α-Phenylselenenylation of aldehydes and ketones with diphenyl diselenide mediated by KF/Al2O3

Article abstract of DOI:10.1016/j.tetlet.2009.01.068

The utility of KF/Al₂O₃ for the synthesis of α-phenylseleno aldehydes and ketones from the corresponding aldehydes or ketones and diphenyl diselenide has been investigated. Simple stirring of a mixture of aldehyde or ketone and diphe

Full text of DOI:10.1016/j.tetlet.2009.01.068

Tetrahedron Letters 50 (2009) 1453–1455
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
a-Phenylselenenylation of aldehydes and ketones with diphenyl diselenide
mediated by KF/Al2O3
*
Mohammad Nazari, Barahman Movassagh
Department of Chemistry, K. N. Toosi University of Technology, PO Box 16315-1618, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
The utility of KF/Al2O3 for the synthesis of a-phenylseleno aldehydes and ketones from the corresponding
aldehydes or ketones and diphenyl diselenide has been investigated. Simple stirring of a mixture of alde-
hyde or ketone and diphenyl diselenide in the presence of KF/Al2O3 at room temperature selectively pro-
Received 8 December 2008
Revised 29 December 2008
Accepted 13 January 2009
Available online 19 January 2009
duces the corresponding
a
-phenylseleno aldehyde or ketone in good to excellent yields.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
a-Phenylselenenylation
Aldehyde
Ketone
KF/Al2O3
Diphenyl diselenide
a
-Phenylseleno aldehydes and ketones are important interme-
makes it a versatile substitute for organic bases in a variety of
reactions such as Suzuki couplings, Sonogashira couplings, Knoeve-
nagel reactions, and N-alkylations of amides and epoxidation
reactions.9
diates in organic synthesis1, which can be converted into the corre-
sponding synthetically useful
a,b-unsaturated aldehydes and
ketones through selenoxide elimination reactions.2 Furthermore,
these compounds can undergo oxidation followed by [2,3]-sigma-
tropic rearrangement to produce allylic alcohols3 and amines.4
In continuation of our work on the utility of KF/Al2O3 in differ-
ent reactions,10 we have examined its application in the synthesis
Various synthetic methods for the preparation of
a-phenylseleno
of a-phenylseleno aldehydes and ketones by reaction of various
aldehydes and ketones have been developed, including direct
a
-
aldehydes and ketones with diphenyl diselenide.
In this Letter, we report a very simple, convenient, and high
yielding one-pot method for the selective preparation of mono a-
phenylseleno aldehydes and ketones, which is mediated by KF/
Al2O3 using stable and commercially available diphenyl diselenide
at room temperature under mild conditions.
selenenylation of aldehydes or ketones,5,2a,c reaction of electro-
philic organoselenium reagents such as PhSeBr or N-(phenylsele-
no)phthalimide (NPSP) with aldehyde or ketone enolates or
enolate derivatives,6 and nucleophilic reaction of phenylseleno-
lates with a
-halo aldehydes or ketones.7 However, most of the re-
ported methods suffer from serious drawbacks such as the
necessity of very low temperature (À78 °C), low yields, and use
of air and moisture sensitive and expensive reagents or poisonous
To optimize the reaction conditions with respect to tempera-
ture, solvent, base, and molar ratio of the components, we first con-
ducted the reaction of hexanal and diphenyl diselenide, as a model
reaction, under air (Scheme 1). The results are listed in Table 1.
When the reaction was performed using other bases (Table 1, en-
tries 1–5), the yields of the desired product were low. In contrast,
transition metal catalysts. Due to the utility of
a-phenylseleno
aldehydes and ketones, the development of new, simple, and con-
venient alternative synthetic methods for their preparation is of
considerable importance.
The versatile solid-supported reagent, potassium fluoride
loaded on alumina, KF/Al2O3, which was originally introduced by
Ando et al.,8 possesses a number of advantages such as simple
work-up and isolation of product, increased yield, and shorter
reaction times. Moreover, the strong basic nature of KF/Al2O3
higher yields of
a-phenylseleno-hexanal were obtained when KF/
Al2O3 (38% by weight KF)10 was used as base. As can be seen from
Table 1, the best result was obtained with KF/Al2O3 in DMF at room
temperature (Table 1, entry 9).
PhSe
Base, (PhSe)2
H3C
H3C
( )3
( )3
CHO
CHO
* Corresponding author. Tel.: +98 21 2288 6575; fax: +98 21 2285 3650.
