ꢀ
S. Lesniak et al. / Tetrahedron 65 (2009) 6364–6369
6368
4.3.8. 4-Benzoyl-1-methyl-pyrrolidin-2-one (2g)
4.12–4.25 (m, 1H), 7.12–7.37 (m, 5H, CHar). 13C NMR (50 MHz, CDCl3,
TMS)
128.04 and 128.46 (2ꢁ2CH), 139.58 (C), 173.45 (C]O). MS (70 eV)
m/z (%): 216 (16), 215 (84.6, Mþ), 214 (53), 131 (11), 105 (24), 104
(95), 103 (17), 84 (100), 83 (43), 78 (13), 77 (16), 55 (18). HRMS m/z
calcd for C14H17NO 215.13101, found 215.13107.
Separated from the major product by standard column chro-
matography (hexane/AcOEt, 1:1) and purified with preparative TLC
(SiO2, hexane/AcOEt, 3:7). Yield: 45 mg (11%). Light yellow very
viscous oil. IR (KBr, cmꢂ1): 2926, 1683 (nC]O ketone/amide), 1595, 1507,
1451, 1408, 1397, 1303, 1263, 1227, 692. 1H NMR (200 MHz, CDCl3,
d¼23.81, 24.33, 28.10, 36.61, 40.70, 40.86, 61.28, 127.00 (CH),
TMS)
d
¼2.77 (d, 3J¼8.7 Hz, 2H, C3–H2), 2.89 (s, 3H, NCH3), 3.63 (dd,
2J¼9.9 Hz, 3J¼8.9 Hz, 1H, C5–H), 3.78 (dd, 2J¼9.9 Hz, 3J¼5.9 Hz, 1H,
4.3.12. 8-Phenyl-hexahydro-pyrrolo[2,1-c][1,4]oxazin-6-one (4c)
Purified by chromatography (AcOEt) as isomeric mixture [trans/
cis w2:1, from the integral of two 0.5H triplets of the minor product
(at 3.79 and 3.86 ppm) and a high-field part of the 1H pseudo
triplet of doublets of the major product (at 3.32 ppm)]. Yield:
299 mg (69%). Both isomers were separated chromatographically
(SiO2/AcOEt) and recrystallized from the hexane/CH2Cl2 mixture.
First (major) eluate: trans-4c. Colourless crystals. Mp 97–99 ꢀC. IR
(KBr, cmꢂ1): 1690 (nC]O), 1453, 1423, 1285, 1097, 1049, 1026, 769,
C5–H), 4.08–4.24 (m, 1H, C4–H), 7.46–7.64 (m, 3H, CHar), 7.91–7.98
(m, 2H, CHar). 13C NMR (50 MHz, CDCl3, TMS)
d¼29.60, 34.19, 38.12,
50.70, 128.65 and 129.11 (2ꢁ2CH), 133.92 (CH), 135.42 (C), 172.43
(C]Oamide), 198.07 (C]Oketone). MS (70 eV) m/z (%): 204 [8,
(Mþ1)þ], 203 (62, Mþ), 186 (11), 175 (23), 160 (33), 145 (10), 105
(100), 98 (18), 77 (53), 70 (26), 51 (13), 42 (12). HRMS m/z calcd for
C12H13NO2 203.09463, found 203.09443.
4.3.9. 1-Methyl-4-phenyl-pyrrolidin-2-thione (2h)
702. 1H NMR (200 MHz, CDCl3, TMS)
2.91 (m, 1H), 2.94–3.12 (m, 2H), 3.13–3.27 (m, 1H), 3.30–3.48 (m,
d
¼2.52–2.69 (m, 1H), 2.72–
Obtained by FVT of 1h.12 Purified by chromatography on SiO2
(hexane/AcOEt, 1:1). Yield: 191 mg (50%). Light brown oil. IR (neat,
cmꢂ1): 2930, 1603, 1526, 1495, 1463, 1399, 1312, 1135, 759, 700. 1H
1H), 3.62–3.75 (m, 1H), 3.90–4.18 (m, 3H), 7.20–7.44 (m, 5H, CHar).
