Cesium carbonate-Catalyzed α-phenylchalcogenation of carbonyl compounds with diphenyl dichalcogenide

Article abstract of DOI:10.3390/molecules14093367

It was found that cesium carbonate has a unique catalytic ability on the reaction of carbonyl compounds with diphenyl diselenide to give the corresponding α-phenylseleno carbonyl compounds in moderate to good yields. Similarly, the α-phenylthiolation of c

Full text of DOI:10.3390/molecules14093367

Molecules 2009, 14, 3367-3375; doi:10.3390/molecules14093367
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Communication
Cesium Carbonate-Catalyzed α-Phenylchalcogenation of
Carbonyl Compounds with Diphenyl Dichalcogenide
Yutaka Nishiyama *, Yuya Koguma, Toshimasa Tanaka and Rui Umeda
Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan
* Author to whom correspondence should be addressed; E-mail: nishiya@kansai-u.ac.jp;
Tel.: 81-6-6368-0902; Fax: 81-6-6339-4026.
Received: 31 July 2009; in revised form: 26 August 2009 / Accepted: 2 September 2009 /
Published: 2 September 2009
Abstract: It was found that cesium carbonate has a unique catalytic ability on the reaction
of carbonyl compounds with diphenyl diselenide to give the corresponding α-phenylseleno
carbonyl compounds in moderate to good yields. Similarly, the α-phenylthiolation of
carbonyl compounds with diphenyl disulfide was promoted by the cesium carbonate
catalyst.
Keywords: cesium carbonate; α-phenylchalcogenation; carbonyl compounds; diphenyl
dichalcogenide
Introduction
α-Phenylselenocarbonyl compounds are useful synthetic intermediates in organic synthesis [1-5]
and much effort is being devoted to accomplish the synthesis of these compounds. There are many
reports on the preparation of α-phenylselenocarbonyl compounds: (i) electrophilic reaction with
PhSeX, PhSeX3, PhSeO2CCF3 or phenylselenium cation (PhSe+), which was generated in situ from the
treatment of diphenyl diselenide with SeO2, benzeneseleninic anhydride, chloramine-T, or Et4NBr or
MgBr2 under electrolysis [6-21]; (ii) nucleophilic displacement of α-halocarbonyl compounds with
sodium and lithium phenylselenolate [22]; (iii) insertion of carbene into carbon-selenium bond of
selenol esters [23]; (iv) palladium-catalyzed coupling of phenyl tributylstannyl selenide and α-
halocarbonyl compounds [24] and (v) organocatalyst-catalyzed reaction of carbonyl compounds with
N-(phenylseleno)phthalimide [25-28]. However, many of these synthetic methods suffer from the the

Molecules 2009, 14
3368
problems of handling the selenium reagents used as selenium sources because of their instability
towards air and moisture, acidic or basic reaction conditions, and the use of stoichiometric amounts of
acid or base. Thus, the development of new synthetic methods using stable selenium reagents under
mild conditions would have significant synthetic value. We now discovered that a cesium salt acts as a
catalyst on the α-phenylselenation of carbonyl compounds with diphenyl diselenide giving the
corresponding α-phenylselenocarbonyl compounds in moderate to good yields (Scheme 1).
Scheme 1. Cesium carbonate-catalyzed α-phenylselenation of carbonyl compounds with
diphenyl diselenide.
cat.Cs2CO3
O
O
+
R2
(PhSe)2
R2
R1
R1
SePh
Results and Discussion
When 5-nonanone (1a; 0.30 mmol) was allowed to react with an equivalent amount of diphenyl
diselenide (0.30 mmol) in the presence of a catalytic amount of cesium carbonate (0.05 mmol,
17 mol%) in DMA solvent at 70 °C for 5 h, the α-phenylselenation of 1a smoothly proceeded to give
4-phenylseleno-5-nonanone (2a) in 0.03 mmol yield (entry 2 in Table 1). In the absence of the cesium
salt, 2a was not formed and the starting materials were recovered (entry 1).
Table 1. Reaction of 5-nonanone with diphenyl diselenide. a
O
O
catalyst (0.05 mmol)
PhSeSePh
+
DMA
under Air
(0.30 mmol)
SePh
1a
2a
entry
1
1a/mmol temp/ °C
time/h
catalyst
yield/mmol b
trace
0.03
0.30
0.30
0.90
1.50
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
70
70
70
70
70
5
5
5
5
5
10
5
5
5
5
5
5
5
5
none
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
CsF
CsCl
CsBr
CsI
K2CO3
Na2CO3
2
3
4
5
0.03
0.05
0.07
0.23
0.59
0.27
0.42
0.06
0.08
0.02
0.48
0.17
6
70
7
100
100
100
100
100
100
100
100
8 c
9
10
11
12
13
14
a Reaction conditions: PhSeSePh (0.30 mmol), catalyst (0.05 mmol), and DMA (2.5 mL);
b GC yield. c Under a nitrogen atmosphere.

