9672
N. Kise et al. / Tetrahedron 70 (2014) 9668e9675
(0.11 mL, 1 mmol) dropwise at 0 ꢀC and then the dark blue sus-
pension was stirred for 1 h at this temperature. To the mixture was
added 1 M HCl (20 mL) at 0 ꢀC and the mixture was stirred for
15 min at 25 ꢀC. The mixture was extracted with ethyl acetate three
times. The organic layer was washed with aqueous NaCl and dried
over MgSO4. After the solvent was removed, the residue was pu-
rified by column chromatography on silica gel to give 3a in 74%
yield (164 mg) with small amounts of 4a (9 mg, 5%) and 5a (8 mg,
4%). Compounds 4a,10e12 4b,10,12,13 4c,11,14 4g,11,14,15 4h,10,14,16 4i,14 E-
12a,17 E-12b,3g,18 Z-12b,18 E-12c,3b,3f E-12d,18 Z-12d,18 E-
12e,2b,2c,19,20 and Z-12e2b,2c,19,20 were known.
A solution of 5a (103 mg, 0.5 mmol) and PPTS (10 mg) in ben-
zene (10 mL) was refluxed using DeaneStark apparatus under ni-
trogen atmosphere for 1 h. After the solvent was removed in vacuo,
the residue was purified by column chromatography on silica gel
(hexaneseEtOAc) to give 4a in 85% yield (80 mg).
2H),1.42e1.68 (m, 5H),1.72e1.82 (m,1H),1.96 (dd,1H, J¼9.2,14.6 Hz),
2.24 (dd, 1H, J¼10.1, 14.6 Hz), 3.20 (s, 3H), 3.65 (br s, 1H), 4.09 (br s,
1H), 6.84e6.88 (m, 1H), 7.02e7.12 (m, 1H), 7.33e7.38 (m, 1H),
7.41e7.45 (m,1H);13C NMR (CDCl3)
d 22.3(t), 22.8(t), 26.0(q), 28.7(t),
29.8 (t), 32.6 (t), 36.1 (t), 79.5 (s), 79.6 (s),108.5 (d),123.0 (d),125.9 (d),
127.1 (s), 129.9 (d), 144.4 (s), 179.3 (s). Anal. Calcd for C16H21NO3: C,
69.79%; H, 7.69%; N, 5.09%. Found: C, 69.72%; H, 7.68%; N, 5.04%.
4.2.6. 3-((1s,4s)-4-(tert-Butyl)-1-hydroxycyclohexyl)-3-hydroxy-1-
methylindolin-2-one (cis-3f). White solid; Rf 0.4 (hexaneseethyl ac-
etate, 1:2); mp 144e146 ꢀC; IR (KBr) 3487, 3447, 3374, 1701, 1614,
1497, 1472, 934, 889, 754, 667, 654 cmꢁ1; 1H NMR (CDCl3)
d 0.81 (s,
9H), 0.98e1.06 (m, 1H), 1.36e1.49 (m, 4H), 1.55e1.67 (m, 3H),
2.14e2.20 (m, 1H), 3.19 (s, 3H), 3.40 (br s, 1H), 3.94 (br s, 1H),
6.84e6.86 (m, 1H), 7.08e7.13 (m, 1H), 7.33e7.37 (m, 1H), 7.43e7.46
(m, 1H); 13C NMR (CDCl3)
d 21.69 (t), 21.71 (t), 25.9 (q), 27.4 (q), 29.6
(t), 31.9 (t), 32.3 (s), 47.5 (d), 75.5 (s), 79.9 (s),108.4 (d),122.9 (d),125.8
(d), 127.6 (s), 129.7 (d), 144.3 (s), 178.8 (s). Anal. Calcd for C19H27NO3:
C, 71.89%; H, 8.57%; N, 4.41%. Found: C, 71.82%; H, 8.54%; N, 4.33%.
4.2.1. 3-Hydroxy-3-(2-hydroxypropan-2-yl)-1-methylindolin-2-one
(3a). White solid; Rf 0.2 (hexaneseethyl acetate, 1:1); mp
148e150 ꢀC; IR (KBr) 3412, 1690, 1614, 1497, 1468, 974, 936,
766, 694 cmꢁ1
;
1H NMR (CDCl3)
d
1.01 (s, 3H), 1.44 (s, 3H), 3.21
4.2.7. 3-Hydroxy-3-(1-hydroxycyclopentyl)indolin-2-one
(3g). White solid; Rf 0.7 (hexaneseethyl acetate, 1:2); mp
158e159 ꢀC; IR (KBr) 3589, 3470, 3194, 1709, 1616, 1470, 762,
(s, 3H), 3.79 (br s, 1H), 3.99 (br s, 1H), 6.85e6.88 (m, 1H), 7.08e7.13
(m, 1H), 7.33e7.38 (m, 1H), 7.42e7.45 (m, 1H); 13C NMR (CDCl3)
d
22.0 (q), 24.5 (q), 25.8 (q), 74.7 (s), 79.3 (s),108.4 (d),123.0 (d),125.3
656 cmꢁ1; 1H NMR (CDCl3)
d 1.33e1.56 (m, 4H), 1.73e1.90 (m, 3H),
(d), 127.7 (s), 129.7 (d), 144.1 (s), 178.5 (s). Anal. Calcd for C12H15NO3:
C, 65.14%; H, 6.83%; N, 6.33%. Found: C, 65.09%; H, 6.85%; N, 6.23%.
