P. Krishnamoorthy et al. / Tetrahedron 62 (2006) 10555–10566
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from diethyl allylmalonate [(130 mg, 0.65 mmol) in dry
THF (5 mL) at 0 ꢀC was added 60% NaH (23 mg,
0.95 mmol and stirred at room temperature for 30 min]
was added and stirred at room temperature for 17 h. The
THF was removed under reduced pressure and the residue
was partitioned between water (2 mL) and CH2Cl2
(15 mL). Organic layer was separated, dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure.
The residue obtained was purified by column chromato-
graphy (hexane/EtOAc; 7:13) to furnish 34 (125 mg, 66%)
yield as thick colorless oil. IR (neat, cmꢁ1): 1729; 1H
NMR (300 MHz): d¼1.20 (t, J¼6.9 Hz, 6H), 2.65 (d,
J¼7.2 Hz, 2H), 2.73 (d, J¼7.5 Hz, 2H), 4.13 (q, J¼6.9 Hz,
4H), 5.01–5.08 (m, 4H), 5.68 (m, 1H), 6.07 (dt, J¼15.6,
7.5 Hz, 1H), 6.27 (d, J¼15.6 Hz, 1H), 6.73 (s, 1H), 7.12
(m, 2H), 7.29–7.35 (m, 3H), 7.42 (s, 1H); 13C NMR
(75 MHz): d¼14.2, 35.9, 36.7, 50.9, 57.7, 61.2, 116.3,
119.1, 122.0, 126.0, 127.3, 128.3, 129.0, 132.6, 136.1,
137.5, 140.7, 170.8; HRMS-ESI: calcd for C23H29N2O4
(M+H)+ 397.2122, found 397.2112.
Pd2(dba)3 (87 mg, 0.09 mmol). After stirring at room tem-
perature for 5 min, freshly generated sodium salt prepared
from N-(diphenylmethylene)glycine ethyl ester [(0.680 g,
2.5 mmol) in dry THF (5 mL) at 0 ꢀC was added 60%
NaH (96 mg, 2.40 mmol) and stirred at room temperature
for 15 min] was added and stirred at 60 ꢀC for 36 h. The
THF was removed under reduced pressure and the residue
was partitioned between water (2 mL) and CH2Cl2
(15 mL). The organic layer was separated, dried (Na2SO4),
filtered, and concentrated under reduced pressure. The resi-
due obtained was purified by column chromatography (hex-
ane/EtOAc; 7:15) to furnish 37 (508 mg, 84%) as a thick
colorless oil. IR (neat, cmꢁ1): 1733, 1621; 1H NMR
(300 MHz): d¼1.22 (t, J¼7.5 Hz, 3H), 2.65–2.84 (m, 2H),
4.15 (m, 3H), 4.99 (s, 2H), 6.11 (dt, J¼15.9, 6.9 Hz, 1H),
6.24–6.29 (d, J¼15.9 Hz, 1H), 6.70 (d, J¼1.2 Hz, 1H),
7.09–7.16 (m, 4H), 7.25–7.36 (m, 5H), 7.37–7.41 (m, 4H),
7.61–7.64 (m, 2H); 13C NMR (75 MHz): d¼14.3, 37.3,
50.8, 60.9, 65.8, 116.1, 124.3, 124.7, 127.3, 128.01,
128.07, 128.3, 128.5, 128.6, 128.9, 129.0, 130.3, 136.2,
136.5, 137.4, 139.7, 141.1, 170.6, 171.9; HRMS-ESI: calcd
for C30H30N3O2 (M+H)+ 464.2317, found 464.2333.
2.1.18. Ethyl (4E)-2-acetyl-5-(1-methoxymethyl-1H-imi-
dazol-4-yl)pent-4-enoate (35). To the degassed reaction
mixture containing 28 (150 mg, 0.714 mmol), PPh3
(15 mg, 0.057 mmol), K2CO3 (197 mg, 1.43 mmol), and
ethyl acetoacetate (115 mg, 0.88 mmol) in CH2Cl2
(10 mL) was added Pd2(dba)3 (26 mg, 0.026 mmol) and
stirred at room temperature for 16 h. The reaction mixture
was concentrated under reduced pressure and residue ob-
tained was purified by column chromatography (hexane/
EtOAc; 3:17) to furnish 35 (148 mg, 74%) as a thick color-
less oil. IR (neat, cmꢁ1): 1733, 1714; 1H NMR (300 MHz):
d¼1.24 (t, J¼6.9 Hz, 6H), 2.24 (s, 3H), 2.71 (t, J¼6.6 Hz,
2H), 3.25 (s, 3H), 3.58 (t, J¼7.2 Hz, 1H), 4.19 (q,
J¼6.9 Hz, 2H), 5.15 (s, 2H), 6.22 (dt, J¼15.3, 6.6 Hz,
1H), 6.34 (d, J¼15.3 Hz, 1H), 6.88 (s, 1H), 7.50 (s, 1H);
13C NMR (75 MHz): d¼14.1, 29.4, 31.4, 56.2, 59.5, 61.5,
77.8, 115.9, 124.1, 124.8, 137.6, 140.9, 169.3, 202.7;
HRMS-ESI: calcd for C14H21N2O4 (M+H)+ 281.1496,
found 281.1492.
