Facile and efficient sulfenylation method using quinone mono-O,S-acetals under mild conditions

Article abstract of DOI:10.1021/jo001710q

A novel sulfenylation method induced by aromatization of quinone mono-O,S-acetals is described. These sulfenylation reagents readily react with silyl enolethers or electron rich aromatic compounds to give sulfenylation products under mild conditions. In particular, O,S-acetal 2j, which possesses a pentafluorophenylthio function, is the most effective reagent from the standpoint of the adaptability for various substrates.

Full text of DOI:10.1021/jo001710q

2434
J . Org. Chem. 2001, 66, 2434-2441
F a cile a n d Efficien t Su lfen yla tion Meth od Usin g Qu in on e
Mon o-O,S-Aceta ls u n d er Mild Con d ition s
Masato Matsugi,† Kenji Murata,† Kentoku Gotanda,† Hisanori Nambu,†
Gopinathan Anilkumar,† Keita Matsumoto,‡ and Yasuyuki Kita*,†
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita,
Osaka 565-0871, J apan, and Research Center, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho,
Omiya, Saitama 330-8530, J apan
kita@phs.osaka-u.ac.jp
Received December 5, 2000
A novel sulfenylation method induced by aromatization of quinone mono-O,S-acetals is described.
These sulfenylation reagents readily react with silyl enolethers or electron rich aromatic compounds
to give sulfenylation products under mild conditions. In particular, O,S-acetal 2j, which possesses
a pentafluorophenylthio function, is the most effective reagent from the standpoint of the
adaptability for various substrates.
Ta ble 1. P r ep a r a tion of Qu in on e Mon o-O,S-a ceta ls 2
In tr od u ction
It is important to effectively introduce sulfur into
organic compounds, since many biologically active com-
pounds contain sulfur functions.1 Furthermore, the sulfur
function has great versatility as a foothold for the
construction of various target molecules.2 Many sulfeny-
lation methods have been studied to date3 that include
electrophilic substitution with sulfur-containing electro-
philes such as sulfenyl chloride, sulfenylamines, thiosul-
fonates, disulfides, nucleophilic substitution of aryl ha-
lides with metal mercaptides, replacement reactions via
diazonium intermediates, and coupling reactions via a
radical cation. However, these approaches usually require
basic, acidic, or heating conditions during the sulfenyla-
tion process except for in limited cases,3q and until now,
a mild sulfenylation reaction under neutral conditions
was not readily available.
We have already reported that various quinone mono-
O,S-acetals 2, which are intermediates in the aromatic
Pummerer-type rearrangement, could be easily isolated
in high yields,4 and recent preliminary communications5
showed that these quinone mono-O,S-acetals 2 readily
aromatize by reaction with some nucleophiles giving
sulfenylation products under mild conditions. In this
paper, we present the full account of these studies along
with the efficient sulfenylation of various substrates. The
starting quinone mono-O,S-acetals 2a -j were readily
prepared from the corresponding sulfoxides 1 by the
reported method4 using 1-ethoxy vinylesters (Table 1).6,7
* To whom correspondence should be addressed.
† Osaka University.
‡ Taisho Pharmaceutical Co., Ltd.
(1) For recent reviews, see: (a) Norcross, R. D.; Paterson, I. Chem.
Rev. 1995, 95, 2041-2114. (b) Faulkner, D. J . Nat. Prod. Rep. 1995,
12, 223-269.
(2) (a) Trost, B. M. Chem. Rev. 1978, 78, 363-382. (b) Akai, S.;
Takeda, Y.; Iio, K.; Takahashi, K.; Fukuda, N.; Kita, Y. J . Org. Chem.
1997, 62, 5526-5536. (c) Kita, Y.; Iio, K.; Kawaguchi, K.; Fukuda, N.;
Takeda, Y.; Ueno, H.; Okunaka, R.; Higuchi, K.; Tsujino, T.; Fujioka,
H.; Akai, S. Chem. Eur. J . 2000, 6, 3897-3905. (d) Akai, S.; Morita,
N.; Iio, K.; Nakamura, Y.; Kita, Y. Org. Lett. 2000, 2, 2279-2282.
(3) For examples: (a) Trost, B. M.; Salzmann, T. N.; Hiroi, K. J .
