Superacidified reaction of sulfides and esters for the direct synthesis of sulfonium derivatives

Full text of DOI:10.1021/jo980473c

7522
J . Org. Chem. 1998, 63, 7522-7524
Sch em e 1
Su p er a cid ified Rea ction of Su lfid es a n d
Ester s for th e Dir ect Syn th esis of
Su lfon iu m Der iva tives
Kenji Miyatake, Kimihisa Yamamoto,†
Kazuhisa Endo, and Eishun Tsuchida*
Department of Polymer Chemistry, Advanced Research
Institute for Science and Engineering, Waseda University,
Tokyo 169-8555, J apan
synthesis of triarylsulfonium salts by the direct arylation
of sulfides. We report herein a novel, general, and high-
yield preparative method that gives a variety of sulfo-
nium compounds bearing alkyl and/or aryl groups by the
acid-promoted reaction of sulfides with esters (Scheme
1).
Dimethyl sulfide was reacted with 2 equiv of methyl
formate in acidic solution at 20 °C to give the trimeth-
ylsulfonium salt. The reaction proceeds rapidly and is
completed within 2 h. A strong acid with an Ho (Ham-
mett acidity function) below -7.0, such as methane-
sulfonic acid (-7.9) and sulfuric acid (-11.9), is required
for the quantitative formation of the sulfonium product.
In particular, trifluoromethanesulfonic acid (-14.1) was
the most effective and provided trimethylsulfonium tri-
flate in 93% yield.
Table 1 summarizes the results of the reaction of
several other sulfides with esters and shows the wide
utility for this transformation. This reaction also pro-
ceeds for diaryl sulfides. Diphenyl sulfide was reacted
with methyl triflate to produce a diphenylmethylsulfo-
nium triflate as a white crystalline powder in 85% yield
(entry 2). Dibenzothiophene and thianthrene could be
quantitatively methylated to the corresponding cyclic
sulfonium salts under the same conditions (entries 9 and
10).11 The reaction is also applicable to other chalcogen
derivatives such as diphenyl selenide for the preparation
of the selenonium salt (entry 11).
Received March 12, 1998
Interest in sulfonium compounds has been stimulated
by their useful application as raw materials for the
synthesis of drugs and sulfur-containing natural com-
pounds,1 and a convenient source of carbon radicals via
a one-electron reduction.2 In addition, aryl sulfonium
salts are highly photosensitive and can be utilized as
efficient photochemical sources of strong Brønsted acids
for cationic polymerization of olefins or epoxides and
chemically amplified photoresists.3 In view of the im-
portant role of these compounds, there is a real need for
a mild and versatile synthetic method. Among a number
of synthetic methods described in the literature,4 the
direct synthesis from the corresponding sulfides is pref-
erable due to the simple overall procedure. Many ap-
plicable alkylating or arylating reagents for sulfides have
been reported such as alkyl iodides,5 diaryliodonium
salts,6 trialkyloxonium salts,7 and alcohols or ethers with
strong acids employed in excess.8 Methyl triflate also
shows a good reactivity to sulfides, while phenyl triflate
does not.9 Quite recently, a synthetic method for aryl
sulfonium salts has been developed by the oxidative
coupling of aryl sulfides through a two-electron-transfer
process.10 These routes, however, are deemed unsatisfac-
tory due to the general lack of applicability to a wide
variety of symmetrical and unsymmetrical, alkyl and aryl
sulfonium salts. There have been few reports on the
The product yield depends on the ester used, with
methyl formate (R2 ) H, R3 ) Me) being the most
appropriate for the methylation of diphenyl sulfide. The
use of acetate esters (R2 ) Me) resulted in a significant
decrease in the product yield (entry 4), although R3 of
an ester does not show a significant effect on it; the
reaction of diphenyl sulfide with ethyl formate or butyl
formate gives diphenylethylsulfonium triflate in 80%
yield (entry 3) or diphenylbutylsulfonium triflate in 82%
yield (entry 5), respectively. It should be pointed out
that, contrary to the classical nucleophilic reaction of
sulfides with alkyl halide, the reaction does not give
diphenyl sec-butylsulfonium triflate; carbon-skeleton re-
arrangement or chain-branching did not take place. A
possible mechanism for this alkylation is shown in
Scheme 2 where the superacidified ester would produce
the butyloxonium cation as the active alkylating spe-
cies.12 The reaction of the butyloxonium cation with
sulfide substrates should give the sulfonium product
* To whom correspondence should be addressed. Fax: +813-3205-
4740. Tel: +813-5286-3120. E-mail: eishun@mn.waseda.ac.jp.
† Present address: Department of Chemistry, Faculty of Science and
Technology, Keio University, Yokohama 223, J apan.
