Efficient Route to Fused Aryltetrahydroindolizinones
tracted with ethyl acetate (2ϫ20 mL). The combined organic layers
were dried, filtered and concentrated under reduced pressure to
give 31 (610 mg, 98%) as a yellow solid; m.p. 135–136 °C. 1H NMR
2 ϫ CH), 127.1 (2 ϫ CH), 122.9 (2 ϫ Cq), 109.1 (O-Cq-O), 64.8
(2ϫOCH ), 36.4 (2ϫCH ), 24.0 (CH ) ppm. IR (ATR-Ge): ν =
˜
2
2
3
1698 (C=O amide), 1647 (C=C), 1568 (C=C arom.), 1343 (C–O),
(250 MHz, CDCl3): δ = 8.32 (s, 2 H), 8.05 (dd, JH,H = 6.0, JH,H 1234 (C–C) cm–1. HRMS (ESI): calcd. for C18H17NO4 [M + Na]+
3
3
3
3
= 3.5 Hz, 2 H), 7.69 (dd, JH,H = 6.3, JH,H = 3.1 Hz, 2 H), 4.03–
334.1055; found 334.1061.
3.92 (m, 4 H, 2ϫOCH2), 3.89 (t, 3JH,H = 7.2 Hz, 2 H, NCH2), 2.13
3-Hydroxy-2-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-2,3-dihydro-1H-
benzo[de]isoquinolin-1-one (35): Compound 35 was obtained from
34 (92%) as described for compound 16, as a yellow solid; m.p.
(t, JH,H = 7.2 Hz, 2 H, CH2), 1.41 (s, 3 H, CH3) ppm. 13C NMR
3
(62.6 MHz, CDCl3): δ = 168.1 (2 ϫ CO), 135.6 (2 ϫ Cq), 130.4
(2ϫCH), 129.2 (2ϫCH), 128.1 (2ϫCq), 124.6 (2ϫCH), 108.9 (O-
Cq-O), 64.8 (2 ϫ OCH2), 36.4 (NCH2 ), 34.0 (CH2 ), 23.9
1
3
174–175 °C. H NMR (250 MHz, [D6]DMSO): δ = 8.23 (d, JH,H
3
3
= 7.1 Hz, 1 H), 8.17 (d, JH,H = 8.3 Hz, 1 H), 8.03 (dd, JH,H
7.3, JH,H = 1.9 Hz, 1 H), 7.72–7.66 (m, 3 H), 6.69 (d, JH,H
=
=
(CH ) ppm. IR (ATR-Ge): ν = 1691 (C=O amide), 1367 (C–O ace-
˜
3
4
3
tal), 1189 (C–N), 1040 (C–C) cm–1. HRMS (ESI): calcd. for
3
8.9 Hz, 1 H), 6.16 (d, JH,H = 8.0 Hz, 1 H, OH), 3.98–3.86 (m, 1
H, NCH2), 3.90 (brs, 4 H, 2ϫOCH2), 3.66–3.54 (m, 1 H, NCH2),
2.08–2.01 (m, 1 H, NCH2CH2), 1.31 (s, 3 H, CH3) ppm. 13C NMR
(62.5 MHz, [D6]DMSO): δ = 161.6 (C=O), 132.1 (Cq), 131.6 (CH),
131.5 (CH), 127.5 (CH), 126.5 (CH), 126.4 (CH), 126.2 (CH), 126.1
(CH), 126.0 (Cq), 124.0 (CH), 108.3 (O-Cq-O), 79.9 (CH), 64.0
(2ϫOCH2), 40.3 (NCH2), 36.5 (CH2), 23.9 (CH3) ppm. IR (ATR-
C18H17NO4 [M + Na]+ 334.1055; found 334.1043.
3-Hydroxy-2-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-2,3-dihydro-1H-
benzo[f]isoindol-1-one (31): Compound 32 was obtained from 30 as
described for compound 16, after 2 h. The crude product was puri-
fied by flash chromatography on silica gel to give 32 (91%) as a
1
white solid; m.p. 197–198 °C. H NMR (250 MHz, [D6]DMSO): δ
Ge): ν = 1199 (C–O), 1044 (C–C), 771 (CH arom.) cm–1. SM (IS)
˜
= 8.26 (s, 1 H, OH), 8.16–8.08 (m, 2 H), 7.67–7.57 (m, 2 H), 6.66
(m/z): 314 [M + H]+.
