Synthesis of functionalized benzofurans by a double heck reaction of 2,3-dibromofurans and subsequent 6-electrocyclization/dehydrogenation

Article abstract of DOI:10.1055/s-0030-1260666

The twofold Heck reaction of 2,3-dibromofurans afforded 2,3-di(alkenyl)furans which were transformed into functionalized benzofurans by a domino 6-electrocyclization/dehydrogenation reaction. Georg Thieme Verlag Stuttgart ? New York.

Full text of DOI:10.1055/s-0030-1260666

2208
SPECIAL TOPIC
Synthesis of Functionalized Benzofurans by a Double Heck Reaction of
2,3-Dibromofurans and Subsequent 6p-Electrocyclization/Dehydrogenation
S
ynthesis of Funct
h
ionalized Be
a
nzofurans
f
z
rom 2,3-D
iw
bromofurans an Ali Salman,a Asad Ali,a,b Munawar Hussain,a Rasheed Ahmad Khera,a,c Peter Langer*a,d
a
b
c
d
Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Department of Chemistry, University of Mardan, Mardan, Pakistan
Department of Chemistry, University Faisalabad, Government College, Faisalabad, Pakistan
Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Fax +49(381)4986412; E-mail: peter.langer@uni-rostock.de
Received 14 March 2011
ligands SPhos or XPhos10 (10 mol%) were used. The em-
ployment of tetrakis(triphenylphosphine)palladium(0) re-
sulted in considerably lower yields (Table 2, entry 1). The
reactions were carried out in N,N-dimethylformamide at
120 °C. A relatively long reaction time (36 h) was neces-
sary to achieve a complete conversion.
Abstract: The twofold Heck reaction of 2,3-dibromofurans afford-
ed 2,3-di(alkenyl)furans which were transformed into functional-
ized benzofurans by
dehydrogenation reaction.
a
domino 6p-electrocyclization/
Key words: catalysis, palladium, Heck reaction, electrocyclization,
furans
R
Br
R
Benzofurans are of considerable pharmacological rele-
vance in medicinal chemistry and occur in many natural
products.1 For example, amiodarone represents a synthet-
ic antiarrhythmic and antianginal drug.2 The core struc-
tures of 7-alkanoylbenzofurans and 7-alkanoyl-2,3-
dihydrobenzofurans are present in a number of natural
products (e.g., longicaudatin,3 the sessiliflorols A and B,
flemistrictin E, tovophenone C, vismiaguianone C and
piperaduncin B).4
R
2a–i
Br
O
i
O
1
3a–i
R
ii
R
O
4a–d
Polyhalogenated compounds represent interesting sub-
strates in palladium(0)-catalyzed cross-coupling reac-
tions.5,6 Bach and Krüger reported Sonogashira and Stille
reactions of 2,3-dibromofuran.7 These reactions proceed
with very good site-selectivity in favor of position 2. de
Meijere and co-workers reported that the combination of
a twofold Heck reaction with 6p-electrocyclization pro-
vides a convenient approach to various carbocycles.8 In
recent years, we have studied the application of this meth-
odology to heterocyclic systems.9 Herein, we report what
is, to the best of our knowledge, the first synthesis of func-
tionalized benzofurans by a double Heck reaction of 2,3-
dibromofurans and subsequent 6p-electrocyclization and
dehydrogenation. This methodology provides a conve-
nient approach to benzofurans containing substituents lo-
cated at positions 5 and 6 which are not readily accessible
by electrophilic substitution reactions.
Scheme 1 Synthesis of 3a–i and 4a–d. Reagents and conditions: (i)
2a–i (2.5 equiv), Pd(OAc)2 (5 mol%), SPhos or XPhos (10 mol%),
Et3N, DMF, 120 °C, 36 h; (ii) (1) Ph2O, 200 °C, 24 h; (2) Pd/C (10
mol%), Ph2O, 200 °C, 24 h.
Table 1 Synthesis of 3a–i and 4a–d
3, 4
a
R
Yielda (%) of 3 Yielda (%) of 4
CO2Me
73b
78c
93b
78c
88c
79c
90c
89b
87c
90
93
92
95
b
c
CO2Et
CO2i-Bu
CO2n-Bu
CO2(CH2)5Me
CO2t-Bu
4-MeOC6H4
4-Tol
d
e
d
–
e
f
–
e
g
–
The Heck reaction of 2,3-dibromofuran (1) with acrylates
and styrenes 2a–i (2.5 equiv) afforded the 2,3-di(alke-
nyl)furans 3a–i in good yields (Scheme 1, Table 1). The
reaction was thoroughly optimized for derivatives 3b and
3f (Table 2). The best yields were obtained when palladi-
um(II) acetate (5 mol%) and the biaryl monophosphine
e
h
i
–
e
4-t-BuOC6H4
–
a Yields of isolated products.
b XPhos was used.
c SPhos was used.
d Reaction was not carried out.
e Decomposition.
SYNTHESIS 2011, No. 14, pp 2208–2214
x
x.
x
x
.
2
0
1
1
Advanced online publication: 09.06.2011
DOI: 10.1055/s-0030-1260666; Art ID: C00811SS
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Synthesis of Functionalized Benzofurans from 2,3-Dibromofurans
2209
Table 2 Optimization of the Reaction Conditions for the Synthesis
of 3b and 3fa
Table 3 Synthesis of 6a–h and 7a–h
2
6, 7
R
Yielda (%) Yielda (%)
Entry Catalyst
Yieldb (%) of Yieldb (%) of 3f
of 6
81
85
83
85
88
84
94
83
of 7
3b
c
e
f
a
b
c
d
e
f
CO2i-Bu
95
1
2
Pd(PPh3)4 (5 mol%) 35
41
CO2(CH2)5Me
CO2t-Bu
97
Pd(OAc)2 (5 mol%), 73
72
b
–
XPhos (10 mol%)
j
CO2(CH2)5CHMe2
CO2n-Bu
88
90
93
94
90
3
4
5
Pd(OAc)2 (5 mol%), 78
SPhos (10 mol%)
79
d
a
b
k
Pd(OAc)2 (3 mol%), 65
Cy3P (6 mol%)
59
CO2Me
g
h
CO2Et
Pd(OAc)2 (2 mol%), traces
(HOCH2CH2)3Nc
traces
4-ClC6H4
a Reactions were carried out in DMF using Et3N as the base.
b Yields of isolated products.
a Yields of isolated products.
b Decomposition.
c Triethanolamine was used as solvent, base and ligand.
kenyl)furan 6h proved to be possible and afforded 7h in
good yield.
Our next target was to find suitable conditions for a 6p-
electrocyclization. In fact, 2,3-di(alkenyl)furans 3 proved
to be rather reluctant to undergo the desired transforma-
tion. Stirring of a diphenyl ether solution of 3a–d at
200 °C for 24 hours was required to induce the desired
electrocyclization. To the reaction mixture was added pal-
ladium on carbon (10 mol%) and the mixture was stirred
for an additional 24 hours at 200 °C to give benzofurans
4a–d by dehydrogenation (see Table 1). Heating of 3f re-
sulted in decomposition of the tert-butyl ester moiety.
Heating of the styrene-derived products 3g–i also resulted
in decomposition.
It was noted above that Sonogashira and Stille reactions of
2,3-dibromofurans are known to proceed with excellent
site-selectivity in favor of position 2. The site-selectivity
of palladium(0)-catalyzed reactions of polyhalogenated
substrates is generally controlled by steric and electronic
effects. More electron-deficient carbon atoms are usually
more reactive than electron-rich atoms; however, all at-
tempts to carry out site-selective mono-Heck reactions of
dibromofuran 1 or 5 failed. All reactions resulted in the
isolation of double-Heck products 3 and 6 and of unreact-
ed starting material. This might be explained by a proxim-
ity effect. The first attack occurs at carbon atom C-2 of the
furan. The palladium catalyst is coordinated by the alkene
and the reactivity of the neighbored carbon atom C-3
might thus be increased. In the case of products 3a–f and
6a–g, the increased reactivity of C-3 might alternatively
be explained by the electron-withdrawing effect of the
acrylate moiety located at carbon C-2.
