(s), 1339 (s), 1303 (w), 1256 (w), 1213 (m), 1163 (s), 1092 (m)
and 1015 (w); δH 2.42 (3H, s, Ar-CH3), 2.60 (2H, m, 3-CH2),
3.57 (3H, s, OCH3), 4.10 (1H, ddd, J = 8.8, 5.7 and 5.7, 2-H),
5.26 (1H, d, J = 8.8, NH), 5.88 (1H, ddd, J = 15.5, 7.7 and 7.7,
4-H), 6.20 (1H, d, J = 15.5, 5-H), 6.27 (1H, d, J = 3.4,
3Ј-H), 6.35 (1H, dd, J = 3.4 and 1.8, 4Ј-H), 7.20 (2H, d, J = 8.2,
2 × Ar-H), 7.32 (1H, app br s, 5Ј-H) and 7.73 (2H, d, J = 8.2,
2 × Ar-H); δC 21.6 (Ar-CH3), 36.7 (3-CH2), 52.6 (OCH3), 55.4
(2-CH), 107.8, 111.2, 122.9, 124.0 (all CH), 127.3 (2 × Ar-CH),
129.7 (2 × Ar-CH), 137.3 (C), 141.9 (5Ј-CH), 143.7, 151.6 (both
homoallylic toluenesulfonamide 5d (0.96 g, 81%) as a colourless
solid which consisted of a mixture of diastereoisomers. The
mixture showed νmax/cmϪ1 3280 (m), 3028 (w), 2953 (m), 2361
(m), 1743 (s), 1598 (m), 1448 (m), 1339 (s), 1164 (s) and 1093
(m). The major diastereoisomer showed δH 1.18 (3H, d, J = 6.9,
3-CH3), 2.39 (3H, s, Ar-CH3), 2.78–2.86 (1H, m, 3-H), 3.48 (3H,
s, OCH3), 3.90–3.94 (1H, m, 2-H), 5.91 (1H, dd, J = 16.0 and
8.0, 4-H), 6.36 (1H, d, J = 16.0, 5-H), 7.21–7.33 (7H, m, Ar-H)
and 7.70 (2H, d, J = 8.3, 2 × Ar-H) while visible resonances due
to the minor diastereoisomer were δH 1.11 (3H, d, J = 6.9, CH3),
2.37 (3H, s, Ar-CH3), 2.54–2.57 (1H, m, 3-H), 3.43 (3H, s,
OCH3), 4.10 (1H, dd, J = 9.5 and 7.0, 2-H), 5.05–5.10 (1H, m,
᎐CH) and 5.40–5.50 (1H, m, ᎐CH); δ 21.5 (Ar-CH3), 40.1
C) and 171.6 (C᎐O); m/z [EI] 349 (Mϩ, 2%), 290 (2), 242 (19),
᎐
178 (49), 155 (64), 107 (80) and 91 (100) [Found [NH4 CI]:
M ϩ NHϩ4 , 367.1328. C17H23N2O5S requires M, 367.1327]
[Found: C, 58.14; H, 5.73; N, 3.89. C17H19NO5S requires C,
58.44; H, 5.48; N, 4.01%].
᎐
᎐
C
(3-CH), 52.3 (OCH ), 60.4 (2-CH) and 171.0 (C᎐O). The
᎐
3
whole sample showed m/z [EI] 374 (M ϩ Hϩ, 5%), 314 (7),
242 (27), 202 (42), 154 (58), 130 (100), 114 (45), 90 (95) and 64
(57) [Found: M ϩ Hϩ, 374.1426. C20H24NO4S requires M,
374.1426].
