F. Bellezza et al. / Catalysis Today 152 (2010) 61–65
63
H-3), 3.76 (s, 3H, OMe), 5.14 (dd, J = 7.1, 4.0 Hz, 1H, H-2), 5.23 (d,
2.3.10. 1-(40-Methoxyphenyl)-2-(400-methylphenyl)-2,3-
J = 7.7 Hz, 1H, H-5), 6.81 (m, 2H, H-20 and H-60), 6.93 (m, 2H, H-30
dihydropyridin-4(1H)-one (4 R55pMe) [16]
and H-50), 7.13 (m, 2H, H-200 and H-600), 7.42 (m, 2H, H-300 and H-500),
Yellow crystals; m.p. 108–110 8C. 1H NMR (400 MHz, CDCl3):
d = 2.30 (s, 3H, Me), 2.75 (dd, J = 16.4, 4.0 Hz, 1H, H-3), 3.23 (dd,
7.51 (d, J = 7.7 Hz, 1H, H-6). 13C NMR (100.6 MHz, CDCl3):
d
= 43.1,
55.5, 61.9, 101.7, 114.7 (2 C), 121.2 (2 C), 121.8, 128.1 (2 C), 132.1 (2
C), 137.3, 138.0, 149.7, 157.1, 189.6. IR (CHCl3): = 1642.9, 1582.4,
J = 16.4, 7.1 Hz, 1H, H-3), 3.75 (s, 3H, OMe), 5.15 (dd, J = 7.1, 4.0 Hz,
1H, H-2) 5.23 (d, J = 7.7 Hz, 1H, H-5), 6.80 (m, 2H, H-20 and H60),
6.96 (m, 2H, H-30 and H-50), 7.11 (m, 4H, H-200, H-300, H-500, H600),
n
1511.5, 1283.1, 1250.6, 1097.7, 831.5, 710.3, 651.3 cmꢂ1. Anal.
Calcd for C18H16BrNO2 (358.23): C, 60.35; H, 4.50; N, 3.91. Found:
C, 60.42; H, 4.57; N, 3.94.
7.53 (d, J = 7.7 Hz, 1H). 13C NMR (100.6 MHz, CDCl3):
d
= 21.0, 43.4,
55.5, 62.2, 101.4, 114.5 (2 C), 121.1 (2 C), 126.2 (2 C), 129.5 (2 C),
135.1, 137.5, 138.3, 149.7, 156.9, 190.1. IR (CHCl3): = 1640.2,
1589.0, 1511.2, 1283.5, 1249.3, 1097.6, 1040.8, 831.4, 711.8,
650.9 cmꢂ1
n
2.3.6. 2-(400-Fluorophenyl)-1-(40-methoxyphenyl)-2,3-
dihydropyridin-4(1H)-one (4 R55pF)
.
Yellow crystals; m.p. 111–112 8C. 1H NMR (400 MHz, CDCl3):
d
= 2.72 (dd, J = 16.4, 4.0 Hz, 1H, H-3), 3.23 (dd, J = 16.4, 7.1 Hz, 1H,
2.3.11. 2-(400-Cyanophenyl)-1-(40-methoxyphenyl)-2,3-
dihydropyridin-4(1H)-one (4 R55pCN)
H-3), 3.75 (s, 3H, OMe), 5.16 (dd, J = 7.1, 4.0 Hz, 1H, H-2), 5.23 (d,
J = 7.7 Hz, 1H, H-5), 6.80 (m, 2H, H-20 and H-60), 6.93 (m, 2H, H-30
and H-50), 6.97 (m, 2H, H-300 and H-500), 7.22 (m, 2H, H-200 and H-600),
Orange crystals; m.p. = 84–85 8C. 1H NMR (400 MHz, CDCl3):
d
= 2.72 (dd, J = 16.5, 3.9 Hz, 1H, H-3), 3.29 (dd, J = 16.5, 7.2 Hz, 1H,
7.51 (d, J = 7.7 Hz, 1H, H-6). 13C NMR (100.6 MHz, CDCl3):
d
= 43.3,
H-3), 3.75 (s, 3H, OMe), 5.24 (dd, J = 7.2, 3.9 Hz, 1H, H-2), 5.25 (d,
J = 7.8 Hz, 1H, H-5), 6.81 (m, 2H, H-20 and H60), 6.91 (m, 2H, H-30
and H-50), 7.39 (m, 2H, H-200 and H600), 7.55 (d, J = 7.8 Hz, 1H, H-6),
55.4, 61.8, 101.4, 114.6 (2 C), 115.8 (d, J = 21.6 Hz, 2 C), 121.3 (2 C),
128.1 (d, J = 8.1 Hz, 2 C), 134.0 (d, J = 3.0 Hz), 138.0, 149.8, 157.0,
162.2 (d, J = 246.8 Hz), 189.8. IR (CHCl3):
n
= 1641.3, 1581.6,
7.61 (m, 2H, H-300 and H-500). 13C NMR (100.6 MHz, CDCl3):
d
= 42.7,
55.5, 62.0, 101.9, 111.9, 114.8 (2 C), 118.2, 121.0 (2 C), 127.2 (2 C),
132.7 (2 C), 137.7, 143.7, 149.5, 157.2, 189.0. IR (CHCl3): = 2233.5,
1510.7, 1284.4, 1249.7, 1099.0, 1040.0, 832.3, 713.8, 651.3 cmꢂ1
.
