Alcaide and Almendros
(M+, 26), 149 (100). Anal. Calcd for C15H18NO4Br: C, 50.58;
H, 5.09; N, 3.93. Found: C, 50.69; H, 5.11; N, 3.90.
(M+ + 2, 100), 289 (M+, 98). Anal. Calcd for C11H16NO3Br: C,
45.53; H, 5.56; N, 4.83. Found: C, 45.62; H, 5.54; N, 4.80.
Bromohomoallyl Alcohol (+)-2b. From 132 mg (0.50
mmol) of 4-oxoazetidine-2-carbaldehyde (+)-1b was obtained
130 mg (67%) of compound (+)-2b as a colorless oil after
purification by flash chromatography (hexanes/ethyl acetate,
Procedure for the Preparation of Bromohomoallylic
Acetate (()-6e. Acetic anhydride (48 mg, 0.468 mmol), DMAP
(catalyst), and triethylamine (95 mg, 0.936 mmol) were
sequentially added dropwise to a stirred solution of the
bromohomoallylic alcohol (()-2e (138 mg, 0.39 mmol), in
dichloromethane (4 mL) at 0 °C, and the mixture was stirred
for 2 h at room temperature. The organic phase was washed
with water (2 × 2 mL), dried (MgSO4), and concentrated under
reduced pressure. Chromatography of the residue eluting with
dichloromethane/ethyl acetate (30/1) gave 150 mg (98%) of
compound (()-6e. Acetates 6 were prepared in a similar way.
Acetate (()-6e. Colorless solid. Mp: 106-107 °C (hexanes/
ethyl acetate). 1H NMR: δ 1.64 (s, 3H), 2.71 (br s, 1H),
2.73 (d, 1H, J ) 0.7 Hz), 3.78 (s, 3H), 4.06 (dd, 1H, J ) 8.8,
5.9 Hz), 4.42 (dd, 1H, J ) 9.3, 5.9 Hz), 5.54 (m, 5H), 6.03 (ddd,
1H, J ) 17.1, 10.0, 8.8 Hz), 6.86 and 7.32 (d, each 2H, J )
9.0 Hz). 13C NMR: δ 169.5, 165.0, 156.8, 130.2, 128.0, 127.4,
123.3, 121.1, 120.5, 114.1, 71.2, 56.4, 55.6, 55.0, 43.1, 20.5. IR
(KBr, cm-1): ν 1740, 1730. MS (EI), m/z: 395 (M+ + 2, 10),
393 (M+, 10), 149 (100). Anal. Calcd for C18H20NO4Br: C, 54.84;
H, 5.11; N, 3.55. Found: C, 54.93; H, 5.09; N, 3.53.
Procedure for Base-Promoted Isomerization of Com-
pound (()-6e: Preparation of (()-(E)-15a and (()-(Z)-15a.
To a solution of 3-vinyl-â-lactam (()-6e (87 mg, 0.22 mmol) in
acetonitrile (3.5 mL) was added potassium carbonate (213 mg,
1.44 mmol), and the mixture was heated for 18 h at 107 °C in
a sealed tube. After the mixture was cooled at room temper-
ature, the organic phase was washed with water (2 × 1 mL),
dried (MgSO4), and concentrated under reduced pressure.
Chromatography of the residue eluting with hexanes/ethyl
acetate (6:1) gave 17 mg (24%) of the less polar compound
(()-(Z)-15a and 33 mg (38%) of the more polar compound
(()-(E)-15a.
Acetate (()-(Z)-15a. Colorless oil. 1H NMR: δ 2.06 (s, 3H),
2.15 (d, 3H, J ) 7.3 Hz), 2.71 (m, 2H), 3.80 (s, 3H), 4.64
(d, 1H, J ) 4.1 Hz), 5.50 (d, 1H, J ) 2.0 Hz), 5.60 (s, 1H), 5.71
(m, 1H), 5.89 (q, 1H, J ) 7.1 Hz), 6.91 and 7.42 (d, each 2H,
J ) 9.0 Hz). 13C NMR: δ 168.6, 161.4, 155.5, 130.9, 129.5,
128.4, 128.2, 119.9, 118.5, 114.6, 69.9, 58.9, 55.5, 40.5, 20.7,
14.9. IR (CHCl3, cm-1): ν 1741, 1728. MS (EI), m/z: 395
(M+ + 2, 16), 393 (M+, 16), 149 (100). Anal. Calcd for
C18H20NO4Br: C, 54.84; H, 5.11; N, 3.55. Found: C, 54.95; H,
5.14; N, 3.53.