The twofold Heck reaction of 2,3-dibromo-5-(ethoxycar-
bonyl)furan (5) with acrylates and styrenes 2a–f,j,k af-
forded the 2,3-di(alkenyl)furans 6a–h (Scheme 2,
Table 3). The reactions proceeded at slightly lower tem-
perature (100 °C, 24 h) as compared to the synthesis of
3a–i. The transformation of 2,3-di(alkenyl)furans 6a,b,d–
h to benzofurans 7a,b,d–h required less drastic conditions
(stirring at 170 °C, 2 × 12 h) as compared to the synthesis
of 4a–d (200 °C, 2 × 24 h). Similar to 3f, heating of tert-
butyl ester 6c resulted in decomposition. In contrast to
3g–i, electrocyclization of the styrene-derived 2,3-di(al-
In conclusion, functionalized benzofurans were prepared
by a twofold Heck reaction of 2,3-dibromofurans and a
subsequent domino 6p-electrocyclization/dehydrogena-
tion reaction. The products are not readily available by
other methods.
R
Br
R
2a–f,j,k
All solvents were dried by standard methods and all reactions were
carried out under an inert atmosphere. For 1H and 13C NMR spectra,
the deuterated solvents indicated were used. Mass spectrometric
data (MS) were obtained by electron ionization (EI, 70 eV), chemi-
cal ionization (CI, isobutane) or electrospray ionization (ESI). For
preparative-scale chromatography, silica gel 60 (0.063–0.200 mm,
70–230 mesh) was used. Melting points are uncorrected.
R
Br
EtO2C
EtO2C
O
O
i
5
6a–h
R
ii
R
EtO2C
O
2,3-Di(alkenyl)furans 3a–i and 6a–h; General Procedure
In a pressure tube (glass bomb), a suspension of Pd(OAc)2 (12 mg,
5 mol%) and XPhos or SPhos (10 mol%) in DMF (5 mL) was
purged with argon and stirred at 20 °C to give a yellowish or brown-
ish clear solution. To the stirred solution were added dibromofuran
1 (0.12 mL, 1.0 mmol) or 5 (300 mg, 1.0 mmol), Et3N (1.1 mL, 8.0
7a–h
Scheme 2 Synthesis of 6a–h and 7a–h. Reagents and conditions: (i)
2a–f,j,k (2.5 equiv), Pd(OAc)2 (5 mol%), XPhos (10 mol%), Et3N,
DMF, 100 °C, 24 h; (ii) (1) Ph2O, 170 °C, 12 h; (2) Pd/C (10 mol%),
Ph2O, 170 °C, 12 h.
Synthesis 2011, No. 14, 2208–2214 © Thieme Stuttgart · New York

2210
G. A. Salman et al.
SPECIAL TOPIC
mmol) and the acrylate or styrene 2a–i (2.5 mmol). The reaction
mixture was stirred at 120 °C for 36 h (for 3a–i) or at 100 °C for 24
h (for 6a–h). The solution was cooled to 20 °C, poured into H2O (25
mL) and CH2Cl2 (25 mL), and the organic layer and the aqueous
layer were separated. The latter was extracted with CH2Cl2 (3 × 25
mL). The combined organic layers were dried (Na2SO4) and con-
centrated under reduced pressure. The residue was purified by flash
silica gel chromatography (heptanes–EtOAc).
13C NMR (75.5 MHz, CDCl3): d = 13.6 (2 CH3), 19.1 (2 CH2), 30.7
(2 CH2), 64.4, 64.5 (CH2O), 109.3, 118.2, 120.3 (CH), 124.7 (C),
127.2, 132.3, 145.1 (CH), 150.5 (C), 166.5, 166.6 (CO).
GC-MS (EI, 70 eV): m/z (%) = 320 (71) [M+], 264 (8), 247 (23),
190 (17), 163 (86), 147 (100), 134 (11), 119 (53).
HRMS (EI, 70 eV): m/z calcd for C18H24O5: 320.16238; found:
320.16236.
Dihexyl (2E,2¢E)-3,3¢-(Furan-2,3-diyl)diacrylate (3e)
Yield: 331 mg (88%); light yellow oil.
Dimethyl (2E,2¢E)-3,3¢-(Furan-2,3-diyl)diacrylate (3a)
Yield: 172 mg (73%); light yellow oil.
IR (KBr): 3122, 3108 (w), 2921, 1711 (s), 1631 (m), 1549, 1500
(w), 1445 (m), 1377 (w), 1292 (m), 1275, 1255, 1167 (s), 1069 (w),
1035 (m), 1018 (w), 959 (m), 933 (w), 862 (m), 825 (w), 749 (m),
746 (w), 721 (m), 648, 607 (w), 538 (m) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.83–0.86 (m, 6 H, 2 CH3), 1.16–
1.34 (m, 12 H, 6 CH2), 1.58–1.68 (m, 4 H, 2 CH2), 4.13 (t, J = 6.8
Hz, 2 H, CH2O), 4.14 (t, J = 6.7 Hz, 2 H, CH2O), 6.16 (d, J = 15.5
Hz, 1 H, CH), 6.35 (d, J = 15.5 Hz, 1 H, CH), 6.57 (d, J = 2.4 Hz, 1
H, ArH), 7.37 (d, J = 1.9 Hz, 1 H, ArH), 7.55 (d, J = 15.5 Hz, 1 H,
CH), 7.60 (d, J = 15.6 Hz, 1 H, CH).
IR (KBr): 3100 (w), 2850 (m), 1711 (s), 1676 (w), 1631 (m), 1510
(w), 1445, 1292 (m), 1275, 1245, 1178 (s), 1035, 970, 872, 749 (m),
861, 756 (w), 721 (m), 530 (m) cm–1.
1H NMR (300 MHz, CDCl3): d = 3.72 (s, 3 H, CH3O), 3.74 (s, 3 H,
CH3O), 6.16 (d, J = 15.8 Hz, 1 H, CH), 6.34 (d, J = 15.8 Hz, 1 H,
CH), 6.57 (d, J = 2.2 Hz, 1 H, ArH), 7.38 (d, J = 1.7 Hz, 1 H, ArH),
7.55 (d, J = 15.8 Hz, 1 H, CH), 7.62 (d, J = 15.8 Hz, 1 H, CH).
13C NMR (75.5 MHz, CDCl3): d = 51.79, 51.85 (CH3O), 109.4,
117.8, 119.8 (CH), 124.8 (C), 127.4, 132.7, 145.2 (CH), 150.5 (C),
166.9, 167.0 (CO).
13C NMR (75.5 MHz, CDCl3): d = 14.0 (2 CH3), 22.5, 22.6, 28.7,
31.4 (2 CH2), 64.9, 65.0 (CH2O), 109.4, 118.3, 120.3 (CH), 124.7
(C), 127.2, 132.4, 145.1 (CH), 150.5 (C), 166.5, 166.6 (CO).
GC-MS (EI, 70 eV): m/z (%) = 236 (11) [M+], 230 (14), 213 (29),
187 (100), 173 (5), 151 (6), 111 (4).
HRMS (EI, 70 eV): m/z calcd for C12H12O5: 236.06847; found:
236.06801.
GC-MS (EI, 70 eV): m/z (%) = 376 (1) [M+], 345 (8), 291 (3), 206
(10), 189 (100), 162 (8).
HRMS (EI, 70 eV): m/z calcd for C22H32O5: 376.22497; found:
376.22397.
Diethyl (2E,2¢E)-3,3¢-(Furan-2,3-diyl)diacrylate (3b)
Compound 3b was directly transformed into 4b without characteri-
zation.
Di-tert-butyl (2E,2¢E)-3,3¢-(Furan-2,3-diyl)diacrylate (3f)
Yield: 252 mg (79%); light yellow oil.
