S. P. Gromov et al.
FULL PAPER
[C(3)], 145.65 [C(4)], 190.21 (d, JC,H ϭ 170.1 Hz, CHϭO) ppm.
IR (film on KBr): ν˜ ϭ 3392 (br., O-H, N-H), 1662 (CϭO) cmϪ1
(t, 3JH,H ϭ 5.9 Hz, 2 H, CH2CH2Cl), 3.86 (m, 2 H, CH2CH2OAr),
1
3
.
4.20 (m, 2 H, CH2OAr), 5.24 (br. s, 1 H, NH), 6.56 [d, JH,H
ϭ
MS (EI, 70 eV): m/z ϭ 371 (100) [Mϩ], 178 (19), 164 (35), 163 (50), 8.1 Hz, 1 H, C(5)-H], 7.27 (d, JH,H ϭ 1.3 Hz, 1 H, C(2)-H], 7.39
151 (84), 150 (83), 149 (25), 136 (75), 121 (29), 89 (33), 80 (18). [dd, 3JH,H ϭ 8.1, 4JH,H ϭ 1.3 Hz, 1 H, C(6)-H], 9.67 (s, 1 H, CHϭ
4
HRMS calcd. for C18H29NO7 [Mϩ] 371.1944, found 371.1951.
O) ppm. 13C NMR (CDCl3, 25 °C): δ ϭ 29.53 (q, 1JC,H ϭ 136.6 Hz,
1 1
MeN), 42.65 (t, JC,H ϭ 149.7 Hz, CH2Cl), 68.02 (t, JC,H
ϭ
Synthesis of Chlorides 3aϪc (General Procedure): A solution of
SOCl2 (1.1 mL, 15.0 mmol) in CHCl3 (10 mL) was slowly added to
1
144.4 Hz, CH2OAr), 69.48 (t, JC,H ϭ 138.0 Hz, CH2CH2OAr),
1
1
70.49 (t, JC,H ϭ 140.4 Hz, CH2O), 70.56 (t, JC,H ϭ 140.4 Hz, 5
a
solution of 2aϪc (2.7 mmol) and dry pyridine (0.25 mL,
CH2O), 71.26 (t, 1JC,H ϭ 143.8 Hz, CH2CH2Cl), 107.10 [d, 1JC,H ϭ
3.0 mmol) in CHCl3 (20 mL) cooled in an ice bath. The resulting
solution was refluxed for 6 h. After cooling, 5% aqueous HCl
(50 mL) was added and the resulting mixture was extracted with
CHCl3. The extract was washed with 5% aqueous Na2CO3 and
then with water and concentrated. The residue was purified by col-
umn chromatography on silica gel using elution with EtOAc in the
case of 3a and with a 20:1 benzene/MeOH solvent system in the
case of 3b,c. The chlorides 3aϪc were isolated as light yellow oils.
1
159.5 Hz, C(5)], 108.40 [d, JC,H ϭ 160.0 Hz, C(2)], 125.36 [dd,
3
1
2JC,H ϭ 23.4, JC,H ϭ 7.8 Hz, C(1)], 129.35 [d, JC,H ϭ 159.3 Hz,
1
C(6)], 145.47 [C(3)], 145.61 [C(4)], 190.23 (d, JC,H ϭ 170.0 Hz,
CHϭO) ppm. IR (film on KBr): ν˜ ϭ 3380 (br., N-H), 1670 (Cϭ
O) cmϪ1. MS (EI, 70 eV): m/z ϭ 391 (17) [Mϩ with 37Cl], 389 (47)
[Mϩ with 35Cl], 178 (28), 151 (86), 150 (92), 148 (29), 122 (26),
109 (31), 107 (80), 94 (29), 65 (63), 63 (100). HRMS calcd. for
C18H28ClNO6 (Mϩ·with 35Cl) 389.1605, found 389.1632.
Chloride 3a: The procedure for the reaction of 2a with SOCl2 to
give 3a was similar to that described above. Yield: 753 mg (93%).
1H NMR (CDCl3, 25 °C): δ ϭ 2.92 (br. s, 3 H, MeN), 3.61 (t,
3JH,H ϭ 5.8 Hz, 2 H, CH2Cl), 3.69 (br. s, 4 H, 2 CH2O), 3.74 (t,
Synthesis of Iodides 4aϪc (General Procedure): A solution of 3aϪc
(2.0 mmol) and NaI (6.0 g, 40 mmol) in dry acetone (35 mL) was
refluxed for 80Ϫ100 h and the solvent was evaporated. Water
(50 mL) was added to the residue and the system was extracted
with CHCl3. The solvent was evaporated from the extract and the
residue was purified by column chromatography on silica gel using
a 5:1 benzene/EtOAc solvent system for 4a and EtOAc for 4b,c.
The iodides 4aϪc were isolated as light yellow oils.
