Palladium-catalyzed dehydrogenative coupling of furans with styrenes

Article abstract of DOI:10.1021/ol901570p

Under palladium(II)-catalyzed and oxidative conditions, the coupling of furans with styrenes leads to the formation of Heck-type products In medium to good yields. The reaction Is highly regio- and stereoselective, giving frans-olefins predominantly.

Full text of DOI:10.1021/ol901570p

ORGANIC
LETTERS
2009
Vol. 11, No. 18
4096-4099
Palladium-Catalyzed Dehydrogenative
Coupling of Furans with Styrenes
Chahinez Aouf, Emilie Thiery, Jean Le Bras,* and Jacques Muzart
Institut de Chimie Mole´culaire de Reims, UMR 6229, CNRS-UniVersite´ de Reims
Champagne-Ardenne, UFR des Sciences exactes et naturelles,
BP 1039, 51687 Reims Cedex 2, France
jean.lebras@uniV-reims.fr
Received July 10, 2009
ABSTRACT
Under palladium(II)-catalyzed and oxidative conditions, the coupling of furans with styrenes leads to the formation of Heck-type products in
medium to good yields. The reaction is highly regio- and stereoselective, giving trans-olefins predominantly.
The formation of C-C bonds plays an important role in
organic synthesis but usually requires prefunctionalized
starting materials. Dehydrogenative couplings,1 in which two
C-H bonds react to form C-C bonds, have the potential to
lead to mild, general, and selective methodologies able to
make already known or new chemical transformations
environmentally sustainable. Among such transformations,
the intermolecular coupling of arenes and alkenes, also called
“oxidative Heck reaction”, introduced by Fujiwara,2 has gain
interest these past years.3 Progress has been achieved on the
regioselectivity,4 the use of oxygen as the reoxidant,4b,c,5 the
heterogenization of the catalyst,6 and the functionalization
of acid-sensitive arenes,4c,f,6a,c or unactivated arenes.7 Despite
these advances, the use of olefins bearing an electron-
withdrawing group, such as acrylates, acrylamides, acry-
lonitriles, and R,ꢀ-unsaturated carbonyl derivatives, is gen-
erally required to achieve fair yields. Styrenes are more
electron-rich compounds than acrylates and are a notoriously
difficult substrate class due to facile polymerization and
cleavage under palladium oxidative conditions.8 Examples
of oxidative Heck reactions have been reported using
styrenes, but with low yields (<40%)4a,b,5b,c,9 or with poor
substrates scope.4f,7b,10 Among the arenes studied, furans
have received less attention, probably because of their high
sensitivity to protic conditions, which are generally used for
(1) Ferreira, E. M.; Zhang, H.; Stoltz, B. M. Tetrahedron 2008, 64, 5987.
(2) Jia, C.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 34, 633.
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2007, 129, 7666. (b) Wang, J.-R.; Yang, C.-T.; Liu, L.; Guo, Q.-X.
Tetrahedron Lett. 2007, 48, 5449. (c) Beck, E. M.; Grimster, N. P.; Hatley,
R.; Gaunt, M. J. J. Am. Chem. Soc. 2006, 128, 2528. (d) Lee, G. T.; Jiang,
X.; Prasad, K.; Repicˇ, O.; Blacklock, T. J. AdV. Synth. Catal. 2005, 347,
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(f) Grimster, N. P.; Gauntlett, C.; Godfrey, C. R. A.; Gaunt, M. J. Angew.
Chem., Int. Ed. 2005, 44, 3125. (g) Boele, M.; van Strijdonck, G.; de Vries,
A.; Kamer, P.; de Vries, J.; van Leeuwen, P. J. Am. Chem. Soc. 2002, 124,
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J.; Dams, M.; Detrembleur, C.; Je´roˆme, R.; Jacobs, P. A.; De Vos, D. E.
Catal. Commun. 2007, 8, 1047. (c) Djakovitch, L.; Rouge, P. J. Mol. Catal.
A: Chem. 2007, 273, 230.
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131, 5072. (b) Cho, S. H.; Hwang, S. J.; Chang, S. J. Am. Chem. Soc.
2008, 130, 9254.
(8) Cornell, C. N.; Sigman, M. S. Inorg. Chem. 2007, 46, 1903.
(9) (a) Maehara, A.; Satoh, T.; Miura, M. Tetrahedron 2008, 64, 5982.
(b) Amatore, C.; Cammoun, C.; Jutand, A. AdV. Synth. Catal. 2007, 349,
292. (c) Jia, C.; Lu, W.; Kitamura, T.; Fujiwara, Y. Org. Lett. 1999, 1,
(5) (a) Yamada, T.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2005, 70,
5471. (b) Tani, M.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2004, 69, 1221.
(c) Yokota, T.; Tani, M.; Sakaguchi, S.; Ishii, Y. J. Am. Chem. Soc. 2003,
125, 1476. (d) Dams, M.; De Vos, D. E.; Celen, S.; Jacobs, P. A. Angew.
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10.1021/ol901570p CCC: $40.75
Published on Web 08/19/2009
 2009 American Chemical Society

