Synthesis of α,β-unsaturated ketones and esters using polymer-supported selenium bromide

Article abstract of DOI:10.1002/jccs.200300042

Treatment of the polymer-supported α-phenylseleno ketones and esters prepared from polymer-supported selenium bromide with ketone and ester enolates with hydrogen peroxide afford α,β-unsaturated ketones and esters in good yields and high purities.

Full text of DOI:10.1002/jccs.200300042

Journal of the Chinese Chemical Society, 2003, 50, 279-281
279
Synthesis of a,b-Unsaturated Ketones and Esters Using
Polymer-supported Selenium Bromide
Shou-Ri Sheng* (
Department of Chemistry, Jiangxi Normal University, Nanchang, 330027, P. R. China
), Xiao-Ling Liu (
) and Xing-Cong Wang (
)
Treatment of the polymer-supported a-phenylseleno ketones and esters prepared from polymer-
supported selenium bromide with ketone and ester enolates with hydrogen peroxide afford a,b-unsaturated
ketones and esters in good yields and high purities.
Keywords: Solid-phase organic synthesis; Polymer-supported selenium bromide; a,b-Unsaturated ke-
tones and esters.
Polymer-supported reagents have attracted growing in-
terest because they have been able to provide attractive and
practical methods for combinatorial chemistry and solid-
produce the a,b-unsaturated ketones and esters in good yield
and high purity (Table 1). Simple work-up procedures replace
the time-consuming isolation and purification step in the cor-
responding solution-phase synthesis. The polymer-supported
phenylseleninic acid is obtained as a by-product, which is
1
phase synthesis in recent years. Organoselenium reagents
are routinely employed in many types of synthesis transfor-
2
6
mations. The syn elimination of selenoxides has been shown
separated by filtration and can be used as an oxidant.
to be a convenient, mild, and high-yield method for the prepa-
3
ration of a,b-unsaturated carbonyl compounds. The precur-
sor a-phenylselenocarbonyl compounds can be prepared
EXPERIMENTAL SECTION
3
from ketones, aldehydes, and esters, as well as from enol ac-
3
c,3d
3c
1
etates
and acetylenes. However, organic selenium re-
H NMR spectra were recorded on a Bruker Avance 400
agents always have a foul smell and are quite toxic, which is
often problematic in organic synthesis. Recently, selenium-
based approaches for solid-phase organic synthesis have
3
MHz spectrometer using CDCl as the solvent and with TMS
as internal standard; IR spectra were determined on a Bruker
Vector 22 spectrophotometer.
4
been reported from different research groups. We have pre-
viously described the formation of polymer-supported vinylic
selenides, as well as the preparation of carbonyl compounds
General Procedure for the Synthesis of a,b-Unsaturated
Ketones and Esters
5
on solid-phase. We report here the very simple preparation
To a stirring solution of 1.3 mmol LDA in 4 mL of THF
under nitrogen at -78 °C was added dropwise a solution of
1.35 mmol carbonyl compounds in 4 mL over 5 min. After
stirring for an additional 10 min, 1.0 g polymer-supported se-
of a,b-unsaturated ketones and esters using polymer-sup-
ported selenium bromide. The method is illustrated using
propiophenone in the Scheme I.
4
a
lenium bromide prepared by a method from the literature
elemental analysis Br, 1.18 mmol/g) was added rapidly. The
(
Scheme I
mixture was warmed to room tempeature over a 15 min pe-
riod and stirred for 30 min. After being acidified with glacial
acetic acid, the carbonyl compound resin was collected by fil-
O
o
Se
O
1
) LDA/THF, -78
SeBr
C
H2O2
2
)
O
tration and washed sucessively with H
2 2 2
O, THF and CH Cl (2
´
3 mL of each). The resin was then suspended in 10 mL of
The polymer-supported a-phenylseleno ketones and
esters are readily formed by treatment of the lithium enolate
of ketones and esters with polymer-supported selenium bro-
mide. Oxidation of the a-phenylseleno ketone and ester res-
ins which are evidenced by strong carbonyl absorptions in the
IR spectra with hydrogen peroxide at room temperature to
THF and treated with 1.0 mL (11.6 mmol) of 30% hydrogen
perioxide. The mixture was stirred for 30 min at room tem-
perature; the polymer-supported phenyl seleninic acid as a
by-product was collected by filtration and washed with ether.
The combined extracts were washed with water, dried over
magnesium sulfate and evaporated to give the final product.

