Silver(I) oxide-promoted chemoselective cross-coupling reaction of (Diborylmethyl)trimethylsilane

Article abstract of DOI:10.1246/cl.130643

The present paper describes a synergistic effect in the Pdcatalyzed SuzukiMiyaura cross-coupling reaction. The chemoselective cross-coupling reaction of (diborylmethyl)trimethylsilane and aryl halides proceeded at room temperature when a silver salt and K

Full text of DOI:10.1246/cl.130643

doi:10.1246/cl.130643
Published on the web August 21, 2013
1363
Silver(I) Oxide-promoted Chemoselective Cross-coupling Reaction
of (Diborylmethyl)trimethylsilane
Kohei Endo,*1,2 Fumiya Kurosawa,1 and Yutaka Ukaji1
1Division of Material Sciences, Graduate School of Natural Science and Technology,
Kanazawa University, Kakuma, Kanazawa 920-1192
2PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012
(Received July 10, 2013; CL-130643; E-mail: kendo@se.kanazawa-u.ac.jp)
Table 1. Screening of reaction conditions
The present paper describes a synergistic effect in the Pd-
catalyzed Suzuki-Miyaura cross-coupling reaction. The chemo-
selective cross-coupling reaction of (diborylmethyl)trimethyl-
silane and aryl halides proceeded at room temperature when a
silver salt and KOH were added. The reaction gave benzyl-
boronate derivatives bearing a trimethylsilyl group at the
benzylic position.
OMe
4-bromoanisole (2a)
[Pd{P(t-Bu)3}2] (5 mol %)
O
B
O
B
O
B
additives (y equiv)
O
O
O
R
R
H2O/dioxane
rt, time
1a, R = SiMe3 (x equiv)
1b, R = H (x equiv)
3a, R = SiMe3
4a, R = H
1c, R = (CH2)2Ph (x equiv)
5a, R = (CH2)2Ph
Substrate Additives
Entrya
Time/h Yield/%b
(x)
(y)
The Suzuki-Miyaura cross-coupling reaction achieves reli-
able C-C bond formation in organic chemistry.1 The use of
alkylboron compounds requires further manipulations, since the
low reactivities of alkylboron compounds and the isomerization
of Pd intermediates often give low chemo- and regioselectivity.2
During our studies of the Suzuki-Miyaura cross-coupling
reaction of diborylmethane derivatives,3 we found that (diboryl-
methyl)trimethylsilane required Ag2O to give the desired
product. We tentatively examined the coupling reaction of
(diborylmethyl)trimethylsilane 1a and 4-bromoanisole (2a)
under the optimum reaction conditions, using [Pd{P(t-Bu)3}2]
as a catalyst for the reaction of diborylmethane 1b (Table 1,
Entries 1 and 2). However, the reaction did not give any of the
cross-coupling product 3a.4 The neighboring bulky SiMe3 group
seems to prevent the coupling reaction at the α-carbon atom.
