Stereoselective synthesis of functionalized 1,3-dienes in water

Article abstract of DOI:10.1002/cjoc.201190194

An efficient synthesis of functionalized 1,3-dienes via one-pot reactions between dialkyl acetylenedicarboxylates, 1,3-dicarbonyl compounds and secondary amines in water as the solvent is described. The mild reaction condition high yields and the new prod

Full text of DOI:10.1002/cjoc.201190194

FULL PAPER
Stereoselective Synthesis of Functionalized 1,3-Dienes
in Water
Rostami, Charati Faramarza
Hossaini, Zinatossadat*,b
Hajinasiri, Rahimehb
Moghaddasi-Kouchaksaraei, Fatemehc
a Department of Chemistry, Faculty of Science, Gonbad Kavous University, P. O. Box 163, Gonbad, Iran
b Department of Chemistry, Qaemshahr branch, Islamic Azad University, P. O. Box 163, Qaemshahr, Iran
c Department of Chemistry, Payamme Noor University, Sari Branch Sari, Iran
An efficient synthesis of functionalized 1,3-dienes via one-pot reactions between dialkyl acetylenedicarboxy-
lates, 1,3-dicarbonyl compounds and secondary amines in water as the solvent is described. The mild reaction con-
dition high yields and the new products are advantages of our method.
Keywords 1,3-dienes, 1,3-dicarbonyl, dialkyl acetylenedicarboxylate, secondary amines
Introduction
Scheme 1 Synthesis of substituted 1,3-dienes
The enlargement of green environmentally compas-
sionate synthetic procedures has been a topic of consid-
erable concern over the past few years both in academia
and in industry.1 Especially, solvent-less reactions and
reactions in water are of increasing interest. Water is
very low-cost, simple to process, and environmentally
benign.2-5 Water has been normally ignored as a me-
dium for organic reactions due to substrate solubility
problems and true or professed reagent incompatibilities.
However, organic reactions carried out in water
frequently show a rate-attractive effect in spite of low
solubility of the substrates in water.6-9
As the sighting of the Diels-Alder reaction substi-
tuted 1,3-dienes have played a significant function in
organic chemistry.10-13 Conjugated dienes represent one
group of broadly occurring and important organic com-
pounds. Their importance stems mainly from their
flexibility in organic transformations,14-17 and the
extensive amount of the 1,3-diene substructure in a vast
array of natural products of biological and medicinal
interest.18-25 The development of methods for the
efficient, stereoselective, and practical synthesis of
conjugated dienes has attracted much interest from syn-
thetic organic chemists. In this paper, we present herein
our results of a novel discovery involving synthesis of
functionalized 1,3-dienes, using commercially available
starting materials in excellent yields. Thus, the reaction
of secondary amines 1, 1,3-dicarbonyls 2 with activated
acetylenes 3, in water as a solvent produced 1,3-diene
derivatives 4 in good yields (Scheme 1).
Results and discussion
As indicated in Scheme 1, secondary amines 1, ace-
tyl acetone 2, and dialkyl acetylenedicarboxylates 3 un-
dergo a smooth 1∶1∶1 addition reaction in water at 45
℃, (secondary amines and acetyl acetone are mixed
first and then activated acetylenes is added) to produced
1,3-diene derivatives 4 in 85%—96% yields (Scheme 1).
We examined the diversity of reaction with different
substitutions as indicated in the Table 1.
Table 1 Synthesis of substituted 1,3-dienes in water
Entry
R
R'
Me
Et
Yields of 4/%
a
b
c
d
e
f
Me
Me
96
90
86
85
95
87
90
85
(CH2)5
Me
Et
(CH2)5
(CH2)4
Me
Et
(CH2)4
g
h
(CH2)2O(CH2)2
(CH2)2O(CH2)2
Me
Et
1
The data obtained from elemental analysis, IR, H
NMR, 13C NMR, and mass spectra confirmed all of the
proposed products. The mass spectrum of 4a displayed
*
E-mail: zshossaini@yahoo.com
Received June 24, 2010; revised September 8, 2010; accepted January 15, 2011.
