Pd-catalyzed tandem chemoselective synthesis of 2-arylbenzofurans using threefold arylating triarylbismuth reagents

Article abstract of DOI:10.1002/ejoc.201201314

A tandem chemoselective synthesis of 2-arylbenzofurans was accomplished from o-hydroxy-gem-(dibromovinyl)benzenes and BiAr₃ reagents under palladium-catalyzed conditions. This unique and synthetically valuable strategy proceeds through three consecutive coupling reactions involving triarylbismuth reagents and provides 2-arylbenzofuran products in high yields. A tandem chemoselective synthesis of 2-arylbenzofurans was accomplished from o-hydroxy-gem-(dibromovinyl)benzenes and BiAr₃ reagents under palladium-catalyzed conditions. This unique and synthetically valuable strategy proceeds through three consecutive coupling reactions involving triarylbismuth reagents and provides 2-arylbenzofuran products in high yields. Copyright

Full text of DOI:10.1002/ejoc.201201314

FULL PAPER
DOI: 10.1002/ejoc.201201314
Pd-Catalyzed Tandem Chemoselective Synthesis of 2-Arylbenzofurans using
Threefold Arylating Triarylbismuth Reagents
Maddali L. N. Rao,*[a] Deepak N. Jadhav,[a] and Priyabrata Dasgupta[a]
Keywords: Fused-ring systems / Domino reactions / Chemoselectivity / Palladium / Bismuth
A tandem chemoselective synthesis of 2-arylbenzofurans
ceeds through three consecutive coupling reactions involv-
was accomplished from o-hydroxy-gem-(dibromovinyl)benz- ing triarylbismuth reagents and provides 2-arylbenzofuran
enes and BiAr3 reagents under palladium-catalyzed condi-
tions. This unique and synthetically valuable strategy pro-
products in high yields.
gents in excess amounts, which results in the formation of
one equivalent of the 2-arylbenzofuran product.
Introduction
However, the usefulness of triarylbismuth reagents as
facile threefold arylating agents in coupling reactions[10]
prompted us to address these issues and to enrich the pro-
cess with additional chemoselective options under palla-
dium conditions. The development of tandem annulations
by using o-hydroxy-gem-(dibromovinyl)benzenes with triar-
ylbismuths were planned as depicted in Scheme 1. This pro-
cess was expected to deliver three equivalents of the 2-aryl-
benzofuran for every one equivalent of the triarylbismuth
reagent employed and was believed to serve as a more ad-
vantageous process (vide supra). Herein, we describe these
efforts under palladium-catalyzed conditions.
The benzofuran scaffold is present in many medicinally
important compounds that show biological activity, includ-
ing anticancer and anti-inflammatory activities.[1] These
scaffolds are widely present in many natural products.[2] Re-
cently, benzofuran derivatives labeled with 18F and 99mTc
tags were studied by positron emission tomography (PET)
and single photon emission computed tomography
(SPECT) imaging, respectively, for β-amyloid plaques in
Alzheimer’s disease.[3] Extended molecular frameworks of
benzofurans are useful as bowl-shaped hosts in supramolec-
ular chemistry.[4]
Tandem or domino couplings are highly sought after ap-
proaches for the construction of molecular skeletons in a
facile manner.[5] Recently, Chelucci excellently reviewed the
chemistry of 1,1-dihaloalkenes as novel molecular synthons
in synthetic organic chemistry.[6] Metal-catalyzed reactions
involving 1,1-dihaloalkenes provide well-defined core skel-
etons dictated by the choice of the substrates.[7,8] However,
other metal-mediated approaches are also available for the
synthesis benzofurans.[9] In particular, o-hydroxy-gem-(di-
bromovinyl)benzenes are of special interest, as they deliver
substituted benzofurans in combination with organometal-
lic reagents through intramolecular couplings. However,
this known approach involving the use of palladium also
employs boron and tin reagents in excess amounts.[8] An-
other serious drawback encountered in this reaction is the
competitive formation of undesired bis-benzofurans. This
can partly be circumvented by using organometallic rea-
Scheme 1. Tandem synthesis by using BiAr3 reagents.
Results and Discussion
To realize this tandem process, a systematic investigation
was carried out (Table 1). For the coupling reaction, o-hy-
droxy-gem-(dibromovinyl)benzene (1) was treated with
BiPh3 in the presence of [Pd(PPh3)4] with different bases in
DMF under heating conditions (Table 1, entries 1 and 2).
These reactions furnished tandem coupled 2-phenylbenzo-
furan (1a) in 54 and 66% yield with K3PO4 and Cs2CO3 as
the base, respectively. Further investigation was carried out
in different solvents to check their efficacy. For example,
reactions in N,N-dimethylacetamide (DMA), N-methyl-2-
pyrrolidone (NMP), and tetrahydrofuran (THF) provided
the products in poor to moderate yields (Table 1, entries 3–
5). So far, DMF with Cs2CO3 provided the desired tandem
[a] Department of Chemistry, Indian Institute of Technology
Kanpur,
Kanpur 208016, India
Fax: +91-512-259-7532
E-mail: maddali@iitk.ac.in
Homepage: http://www.iitk.ac.in
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201314.
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M. L. N. Rao, D. N. Jadhav, P. Dasgupta
FULL PAPER
couplings in better yield. Additional screening was per-
To understand this tandem process, further investigation
formed in DMF with different bases including K2CO3, was carried out with control experiments (Table 2). For ex-
KOAc, and NaOAc (Table 1, entries 6–8), but these bases ample, a reaction without the catalyst provided 2-bromo-
were found to be less effective.
benzofuran (1p) in 80% yield (Table 2, entry 1). Couplings
without base afforded a mixture of 1a, 1p, and 1q in minor
amounts (Table 2, entry 2). Additional control without a
palladium catalyst or BiPh3 also provided 1p as the major
product (Table 2, entry 3). In the presence of a palladium
catalyst but without BiPh3, 1p and homocoupled 1r were
formed (Table 2, entry 4). This study clearly demonstrated
the formation of 2-bromobenzofuran as a reaction interme-
diate during the course of the tandem reaction.