Am. Chem. Soc. 1976, 98, 4887-4902. (b) Scholz, D. Synthesis 1983,
944-945. (c) Bischoff, L.; David, C.; Martin, L.; Meudal, H.; Roques
B.-P.; Fournie´-Zaluski, M.-C. J . Org. Chem. 1997, 62, 4848-4850. (d)
Foray, G.; Pen˜e´n˜ory, A. B.; Rossi, R. A. Tetrahedron Lett. 1997, 38,
2035-2038. (e) Tanaka, T.; Azuma, T.; Fang, X.; Uchida, S.; Iwata,
C.; Ishida, T.; In, Y.; Maezaki, N. Synlett 2000, 33-36. (f) Bottino, F.;
Fradullo, R.; Pappalardo, S. J . Org. Chem. 1981, 46, 2793-2795. (g)
Criatau, H. J .; Chabaud, B.; Chene, A.; Christol, H. Synthesis 1981,
892-894. (h) Oae, S.; Shinhana, K.; Kim, Y. H. Chem. Lett. 1979, 939-
942. (i) Atkinson, J . G.; Hamel, P.; Girard, Y. Synthesis 1988, 480-
481. (j) Anzai, K. J . Heterocycl. Chem. 1979, 16, 567-569. (k) Bates,
D. K.; Tafel, K. A. J . Org. Chem. 1994, 59, 8076-8080. (l) Tomita, K.;
Terada, A.; Tachikawa, R. Heterocycles 1976, 4, 733-737. (m) Franco,
F.; Greenhouse, R.; Muchowski, J . M. J . Org. Chem. 1982, 47, 1682-
1688. (n) Hocker, J .; Ley, K.; Merten, R. Synthesis 1975, 334-335. (o)
Hartke, K.; Teuber, D.; Gerber, H.-D. Tetrahedron 1988, 44, 3261-
3270. (p) Pagnoni, U. M.; Pinetti, A. J . Heterocyclic Chem. 1993, 30,
617-621. (q) Kita, Y.; Takada, T.; Mihara, S.; Whelen, B. A.; Tohma,
H. J . Org. Chem. 1995, 60, 7144-7148.
Resu lt a n d Discu ssion
We first examined the ability of quinone mono-O,S-
acetals 2a -e to undergo sulfenylation of cyclic silyl enol
(4) Kita, Y.; Takeda, Y.; Matsugi, M.; Iio, K.; Gotanda, K.; Murata,
K.; Akai, S. Angew. Chem., Int. Ed. Engl. 1997, 36, 1529-1531.
(5) (a) Matsugi, M.; Gotanda, K.; Murata, K.; Kita, Y. Chem.
Commun. 1997, 1387-1388. (b) Matsugi, M.; Murata, K.; Nambu, H.;
Kita, Y. Tetrahedron Lett. 2001, 42, 1077-1080.
(6) (a) Kita, Y.; Maeda, H.; Omori, K.; Okuno, T.; Tamura, Y. J .
Chem. Soc., Perkin Trans. 1 1993, 2999-3005. (b) Shibata, N.; Matsugi,
M.; Kawano, N.; Fukui, S.; Fujimori, C.; Gotanda, K.; Murata, K.; Kita,
Y. Tetrahedron: Asymmetry 1997, 8, 303-310.
(7) Quinone mono-O,S-acetals (2a -j) are stable for several months
during storage in a refrigerator.
10.1021/jo001710q CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/15/2001

Facile and Efficient Sulfenylation Method
J . Org. Chem., Vol. 66, No. 7, 2001 2435
Ta ble 2. Su lfen yla tion of Silyl En ol Eth er s Usin g Qu in on e Mon o-O,S-a ceta ls 2a -e
ethers (4a , b) and found that 2a -e were excellent
sulfenylating reagents which produce the R-sulfenylcy-
cloalkanone (5a -g) in quantitative yields (Table 2,
entries 1-8). We used 2c as the reagent to examine other
sulfenylation reactions because of its facile preparation
(Table 1). Acyclic silyl enol ethers (6a -f) were similarly
reacted with 2c to give the corresponding R-phenyl-
thioketones (7a -f) in high yields (Table 2, entries 9-14).
