6
Tetrahedron
flash chromatography on silica gel, (50% hexane/ethyl acetate)
(2H, d, J 8.1 Hz), 4.72 (1H, dd, J 7.8, 1.2 Hz), 4.62 (1H, ddd, J
ACCEPTED MANUSCRIPT
to give desired product 5 or 6.
11.7, 7.2, 4.5 Hz), 3.99 (1H, dt, J 12.0, 9.3 Hz), 3.24- 3.30 (2H,
m), 3.15 (1H, dd, J 16.5, 8.1 Hz), 2.95 (1H, dd, J 16.5, 1.5 Hz),
2.31 (3H, s, -CH3); δC (75 MHz, CDCl3, Me4Si) 21.0 (-CH3),
28.6, 37.7, 38.8, 48.8, 126.1, 129.8, 136.4, 137.5, 148.4 (C=C-
NO2), 156.4, 166.4 (C=O); m/z (TOF-MS ES+) 291 (100, MH+),
239 (40), 196 (10), 140 (30), 102 (90%); HRMS (ESI+): MH+,
found 291.0802. C14H15N2O3S requires 291.0803.
4.2.1. 8-Nitro-6,7-dihydro-2H-thiazolo[3,2-a]pyridin-5(3H)-
one (5a). Following the general procedure, heterocyclic
nitroenamine 2 (73.0 mg, 0.5 mmol), acryloyl chloride 4a (50µL,
55 mg, 0.6 mmol) and K2CO3 (138 mg, 1 mmol) were stirred in
o
CH2Cl2 (20 mL) at 25 C for 3 hours and purified by flash
chromatography (50% ethyl acetate/hexane) to afford 5a (90 mg,
90%) as yellow-greenish crystals, m.p. 190-191 ˚C; Rf: (33%
hexane/ethyl acetate) 0.70; νmax (KBr) 2922 (C-H), 2852, 1701
(amide C=O), 1577 (C=C-NO2), 1369, 1274, 1180, 1089, 1035,
819, 740 cm-1; δH (400 MHz, DMSO-d6, Me4Si) 4.12 (2H, t, J
7.6 Hz), 3.27 (2H, t, J 8.0 Hz), 2.96 (2H, t, J 7.6 Hz), 2.72 (2H, t,
J 8.0 Hz); δC (100 MHz, DMSO-d6, Me4Si) 21.6, 28.8, 30.7,
49.0, 123.4, 156.2, 167.2; m/z (TOF-MS ES+) 201 (100, MH+),
189 (18), 181 (2), 55 (2%); HRMS (ESI+): MH+, found
201.0329. C7H9N2O3S requires 201.0334.
4.2.5. 8-Nitro-7-(4-nitrophenyl)-6,7-dihydro-2H-thiazolo[3,2-
a] pyridin-5(3H)-one (5g). Following the general procedure,
heterocyclic nitroenamine
2
(73.0 mg, 0.5 mmol), p-
nitrocinnamoyl chloride 4g (106 mg, 0.5 mmol) and K2CO3 (138
mg, 1 mmol) were stirred in CH3CN (25 mL) at reflux for
overnight and purified by flash chromatography (50% ethyl
acetate/hexane) to afford 5g (93 mg, 58%) as yellow powder,
m.p. 204-206 ˚C; Rf: (33% hexane/ethyl acetate) 0.20; νmax
(KBr) 3074 (arom. C-H), 2906 (C-H), 2848, 1707 (amide C=O),
1572 (C=C-NO2), 1450, 1348, 1284, 1228, 1188, 1157, 1087,
949, 856, 703 cm-1; δH (300 MHz, CDCl3, Me4Si) 8.20 (2H, d, J
8.6 Hz), 7.32 (2H, d, J 9.0 Hz), 4.87 (1H, d, J 7.5 Hz), 4.64 (1H,
ddd, J 11.7, 6.3, 5.1 Hz), 4.06 (1H, dt, J 12.0, 9.3 Hz), 3.30 - 3.36
(2H, m), 3.25 (1H, dd, J 16.8, 8.4 Hz), 2.97 (1H, dd, J 16.8, 1.6
Hz); δC (75 MHz, CDCl3, Me4Si) 28.7, 38.1, 38.2, 49.1, 100.0,
124.5, 127.4, 146.8, 147.5, (C=C-NO2), 157.3, 165.3 (C=O); m/z
(TOF-MS ES+) 322 (55, MH+), 239 (95), 196 (8), 140 (30), 102
(93%); HRMS (ESI+): MH+, found 322.0486. C13H12N3O5S
requires 322.0498.
