A scaffold approach to 3,6,8-trisubstituted flavones

Article abstract of DOI:10.1055/s-2006-939040

An efficient synthetic approach to 3,6,8-trisubstituted flavone scaffolds has been developed based on Pd-mediated coupling reactions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-939040

LETTER
897
A Scaffold Approach to 3,6,8-Trisubstituted Flavones
S
ynthesis of 3,6,8-
r
T
risubst
i
ituted F
s
lavones tian Dahlén, Morten Grøtli, Kristina Luthman*
Department of Chemistry, Medicinal Chemistry, Göteborg University, 412 96 Göteborg, Sweden
Fax +46(31)7723840; E-mail: luthman@chem.gu.se
Received 25 January 2006
was performed using HCl in refluxing AcOH (82%). The
difference in reactivity between aryl chlorides and bro-
mides in palladium-catalyzed reactions should make it
possible to obtain complete selectivity in reactions in the
6- and 8-positions.11 Two different types of palladium re-
actions were tested, the Stille cross-coupling12 and the
Heck reaction.13 The Heck reaction was run using methyl
acrylate, Pd(OAc)2 and tri(o-tolyl)phosphine in DMF
with Et3N as the base under microwave heating to provide
Abstract: An efficient synthetic approach to 3,6,8-trisubstituted
flavone scaffolds has been developed based on Pd-mediated cou-
pling reactions.
Key words: catalysis, flavone, Heck reaction, palladium, scaffold,
Stille reaction
Flavone derivatives (Figure 1) are widely distributed in
nature and have an interesting range of biological activi-
ties,1 including anti-cancer,2–4 anti-HIV,5 and anti-
oxidant6 properties. In addition, the powerful fluorescent
properties of 3-hydroxyflavones have recently been dem-
onstrated.7 Flavones and chromones have also been con-
sidered as privileged structures in drug discovery.8 We
have for some time been interested in the synthesis of
functionalized chromones and flavones and their use in
different pharmacological/biological applications. In the
present study we have focussed our attention on the syn-
thesis of 3,6,8-substituted flavones. We have developed a
scaffold approach to produce a diverse series of such de-
rivatives. Careful choice of reaction conditions in palladi-
um-mediated reactions allows the regioselective
introduction of alkyl substituents with or without hetero-
functionalities.
1
4 in good yield (87%).14 According to H NMR spectral
analysis of the crude reaction mixture the product was
formed in an E/Z isomeric ratio of 95:5. The correspond-
ing Stille coupling using allyltributyltin as reagent and
Pd(PPh3)4 as catalyst in dioxane afforded 3 in 79% yield
without any sign of reaction in the 6-position.15 Thus, Pd-
catalyzed reactions in the 8-position of 2 were possible, in
good yields and with exellent regioselectivity.
Previous studies have shown that it is possible to obtain
efficient palladium-catalyzed coupling reactions of aryl
chlorides using the electron-rich and sterically hindered
P(t-Bu)3 as a ligand.16 In the same study it was also shown
O
O
Cl
Cl
a
89%
O
O
c
Ph
OH
1
2
Br
3
Br
6
b
87%
79%
O
O
O
8
O
Cl
Cl
Figure 1 Structure and numbering of the flavone system
Ph
O
Ph
4
3
Our synthetic strategy was based on the use of compound
1 as starting material (Scheme 1). From 1 it is possible to
synthesize both flavone 2 (Scheme 1) and flavonol 8
(Scheme 3). These derivatives contain functionalities that
allow further chemical transformations by selective palla-
dium-mediated coupling reactions. Our first aim was to
find the optimal reaction conditions for regioselective in-
troduction of substituents in the 6- and 8-positions of 8-
bromo-6-chloroflavone (2). Compound 29 was prepared
from 1 via esterification of the phenol with benzoyl chlo-
ride followed by a Baker–Venkataraman rearrangement in
excellent yield (93% over two steps).10 The cyclization
d 22%
MeO2C
e
79%
O
O
MeO2C
O
Ph
O
Ph
5
6
CO2Me
Scheme 1 Reagents and conditions: (a) i. benzoyl chloride, pyri-
dine, r.t., 1 h; ii. KOH, pyridine, 50 °C, 2 h; (iii) HCl, AcOH, reflux,
14 h; (b) allylSnBu3, Pd(PPh3)4, dioxane, 80 °C, 14 h; (c) methyl acry-
late, Pd(OAc)2, P(o-tolyl)3, Et3N, DMF, 160 °C, 30 min, microwave;
(d) allylSnBu3, Pd2(dba)3, P(t-Bu)3, dioxane, 80 °C, 14 h; (e) methyl
acrylate, Pd2(dba)3, [P(t-Bu)3H]BF4, Et3N, dioxane, 160 °C, 30 min,
microwave.