Table 1. Screening conditions.[a]
Entry
Catalyst
Base
Solvent
Time
[h]
Yield[b]
[%]
Table 2. Control experiments.[a]
1
2
3
4
5
6
7
8
[Pd(PPh3)4]
[Pd(PPh3)4]
[Pd(PPh3)4]
[Pd(PPh3)4]
[Pd(PPh3)4]
[Pd(PPh3)4]
[Pd(PPh3)4]
[Pd(PPh3)4]
K3PO4
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
KOAc
DMF
DMF
DMA
NMP
THF
2
2
2
2
2
2
2
2
4
4
4
4
2
4
4
4
4
2
54
66
54
56
Ͻ1[c]
52
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
32[c]
21[c]
42
NaOAc
9
[PdCl2(PPh3)2] Cs2CO3
10
11
12
13
14
15
16
17
18
[Pd(OAc)2]
[Pd2(dba)3]
[Pd(PPh3)4]
[Pd(PPh3)4]
[Pd(PPh3)4]
[Pd(PPh3)4]
[Pd(PPh3)4]
[Pd(PPh3)4]
[Pd(PPh3)4]
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
38[d]
37[d]
72
Entry BiPh3 [Pd] Base
1
1a
1p
1q
1r
58[e]
75[f]
53[g]
64[h]
56[i]
46[j]
100
(80)
12
100
63
1
+
–
+
–
–
–
–
2
3
4
+
–
–
+
–
+
–
+
+
20
–
–
23
–
–
41
–
–
–
–
8
[a] Conditions: 1 (0.825 mmol, 3.3 equiv.), BiAr3 (0.25 mmol,
1 equiv.), [Pd(PPh3)4] (0.0225 mmol, 0.09 equiv.), Cs2CO3
(1.5 mmol, 6 equiv.), DMF (3 mL), 90 °C, 4 h. GC conversions are
given, and isolated yields are given in parentheses.
[a] Conditions:
1
(0.75 mmol, 3 equiv.), BiPh3 (0.25 mmol,
1 equiv.), Pd catalyst (0.0225 mmol, 0.09 equiv.), base (1.5 mmol,
6 equiv.), solvent (3 mL), 90 °C. [b] Isolated yield. [c] Conversion
based on GC. [d] With 0.18 equiv. of PPh3. [e] With 0.50 mmol of
BiPh3. [f] With 3.3 equiv. of 1. [g] At 60 °C. [h] At 80 °C. [i] At
100 °C. [j] With 3 equiv. of Cs2CO3.
Next, we sought to apply the established protocol condi-
tion (Table 1, entry 14) in the synthesis of various function-
Different catalyst precursors also produced poor yields alized 2-arylbenzofurans (Table 3). Firstly, the reactivity of
(Table 1, entries 9–11). Encouragingly, the reaction with various electronically divergent BiAr3 reagents with dif-
Cs2CO3 as the base in DMF furnished the product in 4 h in ferent dibromides was tested. BiAr3 reagents substituted
72% yield (Table 1, entry 12). Further couplings with excess with p-methyl, p-methoxy, p-ethoxy, p-isopropoxy, p-fluoro,
amounts of BiPh3 did not improve the yield (Table 1, en- and m-methoxy groups furnished high yields of the corre-
try 13). However, coupling with 3.3 equiv. of 1 furnished the sponding 2-arylbenzofurans (Table 3, entries 2–5, 7, 8). The
product in 4 h in 75% yield (Table 1, entry 14). The tandem coupling reactions of 4-chloro-substituted triarylbismuth
process was then evaluated at different temperatures, but and tris-2-thienylbismuth provided moderate yields
only moderate yields of the product were obtained (Table 1, (Table 3, entries 6 and 9). Additionally, various function-
entries 15–17). An attempt with 3 equiv. of Cs2CO3 fur- alized o-hydroxy-gem-(dibromovinyl)benzenes provided
nished the product in lower yield (Table 1, entry 18). In all moderate to high yields of the functionalized 2-arylbenzo-
of these screenings, a minor amount of homocoupled bi- furan products (Table 3, entries 10–15). In these couplings,
phenyl from BiPh3 was formed, and this is inevitable under the presence of acetyl and benzoyl groups in the para posi-
palladium catalysis.[11] However, the amount of homocou- tion to the hydroxy functionality did not affect the process,
pled product formed can be minimized with high cross-cou- and the corresponding products were isolated in high yields
pling conversion. In some cases, the formation of trace (Table 3, entries 13–15). This investigation overall revealed
amounts of homocoupled bis-benzofuran was observed. the high reactivity of BiAr3 as multicoupling organometal-
From this screening, the tandem coupling reaction was es- lic nucleophiles that can act as threefold arylating reagents
tablished to be effective with [Pd(PPh3)4] as the catalyst in with a variety of functionalized o-hydroxy-gem-(dibromovin-
DMF with Cs2CO3 as the base to furnish 1a in 75% yield yl)benzenes. Moreover, the one-pot operation comprising
(Table 1, entry 14). This protocol successfully delivered the three aryl couplings was complete in a reaction time of 4 h.
desired tandem coupling product against the odds of com- This demonstrates the novel reactivity of BiAr3 reagents,
petitive homocoupling in the presence of a palladium cata- which furnished high yields of 2-arylbenzofurans, in com-
lyst.[8]
parison to the corresponding reactivity reported with the
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Pd-Catalyzed Tandem Chemoselective Synthesis of 2-Arylbenzofurans
use of excess amounts of aryl boron or tin reagents, even Table 4. Chemoselective tandem couplings.[a]
for only one C–C coupling.[8]
Table 3. Tandem synthesis of 2-arylbenzofurans.[a]
[a] Conditions: gem-Dibromide (0.825 mmol, 3.3 equiv.), BiAr3
(0.25 mmol, 1 equiv.), [Pd(PPh3)4] (0.0225 mmol, 0.09 equiv.),
Cs2CO3 (1.5 mmol, 6.0 equiv.), DMF (3 mL), 90 °C, 4 h. Biaryls
from BiAr3 were formed in minor amounts. [b] Isolated yield, and
0.75 mmol of product corresponds to 100% yield.
[a] Conditions: gem-Dibromide (0.825 mmol, 3.3 equiv.), BiAr3
The tandem process was further studied in terms of a
chemoselective synthesis, as this was not realized so far in
these couplings.[8] The site-selective and/or chemoselective
study is important from the viewpoint that these reactions
(0.25 mmol, 1 equiv.), [Pd(PPh3)4] (0.0225 mmol, 0.09 equiv.),
Cs2CO3 (1.5 mmol, 6 equiv.), DMF (3 mL), 90 °C, 4 h. Biaryls
from BiAr3 were formed in minor amounts. [b] Isolated yield, and
0.75 mmol of product corresponds to 100% yield.
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783

M. L. N. Rao, D. N. Jadhav, P. Dasgupta
FULL PAPER
furnish molecular skeletons with reactive functionality[12] metal conditions,[18b,18c] McMurry couplings,[9b] cross-cou-
useful for further structural elaboration. This study was car- plings of (E)-1,2-dichlorovinyl ethers with arylboronic ac-
ried out with halogen-substituted dibromides. Under the es- ids,[18d] and intramolecular cyclization of o-alkynylphenols
tablished conditions, 5-bromo- and 5-chloro-substituted o- or their derivatives under metal catalysis.[19] Synthesis of 2-
hydroxy-gem-(dibromovinyl)benzenes reacted in a chemose- arylbenzofurans can also be accomplished through cross-
lective manner with the bismuth reagents to furnish the cor- coupling reactions of preformed 2-halobenzofurans with
responding 5-bromo- and 5-chloro-functionalized 2-aryl- organometallic reagents.[20] Although useful, this approach
benzofurans in excellent yields (Table 4, entries 1–14).
