Benzenesulfonyl Chlorides: Alternative Coupling Partners for Regiocontrolled Palladium-Catalyzed Direct Desulfitative 5-Arylation of Furans

Article abstract of DOI:10.1055/s-0033-1340188

The reactivity of furan derivatives in palladium-catalyzed desulfitative arylation was studied. Alkyl-substituted furan derivatives were successfully coupled with a variety of benzenesulfonyl chlorides using a phosphine-free catalyst; regioselective arylation at C5 of the furan was observed in all cases. This reaction tolerates a wide variety of substituents on the benzenesulfonyl derivative. It should be noted that even bromo- and iodobenzenesulfonyl chlorides were successfully coupled with furan derivatives without cleavage of the C-Br or C-I bonds, thus allowing further transformations. The use of these reactants demonstrates the potential of benzenesulfonyl chlorides as coupling partners to access to functionalized 5-arylfurans.

Full text of DOI:10.1055/s-0033-1340188

PAPER
▌2515
paper
Benzenesulfonyl Chlorides: Alternative Coupling Partners for Regiocon-
trolled Palladium-Catalyzed Direct Desulfitative 5-Arylation of Furans
Pd-Catalyzed Direct Desulfitative Arylation of Furans
Anissa Beladhria,a,b Kedong Yuan,a Hamed Ben Ammar,c Jean-Francois Soulé,a Ridha Ben Salem,*b Henri Doucet*a
a
Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes 1 ‘Organométalliques, Matériaux et Catalyse’,
Campus de Beaulieu, 35042 Rennes, France
Fax +33(223)236939; E-mail: henri.doucet@univ-rennes1.fr
b
Laboratoire de Chimie Organique Physique (UR 11ES74) Université de Sfax, Faculté des Sciences de Sfax, Route de la Soukra km 4,
3038 Sfax, Tunisie
c
Laboratoire de Synthèse Asymétrique et Catalyse Homogène, (UR 11ES56) Université de Monastir, Faculté des Sciences de Monastir,
avenue de l’environnement, Monastir 5000, Tunisie
Received: 07.04.2014; Accepted after revision 29.04.2014
rivatives has proved to be a very powerful method for the
Abstract: The reactivity of furan derivatives in palladium-cata-
synthesis of a wide variety of arylated heterocycles.2 The
lyzed desulfitative arylation was studied. Alkyl-substituted furan
first example of palladium-catalyzed direct arylation of a
derivatives were successfully coupled with a variety of benzenesul-
fonyl chlorides using a phosphine-free catalyst; regioselective ary-
furan was reported by Ohta who obtained a low yield of
lation at C5 of the furan was observed in all cases. This reaction 23% for its coupling with bromobenzene (Scheme 1).1
tolerates a wide variety of substituents on the benzenesulfonyl de-
rivative. It should be noted that even bromo- and iodobenzenesulfo-
Several groups have since developed more effective con-
ditions allowing the formation of arylfurans in high
nyl chlorides were successfully coupled with furan derivatives
yields.3 On the other hand, relatively little effort has been
without cleavage of the C–Br or C–I bonds, thus allowing further
expended toward developing alternative coupling partners
transformations. The use of these reactants demonstrates the poten-
tial of benzenesulfonyl chlorides as coupling partners to access to
functionalized 5-arylfurans.
to aryl halides for the direct arylation of furans.4 Using
arenediazonium salts4a or aryl triflates4b in the presence of
Key words: palladium, C–H bond activation, furans, benzenesulfo-
nyl chlorides, arylation
Ohta1
Pd(PPh3)4 (5 mol%)
Ar
+
ArBr
The synthesis of arylated furans is an important field of re-
search in organic chemistry due to the biological proper-
ties of these derivatives. For example, dantrolene is a
muscle relaxant and lapatinib is used in the treatment of
breast cancer (Figure 1).
KOAc, DMA
150 °C, 12 h
O
O
+
Doucet4b
Pd(OAc)2 (5 mol%)
Ph3P (10 mol%)
OTf
KOAc, DMF
150 °C, 20 h
O
O
n-Bu
n-Bu
51%
MeO
N
Su4d
O
NO2
MeO
HO2C
MeO
Pd(TFA)2 (5 mol%)
PCy3 (10 mol%)
N
N
O
N
HN
+
+
NH
O
dantrolene
Ag2CO3
DMSO–DME
120 °C, 24 h
O
O
O
HN
MeO
54%
O
Shi4c
Cl
MeO2S
Pd(OAc)2 (5 mol%)
(HO)2B Ph
Ph
lapatinib
AcOH, O2
25 °C, 48 h
O
O
F
58%
Goeldner4a
Figure 1 Examples of bioactive arylfurans
–
CF2CO2
+N2 Ar
Pd(OAc)2 (5 mol%)
+
Ar
In 1990, Ohta and co-workers reported the 2- or 5-aryla-
tion of several heteroaromatics with aryl halides as cou-
pling partners via a C–H bond activation using Pd(PPh3)4
as the catalyst.1 Since these exciting results, the palladi-
um-catalyzed so-called direct arylation of heteroaryl de-
EtOH, CH2Cl2
25 °C, 1 h
O
O
43%
This work
PdCl2(MeCN)2
(5 mol%)
ClO2S
+
Li2CO3, dioxane
O
R1
O
R1
140 °C
R2
R2
SYNTHESIS 2014, 46, 2515–2523
Advanced online publication: 12.06.2014
DOI: 10.1055/s-0033-1340188; Art ID: ss-2014-t0227-op
© Georg Thieme Verlag Stuttgart · New York
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
Scheme 1 Reported coupling partners for the palladium-catalyzed
direct arylation of (benzo)furans

2516
A. Beladhria et al.
PAPER
5 mol% of a palladium catalyst gives the aryl-substituted zofurans.12 It should be noted that Deng, Luo, and co-
(benzo)furans in moderate yields (Scheme 1).
workers recently reported that benzenesulfinic acid sodi-
um salts can also be employed for palladium-catalyzed di-
rect arylation of azoles and indoles under oxidative
conditions.11b,c On the other hand, to our knowledge, the
desulfitative direct arylation of furans with benzenesulfo-
nyl chlorides has not yet been described.11 As the use of
benzenesulfonyl chlorides as coupling partners instead of
aryl halides drastically modifies the regioselectivity of the
palladium-catalyzed direct arylations,12a their behavior in
the presence of furans needed to be investigated.
Recently, benzoic acids4d or arylboronic acids,4c using
(benzo)furans as the coupling partner and 5 mol% palladi-
um catalyst under oxidative conditions also afforded aryl-
substituted (benzo)furans (Scheme 1). It should be noted
that two of these procedures were not extended to benzo-
furan derivatives. The synthesis of 5-arylfurans under
metal-catalyzed oxidative coupling conditions5 has also
been reported.