The sulfenylating reagent also reacted with electron-
rich aromatic compounds (8a -g), and the corresponding
thioethers (9a -g) were regioselectively obtained (Table
3, entries 1-7). It should be noted that no other regio
isomers were obtained in these reactions. In these cases,
the electron density of the substrates strongly influenced
the yield of the sulfenylation products. Electron-rich
aromatic compounds gave the sulfenylation products in
quantitative yields (Table 3, entries 1-3). However, the
less electron-rich aromatic compounds gave the corre-
sponding products in lower yields (Table 3, entries 4-7).
Benzene itself did not react at all with 2c (Table 3, entry
8). However, for such cases, the problem has been solved
by using Grignard reagents (8i-l). This approach gave
the corresponding thioethers (9h -k ) in moderate yields
(Table 3, entries 9-12). It is noteworthy that the use of
Grignard reagents could introduce the sulfenyl function
even when the significant electron deficient aromatic
such as trifluorobenzene was used (Table 3, entry 12).
Furthermore, heteroaromatic compounds such as the
indole, pyrrole, or thiophene derivatives (10a -h and
12a -e) also reacted similarly with 2c to give regioselec-
tively the corresponding thioethers (11a -h and 13a -e)
(Table 4).
On the other hand, unexpected results were obtained
when certain electron-rich aromatics were used. Thus,
the reaction of 1,2,3-trimethoxybenzene (8m ) with 2c
gave an unexpected desulfurization product exclusively,
the structure of which was assigned as 14a based on the
following chemical transformation and spectral and
analytical data (Table 5, entry 1). Treatment of 14a with
NaBH4 followed by heating under acidic condition gave
the biaryl compound 15 in 93% yield (Scheme 1). Simi-
larly, 8n , o, and p predominantly afforded the addition
products 14b, c, and e (Table 5, entries 2, 3, 5). When
using 8g, the reaction afforded both the sulfenylation
product (9g) and the C-C bond formation product (14d )
(Table 5, entry 4). Neither the sulfenylation nor the C-C
bond formation product was produced in the case of
mesitylene (8q) (Table 5, entry 6).
The quinone mono-O,S-acetal 2c was useful for the
sulfenylation of standard organic compounds involving

2436 J . Org. Chem., Vol. 66, No. 7, 2001
Ta ble 3. Su lfen yla tion of Ar om a tic Com p ou n d s Usin g Qu in on e Mon o-O,S-a ceta l 2c
Matsugi et al.
a
Isolated yield. Phenol derivative (3b) was formed as a byproduct, but it is readily removed by shaking with aqueous NaHCO3 solution.
Diphenyl disulfide and tetramethylquinone were formed as byproducts. c These reactions were performed in Et2O without TMSOTf.
b
Ta ble 4. Su lfen yla tion of Heter oa r om a tic Com p ou n d s Usin g Qu in on e Mon o-O,S-a ceta l 2c
a
Isolated yield. Phenol derivative (3b) was formed as a byproduct, but it is readily removed by shaking with aqueous NaHCO3 solution.
b
Diphenyl disulfide and tetramethylquinone were formed as byproducts.

Facile and Efficient Sulfenylation Method
J . Org. Chem., Vol. 66, No. 7, 2001 2437
Sch em e 1. Th e F or m a tion of th e Bia r yl Com p ou n d
15
hindered aromatic substrates tend to attack the â-carbon
of the acetal part of 2c.
Next, we investigated a more general method for the
chemoselective sulfenylation of aromatics because sulfur
functionalities on the aromatic ring as well as in aliphatic
compounds are quite useful for synthetic transformations.
For example, the sulfur functional group on aromatics
could be easily converted to an oxygen functional group
by the aromatic Pummerer-type rearrangement2b,c and
also ipso substitution of the sulfur functional group by
carbon substituents through a ligand exchange reaction.2d
We aimed to avoid the side reaction, i.e., the formation
of 14, and planned the use of tuned O,S-acetals which
have more activated sulfur atoms than 2c for nucleophilic
attack. Thus, the newly synthesized quinone mono-O,S-
acetals (2f-j) bearing the electron-withdrawing group on
an aryl thio moiety,7 which were obtained in 60-85%
yields from the corresponding sulfoxides,4 were examined
for the sulfenylation reaction of 8m . The results of the
reaction of these O,S-acetals (2f-j) with 8m are sum-
marized in Table 6. Both the thioether product 16 and
compound 14a were obtained in the reaction of 8m with
quinone mono-O,S-acetals (2g, h , e, i) bearing a moder-
ately strong electron-withdrawing group on the aromatic
ring (Table 6, entries 3-6). On the other hand, we found
that the reaction of 8m with 2j bearing a pentafluoro-
phenyl group on the sulfur atom afforded only the
sulfenylation product (16e) in 81% yield (Table 6, entry
7). Replacement of a trifluorophenyl group by a penta-
fluorophenyl group in 2j makes the sulfur atom more
electrophilic, thus allowing the chemoselective sulfeny-
lation reaction to predominate.
