Cross-coupling of aryl/alkenyl silyl ethers with grignard reagents through nickel-catalyzed CO bond activation

Article abstract of DOI:10.1246/cl.2011.1001

CO activation and its application have drawn much attention since oxygen-based electrophiles are easily available, less toxic, and more environmentally benign. This letter presents systematically results on the Ni-catalyzed KumadaTamaoCorriu coupling based on siloxy arenes/alkenes, which provides a new strategy of silyl protection/CC bond formation sequence in organic synthesis.

Full text of DOI:10.1246/cl.2011.1001

doi:10.1246/cl.2011.1001
Published on the web September 5, 2011
1001
Cross-coupling of Aryl/Alkenyl Silyl Ethers with Grignard Reagents
through Nickel-catalyzed C-O Bond Activation
Fei Zhao,1,2 Da-Gang Yu,1,2 Ru-Yi Zhu,1,2 Zhenfeng Xi,*1,2 and Zhang-Jie Shi*1,2,3
1Beijing National Laboratory for Molecular Sciences (BNLMS), Peking University, Beijing 100871, P. R. China
2Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education,
Peking University, Beijing 100871, P. R. China
3State Key Laboratory of Organometallic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China
(Received May 30, 2011; CL-110457; E-mail: zshi@pku.edu.cn)
C-O activation and its application have drawn much
attention since oxygen-based electrophiles are easily available,
less toxic, and more environmentally benign. This letter presents
systematically results on the Ni-catalyzed Kumada-Tamao-
Corriu coupling based on siloxy arenes/alkenes, which provides
a new strategy of silyl protection/C-C bond formation sequence
in organic synthesis.
Ni cat.
Ar1 OSiR3
Ar2MgBr
Ar1 Ar2
+
R3SiOMgBr
Scheme 1. C-O bond activation of siloxy arenes.
Table 1. Cross-coupling between 2-trimethylsiloxynaphthalene
and PhMgBr under different conditions
Ph
OTMS
[Ni(PCy3)2Cl2] (5 mol%)
Cross-coupling reaction has become one of the most
powerful tools for C-C bond construction in organic synthesis.1
Among the developments of this area, C-O bond activation has
recently drawn more attention since the easy availability, low
toxicity, and environmental friendliness of starting materials.2
Since Wenkert and co-workers reported the first example of
nickel-catalyzed inert C-O bond cleavage in 1979,3 this field
has been increasingly developed in recent years. Besides a few
examples of stoichiometric cleavage of inert C-O bonds,4
various transition-metal-catalyzed C-O transformations includ-
ing C-OMe,5 C-OOCR,6 and C-ONa7 bonds of phenol
derivatives have been reported sequentially.
As a ubiquitous protecting group of phenols and alcohols,
silyl groups are widely used in organic synthesis.8 In general,
siloxy groups are deprotected to give free OH after trans-
formations. It could be a useful synthetic strategy to break the
C-OSi bond followed by the formation of a C-C bond after the
designed transformations in the presence of silyl ether as
protecting groups. Hayashi and Kumada systematically studied
nickel-catalyzed alkenyl C-OSiMe3 bond activation in 1980.9
In previous work, only a few examples of aryl C-OSiMe3
bond activation have been reported.3b,5a,5d,5e Herein, we report
a systematic study of the Kumada-Tamao-Corriu coupling
reaction via nickel-catalyzed C-O bond activation of aryl/
alkenyl silyl ethers (Scheme 1).
Previous work indicated that [Ni(PCy3)2Cl2] is one of
the most effective catalyst for the C-O bond activa-
tion.5a,5d,5e,6a-6c,6e,6h,6m,6n,7 Thus, we ran the first try of the
Kumada-Tamao-Corriu reaction by using 2-trimethylsiloxy-
naphthalene (1a) as the substrate and [Ni(PCy3)2Cl2] as the
catalyst. In the presence of 2.0 equiv of PhMgBr (2a) as the
nucleophile, the desired cross-coupling worked well in arene or
ether as solvents (Table 1). Actually, toluene (Entry 1) and THF
(Entry 9) gave the best results under mild conditions and good to
excellent yields of the product 3a were obtained in 1 h at 30 °C
under various conditions.