Table 1. Optimization of the Coupling of 2-Methylfuran (1a) with Styrene (2a)a
entry
R
cosolvent
Pd(II)
oxidant
yield (%)b
1
2
3
4
5
6
7
8
9
Me
Me
Me
Me
Me
Me
Et
Et
Et
Et
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OCOCF3)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
BQ (2.0 equiv)
BQ (2.0 equiv)
BQ (2.0 equiv)
BQ (2.0 equiv)
BQ (2.0 equiv)
<5
43
40
55
CH2Cl2
EtOAc
Et2O
Et2O
Et2O
Et2O
Et2O
THF
dioxane
51
BQ (10 mol %), Cu(OAc)2 (50 mol %), aird
43-54
65c
60
56
55
d
BQ (10 mol %),Cu(OAc)2 (50 mol %), O2
Cu(OAc)2 (50 mol %), O2
BQ (10 mol %), Cu(OAc)2 (50 mol %), O2
BQ (10 mol %), Cu(OAc)2 (50 mol %), O2
d
d
d
10
a 1a (1.1 mmol), 2a (1.0 mmol), Pd(II) (0.05 mmol), RCO2H (2 mL), cosolvent (2 mL), 40 °C, 24 h. b Isolated yield. c E/Z > 99.9, determined by GC.
d Gas bag.
oxidative Heck reactions. Only few examples are reported,
compounds were obtained as E-isomers. The formation of
palladium black, in certain cases, leads to partial conversions.
π-Acidic alkene ligands, such as dibenzylidene acetone (dba),
can influence Pd-catalyzed cross-coupling reactions, interacting
with both palladium(0) and palladium(II) intermediates.13
Indeed, we have observed less formation of Pd black and full
conversion in the presence of dba as additive (3ab, 3ac). Such
compound probably stabilizes Pd(0) species13 and prevents their
agglomeration leading to insoluble Pd(0). We suspect that when
the Pd deposit was not observed, compounds 3 play a similar
role and act as efficient ligands for Pd(0). The use of 25% BQ
also prevented the formation of Pd black and led to quantitative
conversions and fair yields (3cb, 3cc, 3cd, 3ce, 3da, 3dg, 3ea,
3eb, 3ec). BQ acts probably as an electron-transfer mediator
between the catalyst and the oxidant and facilitates the overall
transformation.14 As observed earlier with acrylates, in the
reaction of 2-substituted furans bearing either an electron-
donating group (1a, 1b) or an electron-withdrawing group (1e),
the coupling takes place at C5.11a Chlorinated and fluorinated
styrenes undergo coupling leaving the carbon-halogen bond
intact (3ab, 3ac, 3af, 3bf, 3cb, 3cc, 3eb, 3ec, 3fb, 3fc), while
brominated derivatives were more reluctant to react. Bis(styryl)-
furans 4ha and 4hh were obtained from furan 1h. The
monosubstituted intermediates 3ha and 3hh were always
obtained as traces, even in the presence of an excess of 1,
suggesting that these intermediates react faster than 1. It should
be noted that 4ha has been recently described as a potentail
organic fluorophore for various applications.15
and they generally require the use of electron-poor
alkenes.9a,c,11 We have recently reported the synthesis of
difurylalkanes through the bis-coupling of 2-alkylfurans with
various alkenes, including styrenes.12 We report herein a
dehydrogenative coupling of furans and styrenes leading to
Heck-type products.
The coupling of 2-methylfuran (1a, 1.1 equiv) with styrene
(2a) in the presence of 0.05 equiv of Pd(OAc)2 and 2.0 equiv
of benzoquinone (BQ) was first attempted in AcOH, but less
than 5% yield was obtained (Table 1, entry 1). Cosolvents
can affect strongly the course of the reaction, since acetone
and acetonitrile led to the formation of difurylalkanes.12 We
have focused our attention on the influence of less coordinat-
ing solvents. CH2Cl2, EtOAc, and Et2O improved the
efficiency of the process, leading to 3aa in up to 55% yield
(entries 2-4). Pd(OCOCF3)2 led to a slighty lower yield
(entry 5). The association of air with catalytic amounts of
both BQ and Cu(OAc)2 as the oxidizing system afforded 3aa
in up to 54% yield, but the results were inconsistent (entry
6). In contrast, reproducible results were obtained in EtCO2H
instead of AcOH and with O2 instead of air, affording 3aa
in fair yield and high stereoselectivity (entry 7). Yields were
lower in the absence of benzoquinone or with THF or
dioxane as the cosolvent (entries 8-10).
The scope of the process was then examined. After slight
modifications of the original procedure, mono-, di-, and trisub-
stituted furans react with various styrenes bearing electron-
withdrawing or -donating groups on the aromatic ring, to give
Heck-type products in medium to good yields (Table 2). R,ꢀ-
Methyl styrenes were reluctant to react. Crude mixtures have
shown good stereoselectivity, and in most cases, the isolated
The kinetic profiles of the formation of 3aa and 3ea, under
similar conditions, have shown an induction period depend-
ing on the nature of 1 (Figure 1); such transformation being
faster with 1a.
Palladium acetate exists as a trimer in the solid state, in
which the Pd(OAc)2 units are joined by double OAc
bridges.16 In AcOH, such structure is maintained, character-
ized by a UV-vis absorption at 370-450 nm.17 The UV-vis
spectra of palladium acetate in EtCO2H and in a mixture of
(11) (a) Zhao, J.; Huang, L.; Cheng, K.; Zhang, Y. Tetrahedron Lett.
2009, 50, 2758. (b) Tsuji, J.; Nagashima, H. Tetrahedron 1984, 40, 2699.
(c) Maruyama, O.; Yoshimodo, M.; Fujiwara, Y.; Taniguchi, H. Chem. Lett.
1979, 1229
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(12) Thiery, E.; Harakat, D.; Le Bras, J.; Muzart, J. Organometallics
2008, 27, 3996.
Org. Lett., Vol. 11, No. 18, 2009
4097