Ta ble 5. Rea ction of Som e Meth oxyben zen es w ith
Qu in on e Mon o-O,S-a ceta l 2c
Similarly, we could produce various types of pentafluo-
rophenylthio compounds (16f, e, g-j) in high yields from
the corresponding mono-, di-, and trimethoxybenzenes
(8i, m -o, g, p ) (Table 7, entries 1-6). When mesitylene
(8q) was used as the substrate, the sulfenylation product
(16k ) was obtained in 96% yield (Table 7, entry 7).
2-Methoxynaphthalene (8r ) also afforded the thioether
product (16l) in quantitative yield (Table 7, entry 8). The
present sulfenylation reagent 2j was quite effective for
the sulfenylation of indole (10f), indole derivatives (10a ,
b, e, i-m ), and various heteroaromatics (12a -c, 12f-i)
(Table 7, entries 9-24). In contrast, 2c did not react at
all with 8q, the N-tosylated indole (10i), and some
heteroaromatics (12f-i).
a
Isolated yield. Phenol derivative (3b) was formed as a byprod-
We performed the calculation of the steric structure
for every quinone mono-O,S-acetal 2 using PM3.8 The
steric structure of 2c as the typical example is shown in
Figure S1. It is assumed that the dienone moiety of 2 is
located between the aromatic ring and carbonyl group
of the ester function. It is suggested that an orbital
interaction exists between the dienone moiety and the
aromatic ring. The stereo environment of the sulfur atom
of 2 is generally less hindered than the â-carbon of the
acetal part of 2. Therefore, most nucleophiles predomi-
nantly attack the sulfur atom rather than the â-carbon
of the acetal part.
In fact, the X-ray structure of the quinone mono-O,S-
acetals 2d and 2j were almost identical to the PM3
calculation result (Figure 1). And because NOE between
the R-methyl proton of acetal carbon and the proton
o-position to the sulfur atom in 2d was observed, it is
uct.
silyl enol ethers and electron-rich aromatic compounds
(Scheme 2, route a), whereas unexpected desulfenylation
products (14) were observed in some very electron-rich
aromatic compounds such as the di- and trimethoxyben-
zenes (8m -p ) in fair yields without the formation of the
expected sulfenylation products (Scheme 2, route b). In
this way, we found that quinone mono-O,S-acetals re-
acted with a nucleophile on the sulfur atom or on the
carbon atom depending on the structural difference in
the substrate. The reason for the difference in the
reactivity of substrates is not completely known. We
think that not only the electron density but also the steric
hindrance of substrates influence the route of the reac-
tions. For example, 8c is a good substrate for sulfenyla-
tion (Table 3, entry 3). On the other hand, 8g gave the
sulfenylation product (9g) and the C-C bond formation
product (14a ) (Table 5, entry 4). It is thought that less
(8) MO calculations were performed by SPARTAN (Ver. 3.1.2) using
the PM3 Hamiltonian.

2438 J . Org. Chem., Vol. 66, No. 7, 2001
Matsugi et al.
Sch em e 2. Su lfen yla tion or Nu cleop h ilic Ad d ition to th e â-p osition of Aceta l Ca r bon
Ta ble 6. Rea ction of Qu in on e Mon o-O,S-a ceta ls 2 w ith
removed by treatment with weak aqueous alkali, and (3)
The corresponding thioethers are obtained in good yields.
When the side reaction, in which the substrates attacked
the â-position of acetal carbon in 2c, occurred, the 2j-
bearing pentafluorophenylthio group was quite effective
for the sulfenylation reaction. It gave the corresponding
thioethers in good yield even in the case of indole
derivatives bearing an electron-withdrawing group. Be-
sides, we confirmed that the pentafluorophenylthio group
works similar to a phenylthio group for oxidation and the
pentafluorophenyl sulfinyl group also behaves similar to
a phenyl sulfinyl group in the Pummerer-type rearrange-
ment on aromatics and syn elimination in aliphatics.9
These reagents might be applied to the synthesis of
biologically active substances having sulfur functional-
ities and labile functional groups which are sensitive to
basic or acidic conditions.
