5-(Acyloxy)pyrrolinones
J . Org. Chem., Vol. 64, No. 26, 1999 9531
Ta ble 1. Atom Typ es a n d P a r tia l Ch a r ges for th e
Acetic Acid 1-P h en yl-5-oxo-2,5-d ih yd r o-1H-p yr r ol-2-yl
Ester (1g). The procedure described above for 1e was followed,
starting from N-phenylpyrrole (3.95 g, 27.6 mmol) in 1.5 L of
1:1 water/THF. The brown solid product was recrystallized
from toluene, yielding 5-hydroxy-1-phenyl-1,5-dihydro-pyrrol-
2-one (0.95 g, 5.40 mmol, 20%) as a beige solid: 1H NMR
(CDCl3) δ 3.09 (d, J ) 10.0 Hz, 1H, OH), 5.98 (d, J ) 10.0 Hz,
1H, OCHN), 6.20 (d, J ) 6.1 Hz, 1H, CHdCHCO), 7.03 (dd, J
) 6.1, 1.7 Hz, 1H, CHdCHCO), 7.15-7.67 (m, 5H) (1H NMR
corresponds to the literature NMR in acetone-d6);14c 13C NMR
(CDCl3) δ 83.89 (d), 121.02 (d), 125.01, (d), 129.01 (d), 136.49
(s), 144.82 (d), 168.35 (s). A solution of the hydroxypyrrolinone
(0.15 g, 0.86 mmol) and acetic anhydride (0.18 g, 1.74 mmol)
in pyridine (2 mL) was stirred at room temperature for 18 h.
The solution was concentrated in vacuo at room temperature.
The resulting brown oil was filtered over silica gel and
concentrated in vacuo. After Kugelrohr distillation (0.001
mmHg, 100 °C), 1g (0.16 g, 0.74 mmol, 86%) was obtained as
a colorless oil: 1H NMR (CDCl3) δ 2.01 (s, 3H, OCOCH3), 6.33
(d, J ) 7.0 Hz, 1H, CHdCHCO), 7.05 (s, 1H, OCHN), 7.06 (dd,
J ) 7.0, 1.8 Hz, 1H, CHdCHCO), 7.18-7.48 (m, 5H); 13C NMR
(CDCl3) δ 20.76 (q), 82.79 (d), 121.90 (d), 125.70 (d), 129.20
(d), 130.20 (d), 135.85 (s), 141.85 (d), 168.51 (s), 170.17 (s).
HRMS: calcd for C12H11NO3, m/z 217.075; found, m/z 217.074.
Lip a se-Su bstr a te 1a Rea ction In ter m ed ia tea
atom name
atom type
charge
Câ
CT
0.05
0.10
-0.65
0.44
Hâ1, Hâ2
HA
OE
CT
Oγ
C7
C8
CT
-0.07
0.12
-0.75
-0.65
-0.08
0.12
-0.20
0.17
-0.20
0.17
0.60
H7, H8, H9
O4
O3
C5
H3
C3
H2
C2
H1
HA
OC
OS
CT
HA
CUA1
HA
CUA1
HA
C
C1
O1
O
0.55
N1
NP
0.40
a
CT ) aliphatic carbon (tetrahedral), HA ) aliphatic or
aromatic hydrogen, OE ) ether or acetal oxygen, OC ) charged
oxygen, OS ) ester oxygen, CUA1 ) carbon in double bond, first
pair, C ) carbonyl carbon, O ) carbonyl oxygen, and NP )
nitrogen in peptide, amide, or related group.
Acetic Acid 1-(2-(Meth ylsu lfa n yl)a cetyl)-5-oxo-2,5-d i-
h yd r o-1H -p yr r ol-2-yl E st er (1h ). First (methylthio)acetic
anhydride was synthesized from (methylthio)acetic acid (3.00
mL, 34.5 mmol) and acetic anhydride (3.25 mL, 34.5 mmol).
