Construction of polysubstituted olefins through Ni-Catalyzed direct activation of Alkenyl C-O of substituted alkenyl acetates

Article abstract of DOI:10.1002/chem.200902785

(Figure Presented) Reliable companion: For the first time cross-coupling between alkenyl acetates and arylboroxines/PhZnCl has been developed via Ni catalysis. Alkenyl acetates could be well-differ-entiated from aryl acetates (see scheme). This reliable method provides a convenient pathway to construct polysubstituted styrene derivatives.

Full text of DOI:10.1002/chem.200902785

DOI: 10.1002/chem.200902785
Construction of Polysubstituted Olefins through Ni-Catalyzed Direct
À
Activation of Alkenyl C O of Substituted Alkenyl Acetates
Chang-Liang Sun,[b] Yang Wang,[b] Xiao Zhou,[b] Zhen-Hua Wu,[b] Bi-Jie Li,[b]
Bing-Tao Guan,[b] and Zhang-Jie Shi*[a, b]
In memory of Professor Xian Huang
Polysubstituted olefins broadly exist in natural and syn-
thetic compounds, which can be constructed through various
pathways,[1] such as Wittig reaction, Julia–Lythgoe olefina-
tion, as well as coupling reactions.[2] Among coupling reac-
tions, the Suzuki–Miyaura coupling is one of the most effi-
cient choices for alkenyl halides and their derivatives.[3]
However, due to the limited availability, high cost and low
reactivity of the coupling partners, this method is not ideal.
Although recent advances have promoted novel synthetic
methods to construct such structural units from alkenyl
methyl ethers via Ni-catalyzed Kumada cross-coupling, the
difficulty to obtain starting materials and the poor compati-
bility of substituents, which arises from the use of Grignard
reagents, limited its applications.[4]
Recently, the cleavage of “inert” aryl C–OMe, followed
by cross-coupling with arylboronic acid derivatives, has been
reported by Chatani and Kakiuchi with and without direct-
ing groups via Ru and Ni catalysis.[5] Very recently, our
group and Garg independently reported that aryl carboxy-
lates could couple with arylboronic acid derivatives via Ni
catalysis.[6] Following studies indicated that coupling of aryl
pivalates with organozinc reagents and alkyl Grignard re-
agents could take place under even milder conditions.[7] This
transformation was further expanded to alkenyl pivalates to
afford styrene derivatives. However, to the best of our
knowledge, there is no example to perform the Suzuki–
Miyaura coupling starting from alkenyl acetates and arylbor-
onic acid derivatives, although benzyl and allyl acetates
have been applied in the corresponding coupling reactions
via Pd catalysis.[8] Herein, we reported for the first time a
useful synthetic method to construct polysubstituted alkenes
from easily available alkenyl acetates through Ni-catalyzed
Suzuki–Miyaura coupling with arylboroxines.
Generally, cross-coupling to afford aryl alkenes proceeded
between aryl organoboron reagents and alkenyl triflates or
phosphates due to their relatively high reactivities, which
could be generated easily from carbonyl compounds with
triflic anhydride or a chlorophosphate.[9,10] However, the
high cost, atomic economic waste, and relative difficulty of
handling those chemicals limits this method. Compared with
such a process, applying alkenyl acetates to the correspond-
ing coupling reaction should be more general and easily
controllable since alkenyl acetates could be easily produced
through ester exchange (Scheme 1).[11] Additionally, as re-
ported previously, the methoxy group might react with orga-
noboron compounds in the presence of Ni complexes,[5b] so
the tolerance of methoxy group is also questionable in the
[a] Prof. Dr. Z.-J. Shi
Beijing National Laboratory of Molecular Sciences (BNLMS)
PKU Green Chemistry Centre and Key Laboratory of Bioorganic
Chemistry and Molecular Engineering of Ministry of Education
College of Chemistry and State Key Laboratory of Natural and
Biomimetic Drugs
Peking University, Beijing 100871 (China)
Fax : (+86)10-62760890
E-mail: zshi@pku.edu.cn
[b] C.-L. Sun, Y. Wang, X. Zhou, Z.-H. Wu, B.-J. Li, B.-T. Guan,
Prof. Dr. Z.-J. Shi
Beijing National Laboratory of Molecular Sciences (BNLMS)
PKU Green Chemistry Centre and Key Laboratory of Bioorganic
Chemistry and Molecular Engineering of Ministry of Education
College of Chemistry and Molecular Engineering
Peking University, Beijing 100871 (China)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200902785.