4.2.2.
7-Methyl-8-nitro-6,7-dihydro-2H-thiazolo[3,2-a]
pyridin-5(3H)-one (5b). Following the general procedure,
heterocyclic nitroenamine 2 (73.0 mg, 0.5 mmol), methacryloyl
chloride 4b (59µL, 63 mg, 0.6 mmol) and K2CO3 (138 mg, 1
mmol) were stirred in CH3CN (25 mL) at reflux for overnight
and purified by flash chromatography (50% ethyl acetate/hexane)
to afford 5b (85 mg, 79%) as orange-yellow crystals, m.p. 170-
172 ˚C; Rf: (50% ethyl acetate/hexane) 0.65; νmax (KBr) 2974 (C-
H), 2916, 1701 (amide C=O), 1581 (C=C-NO2), 1371, 1313,
1292, 1234, 1184, 1062, 995, 877, 717 cm-1; δH (300 MHz,
CDCl3, Me4Si) 4.42 (1H, pentet, J 6.0 Hz), 4.11 (1H, m), 3.35
(1H, q, J 6.0 Hz), 3.21 - 3.27 (2H, m), 2.67 - 2.85 (2H, m), 1.34
(3H, d, J 6.6 Hz); δC (75 MHz, CDCl3, Me4Si) 15.4, 28.7, 29.3,
35.4, 49.0, 122.7, 155.7, 170.2; m/z (TOF-MS AP+) 215 (100,
MH+), 198 (80), 183 (15), 159 (25%); HRMS (AP+): MH+,
found 215.0495. C8H11N2O3S requires 215.0490.
4.2.6.
7-(4-Chlorophenyl)-8-nitro-6,7-dihydro-2H-thiazolo
Following the general
[3,2-a]pyridin-5(3H)-one (5h).
procedure, heterocyclic nitroenamine 2 (73.0 mg, 0.5 mmol), p-
chlorocinnamoyl chloride 4h (100.5 mg, 0.5 mmol) and K2CO3
(138 mg, 1 mmol) were stirred in CH3CN (25 mL) at reflux for 6
hours and purified by flash chromatography (50% ethyl
acetate/hexane) to afford 5h (122 mg, 79%) as white solid, m.p.
162 ˚C (decomp.); Rf: (50% ethyl acetate/hexane) 0.82; νmax
(KBr) 3053 (arom. C-H), 2983 (C-H), 2916, 1701 (amide C=O),
1570 (C=C-NO2), 1438, 1282, 1226, 1147, 1109, 950, 848, 736
cm-1; δH (300 MHz, CDCl3, Me4Si) 7.28 (2H, d, J 8.1 Hz), 7.06
(2H, d, J 8.4 Hz), 4.73 (1H, dd, J 8.1, 1.5 Hz), 4.62 (1H, ddd, J
12.0, 6.9, 4.8 Hz), 4.01 (1H, dt, J 11.7, 9.3 Hz), 3.26 -3.31 (2H,
m), 3.17 (1H, dd, J 16.8, 8.1 Hz), 2.93 (1H, dd, J 16.8, 1.5); δC
(75 MHz, CDCl3, Me4Si) 28.6, 37.6, 38.6, 48.9, 127.7, 129.3,
133.7, 138.0, 144.7, 156.7, 165.9 (C=O); m/z (TOF-MS ES+) 311
(100, MH+), 239 (30), 196 (8), 140 (25), 102 (65%); HRMS
(ESI+): MH+, found 311.0250. C13H12ClN2O3S requires 311.0257.
4.2.3.