requires the additional synthesis of 2-bromobenzofuran
The coupling reactions of 3,5-dichloro-substituted o-hy- through a metal-catalyzed or tetrabutylammonium fluoride
droxy-gem-(dibromovinyl)benzenes also gave 5,7-dichloro- (TBAF)-mediated protocol,[13] and these couplings, in some
substituted 2-arylbenzofurans in high yields (Table 4, en- cases, require high temperatures or reflux conditions and
tries 15–18). This is a unique demonstration of site-selective long reaction times. Further, couplings with preformed 2-
and chemoselective tandem couplings in the synthesis of benzofuranyl organometallic reagents, although suffering
functionalized 2-arylbenzofurans.[8] Given the high reactiv- from stability related issues, can couple with aryl halides
ity of aryl halides to give cross-coupled biaryls, the present under palladium catalysis to give 2-arylbenzofurans.[21]
method is a notable chemoselective tandem coupling pro- From these counts, the present tandem process avoids the
cess involving polyhalogenated systems.[12] Thus, a series of preformation of both 2-halobenzofuran and 2-benzofuranyl
diverse o-hydroxy-gem-(dibromovinyl)benzenes furnished organometallic reagents as coupling partners, which simpli-
facile tandem couplings and an array of functionalized 2- fies the overall synthetic process. The tandem process de-
arylbenzofurans in a one-pot operation.
scribed here is highly advantageous and utilizes in situ gen-
On the basis of the screening and control studies that erated 2-bromobenzoufran and involves three consecutive
were carried out (Tables 1 and 2), a plausible mechanism is arylations by using triarylbismuth reagents. It is of note that
depicted in Scheme 2. The base-mediated cyclization of o- the 2-arylbenzofuran skeleton is ubiquitous in natural prod-
hydroxy-gem-(dibromovinyl)benzene generates 2-bromo- ucts such as moracin M., ailanthoidol, cicerfuran, and so
benzofuran A,[13a] and this species would be involved in the forth.[22] Given the importance of this core skeleton, the
cross-coupling with the bismuth reagent to deliver 2-aryl- present tandem strategy involving triarylbismuths as three-
benzofuran B under palladium-catalyzed conditions.[14]
fold arylating reagents would pave the way for the easy syn-
thesis of various benzofuran analogs in a facile manner.
Conclusions
In summary, we have demonstrated a new, one-pot,
chemoselective, tandem synthesis of functionalized 2-aryl-
benzofurans by using BiAr3 as threefold arylating agents.
This unique and synthetically valuable strategy proceeds
through three consecutive coupling reactions involving tri-
arylbismuth reagents and provides 2-arylbenzofuran prod-
ucts in high yields. This process obviates the use of pre-
formed halobenzofurans or excess amounts of organome-
tallic reagents in the synthesis of 2-arylbenzofurans. The
chemoselective coupling of polyhalogenated systems at the
gem-dibromide terminus is an additional highlight in the
synthesis of halogenated 2-arylbenzofurans under palla-
dium-catalyzed conditions. These products are highly useful
for further core expansion under metal-catalyzed condi-
tions.
Scheme 2. Proposed mechanism.
Exclusive formation of 2-bromobenzofuran without a
metal catalyst is noteworthy.[13a] Formation of 2-bromo-
benzofuran and bis-benzofurans (in minor amounts) in
control reactions is in favor of the proposed catalytic cy-
cle.[8,13a] The possible involvement of in situ formed arylbis-
muth species in subsequent catalytic cycles successfully pro-
vides three aryl couplings from BiAr3 in a one-pot opera-
tion.
Experimental Section
Palladium-catalyzed coupling reactions are well estab-
lished in the synthesis of heterocycles by cyclization and
oxidative addition processes.[15] There are many approaches
reported for the synthesis of benzofuran derivatives[16] in
general and for 2-substituted benzofurans in particular.[17]
Some of the methods known for the synthesis of 2-aryl-
benzofuran include [3,3] sigmatropic rearrangement of oxime
General: All coupling reactions were carried out under a N2 atmo-
sphere. Starting triarylbismuths[23] and 1,1-dibromides[24] were pre-
pared by literature methods. GC analysis of the reaction mixtures
was done with a Clarus 500 (Perkin–Elmer). NMR spectra were
recorded with a JEOL (500 MHz) spectrometer, and HRMS mea-
surements were recorded with a Waters HAB213 system.
Representative Cross-Coupling Procedure: A 50-mL, hot-oven-dried
ethers,[18a] intramolecular o-arylation of enolates under Schlenk tube was charged with Ph3Bi (0.25 mmol, 110 mg,
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Pd-Catalyzed Tandem Chemoselective Synthesis of 2-Arylbenzofurans
1 equiv.), o-hydroxy-gem-(dibromovinyl)benzene (0.825 mmol,
229 mg, 3.3 equiv.), Cs2CO3 (1.5 mmol, 489 mg, 6 equiv.), Pd-
ppm. 13C NMR (125 MHz, CDCl3): δ = 154.8, 154.7, 134.2, 129.0,
126.1, 124.5, 123.0, 120.9, 111.1, 101.7 ppm. IR (KBr): ν = 3057,
˜
(PPh3)4 (0.0225 mmol, 26 mg, 0.09 equiv.), and DMF (3 mL) under 2924, 1601, 1485, 1448, 1403, 1255, 1168, 1093, 1030, 1009, 918,
a N2 atmosphere. The mixture was stirred in a preheated oil bath
at 90 °C for 4 h. The contents were quenched with dilute HCl after
cooling to room temperature and extracted with ethyl acetate. After
usual workup, the crude product was purified by silica gel column
chromatography (petroleum ether/ethyl acetate). Pure product 1a
and other products obtained by following this procedure were ana-
lyzed by evaluation of their spectroscopic data.
883, 835, 804, 746 cm–1. HRMS (EI): calcd. for C14H9ClO [M]+
228.0342; found 228.0343.
2-(4-Fluorophenyl)benzofuran (1g):[14] White solid (124 mg, 78%);
1
m.p. 115–117 °C. H NMR (500 MHz, CDCl3): δ = 7.80–7.85 (m,
2 H, CHAr), 7.56–7.58 (m, 1 H, CHAr), 7.50–7.51 (m, 1 H, CHAr),
7.11–7.29 (m, 4 H, CHAr), 6.95 (s, 1 H, CHAr) ppm. 13C NMR
(125 MHz, CDCl3): δ = 162.8 (d, J = 246.8 Hz), 154.9, 154.8, 129.1,
126.7 (d, J = 8.33 Hz), 124.2, 123.0, 120.8, 115.8 (d, J = 21.46 Hz),
2-Phenylbenzofuran (1a):[19d] White solid (109 mg, 75%); m.p. 108–
1
110 °C. H NMR (500 MHz, CDCl3): δ = 7.97 (d, J = 7.65 Hz, 2
111.1, 100.9 ppm. IR (KBr): ν = 3065, 2922, 1601, 1570, 1451,
˜
H, CHAr), 7.31–7.69 (m, 7 H, CHAr), 7.12 (s, 1 H, CHAr) ppm. 13
C
1410, 1350, 1233, 1156, 1098, 1030, 1009, 840, 802, 746 cm–1.
