Helvetica Chimica Acta Vol. 86 (2003)
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b) To a stirred soln. of (i-Pr)2NH (0.43 ml, 3.03 mmol) in THF (10 ml) at À208, BuLi (2m soln. in pentane,
1.5 ml, 3 mmol) was added under Ar, the soln. was warmed to 08 for 15 min, and then cooled to À788. A soln. of
11 (420 mg, 2.61 mmol) in THF (2 ml) was added dropwise. After 30 min, allyl bromide (0.25 ml, 2.96 mmol)
was added. The mixture was stirred for 30 min at À788, then warmed to r.t., sat. NaHCO3 soln. was added, and
the mixture was extracted with Et2O. The org. phase was washed with sat. NaHCO3 soln. and brine, dried
(MgSO4), and evaporated to give 521 mg (99%) of 9.
2,3-Dihydro-1,3-dimethyl-2-oxo-1H-indol-3-acetaldehyde (14). A flow of ozonoid oxygen was bubbled (G2
frit) through a soln. of 9 (313 mg, 1.56 mmol) in dry CH2Cl2 (60 ml) at À788 until the appearance of blue color
indicated an excess of O3. After blowing out the excess of O3 with dry N2, (EtO)3P (0.50 ml, 2.87 mmol) was
added at À788, and the mixture was allowed to warm to r.t. and stirred for 1 h at r.t. Then, the solvent was
evaporated, and the residue was purified by CC (AcOEt/hexane 1 :2) to yield 278 mg (88%) of 14. Colorless oil.
IR (film): 3056m, 2970s, 2930m, 2889m, 2834m, 2733m, 1714s, 1652m, 1614s, 1495s, 1472s, 1453s, 1422m, 1379s,
1351s, 1309s, 1250s, 1159m, 1127s, 1067m, 1032s, 1019m, 98 6w, 905w, 756s, 700m. 1H-NMR: 9.51 (t-like (ABX),
JAX ꢀ JBX 1.6, CHO); 7.29 (t-like, 1 arom. H); 7.19 (d-like, 1 arom. H); 7.05 (t-like, 1 arom. H); 6.88 (d-like, 1
arom. H); 3.27 (s, MeN); 3.01 2.89 (m (ABX), JAB ꢀ 15.7, JAX ꢀ JBX 1.6, CH2); 1.41 (s, Me). 13C-NMR: 198.6
(d, CHO); 179.4 (s, CO); 143.1, 132.7 (2s, 2 arom. C); 128.2, 122.5, 122.3, 108.2 (4d, 4 arom. CH); 50.4 (t,
.
CH2); 44.9 (s, C(3)); 26.3 (q, MeN); 23.8( q, Me). CI-MS: 205 (14), 204 (100, [M 1] ), 203 (2, M ).
3-(3,3-Diethoxypropyl)-2,3-dihydro-1,3-dimethyl-1H-indol-2-one (15). To soln. of 14 (57.8mg,
a
0.284 mmol) in abs. EtOH (15 ml), 2 drops of conc. HCl were added. The mixture was heated to reflux for
1 h, the solvent was evaporated, and CH2Cl2 was added. The org. phase was washed with 10% aq. HCl, sat.
NaHCO3 soln., and brine, and dried (Na2SO4). CC (AcOEt/hexane 3 :10) gave 71.6 mg (91%) of 15. Colorless
oil. IR (film): 3055m, 2974s, 2927s, 2897s, 1714s, 1613s, 1494s, 1471s, 1452s, 1426m, 1378s, 1349s, 1310m, 1266m,
1248m, 1158s, 1123s, 1060s, 1019s, 1005s, 958w, 918w, 8 53w, 754s, 742s, 702m, 644w. 1H-NMR: 7.26 (t-like, 1 arom.
H); 7.19 (d-like, 1 arom. H); 7.04 (t-like, 1 arom. H); 6.82 (d-like, 1 arom. H); 4.17 4.12 (m, CHO2); 3.51 3.40,
3.32 3.25, 3.11 2.99 (3m, 2 CH2O); 3.21 (s, MeN); 2.51 2.42, 2.07 1.99 (2m, CH2); 1.35 (s, Me); 1.05 1.01,
1.01 0.93 (2t, 2 Me). 13C-NMR: 180.2 (s, CO); 143.3, 133.3 (2s, 2 arom. C); 127.6, 122.7, 122.0, 107.7 (4d, 4
arom. CH); 99.7 (d, CHO2); 61.0, 60.0, 45.6 (3t, 3 CH2); 40.7 (s, C(3)); 26.0 (q, MeN); 25.0, 15.0, 14.7 (3q, 3 Me).
