Condensation of chromone-3-carboxaldehyde with phenylacetic acids: An efficient synthesis of (E)-3-styrylchromones

Article abstract of DOI:10.1055/s-2004-835660

An efficient and diastereoselective synthetic method for preparing (E)-3-styrylchromones has been developed by the reaction of chromone-3- carboxaldehyde with phenylacetic acids in the presence of potassium tert-butoxide under classical heating conditions or microwave irradiation. The Knoevenagel-type reaction followed by a decarboxylation was faster under microwave conditions.

Full text of DOI:10.1055/s-2004-835660

LETTER
2717
Condensation of Chromone-3-carboxaldehyde with Phenylacetic Acids:
An Efficient Synthesis of (E)-3-Styrylchromones
Synthesis of
(
E
)
-
3-
e
Styrylchro
r
a
Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal
Fax +351(234)370084; E-mail: arturs@dq.ua.pt
b
Department of Organic Chemistry, University of Debrecen, P. O. Box 20, 4010 Debrecen, Hungary
Fax +36(52)453836; E-mail: tpatonay@puma.unideb.hu
Received 20 September 2004
reaction of chromone-3-carboxaldehydes was established
by our group and gave a mixture of both (E)- and (Z)-3-
styrylchromones, the Z-isomer being the more abundant
one.10
Abstract: An efficient and diastereoselective synthetic method for
preparing (E)-3-styrylchromones has been developed by the reac-
tion of chromone-3-carboxaldehyde with phenylacetic acids in the
presence of potassium tert-butoxide under classical heating condi-
tions or microwave irradiation. The Knoevenagel-type reaction fol-
lowed by a decarboxylation was faster under microwave conditions.
The reactivity of chromone-3-carboxaldehyde (1) is gov-
erned by the reactivity of its electron-deficient centers at
C-2, C-4 and the C-3 formyl group. Based on the nucleo-
philic reactions of chromone-3-carboxaldehydes with ac-
tive methylene compounds we studied the condensation
of 1 with phenylacetic acids 2a–d in refluxing dry pyri-
dine (Scheme 1). Under these classical conditions a
Knoevenagel-type reaction, followed by decarboxylation,
took place in each case and 3-styrylchromones 3a–d were
obtained.11,12 Different reaction times were tested but the
yields of products were very low with the exception of 4¢-
nitro-3-styrylchromone (3d) which was achieved in mod-
erate yields after 24–30 hours (entries 8–10, Table 1). The
use of different amounts of phenylacetic acids was tried
without any significant improvement in the yields. These
results indicate that the condensation of phenylacetic
acids 2 with aldehyde 1 is favoured by the presence of a
strong electron-withdrawing substituent in the aromatic
ring of the acid component due to the anion-stabilising
effect of this group. However, in the case of 4-tri-
fluoromethylphenylacetic acid (2d), the yields of the
corresponding 3-styrylchromone (3d) were poor and a
considerable decomposition of the starting materials was
observed, probably due to the long reflux time.
Key words: chromone-3-carboxaldehyde, phenylacetic acids, con-
densation, microwave irradiation, (E)-3-styrylchromones
Chromone-3-carboxaldehydes are useful synthetic inter-
mediates for a wide variety of heterocyclic compounds.1
Most of their reactions are nucleophilic additions leading
mainly to condensation products. Active methylene com-
pounds react readily with these compounds in the pres-
ence of a base. Reactions with malonic or cyanoacetic
acids in the presence of pyridine followed by decarboxy-
lation give trans-b-(4-oxo-4H-1-benzopyran-3-yl)acrylic
acid and trans-b-(4-oxo-4H-1-benzopyran-3-yl)acryloni-
trile, respectively, while the base-catalysed condensation
with ethyl acetoacetate, 2,4-pentanedione or ethyl ben-
zoylacetate, also provides condensation products.1 Karale
and co-workers2,3 reported the condensation of 6,8-di-
methylcoumarin-4-acetic acid and of 4-nitrophenylacetic
acid with chromone-3-carboxaldehydes in pyridine and 3-
styrylchromones have been obtained in moderate yields.
The same research group also published the synthesis of
3-styrylchromone derivatives by the condensation of 2,4-
dinitrotoluene with chromone-3-carboxaldehydes in pyri-
dine.4 We now present the results of our study on the con-
densation of chromone-3-carboxaldehyde (1) with several
phenylacetic acid derivatives under classical heating
conditions as well as microwave (MW) irradiation. These
reactions offer a general and diastereoselective method
for the synthesis of (E)-3-styrylchromones 3.