Aryl halides and benzoic acids are generally attractive
couplings partners in terms of cost and availability; the
use of aryl triflates, arylboronic acids or diazonium salts
is less attractive. Therefore, the discovery of new easily
available coupling partners for the regioselective intermo-
lecular direct arylation of furan derivatives especially us-
ing a simple catalyst, base, and substrate would be a
considerable advantage.
Herein, we describe regioselective access to C5-arylated
furans using desulfitative palladium-catalyzed C–H bond
functionalization of furans with benzenesulfonyl chlo-
rides as the coupling partners (Table 1). The influence of
both the benzenesulfonyl chloride and furan substituents
are reported.
We first examined the influence of several reaction condi-
tions on the product formation based on our previous re-
sults on palladium-catalyzed desulfitative coupling with
thiophene derivatives12a (Table 1). The reaction of 2-
butylfuran (1 equiv) and benzenesulfonyl chloride (1.5
equiv) in the presence of 5 mol% PdCl2(MeCN)2 catalyst
with lithium carbonate as the base at 140 °C for 20 hours
gave regioselectively the C5 arylation product 1 in 40%
yield (entry 1). A partial conversion of 2-butylfuran was
observed under these conditions. It should be noted that
the formation of C3- or C4-arylation products or diaryla-
Dong and co-workers recently reported the palladium-cat-
alyzed coupling of 2-phenylpyridine with benzenesulfo-
nyl chlorides for the preparation of sulfones.6 In this
study, in one case they also observed a desulfitative direct
arylation of a quinoline derivative. In 2011, Cheng et al.
extended the use of benzenesulfonyl chlorides7–10 as the
reaction partners for the desulfitative palladium-catalyzed
direct 2-arylation of benzoxazoles derivatives.11a We have
also recently reported the first palladium-catalyzed desul-
fitative β-arylation of thiophenes and α-arylation of ben-
Table 1 Influence of the Reaction Conditions on the Palladium-Catalyzed Direct Arylation of 2-Butylfuran with Benzenesulfonyl Chloridea
Ph
O
n-Bu
[Pd]
1
+
PhSO2Cl
O
n-Bu
(1 equiv)
base
Ph
(1.5 equiv)
O
n-Bu
1'
Entry
Catalyst (mol%)
Solvent
Base
Time (h)
Conv. (%)
Yield (%) of 1
1
2
PdCl2(MeCN)2 (5)
Pd(OAc)2 (5)
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
ethylbenzene
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Li2CO3
Na2CO3
K2CO3
KOAc
20
45
20
20
72
45
45
45
45
20
45
38
21
41
44
16
10
19
17
8
40
25
17
36b
41
13
9
3
PdCl2 (5)
4
PdCl2(MeCN)2 (5)
PdCl2(MeCN)2 (5)
PdCl2(MeCN)2 (5)
PdCl2(MeCN)2 (5)
PdCl2(MeCN)2 (5)
PdCl2(MeCN)2 (5)
PdCl2(MeCN)2 (5)
5
6
7
8
17
13
6
9
K3PO4
Li2CO3
10
a Conditions: 2-butylfuran (1 equiv), benzenesulfonyl chloride (1.5 equiv), base (3 equiv), 140 °C, conversion of 2-butylfuran.
b Benzenesulfonyl chloride (2 equiv).
Synthesis 2014, 46, 2515–2523
© Georg Thieme Verlag Stuttgart · New York

PAPER
Pd-Catalyzed Direct Desulfitative Arylation of Furans
2517
tion products was not detected by GC/MS and 1H NMR of
Table 2 Influence of the Benzenesulfonyl Chloride Substituents on
the crude mixture. Then, we examined the influence of the the Palladium-Catalyzed Direct C5-Arylation of 2-Butylfurana
palladium catalyst. The use of 5 mol% palladium(II) ace-
tate or chloride as the catalyst afforded a lower yield of 1
PdCl2(MeCN)2
(5 mol%)
+
ArSO2Cl
Ar
(entries 2 and 3). A larger excess of benzenesulfonyl chlo-
ride or a longer reaction time did not improve the yield of
1 (entries 4 and 5). The influence of the nature of the base
was also examined. The use of sodium carbonate, potassi-
um carbonate, potassium acetate, or tripotassium phos-
phate led to lower conversions of 2-butylfuran and to
lower yields of 1 than with lithium carbonate (entries 6–
9). The influence of an alternative solvent was then exam-
ined. Ethylbenzene afforded 1 in 6% yield due to a very
low conversion of 2-butylfuran (entry 10).
(1.5–2 equiv)
Li2CO3 (3 equiv)
dioxane,
140 °C 40 h
O
O
n-Bu
n-Bu
(1 equiv)
2–15
Entry
Ar
Product
Yield (%)
1
2
3
4
5
4-O2NC6H4
4-NCC6H4
4-F3CC6H4
4-ClC6H4
4-IC6H4
2
3
4
5
6
7
88
89
79
50
70
Next, the influence of the substituents on benzenesulfonyl
chloride in the coupling with 2-butylfuran was examined
using 5 mol% PdCl2(MeCN)2 as the catalyst, lithium car-
bonate as the base in dioxane at 140 °C (Table 2). We first
employed several 4-substituted benzenesulfonyl chloride
derivatives. In the presence of 4-nitro, 4-cyano, and 4-(tri-
fluoromethyl)-substituted benzenesulfonyl chlorides the
C5-arylated furans 2–4 were obtained regioselectively in
79–89% yields (entries 1–3); using 4-chlorobenzenesulfo-
nyl chloride gave 5 in a lower yield of 50% (entry 4).
Then, we examined the reactivity of 4-iodobenzenesulfo-
nyl chloride as the C–I bond on the benzene ring is known
to be very reactive in the presence of palladium catalysts.
The reaction proceeds nicely without cleavage of the C–I
bond to afford 6 in 70% yield, allowing further transfor-
mations (entry 5). From slightly electron-deficient 4-fluo-
robenzenesulfonyl chloride, a poor 32% yield of 7 was
obtained due to a low conversion of 2-butylfuran (entry
6), and in the presence of the electron-rich 4-methoxyben-
zenesulfonyl chloride the formation of 8 was not observed
by GC/MS analysis of the crude mixture and 2-butylfuran
was recovered (entry 8). We also examined the reactivity
of some meta-substituted benzenesulfonyl derivatives for
this coupling. meta-Substituents have a small influence on
the reactivity of the benzenesulfonyl chlorides. 3-(Trifluo-
romethyl)benzenesulfonyl chloride and 3-chlorobenzene-
sulfonyl chloride afforded 9 and 10 in 62% and 73%
yields, respectively (entries 9 and 10). A moderate yield
of 11 was obtained from a di-meta-substituted benzene-
sulfonyl chloride (entry 11). From the ortho-substituted 2-
cyanobenzenesulfonyl chloride and 2-fluorobenzenesul-
fonyl chloride 12 and 13 were also obtained in good yields
of 83% and 89% (entries 12 and 13); whereas the use of
naphthalene-1-sulfonyl chloride afforded 14 in only 44%
yield (entry 14). The detrimental effect of an ortho-methyl
substituent on benzenesulfonyl chloride was observed as
only a trace amount the desired product 15 was detected
by GC/MS analysis (entry 15).
