Regiospecific [2+2] cycloadditions of electron-poor acetylenes to (Z)-2-acylamino-3-dimethylaminopropenoates: synthesis of highly functionalised buta-1,3-dienes

Article abstract of DOI:10.1016/j.tetlet.2008.04.021

Microwave-assisted [2+2] cycloaddition reactions of 2-amino-3-dimethylaminopropenoates with acetylenecarboxylates furnished highly functionalised 1-amino-4-(dimethylamino)buta-1,3-dienes in 40-94% yields. All reactions were observed to consistently produce single geometrical isomers, and in cases where non-symmetrical acetylenes were employed the reactions proceeded in a regiospecific manner.

Full text of DOI:10.1016/j.tetlet.2008.04.021

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3775–3778
Regiospecific [2+2] cycloadditions of electron-poor acetylenes
to (Z)-2-acylamino-3-dimethylaminopropenoates: synthesis of
highly functionalised buta-1,3-dienes
Urosˇ Ursˇicˇ, Urosˇ Grosˇelj, Anton Meden, Jurij Svete, Branko Stanovnik *
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Asˇkercˇeva 5, 1000 Ljubljana, Slovenia
Received 28 February 2008; revised 19 March 2008; accepted 2 April 2008
Available online 6 April 2008
Abstract
Microwave-assisted [2+2] cycloaddition reactions of 2-amino-3-dimethylaminopropenoates with acetylenecarboxylates furnished
highly functionalised 1-amino-4-(dimethylamino)buta-1,3-dienes in 40–94% yields. All reactions were observed to consistently produce
single geometrical isomers, and in cases where non-symmetrical acetylenes were employed the reactions proceeded in a regiospecific
manner.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Regiospecific [2+2] cycloadditions; (Z)-2-Acylamino-3-dimethylaminopropenoates; Acetylenecarboxylates; Highly functionalised buta-1,3-
dienes; Microwave irradiation
In the last few decades there have been some reports of
reactions of simple tertiary enamines with electron-poor
acetylenes, such as alkyl propiolates and dialkyl acetyl-
enedicarboxylates.1a–d It has been generally accepted that
these reactions initially proceed by a [2+2] cycloaddition.
However, the structure of the final product is strongly
dependant on the structure of the starting compound and
reaction conditions.1d The geometry of the obtained prod-
ucts was, in some cases, unambiguously determined by
Reinhoudt et al. in the early 1980s.1d When these reactions
were extended to other functionalised enamines and enami-
nones, in some cases, a Michael type addition took place
preferentially over the [2+2] cycloaddition.2a–c
aminopropenoates in the synthesis of heterocyclic systems
has encouraged us to study their reactions with acetylenes.
3-Dimethylaminopropenoates and related enaminones
have been demonstrated to be useful reagents in hetero-
cyclic synthesis,3a–e including the preparation of natural
products and their analogues, such as aplysinopsins,4a,b
meridinanines5a,b and dipodazines.6a–c
In this connection, we recently reported an efficient
method for the preparation and functionalisation of highly
substituted 1-aminopyrroline, 1-aminopyrrole and oxazo-
line–pyrroline fused systems from 1,2-diaza-1,3-butadienes
and 3-dimethylaminopropenoates,7 and the regio- and ster-
eoselective one-pot synthesis of oxazoline-fused pyridazine
via a ‘Michael addition–pyridazine cyclisation–oxazoline
cyclisation’ cascade reaction.8
When methyl (Z)-2-acylamino-3-(dimethylamino)pro-
penoates 1 and electron-poor acetylenes 2 were heated in
acetonitrile under microwave irradiation, the correspond-
ing (1E,3E)-1-acylamino-4-(dimethylamino)buta-1,3-dienes
3a–i were isolated as the only isomers in 40–94% yields
(Scheme 1).9–18 The structures of the products were deter-
mined by 1H NMR, IR and elemental analysis and in most
Despite the fact that reactions of electron-poor acetyl-
enes have been performed with many different enaminones,
until now no study has been undertaken on the reactions of
2-acylamino-3-dimethylaminopropenoates with electron-
deficient acetylenes. The wide applicability of 3-dimethyl-
*
Corresponding author. Tel.: +386 1 2419 100; fax: +386 1 2419 220.