+
PhMgBr
solvent, 30 °C, 1 h
1a
2a
3a
Equiv
of PhMgBr
Entry
Solvent
Yield/%a
1
2
3
4
5
6
7
8
9
2.0
1.5
1.2
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
toluene
toluene
toluene
benzene
o-xylene
mesitylene
DME
dioxane
THF
n-Bu2O
(EtO)2CH2
95 (80)b
95
66
92
88
93
92
88
96
10
11
76
92
aYields determined by GC using n-dodecane as an internal
standard. Isolated yields in parenthesis.
b
reagents were not compatible. It is noticed that o-substituted
phenyl Grignard reagents required a higher temperature and
longer time to complete the reaction (3c and 3d). Methoxy and
dimethylamino groups on aryl Grignard reagents survived well
(3e and 3f). Unfortunately, alkenyl, allyl, benzyl, and most alkyl
Grignard reagents failed at this stage while MeMgBr gave the
product 3i in an almost quantitative yield.
We then tested the variation of siloxy groups (Table 3).
Trialkylsiloxy (Entries 1-4), triarylsiloxy (Entry 5), mixed
alkyl/aryl siloxy groups (Entry 6), including bulky groups such
as -OSit-BuMe2 (Entry 4), were efficient leaving groups during
this transformation. To our interest, the presence of vinyl
substituent on silyl group failed producing the desired product
(Entry 7). In this case, Si-O was cleaved and the phenylated
product PhSiMe2(vinyl) was found in a good yield (GC yield ca.
90%), indicating that PhMgBr attacked the silicon center beyond
the desired cross-coupling.10 This inversion of the reactivity is
probably due to the Lewis acidity of vinylsilane11 and/or the
coordinative ability of vinyl groups toward the Ni center. As a
Different Grignard reagents were tested under the standard
conditions (Table 2). Most of the aryl Grignard reagents gave
good to excellent yields. However, aryl C-F bonds on Grignard
Chem. Lett. 2011, 40, 1001-1003
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1002
O
O
Ph
Table 2. Cross-coupling between 2-trimethylsiloxynaphthalene
and various Grignard reagentsa,b
[Ni(PCy3)2Cl2] (5 mol%)
Si
Et2
PhMgBr (4.0 equiv)
toluene 1.0 mL
30 °C, 1 h
Ar
OTMS
1ah
3a: 49%
[Ni(PCy3)2Cl2] (5 mol%)
+
Ar MgBr
toluene 1.0 mL
1a
2
3
30 °C, 1 h
Scheme 2. C-O bond cleavage in bis(2-naphthoxy)diethyl-
silane.
Me
Table 4. Cross-coupling between various aryl/alkenyl silyl
ether and Grignard reagentsa
Ph
Me
[Ni(PCy3)2Cl2] (5 mol%)
3a (80%)
3b (81%)
3c (74%)c
Ar1 Ar2
Ar1 OTMS
Ar2 MgBr
+
toluene 1.0 mL
Me
Me
Ph
NMe2
OMe
30 °C, 1 h
Entry
1
Substrate
Product
Yield/%b
Me
Ph
OTMS
3d (73%)c
3e (70%)
3h (69%)
3f (63%)
1a
3a
80
73
70
71
71
54
59
47
46
77
32
N
Me
OTMS
Ph
2
3
1b
3j
3g (84%)
3i (>99%)
aAll the reactions were carried out in the scale of 0.2 mmol of 1a
and 0.4 mmol of 2. Isolated yields. Conditions: 80 °C, 10 h.