.
GC/EI-MS: 277 (11, M ), 232 (11), 174 (24), 159 (63), 161 (100), 130 (13), 117 (34), 103 (26), 89 (8), 75 (24).
Hydrolysis of 15. a) A soln. of 15 (70 mg, 0.25 mmol) in 10 ml of 5% aq. HCl was heated to reflux for 4 h,
then extracted with CH2Cl2, and the org. phase was washed with sat. NaHCO3 soln. and brine, and dried
(Na2SO4) to give 43 mg (84%) of 14.
b) To a soln. of 15 (30 mg, 0.11 mmol) in toluene (10 ml), TsOH ¥ H2O (23 mg, 0.12 mmol) was added, and
the mixture was heated to reflux for 2 h. Then, the solvent was evaporated, CH2Cl2 was added, and the org.
phase was washed with sat. NaHCO3 soln. and brine, and dried (Na2SO4) to give 20 mg (91%) of 14.
Preparation of Oximes 16a and 16b, and phenylhydrazones 16c and 16d.
General Procedure A (GP A). To a soln. of 14 in 10 ml of THF, NH2OR ¥ HCl was added, and the mixture
was heated to reflux for 2 h and evaporated to dryness. After addition of Et2O, the soln. was washed with 10%
aq. HCl, sat. NaHCO3 soln., and sat. NaCl soln., and dried (Na2SO4) to give 16 as a mixture of syn- and anti-
isomers.
2,3-Dihydro-1,3-dimethyl-2-oxo-1H-indol-3-acetaldehyde Oxime (16a). According to the GP A, 14
(47.5 mg, 0.23 mmol) and NH2OH ¥ HCl (32 mg, 0.46 mmol). Yield: 35.5 mg (70%) of 16a. Colorless oil.
Mixture of isomers (1:0.8, 1H-NMR). Isomer 1: 1H-NMR: 7.20 (t-like (ABX), JAX ꢀ JBX 6.8, CHN); 7.25 (t-
like, 1 arom. H); 7.18( d-like, 1 arom. H); 7.05 (t-like, 1 arom. H); 6.87 (d-like, 1 arom. H); 3.21 (s, MeN); 2.72
2.57 (m (ABX), JAB ꢀ 14.3, CH2); 1.41 (s, Me). 13C-NMR: 179.4 (s, CO); 147.4 (d, CHN); 142.8, 132.6 (2s, 2
arom. C); 128.1, 122.7, 122.6, 108.2 (4d, 4 arom. CH); 46.9 (s, C(3)); 37.3 (t, CH2); 26.2 (q, MeN); 22.9 (q, Me).
Isomer 2: 1H-NMR: 6.49 (t-like (ABX), JAX ꢀ JBX 5.5, CHN); 7.26 (t-like, 1 arom. H); 7.17 (d-like, 1 arom.
H); 7.04 (t-like, 1 arom. H); 6.82 (d-like, 1 arom. H); 3.23 (s, MeN); 2.96 2.81 (m (ABX), JAB ꢀ 16.1, CH2); 1.43
(s, Me). 13C-NMR: 179.5 (s, CO); 147.4 (d, CHN); 142.8, 133.0 (2s, 2 arom. C); 128.2, 122.8, 122.6, 108.2 (4d,
4 arom. CH); 45.9 (s, C(3)); 32.6 (t, CH2); 26.1 (q, MeN); 22.9 (q, Me).
.
GC: Two isomers were detected. EI-MS (mixture): 218(12, M ), 161 (14), 160 (100), 130 (9), 117 (8), 77
(5).
2,3-Dihydro-1,3-dimethyl-2-oxo-1H-indol-3-acetaldehyde O-Methyloxime (16b). According to the GP A,
14 (75 mg, 0.37 mmol) and NH2OMe ¥ HCl (31 mg, 0.37 mmol). Yield: 81.6 mg (87%) of 16b. HPLC: AcOEt/
hexane 3 :10, 0.5 ml/min, 13 atm. Colorless oil. Mixture of isomers (1:0.74, 1H-NMR). IR (film, mixtures of
isomers): 3056m, 2967s, 2937s, 2900s, 2820m, 1715s, 1614s, 1493s, 1471s, 1453s, 1423s, 1378s, 1350s, 1309s, 1252s,
1159m, 1125s, 1102s, 1085s, 1060s, 1041s, 1020s, 951m, 907m, 8 8 m4, 8 55s, 755s, 744s, 700m, 68 6w, 656w, 637w.