A novel synthetic method for β-keto esters

Article abstract of DOI:10.3184/030823407X198311

A novel synthetic method for the preparation of β-keto esters has been developed. α-Phenylseleno acetate was treated with LDA to produce a selenium-stabilised carbanion, which reacted with aldehydes, followed by selenoxide syn-elimination, to give β-keto esters.

Full text of DOI:10.3184/030823407X198311

160 RESEARCH PAPER
MARCH, 160–161
JOURNAL OF CHEMICAL RESEARCH 2007
A novel synthetic method for b-keto esters
Hao Qiana*, Chunrong Gea and Xian Huanga,b
aDepartment of Chemistry, 521 Mail Box, Hangzhou Normal University, Hangzhou 310036, P. R. China
bDepartment of Chemistry, Zhejiang University, Hangzhou 310028, P. R. China
A novel synthetic method for the preparation of b-keto esters has been developed. a-Phenylseleno acetate was
treated with LDA to produce a selenium-stabilised carbanion, which reacted with aldehydes, followed by selenoxide
syn-elimination, to give b-keto esters.
Keywords: a-phenylseleno acetate, selenoxide syn-elimination, b-keto esters, aldehydes
b-Keto esters are an important class of 1,3-dicarbonyl compounds
and have a long history of use in synthesis. Many methods
have been developed for the preparation of b-keto esters.1
Over the past 30 years, organoselenium reagents have been
increasingly utilised in highly selective organic reactions.2
Selenium-stabilised carbanions have played an important role
in organic synthesis because of their easy availability and
because they are particularly good nucleophiles, allowing the
formation of new carbon–carbon bonds when they react with
compounds bearing an electrophilic carbon atom.3,4
Our research group has been interested in the application
of organoselenium reagents in the organic synthesis.5
We have found that b-hydroxyselenides, the addition products
of a-phenylseleno acetate and aldehydes, can be conveniently
converted into b-keto esters by selenoxide syn-elimination
(Scheme 1).
Table 1 Synthesis of b-keto ester
Compound
R
Yield/%a
93
3a
3b
3c
80
90
O
O2N
H3CO
H3C
Cl
3d
3e
83
94
3f
89
Cl
The a-selenocarbanion readily obtained according to
Sharpless (LDA, THF, –78°C) react at this temperature with
aldehydes producing b-hydroxyselenides 2 in high yield.7
The b-hydroxyselenides 2 may be converted to b-keto
esters 3 by oxidation with hydrogen peroxide in good yield.
The results are shown in Table 1.
Cl
3g
87
3h
3i
PhCH2-
(CH3)2CHCH2-
aYields are of pure isolated products.
82
71
In summary, we have developed a novel synthetic method for
the conversion of aldehydes to b-keto esters. The b-hydroxy-
selenides, the addition products of a-phenylseleno acetate and
aldehydes, may be conveniently converted in good yield to b-
keto ester by reaction with hydrogen peroxide.
2a: Yield 84%; oil.7 IR n (cm-1): 3420, 3030, 2979, 1727, 1578, 1257.
1H NMR d (ppm): 1.18(t, J = 7.1 Hz, 3H), 3.49(d, J = 7.8 Hz, 1H),
3.50(s, 1H), 4.10(q, J = 7.1 Hz, 2H), 4.62(d, J = 7.8 Hz, 1H), 7.18–7.65
(m, 10H). MS (m/z): 350(M+), 323, 304, 193, 166, 106, 91, 77.
2b: Yield 70%; oil. IR n (cm-1): 3410, 3130, 2984, 1732, 1571,
1
1247. H NMR d (ppm): 1.24(t, J = 7.1 Hz, 3H), 3.59(m, 2H), 4.16
(q, J = 7.0 Hz, 2H), 5.23(d, J = 5.8 Hz, 1H), 6.58(d, d, J = 3.6, 1.02
Hz, 1H), 7.24(d, J = 3.7 Hz, 1H), 7.60(d, J = 0.9 Hz, 1H). MS (m/z):
341(M+), 314, 295, 183, 110, 97, 67. Anal. Calcd. for C15H16O4Se:
C 53.11, H 4.75. Found: C 53.20, H 4.71%.
Experimental
1H NMR spectra were recorded on a Bruker Avance 400 spectrometer
in CDCl3 with TMS as the internal standard. IR spectra were recorded
on a Bruker Tenson 27 spectrometer. EIMS were run on a HP 5989B
mass spectrometer. Microanalysis was carried out on a Carlo Erba
1106. THF for preparation of b-hydroxyselenides was purified by the
standard method6 before use.
2c:Yield 81%; oil. IR n (cm-1): 3410, 3030, 2982, 1717, 1616, 1531,
1
1351, 1186. H NMR d (ppm): 1.08(t, J = 7.1 Hz, 3H), 3.50(s, 1H),
3.61(d J = 8.0 Hz, 1H), 4.06(q, J = 7.1 Hz, 2H), 4.88(d, J = 8.1 Hz,
1H), 7.20–7.39 (m, 5H), 7.71(d, J = 8.9 Hz, 2H), 8.18(d J = 9.0 Hz,
2H). MS (m/z): 395(M+), 368, 349, 238, 211, 152, 120, 76. Anal.
Calcd. for C17H17NO5Se: C 51.79, H 4.35, N 3.55. Found: C 51.88,
H 4.29, N 3.60%.
Typical procedure for the preparation of b-hydroxyselenides 2a–i
b-Hydroxyselenides
2 were prepared according to literature
procedure.7 Under an N2 atmosphere, LDA (2 mmol) is rapidly added
at –78°C to a a-phenylseleno acetate (2 mmol) solution in THF
(20 ml). After 2 h benzaldehydes (2 mmol) is added and the resulting
solution stirred for 1 h at –78°C and rise to room temperature
about 1 h. Usual work up and purification on preparative layer
chromatography on silica gel to afford 2a (84%).
2d: Yield 75%; oil. IR n (cm-1): 3421, 3030, 2988, 1714, 1587,
1257, 1197. 1H NMR d (ppm): 1.16(t, J = 7.1 Hz, 3H), 3.49(m, 2H),
3.77(s, 3H), 4.1(q, J = 7.1 Hz, 2H), 4.54(d, J = 7.8 Hz, 1H), 7.19–
7.34 (m, 5H), 7.58(d J = 8.8 Hz, 2H), 7.72(d, J = 8.8 Hz, 2H). MS
(m/z): 380(M+), 365, 353, 322, 223,196, 137, 122, 71. Anal. Calcd.
for C18H20O4Se: C 57.00, H 5.31. Found: C 56.87, H 5.24%.
OH
1. LDA, –78°C
PhSeCH2COOEt
O
H2O2
COOEt
COOEt
R
2. RCHO
R
SePh
1
2
3
Scheme 1
* Correspondent. E-mail: qianhao@mail.hz.zj.cn
PAPER: 06/4509