Scheme 1. New design on construction of polysubstituted olefins from ke-
tones.
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Chem. Eur. J. 2010, 16, 5844 – 5847

COMMUNICATION
Table 1. Cross-coupling between 1-phenylvinyl acetate (1a) with phenylboroxine (2a) under different condi-
designed transformation. Our
studies to achieve this goal initi-
ated from the reaction of 1-phe-
nylvinyl acetate (1a) with dif-
ferent organoboron reagents.
Previous research indicated
that Ni complexes were the
best catalysts to cleave aryl/al-
tions.[a]
Entry
Catalyst
Additive (equiv)
Base
Solvent
3aa [%][b]
1
2
3
4
5
6
7
8
[Ni
[Ni
[Ni
[Ni
[Ni
[Ni
[Ni
[Ni
[Ni
[Ni
N
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
–
H2O (0.5)
H2O (1.5)
H2O (2.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (0.5)
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K2CO3
Cs2CO3
CsF
THF
DMF
toluene
dioxane
72
0
51
36
À
kenyl C O bonds of alkenyl
ethers and carboxylates.[4–6] We
first tested the exact reaction
conditions, which were success-
fully applied in the previous
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
toluene/dioxane 1:1
99 (88)[c]
0
35
77
72
0
0
0
system (entries
3
and 4,
9
Table 1).[6a] The designed cou-
pling took place but in low effi-
ciency. Further exploration in-
dicated that the mixed solvent
system (dioxane/toluene 1:1)
gave higher yields (entry 5,
Table 1). Among various Ni
10
11
12
13
14
15
16
17
18
19
20
21
22
23
[Pd
[Pd
–
G
R
0
[Ni
[Ni
[Ni
[Ni
[Ni
[Ni
[Ni
[Ni
[Ni
[Ni
18
52
66
65
79
0
complexes, [NiACHTUNGTRENNUNG(PCy3)2Cl2] was
the most efficient and the load-
ing of catalyst could be de-
creased to 4.0 mol %. Under
these conditions, the homo-cou-
pling of phenylboroxine was
sufficiently suppressed.
Compared with Ni catalysts,
Pd complexes failed to give the
same coupling results (entries
0
0
KOtBu
–
K3PO4
0
70[d]
[a] All the reactions were carried out in the scale of 0.2 mmol of 1a and 0.2 mmol of 2a in the presence of cat-
alyst and additive in 2 mL solvent. [b] GC yields with the use of n-dodecane as an internal standard. [c] Isolat-
ed yield in parenthesis. [d] The reaction was carried out in the scale of 2.0 mmol at 0.05m.
Table 2. Cross-coupling between 1a and various organoboron
reagents.[a;b]
11 and 12, Table 1). Different bases were also investigated
and K3PO4 gave the best results (entries 18–22, Table 1). It
is important to note that the amount of water was very criti-
cal in the transformation (compare entry 5 to entries 14–17,
Table 1). We proposed that water might play an important
role in facilitating the transmetalation between boroxine
and Ni complex.[12] However, alkenyl acetates would hydro-
lyze in the presence of excess water under such basic and
harsh conditions. Furthermore, to expand the application of
this method, a 2.0 mmol scale reaction was carried out
under the slightly modified conditions and the desired prod-
uct was isolated in 70% yield (entry 23, Table 1).
[a] All the reactions were carried out in the scale of 0.2 mmol of 1a and
stirred for 20 h. [b] The yields were determined by GC with n-dodecane
as an internal standard. [c] The organoboron reagents were added in 3.0
equiv.
Compared with phenylboroxine 2a, other phenylboronic
acid derivatives showed different reactivities. Arylboronic
ester 2b could react with 1a but in lower yields. Catechol-
borane derivative 2c, however, failed. Phenylboronic acid
2d facilitated this transformation in moderate yields. The
hydrolysis of alkenyl acetate 1a induced by such an acid
may diminished the efficiency. Potassium phenyltrifluorobo-
rate (2e) was also tested but no desired product was detect-
ed (Table 2). Notably, 3.0 equivalents of aryl boronic reagent
related to 1a are necessary due to the protonation of boron-
ic reagents.