1,2,3-Tr im eth oxyben zen e 8m
Exp er im en ta l Section
Melting points are uncorrected. Infrared (IR) absorption
spectra were recorded as a KBr pellet. The 1H NMR spectra
were measured in CDCl3 on 200, 270, 300, and 500 MHz
spectrometers with SiMe4 as the internal standard. The 19F
NMR spectra were measured in CDCl3 on a 188 MHz spec-
trometer with C6F6 as the internal standard. Mass spectra
were obtained at 70 eV via GC-MS coupling. High-resolution
mass spectra were obtained by EI. Column chromatographic
purifications were performed using silica gel with either a 70-
230 or 200-400 mesh size. The enolsilyl ethers (6a -d )10 were
prepared by a reported method. Diphenyl disulfide and tet-
ramethylquinone were identified with commercially available
compounds.
Gen er a l P r oced u r e for th e P r ep a r a tion of 2. Under a
nitrogen atmosphere, to a stirred suspension of 1c2b (274 mg,
1.00 mmol) and 1-ethoxyvinyl 2-chloroacetate6 (492 mg, 3.00
mmol) in dry toluene (30 mL) was added p-TsOH (8.5 mg, 0.05
mmol). The reaction mixture was stirred at 60 °C for 1 h and
cooled to room temperature. The reaction mixture was con-
centrated in vacuo. The residue was purified by column
chromatography on silica gel (hexane/AcOEt, 3:1) to give 2c
(305 mg, 87% yield).
a
Isolated yield.
thought that the conformation of 2 in solution is similar
to that in crystal. The dienone moiety is sandwiched
between the aromatic ring and the ester carbonyl func-
tion. Especially, the aromatic part of the quinone mono-
O,S-acetal 2j is closest to the dienone moiety in every 2.
Therefore, it is postulated that nucleophiles could not
attack at all the â-carbon of the acetal part. In addition,
the pentafluorophenyl group is quite effective due to the
higher electrophilicity on the sulfur atom.
2,3,5,6-Tetr a m eth yl-4-oxo-1-p h en ylth iocycloh exa -2,5-
Con clu sion
d ien yl 2-Ch lor oa ceta te 2c. 90%; pale yellow crystals; mp
132-133 °C (dec) (AcOEt-hexane). IR 1776, 1662, 1630 cm-1
.
As already described, we have succeeded in developing
some novel sulfenylating reagents by taking advantage
of their activation on the sulfur atom due to the driving
force of their aromatizations. The advantages of this
methodology are as follows: (1) The sulfenylation reac-
tions are complete within 10 min below room tempera-
ture, (2) The dihydroquinone side product is easily
1H NMR δ: 1.64 (d, 6H, J ) 1.0 Hz), 2.01 (d, 6H, J ) 1.0 Hz),
(9) Both cyclic and acyclic R-pentafluorophenylthioalkanones are
readily obtained in quantitative yield by the reaction of 2j and the
corresponding trimethylsilyl enol ethers under standard conditions.
(10) Kita, Y.; Haruta, J .; Segawa, J .; Tamura, Y. Tetrahedron Lett.
1979, 4311-4314.

Facile and Efficient Sulfenylation Method
J . Org. Chem., Vol. 66, No. 7, 2001 2439
Ta ble 7. Su lfen yla tion of Va r iou s Ar om a tic Com p ou n d Usin g Qu in on e Mon o-O,S-a ceta ls 2j
a
Isolated yield. Phenol derivative (3b) was formed as a byproduct in in all cases, but it is readily removed by shaking with aqueous
NaHCO3 solution.
4.16 (s, 2H), 7.01 (brd, 2H, J ) 7.5 Hz), 7.21 (brt, 2H, J ) 7.5
Hz), 7.38 (brt, 1H, J ) 7.5 Hz). HRMS Calcd for C18H19ClO3S:
350.0742. Found: 350.0727. Anal. Calcd for C18H19ClO3S: C,
61.62; H, 5.46. Found: C, 61.61; H, 5.32.
mmol) and 2c (351 mg, 1.00 mmol) in dry MeCN (5 mL) was
added TMSOTf (10 mg, 0.05 mmol) at 0 °C. After 10 min, the
reaction was quenched with saturated aqueous NaHCO3 and
extracted with AcOEt. The organic layer was washed with
brine, dried with Na2SO4, and concentrated in vacuo. The
residue was purified by column chromatography on silica gel
(hexane/AcOEt, 4:1) to give 5b (183 mg, 99% yield).