When the reaction using 1a or 1b was carried out in the presence
of Ag2O as a base, the desired product 3a or 4a, respectively,
was obtained in low yield (Entries 3 and 4). The Suzuki-
Miyaura cross-coupling reaction took place chemoselectively to
give benzylboronate derivatives exclusively. The present results
encouraged us to examine the effect of additives. The use of
KOH and Ag2O significantly promoted the coupling reaction of
1a to give the desired product 3a (Entries 5-7). The reaction in
the presence of a catalytic amount of Ag2O or the absence of
[Pd{P(t-Bu)3}2] did not give the product 3a (Entries 8 and 9).5
Acidic workup seems to be detrimental to the yield of product
3a; simple extraction of the reaction mixture using ether
improved the yield of product 3a (Entries 10 and 11). Although
we confirmed that Ag2O affected the coupling reaction of
diborylmethane 1b in Entry 4, the reaction rate was similar to
that in the absence of Ag2O (Entries 2 and 12). The coupling
reaction of diborylalkane 1c and 2a gave a similar reaction rate,
regardless of the presence or absence of Ag2O (Entries 13 and
14). An unexpected cooperative effect of Si and Ag might play
an important role in the present Pd-catalyzed cross-coupling
reaction. Other silver salts or bases hardly promoted the reaction
(Entries 15-22). This is a rare example of the synthesis of gem-
borylsilyltoluene derivatives under ambient conditions.6-8
The scope of aryl bromides is shown in Table 2. The use of
4-substituted aryl bromides 2a-2f gave the products 3a-3f in
1
2
3
4
5
6
7
8
9c
10
11
12
13
14
15
16
17
18
19
20
21
22
1a (2)
1b (2)
1a (2)
KOH (2)
KOH (2)
Ag2O (2)
24 not obtained
1.5 4a, >98
24 3a, 7
1b (1.5) Ag2O (1.5)
24 4a, 16
1a (2)
1a (3)
1a (3)
1a (3)
1a (3)
1a (3)
1a (3)
1b (3)
1c (3)
1c (3)
1a (3)
1a (3)
1a (3)
1a (3)
1a (3)
1a (3)
1a (3)
1a (3)
KOH (2), Ag2O (2)
3
3
3
2
3a, 53
3a, 78
3a, 79
not detected
KOH (3), Ag2O (3)
KOH (3), Ag2O (1)
KOH (3), Ag2O (0.1)
KOH (3), Ag2O (1)
KOH (3), Ag2O (1)
KOH (3), Ag2O (1)
KOH (3), Ag2O (1)
KOH (3), Ag2O (1)
KOH (3)
KOH (3), Ag2CO3 (1)
KOH (3), AgOAc (1)
KOH (3), AgNO3 (1)
KOH (3), AgOTf (1)
NaOH (3), Ag2O (1)
K2CO3 (3), Ag2O (1)
KOAc (3), Ag2O (1)
CsF (3), Ag2O (1)
24 not obtained
2
2
2
3a, 49
3a, 98
4a, 94
4.5 5a, 31
4.5 5a, 57
2
not obtained
2.5 3a, 16
2.5 not obtained
2.5 not obtained
2.5 3a, 12
2.5 not obtained
2.5 not obtained
2.5 not obtained
aThe reaction was stopped with silica gel (Entries 1-9). The
reaction was stopped with 6 M HCl aq. (Entry 10). The
reaction was stopped with H2O (Entries 11-22). bNMR yields.
cThe reaction was carried out in the absence of [Pd{P(t-
Bu)3}2].
moderate to high yields. However, strong electron-withdrawing
groups such as NO2, CN, and acetyl groups gave unidentified
products. The use of 3-substituted aryl bromides 2g-2i gave the
products 3g-3i in moderate yields, but electron-withdrawing
groups diminished the product yield. Relatively bulky aryl
bromides 2j-2n gave the products 3j-3n in low to moderate
yields. The use of heteroaromatic bromides gave unidentified
products. The subsequent coupling reaction to give diaryl-
methane derivatives was not observed at all.3d In every case,
Chem. Lett. 2013, 42, 1363-1365
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1364
Table 2. Scope of arylhalidesa,b
O
O
ArBr 2a–n (1 equiv)
B
B
[Pd{P(t-Bu)3}2] (5 mol %)
KOH (3 equiv)
O
O
O
O
O
B
B
B
Ar
Si
O
O
O
Me
Me
Me
Ag2O (1 equiv)
OMe
[Pd{P(t-Bu)3}2] (5 mol %)
O
Si
Si
Ag2O (1 equiv)
Me
Me
Me
1a (3 equiv)
Me
Me
1a (3 equiv)
B
H2O/dioxane
rt, time
Me
O
+
3a–n, time, yield
H2O/dioxane
80 °C, 5.5 h
Si
Me
Me
Me
OMe
3a, 53%
Br
OMe
Me
O
O
O
2a
B
B
B
O
O
O
Scheme 1. KOH-free coupling under thermal conditions.
