Michael Acceptors as Precursors to Heterocycles
J . Org. Chem., Vol. 63, No. 16, 1998 5411
over MgSO4, and concentrated. The products were separated
by chromatography on SiO2 eluted with 20% EtOAc-CH2Cl2
to give 0.086 g (15%) of propenamide 11a (mp 177-178 °C
from CH3CN), 0.43 g (75%) of trans-azetidinone 12a (mp 167-
168 °C from CH3CN), and 0.011 g (2%) of cis-azetidinone 12a
(mp 143-144 °C from CH3CN).
F or Z-3-P h en yl-2-(p h en ylsu lfon yl)p r op en oyl Am id e
(11a ): 1H NMR (CDCl3) δ 7.93 (m, 2 H), 7.86 (s, 1 H), 7.45-
7.65 (m, 5 H), 7.39 (m, 3 H), 6.42 (br s, 1 H), 5.70 (br s, 1 H);
IR (CHCl3) 1687, 1620 cm-1; FAB MS, m/z 288 (MH+, C15H13O3-
SN+H+). Anal. Calcd for C15H13O3SN: C, 62.70; H, 4.56; N,
4.87. Found: C, 62.76; H, 4.61; N, 4.83.
Workup and isolation by chromatography as described gave
0.11 g (18%) of amide 11c as a white, crystalline solid (mp
99-102 °C from CH3CN) and 0.46 g (75%) of azetidinone 12c
as a white, crystalline solid (mp 186-187 °C from CH3CN).
F or Z-3-P h en yl-2-(4-m eth ylp h en ylsu lfon yl)p r op en a -
m id e (11c): 1H NMR (CDCl3) δ 7.83 (s, 1 H), 7.80 (d, 2 H, J )
8 Hz), 7.39 (m, 3 H), 7.32 (d, 2 H, J ) 8 Hz), 6.43 (br s, 1 H),
5.78 (br s, 1 H), 2.41 (s, 3 H); IR (KBr) 1655, 1586 cm-1; EI
MS, m/z 301.0810 (calcd for C16H15O3SN 301.0773). Anal.
Calcd for C16H15O3SN: C, 63.77; H, 5.02; N, 4.65. Found: C,
64.01; H, 4.86; N, 4.99.
F or tr a n s-4-P h en yl-3-(4-m eth ylp h en ylsu lfon yl)a zeti-
1
F or tr a n s-4-P h en yl-3-(p h en ylsu lfon yl)a zetid in -2-on e
d in -2-on e (tr a n s-12c): mp 186-187 °C; H NMR (CDCl3) δ
1
(tr a n s-12a ): H NMR (CDCl3) δ 8.03 (d, 2 H), 7.70 (m, 1 H),
7.87 (dxd, 2 H, J ) 3, 8 Hz), 7.37 (dxd, 2 H, J ) 3, 8 Hz), 7.35
(s, 5 H), 6.52 (br s, 1 H), 5.23 (d, 1 H, J ) 2 Hz), 4.34 (d, 1 H,
J ) 2 Hz), 2.44 (s, 3 H); IR (KBr) 1788 cm-1; EI MS, m/z
301.0810 (calcd for C16H15O3SN 301.0773). Anal. Calcd for
7.59 (m, 2 H), 7.36 (m, 5 H), 6.32 (br s, 1 H), 5.26 (d, 1 H, J )
2 Hz), 4.38 (d, 1 H, J ) 2 Hz); 13C NMR (CDCl3) δ 159.3, 138.3,
137.2, 135.2, 130.0, 129.7, 129.6, 129.5, 126.3, 79.4, 53.4; IR
(KBr) 2983, 1791 cm-1; FAB MS, m/z 288 (MH+, C15H13O3-
SN+H+). Anal. Calcd for C15H13O3SN: C, 62.70; H, 4.56; N,
4.87. Found: C, 62.65; H, 4.60; N, 4.83.
C
16H15O3SN: C, 63.77; H, 5.02; N, 4.65. Found: C, 63.68; H,
5.08; N, 4.62.
Ad d ition of Am m on ia to Z-3-P h en yl-2-(3-m eth ylp h e-
n ylsu lfon yl)p r op en oyl Ch lor id e (10d ). Meth od C. Sul-
fone 3d (1.00 g, 3.31 mmol) was dissolved in 3 mL of CDCl3
and 3 mL of oxalyl chloride. To the resulting solution was
added 20 µL of N,N-dimethylformamide. The resulting solu-
tion was heated at reflux for 0.5 h. The reaction mixture was
concentrated in vacuo to give 10d . The residue was dissolved
in 30 mL of CH2Cl2 and was treated with liquid ammonia as
described. The products were separated by chromatography
on SiO2 eluted with 20% EtOAc-CH2Cl2 and recrystallized
from CH3CN to give 0.11 g (11%) of amide 11d (mp 193-194
°C from CH3CN) and 0.66 g (66%) of azetidinone 12d (mp 165-
166 °C from CH3CN) as white, crystalline solids.
