9596
M.A. Sierra et al. / Tetrahedron 64 (2008) 9592–9598
4
3
.2.7. trans-1-(2-(Hydroxymethyl)phenyl)-4-(4-methoxy-phenyl)-
-(pent-4-enamido)azetidin-2-one 7b
A solution of 6b (1.82 g, 3.68 mmol) in 10 mL of anhyd CHCl was
3
1H), 5.83 (ddt, J¼17.1,10.4, 6.4 Hz,1H), 5.50 (ABsyst, JAB¼13.1 Hz,1H),
5.39 (ABsyst, JAB¼13.1 Hz, 1H), 5.16 (d, J¼2.3 Hz, 1H), 5.09 (dq, J¼17.1,
1.6 Hz, 1H), 5.03 (dq, J¼10.4, 1.3 Hz, 1H), 4.70 (dd, J¼7.1, 2.3 Hz, 1H),
13
treated with BF
the solvent and purification by chromatography (SiO
:1) yielded pure 7b (1.03 g, 74%) as orange oil. IR (film):
3
$Et
2
O (1.57 g,11.0 mmol) for 30 min. Evaporation of
3.76 (s, 3H), 2.45–2.31 (m, 4H); C NMR (75 MHz, CDCl
3
):
d
¼172.7,
2
, Hex/AcOEt
165.8,165.2,159.8,136.7, 133.8, 131.3, 130.3,130.1, 129.1, 128.1, 128.0,
127.9, 126.8, 122.4, 115.8, 114.3, 64.6, 64.0, 63.6, 55.2, 35.2, 29.2.
1
ꢁ1 1
n
max¼3420, 3360, 3019, 1750, 1671, 1515, 1249, 755 cm ; H NMR
26 2 5
Anal. Calcd for C25H N O : C, 69.11; H, 6.03; N, 6.45. Found: C,
(
300 MHz, CDCl ):
3
d¼7.43–7.37 (m, 1H), 7.23 (d, J¼8.7 Hz, 2H), 7.19–
68.84; H, 5.99; N, 6.33.
7
.15 (m, 1H), 7.01–6.94 (m, 2H), 6.84 (d, J¼8.7 Hz, 2H), 5.80 (ddt,
J¼17.0, 10.3, 6.3 Hz, 1H), 5.24 (d, J¼2.3 Hz, 1H), 5.06 (dd, J¼17.0,
4.2.11. trans-1-(2-((But-3-enoyloxy)methyl)phenyl)-4-(4-
1
1
.4 Hz, 1H), 5.01 (dd, J¼10.3, 1.2 Hz, 1H), 4.79 (ABsyst, JAB¼12.6 Hz,
methoxyphenyl)-3-(pent-4-enamido)azetidin-2-one 8c
ꢀ
H), 4.58 (ABsyst, JAB¼12.6 Hz, 1H), 4.57 (dd, J¼7.3, 2.3 Hz, 1H), 3.75
Following Method A (Section 4.2.1), a 0 C solution of 7b (0.11 g,
13
(
1
1
C
s, 3H), 2.39–2.28 (m, 4H); C NMR (50 MHz, CDCl
67.0, 159.9, 136.7, 135.1, 133.3, 131.2, 128.7, 127.9, 127.8, 127.0, 122.2,
15.6, 114.4, 64.1, 63.2, 62.1, 55.2, 35.0, 29.1. Anal. Calcd for
: C, 69.46; H, 6.36; N, 7.36. Found: C, 69.70; H, 6.54; N,
3
):
d
¼173.3,
0.3 mmol) in 7 mL of anhyd CH
0.4 mmol) and freshly prepared 3-butenoyl chloride (0.04 mL,
0.4 mmol). Purification by chromatography (SiO , Hex/AcOEt 3:1)
yielded pure 8c (70.0 mg, 52%) as yellow oil. IR (film):
max¼3353,
2 2 3
Cl was treated with Et N (0.05 mL,
19
2
H N
22 24 2
O
4
n
3010, 1755, 1739, 1670, 1516, 1252, 1176, 758 cm ; 1H NMR
ꢁ1
7.18.
