A convenient synthesis of substituted 3-alkoxycarbonyl-β,γ-unsaturated esters with predominant Z-selectivity

Article abstract of DOI:10.1002/hc.10142

The synthesis of substitued 3-alkoxycarbonyl-3β,γ-unsaturated esters with predominant Z-selectivity was discussed. The Z- and E-isomer were separated by column chromatography. The chemical shift of vinyl proton was assigned in the range of δ = 7.82-7.91 as E-isomer, while that in the range of δ = 6.73-6.89 as Z-isomer. The IR spectra of liquid products were determined as films on a Digilab FTS-20E spectrometer.

Full text of DOI:10.1002/hc.10142

Heteroatom Chemistry
Volume 14, Number 3, 2003
A Convenient Synthesis of Substituted
3-Alkoxycarbonyl-β,γ-unsaturated Esters
with Predominant Z-Selectivity
Yanchang Shen and Yuming Zhang
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, People’s Republic of China
Received 31 October 2002
[3]. Among them, the methods of Still [3a] and
ABSTRACT:
The
consecutive
reaction
with sodium
of
Ando [3c–f] have been shown to be the most
versatile and selective. The former used methyl
[bis(trifluoroethyl)phosphono]acetate in the HWE
reaction, while the latter employed ethyl (diarylphos-
phono)acetates as reagents.
bis[2,2,2-trifluoroethyl]phosphite
hydride, dimethyl maleate, and aldehydes gives
3-alkoxycarbonyl-β,γ-unsaturated esters with pre-
dominant Z-selectivity in 62–94% yields (Z/E =
85–60:15–40). The Z- and E-isomer can be sep-
arated conveniently by column chromatography.
ꢀ
C
2003 Wiley Periodicals, Inc. Heteroatom Chem
RESULTS AND DISCUSSION
14:276–279, 2003; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.10142
In recent years, 3-alkoxycarbonyl-ꢀ,ꢁ-unsaturated
esters have attracted much interest because they
are useful intermediates for the synthesis of substi-
tuted tetrahydrofurans, which are essential compo-
nents in a variety of naturally occurring bioactive
compounds [4]. As part of our continuing investi-
gation of synthetic application of consecutive reac-
tion of phosphorus compounds in organic synthe-
sis [5], herein we report a convenient synthesis of
substituted 3-alkoxycarbonyl-ꢀ,ꢁ-unsaturated esters
with predominant Z-selectivity by using bis[2,2,2-
trifluoroethyl]phosphite as a starting material via se-
quential transformations. The reaction sequence is
shown in Scheme 1.
Bis[2,2,2-trifluoroethyl]phosphite (1) was trea-
ted with sodium hydride in tetrahydrofuran (THF)
at 25◦C and the resulting carbanion 2 reacted with
dimethyl maleate 3 to form the intermediate 4,
which was further reacted with aldehydes, followed
by elimination of phosphonate anion, giving sub-
stituted 3-alkoxycarbonyl-ꢀ,ꢁ-unsaturated esters (6)
with predominant Z-selectivity in 62–94% yields
(Z/E = 85–60:15–40). The Z- and E-isomer can be
INTRODUCTION
In the past few decades the use of the Horner–
Wadsworth–Emmons (HWE) reaction in organic
synthesis has increased significantly [1] and it was
employed in a variety of versatile synthetic routes,
enabling the synthesis of many functionalized com-
pounds, particularly of naturally occurring prod-
ucts [2]. However, the usual HWE reagents with
alkylphosphono groups produce thermodynamically
favored E-olefins [le]. For the purpose of prepar-
ing Z-olefins, several attempts have been made
by changing of reaction conditions or phospho-
nate reagents, but the success was still limited
Correspondence to: Yanchang Shen; e-mail: shenyc@pub.sioc.
ac.cn.
Contract grant sponsor: National Natural Science Foundation
of China.
Contract grant sponsor: Chinese Academy of Sciences.
2003 Wiley Periodicals, Inc.
c
ꢀ
276

A Convenient Synthesis of Substituted 3-Alkoxycarbonyl-ꢀ,ꢁ-unsaturated Esters with Predominant Z-Selectivity 277
Bis(2,2,2-trifluoroethyl)phosphite (1) was pre-
pared according to the known method [7].