Chin. J. Chem. 2011, 29, 951— 954
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951

Rostami et al.
FULL PAPER
a molecular ion peak at m/z 227. The most important
absorption band in IR spectrum is due to the C＝O
stretching frequency, which appeared at 1745 and 1737
this reaction for 1,3-butadiene: (Z,Z, E,E, Z,E and E, Z)
that are referred to as s-trans and s-cis. Structure of
compounds 4-s-cis or 4-s-trans could be distinguished
by NOESY spectrum (Figure 1). The NOESY spectrum
showed the correlation between the methyl and the me-
thine protons. Therefore the compound 4-s-trans was
ruled out and 4-s-cis (EZ) is accepted.
Under similar conditions, the reaction of 1 and
1,3-cyclohexandione 9 with 3, produced 1,3-diene de-
rivatives 10 in good yields (Scheme 3).
In summery, we reported an efficient method for the
synthesis of 1,3-diene derivatives. The advantages of
our work are as follows: (1) the reaction is performed
under neutral and mild condition. (2) No catalyst is re-
quired for this reaction. (3) The simplicity of the present
procedure makes it an interesting alternative to the
complex multistep approaches.
－1
1
cm . The H NMR spectrum of 4a exhibited three
sharp singlet signals arising from methyl and methoxy
groups (δ 2.36 and 3.86, 3.91 respectively). One singlet
at δ 2.74 is attributed to NMe2 protons. The 1H decoup-
led 13C NMR spectrum of 4a showed 11 distinct signals,
which were in agreement with the proposed structure.
Characteristic carbons of carbonyls are presented at
δ 167.5 and 170.5. Partial assignment of these
resonances for compounds 4 is given in experimental
section.
Although we have not established the mechanism of
our reaction in an experimental manner, a possible ex-
planation is proposed in Scheme 2. It is conceivable that,
the reaction involves the initial formation of enaminone
5 between secondary amines and acetylacetone, which
reacts with the dialkyl acetylenedicarboxylates to pro-
duce 1∶1 zwitterionic intermediate 6 between enami-
none and dialkyl acetylenedicarboxylates. Compound 4
is apparently formed by addition of water to 6, followed
by elimination of acetic acid.
Experimental
All chemicals were obtained from Fluka and were
used without further purification. Melting points were
measured on an Electrothermal 9100 apparatus. Ele-
mental analyses for C, H and N were performed using a
The four possible stereoisomer could be formed in
Scheme 2 Possible mechanism for the formation of compound 4
Figure 1 Structures of 4-s-cis and 4-s-trans.
Scheme 3 Synthesis of functionalized 1,3-dienes
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Stereoselective Synthesis of Functionalized 1,3-Dienes in Water
Heraeus CHN-O-Rapid analyzer. Mass spectra were
recorded on a FINNIGAN-MATT 8430 spectrometer
operating at an ionization potential of 70 eV. IR spectra
(MeO), 124.8 (CH), 128.5 (CH), 140.6 (C), 152.7 (C),
165.4 (C＝O), 166.8 (C＝O). EI-MS m/z (%): 267 (M＋,
20), 236 (96), 183 (68), 84 (46), 31 (100). IR (KBr) νmax
:
1
－1
were measured on a Shimadzu IR-460 spectrometer. H
1740, 1735, 1658, 1424, 1310, 1258, 1100 cm . Anal.
and 13C NMR spectra were measured with a BRUKER
DRX-500 AVANCE spectrometer at 500.1, and 125.8
MHz, respectively. 1H and 13C spectra were obtained for
solutions in CDCl3 using TMS as an internal standard.
calcd for C14H21NO4 (267.32): C 62.90, H 7.92, N 5.24;
found C 62.78, H 7.82, N 5.14.