R1
O
R2
O
A
+
CHO
R2
O
R1
O
CH2COOH
(E)
1
2
3
d) R1 = NO2; R2 = H
e) R1 = H; R2 = Cl
a) R1 = R2 = H
Styrylchromones constitute a small but significant group
of oxygenated heterocyclic compounds which have
shown marked biological activities.5 The synthesis of 2-
styrylchromones have been extensively studied,6 whereas,
to our knowledge, only a few synthetic methods are avail-
able for the preparation of the isomeric 3-styryl-
chromones.3,4,7–10 The last one based on the Wittig
g) R1 = H; R2 = NO2
b) R1 = Cl; R2 = H
c) R1 = CF3; R2 = H f) R1 = H; R2 = CF3
Scheme 1 A: Classical conditions: dry pyridine, reflux, under nitro-
gen. Microwave conditions: dry pyridine, 180 °C, 1 h.
Since the beneficial effect of microwave activation on the
reactions resulting in higher yields and shorter reaction
time is well-documented,13 we have also studied the
condensation of chromone-3-carboxaldehyde (1) with
phenylacetic acids 2a–d under MW irradiation
SYNLETT 2004, No. 15, pp 2717–2720
0
7
.1
2
.2
0
0
4
Advanced online publication: 10.11.2004
DOI: 10.1055/s-2004-835660; Art ID: D28304ST
© Georg Thieme Verlag Stuttgart · New York

2718
V. L. M. Silva et al.
LETTER
Table 1 Condensation of Chromone-3-carboxaldehyde (1) with
Phenylacetic Acids 2a–d under Classical Heating Conditions
Table 3 Condensation of Chromone-3-carboxaldehyde (1) with 5
Molar Equivalent of Phenylacetic Acids 2a–g in Refluxing Pyridine
or under MW Irradiation, in the Presence of 1.5 Equivalents of
Potassium tert-Butoxide
Entry Amounts of phenylacetic acids
(molar equiv)
Reaction Yield
time (h) (%)
Entry Phenylacetic acids
Classical heating
MW
1
2
1.25 equiv of 2a; R1 = R2 = H
42
24
52
44
70
48
48
24
24
1.6
9.3
Reaction Yield
time (h) (%)
Yield
(%)
5 equiv of 2a; R1 = R2 = H
1a
2
3
4
5
6
7
8
9
2a; R1 = R2 = H
8
31
40
24
15
15
12
12
12
13.3
66.1
66.3
91.9
98.7
47.5
98.4
91.2
98.3
–
3
20 equiv of 2a; R1 = R2 = H
5.6
2a; R1 = R2 = H
86.2
–
4
2.25 equiv of 2b; R1 = Cl, R2 = H
20 equiv of 2b; R1 = Cl, R2 = H
3.2 equiv of 2c; R1 = CF3, R2 = H
12 equiv (4 × 3) of 2c; R1 = CF3, R2 = H
1.5 equiv of 2d; R1 = NO2, R2 = H
3 equiv (3+1) of 2d; R1 = NO2, R2 = H
2.8
2a; R1 = R2 = H
5
9.3
2b; R1 = Cl, R2 = H
2c; R1 = CF3, R2 = H
2d; R1 = NO2, R2 = H
2e; R1 = H, R2 = Cl
2f; R1 = H, R2 = CF3
2g; R1 = H, R2 = NO2
79.9
90.9
56.0
90.3
94.1
80.2
6
14.7
16.7
51.4
60.7
69.3
7
8
9
10
12 equiv (3 × 3) of 2d; R1 = NO2, R2 = H 30
(Scheme 1, Table 2). After several attempts we found that
the use of 12 molar equivalents of phenylacetic acids and
one hour reaction time provided the best experimental
conditions. Under these conditions compounds 3b and 3d
were obtained in moderate to good yields. However, the
yields of compounds 3a and 3c were again very low
(Table 2).
a 1.5 Equiv of 2a were used.
Table 3, entry 2). When these optimised experimental
conditions14 were applied for the condensation of
chromone-3-carboxaldehyde (1) with phenylacetic acids
2b–g, the corresponding 3-styrylchromones 3b,c,e,f15
were obtained in good to excellent yields (Table 3), with
the exception of the 4¢-nitro-3-styrylchromone (3d) which
was obtained only in moderate yield (ca. 48%; Table 3,
entry 6).
