LETTER
reaction was quenched by crashed ice and the solution was
Synthesis of Isoindolo[2,1-a]quinolin-11-ones
847
134.7 (C), 136.8 (C), 140.1 (C), 166.5 (CO), 196.9 (CO).
MS: m/z (%) = 351 (37) [M+], 350 (14), 336 (25), 246 (79),
105 (100), 77 (89). Anal. Calcd (%) for C24H17NO2: C,
82.03; H, 4.88; N, 3.99 Found: C, 81.94; H, 4.84; N, 4.07.
Compound 3j: colorless needles; 131–132 °C. 1H NMR (300
MHz, CDCl3): d = 1.49–1.75 (m, 2 H), 1.81–1.85 (m, 2 H),
2.16–2.31 (m, 2 H), 2.54–2.62 (m, 2 H), 5.40 (s, 1 H, NCH),
7.22 (t, 1 H, J = 8.7 Hz), 7.30–7.35 (m, 2 H), 7.49–7.61 (m,
2 H), 7.67 (d, 1 H, J = 7.8 Hz), 7.95 (d, 1 H, J = 6.5 Hz), 8.05
(d, 1 H, J = 6.9 Hz). 13C NMR (75 MHz CDCl3): d = 22.0
(CH2), 22.2 (CH2), 22.4 (CH2), 27.5 (CH2), 60.8 (NCH),
121.3 (CH), 122.7 (CH), 124.0 (CH), 124.7 (CH), 127.3
(CH), 127.6 (C), 128.4 (CH), 129.2 (C), 130.4 (C), 131.5
(CH), 132.4 (C), 133.6 (C), 141.2 (C), 165.6 (NCO). MS
(EI): m/z (%) = 287 (86) [M+], 286 (67), 270 (4), 258 (100),
232 (10), 216 (11). Anal. Calcd (%) for C20H17NO: C, 83.60;
H, 5.96; N, 4.87 Found: C, 83.67; H, 6.02; N, 4.74.
Compound 5: colorless needles; 172–174 °C. 1H NMR (300
MHz CDCl3): d = 2.20 (s, 3 H, CH3), 2.73 (dd, 1 H, J = 18.6,
9.6 Hz, CHH), 3.15 (dd, 1 H, J = 18.0, 2.4 Hz, CHH), 5.83
(dd, 1 H, J = 9.6, 2.4 Hz CH), 7.49 (d, 1 H, J = 7.5 Hz, C-5),
7.64 (t, 1 H, J = 7.2 Hz, ArH), 7.55 (t, 1 H, J = 7.2 Hz, ArH),
7.88 (d, 2 H, J = 8.7 Hz, H-2′), 7.92 (d, 1 H, J = 7.8 Hz, H-
7), 8.30 (d, 2 H, J = 9.0 Hz, H-3′). 13C NMR (75 MHz,
CDCl3): d = 30.7 (CH3), 46.2 (CH2), 55.7 (C-3), 121.2 (2 C),
122.8 (CH), 124.5 (CH), 124.9 (2 C), 129.1 (CH), 130.1 (C),
133.3 (CH), 142.6 (C), 143.8 (C), 144.8 (C), 167.1 (NCO),
205.6 (CO). MS (EI): m/z (%) = 310 (11) [M+], 293 (10), 281
(7), 267 (27), 253 (44), 234 (18), 43 (100). Anal. Calcd (%)
for C17H14N2O4: C, 65.80; H, 4.55; N, 9.03 Found: C, 65.75;
H, 4.62; N, 9.02.
Compound 6b: mixture of cis- and trans-isomers (30:70).