F or cis-4-P h en yl-3-(p h en ylsu lfon yl)a zetid in -2-on e (cis-
12a ): 1H NMR (CDCl3) δ 8.05 (d, 2 H), 7.63 (m, 3 H), 7.36 (m,
5 H), 7.05 (br s, 1 H), 5.46 (d, 1 H, J ) 4.3 Hz), 4.40 (d, 1 H,
J ) 4.3 Hz); IR (KBr) 1788 cm-1; FAB MS, m/z 288 (MH+,
C
15H13O3SN+H+). Anal. Calcd for C15H13O3SN: C, 62.70; H,
4.56; N, 4.87. Found: C, 62.81; H, 4.66; N, 4.85.
Ad d ition of Am m on ia to Z-3-P h en yl-2-(p h en ylsu lfo-
n yl)p r op en oyl Ch lor id e (10a ). Meth od B. Sulfone 3a
(0.576 g, 2.00 mmol) was dissolved in 3 mL of CDCl3 and 3
mL of oxalyl chloride. The resulting solution was heated at
1
reflux for ≈3 h until reaction was complete (monitored by H
NMR) and was concentrated to give 10a . Acid chloride 10a
was dissolved in 20 mL of dioxane. To this solution was added
3.0 mL of a 28% ammonium hydroxide solution. Workup as
described above for method A gave an 83:17 mixture of 12a
and 11a . Separation as described gave 0.41 g (72%) of 12a
and 0.086 g (15%) of 11a .
F or Z-3-P h en yl-2-(3-m eth ylp h en ylsu lfon yl)p r op en a -
1
m id e (11d ): H NMR (CDCl3) δ 7.87 (s, 1 H), 7.72 (m, 2 H),
7.61 (m, 2 H), 7.35-7.45 (m, 5 H), 6.48 (br s, 1 H), 5.74 (br s,
1 H), 2.43 (s, 3 H); IR (KBr) 3408, 1685 cm-1; EI MS, m/z
301.0785 (calcd for C16H15O3SN 301.0773). Anal. Calcd for
Ad d ition of Am m on ia to Z-3-P h en yl-2-(4-flu or op h e-
n ylsu lfon yl)p r op en oyl Ch lor id e (10b). Meth od A. Sul-
fone 3b (0.61 g, 2.0 mmol) was dissolved in 3 mL of CDCl3
and 3 mL of oxalyl chloride. The resulting solution was heated
at reflux for 1 h and was concentrated in vacuo to give acid
chloride 10b. Acid chloride 10b in 20 mL of dioxane was
treated with 6.0 mL of 1 M ammonia in dioxane as described.
Workup and isolation by chromatography as described gave
0.030 g (5%) of amide 11b as a white, crystalline solid (mp
100-103 °C from CH3CN) and 0.52 g (85%) of azetidinone 12b
as a white, crystalline solid (mp 114.5-117.5 °C from CH3-
CN).
C16H15O3SN: C, 63.77; H, 5.02; N, 4.65. Found: C, 63.58; H,
4.95; N, 4.63.
F or tr a n s-4-p h en yl-3-(3-m eth ylp h en ylsu lfon yl)a zeti-
d in -2-on e (tr a n s-12d ): 1H NMR (CDCl3) δ 7.87 (m, 2 H), 7.50
(m, 2 H), 7.62 (m, 2 H), 7.38 (m, 5 H), 6.32 (br s, 1 H), 5.27 (d,
1 H, J ) 2 Hz), 4.39 (d, 1 H, J ) 2 Hz), 2.45 (s, 3 H); 13C NMR
(CDCl3) δ 159.1, 139.7, 137.4, 136.7, 135.4, 129.2, 129.0, 128.94,
128.90, 125.9, 125.7, 78.5, 52.8, 21.2; IR (CHCl3) 1770 cm-1
;
EI MS, m/z 258 (M+-HNCO). Anal. Calcd for C16H15O3SN:
C, 63.77; H, 5.02; N, 4.65. Found: C, 63.75; H, 5.03; N, 4.70.
Gen er al P r ocedu r e for th e Addition of P r im ar y Am in es
to Z-3-P h en yl-2-(ph en ylsu lfon yl)pr open oyl Ch lor ide (10a).
A solution of amine (2 equiv) in CH2Cl2 (5 mL/mmol) was
added to a solution of 10a in CH2Cl2 (5 mL/mmol) at ambient
temperature. After the addition was complete, the reaction
mixture was stirred at ambient temperature for 0.5 h. The
reaction mixture was diluted with CH2Cl2, and the resulting
solution was washed with cold, 3 N HCl (3×), saturated
NaHCO3 solution, dried over MgSO4, and concentrated. The
residue was purified by chromatography on SiO2 (30-50%
EtOAc-hexanes), and the azetidinones were recrystallized
from CH3CN.
