Drastic effect of bidentate phosphine ligands on Pd-catalyzed hydroarylation of ethyl propiolate: A simple route to arylbutadienes

Article abstract of DOI:10.1039/b810658d

Palladium complexes with bidentate phosphine ligands, Pd(dppe)(OAc) ₂ and Pd(dppm)(OAc)₂, were found to be effective catalysts for reactions of simple arenes with ethyl propiolate, affording arylbutadiene derivatives selectively. The Royal Society of Chemistry.

Full text of DOI:10.1039/b810658d

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Drastic effect of bidentate phosphine ligands on Pd-catalyzed
hydroarylation of ethyl propiolate: a simple route to arylbutadienesw
Juzo Oyamada and Tsugio Kitamura*
Received (in College Park, MD, USA) 24th June 2008, Accepted 21st July 2008
First published as an Advance Article on the web 12th September 2008
DOI: 10.1039/b810658d
Palladium complexes with bidentate phosphine ligands,
Pd(dppe)(OAc)2 and Pd(dppm)(OAc)2, were found to be effec-
tive catalysts for reactions of simple arenes with ethyl propio-
late, affording arylbutadiene derivatives selectively.
ð1Þ
Direct functionalization of C–H bonds is an attractive reaction
because it is a powerful and straightforward method for
First, we investigated the reaction of mesitylene (1a) with 2
in the presence of Pd(dppe)(OAc)2 as a catalyst. The reaction
afforded 4a as a major product along with a small amount of
cis-cinnamate 3a. Investigation of the reaction conditions
revealed that an amount of 1a affected the selectivity of
transformation of organic compounds.1 Especially, the C–H
bond functionalization of
a simple compound leading
to a more complex molecule without pre-functionaliza-
tion is of considerable interest from the viewpoint of green
chemistry.
Table 1 Investigation of reaction conditionsa
Arylbutadienes are useful and versatile compounds and
frequently prepared by the Wittig and related reactions and
by coupling reactions using transition metals.2 Recently, it was
reported that some transition metals catalyzed the reaction of
aryl reagents with two molecule of alkynes to afford aryl-
butadienes.3 These reactions provide a simple route for
arylbutadienes but they need aryl reagents such as aryl iodides
and boronic acids. To the best of our knowledge, little
attention has been paid to the formation of arylbutadiene
derivatives from simple arenes and alkynes by means of
C–H bond functionalization methodology although the
hydroarylation of alkynes with arenes has been studied
extensively.4,5
GC yieldb (%)
Entry
1a (mmol) 2 (mmol)
3a
4a
5a
1
2
3
4
3
2
1
1
2
2
2
2
2
3
2
2
17
17
7
0
16
9
83
83
68
25
83
91
0
0
4
2
0
0
Previously, we reported that Pd(OAc)2-catalyzed hydroaryl-
ation of alkynes with simple arenes in the presence of trifluoro-
acetic acid (TFA) proceeded in regio- and stereoselective
manner to afford cis-aryl substituted alkenes.6 In the case of
ethyl propiolate (2), regio- and stereo-defined arylbutadiene
derivatives 4 were also obtained as minor products, decreasing
the yield of hydroarylation products, ethyl cis-cinnamates 3 (eqn
(1)).6a,b However, we discovered that arylbutadienes 4 were
obtained selectively from the reaction of a simple arene with
ethyl propiolate when a palladium complex with a bidentate
phosphine ligand, Pd(dppe)(OAc)2 (dppe = 1,2-bis(diphenyl-
phosphino)ethane), was used as a catalyst. Here, we report a
simple route to arylbutadienes using hydroarylation of ethyl
propiolate in the presence of a Pd complex with a bidentate
phosphine.