E-mail address: branko.stanovnik@fkkt.uni-lj.si (B. Stanovnik).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.021

3776
U. Ursˇicˇ et al. / Tetrahedron Letters 49 (2008) 3775–3778
R1 R2
COOMe
NHZ
R1
R2
+
COOMe
MeCN, MW
Me2N
Me2N NHZ
2
1
3a-i
Yield Time
Comp.
Z
R1
R2
(%)
(min)
200
100
120
200
120
120
180
120
120
COPh COO-t-Bu COO-t-Bu 62
3a
3b
3c
3d
3e
3f
COMe COOMe
COMe COOEt
COOMe
COOEt
75
62
COMe COO-t-Bu COO-t-Bu 73
Cbz
Cbz
COOMe
COOEt
COOMe
COOEt
H
84
69
40
92
77
COPh COOEt
COPh COOEt
COMe COOEt
3g
3h
3i
CF3
CF3
Fig. 1. ORTEP view of compound 3e.
Scheme 1. Microwave-assisted [2+2] cycloadditions.
1 possesses nucleophilic character,3d as shown by the reso-
nance structure 10, it is apparent that these cycloadditions
proceed preferentially by a stepwise mechanism.
cases also by 13C NMR, MS and HRMS. Additionally, the
structures of 3e,h were confirmed by X-ray diffraction.
For the cycloaddition reactions of acetylenes 2 to methyl
(Z)-2-acylamino-3-(dimethylamino)propenoates 1 we envi-
sion two major pathways, a concerted and a stepwise one.
In the case of a concerted cycloaddition the reaction should
proceed as a [2s+2a] cycloaddition resulting in cyclobutene
intermediate 50, which would undergo a conrotatory retro-
electrocyclisation to afford (1Z,3E)-isomer 7 (R2 ¼ H) and/
The obtained X-ray structure of product 3e (Fig. 1)19
clearly demonstrates the orientation around the double
bonds to be (1E,3E), indicating that these reactions most
probably proceed by a two-step mechanism. In addition,
in the case of a two-step mechanism one would expect that
when a non-symmetrically substituted acetylene is used,
only one regioisomer would be formed. This was in fact
confirmed by performing reactions with ethyl propiolate
and ethyl 4,4,4-trifluorobut-3-ynoate. In all cases only a
single product was obtained. The structure of the regio-
isomer formed in the reaction with ethyl propiolate was
or (1E,3Z)-isomer
8
(R2 ¼ H) or (2E,4E)-isomer
7
(R2 = H) and/or (2Z,4Z)-isomer 8 (R2 = H). In the two-
step mechanism, the initially formed intermediate 4 is
transformed into 40, which gives sterically favoured cyclo-
butene intermediate 5. This is then followed by a conro-
tatory retro-electrocyclisation to produce (1E,3E)-isomer
1
determined by H NMR. The absence of proton-proton
couplings in the butadiene part indicates the formation of
regioisomer 3g and not 3g0 (Fig. 2). Analogously, the cyclo-
addition of ethyl 4,4,4-trifluorobut-3-ynoate was also
regiospecific producing 3h or 3i; the structure of regio-
isomer 3h was determined by X-ray analysis (Fig. 3).20
3
(R2 ¼ H) and/or (1Z,3Z)-isomer
6
(R2 ¼ H) or
(2Z,4E)-isomer 3 (R2 = H) and/or (2E,4Z)-isomer 6
(R2 = H) (Scheme 2). Due to the fact that the C-2 carbon
in methyl (Z)-2-acylamino-3-(dimethylamino)propenoates
R1
R1
R1
Me2N
R2
R1
R2
COOMe
NHZ
R1
R2
R2
R2
2
H
Me2N
COOMe
NHZ
COOMe
COOMe
NHZ
COOMe
H
Me2N NHZ
Me2N
NHZ
H
Me2N
5
1'
3
4'
4
and/or
R1
R2
R1
R2
R1
R2
R1
H
R2
COOMe
R1
2
R2
Me2N
NHZ
COOMe
NHZ and/or
Me2N
COOMe
COOMe
NHZ
6
Me2N COOMe
NHZ
Me2N NHZ
Me2N
7
8
1
5'
Scheme 2. Proposed mechanisms of the cycloadditions.