Methyl (E )-5-phenyl-2-(4-tolylsulfonylamino)pent-4-enoate
5b. Homoallylic amine 10b (2.60 g, 12.7 mmol) was reacted
with tosyl chloride (2.65 g, 13.9 mmol) in the presence of tri-
ethylamine (2.14 ml, 15.3 mmol) in dichloromethane (45 ml)
according to the general procedure. The crude residue was
chromatographed (4 : 1 hexane–ethyl acetate) to give the
homoallylic toluenesulfonamide 5b (1.70 g, 40%) as a colourless
solid, mp 95 ЊC, νmax/cmϪ1 3278 (m), 3031 (w), 1736 (s), 1598
(w), 1446 (m), 1431 (m), 1420 (m), 1366 (m), 1348 (m), 1324 (s),
1224 (m), 1153 (s), 1094 (s) and 966 (m); δH 2.41 (3H, s,
Ar-CH3), 2.64–2.70 (2H, m, 3-CH2), 3.57 (3H, s, OCH3), 4.11
(1H, ddd, J = 8.8, 5.9 and 5.9, 2-H), 5.10 (1H, d, J = 8.8,
NH), 5.96 (1H, ddd, J = 15.5, 7.6 and 7.6, 4-H), 6.40 (1H, d,
J = 15.5, 5-H), 7.23–7.34 (7H, m, Ar-H), and 7.74 (2H, d,
J = 8.2, 2 × Ar-H); δC 21.6 (Ar-CH3), 36.9 (3-CH2), 52.6
(OCH3), 55.4 (2-CH), 122.6, 126.3, 127.3, 127.7, 128.5, 129.7,
Iodocyclisations of homoallylic sulfonamides 5 under acidic
conditions: general procedure
To a stirred solution of the cyclisation precursor (1 mmol,
1.0 eq.) in dry acetonitrile (20 ml) was added a solution of
iodine (3 mmol, 3.0 eq.) in dry acetonitrile (10 ml) at 0 ЊC. The
reaction was then stirred without cooling until complete by
TLC analysis. The mixture was then quenched with saturated
aqueous sodium thiosulfate, which was added until decoloris-
ation was complete, and the resulting mixture extracted with
dichloromethane (3 × 10 ml). The combined organic extracts
were dried, filtered and the solvent evaporated to yield the
crude product, which was purified by column chromatography.
134.6 (all CH), 136.4, 136.5, 143.7 (all C) and 171.4 (C᎐O); m/z
᎐
[EI] 359 (Mϩ, 14%), 300 (10), 242 (51), 188 (61), 155 (72), 117
(59), 115 (65), 91 (100) and 65 (63) [Found [CH4 CI]: M ϩ Hϩ,
360.1270. C19H22NO4S requires M, 360.1269] [Found: C, 63.63;
H, 6.12; N. 3.81. C19H21NO4S requires C, 63.49; H, 5.89; N,
3.90%].
Methyl (2RS,4SR,5RS)-5-(2-furyl)-4-iodo-1-(4-tolylsulfonyl)-
pyrrolidine-2-carboxylate 11a. Homoallylic toluenesulfonamide
5a (0.20 g, 0.59 mmol) was cyclised with iodine (0.45 g, 1.77
mmol) according to the general procedure and the reaction was
complete after 5 minutes. The crude product was chromato-
graphed (4 : 1 hexane–ethyl acetate) to yield the pyrrolidine 11a
(0.11 g, 40%) as a colourless solid, mp 107–109 ЊC, νmax/cmϪ1
2920 (w), 1758 (s), 1741 (s), 1598 (w), 1052 (w), 1440 (w), 1348
(s), 1300 (m), 1198 (m), 1163 (s), 1093 (m), 1025 (m), 1013 (m)
and 978 (w); δH 2.38 (3H, s, Ar-CH3), 2.43 (1H, ddd, J = 13.7,
8.4 and 5.1, 3-Ha), 2.57 (1H, ddd, J = 13.7, 6.9 and 3.6, 3-Hb),
3.78 (3H, s, OCH3), 4.35 (1H, ddd, J = 5.1 and 3.6 and 3.6,
4-H), 4.63 (1H, m, 2-H), 5.06 (1H, d, J = 3.6, 5-H), 6.21 (1H, dd,
J = 3.2 and 1.9, 4Ј-H), 6.56 (1H, d, J = 3.2, 3Ј-H), 7.22 (1H, d,
J = 1.9, 5Ј-H), 7.24 (2H, d, J = 8.3, 2 × Ar-H) and 7.69 (2H,
J = 8.3, 2 × Ar-H); δC 21.5 (Ar-CH3), 21.6 (4-CH), 40.6 (3-CH2),
52.8 (OCH3), 61.0 (2-CH), 68.4 (5-CH), 109.5 (4Ј-CH), 110.6
(3Ј-CH), 128.0 (2 × Ar-CH), 129.5 (2 × Ar-CH), 134.4 (C),
Methyl
(E )-2-(4-tolylsulfonylamino)oct-4-enoate
5c.
