose A. Mata
ꢁ
ꢁ
ꢀ
Departament de Química Inorganica i Organica, Universitat Jaume I, 12080 Castello, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
The anti
mixtures of isomers, giving the syn isomer as the major product. Conversely, anti
-dimethyl naphthoquinones isomerize to furnish the anti isomer as the major product. The crystal
structure of syn -hydroxy- -phenylsulfenyl- -dimethyl naphthoquinone has been determined. The X-
ray and experimental work demonstrated that an attractive 1,4 intramolecular interaction of divalent
sulfur with hydroxyl oxygen is the driving force for the aforementioned stereochemical preference.
Ó 2013 Elsevier Ltd. All rights reserved.
a
-hydroxy-
b
-sulfenyl-
a
,
b
-dimethyl naphthoquinones isomerize in basic media into syn/anti
Received 6 November 2012
Received in revised form 7 January 2013
Accepted 9 January 2013
a
-hydroxy- -alkoxy-
b
a,b
a
b
a,b
Available online 17 January 2013
1. Introduction
sulfureoxygen interactions could control the stereoselectivity of
the reaction. When we determined the crystal structures of syn-
In 1981, Silverman investigated the mechanism of vitamin
K epoxide-reductase using 2,3-dimethyl-1,4-naphthoquinone 2,3-
epoxide as a model for vitamin K 2,3-epoxide.1,2 This study
advanced our understanding of the mechanism of vitamin K
epoxide-reductase during the catalytic conversion of vitamin K 2,3-
epoxide into vitamin K, which is essential for blood coagulation.
esyn lactones, we observed that the sulfureoxygen distances were
less than the sum of the Van der Waals radii (3.3 A), with the angle
ꢂ
formed by the hydroxyl oxygen, sulfur, and quaternary aromatic
carbon being approximately 180ꢀ. In addition, the carbonylic oxy-
genesulfur was directed <40ꢀ from the perpendicular to the
CeSeC. Then two concomitant, attractive 1,4 intramolecular in-
teractions of divalent sulfur with both the carbonyl and the hy-
droxyl oxygens served as the driving force to establish the
stereochemical preference.
This author reported that anti
a-hydroxy-b-ethylsulfenyl-a,b-di-
methyl naphthoquinone (anti-1) isomerized into an 8:2 mixture of
syn/anti isomers when treated with sodium ethylthiolate (Scheme
1) through a retro-aldol/aldol mechanism. A similar result was
observed for
a
-hydroxy-
b
-phenylsulfenyl-
a,
b-dimethyl naph-
SAr
HO
thoquinone 2.2
O
anti-syn
O
O
O
SEt
R
SEt
NaSEt
Me
Me
OH
Me
SAr
OH
SAr
SAr
OH
HO
R
HO
R
Me
O
O
O
anti-1
O
O
syn-1
O
syn-anti
O
syn-syn
20%
O
80%
R
Scheme 1. Isomerization of naphthoquinone derivatives.
SAr
We have recently reported that syneanti-
b
b
-hydroxy-
a
-sulfenyl-
-sulfenyl-
HO
g
g
-butyrolactones isomerized into synesyn-
-hydroxy-
a
-butyrolactones (Scheme 2).3 We proposed that nonbonded
O
anti-anti
O
R
* Corresponding authors. Tel.: þ34 964729156; fax: þ34 964728214; e-mail ad-
Scheme 2. Isomerization of b-hydroxy-a-sulfenyl-g-butyrolactones.
ꢀ
dress: fgonzale@qio.uji.es (F.V. Gonzalez).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.01.033

A. Latorre et al. / Tetrahedron 69 (2013) 2098e2101
2099
Weak nonbonding interactions between sulfur and oxygen
atoms have been invoked to explain the biological activities as well
as their physical properties in a large number of organosulfur
compounds.4
obtained for methyl sulfenyl derivative 3. syn-isomers 1e3 (or anti
isomers 1e3 or any mixture of both) invariably isomerized into
a mixture of syn/anti lactones, with the syn isomer being the major
one in all cases (entries 1e9, Table 1). As already reported,2,10 the
elimination product was also obtained in some cases (Table 1). In
contrast to
b-hydroxy-a-sulfenyl-g
-butyrolactones,3 compounds
2. Results and discussion
1e3 did not isomerize in the presence of bases, such as triethyl-
amine or N-methylmorpholine.