U. Ursˇicˇ et al. / Tetrahedron Letters 49 (2008) 3775–3778
3777
Org. Chem. 1963, 28, 1464–1468; (c) Brannock, K. C.; Burpitt, R. D.;
Goodlett, V. W.; Thweatt, J. G. J. Org. Chem. 1964, 29, 818–823; (d)
Reinhoudt, D. N.; Verboom, W.; Visser, G. W.; Trompenaars, W. P.;
Harkema, S.; van Hummel, G. J. J. Am. Chem. Soc. 1984, 106, 1341–
1350.
4JH-H = 0 Hz
3JH-H = 6-12 Hz
H
EtOOC
H
COOEt
COOMe
H
COOMe
H
Me2N NHCOPh
Me2N NHCOPh
´
2. (a) de Ancos, B.; Maestro, M. C.; Martın, M. R.; Mateo, A. I.
3g
3g'
Tetrahedron 1994, 50, 13857–13864; (b) Puebla, P.; Honores, Z.;
Medarda, M.; Mora´n, L.; Caballero, E.; San Feliciano, A. Tetrahe-
dron 1999, 55, 7915–7922; (c) Wang, M.-X.; Miao, W.-S.; Cheng, Y.;
Huang, Z.-T. Tetrahedron 1999, 55, 14611–14622.
Fig. 2. Structure determination of the product obtained with ethyl
propiolate.
3. (a) Stanovnik, B. J. Heterocycl. Chem. 1999, 36, 1581–1593; (b)
Stanovnik, B.; Svete, J. Synlett 2000, 1077–1091; (c) Stanovnik, B.;
Svete, J. In Targets in Heterocyclic Systems, Synthesis, Reactions and
Properties; Attanasi, O. A., Spinelli, D., Eds.; Italian Society of
Chemistry: Rome, 2000; Vol. 3, pp 105–137; (d) Stanovnik, B.; Svete,
J. Chem. Rev. 2004, 104, 2433–2480; (e) Svete, J. J. Heterocycl. Chem.
2005, 42, 361–373.
4. (a) Selicˇ, L.; Jaksˇe, R.; Lampicˇ, K.; Golicˇ, L.; Golicˇ Grdadolnik, S.;
Stanovnik, B. Helv. Chim. Acta 2000, 83, 2802–2811; (b) Selicˇ, L.;
Stanovnik, B. Tetrahedron 2001, 57, 3159–3164.
5. (a) Jaksˇe, R.; Svete, J.; Stanovnik, B.; Golobicˇ, A. Tetrahedron 2004,
ˇ
60, 4601–4608; (b) Casar, Z.; Bevk, D.; Svete, J.; Stanovnik, B.
Tetrahedron 2005, 61, 7508–7519.
6. (a) Wagger, J.; Bevk, D.; Meden, A.; Svete, J.; Stanovnik, B. Helv.
Chim. Acta 2006, 89, 240–248; (b) Wagger, J.; Golicˇ Grdadolnik, S.;
Grosˇelj, U.; Meden, A.; Stanovnik, B.; Svete, J. Tetrahedron:
Asymmetry 2007, 18, 464–475; (c) Wagger, J.; Grosˇelj, U.; Meden,
A.; Svete, J.; Stanovnik, B. Tetrahedron 2008, 64, 2801–2815.
7. Attanasi, O. A.; Favi, G.; Filippone, P.; Golobicˇ, A.; Stanovnik, B.;
Svete, J. J. Org. Chem. 2005, 70, 4307–4313.
Fig. 3. ORTEP view of compound 3h.
8. Attanasi, O. A.; Favi, G.; Filippone, P.; Golobicˇ, A.; Perulli, F. R.;
Stanovnik, B.; Svete, J. Synlett 2007, 2971–2974.
9. General procedure for the synthesis of 1-acylamino-4-(dimethyl-
amino)buta-1,3-dienes 3a– k: Acetylene 2 (1.49–4 mmol) was added
The X-ray structure of product 3h additionally confirms
the configurations around the double bonds to be the same
as in the case of 3e.
In this manner we have prepared a series of new highly
functionalised buta-1,3-dienes, which in addition to up to
three ester groups possess also a dimethylaminomethyl-
idene moiety and as such offer wide possibilities for further
transformations.
to
a
solution of 2-acylamino-3-(dimethylamino)propenoate
1
(1 mmol) in acetonitrile (4 mL) and the mixture was stirred in a
closed vessel under microwave irradiation at automatically controlled
constant temperature (CEM Corporation Discover microwave unit).