HRMS (EI): calcd. for C14H9FO [M]+ 212.0637; found 212.0637.
NMR (125 MHz, CDCl3): δ = 155.8, 154.8, 130.4, 129.1, 128.7,
128.5, 124.9, 124.2, 122.9, 120.8, 111.1, 101.2 ppm. IR (KBr): ν =
˜
2-(3-Methoxyphenyl)benzofuran (1h):[25] Pale yellow solid (118 mg,
70%); m.p. 50–52 °C. H NMR (500 MHz, CDCl3): δ = 7.58 (d, J
= 7.45 Hz, 1 H, CHAr), 7.52 (d, J = 7.45 Hz, 1 H, CHAr), 7.45 (d,
J = 7.7 Hz, 1 H, CHAr), 7.41 (d, J = 1.7 Hz, 1 H, CHAr), 7.33–7.37
(m, 1 H, CHAr), 7.27–7.30 (m, 1 H, CHAr), 7.21–7.24 (m, 1 H,
CHAr), 7.02 (s, 1 H, CHAr), 6.90 (d, J = 8.0 Hz, 1 H, CHAr), 3.89
3035, 2923, 1608, 1561, 1489, 1453, 1258, 1207, 1169, 1104, 1073,
1037, 1019, 917, 882, 806, 764, 744, 689 cm–1. HRMS (EI): calcd.
for C14H10O [M]+ 194.0732; found 194.0732.
1
2-(4-Methylphenyl)benzofuran (1b):[19d] White solid (126 mg, 81%);
m.p. 116–118 °C. 1H NMR (500 MHz, CDCl3): δ = 7.85 (d, J =
8.0 Hz, 2 H, CHAr), 7.66 (d, J = 7.45 Hz, 1 H, CHAr), 7.61 (d, J = (s, 3 H, -OCH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 159.9,
8.0 Hz, 1 H, CHAr), 7.30–7.38 (m, 4 H, CHAr), 7.06 (s, 1 H, CHAr), 155.7, 154.8, 131.7, 129.8, 129.1, 124.3, 122.9, 120.9, 117.4, 114.4,
2.49 (s, 3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 156.1, 111.1, 110.0, 101.6, 55.3 ppm. IR (KBr): ν = 3064, 2923, 1607,
˜
154.7, 138.5, 129.4, 129.3, 127.7, 124.8, 123.9, 122.8, 120.7, 111.0,
1569, 1487, 1349, 1283, 1258, 1235, 1200, 1164, 1050, 1032, 934,
100.5, 21.3 ppm. IR (KBr): ν = 3029, 2914, 1587, 1502, 1350, 1302,
849, 779, 748, 687 cm–1. HRMS (EI): calcd. for C15H12O2 [M]+
˜
1256, 1205, 1168, 1108, 1032, 1011, 919, 884, 824, 801, 739 cm–1. 224.0837; found 224.0836.
HRMS (EI): calcd. for C15H12O [M]+ 208.0888; found 208.0886.
2-(Thiophen-2-yl)benzofuran (1i):[9b] White solid (77 mg, 51%); m.p.
2-(4-Methoxyphenyl)benzofuran (1c):[21a] White solid (122 mg,
89–92 °C. 1H NMR (500 MHz, CDCl3): δ = 7.47–7.54 (m, 3 H,
72%); m.p. 136–138 °C. 1H NMR (500 MHz, CDCl3): δ = 7.78– CHAr), 7.32–7.33 (m, 1 H, CHAr), 7.19–7.27 (m, 2 H, CHAr), 7.08–
7.80 (m, 2 H, CHAr), 7.48–7.55 (m, 2 H, CHAr), 7.19–7.26 (m, 2 7.10 (m, 1 H, CHAr), 6.86 (s, 1 H, CHAr) ppm. 13C NMR
H, CHAr), 6.97 (d, J = 8.8 Hz, 2 H, CHAr), 6.88 (s, 1 H, CHAr),
3.85 (s, 3 H, -OCH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 159.9,
156.0, 154.6, 129.4, 126.3, 123.7, 123.3, 122.8, 120.5, 114.2,110.9,
(125 MHz, CDCl3): δ = 154.5, 151.2, 133.2, 129.0, 127.8, 125.7,
124.5, 124.2, 123.0, 120.7, 111.0, 101.0 ppm. IR (KBr): ν = 2924,
˜
1585, 1502, 1449, 1419, 1361, 1250, 1224, 1045, 878, 848, 802, 748,
702 cm–1. HRMS (EI): calcd. for C12H8OS [M]+ 200.0296; found
200.0294.
99.6, 55.3 ppm. IR (KBr): ν = 2931, 1609, 1502, 1452, 1248, 1177,
˜
1109, 1039, 1022, 800, 780, 746 cm–1. HRMS (EI): calcd. for
C15H12O2 [M]+ 224.0837; found 224.0839.
7-Methoxy-2-phenylbenzofuran (2a):[9b] White solid (98 mg, 58%);
1
2-(4-Ethoxyphenyl)benzofuran (1d):[14] White solid (130 mg, 73%);
m.p. 78–80 °C. H NMR (500 MHz, CDCl3): δ = 7.89–7.91 (m, 2
1
m.p. 122–123 °C. H NMR (500 MHz, CDCl3): δ = 7.77–7.79 (m,
H, CHAr), 7.43–7.46 (m, 2 H, CHAr), 7.34–7.37 (m, 1 H, CHAr),
2 H, CHAr), 7.54 (d, J = 7.65 Hz, 1 H, CHAr), 7.49 (d, J = 8.05 Hz, 7.14–7.20 (m, 2 H, CHAr), 7.02 (s, 1 H, CHAr), 6.81 (dd, J = 1.15,
1 H, CHAr), 7.19–7.26 (m, 2 H, CHAr), 6.95–6.96 (m, 2 H, CHAr), 7.6 Hz, 1 H, CHAr), 4.06 (s, 3 H, OCH3) ppm. 13C NMR
6.87 (s, 1 H, CHAr), 4.07 (q, J = 6.8 Hz, 2 H, CH2CH3), 1.43 (t, J (125 MHz, CDCl3): δ = 156.0, 145.2, 144.0, 130.8, 130.2, 128.6,
= 6.8 Hz, 3 H, CH2CH3) ppm. 13C NMR (125 MHz, CDCl3): δ =
128.5, 124.9, 123.5, 113.2, 106.6, 101.5, 56.0 ppm. IR (KBr): ν =
˜
159.3, 156.1, 154.6, 129.4, 126.3, 123.6, 123.1, 122.7, 120.5, 114.7,
3032, 2961, 2842, 1620, 1588, 1498, 1450, 1326, 1270, 1176, 1098,
1021, 909, 852, 795, 768, 726, 682 cm–1. HRMS (EI): calcd. for
C15H12O2 [M]+ 224.0837; found 224.0835.