(3ab, 3ac, 3ae, and 3af); however, the protonation of bor-
oxines also produced the corresponding arenes as byprod-
ucts, which may arise from the high reactivity of organobor-
on reagents; 2) in contrast, electron-withdrawing groups de-
creased the rate, but the high efficiency can be achieved by
simply lengthening the reaction time (3ag–3aj); 3) the steric
hindrance also played an important role. When steric hin-
dered substrate was used, the product was observed only in
a very low yield (3ad); 4) 4-biphenylyl and 1-naphthyl bor-
oxines worked well (3ak and 3al).
To expand the application of this method, we further
tested other arylboroxines (Table 3). We found that 1) elec-
tron-donating groups were beneficial for the cross-coupling
The reactivity of different carboxylates was further inves-
tigated (Table 4). We found that sterically hindered carboxy-
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Z.-J. Shi et al.
Table 3. Cross-coupling between 1a and various arylboroxines 2.[a]
The generality of alkenyl acetates was also explored
(Table 4). When different groups were added on the phenyl
ring, we observed that the electron-donating groups were
generally beneficial to this transformation (entries 5 and 8).
Many other functional groups survived well, such as alkoxyl,
aryl, and fluoro groups (entries 6–8). Notably, the steric
effect similarly decreased the efficiency (entry 9). The elec-
tron-withdrawing group decreased the efficiency because of
the lower stability of substrates (entry 10). The 4-cyano-sub-
stituted styryl acetate and pivalate did not afford the prod-
uct and hydrolyzed to form corresponding ketone (entries 11
and 12). Trisubstituted alkenyl acetates underwent this
transformation with lower efficiency than the disubstituted
alkenyl acetates (entries 13 and 14). Interestingly, with the
fused 1, 2-dihydronaphthyl derivative, 4-alkenyl acetate was
much more efficient in this transformation (entries 13 and
14). Moreover, alkenyl pivalates with conjugated carbonyl
group showed acceptable reactivity (entry 15).
Although the Negishi coupling of vinyl pivalates has been
reported before,[7a] the cross-coupling of vinyl acetates with
more reactive organozinc reagents remain challenging due
to their high instability. To our satisfaction, vinyl acetate
could also be applied as an electrophilic partner to couple
with phenyl zinc reagents under milder conditions
(Scheme 2). It is important to note that a mixed solvent
system is required to promote the efficiency. However, aro-
matic substituents at the a-position of vinyl acetates are nec-
essary to retain their high reactivity. Moreover, a,b-unsatu-
rated vinyl carboxylate 3i was not a suitable substrate for
this transformation, which may arise from the instability of
this compound under the reaction conditions. Thus, the re-
ported Suzuki coupling here is a complimentary method to
carry out the arylation of those substrates.
Entry
Ar
3 [%][b]
Entry
Ar
3 [%][b]
1
2
3
4
5
6
C6H5
3aa (88)
3ab (76)
3ac (72)
3ad (<10)
3ae (72)
3af (95)
7
8
9
10
11
12
4-ClC6H4
4-FC6H4
3-O2NC6H4
3-CF3OC6H4
4-PhC6H4
1-C10H7
3ag (60)
3ah (75)
3ai (92)
3aj (83)
3ak (93)
3al (78)
4-MeC6H4
3-MeC6H4
2-MeC6H4
4-tBuC6H4
4-MeOC6H4
[a] All the reactions were carried out in the scale of 0.2 mmol of 1a and
all the arylboroxines were added in 1.0 equiv and the reactions were
quenched after 20 h. [b] Isolated yields.
lates increased the stability of alkenyl carboxylates and pre-
vented the hydrolysis of the substrates, but also decreased
the rate of cross-coupling to lengthen the reaction time
(entry 3). However, better leaving groups made the sub-
strates more liable and the hydrolysis prevailed over the cor-
responding cross-coupling. For example, alkenyl trifluoro-
ACHTUNGTRENNUNGacetate completely failed in this transformation under the
same reaction conditions (entry 4, Table 4).
