Bagley et al.
73.3 (C), 61.9 (CH2), 61.8 (CH2), 53.1 (CH), 52.4 (Me), 52.3 (Me),
52.3 (CH), 47.0 (CH2), 27.2 (Me), 27.2 (Me), 18.9 (Me), 18.8
(Me); MS (APcI) m/z 353 (MH+, 44%), 297 (100), 279 (12), 120
(37).
) 8.2, 3.7 Hz), 3.91 (3H, s), 3.68 (3H, s), 2.05 (3H, s); 13C NMR
(100 MHz, CDCl3) δ 170.5 (C), 167.6 (C), 164.9 (C), 162.8 (C),
148.0 (C), 147.2 (C), 142.2 (C), 139.7 (CH), 137.8 (CH), 132.8
(C), 131.0 (C), 123.5 (CH), 119.9 (CH2), 62.2 (CH2), 55.6 (CH),
53.2 (Me), 52.8 (Me), 18.9 (Me); MS (APcI) m/z 390 (MH+,
100%).
(S)-Enamine 8a. NH4OAc (293 mg, 3.8 mmol) was added
to a stirred solution of 10a (269 mg, 0.76 mmol) in dry MeOH
(15 mL) under N2. After being heated at reflux overnight, the
reaction mixture was cooled to room temperature and evapo-
rated in vacuo. The residue was partitioned between EtOAc
(30 mL) and H2O (30 mL) and the aqueous layer further
extracted with EtOAc. The combined organic extracts were
washed sequentially with saturated aqueous NaHCO3 solution
and brine, dried (Na2SO4), and evaporated in vacuo. Purifica-
tion by flash chromatography on SiO2, eluting with light
petroleum-EtOAc (1:1), gave the title compound (214 mg,
80%) as a pale yellow oil (Found: MH+, 352.1871; C17H25N3O5
requires MH+, 352.1867); [R]24D +51.2 (c 1.0, CHCl3); IR (KBr)
νmax 3452, 3324, 2974, 1748, 1644, 1598, 1540, 1363, 1198,
1098, 1050, 1021, 976, 913, 778; 1H NMR (400 MHz; CDCl3) δ
7.79 (1H, s), 6.82 (2H, br s), 5.90 (1H, s), 5.89 (1H, d, J ) 8.5
Hz), 5.36 (1H, s), 5.00 (1H, s), 4.72 (1H, m), 3.78 (1H, dd, J )
8.9, 2.9 Hz), 3.68 (3H, s), 3.51 (1H, dd, J ) 8.9, 3.2 Hz), 2.10
(3H, s), 1.08 (9H, s); 13C NMR (100 MHz, CDCl3) δ 171.8 (C),
169.8 (C), 162.6 (C), 147.8 (C), 138.6 (C), 135.5 (CH), 131.3
(C), 119.1 (CH2), 84.2 (CH), 73.4 (C), 62.4 (CH2), 52.34 (CH),
52.30 (Me), 27.3 (Me), 19.0 (Me); MS (APcI) m/z 353 (100%),
352 (MH+, 67).
(S)-Oxazoline 29. A solution of (S)-alcohol 28 (41 mg, 0.10
mmol) and Burgess reagent (28 mg, 0.11 mmol) in dry THF
(5 mL) was stirred at 70 °C for 1 h and evaporated in vacuo.
Purification by flash chromatography on SiO2, eluting with
EtOAc-light petroleum (2:1), gave the title compound (24 mg,
63%) as a pale yellow oil (Found: MH+, 372.1191; C18H17N3O6
requires MH+, 372.1191); [R]29D +29.1 (c 0.87, CHCl3); IR (KBr)
νmax 2956, 1741, 1654, 1437, 1325, 1286, 1228, 1139, 1052, 958,
762; 1H NMR (400 MHz, CDCl3) δ 8.25 (1H, s), 8.06 (1H, d, J
) 8.0 Hz), 8.01 (1H, d, J ) 8.0 Hz), 5.93 (1H, s), 5.36 (1H, s),
4.94 (1 H, dd, J ) 10.7, 8.6 Hz), 4.64 (1H, app t, J ) 8.6 Hz),
4.57 (1H, dd, J ) 10.7, 8.6 Hz), 3.95 (3H, s), 3.77 (3H, s), 2.11
(3H, s); 13C NMR (100 MHz, CDCl3) δ 171.2 (C), 165.9 (C),
164.9 (C), 162.3 (C), 149.6 (C), 149.0 (C), 140.2 (C), 139.8 (CH),
139.1 (CH), 131.3 (C), 124.9 (C), 123.1 (CH), 118.8 (CH2), 70.3
(CH2), 68.8 (CH), 53.1 (Me), 52.8 (Me), 19.0 (Me); MS (APcI)
m/z (rel intensity) 372 (MH+, 100%).