Herein, we show that for
a-hydroxy-b-sulfenyl-a,b-dimethyl
naphthoquinones, the intramolecular interaction of divalent sulfur
with the hydroxyl oxygen also control the stereochemical prefer-
Table 1
ence. The crystal structure of syn
methyl naphthoquinone has been determined. Also
alkoxy- -dimethyl naphthoquinones have been prepared for
a
-hydroxy-
b
-sulfenyl-a,b-di-
Ratio of syn/anti isomers resulting from isomerization
a
-hydroxy-
b-
Entry
Substrate
Base
anti/syn
a,b
1
2
3
4
5
6
7
8
syn 1
anti 1
syn 1
syn 2
syn 2
anti 2
anti 2
syn 3
syn 3
anti 4
anti 4
anti 5
anti 5
NaSEt
NaSEt
NaSPh
NaSEt
NaSPh
NaSEt
NaSPh
NaSEt
NaSPh
NaSEt
NaSPh
NaSEt
NaSPh
14/65a
14/71a
5/83a
17/83
13/61a
27/68a
28/69a
8/82a
20/80
70/30
>95/5
58/42
38/62
comparison. The isomerization of these oxygenated analogs under
the same conditions as the sulfurated ones gave either the anti
isomer or an equal mixture of syn/anti isomers.
a
-Hydroxy-b-sulfenyl-a,b-dimethyl naphthoquinones anti-1
and anti-2 were prepared starting from the epoxide5 using the
corresponding thiol in the presence of triethylamine.2 Having al-
ready reported compounds 1 and 2, we went on to prepare com-
pound syn 3 resulting from the opening of the epoxide with sodium
methyl thiolate and further isomerization.6 This reaction furnished
a mixture of isomers with the syn isomer predominating.
9
10
11
12
13
For the preparation of the oxygenated derivatives, acidic condi-
tionswere required.Theepoxidewasopenedwiththecorresponding
alcohol7 using boron trifluoride as a catalyst using conditions we had
previously reported.8 These reactions resulted to be very slow (see
Experimental section). During the coagulation cascade,9 accordingly
vitamin-K-epoxide is selectively opened by a cysteine residue of
vitamin-K-epoxide reductase, but it is not opened by the coagulation
factors, which are serine proteases (Scheme 3).
a
Elimination product was already obtained.
When oxygenated substrates 4e5 were submitted to the same
reaction conditions as their sulfurated counterparts, they un-
derwent an isomerization that furnished a mixture of isomers
(entries 10e13, Table 1). Compound 4 was treated with sodium
ethylthiolate and sodium phenylthiolate giving rise to a mixture of
isomers, with the main product being the anti isomer (entries 10
and 11). This result is opposite to the one observed starting from
sulfurated compound 1, which furnished the syn isomer under the
same conditions (compare 1e3 with 10e11 entries). Similarly
compound 5 gave an equal mixture of syn/anti isomers whilst 3 gave
the syn isomer as the main product (compare 8e9 with 12e13 en-
tries). No elimination products were observed for compounds 4e5,
as expected. Silverman had previously suggested an elimination
mechanism through the formation of disulfide for compound 4.2
O
O
R
Me
O
S
Et3N
+ RSH
Me
Me
Me
OH
O
O
O
anti 1, R = Et
anti 2, R = Ph
O
Me
O
Me
O
O
XR
+ NaSR
XR
Me
OH
Me
SR
base (1eq.)
CH3CN
Me
Me
Me
OH
O
syn 1, R = Et
syn 2, R = Ph
syn 3, R = Me
Me
OH
O
O
O
anti
O
0ºC, 1.5h
syn
O
R
Me
O
O
The crystal structure of compound syn 2 has been determined
BF3·Et2O
(Fig. 1).11 The distance between the hydroxyꢀl oxygen and sulfur was
+ ROH
Me
ꢂ
Me
2.97 A. The azimuthal angle was 4¼113.7 and polar angle was
q
¼99.4ꢀ for the sulfurehydroxyl oxygen contact. These geometric
Me
OH
O
O
features are similar to the ones depicted for b-hydroxy-a-sulfenyl-
g
-butyrolactones.3 For them, the azimuthal angles and polar
anti 4, R = Et
anti 5, R = Me
angles for sulfurehydroxyl oxygen contacts were 107ꢀ and 93ꢀ,
respectively.
