Silver-catalyzed direct couplings of 2-substituted furans with cyclic 1,3-dicarbonyls

Article abstract of DOI:10.1016/j.jorganchem.2007.08.011

Direct alkenylation of 2-substituted furans with cyclic 1,3-dicarbonyls by means of silver catalysis have been explored. Silver salts resulted more efficient than a variety of Lewis acids and p-TsOH.

Full text of DOI:10.1016/j.jorganchem.2007.08.011

Journal of Organometallic Chemistry 692 (2007) 5322–5326
www.elsevier.com/locate/jorganchem
Note
Silver-catalyzed direct couplings of 2-substituted furans
with cyclic 1,3-dicarbonyls
*
Antonio Arcadi , Maria Alfonsi, Fabio Marinelli
Dipartimento di Chimica Ingegneria Chimica e Materiali della Facolta` di Scienze, Universita` di L’Aquila,
Via Vetoio, Coppito Due, I-67100 L’Aquila, Italy
Received 23 July 2007; received in revised form 8 August 2007; accepted 8 August 2007
Available online 15 August 2007
Abstract
Direct alkenylation of 2-substituted furans with cyclic 1,3-dicarbonyls by means of silver catalysis have been explored. Silver salts
resulted more efficient than a variety of Lewis acids and p-TsOH.
Ó 2007 Elsevier B.V. All rights reserved.
Keywords: Silver catalysis; 1,3-Dicarbonyl compounds; C–C bond formation; Furans
1. Introduction
sis. Resin bound b-alkoxy-a,b-enone could, also, be trans-
formed into the corresponding vinyl triflates which
undergo palladium-mediated couplings with orgaboron
derivatives and hydrolysis to give the corresponding alke-
nyl furan derivatives [5]. Hereafter we report that func-
tionalisation of 2-substituted furans can be accomplished
directly through their silver-catalyzed reaction with cyclic
1,3-dicarbonyls.
C–H substitution reactions of heterocyclic derivatives
are an enduring challenge for organic chemists [1]. Particu-
lar focus is devoted on developing new methods to couple
electron rich arenes with carbonyl compounds [2]. We have
successfully applied the catalysis by gold for the cross cou-
pling reaction of indoles/pyrroles with 1,3-dicarbonyl com-
pounds leading the corresponding alkenyl derivatives
(Scheme 1) [3].
2. Results and discussion
As an extension of our studies on this chemistry, we
decided to investigate the alkenylation of furans. To the
best of our knowledge the direct functionalisation of fur-
ans with 1,3-dicarbonyls has not been reported. Accord-
ing to the literature, the target alkenyl derivatives have
been synthesized through a multistep procedure involving
the conversion of 1,3-dicarbonyl compounds into their 3-
alkoxy-2-alkenone derivatives which subsequently gave
the final products by reacting with lithiathed furans [4].
A different route entailed the synthesis of b-furyl-a,b-
enones by addition of organolithium or Grignard reagents
to a resin bound b-alkoxy-a,b-enone followed by hydroly-
To begin our study, we imagined that the results of the
gold-catalyzed alkenylation reaction of indoles/pyrroles
with 1,3-dicarbonyl compounds could be extended to an
analogous coupling of furans. These derivatives have been
reported to hydroarylate alkynes [6], allenyl ketones [7],
a,b-unsaturated carbonyl compounds [8], and imines [9]
in intermolecular gold-catalyzed reactions. Moreover,
cycloisomerization of alkynyl furans afforded the exo
cyclization products by means of Hg(OAc)2 Æ 0.1Sc(OTf)3
catalytic system [10]. We expected that the direct coupling
would link furans to 1,3-dicarbonyl derivatives to their
more nucleophilic a-position. However, by reacting 2-
methylfuran (1a) with 1,3-cyclohexanedione (2a) (Scheme
2) in dichlorethane (DCE) at 80 °C in the presence of the
*
Corresponding author. Tel.: +39 0 862433774; fax: +39 0 862433753.
