Full Paper
3,4-Dihydropyrido[2,1-a]isoindol-6(2H)-one (12): The crude
product was chromatographed on silica gel using petroleum ether/
1-(Benzo[d]thiazol-2-ylsulfonyl)-10b-hydroxy-1,3,4,10b-tetra-
hydropyrido[2,1-a]isoindol-6(2H)-one (20): Compound 20 was
recovered as a white solid after dehydration in 53 % yield. H NMR
1
ethyl acetate (5:5) as eluent to afford pure compound 12 (116 mg,
1
80 %) as a colorless oil. H NMR (300 MHz, CDCl3): δ = 7.74 (d, J = (400 MHz, [D6]DMSO): δ = 8.36–8.29 (m, 2 H), 8.27–8.20 (m, 1 H),
7.4 Hz, 1 H), 7.52 (d, J = 7.5 Hz, 1 H), 7.44 (t, J = 7.0 Hz, 1 H), 7.36
(t, J = 7.1 Hz, 1 H), 5.76 (t, J = 4.5 Hz, 1 H), 3.73 (t, J = 5.9 Hz, 2 H),
7.69 (m, 4 H), 7.61–7.55 (m, 1 H), 4.08–3.97 (m, 2 H), 2.92 (dd, J =
13.0, 9.8 Hz, 1 H), 2.46–2.39 (m, 1 H), 2.33–2.25 (m, 1 H), 1.85 (d, J =
2.32 (m, 2 H), 1.90 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 12.3 Hz, 1 H), 1.56–1.40 (m, 1 H) ppm. 13C NMR (101 MHz,
165.6, 135.0, 134.7, 131.2, 129.8, 128.6, 122.7, 119.3, 104.7, 38.2, 22.2,
[D6]DMSO): δ = 166.3, 163.7, 152.2, 145.5, 136.5, 131.5, 131.3, 129.7,
21.4 ppm. IR: νmax = 2935, 2865, 2842, 1734, 1693, 1664, 1471, 1468, 128.2, 127.9, 126.7, 125.1, 123.4, 122.2, 86.5, 69.2, 34.7, 24.2,
˜
1403, 1359, 1237, 725, 717, 692 cm–1. HRMS (ESI) calcd. for [M + 23.2 ppm. IR: νmax = 3221, 2944, 1670, 1473, 1416, 1317, 1148, 1020,
˜
Na]+: C12H11NNaO 208.0733, found 208.0723.
756, 727, 602, 577, 511 cm–1. HRMS (ESI) calcd. for [M + Na]+:
C19H16N2NaO4S2 423.0444, found 423.0441, m.p. 211–213 °C.
Typical Procedure for Vinylsulfone Synthesis (Method A): To a
solution of 1-[3-(benzo[d]thiazol-2-ylsulfonyl)propyl]-4,4-dimethyl- Typical Procedure for Vinylsulfone Synthesis (Method B): To a
piperidine-2,6-dione 2a (300 mg, 0.79 mmol) in THF (24 mL) at
–78 °C, was added boron trifluoride–diethyl ether (0.2 mL,
solution of 1-[3-(benzo[d]thiazol-2-ylsulfonyl)propyl]-4,4-dimethyl-
piperidine-2,6-dione 2a (300 mg, 0.79 mmol) in THF (24 mL) at
–78 °C, was added boron trifluoride–diethyl ether (0.2 mL,
1.6 mmol) and lithium bis(trimethylsilyl)amide (1.0
M in toluene,
1.6 mL, 1.6 mmol). The mixture was stirred at –78 °C for 30 min. A
phosphate buffer solution was added (3 mL) at –78 °C and the
mixture was extracted three times with ethyl acetate. The combined
organic layers were washed with brine, dried with Na2SO4 and the
solvents evaporated under vacuum. The residue is dissolved in dry
1.6 mmol) and lithium bis(trimethylsilyl)amide (1.0 M in toluene,
1.6 mL, 1.6 mmol). The mixture was stirred at –78 °C for 30 min.