1-(2,3,4,5,6-P en taflu or oph en ylth io)-2,3,5,6-tetr am eth yl-
4-oxocycloh exa -2,5-d ien yl 2-Ch lor oa ceta te 2j. 76%; color-
less crystals; mp 137-138 °C (Et2O-hexane). IR 1782, 1634
1
cm-1. H NMR δ: 1.72 (s, 6H), 2.02 (s, 6H), 4.18 (s, 2H). 19F
2-P h en ylth iocyclop en ta n on e 5b.11 99%; colorless oil. IR
NMR δ: -161.40 (m, 2F), -145.66 (m, 1F), -130.62 (m, 2F).
HRMS (FAB) Calcd for C18H14ClF5O3S (M++1): 441.0350.
Found 441.0352. Anal. Calcd for C18H14ClF5O3S: C, 49.05; H,
3.20. Found: C, 49.30; H, 3.29.
1
1710 cm-1. H NMR δ: 1.62-2.38 (m, 7H), 2.91 (m, 1H), 3.84
(t, 1H, J ) 6.0 Hz), 7.20-7.45 (m, 5H). MS 206 (M+, 68), 110
(100).
Gen er a l P r oced u r e of Su lfen yla tion w ith 2. Under a
nitrogen atmosphere, to a stirred solution of 4a (176 mg, 1.00
(11) Youn, J .-H.; Herrmann, R.; Ugi, I. Synthesis 1987, 159-161.

2440 J . Org. Chem., Vol. 66, No. 7, 2001
Matsugi et al.
F igu r e 1. ORTEP drawing of 2d and 2j. Selected interatomic distances [Å] and dihedral angles between the aromatic plane and
the dienone plane [deg]. 2d : C(3)-(18), 4.327(4); dihedral angle, 33.7(3). 2j: C(3)-C(23), 4.006(3); dihedral angle, 27.3(3).
P h en ylth ioa cetic Acid Meth yl Ester 7a .12 99%; colorless
oil. IR 1740 cm-1. 1H NMR δ: 3.65 (s, 2H), 3.72 (s, 3H), 7.20-
7.42 (m, 5H). MS 182 (M+, 89), 109 (100).
was stirred at room temperature. After 10 min, the reaction
mixture was concentrated in vacuo. The residue was purified
by column chromatography on silica gel (hexane/AcOEt, 3:1)
to give 14a (105 mg, 45%).
1,2,4-Tr im eth oxy-5-p h en ylth ioben zen e 9a . 99%; color-
less oil. 1H NMR δ: 3.78 (s, 3H), 3.82 (s, 3H), 3.93 (s, 3H),
6.60 (s, 1H), 6.95 (s, 1H), 7.10-7.26 (m, 5H). MS 276 (M+, 100).
Anal. Calcd for C15H16O3S: C, 65.19; H, 5.84; S, 11.60. Found:
C, 64.85; H, 5.81; S, 11.58.
2,3,5,6-Tetr a m eth yl-5-(2,3,4-tr im eth oxyp h en yl)-4-oxo-
cycloh exa -1,2-d ien yl 2-Ch lor oa ceta te 14a . 45%; colorless
crystals; mp 106-108 °C (AcOEt-hexane). IR 1775, 1761, 1646
1
cm-1. H NMR δ: 1.38 (s, 3H), 1.49 (s, 3H), 1.97 (s, 3H), 2.00
5-Meth oxy-2-m eth yl-3-p h en ylth ioin d ole 11a .13 99%; col-
orless crystals; mp 132-133 °C (AcOEt-hexane) (lit.13 129-
(s, 3H), 3.62 (s, 3H), 3.77 (s, 3H), 3.86 (s, 3H), 4.25 (s, 2H),
6.65 (d, 1H, J ) 9.0 Hz), 7.05 (d, 1H, J ) 9.0 Hz). MS 410 (M+
+ 2, 5), 408 (M+, 15), 283 (100). Anal. Calcd for C21H25ClO6:
C, 61.69; H, 6.16; Cl, 8.67. Found: C, 61.60; H, 6.08; Cl, 8.51.