We have attempted the reaction of 1 with acid 2a in the
presence of pyridine under the conditions of classical
heating but adding a small amount of base (potassium
tert-butoxide) to promote the carbanion formation at a-
carbon of the phenylacetic acid and a small increase in the
yield of the expected 3-styrylchromone 3a was observed
(entry 1, Table 3).
We have also tried the condensations of aldehyde 1 with
phenylacetic acids 2a–g under microwave irradiation to
achieve shorter reaction times. As expected, we obtained
comparable yields (ca. 56–94%) of the corresponding 3-
styrylchromones 3a–g using one hour irradiation.16
Further studies revealed the beneficial effect of the in-
creased amount of the starting material 2a on the yields.
By using 5 molar equivalents of 2a the expected 3-styryl-
chromone 3a was obtained in good yield (ca. 66%;
All the synthesised 3-styrylchromones 3a–g have been
characterised by NMR, MS and elemental analyses. The
most important features are the resonances of their H-2
(dH = 8.13–8.19 ppm) and vinylic protons (dH-a = 7.02–
7.08 ppm; dH-b = 7.76–7.92 ppm). The coupling constants
3JHa-Hb = ca. 16 Hz indicate trans configurations for such
double bonds. In the case of 3-styrylchromones 3c,f the
carbon resonance of their trifluoromethyl group appear as
a quartet, due to the coupling with fluorine, at d = 122.5
and 124.2 ppm (1JC-H = ca. 272–274 Hz). The resonances
of the carbons in the vicinity of this group also appear as
a quartet but with smaller coupling constants (2JC-H = ca.
29–33 Hz; 3JC-H = ca. 2–4 Hz). However, in the case of 2¢-
trifluoromethyl-3-styrylchromone (3f) we can also ob-
serve long range hydrogen-fluorine (5JHb-F = 2.4 Hz) and
carbon-fluorine (4JCb-F = 5.7 Hz) spin-spin coupling.17
Table 2 Condensation of Chromone-3-carboxaldehyde (1) with
Phenylacetic Acids 2a–d under Microwave Irradiation
Entry Amount of phenylacetic acids (molar equiv)
Yield (%)
3.4
1
2
12 equiv of 2a; R1 = R2 = H
20 equiv of 2a; R1 = R2 = H
5.6
Washing the reaction mixture with KHCO3 (aq)
3
4
12 equiv of 2b; R1 = Cl, R2 = H
39.9
33.0
12 equiv of 2b; R1 = Cl, R2 = H
Washing the reaction mixture with KHCO3 (aq)
5
6
7
8
20 equiv of 2b; R1 = Cl, R2 = H
12 equiv of 2c; R1 = CF3, R2 = H
1.5 equiv of 2d; R1 = NO2, R2 = H
12 equiv of 2d; R1 = NO2, R2 = H
40.1
11.2
18.6
56.1
In conclusion, we have studied the condensation reactions
of chromone-3-carboxaldehyde (1) with phenylacetic
acids 2a–g under classical heating conditions and micro-
wave irradiation. These transformations led to the forma-
tion of (E)-3-styrylchromones 3a–g in a Knoevenagel-
Synlett 2004, No. 15, 2717–2720 © Thieme Stuttgart · New York

LETTER
Synthesis of (E)-3-Styrylchromones
2719
(12) Physical Data of (E)-4¢-Trifluoromethyl-3-
type reaction followed by decarboxylation. Good yields
were obtained when these reactions have been carried out
using an excess of phenylacetic acids 2a–g in the presence
of potassium tert-butoxide. However, 4¢-nitro-3-styryl-
chromone (3d) has been obtained in a slightly better yield
in the absence of base. The beneficial effect of microwave
irradiation was the shortening of the reaction time in com-
parison with the reactions under conventional heating
conditions.
styrylchromone (3c): Mp 206–207 °C. 1H NMR (300.13
MHz, CDCl3): d = 7.02 (d, 1 H, J = 16.3 Hz, H-a), 7.45 (t, 1
H, J = 7.8, 8.0 Hz, H-6), 7.49 (d, 1 H, J = 7.8 Hz, H-8), 7.60
(m, 4 H, H-2¢,3¢,5¢,6¢), 7.69 (dt, 1 H, J = 7.8, 7.8, 1.6 Hz, H-
7), 7.76 (d, 1 H, J = 16.3 Hz, H-b), 8.13 (s, 1 H, H-2), 8.30
(dd, 1 H, J = 8.0, 1.6 Hz, H-5). 13C NMR (75.47 MHz,
CDCl3): d = 118.1 (C-8), 121.2 (C-3), 121.7 (C-a), 124.1 (C-
10), 124.2 (q, J = 271.8 Hz, CF3), 125.5 (C-6), 126.3 (C-5),
125.6 (q, J = 3.9 Hz, C-3¢,5¢), 126.7 (C-2¢,6¢), 129.4 (q,
J = 32.5 Hz, C-4¢), 130.4 (C-b), 133.8 (C-7), 140.9 (C-1¢),
154.0 (C-2), 155.7 (C-9), 176.6 (C-4). 19F NMR (300.13
MHz, CDCl3; ref. C6F6): d = –85.5 (s, CF3). Anal. Calcd for
C18H11O2F3: C, 68.36; H, 3.51. Found: C, 68.04; H, 3.22.
