◦
−78 C for 15 minutes then allowed to warm to rt. The mixture
3-{1-[6-(2-Dimethylaminoethyl)-4-methoxybenzo[1,3]dioxol-5-yl]-
methylidene}-6,7-dimethoxy-2-(4-methoxybenzyl)-2,3-
dihydroisoindol-1-one (3)
was quenched with aq. saturated NH4Cl solution (5 mL), and then
extracted with Et2O (2 × 30 mL), the organic layer was washed
with water (15 mL) and with brine, then dried (Na2SO4). The
solution was concentrated under reduced pressure, then the oily
residue was separated by flash column chromatography on silica
gel (acetone–hexanes, 50 : 50) to afford the two diastereomers 4a
and 4b (50 : 50) as white solids. For atom numbering see Fig. 3.
A solution of 4 (530 mg, 1 mmol) in acetonitrile (10 mL) was
refluxed with an excess of methyl iodide (0.5 mL, 8 mmol) for
4 h. The solvent was removed under reduced pressure to furnish
11 as a white solid. A solution of KHMDS (2.6 mL, 0.5 M in
toluene, 1.3 mmol) was added to a suspension of 11 in dry THF
under N2 at −78 ◦C. The mixture was allowed to warm to rt and
the solution was quenched with water (10 mL) and extracted with
Et2O (3 × 20 mL). The organic layers were washed with water
(10 mL), brine and dried (Na2SO4). The solvent was removed
under reduced pressure and the oily residue was separated by flash
column chromatography on silica gel (AcOEt–Et3N, 90 : 10) to
afford the two isomers (E)-3 and (Z)-3 as yellow solids.
◦
1
(E)-Isomer. Yellow solid (401 mg, 74%), mp 154–155 C. H
NMR dH (CDCl3, 300 MHz): 1.98 (6H, s, 2 × NCH3), 2.06–2.25
(2H, m, CH2), 2.27–2.41 (1H, m, CH2), 2.43–2.57 (1H, m, CH2),
3.73 (3H, s, OCH3), 3.77 (3H, s, OCH3), 3.85 (3H, s, OCH3), 4.11
(3H, s, OCH3), 4.89 (1H, d, J = 15.5 Hz, NCH2Ar), 5.16 (1H, d,
J = 15.5 Hz, NCH2Ar), 5.93 (1H, d, J = 1.3 Hz, OCH2O), 5.97
(1H, d, J = 1.3 Hz, OCH2O), 6.00 (1H, s, CHvinyl), 6.51 (1H, s,
Har), 6.55 (1H, d, J = 8.3 Hz, Har), 6.81–6.88 (3H, m, Har), 7.28
(2H, d, J = 6.5 Hz, 2H, Har); 13C NMR dC (CDCl3, 75 MHz): 31.5
(CH2), 42.5 (CH2), 45.1 (2 × NCH3), 55.2 (OCH3), 56.5 (OCH3),
59.7 (OCH3), 62.4 (OCH3), 60.1 (CH2), 101.0 (OCH2O), 102.7
(CHvinyl), 104.1 (CH), 114.0 (2 × CH), 116.1 (CH), 118.5 (CH),
120.1 (C), 122.1 (C), 128.6 (2 × CH), 129.2 (C), 129.4 (C), 133.8
(C), 135.3 (C), 136.1 (C), 141.4 (C), 146.5 (C), 148.9 (C), 153.3(C),
Fig. 3 Atom numbering for compound 4.
Diastereomer 4a. White◦ solid (440 mg, 33%) mp: thermal
transformation around 190 C. 1H NMR dH (CDCl3, 300 MHz):
2.04 (3H, s, NCH3), 2.44–2.61 [2H, m, (7ꢀ)-H + (8ꢀ)-H], 2.63–2.77
[1H, m, (8ꢀ)-H], 2.97–3.09 [1H, m, (7ꢀ)-H], 3.50 (3H, s, OCH3),
3.65 (3H, s, OCH3), 3.68 [1H, d, J = 14.7 Hz, (8)-H], 3.80 (3H, s,
OCH3), 4.03 [1H, d, J = 2.5 Hz, (5ꢀ-)H], 4.06 (3H, s, OCH3), 4.52
[1H, d, J = 2.5 Hz, (3)-H], 5.23 [1H, d, J = 14.7 Hz, (8)-H], 5.80
(2H, s, OCH2O), 6.31 [1H, s, 1H, (1ꢀ)-Har] 6.61 (2H, d, J = 8.6 Hz,
Har), 6.64 (2H, d, J = 8.6 Hz, Har), 6.78 (1H, d, J = 8.1 Hz, Har),
6.92 (1H, d, J = 8.1 Hz, Har); 13C NMR dC (CDCl3, 75 MHz): 24.6
(8ꢀ-CH2), 43.9 (NCH3), 44.3 (8-CH2), 47.8 (7ꢀ-CH2), 55.2 (OCH3),
56.7 (OCH3), 58.5 (OCH3), 61.3 (3- or 5ꢀ-CH), 61.4 (3- or 5ꢀ-CH),
62.6 (OCH3), 100.5 (OCH2O), 102.5 (CH), 113.5 (2 × CH), 115.8
(CH), 117.1 (CH), 119.2 (C), 124.5 (C), 129.3 (2 × CH), 129.6
(C), 129.8 (C), 133.9 (C), 139.5 (C), 140.8 (C), 147.0 (C), 148.2
=
158.8 (C), 164.9 (C O). CHN Analysis (Found: C, 68.3; H, 6.15;
N, 4.8%. C31H34N2O7 requires C, 68.1; H, 6.3; N, 5.1%).