The reaction mixture was cooled. Volatile components were evapo-
rated in vacuo and the residue was purified by column chromatog-
raphy on silica gel (ethyl acetate/petroleum ether 50–100% of ethyl
acetate). Fractions containing the product were combined and
evaporated in vacuo.
10. 2,3-Di-tert-butyl 1-methyl (1E,3E)-1-(benzoylamino)-4-(dimethyl-
Acknowledgements
amino)buta-1,3-diene-1,2,3-tricarboxylate (3a): Prepared from
1
(Z = COPh) (0.248 g, 1 mmol) and
2
(R1 = R2 = COO-t-Bu)
(0.679 mL, 3 mmol), 80 °C, 200 min, chromatography (ethyl acetate/
petroleum ether =5:1), crystallisation (ethyl acetate/n-heptane = 1:1).
Yield: 0.305 g (62%); mp 160–162 °C. 1H NMR (CDCl3, 300 MHz): d
1.46 (9H, s, CMe3); 1.49 (9H, s, CMe3); 2.84 (6H, s, NMe2); 3.88 (3H,
s, COOMe); 7.29 (1H, br s, NH); 7.43–7.49 (2H, m, 2H of Ph); 7.50
(1H, s, 4-H); 7.53–7.59 (1H, m, 1H of Ph); 7.70–7.75 (2H, m, 2H of
Ph). 13C NMR (CDCl3, 75.5 MHz): d 28.4, 28.8, 53.0, 80.3, 81.6, 91.6,
121.7, 127.5, 129.3, 132.1, 132.9, 133.0, 150.8, 164.8, 165.0, 166.2,
168.4. (C 25H34N2O7 requires: C, 63.27; H, 7.22; N, 5.90. Found: C,
63.15; H, 7.37; N, 6.11); mmax (KBr) 3296, 2974, 2945, 1746, 1737,
1724, 1684, 1650, 1602, 1435, 1366, 1293, 1272, 1255, 1168, 1146,
The financial support from the Slovenian Research
Agency through grants P1-0179 and J1-6689-0103-04 is
gratefully acknowledged. We thank the pharmaceutical
companies Krka d.d. (Novo mesto, Slovenia) and Lek
d.d., a Sandoz company (Ljubljana, Slovenia) for the finan-
cial support. Crystallographic data were collected on a
Kappa CCD Nonius diffractometer in the Laboratory of
Inorganic Chemistry, Faculty of Chemistry and Chemical
Technology, University of Ljubljana, Slovenia. We
acknowledge with thanks the financial contribution of the
Ministry of Science and Technology, Republic of Slovenia
through grant Packet X-2000 and PS-511-102, which made
the purchase of the apparatus possible.
1088, 716 cmꢀ1
.
11. Trimethyl (1E,3E)-1-(acetylamino)-4-(dimethylamino)buta-1,3-diene-
1,2,3-tricarboxylate (3b): Prepared from 1 (Z = COMe) (0.186 g,
1 mmol) and 2 (R1 = R 2 = COOMe) (0.250 mL, 2 mmol), 80 °C, 100
min, chromatography (ethyl acetate), crystallisation (ethyl acetate/
petroleum ether). Yield: 0.246 g (75%); mp 160–163 °C. EI-MS:
m/z = 328 (M+). 1H NMR (CDCl3, 300 MHz): d 2.05 (3H, s, COMe);
2.96 (6H, br s, NMe2); 3.63 (3H, s, COOMe); 3.71 (3H, s, COOMe);
3.84 (3H, s, COOMe); 7.09 (1H, br s, NH); 7.56 (1H, s, 4-H). 13C
NMR (CDCl3, 75.5 MHz): d 23.0, 51.7, 52.7, 53.0, 89.5, 118.5, 134.0,
151.9, 165.1, 167.9, 168.7. (C14H20N2O7 requires: C, 51.22; H, 6.14;
References and notes
1. (a) Huebner, C. F.; Dorfman, L.; Robison, M. M.; Doneghue, E.;
Pierson, W. G.; Strachan, P. J. Org. Chem. 1963, 28, 3134–3140; (b)
Brannock, K. C.; Burpitt, R. D.; Goodlett, V. W.; Thweatt, J. G. J.

