M. Kobayashi et al. / Tetrahedron Letters 47 (2006) 1469–1471
1471
Synlett 1994, 1005–1006; (c) Takaoka, K.; Aoyama, T.;
Shioiri, T. Tetrahedron Lett. 1996, 37, 4973–4976; (d)
Takaoka, K.; Aoyama, T.; Shioiri, T. Tetrahedron Lett.
1996, 37, 4977–4978; (e) Matsumoto, T.; Takaoka, K.;
Aoyama, T.; Shioiri, T. Tetrahedron 1997, 53, 225–236; (f)
Takaoka, K.; Aoyama, T.; Shioiri, T. Tetrahedron Lett.
1999, 40, 3017–3020; (g) Takaoka, K.; Aoyama, T.;
Shioiri, T. Heterocycles 2001, 54, 209–215; (h) Arai, S.;
Sakurai, T.; Asakura, H.; Fuma, S. Heterocycles 2001, 55,
2283–2287.
(100). HRMS (M+): m/z calcd for C16H15NO4: 285.1001;
found: 285.1003.
2-Acetoxy-8-methoxy-pyrrolo[2,1-a]isoquinoline-3-carbox-
ylic acid ethyl ester (4c): Yellow needles of mp 138–
141 °C (EtOAc–hexanes). IR (nujol): 1767, 1670 cmÀ1
.
1H NMR (270 MHz, CDCl3): d = 1.40 (t, J = 7.1 Hz, 3H),
2.37 (s, 3H), 3.92 (s, 3H), 4.36 (q, J = 7.1 Hz, 2H), 6.73 (s,
1H), 6.98 (d, J = 7.6 Hz, 1H), 7.06 (d, J = 2.4 Hz, 1H),
7.16 (dd, J = 8.8, 2.4 Hz, 1H), 7.95 (d, J = 8.8 Hz, 1H),
9.19 (d, J = 7.6 Hz, 1H). 13C NMR (67.8 MHz, CDCl3):
d = 14.9, 21.4, 55.8, 60.3, 94.3, 106.6, 107.9, 112.7,
118.0, 118.8, 125.1, 125.4, 129.9, 133.3, 145.5, 159.5,
160.7, 169.2. EIMS: m/z (%) = 327 (70, M+), 239 (100).
HRMS (M+): m/z calcd for C18H17NO5: 327.1107; found:
327.1101.
´
`
3. For preparation of TMS ketene: Valentı, E.; Pericas, M.
A.; Sarratosa, F. J. Org. Chem. 1990, 55, 395–397.
4. The use of Et3N as a base resulted in no reaction. The
results of solvent effects were as follows: toluene (62%
yield), DMF (complex mixtures).
5. Representative procedure: A mixture of 2-ethoxycarbonyl-
methylisoquinolinium bromide (1a) (118 mg, 0.40 mmol)
and i-Pr2NEt (0.0840 mL, 0.480 mmol) in THF (10 mL)
was refluxed for 2 h under argon and then to this mixture
trimethylsilylketene (2.91 mL, 0.960 mmol, 0.330 M in
toluene solution) was added. The reaction mixture was
refluxed for 24 h, diluted with water, and extracted with
EtOAc. The combined organic layer was washed with
brine, dried over Na2SO4 and concentrated in vacuo. The
residue was purified by silica gel column chromatography
(hexanes/EtOAc, 30:1 to 10:1) to afford 2-hydroxy-pyr-
rolo[2,1-a]isoquinoline-3-carboxylic acid ethyl ester (3a)
(35.1 mg, 34%) as brown powders and 2-acetoxy-pyr-
rolo[2,1-a]isoquinoline-3-carboxylic acid ethyl ester (4a)
(38.4 mg, 32%) as white powders. The spectral data of 3a
were as follows. Mp 77–78 °C (EtOAc–hexanes). IR
2-Hydroxy-7-nitro-pyrrolo[2,1-a]isoquinoline-3-carboxylic
acid ethyl ester (3d): Orange powders of mp 193–194 °C
1
(EtOAc–hexanes). IR (nujol): 3471, 1682 cmÀ1. H NMR
(270 MHz, CDCl3): d = 1.49 (t, J = 7.1 Hz, 3H), 4.53 (q,
J = 7.1 Hz, 2H), 6.67 (s, 1H), 7.58 (dd, J = 8.0, 8.0 Hz,
1H), 7.66 (d, J = 8.0 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H),
8.29 (d, J = 8.0, 1H), 8.86 (br s, 1H). 13C NMR
(67.8 MHz, CDCl3): d = 14.7, 60.9, 90.3, 102.4, 104.8,
121.6, 124.5, 125.5, 126.1, 127.7, 129.0, 132.2, 145.5.