E-mail address: arcadi@univaq.it (A. Arcadi).
0022-328X/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2007.08.011

A. Arcadi et al. / Journal of Organometallic Chemistry 692 (2007) 5322–5326
5323
in poor yield (Table 1, entry 5). Whereas AuCl alone
was unreactive (Table 1, entry 6), the combination
AuCl/AgOTf led to the desired product 3a in 57% (Table
1, entry 8). PPh3AuOTf proved to catalyze the reaction,
but with a far lower efficiency (Table 1, entry 7). A con-
trol experiment employing AgOTf (10 mol%) as the sole
catalyst under the same reaction conditions produced 3a
in 60% yield. Besides gold derivatives, other Lewis acids
such as Cu(OTf)2, FeCl3 Æ 6H2O and ZnCl2 resulted less
efficient than AgOTf in the coupling reaction of 1a with
2a. In addition a catalytic amount of the Brønsted acid
p-TsOH allowed the production of 3a, albeit only in
28% yield. These results are in contrast with those
observed in the condensation of furans with carbonyl
compounds [4]. Furans have been reported to undergo a
twofold condensation with carbonyl compounds and the
reaction was efficiently promoted by gold as well as mer-
cury, thallium and p-toluenesulphonic acid. In view of
their low cost and simplicity we examined a variety of sil-
ver derivatives. Whereas Ag2O and AgNO3 resulted not
effective, herein we report that other silver salts can pro-
mote the alkenylation of 1a in satisfactory yield (Table
1, entries 17–21) and AgClO4 Æ H2O gave the same result
of AgOTf. This finding is especially noteworthy as silver
based catalysts have not been used extensively. They are
commonly employed as innocent anion exchange agents
for the in situ generation of cationic transition (and other)
metal catalysts [11].
O
R
W
W
N
Y
O
O
N
Y
Au catalyst
R
O
W1
R
W2
W1
W2
N
H
N
H
Scheme 1.
O
O
Catalyst
+
O
O
O
3a
2a
1a
Scheme 2.
catalytic system AuBr3/2AgOTf (5 mol% based on gold)
we observed the regioselective formation of the coupling
derivative 3-(5-methyl-furan-2-yl)-cyclohexen-2-one 3a,
but in disappointing 13% yield (Table 1, entry 1). Simi-
larly, 3a was isolated in low yields by using Au(III) and
Au(I) catalysts (Table 1, entries 2–4, 6). Increasing the
reaction temperature resulted also the formation of 3a
Only recently Ag-catalyzed reactions are emerging as
important synthetic methods for a variety of organic trans-
formations [12]. In comparison with other transition met-
als, silver is still in its infancy [13]. Then we set up to
explore the scope of the silver-catalyzed coupling process
of 2-substituted furans with other cyclic 1,3-diketones
and the results are summarized in Table 2.
Table 1
Alkenylationa of 1a with 2a
Entry
1a/2a
Solvent Catalyst
Temperature Yield of
It is clear from our results that the silver-catalyzed reac-
tion of 2-substituted furans with cyclic 1,3-diketones pro-
vides an alternative more simple approach to the
synthesis of 2-alkenylfurans in comparison with the exist-
ing methodologies. Previously, 1,3-diketones have been
reported to give a highly efficient silver-catalyzed inter-
and intramolecular hydroalkylation reaction on unsatu-
rated organic substrates [14]. By contrast, in all the cases
we examined we observed only C–C coupling reaction on
the carbonyl moiety. Overall the oxidative properties of sil-
ver catalysts may direct a stronger coordination than gold
ones to the oxygen atom of the carbonyl function [15]. It is
reasonable to assume that activation of the carbonyl group,
followed by a Friedel-Crafts-type reaction could be respon-
sible of the formation of the corresponding alkenyl deriva-
tive. The stronger activation by silver determines its better
efficiency in the alkenylation of 2-substituted furans. This
latter derivatives are reported to react more slowly than
indoles/pyrroles with electrophilic reagents.
