Diphenyl diselenide-assisted α-phenylthiolation of carbonyl compounds with diphenyl disulfide

Article abstract of DOI:10.1246/bcsj.20110127

For the cesium carbonate-catalyzed α-phenylthiolation of carbonyl compounds with diphenyl disulfide, the yields of the α-phenylthio carbonyl compounds were dramatically improved by the addition of a catalytic amount of diphenyl diselenide.

Full text of DOI:10.1246/bcsj.20110127

1248 Bull. Chem. Soc. Jpn. Vol. 84, No. 11, 1248-1250 (2011)
Short Articles
cat.PhSeSePh
cat. Cs2CO3
O
Diphenyl Diselenide-Assisted
¡-Phenylthiolation of Carbonyl
Compounds with Diphenyl Disulfide
O
R
+ PhSSPh
R
R'
under Air
R'
SPh
Scheme 1.
Table 1. ¡-Phenylthiolation of 5-Nonanone (1a) with
Diphenyl Disulfide in the Presence of Various Additivesa)
Hiroaki Anbou, Rui Umeda,
and Yutaka Nishiyama*
Department of Chemistry and Materials Engineering,
Faculty of Chemistry, Materials and Bioengineering,
Kansai University, Suita, Osaka 564-8680
Entry
Additive (mmol)
Yield/mmolb)
Received May 9, 2011
1
2
3
4
5
6
7
8
none
Cs2CO3 (0.10)
0.00
0.62
1.54
0.24
0.00
0.00
0.32
0.50
E-mail: nishiya@kansai-u.ac.jp
PhSeSePh (0.10)/Cs2CO3 (0.10)
PhSeSePh (0.10)/CsF (0.10)
PhSeSePh (0.10)/CsCl (0.10)
PhSeSePh (0.10)/CsBr (0.10)
PhSeSePh (0.10)/Na2CO3 (0.10)
PhSeSePh (0.10)/K2CO3 (0.10)
For the cesium carbonate-catalyzed ¡-phenylthiolation
of carbonyl compounds with diphenyl disulfide, the yields of
the ¡-phenylthio carbonyl compounds were dramatically
improved by the addition of a catalytic amount of diphenyl
diselenide.
a) Reaction conditions: 1a (2.00 mmol), 2 (1.00 mmol), and
DMA (2 mL) under air at 100 °C for 7 h. b) GLC yield.
¡-Phenylthio carbonyl compounds are useful synthetic
intermediates in organic synthesis and many efforts are being
devoted to accomplish the synthesis of ¡-phenylthio carbonyl
compounds.1 The most common methods for the synthesis of
these compounds are the reaction of enolates with electro-
philics, such as PhSX,2 PhSSPh,3 phenyl benzenethiosulfo-
nate,4 PhSH/NCS,5 N-(phenylthio)amide,6 N-(phenylthio)-
phthalimide,7 N-(phenylthio)caprolactam,8 or N-(phenylthio)-
succinimide,9 and the SN2 displacement of ¡-halogenated
carbonyl derivatives with benzenethiol.10 Generally, these
methods require multistep sequences for the preparation of
substrate, strongly basic and acidic conditions, and anhydrous
conditions.
