4936 J . Org. Chem., Vol. 65, No. 16, 2000
Boto et al.
material, MeOH (1 mL) was added. After stirring for 45 min
at room temperature, the reaction mixture was poured into
10% aqueous Na2S2O3 and extracted, dried, and evaporated
as before. The reaction products were purified by chromatog-
raphy on silica gel, giving the corresponding 2-methoxy
derivatives 14, 17b , and 18b . Methyl 2-methoxy-1-pyr-
rolidinecarboxylate14b (14), obtained in 80% yield from 1f, has
been previously prepared using a different methodology.
2,2-Dim et h yl-N-(4-oxob u t yl)p r op a n a m id e (8a ). Ob-
tained in 82% yield from 1a ; only the acyclic tautomer was
66.8 (CH2), 45.7 (CH2), 32.7 (CH2), 22.7 (CH2); minor rotamer
154.1 (C), 136.4 (C), 128.6 (2 × CH), 128.2 (CH), 127.8 (2 ×
CH), 81.3 (CH), 67.1 (CH2), 46.2 (CH2), 33.6 (CH2), 22.0 (CH2);
MS (EI) m/z (rel intensity) 221 (M+, 1), 203 (42), 91 (100);
HRMS calcd for C12H15NO3 221.1052, found: 221.1060. Anal.
Calcd for C12H15NO3: C, 65.14; H, 6.83; N, 6.33. Found: C,
64.99; H, 6.97; N, 6.30.
Meth yl 2-[(Meth oxyca r bon yl)a m in o]-1-p yr r olid in eca r -
boxyla te (15). Obtained in 89% yield from 2; two rotamers
at 26 °C; one rotamer at 70 °C; mp 130-131.5 °C (white crystal
from EtOAc); IR 3443, 1719, 1697, 1508, 1450, 1383 cm-1; 1H
NMR (500 MHz, 70 °C) δ 5.37 (1H, ddd, J ) 6.3, 3.2, 3.1 Hz),
5.0 (1H, br s), 3.65 (3H, s), 3.61 (3H, s), 3.45 (1H, ddd, J )
10.7, 7.8, 3.9 Hz), 3.31 (1H, ddd, J ) 10.5, 7.8, 7.8 Hz), 2.02
(2H, m), 1.91 (1H, m), 1.82 (1H, m); 13C NMR (125.7 MHz, 70
°C) δ 155.6 (C), 155.3 (C), 66.3 (CH), 52.3 (CH3), 51.7 (CH3),
46.3 (CH2), 33.2 (CH2), 22.6 (CH2); MS (EI) m/z (rel intensity)
202 (M+, <1), 187 (3), 143 (81), 127 (100); HRMS calcd for
C8H14N2O4: 202.0954, found 202.0959. Anal. Calcd for
C8H14N2O4: C, 47.52; H, 6.98; N, 13.85. Found: C, 47.69; H,
6.92; N, 13.47.
observed: syrup; IR 3467, 2831, 2728, 1724, 1653 cm-1 1H
;
NMR (500 MHz) δ 9.76 (1H, s), 5.82 (1H, br s), 3.26 (2H, dd,
J ) 6.8, 6.7 Hz), 2.53 (1H, dd, J ) 7.0, 6.9 Hz), 2.52 (1H, dd,
J ) 6.9, 6.9 Hz), 1.85 (2H, dddd, J ) 6.9, 6.9, 6.8, 6.8 Hz),
1.16 (9H, s); 13C NMR (50.3 MHz) δ 202.1 (C), 178.7 (C), 41.5
(CH2), 39.0 (CH2), 38.6 (C), 27.6 (3 × CH3), 21.8 (CH2); MS
(EI) m/z (rel intensity) 171 (M+, 6), 154 (36), 142 (20), 57 (100);
HRMS calcd for C9H17NO2 171.1259, found 171.1293. Anal.
Calcd for C9H17NO2: C, 63.13; H, 10.01; N, 8.18. Found: C,
63.02; H, 10.10; N, 8.43.