(1) (a) Holland, H. L. Chem. Rev. 1988, 88, 473. (b) Organic Sulfur
Chemistry: Structure and Mechanism; Oae, S., Ed.; CRC Press: Boca
Raton, FL, 1991; Vol. 1. (c) Block, E. Angew. Chem., Int. Ed. Engl.
1992, 31, 1135.
(2) (a) Chung, S. K.; Sasamoto, K. J . Chem. Soc., Chem. Commun.
1981, 346. (b) Hall, E. A. H.; Horner, L. Phosphorus Sulfur 1981, 9,
273. (c) Beak, P.; Sullivan, T. A. J . Am. Chem. Soc. 1982, 104, 4450.
(3) (a) Miller, R. D.; Renaldo, A. F.; Ito, H. J . Org. Chem. 1988, 53,
5571. (b) Saeva, F. D.; Breslin, D. T.; Martic, P. A. J . Am. Chem. Soc.
1989, 111, 1328. (c) Dektar, J . L.; Hacker, N. P. J . Am. Chem. Soc.
1990, 112, 6004. (d) He, X.; Huang, W.-Y.; Reisen, A. J . Org. Chem.
1992, 57, 759. (e) Uhrich, K. E.; Reichmanis, E.; Baiocchi, F. A. Chem.
Mater. 1994, 6, 295.
(4) Lowe, P. A. In The Chemistry of the Sulfonium Group; Stirling,
C. J . M., Patai, S., Eds.; J ohn Wiley & Sons: New York, 1981; Vol. 1,
Chapter 11.
(5) Franzen, V.; Schmidt, H. J .; Mertz, C. Chem. Ber. 1961, 94, 2942.
(6) (a) Crivello, J . V.; Lam, J . H. W. J . Org. Chem. 1978, 43, 3055.
(b) Crivello, J . V.; Lam, J . H. W. Synth. Commun. 1979, 9(3), 151. (c)
Crivello, J . V.; Conlon, D. A.; Lee, J . L. Polym. Bull. 1985, 14, 279.
(7) Trost, B. M.; Arndt, H. C. J . Org. Chem. 1973, 38, 3140.
(8) (a) Badet, B.; J ulia, M. Tetrahedron 1979, 1101. (b) Badet, B.;
J ulia, M.; Lefebvre, Bull. Soc. Chim. Fr. 1984, 11, 431.
(9) (a) Saeva, F. D.; Morgan, B. P. J . Am. Chem. Soc. 1984, 106,
4121. (b) Howells, R. D.; McCown, J . D. Chem. Rev. 1997, 77, 669.
(10) (a) Yamamoto, K.; Shouji, E.; Suzuki, F.; Kobayashi, S.;
Tsuchida, E. J . Org. Chem. 1995, 60, 452. (b) Yamamoto, K.; Koba-
yashi, S.; Shouji, E.; Tsuchida, E. J . Org. Chem. 1996, 61, 1912.
(11) A dimethylated product, S,S′-dimethylthianthrenium bistriflate,
was not formed under these conditions.
(12) The related oxonium cation, RO+H2, appears to form in per-
chloric acid-alcohol mixtures. In such mixtures, alkyl sulfides are
converted into trialkylsulfonium perchlorates without any rearrange-
ment of the alkyl substituents. See: Milligan, T. W.; Minor, B. C. J .
Org. Chem. 1963, 28, 235.
S0022-3263(98)00473-3 CCC: $15.00 © 1998 American Chemical Society
Published on Web 09/26/1998

Notes
J . Org. Chem., Vol. 63, No. 21, 1998 7523
Ta ble 1. Syn th esis of Su lfon iu m Der iva tives fr om
Su lfid es a n d Ester sa
Sch em e 3
1:10 (w/v) solution of phosphorus pentoxide in trifluo-
romethanesulfonic acid, triphenylsulfonium hexafluoro-
antimonate was obtained in 36% yield after metathesis
with NaSbF6 (entry 6). As a main byproduct, phenol was
identified in the phenylation reaction. The reaction also
proceeds for phenyl formate to give triphenylsulfonium
triflate in 45% yield (entry 7). The reaction of phenyl
benzoate with diphenyl sulfide, however, did not give the
sulfonium product (entry 8).