3JH,H ϭ 5.8 Hz, 2 H, CH2CH2Cl), 3.86 (m, 2 H, CH2CH2OAr),
3
4.20 (m, 2 H, CH2OAr), 5.18 (br. s, 1 H, NH), 6.55 [d, JH,H
ϭ
4
8.1 Hz, 1 H, C(5)-H], 7.26 [d, JH,H ϭ 1.2 Hz, 1 H, C(2)-H], 7.38
[dd, 3JH,H ϭ 8.1, 4JH,H ϭ 1.2 Hz, 1 H, C(6)-H], 9.67 (s, 1 H, CHϭ
O) ppm. 13C NMR (CDCl3, 25 °C): δ ϭ 29.49 (q, 1JC,H ϭ 136.6 Hz,
1
1
Iodide 4a: The procedure for the reaction of 3a with NaI to give
MeN), 42.69 (t, JC,H ϭ 151.8 Hz, CH2Cl), 67.93 (t, JC,H
ϭ
4a was similar to that described above. Yield: 713 mg (91%). 1H
1
144.2 Hz, CH2OAr), 69.49 (t, JC,H ϭ 141.5 Hz, CH2CH2OAr),
3
1
NMR (CDCl3, 25 °C): δ ϭ 2.92 (s, 3 H, MeN), 3.23 (t, JH,H
ϭ
70.48 (CH2O), 70.55 (CH2O), 71.28 (t, JC,H
ϭ 144.5 Hz,
3
CH2CH2Cl), 107.09 [d, 1JC,H ϭ 159.3 Hz, C(5)], 108.30 [d, 1JC,H ϭ
6.8 Hz, 2 H, CH2I), 3.64Ϫ3.70 (m, 4 H, 2 CH2O), 3.74 (t, JH,H ϭ
6.8 Hz, 2 H, CH2CH2I), 3.86 (m, 2 H, CH2CH2OAr), 4.20 (m, 2
2
3
158.5 Hz, C(2)], 125.34 [dd, JC,H ϭ 23.5, JC,H ϭ 7.7 Hz, C(1)],
129.28 [d, JC,H ϭ 160.2 Hz, C(6)], 145.42 and 145.52 [C(3), C(4)],
190.18 (d, JC,H ϭ 169.8 Hz, CHϭO) ppm. IR (film on KBr): ν˜ ϭ
3
1
H, CH2OAr), 5.17 (br. s, 1 H, NH), 6.55 [d, JH,H ϭ 8.1 Hz, 1 H,
4
3
1
C(5)-H], 7.26 [d, JH,H ϭ 1.4 Hz, 1 H, C(2)-H], 7.38 [dd, JH,H
ϭ
8.1, JH,H ϭ 1.4 Hz, 1 H, C(6)-H], 9.67 (s, 1 H, CHϭO) ppm. 13C
NMR (CDCl3, 25 °C): δ ϭ 2.84 (t, 1JC,H ϭ 150.7 Hz, CH2I), 29.55
(q, 1JC,H ϭ 136.6 Hz, MeN), 67.92 (t, 1JC,H ϭ 144.3 Hz, CH2OAr),
4
3380 (br., NϪH), 1671 (CϭO) cmϪ1. MS (EI, 70 eV): m/z ϭ 304
(7), 303 (41) [Mϩ with 37Cl], 302 (15), 301 (100) [Mϩ with 35Cl],
178 (8), 151 (53), 150 (46), 107 (20), 65 (13), 63 (24), 58 (43). HRMS
calcd. for C14H20ClNO4 (Mϩ·with 35Cl) 301.1081, found 301.1097.
1
1
69.50 (t, JC,H ϭ 141.1 Hz, CH2CH2OAr), 70.11 (t, JC,H
ϭ
1
141.1 Hz, CH2O), 70.46 (t, JC,H ϭ 141.2 Hz, CH2O), 71.83 (t,
1JC,H ϭ 145.1 Hz, CH2CH2I), 107.08 [d, JC,H ϭ 159.3 Hz, C(5)],
1
Chloride 3b: The procedure for the reaction of 2b with SOCl2 to
give 3b was similar to that described above. Yield: 908 mg (97%).
1H NMR (CDCl3, 25 °C): δ ϭ 2.95 (d, 3JH,H ϭ 4.8 Hz, 3 H, MeN),
1
2
108.27 [d, JC,H ϭ 156.4 Hz, C(2)], 125.33 [dd, JC,H ϭ 23.5,
3JC,H ϭ 7.5 Hz, C(1)], 129.26 [d, JC,H ϭ 160.4 Hz, C(6)], 145.39
1
3
and 145.47 [C(3), C(4)], 190.16 (d, 1JC,H ϭ 170.0 Hz, CHϭO) ppm.
IR (film on KBr): ν˜ ϭ 3401 (br., N-H), 1669 (CϭO) cmϪ1. MS
(EI, 70 eV): m/z ϭ 393 (82) [Mϩ], 199 (33), 162 (26), 155 (100), 151
(89), 150 (87), 149 (27), 148 (35), 122 (39), 94 (47), 58 (52). HRMS
calcd. for C14H20INO4 [Mϩ] 393.0437, found 393.0494.
