T. Satoh et al. / Tetrahedron 63 (2007) 4806–4813
4811
C16H21NO4: M, 291.1469. Found m/z: 291.1472. Anal.
Calcd for C16H21NO4: C, 65.96; H, 7.26; N, 4.81. Found:
C, 65.60; H, 7.19; N, 4.74.
mp 194.5–195 ꢀC (CH2Cl2–hexane); IR (KBr): 2963, 2223
1
(CN), 1603, 1505, 1088, 1047 (SO), 853 cmꢁ1; H NMR:
d 1.55–1.60 (1H, m), 1.80–1.83 (2H, m), 1.86–2.40 (5H,
m), 2.46 (3H, s), 3.26 (1H, s), 3.96–4.03 (4H, m), 6.24 (2H,
d, J¼8.0 Hz), 7.31 (2H, d, J¼8.0 Hz), 7.36 (2H, d, J¼
8.0 Hz), 7.67 (2H, d, J¼8.0 Hz). MS m/z (%): 409 (M+, 14),
269 (100), 183 (46), 154 (36). Calcd for C23H24N2O3S: M,
409.1586. Found m/z: 409.1590. Anal. Calcd for
C23H24N2O3S: C, 67.62; H, 5.92; N, 6.86. Found: C,
67.29; H, 5.70; N, 6.89.
3.1.5. 4,4-Ethylenedioxy-1-[N-(2-methoxyphenyl)amino]-
cyclohexanecarbaldehyde (7c). Colorless crystals; mp
101.5–102.5 ꢀC (AcOEt–hexane); IR (KBr): 3430 (NH),
1722 (CO), 1514, 1255, 1085, 756 cmꢁ1; 1H NMR: d 1.68–
1.77 (4H, m), 1.99–2.07 (4H, m), 3.86 (3H, s), 3.95 (4H, s),
4.64 (1H, s, NH), 6.45 (1H, d, J¼7.6 Hz), 6.70–6.80 (3H, m),
9.65 (1H, s). MS m/z (%): 291 (M+, 10), 262 (100), 200 (19).
Calcd for C16H21NO4: M, 291.1469. Found m/z: 291.1486.
Anal. Calcd for C16H21NO4: C, 65.96; H, 7.27; N, 4.81.
Found: C, 65.94; H, 7.19; N, 4.80.
3.1.11. Methyl[1-(4-iodophenyl)amino-4,4-ethylenedioxy-
cyclohexyl]carboxylate (10a). A 4% solution of potassium
hydroxide in methanol was added dropwise to a solution of
aldehyde 5 (100 mg, 0.383 mmol) and iodine (186 mg,
1.45 mmol) in methanol at 40 ꢀC until the color of
the reaction mixture diminished. The reaction was quenched
by satd aq NH4Cl and the whole was extracted with CHCl3.
The organic layer was washed once with satd aq NH4Cl and
dried over MgSO4. The product was isolated by silica gel
flash column chromatography to give 10a (113 mg; 70%)
as colorless crystals; mp 121–123 ꢀC (AcOEt–hexane); IR
(KBr): 3390 (NH), 1729 (CO), 1591, 1504, 1242,
3.1.6. Imine (8b). Colorless oil; IR (neat): 3391 (NH), 2952,
1
2834, 1651, 1514, 1504, 1246, 1106, 1035, 826 cmꢁ1; H
NMR: d 1.74–1.84 (4H, m), 1.99–2.06 (2H, m), 2.15–2.22
(2H, m), 3.72, 3.79 (each 3H, s), 3.96 (4H, s), 6.71 (4H, s),
6.86, 7.03 (each 2H, d, J¼8.8 Hz), 7.84 (1H, s). MS m/z (%):
396 (M+, 28), 262 (100), 256 (21). Calcd for C23H28N2O4:
M, 396.2049. Found m/z: 396.2047.
3.1.7. 6,6-Ethylenedioxy-1-(2-methoxyphenyl)-2-(p-tolyl-
sulfinyl)-1-azaspiro[2.5]octane (9a). Colorless crystals; mp
161–162 ꢀC (AcOEt–hexane); IR (KBr): 2953, 1501, 1444,
1120, 1035 (SO), 764 cmꢁ1; 1H NMR: d 1.14–1.19 (1H, m),
1.26–1.32 (1H, m), 1.53–1.65 (3H, m), 2.05–2.17 (2H, m),
2.36–2.42 (1H, m), 2.45 (3H, s), 3.30 (1H, s), 3.87 (3H, s),
3.88–3.99 (4H, m), 6.77–6.86 (3H, m), 6.96–7.01 (1H, m),
7.39 (2H, d, J¼8.0 Hz), 7.71 (2H, d, J¼8.0 Hz). MS m/z
(%): 413 (M+, trace), 397 (27), 274 (38), 188 (100), 99 (18).
Calcd for C23H27NO4S: M, 413.1661. Found m/z: 413.1662.
Anal. Calcd for C23H27NO4S: C, 66.80; H, 6.58; N, 3.39; S,
7.75. Found: C, 66.37; H, 6.49; N, 3.43; S, 7.75.
1107 cmꢁ1 1H NMR: d 1.65–1.82 (4H, m), 2.05–2.09
;
(2H, m), 2.19–2.27 (2H, m), 3.68 (3H, s), 3.95 (5H, s, OCH2-
CH2O, NH), 6.36 (2H, d, J¼7.0 Hz), 7.39 (2H, d, J¼7.0 Hz).
MS m/z (%): 417 (M+, 29), 358 (100), 231 (7), 169 (22).
Calcd for C16H20INO4: M, 417.0437. Found m/z: 417.0432.