Anal. Calcd for C18H16FNO2 (2.97.32): C, 72.71; H, 5.42; N, 4.71.
Found: C, 72.83; H, 5.33; N, 4.59.
n
1644.9, 1583.8, 1511.4, 1283.7, 1250.8, 1099.1, 1041.0, 832.0,
721.8, 665.7 cmꢂ1. Anal. Calcd for C19H16N2O2 (304.34): C, 74.98;
H, 5.30; N, 9.20. Found: C, 75.10; H, 5.23; N, 9.36.
2.3.7. 1-(40-Methoxyphenyl)-2-(400-nitrophenyl)-2,3-dihydropyridin-
4(1H)-one (4 R55pNO2)
Orange crystals; m.p. 121–122 8C. 1H NMR (400 MHz, CDCl3):
3. Results and discussion
d
= 2.74 (dd, J = 16.4, 3.9 Hz, 1H, H-3), 3.30 (dd, J = 16.5, 7.2 Hz, 1H,
H-3), 3.75 (m, 3H, OMe), 5.26 (d, J = 7.8 Hz, 1H, H-5), 5.29 (dd,
J = 7.2, 3.9 Hz, 1H, H-2), 6.81 (m, 2H, H-20 and H-60), 6.92 (m, 2H, H-
30 and H-50), 7.45 (m, 2H, H-200 and H-600), 7.57 (d, J = 7.8 Hz, 1H, H-
6), 8.16 (m, 2H, H-300 and H-500). 13C NMR (100.6 MHz, CDCl3):
When the cycloaddition of N-PMP-benzaldimine 1 (R55H) with
Danishefsky’s diene 2 (1.5 equiv.) was carried out at 30 8C with
20 mol% of catalyst in CH2Cl2,
catalytic activity after 1 h (Table 1, entries 1 and 2) while in water
p- ZrP catalyzed the reaction more efficiently than ZrP (entries 3
aZrP and p-aZrP did not show
d
= 42.9, 55.5, 61.9, 102.1, 114.8 (2 C), 121.0 (2 C), 124.2 (2 C), 127.4
a
a
(2 C), 137.6, 145.7, 147.5, 149.4, 157.2, 189.0. IR (CHCl3):
and 4) and allowed the reaction to be completed in 3 h (entry 5).
Unexpectedly, (3Z)-4-[(4-methoxyphenyl)amino]but-3-en-2-one
(5) [22] was present along with the expected dihydro-4-pyridone
4 (R55H) in ca. 1:1 ratio (Scheme 2). Both the benzaldimine 1 and
n
= 1641.5, 1580.2, 1509.4, 1349.1, 1283.0, 1250.5, 1049.3,
830.2, 709.9, 650.9 cmꢂ1. Anal. Calcd for C18H16N2O4 (324.33):
C, 66.66; H, 4.97; N, 8.64. Found: C, 66.78; H, 5.13; N, 8.49.