SYNLETT 2006, No. 6, pp 0897–0900
0
4.
0
4.
2
0
0
6
Advanced online publication: 14.03.2006
DOI: 10.1055/s-2006-939040; Art ID: G04106ST
© Georg Thieme Verlag Stuttgart · New York

898
K. Dahlén et al.
LETTER
that CsF as additive facilitates the coupling. However, re- catalyst in dioxane at 80 °C gave 9 in good yield (89%). A
acting 3 with allylSnBu3, Pd2(dba)3, P(t-Bu)3 and CsF in Heck reaction using methyl acrylate, Pd(OAc)2, tri(o-
dioxane at 80 °C for 14 hours did not afford any of the de- tolyl)phosphine and Et3N as a base in DMF gave 10
sired product. Using the same reaction conditions but (80%). Compound 9 was then converted to the triflate 11
without CsF gave 5 in 22% yield.17,18
(55%) which was used in a Stille coupling with allyltribu-
tyltin and Pd(PPh3)4 in dioxane to afford 12 (72%) without
any sign of rearrangement of the allyl group in the 8-posi-
tion.
A Heck reaction of aryl chloride 4 together with
Pd2(dba)3, [P(t-Bu)3H]BF4 and Et3N using microwave
heating gave 6 in good yield (79%).19 However, applying
the same reaction conditions to 3 gave 7 in 57% yield Modification of the 3-hydroxy group by alkylation was
(Scheme 2). Compound 7 resulted from a Heck reaction also accomplished by reacting 8 with N-(3-bromopro-
together with a Pd-mediated rearrangement of the double pyl)phthalimide and K2CO3 in DMF to obtain 13 in 87%
bond in the allyl group. In these Heck reactions the phos- yield.27 Thereafter, a benzyl group was introduced in the
phine ligand was added as the [P(t-Bu)3H]BF4 salt which 8-position by a Stille coupling using benzyltributyltin as
is more stable and easier to handle than the phosphine it- reagent and Pd(PPh3)4 as catalyst in DMF at 60 °C to af-
self. Previous studies have shown that Cs2CO3 should be ford 14 (63%). A second coupling reaction was then per-
the base of choice for Heck reactions on aryl chlorides.20 formed in the 6-position; a Stille coupling was run with
Unfortunately, using Cs2CO3 in reactions of 4 to 6 did not
result in any product formation.
O
a
Cl
OH
Ph
1
O
O
89%
MeO2C
O
8
Br
3
b or c
87%
f
O
O
Cl
O
NPhth
3
Cl
OH
Ph
7
O
Ph
O
Scheme 2 Reagents and conditions: methyl acrylate, Pd2(dba)3,
[P(t-Bu)3H]BF4, dioxane, 160 °C, 30 min, microwave (57%).