3778
U. Ursˇicˇ et al. / Tetrahedron Letters 49 (2008) 3775–3778
N, 8.53. Found: C, 51.29; H, 6.24; N, 8.58); EI-HRMS: m/z =
58.87; H, 6.17; N, 6.48); EI-HRMS: m/z = 448.185600 (M+);
C22H28N2O8 requires: m/z = 448.184566 (M+); mmax (KBr) 3195,
2982, 1737, 1724, 1714, 1678, 1594, 1504, 1434, 1366, 1328, 1288,
328.128005 (M+); C14H20N2O7 requires: m/z = 328.127051 (M+); mmax
(KBr) 3258, 2998, 2954, 1727, 1692, 1680, 1609, 1493, 1435, 1404,
1372, 1325, 1269, 1222, 1141, 1096, 1060, 1040, 894, 779, 764 cmꢀ1
.
1223, 1093, 1037, 989, 772, 759, 702 cmꢀ1
.
12. 2,3-Diethyl 1-methyl (1E,3E)-1-(acetylamino)-4-(dimethylamino)-
buta-1,3-diene-1,2,3-tricarboxylate (3c): Prepared from 1(Z = COMe)
16. 5-Ethyl 1-methyl (2Z,4E)-2-(acetylamino)-4-[(dimethylamino)meth-
ylene]pent-2-enedioate (3g): Prepared from 1 (Z = COPh) (0.248 g,
1 mmol) and 2 (R1 = COOEt, R2 = H) (0.410 mL, 4 mmol), 100 °C,
180 min, chromatography (ethyl acetate). Yield: 0.137 g (40%); mp
128–132 °C. EI-MS: m/z = 346 (M+). 1H NMR (CDCl3, 300 MHz): d
1.25 (3H, t, J = 7.1 Hz, CH2CH3); 3.13 (6H, s, NMe2); 3.80 (3H, 3,
COOMe); 4.18 (2H, q, J = 7.1 Hz, CH2CH3); 7.06 (1H, s, 3-H); 7.40–
7.54 (3H, m, 3H of Ph); 7.58 (1H, s, 10-H); 7.87–7.92 (2H, m, 2H of
Ph); 8.91 (1H, br s, NH). 13C NMR (CDCl3, 75.5 MHz): d 14.9, 44.5,
52.6, 60.6, 92.8, 123.8, 125.3, 127.8, 128.9, 132.0, 134.2, 154.7, 165.1,
166.3. (C 18H22N2O5 requires: C, 62.42; H, 6.40; N, 8.09. Found: C,
62.45; H, 6.45; N, 8.02); EI-HRMS: m/z = 346.153040 (M+);
C18H22N2O5 requires: m/z = 346.152872 (M+); mmax (KBr) 3270,
2977, 2951, 1719, 1660, 1597, 1507, 1470, 1434, 1403, 1368, 1300,
2
(0.186 g, 1 mmol) and 2 (R1 = R = COOEt) (0.325 mL, 2 mmol),
80 °C, 120 min, chromatography (ethyl acetate), crystallisation (ethyl
acetate/petroleum ether = 1:1). Yield: 0.222 g (62%); mp 155–158 °C.
1H NMR (CDCl3, 300 MHz): d 1.20 (3H, t, J = 7.1 Hz, CH2CH3);
1.25 (3H, t, J = 7.1 Hz, CH2CH3); 2.04 (3H, s, COMe); 2.96 (6H, br s,
NMe2); 3.83 (3H, s, COOMe); 3.96–4.22 (4H, m, 2 ꢁ CH2CH3); 6.98
(1H, br s, NH); 7.56 (1H, s, 4-H). 13C NMR (CDCl3, 75.5 MHz): d
14.4, 14.6, 22.9, 52.9, 60.4, 61.4, 90.0, 119.5, 133.1, 151.9, 165.1,
167.5, 168.8, 169.4. (C16H24N2O7 requires: C, 53.92; H, 6.79; N, 7.86.
Found: C, 54.14; H, 6.95; N, 8.11); m
(KBr): 3269, 2981, 1734,
max
1712, 1665, 1609, 1506, 1407, 1328, 1288, 1268, 1248, 1210, 1107,
1096, 1061, 987, 943, 777 cmꢀ1
13. 2,3-Di-tert-butyl 1-methyl (1E,3E)-1-(acetylamino)-4-(dimethyl-
amino)buta-1,3-diene-1,2,3-tricarboxylate (3d): Prepared from
(Z = COMe) (0.186 g, 1 mmol) and
(R1 = R2 = COO-t-Bu)
.
