Chemistry Letters 2002
625
temperature for 10 min, and the excess pyridine and acetic
anhydride were removed under reduced pressure. The residue was
chromatographed on silica gel (1 : 5 EtOAc-hexane) to give 8a
(0.15 g, 51%).5
The pathway which leads to 7 from 6 and isocyanides is
outlined in Scheme 4. Thus, attack of the isocyano carbon to the
activated aldehyde 9 generates the intermediate 10. An
intramolecular combination of the 2-carbon of the pyrrole and
the cation center of 10 affords 11, which gives rise to 7.
J. Chem. Soc., Perkin Trans. 1, 1993, 1809; I. Cardinaud, A.
Gueiffier, J. C. Debouzy, J. C. Milhavet, and J. P. Chapat,
Heterocycles, 36, 2513 (1993); X. Wei, Y. Hu, T. Li, and H.
Hu, J. Chem. Soc., Perkin Trans. 1, 1993, 2487; M. L. Bode, P.
T. Kaye, R. George, J. Chem. Soc., Perkin Trans. 1, 1994,
3023; B. Abarca, R. Ballesteros, and N. Houari, Tetrahedron,
53, 12765 (1997); B. Abarca, R. Ballesteros, N. Houari, and
A. Samadi, Tetrahedron, 54, 3913 (1998).
5
All the stable new compounds gave satisfactory spectral data
1
(IR, H NMR, EIMS, and HRMS). 6: a yellow liquid: bp
130 ꢁC (bath temp)/0.045 Torr; IR (neat) 3140, 3103, 2856,
2759, 1691, 1599 cmꢂ1; 1H NMR (270 MHz, CDCl3) ꢀ 6.39
(2H, t, J ¼ 2:3 Hz), 6.93 (2H, t, J ¼ 2:3 Hz), 7.43 (1H, dd,
J ¼ 7:6, 1.0 Hz), 7.49 (1H, td, J ¼ 7:6, 1.0 Hz), 7.67 (1H, td,
J ¼ 7:6, 1.0 Hz), 7.99 (1H, dd, J ¼ 7:6, 1.0 Hz), 9.81 (1H, s).
MS m=z 171 (Mþ, 58), 143 (93), 115 (100). HRMS (m=z)
Found: 171.0690. Calcd for C11H9NO: Mþ, 171.0684. 8a: mp
125–128 ꢁC (decomp) (hexane–Et2O); IR (KBr disk) 3328,
1751 cmꢂ1; 1H NMR (270 MHz, CDCl3) ꢀ 1.28 (9H, s), 2.12
(3H, s), 5.51 (1H, s), 6.60 (1H, dd, J ¼ 4:0, 1.6 Hz), 6.73 (1H,
dd, J ¼ 4:0, 3.0 Hz), 7.30 (1H, dd, J ¼ 7:9, 1.3 Hz), 7.43 (1H,
td, J ¼ 7:3, 1.3 Hz), 7.52(1H, ddd, J ¼ 7:9, 7.3, 1.3 Hz), 7.79
(1H, dd, J ¼ 3:0, 1.6 Hz), 7.83 (1H, dd, J ¼ 7:3, 1.3 Hz); MS
m=z 296 (Mþ, 4), 253 (6.0), 223 (7.3), 197 (100). HRMS (m=z)
Found: 296.1524. Calcd for C18H20N2O2: Mþ, 296.1525. 8b:
mp 141–142 ꢁC (decomp) (hexane–Et2O); IR (KBr disk)
3362, 1751 cmꢂ1; 1H NMR (270 MHz, CDCl3) ꢀ 2.04 (3H, s),
5.53 (1H, br. s), 6.41 (1H, dd, J ¼ 3:6, 1.6 Hz), 6.69 (1H, dd,
J ¼ 3:6, 2.7 Hz), 6.85 (2H, d, J ¼ 8:1 Hz), 6.90 (1H, t, J ¼
8:1 Hz), 7.24 (2H, t, J ¼ 8:1 Hz), 7.32(1H, t, J ¼ 7:8 Hz),
7.45 (1H, t, J ¼ 7:8 Hz), 7.59 (1H, d, J ¼ 7:8 Hz), 7.82(1H,
dd, J ¼ 2:7, 1.6 Hz), 7.85 (1H, d, J ¼ 7:8 Hz); MS m=z 316
(Mþ, 35), 274 (100). HRMS (m=z) Found: 316.1134. Calcd
for C20H16N2O2: Mþ, 316.1212. 8c: mp 144–145 ꢁC
(decomp) (hexane–CHCl3); IR (KBr disk) 3361,
Scheme 4.