Scheme 3. Preparation of substrates.
The short atomic distance observed is interpreted as a non-
bonded interaction between oxygen and sulfur atoms, an in-
teraction that would stabilize the syn isomer.
The linear alignment of the CeS covalent bond and the co-
ordinating hydroxyl oxygen should allows an effective orbital in-
Compounds 1e5 were submitted to the isomerization reaction
using sodium ethylthiolate or sodium phenylthiolate. Compounds 1
and 2 gave the same results as previously reported, giving rise to
the syn isomer as the major form.2 Similar results were also
teraction between the oxygen lone electron pair and the s* orbital

2100
A. Latorre et al. / Tetrahedron 69 (2013) 2098e2101
a flow of 400 and 60 L/h, respectively. The temperature of the
source block was set to 120 ꢀC and the desolvation temperature to
150 ꢀC. A capillary voltage of 3 kV was used in the positive scan
mode, and the cone voltage was set to 15 V. Sample solutions
were infused via syringe pump directly connected to the ESI
source at a flow rate of 10 mL/min. ESI mass spectra were domi-
nated by the presence of sodium adducts of the target compound.
For the accurate mass measurements, a 2 mg/L standard solution
of leucine enkephalin was introduced via the lock spray needle at
a cone voltage set to 45 V and a flow rate of 30 mL/min. IR spectra
were recorded as oil films or KBr discs or NaCl pellets on a FT-IR
spectrometer. EM Science Silica Gel 60 was used for column
chromatography while TLC was performed with precoated plates
(Kieselgel 60, F254, 0.25 mm). Unless otherwise specified, all re-
actions were carried out under nitrogen atmosphere with mag-
netic stirring.
4.2. General experimental procedure for the preparation of
thioethers anti-1 and anti-2
To an ice-bath cold solution of 2,3-dimethyl-1,4-napht-
hoquinone-2,3-epoxide (202 mg, 1.0 mmol) in dry acetonitrile
(2.0 mL) was added drop wise the corresponding thiol (3.0 mmol)
and then triethylamine (140 mL, 1.0 mmol). The resulting mixture
Fig. 1. X-ray structure of compound syn-2.
was stirred cold with an ice-bath for 3.5 h. Then was quenched with
dichloromethane (15 mL) and 5% Na2CO3 (15 mL). The organic layer
was separated, the aqueous layer was extracted with dichloro-
methane (3ꢁ15 mL), and then the organic layers were dried
(Na2SO4) and concentrated. The crude was purified through chro-
matography (silica-gel, hexanes/ethyl acetate (7:3)) to afford the
desired compound. The resulting solid mixture was recrystallized
from hexanes.
ꢂ
of the SeC bond, which may elongate the SeC bond (1.77 A for syn
2, 1.75 A for the diphenyl disulfide). The phenyl ring attached to the
sulfur atom is oriented away from the hydroxyl, permitting the
interaction to take place. Sulfureoxygen interactions type I have
nucleophilic oxygen tending to approach along the extension of the
covalent bonds to sulfur.12
ꢂ
The distance between the carbonyl oxygen and sulfur was
ꢀ
ꢂ
3.55 A. For this contact, the azimuthal angle was 94.9 and the polar
angle was 97.9ꢀ. These parameters cannot be attributed to a sul-
fureoxygen interaction. The planar structure of the naph-
thoquinone imposes rigidity that does not permit the sulfur atom
to contact the carbonyl oxygen. This orientation might be at the
origin of the lower selectivity observed during isomerization of
4.2.1. (2R,3S)-2-(Ethylthio)-3-hydroxy-2,3-dimethyl-2,3-dihy-
dronaphthalene-1,4-dione anti-1. Recrystallized from hexanes gave
white crystals, mp 91e92 ꢀC (lit.2 93e93.5 ꢀC) (Yield¼251 mg, 95%).