N-(4-Oxobu tyl)ben zam ide/1-Ben zoyl-2-pyr r olidin ol (9a/
9b). Obtained in 66% yield from 1b; tautomeric equilibrium
mixture aldehyde/hemiaminal, [1/1.3 (two rotamers at 26 °C
(7:1)]; [1/1 (one rotamer at 70 °C)]: syrup; IR 3450, 3362, 2830,
1700, 1653, 1525 cm-1; 1H NMR (500 MHz, 70 °C) δ 9.42 (1H,
s), 7.81 (2H, d, J ) 8.3 Hz), 7.72 (2H, d, J ) 8.4 Hz), 7.47 (1H,
dd, J ) 7.4, 7.4 Hz), 7.44 (1H, dd, J ) 7.4, 7.4 Hz), 7.42 (2H,
dd, J ) 7.5, 7.4 Hz), 7.34 (2H, dd, J ) 7.8, 7.7 Hz), 6.70 (1H,
br s), 6.64 (1H, dd, J ) 7.5, 7.4 Hz), 6.44 (1H, br s), 3.54 (2H,
dd, J ) 6.5, 6.5 Hz), 3.53 (2H, dd, J ) 6.4, 6.4 Hz), 2.65 (2H,
dd, J ) 6.0, 6.0 Hz), 2.59 (1H, dd, J ) 7.5, 7.5 Hz), 2.58 (1H,
dd, J ) 7.0, 7.0 Hz), 1.92 (2H, ddd, J ) 7.0, 7.0, 6.9 Hz), 1.44
(2H, br s); 13C NMR (125.7 MHz, 70 °C) δ 202.1 (CH), 170.9
(C), 167.6 (C), 135.7 (C), 134.3 (C), 131.2 (CH), 130.3 (CH),
128.4 (2 × CH), 128.3 (2 × CH), 127.1 (2 × CH), 126.7 (2 ×
CH), 82.3 (CH), 49.1 (CH2), 41.4 (CH2), 39.3 (CH2), 32.1 (CH2),
23.6 (CH2), 21.7 (CH2); MS (EI) m/z (rel intensity) 191 (M+,
Meth yl 5-Oxo-tetr a h yd r o-2-fu r a n ylca r ba m a te (16). Ob-
tained in 66% yield from 3; syrup; IR 3437, 1772, 1735, 1510
1
cm-1; H NMR (500 MHz) δ 5.99 (2H, br s), 3.72 (3H, s), 2.67
(1H, dd, J ) 13.0, 9.8 Hz), 2.55 (2H, m), 2.08 (1H, m); 13C NMR
(50.3 MHz) δ 175.7 (C), 155.8 (C), 83.7 (CH), 52.7 (CH3), 28.6
(CH2), 27.8 (CH2); MS (EI) m/z (rel intensity) 159 (M+, 3), 115
(100); HRMS calcd for C6H9NO4 159.0532, found 159.0535.
Anal. Calcd for C6H9NO4: C, 45.28; H, 5.70; N, 8.80. Found:
C, 45.33; H, 6.04; N, 8.70.
Meth yl (2S,4R)-4-Acetoxy-2-h yd r oxy-1-p yr r olid in eca r -
boxyla te (17a ) a n d Meth yl (2R,4R)-4-Acetoxy-2-h yd r oxy-
1-p yr r olid in eca r boxyla te (18a ). Obtained in 86% yield (1:
1) from 7a ; separable mixture (hexanes-EtOAc, 80:20).