Molecules 2009, 14
3369
Increasing the amount of 1a, extending the reaction time, and elevating the reaction temperature led
to the increase the yield of 2a (entries 2-7). When diphenyl diselenide was treated with ten equivalent
amounts of 1a (3.00 mmol) under air at 100 °C for 5 h, 2a was obtained in 0.59 mmol yield, along with
a formation of a small amount of 4,4-bisphenylseleno-5-nonanone (entry 7). It is interested to note that
both phenylseleno groups on diphenyl diselenide are efficiently utilized on the reaction. When the
reaction was carried out under a nitrogen atmosphere, the yield of 2a was decreased (entry 8).
Similarly, in the presence of a catalytic amount of cesium fluoride, the α-phenylselenation of 1a
occurred to give 2a in 0.42 mmol yield (entry 9). In contrast to cesium carbonate and fluoride, in the
case of the other cesium salts, such as cesium chloride, bromide and iodide, the α-phenylselenation did
not proceed (entries 10-12). In the presence of another alkaline metal carbonates, the yields of 2a
decreased slightly (entries 13 and 14) [29].
To determine the scope and limitation of the cesium salt-catalyzed α-phenylselenation of carbonyl
compounds with diphenyl diselenide, various carbonyl compounds were allowed to react with
diphenyl diselenide in the presence of a catalytic amount of cesium carbonate (17 mol%) and these
results are shown in Table 2. The treatment of cyclohexanone with diphenyl diselenide under the same
reaction conditions as that of 5-nonanone afforded 2-phenylselenocyclohexanone in 0.43 mmol yield
(entry 2). For the reaction of the acetophenone and propiophenone, which have an aromatic ring
adjacent to the carbonyl group, the α-phenylselenation of these compounds took place smoothly to
give the corresponding α-phenylselenoacetophenone and -propiophenone in 0.51 and 0.59 mmol
yields, respectively (entries 4 and 8).
4’-Methyl-, 4’-methoxy-, and 4’-chloro-α-phenylselenoacetophenone were prepared by the cesium
carbonate-catalyzed reaction of the corresponding acetophenone derivatives with diphenyl diselenide
in moderate to good yields (entries 5-7). When an unsymmetrical dialkyl ketone such as 2-octanone
was treated with diphenyl diselenide in the presence of cesium carbonate, the phenylselenation of
methylene carbon predominantly proceeded to give 3-phenylseleno-2-octanone in 0.41 mmol yield
with the formation of 1-phenylseleno-2-octanone (0.17 mmol) (entry 3). In the case of hexanal, the
yield of α-phenylselenoaldehyde was low (0.13 mmol) under the same reaction conditions as that of 5-
nonanone, owing to the formation of a complex reaction mixture that included the aldol type products;
however, the α-phenylselenated product yield was improved, when the reaction was carried out under
the lower reaction temperature (65 °C) (entry 9).
Next, the cesium carbonate-catalyzed reaction of carbonyl compounds with diphenyl disulfide was
examined (Table 3). When 5-nonanone (3.0 mmol) was allowed to react with diphenyl disulfide (1.0
mmol) in the presence amount of cesium carbonate at 100 °C for 5 h, the α-phenylthiolation of 5-
nonanone was successfully occurred and 4-phenylthio-5-nonanone was obtained in 0.44 mmol yield
(entry 1). The treatment of cyclohexanone or acetophenone with diphenyl disulfide also afforded the α-
phenylthioketone in 0.60 or 0.51 mmol yields (entries 2 and 3).

Molecules 2009, 14
3370
Table 2. Cesium carbonate-catalyzed α-phenylselenation of carbonyl compounds with
diphenyl diselenides. a
entry
carbonyl compound
product
yield/mmol b
O
O
O
1
0.59
SePh
2a
2b
O
SePh
2
3
0.43
O
0.41
0.17
SePh
O
O
2c
PhSe
2c’
O
O
SePh
X
X
4
5
6
7
X = H
2d; X = H
0.51
0.54
0.48
0.56
X = CH3
X = OCH3
X = Cl
2e; X = CH3
2f; X = OCH3
2g; X = Cl
O
O
8
9
0.59
0.43
SePh
2h
O
O
H
SePh
H
2i
a
Reaction conditions: PhSeSePh (0.30 mmol), carbonyl compound (3.00 mmol), Cs2CO3
(0.05 mmol), and DMA (2.5 mL) under air at 100 °C for 5 h. b GC yield.