(
300 MHz, CDCl ):
3
d
¼7.39–7.36 (m,1H), 7.28 (d, J¼8.7 Hz, 2H), 7.22–
4
3
.2.8. trans-1-(2-(Hydroxymethyl)phenyl)-4-(4-methoxy-phenyl)-
-(pent-4-enoyloxy)azetidin-2-one 14
7.15 (m, 2H), 7.09–7.06 (m, 1H), 6.97 (br d, J¼7.3 Hz, 1H), 6.84 (d,
J¼8.7 Hz, 2H), 5.93 (ddt, J¼17.4, 9.6, 7.0 Hz, 1H), 5.80 (ddt, J¼16.7,
10.5, 6.2 Hz,1H), 5.43 (d, J¼13.3 Hz,1H), 5.27 (d, J¼13.3 Hz,1H), 5.18
(d, J¼2.3 Hz, 1H), 5.17 (dq, J¼10.5, 1.2 Hz, 1H), 5.16 (dq, J¼16.7,
1.4 Hz, 1H), 5.06 (dq, J¼17.4, 1.6 Hz, 1H), 5.00 (dq, 1H, J¼9.6, 1.4 Hz,
A solution of 13 (0.10 g, 0.2 mmol) in 2 mL of anhyd CHCl
treated with BF $Et O (0.09 g, 0.6 mmol) for 1 h. Evaporation of the
solvent and purification by chromatography (SiO , Hex/AcOEt 3:1)
yielded pure 14 (0.07 g, 92%) as orange oil. IR (film):
max¼3297,
053, 1743, 1685, 1515, 1253, 772 cm ; H NMR (300 MHz, CDCl ):
¼7.49–7.46 (m, 1H), 7.27–7.20 (m, 4H), 7.00–6.93 (m, 1H), 6.87 (d,
J¼8.8 Hz, 2H), 5.85 (ddt, J¼17.0, 10.4, 6.4 Hz, 1H), 5.51 (d, J¼1.9 Hz,
H), 5.12 (d, J¼1.9 Hz, 1H), 5.11 (dq, J¼17.0, 1.5 Hz, 1H), 5.07 (dq,
3
was
3
2
2
n
1H), 4.68 (dd, J¼7.3, 2.3 Hz, 1H), 3.74 (s, 3H), 3.13 (dt, J¼6.9, 1.4 Hz,
ꢁ1
1
13
3
d
3
2H), 2.38–2.28 (m, 4H); C NMR (50 MHz, CDCl
3
):
d¼172.8, 171.2,
165.4, 159.8, 136.7, 133.7, 130.1, 130.0, 129.9, 129.0, 128.0, 127.8,
126.7, 122.4, 118.8, 115.6, 114.3, 64.4, 63.8, 63.6, 55.2, 39.0, 35.0, 29.1.
1
Anal. Calcd for C26
69.37; H, 6.45; N, 6.07.
28 2 5
H N O : C, 69.63; H, 6.29; N, 6.25. Found: C,
J¼10.4, 1.5 Hz, 1H), 4.82 (ABsyst, JAB¼12.6 Hz, 1H), 4.62 (ABsyst
,
J
AB¼12.6 Hz, 1H), 3.77 (s, 3H), 2.60 (dd, J¼6.8, 1.5 Hz, 1H), 2.57
13
(
dd, J¼6.8, 0.6 Hz, 1H), 2.49–2.40 (m, 2H); C NMR (75 MHz,
):
¼171.7, 164.2, 160.2, 136.1, 134.6, 131.7, 128.8, 128.3, 127.9,
27.2, 126.5, 121.1, 116.0, 114.5, 80.3, 63.8, 62.3, 55.3, 32.9, 28.6. Anal.