Br
R
13
9
R: CH2CH=CH2 89%
10 R: CH=CHCO2Me 80%
Our second aim was to develop a convenient method to in-
troduce different substituents in the 3-position of the fla-
vone system (Scheme 3). This has been achieved either
via O-alkylation reactions using different alkyl halides in
the presence of base5,21 or via palladium-catalyzed Sono-
gashira and Suzuki reactions on the corresponding
iodide22 or bromide.23 We planned to use the correspond-
ing triflate in Stille reactions. Triflates have been success-
fully used in palladium-mediated coupling reactions in
other aromatic systems.24,25 First, 8-bromo-6-chloro-3-hy-
droxyflavone (8) was prepared from 1 with benzaldehyde
and KOH in ethanol to give an intermediate chalcone
which was cyclized using NaOH/H2O2 to afford 8 in ex-
cellent yield (89% over two steps).5,26 The triflate of 8 was
synthesized using triflic anhydride and pyridine in dichlo-
romethane (67%). Previous studies have shown that it is
possible to obtain selectivity between triflates and bro-
mides in palladium-catalyzed coupling reactions.24 How-
ever, when using the triflate in a Stille coupling we
observed that the regioselectivity was low as mixtures of
products originating from reactions in either the 3- or the
8-positions (or both) were isolated. Thus, the reactivity of
triflate and bromide seems to be similar in the flavone sys-
tem. As the reactivity difference is expected to be larger
between triflate and chloride it would be an advantage to
carry out the coupling reaction in position 8 prior to con-
version of the hydroxy group into a triflate. A Stille cou-
pling using allyltributyltin as reagent and Pd(PPh3)4 as
g
63%
d 55%
O
O
Cl
O
NPhth
Cl
OTf
Ph
3
O
Ph
O
11
14
Ph
e 72%
h or i
O
O
R
O
NPhth
Cl
3
O
Ph
O
Ph
Ph
12
15 R: CH2CH=CH2 77%
16 R: CH=CHCO2Me 86%
Scheme 3 Reagents and conditions: (a) i. benzaldehyde, KOH,
EtOH, 50 °C for 3 h, then r.t. for 14 h; ii. NaOH, H2O2, THF–MeOH–
H2O, 0 °C then r.t. for 14 h; (b) allylSnBu3, Pd(PPh3)4, dioxane, 80 °C,
14 h; (c) methyl acrylate, Pd(OAc)2, P(o-tolyl)3, Et3N, DMF, 160 °C,
30 min, microwave; (d) Tf2O, pyridine, CH2Cl2, 0 °C then r.t. for
14 h; (e) allylSnBu3, Pd(PPh3)4, dioxane, 150 °C, 30 min, micro-
wave; (f) N-(3-bromopropyl)phthalimide, K2CO3, DMF, 50 °C, 15 h;
(g) benzylSnBu3, Pd(PPh3)4, DMF, 60 °C, 14 h; (h) allylSnBu3,
Pd2(dba)3, P(t-Bu)3, dioxane, 80 °C, 14 h; (i) methyl acrylate,
Pd2(dba)3, [P(t-Bu)3H]BF4, Et3N, dioxane, 160 °C, 30 min, micro-
wave; (Phth = phthalimide).
Synlett 2006, No. 6, 897–900 © Thieme Stuttgart · New York

LETTER
Synthesis of 3,6,8-Trisubstituted Flavones
899
(10) (a) Braña, M. F.; Morán, M.; Emling, F.; Schlick, E. Drug
Des. Discov. 1994, 11, 329. (b) Mazumdar, A. K. D.;
Karmakar, P. K. J. Indian Chem. Soc. 1990, 67, 911.
(c) Banerji, K. D.; Poddar, D. J. Indian Chem. Soc. 1976, 53,
1119. (d) Banerji, K. D.; Poddar, D. J. Indian Chem. Soc.
1979, 56, 62.
(11) (a) de Meijere, A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl.
1994, 33, 2379; and references therein. (b) Reetz, M. T.;
Lohmer, G.; Schwickardi, R. Angew. Chem. Int. Ed. 1998,
37, 481.
allyltributyltin, Pd2(dba)3 and P(t-Bu)3 in dioxane to
produce 15 (77%) and a Heck reaction using Pd2(dba)3,
[P(t-Bu)3H]BF4, Et3N and methyl acrylate in dioxane to
obtain 16 (86%).
Deprotection of the phthalimide to obtain the correspond-
ing amine is possible using ethylene diamine in refluxing
ethanol. As an example 14 was deprotected using this pro-
cedure, the primary amine was not isolated but directly
protected with a Boc group in good yield (87% over two
steps).
(12) Espinet, P.; Echavarren, A. M. Angew. Chem. Int. Ed. 2004,
43, 4704; and references therein.
(13) (a) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000,
100, 3009; and references therein. (b) Davies, S. G.; Mobbs,
B. E.; Goodwin, C. J. J. Chem. Soc., Perkin Trans. 1 1987,
2597.
(14) General Procedure for the Heck Reaction in Position 8 –
Synthesis of 6-Chloro-8-(2-methoxycarbonylethenyl)-
flavone (4).
In conclusion, we have developed an efficient strategy to
obtain 3,6,8-trisubstituted flavone derivatives using Pd-
mediated coupling reactions. We have used a scaffold that
makes it possible to selectively introduce different substit-
uents in the 3-, 6- and 8-positions. This strategy is expect-
ed to be general also for other flavone derivatives with
different substitution patterns and should be possible to
use for the production of series of structurally diverse de-
rivatives of interest in many different pharmacological
and biological applications. Synthesis of such derivatives
is presently under way in our laboratory.