6
7
4-FC6H4
32
31b
8
9
4-MeOC6H4
3-F3CC6H4
3-ClC6H4
8
9
<5
62
73
75
83
89
44
<5
10
11
12
13
14
15
10
11
12
13
14
15
3,5-(F3C)2C6H3
2-NCC6H4
2-FC6H4
1-naphthyl
2-MeC6H4
a Conditions: PdCl2(MeCN)2 (0.05 equiv), 2-butylfuran (1 equiv),
benzenesulfonyl chloride derivative (1.5 equiv), Li2CO3 (3 equiv), di-
oxane, 140 °C, 40 h, isolated yields.
b Benzenesulfonyl chloride derivative (2 equiv).
ratio, which confirms the higher reactivity of electron-
deficient benzenesulfonyl chlorides for such couplings.
The influence of electron-withdrawing and electron-
donating substituents on the furan derivative was also inves-
tigated (Scheme 3). In the presence of furan-2-carbonitrile
and benzenesulfonyl chloride or 4-nitrobenzenesulfonyl
chloride as the coupling partners the formation of 16a or
16b was not observed and the furan derivative was recov-
ered unreacted. The presence of an electron-donating sub-
O
n-Bu
(1 equiv)
O
n-Bu
PdCl2(MeCN)2
(5 mol%)
1 23%
+
+
ClO2S
Li2CO3 (3 equiv)
dioxane, 140 °C
40 h
CF3
(1.5 equiv)
(1.5 equiv)
To gain more insight into the electronic effect of the sub-
stituent on the benzenesulfonyl chloride, a competition re-
action using an equimolar mixture of benzenesulfonyl
chloride and 4-(trifluoromethyl)benzenesulfonyl chloride
in the presence of 2-butylfuran was performed (Scheme
2). A mixture of products 1 and 4 was obtained in a 23:77
O
n-Bu
4 77%
ClO2S
CF3
Scheme 2 Competitive palladium-catalyzed direct arylations using
an equimolar mixture of benzenesulfonyl chloride derivatives
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2515–2523

2518
A. Beladhria et al.
PAPER
stituent was also not tolerated, as no trace of coupling tions employing benzenesulfonyl chlorides. The different
products 17a or 17b was detected in the presence of 2-me- behavior of these two catalytic systems might allow a sim-
thoxyfuran.
pler control of the regioselectivity for direct arylations of
polyheteroaromatic substrates.
PdCl2(MeCN)2
(5 mol%)
A similar competition reaction was performed using an
equimolar mixture of 2-butylfuran and 2-methoxyfuran in
the presence of 4-nitrobenzenesulfonyl chloride or 1-bro-
mo-4-nitrobenzene (Scheme 5). In both cases, only the
+
ArSO2Cl
Ar
Li2CO3 (3 equiv)
dioxane, 140 °C
40 h
(1.5 equiv)
O
R
O
R
(1 equiv)
1
formation of 2 was observed by GC/MS and H NMR
analysis of the crude mixture.
Ar
Ar
O
O
MeO
17a Ar = Ph
17b Ar = 4-O2NC6H4
CN
16a Ar = Ph
16b Ar = 4-O2NC6H4
NO2
O
PdCl2(MeCN)2 n-Bu
(5 mol%)
O
O
2 100%
n-Bu
MeO
(1 equiv)
Scheme 3 Influence of the furan C2-substituent on palladium-cata-
lyzed direct arylation with benzenesulfonyl chloride derivatives
(1 equiv)
Li2CO3 (3 equiv)
dioxane, 140 °C
40 h
NO2
+
O
MeO
ClO2S
NO2
17b 0%
In order to gain more insight into the influence of furan
substituents, we also performed competition reactions to
probe the substituent preference of this catalyst system for
such couplings (Schemes 4 and 5). From an equimolar
mixture of 2-butylfuran and furan-2-carbonitrile using 4-
nitrobenzenesulfonyl chloride as the coupling partner, in
the presence of 5 mol% PdCl2(MeCN)2 catalyst, the ex-
clusive formation of 2 from coupling with 2-butylfuran
was observed (Scheme 4). This result indicates that an
electron-withdrawing substituent at the C2-position of fu-
ran is strongly deactivating, but has no poisoning effect on
the palladium catalyst. In order to compare the selectivity
of this arylation procedure with direct arylation using aryl
halides, a competition experiment using again an equimo-
lar mixture of 2-butylfuran and furan-2-carbonitrile, but
with 1-bromo-4-nitrobenzene as the coupling partner was
performed (Schemes 4). A mixture of C5-arylated furans
2 and 16b was obtained in a 72:28 ratio; revealing that the
direct arylations with aryl bromides are less sensitive to
electron-withdrawing substituents on the furan than reac-
(0.75 equiv)
NO2
NO2
Pd(OAc)2
(1 mol%)
O
n-Bu
O
O
(1 equiv)
n-Bu
MeO
2 100%
(1 equiv)
KOAc (3 equiv)
DMA, 130 °C,
20 h
NO2
+
O
Br
MeO
17b 0%
0.75 equiv.
Scheme 5 Competitive palladium-catalyzed direct arylations using
an equimolar mixture of furans
We also studied consecutive palladium-catalyzed direct
arylations employing 4-bromobenzenesulfonyl chloride
as the central unit (Scheme 6). Using PdCl2(MeCN)2 cat-
alyst in the presence of lithium carbonate in dioxane, this
reactant was coupled at C5 of 2-butylfuran without cleav-
age of the C–Br bond to afford 18 in 64% yield. Then,
from 18 and 2-ethyl-4-methylthiazole as the coupling
partner, using PdCl(C3H5)(dppb) catalyst13 with potassi-
um acetate as the base in N,N-dimethylacetamide (DMA),
the desired product 19 was obtained in 95% yield.