We have recently found that the cesium salt-catalyzed
¡-phenylselenation of carbonyl compounds with diphenyl
diselenide gave the corresponding ¡-phenylseleno carbonyl
compounds in moderate to good yields.11 This method has
some advantages: (i) the use of reagents which are stable
toward air and moisture, (ii) under nearly neutral reaction
conditions, (iii) moderate to good product yields, (iv) one-step
procedure, (v) the efficient use of both phenylseleno groups
of diphenyl diselenide, and (vi) catalytic use of a cesium
salt. Thus, if diphenyl disulfide instead of diphenyl disele-
nide was used as a dichalcogenide, it is expected that the
¡-phenylthio carbonyl compounds could be conveniently
synthesized by the cesium salt catalytic method. Although
carbonyl compounds were treated with diphenyl disulfide
in the presence of a catalytic amount of cesium carbonate,
the yields of the ¡-phenylthio carbonyl compounds were low.11
We now find that an ¡-phenylthiolation of carbonyl com-
pounds with diphenyl disulfide proceeds successfully in
the presence of a catalytic amount of diphenyl diselenide
(Scheme 1).12
When 5-nonanone (1a) (2.00 mmol) was allowed to react
with PhSSPh (2) (1.00 mmol) in the presence of a catalytic
amount of cesium carbonate (0.10 mmol) in DMA solvent under
air at 100 °C for 7 h, the ¡-phenylthiolated product, 4-phenyl-
thio-5-nonanone (3a), was formed in only 0.62 mmol (Table 1,
Entry 2).13 It is interesting to note that the addition of a small
amount of PhSeSePh (0.10 mmol) led to an increase in the yield
of 3a (1.54 mmol) (Entry 3). The result showed that both
phenylthio groups on PhSSPh are effectively introduced on the
¡-carbon of the 5-nonanone. In the absence of both Cs2CO3 and
PhSeSePh, 3a was not formed at all and 1a was recovered
(Entry 1). We next investigated the effect of the alkaline metal
salts on the reaction and the results are shown in Table 1. In the
case of other cesium salts such as cesium fluoride, chloride, and
bromide, the reaction hardly proceeded (Entries 4-6). When
using another alkaline metal carbonate, the ¡-phenylthiolation
of 5-nonanone occurred, however, the product yield was lower
than that of cesium carbonate (Entries 7 and 8).
The reaction of various carbonyl compounds with PhSSPh
was carried out under the same reaction conditions as those of
Entry 3 in Table 1 and these results are shown in Table 2. For
the reaction of octanal, cyclohexanone, and acetophenone, the
corresponding ¡-phenylthio carbonyl compounds, 3b-3d, were
formed in 0.94, 1.30, and 1.24 mmol, respectively (Entries
1-3). When 2-nonanone, which has primary and secondary
carbon atoms at the ¡-position, was allowed to react with
PhSSPh, the secondary carbon atom was predominantly phen-
ylthiolated to give 3-phenylthio-2-nonanone (3e) (Entry 4).
In the case of 3-methyl-2-butanone and 2-methyl-3-pentanone,
the phenylthiolation on the tertiary carbon atom proceeded to
give the corresponding ¡-phenylthio ketones 3f and 3g (Entries
5 and 6).
Published on the web November 3, 2011; doi:10.1246/bcsj.20110127

H. Anbou et al.
Bull. Chem. Soc. Jpn. Vol. 84, No. 11 (2011) 1249
O
Table 2. Synthesis of Various ¡-Phenylthio Carbonyl
R'
Compoundsa)
R
1
cat.PhSeSePh
O
O
Cs2CO3
R'
PhSeSePh
R
cat. Cs2CO3
O
O
R
SPh
+ PhSSPh
3
R'
R
R'
R
PhSe
R'
under Air
O
R'
SPh
R'
R
R
1
Entry
1
Substrate
Product, Yieldb)/mmol
O
O
O
O
0.94
(0.11)
R
C6H13
R'
C6H13
H
SePh
H
4
3b
SPh
3c
SPh
6
SPh
O
O
PhSSPh, PhSeSPh
or PhSeSePh
1.30
(0.62)
Cs2CO3
2
3
4
O
O
or
PhSe
SPh
R'
PhS
R'
SePh
O
R
O
1.24
R
PhS
Ph
3d
SePh
(0.34)
Ph
5
O
PhSSPh
PhS
O
0.57
C6H13
C6H13
(0.08)
Scheme 2. A possible reaction pathway.
3e
SPh
O
0.23
(0.04)
It was clearly shown that good catalytic activity of PhSeSePh
occurred during the reaction.
