Synthesis of 4b,5,10a,11-tetrahydroindeno[1,2-b]quinolin-10-ones from Baylis-Hillman adducts

Article abstract of DOI:10.1016/j.tetlet.2004.08.075

We developed an efficient synthetic method for indenoquinoline skeletons from Baylis-Hillman adducts. 4b,5,10a,11-Tetrahydroindeno[1,2-b]quinolin-10-ones and 7H-indeno[2,1-c]quinolines were prepared from Baylis-Hillman adducts in polyphosphoric acid.

Full text of DOI:10.1016/j.tetlet.2004.08.075

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 7409–7413
Synthesis of 4b,5,10a,11-tetrahydroindeno[1,2-b]-
quinolin-10-ones from Baylis–Hillman adducts
Chang Gon Lee, Ka Young Lee, Saravanan GowriSankar and Jae Nyoung Kim*
Department of Chemistry and Institute of Basic Science, Chonnam National University, Kwangju 500-757, Republic of Korea
Received 30 June 2004; revised 9 August 2004; accepted 13 August 2004
Abstract—We developed an efficient synthetic method for indenoquinoline skeletons from Baylis–Hillman adducts. 4b,5,10a,11-
Tetrahydroindeno[1,2-b]quinolin-10-ones and 7H-indeno[2,1-c]quinolines were prepared from Baylis–Hillman adducts in polyphos-
phoric acid.
Ó 2004 Elsevier Ltd. All rights reserved.
Recently, Basavaiah et al. have reported the synthesis of
3-benzylidenechroman-4-ones from Baylis–Hillman
adducts via the Friedel–Crafts acylation reaction as
the key step.1 During the continuing efforts for the con-
struction of various types of heterocyclic compounds
from Baylis–Hillman adducts,2 we envisioned that we
could synthesize the 7H-indeno[2,1-c]quinoline ring sys-
tem from the Baylis–Hillman adducts via successive
Friedel–Crafts type reaction (Scheme 1). As shown, Frie-
del–Crafts acylation of cinnamic acid derivative to
form 3-benzylidene-2,3-dihydro-4(1H)quinolone and
the following dehydrative cyclization would furnish the
desired 7H-indeno[2,1-c]quinoline.
ported in a similar system2,7 and we could isolate the
E-form in pure state. The carboxylic acid derivatives
4a–e were made by KOH-assisted hydrolysis of 3a–e
(Scheme 2).7
With 3 and 4 in our hands we examined the possibility
for the synthesis of 7H-indeno[2,1-c]quinoline deriva-
tives. Initially, we examined the reaction of 3a in various
reaction conditions. As examples, we examined the fol-
lowing conditions including heating in TFA, heating in
CH2Cl2 in the presence of TFAA,1 heating in benzene
with H2SO4, and heating in PPA. Among the examined
reaction conditions we found some major components
on TLC when we conducted the reaction in polyphos-
phoric acid (PPA) at around 120°C.8 We isolated three
compounds, and after careful examination of the spectro-
scopic data, we finally found that the compounds have
the structures of 6a (3%), 7a (62%), and 8a (4%) (Scheme
3).9
Indenoquinoline derivatives3–6 showed a wide range of
biological activities such as 5-HT-receptor binding activ-
ity,3b anti-inflammatory activity,4c and also act as anti-
tumor agents,3c,5b,d inhibitor for steroid reductase,3d
acetylcholonesterase inhibitors,5e and antimalarials.5a
These compounds are frequently synthesized via the
aza-Bergman cyclization5c or via the imino Diels–Alder
reaction.4a,b
The structure of 7a was confirmed by 1H, 13C, IR, mass,
and NOE experiments (Fig. 1).9 Irradiation of the pro-
ton Ha (d = 4.65ppm) showed increments of the intensi-
ties of Hb and He in 1.9% and 1.1%, respectively.
Irradiation of the Hb proton (d = 3.21ppm) showed
enhancements of the intensities of Ha and Hc in 2.4%
and 1.6%, respectively. From the NOE experiments,
we could conclude that the stereochemistry of ring junc-
tion of 7a as cis. In the 1H NMR spectrum of 8a, singlet
of H-6 appeared at 9.14ppm. One doublet and two doub-
lets of doublet (presumably corresponding to H-1, H-11,
H-4) appeared at 8.43, 8.24, and 8.69ppm, respectively.