3.1.12. Methyl [1-(4-chlorophenyl)amino-4,4-ethylene-
dioxycyclohexyl]carboxylate (10b). Colorless crystals;
mp 111–114 ꢀC (AcOEt–hexane); IR (KBr): 3408 (NH),
2951, 1731 (CO), 1493, 1107, 756 cmꢁ1; 1H NMR: d 1.66–
1.69 (2H, m), 1.70–1.83 (2H, m), 2.05–2.10 (2H, m), 2.19–
2.25 (2H, m), 3.68 (3H, s), 3.90 (1H, br s, NH), 3.95 (4H, s),
6.51 (2H, d, J¼9.0 Hz), 7.09 (2H, d, J¼9.0 Hz). MS m/z (%):
325 (M+, 14), 266 (100), 204 (13), 169 (13). Calcd for
C16H20ClNO4: M, 325.1080. Found m/z: 325.1081. Anal.
Calcd for C16H20ClNO4: C, 58.99; H, 6.19; N, 4.30; Cl,
10.88. Found: C, 58.83; H, 6.07; N, 4.22; Cl, 10.92.
3.1.8. 6,6-Ethylenedioxy-1-(4-methoxyphenyl)-2-(p-tolyl-
sulfinyl)-1-azaspiro[2.5]octane (9b). Colorless amorphous;
IR (KBr): 3452, 2950, 1507, 1241, 1086, 1035 (SO) cmꢁ1; 1H
NMR: d 1.14–1.20 (1H, m), 1.37–1.44 (1H, m), 1.51–1.58
(1H, m), 1.69–1.77 (2H, m), 1.94–2.01 (1H, m), 2.14–2.29
(2H, m), 2.45 (3H, s), 3.23 (1H, s), 3.74 (3H, s), 3.91–4.00
(4H, m), 6.73 (2H, d, J¼9.0 Hz), 6.83 (2H, d, J¼9.0 Hz),
7.39 (2H, d, J¼8.0 Hz), 7.68 (2H, d, J¼8.0 Hz). MS m/z
(%): 413 (M+, trace), 274 (45), 188 (100), 186 (63). Calcd
for C23H27O4NS: M, 413.1661. Found m/z: 413.1668.
3.1.13. Methyl [1-(4-methoxyphenyl)amino-4,4-ethylene-
dioxycyclohexyl]carboxylate (10c). Colorless oil; IR
(neat): 3392 (NH), 2951, 1729 (CO), 1509, 1242, 1107,
1
1036 cmꢁ1; H NMR: d 1.61–2.22 (8H, m), 3.67 (3H, s),
3.74 (3H, s), 3.90 (1H, br s, NH), 3.95 (4H, s), 6.64 (2H,
d, J¼6.8 Hz), 6.74 (2H, d, J¼6.8 Hz). MS m/z (%): 321
(M+, 27), 262 (100), 200 (23). Calcd for C17H23NO5: M,
321.1575. Found m/z: 321.1585.
3.1.9. 6,6-Ethylenedioxy-1-(4-chlorophenyl)-2-(p-tolyl-
sulfinyl)-1-azaspiro[2.5]octane (9c). Colorless crystals;
mp 144–146 ꢀC (AcOEt–hexane); IR (KBr): 2951, 1491,
1
1400, 1091, 1049 (SO), 836 cmꢁ1; H NMR: d 1.07–1.11
3.1.14. Methyl [1-(4-iodo-2-methoxyphenyl)amino-4,4-
ethylenedioxycyclohexyl]carboxylate (10d). Colorless
oil; IR (neat): 3428 (NH), 1732 (CO), 1513, 1224,
(1H, m), 1.41–1.44 (1H, m), 1.62–1.73 (3H, m), 1.93–1.97
(1H, m), 2.20–2.27 (2H, m), 2.45 (3H, s), 3.20 (1H, s),
3.93–3.99 (4H, m), 6.80 (2H, d, J¼8.5 Hz), 7.14 (2H, d, J¼
8.5 Hz), 7.40 (2H, d, J¼8.0 Hz), 7.68 (2H, d, J¼8.0 Hz). MS
m/z (%): 417 (M+, trace), 278 (45), 192 (100), 99 (44). Calcd
for C22H24ClNO3S: M, 417.1166. Found m/z: 417.1165.
Anal. Calcd for C22H24ClNO3S: C, 63.22; H, 5.79; N,
3.35; S, 7.67; Cl, 8.48. Found: C, 62.86; H, 5.64; N, 3.35;
S, 7.62; Cl, 8.61.
1110 cmꢁ1 1H NMR: d 1.65–1.83 (4H, m), 2.10–2.31
;
(4H, m), 3.68 (3H, s), 3.82 (3H, s), 3.95 (4H, s), 6.44 (1H, d,
J¼6.6 Hz), 6.67 (1H, t, J¼8.0 Hz), 6.76 (1H, t, J¼7.0 Hz).
MS m/z (%): 447 (M+, 34), 388 (100), 262 (35). Calcd for
C17H22INO5: M, 447.0542. Found m/z: 447.0534.
3.1.15. Methyl [1-(2-methoxyphenyl)amino-4,4-ethylene-
dioxycyclohexyl]carboxylate (10e). A solution of I2
(558 mg, 2.2 mmol) and potassium hydroxide (271 mg,
4.83 mmol) in methanol (10 mL) was stirred at room
3.1.10. 6,6-Ethylenedioxy-1-(4-cyanophenyl)-2-(p-tolyl-
sulfinyl)-1-azaspiro[2.5]octane (9d). Colorless crystals;