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added a solution of 4 (2.04 g, 11.0 mmol) in DMF (10 mL) at
0 ꢀC under an argon atmosphere. After stirring for 30 min at
0 ꢀC, a solution of 2-trimethylsilanylethanesulfonyl chloride
(2.81 g, 14.0 mmol) in DMF (15 mL) was slowly added at
0 ꢀC. The reaction mixture was stirred for 1 h at 0 ꢀC, and
subsequently allowed to warm up to room temperature
over 1 h. A saturated aqueous ammonium chloride solution
was added (50 mL) and the mixture was extracted with ethyl
acetate (3ꢂ75 mL). The combined organic layers were
washed with water (100 mL), brine (100 mL) and dried
over anhydrous sodium sulfate. Removal of the solvents un-
der reduced pressure afforded a black oil, which was purified
by flash column chromatography on silica gel using
cyclohexane/ethyl acetate 97:3 as an eluent to afford 5 as
a yellow oil. Yield: 1.49 g (39%, 4.3 mmol). Rf (SiO2/cyclo-
EtOAc 90:10)¼0.20; 1H NMR (400.13 MHz, CDCl3,
298 K): d 7.18 (d, J¼7.8 Hz, 1H), 7.03 (t, J¼7.8 Hz, 1H),
6.65 (t, J¼7.8 Hz, 1H), 6.48 (d, J¼7.8 Hz, 1H), 4.51 (br
s, 1H), 3.20–3.11 (m, 1H), 2.87–2.80 (m, 1H), 2.59–2.48
(m, 1H), 2.09–1.99 (m, 1H), 1.78–1.39 (m, 8H), 1.27–1.12
(m, 2H); MS (70 eV) m/z 267 (M+ (C14H1535Cl2N), 19),
232 (100).
4.1.5. 5,7,8,9,10,11-Hexahydrocycloocta[b]indol-6-one
(10). To a solution of 7 (199 mg, 0.75 mmol) in dry
DMSO (10 mL) was added during a period of 1 h t-BuOK
(92 mg, 0.82 mmol). After another 1 h of stirring, the reac-
tion mixture was partitioned between ice water (200 mL)
and diethyl ether (75 mL). The layers were separated and
the aqueous layer was extracted four times with diethyl
ether. The combined organic layers were washed with water
(3ꢂ), dried (MgSO4) and concentrated under reduced pres-
sure to afford a yellow oil. The crude product was purified
by flash column chromatography (Al2O3/CH2Cl2) to afford
10 as colorless crystals. Yield: 36 mg (23%, 0.17 mmol);
1H NMR (400.13 MHz, CDCl3, 298 K): d 8.95 (br s, 1H),
7.72 (d, J¼6.7 Hz, 1H), 7.41–7.08 (m, 3H), 3.32 (t,
J¼7.0 Hz, 2H), 3.03 (t, J¼7.3 Hz, 2H), 1.92–1.68 (m, 4H),
1.54–1.36 (m, 2H); 13C NMR (100.64 MHz, CDCl3,
298 K): d 193.7, 136.2, 135.0, 127.8, 126.2, 121.7, 120.8,
119.9, 111.9, 40.4, 25.2, 23.6, 23.1, 22.5; HRMS: [M]+,
found 213.1157. C14H15NO requires 213.1154.
1
hexane/ethyl acetate 95:5)¼0.44; H NMR (400.13 MHz,
CDCl3, 298 K): d 8.05–8.01 (m, 1H), 7.48–7.44 (m, 1H),
7.29–7.23 (m, 2H), 3.27–3.22 (m, 2H), 3.13–3.07 (m, 2H),
2.81–2.77 (m, 2H), 1.93–1.87 (m, 2H), 1.84–1.74 (m,
4H), 0.87–0.81 (m, 2H), ꢁ0.05 (s, 9H); 13C NMR
(100.64 MHz, CDCl3, 298 K): d 139.8, 136.6, 130.6,
124.0, 123.3, 122.7, 118.2, 114.9, 51.4, 31.4, 27.2, 27.1,
26.9, 23.9, 10.1, ꢁ1.8 (3C, SiMe3); MS (70 eV) m/z 349
(M+ (C18H17NO2SSi), 15.9), 285 (11.6), 257 (17.1), 184
(16.2), 73 (100); HRMS: [M]+, found 349.1532.
C18H27NO2SSi requires 349.1532.