Other peaks were overlapped and appeared at around
7.46–7.78ppm. The postulated reaction mechanism
The required starting materials 3a–e were prepared in
moderate to good yields as shown in Scheme 2 by simply
heating the corresponding anilines 2 and the acetates of
the Baylis–Hillman adducts 1 in THF for 14–18h. E-
form of 3 was generated as the major product as re-
Keywords: Tetrahydroindeno[1,2-b]quinolin-10-ones; 7H-Indeno[2,1-c]-
quinolines; Baylis–Hillman adducts; Polyphosphoric acid.
*
Corresponding author. Tel.: +82 62 530 3381; fax: +82 62 530
3389; e-mail: kimjn@chonnam.ac.kr
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.08.075

7410
C. G. Lee et al. / Tetrahedron Letters 45 (2004) 7409–7413
COOH
acid catalyst
For X = NH
X
For X = O
Ref. 1
N
7H-indeno[2,1-c]quinoline
O
1. Friedel-Crafts
2. dehydration
Friedel-Crafts
O
O
3-benzylidene
chroman-4-one
1,3-H transfer
O
free
N
H
rotation
3-benzylidene-2,3-
N
H
dihydro-4(1H)quinolone
Scheme 1. Synthetic rationale for 7H-indeno[2,1-c]quinoline.
OAc
COOMe
COOMe
THF, reflux, 14-18 h
H2N R2
R1
R1
N
H
R2
1
3 (67-78%)
2
aq. MeOH
a: R1 = H, R2 = H
b: R1 = H, R2 = Me
c: R1 = H, R2 = Cl
d: R1 = Me, R2 = H
e: R1 = Cl, R2 = H
KOH (1.5 equiv)
rt, 9-16 h
COOH
R1
N
H
R2
4 (73-85%)
Scheme 2. Synthesis of starting materials 3 and 4.
1
11
11b
COOMe
PPA, 120 oC
16 h
H
O
10
1
10a
4b
+
N
H
4
H
N
4
7
6a
N
3a
H
8a (4%)
7a (62%)
1,3-H transfer
COOMe
Friedel-Crafts
COOMe
N
H
HN
6a
5a
H
COOMe
N
H
5a'
Scheme 3. Synthesis of indenoquinolines 7a and 8a.
for the formation of 6a and 7a is depicted in Scheme 3.
The double bond of 3a can be isomerized to form 5a as
already reported in similar systems by us and other
groups.10 In our acidic medium, 5a can be protonated
to generate the corresponding iminium ion 5a0.
The intramolecular aromatic Mannich type reaction11
of 5a0 furnished 6a, which can be converted to
the 4b,5,10a,11-tetrahydroindeno[1,2-b]quinolin-10-one

C. G. Lee et al. / Tetrahedron Letters 45 (2004) 7409–7413
7411
PPA
3a
PPA
6a
7a
(85%)
2.4%
(73%)
90 oC, 8 h
120 oC, 16 h
1.6%
Hc
(9% of 7a)
Hd
Hb
O
Scheme 4.
Jab = 8.1 Hz
Jbc = 2.7 Hz
tained the intermediate 6a as the major product (73%)
together with 9% of 7a. From the reaction of 6a at ele-
vated temperature (120°C, 16h) the formation of 7a
from 6a could be confirmed as in Scheme 4.
Jbd = 4.8 Hz
Jcd = 11.1 Hz
Ha
N
He
1.1%
H
1.9%
As a next trial, in order to find better conditions for the
formation of 8a, we examined a variety of conditions.
As shown in Scheme 1, initially we expected that Frie-
del–Crafts acylation of 4a might proceed without diffi-
culty to produce 3-benzylidene-2,3-dihydro-4(1H)
quinolone.1 If the double bond of 3-benzylidene-2,3-di-
hydro-4(1H)quinolone (4a) could be isomerized into its
Figure 1. NOE and coupling constant data of 7a.