2.13e2.21 (m, 1H), 3.45 (br s, 1H), 4.07 (br s, 1H), 6.86e6.90 (m, 1H),
7.06e7.11 (m, 1H), 7.28e7.32 (m, 1H), 7.45e7.49 (m, 1H), 7.72 (br s,
1H); 13C NMR (CDCl3)
d 23.6 (t), 24.0 (t), 33.5 (t), 35.1 (t), 78.5 (s),
4.2.2. 3-Hydroxy-3-(2-hydroxypropan-2-yl)indolin-2-one
(3b). White solid; Rf 0.7 (hexaneseethyl acetate, 1:2); mp
116e117 ꢀC; IR (KBr) 3374, 3179, 1734, 1721, 1680, 1626, 1601, 1474,
85.0 (s), 109.8 (d), 121.8 (d), 125.3 (d), 128.8 (s), 129.0 (d), 142.0 (s),
180.0 (s). Anal. Calcd for C11H15NO3: C, 66.94%; H, 6.48%; N, 6.00%.
Found: C, 66.86%; H, 6.45%; N, 5.94%.
928, 845, 750, 741, 683, 654 cmꢁ1 1H NMR (CDCl3)
; d 1.12 (s, 3H),
1.45 (s, 3H), 3.64 (br s, 1H), 4.06 (br s, 1H), 6.88e6.92 (m, 1H),
7.06e7.10 (m, 1H), 7.27e7.31 (m, 1H), 7.41e7.44 (m, 1H), 8.08 (br s,
4.2.8. 3-Hydroxy-3-(1-hydroxycyclohexyl)indolin-2-one
(3h). White solid; Rf 0.75 (hexaneseethyl acetate, 1:1); mp
162e163 ꢀC; IR (KBr) 3356, 3293, 1724, 1622, 1472, 937,
1H); 13C NMR (CDCl3)
d 22.2 (q), 24.2 (q), 74.7 (s), 80.1 (s), 110.6 (d),
122.6 (d), 125.5 (d), 128.5 (s), 129.6 (d), 141.4 (s), 180.9 (s). Anal.
Calcd for C11H13NO3: C, 63.76%; H, 6.32%; N, 6.76%. Found: C,
63.71%; H, 6.30%; N, 6.68%.
746, 691 cmꢁ1; 1H NMR (CDCl3)
d 0.95e1.06 (m, 1H), 1.30e1.52 (m,
4H), 1.54e1.68 (m, 4H), 1.75e1.82 (m, 1H), 3.68 (br s, 1H), 5.13 (br s,
1H), 6.83e6.87 (m, 1H), 6.95e6.99 (m, 1H), 7.18e7.22 (m, 1H),
7.38e7.42 (m, 1H), 10.05 (br s, 1H); 13C NMR (CDCl3)
d 20.1 (t), 20.2
4.2.3. 3-Hydroxy-3-(1-hydroxycyclopentyl)-1-methylindolin-2-one
(3c). White solid; Rf 0.65 (hexaneseethyl acetate, 1:1); mp
142e143 ꢀC; IR (KBr) 3401, 3316, 1713, 1614, 1497, 1468, 880, 750,
(t), 24.7 (t), 28.7 (t), 29.8 (t), 74.3 (s), 79.7 (s), 109.1 (d), 120.9 (d),
125.2 (d), 128.2 (d), 128.9 (s), 141.7 (s), 179.4 (s). Anal. Calcd for
C14H17NO3: C, 68.00%; H, 6.93%; N, 5.66%. Found: C, 67.91%; H,
741, 721, 691, 658 cmꢁ1
;
1H NMR (CDCl3)
d
1.18e1.26 (m, 1H),
6.90%; N, 5.57%.
1.39e1.48 (m, 1H), 1.70e1.88 (m, 1H), 2.14e2.21 (m, 1H), 3.21 (s,
3H), 3.66 (br s, 1H), 4.06 (br s, 1H), 6.85e6.88 (m, 1H), 7.08e7.12 (m,
4.2.9. 3-((1s,4s)-4-(tert-Butyl)-1-hydroxycyclohexyl)-3-
1H), 7.34e7.38 (m, 1H), 7.46e7.49 (m, 1H); 13C NMR (CDCl3)
d
23.7
hydroxyindolin-2-one
(cis-3j). White
solid;
Rf
0.25
(t), 24.3 (t), 25.9 (q), 33.6 (t), 35.6 (t), 78.4 (s), 85.5 (s), 108.4 (d),
123.0 (d), 125.4 (d), 127.6 (s), 129.7 (d), 144.1 (s), 178.5 (s). Anal.
