Cycloadditions of 2-Azetidinone-Tethered Nitrones
4.95 (dt, 1H, J ) 5.0, 1.5 Hz), 6.80 (d, 2H, J ) 9.2 Hz), 7.21
(m, 6H), 7.53 (m, 2H). 13C NMR: δ 162.3, 156.8, 133.6, 130.7,
130.3, 129.6, 128.1, 127.9, 117.6, 114.7, 71.2, 55.5, 55.4, 51.8,
29.9. IR (KBr, cm-1): ν 1745, 1629. MS (EI) m/z: 401 (M+, 7),
179 (100). Anal. Calcd for C19H18N2O3Se: C, 56.86; H, 4.52;
N, 6.98. Found: C, 56.97; H, 4.48; N, 6.94.
Bicyclic Nitr on e (()-5a m . Colorless solid. Mp: 164-166
°C (hexanes/ethyl acetate). 1H NMR: δ 3.10 (dd, 1H, J ) 12.5,
10.6 Hz), 3.80 (s, 3H), 3.90 (dd, 1H, J ) 12.5, 3.7 Hz), 4.32 (m,
1H), 4.36 (d, 1H, J ) 4.8 Hz), 4.90 (dt, 1H, J ) 4.8 Hz, 1.5
Hz), 6.90 (d, 2H, J ) 8.9 Hz), 7.40 (m, 6H), 7.62 (m, 2H). 13C
NMR: δ_160.9, 156.8, 132.9, 130.3, 129.9, 129.4, 129.0, 127.6,
117.6, 114.7, 71.3, 55.6, 53.9, 51.2, 26.1. IR (KBr, cm-1): ν
1728, 1514. MS (EI) m/z: 401 (M+, 8), 179 (100). Anal. Calcd
for C19H18N2O3Se: C, 56.86; H, 4.52; N, 6.98. Found: C, 56.99;
H, 4.56; N, 6.89.
J ) 13.4, 6.0, 2.4 Hz), 2.50 (ddd, 0.5H, J ) 13.4, 9.0, 1.7 Hz),
2.90 (m, 1H), 3.61 (s, 1.5H), 3.63 (s, 1.5H), 3.64 (d, 0.5H, J )
12.0 Hz), 3.77 (d, 0.5H, J ) 12.0 Hz), 3.79 (s, 1.5H), 3.80 (s,
1.5H), 3.81 (s, 1.5H), 3.81 (s, 1.5H), 3.91 and 4.12 (d, each 0.5H,
J ) 12.0 Hz), 4.22 (dd, 1H, J ) 9.7, 5.4 Hz), 4.53 (d, 0.5H, J
) 5.4 Hz), 4.54 (d, 0.5H, J ) 5.7 Hz), 4.65 (t, 0.5H, J ) 8.4
Hz), 4.76 (dd, 0.5H, J ) 9.6, 6.0 Hz), 6.85 (m, 2H), 6.94 (m,
2H), 7.14 (m, 3H), 7.56 (m, 2H). 13C NMR: δ 172.8, 171.4,
165.3, 165.1, 156.4, 156.3, 136.7, 136.1, 130.9, 128.7, 128.6,
128.1, 127.9, 127.3, 127.1, 120.3, 120.1, 113.6, 113.5, 82.0, 81.9,
76.6, 74.4, 66.6, 66.5, 62.0, 60.8, 59.4, 59.3, 58.9, 58.2, 55.5,
55.5, 52.6, 52.5, 35.5, 34.7. IR (CHCl3, cm-1): ν 1743, 1720.
MS (CI) m/z: 427 (M+ + 1, 100), 426 (M+, 12).
Rea ction betw een Nitr on es 3 a n d N-P h en ylm a leim -
id e. Gen er a l P r oced u r e for th e Syn th esis of Isoxa zolid i-
n yl â-La cta m s 12. A solution of the corresponding nitrone 3
(0.50 mmol) and N-phenylmaleimide (0.60 mmol) in anhydrous
toluene (30 mL) was stirred at reflux temperature under argon
atmosphere. After complete disappearance of the nitrone
(TLC), the mixture was concentrated under reduced pressure.
Chromatography of the residue eluting with ethyl acetate/
hexanes mixtures gave analytically pure compounds 12.
Bicyclic Nitr on e (()-6. From 82 mg (0.30 mmol) of nitrone
(()-4c, 108 mg (83%) of compound (()-6 was obtained as a
pale orange solid after purification by flash chromatography
1
(ethyl acetate). Mp: 119-121 °C (hexanes/ethyl acetate). H
NMR: δ 2.90 (m, 2H), 3.64 (s, 3H), 3.95 (m, 1H), 4.48 (dd, 1H,
J ) 7.9, 5.7 Hz), 6.75 (s, 1H), 6.83 (d, 2H, J ) 8.9 Hz), 7.32
(m, 5 h), 7.49 (m, 3H). 13C NMR: δ 164.8, 156.1, 147.6, 132.5,
131.4, 129.5, 128.3, 127.9, 118.0, 117.5, 114.2, 111.2, 55.3, 53.3,
51.4, 30.6. IR (KBr, cm-1): ν 1722, 1512. MS (EI) m/z: 413
(M+, 16), 179 (100). Anal. Calcd for C20H18N2O3Se: C, 58.12;
H, 4.39; N, 6.78. Found: C, 58.20; H, 4.37; N, 6.75.