Calcd for C22 : C, 69.28; H, 6.08; N, 3.67. Found: C, 69.60; H,
4.2.12. trans-4-(4-Methoxyphenyl)-3-(pent-4-enamido)-1-(2-
((pent-4-enoyl-oxy)methyl)phenyl)azetidin-2-one 8d
CDCl
1
3
d
ꢀ
Following Method A (Section 4.2.1), a 0 C solution of 7b (0.09 g,
H23NO
5
0.2 mmol) in 5 mL of anhyd CH
0.3 mmol) and 4-pentenoyl chloride (0.03 mL, 0.3 mmol). Purifi-
cation by chromatography (SiO , Hex/AcOEt 2:1) yielded pure 8d
(53.0 mg, 57%) as yellow oil. IR (film):
max¼3351, 3016, 1753, 1739,
H NMR (300 MHz, CDCl ):
¼7.43–
2 2 3
Cl was treated with Et N (0.04 mL,
6
.31; N, 3.72.
2
4.2.9. trans-3-(But-3-enamido)-1-(2-((but-3-enoyloxy)-
n
ꢁ
1
1
methyl)phenyl)-4-(4-methoxyphenyl)azetidin-2-one 8a
1684, 1515, 1254, 755 cm
;
3
d
Following Method B (Section 4.2.2), a solution of
b
-lactam 7a
7.39 (m, 1H), 7.31 (d, J¼8.8 Hz, 2H), 7.25–7.18 (m, 2H), 7.11–7.08 (m,
1H), 6.86 (d, J¼8.8 Hz, 2H), 6.40 (d, J¼6.9 Hz,1H), 5.92–5.75 (m, 2H),
5.44 (d, J¼13.0 Hz, 1H), 5.29 (d, J¼13.0 Hz, 1H), 5.16 (d, J¼2.3 Hz,
1H), 5.15–4.98 (m, 4H), 4.71 (dd, J¼6.9, 2.3 Hz, 1H), 3.77 (s, 3H),
(
0
0.41 g, 1.1 mmol) in 18 mL of anhyd CH
.14 mL (1.7 mmol) of 3-butenoic acid in 18 mL of anhyd CH
DMAP (0.16 g, 1.3 mmol), and DCC (0.38 g, 1.9 mmol) for 2 h. Puri-
fication by chromatography (SiO , Hex/AcOEt 3:1) yielded pure 8a
0.30 g, 62%) as orange oil. IR (film):
max¼3350, 3018, 1751, 1739,
683,1515,1257, 754 cm ; H NMR (200 MHz, CDCl ):
¼7.41–7.35
m, 1H), 7.30–7.05 (m, 5H), 6.83 (d, J¼8.8 Hz, 2H), 5.92 (ddt, J¼16.2,
2
Cl
2
was treated with
2
Cl ,
2
13
2
2.50–2.35 (m, 8H); C NMR (50 MHz, CDCl
3
):
d
¼172.8, 172.7, 165.4,
(
1
(
1
n
159.9, 136.7, 136.5, 133.8, 130.3, 130.2, 129.0, 128.0, 127.9, 126.8,
122.6, 115.7, 115.6, 114.3, 64.5, 64.1, 63.3, 55.2, 35.2, 33.5, 29.2, 28.7.
Anal. Calcd for C27
ꢁ
1 1
3
d
30 2 5
H N O : C, 70.11; H, 6.54; N, 6.06. Found: C,
0.2, 7.0 Hz, 1H), 5.91 (ddt, J¼16.9, 9.8, 7.0 Hz, 1H), 5.42 (d,
70.36; H, 6.71; N, 5.94.
J¼13.2 Hz, 1H), 5.27 (d, J¼13.2 Hz, 1H), 5.24–5.11 (m, 5H), 4.67 (d,
J¼2.2 Hz, 1H), 3.74 (s, 3H), 3.12 (dt, J¼7.0, 1.3 Hz, 2H), 3.03 (dt, J¼7.0,
4.2.13. trans-1-(2-((But-3-enoyloxy)methyl)phenyl)-4-(4-
methoxyphenyl)-3-(pent-4-enoyloxy)azetidin-2-one 11a
1
1
.1 Hz, 2H); 13C NMR (75 MHz, CDCl
3
):
d
¼171.3, 171.0, 165.4, 159.7,
ꢀ
33.6, 130.5, 129.9, 128.9, 128.1, 127.9, 127.8, 126.6, 122.3, 122.2,
Following Method A (Section 4.2.1), a 0 C solution of 14 (0.14 g,
1
C
6
19.5, 118.6, 114.2, 63.5, 63.3, 60.2, 55.1, 40.7, 38.9. Anal. Calcd for
H N O : C, 69.11; H, 6.03; N, 6.45. Found: C, 68.81; H, 5.88; N,
25 26 2 5
.61.