E-mail address: bmovass1178@yahoo.com (B. Movassagh).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.01.068

1454
M. Nazari, B. Movassagh / Tetrahedron Letters 50 (2009) 1453–1455
Table 1
Table 3
Optimization of the
a-phenylselenenylation of hexanal
Reaction of ketones with diphenyl diselenide mediated by KF/Al2O3
a
Entry
Base (mmol)
Solvent
Conditions
Yielda (%)
Entry
1
Product
Time (h)
Yieldb (%)
95
O
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Basic Al2O3 (3)
NaH (3)
Et3 N (3)
K2CO3 (3)
KOH (3)
KF/Al2O3 (3)
KF/Al2O3 (4)
KF/Al2O3 (1.5)
KF/Al2O3 (2)
KF/Al2O3 (2)
KF/Al2O3 (2)
KF/Al2O3 (2)
KF/Al2O3 (2)
KF/Al2O3 (2)
KF/Al2O3 (2)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
CH2Cl2
CH3CN
THF
25 °C, 2 h
25 °C, 1 h
25 °C, 24 h
25 °C, 2 h
25 °C, 1 h
25 °C, 20 min
25 °C, 20 min
25 °C, 20 min
25 °C, 20 min
25 °C, 30 min
50 °C, 20 min
25 °C, 24 h
25 °C, 6 h
48
39
Trace
43
38
76
57
63
79
77
30
0
2i6d
18
H3C
SePh
CH3
O
SePh
2
3
4
2j6d
26
22
25
75
88
65
O
SePh
61
0
0
25 °C, 24 h
55 °C, 24 h
2k6d
THF
N
a
Isolated yield.
CH3
O
SePh
2l6d
O
O
KF/Al2O3, (PhSe)2
DMF, RT
R1
R1
SePh
R2
R2
2
O
5
6
7
2m6d
2n6d
2o7a
2p7a
18
20
21
20
88
80
92
89
1
SePh
SePh
H3C
R1 = H, alkyl, aryl
R2 = H, alkyl
O
Scheme 2.
O
In order to probe the scope of the KF/Al2O3-mediated
-phenylselenenylation, a variety of aldehydes were treated with
SePh
SePh
a
Ph
Ph
diphenyl diselenide (Scheme 2). The results are shown in Table
O
8
CH3
Table 2
a
References provided for known compounds.
Isolated yield.
Reaction of aldehydes with diphenyl diselenide mediated by KF/Al2O3
b
Entry
Producta
SePh
CHO
SePh
CHO
SePh
CHO
SePh
CHO
SePh
CHO
SePh
CHO
SePh
CHO
SePh
CHO
Yieldb (%)
74
1
2a6d
2b6d
2c6d
2d6d
2e6d
2f6d
2g6d
2h6d
H3C
H3C
H3C
H3C
H3C
H3C
H3C
2. Interestingly, neither condensation adducts nor double
nylselenenylated products were detected in the course of these
a-phe-
2
3
4
5
6
7
90
79
88
86
76
74
85
reactions when performed under the optimized reaction condi-
( )2
( )3
( )4
( )5
( )6
( )7
tions.11 The corresponding
a
-phenylselenenylated aldehydes
2a–h were obtained in 74–90% yields.
We then examined the -phenylselenenylation reaction of ke-
a
tones with diphenyl diselenide (Scheme 2). In our first attempt,
3-pentanone was allowed to react with diphenyl diselenide in
the presence of KF/Al2O3. Under the previously optimized reaction
conditions,11 the corresponding mono
a-phenylselenyl ketone, 2-
(phenylselenyl)pentan-3-one, was obtained in 95% yield after
18 h (2i, entry 1, Table 3). Encouraged by this result, we performed
the same reaction with various aliphatic and aromatic ketones. The
results are presented in Table 3.
were obtained selectively in 65–95% yields under very mild reac-
a-Phenylselenenylated ketones
tion conditions.
In summary, we have described a straightforward, selective,
simple, and efficient KF/Al2O3-mediated one-pot procedure for
the synthesis of
a-phenylseleno aldehydes and ketones under
mild reaction conditions with good to excellent yields. Regarding
operational simplicity, mild reaction conditions, and cost, this
method offers significant advantages over previously reported
methods.
8
Ph
a
References provided for known compounds. Reaction time = 20 min.