Compound 17a : two rotamers at 26 °C (1.3:1); syrup; [R]D -31
(c ) 0.2); IR 3580, 1737, 1694, 1456, 1283, 1245 cm-1; 1H NMR
(500 MHz, 26 °C) δ major rotamer 5.58 (1H, d, J ) 6.0 Hz),
5.30 (1H, m), 4.10 (1H, br b), 3.75 (1H, m), 3.72 (3H, s), 3.65
(1H, m), 2.29 (1H, dd, J ) 6.0, 6.0 Hz), 2.12 (1H, m), 2.07 (3H,
s); minor rotamer 5.62 (1H, dd, J ) 5.5, 5.4 Hz), 5.49 (1H, d,
J ) 4.9 Hz), 5.25 (1H, m), 3.77 (3H, s), 3.47 (1H, d, J ) 12.1
Hz), 3.45 (1H, br b), 2.25 (1H, dd, J ) 6.0 6.0 Hz), 2.12 (1H,
m), 2.03 (3H, s); 13C NMR (125.7 MHz, 26 °C) δ major rotamer
170.4 (C), 155.6 (C), 81.3 (CH), 71.8 (CH), 51.7 (CH3), 39.6
(CH2), 38.4 (CH2), 21.1 (CH3); minor rotamer 170.6 (C), 155.9
(C), 81.2 (CH), 72.3 (CH), 50.8 (CH3), 39.6 (CH2), 38.6 (CH2),
20.9 (CH3); MS(EI) m/z (rel intensity) 202 (M+ - H, 12), 188
(2), 186 (5), 142 (20), 126 (100); HRMS calcd for C8H12NO5
202.0715, found 202.0717. Anal. Calcd for C8H13NO5: C, 47.29;
H, 6.89; N, 6.89. Found: C, 47.08; H, 6.65; N, 6.88. Compound
18a : two rotamers at 26 °C (4:1); syrup; [R]D -19.5 (c ) 0.22);
IR 3581, 3454, 1737, 1692 cm-1; 1H NMR (500 MHz, 26 °C) δ
major rotamer 5.63 (1H, dd, J ) 5.6, 5.5 Hz), 5.29 (1H, m),
4.07 (1H, br s), 3.76 (1H, m), 3.71 (3H, s), 3.46 (1H, d, J )
12.2 Hz), 2.10 (1H, dd, J ) 5.3, 4.0 Hz), 2.13 (1H, dd, J ) 5.3,
5.3 Hz), 2.02 (3H, s); minor rotamer 5.57 (1H, m), 5.29 (1H,
m), 3.76 (1H, m), 3.76 (3H, s); 3.57 (1H, d, J ) 8.8 Hz), 3.30
(1H, br s), 2.10 (1H, dd, J ) 5.3, 4.0 Hz), 2.16 (1H, dd, J )
3.9, 3.8 Hz), 2.02 (3H, s); 13C NMR (125.7 MHz, 26 °C) δ major
rotamer 170.4 (C), 155.8 (C), 81.3 (CH), 71.8 (CH), 52.5 (CH3),
50.8 (CH2), 38.6 (CH2), 21.0 (CH3); δ minor rotamer 170.4 (C),
155.8 (C), 80.6 (CH), 71.3 (CH), 52.8 (CH3), 51.1 (CH2), 39.6
(CH2), 21.0 (CH3); MS (EI) m/z (rel intensity) 202 (M+ - H, 6),
186 (4), 143 (26), 126 (100); HRMS calcd for C8H12NO5
202.0715, found 202.0709. Anal. Calcd for C8H13NO5: C, 47.29;
H, 6.45; N, 6.89. Found: C, 47.39; H, 6.42; N, 6.81.
6), 173 (105 (100), 77 (35); HRMS calcd for
C11H13NO2
191.0946, found 191.0956. Anal. Calcd for C11H13NO2: C,
69.09; H, 6.85; N, 7.32. Found: C, 69.13; H, 6.87; N, 7.25.
N-(5-Oxop en tyl)ben za m id e (10a ). Obtained in 61% yield
from 1c; only the acyclic tautomer was observed; syrup; IR
3451, 3369, 2726, 1722, 1653, 1625, 1522, 1429, 1277, 998
cm-1 1H NMR (500 MHz) 9.75 (1H, s), 7.76 (1H d, J ) 7.2
;
Hz), 7.48 (1H, dd, J ) 7.4, 7.3 Hz), 7.39 (2H, dd, J , ) 7.5, 7.4
Hz), 6.66 (1H, br s), 3.42 (2H, dd, J ) 12.9, 6.6 Hz), 2.49 (2H,
dd, J ) 6.0, 6.0 Hz), 1.68 (2H, m), 1.63 (2H, m); 13C NMR (125.7
MHz) 202.3 (CH), 167.6 (C), 135.5 (C), 131.3 (CH), 128.4 (2 ×
CH), 126.8 (2 × CH), 43.3 (CH2), 39.4 (CH2), 28.9 (CH2), 18.5
(CH2); MS (EI) m/z (rel intensity) 188 (M+ - OH, 46), 105 (100),
77 (33); HRMS calcd for C12H14NO 188.1075, found 188.1080.