1281, 1242, 1214, 1152, 1112, 1083, 757, 708 cmꢀ1
17. 5-Ethyl 1-methyl(2E,4E)-2-(benzoylamino)-4-[(dimethylamino)meth-
ylene]-3-(trifluoromethyl)pent-2-enedioate (3h): Prepared from
.
1
2
1
(0.679 mL, 3 mmol), 80 °C, 200 min, chromatography (ethyl acetate/
petroleum ether = 4:1), crystallisation (n-hexane). Yield: 0.300 g
(73%); mp 73–77 °C. EI-MS: m/z = 412 (M+). 1H NMR (CDCl3,
300 MHz): d 1.44 (9H, s, CMe3); 1.46 (9H, s, CMe3); 2.03 (3H, s,
COMe); 2.93 (6H, br s, NMe2); 3.82 (3H, s, COOMe); 6.65 (1H, br s,
NH); 7.49 (1H, s, 4-H). 13C NMR (CDCl3, 75.5 MHz): d 23.3, 28.3,
28.7, 52.9, 80.2, 81.5, 91.4, 121.3, 131.9, 151.1, 165.1, 166.3, 168.0,
168.6. (C 20H32N2O7 requires: C, 58.24; H, 7.82; N, 6.79. Found: C,
58.25; H, 8.04; N, 6.75); EI-HRMS: m/z = 412.221850 (M+);
C20H32N2O7 requires: m/z = 412.220952 (M+); mmax (KBr) 3274,
2978, 2931, 1739, 1714, 1692, 1666, 1608, 1479, 1434, 1391, 1367,
(Z = COPh) (0.248 g, 1 mmol) and 2 (R1 = COOEt, R2 = CF3)
(0.262 mL, 1.58 mmol), 80 °C, 120 min, chromatography (ethyl ace-
tate/petroleum ether = 1:1), crystallisation (ethyl acetate/petroleum
ether = 1:1). Yield: 0.382 g (92%); mp 129–130 °C. 1H NMR (CDCl3,
300 MHz): d 1.24 (3H, t, J = 7.1 Hz, CH2CH3); 3.00 (6H, br s,
NMe2); 3.94 (3H, s, COOMe); 4.05–4.16 (1H, m, Ha–CH–CH3); 4.20–
4.30 (1H, m, Hb–CH–CH ); 7.44–7.51 (2H, m, 2H of Ph); 7.55–7.62
3
(1H, m, 1H of Ph); 7.66 (1H, br s, NH); 7.67 (1H, s, 10-H); 7.70–7.74
(2H, m, 2H of Ph). 13C NMR (CDCl3, 75.5 MHz): d 14.2, 52.9, 60.2,
84.3 (q, J = 1.6 Hz), 112.5 (q, J = 33.6 Hz), 122.8 (q, J = 273 Hz),
127.2, 128.9, 132.0, 132.8, 134.4 (q, J = 3.1 Hz), 151.8, 163.3, 164.2,
168.2. (C19H21F3N2 O5 requires: C, 62.42; H, 6.40; N, 8.09. Found:
C, 62.45; H, 6.45; N, 8.02); mmax (KBr) 3220, 2952, 1746, 1691, 1673,
1637, 1592, 1503, 1483, 1436, 1367, 1327, 1295, 1266, 1223, 1153,
1303, 1251, 1204, 1166, 1092, 999, 841, 768 cmꢀ1
14. Trimethyl (1E,3E)-1-[(benzyloxycarbonyl)amino]-4-(dimethylamino)-
buta-1,3-diene-1,2,3-tricarboxylate (3e): Prepared from (Z =
Cbz) (0.278 g, 1 mmol) and
(R1 = R2 = COOMe) (0.338 mL,
.
1
2
1112, 1083, 979, 761 cmꢀ1
18. 5-Ethyl 1-methyl (2E,4E)-2-(acetylamino)-4-[(dimethylamino)meth-
ylene]-3-(trifluoromethyl)pent-2-enedioate (3i): Prepared from
.
2.5 mmol), 90 °C, 120 min, chromatography (ethyl acetate/petroleum
ether = 1:1), crystallisation (ethyl acetate/petroleum ether = 1:1).