2
2
(d, JH,H = 9.2 Hz, 1 H), 5.99 (d, JH,H = 9.2 Hz, 1 H), 3.90 (brs,
4 H, 2ϫOCH2), 3.81–3.69 (m, 1 H, N-CH2), 3.49–3.34 (m, 1 H,
NCH2), 2.13 (m, 2 H, CH2), 1.31 (s, 3 H, CH3) ppm. 13C NMR
(62.5 MHz, [D6]DMSO): δ = 165.5 (CO), 140.3 (Cq), 134.7 (Cq),
133.0 (Cq), 129.8 (Cq), 129.3 (CH), 128.3 (CH), 127.6 (CH), 126.6
(CH), 122.5 (CH), 122.2 (CH), 108.1 (O-Cq-O), 80.6 (CH), 64.0
(2ϫOCH2), 36.5 (NCH2), 34.6 (CH2), 23.7 (CH3). IR (ATR-Ge):
9,10,12,12a-Tetrahydro-7H-spiro[benzo[de]pyrido[2,1-a]isoquinoline-
11,2Ј-[1,3]dioxolan]-7-one (36): Compound 36 was obtained by Ge-
neral Procedure B from 35 after purification by flash chromatog-
raphy (petroleum ether/ethyl acetate, 3:2) in an 80% yield and as a
white solid; m.p. 157–158 °C. 1H NMR (250 MHz, CDCl3): δ =
3
4
3
8.38 (dd, JH,H = 7.2, JH,H = 1.1 Hz, 1 H), 7.97 (dd, JH,H = 8.3,
ν = 1203 (C–O), 1047 (C–C), 778 (CH arom.) cm–1. SM (IS) (m/z):
4JH,H = 1.0 Hz, 1 H), 7.80 (d, 3JH,H = 8.2 Hz, 1 H), 7.60 (dd, 3JH,H
= 8.2, JH,H = 7.3 Hz, 1 H), 7.52 (t, JH,H = 7.5 Hz, 1 H), 7.37 (d,
3JH,H = 7.2 Hz, 1 H), 5.20–5.07 (m, 2 H, H12a and H9), 4.15–4.00
˜
314.5 [M + H]+.
3
3
1,3,4,12b-Tetrahydro-6H-spiro[benzo[f]pyrido[2,1-a]isoindole-2,2Ј-
1,3-dioxolan]-6-one (32): Compound 32 was obtained by General
Procedure B from 27 and 31 after purification by flash chromatog-
raphy (petroleum ether/ethyl acetate, 1:2) in 30% and 70% yields,
respectively, as a white solid; m.p. 129–130 °C. 1H NMR
2
3
(m, 4 H, 2ϫOCH2), 3.01 (dt, JH,H = 13.8, JH,H = 8.1 Hz, 1 H,
2
2
H9), 2.12 (d, JH,H = 12.9 Hz, 1 H, H12), 1.96 (d, JH,H = 12.2 Hz,
1 H, H12), 1.90–1.85 (m, 2 H, H10) ppm. 13C NMR (62.6 MHz,
CDCl3): δ = 161.6 (C=O), 132.6 (Cq), 132.0 (Cq), 131.6 (CH),
127.6 (Cq), 126 ppm. (CH), 126.5 (CH), 126.4 (Cq), 126.1 (CH),
124.2 (CH), 123.0 (CH), 107.2 (O-Cq-O), 64.8 (2ϫOCH2), 57.9
3
(250 MHz, CDCl3): δ = 8.36 (s, 1 H), 8.00 (d, JH,H = 9.2 Hz, 1
3
H), 7.90 (d, JH,H = 8.7 Hz, 1 H), 7.80 (s, 1 H), 7.62–7.52 (m, 2
(CH), 47.7 (CH ), 40.8 (CH ), 35.2 (CH ) ppm. IR (ATR-Ge): ν =
2
3
˜
2
2
2
H), 4.75 (dd, JH,H = 12.1, JH,H = 3.8 Hz, 1 H, H12b), 4.55 (ddd,
1638 (C=O amide), 1615 (C=C arom.), 1071 (C–C) cm–1. HRMS
3
3
2JH,H = 13.3, JH,H = 5.6, JH,H = 1.4 Hz, 1 H, H4eq), 4.16–4.00
(ESI): calcd. for C18H18NO3 [M + H]+ 296.1287; found 296.1284.
2
3
3
(m, 4 H, 2ϫOCH2), 3.29 (td, JH,H = 13.0, JH,H = 13.0, JH,H
3.9 Hz, 1 H, H4ax), 2.42 (ddd, JH,H = 12.8, JH,H = 3.8, JH,H
=
=
2
3
3
1,3,4,10b-Tetrahydropyrido[2,1-a]isoindole-2,6-dione (37): Com-
pound 37 was obtained from 12 after 1 h 30 min by General Pro-
cedure C with purification by flash chromatography on silica gel
3
2.4 Hz, 1 H, H1eq), 1.90–1.84 (m, 1 H, H3), 1.72 (td, JH,H = 12.8,
3
3JH,H = 12.8, JH,H = 5.6 Hz, 1 H, H1ax), 1.48 (m, 1 H, H3) ppm.