110.9, 99.5, 63.5, 14.7 ppm. IR (KBr): ν = 3059, 2980, 1610, 1503,
˜
1474, 1451, 1252, 1177, 1115, 1046, 919, 837, 796, 747 cm–1. HRMS
(EI): calcd. for C16H14O2 [M]+ 238.0994; found 238.0997.
5-Methyl-2-phenylbenzofuran (3a):[9b] White solid (81 mg, 52%);
m.p. 112–115 °C. 1H NMR (500 MHz, CDCl3): δ = 7.86 (d, J =
7.3 Hz, 2 H, CHAr), 7.33–7.46 (m, 5 H, CHAr), 7.07–7.11 (m, 1 H,
2-(4-Isopropoxyphenyl)benzofuran (1e): White solid (156 mg, 82%);
m.p. 128–130 °C. 1H NMR (500 MHz, CDCl3): δ = 7.77 (d, J =
8.8 Hz, 2 H, CHAr), 7.54 (d, J = 7.65 Hz, 1 H, CHAr), 7.49 (d, J = CHAr), 6.96 (s, 1 H, CHAr), 2.45 (s, 1 H, CH3) ppm. 13C NMR
8.05 Hz, 1 H, CHAr), 7.19–7.26 (m, 2 H, CHAr), 6.95 (d, J = 8.8 Hz, (125 MHz, CDCl3): δ = 155.9, 153.2, 132.3, 130.5, 129.2, 128.7,
2 H, CHAr), 6.87 (s, 1 H, CHAr), 4.57–4.64 [m, 1 H, CH(CH3)2],
128.3, 125.5, 124.8, 120.6, 110.6, 101.0, 21.3 ppm. IR (KBr): ν =
˜
1.36 [d, J = 6.1 Hz, 6 H, CH(CH3)2] ppm. 13C NMR (125 MHz, 3058, 2918, 1610, 1465, 1444, 1329, 1265, 1197, 1072, 1039, 1020,
CDCl3): δ = 158.3, 156.1, 154.6, 129.4, 126.4, 123.6, 123.0, 122.7,
913, 803, 760, 741, 687 cm–1. HRMS (EI): calcd. for C15H12O
[M]+ 208.0888; found 208.0887.
120.5, 115.9, 110.9, 99.5, 69.9, 22.0 ppm. IR (KBr): ν = 2923, 1610,
˜
1499, 1449, 1381, 1248, 1174, 1118, 1029, 950, 831, 801, 740 cm–1.
HRMS (EI):calcd. for C17H16O2 [M]+ 252.1150; found 252.1151.
2,5-Diphenylbenzofuran (4a):[9a] White solid (120 mg, 59%); m.p.
148–150 °C. 1H NMR (500 MHz, CDCl3): δ = 7.89 (d, J = 7.65 Hz,
2 H, CHAr), 7.78 (s, 1 H, CHAr), 7.64 (d, J = 7.6 Hz, 2 H, CHAr),
7.58 (d, J = 8.4 Hz, 1 H, CHAr), 7.52 (d, J = 8.4 Hz, 1 H, CHAr),
2-(4-Chlorophenyl)benzofuran (1f):[14] White solid (104 mg, 61%);
m.p. 145–147 °C. 1H NMR (500 MHz, CDCl3): δ = 7.82 (d, J =
8.3 Hz, 2 H, CHAr), 7.61 (d, J = 8.3 Hz, 1 H, CHAr), 7.55 (d, J = 7.47 (t, J = 7.65 Hz, 4 H, CHAr), 7.34–7.39 (m, 2 H, CHAr), 7.07
8.0 Hz, 1 H, CHAr), 7.45 (d, J = 8.6 Hz, 2 H, CHAr), 7.31–7.34 (m, (s, 1 H, CHAr) ppm. 13C NMR (125 MHz, CDCl3): δ = 156.5,
1 H, CHAr), 7.28 (d, J = 7.75 Hz, 1 H, CHAr), 7.04 (s, 1 H, CHAr
)
154.4, 141.6, 136.6, 130.3, 129.7, 128.8, 128.7, 128.6, 127.4, 126.8,
785
Eur. J. Org. Chem. 2013, 781–788
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org

M. L. N. Rao, D. N. Jadhav, P. Dasgupta
FULL PAPER
124.9, 123.9, 119.3, 111.2, 101.4 ppm. IR (KBr): ν = 3057, 2923,
1251, 1176, 1116, 1044, 922, 872, 836, 794 cm–1. HRMS (EI): calcd.
˜
1562, 1490, 1461, 1444, 1278, 1126, 1072, 1018, 905, 881, 806, 756, for C16H13BrO2 [M]+ 316.0099 and [M + 2]+ 318.0078; found
686 cm–1. HRMS (EI): calcd. for C20H14O [M]+ 270.1045; found
270.1046.
316.0096 and 318.0254.
5-Bromo-2-(4-isopropoxyphenyl)benzofuran (7d): White solid
5-Acetyl-2-phenylbenzofuran (5a):[14] White solid (128 mg, 72%);
m.p. 144–145 °C. 1H NMR (500 MHz, CDCl3): δ = 8.22 (s, 1 H,
(192 mg, 77%); m.p. 142–144 °C. H NMR (500 MHz, CDCl3): δ
1
= 7.75 (d, J = 8.85 Hz, 2 H, CHAr), 7.66 (d, J = 2.0 Hz, 1 H,
CHAr), 7.94 (d, J = 8.8 Hz, 1 H, CHAr), 7.86 (d, J = 8.0 Hz, 2 H, CHAr), 7.31–7.36 (m, 2 H, CHAr), 6.95 (d, J = 8.85 Hz, 2 H, CHAr),
CHAr), 7.37–7.56 (m, 4 H, CHAr), 7.07 (s, 1 H, CHAr), 2.66 (s, 3
H, COCH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 197.6, 157.5,
157.3, 132.8, 129.7, 129.2, 129.0, 128.8, 125.0, 122.1, 111.1, 101.5,
6.80 (s, 1 H, CHAr), 4.59–4.64 [m, 1 H, CH(CH3)2], 1.37 [d, J =
6.0 Hz, 6 H, CH(CH3)2] ppm. 13C NMR (125 MHz, CDCl3): δ =
158.6, 157.4, 153.3, 131.5, 126.5, 126.4, 123.0, 122.3, 115.9, 115.8,
26.7 ppm. IR (KBr): ν = 2922, 1672, 1606, 1439, 1352, 1271, 1239,
112.3, 98.8, 69.9, 21.9 ppm. IR (KBr): ν = 2976, 2925, 1608, 1501,
˜
˜
1156, 1128, 1072, 1019, 908, 808, 761 cm–1. HRMS (EI): calcd. for
C16H12O2 [M]+ 236.0837; found 236.0833.
1442, 1378, 1321, 1303, 1255, 1179, 1034, 950, 894, 867, 835,
793 cm–1. HRMS (EI): calcd. for C17H15BrO2 [M]+ 330.0255 and
[M + 2]+ 332.0235; found 330.0258 and 332.0334.