5c
6d
a
Reaction conditions: Pd(dppe)(OAc)2 (0.005 mmol), 1a, 2 and TFA
b
c
(1 mL) at 30 1C for 5 h. The yields based on 2. TFA (0.5 mL) and
CH2Cl2 (0.5 mL). TFA (0.25 mL) and CH2Cl2 (0.75 mL).
d
Table 2 Effect of phosphine ligandsa
GC yieldb (%)
Entry
Pd catalyst
3a
4a
5a
1
2
3
4
Pd(OAc)2
37
36
0
23
2
20
18
1
57
54
85
3
3
0
1
3
1
Pd(PPh3)2(OAc)2
[Pd(dppe)2](OAc)2
Pd(dppp)(OAc)2
Pd(dppm)(OAc)2
Pd(dppm)(OAc)2
5c
6cd
a
Department of Chemistry and Applied Chemistry, Faculty of Science
and Engineering, Saga University, 1 Honjo-machi, Saga, 840-8502,
Japan. E-mail: kitamura@cc.saga-u.ac.jp; Fax: 81-952-28-8548;
Tel: 81-952-28-8550
w Electronic supplementary information (ESI) available: Experimental
procedures and spectral data of all products. See DOI: 10.1039/
b810658d
4
Reaction conditions: Pd catalyst (0.005 mmol), 1a (2 mmol),
2 (2 mmol), TFA (0.25 mL) and CH2Cl2 (0.75 mL) at 30 1C for
5 h. The yields based on 2. Pd(dppm)Cl2 (0.005 mmol) and AgOAc
b
c
d
(0.02 mmol). TFA (1 mL) and CH2Cl2 (0 mL).
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product 4a (Table 1, entries 1ꢁ4). Use of an excess amount of
1a prevented products 3a and 4a from further reaction,
resulting in higher yields. The amount of TFA also affected
the selectivity of 4a (entries 5 and 6). A low amount of TFA is
favorable for selective formation of 4a although the reaction
did not proceed in the absence of TFA. As a result, the best
result was obtained when 0.25 mL of TFA was used (entry 6).
Furthermore, similar Pd complexes were examined as catalysts
(Table 2). In contrast to Pd(dppe)(OAc)2, Pd(PPh3)2(OAc)2
bearing monodentate phosphine ligands resulted in low selecti-
vity of 4a, which was almost the same as that of Pd(OAc)2
(entries 1 and 2). [Pd(dppe)2](OAc)2 was completely inactive
(entry 3). In the case of Pd(dppp)(OAc)2 (dppp = 1,2-bis-
(diphenylphosphino)propane), the selectivity of 4a decreased
Table 3 Reaction of ethyl propiolate (2) with arenesa
Solvent/mL
Product and isolated yieldb (%)
Entry
1c
Ar–H
TFA
0.25
CH2Cl2
0.75
4
3
82
76
73
3b
9
7
5
2
3
0.25
0.25
0.75
0.75
3c
3d
4
1
0.5
66
3e
12
5d
6
1e
1
0.25
0.5
0.75
4e
69
70
3e
3f
2
11
7e
0.5
0.5
53
3g
18
8de
9f
1g
1h
1
0.5
0.5
0
4g
4h
67
(54)
3g
3h
8
(22)
10dg
11
1
0.5
0
0.5
75
72
3h
5a
7
6
12
1
0
75
4i
7
a
b
Reaction conditions: Pd(dppe)(OAc)2 (0.005 mmol), 2 (2 mmol), an arene (2 mmol), TFA and CH2Cl2 at 30 1C for 5 h. The yields based on 2.
The yields in the parentheses were determined by GC. 1b (1.1 mmol) was used. Pd(dppm)Cl2 (0.005 mmol) and AgOAc (0.02 mmol) were used
c
d
e
instead of Pd(dppe)(OAc)2. 10 h. 1h (0.5 mL, ca. 4.3 mmol) was used. 1h (3 mmol) was used.
f
g
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compared to Pd(dppe)(OAc)2 although it was higher than that of
Pd(OAc)2 (entry 4). On the other hand, Pd(dppm)(OAc)2 (dppm
= 1,2-bis(diphenylphosphino)methane) which was prepared
in situ from Pd(dppm)Cl2 and AgOAc showed high selectivity
but the yield of 4a was low (entry 5). However, Pd(dppm)(OAc)2
gave 4a in high yield when only TFA was used as solvent (entry
6). Among Pd complexes having bidentate phosphine ligands
with
different
tether
length,
Pd(dppe)(OAc)2
and
Pd(dppm)(OAc)2 were effective catalysts for formation of 4a.