(7a) via the following Friedel–Crafts acylation. The for-
mation and isolation of 6a provided us with definite
proof for the reaction mechanism of 7a. In a suitably
controlled reaction conditions (PPA, 90°C, 8h) we ob-
Table 1. Synthesis of 7a–f and 8a–e
Entry
3 or 4a
Conditions
Products
Yield (%), mp (°C)
O
O
1
2
3a
4a
PPA 120°C, 16h
PPA 170°C, 1h
7a (62), (149–150), 8a (4)b
7a,c 8a (18)
HN
HN
7a
7b
7c
8a
8b
8c
N
N
CH3
3
4
3b
4b
PPA 120°C, 15h
PPA 170°C, 30min
7b (55), (144–145), 8bb,c
7b (4), 8b (17)
CH3
Cl
O
5
6
3c
4c
PPA 120°C, 13h
PPA 170°C, 1h
7c (50), (182–183), 8cb,c
7c (3), 8c (14)
HN
Cl
O
N
CH3
7
8
3d
4d
PPA 120°C, 18h
PPA 170°C, 30min
7d (54), (156–157), 8db,c
7d (4), 8d (22)
H3C
HN
7d
8d
Cl
N
N
O
9
10
3e
4e
PPA 120°C, 17h
PPA 170°C, 1h
7e (52), (103–104), 8eb,c
7e,c 8e (13)
Cl
HN
7e
8e
11
12
3b-Zd
PPA 120°C, 15h
PPA 120°C, 15h
7b
7b (57), (144–145), 8bc
7f (53), (150–151)
O
N
O
OCH3
N
H3C
CH3
3fe
7f
a E-isomer.
b Oil.
c Trace amounts on TLC observation.
d Z-isomer.
e E/Z = 4:1 mixture.

7412
C. G. Lee et al. / Tetrahedron Letters 45 (2004) 7409–7413
Utsugi, Y.; Yamada, Y. Jp. Appl. 1994, 94/107, 190
(Chem. Abstr. 1996, 124, 232268a); (d) Brooks, J. R.;
Berman, C.; Hichens, M.; Primka, R. L.; Reynolds, G. F.;
Rasmusson, G. H. Proc. Soc. Exp. Biol. Med. 1982, 169,
67.
endo-position via 1,3-hydrogen shift under the acidic
conditions,10 then, the following Friedel–Crafts reaction
and dehydration would afford the desired 7H-indeno-
[2,1-c]quinoline (8a). But, unfortunately, the reaction
of 4a in PPA showed the formation of complex mixtures
as compared in the reaction of 3a in PPA (vide supra).
When we used 4a as the starting material we could
obtain low yield of 7a (<5%) and 8a (18%) by using
PPA at around 170°C. Until now, this is the best result
for the synthesis of 8a. Some representative results for
the synthesis of 7 and 8 are summarized in Table 1.
4. For the synthesis and biological activities of indeno[2,1-
c]quinolines, see: (a) Babu, G.; Perumal, P. T. Tetrahedron
Lett. 1998, 39, 3225; (b) Yadav, J. S.; Subba Reddy, B. V.;
Srinivas, R.; Madhuri, Ch.; Ramalingam, T. Synlett 2001,
240; (c) Quraishi, M. A.; Thakur, V. R.; Dhawan, S. N.
Indian J. Chem. Sect. B 1989, 28B, 891.
5. For the synthesis and biological activities of indeno[1,2-
b]quinolines, see: (a) Venugopalan, B.; Bapat, C. P.;
Desouza, E. P.; DeSouza, N. J. Indian J. Chem. Sect. B
1992, 31B, 35; (b) Yamato, M.; Takeuchi, Y.; Hashigaki,
K.; Ikeda, Y.; Ming-rong, C.; Takeuchi, K.; Matsushima,
M.; Tsuruo, T.; Tasiro, T.; Tsukagoshi, S.; Yamashita, Y.;
Nakano, H. J. Med. Chem. 1989, 32, 1295; (c) Lu, X.;
Petersen, J. L.; Wang, K. K. Org. Lett. 2003, 5, 3277; (d)
Deady, L. W.; Desneves, J.; Kaye, A. J.; Finlay, G. J.;
Baguley, B. C.; Denny, W. A. Bioorg. Med. Chem. 2000, 8,
977; (e) Rampa, A.; Bisi, A.; Belluti, F.; Gobbi, S.;
Valenti, P.; Andrisano, V.; Cavrini, V.; Cavalli, A.;
Recanatini, M. Bioorg. Med. Chem. 2000, 8, 497; (f)
Deady, L. W.; Desneves, J.; Kaye, A. J.; Finlay, G. J.;
Baguley, B. C.; Denny, W. A. Bioorg. Med. Chem. 2001, 9,
445; (g) Bu, X.; Deady, L. W. Synth. Commun. 1999, 29,
4223.