(°C)/time (h) 3a (%)
1
2
3
4
5
6
7
8
0.5
0.5
0.5
2.0
0.5
2.0
2.0
2.0
0.5
2.0
3.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
DCE
DCE
AuBr3/AgOTf
AuBr3
80/24
80/24
13
–
MeCN NaAuCl4 Æ 2H2O 80/24
MeCN NaAuCl4 Æ 2H2O 120/3.5
19
10
25
–
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
AuBr3/AgOTf
AuCl
Ph3AuOTf
AuCl/AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
Cu(OTf)2
FeCl3 Æ H2O
ZnCl2
p-TsOH
AgClO4 Æ H2O
AgClO4
AgNTf2
AgSbF6
AgBF4
140/1
120/3.5
120/3.5
120/3.5
80/24
80/24
80/24
120/3.5
120/3.5
120/3.5
120/3.5
120/3.5
120/3.5
120/3.5
120/3.5
120/3.5
120/3.5
120/3.5
120/3.5
13
57
26
51
63
60
40
23
12
28
60
47
46
43
30
–
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
a
AgNO3
Ag2O
In conclusion, we have shown that the traditional step-
wise formation of a-alkenyl furans can be replaced by
one-step procedure by means of silver catalysis. Additional
–
Yields refer to single runs, and are given for pure isolated 3a.

5324
A. Arcadi et al. / Journal of Organometallic Chemistry 692 (2007) 5322–5326
Table 2
Silver-catalyzed alkenylation of 2-substituted furansa with cyclic 1,3-dicarbonyl compounds
Entry
1
HetAr-H 1
1,3-Dicarbonyl 2
Time (h)
3.5
Product 3
Yield (%)b
60
O
O
O
O
1a
O
2a
3a
2
1a
5.5
64
O
O
O
O
O
Ph
2b
Ph
3b
3
1a
7.0
40
O
O
2c
3c
4
5
2a
1.5
3.0
82
88
O
O
O
O
O
1b
3d
1b
2b
Ph
3e
6
1b
2c
7.5
56
O
O
O
O
3f
7
1b
2.0
85
O
O
2d
3g
70c
O
8
2a
2.0
Ph
O
Ph
O
1c
3h
a
Reactions were carried out by using the following molar ratios and at 120 °C: 1:2:AgOTf = 2:1:0.1 in ClCH2CH2Cl.
Yield of pure isolated product.
Molar ratios: 1c:2a:AgOTf = 2:1:0.5.
b
c
advantages towards the previous reported procedures of
condensations of electron rich heteroarenes with carbonyl
compounds are represented by the lower toxicity of silver
catalyst compared to Tl and Hg derivatives. The silver salts
are more active than gold catalysts in promoting the alke-
nylation of furans.

A. Arcadi et al. / Journal of Organometallic Chemistry 692 (2007) 5322–5326
5325
3. Experimental
150.8, 155.7, 199.3. MS (70 EV, EI, relative intensity):
204 (M+, 96), 189 (11), 176 (24), 148 (100), 120 (54). ESI-
HRMS calculated for C13H17O2: 205.1229. Found:
205.1218%.
Temperatures are reported as bath temperature. Com-
pounds were visualized on analytical thin-layer chromato-
grams (TLC) by UV light (254 nm). The products, after
usual work-up, were purified by flash chromatography on
silica gel (230–400 mesh) eluting with n-hexane/ethyl ace-
tate mixtures. These solvents were distilled prior to use.