The mixture was refluxed for 4 h, and the reaction was forced
to completion by distilling off the acetic acid. After Kugelrohr
distillation (0.05 mmHg, 80-100 °C), (methylthio)acetic an-
hydride (2.81 g, 14.45 mmol, 84% yield) was obtained as a
solution of 1a (0.37 g, 2.00 mmol) in 40 mL of dichloromethane
at -10 °C. The mixture was stirred at -10 °C for 1 h and
subsequently at room temperature for 1 night. The solvent was
removed by passing air through the solution. The addition
product of diazomethane was obtained pure as a white solid
(0.44 g, 1.94 mmol, 97%), a mixture of two trans diastereo-
mers: 1H NMR (CDCl3) δ 1.94 (s, 3H, OCOCH3), 2.37 (s, 3H,
NCOCH3), 2.41-2.55 (m, 1H, CHCHCO), 4.65-4.74 (m, 1H,
HCHNdN), 4.95-5.05 (m, 1H, HCHNdN), 5.69-5.72 (m, 1H,
CHCO), 6.17 (s, 1H, OCHN); 13C NMR (CDCl3) δ 18.11 (q),
32.23 (q), 81.72 (t), 81.86 (d), 92.56 (d), 163.35 (s), 166.92 (s),
167.34 (s). The addition product (0.22 g, 0.97 mmol) was
dissolved in 20 mL of toluene and heated at reflux for 1 night
under a nitrogen atmosphere. After evaporation of the solvent
a light yellow solid was obtained. Purification by flash chro-
matography (silica gel, 1:1 hexane/EtOAc) afforded pure 1j
(0.16 g, 0.81 mmol, 84%) as a white solid: 1H NMR (CDCl3) δ
1.99 (s, 3H), 2.10 (s, 3H, OCOCH3), 2.47 (s, 3H, NCOCH3), 5.88
(s, 1H, CHdCHCO), 7.05 (s, 1H, OCHN); 13C NMR (CDCl3) δ
13.54 (q), 20.29 (q), 24.25 (q), 80.50 (d), 123.27 (d), 158.20 (s),
168.28 (s), 168.72 (s), 169.41 (s); HRMS calcd for C9H11NO4
m/z 197.069, found m/z 197.069.
colorless oil: 1H NMR (CDCl3) δ 2.13 (s, 3H), 3.12 (s, 2H); 13
C
NMR (CDCl3) δ 15.88 (q), 36.17 (t), 165.02 (s). To a mixture of
acetic acid 5-oxo-2,5-dihydro-1H-pyrrol-2-yl ester (1f) (1.00 g,
7.09 mmol), DMAP (0.09 g, 0.71 mmol), and pyridine (7 mL)
was added slowly (methylthio)acetic anhydride (1.89 g, 10.6
mmol). After 1 night of stirring at room temperature the
1
conversion was 58% (as judged by H NMR). Water (300 mL)
was added, and the solution was concentrated in vacuo, taking
care that the temperature not exceeds 25 °C. Toluene (100 mL)
was added, and the solution was concentrated in vacuo again.