13C NMR (62.5 MHz, [D6]DMSO): δ = 164.5 (CO), 140.4 (Cq),
134.4 (Cq), 132.5 (Cq), 130.0 (Cq), 129.2 (CH), 127.9 (CH), 127.5
(CH), 126.2 (CH), 122.9 (CH), 120.9 (CH), 106.7 (O-Cq-O), 64.2
(–OCH2), 63.9 (OCH2), 56.1 (CH), 39.9 (CH2), 36.2 (CH2), 33.4
(petroleum ether/ethyl acetate, 1:2) as a white solid (quant.); m.p.
3
123–124 °C. 1H NMR (250 MHz, CDCl3): δ = 7.90 (d, JH,H
=
3
6.8 Hz, 1 H), 7.62–7.52 (m, 2 H), 7.42 (d, JH,H = 7.2 Hz, 1 H),
3
3
4.82–4.73 (m, 1 H, H4), 4.71 (dd, JH,H = 12.5, JH,H = 3.9 Hz, 1
(CH ) ppm. IR (NaCl): ν = 1703 cm–1 (C=O amide), 1644 (C=C),
2
3
˜
2
H, H1eq), 3.46–3.34 (m, 1 H, H4), 3.02 (dd, JH,H = 14.0, JH,H =
1424 (C=C aromatic), 1391 (C–O), 1265 (C–C) cm–1. HRMS (ESI):
2
4.2 Hz, 1 H, H1), 2.59–2.54 (m, 2 H, H3), 2.25 (dd, JH,H = 14.0,
3JH,H = 12.5 Hz, 1 H, H1ax) ppm. 13C NMR (62.6 MHz, CDCl3):
δ = 205.9 (C=O), 166.5 (C=O), 144.3 (Cq), 132.1 (Cq), 131.7 (Cq),
129.0 (Cq), 124.3 (CH), 121.9 (CH), 57.9 (CH), 46.5 (CH2), 39.9
calcd. for C18H18NO3 [M + H]+ 296.1287; found 296.1288.
2-[2-(2-Methyl-1,3-dioxolan-2-yl)ethyl]-1H-benzo[de]isoquinoline-
1,3(2H)-dione (34): A mixture of anhydride 33 (991 mg, 5.0 mmol)
and 2-(2-methyl-1,3-dioxolan-2-yl)ethylamine (1, 720 mg,
5.5 mmol) in toluene (60.0 mL) was heated at reflux overnight un-
der a Dean–Stark apparatus. After cooling, the mixture was
washed with water (40 mL) and extracted with ethyl acetate
(3ϫ20 mL). The combined organic layers were dried, filtered and
concentrated under reduced pressure to give 34 (1.60 g, quant.) as
(CH ), 37.5 (CH ) ppm. IR (ATR-Ge): ν = 1692 (CO ketone), 1775
˜
2
2
(CO amide), 1245 (C–O), 1073–1051 (C–N) cm–1. HRMS (ESI):
calcd. for C12H12NO2 [M + H]+ 202.0868; found 202.0884.
7,8-Dimethoxy-1,3,4,10b-tetrahydropyrido[2,1-a]isoindole-2,6-dione
(38): Compound 38 was obtained from 13 after 1 h 30 min by Ge-
neral Procedure C with purification by flash chromatography on
silica gel (petroleum ether/ethyl acetate, 1:2) as a white solid (81%);
1
a yellow solid; m.p. 137–138 °C. H NMR (250 MHz, CDCl3): δ =
3
4
3
1
3
8.61 (dd, JH,H = 7.3, JH,H = 1.0 Hz, 2 H), 8.21 (dd, JH,H = 8.3,
m.p. 157–158 °C. H NMR (250 MHz, CDCl3): δ = 7.12 (d, JH,H
4JH,H = 0.9 Hz, 2 H), 7.76 (t, JH,H = 8.1 Hz, 2 H), 4.35–4.29 (m,
= 8.2 Hz, 1 H), 7.04 (d, JH,H = 8.2 Hz, 1 H), 4.77–4.68 (m, 1 H,
3
3
3
3
2 H, NCH2), 4.03–3.97 (m, 4 H, 2ϫOCH2), 2.14–2.08 (m, 2 H,
NCH2CH2), 1.48 (s, 3 H, CH3) ppm. 13C NMR (62.5 MHz,
CDCl3): δ = 164.2 (2 ϫ C=O), 134.0 (2 ϫCH), 131.3 (2 ϫCq +
H4), 4.60 (dd, JH,H = 11.9, JH,H = 4.2 Hz, 1 H, H10b), 4.10 (s, 3
H, OMe), 3.91 (s, 3 H, OMe), 3.39–3.28 (m, 1 H, H4), 2.94 (dd,
2JH,H = 14.0, JH,H = 4.2 Hz, 1 H, H1eq), 2.57–2.51 (m, 2 H, H3),
3
Eur. J. Org. Chem. 2009, 3011–3021
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3019