Si
Si
Me
Si
Me
Me
Me
Me
Me
Me
Me
Me
3a, 2 h, 88% (98%)
3b, 3.5 h, 80% (quant)
3c, 1.5 h, 54%
O
O
Ph
F
Cl
B
B
O
O
O
O
O
B
B
B
Si
O
O
O
Me
Me
Me
OMe
[Pd{P(t-Bu)3}2] (5 mol %)
O
Si
Si
Me
Si
Me
additive
Me
Me
Me
Me
Me
Me
Me
1a (3 equiv)
B
O
+
H2O/dioxane
rt or reflux
3d, 27 h, 51%
3e, 3.5 h, 65% (93%)
3f, 4 h, 49%
Si
Me
Me
Me
OMe
O
O
O
3a
not obtained under Condition A–B
X
B
B
B
O
O
O
OMe
Me
Cl
2a-Cl; X = Cl
2a-I; X = I
Si
Me
Si
Si
Me
Me
Me
Me
Me
Me
Me
Me
condition A: additive-free
condition B: Ag2O (1 equiv)
condition C: KOH (3 equiv)
condition D: KOH (3 equiv), Ag2O (1 equiv)
3g, 3 h, 53% (75%)
3h, 3.5 h, 70% (84%)
3i, 3.5 h, 20%
MeO
O
Me
O
Ph
O
Scheme 2. Use of ArCl or ArI with or without KOH and/or
Ag2O.
B
B
B
O
O
O
Si
Me
Si
Si
Me
Me
Me
Me
Me
Me
Me
3k, 2.5 h, 35%
Me
3l, 5 h, 23%
3j, 3 h, trace
temperature. DFT calculations (B3LYP/6-31G*) provided
LUMO maps of (diborylmethyl)trimethylsilane 1a and diboryl-
methane 1b.11 The LUMO was observed around the B-C-B
moieties in 1a and 1b, which seem to have similar distributions,
although the boronate moieties B-C-B in 1a are distorted.
Previous reports have indicated that Ag2O activates ArPdX
after oxidative addition of Pd(0) to ArX. The reaction of ArPdX
in the presence or absence of Ag2O could generate ArPd(OH)
with a base or H2O.12 Accordingly, the generation of ArPd(OH)
would promote the transmetalation step without any base such as
KOH.13,14 We confirmed that the present reaction of 1a and 2a
proceeded to give the product 3a in 53% yield and unidentified
by-products in the absence of KOH at 80 °C after 5.5 h; the
generation of ArPd(OH) might be possible at high reaction
temperatures (Scheme 1). The present results indicated that
KOH accelerated the reaction at room temperature. However,
reports in the literature showed that the conversion of ArPdBr
to ArPd(OH) hardly proceeded without any base; the use of
additional base could promote the reaction. In contrast, the
conversion of ArPdI to ArPd(OH) typically proceeded in the
presence of a trace amount of H2O without any base.2a,2c,2f,2g
We, therefore, examined the reaction using 4-iodoanisole or
4-chloroanisole under the same reaction conditions without
KOH; unexpectedly, the reaction did not proceed at all
(Scheme 2). Moreover, the addition of Ag2O and/or KOH to
promote the reaction did not give any of the desired product.
Reflux conditions gave a small amount of unidentified by-
products. We previously reported that the reaction of simple
diborylmethane 1b or diborylalkanes and iodoarene occur-
red.3a,3b The previous results suggested that there is a mecha-
O
O
B
B
O
O
Si
Si
Me
Me
Me
Me
Me
Me
3m, 1.5 h, 43%
3n, 1.5 h, trace
aIsolated yields. NMR yields were described in parentheses.