Anal. Calcd for C12H15NO2: C, 70.22; H, 7.37; N, 6.82. Found:
C, 70.20; H, 7.54; N, 6.87.
P h en yl 2-Hyd r oxy-1-p yr r olid in eca r boxyla te (11). Ob-
tained in 95% yield from 1d ; two rotamers at 26 °C (2:1); one
1
rotamer at 70 °C; syrup; IR 3594, 1709, 1595, 1385 cm-1; H
NMR (500 MHz, 70 °C) δ 7.36 (2H, m), 7.17 (3H, m), 5.62 (1H,
br b), 3.73 (1H, br b), 3.53 (1H, br b), 3.52 (1H, m), 2.16 (1H,
m), 2.09 (1H, m), 1.99 (1H, m), 1.91 (1H, m); 13C NMR (125.7
MHz, 26 °C) δ major rotamer 169.9 (C), 150.9 (C), 129.3 (2 ×
CH), 125.4 (CH), 121.6 (2 × CH), 82.3 (CH), 46.2 (CH2), 32.7
(CH2), 22.8 (CH2); δ minor rotamer 169.9 (C), 153.8 (C), 129.3
(2 × CH), 125.5 (CH), 121.7 (2 × CH), 81.6 (CH), 46.4 (CH2),
33.8 (CH2), 22.0 (CH2); MS (EI) m/z (rel intensity) 207 (M+,
12), 189 (15), 114 (2), 94 (100); HRMS calcd for C11H13NO3
207.0921, found 207.0885. Anal. Calcd for C11H13NO3: C,
63.76; H, 6.32; N, 6.76. Found: C, 63.73; H, 6.19; N, 6.53.
Ben zyl 2-Hyd r oxy-1-p yr r olid in eca r boxyla te (12). Ob-
tained in 54% yield from 1e; two rotamers at 26 °C (2.5:1);
Meth yl (2S,4R)-4-Acetoxy-2-m eth oxy-1-p yr r olid in eca r -
boxyla te (17b) a n d Meth yl (2R,4R)-4-Acetoxy-2-m eth oxy-
1-p yr r olid in eca r boxyla te (18b). Obtained in 84% yield (1:
1) from 7a ; separable mixture (hexanes-EtOAc, 95:5). Product
17b: two rotamers at 26 °C (2:1); one rotamer at 70 °C; syrup;
[R]D +1.3 (c ) 0.45); IR 1737, 1704, 1459, 1391, 1247, 1089
cm-1; 1H NMR (500 MHz, 70 °C) δ 5.24 (2H, m), 3.89 (1H, dd,
J ) 12.6, 6.5 Hz), 3.74 (3H, s), 3.48 (1H, dd, J ) 12.6, 2.6 Hz),
3.39 (3H, s), 2.21 (1H, ddd, J ) 14.8, 6.7, 5.9 Hz), 2.12 (1H,
one rotamer at 70 °C; syrup; IR 3590, 3451, 1693, 1416 cm-1
;
1H NMR (500 MHz, 70 °C) δ 7.37-7.29 (5H, m), 5.52 (1H, d,
J ) 4.4 Hz), 5.18 (2H, s), 3.60 (1H, m), 3.39 (1H, m), 2.07 (1H,
m), 2.02 (1H, m), 1.94 (1H, m), 1.83 (1H, m), 1.46 (1H, br s);
13C NMR (125.7 MHz, 26 °C) δ major rotamer 155.4 (C), 136.5
(C), 128.5 (2 × CH), 128.0 (CH), 127.8 (2 × CH), 82.1 (CH),