Diisobutyl (2E,2¢E)-3,3¢-(Furan-2,3-diyl)diacrylate (3c)
Yield: 297 mg (93%); light yellow oil.
IR (KBr): 2976, 2931 (m), 1705 (s), 1636, 1454, 1392, 1367, 1313,
1283, 1253 (m), 1146 (s), 1018, 977, 844, 767 (m), 711, 685, 594,
574 (w) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.46 (s, 18 H, 6 CH3), 6.03 (d,
J = 16.1 Hz, 1 H, CH), 6.27 (d, J = 15.5 Hz, 1 H, CH), 6.54 (d,
J = 2.3 Hz, 1 H, ArH), 7.34 (d, J = 2.3 Hz, 1 H, ArH), 7.44 (d,
J = 15.5 Hz, 1 H, CH), 7.45 (d, J = 15.7 Hz, 1 H, CH).
13C NMR (75.5 MHz, CDCl3): d = 28.2 (6 CH3), 80.7, 80.8 (C),
109.4, 120.1, 122.1 (CH), 124.4 (C), 126.5, 131.6, 144.8 (CH),
150.5 (C), 165.8, 165.9 (CO).
IR (KBr): 3119 (w), 2935 (s), 2852 (m), 1711 (s), 1631 (m), 1579,
1509 (w), 1290 (m), 1272, 1257 (s), 1045, 832, 740 (m), 658, 606
(w), 530 (m) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.89 (d, J = 6.8 Hz, 12 H, 4 CH3),
1.86–1.97 (m, 2 H, 2 CH), 3.90 (d, J = 6.7 Hz, 2 H, CH2O), 3.91 (d,
J = 6.7 Hz, 2 H, CH2O), 6.17 (d, J = 15.6 Hz, 1 H, CH), 6.35 (d,
J = 15.6 Hz, 1 H, CH), 6.58 (d, J = 1.8 Hz, 1 H, ArH), 7.37 (d,
J = 2.0 Hz, 1 H, ArH), 7.55 (d, J = 15.6 Hz, 1 H, CH), 7.59 (d,
J = 15.6 Hz, 1 H, CH).
13C NMR (62.9 MHz, CDCl3): d = 19.1 (4 CH3), 27.8 (2 CH), 70.7,
70.8 (CH2O), 109.3, 118.2, 120.3 (CH), 124.7 (C), 127.2, 132.4,
145.1 (CH), 150.5 (C), 166.4, 166.5 (CO).
GC-MS (EI, 70 eV): m/z (%) = 320 (71) [M+], 305 (18), 290 (11),
262 (11), 249 (20), 189 (17), 153 (19), 147 (100).
GC-MS (EI, 70 eV): m/z (%) = 320 (15) [M+], 247 (11), 208 (100),
163 (31), 147 (21), 119 (26).
HRMS (EI, 70 eV): m/z calcd for C18H24O5: 320.16237; found:
320.16232.
2,3-Bis(4-methoxystyryl)furan (3g)
Yield: 299 mg (90%); light yellow oil.
HRMS (EI, 70 eV): m/z calcd for C18H24O5: 320.16237; found:
320.16360.
IR (KBr): 3030, 2996, 2992, 2930, 2833 (w), 1599, 1571, 1508,
1497, 1456, 1436, 1417, 1298, 1290, 1267 (m), 1246 (s), 1174,
1145, 1109, 1061, 958, 934, 895, 852, 845 (m), 815 (s), 740, 720
(m), 696, 659, 637, 610, 561, 547 (w) cm–1.
1H NMR (300 MHz, CDCl3): d = 3.74 (s, 6 H, 2 CH3O), 6.56 (d,
J = 2.1 Hz, 1 H, ArH), 6.71 (d, J = 16.2 Hz, 1 H, CH), 6.82 (d,
J = 8.8 Hz, 4 H, ArH), 6.87–6.92 (m, 3 H), 7.25 (d, J = 2.0 Hz, 1 H,
ArH), 7.34 (d, J = 8.6 Hz, 2 H, ArH), 7.38 (d, J = 8.7 Hz, 2 H, ArH).
13C NMR (62.9 MHz, CDCl3): d = 55.3 (CH3O), 108.7, 112.1,
114.1, 114.2, 116.0 (CH), 121.6 (C), 126.8, 127.4, 127.7, 128.1
(CH), 130.0, 130.3 (C), 142.1 (CH), 150.0, 159.2, 159.4 (C).
GC-MS (EI, 70 eV): m/z (%) = 332 (100) [M+], 207 (20), 166 (10),
121 (17).
Dibutyl (2E,2¢E)-3,3¢-(Furan-2,3-diyl)diacrylate (3d)
Yield: 249 mg (78%); light yellow oil.
IR (KBr): 3133, 3118 (w), 2925 (s), 2850 (m), 1711 (s), 1676 (w),
1631 (m), 1549, 1500 (w), 1445 (m), 1290 (m), 1275, 1255, 1168
(s), 1035, 969, 862, 749 (m), 746 (w), 720 (m), 648, 606 (w), 539
(m) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.86 (t, J = 7.3 Hz, 6 H, 2 CH3),
1.28–1.40 (m, 4 H, 2 CH2), 1.56–1.65 (m, 4 H, 2 CH2), 4.10–4.15
(m, 4 H, 2 CH2O), 6.14 (d, J = 15.6 Hz, 1 H, CH), 6.32 (d, J = 15.6
Hz, 1 H, CH), 6.56 (d, J = 1.9 Hz, 1 H, ArH), 7.36 (d, J = 2.0 Hz, 1
H, ArH), 7.52 (d, J = 15.6 Hz, 1 H, CH), 7.57 (d, J = 15.5 Hz, 1 H,
CH).
Synthesis 2011, No. 14, 2208–2214 © Thieme Stuttgart · New York

SPECIAL TOPIC
Synthesis of Functionalized Benzofurans from 2,3-Dibromofurans
2211
HRMS (EI, 70 eV): m/z calcd for C22H20O3: 332.14070; found:
332.14073.
Dihexyl (2E,2¢E)-3,3¢-[5-(Ethoxycarbonyl)furan-2,3-diyl]di-
acrylate (6b)
Yield: 382 mg (85%); yellow solid; mp 162–164 °C.
2,3-Bis(4-methylstyryl)furan (3h)
Yield: 270 mg (89%); light yellow oil.
IR (KBr): 3107, 2953, 2929, 2857 (w), 1715, 1632 (s), 1579, 1518,
1467 (m), 1453, 1392, 1368, 1346 (w), 1321 (s), 1301, 1265, 1252,
1240 (w), 1223 (m), 1175 (s), 1123, 1107, 1052, 1038 (w), 1024,
977, 961 (m), 910 (w), 875, 860 (m), 822, 799 (w), 764, 724, 661,
596 (m) cm–1.
IR (KBr): 3020, 2992, 2963, 2833 (w), 1599, 1571, 1508, 1498,
1456, 1436, 1418, 1298, 1290 (m), 1246, 1174 (s), 1029, 959, 815,
740, 720 (m), 659, 638, 610, 562, 548 (w) cm–1.
1H NMR (300 MHz, CDCl3): d = 2.24 (s, 6 H, 2 CH3), 6.54 (d,
J = 2.0 Hz, 1 H, ArH), 6.68 (d, J = 16.2 Hz, 1 H, CH), 6.97 (m, 3
H), 7.05 (d, J = 7.9 Hz, 4 H, ArH), 7.22 (d, J = 2.0 Hz, 1 H, ArH),
7.28 (d, J = 7.9 Hz, 2 H, ArH), 7.29 (d, J = 8.2 Hz, 2 H, ArH).
13C NMR (62.9 MHz, CDCl3): d = 21.3, 21.4 (CH3), 108.8, 113.1,
117.1 (CH), 122.0 (C), 126.2, 126.5, 127.4, 128.7, 129.4, 129.5
(CH), 134.4, 134.8, 137.3, 137.7 (C), 142.3 (CH), 150.1 (C).