1
130 °C). IR 3395 cm-1. H NMR δ: 2.48 (s, 3H), 3.79 (s, 3H),
6.83 (dd, 1H, J ) 8.5, 2.5 Hz), 6.99-7.25 (m, 7H), 8.18 (bs,
1H). MS 269 (M+, 100).
F or m a tion of th e Bia r yl Com p ou n d 15. To a solution of
14a (100 mg, 0.26 mmol) in EtOH (5 mL) was added NaBH4
(10 mg, 0.26 mmol) and the mixture was stirred for 1 h at
room temperature. The reaction mixture was concentrated in
vacuo. The residue was diluted with MeCN (4 mL), KI (60 mg,
0.35 mmol), TMSCl (38 mg, 0.35 mmol), and NaBH4 (10 mg,
0.26 mmol) were added, and the mixture was stirred for 12 h
at room temperature. Saturated aqueous Na2S2O3 solution was
added to the above reaction mixture and extracted with AcOEt.
The extract was then washed with brine, dried over anhydrous
Na2SO4, and concentrated in vacuo. The residue was diluted
with toluene (1 mL), treated with p-TsOH (45 mg, 0.26 mmol),
and the mixture was stirred for 3 h under reflux. The resulting
reaction mixture was concentrated in vacuo, and the residue
was purified by column chromatography on silica gel (hexane/
AcOEt, 3:1) to give 15 (81 mg, 93% yield).
2,5-Dim eth yl-3-p h en ylth iop yr r ole 13a .14 98%; colorless
oil. IR 3395 cm-1 1H NMR δ: 2.25 (s, 6H), 5.90 (d, 1H, J )
.
2.5 Hz), 7.00-7.26 (m, 5H), 7.86 (bs, 1H). MS 203 (M+, 100).
4-(4-F lu or op h en ylth io)-1,2,3-tr im eth oxyben zen e 16a .
16%; colorless crystals; mp 195 °C (AcOEt-hexane). 1H NMR
δ: 3.84 (s, 3H), 3.87 (s, 3H), 3.88 (s, 3H), 6.43 (d, 1H, J ) 8.5
Hz), 6.93 (d, 2H, J ) 7.0 Hz), 7.00 (d, 1H, J ) 8.5 Hz), 7.28 (d,
2H, J ) 7.0 Hz). MS 294 (M+, 100). HRMS. Calcd for C15H15
FO3S: 294.0726. Found 294.0720.
-
Gen er a l P r oced u r e of Su lfen yla tion w ith 2c a n d Gr ig-
n a r d Rea gen ts. Under a nitrogen atmosphere, to a stirred
suspension of Mg (24 mg, 1.0 mmol) in dry Et2O (4 mL) was
added dibromoethane (2 mg, 0.10 mmol) at room temperature.
After 10 min, 2-bromoanisol (150 mg, 0.8 mmol) was added to
the solution and the mixture was stirred for 15 min at the
same temperature. The solution was added to 2c (70 mg, 0.20
mmol) in dry Et2O at -30 °C and the mixture was stirred for
10 min at the same temperature. The reaction mixture was
quenched with saturated aqueous NaHCO3 and extracted with
AcOEt. The organic layer was washed with brine, dried with
Na2SO4, and concentrated in vacuo. The residue was purified
by column chromatography on silica gel (eluent: hexane/
AcOEt, 10:1) to give 9i (15 mg, 62% yield).
4-(2,3,4-Tr im et h oxyp h en yl)-2,3,5,6-t et r a m et h ylp h e-
n ol 15. 93%; colorless crystals; mp 165-167 °C (AcOEt-
1
hexane). IR 3500 cm-1. H NMR δ: 1.95 (s, 6H), 2.21 (s, 6H),
3.58 (s, 3H), 3.91 (s, 6H), 4.65 (brs, 1H), 6.66 (d, 1H, J ) 8.0
Hz), 6.72 (d, 1H, J ) 8.0 Hz). MS 316 (M+, 92), 73 (100).
HRMS. Calcd for C19H24O4: 316.1674. Found 316.1673.