1H NMR (300 MHz, CDCl3): d (trans-isomer) = 1.48 (d, 3
H, J = 7.8 Hz, CH3), 1.78 (dt, 1 H, J = 9.3, 3.3 Hz, CHH),
2.30 (dd, 1 H, J = 12.9, 1.2 Hz, CHH), 2.33 (s, 3 H, CH3),
3.18 (t, 1 H, J = 6.6 Hz, CH), 4.78 (d, 1 H, J = 12.3, Hz
NCH), 7.06 (s, 1 H, H-4), 7.11 (d, 1 H, J = 8.4 Hz, H-2),
7.48–7.51 (m, 2 H), 7.57 (d, 1 H, J = 7.5 Hz), 7.92 (d, 1 H,
J = 8.4 Hz), 8.46 (d 1 H, J = 8.1 Hz); d (cis-isomer) = 1.42
(d 3 H, J = 6.9 Hz, CH3), 2.35 (s 3 H, CH3), 2.60 (dt 1 H,
J = 13 5, 1 2 Hz, CHH), 3 21 (t 3 H, J = 6 9 Hz, CH3), 4 70
(dd 1 H, J = 12 3, 2.4 Hz, NCH), 7.11 (d, 1 H, J = 8.4 Hz, H-
2), 7.18 (s, 1 H, H-4), 7.48–7.51 (m, 2 H), 7.59 (d, 1 H,
J = 6.9 Hz), 7.92 (d, 1 H, J = 8.4 Hz), 8.44 (d, 1 H, J = 7.8
Hz). 13C NMR (75 MHz, CDCl3): d (trans-isomer) = 21.0,
24.5, 30.8, 34.8, 54.2 (NCH), 120.1 (CH), 121.7 (CH), 124.1
(CH), 127.6 (CH), 128.3 (CH), 129.6 (CH), 131.0 (C), 131.8
(CH), 132.8 (C), 133.4 (C), 144.6 (C), 165.9 (NCO); d (cis-
isomer) = 20.9, 21.1, 31.4, 37.5, 58.7, 120.0 (CH), 121.7
(CH), 124.1 (CH), 127.6 (CH), 128.4 (CH), 129.6 (CH),
131.0 (C), 131.8 (CH), 132.9 (C), 133.4 (C), 144.6 (C),
165.9 (NCO). MS (EI): m/z = 263 (87) [M+], 248 (100), 232
(16), 220 (17), 115 (25), 77 (38).
extracted with CH2Cl2 (2 × 10 mL).The organic phase was
washed with sat. aq NaHCO3 (10 mL) and H2O, respectively
and dried with anhyd Na2SO4, concentrated at reduced
pressure to furnish the crude products 3a which was purified
by silica gel column chromatography using EtOAc–hexane
(1:9) as eluents and further purified by recrystallization from
EtOH.
Method B
The procedure is similar to method A, only P2O5 was
replaced by H2SO4 (2 mL, 98%) which was added dropwise
into the mixture of 1a (1.0 mmol), 2a (1.2 mmol), and H3PO4
(2 mL).