Homoallylic amine 10c (4.80 g, 28.1 mmol) was reacted with
tosyl chloride (5.89 g, 30.9 mmol) in the presence of tri-
ethylamine (4.7 ml, 33.7 mmol) in dichloromethane (100 ml)
according to the general procedure. The crude residue was
chromatographed (4 : 1 hexane–ethyl acetate) to give the
homoallylic toluenesulfonamide 5c (7.5 g, 81%) as a colourless
solid, mp 63–65 ЊC, νmax/cmϪ1 3261 (m), 2955 (m), 2928 (w),
2870 (w) 1743 (s), 1598 (w), 1496 (w), 1440 (w), 1431 (m), 1333
(s), 1281 (m), 1244 (m), 1161 (s), 1093 (m), 1010 (w) and 970
(w); δH 0.87 (3H, t, J = 7.2, 8-CH3), 1.32 (2H, sextet, J = 7.2,
7-CH2), 1.92 (2H, q, J = 7.2, 6-CH2), 2.39 (2H, m, 3-CH2),
2.42 (3H, s, Ar-CH3), 3.53 (3H, s, OCH3), 3.98 (1H, ddd,
J = 8.9, 5.7 and 5.7, 2-H), 5.10 (1H, d, J = 8.9, NH), 5.19 (1H,
ddd, J = 15.0, 7.4 and 7.4, 4-H), 5.46 (1H, ddd, J = 15.0, 7.0
and 7.0, 5-H), 7.29 (2H, d, J = 8.2, 2 × Ar-H) and 7.72 (2H, d,
J = 8.2, 2 × Ar-H); δC 13.6 (8-CH3), 21.6 (Ar-CH3), 22.3
(7-CH2), 34.6 (6-CH2), 36.5 (3-CH2), 52.4 (OCH3), 55.5 (2-CH),
122.4 (5(4)-CH), 127.3 (4(5)-CH), 129.6 (2 × Ar-CH), 136.2
142.5 (5Ј-CH), 144.0, 151.7 (both C) and 171.5 (C᎐O); m/z [EI]
᎐
475 (Mϩ, 2%), 419 (16), 293 (30), 149 (81), 129 (36), 85 (32), 71
(75) and 56 (100) [Found [CI]: M ϩ Hϩ, 476.002. C17H19INO5S
requires M, 476.003].
NOE data: 2-Ha–3-Ha, 4%; 3-Ha–3-Hb, 12%; 3-Hb–4-Hb, 6%.
Methyl (2RS,4SR,5RS)-4-iodo-5-phenyl-1-(4-tolylsulfonyl)-
pyrrolidine-2-carboxylate 11b. Homoallylic toluenesulfonamide
5b (3.0 g, 8.85 mmol) was cyclised with iodine (11.2 g, 44.3
mmol, 5.0 eq.) according to the general procedure and the reac-
tion was complete after 16 h. The crude product was chromato-
graphed (5 : 1 hexane–ethyl acetate) to give the pyrrolidine 11b
(3.20 g, 75%) as a colourless solid, mp 99–100 ЊC, νmax/cmϪ1
2954 (w), 1747 (s), 1597 (w), 1494 (w), 1442 (m), 1348 (s), 1296
(s), 1254 (w), 1162 (s), 1140 (m), 1093 (m), 1030 (m) and 1012
(m); δH 2.41 (3H, s, Ar-CH3), 2.43–2.48 (1H, m, 3-Ha), 2.55 (1H,
ddd, J = 12.1, 7.0 and 7.0, 3-Hb), 3.87 (3H, s, OCH3), 4.15–4.19
(1H, m, 4-H), 4.75 (1H, dd, J = 7.0 and 7.0, 2-H), 5.02 (1H, d,
J = 4.6, 5-H), 7.23 (2H, d, J = 8.1, 2 × Ar-H), 7.27–7.28 (3H, m,
(2 × Ar-CH), 137.0, 143.6 (both C) and 171.5 (C᎐O); m/z [NH
᎐
4
CI] 343 (M ϩ NHϩ4 , 100%) and 327 (M ϩ Hϩ, 10%) [Found: M
ϩ NHϩ4 , 343.1692. C16H27N2O4S requires M 343.1691] [Found:
C, 59.25; H, 7.30; N, 4.27. C16H23NO4S requires C, 59.05; H,
7.12; N, 4.30%].
Methyl (E )-3-methyl-5-phenyl-2-(4-tolylsulfonylamino)pent-
4-enoate 5d. Homoallylic amine 10d (0.70 g, 3.20 mmol) was
reacted with tosyl chloride (0.67 g, 3.52 mmol) and triethyl-
amine (0.54 ml, 3.8 mmol) in dichloromethane (11 ml)
according to the general procedure. The crude residue was
chromatographed (6 : 1 hexane–ethyl acetate) to give the
J. Chem. Soc., Perkin Trans. 1, 2001, 2874–2883
2879