A solution of 2 (150 mg, 0.45 mmol), Pd(OAc)2 (10 mg,
0.045 mmol), Pd(o-tolyl)3 (30 mg, 0.9 mmol), Et3N (0.12
mL, 0.9 mmol) and methyl acrylate (0.08 mL, 0.9 mmol) in
DMF (4 mL) in a microwave tube was heated in a
microwave cavity for 30 min at 160 °C. The solution was
filtered through Celite® and H2O (10 mL) was added. The
mixture was extracted with CH2Cl2 (4 × 10 mL). The
combined organic phases were dried over anhyd Na2SO4
before the solvent was removed under vacuum. The residue
was purified by column chromatography on silica gel using
CH2Cl2 as eluent to afford 133 mg (87%) of 4 as a light-
yellow powder; mp 181–182 °C. 1H NMR (400 MHz,
CDCl3): d = 3.87 (s, 3 H), 6.66 (d, J = 16.1 Hz, 1 H), 6.84 (s,
1 H), 7.56–7.59 (m, 3 H), 7.86 (d, J = 2.6 Hz, 1 H), 7.90–
7.92 (m, 2 H), 8.21 (d, J = 2.6 Hz, 1 H), 8.21 (d, J = 16.1 Hz,
1 H). 13C NMR (100 MHz, CDCl3): d = 52.3, 108.0, 122.7,
125.7, 126.6, 126.8, 127.1, 129.6, 131.4, 131.5, 131.8,
132.3, 135.7, 152.5, 163.9, 166.7, 176.9. Anal. Calcd for
C19H13ClO4: C, 66.97, H, 3.85. Found: C, 66.82, H, 3.77.
(15) General Procedure for Stille Coupling in Positions 3 and
8 – Synthesis of 8-Allyl-6-chloro-flavone (3).
A solution of 2 (400 mg, 1.2 mmol), Pd(PPh3)4 (140 mg, 0.12
mmol) and allyltributyltin (600 mg, 1.8 mmol) in dioxane
(30 mL) under N2 was warmed to 80 °C for 14 h. The
mixture was allowed to cool to r.t. and filtered through
Celite®. A sat. aq KF solution (15 mL) was added and stirred
for 30 min. The solution was extracted with CH2Cl2 (4 × 30
mL). The combined organic phases were washed with H2O
(2 × 10 mL), dried over anhyd MgSO4 before the solvent
was removed under vacuum. The residue was purified by
column chromatography on silica gel using CH2Cl2 as eluent
to afford 282 mg (79%) of 3 as a white powder; mp 127–128
°C. 1H NMR (400 MHz, CDCl3): d = 3.74 (d, J = 6.6 Hz, 2
H), 5.19–5.25 (m, 2 H), 6.01–6.12 (m, 1 H), 6.83 (s, 1 H),
7.50 (d, J = 2.6 Hz, 1 H), 7.54–7.57 (m, 3 H), 7.89–7.91 (m,
2 H), 8.07 (d, J = 2.6 Hz, 1 H). 13C NMR (100 MHz, CDCl3):
d = 33.9, 107.5, 118.1, 123.4, 125.1, 126.4, 129.4, 131.1,
131.8, 132.0, 134.2, 134.5, 152.8, 163.4, 177.6. Anal. Calcd
for C18H13ClO2: C, 72.85, H, 4.42. Found: C, 72.67, H, 4.35.
(16) (a) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 2002, 41,
4176; and references therein. (b) Littke, A. F.; Schwarz, L.;
Fu, G. C. J. Am. Chem. Soc. 2002, 124, 6343.
Acknowledgment
The authors would like to thank The Knut and Alice Wallenberg
Foundation and The Swedish Research Council for financial sup-
port. We also thank Dr. Erik Wallén for valuable discussions.
References and Notes
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Valenti, P.; Caputo, A.; Zampiron, A.; Carrara, M. J. Med.
Chem. 2003, 46, 3662; and references therein.
(4) Atassi, G.; Briet, P.; Berthelon, J. J.; Collonges, F. Eur. J.
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(5) (a) Yu, D.; Chen, C. H.; Brossi, A.; Lee, K. H. J. Med. Chem.
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K.; Shi, Q.; Kilkuskie, R. E.; Chen, Y.; Lee, K. H. J. Nat.