Selected Spectroscopic Data
Compound 3a: colorless needles; mp 124–126 °C. 1H NMR
(300 MHz, CDCl3): d = 1.33 (t, 3 H, J = 7.5 Hz, CH3), 2.21
(s, 3 H, CH3), 4.35 (q, 2 H, J = 7.5 Hz, OCH2), 5.92 (s, 1 H,
H-6a), 7.23 (t, 1 H, J = 7 8 Hz), 7.42–7.60 (m, 5 H), 7.96 (d,
1 H, J = 7.2 Hz H-10), 8.05 (d, 1 H, J = 7 8 Hz H-1). 13
C
NMR (75 MHz, CDCl3): d = 14.2 (CH3), 15.6 (CH3), 58.7
(OCH2), 61.0 (C-6a), 122.0 (CH), 123.7 (CH), 124.3 (CH),
125.0 (CH), 125.2 (CH), 126.8 (C), 127.5 (C), 128.9 (CH),
129.7(CH), 132.0 (C), 132.5 (CH), 133.7 (C), 134.7 (C),
140.7 (C), 166.5 (CO), 166.9 (CO). MS (EI): m/z (%) = 319
(18) [M+], 304 (8), 290 (30), 274 (4), 262 (6), 246 (99), 86
(100). Anal. Calcd (%) for C20H17NO3: C, 75.22; H, 5.37; N
4.39 Found: C, 75.13; H, 5.45; N 4.25.
Compound 3c: colorless needles; mp 151–153 °C. 1H NMR
(300 MHz, CDCl3): d = 1.33 (t, 3 H, J = 7.2 Hz, CH3), 2.17
(s, 3 H, CH3), 4.35 (q, 2 H, J = 7.5 Hz, OCH2), 5.90 (s, 1 H,
H-6a), 7.39 (dd, 1 H, J = 7.5, 1.5 Hz), 7.42 (d, 1 H, J = 1.5
Hz, H-4), 7.52–7.60 (m, 3 H), 7.94 (d, 1 H, J = 7.5 Hz, H-1),
8.00 (d, 1 H, J = 8.1 Hz, H-10). 13C NMR (75 MHz, CDCl3):
d = 14.2 (CH3), 15.6 (CH3), 58.5 (OCH2), 61.2 (C-6a), 123.1
(CH), 123.7 (CH), 124.4 (CH), 125.2 (CH), 128.0 (C), 129.0
(CH), 129.4 (CH), 130.4 (C), 131.7 (C), 132.5 (C), 132.7
(CH), 133.1 (C), 140.5 (C), 166.5 (CO), 166.7 (CO). MS
(EI): m/z (%) = 355 (8) [M + 2+], 353 (25 [M+], 340 (20), 338
(62), 326 (31), 324 (87), 310 (28), 296 (5), 282 (29), 280
(100). Anal. Calcd (%) for C20H18ClNO3: C, 67.90; H, 4.56;
N, 3.96 Found: C, 67.83; H, 4.63; N, 4.07.
Compound 3f: colorless needles; 141–143 °C. 1H NMR (300
MHz, CDCl3): d = 2.09 (s, 3 H, CH3), 2.16 (s, 3 H, CH3),
2.39 (s, 3 H, CH3), 5.80 (s, 1 H, H-6a), 7.23 (s, 1 H, H-4),
7.26 (t, 1 H, J = 6.0 Hz), 7.41 (d, 1 H, J = 7.2 Hz, H-2), 7.50–
7.59 (m, 3 H), 7.95 (d, 2 H, J = 8.7 Hz, H-1, H-10). 13C NMR
(75 MHz, CDCl3): d = 15.6 (CH3), 21.2 (CH3), 32.8 (CH3),
58.5 (C-6a), 121.5 (CH), 123.7 (CH), 124.3 (CH), 125.2
(CH), 127.2 (C), 128.9 (CH), 129.1 (C), 130.1 (CH), 132.1
(C), 132.2 (C), 132.4 (CH), 134.5 (C), 134.8 (C), 140.1 (C),
166.1 (CO), 204.6 (CO). MS (EI): m/z (%) = 303 (16) [M+],
302 (10), 288 (36), 260 (62), 246 (18), 230 (5), 217 (13), 43
(100). Anal. Calcd (%) for C20H17NO2: C, 79.18; H, 5.65; N,
4.62 Found: C, 79.12; H, 5.74; N, 4.55.
(9) (9) Crystal Data for Compound 3c
Compound 3g: colorless needles; 156–158 °C. 1H NMR
(300 MHz, CDCl3): d = 1.94 (s, 3 H, CH3), 6.06 (s, 1 H, H-
6a), 7.22–7.54 (m, 9 H), 7.80 (d, 2 H, J = 7.8 Hz, H-2¢), 7.90
(d, 1 H, J = 6.9 Hz, H-10), 8. 16 (d, 1 H, J = 7.5 Hz, H-1).
13C NMR (75 MHz, CDCl3): d = 16.4 (CH3), 59.2 (C-6a),
121.7 (CH), 124.0 (2 CH), 124.8 (CH), 125.0 (CH), 127.6
(C), 128.7 (CH), 128.9 (2 CH), 129.2 (2 CH), 129.6 (CH),
131.3 (C), 131.7 (C), 131.9 (C), 132.3 (CH), 134.1 (CH),
Formula: C20H16ClNO3; Mr = 353.79 monoclinic;
a = 9.3133(17) Å, b = 7.3351(14) Å, c = 24.716(5) Å,
b = 96.800(3)°; space group P2(1)/n; V = 1676.6(5) Å3;
colorless plates r = 1.402 g cm–3, T = 296(2) K, space group
P2(1)/c Z = 4, m(Mo Ka) = 0.71073 mm–1, cmax = 25.82°,
3217 reflections collected 2045 unique (Rint = 0.1585) which
was used in all calculations. Final wR (F2) = 0.0830 (all
data); CCDC No: 695063
Synlett 2009, No. 5, 843–847 © Thieme Stuttgart · New York