1H NMR (300 MHz, CDCl3): d = 0.81–0.86 (m, 6 H, 2 CH3), 1.23–
1.28 (m, 12 H, 6 CH2), 1.38 (t, J = 7.3 Hz, 3 H, CH3), 1.59–1.68 (m,
4 H, 2 CH2), 4.02 (d, J = 3.7 Hz, 2 H, CH2O), 4.05 (d, J = 3.6 Hz, 2
H, CH2O), 4.32 (q, J = 7.1 Hz, 2 H, CH2O), 6.23 (d, J = 15.7 Hz, 1
H, CH), 6.61 (d, J = 15.8 Hz, 1 H, CH), 7.27 (s, 1 H, ArH), 7.53 (d,
J = 8.0 Hz, 1 H, CH), 7.58 (d, J = 8.0 Hz, 1 H, CH).
13C NMR (75.5 MHz, CDCl3): d = 14.0 (2 CH3), 14.3 (CH3), 22.5,
25.6, 28.6, 31.4 (2 CH2), 61.7, 65.0, 65.2 (CH2O), 115.8, 121.6,
121.7 (CH), 125.2 (C), 126.5, 131.5 (CH), 145.8, 152.4 (C), 158.0,
166.2, 166.5 (CO).
GC-MS (EI, 70 eV): m/z (%) = 300 (100) [M+], 281 (33), 245 (8),
216 (10), 204 (8), 198 (10).
HRMS (EI, 70 eV): m/z calcd for C22H20O: 300.15142; found:
300.15133.
GC-MS (EI, 70 eV): m/z (%) = 449 (14), 448 (49) [M+], 403 (17),
347 (18), 320 (10), 291 (7), 280 (19), 246 (22), 235 (100).
2,3-Bis(4-tert-butoxystyryl)furan (3i)
Yield: 361 mg (87%); light yellow oil.
HRMS (EI, 70 eV): m/z calcd for C25H36O7: 448.24555; found:
448.24519.
IR (KBr): 3033, 2972, 2929, 2872, 1623 (w), 1503, 1362, 1271 (m),
1159 (s), 1102, 1060, 1029, 968, 959, 947 (w), 891, 864, 832, 743,
690, 677, 591 (m) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.37 (s, 18 H, 6 CH3), 6.54 (d,
J = 2.0 Hz, 1 H, ArH), 6.67 (d, J = 16.1 Hz, 1 H, CH), 6.80–6.94 (m,
7 H), 7.23 (d, J = 2.0 Hz, 1 H, ArH), 7.30 (d, J = 8.5 Hz, 2 H, ArH),
7.31 (d, J = 8.6 Hz, 2 H, ArH).
13C NMR (62.9 MHz, CDCl3): d = 28.9 (6 CH3), 78.7, 78.8 (CO),
108.8, 112.9, 116.9 (CH), 121.8 (C), 124.2, 124.3, 126.7, 126.9,
127.0, 128.3 (CH), 132.4, 132.7 (C), 142.3 (CH), 150.1, 155.0,
155.3 (C).
Di-tert-butyl (2E,2¢E)-3,3¢-[5-(Ethoxycarbonyl)furan-2,3-
diyl]diacrylate (6c)
Yield: 326 mg (83%); orange solid; mp 158–160 °C.
IR (KBr): 3109, 2979, 2930 (w), 1714, 1699 (s), 1633 (m), 1575,
1509, 1475, 1455, 1391 (w), 1367, 1322, 1280, 1256, 1220 (m),
1141 (s), 1079, 1019 (w), 975, 958 (m), 885, 863, 844 (w), 763, 750,
722, 653 (m), 607, 579 (w) cm–1.
1H NMR (250 MHz, CDCl3): d = 1.32 (t, J = 7.2 Hz, 3 H, CH3),
1.46 (s, 18 H, 6 CH3), 4.31 (q, J = 7.2 Hz, 2 H, CH2O), 6.14 (d,
J = 15.4 Hz, 1 H, CH), 6.53 (d, J = 15.7 Hz, 1 H, CH), 7.24 (s, 1 H,
ArH), 7.42 (d, J = 4.3 Hz, 1 H, CH), 7.48 (d, J = 4.3 Hz, 1 H, CH).
GC-MS (EI, 70 eV): m/z (%) = 416 (14) [M+], 360 (7), 304 (100),
210 (7).
13C NMR (62.9 MHz, CDCl3): d = 14.3 (CH3), 28.1 (6 CH3), 61.5
(CH2), 81.1, 81.2 (C), 115.9, 123.4, 123.5 (CH), 124.9 (C), 125.7,
130.5 (CH), 145.6, 152.3 (C), 158.1, 165.3, 165.4 (CO).
HRMS (EI, 70 eV): m/z calcd for C28H32O3: 416.23460; found:
416.23516.
GC-MS (EI, 70 eV): m/z (%) = 392 (11) [M+], 336 (9), 280 (100),
235 (23), 219 (17), 206 (34).
Diisobutyl (2E,2¢E)-3,3¢-[5-(Ethoxycarbonyl)furan-2,3-diyl]di-
acrylate (6a)
HRMS (EI, 70 eV): m/z calcd for C21H28O7: 392.18295; found:
Yield: 318 mg (81%); light yellow solid; mp 152–154 °C.
392.18307.
IR (KBr): 3109, 2958, 2874 (w), 1709 (s), 1633, 1578, 1515, 1469
(m), 1394 (w), 1368 (m), 1343 (w), 1318 (s), 1300, 1270 (w), 1255
(m), 1239 (w), 1220 (m), 1171 (s), 1114 (m), 1080 (w), 1008, 962
(s), 875, 861, 837 (w), 765, 748, 720, 693, 657 (m), 609, 595, 542
(w) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.89 (d, J = 6.7 Hz, 12 H, 4 CH3),
1.40 (t, J = 7.3 Hz, 3 H, CH3), 1.96–2.01 (m, 2 H, 2 CH), 4.01 (d,
J = 3.6 Hz, 2 H, CH2O), 4.03 (d, J = 3.5 Hz, 2 H, CH2O), 4.41 (q,
J = 7.1 Hz, 2 H, CH2O), 6.34 (d, J = 15.8 Hz, 1 H, CH), 6.71 (d,
J = 15.8 Hz, 1 H, CH), 7.37 (s, 1 H, ArH), 7.62 (d, J = 8.6 Hz, 1 H,
CH), 7.67 (d, J = 8.4 Hz, 1 H, CH).
13C NMR (75.5 MHz, CDCl3): d = 14.3 (CH3), 19.1 (4 CH3), 27.8
(2 CH), 61.7, 71.0, 71.1 (CH2O), 115.8, 121.5, 121.6 (CH), 125.2
(C), 126.5, 131.5 (CH), 145.5, 152.4 (C), 158.0, 166.2, 166.5 (CO).
GC-MS (EI, 70 eV): m/z (%) = 393 (22), 392 (80) [M+], 347 (22),
336 (18), 320 (10), 319 (49), 280 (53), 263 (16), 235 (72), 219
(100), 206 (44).
Bis(6-methylheptyl) (2E,2¢E)-3,3¢-[5-(Ethoxycarbonyl)furan-
2,3-diyl]diacrylate (6d)
Yield: 430 mg (85%); yellow solid; mp 153–155 °C.
IR (KBr): 3107, 2956, 2948, 2857 (w), 1717, 1635 (s), 1579, 1517,
1469 (m), 1457, 1392, 1368, 1346 (w), 1323 (s), 1311, 1266, 1253,
1242 (w), 1224 (m), 1178 (s), 1125, 1105, 1053, 1039 (w), 1021,
978, 962 (m), 910 (w), 875, 861 (m), 823, 798 (w), 764, 723, 663,
598 (m) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.72–0.87 (m, 12 H, 4 CH3), 0.89–
0.90 (m, 2 H, 2 CH), 1.10–1.23 (m, 8 H, 4 CH2), 1.32 (t, J = 7.3 Hz,
3 H, CH3), 1.36–1.39 (m, 8 H, 4 CH2), 4.10–4.22 (m, 4 H, 2 CH2O),
4.32 (q, J = 7.1 Hz, 2 H, CH2O), 6.23 (dd, J = 2.8, 15.8 Hz, 1 H,
CH), 6.61 (dd, J = 2.8, 15.8 Hz, 1 H, CH), 7.27 (s, 1 H, ArH), 7.53
(d, J = 8.2 Hz, 1 H, CH), 7.58 (d, J = 8.2 Hz, 1 H, CH).