In conclusion, we have shown that 4-alkyl(or aryl)amino-
pyrrolo[1,2-a]quinolin-5-ol derivatives can be obtained from
readily available starting materials. Application of this meth-
odology using 2-(1-pyrrolyl)benzaldehyde and isocyanides in the
synthesis of other functionalized pyrrolo[1,2-a]quinoline deriva-
tives are currently under way in our laboratory and the results will
be reported in due course.
We wish to thank Mrs. Miyuki Tanmatsu of this Department
for determining MS spectra.
1750 cmꢂ1 1H NMR (270 MHz, CDCl3) ꢀ 1.97 (3H, s),
;
2.30 (3H, s), 5.30 (1H, br. s), 6.39 (1H, d, J ¼ 3:0 Hz), 6.71
(1H, t, J ¼ 3:0 Hz), 6.81 (1H, d, J ¼ 7:6 Hz), 6.90 (1H, t,
J ¼ 7:6 Hz), 7.08 (1H, t, J ¼ 7:6 Hz), 7.17 (1H, d, J ¼
7:6 Hz), 7.32(1H, t, J ¼ 7:9 Hz), 7.44 (1H, d, J ¼ 7:9 Hz),
7.57 (1H, d, J ¼ 7:9 Hz), 7.84 (1H, d, J ¼ 3:0 Hz), 7.86 (1H,
d, J ¼ 7:9 Hz); MS m=z 330 (Mþ, 26), 288 (79), 170 (100).
HRMS (m=z) Found: 330.1370. Calcd for C21H18N2O2: Mþ,
330.1368. 8d: mp 172–175 ꢁC (decomp) (hexane–CH2Cl2);
IR (KBr disk) 3422, 1763 cmꢂ1; 1H NMR (270 MHz, CDCl3)
ꢀ 2.21 (3H, s), 5.95 (1H, br. s), 6.56 (1H, d, J ¼ 3:0 Hz), 6.67
(1H, t, J ¼ 3:0 Hz), 6.89 (1H, t, J ¼ 7:6 Hz), 7.03 (1H, d,
J ¼ 7:6 Hz), 7.1–7.4 (4H, m), 7.5–7.65 (2H, m), 8.05 (1H, d,
J ¼ 8:1 Hz); MS m=z 384 (Mþ, 25), 342 (100). HRMS (m=z)
Found: 384.1105. Calcd for C21H15N2O2F3: Mþ, 384.1086.
8e: mp 153–155 ꢁC (decomp) (hexane–CH2Cl2); IR (KBr
disk) 3385, 1764 cmꢂ1; 1H NMR (270 MHz, CDCl3) d 1.68
(3H, s), 2.21 (6H, s), 5.29 (1H, br. s), 6.36 (1H, dd, J ¼ 3:0,
1.6 Hz), 6.72(1H, t, J ¼ 3:0 Hz), 7.05–7.15 (3H, m), 7.2–7.4
(3H, m), 7.8–7.85 (2H, m); MS m=z 344 (Mþ, 46), 301 (100).
HRMS (m=z) Found: 344.1505. Calcd for C22H20N2O2: Mþ,
344.1525.
References and Notes
1
K. Kobayashi, T. Matoba, S. Irisawa, T. Matsumoto, O.
Morikawa, and H. Konishi, Chem. Lett., 1998, 551; K.
Kobayashi, S. Irisawa, T. Matoba, T. Matsumoto, K. Yoneda,
O. Morikawa, and H. Konishi, Bull. Chem. Soc. Jpn., 74, 1109
(2001).
2For recent reports on the synthesis utilizing the Lewis acid
catalyzed reaction of isocyanides with aldehydes, see: D.
Seebach, G. Adam, T. Gees, M. Schiess, and W. Weigand,
Chem. Ber., 121, 507 (1988); H. Kunz, W. Pfrengle, and W.
Sager, Tetrahedron Lett., 39, 5469 (1989); J. P. G. Versleijen,
P. M. Faber, H. H. Bodewes, A. H. Braker, D. van Leusen, and
A. M. van Leusen, Tetrahedron Lett., 36, 2109 (1995); C.
Blackburn, B. Guan, P. Fleming, K. Shiosaki, and S. Tsai,
Tetrahedron Lett., 39, 3635 (1998); C. Blackburn, Tetra-
hedron Lett., 39, 5469 (1998).
3
F. T. Swinbourne, J. H. Hunt, and K. Kinkert, in ‘‘Advances in
Heterocyclic Chemistry,’’ ed. by A. R. Katritzky and A. J.
Boulton, Academic Press, New York (1978), Vol. 32, p 103.
L. Bouyazza, J.-C. Lancelot, S. Rault, and M. Robba, J.
Heterocycl. Chem., 28, 77 (1991); M. L. Bode and P. T. Kaye,
4