EIMS: m/z (%) = 300 (38, M+), 254 (100). Anal. Calcd for
C15H12N2O5: C, 60.00; H, 4.03; N, 9.33. Found: C, 59.76;
H, 4.14; N, 9.11.
2-Oxo-2H-pyrrolo[2,1-a]isoquinoline-3,3-dicarboxylic acid
diethyl ester (11): A yellow oil. IR (neat): 1732, 1683,
1634 cmÀ1 1H NMR (270 MHz, CDCl3): d = 1.33 (t,
.
J = 7.1 Hz, 6H), 4.35 (q, J = 7.1 Hz, 2H), 4.36 (q,
J = 7.1 Hz, 2H), 5.59 (s, 1H), 6.57 (d, J = 7.3 Hz, 1H),
7.28 (d, J = 7.3 Hz, 1H), 7.45–7.53 (m, 2H), 7.63–7.69 (m,
1H), 7.83 (d, J = 8.1 Hz, 1H). 13C NMR (67.8 MHz,
CDCl3): d = 14.0, 63.6, 78.6, 88.7, 108.0, 121.8, 126.7,
127.4, 127.5, 128.6, 133.3, 134.9, 162.7, 166.8, 183.1.
EIMS: m/z (%) = 327 (59, M+), 209 (100). HRMS (M+):
m/z calcd for C18H17NO5: 327.1107; found: 327.1083.
6. Kato, T.; Chiba, T.; Tanaka, S.; Sasaki, T. Heterocycles
1978, 11, 227–230.
(nujol): 3356, 1638 cmÀ1 1H NMR (270 MHz, CDCl3):
.
d = 1.46 (t, J = 7.1 Hz, 3H), 4.47 (q, J = 7.1 Hz, 2H), 6.50
(s, 1H), 6.79 (d, J = 7.6 Hz,1H), 7.39–7.46 (m, 2H), 7.51–
7.56 (m, 1H), 7.90–7.94 (m, 1H), 8.59 (br s, 1H). 13C NMR
(67.8 MHz, CDCl3): d = 14.6, 60.2, 88.5, 101.5, 110.5,
123.3, 123.6, 124.4, 126.5, 127.0, 127.5, 128.3, 134.0.
EIMS: m/z (%) = 255 (87, M+), 209 (100). HRMS (M+):
m/z calcd for C15H13NO3: 255.0896; found: 255.0929. The
spectral data of 4a were comparable to those reported.10
The spectral data of selected pyrrolo[2,1-a]isoquinoline
derivatives were as follows.
7. Other bases such as pyridine, NaOAc, and NaHCO3 gave
less satisfactory results.
2-Hydroxy-8-methoxy-pyrrolo[2,1-a]isoquinoline-3-carbox-
ylic acid ethyl ester (3c): Yellow plates of mp 173–175 °C
8. We previously demonstrated that the [4+2] cycloaddition
of TMS ketene and a 1,3-diene proceeded by a stepwise
process.2a However, in the case of Scheme 1, a concerted
mechanism might be considered.
9. For a recent example of the 1,3-dipolar cyclization of N-
ylides, see: Fang, X.; Wu, Y.-M.; Deng, J.; Wang, S.-W.
Tetrahedron 2004, 60, 5487–5493, and references cited
therein.
1
(EtOAc–hexanes). IR (nujol): 3271, 1636 cmÀ1. H NMR
(270 MHz, CDCl3): d = 1.48 (t, J = 7.1 Hz, 3H), 3.92 (s,
3H), 4.49 (q, J = 7.1 Hz, 2H), 6.46 (s, 1H), 6.85 (d,
J = 7.3 Hz, 1H), 7.02 (d, J = 2.3 Hz, 1H), 7.14 (dd,
J = 8.9, 2.3 Hz, 1H), 7.93 (d, J = 8.9 Hz, 1H), 8.50 (br s,
0.5H), 9.30 (br s, 0.5H). 13C NMR (67.8 MHz, CDCl3):
d = 14.8, 55.4, 60.2, 87.6, 107.5, 110.4, 117.4, 118.1, 125.2,
130.2, 159.3. EIMS (EI): m/z (%) = 285 (48, M+), 239
10. Kato, T.; Chiba, T.; Sasaki, T. Heterocycles 1979, 12, 925–
928.