General Procedure for the Synthesis
of 3-Alkoxy-ꢀ,ꢁ-unsaturated Esters (6)
Bis(2,2,2-trifluoroethyl)phosphite (2.5 mmol) was
added slowly with stirring to a suspension of
sodium hydride [NaH, 0.1 g (60%), 2.5 mmol] in
THF (20 ml) at 20◦C under nitrogen. The reac-
tion mixture was stirred for 0.5 h at 20◦C and
dimethyl maleate (0.34 g, 2.5 mmol) was slowly
added. The mixture was further stirred for 0.5 h
and the aldehyde (2 mmol) was added. After addi-
tion, the mixture was stirred further for 3 h and
HCl solution (2 M, 30 ml) was added. The reac-
tion mixture was extracted with ethyl acetate (3 ×
20 ml). The combined organic layer was washed
with brine (20 ml) and dried over anhydrous Na2SO4.
Evaporation of the solvent gave a residue, which was
purified by flash chromatography on silica gel, elut-
ing with light petroleum ether (bp 60–90◦C)/ethyl ac-
etate (10:1) to give the product 6. The component
in front was identified as E-isomer (minor product),
while the one behind was the Z-isomer (major prod-
uct). In the cases of 6e and 6f, the reverse is true.
SCHEME 1
separated conveniently by column chromatography.
The results are summarized in Table 1.
The chemical shift of vinyl proton in E-isomer
of substituted 3-alkoxycarbonyl-ꢀ,ꢁ-unsaturated es-
ters has been reported in the range of δ = 7.83–8.00
ppm [6]. Thus, we assigned the chemical shift of vinyl
proton in the range of δ = 7.82–7.91 as E-isomer,
while that in the range of δ = 6.73–6.89 as Z-isomer.
For the further confirmation of the configuration of
the products we performed the NOESY spectrum of
the major product of 6b. It showed that the vinyl
proton is cis with respect to the CH2CO2Me group
(Z-isomer).
Z-Methyl 4-(4-Dimethylaminophenyl)-3-methoxy-
carbonylbut-3-enoate (Z-6a). Yield: 77%; oil. IR
(neat): ν = 2950, 1740, 1710, 1610, 1530, 1440, 1360,
1
1220, 1190, 1170, 810 cm−1. H NMR (CDCl3/TMS):
δ = 7.32 (d, J = 8.2 Hz, 2H), 6.73 (s, 1H), 6.62
(d, J = 8.2 Hz, 2H), 3.71 (s, 3H), 3.69 (s, 3H), 3.42
(s, 2H), 2.96 (s, 6H). MS: m/z (%) = 278 (M+ + 1, 20),
277 (M+, 100), 218 (56), 159 (32), 158 (94). Anal. Calc.
for C15H19NO4 (277.32): C, 64.97; H, 6.91; N, 5.05.
Found: C, 64.74; H, 6.90; N, 4.83.
EXPERIMENTAL
All boiling points are uncorrected. The IR spectra of
liquid products were determined as films on a Dig-
ilab FTS-20E spectrometer. H NMR spectra were
recorded on a Bruker AM-300 (300 MHz) spectrom-
eter (values in ppm from SiMe4, in CDCl3; J values
are given in Hz). Mass spectra were measured on a
Finnigan GC-MS-4021 mass spectrometer.
1
E-Methyl 4-(4-Dimethylaminophenyl)-3-methoxy-
carbonylbut-3-enoate (E-6a). Yield: 13%; oil. IR
(neat): ν = 2960, 1740, 1720, 1700, 1610, 1530,
1
1440, 1240, 1200, 1170, 1080, 810 cm−1. H NMR
(CDCl3/TMS): δ = 7.82 (s, 1H), 7.31 (d, J = 8.9 Hz,
2H), 6.69 (d, J = 8.9 Hz, 2H), 3.80 (s, 3H), 3.74 (s,
3H), 3.63 (S, 2H), 3.00 (s, 6H). MS: m/z (%) = 278
(M+ + 1, 17), 277 (M+, 93), 218 (56), 159 (35), 158
(100). Anal. Calc. for C15H19NO4 (277.32): C, 64.97;
H, 6.91; N, 5.05. Found: C, 64.62; H, 7.00; N, 5.00.
TABLE
1 Substituted 3-Alkoxycarbonyl-β,γ-unsaturated
Esters Prepared
R
Yield (%)a
Ratio ( Z/E)b
6a
6b
6c
6d
6e
6f
4-(CH3)2NC6H4
4-CH3C6H4
4-ClC6H4
90
94
76
80
93
86
62
85:15
82:18
81:19
78:22
71:29
68:32
60:40
Z-Methyl 4-(4-Methylphenyl)-3-Methoxycarbonyl-
but-3-enoate (Z-6b). Yield: 77%; bp 120◦C/0.5
mm Hg. IR (neat): ν = 2950, 1740, 1710, 1440,
1240, 1210, 1170, 1130 cm−1. 1H NMR (CDCl3/TMS):
δ = 7.19 (d, J = 8.2 Hz, 2H), 7.11 (d, J = 8.2 Hz,
2H), 6.83 (s, 1H), 3.70 (s, 3H), 3.66 (s, 3H), 3.46
C H5
E-CH36CH CH
E-C6H4CH CH
2,4-Cl2C6H3
6g
aIsolated yields.
bIsolated ratios.