Isolated yield.
b

M. Nazari, B. Movassagh / Tetrahedron Letters 50 (2009) 1453–1455
1455
M.; Namboodiri, V. Synthesis 2003, 217; (d) Blass, B. E. Tetrahedron 2002, 58,
9301. including references therein; (e) Kabalka, G.; Wang, L.; Pagni, R. M.
Synlett 2001, 108; (f) Kabalka, G. W.; Pagni, R. M.; Wang, L.; Namboodiri, V.;
Hair, C. M. Green Chem. 2002, 2, 120.
Acknowledgments
We gratefully acknowledge the K. N. Toosi University of Tech-
nology research council and Iranian National Science Foundation
(INSF, Grant No. 86063/21) for financial support.
10. (a) Movassagh, B.; Soleiman-Beigi, M.; Nazari, M. Chem. Lett. 2008, 22; (b)
Movassagh, B.; Shokri, S. Tetrahedron Lett. 2005, 46, 6923; (c) Movassagh, B.;
Zakinezhad, Y. J. Chem. Res. 2006, 369; (d) Movassagh, B.; Shokri, S. Synth.
Commun. 2005, 35, 887.
11. General procedure for the KF/Al2O3-mediated a-phenylselenenylation of aldehydes
References and notes
and ketones: To a stirred solution of aldehyde or ketone (0.5 mmol) and KF/
Al2O3 (320 mg, 38 wt %, KF) in DMF (5 mL), diphenyl diselenide (156 mg,
0.5 mmol) was added, and the reaction mixture was stirred at room
temperature (25 °C) for the time indicated in Tables 2 and 3. The progress of
the reaction was monitored by TLC. After the reaction was complete, the
mixture was filtered, and the solid support was washed thoroughly with ethyl
acetate. After evaporation of solvents, the crude product was purified by
preparative TLC (silica gel, eluent n-hexane/EtOAc). Excess diphenyl diselenide
1. (a) Liotta, D. Organoselenium Chemistry; Wiley: New York, 1987; (b) Back, T. G.
Organoselenium Chemistry:
A Practical Approach; Oxford University Press:
Oxford, UK, 1999; (c) Reich, H. J. Acc. Chem. Res. 1979, 12, 22.
2. (a) Sharpless, K. B.; Young, M. W. J. Org. Chem. 1975, 40, 947; (b) Reich, H. J.;
Renga, J. M.; Reich, I. L. J. Am. Chem. Soc. 1975, 97, 5434; (c) Reich, H. J.; Lenga, I.
L.; Reich, I. L. J. Am. Chem. Soc. 1973, 95, 5813.
3. (a) Lerouge, P.; Paulmier, C. Tetrahedron Lett. 1984, 25, 1983; (b) Lerouge, P.;
Paulmier, C. Tetrahedron Lett. 1987, 25, 1987.
4. (a) Fitzer, J. N.; Shea, R. G.; Fankhauser, J. E.; Hopkins, P. B. J. Org. Chem. 1985, 50,
417; (b) Shea, R. G.; Fitzner, J. N.; Fankhauser, J. E.; Spaltenstein, A.; Carpino, P.
A.; Peevey, R. M.; Pratt, D. V.; Tenge, B. J.; Hopkins, P. B. J. Org. Chem. 1986, 51,
5243.
5. Sharpless, K. B.; Lauer, R. F.; Teranishi, A. Y. J. Am. Chem. Soc. 1973, 95,
6137.
6. (a) Nicolaou, K. C.; Claremon, D. A.; Branette, W. E.; Sitz, S. P. J. Am. Chem. Soc.
1979, 101, 3704; (b) Schwartz, J.; Hayasi, Y. Tetrahedron Lett. 1980, 21, 1497; (c)
Jackson, W. P.; Ley, S. V.; Morton, J. A. Tetrahedron Lett. 1981, 22, 2601; (d)
Wang, J.; Li, H.; Mei, Y.; Lou, B.; Xu, D.; Xie, D.; Guo, H.; Wang, W. J. Org. Chem.
2005, 70, 5678; (e) Liotta, D.; Zima, G.; Barnum, C.; Saindane, M. Tetrahedron
Lett. 1980, 21, 3643; (f) Sundén, H.; Rios, R.; Córdova, A. Tetrahedron Lett. 2007,
48, 7865; (g) Tiecco, M.; Carlone, A.; Sternativo, S.; Marini, F.; Bartoli, G.;
Melchiorre, P. Angew. Chem., Int. Ed. 2007, 46, 6882.
7. (a) Nishiyama, Y.; Kawamatsu, H.; Funato, S.; Tokunaga, K.; Sonoda, N. J. Org.