(13) (a) Xu, Y.; Guo, Q.-X. Heterocycles 2004, 63, 903.
(b) Díaz-Ortiz, A.; Elguero, J.; Foces-Foces, C.; de la Hoz,
A.; Moreno, A.; Mateo, M. C.; Sánchez-Migallón, A.;
Valiente, G. New J. Chem. 2004, 28, 95. (c) Selected
reviews: Caddick, S. Tetrahedron 1995, 51, 10403.
(d) Strauss, C. R.; Trainor, R. W. Aust. J. Chem. 1995, 48,
1665. (e) Galema, S. A. Chem. Soc. Rev. 1997, 26, 233.
(f) Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet, F.;
Jacqualt, P.; Mathe, D. Synthesis 1998, 1213. (g) Varma, R.
S. Green Chem. 1999, 43. (h) Varma, R. S. Tetrahedron
2002, 58, 1235.
Acknowledgment
Thanks are due to the University of Aveiro, ‘Fundação para a
Ciência e Tecnologia’ and FEDER for funding the Organic Chemi-
stry Research Unit and the project POCTI/QUI/38394/2001. One of
us (V. L. M. Silva) also thanks the University of Aveiro for a PhD
grant (SFRH/BD/6647/2001).
References
(1) Sabitha, G. Aldrichimica Acta 1996, 29, 15.
(2) Karale, B. K.; Chavan, V. P.; Hangarge, R. V.; Mane, A. S.;
Gill, C. H.; Shingare, M. S. Indian J. Heterocycl. Chem.
2001, 11, 81.
(3) Sonawane, S. A.; Chavan, V. P.; Shingare, M. S.; Karale, B.
K. Indian J. Heterocycl. Chem. 2002, 12, 65.
(14) Typical Experimental Procedure under Classical
Heating Conditions: A mixture of chromone-3-
carboxaldehyde (1, 0.10 g, 5.74 × 10–1 mmol), the
appropriate phenylacetic acid 2a–g (0.39 g, 2.87 mmol) and
tert-BuOK (0.10 g, 8.61 × 10–1 mmol) in dry pyridine (15
mL) was refluxed until complete disappearance of 1. After
that period the contents were cooled to r.t. and poured over
H2O and ice. The mixture was acidified at pH 2 with a
solution of HCl. The pale yellow precipitate was separated
by filtration washed with H2O and purified by thin layer
chromatography with a 7:3 mixture of CH2Cl2–light
petroleum ether as eluent. The obtained residue was
crystallised from EtOH giving 3-styrylchromones 3a–g in
good yields (Table 3).
(4) Karale, B. K.; Gill, C. H.; Shingare, M. S. Indian J.
Heterocycl. Chem. 2003, 12, 267.
(5) (a) Doria, G.; Romeo, C.; Forgione, A.; Sberze, P.; Tibolla,
N.; Corno, M. L.; Cruzzola, G.; Cadelli, G. Eur. J. Med.
Chem. 1979, 14, 347. (b) Gerwick, W. H.; Lopez, A.; Van
Duyne, G. D.; Clardy, J.; Ortiz, W.; Baez, A. Tetrahedron
Lett. 1986, 27, 1979. (c) Gerwick, W. H. J. Nat. Prod. 1989,
52, 252. (d) Brion, J. D.; Le Baut, G.; Zammattio, F.; Pierre,
A.; Atassi, G.; Belachmi, L. Eur. Pat. Appl. EP 454,587,
1991; Chem Abstr. 1992, 116, 106092K. (e) Desideri, N.;
Conti, C.; Mastropaolo, F. Antiviral Chem. Chemother.
2000, 11, 373. (f) Peixoto, F.; Barros, A. I. R. N. A.; Silva,
A. M. S. J. Biochem. Mol. Toxicol. 2002, 16, 220.
(g) Fernandes, E.; Carvalho, M.; Carvalho, F.; Silva, A. M.