In conclusion, we have developed a new valuable
methodology for the preparation of arylsulfonium com-
pounds as well as alkylsulfonium and selenonium deriva-
tives by a simple procedure. The selective transformation
of sulfides to sulfonium derivatives should be well suited
for the synthesis of natural products containing sensitive
subunits. Mechanistic studies and the use of this syn-
thetic methodology to develop other alkylation/arylation
reactions are currently in progress.
Exp er im en ta l Section
IR spectra were obtained using a FT-IR spectrometer. 1H and
13C NMR spectra were recorded on a 500 MHz spectrometer.
Chemical shifts are referenced downfield from TMS. All chemi-
cals used were commercially available reagent grade, which were
checked for purity by boiling point and/or IR and NMR spec-
troscopies. Solids were recrystallized and liquids were distilled
before use.
Gen er a l P r oced u r es for th e Rea ction of Su lfid es w ith
Ester s. Four examples of the reaction of sulfides with esters
for the preparation of sulfonium derivatives are given which
typify the general synthetic methods used during the course of
this work.
Tr im eth ylsu lfon iu m Tr ifla te. To a stirred mixture of 0.62
g (10 mmol) of dimethyl sulfide and 1.20 g (20 mmol) of methyl
formate was added 5 mL of trifluoromethanesulfonic acid, and
the mixture was held at 0 °C in an ice bath. The reaction
mixture was stirred for 10 h while it warmed to 20 °C. The
progress of the reaction was followed by TLC analysis (CHCl3).
After the reaction, the mixture was poured into 100 mL of diethyl
ether causing precipitation of a white powder. The product was
isolated by filtration, washed with ether, and dried at 20 °C in
a vacuum to give trimethylsulfonium triflate (93% yield): IR
Sch em e 2
without the rearrangement of the alkyl substituents. The
increased yields with formates instead of acetates prob-
ably reflects the stability of the oxonium cations, where
those from the acetate are more stabilized by hypercon-
jugative interactions from the methyl group. Since under
the reaction conditions the esters are all protonated the
differences in ion stability get translated into leaving
group efficiency, the protonated formate being the more
reactive species relative to the protonated acetates.
In attempts to prepare triarylsulfonium salts, the
reaction of diphenyl sulfide with phenyl acetate in
trifluoromethanesulfonic acid did not yield triphenylsul-
fonium triflate, but bis(4-acetylphenyl) sulfide in 75%
yield (Scheme 3). When the reaction is conducted in a
(KBr) 3030 (νCH ), 1272, 1093 (νSO), 1263, 1161, 634 (νCF) cm-1
;
3
1H NMR (D2O) δ 2.89 (s, 9H); 13C NMR (D2O) δ 26.7. Anal. Calcd
for C4H9F3O3S2: C, 21.24; H, 4.01; S, 28.35. Found: C, 21.51;
H, 4.22; S, 28.07.
Dip h en ylm eth ylsu lfon iu m Tr ifla te. To a stirred mixture
of 1.86 g (10 mmol) of diphenyl sulfide and 1.20 g (20 mmol) of
methyl formate was added 5 mL of trifluoromethanesulfonic
acid, and the mixture was held at 0 °C in an ice bath. The
reaction mixture was stirred for 10 h while it warmed to 20 °C.
The progress of the reaction was followed by TLC analysis
(CHCl3). After the reaction, the mixture was poured into 100
mL of distilled water. The resulting white suspension was
extracted with three 100 mL portions of dichloromethane. The
combined dichloromethane solution was evaporated to 10 mL

7524 J . Org. Chem., Vol. 63, No. 21, 1998
Notes
and then poured into 200 mL of diethyl ether causing precipita-
tion of a white powder. The product was isolated by filtration,
washed with ether, and dried at 20 °C in a vacuum to give
diphenylmethylsulfonium triflate (85% yield): IR (KBr) 3098
Dip h en ylbu tylsu lfon iu m Tr ifla te. See the preparation of
diphenylmethysulfonium triflate for details. Compounds used
were diphenyl sulfide (1.86 g, 10 mmol), butyl formate (2.04 g,
20 mmol), and trifluoromethanesulfonic acid (5 mL). The
extraction/precipitation solvents were dichloromethane/diethyl
ether to afford 3.22 g (82%) of the title compound: IR (KBr) 3073
(νCH), 1267, 1094 (νSO), 1155, 637 (νCF) cm-1; 1H NMR (acetone-
d6) δ 0.93 (t, 3H, J ) 7.3 Hz), 1.56-1.65 (m, 2H), 1.77-1.85 (m,
2H), 4.47 (t, 2H, J ) 7.5 Hz), 7.76-8.22 (m, 10H); 13C NMR
(acetone-d6) δ 13.6, 21.9, 27.2, 44.6, 126.3, 131.7, 132.2, 135.3.