Cycloa d d u ct (+)-12a . From 50 mg (0.15 mmol) of nitrone
(+)-3a , 71 mg (95%) of compound (+)-12a was obtained as a
colorless solid after purification by flash chromatography
(hexanes/ethyl acetate 6/4). Mp: 123-125 °C (hexanes/ethyl
1
acetate). [R]D ) +60.3 (c 1.0, CHCl3). H NMR (acetone-d6): δ
3.65 and 3.82 (s, each 3H), 3.96 and 4.12 (d, each 1H, J ) 13.2
Hz), 4.18 (dd, 1H, J ) 7.8, 1.1 Hz), 4.24 (dd, 1H, J ) 9.1, 1.1
Hz), 4.56 (dd, 1H, J ) 9.1, 5.4 Hz), 4.81 (d, 1H J ) 5.4 Hz),
5.21 (d, 1H, J ) 7.8 Hz), 6.76 (m, 4H), 7.01 (m, 3H), 7.34 (m,
7H). 13C NMR (acetone-d6): δ 175.3, 174.9, 165.7 157.3, 137.2,
134.2, 132.2, 129.9, 129.8, 129.4, 128.8, 128.1, 127.1, 120.8,
114.3, 83.6, 79.5, 69.4, 63.6, 59.9, 59.2, 55.7, 53.8. IR (KBr,
cm-1): ν 1741, 1718. MS (EI) m/z: 513 (M+ + 1, 7), 512 (M+,
100). Anal. Calcd for C29H27N3O6: C, 67.83; H, 5.30; N, 8.18.
Found: C, 67.89; H, 5.34; N, 8.13.
Rea ction betw een Nitr on es 3 a n d Acyclic Alk en es.
Gen er a l P r oced u r e for th e Syn th esis of Isoxa zolid in yl
â-La cta m s 7-11. To a solution of the corresponding nitrone
3 (0.50 mmol) in anhydrous toluene (30 mL) was added the
appropriate dipolarophile (0.60 mmol) under argon atmo-
sphere. The reaction was stirred at reflux temperature until
complete disappearance of the nitrone (TLC), and the mixture
was concentrated under reduced pressure. Chromatography
of the residue eluting with ethyl acetate/hexanes mixtures gave
analytically pure compounds 7-11.
Cycloa d d u ct (()-12b. From 336 mg (1.00 mmol) of nitrone
(()-3c, 480 mg (94%) of compound (()-12b was obtained as a
colorless solid after purification by flash chromatography
(hexanes/ethyl acetate 1/1). Mp: 136-138 °C (hexanes/ethyl
Cycloa d d u ct (+)-7. From 100 mg (0.33 mmol) of nitrone
(+)-3a , 135 mg (95%) of compound (+)-7 was obtained as a
colorless solid after purification by flash chromatography
(hexanes/ethyl acetate 1/1). Mp: 141-143 °C (hexanes/ethyl
acetate). [R]D ) +84.3 (c 1.0, CHCl3). 1H NMR: δ 3.60 (s, 3H),
3.63 (s, 3H), 3.74 (dd, 1H, J ) 9.2, 3.3 Hz), 3.75 (s, 3H,), 3.79
(s, 3H), 3.96 (d, 1H, J ) 13.1 Hz), 4.03 (dd, 1H, J ) 8.4, 3.3
Hz), 4.15 (dd, 1H, J ) 8.4, 4.9 Hz), 4.36 (d, 1H, J ) 13.1 Hz),
4.53 (d, 1H, J ) 4.9 Hz), 4.91(d, 1H, J ) 9.2 Hz), 6.82 (d, 2H,
J ) 9.0 Hz), 7.10 (m, 2H), 7.18 (m, 2H), 7.36 (d, 2H, J ) 9.0
Hz). 13C NMR: δ 170.9, 169.6, 164.7, 156.5, 136.4, 130.4, 129.7,
128.0, 127.3, 119.7, 113.8, 82.6, 79.0, 69.3, 61.9, 59.7, 58.4, 55.4,
54.5, 52.4. IR (KBr, cm-1): ν 1742, 1735. MS (CI) m/z: 486
(M+ + 1, 100), 485 (M+, 32). (Anal. Calcd for C25H28N2O8: C,
61.98; H, 5.83; N, 5.78. Found: C, 61.93; H, 5.80; N, 5.75).
1
acetate). H NMR: δ 3.67 (d, 1H, J ) 12.1 Hz), 3.76 (dd, 1H,
J ) 8.1, 0.7 Hz), 3.83 (s, 3H), 4.09 (m, 3H), 4.31 (dd, 1H, J )
9.9, 5.9 Hz), 5.05 (d, 1H, J ) 8.1 Hz), 5.49 (m, 2H), 6.11 (m,
1H), 6.72 (m, 2H), 6.87 (d, 2H, J ) 8.7 Hz), 7.11 (m, 2H), 7.19
(m, 1H), 7.34 (m, 2H), 7.40 (d, 2H, J ) 8.7 Hz), 7.53 (m, 3H).
