5740
S. B. Rosenblum et al. / Tetrahedron 56 (2000) 5735±5742
argon. A solution of acid chlorides derived from 12 and 13
(Oxalyl chloride, CH2Cl2, 1 h, 228C, 11.3 mmol) in toluene
(50 mL) was added dropwise over 0.5 h. The solution was
stirred at 808C for 18 h. The solution was cooled and
quenched with 1 N HCl, and diluted with ethyl acetate.
The solution was washed with 1 N HCl (2£), H2O, dried
with MgSO4 and concentrated in vacuo. The crude product
mixture was puri®ed by ¯ash chromatography, eluting with
1.91±2.10 (m), 2.77 (t), 3.20 (t), 3.83 (s, 3H, OCH3), 4.71
(d, J2.2 Hz), 4.78 (s, 2H, CH2OH), 7.00±7.50 (13H, Ar).
HRMS (FAB) calcd for C26H27NO3 401.1991, found
1
401.1984. 9d H NMR d 1.90±2.10 (m), 2.75 (t), 3.20 (t),
3.90 (s, 3H, OCH3), 4.71 (d, J2.2 Hz), 4.80 (s, 2H,
CH2OH), 7.00±7.50 (13H, Ar). HRMS (FAB) calcd for
C26H27NO3 401.1991, found 401.1985. 9e 1H NMR d
1.90±2.08 (m), 2.80 (t), 3.19 (t), 3.89 (s, 3H, OCH3), 4.68
(d, 2.3 Hz), 6.95±7.64 (13H, Ar). HRMS (FAB) calcd for
1
hexane±ethyl acetate (9:1) to yield 8j (65%) H NMR d
2.82 (p, J8.3, 15.9 Hz), 2.99 (sx, J5.0, 15.3 Hz), 3.39
1
C26H22NO2F3 439.1759, found 439.1760. 9f H NMR d
(d, J2.3, 5.4, 9.3 Hz), 3.93 (s, 3H, OCH3), 4.79 (d,
1.9±2.05 (m), 2.80 (t), 3.15 (t), 3.88 (s, 3H, OCH3), 4.67
(d, J2.0 Hz), 6.9±8.1 (13H, Ar). Anal. calcd for
C26H25NO4: C, 75.16; H, 6.06; N, 3.37. Found: C, 74.75;
H, 6.06; N, 3.42. 9g 1H NMR d 1.86±2.05 (m), 2.70 (t), 3.14
(t), 3.86 (s, 3H, OCH3), 4.64 (d, J2.2 Hz), 6.93±8.48 (13H,
Ar); HRMS (FAB) calcd for C24H24N2O2 372.1838, found:
0
J2.3 Hz), 6.27 (sx, J6.7, 15.7 Hz, H2 ), 6.58 (d,
0
J15.9 Hz, H3 ), 7.00±7.42 (12H, Ar); MS (CI) m/z 406
(M1H). Anal. calcd for C25H21F2NO2: C, 74.02; H, 5.22;
N, 3.45. Found: C, 73.69; H, 5.36; N, 3.46; and 14j (,2%)
1H NMR d 3.45 (d, J6.1 Hz, 2H), 3.76 (dd, 1H), 3.86 (s,
3H, OCH3), 5.71 (dd, 1H), 5.99 (sx, J8.0, 15.3 Hz), 6.9±
7.4 (12H, Ar); HRMS (FAB) calcd for C25H21N02F2
405.1540, found 405.1533.
1
372.1842. 9h H NMR d 1.9±2.09 (m), 2.82 (t), 3.19 (t),
3.87 (s, 3H, OCH3), 4.68 (d, J2.3 Hz), 6.55±8.34 (15H,
Ar). HRMS (FAB) calcd for C27H26N2O2 410.1994, found
410.1986. 9i H NMR d 1.80±2.09 (m), 2.72 (t), 3.17 (t),
1
1-(4-Fluorophenyl)-3-(3-(4-¯uorophenyl)-2/1-E-propenyl)-
4-(4-benzyloxyphenyl)-2-azetidinones 8k, 14k. Using the
method above, 8k and 14k were prepared from 4-benzyl-
oxybenzylidene-N-(4-¯uoro)phenylanisidine and the mix-
ture of 12 and 13. The crude product mixture was puri®ed
by ¯ash chromatography to afford 8k 1H NMR d 2.80 (sx),
2.94 (p), 3.36 (m), 4.74 (d, J2.2 Hz), 5.14 (s, 2H), 6.23 (sx,
3.85 (s, 3H, OCH3), 4.68 (d, J2.2 Hz), 6.96±9.14 (12H,
Ar); Anal. calcd for C23H25N3O2: C, 73.97; H, 6.21; N,
11.25. Found: C, 73.45; H, 6.24; N, 10.95. 9j H NMR d
1
1.75±2.10 (m), 2.72 (t), 3.15 (t), 3.85 (s, 3H, OCH3), 4.7 (d,
J2.2 Hz), 6.90±7.5 (12H, Ar); MS (CI) m/z 408 (M1H).