JOURNAL OF CHEMICAL RESEARCH 2007 161
2e: Yield 86%; oil. IR n (cm-1): 3414, 3030, 2984, 1724, 1589,
1236. 1H NMR d (ppm): 1.18(t, J = 7.2 Hz, 3H), 2.41(s, 3H), 3.49(m,
2H), 4.06(q, J = 7.1 Hz, 2H), 4.57(d, J = 7.8 Hz, 1H), 7.27(m, 5H),
7.57(d, J = 8.1 Hz, 2H), 7.75(d, J = 8.1 Hz, 2H). MS (m/z): 364(M+),
337, 318, 207, 180, 121, 97, 77. Anal. Calcd. for C18H20O3Se:
C 59.51, H 5.55. Found: C 59.45, H 5.51%.
3d: Yield 83%; oil.1b IR n (cm-1): 2981, 1739, 1679, 1602, 1576,
1
1368, 1174. H NMR d (ppm): 1.25(t, J = 7.2 Hz, 3H), 3.87(s, 3H),
3.94(s, 3H), 4.20(q, J = 7.2 Hz, 2H), 6.94(d, J = 8.8 Hz, 2H), 7.92
(d, J = 8.8 Hz, 2H). MS (m/z): 222(M+), 176, 150, 135, 119, 105, 91,
77, 57.
3e: Yield 94%; oil. 1b IR n (cm-1): 3054, 2983, 1743, 1685, 1609,
1572, 1367, 1187. 1H NMR d (ppm): 1.26(t, J = 7.1 Hz, 3H), 2.42(s,
3H), 3.97(s, 2H), 4.20(q, J = 7.1 Hz, 2H), 7.28(d, J = 8.0 Hz, 2H),
7.84(d, J = 8.1 Hz, 2H). MS (m/z): 206(M+), 160, 134, 120, 119, 91,
77, 65.
2f: Yield 83%; oil. IR n (cm-1): 3401, 3030, 2982, 1714, 1582,
1351, 1186. 1H NMR d (ppm): 1.19(t, J = 7.1 Hz, 3H), 3.50(m, 2H),
4.12(q, J = 7.2 Hz, 2H), 4.74(d, J = 7.9 Hz, 1H), 7.19–7.34(m, 7H),
7.58(d J = 8.1 Hz, 2H). MS (m/z): 384(M+), 338, 303, 227, 142, 111,
75. Anal. Calcd. for C17H17ClO3Se: C 53.21, H 4.47. Found: C 53.34,
H 4.46%.
3f: Yield 89%; oil. 1b IR n (cm-1): 2983, 1742, 1689, 1623, 1589,
1570, 1490, 1198. 1H NMR d (ppm): 1.26(t, J = 7.1 Hz, 3H),
3.96(2H), 4.21(q, J = 7.2 Hz, 2H), 7.46(d, J = 8.7 Hz, 2H), 7.89(d,
J = 8.7 Hz, 2H). MS (m/z): 226(M+), 180, 154, 141, 139, 111, 75.
3g: Yield 87%; oil. IR n (cm-1): 3092, 2983, 1744, 1701, 1629,
2g: Yield 76%; oil. IR n (cm-1): 3424, 3037, 2983, 1729, 1589,
1569, 1197. 1H NMR d (ppm): 1.22(t, J = 7.2 Hz, 3H), 3.49(m, 2H),
4.1(q, J = 7.1 Hz, 2H), 5.78(d, J = 8.1 Hz, 1H), 7.29–7.82(m, 8H).
MS (m/z): 419(M+), 383, 355, 261, 189, 175, 145, 139, 109, 75.
Anal. Calcd. for C17H16Cl2O3Se: C 48.83, H 3.86. Found: C 48.75,
H 3.82%.
1
1584, 1473, 1374, 1197. H NMR d (ppm): 1.25(t, J = 7.1 Hz, 3H),
4.03(s, 2H), 4.19(q, J = 7.1 Hz, 2H), 7.32(m, 1H), 7.60(d, 1H),