1H NMR and 13C NMR spectra were recorded with a Bru-
ker AC 200 E spectrometer. EI (70 eV). Mass spectra were
recorded with a Varian Saturn 2100 T GC/MS instrument
and ESI accurate mass measurements were recorded with a
Mass spectrometer Finnigan TSQ Quantum Ultra with
accurate mass options instrument. IR were recorded with
a Perkin–Elmer 683 spectrometer. Only the most signifi-
cant IR absorptions are given. All starting materials, cata-
lysts, and solvents if not otherwise stated, are commercially
available and were used as purchased, without further puri-
fication. The 2-phenylfuran 1c, was prepared by published
procedure [16]. The product 3a [17] is known and was
determined using comparison of its physical and spectral
data with those reported in the literature.
3.4. 3-(4,5-Dimethyl-furan-2-yl)-cyclohex-2-enone (3d)
IR (neat): m = 1680, 1640, 1590, 740 cmÀ1 1H NMR
.
(CDCl3, 200 MHz) d = 1.96 (s, 3H), 2.03–2.13 (m, 2H),
2.24 (s, 3H), 2.42 (t, J = 5.9 Hz, 2H), 2.57 (t, J = 6.2 Hz,
2H), 6.36 (s, 1H), 6.55 (s, 1H). 13C NMR (CDCl3,
50.3 MHz) d = 9.4, 11.4, 22.2, 24.9, 37.2, 116.3, 117.3,
118.9, 147.0, 148.9, 151.2, 198.9. MS (70 EV, EI, relative
intensity): 190 (M+, 100), 162 (60), 134 (43). ESI-HRMS
calculated for C12H15O2: 191.1072. Found: 191.1065%.
3.5. 3-(4,5-Dimethyl-furan-2-yl)-5-phenyl-cyclohex-2-enone
(3e)
1
IR (neat): m = 1695, 1625, 1580, 745 cmÀ1.; H NMR
(CDCl3, 200 MHz) d = 1.95 (s, 3H), 2.25 (s, 3H), 2.62–
2.95 (m, 4H), 3.30–3.40 (m, 1H), 6.46 (d, J = 1.7 Hz,
1H), 6.55 (s, 1H), 7.25–7.40 (m, 5H). 13C NMR (CDCl3,
50.3 MHz) d = 9.7, 11.7, 33.1, 40.6, 44.3, 116.9, 117.7,
118.8, 126.7, 127.0, 128.7, 143.3, 146.3, 148.9, 151.9,
198.6. MS (70 EV, EI, relative intensity): 267 [(M+1)+,
100]. ESI-HRMS calculated for C18H19O2: 267.1380.
Found: 267.1376%.
3.1. General procedure for the silver-catalyzed alkenylation
of 2-substituted furans 1 with cyclic 1,3-dicarbonyls (2)
To a solution of the furan derivative 1 (1 mmol) in
ClCH2CH2Cl (2 mL) were added the cyclic 1,3-dicarbonyl
compound 2 (2 mmol) and AgOTf or AgClO4 Æ H2O
(0.10 mmol). The mixture was stirred at 120 °C for the
appropriate time and monitored by TLC or GC–MS. After
completion, the solvent was removed by evaporation. The
residue was purified by chromatography on silica gel
(230–400 mesh) eluting with n-hexane/ethyl acetate mix-
tures to afford the pure derivative 3.
3.6. 3-(4,5-Dimethyl-furan-2-yl)- 5,5-dimethyl-cyclohex-2-
enone (3f)
IR (neat): m = 1700, 1640, 1580 cmÀ1. 1H NMR (CDCl3,
200 MHz) d = 1.08 (s, 6H), 1.96 (s, 2H), 2.25 (s, 3H), 2.28
(s, 3H), 2.45 (s, 2H), 6.38 (s, 1H), 6.56 (s, 1H). 13C NMR
(CDCl3, 50.3 MHz) d = 9.7, 11.7, 28.3, 33.3, 39.1, 51.2,
116.4, 117.5, 118.2, 145.1, 149.5, 151.5, 199.3. MS (70
EV, EI, relative intensity): 219 [(M+1)+, 100]. ESI-HRMS
calculated for C14H19O2: 219.1385. Found: 219.1384%.