6. For the other types of indenoquinolines, see: (a) Schmittel,
M.; Strittmatter, M.; Vollmann, K.; Kiau, S. Tetrahedron
Lett. 1996, 37, 999; (b) Cho, C. S.; Kim, B. T.; Choi, H.-J.;
Kim, T.-J.; Shim, S. C. Tetrahedron 2003, 59, 7997.
7. Buchholz, R.; Hoffmann, H. M. R. Helv. Chim. Acta 1991,
74, 1213.
8. The use of PPA or H2SO4 in the cyclization of similar
systems, see: (a) Zhang, J.; Hertzler, R. L.; Holt, E. M.;
Vickstrom, T.; Eisenbraun, E. J. J. Org. Chem. 1993, 58,
556; (b) So, Y.-H.; Heeschen, J. P. J. Org. Chem. 1997, 62,
3552; (c) Koo, J. J. Org. Chem. 1963, 28, 1134; (d) Feng,
S.; Panetta, C. A.; Graves, D. E. J. Org. Chem. 2001, 66,
612.
We used para-substituted arenes both at the Baylis–Hill-
man moiety and at the aniline moiety in order to pro-
duce only pure regioisomeric products. The
stereochemistry of the double bond of starting materials
are E-form in all cases except entry 11.12 We separated
the Z-form of 3b and examined the reaction in PPA
(entry 11). The reaction of 3b-Z in PPA gave the same
product 7b in 57% yield as in the reaction of 3b-E as
expected. This means that the configuration of the dou-
ble bond of 3 did not affect the whole reaction due to the
involvement of the double bond isomerization step dur-
ing the reaction. In another experiment, the reaction of
3f (E/Z = 4:1 in this case, made from N-methylaniline)
afforded the corresponding 7f in a similar yield (53%,
entry 12).
In summary, we have disclosed an efficient entry for the
synthesis of valuable indenoquinoline skeletons from the
easily available Baylis–Hillman adducts in PPA med-
ium. We are currently searching the improved condi-
tions for the synthesis of 7H-indeno[2,1-c]quinolines.
Acknowledgements
This work was supported by Korea Research Founda-
tion Grant (KRF-2002-015-CP0215).
9. Typical procedure for the synthesis of 6a, 7a, and 8a: The
reaction of 1a and aniline (3equiv) in refluxing THF (15h)
gave 3a in 69% yield. A stirred solution of 3a (534mg,
2mmol) in PPA (6mL) was heated to 120°C for 16h. After
pouring the reaction mixture into cold water the aqueous
phase was neutralized cautiously with NaHCO3. Extrac-
tion with ether, removal of solvent, and flash column
chromatographic separation process (hexanes/ether, 2:1)
gave 6a (16mg, 3%), 7a (292mg, 62%), and 8a (18mg, 4%).
Compound 6a: 1H NMR (CDCl3) d 2.97–3.04 (m, 1H),
3.57 (s, 3H), 3.32–3.60 (m, 2H), 3.95 (br s, 1H), 4.48 (d,
J = 7.2Hz, 1H), 6.55–6.62 (m, 2H), 6.72 (d, J = 7.5Hz,
1H), 7.00 (t, J = 7.8Hz, 1H), 7.11–7.31 (m, 5H); 13C NMR
(CDCl3) d 41.90, 45.26, 46.83, 51.83, 114.40, 117.76,
122.52, 126.61, 127.30, 128.38, 128.93, 130.47, 143.86,
144.42, 173.45.
References and notes
1. Basavaiah, D.; Bakthadoss, M.; Pandiaraju, S. Chem.
Commun. 1998, 1639.
2. For our recent publications on Baylis–Hillman chemistry,
see: (a) Kim, J. M.; Lee, K. Y.; Lee, S.-k.; Kim, J. N.
Tetrahedron Lett. 2004, 45, 2805; (b) Lee, K. Y.; Kim, J.
M.; Kim, J. N. Tetrahedron Lett. 2003, 44, 6737; (c) Kim,
J. N.; Kim, J. M.; Lee, K. Y. Synlett 2003, 821; (d) Im, Y.
J.; Lee, C. G.; Kim, H. R.; Kim, J. N. Tetrahedron Lett.
2003, 44, 2987; (e) Lee, K. Y.; Kim, J. M.; Kim, J. N.
