Pd-catalyzed olefination of furans and thiophenes with allyl esters

Article abstract of DOI:10.1021/ol203013p

A direct Pd(II)-catalyzed olefination of furans and thiophenes with allyl esters is demonstrated. Under the typical conditions, the dehydrogenative Heck coupling reactions of heteroarenes with allylic esters proceeded via a β-H elimination rather than a β

Full text of DOI:10.1021/ol203013p

ORGANIC
LETTERS
2012
Vol. 14, No. 1
226–229
Pd-Catalyzed Olefination of Furans and
Thiophenes with Allyl Esters
Yuexia Zhang, Zejiang Li, and Zhong-Quan Liu*
State Key Laboratory of Applied Organic Chemistry, Lanzhou University,
Lanzhou Gansu 730000, P. R. China
liuzhq@lzu.edu.cn
Received November 8, 2011
ABSTRACT
A direct Pd(II)-catalyzed olefination of furans and thiophenes with allyl esters is demonstrated. Under the typical conditions, the dehydrogenative
Heck coupling reactions of heteroarenes with allylic esters proceeded via a β-H elimination rather than a β-OAc elimination to give the
corresponding γ-substituted allylic esters.
The Pd-catalyzed direct cross-couplings of arenes with
alkenes, which are called an oxidative Heck reaction,1 an
intermolecular dehydrogenative Heck reaction (DHR),2
or a FujiwaraÀMoritani reaction,3 have drawn much
attention in recent years. Among them, several efficient
olefinations of heteroarenes with alkenes have also been
developed by Fujiwara,4 Itahara,5 Gaunt,6 Yu,7 Le Bras
and Muzart,8 Zhang,9 Satoh and Miura,10 and Jiang11
et al.12 Despite significant progress in DHRs, most of them
suffer from limited substrate scope to electron-deficient olefins
and styrenes as the coupling partners. Thus, new systems with
a broad substrate scope would be highly desirable. Herein, we
wish to report the first example of a Pd-catalyzed direct
oxidative olefination of furans and thiophenes with electron-
rich alkenes such as allyl esters and ethers.
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A. L.; Brown, J. M. Chem. Commun. 2009, 3874. (c) Rodriguez, A.;
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Elhamifar, D.; Akhavan, P. F.; Esfahani, F. K.; Zamani, A. Synthesis
2010, 1399.
Allyl esters have been widely applied as allylation
reagents to form a CÀC bond in organic synthesis.13
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G. Angew. Chem., Int. Ed. 1999, 38, 1698. (c) Fujiwara, Y.; Jia, C. Pure
Appl. Chem. 2001, 73, 319. (d) Jia, C.; Kitamura, T.; Fujiwara, Y. Acc.
Chem. Res. 2001, 34, 633. (e) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem.
Rev. 2002, 102, 1731. (f) Kakiuchi, F.; Chatani, N. Adv. Synth. Catal.
2003, 345, 1077. (g) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q.
Angew. Chem., Int. Ed. 2009, 48, 5094. (h) Lyons, T. W.; Sanford, M. S.
Chem. Rev. 2010, 110, 1147. (i) Satoh, T.; Miura, M. Synthesis 2010,
3395. (j) Satoh, T.; Miura, M. Chem.;Eur. J. 2010, 16, 11212.
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Soc. Jpn. 1973, 46, 663. (b) Fujiwara, Y.; Maruyama, O.; Yoshidomi, M.;
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Y.; Taniguchi, H. Bull. Chem. Soc. Jpn. 1981, 46, 2851.
(5) (a) Itahara, T.; Kawasaki, K.; Ouseto, F. Synthesis 1984, 236.
(b) Itahara, T.; Ouseto, F. Synthesis1984, 488. (c) Itahara, T.; Kawasaki,
K.; Ouseto, F. Bull. Chem. Soc. Jpn. 1984, 57, 3488. (d) Itahara, T.
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r
10.1021/ol203013p
Published on Web 12/14/2011
2011 American Chemical Society