the diene
producing benzaldehyde, p-methoxyaniline (6) and (3E)-4-meth-
oxybut-3-en-2-one (7). The conjugative addition of 6 to the a,b-
2 hydrolyze partially in acidic aqueous medium
2.3.8. 1-(40-Methoxyphenyl)-2-[400-(methylthio)phenyl]-2,3-
dihydropyridin-4(1H)-one (4 R55pSMe)
Orange crystals; m.p. 79–81 8C. 1H NMR (400 MHz, CDCl3):
unsaturated ketone 7 generates the (Z)-enaminone 5 (Scheme 2)
d
= 2.42 (s, 3H, SMe), 2.70 (dd, J = 16.4, 3.9 Hz, 1H, H-3), 3.21 (dd,
J = 16.4, 7.1 Hz, 1H, H-3), 3.72 (s, 3H, OMe), 5.12 (dd, J = 7.1,
3.9 Hz, 1H, H-2), 5.19 (d, J = 7.7 Hz, 1H, H-5), 6.78 (m, 2H, H-20 and
H-60), 6.93 (m, 2H, H-30 and H-50), 7.15 (m, 4H, H-200, H-300, H-500,
H-600), 7.50 (d, J = 7.7 Hz, 1H, H-6). 13C NMR (100.6 MHz, CDCl3):
Table 1
Aza-Diels–Alder reaction of benzaldimine 1 (R5H) with Danishefsky’s diene 2.
Entrya
Cat.
Reaction medium
SDS (equiv.)
Conv. (%)b
4/5
d
= 15.6, 43.3, 55.4, 62.0, 101.5, 114.6 (2 C), 121.1 (2 C), 126.81 (2
C), 126.83 (2 C), 134.9, 138.15, 138.17, 149.6, 156.9, 189.9. IR
(CHCl3): = 1640.5, 1581.4, 1510.9, 1283.0, 1250.3, 1094.8,
1
2
a
p-
ZrP
CH2Cl2
CH2Cl2
H2O
–
–
–
–
aZrP
–
–
n
3
aZrP
–
2
–
1040.2, 831.0, 711.9, 650.9 cmꢂ1. Anal. Calcd for C19H19NO2S
(325.43): C, 70.12; H, 5.88; N, 4.30; S, 9.58. Found: C, 70.28; H,
5.93; N, 4.39; S, 9.45.
4
p-
p-
p-
aZrP
aZrP
aZrP
H2O
–
67
99c
99
–
55/45
53/47
66/34
–
5
H2O
–
6
H2O
(0.4)
–
7
aZrP
SolFC
SolFC
SolFC
SolFC
SolFC
SolFC
SolFC
SolFC
8
p-
p-
p-
p-
p-
p-
p-
a
a
a
a
a
a
a
ZrP
–
21
57d
97
99
96
95
99g
90/10
86/14
84/16
99/1
94/6
86/14
99/1
9
ZrP
–
2.3.9. 1,2-Bis(4-methoxyphenyl)-2,3-dihydropyridin-4(1H)-one(4
R55pOMe) [12]
10
11
12
13
14f
ZrP
(0.4)
(0.4)
(0.2)
(0.1)
(0.2)
ZrPe
ZrPe
ZrPe
ZrPe
Pale yellow crystals; m.p. 112–116 8C. 1H NMR (400 MHz,
CDCl3):
d = 2.71 (dd, J = 16.4, 4.0 Hz, 1H, H-3), 3.19 (dd, J = 16.4,
7.0 Hz, 1H, H-3), 3.72 (s, 3H, OMe), 3.73 (s, 3H, OMe) 5.12 (dd,
J = 7.0, 4.0 Hz, 1H, H-2), 5.19 (d, J = 7.7 Hz, 1H, H-5), 6.79 (m, 4H, H-
20, H60, H-300, H-500), 6.94 (m, 2H, H-30 and H-50), 7.14 (m, 2H, H-200
and H600), 7.49 (d, J = 7.7 H, 1H, H-6). 13C NMR (100.6 MHz, CDCl3):
a
Reaction conditions: imine 1, Danishefsky’s diene
2 (1.5 equiv.), catalyst
20 mol%, SDS (0.2 equiv.) at 30 8C under solFC for 1 h, unless specified otherwise.
b
The complement to 100% is unreacted 1.
c
Reaction time 3 h.
d
= 43.4, 55.1, 55.4, 61.8, 101.1, 114.1 (2 C), 114.4 (2 C), 121.2 (2 C),
127.5 (2 C), 130.1, 138.1, 149.7, 156.8, 159.0, 190.1. IR (CHCl3):
= 1639.8, 1578.4, 1511.2, 1282.5, 1250.5, 1097.6, 1038.5, 830.5,
716.0, 651.1 cmꢂ1
d
Reaction time 15 h.
e
The catalyst was dried at 80 8C for 15 h.
Danishefsky’s diene 2 equiv.
f
n
g
.
Yield of isolated product 89%.