Synlett 2003, 357; (f) Kim, J. N.; Lee, H. J.; Lee, K. Y.;
Gong, J. H. Synlett 2002, 173; (g) Chung, Y. M.; Gong, J.
H.; Kim, T. H.; Kim, J. N. Tetrahedron Lett. 2001, 42,
9023; (h) Lee, K. Y.; Kim, J. M.; Kim, J. N. Tetrahedron
2003, 59, 385, and further references cited therein.
3. For the biological activities of indenoquinoline deriva-
tives, see: (a) Bierer, D. E.; Dubenko, L. G.; Zhang, P.;
Lu, Q.; Imbach, P. A.; Garofalo, A. W.; Phuan, P.-W.;
Fort, D. M.; Litvak, J.; Gerber, R. E.; Sloan, B.; Luo, J.;
Cooper, R.; Reaven, G. M. J. Med. Chem. 1998, 41, 2754;
(b) Anzino, M.; Cappelli, A.; Vomero, S.; Cagnotto, A.;
Skorupska, M. Med. Chem. Res. 1993, 3, 44; (c) Okazaki,
S.; Asao, T.; Wakida, M.; Jshida, K.; Washinosu, M.;
Compound 7a: IR (neat) 3340, 1709cmꢀ1 1H NMR
;
(CDCl3) d 3.21 (ddd, J = 8.1, 4.8, and 2.7Hz, 1H), 3.31
(dd, J = 11.1 and 4.8Hz, 1H), 3.65 (br s, 1H), 3.74 (dd,
J = 11.1 and 2.7Hz, 1H), 4.65 (d, J = 8.1Hz, 1H), 6.52
(dd, J = 7.8 and 1.2Hz, 1H), 6.85 (td, J = 7.5 and 1.2Hz,
1H), 7.01 (td, J = 7.8 and 1.2Hz, 1H), 7.25–7.36 (m, 1H),
7.48–7.63 (m, 3H), 7.73 (d, J = 7.5Hz, 1H); 13C NMR
(CDCl3) d 40.23, 44.35, 50.28, 115.90, 119.60, 123.28,
124.43, 126.25, 127.24, 127.74, 129.20, 135.26, 135.65,
146.54, 156.52, 207.77; EI-MS (70eV) m/z (rel. intensity)
77 (12), 130 (31), 178 (14), 206 (24), 218 (30), 234 (67), 235
(M+, 100).

C. G. Lee et al. / Tetrahedron Letters 45 (2004) 7409–7413
7413
Compound 8a: 1H NMR (CDCl3) d 4.08 (s, 2H), 7.46–7.58
(m, 2H), 7.65–7.78 (m, 3H), 8.24 (dd, J = 8.4 and 1.2Hz,
1H), 8.43 (d, J = 7.5Hz, 1H), 8.69 (dd, J = 8.4 and 1.2Hz,
1H), 9.14 (s, 1H); 13C NMR (CDCl3) d 35.72, 123.65,
124.43, 124.64, 125.47, 126.83, 127.38, 128.22, 128.43,
130.51, 135.85, 140.70, 144.47, 144.97, 147.63, 147.91; MS
(MALDI-TOF) 217.4 (M+).
1H); 13C NMR (CDCl3) d 39.74, 41.09, 50.66, 53.99,
112.78, 119.35, 123.35, 126.34, 126.42, 127.78, 127.90,
128.98, 135.44, 136.02, 149.16, 156.78, 208.37; EI-MS
(70eV) m/z (rel. intensity) 144 (29), 178 (11), 204 (14), 220
(17), 232 (29), 249 (M+, 100).
1
Compound 8b: H NMR (CDCl3) d 2.66 (s, 3H), 4.06 (s,
2H), 7.45–7.59 (m, 3H), 7.70 (d, J = 6.0Hz, 1H), 8.12 (d,
J = 6.0Hz, 1H), 8.42–8.44 (m, 2H), 9.06 (s, 1H); 13C NMR
(CDCl3) d 22.34, 35.92, 122.90, 124.64, 124.89, 125.66,
127.52, 128.28, 130.38, 130.87, 136.11, 136.98, 141.09,
143.98, 145.17, 146.71, 146.95; EI-MS (70eV) m/z (rel.
intensity) 115 (5), 189 (5), 202 (11), 216 (17), 231 (M+,
100).