Diethyl (Z)-2-[(E)-2-piperidino-1-propenyl]-2-bute-
nedioate (4d)
General procedure for the preparation of com-
pounds 4 and 10
Pale yellow crystals, yield 0.50 g (85%), m.p. 146—
148 ℃. 1H NMR (CDCl3, 500 MHz) δ: 1.24 (t, 3J＝7.2
Hz, 3H, Me), 1.36 (t, 3J＝7.2 Hz, 3H, Me), 1.58 (m, 6H,
3CH2), 2.27 (s, 3H, Me), 3.15 (m, 4H, 2CH2), 4.23 (q,
To a magnetically stirred solution of secondary
amines 1 (2 mmol) and 1,3-dicarbonyles 2 or 9 (2 mmol)
in water (5 mL) was added dialkyl acetylenedicarboxy-
lates 3 (2 mmol) slowly and the reaction heated for 8 h
at 45 ℃. After completion of the reaction as indicated
by TLC (ethyl acetate/n-hexane, 4∶1), the reaction
mixture was filtered and washed with water (10 mL×2)
and the solid residue was purified by chromatography
over silica gel (Merck 230 — 400 mesh) using an
n-hexane-AcOEt mixture (4∶1) as eluant.
3J＝7.2 Hz, 2H, OCH2), 4.34 (q, 3J＝7.2 Hz, 2H, OCH2),
7.08 (s, 1H, CH), 7.28 (s, 1H, CH); 13C NHR (CDCl3,
125.7 MHz,) δ: 14.0 (Me), 14.3 (Me), 21.8 (Me), 23.6
(CH2), 26.2 (2CH2), 48.6 (2CH2), 60.8 (OCH2), 61.4
(OCH2), 124.7 (CH), 129.0 (CH), 141.3 (C), 153.2 (C),
165.6 (C＝O), 167.3 (C＝O). IR (KBr) νmax: 1744, 1737,
1695, 1547, 1324, 1125 cm － 1. Anal. calcd for
C16H25NO4 (295.38): C 65.06, H 8.53, N 4.74; found C
64.92, H 8.43, N 4.68.
Dimethyl (Z)-2-[(E)-2-(dimethylamino)-1-propenyl]-
2-butenedioate (4a)
Dimethyl (Z)-2-[(E)-2-(pyrrolidinyl)-1-propenyl]-2-
butenedioate (4e)
Yellow powder, yield 0.44 g (96%), m.p. 130—132
1
℃. H NMR (CDCl3, 500 MHz) δ: 2.36 (s, 3H, Me),
Yellow powder, yield 0.48 g (95%), m.p. 158—160
1
2.74 (s, 6H, 2NMe), 3.86 (s, 3H, MeO), 3.91 (s, 3H,
MeO), 7.11 (s, 1H, CH), 7.43 (s, 1H, CH); 13C NMR
(CDCl3, 125.7 MHz) δ: 21.0 (Me), 45.8 (2NMe), 53.2
(MeO), 53.3 (MeO), 125.4 (CH), 129.7 (CH), 140.7 (C),
152.9 (C), 167.5 (C＝O), 170.5 (C＝O). EI-MS m/z (%):
227 (M＋, 25), 196 (68), 183 (45), 44 (58), 31 (100). IR
℃. H NHR (CDCl3, 500 MHz) δ: 1.89—1.94 (m, 4H,
2CH2), 2.30 (s, 3H, Me), 3.25—3.28 (m, 4H, 2CH2),
3.84 (s, 3H, MeO), 3.86 (s, 3H, MeO), 6.69 (s, 1H, CH),
7.02 (s, 1H, CH). 13C NHR (CDCl3, 125.7 MHz) δ: 21.5
(Me), 25.8 (2CH2), 49.8 (2CH2), 52.3 (MeO), 52.5
(MeO), 120.1 (CH), 130.5 (CH), 146.1 (C), 153.4 (CH),
167.7 (C＝O), 170.6 (C＝O). IR (KBr) νmax: 1743, 1738,
－1
(KBr) νmax: 1745, 1737, 1625, 1450, 1129 cm . Anal.
－1
calcd for C11H17NO4 (227.26): C 58.14, H 7.54, N 6.16;
found C 57.97, H 7.38, N 6.02.
1699, 1523, 1489, 1358, 1124 cm . Anal. calcd for
C13H19NO4 (253.29): C 61.64, H 7.56, N 5.53; found
C61.52, H 7.45, N 5.47.