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Pimthon, J. J. Mol. Struct. 2004, 689, 99.
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2774; and references therein. (b) Rackova, L.; Firakova, S.;
Kostalova, D.; Stefek, M.; Sturdik, E.; Majekova, M.
Bioorg. Med. Chem. 2005, 13, 6477. (c) Soobrattee, M. A.;
Neergheen, V. S.; Luximon-Ramma, A.; Aruoma, O. I.;
Bahorun, T. Mutation Res. 2005, 579, 200.
(7) Klymchenko, A. S.; Mély, Y. Tetrahedron Lett. 2004, 45,
8391; and references therein.
(8) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev.
2003, 103, 893.
(9) All compounds reported herein gave spectral data consistent
with the assigned structures as well as satisfactory elemental
analyses.
(17) General Procedure for the Stille Coupling in Position 6 –
Synthesis of 6,8-Diallyl-flavone (5).
A solution of 3 (51 mg, 0.17 mmol), allyltributyltin (85 mg,
0.26 mmol), Pd2(dba)3 (10 mg, 0.01 mmol) and P(t-Bu)3 (8
mg, 0.04 mmol) in dioxane (15 mL) under N2 was warmed
to 80 °C for 14 h. The mixture was allowed to cool to r.t. and
Synlett 2006, No. 6, 897–900 © Thieme Stuttgart · New York

900
K. Dahlén et al.
LETTER
(20) Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10.
(21) Demeyer, N.; Haemers, A.; Mishra, L.; Pandey, H. K.;
Pieters, L. A. C.; Vandenberghe, D. A.; Vlietinck, A. J. J.
Med. Chem. 1991, 34, 736.
(22) (a) Pal, M.; Dakarapu, R.; Parasuraman, K.; Subramanian,
V.; Yeleswarapu, K. R. J. Org. Chem. 2005, 70, 7179; and
references therein. (b) Pal, M.; Parasuraman, K.;
Subramanian, V.; Dakarapu, R.; Yeleswarapu, K. R.
Tetrahedron Lett. 2004, 45, 2305. (c) Pal, M.;Subramanian,
V.; Parasuraman, K.; Yeleswarapu, K. R. Tetrahedron 2003,
59, 9563. (d) Larock, R. C.; Tian, Q. P. J. Org. Chem. 1998,
63, 2002.
filtered through Celite®. A sat. aq KF solution (10 mL) was
added and stirred for 30 min. The solution was extracted
with CH2Cl2 (4 × 20 mL). The combined organic phases
were washed with H2O (2 × 10 mL), dried over anhyd
MgSO4 before the solvent was removed under vacuum. The
residue was purified by column chromatography on silica
gel using a manual gradient of CH2Cl2–Et2O (100:0 to 95:5)
as eluent to afford 12 mg (22%) of 5 as light crystals; mp 86–
87 °C. 1H NMR (400 MHz, CDCl3): d = 3.48 (d, J = 6.4 Hz,
2 H), 3.75 (d, J = 6.8 Hz, 2 H), 5.10–5.19 (m, 4 H), 5.94–
6.14 (m, 2 H), 6.84 (s, 1 H), 7.39 (d, J = 2.2 Hz, 1 H), 7.52–
7.55 (m, 3 H), 7.91–7.94 (m, 3 H). 13C NMR (100 MHz,
CDCl3): d = 34.3, 39.9, 107.6, 116.8, 117.2, 123.3, 124.1,
126.5, 129.3, 129.7, 131.8, 132.3, 135.0, 135.6, 136.8,
137.2, 137.3, 163.2, 179.0. Anal. Calcd for
(23) Joo, Y. H.; Kim, J. K.; Kang, S. H.; Noh, M. S.; Ha, J. Y.;
Choi, J. K.; Lim, K. M.; Lee, C. H.; Chung, S. Bioorg. Med.
Chem. Lett. 2003, 13, 413.
(C21H18O2)2·H2O: C, 81.00, H, 6.15. Found: C, 80.78, H,
5.86.
(24) Echavarren, A. M.; Stille, J. K. J. Am. Chem. Soc. 1987, 109,
5478.
(18) According to NMR spectroscopy the major side products
showed a Pd-mediated rearrangement of the double bond in
the allyl group with or without a concomitant Stille coupling
in position 6.
(19) General Procedure for the Heck Reaction in Position 6 –
Synthesis of 6,8-Bis(2-methoxycarbonylethenyl)-flavone
(6).