278 Shen and Zhang
(d, J = 0.7 Hz, 2H), 2.33 (s, 3H). MS: m/z (%) = 248
(M+, 49), 216 (45), 188 (30), 129 (100), 115 (28), 59
(18). Anal. Calc. for C14H16O4 (248.27): C, 67.73; H,
6.50. Found: C, 67.62; H, 6.50.
NMR (CDCl3/TMS): δ = 7.14 (ddq, J = 14.9, 11.1,
1.5 Hz, 1H), 6.42 (d, J = 11.1 Hz, 1H), 5.90–6.10 (m,
1H), 3.71 (s, 3H), 3.64 (s, 3H), 3.24 (s, 2H), 1.82 (dd,
J = 6.9, 1.5 Hz, 3H). MS: m/z (%) = 199 (M+ + 1,
19), 198 (M+, 55), 183 (23), 167 (100), 139 (18), 79
(15). Anal. Calc. for C10H14O4 (198.21): C, 60.59; H,
7.12. Found: C, 60.44; H, 7.17.
E-Methyl 4-(4-Methylphenyl)-3-methoxycarbonyl-
but-3-enoate (E-6b) [8]. Yield: 17%; oil. IR (neat):
ν = 3030, 2950, 1740, 1710, 1640, 1610, 1510, 1440,
1270, 1200, 1170, 1000 cm−1. 1H NMR (CDCl3/TMS):
δ = 7.87 (s, 1H), 7.25 (d, J = 8.3 Hz, 2H), 7.19 (d,
J = 8.3 Hz, 2H), 3.82 (s, 3H), 3.72 (s, 3H), 3.56 (s,
2H), 2.36 (s, 3H). MS: m/z (%) = 248 (M+, 70), 216
(46), 216 (50), 129 (100), 115 (28), 59 (16).
E-Methyl 3-Methoxycarbonylhepta-3,5-dienoate
(E-6e). Yield: 26%; oil. IR (neat): ν = 2960, 1740,
1710, 1650, 1440, 1300, 1250, 1200, 1170, 1090, 780
1
cm−1. H NMR (CDCl3/TMS): δ = 7.30 (d, J = 10.5
Hz, 1H), 7.10–7.35 (m, 2H), 3.73 (s, 3H), 3.67 (s,
3H), 3.41 (s, 2H), 1.86 (d, J = 6.2 Hz, 3H). MS: m/z
(%) = 199 (M+ + 1, 24), 198 (M+, 46), 183 (21), 167
(100), 139 (16). Anal. Calc. for C10H14O4 (198.21): C,
60.59; H, 7.12. Found: C, 60.29; H, 7.26.
Z-Methyl 4-(4-Chlorophenyl)-3-methoxycarbonyl-
but-3-enoate (Z-6c). Yield: 58%; bp 128◦C/0.5 mm
Hg. IR (neat): ν = 2950, 1740, 1720, 1590, 1490,
1440, 1240, 1210, 1170, 1020 cm−1. 1H NMR
(CDCl3/TMS): δ = 7.28 (d, J = 8.6 Hz, 2H), 7.21 (d,
J = 8.6 Hz, 2H), 6.81 (s, 1H), 3.70 (s, 3H), 3.64
(s, 3H), 3.45 (s, 2H). MS: m/z (%) = 270 (M+ + 2, 25),
268 (M+, 70), 236 (81), 151 (49), 149 (91), 130
(38), 115 (100), 59 (57). Anal. Calc. for C13H13ClO4
(268.69): C, 58.11; H, 4.88. Found: C, 58.10; H, 4.94.
Z-Methyl 5-Phenyl-3-methoxycarbonylhexa-3,5-
dienoate (Z-6f). Yield: 58%; oil. IR (neat): ν = 3020,
1740, 1700, 1630, 1440, 1290, 1210, 980, 800, 750,
690 cm−1. 1H NMR (CDCl3/TMS): δ = 7.97 (dd,
J = 15.6, 11.2 Hz, 1H), 7.45–7.60 (m, 2H), 7.20–7.45
(m, 3H), 6.78 (d, J = 15.6 Hz, 1H), 6.66 (d, J = 11.2
Hz, 1H), 3.79 (s, 3H), 3.69 (s, 3H), 3.37 (s, 2H).