Diethyl (Z)-2-[(E)-2-(dimethylamino)-1-propenyl]-2-
butenedioate (4b)
Diethyl
(Z)-2-[(E)-2-(pyrrolidinyl)-1-propenyl]-2-
butenedioate (4f)
Pale yellow crystals, yield 0.46 g (90%), m.p. 136—
138 ℃. 1H NMR (CDCl3, 500 MHz) δ: 1.28 (t, 3J＝7.3
Yellow powder, yield 0.49 g (87%), m.p. 147—149
3
1
3
Hz, 3H, Me), 1.35 (t, J＝7.4 Hz, 3H, Me), 2.34 (s, 3H,
℃. H NHR (CDCl3, 500 MHz) δ: 1.31 (t, J＝7.2 Hz,
3
3
Me), 2.78 (s, 6H, 2NMe), 4.18 (q, J＝7.4 Hz, 2H,
3H, Me), 1.34 (t, J＝7.2 Hz, 3H, Me), 1.89 (m, 4H,
3
OCH2), 4.32 (q, J＝7.4 Hz, 2H, OCH2), 6.98 (s, 1H,
2CH2), 2.29 (s, 3H, Me), 3.26 (m, 4H, 2CH2), 4.27 (q,
3J＝7.2 Hz, 2H, OCH2), 4.32 (q, 3J＝7.2 Hz, 2H, OCH2),
6.68 (s, 1H, CH), 6.99 (s, 1H, CH); 13C NHR (CDCl3,
125.7 MHz) δ: 13.8 (Me), 14.1 (Me), 21.4 (Me), 25.6
(2CH2), 49.8 (2CH2), 61.0 (OCH2), 61.3 (OCH2), 118.4
(CH), 129.6 (CH), 141.2 (C), 148.6 (C), 166.7 (C＝O),
169.6 (C＝O). IR (KBr) νmax: 1746, 1736, 1658, 1547,
1421, 1358, 1268, 1124 cm － 1. Anal. calcd for
C15H23NO4 (281.35): C 64.04, H 8.24, N 4.98; found C
64.13, H 8.32, N 5.08.
CH), 7.25 (s, 1H, CH); 13C NMR (CDCl3, 125.7 MHz) δ:
14.3 (Me), 14.5 (Me), 21.2 (Me), 44.3 (2 NMe), 61.2
(OCH2), 62.4 (OCH2), 123.4 (CH), 128.7 (CH), 141.2
(C), 152.8 (C), 166.2 (C＝O), 167.4 (C＝O). IR (KBr)
νmax: 1745, 1738, 1658, 1587, 1489, 1365, 1258, 1157
－1
cm . Anal. calcd for C13H21NO4 (255.31): C 61.16, H
8.29, N 5.49; found C 60.95, H 8.08, N 5.24.
Dimethyl (Z)-2-[(E)-2-piperidino-1-propenyl]-2-bute-
nedioate (4c)
Dimethyl
(Z)-2-[(E)-2-morpholino-1-propenyl]-2-
Yellow crystals, yield 0.46 g (86%), m.p. 143—145
℃. 1H NMR (CDCl3, 500 MHz) δ: 1.61 (m, 6H, 3CH2),
2.28 (s, 3H, Me), 3.14 (m, 4H, 2CH2), 3.61 (s, 3H,
MeO), 3.89 (s, 3H, MeO), 6.94 (s, 1H, CH), 7.27 (s, 1H,
CH); 13C NMR (CDCl3, 125.7 MHz) δ: 21.6 (Me), 23.4
(CH2), 25.9 (2CH2), 49.4 (2CH2), 51.6 (MeO), 53.7
butenedioate (4g)
Yellow powder, yield 0.48 g (90%), m.p. 150—152
1
℃. H NHR (CDCl3, 500 MHz) δ: 2.32 (s, 3H, Me),
3.09—3.11 (m, 4H, 2 CH2), 3.69—3.71 (m, 4H, 2CH2),
3.78 (s, 3H, MeO), 3.85 (s, 3H, MeO), 6.95 (s, 1H, CH),
Chin. J. Chem. 2011, 29, 951— 954
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953

Rostami et al.