(25) (a) Dounay, A. B.; Overman, L. E. Chem. Rev. 2003, 103,
2945. (b) Crisp, G. T.; Glink, P. T. Tetrahedron 1992, 48,
3541. (c) Cabri, W.; Candiani, I.; Bedeschi, A.; Santi, R. J.
Org. Chem. 1992, 57, 3558. (d) Cabri, W.; Candiani, I.;
Debernardinis, S.; Francalanci, F.; Penco, S.; Santi, R. J.
Org. Chem. 1991, 56, 5796.
(26) Utale, P. S.; Raghuwanshi, P. B.; Doshi, A. G. Asian J.
Chem. 1999, 11, 644.
(27) 8-Bromo-6-chloro-3-[3-(N-phthalimido)propoxy]-
flavone (13).
Et3N (0.04 mL, 0.26 mmol) was added to a suspension of 4
(46 mg, 0.13 mmol), Pd2(dba)3 (10 mg, 0.01 mmol), methyl
acrylate (0.03 mL, 0.33 mmol) and [P(t-Bu)3H]BF4 (12 mg,
0.04 mmol) in dioxane (4 mL) under N2 in a microwave tube.
The mixture was heated in a microwave cavity for 30 min at
160 °C. The solution was filtered through Celite® and H2O
(10 mL) was added. The mixture was extracted with CH2Cl2
(4 × 10 mL). The combined organic phases were dried over
anhyd MgSO4 before the solvent was removed under
vacuum. The residue was purified by column
chromatography on silica gel using a manual gradient of
CH2Cl2–Et2O (100:0 to 95:5) as eluent to afford 40 mg
(79%) of 6 as a white powder; mp 214–215 °C. 1H NMR
(400 MHz, CDCl3): d = 3.83 (s, 3 H), 3.87 (s, 3 H), 6.56 (d,
J = 15.9 Hz, 1 H), 6.71 (d, J = 16.4 Hz, 1 H), 6.85 (s, 1 H),
7.56–7.58 (m, 3 H), 7.73 (d, J = 15.9 Hz, 1 H), 7.90–7.93 (m,
2 H), 8.01 (d, J = 2.2 Hz, 1 H), 8.24 (d, J = 16.4 Hz, 1 H),
8.39 (d, J = 2.2 Hz, 1 H). 13C NMR (100 MHz, CDCl3):
d = 52.0, 52.2, 108.1, 120.2, 122.2, 124.8, 125.6, 126.5,
127.0, 129.5, 131.0, 131.3, 131.6, 132.2, 136.3, 142.3,
154.6, 163.7, 166.8, 166.9, 177.4. Anal. Calcd for C23H18O6:
C, 70.76, H, 4.65. Found: C, 70.59, H, 4.74.
A solution of 8 (6.2 g, 17.7 mmol), N-(3-bromo-
propyl)phthalimide (9.5 g, 35.4 mmol) and K2CO3 (4.5 g,
35.4 mmol) in DMF (50 mL) was stirred at 50 °C for 15 h.
The mixture was allowed to cool and H2O was added. The
solution was acidified with HCl (1 M). The precipitate was
filtered off and the solid was recrystallized from EtOH to
afford 8.5 g (87%) of 13 as white crystals; mp 185–186 °C.
1H NMR (400 MHz, CDCl3): d = 2.10–2.17 (m, 2 H), 3.83
(t, J = 7.0 Hz, 2 H), 4.18 (t, J = 6.2 Hz, 2 H), 7.52–7.58 (m,
3 H), 7.70–7.72 (m, 2 H), 7.83–7.85 (m, 2 H), 7.88 (d,
J = 1.3 Hz, 1 H), 8.14 (d, J = 1.3 Hz, 1 H), 8.23–8.25 (m, 2
H). 13C NMR (100 MHz, CDCl3): d = 29.5, 53.5, 70.5, 112.9,
123.4, 124.8, 125.8, 128.9, 129.1, 130.5, 130.9, 131.5,
132.3, 134.1, 136.6, 140.7, 150.5, 156.2, 168.4, 173.5. Anal.
Calcd for C26H17BrClNO5: C, 57.96, H, 3.18, N, 2.60.
Found: C, 57.79, H, 3.07, N, 2.48.
Synlett 2006, No. 6, 897–900 © Thieme Stuttgart · New York