(S)-Thioamide 30. A solution of oxazoline 29 (23 mg, 0.06
mmol) in MeOH-Et3N (2:1) (3 mL) was saturated with H2S,
stirred at room temperature for 3.5 h, and evaporated in vacuo.
Purification by flash chromatography on SiO2, eluting with
ether-acetone (5:1), gave the title compound (17 mg, 71%) as
a pale yellow oil (Found: MH+, 406.1062; C18H19N3O6S re-
quires MH+, 406.1067); [R]20D -29.6 (c 0.90, CHCl3); IR (KBr)
νmax 3400, 2956, 1736, 1542, 1437, 1388, 1293, 1262, 1232,
1140, 1087, 1027, 802, 761; 1H NMR (400 MHz, CDCl3) δ 9.18
(1H, d, J ) 6.1 Hz), 8.31 (1H, s), 7.91 (1H, d, J ) 8.0 Hz), 7.81
(1H, d, J ) 8.0 Hz), 5.89 (1H, s), 5.37 (1H, s), 5.18 (1H, m),
4.34 (1H, dd, J ) 11.9, 3.2 Hz), 4.05 (1H, dd, J ) 11.9, 2.9
(S)-Pyridine 7a from Enamine 8a. A solution of (S)-
enamine 8a (88 mg, 0.25 mmol) and methyl 2-oxo-4-(trimeth-
ylsilyl)but-3-ynoate (9) (61 mg, 0.33 mmol) in MeOH (10 mL)
was stirred at room temperature for 24 h and evaporated in
vacuo. Purification by flash chromatography on SiO2, eluting
with light petroleum-EtOAc (1:2), gave the title compound
(104 mg, 93%) as a pale yellow oil (Found: MH+, 446.1925;
C22H27N3O7 requires MH+, 446.1927); [R]29 +12.0 (c 1.8,
D
CHCl3); IR (KBr) νmax 2966, 1751, 1670, 1540, 1436, 1364, 1323,
Hz), 3.93 (3H, s), 3.83 (1H, br s), 3.77 (3H, s), 2.04 (3H, s); 13
C
1
1262, 1099, 801, 760; H NMR (400 MHz; CDCl3) δ 8.18 (1H,
NMR (100 MHz, CDCl3) δ 197.9 (C), 169.6 (C), 164.9 (C), 162.7
(C), 146.7 (C), 144.8 (C), 140.2 (CH), 139.7 (C), 138.5 (C), 137.7
(CH), 130.8 (C), 123.3 (CH), 120.1 (CH2), 61.2 (CH2), 61.0 (CH),
53.2 (Me), 52.9 (Me), 18.9 (Me); MS (APcI) m/z (rel intensity)
406 (MH+, 87%), 181 (68), 130 (100).
s), 8.05 (1H, d, J ) 8.0 Hz), 8.01 (1H, d, J ) 8.0 Hz), 7.00 (1H,
d, J ) 8.0 Hz), 5.93 (1H, s), 5.35 (1H, s), 4.85 (1H, m), 3.95
(3H, s), 3.80 (1H, dd, J ) 9.1, 3.0 Hz), 3.69 (3H, s), 3.57 (1H,
dd, J ) 9.1, 3.2 Hz), 2.10 (3H, s), 1.01 (9H, s); 13C NMR (100
MHz, CDCl3) δ 170.5 (C), 167.0 (C), 165.0 (C), 162.6 (C), 148.5
(C), 147.5 (C), 139.5 (C), 139.0 (CH), 138.1 (CH), 133.3 (C),
131.4 (C), 123.6 (CH), 119.0 (CH2), 73.6 (C), 61.8 (CH2), 53.5
(CH), 53.1 (Me), 52.5 (Me), 27.2 (Me), 19.0 (Me); MS (APcI)
m/z 446 (MH+, 100%).
(R)-Thiazoline 31. A solution of thioamide 30 (33 mg, 0.08
mmol) and Burgess reagent (24 mg, 0.10 mmol) in dry THF
(5 mL) was stirred at 70 °C for 30 min and evaporated in vacuo.