The reaction was quenched with acetyl chloride (115 μL, 1.6 mmol)
at –78 °C. The reaction was warmed to room temperature and
stirred for 12 h. A phosphate buffer solution was added (3 mL) at
THF (24 mL) and MgBr2 (291 mg, 1.58 mmol) was added. The mix- –78 °C and the mixture was extracted three times with ethyl acet-
ture was stirred overnight at 50 °C. A phosphate buffer solution was
added (3 mL) at –78 °C and the mixture was extracted three times
with ethyl acetate. The combined organic layers were washed with
brine, dried with Na2SO4 and the solvents evaporated under
vacuum.
ate. The combined organic layers were washed with brine, dried
with Na2SO4 and the solvents evaporated under vacuum. The crude
product was chromatographed on silica gel using petroleum ether/
EtOAc mixtures as eluent.
1-(Benzo[d]thiazol-2-ylsulfonyl)-2,6,7,8-tetrahydroindolizin-5-
(3H)-one (14): The crude product was chromatographed on silica
gel using 2:3 petroleum ether/EtOAc mixture as eluent to afford
pure compound 14 (240 mg, 91 %) as a white-brown solid. 1H NMR
(300 MHz, CDCl3): δ = 8.15 (d, J = 7.8 Hz, 1 H), 7.96 (d, J = 7.7 Hz,
1 H), 7.55 (m, 2 H), 3.90 (t, J = 9.5 Hz, 2 H), 3.09 (t, J = 6.0 Hz, 2 H),
2.97 (t, J = 9.4 Hz, 2 H), 2.47 (t, J = 6.3 Hz, 2 H), 1.91 (m, 2 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 168.7, 167.4, 155.6, 152.9, 136.7, 127.8,
1-(Benzo[d]thiazol-2-ylsulfonyl)-7,7-dimethyl-2,6,7,8-tetra-
hydroindolizin-5-(3H)-one (4): The crude product was chromato-
graphed on silica gel using petroleum ether/ethyl acetate (4:6) as
eluent to afford pure compound 4 (261 mg, 92 %) as a white solid.
1H NMR (300 MHz, CDCl3): δ = 8.20–8.15 (m, 1 H), 8.01–7.96 (m, 1
H), 7.65–7.52 (m, 2 H), 3.94 (t, J = 9.0 Hz, 2 H), 3.07–2.94 (m, 4 H),
2.34 (s, 2 H), 1.06 (s, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 168.3,
167.5, 155.0, 153.0, 136.9, 127.9, 127.7, 125.5, 122.4, 113.0, 45.8, 44.4, 127.5, 125.4, 122.3, 111.6, 44.6, 32.0, 26.8, 22.8, 19.0 ppm. IR: νmax
=
˜
35.9, 31.4, 27.8, 27.2 ppm. IR: νmax = 2954, 2948, 2925, 1680, 1602, 2962, 2904, 2879, 2871, 1679, 1600, 1470, 1388, 1333, 1315, 1280,
˜
1465, 1389, 1339, 1321, 1291, 1281, 1274, 1149, 1106, 1083, 774,
732, 605 cm–1. HRMS (ESI) calcd. for [M + H]+: C17H19N2O3S2
363.0832, found 363.0822, m.p. 154–156 °C.
1143, 1108, 763, 629 cm–1. HRMS (ESI) calcd. for [M + H]+:
C15H15N2O3S2 335.0519, found 335.0525, m.p. 143–144 °C.
8-(Benzo[d]thiazol-2-ylsulfonyl)-1,5,6,7-tetrahydroindolizin-3-
9-(Benzo[d]thiazol-2-ylsulfonyl)-2,2-dimethyl-1,2,3,6,7,8-hexa- (2H)-one (15): The crude product was chromatographed on silica
hydro-4H-quinolizin-4-one (13): Evaporation gives pure com-
pound 13 (300 mg, quant.) without further purification as a yellow-
orange solid. 1H NMR (300 MHz, CDCl3): δ = 8.16 (d, J = 7.1 Hz, 1
H), 7.99 (d, J = 7.4 Hz, 1 H), 7.59 (m, 2 H), 3.76 (m, 2 H), 3.19 (s, 2
H), 2.72 (t, J = 6.2 Hz, 2 H), 2.40 (s, 2 H), 1.86 (m, 2 H), 0.98 (s, 6
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 169.2, 168.3, 152.7, 150.6,
136.7, 127.8, 127.6, 125.3, 122.3, 114.5, 46.4, 40.8, 39.3, 29.7, 27.4,
gel using petroleum ether/ethyl acetate mixture (4:6) as eluent to
afford pure compound 15 (248 mg, 95 %) as a white-brown solid.