13C NMR: δ 173.9, 173.5, 164.8, 156.6, 134.5, 131.2, 130.5,
129.5, 129.2, 129.1, 128.4, 128.1, 128.0, 125.5, 123.2, 120.9,
113.6, 78.0, 69.5, 63.1, 55.8, 55.5, 54.9, 52.5. IR (KBr, cm-1):
ν 1744, 1730. MS (EI) m/z: 510 (M+ + 1, 3), 509 (M+, 5), 91
(100). Anal. Calcd for C30H27N3O5: C, 70.71; H, 5.34; N, 8.25.
Found: C, 70.62; H, 5.30; N, 8.30.
Cycloa d d u ct (+)-12d . From 75 mg (0.28 mmol) of nitrone
(-)-3e, 81 mg (66%) of compound (+)-12d was obtained as a
colorless solid after purification by flash chromatography
(hexanes/ethyl acetate 6/4). Mp: 198-200 °C (hexanes/ethyl
acetate). [R]D ) +64.7 (c 1.2, CHCl3). 1H NMR: δ 2.76 (s, 3H),
3.73 (s, 3H), 3.79 (s, 3H), 3.95 and4.09 (dd, each 1H, J ) 7.8,
1.5 Hz), 4.33 (dd, 1H, J ) 7.8, 5.4 Hz), 4.70 (d, 1H, J ) 5.4
Hz), 4.94 (d, 1H, J ) 7.8 Hz), 6.87 (d, 2H, J ) 9.0 Hz), 7.25
(m, 2H), 7.52 (m, 5H). 13C NMR: δ 174.0, 173.4, 164.9, 156.7,
131.3, 130.4, 129.3, 128.9, 125.7, 119.9, 114.0, 82.4, 71.0, 59.8,
58.6, 55.4, 52.7, 46.7. IR (KBr, cm-1): ν 1749, 1720. MS (CI)
m/z: 438 (M+ + 1, 100), 437 (M+, 15). Anal. Calcd for
Cycloa d d u ct (+)-8a . From 100 mg (0.33 mmol) of nitrone
(+)-3a , 127 mg (89%) of compound (+)-8a was obtained as a
colorless oil after purification by flash chromatography (hex-
anes/ethyl acetate 1/1). [R]D ) +102.5 (c 2.0, CHCl3). 1H
NMR: δ 3.52 (dd, 1H, J ) 7.1, 3.2 Hz), 3.57(s, 3H), 3.79 (s,
3H), 3.80 (s, 3H), 3.85 (s, 3H), 3.87 (d, 1H, J ) 12.9 Hz), 3.98
(dd, 1H, J ) 9.5, 3.2 Hz), 4.11 (d, 1H, J ) 12.9 Hz), 4.43 (dd,
1H, J ) 9.5, 5.4), 4.55 (d, 1H, J ) 5.4 Hz), 4.97 (d, 1H, J ) 7.1
Hz), 6.83 (d, 2H, J ) 9.3 Hz), 6.95 (m, 2H), 7.13 (m, 2H), 7.46
(d, 2H, J ) 9.3 Hz). 13C NMR: δ 171.8, 169.3, 164.8, 156.4,
135.5, 130.4, 129.0, 128.0, 127.3, 120.2 113.6, 82.0 78.6, 70.0,
60.0, 59.2, 58.6, 55.5, 55.3, 52.7, 52.6. IR (CHCl3, cm-1): ν 1743,
1710. MS (EI) m/z: 486 (M+ + 1, 12), 485 (M+, 100). Anal. Calcd
for C25H28N2O8: C, 61.98; H, 5.83; N, 5.78. Found: C, 62.07;
H, 5.81; N, 5.83.
C
23H23N3O6: C, 63.15; H, 5.30; N, 9.61. Found: C, 63.22; H,
5.33; N, 9.55.
Rea ction betw een Nitr on es 3 a n d Alk yn es. Gen er a l
P r oced u r e for th e Syn th esis of Isoxa zolin yl â-La cta m s
13-15. To a solution of the corresponding nitrone 3 (0.50
mmol) in anhydrous toluene (30 mL) was added the appropri-
ate dipolarophile (0.60 mmol) under argon atmosphere. The
reaction was stirred at room temperature until complete
Cycloa d d u cts 10a a n d 11a . From 100 mg (0.33 mmol) of
nitrone (+)-3a , 115 mg (92%) of compound 10a , containing ca.
48% of its epimer 11a , was obtained as a colorless oil after
purification by flash chromatography (hexanes/ethyl acetate
1/1). [R]D ) +114.2 (c 1.3, CHCl3). 1H NMR: δ 2.28 (ddd, 0.5H,
J . Org. Chem, Vol. 67, No. 20, 2002 7011