bThe unidentified by-products generated in all cases. The
careful purification by silica gel column decreased the product
yields.9
careful purification to remove unidentified by-products and/or
decomposition of the desired products by silica gel column
chromatography decreased the product yield.9,10
To clarify the effects of Si and Ag, 11B NMR spectroscopic
analyses of the borate intermediates derived from (diboryl-
methyl)trimethylsilane 1a were performed.11 A solution of 1a in
dioxane-d8 was treated with 8 M KOH (aq) (1 or 3 equiv); the
NMR spectrum revealed only a trace amount, if any, of borate
intermediate. Our previous studies using diborylmethane or
diborylalkanes showed that we could obtain borate intermediates
using KOH at room temperature.3a,3b Furthermore, the addition
of Ag2O to the mixture of 1a and KOH in dioxane-d8 did not
change the chemical shift. These results clearly indicated that
Ag2O did not affect the generation of borate intermediates
derived from 1a. The present reaction using 1a should, therefore,
proceed via a different pathway from the reaction pathways of
1b and 1c, which easily generated borate intermediates at room
Chem. Lett. 2013, 42, 1363-1365
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1365
3
This work was supported by JST PRESTO program, Grants-
in-Aid for Young Scientists (B) (Nos. 21750108 and 23750049)
from the Japan Society for the Promotion of Science.
Br–Ar
Pd
O
B
PdAr
BrPd Ar
O
This paper is dedicated to Professor Teruaki
Mukaiyama in celebration of the 40th anniversary of the
Mukaiyama aldol reaction.
Si
Me
Me
1a
Me
Ag2O
KOH
References and Notes
O
B
Ag
1
For reviews of the Suzuki-Miyaura cross-coupling reaction, see: a)
N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457. b) S. R.
Chemler, D. Trauner, S. J. Danishefsky, Angew. Chem., Int. Ed.
2001, 40, 4544. c) A. Suzuki, H. C. Brown, Organic Syntheses Via
Boranes, Aldrich Chemical Co., Inc., Milwaukee, WI, 2002, Vol. 3.
d) S. Kotha, K. Lahiri, D. Kashinath, Tetrahedron 2002, 58, 9633. e)
F. Bellina, A. Carpita, R. Rossi, Synthesis 2004, 2419.
O
B
[pinB(OH)(OAg)]K
AgBr
Pd
Ar
Me
O
Br
Si
Ag
Me
Me
Figure 1. Proposed mechanism.
2
a) H. Chen, M.-Z. Deng, J. Org. Chem. 2000, 65, 4444. b) A. F.
Littke, C. Dai, G. C. Fu, J. Am. Chem. Soc. 2000, 122, 4020. c) T.
Korenaga, T. Kosaki, R. Fukumura, T. Ema, T. Sakai, Org. Lett.
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Molander, J. Am. Chem. Soc. 2008, 130, 9257. e) T. Ohmura, T.
Awano, M. Suginome, Chem. Lett. 2009, 38, 664. f) D. Imao, B. W.
Glasspoole, V. S. Laberge, C. M. Crudden, J. Am. Chem. Soc. 2009,
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Burke, J. Am. Chem. Soc. 2010, 132, 6941. h) T. Ohmura, T. Awano,
M. Suginome, J. Am. Chem. Soc. 2010, 132, 13191. i) D. L.
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Shibata, J. Org. Chem. 2012, 77, 7223.
The Suzuki-Miyaura cross-coupling reaction of (borylmethyl)tri-
methylsilane was reported: a) J. A. Soderquist, B. Santiago, I. Rivera,
Tetrahedron Lett. 1990, 31, 4981. b) G. A. Molander, C.-S. Yun, M.
Ribagorda, B. Biolatto, J. Org. Chem. 2003, 68, 5534. c) S. D.
Dreher, S.-E. Lim, D. L. Sandrock, G. A. Molander, J. Org. Chem.
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Silver-catalyzed Suzuki-Miyaura cross-coupling reaction: R. Das, D.
Chakraborty, Tetrahedron Lett. 2012, 53, 7023.
Other silyl groups, such as dimethylphenylsilyl, tert-butyldimethyl-
silyl, drastically decreased the yield of products.
nistic change when 1a is used. The generation of ArPd(OH)
does not seem to be necessary in the present reaction, since
ArPdI, which was more reactive for the generation of ArPd(OH),
did not give any of the desired product.2c,15 A different active
intermediate may be generated via ArPdBr.