Gen er a l P r oced u r e of Su lfen yla tion w ith 2j. Under a
nitrogen atmosphere, to a stirred solution of 8m (40.0 mg,
0.238 mmol) and 2j (105 mg, 0.238 mmol) in dry MeCN (2 mL)
was added TMSOTf (3 mg, 0.012 mmol) at 0 °C. After 10 min,
it was quenched with saturated aqueous NaHCO3 and then
extracted with AcOEt. The organic layer was washed with
brine, dried with Na2SO4, and concentrated in vacuo. The
residue was purified by column chromatography on silica gel
(hexane/AcOEt, 5:1) to give 16e (70.6 mg, 81% yield).
1-Meth oxy-2-p h en ylth ioben zen e 9i.15 62%; colorless oil.
1H NMR δ: 3.87 (s, 3H), 6.89, (t, 2H, J ) 8.0 Hz), 7.08 (d, 1H,
J ) 8.0 Hz), 7.24-7.37 (m, 6H). MS 216 (M+, 100).
Gen er a l P r oced u r e for SN2′ Rea ction of 2c w ith 8.
Under a nitrogen atmosphere, to a solution of 2c (301 mg,
0.855 mmol) and 8m (200 mg, 0.570 mmol) in dry MeCN (10
mL) was added TMSOTf (20 mg, 0.090 mmol) and the mixture
(12) Yoshimura, T.; Motoyama, A.; Morishige, A.; Tsukurimichi, E.;
Shimasaki, C.; Hasegawa, K. Bull. Chem. Soc. J pn. 1993, 66, 174-
180.
4-(2,3,4,5,6-P en t a flu or op h en ylt h io)-1,2,3-t r im et h oxy-
ben zen e 16e. 78%; pale yellow crystals; mp 43-44 °C
1
(13) Hamel, P.; Zajac, N.; Atkinson, J . G.; Girard, Y. J . Org. Chem.
1994, 59, 6372-6377.
(AcOEt-hexane). H NMR δ: 3.84 (s, 3H), 3.85 (s, 3H), 3.91
(s, 3H), 6.61 (d, 1H, J ) 9.0 Hz), 7.04 (d, 1H, J ) 9.0 Hz). 19F
NMR δ: -162.34 (m, 2F), -153.89 (m, 1F), -133.79 (m, 2F).
MS 366 (M+, 100). HRMS. Calcd for C15H11F5O3S: 366.0365.
Found 366.0349.
(14) J eng, H.-J .; Fang, J .-M. J . Chin. Chem. Soc. 1994, 41, 803-
811.
(15) Nagata, T.; Fujimori, K.; Yoshimura, T.; Furukawa, N.; Oae,
S. J . Chem. Soc., Perkin. Trans. 1 1989, 1431-1435.

Facile and Efficient Sulfenylation Method
J . Org. Chem., Vol. 66, No. 7, 2001 2441
3-(2,3,4,5,6-P en ta flu or op h en ylth io)-5-m eth oxy-2-m eth -
MS 293 (M+, 100). HRMS Calcd for C12H8F5NS: 293.0298.
Found: 293.0297.
ylin dole 17a. 99%; colorless crystals; mp 149-150 °C (AcOEt-
1
hexane). IR 3389 cm-1. H NMR δ: 2.60 (s, 3H), 3.87 (s, 3H),
6.79 (dd, 1H, J ) 9.0, 2.0 Hz), 7.10-7.17 (m, 2H), 8.12 (brs,
1H). 19F NMR δ: -162.35 (m, 2F), -154.82 (t, 1F, J ) 21 Hz),
-134.26 (m, 2F). MS 359 (M+, 100). Anal. Calcd for C16H10F5-
NOS: C, 53.48; H, 2.81; N, 3.90. Found: C, 53.55; H, 2.88; N,
3.91.
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for compounds not included in the Experimental Section,
calculated structure for 2c, crystal data, structure solution and
refinement, atomic coordinates, bond lengths and angles, and
anisotropic thermal parameters for 2d and 2j. This material
is available free of charge via the Internet at http://pubs.acs.org.
3-(2,3,4,5,6-P en t a flu or op h en ylt h io)-2,5-d im et h ylp yr -
r ole 18a . 82%; colorless oil. IR 3375 cm-1 1H NMR δ: 2.16
.
(s, 3H), 2.34 (s, 3H), 5.91 (s, 1H), 7.70 (brs, 1H). 19F NMR δ:
-162.68 (m, 2F), -155.52 (t, 1F, J ) 21 Hz), -134.92 (m, 2F).
J O001710Q