F or Z-3-P h en yl-2-(4-flu or op h en ylsu lfon yl)p r op en a -
1
m id e (11b): H NMR (CDCl3) δ 8.05 (dxd, 2 H, J ) 5, 9 Hz),
7.85 (s, 1 H), 7.39 (m, 2 H), 7.32 (m, 3 H), 7.27 (dxd, 2 H, J )
8, 9 Hz), 6.43 (br s, 1 H), 5.78 (br s, 1 H), (the CH3CN of
crystallization was observed as a singlet at δ 1.97); IR (KBr)
1655, 1586 cm-1; FAB MS, m/z 306 (MH+, C15H12FO3SN+H+).
Anal. Calcd for C15H12FO3SN‚1/2CH3CN: C, 58.97; H, 4.18;
N, 6.45. Found: C, 58.98; H, 4.34; N, 6.80.
For tr a n s-4-P h en yl-3-(4-flu or oph en ylsu lfon yl)azetidin -
2-on e (tr a n s-12b): 1H NMR (CDCl3) δ 8.05 (dxd, 2 H, J ) 5,
9 Hz), 7.40 (s, 5 H), 7.27 (dxd, 2 H, J ) 8, 9 Hz), 6.42 (br s, 1
H), 5.29 (d, 1 H, J ) 2.4 Hz), 4.37 (dxd, 1 H, J ) 1.0, 2.4 Hz),
(the CH3CN of crystallization was observed as a singlet at δ
1.97); 13C NMR (CDCl3) δ 167.0 (d, J ) 240 Hz), 159.2, 137.1,
132.6, 132.5, 129.8, 129.7, 126.3, 117.3 (d, J ) 23 Hz), 79.4,
53.4; IR (KBr) 2927, 2855, 1797 cm-1; FAB MS, m/z 306 (MH+,
F or tr a n s-1-Meth yl-4-p h en yl-3-(p h en ylsu lfon yl)a zeti-
d in -2-on e (13): 37%; mp 153-155 °C; 1H NMR (CDCl3) δ 7.99
(dxd, 2 H, J ) 2, 8 Hz), 7.68 (t, 1 H, J ) 7.5 Hz), 7.57 (t, 2 H,
J ) 7.8 Hz), 7.38 (m, 2 H), 7.25 (dxd, 2 H, J ) 2, 7.5 Hz), 5.02
(d, 1 H, J ) 2 Hz), 4.32 (d, 1 H, J ) 2 Hz), 2.84 (s, 3 H); IR
(KBr) 2983, 1767 cm-1; EI MS, m/z 301.0810 (calcd for
C16H15O3SN 301.0773). Anal. Calcd for C16H15O3SN: C, 63.77;
H, 5.02; N, 4.65. Found: C, 63.65; H, 4.80; N, 4.83.
F or tr a n s-1-Ben zyl-4-p h en yl-3-(p h en ylsu lfon yl)a zeti-
d in -2-on e (14): 51%; mp 153-155 °C; 1H NMR (CDCl3) δ 8.00
(dxd, 2 H, J ) 2, 8 Hz), 7.68 (t, 1 H, J ) 7.5 Hz), 7.56 (t, 2 H,
J ) 7.8 Hz), 7.35 (m, 3 H), 7.25 (m, 3 H), 7.21 (m, 2 H), 7.03
(m, 2 H), 4.85 (d, 1 H, J ) 15.1 Hz), 4.82 (d, 1 H, J ) 2 Hz),
4.41 (d, 1 H, J ) 2 Hz), 3.81 (d, 1 H, J ) 15.1 Hz); 13C NMR
(CDCl3) δ 158.8, 137.8, 134.6, 134.5, 133.8, 129.3, 129.2, 129.0,
128.9, 128.2, 128.0, 126.6, 76.6, 55.8, 45.2; IR (KBr) 3001, 1765
C
15H12FO3SN+H+), 262 (M-HNCO), 197 (M-HNCO-SO2H).
Anal. Calcd for C15H12FO3SN‚1/2CH3CN: C, 58.97; H, 4.18;
N, 6.45. Found: C, 58.89; H, 4.36; N, 6.72.
Ad d ition of Am m on ia to Z-3-P h en yl-2-(4-m eth ylp h e-
n ylsu lfon yl)p r op en oyl Ch lor id e (10c). Meth od A. Sul-
fone 3c (0.602 g, 2.00 mmol) was dissolved in 3 mL of CDCl3
and 3 mL of oxalyl chloride. The resulting solution was heated
at reflux for 1 h and was concentrated in vacuo to give acid
chloride 10c. Acid chloride 10c in 20 mL of dioxane was
treated with 6.0 mL of 1 M ammonia in dioxane as described.