Anal. Calcd for C17H19F3O3S2: C, 52.03; H, 4.88; S, 16.34.
Found: C, 52.00; H, 5.11; S, 16.02.
(νCH), 1271, 1092 (νSO), 1258, 1159, 637 (νCF) cm-1 1H NMR
;
(acetone-d6) δ 3.99 (s, 3H), 7.78-8.16 (m, 10H); 13C NMR
(acetone-d6) δ 28.0, 128.0, 130.9, 132.0, 135.1. Anal. Calcd for
C14H13F3O3S2: C, 47.99; H, 3.74; S, 18.30. Found: C, 48.06; H,
3.98; S, 18.13.
Tr ip h en ylsu lfon iu m Hexa flu or oa n tim on a te. To a stirred
mixture of 1.86 g (10 mmol) of diphenyl sulfide and 2.72 g (20
mmol) of phenyl acetate was added 5 mL of freshly prepared
1:10 solution of phosphorus pentoxide (0.50 g) in trifluo-
romethanesulfonic acid, and the mixture was held at 0 °C in an
ice bath. The reaction mixture was stirred for 10 h while it
warmed to 20 °C. The progress of the reaction was followed by
TLC analysis (CHCl3). The color of the reaction gradually
became dark red. After the reaction, the mixture was poured
into 100 mL of distilled water. To the slightly turbid solution
there was then added 7.76 g (30 mmol) of sodium hexafluoro-
antimonate, and a pale brown oil separated. The oil was
extracted with three 100 mL portions of dichloromethane. The
combined dichloromethane solution was evaporated to 10 mL
and then poured into 200 mL of diethyl ether to precipitate a
powder. The product was recrystallized from ethanol/2-propanol
to give triphenylsulfonium hexafluoroantimonate (36% yield):
IR (KBr) 3058 (νCH), 1679, 1580 (νCdC) cm-1; 1H NMR (CDCl3) δ
7.67-7.72 (m, 15H); 13C NMR (CDCl3) δ 126.6, 131.5, 131.9,
133.8. Anal. Calcd for C18H15F6SSb: C, 43.32; H, 3.03; S, 6.42.
Found: C, 43.15; H, 3.33; S, 6.35.
S-Meth yld iben zoth iop h en iu m Tr ifla te. See the prepara-
tion of diphenylmethysulfonium triflate for details. Compounds
used were dibenzothiophene (1.84 g, 10 mmol), methyl formate
(1.20 g, 20 mmol), and trifluoromethanesulfonic acid (5 mL). The
extraction/precipitation solvents were dichloromethane/diethyl
ether to afford 3.00 g (86%) of the title compound: IR (KBr) 3053,
3010 (νCH), 1260, 1092 (νSO), 1159, 637 (νCF) cm-1 1H NMR
;
(acetone-d6) δ 3.70 (s, 3H), 7.82-8.02 (m, 4H), 8.47 (d, 2H, J )
7.9 Hz), 8.57 (d, 2H, J ) 8.3 Hz); 13C NMR (acetone-d6) δ 35.2,
125.1, 128.9, 132.0, 132.5, 134.8, 140.3. Anal. Calcd for
C
14H11F3O3S2: C, 48.27; H, 3.18; S, 18.41. Found: C, 48.50; H,
3.34; S, 18.35.