C6H13
SPh
3e′
For the PhSeSePh-assisted reaction of 1 with PhSSPh, the
formation of seleno sulfide (PhSSePh) and ¡-phenylseleno-¡-
phenylthio ketones were identified with GC mass analysis. To
gain insight into the reaction pathway, the reaction of isolated
4-phenylseleno-5-nonanone (0.50 mmol) with diphenyl disul-
fide (0.50 mmol) in the presence of cesium carbonate at 100 °C
for 7 h gave rise to 0.43 mmol 4-phenylthio-5-nonanone (3a).14
From these results, we suggest that the ¡-phenylseleno ketone
4 was an intermediate in the reaction.
Although we cannot clearly determine the reaction pathway,
one of the plausible reaction pathways is shown in Scheme 2.
The removal of the ¡-proton with cesium carbonate to give the
enolate anion is the first step for the reaction. The reaction
of the enolate anion with diphenyl diselenide leads to the
¡-phenylseleno carbonyl compound 4 with phenylselenolate.
The deprotonation of 4 with Cs2CO3 followed by quenching
with PhSSPh gives ¡-phenylseleno-¡-phenylthio ketone 5.15,16
5 is reacted with selenolate or thiolate giving the enolate 6.
6 abstracts an ¡-proton from the carbonyl compound to provide
a thermodynamically more stable product, 3, and regenerates
the enolate anion.
O
O
O
1.04
(0.30)
5
6
3f
SPh
O
0.18
(0.10)
SPh
3f′
3g
O
1.12
(0.86)
SPh
O
0.28
(0.10)
SPh
3g′
a) Reaction conditions: carbonyl compound (2.00 mmol),
PhSSPh (1.00 mmol), PhSeSePh (0.10 mmol), Cs2CO3
(0.10 mmol), and DMA (2 mL) under air at 100 °C for 7 h.
b) GLC yields. The numbers in parentheses show the yields in
the absence of PhSeSePh.
We found a new synthetic method of ¡-phenylthio carbonyl
compounds by the diphenyl diselenide-assisted reaction of
carbonyl compounds with diphenyl disulfide in the presence of
a catalytic amount of cesium carbonate.
Experimental
1
General Procedures. The H and 13C NMR spectra were
recorded on 270 and 67.5 MHz spectrometers using CDCl3 as
the solvent with tetramethylsilane as the internal standard. The
IR spectra were recorded by FT-IR spectrometry. ESI mass
spectra were obtained by a triple quadrupole mass spectrometer
in a positive ion mode. Gas chromatography (GC) was carried
out using a flame-ionizing detector equipped instrument and a
capillary column (0.25 mm © 1200 mm).
Figure 1. Time dependent curves for the reaction of 1a and 2.
Comparison of plots of the yield of ¡-phenylthio ketone,
3a, vs. the reaction time in the presence of PhSeSePh-catalyst
with those without PhSeSePh-catalyst are shown in Figure 1.

1250 Bull. Chem. Soc. Jpn. Vol. 84, No. 11 (2011)
© 2011 The Chemical Society of Japan
3
a) R. M. Coates, H. D. Pigott, J. Ollinger, Tetrahedron Lett.
Reagents. Diphenyl disulfide, the carbonyl compounds,
and Cs2CO3 were commercially available and were used
without further purification. The diphenyl diselenide17 and
4-phenylseleno-5-nonanone11 were prepared by a literature
method. DMA was commercially obtained and purified by
distillation.
1974, 15, 3955. b) B. M. Trost, T. N. Salzmann, K. Hiroi, J. Am.
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4
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General Procedure for Reaction of Carbonyl Com-
pounds with Diphenyl Disulfide in the Presence of a
5
J. S. Yadav, B. V. Subba Reddy, R. Jain, G. Baishya,
Tetrahedron Lett. 2008, 49, 3015.
T. Kumamoto, S. Kobayashi, T. Mukaiyama, Bull. Chem.
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Catalytic Amount of Diphenyl Diselenide.