Calcd for C14H17NO3: C, 68.00%; H, 6.93%; N, 5.66%. Found: C,
67.96%; H, 6.93%; N, 5.62%.
(hexaneseethyl acetate, 2:1); mp 214e216 ꢀC; IR (ATR) 3466, 3420,
3275, 3246, 1705, 1690, 1622, 957, 922, 917, 864, 856, 752, 743,
702, 667 cmꢁ1 1H NMR (CDCl3, DMSO-d6)
; d 0.78e0.85 (m, 1H),
0.81 (s, 9H), 1.31e1.58 (m, 6H), 1.64e1.71 (m, 1H), 1.83e1.90 (m, 1H),
3.61 (br s, 1H), 5.01 (br s, 1H), 6.83e6.87 (m, 1H), 6.95e7.00
(m, 1H), 7.18e7.23 (m, 1H), 7.38e7.42 (m, 1H), 10.02 (br s, 1H);
4.2.4. 3-Hydroxy-3-(1-hydroxycyclohexyl)-1-methylindolin-2-one
(3d). White solid; Rf 0.7 (hexaneseethyl acetate, 2:1); mp
155e157 ꢀC; IR (KBr) 3430, 3403, 1701, 1613, 1497, 1474, 930, 889,
13C NMR (CDCl3, DMSO-d6)
d 20.5(t), 20.6(t), 26.4(q), 29.0(t), 29.8(t),
31.1 (s), 46.3 (d), 73.4 (s), 79.4 (s), 108.6 (d), 120.5 (d), 125.0 (d),
127.8 (d), 129.0 (s), 141.3 (s), 178.9 (s). Anal. Calcd for C18H25NO3: C,
71.26%; H, 8.31%; N, 4.62%. Found: C, 71.25%; H, 8.33%; N, 4.56%.
746, 658 cmꢁ1; 1H NMR (CDCl3)
d 0.95e1.04 (m, 2H), 1.30e1.36 (m,
1H),1.38e1.45 (m,1H),1.52e1.72 (m, 5H), 2.09e2.16 (m,1H), 3.19 (s,
3H), 3.44 (br s, 1H), 3.95 (br s, 1H), 6.84e6.87 (m, 1H), 7.09e7.13 (m,
1H), 7.33e7.37 (m, 1H), 7.44e7.46 (m, 1H); 13C NMR (CDCl3)
d
20.75
4.2.10. 3-Cyclopentylidene-1-methylindolin-2-one (4c). Pale yellow
solid; Rf 0.2 (hexaneseethyl acetate¼1:1); mp 82e84 ꢀC (lit.11
(t), 20.79 (t), 25.7 (t), 25.8 (q), 29.1 (t), 31.2 (t), 75.8 (s), 80.0 (s),
108.3 (d), 122.8 (d), 125.7 (d), 127.7 (s), 129.6 (d), 144.2 (s), 178.7 (s).
Anal. Calcd for C15H19NO3: C, 68.94%; H, 7.33%; N, 5.36%. Found: C,
68.91%; H, 7.35%; N, 5.28%.
85e86); 1H NMR (CDCl3)
d 1.81e1.92 (m, 4H), 2.85e2.90 (m, 2H),
3.13e3.18 (m, 2H), 3.26 (s, 3H), 6.82e6.85 (m, 1H), 7.03e7.07 (m,
1H), 7.23e7.27 (m, 1H), 7.41e7.44 (m, 1H); 13C NMR (CDCl3)
d
25.3
(q), 25.6 (t), 26.0 (t), 34.1 (t), 34.5 (t), 107.2 (d), 119.3 (s), 121.3 (d),
122.1 (d),123.3 (s), 127.0 (d), 142.0 (s), 164.4 (s), 167.2 (s).
4.2.5. 3-Hydroxy-3-(1-hydroxycycloheptyl)-1-methylindolin-2-one
(3e). White solid; Rf 0.6 (hexaneseethyl acetate, 1:2); mp
133e135 ꢀC; IR (KBr) 3433, 3410, 1701, 1613, 1495, 1474, 1464, 926,
4.2.11. 3-Cyclohexylidene-1-methylindolin-2-one
(4d). Colorless
745, 664 cmꢁ1
;
1H NMR (CDCl3)
d
1.10e1.20 (m. 2H), 1.28e1.40 (m,
paste; Rf 0.2 (hexaneseethyl acetate¼2:1); 1H NMR (CDCl3)