13C NMR (50 MHz, CDCl3, TMS)
d
¼38.93, 40.20, 41.90, 61.60, 65.94,
NMR (200 MHz, CDCl3, TMS)
d
¼3.08–3.24 (1H, m, one of C3–H2), 3.31
71.97, 127.20 (2CH), 127.50 (CH), 129.07 (2CH), 140.34 (C), 172.01
(C]O). MS (70 eV) m/z (%): 218 [10, (Mþ1)þ], 217 (69, Mþ), 187 (13),
104 (100), 103 (11), 86 (20). HRMS m/z calcd for C13H15NO2
217.11028, found 217.11022. Second (minor) eluate: cis-4d. Colour-
less solids. Mp 84–87 ꢀC. IR (KBr, cmꢂ1): 2902, 1686 (nC]O), 1452,
1424, 1386, 1352, 1292, 1261, 1094, 769, 702, 626. 1H NMR
(s, 3H, NCH3), 3.36–3.82 (m, 3H), 4.10 (1H, dd, J¼11.0 and 8.1 Hz, one
of C5–H2), 7.16–7.39 (m, 5H, CHar). 13C NMR (50 MHz, CDCl3, TMS)
d
¼35.43 (NCH3), 38.85 (CH), 52.17 (CH2), 63.85 (CH2), 126.68 (2CH),
127.27 (CH), 128.99 (2CH), 141.57 (C), 200.30 (C]S). MS (70 eV) m/z
(%): 192 [14, (Mþ1)þ], 191 (100, Mþ), 147 (13), 115 (20), 104 (31), 87
(12). HRMS m/z calcd for C11H13NS 191.07687, found 191.07674.
(200 MHz, CDCl3, TMS)
3.13–3.29 (m, 1H), 3.36–3.50 (m, 1H), 3.62–4.10 (m, 4H), 7.13–7.42
(m, 5H, CHar). 13C NMR (50 MHz, CDCl3, TMS)
d
¼2.63–2.98 (m, 3H), 2.99–3.12 (m, 1H),
4.3.10. 1-Phenyl-hexahydro-pyrrolizin-3-one (4a)
d
¼36.95, 38.62, 40.80,
Purified by SiO2 chromatography (AcOEt) as a partially separable
diastereomeric mixture (ratio trans/cis w2:1, from the integrals of
1H multiplets at 3.95 and 4.27 ppm, respectively). Yield: 285 mg
(71%). Light yellowoil. IR (neat, cmꢂ1): 2971, 2879,1697 (nC]O),1497,
1454,1416,1333, 755, 702. MS (70 eV) m/z (%): 201 (47, Mþ),105 (10),
104 (100), 103 (14), 78 (10), 70 (57). HRMS m/z calcd for C13H15NO
201.11536, found 201.11552. 1H NMR (200 MHz, CDCl3, TMS) for
58.26, 65.68, 69.44, 127.52 (CH), 127.65 and 128.82 (2ꢁ2CH), 138.43
(C), 173.55 (C]O). MS (70 eV) m/z (%): 218 [9, (Mþ1)þ], 217 (62,
Mþ), 187 (11), 104 (100), 103 (11), 86 (20). HRMS m/z calcd for
C13H15NO2 217.11028, found 217.11025.
4.3.13. 8-Phenyl-hexahydro-pyrrolo[2,1-c][1,4]thiazin-6-one (4d)
Purified by chromatography (AcOEt) to give an isomeric mixture
[trans/cis w2:1, from integrals of the 1H multiplet signals at 3.61
and two 0.5H signals at 4.05 and 4.37 ppm, respectively]. Yield
298 mg (64%). Both isomers were separated and purified as for 4c.
First (major) eluate: trans-4d. Almost colourless solids. Mp 99–
102 ꢀC. IR (KBr, cmꢂ1): 1686 (nC]O), 1419, 1365, 1361, 1266, 1252,
w1:1 mixture
d
¼0.81–1.02 (m, 0.5H, cis), 1.41–1.68 (m, 1H), 1.72–
1.98 (m, 1H), 1.98–2.22 (m, 1.5H), 2.66 (dd, 2J¼16.7 Hz, 3J¼2.3 Hz,
0.5H, one of C2–H2, cis), 2.81 (dd, 2J¼16.0 Hz, 3J¼8.7 Hz, 0.5H, one of
C2–H2, trans), 2.92–3.38 (m, 2.5H), 3.44–3.75 (m, 1.5H), 3.88–4.02
(m, 0.5H, C7a–H, trans), 4.20–4.34 (m, 0.5H, C7a–H, cis), 7.07–7.14
(m,1H, CHar), 7.22–7.42 (m, 4H, CHar). First (less polar) eluate: trans-
773, 707. 1H NMR (200 MHz, CDCl3, TMS)
d
¼0.82–0.96 (m, 1H),
4b. 13C NMR (50 MHz, CDCl3, TMS)
d
¼27.04, 31.41, 41.39, 43.18,
1.10–1.60 (m, 2H), 2.45–3.25 (m, 5H), 3.40–3.80 (m, 1H), 4.40–4.50
48.62, 68.67, 127.06 (2CH), 127.16 (CH), 128.84 (2CH), 140.58 (C),
(m, 1H), 7.10–7.45 (m, 5H, CHar). 13C NMR (50 MHz, CDCl3, TMS)
173.17 (C]O). Second (more polar) eluate: cis-4b. 13C NMR (CDCl3,
d
¼26.90, 33.00, 38.48, 42.33, 45.76, 65.02, 127.31 (2CH), 127.46
50 MHz, TMS)
127.69 (2CH), 128.65 (2CH), 140.62 (C), 174.27 (C]O).