A DMA
6
(2 mL) solution of PhSSPh (218 mg, 1.00 mmol), carbonyl
compound (2.00 mmol), PhSeSePh (31 mg, 0.10 mmol), and
Cs2CO3 (32 mg, 0.10 mmol) was stirred at 100 °C for 7 h in
air. After the reaction was complete, H2O was added to the
reaction mixture and then extracted with diisopropyl ether. The
organic layer was dried over MgSO4. The resulting mixture
was filtered, and the filtrate concentrated. Purification of the
residue by HPLC afforded the corresponding ¡-phenylthiolated
product. The product was characterized by comparing its
spectral data with those of an authentic sample or previous
reports for 3a,18 3b,7 3c,10c 3d,8 3f,6 3f¤,19 3g,20 and 3g¤.21 The
structure of the 3e was assigned based on the 1H and 13C NMR,
IR, and mass spectrum.
7
W. Wang, H. Li, J. Wang, L. Liao, Tetrahedron Lett. 2004,
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8
G. Foray, A. B. Peñéñory, R. A. Rossi, Tetrahedron Lett.
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9
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11 Y. Nishiyama, Y. Koguma, T. Tanaka, R. Umeda, Mole-
cules 2009, 14, 3367.
12 Ogawa, Sonoda, et al. have reported the results on the
PhSeSePh-assisited dithiolation of 1,3-dienes with PhSSPh upon
irradiation with near-UV light, see: A. Ogawa, R. Obayashi, N.
Sonoda, T. Hirao, Tetrahedron Lett. 1998, 39, 1577.
13 Under an atmosphere of N2, the yield of 3a (12%) was
dramatically decreased.
14 In the absence of Cs2CO3, the reaction did not proceed and
4-phenylseleno-5-nonanone was recoverd in almost quantitatively
yield.
15 R. M. Coates et al. have measured the position of
equilibrium established between lithium enolate of cyclohexanone
and 2-phenylthiocyclohexanone. See Ref. 3a.
16 It is reported that the introducing of phenylthio group at
¡-position increases the acidity of cyclohexanone by at least 3 pKa
units, see Ref. 3a.
Mixture of 3-Phenylthio-2-nonanone (3e) and 1-Phenyl-
thio-2-nonanone (3e¤) (3e:3e¤ = 71:29): 1H NMR (270 MHz,
CDCl3): ¤ 7.37-7.16 (m, 5H), 3.65 (s, 2 © 0.29H), 3.62 (t, J =
7.2 Hz, 1 © 0.71H), 2.56 (t, J = 7.2 Hz, 2 © 0.29H), 2.23
(s, 3 © 0.71H), 1.82-1.24 (m, 20H), 0.87 (t, J = 7.2 Hz,
3 © 0.71H), 0.85 (t, J = 7.2 Hz, 3 © 0.29H); 13C NMR (67.5
MHz, CDCl3): ¤ 205.7, 205.5, 134.9, 133.1, 132.1, 129.04,
129.02, 128.96, 128.93, 127.7, 57.7, 57.6, 43.9, 43.8, 40.5,
31.5, 31.5, 30.3, 28.8, 27.1, 26.3, 26.2, 22.5, 22.4, 14.0; IR
(KBr): 2927, 2856, 1709, 1438, 1354, 740, 690 cm¹1; ESI:
[M + Na+] 272.67.
This research was supported by a Grant-in-Aid for Science
Research, and Strategic Project to Support the Formation of
Research Bases at Private Universities from the Ministry of
Education, Culture, Sports, Science and Technology of Japan.
17 H. J. Reich, J. M. Renga, I. L. Reich, J. Am. Chem. Soc.
1975, 97, 5434.
18 I. Paterson, S. Osborne, Synlett 1991, 145.
19 I. Kuwajima, M. Shimizu, H. Urabe, J. Org. Chem. 1982,
47, 837.
References
1
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2
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