OTMS
Ph
Ph
3k
1c
b
c
Ph
Ph
OTMS
1d
3k
Ph
4c
TMSO
Ph
OTMS
Table 3. Cross-coupling between various 2-siloxynaphthalene
TMSO
Ph
3l
5c
and PhMgBra
1e
OSiR1R2R3
Ph
[Ni(PCy3)2Cl2] (5 mol%)
+
PhMgBr
MeO
OTMS
OTMS
Ph
3m
Ph
toluene 1.0 mL
30 °C, 1 h
6c
1f
1
2a
3a
Yield/%b
Entry
Substrate
tBuO
Me
Me
O
O
O
O
O
O
7c
Si
3m
1g
1
2
3
4
5
1a
80
76
89
85
80
Me
Me
Et
OTMS
Si
Et
8d,e
1ab
1ac
1ad
1ae
Et
3n
3o
1h
1i
iPr
iPr
Si
OTMS
iPr
9f
tBu
Me
Si
Me
Ph
Ph
Ph
OTMS
3p
3q
1j
10
Ph
Si
Ph
Ph
OTMS
11g,h
1k
Ph
Si
Me
6
7
1af
88
0
Me
aAll the reactions were carried out in the scale of 0.2 mmol of 1
and 0.4 mmol of PhMgBr unless otherwise noticed. bIsolated
c
yields. 0.8 mmol of PhMgBr was used. dUsing p-tolylmagne-
O
Si
Me
1ag
Me
sium bromide as Grignard reagent, the yield is determined by
e
f
g
GC. Conditions: 80 °C, 24 h. Conditions: 110 °C, 24 h. Using
2-naphthylmagnesium bromide as Grignard reagent. hCondi-
tions: 80 °C, 10 h.
aAll the reactions were carried out in the scale of 0.2 mmol of
2-siloxynaphthalene and 0.4 mmol of PhMgBr. Isolated yields.
b
Chem. Lett. 2011, 40, 1001-1003
© 2011 The Chemical Society of Japan
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1003
2002, 124, 13856.
result, the naphthoxy group performed as a leaving group.
Notably, when bis(2-naphthoxy)diethylsilane served as the
substrate, only one C-OSi bond was cleaved even at a higher
temperature (Scheme 2).12
2
3
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Finally, different functional groups on the naphthalene
moiety of naphthyl trimethylsilyl ether were surveyed (Table 4,
Entries 1-7). 1-Siloxynaphthalene 1b gave a similar result as
2-siloxynaphthalene 1a (Entry 2). It is important to note that
disilyl ethers of different naphthalenediols at 1,7- or 2,6-position
lead the diphenylation products in good yields in the presence of
4.0 equivalent of PhMgBr (2a), companied with a small amount
of monophenylated products as by-products (Entries 4 and 5).
Moreover, even methoxy and tert-butoxy groups could not be
well discriminated beyond siloxy groups and only diphenylated
products were isolated in good yields in the presence of large
amount of 2a (Entries 6 and 7). Moreover, phenyl and biphenyl
trimethylsilyl ether required higher temperature and longer time
to yield cross-coupling products in moderate yields, probably
due to their better aromaticity (Entries 8 and 9). It is noteworthy
that vinyl silyl ether, which could be easily prepared from
carbonyl compounds,13 also leads to such a cross-coupling. It
should be noticed that ¡-siloxystyrene showed much higher
reactivity than inactivated 1-siloxycyclohexene (Entries 10 and
11).
In summary, we have systematically invested nickel-
catalyzed cross-coupling of aryl/alkenyl silyl ether with
Grignard reagents via C-OSi bonds activation.14 With this
investigation, siloxy groups are not the ubiquitous protection
group of oxygen-contained molecule in organic synthesis but
also a leaving group for further organic transformations. This
study could offer a new strategy of silyl protection/C-C bond
formation sequence in organic synthesis. Further studies on
exploring other transformations of siloxy group and their
application are under investigation.
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This paper is in celebration of the 2010 Nobel Prize
awarded to Professors Richard F. Heck, Akira Suzuki, and
Ei-ichi Negishi.
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Chem. Lett. 2011, 40, 1001-1003
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/