NO2
O
PdCl2(MeCN)2
(5 mol%)
n-Bu
O
O
2 100%
n-Bu
NC
PdCl2(MeCN)2
(5 mol%)
(1 equiv)
(1 equiv)
Li2CO3 (3 equiv)
dioxane, 140 °C
40 h
NO2
Br
+
O
Li2CO3 (3 equiv)
dioxane, 140 °C
40 h
O
O
NC
n-Bu
n-Bu
ClO2S
NO2
16b 0%
18 64%
(1 equiv)
+
(0.75 equiv)
PdCl(C3H5)(dppb)
(2 mol%)
DMA, KOAc (3 equiv)
130 °C, 20 h
N
ClO2S
Br
S
NO2
NO2
(2 equiv)
(2 equiv)
O
Pd(OAc)2
(1 mol%)
n-Bu
O
O
n-Bu
2 72%
NC
(1 equiv)
(1 equiv)
N
S
KOAc (3 equiv)
DMA, 130 °C, 20 h
+
O
O
n-Bu
NC
Br
NO2
16b 28%
19 95%
(0.75 equiv)
Scheme 6 Consecutive palladium-catalyzed direct arylations using
4-bromobenzenesulfonyl chloride
Scheme 4 Competitive palladium-catalyzed direct arylations using
an equimolar mixture of furans
Synthesis 2014, 46, 2515–2523
© Georg Thieme Verlag Stuttgart · New York

PAPER
Pd-Catalyzed Direct Desulfitative Arylation of Furans
2519
Finally, we examined the reactivity of menthofuran, zenesulfonyl chloride to Pd(II) has been reported to pro-
which is naturally present in mint oil, for direct arylation ceed even at room temperature.6b Then, after elimination
using a set of benzenesulfonyl chlorides as coupling part- of SO2 and coordination of furan to palladium, a migration
ners (Table 3). This 2,3,4-trisubstituted furan was also of the aryl group to C5 of furan followed by proton ab-
found to be very reactive in the direct arylation using elec- straction assisted by the base gives the 5-arylfurans and
tron-deficient benzenesulfonyl chlorides. From 1.5 equiv- regenerates the Pd(II) species.
alents of benzenesulfonyl chlorides and 5 mol%
In summary, we report here the first palladium-catalyzed
PdCl2(MeCN)2 catalyst in the presence of lithium carbon-
desulfitative arylations of furan derivatives. The reaction
ate in dioxane, the desired coupling products 21–31 were
proceeds
with
easily
accessible
ligand-free
obtained in 63–88% yields. Again, using both 4-bromo-
benzenesulfonyl chloride and 4-iodobenzenesulfonyl
chloride cleavage of the C–Br and C–I bonds was not ob-
served to afford 25 and 26 in 76% and 65% yields, respec-
tively, allowing further transformations. A slightly lower
yield of 61% for 20 was obtained in the presence of ben-
zenesulfonyl chloride due to a partial conversion of men-
thofuran.
PdCl2(MeCN)2 catalyst and lithium carbonate as base, and
affords very selectively the C5-arylated furans. Moreover,
this procedure tolerates a wide variety of substituents on
the benzenesulfonyl chloride such as nitro, cyano, trifluo-
romethyl, fluoro, chloro, bromo, or even iodo. As several
benzenesulfonyl chlorides with diverse functionalities are
available at an affordable cost, such simple reaction con-
ditions (no expensive base and ligand) should be very at-
tractive to synthetic chemists to access to 5-arylfurans.
Moreover, from 4-bromobenzenesulfonyl chloride, the 5-
arylfuran was obtained without cleavage of the C–Br bond
allowing a second palladium-catalyzed C–H bond func-
tionalization with another heteroarene to afford the 1,4-
di(heteroaryl)benzene with two different heteroaryl
groups.
Table 3 Palladium-Catalyzed Direct Arylations of Menthofuran
with Benzenesulfonyl Chloride Derivativesa
PdCl2(MeCN)2
(5 mol%)
O
Ar
(1 equiv)
Li2CO3 (3 equiv),
dioxane, 140 °C,
40 h
O
+
ArSO2Cl
(1.5 equiv)
All reactions were carried out under argon atmosphere with stan-
dard Schlenk techniques. HPLC grade 1,4-dioxane was used and
stored under argon without further purification. H NMR spectra
1
Entry
Ar
Product
Yield (%)
were recorded on a Bruker GPX (400 MHz) spectrometer relative
to residual CHCl3 (δ = 7.26 for 1H; 77.0 for 13C). 13C NMR spectra
were recorded at 100 MHz on the same spectrometer. All reagents
were weighed and handled in air.
1
2
Ph
20
21
22
23
24
25
26
27
28
29
30
31
61
80
82
78
63
76
65
70
68
79
83
88
4-O2NC6H4
4-NCC6H4
4-F3CC6H4
4-ClC6H4
4-BrC6H4
4-IC6H4
3
Preparation of PdCl(C3H5)(dppb)13
An oven-dried 40-mL Schlenk tube equipped with a magnetic stir-
ring bar under argon, was charged with [Pd(C3H5)Cl]2 (182 mg, 0.5
mmol) and dppb (426 mg, 1 mmol). Anhyd CH2Cl2 (10 mL) was
added, and the solution was stirred at r.t. for 20 min. The solvent
was removed under vacuum. The yellow powder was used without
purification.
4
5
6
7
31P NMR (81 MHz, CDCl3): δ = 19.3 (s).
8
4-FC6H4
C5-Arylated Furans; General Procedure
To a 25-mL oven-dried Schlenk tube, arenesulfonyl chloride (1.5–
2 mmol), furan derivative (1 mmol), Li2CO3 (0.222 g, 3 mmol), 1,4-
dioxane (2 mL) and PdCl2(MeCN)2 (12.9 mg, 0.05 mmol) were
added successively. The mixture was evacuated by vacuum-argon
cycles (5 ×) and stirred at 140 °C (oil bath temperature) for 20–72 h
(see tables and schemes). After cooling the reaction at r.t. and con-
centration, the crude mixture was purified by column chromatogra-
phy (silica gel) to afford the C5-arylated furans.
9
3-ClC6H4
3,5-(F3C)2C6H3
2-NCC6H4
2-FC6H4
10
11
12
a Conditions: PdCl2(MeCN)2 (0.05 equiv), menthofuran (1 equiv),
benzenesulfonyl chloride derivative (1.5 equiv), Li2CO3 (3 equiv), di-
oxane, 140 °C, 40 h, isolated yields.
2-Butyl-5-phenylfuran (1)14
2-Butylfuran (0.124 g, 1 mmol) and benzenesulfonyl chloride
(0.264 g, 1.5 mmol) afforded 1 (0.082 g, 41%) as a colorless oil.