3.2. 3-(5-Methyl-furan-2-yl)-5-phenyl-cyclohex-2-enone
(3b)
IR (neat): m = 1700, 1600, 1540, 740 cmÀ1 1H NMR
.
(CDCl3, 200 MHz) d = 2.34 (s, 3H), 2.64–2.91 (m, 4H),
3.35–3.45 (m, 1H), 6.11 (d, J = 3.3 Hz, 1H), 6.49 (d,
J = 1.9 Hz, 1H), 6.64 (d, J = 3.3 Hz, 1H), 7.26–735 (m,
5H). 13C NMR (CDCl3, 50.3 MHz) d = 33.1, 40.5, 44.2,
108.9, 114.4, 119.3, 126.7, 127.0, 128.7, 143.2, 146.2,
150.3, 156.0, 198.6. MS (70 EV, EI, relative intensity):
253 [(M+1)+, 100], 148 (43). ESI-HRMS calculated for
C17H17O2: 253.1229. Found: 253.1233%.
3.7. 3-(4,5-Dimethyl-furan-2-yl)-5-methyl-cyclohex-2-enone
(3g)
IR (neat): m = 1680, 1640, 1560 cmÀ1. 1H NMR (CDCl3,
200 MHz) d = 1.13 (d, J = 5.9 Hz, 3H), 1.96 (s, 3H), 2.10–
2.17 (m, 2H), 2.25 (s, 3H), 2.50 (d, J = 14.8 Hz, 1H), 2.70
(d, J = 13.2 Hz, 1H), 6.37 (s, 1H), 6.56 (s, 1H). 13C
NMR (CDCl3, 50.3 MHz) d = 9.7, 11.7, 21.2, 29.7, 33.4,
45.7, 116.4, 117.5, 119.0, 146.5, 149.3, 151.5, 199.5. MS
(70 EV, EI, relative intensity): 205 [(M+1)+, 100]. ESI-
HRMS calculated for C13H17O2: 205.1229. Found:
205.1217%.
3.3. 5,5-Dimethyl-3-(5-methyl-furan-2-yl)-cyclohex-2-enone
(3c)
IR (neat): m = 1710, 1595, 1540, 760 cmÀ1 1H NMR
.
(CDCl3, 200 MHz) d = 1.09 (s, 6H), 2.29 (s, 2H), 2.35 (s,
3H), 2.47 (s, 2H), 6.12 (d, J = 3.3 Hz, 1H), 6.42 (s, 1H),
6.65 (d, J = 3.3 Hz, 1H). 13C NMR (CDCl3, 50.3 MHz)
d = 13.7, 28.2, 33,3, 39.0, 51.1, 108.8, 113.9, 118.5, 145.0,
3.8. 3-(5-Phenyl-furan-2-yl)-cyclohex-2-enone (3h)
IR (neat): m = 1700, 1690, 1600, 745, 640 cmÀ1
NMR (CDCl3, 200 MHz) d = 2.05–2.19 (m, 2H), 2.49 (t,
.
1H

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A. Arcadi et al. / Journal of Organometallic Chemistry 692 (2007) 5322–5326
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J = 6.6 Hz, 2H), 2.69 (t, J = 5.9 Hz, 2H),.6.60 (s, 1H), 6.77
(d, J = 3.6 Hz, 1H), 6.82 (d, J = 3.6 Hz, 1H), 7.38–7.42 (m,
3H), 7.70–7.74 (m, 2H). 13C NMR (CDCl3, 50.3 MHz)
d = 22.5, 25.2, 37.5, 107.6, 114.9, 120.7, 123.5, 124.3,
128.5, 128.8, 146.8, 151.4, 156.4, 199.2. MS (70 EV, EI, rel-
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for C16H15O2: 239.1072. Found: 239.1076%.
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Acknowledgements
The work was supported by the Ministero dell’Univer-
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`
sita e della Ricerca Scientifica e Tecnologica, Rome, and
by the University of L’Aquila (Italy).
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