2
80 J. Chin. Chem. Soc., Vol. 50, No. 2, 2003
Sheng et al.
Table 1. Conversion of Ketones and Esters to Their a,b-
2.1; 15.8 Hz, 1H), 6.75 (dq, J = 15.7; 6.8 Hz, 1H).
6-Methyl-2-cyclohexen-1-one3g
Unsaturated Analogs
a
b
Entry
Ph
Product
Yield (%)
Purity (%)
94
-
1
IR nmax (film): 1671 (s, C=O), 1630 (s, C=C) cm ;
H-NMR: d 1.12 (d, J = 6.7 Hz, 3H), 1.46-2.54 (m, 5H), 5.90
dt, J = 10; 2.1 Hz, 1H), 6.85 (dt m, J = 10; 4.1; 2.0 Hz, 1H).
O
O
1
9
2
Ph
(
O
E)-Ethyl cinnamate3a
O
(
c
-
1
8
2
94
92
IR nmax (film): 1705 (s, C=O), 1635 (s, C=C) cm ;
H-NMR: d 1.31 (t, J = 6.9 Hz, 3H), 4.15 (q, J = 6.8 Hz 2H),
1
O
O
6.32 (d, J = 15.8 Hz, 1H), 7.27-7.72 (m, 1H).
7
8
(
E)- and (Z)-Ethyl 2-phenyl-2-butenoates3g (55/45 mix-
ture)
-
1 1
IR nmax (film): 1710 (s, C=O), 1642 (s, C=C) cm ; H-
Ph
COOEt
Ph
c
COOEt
9
4
95
94
NMR: d 1.22, 1.26 (t, J = 7.0 Hz, 3H), 1.75, 2.01 (d, J = 7.2
Hz, 3H), 4.11, 4.20 (q, J = 7.0 Hz, 2H), 6.15, 7.05 (q, J = 7.2
Hz, 1H), 7.12-7.52 (m, 5H).
O
O
d
8
2
OEt
OEt
Ph
Methyl 1-cyclohexenecarboxylate3g
Ph
-
1
IR nmax (film): 1715 (s, C=O), 1625 (s, C=C) cm ;
H-NMR: d 1.45-1.85 (m, 4H), 2.01-2.40 (m, 4H), 3.68 (s,
1
COOMe
COOMe
9
5
94
90
93
3
H), 6.92 (m, 1H).
O
O
6
-Hydroxy-2-hexenoic acid e-lactone3g
O
O
7
8
4
5
-1 1
IR nmax (film): 1709 (s, C=O), 1640 (s, C=C) cm ; H-
NMR: d 1.78-2.28 (m, 2H), 2.31-2.70 (m, 2H), 4.18 (m, 2H),
O
O
O
O
5
.90 (dt, J = 12.6; 1.6 Hz, 1H), 6.23 (dt, J = 12.6; 4.3 Hz, 1H).
2
-Acetyl-2-cyclohexen-1-one3f
-
1
a
IR nmax (film): 1695 (s, C=O), 1605 (s, C=C) cm ;
Overall yields based on polymer-supported selenium bromide
1.18 mmol Br/g).
Purity determined by H NMR of crude cleavage product (400
1
H-NMR: d 1.92-2.22 (m, 2H), 2.36 (s, 3H), 2.31-2.72 (m,
4H), 7.59 (t, J = 4.31 Hz, 1H).
(
b
c
d
1
MHz).
The E Ketones and esters were the only products determined in
these eliminations.
The product (E/Z = 45/55) was determined by H NMR.
1
ACKNOWLEDGEMENTS
We are grateful for the financial support from the Natu-
ral Science Foundation of Jiangxi Province, P. R. China. We
are indebted to Prof. Xian Huang, Zhejiang University, P. R.
China for a valuable discussion.
1
-Phenyl-2-propen-1-one3g
IR nmax (film): 1670 (s, C=O), 1665 (s, C=C), 1597 (m,
-
1 1
Ar) cm ; H-NMR: d 5.80 (dd, J = 2.1; 10.5 Hz, 1H), 6.40
dd, J = 2.1; 17.4 Hz, 1H), 7.15 (dd, J = 10.5; 17.4 Hz, 1H),
.41-7.90 (m, 5H).
(
7
Received June 12, 2002.
(
E)-2-Hepten-4-one3g
-
1
IR nmax (film): 1680 (s, C=O), 1630 (s, C=C) cm ;
H-NMR: d 0.88 (t, J = 7.1 Hz, 3H), 1.50-1.58 (m, 2H), 1.88
dd, J = 2.1; 6.8 Hz, 3H), 2.45 (t, J = 7.1 Hz, 2H), 6.04 (dd, J =
REFERENCES
1
(
1. For recent reviews on SPOS, see: (a) Brown, R. C. D. J.

