DOI: 10.1002/chem.201101992
Dehydrogenative Heck Reaction of Furans and Thiophenes with Styrenes
under Mild Conditions and Influence of the Oxidizing Agent on the Reaction
Rate
Alexandre Vasseur, Jacques Muzart, and Jean Le Bras*[a]
À
Transition-metal-catalyzed reactions dealing with C H ac-
ence of the solvent on the DHR of heterocycles with styr-
enes. The coupling of 2-methylfuran (1a) and 2-methylthio-
phene (1b) with styrene (2a) has been studied at room tem-
tivation is a challenging task in organic chemistry.[1] The Pd-
À
catalyzed couplings of arenes with alkenes through C H ac-
tivation, also called intermolecular dehydrogenative Heck
reactions (DHRs), have gained interest these past years.[2]
Despite noticeable progresses, the substrate scope is often
limited to olefins bearing an electron-withdrawing group as
the coupling partner, which limits the applications of these
reactions. We have recently reported an efficient method for
the coupling of furans with styrenes, which allowed the use
of chlorinated and fluorinated substrates.[3] However, bromi-
nated substrates were reluctant to react. These compounds
would allow the synthesis of valuable products for further
functionalization through other cross-coupling reactions.
Glorius et al. have recently shown that brominated com-
pounds can be formed with no proto-debromination using
Rh catalysts; however few examples have been reported
perature over 4 h, in the presence of PdACTHNGURETNNU(G OAc)2 as catalyst,
benzoquinone (BQ) as oxidizing agent, AcOH as solvent,
and a series of co-solvents (Table 1). The reaction was gen-
erally ineffective (Table 1, entries 1–7). Only DMSO strong-
ly improved the efficiency of the reaction leading to 3aa in
64% isolated yield (Table 1, entry 8). This is a surprising
result since DMSO is a coordinating solvent, and we expect-
ed the formation of difurylalkanes under such conditions.[8]
Interestingly, 2-methylthiophene (1b) could also be coupled
with 2a in 58% yield at room temperature over 4 h
(Table 1, entry 9). The yield of 3ba was increased to 67%
when the reaction time was prolonged to 24 h (Table 1,
entry 10). This is an interesting improvement, since reported
methods for the DHR of thiophenes require 60–1208C and
are limited to olefins bearing an electron-withdrawing
group.[6] The use of catalytic amounts of BQ and CuII in as-
sociation with O2 reduced the yield of 3ba (Table 1,
entry 11). The scope of the process was then examined
(Table 2). After slight modifications to the original proce-
and the scope of substrates remains to be developed.[4]
A
recent example has been reported by Zhang et al. using pal-
ladium catalysts, but the method requires the presence of a
removable pyridylsulfinyl group on the arenes.[5] Among the
arenes used in DHRs, furans and thiophenes have received
little attention. The former are acid sensitive and the latter
require elevated temperatures,[6] due to their higher aromat-
ic resonance energy and stability.[7] We report herein the
DHRs, under mild conditions, of furans and thiophenes with
styrenes, including brominated substrates. The influence and
the role of the oxidizing agent on the activity of the catalyst
are also discussed.
Table 1. Optimization of the coupling of 2-methylfuran (1a) and 2-meth-
ylthiophene (1b) with styrene (2a).[a]
We noticed an induction period during our previous study
that depends on the nature of the furan, the transformation
being faster with electron-rich furans.[3] We also observed
that the solvent can have a decisive influence on the course
of the reaction. Low-coordinating solvents led to Heck-type
products,[3] whereas coordinating solvents gave difurylal-
kanes.[8] We have pursued our investigations on the influ-
Entry
1
Co-solvent
3
[%][b]
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
Et2O
11
8
8
9
11
9
8
67 (64)
58
(67)
45
CF3CH2OH
MeOH
tBuOH
CH2Cl2
DMF
DMA
DMSO
DMSO
DMSO
DMSO
[a] A. Vasseur, Dr. J. Muzart, Dr. J. Le Bras
Institut de Chimie Molꢀculaire de Reims-UMR 6229
CNRS-Universitꢀ de Reims Champagne-Ardenne
UFR des Sciences Exactes et Naturelles
BP 1039, 51687 REIMS Cedex 2 (France)
Fax : (+33)3-26-91-31-66
9
10[c]
11[d]
[a] 1 (2.0 mmol), 2a (1.0 mmol), PdACHTNUTRGNENG(U OAc)2 (0.05 mmol), BQ (2.0 mmol),
AcOH (2 mL), co-solvent (2 mL), RT, 4 h. [b] GC yield, isolated yield in
parenthesis. [c] The reaction was performed over 24 h. [d] BQ
Supporting information for this article is available on the WWW
(0.5 equiv), Cu
(2.0 mmol), 24 h.
ACHTUNGTERN(NUNG OAc)2 (0.1 equiv), O2 (gas bag) instead of BQ
12556
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 12556 – 12560