S.; Santos, C. M. M.; Pinto, D. C. G. A.; Cavaleiro, J. A. S.;
Bastos, M. L. Arch. Toxicol. 2003, 77, 500. (h) Filipe, P.;
Silva, A. M. S.; Morlière, P.; Brito, C. M.; Patterson, L. K.;
Hug, G. L.; Silva, J. N.; Cavaleiro, J. A. S.; Mazière, J.-C.;
Freitas, J. P.; Santus, R. Biochem. Pharmacol. 2004, 67,
2207.
(15) Physical Data of 3-Styrylchromones 3e–f
(E)-2¢-Chloro-3-styrylchromone (3e): Mp 125.1–125.4 °C.
1H NMR (300.13 MHz, CDCl3): d = 7.03 (dd, 1 H, J = 16.4,
0.5 Hz, H-a), 7.21 (ddd, 1 H, J = 7.5, 7.6, 1.8 Hz, H-5¢), 7.28
(ddd, 1 H, J = 7.5, 7.7, 1.5 Hz, H-4¢), 7.39 (dd, 1 H, J = 7.7
and 1.5 Hz, H-6¢), 7.44 (ddd, 1 H, J = 7.6, 7.8, 0.9 Hz, H-6),
7.49 (dd, 1 H, J = 8.2, 0.9 Hz, H-8), 7.69 (ddd, 1 H, J = 7.6,
8.2, 1.7 Hz, H-7), 7.70 (dd, 1 H, J = 7.5, 1.8 Hz, H-3¢), 7.92
(d, 1 H, J = 16.4 Hz, H-b), 8.19 (d, 1 H, J = 0.5 Hz, H-2),
8.32 (dd, 1 H, J = 7.8, 1.7 Hz, H-5). 13C NMR (75.47 MHz,
CDCl3): d = 118.1 (C-8), 121.5 (C-a), 121.8 (C-3), 124.1 (C-
10), 125.4 (C-6), 126.3 (C-5), 126.6 (C-3¢), 126.9 (C-4¢),
127.3 (C-b), 128.9 (C-5¢), 129.8 (C-6¢), 133.5 (C-2¢), 133.6
(C-7), 135.4 (C-1¢), 153.2 (C-2), 155.9 (C-9), 176.5 (C-4).
Anal. Calcd for C17H11O2Cl: C, 72.22; H, 3.92. Found: C,
71.99; H, 3.63.
(6) (a) Price, W. A.; Silva, A. M. S.; Cavaleiro, J. A. S.
Heterocycles 1993, 36, 2601. (b) Pinto, D. C. G. A.; Silva,
A. M. S.; Cavaleiro, J. A. S. J. Heterocycl. Chem. 1996, 33,
1887. (c) Silva, A. M. S.; Pinto, D. C. G. A.; Tavares, H. R.;
Cavaleiro, J. A. S.; Jimeno, M. L.; Elguero, J. Eur. J. Org.
Chem. 1998, 2031. (d) Pinto, D. C. G. A.; Silva, A. M. S.;
Cavaleiro, J. A. S. New J. Chem. 2000, 24, 85.
(E)-2¢-Trifluoromethyl-3-styrylchromone (3f): Mp 137.2–
137.5 °C. 1H NMR (300.13 MHz, CDCl3): d = 7.03 (d, 1 H,
J = 16.1 Hz, H-a), 7.37 (t, 1 H, J = 7.6, 7.6 Hz, H-4¢), 7.44
(dt, 1 H, J = 7.5, 7.5, 1.0 Hz, H-6), 7.49 (dd, 1 H, J = 8.4, 1.0
Hz, H-8), 7.80 (d, 1 H, J = 8.0 Hz, H-3¢), 7.87 (dq, 1 H,
(7) Davies, S. G.; Mobbs, B. E.; Goodwin, C. J. J. Chem. Soc.,
Perkin Trans. 1 1987, 2597.
(8) Alonso, R.; Brossi, A. Tetrahedron Lett. 1988, 29, 735.
(9) Silva, A. M. S.; Cavaleiro, J. A. S.; Elguero, J. Liebigs Ann.
Recl. 1997, 2065.
(10) Sandulache, A.; Silva, A. M. S.; Pinto, D. C. G. A.; Almeida,
L. M. P. M.; Cavaleiro, J. A. S. New J. Chem. 2003, 27,
1592.