8-Nitro-7-phenyl-6,7-dihydro-2H-thiazolo[3,2-a]
pyridin-5(3H)-one (5c). Following the general procedure,
heterocyclic nitroenamine 2 (73.0 mg, 0.5 mmol), cinnamoyl
chloride 4c (83 mg, 0.5 mmol) and Cs2CO3 (163 mg, 0.5 mmol)
o
were stirred in CH3CN (25 mL) at 25 C for overnight and
purified by flash chromatography (33% ethyl acetate/hexane) to
afford 5c (123 mg, 89%) as yellow powder, m.p. 155-157 ˚C; Rf:
(50% ethyl acetate/hexane) 0.47; νmax (KBr) 3063 (arom. C-H),
2922 (C-H), 2854, 1703 (amide C=O), 1579 (C=C-NO2), 1450,
1371, 1278, 1226, 1157, 1091, 952, 844, 700 cm-1; δH (300 MHz,
CDCl3, Me4Si) 7.26 - 7.34 (3H, m, Ph), 7.13 (2H, d, J 8.1 Hz,
Ph), 4.76 (1H, dd, J 8.1, 1.2 Hz), 4.63 (1H, ddd, J 14.7, 6.9, 4.5
Hz), 4.00 (1H, dt, J 11.7, 9.3 Hz), 3.25 - 3.35 (2H, m), 3.17 (1H,
dd, J 16.8, 8.1 Hz), 2.97 (1H, dd, J 16.8, 1.8 Hz); δC (75 MHz,
CDCl3, Me4Si) 28.6, 38.1, 38.8, 48.9, 126.2, 127.8, 129.1, 129.2,
139.5(C=C-NO2), 156.5, 166.2 (C=O); m/z (TOF-MS APCI) 277
(100, MH+), 260 (40), 243 (8), 215 (8), 181 (1%); HRMS
(APCI): MH+, found 277.0653. C13H13N2O3S requires 277.0647.
4.2.7.
[3,2-a]pyridin-5(3H)-one (5i). Following the general procedure,
heterocyclic nitroenamine (73.0 mg, 0.5 mmol), p-
7-(4-Bromophenyl)-8-nitro-6,7-dihydro-2H-thiazolo
2
bromocinnamoyl chloride 4i (122.5 mg, 0.5 mmol) and K2CO3
(138 mg, 1 mmol) were stirred in CH3CN (25 mL) at reflux for 4
hours and purified by flash chromatography (50% ethyl
acetate/hexane) to afford 5i (100 mg, 57%) as yellow crystals,
m.p. 145 ˚C (decomp.); Rf: (50% ethyl acetate/hexane) 0.63; νmax
(KBr) 3053 (arom. C-H), 2929 (C-H), 2858, 1701 (amide C=O),
1581 (C=C-NO2), 1450, 1282, 1226, 1192, 1157, 1087, 952, 844,
763 cm-1; δH (300 MHz, CDCl3, Me4Si) 7.42 (2H, d, J 8.4 Hz),
6.99 (2H, d, J 8.4 Hz), 4.71 (1H, dd, J 6.9, 0.9 Hz), 4.61 (1H,
ddd, J 11.7, 6.6, 4.5 Hz), 3.99 (1H, dt, J 12.0, 9.3 Hz), 3.24 - 3.31
(2H, m), 3.16 (1H, dd, J 16.5, 8.1 Hz), 2.92 (1H, dd, J 13.5, 1.5
Hz); δC (75 MHz, CDCl3, Me4Si) 28.6, 37.7, 38.5, 48.9, 121.8,
125.5, 128.0, 132.3, 138.5 (C=C-NO2), 156.8, 165.9 (C=O); m/z
(TOF-MS ES+) 354 (50, MH+), 301 (25), 266(50), 239 (45), 140
4.2.4.
pyridin-5(3H)-one (5f). Following the general procedure,
heterocyclic nitroenamine (73.0 mg, 0.5 mmol), p-
8-Nitro-7-p-tolyl-6,7-dihydro-2H-thiazolo[3,2-a]
2
methylcinnamoyl chloride 4f (90 mg, 0.5 mmol) and Cs2CO3
o
(326 mg, 1 mmol) were stirred in CH3CN (25 mL) at 25 C for
overnight and purified by flash chromatography (50% ethyl
acetate/hexane) to afford 5f (97 mg, 67%) as yellow powder,
m.p. 213-214 ˚C; Rf: (33% hexane/ethyl acetate) 0.67; νmax (KBr)
3016 (arom.CH), 2916 (C-H), 2852, 1701 (amide C=O), 1581
(C=C-NO2), 1444, 1367, 1282, 1226, 1192, 1087, 950, 848, 723
cm-1; δH (300 MHz, CDCl3, Me4Si) 7.11 (2H, d, J 8.1 Hz), 7.01