1H NMR (400 MHz, CDCl3): δ = 7.55 (d, J = 8.0 Hz, 2 H), 7.27 (t,
J = 8.0 Hz, 2 H), 7.13 (t, J = 8.0 Hz, 1 H), 6.46 (d, J = 3.2 Hz, 1 H),
5.98 (d, J = 3.2 Hz, 1 H), 2.61 (t, J = 7.3 Hz, 2 H), 1.59 (quint, J =
7.3 Hz, 2 H), 1.33 (sext, J = 7.3 Hz, 2 H), 0.87 (t, J = 7.3 Hz, 3 H).
Although the mechanism has not yet been elucidated, the
reactions with 4-bromo- or 4-iodobenzenesulfonyl chlo-
rides, which afford the coupling products without cleav-
age of the C–Br or C–I bonds, seem to reveal that the first
step of the catalytic cycle is the oxidative addition of the
benzenesulfonyl chloride to Pd(II) to afford an ArSO2–
Pd(IV)Cl intermediate. The oxidative addition of ben-
2-Butyl-5-(4-nitrophenyl)furan (2)14
2-Butylfuran (0.124 g, 1 mmol) and 4-nitrobenzenesulfonyl chlo-
ride (0.332 g, 1.5 mmol) afforded 2 (0.216 g, 88%) as a yellow sol-
id; mp 65–68 °C.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2515–2523

2520
A. Beladhria et al.
PAPER
1H NMR (400 MHz, CDCl3): δ = 8.10 (d, J = 8.6 Hz, 2 H), 7.61 (d,
J = 8.6 Hz, 2 H), 6.68 (d, J = 3.2 Hz, 1 H), 6.05 (d, J = 3.2 Hz, 1 H),
2.61 (t, J = 7.4 Hz, 2 H), 1.58 (quint, J = 7.4 Hz, 2 H), 1.34 (sext,
J = 7.4 Hz, 2 H), 0.87 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 157.4, 150.6, 131.9, 131.0 (q, J =
31.8 Hz), 129.0, 126.2, 124.1 (q, J = 272.6 Hz), 123.2 (q, J = 4.0
Hz), 119.9 (q, J = 4.0 Hz), 107.1, 107.0, 30.2, 27.9, 22.3, 13.8.
MS: m/z = 268 (M+).
2-Butyl-5-(4-cyanophenyl)furan (3)14
2-Butylfuran (0.124 g, 1 mmol) and 4-cyanobenzenesulfonyl chlo-
ride (0.303 g, 1.5 mmol) afforded 3 (0.200 g, 89%) as a yellow sol-
id; mp 80–84 °C.
1H NMR (400 MHz, CDCl3): δ = 7.58 (d, J = 8.6 Hz, 2 H), 7.51 (d,
J = 8.6 Hz, 2 H), 6.61 (d, J = 3.2 Hz, 1 H), 6.02 (d, J = 3.2 Hz, 1 H),
2.60 (t, J = 7.4 Hz, 2 H), 1.59 (quint, J = 7.4 Hz, 2 H), 1.33 (sext,
J = 7.4 Hz, 2 H), 0.87 (t, J = 7.4 Hz, 3 H).
Anal. Calcd for C15H15F3O (268.27): C, 67.16; H, 5.64; found: C,
67.01; H, 5.79.
2-Butyl-5-(3-chlorophenyl)furan (10)
2-Butylfuran (0.124 g, 1 mmol) and 3-chlorobenzenesulfonyl chlo-
ride (0.317 g, 1.5 mmol) afforded 10 (0.171 g, 73%) as a colorless
oil.
1H NMR (400 MHz, CDCl3): δ = 7.48 (s, 1 H), 7.36 (d, J = 8.6 Hz,
1 H), 7.13 (t, J = 8.6 Hz, 1 H), 7.03 (d, J = 8.6 Hz, 1 H), 6.44 (d, J =
3.2 Hz, 1 H), 5.93 (d, J = 3.2 Hz, 1 H), 2.55 (t, J = 7.4 Hz, 2 H), 1.54
(quint, J = 7.4 Hz, 2 H), 1.29 (sext, J = 7.4 Hz, 2 H), 0.82 (t, J = 7.4
Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 157.4, 150.9, 134.9, 133.1, 130.1,
126.8, 123.5, 121.6, 107.3, 107.1, 30.4, 28.1, 22.5, 14.1.
2-Butyl-5-[4-(trifluoromethyl)phenyl]furan (4)14
2-Butylfuran (0.124 g, 1 mmol) and 4-(trifluoromethyl)benzenesul-
fonyl chloride (0.367 g, 1.5 mmol) afforded 4 (0.212 g, 79%) as a
colorless oil.
1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.6 Hz, 2 H), 7.59 (d,
J = 8.6 Hz, 2 H), 6.67 (d, J = 3.2 Hz, 1 H), 6.10 (d, J = 3.2 Hz, 1 H),
2.70 (t, J = 7.4 Hz, 2 H), 1.69 (quint, J = 7.4 Hz, 2 H), 1.45 (sext,
J = 7.4 Hz, 2 H), 0.96 (t, J = 7.4 Hz, 3 H).
MS: m/z = 234 (M+).
Anal. Calcd for C14H15ClO (234.72): C, 71.64; H, 6.44; found: C,
71.79; H, 6.30.
2-Butyl-5-(4-chlorophenyl)furan (5)
2-Butylfuran (0.124 g, 1 mmol) and 4-chlorobenzenesulfonyl chlo-
ride (0.317 g, 1.5 mmol) afforded 5 (0.117 g, 50%) as a yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.45 (d, J = 8.6 Hz, 2 H), 7.20 (d,
J = 8.6 Hz, 2 H), 6.42 (d, J = 3.2 Hz, 1 H), 5.95 (d, J = 3.2 Hz, 1 H),
2.58 (t, J = 7.4 Hz, 2 H), 1.56 (quint, J = 7.4 Hz, 2 H), 1.33 (sext,
J = 7.4 Hz, 2 H), 0.86 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 157.1, 151.3, 132.5, 130.0, 129.0,
124.8, 107.2, 106.4, 30.4, 28.1, 22.5, 14.1.
MS: m/z = 234 (M+).
2-[3,5-Bis(trifluoromethyl)phenyl]-5-butylfuran (11)
2-Butylfuran (0.124 g, 1 mmol) and 3,5-bis(trifluoromethyl)ben-
zenesulfonyl chloride (0.469 g, 1.5 mmol) afforded 11 (0.252 g,
75%) as a yellow solid; mp 38–40 °C.
1H NMR (400 MHz, CDCl3): δ = 8.00 (s, 2 H), 7.68 (s, 1 H), 6.74
(d, J = 3.3 Hz, 1 H), 6.14 (d, J = 3.3 Hz, 1 H), 2.72 (t, J = 7.4 Hz, 2
H), 1.71 (quint, J = 7.4 Hz, 2 H), 1.43 (sext, J = 7.4 Hz, 2 H), 0.98
(t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.2, 148.8, 132.6, 131.7 (q, J =
33.3 Hz), 123.0 (q, J = 272.7 Hz), 122.5 (m), 119.3 (quint, J = 3.8
Hz), 108.4, 107.2, 29.8, 27.5, 22.0, 13.4.