4.1.3. 15,15-Dichloro-8-(2-trimethylsilanylethanesul-
fonyl)-8-azatetracyclo[7.5.1.01,9.02,7]pentadeca-2(3),4,6-
triene (6). To a solution of 5 (979 mg, 2.80 mmol), hexa-
decyltrimethylammonium bromide (10.2 mg, 0.028 mmol)
and one drop of ethanol in CHCl3 (6.02 g, 50.4 mmol)
50% aqueous NaOH (1.68 g, 42.0 mmol) was added under
cooling with ice. The resulting brown two-phase system
was vigorously stirred for 18 h at room temperature, poured
into ice water and extracted with CH2Cl2 (3ꢂ). The com-
bined organic layers were washed with water (2ꢂ), brine
(1ꢂ), dried over Na2SO4 and concentrated at reduced pres-
sure. The crude product was purified by flash column chro-
matography (silica gel, cyclohexane/EtOAc 98:2) to afford 6
as a pale yellow solid. Yield: 839 mg (69%, 1.94 mmol). Rf
(SiO2/cyclohexane/EtOAc 98:2)¼0.27. Mp 138 ꢀC; 1H
NMR (400.13 MHz, CDCl3, 298 K): d 7.23–7.17 (m, 3H),
7.01–6.96 (m, 1H), 3.19–3.07 (m, 2H), 2.87 (dd,
JAB¼ꢁ15.7 Hz, 5.9 Hz, 1H), 2.60 (dd, JAB¼ꢁ15.6 Hz,
6.6 Hz, 1H), 191–1.73 (m, 5H), 1.39–1.28 (m, 1H), 1.23–
1.03 (m, 4H); 13C NMR (100.64 MHz, CDCl3, 298 K):
d 146.2, 130.5, 129.3, 124.6, 123.1, 113.9, 70.7, 63.7,
53.3, 47.6, 31.7, 28.8, 28.4, 27.3, 26.6, 10.3, ꢁ1.7 (3C);
HRMS: [M]+, found 431.0908. C19H27Cl2NO2SSi requires
431.0909.
4.1.6. 9,9,16-Trichloro-8-azatetracyclo[8.5.1.02,7.08,10]-
hexadeca-1(16),2,4,6-tetraene (11) and 10-chloro-
2,3,4,5-tetrahydro-1H-cyclohepta[1,2,-b]quinoline (3).
To a solution of 4 (925 mg, 5.0 mmol) in anhydrous benzene
(50 mL) was added PhHgCCl3 (4.35 g, 11.0 mmol). The
reaction mixture was heated under reflux for 24 h. After
removal of the solvent at reduced pressure the residue was
subjected to flash column chromatography using pentane
as an eluent to afford 11 and 3 as white solids. 11: yield:
175 mg (11%, 0.56 mmol); Rf (SiO2/pentane)¼0.50. Mp
94 ꢀC; 1H NMR (400.13 MHz, CDCl3, 298 K): d 7.27–
7.18 (m, 3H), 7.12–7.07 (ddd, J¼7.8 Hz, 7.6 Hz, 1.6 Hz,
1H), 3.28–3.20 (m, 1H), 2.82–2.71 (m, 2H), 2.25–2.14 (m,
2H), 1.93–1.66 (m, 4H), 1.53–1.43 (m, 1H); 13C NMR
(100.64 MHz, CDCl3, 298 K): d 140.7, 135.5, 129.5,
128.0, 125.9, 124.5, 123.3, 122.8, 69.2, 60.5, 40.4, 38.3,
31.2, 28.7, 26.0; HRMS: [M]+, found 313.0912.
C15H14Cl3N requires 313.0912. 3: yield: 20 mg (2%,
0.09 mmol); all spectroscopic data are in accord with those
reported in the literature.20
4.1.7. Synthesis of 11 under phase transfer conditions. To
a solution of 4 (1.85 g, 10.0 mmol), hexadecyltrimethyl-
ammonium bromide (20.4 mg, 0.056 mmol) and one drop
of ethanol in CHCl3 (21.5 g, 180 mmol) was added under
cooling with ice 50% aqueous NaOH (6.0 g, 150 mmol).
The resulting brown two-phase system was vigorously
stirred for 18 h at room temperature, poured into ice water
and extracted with CH2Cl2 (3ꢂ). The combined organic
layers were washed with water (2ꢂ), brine (1ꢂ), dried
over Na2SO4 and concentrated at reduced pressure. The
crude product was purified by flash column chromatography
(silica gel, cyclohexane/EtOAc 99:1/98:2) to afford 11 as
a yellow oil, which crystallized upon standing. Yield:
650 mg (21%, 2.08 mmol).
4.1.4. 15,15-Dichloro-8-azatetracyclo[7.5.1.01,9.02,7]-
pentadeca-2(3),4,6-triene (7). To a solution of 6 (432 mg,
1.0 mmol) in dry THF (25 mL) was added TBAF$3H2O
(1.29 g, 3.5 mmol) and Na2CO3 (198 mg, 2.0 mmol). After
stirring for 2 h at room temperature, the reaction mixture
was partitioned between brine (50 mL) and diethyl ether
(50 mL). The layers were separated and the aqueous layer
was extracted with diethyl ether. The combined organic
layers were washed with brine, dried (Na2SO4) and concen-
trated under reduced pressure to afford 7 as a yellow oil.
Yield: 200 mg (75%, 0.75 mmol). Rf (SiO2/cyclohexane/