MS: m/z (%) = 260 (M+, 30), 200 (36), 187 (10),
169 (30), 155 (14), 141 (100), 115 (26). Anal. Calc.
for C15H16O4 (260.28): C, 69.22; H, 6.20. Found: C,
69.26; H, 5.97.
E-Methyl 4-(4-Chlorophenyl)-3-methoxycarbonyl-
but-3-enoate (E-6c) [8]. Yield: 15%; oil. IR (neat):
ν = 3000, 2950, 1740, 1720, 1640, 1590, 1490, 1440,
1
1330, 1280, 1200, 1170, 1090, 1010 cm−1. H NMR
(CDCl3/TMS): δ = 7.84 (s, 1H), 7.36 (d, J = 8.4 Hz,
2H), 7.27 (d, J = 8.4 Hz, 2H), 3.82 (s, 3H), 3.73 (s,
3H), 3.50 (s, 2H). MS: m/z (%) = 270 (M+ + 2, 35),
268 (M+, 97), 237 (62), 236 (91), 208 (62), 151 (46),
149 (95), 130 (37), 115 (100), 59 (46).
E-Methyl 5-Phenyl-3-methoxycarbonylhexa-3,5-
dienoate (E-6f). Yield: 28%; oil. IR (neat): ν = 2950,
1740, 1710, 1630, 1440, 1290, 1240, 1200, 1170,
1080, 980, 750 cm−1. 1H NMR (CDCl3/TMS): δ =
7.45–7.65 (m, 3H), 7.25–7.45 (m, 3H), 6.90–7.00 (m,
2H), 3.80 (s, 3H), 3.71 (s, 3H), 3.57 (s, 2H). MS: m/z
(%) = 260 (M+, 31), 200(39), 169(30), 141(100), 115
(26). Anal. Calc. for C15H16O4 (260.28): C, 69.22; H,
6.20: Found: C, 69.41; H, 6.26.
Z-Methyl 4-(Phenyl)-3-methoxycarbonylbut-3-en-
oate (Z-6d) [9]. Yield: 62%; oil. IR (neat): ν = 3030,
2950, 1740, 1720, 1440, 1245, 1210, 1170, 1130, 700
cm−1. 1H NMR (CDCl3/TMS): δ = 7.25–7.50 (m, 5H),
6.87 (s, 1H), 3.70 (s, 3H), 3.63 (s, 3H), 3.47 (s, 2H).
MS: m/z (%) = 234 (M+, 76), 203 (63), 202 (64), 174
(24), 116 (39), 115 (100), 91 (19).
Z-Methyl4-(2,4-Dichlorophenyl)-3-methoxycarbo-
nylbut-3-enoate (Z-6g). Yield: 37%; oil. IR (neat):
ν = 2950, 1740, 1720, 1590, 1470, 1440, 1220, 1180
cm−1. 1H NMR (CDCl3/TMS): δ = 7.38 (s, 1H), 7.10–
7.30 (m, 2H), 6.89 (s, 1H), 3.69 (s, 3H), 3.59 (s, 3H),
3.49 (s, 2H). MS: m/z (%) = 302 (M+, 3), 269 (36), 267
(100), 149 (12). Anal. Calc. for C13H12Cl2O4 (303.14):
C, 51.50; H, 3.99. Found: C, 51.48; H, 3.61.
E-Methyl 4-(Phenyl)-3-methoxycarbonylbut-3-en-
oate (E-6d) [8]. Yield: 18%; oil. IR (neat): ν = 3060,
2950, 1740, 1710, 1640, 1490, 1450, 1440, 1330, 1270,
1220, 1200, 1170, 1100 cm−1. 1H NMR (CDCl3/TMS):
δ = 7.91 (s, 1H), 7.26–7.40 (m, 5H), 3.84 (s, 3H), 3.74
(s, 3H), 3.55 (s, 2H). MS: m/z (%) = 234 (M+, 49), 203
(41), 202 (57), 174 (28), 116 (39), 115 (100), 91 (19),
59 (15).
E-Methyl 4-(2,4-Dichlorophenyl)-3-methoxycarbo-
nylbut-3-enoate (E-6g) [10]. Yield: 25%; oil. IR
(neat): ν = 3090, 2960, 1740, 1720, 1590, 1470, 1440,
1290, 1210, 1180, 1100 cm−1. 1H NMR (CDCl3/TMS):
δ = 7.83 (s, 1H), 7.40 (d, J = 1.7 Hz, 1H), 7.15–7.25
Z-Methyl 3-Methoxycarbonylhepta-3,5-dienoate
(Z-6e). Yield: 67%; oil. IR (neat): ν = 2950, 1740,
1
1720, 1640, 1440, 1230, 1200, 1180, 980 cm−1. H

A Convenient Synthesis of Substituted 3-Alkoxycarbonyl-ꢀ,ꢁ-unsaturated Esters with Predominant Z-Selectivity 279
P.-O.; Tanner, D. J Am Chem Soc 2001, 123, 9738; (j)
Hillier, M. C.; Price, A. T.; Meyers, A. I. J Org Chem
2001, 66, 6037; (k) Vicario, J. L.; Job, A.; Wolberg, M.;
Mueller, M.; Enders, D. Org Lett 2002, 4, 1023.