Table 1. Modification of the Typical Reaction Conditionsa
Scheme 1. β-H Elimination vs β-OAc Elimination in Heck-Type
Reactions of Allylic Esters with Furans and Thiophenes
solvent
(v/v)
yield
(%)b
entry
catalyst
additive
1
2
3
4
5
6
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
DMSO
0
Dioxane
15
38
42
43
43
5% DMSO/DCE
5% DMSO/THF
5% DMSO/DMF
5% DMSO/
Dioxane
However, among these systems, Pd-catalyzed Heck cross-
coupling reactions of allyl esters used as the coupling part-
ners with aryl halides and boronic acids have rarely been
achieved.14 As expected from the mechanism for the DHR,
the β-H elimination may be promoted by the electron-rich
arene to stabilize the positively charged benzylic carbon in the
four-membered transition state. Otherwise, the β-OAc elim-
ination may occur.3 Inspired by previous work in DHRs,2 we
pondered the possibility of the direct oxidative cross-coupling
of heteroarenes with allylic esters. Fortunately, we successfully
accomplished an efficient olefination of furans and thiophenes
with allyl esters via a highly selective β-H elimination process
in the FujiwaraÀMoritani reaction (Scheme 1).15
7
Pd(OAc)2
PdCl2
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
Ag2CO3
Ag2O
10% DMSO/
Dioxane
35
40
43
30
41
60
16
10
0
8
5% DMSO/
Dioxane
9
Pd(TFA)2
Pd(PCy3)2Cl2
Pd(acac)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
5% DMSO/
Dioxane
10
11
12
13
14
15
16
17
18c
19d
20e
5% DMSO/
Dioxane
5% DMSO/
Dioxane
5% DMSO/
Dioxane
5% DMSO/
Dioxane
Ag2SO4
AgNO3
Cu(OAc)2
NaIO4
5% DMSO/
Dioxane
Initially, we chose thiophene and allyl acetate as the
model substrates to optimize suitable conditions for this
reaction (Table 1). It was found that the solvent, catalysts,
and additives critically affect the efficiency of this reaction.
No products were observed in DMSO (entry 1). Only 15%
yield of product was obtained in 1,4-dioxane (entry 2). The
yields of the desired products increased significantly by the
addition of 5% (v) DMSO as cosolvent into DCE, THF,
DMF, and 1,4-dioxane (entries 3À6). The yield slightly
decreased by using 10% DMSO/Dioxane (v/v) as the solvent
(entry 7). The solvent effect indicates that a specified volume
of DMSO plays an important role in this system. Catalysts
were screened (entries 8À11), and as a result, Pd(OAc)2 was
selected as the most effective catalyst. The additive Ag2CO3
was the best compared to others such as Ag2O, Ag2SO4,
AgNO3, and Cu(OAc)2 (entries 12À16). Interestingly,
NaIO4 gave a 42% yields of the products (entry 17). More-
over, the yield decreased with decreasing amounts of Ag2CO3
(entry 18). A very slightly increased yield was gained by using
1.5 equiv of Ag2CO3 (entry 19). The yield increased to 66%
with increasing amounts of thiophene (entry 20).
5% DMSO/
Dioxane
5% DMSO/
Dioxane
19
42
53
61
66
5% DMSO/
Dioxane
Ag2CO3
Ag2CO3
Ag2CO3
5% DMSO/
Dioxane
5% DMSO/
Dioxane
5% DMSO/
Dioxane
a Reaction conditions: thiophene (1.5 mmol), allyl acetate (0.5mmol),
additive (1 equiv), catalyst (5 mol %), 110 °C, 12 h, unless otherwise
noted. b Isolated yields of the E/Z and B isomers. c Ag2CO3 (0.5 equiv).
d Ag2CO3 (1.5 equiv). e Thiophene (2.5 mmol).
ethers are summarized in Table 2. Alkyl-substituted thio-
phenes give moderate to good yields of the corresponding
products under the typical conditions (3aÀ3d). Surprisingly,
olefination of 3-methylthiophene with allyl acetate occurs
at a more sterically hindered position (3c). However,
2-thienyl halides give relatively low yields of the oxidative
vinylic CÀH/CÀH cross-coupling products (3e and 3f).
Thiophenes with an electron-withdrawing acyl group
could also be coupled with allyl acetate in moderate yields
(3g and 3h). Moreover, benzothiophene, furan, and benzo-
furan could also give moderate yields of the desired products
(3i, 3j, and 3k). However, nitrogen-based heteroarenes
such as indoles, azoles, and thiazoles do not work in this
To investigate the substrate scope of this reaction, the
direct olefination of various thiophenes, benzothiophene,
furans, and benzofurans with substituted allylic esters and
(14) (a) Pan, D.; Chen, A.; Su, Y.; Zhou, W.; Li, S.; Jia, W.; Xiao, J.;
Liu, Q.; Zhang, L.; Jiao, N. Angew. Chem., Int. Ed. 2008, 47, 4729. (b) Su,
Y.; Jiao, N. Org. Lett. 2009, 11, 2980. (c) Pan, D.; Yu, M.; Chen., W.;
Jiao, N. Chem.;Asian J. 2010, 5, 1090.
(15) Fujiwara, Y.; Moritani, I.; Danno, S.; Asano, R.; Teranishi, S.
J. Am. Chem. Soc. 1969, 91, 7166.
Org. Lett., Vol. 14, No. 1, 2012
227