Yield: 0.354 g (84%); mp 159–161 °C. 1H NMR (CDCl3, 300 MHz): d
2.85 (6H, br s, NMe2); 3.62 (3H, s, COOMe); 3.71 (3H, s COOMe);
3.85 (3H, br s, COOMe); 5.06 (1H, d, J = 12.0 Hz, Ha–CH–Ph); 5.21
(1H, d, J = 12.0 Hz, Hb–CH–Ph); 6.23 (1H, br s, NH); 7.33–7.38 (5H,
m, Ph); 7.53 (1H, s, 4-H). 13C NMR (CDCl3, 75.5 MHz): d 51.8, 52.7,
53.2, 68.4, 88.6, 115.0, 129.0, 129.0, 129.1, 135.3, 135.7, 151.6, 152.6,
164.7, 167.5, 169.2.(C 20H24N2O8 requires: C, 57.14; H, 5.75; N, 6.66.
Found: C, 57.18; H, 5.87; N, 6.85); mmax (KBr) 3210, 2954, 1747, 1737,
1712, 1682, 1615, 1594, 1503, 1437, 1343, 1290, 1261, 1219, 1191,
1
(Z = COMe) (0.186 g, 1 mmol) and 2 (R1 = COOEt, R2 = CF3)
(0.248 mL, 1.49 mmol), 80 °C, 120 min, chromatography (ethyl
acetate), crystallisation (ethyl acetate/petroleum ether = 1:1). Yield:
0.271 g (77%); mp 167–170 °C. 1H NMR (CDCl3, 300 MHz): d 1.23
(3H, t, J = 7.1 Hz, CH2CH3); 2.07 (3H, s, COMe); 3.01 (6H, br s,
NMe2); 3.87 (3H, s, COOMe); 4.00–4.12 (1H, m, Ha–CH–CH 3);
4.16–4.28 (1H, m, Hb–CH–CH 3); 7.05 (1H, br s, NH); 7.62 (1H, s, 10-
H). (C 14H19F3N2 O5 requires: C, 47.73; H, 5.44; N, 7.95. Found: C,
47.71; H, 5.60; N, 7.80); mmax (KBr) 3252, 2983, 2955, 1746, 1706,
1686, 1638, 1594, 1503, 1434, 1332, 1297, 1271, 1236, 1147, 1114,
1144, 1098, 1079, 1036, 1001, 766, 736, 696 cmꢀ1
15. 2,3-Diethyl 1-methyl (1E,3E)-1-[(benzyloxycarbonyl)amino]-4-
.
1092, 1019, 765 cmꢀ1
.
(dimethylamino)buta-1,3-diene-1,2,3-tricarboxylate (3f): Prepared
from 1 (Z = Cbz) (0.278 g, 1 mmol) and 2 (R1 = R2 = COOEt)
(0.400 mL, 2.5 mmol), 90 °C, 120 min, chromatography (ethyl ace-
tate/petroleum ether = 1:1), crystallisation (ethyl acetate/petroleum
ether = 1:1). Yield: 0.311 g (69%); mp 78–80 °C. EI-MS: m/z = 448
(M+). 1H NMR (CDCl3, 300 MHz): d 1.18 (3H, t, J = 7.1 Hz,
CH2CH3); 1.24 (3H, t, J = 7.1 Hz, CH2CH3); 2.83 (6H, br s, NMe2);
3.83 (3H, br s, COOMe); 3.98–4.20 (4H, m, 2 ꢁ CH2CH3); 5.05 (1H,
d, J = 12.0 Hz, Ha–CH–Ph); 5.22 (1H, d, J = 12.0 Hz, Hb–CH–Ph);
6.22 (1H, br s, NH); 7.33–7.38 (5H, m, Ph); 7.52 (1H, s, 4-H). 13C
NMR (CDCl3, 75.5 MHz): d 14.5, 14.8, 53.1, 60.3, 61.4, 68.3, 89.3,
115.3, 129.0, 129.0, 129.1, 134.2, 135.8, 151.5, 152.7, 164.7, 167.1,
19. Crystallographic data (excluding structure factors) for structure 3g in
this Letter have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication number CCDC 679308.
Copies of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [fax: +44 0 1223
336033 or e-mail: deposit@ccdc.cam.ac.uk].
20. Crystallographic data (excluding structure factors) for structure 3j in
this Letter have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication number CCDC 679309.
Copies of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [fax: +44 0 1223
336033 or e-mail: deposit@ccdc.cam.ac.uk].
168.8. (C H28N2O8 requires: C, 58.92; H, 6.26; N, 6.25. Found: C,
22