Chem. 2003, 68, 3599; (b) Bao, W.; Zhang, Y. Synlett 1996, 1187; (c) Reich, J. H. J.
Org. Chem. 1974, 39, 428.
8. (a) Yamawaki, J.; Ando, T. Chem. Lett. 1979, 755; (b) Ando, T.; Clark, J. H.; Cork,
D. G. Tetrahedron Lett. 1987, 28, 1421.
was recovered in high purity. Selected data, (2a): IR (neat): 1707 cmÀ1 1H
;
NMR (300 MHz, CDCl3) d 1.09 (t, J = 7.4 Hz, 3H), 1.64–1.77 (m, 1H), 1.82–1.94
(m, 1H), 3.54 (dt, J = 7.4, 3.4 Hz, 1H), 7.27–7.33 (m, 3H), 7.51–7.59 (m, 2H), 9.43
(d, J = 3.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 12.6, 21.1, 54.7, 125.9, 128.8,
129.2, 135.9, 193.1; (2b): IR (neat): 1709 cmÀ1 1H NMR (300 MHz, CDCl3) d
;
0.95 (t, J = 7.3 Hz, 3H), 1.38–1.61 (m, 2H), 1.62–1.69 (m, 1H), 1.70–187 (m, 1H),
3.62 (dt, J = 7.4, 3.7 Hz, 1H), 7.23–7.38 (m, 3H), 7.48–7.55 (m, 2H), 9.39 (d,
J = 3.7 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 13.7, 21.2, 29.7, 52.6, 126.0, 128.8,
129.2, 135.8, 193.0; (2h): IR (neat): 1704 cmÀ1 1H NMR (300 MHz, CDCl3) d
;
3.02 (dd, J = 14.5, 6.6 Hz, 1H), 3.26 (dd, J = 14.5, 8.3 Hz, 1H), 3.91 (ddd, J = 8.3,
6.6, 3.0 Hz, 1H), 7.19–7.40 (m, 8H) 7.48–7.53 (m, 2H), 9.50 (d, J = 3.0 Hz, 1H);
13C NMR (75 MHz, CDCl3) d 34.1, 53.5, 125.8, 126.8, 128.6, 129.0, 129.3, 136.1,
138.3, 192.2; (2k): IR (neat): 1707 cmÀ1 1H NMR (300 MHz, CDCl3) d 2.32–2.35
;
(m, 1H), 2.39 (s, 3H), 2.43–2.56 (m, 1H), 2.88–3.00 (m, 2H), 3.09–3.20 (m, 1H),
3.22–3.36 (m, 1H), 3.74–3.81 (m, 1H), 7.22–7.33 (m, 3H), 7.51–7.58 (m, 2H);
13C NMR (75 MHz, CDCl3) d 37.6, 45.7, 50.1, 55.5, 61.7, 127.9, 129.2, 129.3,
134.0, 205.1; (2n): IR (neat): 1702 cmÀ1 1H NMR (300 MHz, CDCl3) d 1.09 (t,
;
J = 7.3 Hz, 3H), 1.49 (d, J = 7.0, 3H), 2.50 (dq, J = 17.3, 7.3 Hz, 1H), 2.79 (dq,
J = 17.3, 7.3, 1H), 3.82 (q, J = 7.0 Hz, 1H), 7.25–7.36 (m, 3H), 7.49–7.56 (m, 2H);
13C NMR (75 MHz, CDCl3) d 8.4, 16.5, 33.0, 45.1, 127.2, 128.7, 129.1, 135.8,
207.5; (2p): IR (neat): 1673 cmÀ1 1H NMR (300 MHz, CDCl3)
; d 1.67 (d,
9. (a) Hosseinzadeh, R.; Tajbakhsh, M.; Mohadjerani, M.; Mehdinejad, H. Synlett
2004, 1517; (b) Kawanami, Y.; Yuasa, H.; Toriyama, F.; Yoshida, S.; Baba, T.
Catal. Commun. 2003, 4, 455; (c) Kabalka, G. W.; Wang, L.; Pagni, R. M.; Hair, C.
J = 6.8 Hz, 3H), 4.71 (q, J = 6.8, 1H), 7.22–7.60 (m, 8H), 7.91 (d, J = 7.3, 2H); 13C
NMR (75 MHz, CDCl3) d 17.3, 39.8, 127.0, 128.4, 128.5, 128.9, 129.0, 132.8,
135.9, 136.6, 196.3.