Synthesis of a,b-Unsaturated Ketones and Esters
J. Chin. Chem. Soc., Vol. 50, No. 2, 2003 281
Chem. Soc., Perkin Trans.I 1998, 3293-3320. (b) Fruchtel, J.
S.; Jung, G. Angew. Chem. Int. Ed. 1996, 35, 17-42. (c)
Lorsbach, B. A.; Kurth, M. J. Chem. Rev. 1999, 99, 1549-
Chem. Commun. 1998, 1947-1948. (b) Ruhland, T.;
Andersen, K.; Pedersen, H. J. Org. Chem. 1998, 63,
9204-9211. (c) Yanda, K.; Fujita, T.; Yanada, R. Synlett
1998, 971-972. (d) Fujita, K.; Watanabe, K.; Oishi, A.;
Ikeda, Y.; Taguchi, Y. Synlett 1999, 1760-1762. (e)
Nicolaou, K. C.; Pfefferkorn, J. A.; Cao, G.-Q.;. Kim, S.;
Kessabi, J. Org. Lett. 1999, 1, 807-810. (f) Nicolaou, K. C.;
Pfefferkorn, J. A.; Cao, G.-Q. Angew. Chem. Int. Ed. 2000,
39, 734-739. (g) Nicolaou, K. C.; Cao, G.-Q.; Pfefferkorn, J.
A. Angew. Chem. Int. Ed. 2000, 39, 739-743. (h) Nicolaou,
K. C.; Winssinger, N.; Hughes, R.; Smethurst, C.; Cho, S. Y.
Angew. Chem. Int. Ed. 2000, 39, 1084-1088. (i) Nicolaou, K.
C.; Mitchell, H. J.; Fylaktakidou, K. C.; Suzuki, H.; Rodri-
guez, R. M. Angew. Chem. Int. Ed. 2000, 39, 1089-1093. (j)
Nicolaou, K. C.; Roecker, A. J.; Pfefferkorn, J. A.; Cao,
G.-Q. J. Am. Chem. Soc. 2000, 122, 2966-2967. (k) Fujita,
K.; Taka, H.; Oishi, A.; Ikeda, Y.; Taguchi, Y.; Fujie, K.;
Saeki, T.; Sakuma, M. Synlett 2000, 1509-1151. (l) Uehlin,
L.; Wirth, T. Chimia 2001, 55, 65-67.(m) Uehlin, L.; Wirth,
T. Org. Lett. 2001, 3, 2931-2933.
1
2
581. (d) Guillier, F.; Orain, D.; Bradley, M. Chem. Rev.
000, 100, 2091-2157. (e) Hermkens, P. H. H.; Ottenhijm, H.
C. J.; Rees, D. C. Tetrahedron 1997, 53, 5643-5678.
. (a) Liotta, D. (Ed). Organoselenium Chemistry; Wiley: New
York, 1987. (b) Paulmier, C. (Ed). Selenium Reagents and
Intermediates in Organic Synthesis; Pergamon Press: Ox-
ford, 1986. (c) Back, T. G. In The Chemistry of Organic Sele-
nium and Tellurium Compounds; Patai, S. (Ed). Wiley:
Chichester, 1987, pp 91-120. (d) Nicolaou, K. C.; Petasis, N.
A. Selenium in Natural Product Synthesis; CIS: Philadel-
phia, 1984.
. (a) Sharpless, K, B.; Lauer, R. F.; Teranishi, A. Y. J. Am.
Chem. Soc. 1973, 95, 6137-6139. (b) Reich, H. J.; Reich, I.
L.; Renga, J. M. J. Am. Chem. Soc. 1973, 95, 5813-5815. (c)
Reich, H. J. J. Org. Chem. 1974, 39, 428-429. (d) Clive, D.
L. J. Chem. Commun. 1973, 695-696. (e) Grieco, P. A.
Miyashita, M. J. Org. Chem. 1974, 39, 120-122. (f) Reich,
H. J.; Renga, J. M.; Reich, I. L. J. Org. Chem. 1974, 39,
2
3
5. Huang, X.; Sheng, S.-R. Tetrahedron Lett. 2001, 42,
9035-9037.
2
133-2135. (g) Reich, H. J.; Renga, J. M.; Reich, I. L. J. Am.
Chem. Soc. 1975, 97, 5434-5447.
. (a) Nicolaou, K. C.; Pastor, J.; Barluenga, S.; Winssinger, N.
6. Taylor, R. T.; Flood, L. A. J. Org. Chem. 1983, 48,
5160-5164.
4