Table 2. Pd-Catalyzed Oxidative Heck Reaction of Thiophenes and Furans with Allyl Esters and Ethersa
a Reaction conditions: heteroarene (2.5 mmol, 5 equiv), allyl esters or ethers (0.5 mmol, 1 equiv), Ag2CO3 (1 equiv), Pd(OAc)2 (5 mol %), 5% DMSO/
Dioxane (2 mL, v/v), 110 °C, unless otherwise noted. b Reaction time, indicated by TLC. c Isolatedoverall yields of the E/Z and B isomers. d Ratio of E/Z/
B determined by crude 1H NMR.
procedure. It might be attributed to the lower electrophi-
licity of the intermediate Ar-PdLn-OAc which could not
chelate with the electron-rich olefins efficiently.3,15
Various substituted allylic esters give moderate to high
yields of the coupling products in this reaction (Table 2,
3lÀ3q). A branched cross-coupling product is obtained as
the major product whichmight proceedvia a β-elimination
of the H-atom from the methyl group (3l). Both allyl
benzoate and allyl cinnamate give high yields of the
products (3n and 3q). In addition, allyl acrylate and allyl
methacrylate give the corresponding products in 33% and
57% yields, respectively (3o and 3p). It is noteworthy that
allylic ether is also used successfully as the olefination
partner under these reaction conditions (3r).
228
Org. Lett., Vol. 14, No. 1, 2012

There may be a competing cross-coupling of a hetero-
arene between the allylic and the acrylic double bonds. The
alkyl-Pd-intermediate might be stabilized by chelation of a
Pd-atom with the carbonyl O-atom which was previously
proposed.13f,16 As expected from the chelation effect, the
yields of olefination of thiophene with allyl acetates would
be much higher than that with acrylates. However, as a
matter of fact, the difference is not remarkable. An inter-
molecular competing reactionwascarried out (eq1), which
indicates that the difference between allyl acetate and butyl
acrylate in the olefination of thiophene is not obvious. The
same conclusion can be obtained from an intramolecular
competing reaction of an allyl acrylate with thiophene
under the typical conditions (eq 2). Additionally, coupling
of thiophene with 1-octene gives a 64% yield of the desired
products (eq 3), which provides further evidence suggest-
ing the chelation effect was not significant.
In summary, we developed a convenient and direct
Pd(II)-catalyzed olefination of thiophenes and furans
by using allylic esters and ethers. In the present system,
electron-rich olefins such as allyl esters and ethers are used
as the olefination partners in the oxidative Heck coupling
of heteroarenes for the first time. A variety of γ-substituted
allylic esters havebeen prepared by an oxidative Heck-type
reaction via β-H elimination rather than β-OAc elimina-
tion. Additionally, a series of allylic esters even bearing
another CdC bond such as allyl methacrylate and allylic
ether give moderate to good yields of the desired products.
Further investigation of this procedure is underway in our
laboratory.
Acknowledgment. This project is supported by the
National Science Foundation of China (No. 21002045).
We thank the State Key Laboratory of Applied Organic
Chemistry and Lanzhou University for financial support.
We are also grateful to Prof. Yu Wei at this institute for
helpful discussions.
Supporting Information Available. Full experimental
details and characterization data for all products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
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Org. Lett., Vol. 14, No. 1, 2012
229