1
2/1). [R]D +133.1 (c 1.1, CHCl3). H NMR: δ 2.66 (d, 2H, J )
6.4 Hz), 3.78 (s, 3H), 4.36 (m, 3H), 4.43 (d, 1H, J ) 4.9 Hz),
4.79 (d, 1H, J ) 4.6 Hz), 5.29 (d, 1H, J ) 10.5 Hz), 5.37
(d, 1H, J ) 17.3 Hz), 5.52 (d, 1H, J ) 1.5 Hz), 5.63 (s, 1H),
5.96 (m, 1H), 6.86 and 7.38 (d, each 2H, J ) 9.0 Hz).
13C NMR: δ 165.0, 156.9, 133.1, 130.5, 129.7, 120.5, 120.0,
118.7, 114.3, 80.6, 72.7, 68.8, 60.0, 55.5, 45.4. IR (CHCl3, cm-1):
ν 3428, 1740. MS (EI), m/z: 383 (M+ + 2, 14), 381 (M+, 14),
149 (100). Anal. Calcd for C17H20NO4Br: C, 53.42; H, 5.27; N,
3.66. Found: C, 53.52; H, 5.24; N, 3.64.
Preparation of Bromohomoallyl Alcohol (()-2e. From
230 mg (0.996 mmol) of 4-oxoazetidine-2-carbaldehyde (()-1e
and after column chromatography eluting with dichloromethane/
ethyl acetate (20:1) were obtained 309 mg (88%) of the less
polar compound (()-2e and 27 mg (8%) of the more polar
compound, its anti-epimer.
Bromohomoallyl Alcohol syn-(()-2e. Colorless solid.
Mp: 119-120 °C (hexanes/ethyl acetate). 1H NMR: δ 2.26
(d, 1H, J ) 3.9 Hz), 2.53 (dd, 1H, J ) 14.5, 8.9 Hz), 2.69
(d, 1H, J ) 14.4 Hz), 3.78 (s, 3H), 4.00 (dd, 1H, J ) 8.8,
5.6 Hz), 4.21 (m, 2H), 5.43 (ddd, 1H, J ) 10.0, 1.5, 0.5 Hz),
5.47 (dt, 1H, J ) 17.1, 1.5 Hz), 5.55 (d, 1H, J ) 1.5 Hz), 5.69
(s, 1H), 5.99 (ddd, 1H, J ) 17.1, 10.0, 8.8 Hz), 6.85 and 7.47
(d, each 2H, J ) 9.0 Hz). 13C NMR: δ 165.8, 156.7, 131.2, 129.0,
128.8, 122.8, 120.7, 120.6, 114.1, 70.3, 59.2, 55.6, 55.1, 45.9.
IR (KBr, cm-1): ν 3431, 1741. MS (EI), m/z: 353 (M+ + 2, 22),
351 (M+, 22), 149 (100). Anal. Calcd for C16H18NO3Br: C, 54.56;
H, 5.15; N, 3.98. Found: C, 54.65; H, 5.11; N, 4.00.
Bromohomoallyl Alcohol anti-(()-2e. Colorless oil.
1H NMR: δ 2.17 (d, 1H, J ) 5.7 Hz), 2.68 (m, 2H), 3.80
(s, 3H), 4.09 (dd, 1H, J ) 8.5, 5.9 Hz), 4.28 (dd, 1H, J ) 5.9,
2.9 Hz), 4.53 (m, 2H), 5.38 (dd, 1H, J ) 11.0, 1.0 Hz), 5.45
(dt, 1H, J ) 18.3, 1.3 Hz), 5.56 and 5.70 (d, each 1H, J ) 1.7
Hz), 6.25 (ddd, 1H, J ) 17.1, 10.2, 8.9 Hz), 6.90 and 7.41
(d, each 2H, J ) 9.0 Hz). 13C NMR: δ 165.4, 156.6, 130.7, 130.0,
129.4, 121.8, 120.5, 119.3, 114.6, 66.9, 58.7, 55.8, 55.6, 44.9.
IR (CHCl3, cm-1): ν 3427, 1739. MS (EI), m/z: 353 (M+ + 2,
26), 351 (M+, 26), 149 (100). Anal. Calcd for C16H18NO3Br: C,
54.56; H, 5.15; N, 3.98. Found: C, 54.46; H, 5.12; N, 3.95.
Bromohomoallyl Alcohol (()-2f. From 123 mg
(0.50 mmol) of 4-oxoazetidine-2-carbaldehyde (()-1f was ob-
tained 123 mg (67%) of compound (()-2f as a colorless solid
after purification by flash chromatography (dichloromethane/
ethyl acetate, 12/1). Mp: 90-91 °C (hexanes/ethyl acetate).