1H NMR (500 MHz, CDCl3)
d
7.97 (1H, d, J¼7.3 Hz), 7.85 (1H, d,
J¼7.2 Hz), 7.57e7.64 (2H, m), 3.84 (1H, br s), 2.44 (m, 1H), 2.16 (m,
1H), 1.64 (3H, s), 1.55 (3H, s), 1.00 (3H, t, J¼7.4 Hz). 13C NMR
compounds 1e3 as compared to the
b-hydroxy-a-sulfenyl-g-
(125 MHz, CDCl3)
d 195.2, 192.8, 134.1, 133.8, 132.7, 132.2, 127.1,
butyrolactones.
126.8, 80.2, 60.9, 23.8, 18.5, 16.3, 13.8 ppm. IR (NaCl)
d 3018, 2951,
2930, 1696, 1595, 1539, 1455, 1371, 1281, 1188, 1110, 1016, 975,
937 cmꢂ1. HRMS m/z calcd for C14H16O3SNa [MþNaþ]: 287.0718,
found: 287.0720.
3. Conclusions
In summary, an attractive 1,4 intramolecular interaction of di-
valent sulfur with hydroxyl oxygen has been observed in the X-ray
structure of syn
thoquinone. This sulfureoxygen interaction can be invoked to ac-
count for the tendency of -hydroxy- -sulfenyl- -dimethyl
naphthoquinones to assume the syn configuration. This study
should contribute to the understanding of the role played by this
subtle noncovalent interaction in determining the biochemical
processing of vitamin-K-epoxide during blood coagulation.
4.2.2. (2R,3S)-2-Hydroxy-2,3-dimethyl-3-(phenylthio)-2,3-dihy-
dronaphthalene-1,4-dione anti-2. Recrystallized from hexanes gave
white crystals, mp 109e112 ꢀC (lit.2 115.5e116.5 ꢀC) (Yield¼287 mg,
a-hydroxy-b-phenylsulfenyl-a,b-dimethyl naph-
92%). 1H NMR (500 MHz, CDCl3)
d 7.87e7.98 (2H, m), 7.62e7.67 (2H,
a
b
a,b
m), 7.13e7.32 (2H, m), 3.64 (1H, s), 1.68 (3H, s), 1.58 (3H, s). 13C NMR
(125 MHz, CDCl3) 194.9, 192.7, 137.0, 134.2, 133.8, 133.5, 132.2,
d
129.9, 128.8, 127.2, 127.0, 80.2, 64.4, 18.5, 17.0 ppm. IR (NaCl) d 3035,
2929, 1698, 1601, 1507, 1370, 1113, 1047, 949, 888 cmꢂ1. HRMS m/z
calcd for C18H16O3SNa [MþNaþ]: 335.0718, found: 335.0719.
4. Experimental section
4.3. General experimental procedure for the preparation of
4.1. General experimental methods
thioethers syn-1, syn-2 and syn-3
All solvents used in reactions were freshly distilled from ap-
propriate drying agents before use. 1H NMR spectra and 13C NMR
spectra were measured in CDCl3 (1H, 7.24 ppm; 13C 77.0 ppm)
solution at 30 ꢀC on a 300 MHz or a 500 MHz NMR spectrometer.
Mass spectra were measured in a hybrid quadrupole-t-TOF mass
spectrometer operating at a resolution ca. 15000 FWHM (W-
mode) with an orthogonal Z-spray-electrospray interface was
used. The drying gas as well as nebulizing gas was nitrogen at
To an ice-bath cold solution of 2,3-dimethyl-1,4-naphtho-
quinone-2,3-epoxide (202 mg, 1.0 mmol) in dry tetrahydrofuran
(5.0 mL) was added drop in one portion the corresponding so-
dium thiolate (1.0 mmol). The resulting mixture was stirred cold
with an ice-bath for 1 h. Then was quenched with dichloro-
methane (15 mL) and water (15 mL). The organic layer was sep-
arated, the aqueous layer was extracted with dichloromethane
(3ꢁ15 mL), and then the organic layers were dried (Na2SO4) and

A. Latorre et al. / Tetrahedron 69 (2013) 2098e2101
2101
concentrated. The crude was purified through chromatography
(silica-gel, hexanes/ethyl acetate (7:3)) to afford the desired
compound.