5-Acetyl-2-(4-fluorophenyl)benzofuran (5b):[14] White solid (145 mg,
1
76%); m.p. 135–137 °C. H NMR (500 MHz, CDCl3): δ = 8.22 (d,
5-Bromo-2-(4-fluorophenyl)benzofuran (7e):[14] White solid (163 mg,
J = 1.55 Hz, 1 H, CHAr), 7.94–7.96 (m, 1 H, CHAr), 7.82–7.86 (m, 75%); m.p. 128–130 °C. 1H NMR (500 MHz, CDCl3): δ = 7.80–
2 H, CHAr), 7.54 (d, J = 8.4 Hz, 1 H, CHAr), 7.13–7.18 (m, 2 H, 7.82 (m, 2 H, CHAr), 7.68 (s, 1 H, CHAr), 7.37 (s, 2 H, CHAr),
CHAr), 7.01 (s, 1 H, CHAr), 2.67 (s, 3 H, COCH3) ppm. 13C NMR 7.12–7.16 (m, 2 H, CHAr), 6.87 (s, 1 H, CHAr) ppm. 13C NMR
(125 MHz, CDCl3): δ = 197.6, 163.1 (d, J = 247.9 Hz), 157.3, 156.6,
(125 MHz, CDCl3): δ = 163.0 (d, J = 248 Hz), 156.2, 153.5, 131.1,
132.9, 129.3, 126.9 (d, J = 8.35 Hz), 126.1, 125.0, 122.0, 116.0 (d, 127.0, 126.9 (d, J = 8.35 Hz), 126.1, 123.4, 116.0 (d, J = 21.46 Hz),
J = 22.65 Hz), 111.0, 101.3, 26.7 ppm. IR (KBr): ν = 2928, 1673,
112.5, 100.3 ppm. IR (KBr): ν = 2923, 1605, 1567, 1501, 1441,
˜
˜
1606, 1503, 1438, 1355, 1282, 1233, 1157, 1098, 1030, 975, 836,
804, 748 cm–1. HRMS (EI): calcd. for C16H11FO2 [M]+ 254.0743;
found 254.0743.
1241, 1157, 1099, 1049, 1031, 922, 874, 842, 797, 738 cm–1. HRMS
(EI): calcd. for C14H8BrFO [M]+ 289.9743 and [M + 2]+ 291.9722;
found 289.9742 and 291.9752.
5-Benzoyl-2-phenylbenzofuran (6a):[26] White solid (158 mg, 71%);
m.p. 115–117 °C. 1H NMR (500 MHz, CDCl3): δ = 8.06 (s, 1 H,
CHAr), 7.88 (d, J = 8.0 Hz, 2 H, CHAr), 7.81–7.84 (m, 3 H, CHAr),
5-Bromo-2-(3-methoxyphenyl)benzofuran (7f): White solid (172 mg,
76%); m.p. 92–94 °C. H NMR (500 MHz, CDCl3): δ = 7.69 (s, 1
1
H, CHAr), 7.34–7.44 (m, 5 H, CHAr), 6.91–6.94 (m, 2 H, CHAr),
7.59–7.62 (m, 2 H, CHAr), 7.46–7.52 (m, 4 H, CHAr), 7.38–7.40 (m, 3.89 (s, 1 H, OCH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 159.9,
1 H, CHAr), 7.08 (s, 1 H, CHAr) ppm. 13C NMR (125 MHz, 156.9, 153.5, 131.1, 129.9, 127.1, 123.4, 117.5, 115.9, 114.8, 112.5,
CDCl3): δ = 196.6, 157.6, 157.2, 138.3, 133.0, 132.2, 130.1, 129.1,
110.2, 100.9, 55.3 ppm. IR (KBr): ν = 3001, 2964, 1612, 1571, 1489,
˜
129.0, 128.3, 126.9, 125.1, 124.1, 111.1, 101.6 ppm. IR (KBr): ν =
1454, 1435, 1285, 1221, 1159, 1056, 1036, 874, 856, 800, 774 cm–1.
HRMS (EI): calcd. for C15H11BrO2 [M]+ 301.9942 and [M + 2]+
303.9922; found 301.9940 and 303.9945.
˜
3056, 3022, 2932, 1650, 1600, 1567, 1492, 1464, 1441, 1343, 1283,
1172, 1109, 1017, 976, 826, 764, 748 cm–1. HRMS (EI): calcd. for
C21H14O2 [M]+ 298. 0994; found 298.0995.
5-Chloro-2-phenylbenzofuran (8a):[9b,27] White solid (133 mg, 78%);
5-Bromo-2-phenylbenzofuran (7a):[14] White solid (143 mg, 70%);
m.p. 140–141 °C. 1H NMR (500 MHz, CDCl3): δ = 7.85 (d, J =
7.45 Hz, 2 H, CHAr), 7.70 (s, 1 H, CHAr), 7.44–7.47 (m, 2 H,
m.p. 133–134 °C. H NMR (500 MHz, CDCl3): δ = 7.77–7.79 (m,
1
2 H, CHAr), 7.58 (d, J = 7.65 Hz, 1 H, CHAr), 7.51 (d, J = 8.05 Hz,
1 H, CHAr), 7.40–7.42 (m, 2 H, CHAr), 7.22–7.31 (m, 2 H, CHAr),
CHAr), 7.36–7.40 (m, 3 H, CHAr), 6.95 (s, 1 H, CHAr) ppm. 13C 7.00 (s, 1 H, CHAr) ppm. 13C NMR (125 MHz, CDCl3): δ = 154.8,
NMR (125 MHz, CDCl3): δ = 157.1, 153.5, 131.1, 129.8, 128.9,
154.7, 134.2, 129.0, 128.9, 126.0, 124.5, 123.0, 120.9, 111.1,
128.8, 127.0, 125.0, 123.4, 115.9, 112.5, 100.5 ppm. IR (KBr): ν =
101.7 ppm. IR (KBr): ν = 3094, 2923, 1608, 1581, 1490, 1438, 1324,
˜
˜
3075, 2996, 2919, 1678, 1598, 1400, 1360, 1262, 1005, 837, 764,
686, 593 cm–1. HRMS (EI): calcd. for C14H9BrO [M]+ 271.9837
and [M + 2]+ 273.9816; found 271.9837 and 273.9895.
1261, 1162, 1114, 1061, 1038, 1019, 903, 878, 807, 763, 738,
689 cm–1. HRMS (EI): calcd. for C14H9ClO [M]+ 228.0342; found
228.0348.