Purification by flash chromatography on SiO2, eluting with
EtOAc, gave the title compound (27 mg, 87%) as a pale yellow
oil (Found: MH+, 388.0962; C18H17N3O5S requires MH+,
(S)-Pyridine 7a from â-Ketoester 10a. A solution of (S)-
â-ketoester 10a (35 mg, 0.1 mmol), methyl 2-oxo-4-(trimeth-
ylsilyl)but-3-ynoate (9) (49 mg, 0.25 mmol), and NH4OAc (77
mg, 1.0 mmol) in MeOH (10 mL) was stirred at reflux for 5 h.
After cooling, the mixture was evaporated in vacuo. The
residue was partitioned between saturated aqueous NaHCO3
solution (5 mL) and EtOAc (8 mL) and the aqueous layer was
further extracted with EtOAc. The combined organic extracts
were washed sequentially with saturated aqueous NaHCO3
solution and brine, dried (Na2SO4), and evaporated in vacuo.
Purification by column chromatography on SiO2, eluting with
EtOAc-light petroleum (2:1), gave the title compound (36 mg,
81%) as a pale yellow oil with identical physical and spectro-
scopic properties.
388.0962); [R]23 +18.4 (c 1.06, CHCl3); IR (KBr) νmax 2952,
D
1
1742, 1618, 1436, 1323, 1281, 1227, 1137, 931, 851, 759; H
NMR (400 MHz, CDCl3) δ 8.16 (1H, s), 8.02 (1H, d, J ) 8.0
Hz), 7.91 (1H, d, J ) 8.0 Hz), 5.92 (1H, s), 5.35 (1H, s), 5.21
(1H, app t, J ) 9.7 Hz), 3.95 (3H, s), 3.77 (3H, s), 3.77 (1H, dd,
J ) 11.2, 9.7 Hz), 3.67 (1H, dd, J ) 11.2, 9.7 Hz), 2.12 (3H, s);
13C NMR (100 MHz, CDCl3) δ 170.8 (C), 169.6 (C), 165.0 (C),
162.4 (C), 148.6 (C), 148.5 (C), 139.4 (C), 139.3 (CH), 138.6
(CH), 131.4 (C), 130.8 (C), 123.2 (CH), 78.6 (CH), 53.1 (Me),
53.0 (Me), 37.0 (CH2), 19.1 (Me); MS (APcI) m/z (rel intensity)
388 (MH+, 100%).
Thiazole 32. A mixture of thiazoline 31 (27 mg, 0.07 mmol)
and activated MnO2 (121 mg, 1.39 mmol) in CH2Cl2 (3 mL)
was irradiated at 100 °C (initial power 300 W) for 150 min in
a sealed pressure-rated reaction tube (10 mL), using a CEM
Discover Microwave Synthesizer. The mixture was cooled
rapidly to room temperature in a flow of compressed air for 5
min, filtered through Celite, washed with CH2Cl2 (2 × 10 mL),
and evaporated in vacuo. Purification by flash chromatography
on SiO2, eluting with EtOAc-light petroleum (2:1), gave the
title compound (21 mg, 79%) as a pale yellow oil (Found: MH+,
386.0812; C18H15N3O5S requires MH+, 386.0805); IR (KBr) νmax
2956, 2919, 1724, 1560, 1542, 1438, 1322, 1229, 1139, 1087,
761; 1H NMR (400 MHz, CDCl3) δ 8.27 (1H, s), 8.20 (1H, d, J
) 8.0 Hz), 8.10 (1H, d, J ) 8.0 Hz), 7.96 (1H, s), 5.83 (1H, s),
(S)-Alcohol 28. A solution of pyridine 7a (60 mg, 0.14
mmol) in TFA-CH2Cl2 (1:1) (20 mL) was stirred at room
temperature for 20 min and evaporated in vacuo. Purification
by flash column chromatography on SiO2, eluting with EtOAc,
gave the title compound (50 mg, 96%) as colorless crystals,
mp 74-76 °C (aqueous EtOH) (Found: MH+, 390.1301;
C18H19N3O7 requires MH+, 390.1296); [R]25 -8.8 (c 0.5,
D
CHCl3); IR (KBr) νmax 3439, 2954, 1734, 1654, 1542, 1438, 1323,
1293, 1234, 1174, 1140, 760; 1H NMR (400 MHz; CDCl3) δ 8.22
(1H, s), 7.89 (1H, d, J ) 7.9 Hz), 7.84 (1H, d, J ) 7.9 Hz), 7.50
(1H, d, J ) 7.1 Hz), 5.89 (1H, s), 5.35 (1H, s), 4.70 (1H, m),
4.32 (1H, br s), 4.01 (1H, dd, J ) 8.2, 3.1 Hz), 3.94 (1H, dd, J
1398 J. Org. Chem., Vol. 70, No. 4, 2005