4.4.1. (2S,3S)-2-Ethoxy-3-hydroxy-2,3-dimethyl-2,3-dihy-
dronaphthalene-1,4-dione anti-4. White needles, mp 67e70 ꢀC
(Yield¼372 mg, 60%) (Quantitative yield based on recovered
starting material). 1H NMR (500 MHz, CDCl3)
d 7.90e7.93 (2H, m),
4.3.1. (2S,3S)-2-(Ethylthio)-3-hydroxy-2,3-dimethyl-2,3-dihy-
7.59e7.64 (2H, m), 4.01 (1H, br s), 3.47e3.53 (1H, m), 3.22e3.28
dronaphthalene-1,4-dione syn-1. Yield¼243 mg, 92%. 1H NMR
(1H, m), 1.38 (3H, s), 1.34 (3H, s), 0.90 (3H, t, J¼7.1 Hz). 13C NMR
(300 MHz, CDCl3)
d
8.03e8.06 (1H, m), 7.96e7.99 (1H, m), 7.64e7.74
(125 MHz, CDCl3) d 197.35, 197.14, 134.3, 134.0, 133.3, 132.5, 126.9,
(2H, m), 4.11 (1H, br s), 2.34 (m, 1H), 2.07 (m, 1H), 1.64 (3H, s), 1.26
126.8, 85.0, 81.0, 60.1, 19.3, 15.5, 13.9 ppm. IR (NaCl) d 3046, 2981,
(3H, s), 0.94 (3H, t, J¼7.5 Hz). 13C NMR (75 MHz, CDCl3)
d
198.8,
1697,1507,1456,1276,1054, 984, 707, 667 cmꢂ1. HRMS m/z calcd for
C14H16O4Na [MþNaþ]: 271.0946, found: 271.0948.
191.5,134.8,134.1,133.1,131.1,127.5,126.7, 80.0, 62.5, 24.7, 23.7,15.2,
13.7 ppm. IR (NaCl) d 3040, 2930, 1730, 1600, 1442, 1332, 1225, 1159,
1068, 1025, 859, 777, 750, 597 cmꢂ1
.
HRMS m/z calcd for
4.4.2. (2S,3S)-2-Hydroxy-3-methoxy-2,3-dimethyl-2,3-dihy-
dronaphthalene-1,4-dione anti-5. White needles, mp 97e99 ꢀC
(Yield¼322 mg, 55%) (Quantitative yield based on recovered
C14H16O3SNa [MþNaþ]: 287.0718, found: 287.0715.
4.3.2. (2S,3S)-2-Hydroxy-2,3-dimethyl-3-(phenylthio)-2,3-dihy-
dronaphthalene-1,4-dione syn-2. Recrystallized from CH2Cl2e
hexanes gave white crystals, mp 86e87 ꢀC (lit.2 85.5e89 ꢀC)
starting material). 1H NMR (500 MHz, CDCl3)
d 7.94e7.99 (2H, m),
7.63e7.69 (2H, m), 3.92 (1H, br s), 3.27 (3H, s), 1.37 (3H, s), 1.34 (3H,
s). 13C NMR (125 MHz, CDCl3)
197.8, 196.8, 134.5, 134.1, 133.3,
132.2, 127.1, 127.0, 85.1, 81.3, 52.5, 20.2, 13.9 ppm. IR (NaCl) 3019,
d
(Yield¼281 mg, 90%). 1H NMR (500 MHz, CDCl3)
d
8.10 (1H, m), 7.92
d
(1H, m), 7.71e7.75 (2H, m), 7.27 (1H, t, J¼7.4 Hz), 7.16 (2H, t,
J¼7.8 Hz), 7.06 (2H, d, J¼7.3 Hz), 4.37 (1H, s),1.66 (3H, s),1.34 (3H, s).
2958, 2938, 1698, 1596, 1539, 1455, 1372, 1281, 1189, 1122, 1017,
938 cmꢂ1. HRMS m/z calcd for C13H14O4Na [MþNaþ]: 257.0790,
found: 257.0792.