13C NMR (62.9 MHz, CDCl3): d = 14.3 (CH3), 19.5 (4 CH3), 23.4,
25.7, 28.6, 31.4 (2 CH2), 27.7 (2 CH), 61.6, 65.1, 65.4 (CH2O),
115.7, 121.4, 121.8 (CH), 125.2 (C), 126.7, 131.8 (CH), 145.7,
152.6 (C), 158.4, 166.2, 166.4 (CO).
HRMS (EI, 70 eV): m/z calcd for C21H28O7: 392.18295; found:
392.18259.
Synthesis 2011, No. 14, 2208–2214 © Thieme Stuttgart · New York

2212
G. A. Salman et al.
SPECIAL TOPIC
GC-MS (EI, 70 eV): m/z (%) = 504 (40) [M+], 459 (30), 457 (60),
392 (35), 376 (100), 348 (53), 317 (33), 280 (26), 246 (50), 219
(72).
13C NMR (62.9 MHz, CDCl3): d = 14.2 (2 CH3), 14.3 (CH3), 60.8,
61.0, 61.6 (CH2O), 115.7, 121.6, 121.7 (CH), 125.2 (C), 126.5,
131.4 (CH), 145.9, 152.3 (C), 158.0, 166.0, 166.1 (CO).
HRMS (EI, 70 eV): m/z calcd for C29H44O7: 504.30816; found:
GC-MS (EI, 70 eV): m/z (%) = 336 (100) [M+], 291 (53), 263 (89),
504.30782.
235 (45), 219 (46), 217 (35), 191 (70).
HRMS (EI, 70 eV): m/z calcd for C17H20O7: 336.12035; found:
336.11988.
Dibutyl (2E,2¢E)-3,3¢-[5-(Ethoxycarbonyl)furan-2,3-diyl]di-
acrylate (6e)
Yield: 346 mg (88%); light yellow solid; mp 158–160 °C.
Ethyl 4,5-Bis(4-chlorostyryl)furan-2-carboxylate (6h)
Compound 6h was directly transformed into 7h without characteri-
zation.
IR (KBr): 3107, 2953, 2929, 2857 (w), 1715, 1632 (s), 1579, 1518,
1467 (m), 1453, 1392, 1368, 1346 (w), 1321 (s), 1301, 1265, 1252,
1240 (w), 1223 (m), 1175 (s), 1123, 1107, 1052, 1038 (w), 1024,
977, 961 (m), 910 (w), 875, 860 (m), 822, 799 (w), 764, 724, 661,
596 (m) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.89 (t, J = 7.4 Hz, 6 H, 2 CH3),
1.32 (t, J = 7.1 Hz, 3 H, CH3), 1.35–1.42 (m, 4 H, 2 CH2), 1.57–1.67
(m, 4 H, 2 CH2), 4.12–4.18 (m, 4 H, 2 CH2O), 4.32 (q, J = 7.1 Hz,
2 H, CH2O), 6.23 (d, J = 15.8 Hz, 1 H, CH), 6.61 (d, J = 15.5 Hz, 1
H, CH), 7.27 (s, 1 H, ArH), 7.53 (d, J = 8.1 Hz, 1 H, CH), 7.58 (d,
J = 8.1 Hz, 1 H, CH).
13C NMR (75.5 MHz, CDCl3): d = 13.7 (2 CH3), 14.3 (CH3), 19.1
(2 CH2), 30.7 (2 CH2), 61.6, 64.8, 64.9 (CH2O), 115.8, 121.6, 121.7
(CH), 125.2 (C), 126.5, 131.4 (CH), 145.9, 152.3 (C), 158.0, 166.1,
166.2 (CO).
GC-MS (EI, 70 eV): m/z (%) = 392 (43) [M+], 347 (9), 336 (11),
319 (23), 291 (16), 263 (15), 235 (60), 219 (49), 191 (100).
Functionalized Benzofurans 4a–d and 7a–h; General Procedure
A diphenyl ether solution (3 mL) of a 2,3-di(alkenyl)furan 3a–d or
6a–h (0.5 mmol) was stirred at 200 °C for 24 h (for 3a–d) or at
170 °C for 12 h (for 6a–h) in a pressure tube. The solution was al-
lowed to cool to 20 °C and Pd/C (10 mol%) was added. The solution
was stirred at 200 °C for 24 h (for 3a–d) or at 170 °C for 12 h (for
6a–h) under argon atmosphere. The reaction mixture was filtered
and the filtrate was concentrated under reduced pressure. The resi-
due was purified by flash silica gel chromatography (heptanes–
EtOAc).
Dimethyl Benzofuran-5,6-dicarboxylate (4a)
Yield: 105 mg (90%); light yellow oil.
IR (KBr): 3010, 2850 (w), 1723, 1716 (s), 1583, 1486, 1435 (w),
1229, 1202, 1165, 1071, 1021, 981, 865, 797, 750, 692, 666 (s)
cm–1.
HRMS (EI, 70 eV): m/z calcd for C21H28O7: 392.18295; found:
1H NMR (300 MHz, CDCl3): d = 3.81 (s, 3 H, CH3O), 3.82 (s, 3 H,
CH3O), 6.75 (d, J = 2.1 Hz, 1 H, ArH), 7.63 (d, J = 2.2 Hz, 1 H,
ArH), 7.80 (s, 1 H, ArH), 7.90 (s, 1 H, ArH).
13C NMR (75.5 MHz, CDCl3): d = 52.6, 52.7 (CH3O), 107.0, 112.6,
122.6 (CH), 127.4, 128.2, 129.6 (C), 148.3 (CH), 155.2 (C), 167.9,
168.4 (CO).
392.18324.
Dimethyl (2E,2¢E)-3,3¢-[5-(Ethoxycarbonyl)furan-2,3-diyl]di-
acrylate (6f)
Yield: 259 mg (84%); orange solid; mp 150–152 °C.
IR (KBr): 3397, 3109, 2985 (w), 1708 (s), 1639 (m), 1580, 1517,
1443, 1395 (w), 1367, 1321 (m), 1267, 1256, 1234, 1223 (w), 1182
(s), 1117, 1083 (w), 1036, 968, 957 (s), 893, 874, 863, 810 (w), 763,
746, 722, 656 (m), 607, 585 (w) cm–1.
GC-MS (EI, 70 eV): m/z (%) = 234 (10) [M+], 204 (4), 187 (100),
171 (5), 149 (6), 111 (4).
HRMS (EI, 70 eV): m/z calcd for C12H10O5: 234.05282; found:
234.05277.
1H NMR (300 MHz, CDCl3): d = 1.32 (t, J = 7.1 Hz, 3 H, CH3),
3.74 (s, 3 H, CH3O), 3.76 (s, 3 H, CH3O), 4.32 (q, J = 7.3 Hz, 2 H,
CH2O), 6.23 (d, J = 15.9 Hz, 1 H, CH), 6.59 (d, J = 15.9 Hz, 1 H,
CH), 7.27 (s, 1 H, ArH), 7.54 (d, J = 8.7 Hz, 1 H, CH), 7.59 (d,
J = 8.7 Hz, 1 H, CH).
Diethyl Benzofuran-5,6-dicarboxylate (4b)
Yield: 122 mg (93%); light yellow oil.