3.63 (t, JH,H ϭ 5.9 Hz, 2 H, CH2Cl), 3.68 (s, 4 H, 2 CH2O), 3.71
3
(m, 4 H, 2 CH2O), 3.75 (t, JH,H ϭ 5.9 Hz, 2 H, CH2CH2Cl), 3.88
(m, 2 H, CH2CH2OAr), 4.22 (m, 2 H, CH2OAr), 5.21 (br. q, 1 H,
3
4
NH), 6.58 [d, JH,H ϭ 8.1 Hz, 1 H, C(5)-H], 7.29 [d, JH,H
ϭ
3
4
1.4 Hz, 1 H, C(2)-H], 7.41 [dd, JH,H ϭ 8.1, JH,H ϭ 1.4 Hz, 1 H,
C(6)-H], 9.69 (s, 1 H, CHϭO) ppm. 13C NMR (CDCl3, 25 °C):
Iodide 4b: The procedure for the reaction of 3b with NaI to give
4b was similar to that described above. Yield: 850 mg (97%). 1H
δ ϭ 29.48 (q, 1JC,H ϭ 136.5 Hz, MeN), 42.63 (t, JC,H ϭ 149.7 Hz,
1
1
1
CH2Cl), 67.99 (t, JC,H ϭ 144.3 Hz, CH2OAr), 69.43 (t, JC,H
ϭ
NMR (CDCl3, 25 °C): δ ϭ 2.95 (br. s, 3 H, MeN), 3.26 (t, 3JH,H ϭ
138.7 Hz, CH2CH2OAr), 70.50 (br., 3CH2O), 70.56 (CH2O), 71.22
3
6.9 Hz, 2 H, CH2I), 3.65Ϫ3.74 (m, 8 H, 4 CH2O), 3.75 (t, JH,H
ϭ
1
1
(t, JC,H ϭ 144.6 Hz, CH2CH2Cl), 107.06 [dd, JC,H ϭ 159.4,
6.9 Hz, 2 H, CH2CH2I), 3.88 (m, 2 H, CH2CH2OAr), 4.22 (m, 2
2JC,H ϭ 4.5 Hz, C(5)], 108.39 [d, JC,H ϭ 159.0 Hz, C(2)], 125.32
[dd, JC,H ϭ 23.4, JC,H ϭ 7.5 Hz, C(1)], 129.25 [d, JC,H
159.0 Hz, C(6)], 145.42 [C(3)], 145.55 [C(4)], 190.15 (d, JC,H
1
3
H, CH2OAr), 5.21 (br. s, 1 H, NH), 6.58 [d, JH,H ϭ 8.1 Hz, 1 H,
2
3
1
ϭ
4
3
C(5)-H], 7.29 [d, JH,H ϭ 1.4 Hz, 1 H, C(2)-H], 7.41 [dd, JH,H
ϭ
1
ϭ
8.1, JH,H ϭ 1.4 Hz, 1 H, C(6)-H], 9.70 (s, 1 H, CHϭO) ppm. 13C
NMR (CDCl3, 25 °C): δ ϭ 2.84 (t, 1JC,H ϭ 150.8 Hz, CH2I), 29.58
(q, 1JC,H ϭ 136.8 Hz, MeN), 67.95 (t, 1JC,H ϭ 144.3 Hz, CH2OAr),
4
169.9 Hz, CHϭO) ppm. IR (film on KBr): ν˜ ϭ 3400 (br., N-H),
1667 (CϭO) cmϪ1. MS (EI, 70 eV): m/z ϭ 347 (30) [Mϩ with 37Cl],
345 (64) [Mϩ with 35Cl], 151 (91), 150 (90), 148 (42), 122 (39), 109
(49), 107 (90), 94 (54), 77 (42), 65 (83), 63 (100). HRMS calcd. for
C16H24ClNO5 (Mϩ·with 35Cl) 345.1343, found 345.1365.
1
1
69.52 (t, JC,H ϭ 141.6 Hz, CH2CH2OAr), 70.14 (t, JC,H
ϭ
1
141.3 Hz, CH2O), 70.56 (t, JC,H ϭ 141.1 Hz, 2 CH2O), 70.63 (t,
1JC,H ϭ 140.1 Hz, CH2O), 71.88 (t, JC,H ϭ 144.5 Hz, CH2CH2I),
1
1
1
Chloride 3c: The procedure for the reaction of 2c with SOCl2 to
give 3c was similar to that described above. Yield: 970 mg (92%).
107.10 [d, JC,H ϭ 159.1 Hz, C(5)], 108.27 [d, JC,H ϭ 157.0 Hz,
C(2)], 125.35 [dd, JC,H ϭ 23.5, JC,H ϭ 7.5 Hz, C(1)], 129.41 [d,
2
3
1H NMR (CDCl3, 25 °C): δ ϭ 2.93 (br. s, 3 H, MeN), 3.61 (t, 1JC,H ϭ 159.8 Hz, C(6)], 145.46 and 145.57 [C(3), C(4)], 190.29 (d,
3JH,H ϭ 5.9 Hz, 2 H, CH2Cl), 3.63Ϫ3.71 (m, 12 H, 6 CH2O), 3.73 1JC,H ϭ 170.3 Hz, CHϭO) ppm. IR (film on KBr): ν˜ ϭ 3380 (br.,
3196
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2003, 3189Ϫ3199