Molecules 2009, 14
3371
Table 3. Cesium carbonate-catalyzed α-phenylthiolation of carbonyl compounds with
diphenyl disulfide. a
entry
carbonyl compound
product
yield/mmol b
O
O
1
2
0.44
SPh
3a
O
O
SPh
0.60
0.51
3b
O
O
SPh
3
3c
a
Reaction conditions: PhSSPh (1.0 mmol), carbonyl compound (3.0 mmol), Cs2CO3 (0.2 mmol),
and DMA (2.5 mL) under air at 100 °C for 5 h. b GC yield.
Although we cannot explain the reaction pathway of the carbonyl compounds with diphenyl
diselenide in the presence of cesium carbonate catalyst in detail, one possible reaction pathway is
shown in Scheme 2. The first step of the reaction is the generation of the enolate anion by the
deprotonation of carbonyl compound with the cesium salt [30]. The enolate anion was trapped with
diselenide to form α-phenylselenocarbonyl compounds, and the phenylselenolate [31]. When the
reaction was carried out under air, the product yield was higher than when performed under a nitrogen
atmosphere (entries 7 and 8 in Table 1). From the result, it was suggested that phenylselenolate was
oxidized by oxygen to form phenylseleno radical and subsequently dimerized giving the diphenyl
diselenide.
Scheme 2. A plausible reaction path.
O
R2
R1
PhSe
Cs2CO3
PhSeSePh
O
R2
R1
PhSe
O
R2
O2
R1
PhSe
SePh
O2

Molecules 2009, 14
3372
In summary, we found a unique catalytic ability of cesium carbonate in the reaction of carbonyl
compounds with diphenyl dichalogenides. The α-phenylchalcogenation of carbonyl compounds with
diphenyl dichalcogenides, such as the diselenide or disulfide in the presence of cesium carbonate
catalyst efficiently proceeded to give the α-phenylchalcogenocarbonyl compounds in moderate to good
yields.
Experimental
General
1
13
The H- and C-NMR spectra were recorded on a JEOL AL400 spectrometer using CDCl3 as the
solvent with tetramethylsilane as the internal standard. The IR spectra were recorded with a
PerkinElmer FT-IR2000 spectrometer. Gas chromatography (GC) was performed on a Shimadzu GC-
14B gas chromatograph using a flame-ionizing detector-equipped instrument and a CBP1 capillary
column (0.25 mm × 1200 mm). Preparative HPLC separation was undertaken with a JAI LC-908
chromatograph using 600-mm × 20-mm JAIGEL-1H and 2H GPC columns with CHCl3 as an eluent.
Reagents
Diphenyl disulfide, carbonyl compounds, cesium salts, and alkaline metal salts were purchased as
high grade products, and used without purfication. Diphenyl diselenide was synthesized as described
in the literature [22]. The solvents were purified before use by the usual methods.
General procedure for cesium salt-catalyzed reaction of carbonyl componds with diphenyl diselenide
A DMA (2.5 mL) solution of diphenyl diselenide (94 mg, 0.30 mmol), carbonyl compound (3.00
mmol), and cesium carbonate (16 mg, 0.05 mmol) was stirred at 100 °C for 5 h under air. After the
reaction was complete, H2O was added to the reaction mixture and extracted with diisopropyl ether.
The organic layer was dried over MgSO4. The resulting mixture was filtered, and the filtrate was
concentrated. Purification of the residue by HPLC afforded the corresponding α-phenylselenated
product. The product was characterized by comparing its spectral date with those of authentic samples
(2a [32], 2b [27], 2d [24], 2e [24], 2f [24], 2g [24], 2h [24], and 2i [27]). The structures of the product
were assigned by their 1H- and 13C-NMR, IR, and Mass spectra.
Mixture 2c and 2c’ (2c:2c’ = 41:17): 1H-NMR (CDCl3) δ 7.53-7.46 (m, 2H), 7.33-7.20 (m, 3H), 3.63 (t,
J = 7.4 Hz, 0.70H), 3.56 (s, 0.61H), 2.53 (t. J = 7.4 Hz, 0.61H), 2.26 (s, 2.1H), 1.87-1.76 (m, 0.70H),
1.73-1.62 (m, 0.70H), 1.58-1.48 (m, 0.70H), 1.47-1.38 (m, 0.70H), 1.37-1.14 (m, 7.2H), 0.87 (t,
J = 6.8 Hz, 3H); 13C-NMR (CDCl3) δ 205.56, 204.04, 135.36, 135.31, 133.01, 129.06, 128.95, 128.41,
127.60, 127.18, 52.29, 40.51, 35.80, 31.46, 31.40, 30.14, 28.86, 28.81, 28.74, 27.85, 27.19, 23.80,
22.41, 22.35, 13.90, 13.86; IR (NaCl) 3388, 3058, 2925, 2855, 1703, 1578, 1477, 1438, 1355, 1066,
1022, 1000, 739, 691, 670 cm-1; MS m/z 298.