IR (KBr): 3411, 3120, 2931, 2872 (w), 1715 (s), 1619, 1586, 1529
(w), 1488, 1465 (m), 1391 (w), 1367 (m), 1300, 1219, 1149, 1125,
1102, 1039 (s), 896, 859, 772, 691, 588 (m) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.86 (t, J = 7.5 Hz, 6 H, 2 CH3),
4.30–4.35 (m, 4 H, 2 CH2O), 6.77 (d, J = 2.2 Hz, 1 H, ArH), 7.69
(d, J = 2.2 Hz, 1 H, ArH), 7.81 (s, 1 H, ArH), 7.91 (s, 1 H, ArH).
13C NMR (75.5 MHz, CDCl3): d = 14.1 (2 CH3), 61.6, 61.7 (CH2O),
107.3, 112.4, 122.5 (CH), 127.8, 128.8, 129.5 (C), 148.2 (CH),
155.2 (C), 167.6, 168.0 (CO).
13C NMR (75.5 MHz, CDCl3): d = 13.2 (CH3), 50.9, 51.1 (CH3O),
60.7 (CH2O), 114.7, 120.1, 120.2 (CH), 124.2 (C), 125.7, 130.7
(CH), 145.0, 151.3 (C), 157.0, 165.4, 165.5 (CO).
GC-MS (EI, 70 eV): m/z (%) = 308 (100) [M+], 277 (36), 263 (20),
249 (63), 235 (91), 217 (31), 205 (55), 177 (44), 162 (30), 145 (92).
HRMS (EI, 70 eV): m/z calcd for C15H16O7: 308.08905; found:
308.08870.
Diethyl (2E,2¢E)-3,3¢-[5-(Ethoxycarbonyl)furan-2,3-diyl]di-
acrylate (6g)
GC-MS (EI, 70 eV): m/z (%) = 262 (18) [M+], 234 (4), 217 (19),
Yield: 317 mg (94%); yellow solid; mp 168–170 °C.
189 (100), 175 (5), 145 (6), 133 (4), 116 (7).
IR (KBr): 3399, 3108, 2983 (w), 1705 (s), 1637 (m), 1579, 1515,
1444, 1392 (w), 1366, 1320 (m), 1268, 1255, 1234, 1221 (w), 1180
(s), 1116, 1081 (w), 1037, 969, 958 (s), 893, 874, 863, 810 (w), 763,
746, 722, 656 (m), 607, 585 (w) cm–1.
HRMS (EI, 70 eV): m/z calcd for C14H14O5: 262.08458; found:
262.08413.
Diisobutyl Benzofuran-5,6-dicarboxylate (4c)
Yield: 146 mg (92%); light yellow oil.
1H NMR (300 MHz, CDCl3): d = 1.25–1.35 (m, 9 H, 3 CH3), 4.17–
4.25 (m, 4 H, 2 CH2O), 4.32 (q, J = 7.3 Hz, 2 H, CH2O), 6.23 (d,
J = 15.7 Hz, 1 H, CH), 6.60 (d, J = 15.7 Hz, 1 H, CH), 7.27 (s, 1 H,
ArH), 7.54 (d, J = 8.1 Hz, 1 H, CH), 7.59 (d, J = 8.1 Hz, 1 H, CH).
IR (KBr): 3434 (w), 2959, 2874 (m), 1769 (w), 1716 (s), 1614,
1585, 1529 (w), 1468, 1377 (m), 1305, 1218 (s), 1125 (m), 1103,
1035, 938 (s), 893, 773 (m), 691, 632 (w) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.92 (d, J = 6.7 Hz, 6 H, 2 CH3),
0.93 (d, J = 6.8 Hz, 6 H, 2 CH3), 1.96–2.01 (m, 2 H, 2 CH), 4.02 (d,
Synthesis 2011, No. 14, 2208–2214 © Thieme Stuttgart · New York

SPECIAL TOPIC
Synthesis of Functionalized Benzofurans from 2,3-Dibromofurans
2213
J = 6.7 Hz, 2 H, CH2O), 4.03 (d, J = 6.7 Hz, 2 H, CH2O), 6.76 (d,
J = 2.2 Hz, 1 H, ArH), 7.71 (d, J = 2.1 Hz, 1 H, ArH), 7.81 (s, 1 H,
ArH), 7.91 (s, 1 H, ArH).
13C NMR (75.5 MHz, CDCl3): d = 19.1 (4 CH3), 27.5 (2 CH), 71.8,
71.9 (CH2O), 107.0, 112.6, 122.6 (CH), 127.9, 128.8, 129.5 (C),
148.2 (CH), 155.2 (C), 167.6, 168.0 (CO).
GC-MS (EI, 70 eV): m/z (%) = 446 (20) [M+], 401 (20), 363 (20),
345 (10), 278 (14), 261 (100), 233 (12).
HRMS (EI, 70 eV): m/z calcd for C25H34O7: 446.22990; found:
446.22914.
2-Ethyl 5,6-Bis(6-methylheptyl) Benzofuran-2,5,6-tricarboxy-
late (7d)
Yield: 221 mg (88%); light yellow oil.
GC-MS (EI, 70 eV): m/z (%) = 318 (1) [M+], 263 (3), 189 (100),
162 (9), 144 (4), 133 (2), 116 (6).
IR (KBr): 3109, 2958, 2874 (w), 1709 (s), 1633, 1578, 1515, 1469
(m), 1394 (w), 1368 (m), 1343 (w), 1318 (s), 1300, 1270 (w), 1255
(m), 1239 (w), 1220 (m), 1171 (s), 1114 (m), 1080 (w), 1008, 962
(s), 875, 861, 837 (w), 765, 748, 720, 693, 657 (m), 609, 595, 542
(w) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.74–0.89 (m, 12 H, 4 CH3), 0.90–
0.91 (m, 2 H, 2 CH), 1.11–1.23 (m, 8 H, 4 CH2), 1.33 (t, J = 7.3 Hz,
3 H, CH3), 1.37–1.41 (m, 8 H, 4 CH2), 4.12–4.24 (m, 4 H, 2 CH2O),
4.34 (q, J = 7.1 Hz, 2 H, CH2O), 7.49 (s, 1 H, ArH), 7.85 (s, 1 H,
ArH), 8.00 (s, 1 H, ArH).
13C NMR (75.5 MHz, CDCl3): d = 14.4 (CH3), 19.8 (4 CH3), 23.5,
25.8, 28.7, 31.6 (2 CH2), 27.3 (2 CH), 61.7, 65.2, 65.5 (CH2O),
113.6, 113.7, 124.5 (CH), 128.7, 128.9, 131.7, 148.4, 155.8 (C),
158.6, 166.3, 166.5 (CO).
HRMS (ESI+): m/z calcd for C18H22O5: 318.14674; found:
318.14664.
Dibutyl Benzofuran-5,6-dicarboxylate (4d)
Yield: 151 mg (95%); light yellow, highly viscous oil.
IR (KBr): 3144, 3117 (w), 2959, 2921, 2852 (m), 1711 (s), 1631,
1462, 1446, 1377, 1292 (w), 1275, 1255, 1223, 1169 (m), 1036,
969, 862, 794, 721, 539 (w) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.86 (t, J = 7.3 Hz, 6 H, 2 CH3),
1.30–1.43 (m, 4 H, 2 CH2), 1.60–1.69 (m, 4 H, 2 CH2), 4.24 (t,
J = 6.7 Hz, 2 H, CH2O), 4.25 (t, J = 6.7 Hz, 2 H, CH2O), 6.74 (d,
J = 2.2 Hz, 1 H, ArH), 6.67 (d, J = 2.2 Hz, 1 H, ArH), 7.78 (s, 1 H,
ArH), 7.88 (s, 1 H, ArH).
13C NMR (75.5 MHz, CDCl3): d = 13.7 (2 CH3), 19.2 (2 CH2), 30.6
(2 CH2), 65.5, 65.6 (CH2O), 107.0, 112.5, 122.5 (CH), 127.8, 128.7,
129.4 (C), 148.1 (CH), 155.1 (C), 167.5, 168.0 (CO).
GC-MS (EI, 70 eV): m/z (%) = 502 (20) [M+], 457 (30), 391 (28),
279 (21), 261 (100), 233 (15).