The other experiments were carried out analogously and
the spectroscopic data of the prepared compounds are as
follows.
Compound 7b: IR (neat) 3344, 1712cmꢀ1 1H NMR
;
(CDCl3) d 2.32 (s, 3H), 3.17–3.22 (m, 1H), 3.26–3.31 (m,
1H), 3.52 (br s, 1H), 3.74 (dd, J = 11.1 and 2.7Hz, 1H),
4.60 (d, J = 7.8Hz, 1H), 6.44 (d, J = 7.8Hz, 1H), 6.83 (dd,
J = 7.8 and 1.5Hz, 1H), 7.31–7.36 (m, 2H), 7.53–7.63 (m,
2H), 7.73 (d, J = 7.5Hz, 1H); 13C NMR (CDCl3) d 20.71,
40.29, 44.68, 50.26, 115.83, 123.24, 124.45, 126.26, 127.70,
127.86, 128.88, 129.60, 135.26, 135.70, 144.12, 156.55,
208.02; EI-MS (70eV) m/z (rel. intensity) 144 (27), 234
(24), 248 (64), 249 (M+, 100).
Compound 8c: 1H NMR (CDCl3) d 4.09 (s, 2H), 7.48–7.61
(m, 2H), 7.67–7.74 (m, 2H), 8.17 (d, J = 9.0Hz, 1H), 8.37
(d, J = 7.2Hz, 1H), 8.65 (d, J = 2.4Hz, 1H), 9.12 (s, 1H);
13C NMR (CDCl3) d 35.73, 122.80, 124.19, 125.10, 125.56,
127.56, 128.55, 129.36, 132.02, 132.74, 136.69, 140.09,
143.80, 144.85, 146.30, 147.79; EI-MS (70eV) m/z (rel.
intensity) 94 (10), 125 (9), 189 (20), 216 (96), 251 (M+,
100).
Compound 7c: IR (neat) 3340, 1712cmꢀ1 1H NMR
;
1
(CDCl3) d 3.18–3.31 (m, 1H), 3.26–3.32 (m, 1H), 3.68 (br
s, 1H), 3.76 (dd, J = 11.1 and 2.7Hz, 1H), 4.58 (d,
J = 8.1Hz, 1H), 6.46 (d, J = 8.4Hz, 1H), 6.96 (dd, J = 8.1
and 2.1Hz, 1H), 7.34–7.40 (m, 1H), 7.46 (dd, J = 2.4 and
0.6Hz, 1H), 7.59–7.61 (m, 2H), 7.74 (d, J = 7.5Hz, 1H);
13C NMR (CDCl3) d 40.09, 44.19, 49.96, 117.01, 123.42,
123.96, 125.94, 126.19, 127.15, 128.04, 128.80, 135.47,
135.64, 145.13, 155.69, 207.18; EI-MS (70eV) m/z (rel.
intensity) 164 (32), 204 (26), 233 (24), 251 (21), 269 (M+,
100).
Compound 8d: H NMR (CDCl3) d 2.57 (s, 3H), 4.03 (s,
2H), 7.31 (dd, J = 7.5 and 0.6Hz, 1H), 7.59 (d, J = 7.5Hz,
1H), 7.66–7.78 (m, 2H), 8.22–8.25 (m, 2H), 8.71 (dd,
J = 8.4 and 1.2Hz, 1H), 9.11 (s, 1H); 13C NMR (CDCl3) d
21.84, 35.35, 123.75, 124.71, 125.06, 125.10, 126.74,
128.39, 129.24, 130.50, 136.28, 137.05, 140.94, 142.13,
144.53, 147.67, 147.92; EI-MS (70eV) m/z (rel. intensity)
101 (5), 189 (6), 202 (15), 216 (23), 231 (M+, 100).
Compound 8e: IR (neat) 2924, 1562, 1508cmꢀ1; 1H NMR
(CDCl3) d 4.05 (s, 2H), 7.43–7.80 (m, 4H), 8.24 (d,
J = 8.1Hz, 1H), 8.37 (s, 1H), 8.58 (d, J = 8.1Hz, 1H), 9.12
(s, 1H); 13C NMR (CDCl3) d 35.60, 123.52, 124.57, 124.73,
126.54, 127.46, 128.40, 128.93, 130.84, 133.58, 136.68,
142.52, 143.27, 143.54, 147.78, 148.11.