Anal. Calcd for C14H15ClO (234.72): C, 71.64; H, 6.44; found: C,
71.55; H, 6.51.
MS: m/z = 326 (M+).
2-Butyl-5-(4-iodophenyl)furan (6)
Anal. Calcd for C16H14F6O (336.27): C, 57.15; H, 4.20; found: C,
57.31; H, 4.14.
2-Butylfuran (0.124 g, 1 mmol) and 4-iodobenzenesulfonyl chlo-
ride (0.453 g, 1.5 mmol) afforded 6 (0.228 g, 70%) as a yellow sol-
id; mp 45–48 °C.
2-Butyl-5-(2-cyanophenyl)furan (12)14
2-Butylfuran (0.124 g, 1 mmol) and 2-cyanobenzenesulfonyl chlo-
ride (0.303 g, 1.5 mmol) afforded 12 (0.187 g, 83%) as a yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.57 (d, J = 8.6 Hz, 2 H), 7.26 (d,
J = 8.6 Hz, 2 H), 6.46 (d, J = 3.2 Hz, 1 H), 5.97 (d, J = 3.2 Hz, 1 H),
2.58 (t, J = 7.4 Hz, 2 H), 1.56 (quint, J = 7.4 Hz, 2 H), 1.32 (sext,
J = 7.4 Hz, 2 H), 0.86 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 157.2, 151.3, 137.8, 130.9, 125.2,
107.3, 106.7, 91.7, 30.4, 28.1, 22.5, 14.1.
1H NMR (400 MHz, CDCl3): δ = 7.86 (d, J = 8.0 Hz, 1 H), 7.67 (d,
J = 8.0 Hz, 1 H), 7.59 (t, J = 7.8 Hz, 1 H), 7.29 (t, J = 7.8 Hz, 1 H),
7.23 (d, J = 3.3 Hz, 1 H), 6.18 (d, J = 3.3 Hz, 1 H), 2.74 (t, J = 7.4
Hz, 2 H), 1.73 (quint, J = 7.4 Hz, 2 H), 1.42 (sext, J = 7.4 Hz, 2 H),
0.99 (t, J = 7.4 Hz, 3 H).
MS: m/z = 326 (M+).
2-Butyl-5-(2-fluorophenyl)furan (13)
2-Butylfuran (0.124 g, 1 mmol) and 2-fluorobenzenesulfonyl chlo-
ride (0.343 g, 1.5 mmol) afforded 13 (0.194 g, 89%) as a yellow oil.
Anal. Calcd for C14H15IO (326.17): C, 51.55; H, 4.64; found: C,
51.47; H, 4.73.
2-Butyl-5-(4-fluorophenyl)furan (7)14
2-Butylfuran (0.124 g, 1 mmol) and 4-fluorobenzenesulfonyl chlo-
ride (0.343 g, 1.5 mmol) afforded 7 (0.070 g, 32%) as a colorless oil.
1H NMR (400 MHz, CDCl3): δ = 7.58 (dd, J = 8.6, 5.5 Hz, 2 H),
7.06 (t, J = 8.6 Hz, 2 H), 6.48 (d, J = 3.2 Hz, 1 H), 6.05 (d, J = 3.2
Hz, 1 H), 2.68 (t, J = 7.4 Hz, 2 H), 1.70 (quint, J = 7.4 Hz, 2 H), 1.42
(sext, J = 7.4 Hz, 2 H), 0.95 (t, J = 7.4 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.75–7.70 (m, 1 H), 7.10–6.95 (m,
3 H), 6.66 (d, J = 3.3 Hz, 1 H), 6.02 (d, J = 3.3 Hz, 1 H), 2.60 (t,
J = 7.4 Hz, 2 H), 1.58 (quint, J = 7.4 Hz, 2 H), 1.34 (sext, J = 7.4
Hz, 2 H), 0.86 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.4 (d, J = 248.7 Hz), 156.4,
146.1 (d, J = 3.0 Hz), 127.5 (d, J = 8.1 Hz), 125.6 (d, J = 3.3 Hz),
124.1 (d, J = 3.3 Hz), 119.5 (d, J = 12.1 Hz), 115.8 (d, J = 21.5 Hz),
111.0 (d, J = 11.8 Hz), 107.2, 30.2, 27.8, 22.3, 13.8.
2-Butyl-5-[3-(trifluoromethyl)phenyl]furan (9)
2-Butylfuran (0.124 g, 1 mmol) and 3-(trifluoromethyl)benzenesul-
fonyl chloride (0.367 g, 1.5 mmol) afforded 9 (0.166 g, 62%) as a
colorless oil.
MS: m/z = 218 (M+).
Anal. Calcd for C14H15FO (218.27): C, 77.04; H, 6.93; found: C,
77.10; H, 7.07.
1H NMR (400 MHz, CDCl3): δ = 7.77 (s, 1 H), 7.69 (m, 1 H), 7.40–
7.33 (m, 2 H), 6.54 (d, J = 3.2 Hz, 1 H), 6.00 (d, J = 3.2 Hz, 1 H),
2.61 (t, J = 7.4 Hz, 2 H), 1.60 (quint, J = 7.4 Hz, 2 H), 1.35 (sext,
J = 7.4 Hz, 2 H), 0.88 (t, J = 7.4 Hz, 3 H).
2-Butyl-5-naphthalen-1-ylfuran (14)15
2-Butylfuran (0.124 g, 1 mmol) and 1-naphthalenesulfonyl chloride
(0.340 g, 1.5 mmol) afforded 14 (0.110 g, 44%) as a yellow oil.
Synthesis 2014, 46, 2515–2523
© Georg Thieme Verlag Stuttgart · New York

PAPER
Pd-Catalyzed Direct Desulfitative Arylation of Furans
2521
1H NMR (400 MHz, CDCl3): δ = 8.46 (d, J = 8.2 Hz, 1 H), 7.88 (d,
J = 8.1 Hz, 1 H), 7.80 (d, J = 8.2 Hz, 1 H), 7.72 (d, J = 8.2 Hz, 1 H),
7.55–7.45 (m, 3 H), 6.63 (d, J = 3.2 Hz, 1 H), 6.18 (d, J = 3.2 Hz, 1
H), 2.77 (t, J = 7.4 Hz, 2 H), 1.76 (quint, J = 7.4 Hz, 2 H), 1.48 (sext,
J = 7.4 Hz, 2 H), 0.98 (t, J = 7.4 Hz, 3 H).
4-(3,6-Dimethyl-4,5,6,7-tetrahydrobenzofuran-2-yl)benzoni-
trile (22)14
Menthofuran (0.150 g, 1 mmol) and 4-cyanobenzenesulfonyl chlo-
ride (0.303 g, 1.5 mmol) afforded 22 (0.206 g, 82%) as a yellow sol-
id; mp 137–141 °C.