13C NMR (125 MHz, CDCl3)
d 198.9, 191.3, 136.9, 135.0, 134.1, 134.0,
131.0, 129.9, 129.4, 128.8, 127.6, 126.9, 80.1, 66.5, 25.2, 16.0 ppm. IR
Acknowledgements
(NaCl)
d 3060, 2980, 2935, 1885, 1731, 1563, 1442, 1330, 1253,
1160, 1075, 1025, 897, 859, 776, 691 cmꢂ1. HRMS m/z calcd for
C18H16O3SNa [MþNaþ]: 335.0718, found: 335.0723.
This work was financed by Bancaixa-UJI foundation (P11B2011-
59 and P1 1B2011-28). The authors also are grateful to the Serveis
ꢀ
Centrals d’Instrumentacio Científica (SCIC) of the Universitat Jaume
4.3.3. (2S,3S)-2-Hydroxy-2,3-dimethyl-3-(methylthio)-2,3-dihy-
dronaphthalene-1,4-dione syn-3. Recrystallized from CH2Cl2e
hexanes gave orange solid, mp 81e83 ꢀC (Yield¼223 mg, 89%). 1H
I for providing us with mass spectrometry and NMR.
Supplementary data
NMR (300 MHz, CDCl3)
d 8.01e8.04 (1H, m), 7.93e7.96 (1H, m),
7.62e7.72 (2H, m), 4.15 (1H, br s), 1.70 (3H, s), 1.57 (3H, s), 1.26 (3H,
s). 13C NMR (75 MHz, CDCl3)
198.9, 190.1, 134.9, 134.1, 132.9, 131.0,
127.4, 126.7, 80.0, 61.9, 25.0, 14.1, 12.4 ppm. IR (NaCl) 3019, 2987,
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.01.033.
d
d
2937, 1680, 1592, 1507, 1455, 1386, 1311, 1292, 1263, 1174, 1005, 885,
713 cmꢂ1. HRMS m/z calcd for C13H14O3SNa [MþNaþ]: 273.0561,
found: 273.0562.
References and notes
1. Silverman, R. B. J. Am. Chem. Soc. 1981, 103, 5939e5941.
2. Silverman, R. B. J. Org. Chem. 1981, 46, 4789e4791.
ꢀ
ꢀ
3. Gonzalez, F. V.; Jain, A.; Rodríguez, S.; Saez, J.; Vicent, C.; Peris, G. J. Org. Chem.
2010, 75, 5888e5894.
4.4. General experimental procedure for the preparation of
ethers 4e5
4. Iwaoka, M.; Isozumi, N. Molecules 2012, 17, 7266e7283 and cites herein.
5. Fieser, L. F.; Campbell, W. P.; Fry, E. M.; Gates, M. D., Jr. J. Am. Chem. Soc. 1939, 61,
3216e3223.
6. This result is in accordance with the isomerization ratios commented below
(Table 1, entries 8e9).
To an ice-bath cold solution of 2,3-dimethyl-1,4-naphtho-
quinone-2,3-epoxide (506 mg, 2.5 mmol) in dry dichloromethane
(12.5 mL) and methanol (12.5 mL) was added drop wise boron
trifluoride etherate (0.48 mL, 3.8 mmol). The resulting mixture was
heated at 50 ꢀC for 14 days. Then was quenched with saturated
aqueous sodium bicarbonate (15 mL) and extracted with
dichloromethane (3ꢁ15 mL), and then the organic layers were
washed (brine), dried (Na2SO4) and concentrated. The crude was
purified through chromatography (silica-gel, hexanes/ethyl acetate
(7:3)) to afford the desired compound.
7. Ethanol and methanol gave desired opened product but phenol did not.
8. Izquierdo, J.; Rodríguez, S.; Gonzalez, F. V. Org. Lett. 2011, 13, 3856e3859.
ꢀ
9. Furie, B.; Furie, B. C. Blood 1990, 75, 1753e1762.
10. The elimination reaction results from the attack of thiolate to the sulfur
atom and the products are the corresponding naphthoquinone and disulfide as
already reported in Ref. 2.
11. The crystal structure has been deposited at the CCDC and allocated the
deposition number CCDC 906980.
12. Rosenfield, R. E., Jr.; Partharasathy, R.; Dunitz, J. D. J. Am. Chem. Soc. 1977, 99,
4860e4862.