The brown solid was dissolved in dichloromethane, and the
mixture was filtered over silica gel. The yellow solution was
concentrated in vacuo. Purification by flash chromatography
(silica gel, 7:1 hexane/EtOAc) afforded pure 1h (0.87 g, 3.77
mmol, 53%) as a colorless oil: 1H NMR (CDCl3) δ 2.04 (s, 3H),
2.08 (s, 3H), 3.71 (s, 2H), 6.21 (dd, J ) 5.5, 0.6 Hz, 1H, CHd
CHCO), 7.08-7.16 (m, 2H, OCHN and CHdCHCO); 13C NMR
(CDCl3) δ 15.19 (q), 20.30 (q), 37.14 (t), 80.11 (d), 128.52 (d),
Acetic Acid 5-Acetyl-6-oxo-3,3a ,4,5,6,6a -h exa h yd r op yr -
r olo[3,4-c]pyr azo-4-yl Ester (1k). Racemic acetic acid 1-acetyl-
5-oxo-2,5-dihydro-1H-pyrrol-2-yl ester (1a ) (0.18 g, 1.00 mmol)
and cyclopentadiene (0.30 mL, 3.00 mmol) were dissolved in
3 mL of dry toluene, and the solution was stirred at 100 °C in
a sealed flask for 6 h. After evaporation of the solvent a light
yellow oil was obtained. Purification by flash chromatography
(silica gel, 1: 3 hexane/EtOAc) afforded the pure Diels-Alder
product 1k (0.22 g, 0.89 mmol, 89%) as a white solid, mixture
of two trans diastereomers: 1H NMR (CDCl3) δ 1.31-1.56 (m,
2H, CH2), 1.97 and 1.98 (s, 3H, OCOCH3), 2.32 and 2.33 (s,
3H, NCOCH3), 2.56-2.62 (m, 1H, CHCO), 3.28-3.32 (m, 3H,
CHCH2CH and NCOCH), 6.02 (s, 1H, OCHN), 6.05-6.13 (m,
3H, CHdCH); 13C NMR (CDCl3) δ 20.58 (q), 24.84 (q), 42.90
(d), 44.90 (d), 49.84 (d), 82.64 (d), 133.88 (d), 135,48 (d), 169.48
(s), 170.00 (s), 175.90 (s). Anal. Calcd for C13H15NO4: C, 62.64;
H, 6.07; N, 5.62. Found: C, 62.84; H, 6.19; N, 5.73.
145.14 (d), 167.19 (s), 167.58 (s), 169.28 (s); MS (CI) for C9H11
-
NO4S m/z 247 (M + NH4)+.
Acetic Acid 1-Acetyl-5-oxop yr r olid in -2-yl Ester (1i). A
solution of acetic acid 1-acetyl-5-oxo-2,5-dihydro-1H-pyrrol-2-
yl ester (1a ) (0.16 g, 0.88 mmol) and 0.2 mL of triethylamine
in 1 mL of ethyl acetate was hydrogenated (at normal
pressure) in the presence of 10 mg of Pd/C (10%). After 1 night
of stirring at room temperature the reaction was complete (as
judged by 1H NMR). The reaction mixture was filtered over
Celite and washed with ethyl acetate. The solution was
concentrated under vacuum to give almost pure 1i in quan-
titative yield: 1H NMR (CDCl3) δ 2.12 (s, 3H, OCOCH3), 2.05-
2.19 (m, 1H), 2.31-2.45 (m, 1H), 2.54-2.70 (m, 1H), 2.58 (s,
3H, NCOCH3), 2.82-2.94 (m, 1H), 6.85 (d, J ) 5.5 Hz, 1H,
OCHN); 13C NMR (CDCl3) δ 20.52 (q), 24.60 (q), 24.75 (t), 30.23
(t), 81.05 (d), 169.36 (s), 169.77 (s), 174.70 (s); MS (CI) for
C8H11NO4 m/z 203 (M + NH4)+.
Gen er a l P r oced u r e for th e Lip a se-Ca ta lyzed Tr a n s-
ester ifica tion s of P yr r olin on es. A typical procedure is as
follows: 10 mg of immobilized enzyme (CALB) was added to
a solution of 0.15 mmol of substrate and 8 mg of tridecane
(internal standard) in 3 mL of hexane/n-BuOH (3:1). Dichlo-
romethane was added until the solution was clear (0-0.3 mL).
The suspension was stirred at room temperature for the time
indicated (Table 2). During the reaction aliquots of 0.3 mL
Acetic Acid 1-Acetyl-3-m eth yl-5-oxo-2,5-d ih yd r o-1H-
p yr r ol-2-yl Ester (1j). Diazomethane (ca. 12 mmol) could be
obtained rapidly from p-tolylsulfonylmethylnitrosamide (4.00
g, 18.7 mmol of Diazald) according to a literature procedure15
and was introduced, using a stream of nitrogen gas, into a
(15) Lombardi, P. Chem. Ind. 1990, 21, 708.