FULL PAPER
7.09 (s, 1H, CH). 13C NHR (CDCl3, 125.7 MHz) δ: 21.4
(Me), 46.5 (2CH2), 51.4 (MeO), 52.5 (MeO), 66.5
(2CH2), 120.8 (CH), 129.4 (CH), 141.2 (C), 158.4 (C),
165.8 (C＝O), 168.4 (C＝O). IR (KBr) νm－a1x: 1748, 1735,
1654, 1587, 1469, 1387, 1256, 1123 cm . Anal. calcd
for C13H19NO5 (269.29): C 57.98, H 7.11, N 5.20; found
C 57.84, H 7.00, N 5.12.
References
1
Anastas, P. T.; Warner, J. C. Green Chemistry, Oxford
University Press, Oxford, 1998.
2
Green Reaction Media for Organic Synthesis, Ed.: Kochi,
M., Blackwell, Oxford, 2002.
3
4
5
Li, C. J. Chem. Rev. 2005, 105, 3095.
Lindstrom, U. M. Chem. Rev. 2002, 102, 2751.
Lindstrom, U. M.; Anderson, F. Angew. Chem., Int. Ed.
2006, 45, 548.
Diethyl (Z)-2-[(E)-2-morpholino-1-propenyl]-2-bute-
nedioate (4h)
Yellow powder, yield 0.50 g (85%), m.p. 153—155
6
7
8
Rideout, D. C.; Breslow, R. J. Am. Chem. Soc. 1980, 102,
7816.
1
3
℃. H NHR (CDCl3, 500 MHz) δ: 1.19 (t, J＝7.4 Hz,
3H, Me), 1.32 (t, 3J＝7.2 Hz, 3H, Me), 2.35 (s, 3H, Me),
3.12—3.14 (m, 4H, 2CH2), 3.58—3.61 (m, 4H, 2CH2),
Grieco, P. A.; Garner, P.; He, Z. Tetrahedron Lett. 1983, 24,
1897.
3
3
4.07 (q, J＝7.3 Hz, 2H, OCH2), 4.35 (q, J＝7.3 Hz,
2H, OCH2), 6.98 (s, 1H, CH), 7.12 (s, 1H, CH); 13C
NHR (CDCl3, 125.7 MHz) δ: 14.8 (Me), 14.9 (Me),
21.6 (Me), 47.8 (2CH2), 61.3 (OCH2), 62.0 (OCH2),
66.7 (2CH2), 121.0 (CH), 128.7 (CH), 140.1 (C), 156.2
(C), 166.4 (C＝O), 168.6 (C＝O). IR (KBr) νmax: 1746,
Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.; Kolb,
H. C.; Sharpless, K. B. Angew. Chem., Int. Ed. 2005, 44,
3275.
9
Nicolaou, K. C.; Xu, H.; Wartmann, M. Angew. Chem., Int.
Ed. 2005, 44, 756.
－1
10 Diels, O.; Alder, K. Liebigs Ann. Chem. 1928, 460, 98.
11 Fringuelli, F.; Taticchi, A. The Diels-Alder Reaction: Se-
lected Practical Methods, John Wiley & Sons, West Sussex,
England, 2002, p. 340.
1732, 1645, 1584, 1412, 1329, 1204, 1100 cm . Anal.
calcd for C15H23NO5 (297.35): C 60.59, H 7.80, N 4.71;
found C 60.67, H 7.89, N 4.82.
Dimethyl
(Z)-2-[2-(dimethylamino)-6-oxo-1-cyclo-
12 Reymond, S.; Cossy, J. Chem. Rev. 2008, 108, 5359.
13 Sauer, J.; Sustmann, R. Angew. Chem., Int. Ed. Engl. 1980,
19, 779.