1H NMR (300 MHz, CDCl3): δ = 8.17 (dd, J = 7.5, 1.4 Hz, 1 H), 7.98
(dd, J = 7.3, 1.5 Hz, 1 H), 7.65–7.52 (m, 2 H), 3.53 (t, J = 5.9 Hz, 2 H),
3.50–3.42 (m, 2 H), 2.65–2.55 (m, 4 H), 1.87 (m, 2 H) ppm. 13C NMR
(101 MHz, CDCl3): δ = 175.8, 168.1, 155.1, 153.0, 136.7, 127.7, 127.6,
125.4, 122.3, 106.4, 39.4, 28.0, 24.4, 23.0, 19.9 ppm. IR: νmax = 2963,
˜
25.4, 20.8 ppm. IR: νmax = 2956, 2931, 2894, 2871, 1685, 1579, 1469, 2916, 2360, 2339, 1722, 1600, 1467, 1453, 1403, 1359, 1319, 1307,
˜
1357, 1309, 1255, 1144, 1116, 762, 624 cm–1. HRMS (ESI) calcd. for 1245, 1146, 1116, 1091, 1079, 1048, 1010, 991, 875, 850, 827, 807,
[M + H]+: C18H21N2O3S2 377.0988, found 377.0994, m.p. 183–185 °C. 774, 631 cm–1. HRMS (ESI) calcd. for [M + Na]+: C15H14N2NaO3S2
357.0338, found 357.0341, m.p. 206–207 °C.
1-(Benzo[d]thiazol-2-ylsulfonyl)-9b-hydroxy-1,2,3,9b-tetra-
hydro-5H-pyrrolo[2,1-a]isoindol-5-one (19): Compound 19 was
recovered as a white solid after dehydration in 47 % yield. H NMR
(400 MHz, [D6]DMSO): δ = 8.34–8.28 (m, 1 H), 8.25–8.21 (m, 1 H),
7.98 (d, J = 7.6 Hz, 1 H), 7.75–7.56 (m, 5 H), 4.34 (dd, J = 11.2, 8.1 Hz,
1 H), 3.59 (m, 1 H), 3.48–3.42 (m, 1 H), 3.23–3.10 (m, 1 H), 2.72–2.61
(m, 1 H) ppm. 13C NMR (101 MHz, [D6]DMSO): δ = 168.4, 167.2,
9-(Benzo[d]thiazol-2-ylsulfonyl)-1,2,3,6,7,8-hexahydro-4H-quin-
olizin-4-one (17): The crude product was chromatographed on sil-
ica gel using petroleum ether/ethyl acetate (4:6) as eluent to afford
pure compound 17 (247 mg, 88 %) as an orange solid. 1H NMR
(300 MHz, CDCl3): δ = 8.13 (dd, J = 7.4, 1.5 Hz, 1 H), 7.95 (dd, J =
7.3, 1.6 Hz, 1 H), 7.54 (m, 2 H), 3.70 (m, 2 H), 3.30 (t, J = 6.0 Hz, 2
1
152.3, 145.2, 136.5, 132.8, 131.7, 130.2, 128.2, 127.9, 125.2, 125.0, H), 2.65 (t, J = 6.3 Hz, 2 H), 2.54 (t, J = 6.5 Hz, 2 H), 1.82 (m, 4
123.4, 122.7, 94.8, 67.0, 39.5, 29.5 ppm. IR: ν
= 3251, 2965, 2900,
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 169.7, 168.2, 152.7, 151.6,
136.6, 127.7, 127.4, 125.3, 122.2, 112.8, 41.0, 33.0, 26.7, 25.0, 20.6,
˜
max
1686, 1472, 1389, 1334, 1310, 1257, 1150, 1087, 761, 615,
522 cm–1. HRMS (ESI) calcd. for [M + Na]+: C18H14N2NaO4S2
409.0287, found 409.0285, m.p. 186–187 °C.
18.5 ppm. IR: νmax = 2952, 2900, 2883, 1687, 1578, 1469, 1381, 1356,
˜
1332, 1305, 1259, 1140, 1116, 1085, 1043, 766, 690, 628 cm–1. HRMS
Eur. J. Org. Chem. 2016, 2944–2953
2951
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim