Ruthenium-catalyzed C-H silylation of methylboronic acid using a removable α-directing modifier on the boron atom

Article abstract of DOI:10.1246/cl.2011.972

Ruthenium-catalyzed C-H silylation of methylboronic acid was achieved by use of 2-(1H-pyrazol-3-yl)aniline as a removable α-directing modifier on the boron atom. Crosscoupling of the product, i.e., (phenyldimethylsilyl) methylpinacolborane, with aryl halides proceeded in the presence of a [PdCl ₂(dppf)] catalyst and CsOH as a base.

Full text of DOI:10.1246/cl.2011.972

doi:10.1246/cl.2011.972
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72
Published on the web September 5, 2011
Copper-catalyzed Sila-Sonogashira­Hagihara Cross-coupling Reactions
of Alkynylsilanes with Aryl Iodides under Palladium-free Conditions
Yasushi Nishihara,* Shintaro Noyori, Takeru Okamoto, Masato Suetsugu, and Masayuki Iwasaki
Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology,
Okayama University, 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530
(
Received May 31, 2011; CL-110464; E-mail: ynishiha@cc.okayama-u.ac.jp)
An efficient and inexpensive catalytic system using a
Table 1. A stoichiometric reaction of trimethyl(phenylethyn-
a
readily available CuCl/PPh3 combination for the catalytic
cross-coupling reactions of alkynylsilanes with a variety of aryl
iodides affords unsymmetrical diarylethynes in good to excellent
yields.
yl)silane (1a) with 4-iodobenzonitrile (2a)
Cu salt (120 mol%)
Ph
SiMe3
+
I
CN
Ph
CN
DMI
120 °C, 12 h
1
a
2a
(0.3 mmol)
3a
(0.36 mmol)
Yield/%b
Yield/%c
4 (homo)
Entry
Cu salt
3
a (cross)
Aryl alkynes and related conjugated enynes are important
intermediates in pharmaceutical chemistry, natural products, and
materials science. These compounds can conveniently be
1
2
3
4
5
6
7
8
9
CuCl
CuBr
CuI
Cu2O
CuOAc
Cu(OAc)2
CuTC
CuPC
CuFC
0
22
8
0
0
0
1
synthesized from terminal alkynes and aryl or vinyl halides or
triflates by the Sonogashira­Hagihara cross-coupling reaction
5
5
2
18
20
>99
4
16
38
8
0
0
between sp and sp carbon centers, employing palladium
2,3
catalysts in conjunction with a copper(I) salt. A decade before
the discovery of the Sonogashira­Hagihara cross-coupling,
Stephens and Castro reported stoichiometric couplings between
aryl iodides and copper acetylides, in the absence of palladium,
0
4
aThe reactions were carried out with 1a (0.36 mmol) and 2a
(0.30 mmol), a copper compound (120 mol %) in 0.15 mL
(2.0 M) of DMI at 120 °C for 12 h. GC yield based on an aryl
in refluxing pyridine under a nitrogen atmosphere. Although
application of the Stephens­Castro reaction became far less
common with the advent of the usually more efficient Pd/Cu-
catalyzed Sonogashira­Hagihara coupling, recently the palla-
dium-free Sonogashira­Hagihara coupling (copper-catalyzed
Stephens­Castro coupling; eq 1) of alkynes with aryl halides
b
c
iodide 2a. GC yield based on an alkynylsilane 1a.
5
has gained increasing attention due to the expense of palladium.
acetate were found to afford the undesired homocoupled
product, 1,4-diphenyl-1,3-butadiyne (4) (Table 1, Entries 4­6).
Gratifyingly, when the copper salt was changed to copper(I)
Sonogashira-Hagihara coupling: [Pd0/CuI]
R1
H
+
X
R2
R1
R2 ð1Þ
or
catalytic Stephens-Castro coupling: [Cu ]
I
21
thiophene-2-carboxylate (CuTC), 3a was obtained quantita-
Developments in catalytic Stephens­Castro coupling reac-
tions have involved copper complexes with various ligands
tively, albeit contaminated with 4 (Table 1, Entry 7). In contrast,
the alternate carboxylates, copper(I) pyridine-2-carboxylate
(CuPC) and copper(I) furan-2-carboxylate (CuFC), did not
promote coupling (Table 1, Entries 8 and 9).
In order to investigate catalytic use of CuTC in this
coupling, various aryl iodides 2a­2c were subjected to the
reaction conditions of Table 1, Entry 7. Although the desired
cross-coupling was ultimately achieved with 10 mol % of CuTC
for 2a which bears an electron-withdrawing group, neutral or
electron-donating substituents on the benzene ring retarded the
reaction (eq 2).
6­16
(
for example, a recently reported bis(®-iodo)bis[(¹)-sparteine]-
1
7
18
dicopper(I) complex ) as well as microwave-assisted and
copper nanoparticle-catalyzed variants.19
The terminal acetylene component of Sonogashira­
Hagihara cross-coupling is often ultimately derived from
trimethylsilylethyne, and thus silyl-group deprotection to afford
the terminal alkyne coupling partner often precedes the cross-
coupling step. Methods which allow a direct coupling of the
alkynylsilanes are thus desirable as they enhance the overall
efficiency of the process. In continuation of our studies on a
direct activation of a carbon­silicon bond in alkynylsilanes by a
CuTC (10 mol%)
Ph
SiMe3
+
I
R
Ph
R
ð2Þ
DMI
1
20 °C, 12 h
2
0
1a
0.36 mmol)
2a-2c
(0.3 mmol)
copper(I) salt, we herein report copper-catalyzed cross-cou-
pling reaction of alkynylsilanes with aryl iodides in DMI (N,N¤-
dimethylimidazolidinone) under palladium-free conditions.
Initially, the coupling reaction between trimethyl(phenyl-
ethynyl)silane (1a) and 4-iodobenzonitrile (2a) was chosen as
a model reaction for the discovery of copper species which
promote stoichiometric Stephens­Castro-type reaction. As sum-
marized in Table 1, copper(I) halides, such as CuCl, CuBr, and
CuI gave the cross-coupled product 3a in up to 22% yield
(
3a: R = CN; 77%
3b: R = H; 18%
3c: R = OMe; 8%
We next screened conditions for the reaction of 1a with less
reactive 4-iodoanisole (2c) in the presence of 10 mol % of a
copper salt in DMI at 120 °C for 12 h. As shown in Table 2,
Entry 2, the yield of 3c with a combination of CuCl with NaTC,
which presumably generates CuTC in situ, gave a comparable
result to that with stoichiometric CuTC. We thus employed CuCl
as a copper catalyst hereafter owing to its low cost and ease of
(
Entries 1­3). Copper(I) oxide and copper(I) or copper(II)
Chem. Lett. 2011, 40, 972­974
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

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Table 2. Catalytic reaction of trimethyl(phenylethynyl)silane
Table 3. Cu-catalyzed cross-coupling reaction of alkynyl-
1a) with 4-iodoanisole (2c)a
silanes 1 with aryl iodides 2
a
(
Cu salt (10 mol%)
ligand
CuCl (5 mol%)
PPh3 (5 mol%)
additive
+
I
OMe
Ph
OMe
R1
PhCO2K (1.0 equiv)
Ph
SiMe3
R2
R1
R2
DMI
SiMe3
(1.2 equiv)
1a-1h
+
I
DMI
120 °C, 12 h
1
20 °C, 12 h
1
a
2c
(1.0 mmol)
3c
(1.0 equiv)
(
1.2 mmol)
2a-2r
3a-3y
Entry Cu salt Ligand
Additive Yield/%b
Alkynylsilane 1,
R =
Aryl Halide 2,
R =
Yield
/%
Entry
1
Product, 3
1
2
b
1
2
3
4
5
6
7
8
9
0
CuTC
CuCl
none
none
Pn-Bu3 (10 mol %)
PCy3 (10 mol %)
Pt-Bu3 (10 mol %)
none
NaTC
8
8
C6H5- (1a)
4-NC-C6H4 (2a)
C6H5 (2b)
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
3t
3u
3s
3u
3v
3w
3x
3y
88
91
89
97
85
76
79
78
87
91
63
64
69
55
51
44
92
94
93
80
83
97
63
80
93
80
62
c
29
5
<1
64
21
6
2
1a
1a
1a
1a
1a
1a
1a
1a
3
4
5
6
7
8
4-MeO-C6H4 (2c)
4-Me-C6H4 (2d)
4-MeCO-C6H4 (2e)
4-O2N-C6H4 (2f)
4-Cl-C6H4 (2g)
4-EtO2C-C6H4 (2h)
4-H2N-C6H4 (2i)
4-Br-C6H4 (2j)
2-Br-C6H4 (2k)
2-MeO-C6H4 (2l)
2-Me-C6H4 (2m)
2-MeCO-C6H4 (2n)
2,4,6-Me3-C6H2 (2o)
2-H2N-C6H4 (2p)
1-naphthyl (2q)
2-pyridyl (2r)
PPh (10 mol %)
3
PPh3 (20 mol %)
PPh (30 mol %)
3
PPh3 (10 mol %)
AcONa
AcOK
AcOK
84
>98
63
95
c
9
1
c
c
10 1a
1
1
1
1
1a
1a
1a
1a
1a
12
13
14
15
PhCO2K
c
12
13
14
15
PhCO K >98 (89)
2
c
PhCO2Na
PhCO2Li
67
32
c
aThe reactions were carried out with 1a (1.2 mmol) and 2c
1.0 mmol), a copper salt (10 mol %), additive (1.0 mmol) in
16 1a
17 1a
18 1a
19 4-MeO-C6H4- (1b) 2a
20 1b
(
b
d
0
.5 mL (2.0 M) of DMI at 120 °C, unless otherwise stated. GC
yield based on an aryl iodide 2c. An isolated yield is shown in
c
parenthesis. 5 mol % of CuCl and PPh3 was used.
2d
2e
2c
2
2
1
2
1b
4-NC-C6H4 (1c)
handling. When 10 mol % of Pn-Bu3 was added to CuCl
Cu/P = 1/1), the cross-coupled product 3c was obtained in
9% yield (Table 2, Entry 3). Although other phosphane ligands
23 4-MeCO-C H (1d) 2c
6
4
(
24 4-O N-C H (1e)
2c
2c
2a
2a
2
6
4
2
25 4-CF3-C6H4 (1f)
26 2-thienyl (1g)
27 n-C6H13 (1h)
PCy3 and Pt-Bu3 were examined as ligands, none of them were
superior to PPh3, which gave 3c in 64% yield (Table 2, Entries 4
and 5 vs. Entry 6). The reaction was found to be very sensitive
to the amount of the PPh3 ligand added; a lower product yield
was obtained when the PPh3/Cu ratio was more than 2 (Table 2,
Entries 6­8). After screening various carboxylate additives, it
c
aConditions: 1 (1.2 mmol), 2 (1.0 mmol), CuCl (5 mol %), PPh3
(
5 mol %), PhCO2K (1.0 mmol), DMI (0.5 mL) unless other-
b
c
wise stated. Isolated yields based on aryl iodides 2. CuCl
10 mol %), PPh3 (10 mol %), 24 h. dCuCl (10 mol %), PPh3
(
(
was discovered that PhCO K afforded a quantitative yield of 3c,
2
10 mol %).
even when just 5 mol % of CuCl/PPh3 was used as a catalyst
(
Table 2, Entries 9­15).22 No reaction occurred in the absence of
a copper catalyst.
1
Furthermore, analysis of the reaction mixture by H NMR
and GC-MS revealed no trace of homocoupled product 4.
Compared to the copper-mediated versions, the present copper-
catalyzed protocols have significant advantages. First, because
the formed alkynylcopper species can undergo oxidative
homocoupling (Glaser coupling)23 leading to lower yields of
the desired cross-coupling products and in turn, complicating
their purification, a gradually generated alkynylcopper species in
the reaction mixture can be selectively transformed to the cross-
coupled products.
Next, we were able to apply this new method to a broad
range of targets, including aryl-, heteroaryl-, and alkyl-sub-
stituted alkynylsilanes 1a­1h and various aryl iodides 2a­2r
substituted by electron-withdrawing and electron-donating
groups, using 5 mol % of CuCl/PPh3. The results obtained are
presented in Table 3. This protocol is rather general in scope for
reaction of 4-substituted aryl iodides with trimethyl(phenyl-
ethynyl)silane (1a), good to excellent yields of the cross-coupled
products 3a­3i (Entries 1­9) were obtained for systems featuring
either electron-donating or electron-withdrawing groups at C-4.
In a sharp contrast, aryl bromides did not react at all under these
reaction conditions. Therefore, 4- and 2-bromoiodobenzenes
reacted with 1a to afford 3j and 3k, respectively, in which the
bromides remain intact (Entries 10 and 11). Bulkier aryl iodides
like 2-iodoanisole, 2-iodotoluene, 2-iodoacetophenone, and,
2,4,6-trimethyliodobenzene required longer reaction times and
increased catalyst loadings to afford the cross-coupled products
3l­3o in moderate yields (Entries 12­15). When 2-iodoaniline
(2p) was reacted with 1a, 2-(phenylethynyl)aniline (3p) was
obtained in 44% yield rather than 2-phenylindole (<1%)
(Entry 16). As demonstrated in Table 3, Entries 17­26, the
present catalytic systems proved to accelerate the cross-coupling
reactions to generate the desired products 3q­3x in moderate to
excellent yields. The reactions of aliphatic alkynylsilane 1h
Chem. Lett. 2011, 40, 972­974
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

9
74
proceeded slowly to afford the desired product 3y albeit in 62%
yield (Entry 27).
b) R. D. Stephens, C. E. Castro, J. Org. Chem. 1963, 28, 3313.
c) C. E. Castro, E. J. Gaughan, D. C. Owsley, J. Org. Chem.
1
966, 31, 4071.
Concerning the mechanism, we can only present a working
hypothesis for the palladium-free cross-coupling reactions.
On the basis of our previous studies,2 it seems reasonable
to propose copper chloride(I) as a catalytic species, with a
triphenylphosphane ligand coordinating to copper giving a more
soluble and/or active species. In the first step, transmetalation of
alkynylsilanes 1 could generate an alkynylcopper species, which
would react, by oxidative addition, with aryl iodides 2 to form -a
four-coordinated copper(III) complex from which reductive
elimination expels the cross-coupled product 3 to give copper
iodide. We have already found that copper iodide is less
effective for transmetalation of alkynylsilanes 1 than CuCl and
5
6
For recent reviews for the Cu-catalyzed Sonogashira­Hagihara
coupling: see, H. Plenio, Angew. Chem., Int. Ed. 2008, 47, 6954.
a) K. Okuro, M. Furuune, M. Enna, M. Miura, M. Nomura,
J. Org. Chem. 1993, 58, 4716. b) J. T. Guan, G.-A. Yu, L. Chen,
T. Q. Weng, J. J. Yuan, S. H. Liu, Appl. Organomet. Chem.
2009, 23, 75.
P. Saejueng, C. G. Bates, D. Venkataraman, Synthesis 2005,
1706.
D. Ma, Q. Cai, Acc. Chem. Res. 2008, 41, 1450.
J.-H. Li, J.-L. Li, D.-P. Wang, S.-F. Pi, Y.-X. Xie, M.-B. Zhang,
X.-C. Hu, J. Org. Chem. 2007, 72, 2053.
0g
7
8
9
1
0 J. Mao, J. Guo, S.-J. Ji, J. Mol. Catal. A: Chem. 2008, 284, 85.
1
1 F. Monnier, F. Turtaut, L. Duroure, M. Taillefer, Org. Lett.
008, 10, 3203.
2 M. Wu, J. Mao, J. Guo, S. Ji, Eur. J. Org. Chem. 2008, 4050.
2
0d
CuOTf. The additive, potassium benzoate, might play dual
roles: transforming relatively inactive CuI into more active
2
1
CuOCOPh, while also trapping Me SiCl which would otherwise
13 K. G. Thakur, E. A. Jaseer, A. B. Naidu, G. Sekar, Tetrahedron
Lett. 2009, 50, 2865.
14 H.-J. Chen, Z.-Y. Lin, M.-Y. Li, R.-J. Lian, Q.-W. Xue, J.-L.
Chung, S.-C. Chen, Y.-J. Chen, Tetrahedron 2010, 66, 7755.
3
retard transmetalation from silicon to copper to generate the
requisite organocopper species. However, it can be ruled out that
the terminal alkynes were formed in the presence of potassium
benzoate, because we confirmed that desilylation of 1 never
occurred (<5%) in the presence of potassium benzoate and that
the desilylated compound of 1a, phenylethyne gave only a trace
amount of cross-coupled product under the optimized condi-
tions.
1
1
1
5 E. Zuidema, C. Bolm, Chem.®Eur. J. 2010, 16, 4181.
6 C.-H. Lin, Y.-J. Wang, C.-F. Lee, Eur. J. Org. Chem. 2010, 4368.
7 S. Priyadarshini, P. J. A. Joseph, P. Srinivas, H. Maheswaran,
M. L. Kantam, S. Bhargava, Tetrahedron Lett. 2011, 52, 1615.
8 a) H. He, Y.-J. Wu, Tetrahedron Lett. 2004, 45, 3237. b) E.