S-Meth ylth ia n th r en iu m Tr ifla te. See the preparation of
diphenylmethysulfonium triflate for details. Compounds used
were thianthrene (2.16 g, 10 mmol), methyl formate (1.20 g, 20
mmol), and trifluoromethanesulfonic acid (5 mL). The extrac-
tion/precipitation solvents were dichloromethane/diethyl ether
to afford 3.58 g (94%) of the title compound: IR (KBr) 3083 (νCH),
1272, 1069 (νSO), 1263, 1159, 637 (νCF) cm-1; 1H NMR (acetone-
d6) δ 3.50 (s, 3H), 7.76-8.36 (m, 8H); 13C NMR (acetone-d6) δ
25.5, 120.3, 130.6, 131.1, 134.7, 135.3, 136.6. Anal. Calcd for
C14H11F3O3S3: C, 44.20; H, 2.91; S, 25.29. Found: C, 44.28; H,
3.03; S, 25.03.
Tr ip h en ylsu lfon iu m Tr ifla te. To a stirred mixture of 1.86
g (10 mmol) of diphenyl sulfide and 2.44 g (20 mmol) of phenyl
formate was added 5 mL of freshly prepared 1:10 solution of
phosphorus pentoxide (0.50 g) in trifluoromethanesulfonic acid,
and the mixture was held at 0 °C in an ice bath. The reaction
mixture was stirred for 10 h while it warmed to 20 °C. The
progress of the reaction was followed by TLC analysis (CHCl3).
The color of the reaction gradually became dark purple. After
the reaction, the mixture was poured into 100 mL of distilled
water. The slightly turbid solution was extracted with three
100 mL portions of dichloromethane. The combined dichlo-
romethane solution was evaporated to 10 mL and then poured
into 200 mL of diethyl ether, causing precipitation of a pale red
powder. The crude product was washed with water and
recrystallized twice from ethyl acetate to give triphenylsulfonium
triflate (45% yield): IR (KBr) 3060 (νCH), 1273, 1066 (νSO), 1258,
Dip h en ylm eth ylselen on iu m Tr ifla te. See the preparation
of diphenylmethysulfonium triflate for details. Compounds used
were diphenyl selenide (2.33 g, 10 mmol), methyl formate (1.20
g, 20 mmol), and trifluoromethanesulfonic acid (5 mL). The
extraction/precipitation solvents were dichloromethane/diethyl
ether to afford 3.89 g (98%) of the title compound: IR (KBr) 3048
(νCH), 1271, 1073 (νSO), 1258, 1175, 637 (νCF) cm-1 1H NMR
;
(CDCl3) δ 3.48 (s, 3H), 7.58-7.72 (m, 10H); 13C NMR (CDCl3) δ
26.8, 127.3, 130.3, 131.3, 133.2. Anal. Calcd for C14H13F3O3-
SSe: C, 42.33; H, 3.30; S, 8.07. Found: C, 42.47; H, 3.02; S,
8.40.
1156, 639 (νCF) cm-1
13C NMR (CDCl3) δ 124.6, 131.4, 131.6, 135.1. Anal. Calcd for
19H15F3O3S2: C, 55.33; H, 3.67; S, 15.55. Found: C, 55.74; H,
;
1H NMR (CDCl3) δ 7.61-7.70 (m, 15H);
C
3.99; S, 15.13.
Ack n ow led gm en t. This work was partially sup-
ported by a Grant-in-Aid for Scientific Research (Nos.
09555297 and 09650982) and International Scientific
Research (J oint Research No. 08044174) from the
Ministry of Education, Science, Sports and Culture,
J apan. E.T. is a CREST Investigator, J apan Science and
Technology Corporation (J ST). K.M. thanks Research
Fellowships of the J apan Society for the Promotion of
Science for Young Scientists (No. 085410).
Dip h en yleth ylsu lfon iu m Tr ifla te. See the preparation of
diphenylmethysulfonium triflate for details. Compounds used
were diphenyl sulfide (1.86 g, 10 mmol), ethyl formate (1.48 g,
20 mmol), and trifluoromethanesulfonic acid (5 mL). The
extraction/precipitation solvents were dichloromethane/diethyl
ether to afford 2.80 g (80%) of the title compound: IR (KBr) 3063
(νCH), 1269, 1092 (νSO), 1260, 1161, 637 (νCF) cm-1 1H NMR
;
(acetone-d6) δ 1.40 (t, 3H, J ) 7.2 Hz), 4.40 (q, 2H, J ) 7.2 Hz),
7.76-8.18 (m, 10H); 13C NMR (acetone-d6) δ 8.2, 38.5, 124.3,
130.0, 130.6, 133.7. Anal. Calcd for C15H15F3O3S2: C, 49.44;
H, 4.15; S, 17.60. Found: C, 49.76; H, 4.45; S, 17.29.
J O980473C