1H NMR (400 MHz, CDCl3): δ = 7.57 (d, J = 8.6 Hz, 2 H), 7.52 (d,
J = 8.6 Hz, 2 H), 2.70–2.60 (m, 1 H), 2.40–2.10 (m, 3 H), 2.10 (s, 3
H), 1.90–1.70 (m, 2 H), 1.40–1.10 (m, 1 H), 1.02 (d, J = 7.5 Hz, 3
H).
2-Butyl-5-(4-bromophenyl)furan (18)16
2-Butylfuran (0.124 g, 1 mmol) and 4-bromobenzenesulfonyl chlo-
ride (0.382 g, 1.5 mmol) afforded 18 (0.179 g, 64%) as a yellow sol-
id; mp 50–54 °C.
1H NMR (400 MHz, CDCl3): δ = 7.39 (d, J = 8.6 Hz, 2 H), 7.36 (d,
J = 8.6 Hz, 2 H), 6.44 (d, J = 3.2 Hz, 1 H), 5.95 (d, J = 3.2 Hz, 1 H),
2.57 (t, J = 7.4 Hz, 2 H), 1.56 (quint, J = 7.4 Hz, 2 H), 1.32 (sext,
J = 7.4 Hz, 2 H), 0.86 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 157.2, 151.3, 131.9, 130.4, 125.0,
120.5, 107.3, 106.5, 30.4, 28.1, 22.5, 14.1.
3,6-Dimethyl-2-[4-(trifluoromethyl)phenyl]-4,5,6,7-tetrahydro-
benzofuran (23)
Menthofuran (0.150 g, 1 mmol) and 4-(trifluoromethyl)benzenesul-
fonyl chloride (0.367 g, 1.5 mmol) afforded 23 (0.229 g, 78%) as a
yellow solid; mp 75–78 °C.
1H NMR (400 MHz, CDCl3): δ = 7.59 (d, J = 8.6 Hz, 2 H), 7.51 (d,
J = 8.6 Hz, 2 H), 2.70–2.60 (m, 1 H), 2.40–2.10 (m, 3 H), 2.09 (s, 3
H), 1.90–1.70 (m, 2 H), 1.40–1.20 (m, 1 H), 1.02 (d, J = 7.5 Hz, 3
H).
13C NMR (100 MHz, CDCl3): δ = 150.7, 145.4, 135.6, 127.3 (q, J =
32.5 Hz), 125.4 (q, J = 3.9 Hz), 124.4, 124.3 (q, J = 271.8 Hz),
120.3, 118.4, 31.4, 31.2, 29.6, 21.4, 19.9, 10.0.
5-[4-(5-Butylfuran-2-yl)phenyl]-2-ethyl-4-methylthiazole (19)
Compound 18 (0.140 g, 0.5 mmol), 2-ethyl-4-methylthiazole (0.127
g, 1 mmol), and AcOK (0.147 g, 1.5 mmol) was reacted at 130 °C
during 20 h in DMA (3 mL) in the presence of PdCl(C3H5)(dppb)
complex (6.1 mg, 0.01 mmol) under argon; evaporation of the sol-
vent and filtration (silica gel, pentane–Et2O) (0.154 g, 95%) afford-
ed 19 as a yellow oil.
MS: m/z = 294 (M+).
1H NMR (400 MHz, CDCl3): δ = 7.55 (d, J = 8.6 Hz, 2 H), 7.30 (d,
J = 8.6 Hz, 2 H), 6.47 (d, J = 3.2 Hz, 1 H), 5.97 (d, J = 3.2 Hz, 1 H),
2.90 (q, J = 7.4 Hz, 2 H), 2.59 (t, J = 7.4 Hz, 2 H), 2.39 (s, 3 H), 1.59
(quint, J = 7.4 Hz, 2 H), 1.32 (sext, J = 7.4 Hz, 2 H), 1.29 (t, J = 7.4
Hz, 3 H), 0.86 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 170.1, 156.9, 151.6, 147.0, 130.9,
130.7, 130.4, 129.3, 123.5, 107.1, 106.3, 30.3, 28.0, 27.0, 22.4,
16.3, 14.4, 13.9.
Anal. Calcd for C17H17F3O (294.31): C, 69.38; H, 5.82; found: C,
69.37; H, 5.90.
2-(4-Chlorophenyl)-3,6-dimethyl-4,5,6,7-tetrahydrobenzofu-
ran (24)
Menthofuran (0.150 g, 1 mmol) and 4-chlorobenzenesulfonyl chlo-
ride (0.317 g, 1.5 mmol) afforded 24 (0.164 g, 63%) as a yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.43 (d, J = 8.6 Hz, 2 H), 7.24 (d,
J = 8.6 Hz, 2 H), 2.70–2.58 (m, 1 H), 2.40–2.10 (m, 3 H), 2.05 (s, 3
H), 1.90–1.70 (m, 2 H), 1.40–1.20 (m, 1 H), 1.01 (d, J = 7.5 Hz, 3
H).
13C NMR (100 MHz, CDCl3): δ = 150.0, 145.9, 131.7, 131.1, 128.8,
126.2, 120.2, 116.8, 31.6, 31.5, 29.9, 21.7, 20.2, 10.1.
MS: m/z = 325 (M+).
Anal. Calcd for C20H23NOS (325.47): C, 73.81; H, 7.12; found: C,
73.99; H, 7.20.
3,6-Dimethyl-2-phenyl-4,5,6,7-tetrahydrobenzofuran (20)
Menthofuran (0.150 g, 1 mmol) and benzenesulfonyl chloride
(0.264 g, 1.5 mmol) afforded 20 (0.138 g, 61%) as a yellow solid;
mp 85–88 °C.
MS: m/z = 260 (M+).
Anal. Calcd for C16H17ClO (260.76): C, 73.70; H, 6.57; found: C,
73.61; H, 6.66.
1H NMR (400 MHz, CDCl3): δ = 7.51 (d, J = 8.0 Hz, 2 H), 7.29 (t,
J = 8.0 Hz, 2 H), 7.11 (t, J = 8.0 Hz, 1 H), 2.70–2.60 (m, 1 H), 2.40–
2.10 (m, 3 H), 2.08 (s, 3 H), 1.90–1.70 (m, 2 H), 1.40–1.20 (m, 1 H),
1.01 (d, J = 7.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 149.7, 146.9, 132.7, 128.6, 126.2,
125.2, 120.0, 116.3, 31.6, 31.5, 29.9, 21.7, 20.3, 10.0.