Table 4. Cross-coupling between different alkenyl acetates 1 and arylbor-
oxine.[a,b]
Entry
1
1
3 [%][c] Entry
R =
1
3 [%][c]
3ad
(<5)
Ac, 3ba
9
(85)
3bf
2
10
3ea (56)
(93)[d]
R =
Ac, 3 fa
(<5)
R =
Piv, 3 fa
(<5)
Piv, 3ba
(89)
3
4
11
12
TFA,
3ba
(<5)
3ab
(92)
Scheme 2. Negishi coupling with vinyl acetate via Ni catalysis.a
5
6
7
8
13
3ga (70)
3ha (46)
3ia (60)
3al (79) 14
3ca (72) 15
Supposedly, a reaction mechanism was proposed for the
cross-coupling between aryl carboxylates and arylboroxines/
aryl zinc reagents. Under such conditions, either arylborox-
ines or aryl zinc reagents played a key role in reducing NiII
to Ni0, which underwent oxidative addition of alkenyl ace-
tates. After transmetalation with arylboroxines/ArZnCl, the
reductive elimination occurred to produce the desired prod-
ucts under regeneration of Ni0 to fulfill the catalytic cycle.
With this method, different acetates could well be differ-
entiated in the same molecule. Through simple ester ex-
change with 2-propenyl acetate, estrone 4 was transformed
3da
(89)
[a] All the reactions were carried out in the scale of 0.2 mmol of 1 and
the reactions were quenched after 20 h. [b] The arylboroxines were
added in 1.0 euqiv. [c] Isolated yields. [d] (p-Methoxyphenyl)boroxine
was used.
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Chem. Eur. J. 2010, 16, 5844 – 5847

Polysubstituted Olefins
COMMUNICATION
À
into diacetates 5. As predicted, the corresponding cross-cou-
pling only took place at the alkenyl position in acceptable
yields, leaving aryl C–OAc untouched and then hydrolyzed
to hydroxyl group in a one-pot reaction, which allowed fur-
ther functionalization of the phenyl ring to build different
derivatives (Scheme 3). Further efforts to expand the appli-
cation of this methodology are currently underway.
Keywords: alkenyl acetate
activation · cross-coupling · nickel
·
arylboroxines
·
C O
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construct polysubstituted styrenes.[13] Alkenyl C–OAc and
aryl C–OAc can be well differentiated under these condi-
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functionalize various compounds. Further studies to expand
the substrate scope and promote the efficiency of this trans-
formation are under investigation.
Experimental Section
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General procedure for Ni-catalyzed cross-coupling of alkenyl acetates 1
with arylboroxines 2: The reactions were carried out in Schlenk tubes,
which were dried by heating under vacuum. [NiACHTUNGTRNEG(UN PCy3)2Cl2] (4 mol %,
0.04 mmol), boroxines (1.0 equiv, 0.2 mmol) and K3PO4 (4.0 equiv,
0.8 mmol) were added into tubes in glove box under dry N2 atmosphere.
Then the solutions of alkenyl acetates (1.0 equiv, 0.2 mmol) and H2O (1.0
equiv, 0.2 mmol) in toluene (1.0 mL)/dioxane (1.0 mL) were added to the
tubes (0.2 mmol, 3.6 mL H2O was added in the mixed solvent by micro-
scale syringe). The tubes were degassed in liquid N2 and refilled with N2
three times. Then the mixtures were stirred and heated at 1108C for 20 h.
After cooling down to room temperature, the reaction mixture was ex-
tracted by Et2O and washed with water. The organic layer was dried by
MgSO4 and then concentrated under vacuum to afford a liquid or solid
residue. The desired product was purified by chromatography on silica
gel with petroleum ether as the eluent.
Acknowledgements
Support of this work by a starter grant from Peking University and the
grant from National Sciences of Foundation of China (No. 20672006,
20821062) and the “973” Project from the MOST of China
(2009CB825300) is gratefully acknowledged.
Received: October 9, 2009
Revised: December 12, 2009
Published online: April 14, 2010
Chem. Eur. J. 2010, 16, 5844 – 5847
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5847