Compound 7d: IR (neat) 3363, 1709cmꢀ1 1H NMR
;
(CDCl3) d 2.36 (s, 3H), 3.19–3.24 (m, 1H), 3.28–3.34 (m,
1H), 3.62 (br s, 1H), 3.74 (dd, J = 10.8 and 2.7Hz, 1H),
4.61 (d, J = 8.1Hz, 1H), 6.52 (dd, J = 7.8 and 1.2Hz, 1H),
6.84 (td, J = 7.2 and 1.2Hz, 1H), 7.01 (td, J = 7.8 and
1.5Hz, 1H), 7.37 (dd, J = 8.1 and 1.2Hz, 1H), 7.47–7.53
(m, 3H); 13C NMR (CDCl3) d 20.98, 39.92, 44.47, 50.64,
115.89, 119.60, 123.18, 124.75, 125.93, 127.16, 129.17,
135.82, 136.56, 137.78, 146.49, 154.02, 207.87; EI-MS
(70eV) m/z (rel. intensity) 130 (31), 204 (17), 220 (17), 232
(39), 249 (M+, 100).
10. For the related isomerization phenomena, see: (a) Kim, J.
N.; Kim, H. S.; Gong, J. H.; Chung, Y. M. Tetrahedron
Lett. 2001, 42, 8341, and further references cited therein;
(b) Diaba, F.; Houerou, C. L.; Grignon-Dubois, M.;
Gerval, P. J. Org. Chem. 2000, 65, 907; (c) Diaba, F.;
Lewis, I.; Grignon-Dubois, M.; Navarre, S. J. Org. Chem.
1996, 61, 4830; (d) Carelli, V.; Liberatore, F.; Tortorella,
S. Gazz. Chim. Ital. 1983, 113, 569; (e) Minter, D. E.;
Stotter, P. L. J. Org. Chem. 1981, 46, 3965; (f) Fowler, F.
W. J. Org. Chem. 1972, 37, 1321; (g) Comins, D. L.;
Abdullah, A. H. J. Org. Chem. 1982, 47, 4315; (h)
Grignon-Dubois, M.; Diaba, F.; Grellier-Marly, M.-C.
Synthesis 1994, 800.
11. For the intramolecular aromatic Mannich type reaction,
see: Overman, L. E.; Ricca, D. J. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1991; Vol. 2, pp 1007–1046.
12. As already published,2,7 the SN20 reaction of the Baylis–
Hillman acetate and nucleophiles including aniline
afforded the E-form product as the major component.
The corresponding Z-form was generated in about 5–20%
depending on the substrates. Thus, we scaled up the
reaction and obtained the minor component 3b-Z.
Compound 7e: IR (neat) 3351, 1709cmꢀ1 1H NMR
;
(CDCl3) d 3.20–3.31 (m, 2H), 3.63 (br s, 1H), 3.73 (dd,
J = 10.8 and 2.4Hz, 1H), 4.60 (d, J = 7.8Hz, 1H), 6.52
(dd, J = 7.8 and 1.2Hz, 1H), 6.85 (td, J = 7.8 and 1.2Hz,
1H), 7.02 (td, J = 7.8 and 1.2Hz, 1H), 7.43–7.53 (m, 3H),
7.66 (d, J = 2.1Hz, 1H); 13C NMR (CDCl3) d 39.88, 44.44,
50.74, 115.98, 119.75, 122.89, 123.89, 127.42, 127.54,
129.00, 134.15, 135.18, 137.02, 146.51, 154.56, 206.58;
EI-MS (70eV) m/z (rel. intensity) 130 (33), 204 (30), 233
(20), 252 (36), 269 (M+, 100).
1
Compound 7f: IR (neat) 1712cmꢀ1; H NMR (CDCl3) d
2.61 (s, 3H), 3.02 (dd, J = 11.1 and 5.1Hz, 1H), 3.09–3.15
(m, 1H), 3.51 (dd, J = 11.1 and 2.1Hz, 1H), 4.55 (d,
J = 8.1Hz, 1H), 6.53 (dd, J = 8.1 and 0.9Hz, 1H), 6.81 (td,
J = 7.5 and 1.2Hz, 1H), 7.05 (td, J = 7.8 and 1.5Hz, 1H),
7.21–7.27 (m, 1H), 7.40–7.50 (m, 3H), 7.64 (d, J = 7.8Hz,