d
¼26.37, 26.79, 41.47, 41.63, 41.79, 66.00,127.06 (CH),
(CH), 128.98 (2CH), 140.43 (C), 173.00 (C]O). MS (70 eV) m/z (%):
234 (15), 233 (92, Mþ), 187 (16), 186 (11), 172 (13), 159 (10), 104
(100), 103 (15), 102 (17), 77 (10). HRMS m/z calcd for C13H15NOS
233.08744, found 233.08747. Second (minor) eluate: cis-4d. Light
yellow solids. Mp 101–103 ꢀC. IR (KBr, cmꢂ1): 1686 (nC]O), 1452,
1424, 1291, 1094, 769, 702, 626. 1H NMR (200 MHz, CDCl3, TMS)
4.3.11. 1-Phenyl-hexahydro-indolizin-3-one (4b)
Purified by SiO2 chromatography (AcOEt) as an isomeric mixture
[trans/cis w2:1, from integrals of the multiplet signals at 3.30 ppm
(1H) and 3.66 ppm (2H), respectively]. Yield: 314 mg (73%). Both
products were separated chromatographically on SiO2 (AcOEt).
First (major) eluate: trans-4b. Light yellow oil. IR (film, cmꢂ1): 1686
d
¼2.44–3.44 (m, 7.5H), 3.84–3.99 (m, 0.5H), 4.00–4.12 (m, 0.5H),
4.32–4.44 (m, 0.5H), 4.52–4.64 (m, 0.5H), 4.66–4.70 (m, 0.5H), 7.10–
7.45 (m, 5H, CHar). 13C NMR (50 MHz, CDCl3, TMS)
d
¼34.32, 37.39,
(
nC]O), 1444, 1421, 1289, 1260, 1145, 762, 701. 1H NMR (200 MHz,
37.51, 38.01, 39.65, 44.44, 49.82, 50.16, 53.46, 55.93, 58.75, 62.47,
127.24 and 127.75 (2ꢁ2CH), 128.30 and 128.42 (2ꢁCH), 128.47
(2ꢁ2CH), 136.06 and 139.02 (2ꢁC), 172.74 and 173.33 (2ꢁC]O). MS
(70 eV) m/z (%): 234 (16), 233 (100, Mþ), 187 (17), 186 (13), 172 (16),
159 (13), 104 (97), 103 (15), 102 (20), 101 (10), 77 (10). HRMS m/z
calcd for C13H15NOS 233.08744, found 233.08784.
CDCl3, TMS)
3H), 2.98–3.13 (m, 1H), 3.28–3.41 (m, 1H), 4.13–4.25 (m, 1H), 7.21–
7.39 (m, 5H, CHar). 13C NMR (50 MHz, CDCl3, TMS)
d
¼1.10–1.50 (m, 3H), 1.60–2.04 (m, 3H), 2.46–2.90 (m,
d¼23.52, 24.26,
32.09, 39.11, 40.29, 46.27, 64.56, 127.23 (CH), 127.45 and 128.92
(2ꢁ2CH), 141.47 (C), 172.46 (C]O). MS (70 eV) m/z (%): 216 (16), 215
(100, Mþ), 214 (63), 104 (87), 103 (12), 84 (76), 83 (35). HRMS m/z
calcd for C14H17NO 215.13101, found 215.13092. Second (minor)
eluate: cis-4b. Colourless semi-solid. IR (KBr, cmꢂ1): 1694 (nC]O),
1454, 1424, 1353, 1285, 1097, 769, 703, 625, 613. 1H NMR (CDCl3,
4.3.14. 3-Oxo-hexahydro-pyrrolizine-1-carboxylic acid methyl
ester (4e)
Purified by chromatography on SiO2 (hexane/AcOEt, 1:3). Yield:
227 mg (62%) of a diastereomeric mixture of the isomers trans and
cis [2:1, from integrals of the C(O)OCH3 singlets at 3.75 and 3.72 ppm,
200 MHz, TMS)
d
¼0.64–0.86 (m, 1H), 1.10–1.46 (m, 3H), 1.54–1.68
(m, 1H), 1.72–1.86 (m, 1H), 2.56–2.86 (m, 3H), 3.58–3.76 (m, 2H),