HRMS (EI, 70 eV): m/z calcd for C29H42O7: 502.29251; found:
502.29179.
GC-MS (EI, 70 eV): m/z (%) = 318 (5) [M+], 245 (5), 189 (100),
116 (10).
HRMS (ESI+): m/z calcd for C18H22O5: 318.14623; found:
318.14626.
5,6-Dibutyl 2-Ethyl Benzofuran-2,5,6-tricarboxylate (7e)
Yield: 176 mg (90%); highly viscous, yellow oil.
IR (KBr): 2873 (w), 1719 (s), 1621 (w), 1583 (m), 1563, 1508, 1488
(w), 1462 (m), 1369, 1344 (w), 1302 (s), 1257, 1242 (w), 1193,
1156, 1100 (s), 1060, 1037, 1015, 961 (w), 941 (m), 901, 840 (w),
765, 740, 691 (m), 643, 603, 579 (w) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.89 (t, J = 7.3 Hz, 6 H, 2 CH3),
1.32 (t, J = 7.2 Hz, 3 H, CH3), 1.35–1.45 (m, 4 H, 2 CH2), 1.62–1.71
(m, 4 H, 2 CH2), 4.12–4.18 (m, 4 H, 2 CH2O), 4.40 (q, J = 7.2 Hz,
2 H, CH2O), 7.49 (s, 1 H, ArH), 7.86 (s, 1 H, ArH), 8.00 (s, 1 H,
ArH).
13C NMR (75.5 MHz, CDCl3): d = 13.7 (2 CH3), 14.3 (CH3), 19.2
(2 CH2), 30.5, 30.6 (CH2), 62.0, 65.8, 65.9 (CH2O), 113.4, 113.5,
124.3 (CH), 128.5, 128.7, 131.9, 148.7, 155.7 (C), 158.8, 167.1,
167.3 (CO).
2-Ethyl 5,6-Diisobutyl Benzofuran-2,5,6-tricarboxylate (7a)
Yield: 185 mg (95%); light yellow oil.
IR (KBr): 2874 (w), 1719 (s), 1621 (w), 1583, 1467 (m), 1442, 1394
(w), 1369, 1345 (m), 1309 (s), 1259 (m), 1194, 1155, 1100 (s),
1038, 982, 943 (m), 901, 846 (w), 765, 740, 690 (m) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.92 (d, J = 6.5 Hz, 12 H, 4 CH3),
1.37 (t, J = 7.1 Hz, 3 H, CH3), 1.96–2.01 (m, 2 H, 2 CH), 4.03 (d,
J = 3.4 Hz, 2 H, CH2O), 4.05 (d, J = 3.3 Hz, 2 H, CH2O), 4.40 (q,
J = 7.1 Hz, 2 H, CH2O), 7.49 (s, 1 H, ArH), 7.87 (s, 1 H, ArH), 8.01
(s, 1 H, ArH).
13C NMR (75.5 MHz, CDCl3): d = 14.3 (CH3), 19.1, 19.2 (4 CH3),
27.7 (2 CH), 62.0, 72.0, 72.1 (CH2O), 113.4, 113.5, 124.3 (CH),
128.6, 128.8, 131.9, 148.7, 155.7 (C), 158.8, 167.1, 167.1 (CO).
GC-MS (EI, 70 eV): m/z (%) = 390 (5) [M+], 345 (20), 278 (30),
261 (100), 233 (16).
GC-MS (EI, 70 eV): m/z (%) = 390 (43) [M+], 345 (30), 335 (11),
317 (40), 278 (18), 261 (100), 233 (17).
HRMS (EI, 70 eV): m/z calcd for C21H26O7: 390.16730; found:
390.16658.
HRMS (EI, 70 eV): m/z calcd for C21H26O7: 390.16730; found:
390.16659.
2-Ethyl 5,6-Dimethyl Benzofuran-2,5,6-tricarboxylate (7f)
Yield: 142 mg (93%); light yellow oil.
2-Ethyl 5,6-Dihexyl Benzofuran-2,5,6-tricarboxylate (7b)
Yield: 216 mg (97%); light yellow oil.
IR (KBr): 2951, 2925, 2853 (w), 1721 (s), 1620, 1578 (w), 1564
(m), 1535, 1488, 1475, 1465 (w), 1431, 1372, 1347 (m), 1310 (s),
1265, 1242 (m), 1207, 1156, 1100 (s), 1043, 1019, 966 (m), 934,
919, 876 (w), 854, 825, 785 (m), 765 (s), 742, 690, 667, 641, 568
(m) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.37 (t, J = 7.1 Hz, 3 H, CH3),
3.86 (s, 3 H, CH3O), 3.88 (s, 3 H, CH3O), 4.40 (q, J = 7.3 Hz, 2 H,
CH2O), 7.49 (s, 1 H, ArH), 7.86 (s, 1 H, ArH), 8.03 (s, 1 H, ArH).
IR (KBr): 2955, 2928, 2857 (w), 1720 (s), 1621, 1582 (w), 1462
(m), 1369, 1344 (w), 1302 (s), 1258 (m), 1193, 1156, 1101 (s), 1017
(m), 944, 900, 836 (w), 765 (m), 740, 690, 574 (w) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.81–0.85 (m, 6 H, 2 CH3), 1.24–
1.28 (m, 12 H, 6 CH2), 1.37 (t, J = 7.2 Hz, 3 H, CH3), 1.63–1.72 (m,
4 H, 2 CH2), 4.22–4.28 (m, 4 H, 2 CH2O), 4.40 (q, J = 7.4 Hz, 2 H,
CH2O), 7.50 (s, 1 H, ArH), 7.86 (s, 1 H, ArH), 8.01 (s, 1 H, ArH).
13C NMR (75.5 MHz, CDCl3): d = 14.0 (2 CH3), 14.3 (CH3), 22.5,
25.6, 28.5, 31.5 (2 CH2), 62.0, 66.1, 66.2 (CH2O), 113.4, 113.5,
124.3 (CH), 128.5, 128.7, 131.9, 148.7, 155.7 (C), 158.8, 167.1,
167.3 (CO).
13C NMR (75.5 MHz, CDCl3): d = 14.3 (CH3), 52.8, 53.0 (CH3O),
62.1 (CH2O), 113.4, 113.5, 124.4 (CH), 128.0, 128.9, 131.5, 148.8,
155.8 (C), 158.8, 167.6, 167.7 (CO).
GC-MS (EI, 70 eV): m/z (%) = 306 (40) [M+], 276 (15), 275 (100),
261 (8), 247 (44), 217 (5).
Synthesis 2011, No. 14, 2208–2214 © Thieme Stuttgart · New York

2214
G. A. Salman et al.
SPECIAL TOPIC
HRMS (EI, 70 eV): m/z calcd for C15H14O7: 306.07340; found:
306.07314.
Lett. 2000, 2, 3521. (g) Schneider, B. Phytochemistry 2003,
64, 459. (h) Katritzky, A. R.; Kirichenkok, K.; Ji, Y.; Steel,
P. J.; Karelson, M. ARKIVOC 2003, (vi), 49.
Triethyl Benzofuran-2,5,6-tricarboxylate (7g)
Yield: 157 mg (94%); highly viscous, orange oil.
(2) (a) Wendt, B.; Ha, H. R.; Hesse, M. Helv. Chim. Acta 2002,
85, 2990. (b) Carlsson, B.; Singh, B. N.; Temciuc, M.;
Nilsson, S.; Li, Y. L.; Mellin, C.; Malm, J. J. Med. Chem.
2002, 45, 623; and references cited therein. (c) Kwiecien,
H.; Baumann, E. J. Heterocycl. Chem. 1997, 34, 1587.
(d) Larock, R. C.; Harrison, L. W. J. Am. Chem. Soc. 1984,
106, 4218. (e) Mátyus, P.; Varga, I.; Rettegi, T.; Simay, A.;
Kállay, N.; Károlyházy, L.; Kocsis, A.; Varró, A.; Pénzes, I.;
Papp, J. G. Curr. Med. Chem. 2004, 11, 61. (f) Wong, H. N.