1
9k H NMR d 1.76±2.12 (m), 2.72 (t), 3.2 (t), 4.7 (d,
J2.2 Hz), 4.9 (s, 2H, CH2), 6.96±7.7 (17H, Ar). MS (CI)
m/z 484 (M1H). 9l 1H NMR d 1.80±2.09 (m), 2.72 (t), 3.17
(t), 4.68 (d, J2.2 Hz), 5. 3 (br s, 1H, OH), 6.96±7.4 (12H,
0
0
J7.5, 15.0 Hz, H21), 6.54 (d, J15.0 Hz, H3 ), 7.00±7.53
0
(17H, Ar); and 14k H NMR d 3.45 (d, J7.5 Hz, 2H, H3 ),
1
3.78 (d, J7.5 Hz), 4.76 (d, J2.3 Hz), 5.13 (s, 2H, CH2),
Ar). MS (CI) m/z 394 (M1H). 9n H NMR d 1.95±2.20
0
5.73 (dd, J7.5, 15.0 Hz), 5.98 (sx, J7.5, 15.0 Hz, H2 ),
(m), 2.82 (t), 3.23 (t), 3.92 (s, 3H, OCH3), 4.74 (d, J
6.98±7.48 (17H, Ar); MS (CI) m/z 482 (M1H).
2.2 Hz), 7.00±7.45 (13H, Ar). MS (CI) m/z 448 (M1H).
9o H NMR d 1.01 (t, 3H, CH3), 1.45 (sx, 2H, CH2), 1.68
1
1-(4-Fluorophenyl)-3-[3-(4-¯uorophenyl)-2-E-propenyl]-
4-(4-hydroxyphenyl)-2-azetidinone (8l). A solution of 8k
(34.3 mg, 0.07 mmol), boron trichloride-dimethyl sul®de
complex (127.7 mg, 0.71 mmol) and CH2Cl2 (2 mL) was
stirred at room temperature for 18 h. The reaction was
quenched with saturated NaHCO3 and extracted with ethyl
acetate. The organic phase was dried with MgSO4 and
concentrated in vacuo to yield 8l (18.9 mg, 68%). 1H
NMR d 2.80 (p), 2.97 (sx), 3.36 (m), 4.75 (d, J2.2 Hz),
(q, 2H, CH2), 1.88±2.10 (m), 2.62±2.71 (m, 2H, CH2), 3.19
(t), 3.88 (s, 3H, OCH3), 4.69 (d, J2.2 Hz), 6.94±7.38 (13H,
Ar). HRMS (FAB) calcd for C29H36NO2 428.2582, found
1
428.2590. 9p H NMR d 1.85±2.12 (m), 2.73 (t), 3.21 (t),
3.92 (s, 3H, OCH3), 4.68 (d, J2.2 Hz), 6.80±7.39 (12H,
Ar); MS (CI) m/z 408 (M1H); Anal. calcd for
C25H23F2NO2: C, 73.69; H, 5.69; N, 3.44. Found: C,
73.45; H, 5.73; N, 3.70.
0
5.15 (s br, 1H, 0H), 6.25 (sx, J7.5, 15.0 Hz, H2 ), 6.55 (d,
5-(4-Fluorophenyl)-4-pentenoic acid (12). A solution of
4-pentenoic acid 11 (5.0 g, 50 mmol), 4-¯uoroiodobenzene
10 (8.7 mL, 75.4 mmol), palladium acetate (2.25 g,
10.0 mmol), triphenylphosphine (2.62 g, 10.0 mmol), potas-
sium acetate (oven dried, 15.0 g, 153 mmol), anhydrous
tetrabutylammonium chloride (20.8 g, 74.8 mmol) and
DMF (40 mL) was heated to 808C for 18 h. The solution
was cooled, poured into a solution of 3 N NaOH (40 mL)
and extracted with ethyl acetate. The organic phase was
washed with 3 N NaOH (2£). The combined aqueous
phases were acidi®ed with 3 N HCl to pH 2, and extracted
with ethyl acetate. The product was recrystallized partially
with hexane yielding 12 (1.69 g, 17%) plus the mother
liquors which were further processed below. Total yield:
0
J15.8 Hz, H3 ), 6.90±7.39 (12H, Ar); MS (CI) m/z 392
(M1H).
3-(3-Arylpropyl)-2-azetidinones 9a±9p.
General procedure
A ¯ask was charged with either 8a±8l, 14j±14k or 16m±
16p (0.72 mmol), 10% palladium on carbon (33 mg) and
ethyl acetate (10 mL) were added. The heterogeneous
mixture was stirred under 1 atm of hydrogen gas (balloon)
for 2 h. The reaction mixture was ®ltered through celite and
concentrated in vacuo. The crude product mixture was puri-
®ed by ¯ash chromatography, eluting with hexane±ethyl
1
1
12 (5.38 g, 56%); H NMR d 2.70 (m, 4H, CH2), 6.25 (m,
1H, CvCH), 6.55 (d, J15.9 Hz, 1H, CvCH±Ar), 7.09±
acetate (4:1). 9a H NMR d 1.89±2.15 (m), 2.80 (m), 3.25
(t), 3.90 (s, 3H, OCH3), 4.73 (1H, d, J2.2 Hz), 6.1 (br s,
1H, OH) 6.9±7.5 (13H, Ar); MS (CI) m/z 388 (M1H). 9b
1H NMR d 1.87±2.10 (m), 2.71 (t), 3.20 (t), 3.58 (s, 3H,
OCH3), 3.90 (s, 3H, OCH3), 4.70 (d, J2.2 Hz), 5.25 (s, 2H,
CH2), 6.99±7.39 (13H, Ar); HRMS (FAB) calcd for
C27H29NO4 431.2097, found 431.2097. 9c 1H NMR d
7.44 (m, 4H, Ar).
5-(4-Fluorophenyl)-3-pentenoic acid (13). The mother
liquors from 12 prepared above contained a mixture of
both 12 and 13 (7.86 g, 1:1 mixture). Further puri®cation