[3] (a) Still, W. C.; Gennari, C. Tetrahedron Lett 1983, 24,
4405; (b) Ando, K. Tetrahedron Lett 1995, 36, 4105;
(c) Ando, K. J Org Chem 1997, 62, 1934 and the ref-
erences cited therein; (d) Ando, K. J Org Chem 1998,
63, 8411; (e) Ando, K. J Org Chem 1999, 63, 8406; (f)
Ando, K.; Oishi, T.; Hirama, M.; Ohno, H.; Ibuka, T. J
Org Chem 2000, 65, 4745.
[4] (a) Gordaliza, M.; del Corral, J. M. M.; Castro, M. A.;
Salinero, M. A.; San Feliciano, A.; Dorado, J. M.; Valle,
F. Synlett 1996, 1202 and references cited therein; (b)
Perron, F.; Abizafi, K. F. Chem Rev 1989, 89, 1617.
[5] (a) Shen, Y.; Ni, J. J Org Chem 1997, 62, 7260; (b)
Shen, Y.; Li, P.; Ni, J.; Sun, J. J Org Chem 1998, 63,
9396; (c) Shen, Y.; Zhang, Z. J Chem Res (s) 1998,
642; (d) Shen, Y.; Jiang, G.-F. Synthesis 2000, 502; (e)
Shen, Y.; Wang, G.; Sun, J. J Chem Soc, Perkin Trans 1
2001, 519.
(m, 2H), 3.80 (s, 3H), 3.69 (s, 3H), 3.35 (s, 2H). MS:
m/z (%) = 302 (M+, 1), 269 (35), 267 (100), 149 (24).
REFERENCES
[1] (a) Maryanoff, B. E.; Reitz, A. B. Chem Rev 1989, 89,
863; (b) Thompson, S. K.; Heathcock, C. H. J Org
Chem 1990, 55, 3386; (c) Williams, J. M. J. (Ed.).
The Wittig Reaction and Related Method; Oxford
University Press: Oxford, UK, 1996; (d) Burton, D.
J.; Yang, Z.; Qiu, W. Chem Rev 1996, 96, 1641; (e)
Motoyoshiya, J. Trends Org Chem 1998, 7, 63; (e)
Iorga, B.; Eymery, F.; Mouries, V.; Savignac, P. Tetra-
hedron 1998, 54, 14637.
[2] (a) Paterson, I.; Yeung, K.-S.; Smaill, J. B. Synlett
1993, 774; (b) Paterson, I.; McLeod, M. D. Tetrahe-
dron Lett 1997, 38, 4183; (c) Hulme, A. N.; Howells,
G. E. Tetrahedron Lett 1997, 38, 8245; (d) Mulzer,
J.; Berger, M. Tetrahedron Lett 1998, 39, 803; (e)
Paterson, I.; Yeung, K.-S.; Watson, C.; Ward, R.
A.; Wallace, P. A. Tetrahedron 1998, 54, 11935; (f)
Burke, S. D.; Hong, J.; Mongin, A. P. J Org Chem
1998, 63, 6952; (g) Mermet-Mouttet, M.-P.; Gabriel,
K.; Heissler, D. Tetrahedron Lett 1999, 40, 843; (h)
Hanazawa, T.; Inamori, H.; Masuda, T.; Okjamoto,
S.; Sato, F. Org Lett 2001, 3, 2205; (i) Pedersen, T. M.;
Hansen, E. L.; Kane, J.; Rein, T.; Helquist, P.; Norrby,
[6] McCombie, S. W.; Luchaco, C. A. Tetrahedron Lett
1997, 38, 5775.
[7] Gibbs, D. E.; Larsen, C. Synthesis 1984, 410.
[8] Linke, S.; Kurz, J.; Lipinski, D.; Gau, W. Leibigs Ann
Chem 1980, 542.
[9] El-Assal, C. S.; Shehab, A. H. J Chem Soc 1963, 2983.
[10] Bartmann, E. Ger Offen DE 3010968, Oct. 1, 1981;
CA 1982, 96,35864u.