hexenyl]-2-butenedioate (10a)
Yellow crystals, yield 0.49 g (87%), m.p. 164—166
1
℃. H NHR (CDCl3, 500 MHz) δ: 2.52 (m, 2H, CH2),
14 Deagostino, A.; Prandi, C.; Zavattaro, C.; Venturello, P. Eur.
J. Org. Chem. 2006, 2463.
3
2.67 (s, 6H, 2NMe), 2.81 (t, J＝7.2, 2H, CH2), 3.28 (t,
3J＝7.2, 2H, CH2), 3.76 (s, 3H, MeO), 3.87 (s, 3H,
MeO), 7.28 (s, 1H, CH). 13C NHR (CDCl3, 125.7 MHz)
δ: 23.6 (CH2), 28.5 (CH2), 37.5 (CH2), 40.7 (2NMe),
51.4 (MeO), 52.6 (MeO), 120.1 (C), 124.2 (CH), 142.5
(C), 153.7 (C), 166.0 (C＝O), 169.4 (C＝O), 187.4
(C＝O). IR (KBr) νmax: 1746, 1737, 1645, 1554, 1398,
1329, 1210, 1151 cm－1. Anal. calcd for C14H19NO5
(281.31): C 59.78, H 6.81, N 4.98; found C 59.67, H
6.75, N 4.84.
15 Nicolaou, K. C.; Snyder, S. S.; Montagnon, T.;
Vassilikogiannakis, G. Angew. Chem., Int. Ed. 2002, 41,
1668.
16 Friebe, L.; Nuyken, O.; Obrecht, W. Adv. Polym. Sci. 2006,
204, 1.
17 Fischbac, H. A. A.; Anwander, R. Adv. Polym. Sci. 2006,
204, 155.
18 Negishi, E. I., Huang, Z.; Wang, G.; Mohan, S.; Wang, C.;
Hattori, H. Acc. Chem. Res. 2008, 41, 1474.
Dimethyl (Z)-2-[2-(pyrrolidinyl)-6-oxo-1-cyclohexen-
yl]-2-butenedioate (10b)
19 Glasby, J. S. Encyclopaedia of the Terpenoids, Wiley,
Chichester, UK, 1982.
20 Devon, T. K.; Scott, A. I. Handbook of Naturally Occurring
Compounds, Vol. II, Academic, New York, 1972,
21 DellaGreca, M.; Marino, C. D.; Zarrelli, A.; Abrosca, B. D.
J. Nat. Prod. 2004, 67, 1492.
Yellow crystals, yield 0.58 g (94%), m.p. 167—169
1
℃. H NHR (CDCl3, 500 MHz) δ: 1.86 (m, 4H, 2CH2),
3
2.47 (m, 2H, CH2), 2.76 (t, J＝7.2 Hz, 2H, CH2), 3.28
3
(m, 4H, 2CH2), 3.32 (t, J＝7.2 Hz, 2H, CH2), 3.82 (s,
3H, MeO), 3.90 (s, 3H, MeO), 7.26 (s, 1H, CH); 13C
NHR (CDCl3, 125.7 MHz) δ: 23.4 (CH2), 25.5 (2CH2),
28.4 (CH2), 38.4 (CH2), 48.6 (2CH2), 51.7 (MeO), 52.3
(MeO), 120.6 (C), 123.5 (CH), 141.8 (C), 152.6 (C),
166.3 (C＝O), 169.7 (C＝O), 188.6 (C＝O). IR (KBr)
νmax: 1742, 1730, 1648, 1537, 1459, 1338, 1225, 1145
22 Lu, F.; Deng, Z.; Li, J.; Fu, H.; Van Soest, R. W. M.; Proksc,
H. P.; Lin, W. J. Nat. Prod. 2004, 67, 2033.
23 Cheng, Y.; Schneider, B.; Riese, U.; Schubert, B.; Li, Z.;
Hamburger, M. J. Nat. Prod. 2004, 67, 1854.
24 Rogers, E. W.; Molinski, T. F. J. Nat. Prod. 2005, 68, 450.
25 Mohamad, H.; Lajis, N. H.; Abas, F.; Ali, A. M.; Sukari, M.
A.; Kikuzaki, H.; Nakatani, N. J. Nat. Prod. 2005, 68, 285.
－1
cm . Anal. calcd for C16H21NO5 (307.34): C 62.53, H
6.89, N 4.56; found C 62.43, H 6.78, N 4.48.
(E1006245 Zhao, X.; Lu, Z)
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