Molecules 2009, 14
3373
General procedure for cesium salt-catalyzed reaction of carbonyl compounds with diphenyl disulfide
A DMA (2.5 mL) solution of diphenyl disulfide (218 mg, 1.0 mmol), carbonyl compound
(3.0 mmol), and cesium carbonate (64 mg, 0.2 mmol) was stirred at 100 °C for 5 h under air. After the
reaction was complete, H2O was added to the reaction mixture and extracted with diisopropyl ether.
The organic layer was dried over MgSO4. The resulting mixture was filtered, and the filtrate was
concentrated. Purification of the residue by HPLC afforded the corresponding α-phenylselenated
product. The product was characterized by comparing its spectral date with those of authentic samples
(3a [32], 3b [33], and 3c [34]). The structures of the product were assigned by their 1H- and 13C-NMR,
IR, and Mass spectra.
Acknowledgments
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.
References and Notes
1. Back, T.G., Ed. In Organoselenium Chemistry: A Practical Approach; Oxford University Press:
New York, NY, USA, 1999.
2. Krief. A. In Comprehensive Organic Synthesis; Trost, B.M., Fleming, I., Eds.; Pergamon Press:
Oxford, UK, 1991; Vol. 3, pp. 85-192.
3. Krief, A.; Hevesi, L. Organoselenium Chemistry; Springer-Verlag: Berlin, Germany, 1988; Vol. 1.
4. Paulmier, C. Selenium Reagents and Intermediates in Organic Synthesis; Pergamon Press:
Oxford, UK, 1986.
5. Patai, S.; Rappoport, Z., Eds. The Chemistry of Organic Selenium and Tellurium Compounds;
Wiley: New York, NY, USA, 1986; Vols. 1 and 2 and references therein.
6. Sharpless, K.B.; Lauer, R.F.; Teranishi, A.Y. Electrophilic and nucleophilic organoselenium
reagents. New routes to α,β-unsaturated carbonyl compounds. J. Am. Chem. Soc. 1973, 95,
6137-6139.
7. Clive, D.L. Fragmentation of selenoxides: A new method for dehydrogenation of ketones. J.
Chem. Soc. Chem. Commun. 1973, 695-696.
8. Reich, H.J. Organoselenium chemistry. Benzeneselenenyl trifluoroacetate additions to olefins and
acetylenes. J. Org. Chem. 1974, 39, 428-429.
9. Sharpless, K.B.; Gordon, K.M.; Lauer, R.F.; Singers, S.P.; Young, M.W. The utility of selenium
reagents in organic synthesis. Chem. Scr. 1975, 8A, 9-13.
10. Reich, H.J.; Renga, J.M.; Reich, I.L. Organoselenium chemistry. Conversion of ketones to enones
by selenoxide syn elimination. J. Am. Chem. Soc. 1975, 97, 5434-5447.
11. Ryu, I.; Murai, S.; Niwa, I.; Sonoda, N. A convenient synthesis of α-phenylseleno ketones and
aldehydes from enol silyl ethers and phenylselenenyl bromide. Synthesis 1977, 874-875.
12. Raucher, S. The regiospecific synthesis of α-phenylseleno ketones from monosubstituted alkenes.
Tetrahedron Lett. 1978, 19, 2261-2262.