Colacino, L. Daïch, J. Martinez, F. Lamaty, Synlett 2007, 1279.
1
In summary, we have discovered conditions for the cross-
coupling reactions of alkynylsilanes with aryl iodides using
CuCl/PPh3 as a catalyst. Since this novel catalytic system is
tolerant, versatile, and significantly less expensive than “tradi-
tional” Pd/Cu-cocatalyzed Sonogashira­Hagihara cross-cou-
plings, practical use should be found for the synthesis of
unsymmetrical diarylethynes.24 Efforts to clarify the reaction
mechanism, to modify the reaction conditions, and to apply the
reaction to the less reactive aryl bromides and chlorides are in
progress.
19 B.-X. Tang, F. Wang, J.-H. Li, Y.-X. Xie, M.-B. Zhang, J. Org.
Chem. 2007, 72, 6294.
20 a) K. Ikegashira, Y. Nishihara, K. Hirabayashi, A. Mori, T.
Hiyama, Chem. Commun. 1997, 1039. b) Y. Nishihara, K.
Ikegashira, A. Mori, T. Hiyama, Chem. Lett. 1997, 1233. c) A.
Mori, A. Fujita, Y. Nishihara, T. Hiyama, Chem. Commun.
1
997, 2159. d) Y. Nishihara, K. Ikegashira, A. Mori, T. Hiyama,
Tetrahedron Lett. 1998, 39, 4075. e) Y. Nishihara, K.
Ikegashira, K. Hirabayashi, J.-i. Ando, A. Mori, T. Hiyama,
J. Org. Chem. 2000, 65, 1780. f) Y. Nishihara, J.-i. Ando, T.
Kato, A. Mori, T. Hiyama, Macromolecules 2000, 33, 2779. g)
Y. Nishihara, K. Ikegashira, F. Toriyama, A. Mori, T. Hiyama,
Bull. Chem. Soc. Jpn. 2000, 73, 985. h) Y. Nishihara, M.
Takemura, A. Mori, K. Osakada, J. Organomet. Chem. 2001,
This work was supported by a Grant-in-Aid for Scientific
Research on Priority Areas “Advanced Molecular Transforma-
tions of Carbon Resources” from the Ministry of Education,
Culture, Sports, Science and Technology, Japan. Y. N. is grateful
to Chisso Petrochemical Corporation for generous donation of
trimethylsilylacetylene to prepare 1.
6
20, 282. i) Y. Nishihara, T. Kato, J.-i. Ando, A. Mori, T.
Hiyama, Chem. Lett. 2001, 950. j) Y. Nishihara, E. Inoue, Y.
Okada, K. Takagi, Synlett 2008, 3041. k) Y. Nishihara, E.
Inoue, D. Ogawa, Y. Okada, S. Noyori, K. Takagi, Tetrahedron
Lett. 2009, 50, 4643.
2
1 Y. Nishihara, Y. Inoue, M. Fujisawa, K. Takagi, Synlett 2005,
2309.
This paper is in celebration of the 2010 Nobel Prize
awarded to Professors Richard F. Heck, Akira Suzuki, and
Ei-ichi Negishi.
22 Typical procedure is as follows. To a solution of CuCl (5 mg,
0.05 mmol, 5 mol %), PPh3 (13.1 mg, 0.05 mmol, 5 mol %), and
potassium benzoate (160 mg, 1.0 mmol) in DMI (0.5 mL) were
added 1a (236 ¯L, 1.2 mmol), and 2c (234 mg, 1.0 mmol) at
room temperature. The reaction mixture was stirred for 12 h at
120 °C, quenched with 3 M HCl, and extracted with diethyl
ether (25 mL © 2). The combined ethereal layer was washed
with aq NaHCO3 solution and brine and dried over MgSO4.
Filtration and evaporation provided a brown oil (GC yield
>98%). Purification by column chromatography (SiO2, hex-
ane:diethyl ether = 9:1; Rf = 0.49) gave 3c (185 mg, 89%
yield) as white solid.
References and Notes
1
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1
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3
4
For reviews on the Sonogashira­Hagihara reaction: a) E.-i.
Negishi, L. Anastasia, Chem. Rev. 2003, 103, 1979. b) R.
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23 For a review, see: P. Siemsen, R. C. Livingston, F. Diederich,
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24 Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
Chem. Lett. 2011, 40, 972­974
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/