5-Bromo-2-(4-methylphenyl)benzofuran (7b):[14] White
(173 mg, 80%); m.p. 161–164 °C. H NMR (500 MHz, CDCl3): δ (134 mg, 74%); m.p. 158–160 °C. H NMR (500 MHz, CDCl3): δ
solid
5-Chloro-2-(4-methylphenyl)benzofuran (8b):[27] White solid
1
1
= 7.72 (d, J = 8.3 Hz, 2 H, CHAr), 7.67 (d, J = 1.7 Hz, 1 H, CHAr),
= 7.73 (d, J = 8.4 Hz, 2 H, CHAr), 7.51 (d, J = 2.3 Hz, 1 H, CHAr),
7.40 (d, J = 8.8 Hz, 1 H, CHAr), 7.19–7.26 (m, 3 H, CHAr), 6.89
7.32–7.37 (m, 2 H, CHAr), 7.24–7.26 (m, 2 H, CHAr), 6.88 (s, 1 H,
CHAr), 2.39 (s, 3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ (s, 1 H, CHAr), 2.39 (s, 3 H, CH3) ppm. 13C NMR (125 MHz,
= 157.4, 153.4, 139.1, 131.3, 129.5, 127.1, 126.7, 124.9, 123.2, 115.8,
CDCl3): δ = 157.6, 153.1, 139.1, 130.6, 129.5, 128.3, 127.2, 124.9,
112.4, 99.8, 21.4 ppm. IR (KBr): ν = 2915, 1606, 1578, 1502, 1441,
124.0, 120.2, 111.9, 100.0, 21.4 ppm. IR (KBr): ν = 2918, 1609,
˜
˜
1376, 1322, 1262, 1205, 1115, 1048, 1015, 921, 875, 823, 796, 738,
670 cm–1. HRMS (EI): calcd. for C15H11BrO [M]+ 285.9993 and
[M + 2]+ 287.9973; found 285.9991 and 288.0038.
1583, 1503, 1443, 1263, 1162, 1059, 1034, 904, 876, 823, 796,
739 cm–1. HRMS (EI): calcd. for C15H11ClO [M]+ 242.0498; found
242.0498.
5-Bromo-2-(4-ethoxyphenyl)benzofuran
(171 mg, 72%); m.p. 173–175 °C. H NMR (500 MHz, CDCl3): δ (137 mg, 71%); m.p. 161–163 °C. H NMR (500 MHz, CDCl3): δ
(7c):[14]
White
solid
5-Chloro-2-(4-methoxyphenyl)benzofuran (8c):[27] White solid
1
1
= 7.75 (d, J = 8.8 Hz, 2 H, CHAr), 7.65 (s, 1 H, CHAr), 7.31–7.36
(m, 2 H, CHAr), 6.96 (d, J = 8.8 Hz, 2 H, CHAr), 6.79 (s, 1 H,
= 7.77 (d, J = 8.85 Hz, 2 H, CHAr), 7.50 (d, J = 2.0 Hz, 1 H,
CHAr), 7.40 (d, J = 8.6 Hz, 1 H, CHAr), 7.18–7.20 (m, 1 H, CHAr),
CHAr), 4.08 (q, J = 6.9 Hz, 2 H, CH2CH3), 1.44 (t, J = 6.9 Hz, 3 6.97 (d, J = 8.9 Hz, 2 H, CHAr), 6.81 (s, 1 H, CHAr), 3.86 (s, 3 H,
H, CH2CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 159.6, 157.4,
OCH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 160.2, 157.5, 153.0,
153.3, 131.5, 126.5, 126.4, 123.0, 122.4, 115.8, 114.7, 112.3, 98.8,
130.8, 128.3, 126.5, 123.7, 122.7, 120.0, 114.3, 111.8, 99.1,
63.5, 14.7 ppm. IR (KBr): ν = 2975, 2928, 1609, 1501, 1442, 1393,
55.3 ppm. IR (KBr): ν = 2928, 1608, 1582, 1444, 1420, 1306, 1253,
˜
˜
786
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 781–788

Pd-Catalyzed Tandem Chemoselective Synthesis of 2-Arylbenzofurans
1208, 1176, 1110, 1060, 1038, 904, 877, 831, 794, 739, 695 cm–1. 5,7-Dichloro-2-(4-methylphenyl)benzofuran (9b):[14] White solid
1
HRMS (EI): calcd. for C15H11ClO2 [M]+ 258.0448; found 258.0444.
(164 mg, 79%); m.p. 106–108 °C. H NMR (500 MHz, CDCl3): δ
= 7.75 (d, J = 8.3 Hz, 2 H, CHAr), 7.40 (d, J = 2.0 Hz, 1 H, CHAr),
7.24–7.26 (m, 3 H, CHAr), 6.90 (s, 1 H, CHAr), 2.40 (s, 3 H, CH3)
ppm. 13C NMR (125 MHz, CDCl3): δ = 158.4, 149.1, 139.6, 131.6,
129.5, 128.5, 126.5, 125.1, 123.9, 118.8, 116.9, 100.4, 21.4 ppm. IR
5-Chloro-2-(4-ethoxyphenyl)benzofuran (8d): White solid (156 mg,
1
76%); m.p. 164–166 °C. H NMR (500 MHz, CDCl3): δ = 7.76 (d,
J = 8.0 Hz, 2 H, CHAr), 7.50 (s, 1 H, CHAr), 7.39 (d, J = 8.4 Hz,
1 H, CHAr), 7.18–7.20 (m, 1 H, CHAr), 6.96 (d, J = 7.65 Hz, 2 H,
CHAr), 6.80 (s, 1 H, CHAr), 4.08 (q, J = 6.9 Hz, 2 H, CH2CH3),
1.44 (t, J = 6.9 Hz, 3 H, CH2CH3) ppm. 13C NMR (125 MHz,
CDCl3): δ = 159.6, 157.6, 153.0, 130.8, 128.3, 126.5, 123.7, 122.5,
(KBr): ν = 2917, 1574, 1500, 1442, 1408, 1326, 1276, 1231, 1171,
˜
1033, 976, 908, 866, 831, 791, 756, 732 cm–1. HRMS (EI): calcd.
for C15H10Cl2O [M]+ 276.0109; found 276.0109.
5,7-Dichloro-2-(4-chlorophenyl)benzofuran (9c):[14] White solid
120.0, 114.8, 111.8, 99.0, 63.5, 14.7 ppm. IR (KBr): ν = 2977, 1609,
˜
1
1502, 1445, 1394, 1306, 1250, 1176, 1116, 1045, 923, 874, 836,
794 cm–1. HRMS (EI): calcd. for [M]+ C16H13ClO2 272.0604; found
272.0605.
(160 mg, 72%); m.p. 139–141 °C. H NMR (500 MHz, CDCl3): δ
= 7.77 (d, J = 5.7 Hz, 2 H, CHAr), 7.40–7.42 (m, 3 H, CHAr), 7.24–
7.26 (m, 1 H, CHAr), 6.93 (d, J = 2.85 Hz, 1 H, CHAr) ppm. 13C
NMR (125 MHz, CDCl3): δ = 156.9, 149.2, 135.3, 131.2, 129.1,
5-Chloro-2-(4-isopropoxyphenyl)benzofuran (8e): White solid
1
128.8, 127.7, 126.4, 124.5, 119.1, 117.1, 101.5 ppm. IR (KBr): ν =
˜
(167 mg, 78%); m.p. 133–135 °C. H NMR (500 MHz, CDCl3): δ
2923, 1606, 1576, 1486, 1442, 1403, 1327, 1282, 1169, 1091, 1035,
1012, 985, 909, 862, 825, 758, 732 cm–1. HRMS (EI): calcd. for
C14H7Cl3O [M]+ 295.9562; found 295.9565.