This reaction is also applicable to other arenes (Table 3).
In all cases, the reactions gave arylbutadienes 4 regio- and
stereoselectively. In the presence of Pd(dppe)(OAc)2, penta-
methylbenzene (1b), 1,2,4,5-tetramethylbenzene (1c) and 2,4,6-
trimethylphenol (1d) gave the corresponding arylbutadienes 4 in
good to high yields along with a small amounts of cinnamates 3
(entries 1–3). 2-Bromomesitylene (1e) also gave 4e in good yield
although 1 mL of TFA was required because of the lower
reactivity of 1e. Use of Pd(dppm)(OAc)2 improved the selectivity
but gave 4e in similar yield (entry 5). For 2-methoxynaphthalene
(1f), Pd(dppe)(OAc)2 gave 4f in good yield. In the case of
naphthalene (1g) and p-xylene (1h), 1 mL of TFA was required
to complete the reaction because of the low reactivity of 1g and
1h. However, Pd(dppe)(OAc)2 showed low selectivity of aryl-
butadienes 4 when 1 mL of TFA was used. As a result,
Pd(dppe)(OAc)2 gave 4g and 4h in 53 and 54% yield, respec-
tively when 0.5 mL of TFA was used (entries 7 and 9). In
contrast, Pd(dppm)(OAc)2 showed good selectivity by using
1 mL of TFA. Thus, 1g and 1h gave 4g and 4h in 67 and 75%
yields, respectively (entries 8 and 10). These results indicate that
Pd(dppm)(OAc)2 is an effective catalyst for less reactive arenes
which require a large amount of TFA. Hydroarylation products
3a and 4a also participated in the reaction, affording 4i and 4j in
good yields, respectively. The reaction of 4a explains clearly that
an excess amount of 1a is required in the reaction of 1a with 2 to
prevent further reaction of 4a. Other substituted propiolates
were not effective for this reaction.
Scheme 1 A possible mechanism.
Notes and references
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The reaction of 3b with 2 did not take place in the presence
of Pd(dppe)(OAc)2, indicating that 3 is not an intermediate of
4. Although the reaction mechanism is not clear, the conjec-
ture that products 3 and 4 formed via a similar intermediate is
acceptable because the stereochemistry of 3 and 4 is similar. A
possible reaction mechanism is depicted in Scheme 1.6b,7 Ethyl
propiolate (2) is first activated by coordination of a cationic Pd
species generated in situ from a Pd catalyst and then undergoes
electrophilic aromatic substitution to afford a 2-arylvinyl
palladium intermediate A, followed by insertion of 2 into a
Pd–C bond in syn fashion. Protonation of the resulting
arylbutadienyl palladium intermediate gives 4 with concomi-
tant regeneration of the catalyst. The protonation of inter-
mediate A prior to insertion of 2 leads to the formation of 3.
In summary, we have demonstrated that Pd(dppe)(OAc)2
and Pd(dppm)(OAc)2 show an effective, catalytic activity for
the reaction of simple arenes with ethyl propiolate leading to
regio- and stereo-defined arylbutadiene 4. In the case of rela-
tively reactive arenes, Pd(dppe)(OAc)2 gave good selectivity in
the presence of a smaller amount of TFA. Pd(dppm)(OAc)2 was
superior for less reactive arenes, giving higher selectivity in the
presence of a larger amount of TFA. Further investigation on
catalysts and extension of the scope are now in progress.
4 For a recent review, see: C. Nevado and A. M. Echavarren,
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4994 | Chem. Commun., 2008, 4992–4994