7.45(s, 1H). MS (m/z): 260(M+), 227, 225, 197, 175, 173, 145, 109,
75. Anal. Calcd. for C11H10Cl2O3: C 50.60, H 3.86. Found: C 50.47,
H 3.80%.
2h: Yield 73%; oil. IR n (cm-1): 3406, 3030, 2957, 1723, 1584,
1272. 1H NMR d (ppm): 1.25(t, J = 7.2 Hz, 3H), 2.27(d, J = 6.4 Hz,
2H), 3.50(m, 1H), 3.60(s, 1H), 4.18(q, J = 7.2 Hz, 2H), 4.54
(d, J = 7.6 Hz, 1H), 7.15–7.79(m, 10H). MS (m/z): 364(M+), 337,
318, 207, 180, 121, 97, 77. Anal. Calcd. for C18H20O3Se: C 59.51,
H 5.55. Found: C 59.42, H 5.51%.
3h: Yield 82%; oil. 1c IR n (cm-1): 3063, 2927, 1743, 1718, 1656,
1584, 1495, 1454, 1367, 1171. 1H NMR d (ppm): 1.26(t, J = 7.1 Hz,
3H), 3.38(s, 2H), 3.78(s, 2H), 4.20(q, J = 7.1 Hz, 2H), 7.21(m, 3H),
7.48(d, J = 7.2 Hz, 2H). MS (m/z): 206(M+), 160, 134, 119, 91, 77.
3i: Yield 71%; oil. 1b IR n (cm-1): 2962, 1775, 1732, 1629, 1467,
1370, 1183. 1H NMR d (ppm): 0.98(d, 6H), 1.28(t, J = 7.2 Hz, 3H),
1.46(m, 1H), 2.50(d, 2H), 3.50(s, 2H), 4.25(q, J = 7.1 Hz, 2H).
MS (m/z): 172(M+), 126, 100, 85, 57, 43.
2i: Yield 71%; oil. IR n (cm-1): 3412, 2961, 2873, 1731, 1467,
1370, 1182. 1H NMR d (ppm): 0.92(d, J = 6.0 Hz, 6H), 1.07
(t, J = 7.2 Hz, 3H), 1.80(m, 1H), 2.38(m, 2H), 3.51(m, 2H), 4.10
(m, 3H), 7.19(m, 3H), 7.37(m, 2H). MS (m/z): 330(M+), 303, 284,
173, 146, 131, 73. Anal. Calcd. for C15H22O3Se: C 54.71, H 6.73.
Found: C 54.66, H 6.67%.
This work was supported by the Science Foundation of
Hangzhou Normal College (No.131901, No. 131001).
General procedure for the preparation of b-keto esters 3a–i
30% H2O2 (2 ml) was added to b-Hydroxyselenides 2 (1 mmol) in
THF (20 ml). The mixture was stirred for 1 h at room temperature and
2 h at 50°C. Upon completion of the reaction (monitored by tlc), the
mixture was added to CHCl3 (30 ml) and washed with H2O (20 ml ¥ 2).
The mixture was purified by preparative layer chromatography on
silica gel to afford the b-keto esters 3.
Received 26 February 2007; accepted 10 March 2007
Paper 07/4509
doi: 10.3184/030823407X198311
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5
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1
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PAPER: 06/4509