2.1.21. Ethyl (4E)-5-(1-benzyl-1H-imidazol-4-yl)-2-nitro-
pent-4-enoate (38). To the degassed reaction mixture con-
taining 25 (1.00 g, 3.91 mmol), PPh3 (122 mg, 0.47 mmol),
and ethyl nitroacetate (623 mg, 4.68 mmol) in CH2Cl2
(10 mL), was added Pd2(dba)3 (214 mg, 0.23 mmol) and
stirred at reflux for 12 h. After cooling to room temperature,
the reaction mixture was concentrated under reduced pres-
sure. The residue obtained was purified by column chromato-
graphy (hexane/EtOAc; 3:17) to furnish 38 (0.94 g, 73%) as
a thick colorless oil. IR (neat, cmꢁ1): 1747, 1559; 1H NMR
(300 MHz): d¼1.25 (t, J¼7.2 Hz, 3H), 3.04 (m, 2H), 4.25
(q, J¼7.2 Hz, 2H), 5.00 (s, 2H), 5.15 (dd, J¼9.3, 6.0 Hz,
1H), 6.16 (dt, J¼15.6, 6.9 Hz, 1H), 6.36 (d, J¼15.6 Hz,
1H) 6.75 (s, 1H), 7.11 (m, 2H), 7.29 (m, 3H), 7.43 (s, 1H);
13C NMR (75 MHz): d¼13.9, 33.7, 50.9, 63.1, 87.8, 117.3,
119.4, 126.9, 127.4, 128.4, 129.1 (2C), 135.9, 137.7, 139.8,
164.2; HRMS-ESI: calcd for C17H20N3O4 (M+H)+
330.1448, found 330.1439.
2.1.19. 5,5-Bis-[(1E)-3-(1-methoxymethyl-1H-imidazol-
4-yl)-1-propenyl]-2,2-dimethyl-[1,3]dioxane-4,6-dione
(36). To the degassed reaction mixture containing 28
(150 mg, 0.71 mmol), PPh3 (15 mg, 0.057 mmol), K2CO3
(197 mg, 1.43 mmol), and Meldrum’s acid (124 mg,
0.86 mmol) in CH2Cl2 (10 mL) was added Pd2(dba)3
(26 mg, 0.026 mmol) and stirred at room temperature for
14 h. The reaction mixture was concentrated under reduced
pressure and purified by column chromatography (MeOH/
EtOAc; 1:9) to furnish 36 (120 mg, 76%) as a pale orange
2.1.22. Ethyl (4E)-5-(1-methoxymethyl-1H-imidazol-4-
yl)-2-nitropent-4-enoate (39). To the degassed reaction
mixture containing 28 (152 mg, 0.72 mmol), PPh3 (15 mg,
0.057 mmol), and ethyl nitroacetate (115 mg, 0.86 mmol)
in CH2Cl2 (10 mL), was added Pd2(dba)3 (26 mg,
0.029 mmol) and stirred at reflux for 12 h. After cooling to
room temperature, the reaction mixture was concentrated
under reduced pressure. The residue obtained was purified
by column chromatography (hexane/EtOAc; 1:9) to furnish
39 (125 mg, 62%) as a thick colorless oil. IR (neat, cmꢁ1):
2933, 1747, 1560; 1H NMR (300 MHz): d¼1.27 (t,
J¼7.2 Hz, 3H), 3.02–3.10 (m, 2H), 3.23 (s, 3H), 4.27 (q,
J¼7.2 Hz, 2H), 5.14 (s, 2H), 5.18 (dd, J¼6.0, 9.3 Hz, 1H),
6.21 (dt, J¼15.3, 6.6 Hz, 1H), 6.39 (d, J¼15.3 Hz, 1H),
6.90 (s, 1H), 7.49 (s, 1H); 13C NMR (75 MHz): d¼13.9,
33.7, 56.2, 63.1, 77.8, 87.7, 116.7, 120.2, 126.6, 137.8,
140.2, 164.1; HRMS-ESI: calcd for C12H18N3O5 (M+H)+
284.1241, found 284.1237.
1
solid; mp: 134–136 ꢀC. IR (neat, cmꢁ1): 2936, 1736; H
NMR (300 MHz): d¼1.55 (s, 6H), 2.88 (d, J¼7.5 Hz, 4H),
3.23 (s, 6H), 5.14 (s, 4H), 6.22 (dt, J¼15.6, 7.5 Hz, 2H),
6.37 (d, J¼15.6 Hz, 2H), 6.88 (s, 2H), 7.46 (s, 2H); 13C
NMR (75 MHz): d¼29.2, 42.1, 56.2, 56.5, 77.7, 106.1,
116.7, 120.9, 127.17, 137.8, 140.4, 168.7; HRMS-ESI: calcd
for C22H29N4O6 (M+H)+ 445.2082, found 445.2073.
2.1.20. Ethyl (4E)-2-(benzhydrylideneamino)-5-(1-
benzyl-1H-imidazol-4-yl)pent-4-enoate (37). To the de-
gassed reaction mixture containing 24 (500 mg, 1.59 mmol),
PPh3 (50 mg, 0.19 mmol) in dry THF (3 mL), was added
2.1.23. Benzyl (1H-pyrrole-2-carbonyl)carbamate (40).
Benzyloxycarbonyl isocyanate (22.2 g, 0.125 mol) in