2-(4-Bromophenyl)-3,6-dimethyl-4,5,6,7-tetrahydrobenzofu-
ran (25)
Menthofuran (0.150 g, 1 mmol) and 4-bromobenzenesulfonyl chlo-
ride (0.382 g, 1.5 mmol) afforded 25 (0.232 g, 76%) as a yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.40 (d, J = 8.6 Hz, 2 H), 7.36 (d,
J = 8.6 Hz, 2 H), 2.70–2.60 (m, 1 H), 2.40–2.10 (m, 3 H), 2.05 (s, 3
H), 2.00–1.75 (m, 2 H), 1.40–1.25 (m, 1 H), 1.02 (d, J = 7.5 Hz, 3
H).
13C NMR (100 MHz, CDCl3): δ = 150.1, 145.9, 131.7, 131.5, 126.5,
120.2, 119.7, 117.0, 31.6, 31.4, 29.8, 21.7, 20.2, 10.1.
MS: m/z = 226 (M+).
Anal. Calcd for C16H18O (226.31): C, 84.91; H, 8.02; found: C,
84.99; H, 7.89.
2-(4-Nitrophenyl)-3,6-dimethyl-4,5,6,7-tetrahydrobenzofuran
(21)
MS: m/z = 304 (M+).
Menthofuran (0.150 g, 1 mmol) and 4-nitrobenzenesulfonyl chlo-
ride (0.332 g, 1.5 mmol) afforded 21 (0.217 g, 80%) as a yellow oil.
Anal. Calcd for C16H17BrO (305.21): C, 62.96; H, 5.61; found: C,
63.07; H, 5.48.
1H NMR (400 MHz, CDCl3): δ = 8.22 (d, J = 8.6 Hz, 2 H), 7.71 (d,
J = 8.6 Hz, 2 H), 2.80–2.60 (m, 1 H), 2.50–2.24 (m, 3 H), 2.23 (s, 3
H), 2.00–1.80 (m, 2 H), 1.50–1.30 (m, 1 H), 1.12 (d, J = 7.5 Hz, 3
H).
13C NMR (100 MHz, CDCl3): δ = 152.4, 145.1, 145.0, 138.4, 124.3,
124.2, 121.2, 121.1, 31.6, 31.2, 29.2, 21.5, 120.0, 10.5.
2-(4-Iodophenyl)-3,6-dimethyl-4,5,6,7-tetrahydrobenzofuran
(26)
Menthofuran (0.150 g, 1 mmol) and 4-iodobenzenesulfonyl chlo-
ride (0.453 g, 1.5 mmol) afforded 26 (0.229 g, 65%) as a yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.58 (d, J = 8.6 Hz, 2 H), 7.23 (d,
J = 8.6 Hz, 2 H), 2.65–2.55 (m, 1 H), 2.35–2.05 (m, 3 H), 2.03 (s, 3
H), 1.90–1.70 (m, 2 H), 1.35–1.20 (m, 1 H), 1.00 (d, J = 7.5 Hz, 3
H).
13C NMR (100 MHz, CDCl3): δ = 150.2, 145.9, 137.7, 132.1, 126.7,
120.3, 117.2, 91.0, 31.6, 31.4, 29.9, 21.7, 20.2, 10.1.
MS: m/z = 271 (M+).
Anal. Calcd for C16H17NO3 (271.31): C, 70.83; H, 6.32; found: C,
70.99; H, 6.48.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2515–2523

2522
A. Beladhria et al.
PAPER
MS: m/z = 352 (M+).
2.70–2.55 (m, 1 H), 2.40–2.20 (m, 3 H), 1.88 (s, 3 H), 1.85–1.70 (m,
2 H), 1.40–1.20 (m, 1 H), 0.97 (d, J = 7.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.9 (d, J = 248.8 Hz), 150.6,
141.9, 129.6 (d, J = 3.2 Hz), 128.5 (d, J = 7.9 Hz), 123.9 (d, J = 4.0
Hz), 120.1 (d, J = 14.3 Hz), 119.3, 118.5, 116.0 (d, J = 22.2 Hz),
31.4, 31.2, 29.6, 21.5, 20.1, 9.1 (d, J = 7.2 Hz).
Anal. Calcd for C16H17IO (352.21): C, 54.56; H, 4.86; found: C,
54.60; H, 5.00.
2-(4-Fluorophenyl)-3,6-dimethyl-4,5,6,7-tetrahydrobenzofu-
ran (27)14
Menthofuran (0.150 g, 1 mmol) and 4-fluorobenzenesulfonyl chlo-
ride (0.343 g, 1.5 mmol) afforded 27 (0.171 g, 70%) as a yellow oil.
MS: m/z = 244 (M+).
1H NMR (400 MHz, CDCl3): δ = 7.47 (dd, J = 8.6, 5.3 Hz, 2 H),
6.99 (t, J = 8.6 Hz, 2 H), 2.70–2.60 (m, 1 H), 2.40–2.10 (m, 3 H),
2.05 (s, 3 H), 2.00–1.75 (m, 2 H), 1.40–1.25 (m, 1 H), 1.02 (d, J =
7.5 Hz, 3 H).
Anal. Calcd for C16H17FO (244.30): C, 78.66; H, 7.01; found: C,
78.47; H, 7.11.
Acknowledgement
2-(3-Chlorophenyl)-3,6-dimethyl-4,5,6,7-tetrahydrobenzofu-
ran (28)
Menthofuran (0.150 g, 1 mmol) and 3-chlorobenzenesulfonyl chlo-
ride (0.317 g, 1.5 mmol) afforded 28 (0.177 g, 68%) as a yellow oil.
We thank the ministère de la recherche for a fellowship to K. Y. and
the Centre National de la Recherche Scientifique, UTIQUE and
‘Rennes Metropole’ for providing financial support.
1H NMR (400 MHz, CDCl3): δ = 7.48 (s, 1 H), 7.37 (d, J = 8.2 Hz,
1 H), 7.19 (t, J = 8.2 Hz, 1 H), 7.06 (d, J = 8.2 Hz, 1 H), 2.70–2.58
(m, 1 H), 2.40–2.10 (m, 3 H), 2.06 (s, 3 H), 1.90–1.70 (m, 2 H),
1.40–1.20 (m, 1 H), 1.01 (d, J = 7.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 150.4, 145.5, 134.7, 134.3, 129.9,
126.0, 124.9, 122.9, 120.3, 117.6, 31.6, 31.4, 29.9, 21.7, 20.2, 10.1.
Supporting Information for this article is available online
at
http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000084.SunogIpimrfiantoSuIpg
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References
MS: m/z = 260 (M+).
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2-(2-Cyanophenyl)-3,6-dimethyl-4,5,6,7-tetrahydrobenzofuran
(30)
Menthofuran (0.150 g, 1 mmol) and 2-cyanobenzenesulfonyl chlo-
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1H NMR (400 MHz, CDCl3): δ = 7.57 (d, J = 8.0 Hz, 1 H), 7.45 (t,
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