= 7.75 (d, J = 8.8 Hz, 2 H, CHAr), 7.50 (d, J = 1.9 Hz, 1 H, CHAr),
7.39 (d, J = 8.4 Hz, 1 H, CHAr), 7.17–7.20 (m, 1 H, CHAr), 6.95
(d, J = 8.8 Hz, 2 H, CHAr), 6.80 (s, 1 H, CHAr), 4.57–4.65 [m, 1
H, CH(CH3)2], 1.37 [d, J = 6.15 Hz, 6 H, CH(CH3)2] ppm. 13C
NMR (125 MHz, CDCl3): δ = 158.6, 157.6, 153.0, 130.9, 128.3,
126.5, 123.7, 122.4, 120.0, 116.0, 111.8, 99.0, 70.0, 22.0 ppm. IR
5,7-Dichloro-2-(4-fluorophenyl)benzofuran] (9d):[14] White solid
1
(164 mg, 78%); m.p. 135–137 °C. H NMR (500 MHz, CDCl3): δ
= 7.82–7.85 (m, 2 H, CHAr), 7.42 (s, 1 H, CHAr), 7.24–7.26 (m, 1
H, CHAr), 7.13–7.16 (m, 2 H, CHAr), 6.90 (d, J = 1.9 Hz, 1 H,
CHAr) ppm. 13C NMR (125 MHz, CDCl3): δ = 163.3 (d, J =
249.18 Hz), 157.1, 149.1, 131.4, 128.7, 127.1 (d, J = 8.35 Hz), 124.3,
(KBr): ν = 2978, 1607, 1501, 1444, 1382, 1303, 1255, 1120, 1034,
˜
905, 865, 835, 793, 696 cm–1. HRMS (EI): calcd. for C17H15ClO2
[M]+ 286.0761; found 286.0763.
119.0, 117.0, 116.0 (d, J = 21.46 Hz), 100.9 ppm. IR (KBr): ν =
˜
5-Chloro-2-(4-chlorophenyl)benzofuran (8f): White solid (143 mg,
72%); m.p. 152–154 °C. 1H NMR (500 MHz, CDCl3): δ = 7.74–
7.76 (m, 2 H, CHAr), 7.52 (s, 1 H, CHAr), 7.40–7.41 (m, 3 H, CHAr),
7.21–7.25 (m, 1 H, CHAr), 6.92 (s, 1 H, CHAr) ppm. 13C NMR
(125 MHz, CDCl3): δ = 156.1, 153.2, 134.7, 130.3, 129.0, 128.6,
2921, 1605, 1569, 1501, 1442, 1294, 1029, 868, 831, 792, 759,
732 cm–1. HRMS (EI): calcd. for C14H7Cl2FO [M]+ 279.9858;
found 279.9853.
Supporting Information (see footnote on the first page of this arti-
cle): NMR (proton and carbon), mass spectra and HPLC traces of
products.
128.4, 126.2, 124.6, 120.4, 112.1, 101.1 ppm. IR (KBr): ν = 2922,
˜
1599, 1580, 1484, 1441, 1402, 1323, 1259, 1204, 1162, 1091, 1059,
1032, 1009, 905, 873, 829, 800, 729, 697 cm–1. HRMS (EI): calcd.
for C14H8Cl2O [M]+ 261.9952; found 261.9957.
Acknowledgments
5-Chloro-2-(4-fluorophenyl)benzofuran (8g): White solid (135 mg,
73%); m.p. 126–128 °C. 1H NMR (500 MHz, CDCl3): δ = 7.79–
7.83 (m, 2 H, CHAr), 7.52 (d, J = 1.95 Hz, 1 H, CHAr), 7.41 (d, J
= 8.4 Hz, 1 H, CHAr), 7.11–7.25 (m, 3 H, CHAr), 6.88 (s, 1 H,
CHAr) ppm. 13C NMR (125 MHz, CDCl3): δ = 163.0 (d, J =
248 Hz), 156.4, 153.1, 130.5, 128.5, 126.9 (d, J = 8.35 Hz), 126.2,
124.4, 120.3, 115.9 (d, J = 21.46 Hz), 112.0, 100.4 ppm. IR (KBr):
The authors thank the Department of Science and Technology
(DST), New Delhi for supporting this work under the green chem-
istry program (SR/S5/GC-11/2008). D. N. J. and P. D. thank the
Council of Scientific and Industrial Research (CSIR), New Delhi
for research fellowships.
ν = 1603, 1569, 1500, 1442, 1323, 1240, 1157, 1098, 1031, 1011,
˜
926, 904, 875, 843, 797, 739, 695 cm–1. HRMS (EI): calcd. for
C14H8ClFO [M]+ 246.0248; found 246.0246.
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5-Chloro-2-(3-methoxyphenyl)benzofuran (8h): White solid (144 mg,
1
74%); m.p. 65–67 °C. H NMR (500 MHz, CDCl3): δ = 7.53 (d, J
= 1.9 Hz, 1 H, CHAr), 7.42–7.44 (m, 2 H, CHAr), 7.34–7.38 (m, 2
H, CHAr), 7.22–7.24 (m, 1 H, CHAr), 6.91–6.95 (m, 2 H, CHAr),
3.89 (s, 3 H, OCH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 159.9,
157.1, 153.1, 131.1, 130.4, 129.9, 128.4, 124.4, 120.4, 117.6, 114.8,
112.1, 110.2, 101.1, 55.3 ppm. IR (KBr): ν = 2940, 1613, 1567,
˜
1489, 1454, 1326, 1285, 1220, 1157, 1056, 1036, 938, 908, 875, 856,
800, 773, 687 cm–1. HRMS (EI): calcd. for C15H11ClO2 [M]+
258.0448; found 258.0445.
5,7-Dichloro-2-phenylbenzofuran (9a):[19d] White solid (149 mg,
1
75%); m.p. 114–116 °C. H NMR (500 MHz, CDCl3): δ = 7.87 (d,
J = 7.25 Hz, 2 H, CHAr), 7.38–7.48 (m, 4 H, CHAr), 7.27 (d, J =
1.9 Hz, 1 H, CHAr), 6.97 (s, 1 H, CHAr) ppm. 13C NMR (125 MHz,
CDCl3): δ = 158.1, 149.2, 131.4, 129.4, 129.2, 128.8, 128.6, 125.2,
124.2, 119.0, 117.1, 101.1 ppm. IR (KBr): ν = 3086, 1607, 1577,
˜
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838, 797, 757, 732 cm–1. HRMS (EI): calcd. for C14H8Cl2O [M]+
261.9952; found 261.9956.
Eur. J. Org. Chem. 2013, 781–788
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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M. L. N. Rao, D. N. Jadhav, P. Dasgupta
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Published Online: December 10, 2012
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Eur. J. Org. Chem. 2013, 781–788