(11) (E)-3-Styrylchromones 3a,b,d were shown to possess
spectroscopic and analytical data identical to those
previously reported.10
J = 16.1, 2.4 Hz, H-b), 8.17 (dd, 1 H, J = 0.6 Hz, H-2). 13
C
NMR (75.47 MHz, CDCl3): d = 118.1 (C-8), 122.5 (C-3),
122.5 (q, J = 273.9 Hz, CF3), 123.0 (C-a), 124.1 (C-10),
125.4 (C-6), 125.9 (q, 1 H, J = 5.7 Hz, C-b), 126.3 (C-5),
127.0 (q, J = 2.2 Hz, C-3¢), 127.1 (C-6¢), 127.5 (C-4¢), 127.6
(q, J = 29.8, C-2¢), 131.9 (C-5¢), 133.7 (C-7), 136.3 (q,
J = 1.7 Hz, C-1¢), 153.3 (C-2), 155.9 (C-9), 176.5 (C-4).
Synlett 2004, No. 15, 2717–2720 © Thieme Stuttgart · New York

2720
V. L. M. Silva et al.
LETTER
(16) Typical Experimental Procedure under Microwave
19F NMR (300.13 MHz, CDCl3; ref. C6F6): d = –82.9 (s,
CF3). Anal. Calcd for C18H11O2F3: C, 68.36; H, 3.51. Found:
C, 68.66; H, 3.53.
Irradiation: A mixture of chromone-3-carboxaldehyde (1,
0.10 g, 5.74 × 10–1 mmol), the appropriate phenylacetic acid
2a–g (0.39 g, 2.87 mmol) and tert-BuOK (0.10 g, 8.61 ×
10–1 mmol) in dry pyridine (15 mL) was irradiated in a 100
mL PFA sealed vessel of a high-pressure rotor segment in an
Ethos SYNTH microwave (Milestone Inc.), at a maximum
temperature of 180 °C for 1 h (800 W of power). After that
period the contents were cooled to r.t. and poured over H2O
and ice. The mixture was acidified at pH 2 with a solution of
HCl. The pale yellow precipitate was separated by filtration
washed with H2O and purified by thin layer chromatography
with a 7:3 mixture of CH2Cl2–light petroleum ether as
eluent. The obtained residue was crystallised from EtOH
giving 3-styrylchromones 3a–g in good yields (3a, 86.2%;
3b, 79.9%; 3c, 90.9%; 3d, 56.0%; 3e, 90.3%; 3f, 94.1%; 3g,
80.2%).
(E)-2¢-Nitro-3-styrylchromone (3g): Mp 194–195 °C. 1H
NMR (300.13 MHz, CDCl3): d = 7.08 (dd, 1 H, J = 16.3, 0.7
Hz, H-a), 7.43 (ddd, 1 H, J = 7.8, 7.7, 1.4 Hz, H-4¢), 7.45
(ddd, 1 H, J = 7.7, 7.8, 1.0 Hz, H-6), 7.50 (dd, 1 H, J = 7.9,
1.0 Hz, H-8), 7.63 (ddd, 1 H, J = 7.7, 7.9, 1.4 Hz, H-5¢), 7.70
(ddd, 1 H, J = 7.7, 7.9, 1.7 Hz, H-7), 7.79 (dd, 1 H, J = 8.0,
1.4 Hz, H-6¢), 7.91 (d, 1 H, J = 16.3 Hz, H-b), 7.98 (dd, 1 H,
J = 8.0, 1.4 Hz, H-3¢), 8.22 (d, 1 H, J = 0.7 Hz, H-2), 8.31
(dd, 1 H, J = 7.8, 1.7 Hz, H-5). 13C NMR (75.47 MHz,
CDCl3): d = 118.2 (C-8), 121.5 (C-3), 124.0 (C-a and C-10),
124.8 (C-3¢), 125.5 (C-6), 126.0 (C-b), 126.3 (C-5¢), 128.3
(C-4¢), 128.6 (C-6¢), 133.0 (C-1¢), 133.2 (C-5), 133.8 (C-7),
147.9 (C-2), 153.4 (C-2¢), 156.0 (C-9), 176.3 (C-4). Anal.
Calcd for C17H11O4N: C, 69.62; H, 3.78; N, 4.78. Found: C,
69.57; H, 3.79; N, 4.75.
(17) Gribble, G. W.; Kelly, W. J. Tetrahedron Lett. 1985, 26,
3779.
Synlett 2004, No. 15, 2717–2720 © Thieme Stuttgart · New York