C.; Yu, P.; Yick, C.-Y. Pure Appl. Chem. 1999, 71, 1041.
(3) For longicaudatin, see: (a) Joshi, A. S.; Li, X.-C.; Nimrod,
A. C.; ElSohly, H. N.; Walker, L. A.; Clark, A. M. Planta
Med. 2001, 67, 186. For related natural products, see:
(b) Sigstad, E.; Catalan, C. A. N.; Diaz, J. G.; Herz, W.
Phytochemistry 1993, 33, 165. (c) Drewes, S. E.; Hudson,
N. A.; Bates, R. B. J. Chem. Soc., Perkin Trans. 1 1987,
2809.
IR (KBr): 3055, 2981, 2929 (w), 1714 (s), 1622 (w), 1581, 1564
(m), 1536, 1504 (w), 1488, 1474, 1445, 1396 (m), 1368 (s), 1345
(w), 1305, 1238, 1198, 1156, 1102 (s), 1043, 1020, 906, 868, 837,
785 (m), 765 (s), 740, 691, 671, 643, 562 (w) cm–1.
1H NMR (250 MHz, CDCl3): d = 1.29–1.40 (m, 9 H, 3 CH3), 4.18–
4.45 (m, 6 H, 3 CH2O), 7.49 (s, 1 H, ArH), 7.86 (s, 1 H, ArH), 8.03
(s, 1 H, ArH).
13C NMR (62.9 MHz, CDCl3): d = 14.0, 14.1, 14.3 (CH3), 61.8,
61.9, 62.0 (CH2O), 113.3, 113.4, 124.3 (CH), 128.4, 128.7, 131.8,
148.7, 155.7 (C), 158.8, 167.1, 167.2 (CO).
GC-MS (EI, 70 eV): m/z (%) = 334 (25) [M+], 306 (4), 289 (26),
261 (100), 247 (7), 233 (32), 217 (6).
HRMS (EI, 70 eV): m/z calcd for C17H18O7: 334.10470; found:
334.10407.
(4) For sessiliflorol A, see: (a) Chan, J. A.; Shultis, E. A.; Carr,
S. A.; DeBrosse, C. W.; Eggleston, D. S. J. Org. Chem.
1989, 54, 2098. For sessiliflorol B, see: (b) Marston, A.;
Zagorski, M. G.; Hostettmann, K. Helv. Chim. Acta 1988,
71, 1210. (c) Drewes, S. E.; Hudson, N. A.; Bates, R. B.;
Linz, G. S. Tetrahedron Lett. 1984, 25, 105. For
Ethyl 5,6-Bis(4-chlorophenyl)benzofuran-2-carboxylate (7h)
Yield: 185 mg (90%); light brown, highly viscous oil.
IR (KBr): 2957, 2922, 2852 (w), 1720 (s), 1657, 1622, 1581, 1566,
1555 (w), 1494, 1455 (m), 1434, 1392 (w), 1368, 1328, 1301, 1285,
1261, 1240, 1228 (m), 1183, 1152, 1089, 1012 (s), 953 (m), 934,
889, 871, 854 (w), 827 (s), 765, 756, 743, 728 (m), 697, 682, 646,
636, 625, 590, 537 (w).
1H NMR (250 MHz, CDCl3): d = 1.37 (t, J = 7.1 Hz, 3 H, CH3),
4.39 (q, J = 7.1 Hz, 2 H, CH2O), 6.96–7.00 (dd, J = 2.3, 8.6 Hz, 4
H, ArH), 7.13–7.17 (dd, J = 2.0, 8.5 Hz, 4 H, ArH), 7.48 (s, 1 H,
ArH), 7.51 (s, 1 H, ArH), 7.59 (s, 1 H, ArH).
13C NMR (62.9 MHz, CDCl3): d = 13.3 (CH3), 60.6 (CH2O), 112.5,
112.7, 123.3 (CH), 125.6 (C), 127.2, 127.3, 130.1, 130.2 (CH),
131.9, 132.2, 135.0, 138.2, 138.3, 138.5, 145.8, 154.2 (C), 158.3
(CO).
flemistrictin E, see: (d) Subrahmanyam, K.; Rao, J. M.;
Vemuri, V. S. S.; Babu, S. S.; Roy, C. P.; Rao, K. V. J.
Indian J. Chem., Sect. B 1982, 21, 895. For tovophenone C,
see: (e) Seo, E.-K.; Wall, M. E.; Wani, M. C.; Navarro, H.;
Mukherjee, R.; Farnsworth, N. R.; Kinghorn, A. D.
Phytochemistry 1999, 52, 669. For vismiaguianone C, see:
(f) Seo, E.-K.; Wani, M. C.; Wall, M. E.; Navarro, H.;
Mukherjee, R.; Farnsworth, N. R.; Kinghorn, A. D.
Phytochemistry 2000, 55, 35. (g) For piperaduncin B, see
ref. 3a and: Bohlmann, F.; Zdero, C. Chem. Ber. 1976, 109,
1436.
(5) For reviews of cross-coupling reactions of polyhalogenated
heterocycles, see: (a) Schröter, S.; Stock, C.; Bach, T.
Tetrahedron 2005, 61, 2245. (b) Schnürch, M.; Flasik, R.;
Khan, A. F.; Spina, M.; Mihovilovic, M. D.; Stanetty, P. Eur.
J. Org. Chem. 2006, 3283.
(6) (a) Dang, T. T.; Ahmad, R.; Dang, T. T.; Reinke, H.; Langer,
P. Tetrahedron Lett. 2008, 49, 1698. (b) Dang, T. T.;
Villinger, A.; Langer, P. Adv. Synth. Catal. 2008, 350, 2109.
(c) Dang, T. T.; Dang, T. T.; Rasool, N.; Villinger, A.;
Langer, P. Adv. Synth. Catal. 2009, 351, 1595.
(7) (a) Bach, T.; Krüger, L. Tetrahedron Lett. 1998, 39, 1729.
(b) Bach, T.; Krüger, L. Eur. J. Org. Chem. 1999, 2045.
(c) Bach, T.; Krüger, L. Synlett 1998, 1185.
(8) de Meijere and co-workers reported twofold Heck reactions
of 1,2-dibromocycloalk-1-enes and related substrates and
subsequent 6p-electrocyclization; see: Voigt, K.;
von Zezschwitz, P.; Rosauer, K.; Lansky, A.; Adams, A.;
Reiser, O.; de Meijere, A. Eur. J. Org. Chem. 1998, 1521;
and references cited therein.
GC-MS (EI, 70 eV): m/z (%) = 412 (68), 411 (26), 410 (100) [M+],
382 (5), 367 (4), 365 (5), 347 (4), 312 (14), 302 (10).
HRMS (ESI+): m/z calcd for C23H16O3Cl2: 410.04710; found:
410.04713.
Acknowledgment
Financial support by the DAAD (scholarships for A.A., G.A.S. and
R.A.K.), by the State of Pakistan (HEC scholarships for M.H. and
R.A.K.) and by the State of Mecklenburg-Vorpommern (scholar-
ship for M.H.) is gratefully acknowledged.
References
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Biomol. Chem. 2003, 1, 254. (b) Xie, X.; Chen, B.; Lu, J.;
Han, J.; She, X.; Pan, X. Tetrahedron Lett. 2004, 45, 6235.
(c) Zhang, H.; Ferreira, E. M.; Stoltz, B. M. Angew. Chem.
Int. Ed. 2004, 43, 6144. (d) Hagiwara, H.; Sato, K.; Nishino,
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Gutnow, A. V.; Abaev, V. T.; Krapivin, G. D. Molecules
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(10) Billingsley, K.; Buchwald, S. L. J. Am. Chem. Soc. 2007,
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Synthesis 2011, No. 14, 2208–2214 © Thieme Stuttgart · New York