0.4 mmol) in 16 mL of anhyd CH
(0.08 mL, 0.6 mmol) and freshly prepared 3-butenoyl chloride
(from 0.06 g, 0.57 mmol of 3-butenoic acid). Purification by chro-
matography (SiO , Hex/AcOEt 4:1) yielded pure 11a (0.12 g, 70%) as
2 2 3
Cl was treated with Et N
2
0
2
4
.2.10. trans-4-(4-Methoxyphenyl)-3-(pent-4-enamido)-1-(2-
yellow oil. IR (film):
1251, 1156, 755 cm ; H NMR (300 MHz, CDCl
n
max¼3080, 2923, 2853, 1769, 1747, 1642, 1516,
ꢁ
1 1
(
(prop-2-enoyloxy)methyl)phenyl)azetidin-2-one 8b
3
):
d
¼7.33–7.30 (m,
ꢀ
Following Method A (Section 4.2.1), a 0 C solution of 7b (0.12 g,
1H), 7.22–7.03 (m, 5H), 6.78 (d, J¼8.8 Hz, 2H), 5.87 (ddt, J¼17.7, 9.6,
6.9 Hz, 1H), 5.78 (ddt, J¼17.0, 10.5, 6.5 Hz,1H), 5.41 (d, J¼1.8 Hz, 1H),
5.35 (ABsyst, JAB¼13.3 Hz,1H), 5.19 (ABsyst, JAB¼13.3 Hz,1H), 5.11 (dq,
J¼10.5, 1.4 Hz, 1H), 5.10 (dq, J¼17.0, 1.5 Hz, 1H), 5.03 (dq, J¼17.7,
1.6 Hz, 1H), 5.02 (d, J¼1.8 Hz, 1H), 4.98 (dq, J¼9.6, 1.4 Hz, 1H), 3.68
(s, 3H), 3.07 (dt, J¼6.9, 1.4 Hz, 2H), 2.51 (dd, J¼6.8, 1.6 Hz, 1H), 2.49
0
0
.3 mmol) in 7 mL of anhyd CH
.4 mmol) and acryloyl chloride (0.03 mL, 0.4 mmol). Purification
Hex/AcOEt 3:1) yielded pure 8b
59.0 mg, 45%) as yellow oil. IR (film):
max¼3300, 2962, 1751, 1733,
H NMR (300 MHz, CDCl ):
¼7.44–
.41 (m, 1H), 7.29 (d, J¼8.8 Hz, 2H), 7.24–7.17 (m, 2H), 7.10–7.07 (m,
H), 6.84 (d, J¼8.8 Hz, 2H), 6.66 (br d, J¼7.1 Hz,1H), 6.45 (dd, J¼17.3,
.5 Hz, 1H), 6.17 (dd, J¼17.3, 10.4 Hz, 1H), 5.87 (dd, J¼10.4, 1.5 Hz,
2 2 3
Cl was treated with Et N (0.05 mL,
2
by chromatography (SiO ,
(
n
ꢁ
1
1
1683, 1533, 1261, 754 cm
;
3
d
1
3
7
1
1
(d, J¼7.0 Hz, 1H), 2.40–2.31 (m, 2H); C NMR (75 MHz, CDCl
3
):
¼171.7, 170.9, 162.5, 160.1, 136.1, 133.4, 130.2, 129.9, 129.7, 129.0,
128.0, 126.9, 126.8, 122.2, 118.8, 116.0, 114.4, 81.1, 64.3, 63.8, 55.2,
d