◦
1
(Z)-Isomer. Yellow solid (73 mg, 13%), mp 124–125 C. H
NMR dH (CDCl3, 300 MHz): 2.01 (6H, s, 2 × NCH3), 2.05–2.25
(3H, m, 3H, CH2), 2.30–2.47 (1H, m, CH2), 3.63 (3H, s, OCH3),
3.67 (3H, s, OCH3), 3.87 (3H, s, OCH3), 4.08 (3H, s, OCH3),
4.57 (1H, d, J = 15.6 Hz, NCH2Ar), 4.72 (1H, d, J = 15.6 Hz,
NCH2Ar), 5.84 (1H, d, J = 1.3 Hz, OCH2O), 5.88 (1H, d, J =
1.3 Hz, OCH2O), 6.10 (1H, s, CHvinyl), 6.32 (1H, s, Har), 6.46 (2H,
d, J = 8.7 Hz, Har), 6.54 (2H, d, J = 8.7 Hz, Har), 7.07 (1H, d,
J = 8.3 Hz, Harom), 7.35 (1H, d, J = 8.3 Hz, Harom); 13C NMR dC
(CDCl3, 75 MHz): 31.5 (CH2), 43.4 (CH2), 45.3 (2 × NCH3), 55.2
(OCH3), 56.8 (OCH3), 59.1 (OCH3), 59.7 (CH2), 62.5 (OCH3),
99.3 (CHvinyl), 100.8 (OCH2O), 103.0 (CH), 113.3 (2 × CH), 114.9
(CH), 116.7 (CH), 119.0 (C), 120.3 (C), 127.7 (2 × CH), 129.8
(C), 132.0 (C), 134.0 (C), 134.5 (C), 134.9 (C), 141.5 (C), 145.7
=
(C), 152.0 (C), 158.7 (C), 167.6 (C O); CHN Analysis (Found:
C, 67.8; H, 6.0; N, 5.1%. C30H32N2O7 requires C, 67.7; H, 6.1; N,
5.3%).
Diastereomer 4b. White◦ solid (429 mg, 32%) mp: thermal
transformation around 190 C. 1H NMR dH (CDCl3, 300 MHz):
1.86–1.96 [1H, m, (8ꢀ)-H], 2.00–2.10 [1H, m, (7ꢀ)-H], 2.15–2.25
[1H, m, (7ꢀ)-H], 2.30 (3H, s, NCH3), 2.45–2.60 [1H, m, (8ꢀ)-H],
3.67 (3H, s, OCH3), 3.71 (3H, s, OCH3), 3.73 (3H, s, OCH3), 3.91
[1H, d, J = 14.9 Hz, (8)-H], 4.03 (3H, s, OCH3), 4.24 [1H, s, (5ꢀ-
)H], 4.55 [1H, s, (3)-H], 5.40 [1H, d, J = 2.5 Hz, (8)-H], 5.78 [2H,
d, J = 8.2 Hz, Har], 5.81 (2H, s, OCH2O), 6.23 [1H, s, 1H, (1ꢀ)-Har],
6.68 (2H, d, J = 8.2 Hz, Har), 6.78 (1H, d, J = 8.4 Hz, Har), 7.22
(1H, d, J = 8.4 Hz, Har); 13C NMR dC (CDCl3, 75 MHz): 23.1
(8ꢀ-CH2), 44.1 (NCH3), 43.4 (8-CH2), 46.6 (7ꢀ-CH2), 55.3 (OCH3),
56.5 (OCH3), 58.0 (OCH3), 59.0 (3- or 5ꢀ-CH), 60.1 (3- or 5ꢀ-CH),
62.6 (OCH3), 100.5 (OCH2O), 102.6 (CH), 113.8 (2 × CH), 115.2
(CH), 118.4 (CH), 117.5 (C), 125.3 (C), 129.3 (C), 129.8 (2 ×
CH), 130.4 (C), 133.8 (C), 137.7 (C), 140.4 (C), 147.0 (C), 148.2
=
(C), 149.0 (C), 153.0 (C), 158.5 (C), 166.7 (C O); CHN Analysis
(Found: C, 68.2; H, 6.0; N, 4.8%. C31H34N2O7 requires C, 68.1; H,
6.3; N, 5.1%).
Narceine imide (1a)
A solution of 3 (275 mg, 0.5 mmol) and anisole (540 mg, 5.0 mmol)
in trifluoroacetic acid (10 mL) was refluxed under N2 for 24 h. The
reaction mixture was concentrated in vacuo, the residue was dis-
solved in CH2Cl2 (20 mL) and Et3N (0.5 mL) was added with stir-
ring. Water (3 × 50 mL) was then added, and the separated organic
layer was washed with brine, dried (MgSO4) and concentrated to
=
(C), 152.0 (C), 158.9 (C), 166.9 (C O); CHN Analysis (Found:
C, 67.4; H, 6.2; N, 5.2%. C30H32N2O7 requires C, 67.7; H, 6.1; N,
5.3%).
1470 | Org. Biomol. Chem., 2007, 5, 1466–1471
This journal is
The Royal Society of Chemistry 2007
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