In the Hiyama coupling reaction using organosilanes as a
coupling partner, it has been reported that Ag2O promotes the
transmetalation step, with activation of the ArPd-X bond.16
Such activation of ArPdX and organoboron compounds using
Ag2O has also been deduced and reported in the Suzuki-
Miyaura cross-coupling reaction, although the exact role is
unclear.2a,2c,2f,2g We assumed that similar activation would be
possible in the transmetalation step. The Ag2O-assisted trans-
metalation step with a silyl group in the diborylmethane
derivative 1a seems to be reasonable, since acceleration of the
reaction was not observed using 1b or 1c and Ag2O. The use
of iodoarene, which did not give any of the desired product,
would generate ArPd(OH) in the presence of Ag2O; thus, the
generation of ArPd(OH) might not be preferable in the present
reaction using (diborylmethyl)trimethylsilane.13 It is unclear
how KOH participates in the transmetalation step, although the
use of KOH and Ag2O promoted the present reaction at room
temperature.
The proposed mechanism according to the literature is
shown in Figure 1. The oxidative addition of a Pd(0) inter-
mediate to an aryl halide proceeds to give an ArPd(II)
intermediate. Transmetalation between an ArPd(II) intermediate
and (diborylmethyl)trimethylsilane 1a proceeds in the presence
of a silver salt. Finally, reductive elimination gives the desired
coupling product and regenerates the Pd(0) intermediate. The
cooperative activation of the boronate moiety with Ag2O and/or
KOH could not be confirmed at present. The detailed behavior
of a silver salt and Si group was unclear; further studies are
therefore required to elucidate the mechanism.
3
4
5
6
7
Other ligand, such as PCy3, dppf, and NHC, gave the desired product
in low yield.
J. Kondo, H. Shinokubo, K. Oshima, Org. Lett. 2006, 8, 1185.
S. Hitosugi, D. Tanimoto, W. Nakanishi, H. Isobe, Chem. Lett. 2012,
41, 972.
8
9
10 The reaction of 1a and cinnamyl bromide and benzyl bromide did
not proceed; the further examination should be required.
11 Supporting Information is available electronically on the CSJ-
Journal Web site, http://www.csj.jp/journals/chem-lett/index.html.
12 CsOH-promoted generation of ArPdOH: a) Y. Hayashi, S. Wada,
M. Yamashita, K. Nozaki, Organometallics 2012, 31, 1073.
KOH-promoted generation of ArPdOH: b) V. V. Grushin, H.
Alper, Organometallics 1993, 12, 1890.
13 Since we could not find the procedure for the preparation of
ArPd(OH) bearing P(t-Bu)3 as a ligand in literatures, the exact
activity of ArPd(OH) bearing P(t-Bu)3 could not be confirmed.
Literature-known [(PPh3)2PhPd(OH)] and 1a was tentatively used,
but the product was not obtained at all (ref 12).
14 C. Adamo, C. Amatore, I. Ciofini, A. Jutand, H. Lakmini, J. Am.
Chem. Soc. 2006, 128, 6829.
15 J. P. Flemming, M. C. Pilon, O. Y. Borbulevitch, M. Y. Antipin, V. V.
Grushin, Inorg. Chim. Acta 1998, 280, 87.
16 a) K. Hirabayashi, J. Kawashima, Y. Nishihara, A. Mori, T. Hiyama,
Org. Lett. 1999, 1, 299. b) H. Zhou, C. Moberg, J. Am. Chem. Soc.
2012, 134, 15992.
In conclusion, we found that Ag2O significantly affected the
chemoselective cross-coupling reaction of (diborylmethyl)trime-
thylsilane at room temperature. The results of a 11B NMR
spectroscopic experiment showed that there are apparently no
borate intermediates derived from KOH and/or Ag2O. The
reaction in the absence of silver oxide did not proceed. We,
therefore deduced that silver oxide promotes the transmetalation
step between (diborylmethyl)trimethylsilane and an arylpalla-
dium intermediate. The present cooperative effect may contrib-
ute to the discovery of reaction conditions for various types of
metal-catalyzed reactions.
Chem. Lett. 2013, 42, 1363-1365
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/