Molecules 2009, 14
3374
13. Clive, D.L. Modern organoselenium chemistry. Tetrahedron 1978, 34, 1049-1132.
14. Torii, S.; Uneyama, K. Handa, K. A facile access to α-phenylselenenyl carbonyl compounds by
electrochemical oxidation. Tetrahedron Lett. 1980, 21, 1863-1866.
15. Liotta, D.; Zima, G.; Barnum, C.; Saindane, M. Reactions involving selenium metal as an
electrophile. The enolate - selenolate transformation. Tetrahedron Lett. 1980, 21, 3643-3646.
16. Williams, D.R. Nishitani, T. A mild oxidation of aldehydes to α,β-unsaturated aldehydes.
Tetrahedron Lett. 1980, 21, 4417-4420.
17. Miyoshi, N.; Yamamoto, T.; Kambe, N.; Murai, S.; Sonoda, N. A convenient method for the
synthesis of α-phenylselenenyl carbonyl compounds. Tetrahedron Lett. 1982, 23, 4813-4816.
18. Magnus, P.; Rigollier, P. New mild methodology for the synthesis of α-phenylthio and α-
phenylseleno ketones. Tetrahedron Lett. 1992, 33, 6111-6114.
19. Houllemare, D.; Ponthieux, S.; Outurquin, F.; Paulmier, C. Use of phenylselenium trichloride for
simple and rapid preparation of α-phenylselanyl aldehydes and ketones. Synthesis 1997, 101-106.
20. Yang, M.H.; Wang, H.S.; Zheng, Y.F.; Zhu, C.J. Synthesis of α-phenylseleno ketone directly
catalyzed by amine. Youji Huaxue 2006, 26, 1268-1271.
21. Nazari, M.; Movassagh, B. α-Phenylselenenylation of aldehydes and ketones with diphenyl
diselenide mediated by KF/Al2O3. Tetrahedron Lett. 2009, 50, 1453-1455.
22. Sharpless, K.B.; Lauer, R.F. Mild procedure for the conversion of epoxides to allylic alcohols.
First organoselenium reagent. J. Am. Chem. Soc. 1973, 95, 2697-2699.
23. Back, T.G.; Kerr, R.G. Homologation of selenoesters to (phenylseleno)- or (methylseleno)methyl
ketones with diazomethane. Tetrahedron Lett. 1982, 23, 3241-3244.
24. Nishiyama, Y.; Kawamatsu, H.; Funato, S.; Tokunaga, K.; Sonoda, N. Phenyl tributylstannyl
selenide as a promising reagent for introducion of the phenylseleno group. J. Org. Chem. 2003,
68, 3599-3602.
25. Cossy, J.; Furet, N. N-(Phenylseleno)phthalimide: A useful reagent for the α-selenylation of
ketones and aldehydes. Tetrahedron Lett. 1993, 34, 7755-7756.
26. Wang, W.; Wang, J.; Li, H. A Simple and efficient l-prolinamide-catalyzed α-selenenylation
reaction of aldehydes. Org. Lett. 2004, 6, 2817-2820.
27. Wang, J.; Li, H.; Mei, Y.; Lou, B.; Xu, D.; Xie, D.; Guo, H.; Wang, W. Direct, facile aldehyde
and ketone α-selenenylation reactions promoted by l-prolinamide and pyrrolidine sulfonamide
organocatalysts. J. Org. Chem. 2005, 70, 5678-5687.
28. Giacalone, F.; Gruttadauria, M.; Marculescu, A. Noto, R. Polystyrene-supported proline and
prolinamide. Versatile heterogeneous organocatalysts both for asymmetric aldol reaction in water
and α-selenenylation of aldehydes. Tetrahedron Lett. 2006, 48, 255-259.
29. When diphenyl diselenide was treated with 1a in the presence of cesium oxide, no α-
phenylselenation was observed.
30. The generation of carbon dioxide was not ascertained by the bubbling of the resulting gas into the
aq. Ba(OH)2.
31. Reich et al. have described that diphenyl diselenide does not react with lithium enolates of
ketones but react with ester enolates and more reactive carbanions [10]. In this manuscript, they
suggested that the failure is more the result of an unfavorable equilibrium than of a kinetic barrier.

Molecules 2009, 14
3375
32. Paterson, I.; Osbone, S. Enol borinates in organic synthesis: Regioselective α-sulphenylation and
α-selenenylation of ketones. Synlett 1991, 145-146.
33. Leriverend, P.; Leriverend, M. Chemoselektive methode zur herstellung von phenyl-sulfoxiden
durch oxidation von phenyl-sulfiden mit 2-hydroperoxy-2-methoxypropan. Synthesis 1987,
587-588.
34. Padmanabhan, S.; Ogawa, T.; Suzuki, H. Sodium telluride-mediated sulfenylation of α-halo
carbonyl compounds with diphenyl disulfide. Bull. Chem. Soc. Jpn. 1989, 62, 1358-1360.
Sample Availability: Samples of the compounds 2a-2i and 3a-3c are available from the authors.
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.
This article is an open-access article distributed under the terms and conditions of the Creative
Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).