1H NMR: δ 2.05 (d, 1H, J ) 5.1 Hz), 2.58 (m, 4H), 3.47 (ddd,
1H, J ) 8.3, 7.1, 5.4 Hz), 3.78 (s, 3H), 4.23 (t, 1H, J ) 5.5 Hz),
4.29 (m, 1H), 5.14 (dq, 1H, J ) 9.5, 1.4 Hz), 5.21 (dq, 1H,
J ) 16.6, 1.5 Hz), 5.56 (d, 1H, J ) 1.7 Hz), 5.68 (d, 1H,
J ) 0.7 Hz), 5.98 (m, 1H), 6.86 and 7.39 (d, each 2H, J )
9.0 Hz). 13C NMR: δ 164.4, 156.7, 135.5, 131.0, 129.2, 121.0,
120.6, 116.8, 114.2, 69.0, 58.3, 55.5, 50.7, 47.3, 29.1. IR (KBr,
cm-1): ν 3433, 1742. MS (EI), m/z: 367 (M+ + 2, 11), 365
(M+, 11), 149 (100). Anal. Calcd for C17H20NO3Br: C, 55.75;
H, 5.50; N, 3.82. Found: C, 55.86; H, 5.48; N, 3.79.
Bromohomoallyl Alcohol (+)-2j. From 106 mg (0.63
mmol) of 4-oxoazetidine-2-carbaldehyde (+)-1j was obtained
128 mg (70%) of compound (+)-2j as a colorless oil after
purification by flash chromatography (hexanes/ethyl acetate,
1/1). [R]D +44.9 (c 1.0, CHCl3). 1H NMR: δ 2.60 (br s, 1H),
2.64 (s, 1H), 2.67 (d, 1H, J ) 1.0 Hz), 3.63 (s, 3H), 3.76 (t, 1H,
J ) 4.5 Hz), 3.83 (dt, 1H, J ) 6.8, 1.1 Hz), 4.10 (dt, 1H,
J ) 5.4, 1.6 Hz), 4.21 (m, 1H), 4.52 (d, 1H, J ) 5.1 Hz), 5.22
(d, 1H, J ) 1.0 Hz), 5.29 (dq, 1H, J ) 7.6, 1.2 Hz), 5.56 (d, 1H,
J ) 1.7 Hz), 5.72 (d, 1H, J ) 1.2 Hz), 5.79 (m, 1H). 13C NMR:
δ 167.4, 132.0, 129.5, 120.0, 118.7, 83.3, 68.4, 59.9, 59.5, 45.7,
44.2. IR (CHCl3, cm-1): ν 3430, 1741. MS (EI), m/z: 291
Acetate (()-(E)-15a. Colorless oil. 1H NMR: δ 1.91 (d, 3H,
J ) 7.1 Hz), 2.16 (s, 3H), 2.66 (m, 2H), 3.81 (s, 3H), 4.77
(s, 1H), 5.45 (d, 1H, J ) 1.9 Hz), 5.59 (d, 1H, J ) 1.2 Hz), 5.78
(m, 1H), 6.41 (qd, 1H, J ) 7.3, 1.2 Hz), 6.93 and 7.48 (d, each
2H, J ) 9.0 Hz). 13C NMR: δ 170.2, 162.5, 156.4, 130.7, 128.3,
125.0, 119.7, 118.5, 114.7, 68.6, 59.9, 55.5, 40.6, 20.9, 14.8. IR
(CHCl3, cm-1): ν 1742, 1732. MS (EI), m/z: 395 (M+ + 2, 14),
393 (M+, 14), 149 (100). Anal. Calcd for C18H20NO4Br: C, 54.84;
H, 5.11; N, 3.55. Found: C, 54.94; H, 5.08; N, 3.58.
General Procedure for the Intramolecular Heck Re-
action. Preparation of Bicyclic â-Lactams 7-14. Pal-
ladium(II) acetate (0.03 mmol), triphenylphosphine
(0.07 mmol), and potassium carbonate (7.0 mmol) were se-
quentially added to a solution of the corresponding bromo-
homoallylic acetate 6 (1.0 mmol) in dimethylformamide
(15 mL), and the mixture was heated at the appropriate
temperature (see Table 2 and Schemes 2 and 3) in a sealed
tube. After the disappearance of the starting material (TLC),
the reaction mixture was cooled at room temperature and
diluted with ethyl acetate (10 mL). The organic phase was
washed with water (4 × 5 mL) and brine (3 × 5 mL), dried
(MgSO4), and concentrated under reduced pressure. Chroma-
tography of the residue eluting with hexanes/ethyl acetate or
dichloromethane/ethyl acetate mixtures gave analytically pure
fused â-lactams 7-14. Spectroscopic and analytical data for
some representative forms of 7-14 follow.
2718 J. Org. Chem., Vol. 70, No. 7, 2005