Table 2. Coupling of Furan 1 with Styrene 2a
a 1 (0.45-2.0 mmol), 2 (1.0 mmol), BQ (0.1-0.25 mmol), Cu(OAc)2 (0.5 mmol), O2 (gas bag), EtCO2H (2 mL), cosolvent (2 mL), Et2O/40 °C or
THF/60 °C, conv 100%, 24 h. b Isolated yield. c Dibenzylidene acetone (dba) as additive (0.2 mmol). d 48 h.
4098
Org. Lett., Vol. 11, No. 18, 2009

transformation is then considered to proceed via a reaction
path similar to that proposed by Fujiwara et al. (Scheme 1).18
The formation of C involves probably an electrophilic
aromatic palladation. Such transformation is usually the
rate-determining step in intermolecular oxidative Heck
reactions.4g,5b,d,9c The kinetics have shown that the nature
of 1 has a strong influence on the rate of the transformation
(1a > 1e, Figure 1). Such results are compatible with an
electrophilic palladium pathway for the formation of C, since
electron-rich arene 1a reacts faster than electron-poor arene
1e (Scheme 2). In addition, the most thermodynamically
Figure 1. Kinetic profiles of the formation of 3aa, and 3ea.
Conditions: 1 (2.0 mmol), 2a (1.0 mmol), Pd(OAc)2 (0.1 mmol),
BQ (0.1 mmol), Cu(OAc)2 (0.5 mmol), O2 (gas bag), EtCO2H (2
mL), THF (2 mL), 60 °C. Data are averaged from two reactions.
Scheme 2. Electrophilic Palladation
favored cation will result in the addition of [(L)Pd(O2CR)]+
on C5 of 1a rather than on C5 of 1e. The coordination of
alkene 2 to C leads to D, followed by the insertion of the
CdC bond into the Ar-Pd bond affording the σ-alkyl-
palladium(II) complex E. ꢀ-Hydride elimination leads to
product 3, and HPd(L)O2CR. The elimination of RCO2H
affords Pd(0), which is stabilized by either 3 or an additive
such as dba.13 Finally Pd(0) is reoxidized to Pd(II) by the
multistep electron transfer system BQ/Cu(II)/RCO2H.
In summary, we have developed a palladium-catalyzed
dehydrogenative coupling of furans and styrenes. The trans-
formation occurs under mild conditions and is compatible
with various substituted furans and styrenes. The method
provides Heck-type products in medium to good yields and
with high regio- and stereoselectivities. Kinetic investigations
have shown an induction period that depends on the nature
of the furan.
EtCO2H/THF show such similar absortions, signifying that
Pd(II) is also a trimer in these solvents (Figure S1, Supporting
Information). We propose that the trimer A is an inactive
catalytic species and that the induction period is associated
to the complexation of A by 1, leading to dimer or monomer
derivatives B as active catalysts (Scheme 1). Such steps are
promoted by electron rich arenes, such as 1a. The overall
Scheme 1. Proposed Mechanism
Supporting Information Available: Experimental pro-
cedures and NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL901570P
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