Straightforward synthesis of HOMSi reagents via sp2 C-H silylation

Article abstract of DOI:10.1246/cl.150359

Straightforward C-H silylation of heteroarenes and alkenes was found to provide efficient access to organo-HOMSi reagents as stable silicon reagents for cross-coupling. Various heteroarenes and terminal alkenes were silylated to show the versatility of the reaction. This method was applied in double silylation reactions to give bisHOMSi reagents. The silylation products could be used in the cross-coupling reaction with haloarenes easily.

Full text of DOI:10.1246/cl.150359

Received: April 17, 2015 | Accepted: May 8, 2015 | Web Released: May 19, 2015
CL-150359
Straightforward Synthesis of HOMSi Reagents
via sp2 C-H Silylation
Yasunori Minami,*1,2 Takeshi Komiyama,3 and Tamejiro Hiyama*1,2
1Research and Development Initiative, Chuo University, Kasuga, Bunkyo-ku, Tokyo 112-8551
2ACT-C, JST, Chiyoda-ku, Tokyo 102-0076
3Department of Applied Chemistry, Chuo University, Kasuga, Bunkyo-ku, Tokyo 112-8551
(E-mail: yminami@kc.chuo-u.ac.jp, thiyama@kc.chuo-u.ac.jp)
Straightforward C-H silylation of heteroarenes and alkenes
was found to provide efficient access to organo-HOMSi reagents
as stable silicon reagents for cross-coupling. Various heteroarenes
and terminal alkenes were silylated to show the versatility of the
reaction. This method was applied in double silylation reactions to
give bisHOMSi reagents. The silylation products could be used in
the cross-coupling reaction with haloarenes easily.
groups, we assumed that iridium and rhodium-catalytic systems
are suitable for the silylation using 1 because 1 seemed unstable
in the presence of acids or cationic metal species, which might
interact with the oxygen atom in 1 to cleave the C-O bond. First,
we attempted a reaction of benzo[b]thiophene (2a) with 3 equiv
of MOM-protected H-HOMSi 1a under Falck’s conditions:
[Ir(OMe)(cod)]2, dtbpy, and norbornene in THF at 80 °C,6c but
only 9% yield of 3a was obtained (Table 1, Run 1). The rhodium
catalyst developed by Hartwig6d did not show any catalysis. This
is probably because of the lower reactivity, steric bulkiness, and
instability of 1a derived from the pendant alkoxymethyl group.
Therefore, to enhance the reactivity of 1a, we screened various
ligands, hydrogen acceptors, and solvents (see the SI, Table S1). We
found that Me4-phen as a more electron-donating ligand in higher
concentration (2 M) of iPr2O was effective for this iridium-catalyzed
silylation to give 3a in 75% isolated yield (Run 2). Moreover, the
conditions allowed a low loading of both 1a and norbornene without
loss of efficiency. Other protecting groups were examined and THP
(1b), SEM (1c), acetyl (1d), and pivaloyl (1e) did not interfere with
the silylation of 2a to give corresponding silanes (Runs 3-6).7 Of
note, hydrosilane-sensitive acetoxy and pivaloxy groups were used
in the C-H silylation to give the corresponding 2-silylbenzothio-
phenes, albeit in modest yields (Runs 5 and 6). Especially, THP-
protected HOMSi 3b was obtained in the shortest reaction time
in the highest (89%) yield probably owing to the stability of the
THP group under the conditions (Run 3). Thus, we chose THP-
protected 1b as a silylating reagent and applied to reaction partners.
Cross-coupling reaction for a targeted sp2C-sp2C bond
formation has allowed us to construct a wide variety of functional
π-electron-conjugated molecules. This system can be applied to
cross-coupling polymerization to form π-electron-conjugated poly-
mers for electronic devices such as conductive polymers, organic
solar cells, and organic light-emitting diodes.1 Thus, it is of great
importance to readily provide user-friendly functionalized organo-
metallic reagents with high solubility, stability, and reactivity.
Silicon-based reagents are among all useful for cross-coupling
because of their stability, solubility, reactivity, and easy-handling
and preparation.2 We have already found that the tetraorganosili-
con-type coupling reagents, organo-{2-(hydroxymethyl)phenyl}-
dimethylsilanes (R-HOMSi) 4 are applicable to the synthesis of
functionalized oligoarenes and polyarenes.2f,2g,3 After cross-cou-
pling, coproduced cyclic silyl ether 5 can be easily recovered and
converted into 4 by treatment with organolithium or magnesium
reagents.4 Silyl ether 5 can also be transformed into hydroxy-
protected H-HOMSi 1, H-SiMe2{2-(PGOCH2)C6H4} (PG: pro-
tecting group), via sequential reduction and protection.3a Thus,
HOMSi-based coupling reaction enables us to construct π-
electron-conjugated functional molecules with high performance
and low waste. For achieving the straightforward and environ-
mentally benign silicon-circulated cross-coupling protocol, it is
essential to develop a simple and straightforward synthetic method
for HOMSi. Thus, we focused on catalytic C-H silylation of
(hetero)arenes using 1 without directing groups (Figure 1).5,6
Herein, we report the synthesis of sp2C-HOMSi reagents via
straightforward silylation with an iridium catalyst.
Table 1. Reaction of 2a with 1a,b
O(PG)
O(PG)
[Ir(OMe)(cod)]2 (5 mol%)
ligand (10 mol%)
H
+
H
norbornene
solvent, 80 °C
Si
Me2
Si
Me2
S
S
3
2a
1
Time
/h
Run 1, PG (equiv) Ligand
Solvent (M)
THF (0.2)
Product, yield/%c
1
2
3
4
5
6
1a, MOM (3) dtbpy
16 3a, 9d
48 3a, 75
3b, 89
Based on the previous findings by Murata,6b Falck,6c or
Hartwig6a,6d,6e for C-H silylation without the assistance of directing
1a, MOM (1.5) Me4-phen iPr2O (2)
1b, THP (1.5) Me4-phen iPr2O (2)
1c, SEM (1.5) Me4-phen iPr2O (2)
3
R2
Pd cat.
base
X
R1
H
40 3c, 52
11 3d, 54
15 3e, 31
OH
O(PG)
O(PG)
R1 R2
+
1d, Ac (1.5)
1e, Piv (1.5)
Me4-phen iPr2O (2)
Me4-phen iPr2O (2)
2
Ir cat.
R1
H
R1
Si
Me2
aUnless otherwise noted, a mixture of 1 (1.5-3 equiv), 2a (1 equiv),
[Ir(OMe)(cod)]2 (0.05 equiv), ligand (0.1 equiv), and norbornene
(3 equiv for Run 1, 1.5 equiv for Runs 2-6) in solvent was heated
at 80 °C. bdtbpy: 4,4¤-di-tert-butyl-2,2¤-bipyridyl; Me4-phen: 3,4,7,8-
tetramethyl-1,10-phenanthroline; MOM: methoxymethyl; THP: 2-
tetrahydropyranyl; SEM: 2-(trimethylsilyl)ethoxymethyl; Ac: acetyl;
Si
Si
O
This work
Me2
Me2
4
1
3
Si
deprotection
Me2
5
1) LiAlH4
2) PG-X
PG: protecting group
c
d
Figure 1. HOMSi-cycle for cross-coupling.
Piv: pivaloyl. Isolated yield. NMR yield.
Chem. Lett. 2015, 44, 1065–1067 | doi:10.1246/cl.150359
© 2015 The Chemical Society of Japan | 1065

Table 2. Silylation of aromatic C-H bonda
Table 3. Double silylation of aromatic C-H bondsa
[Ir(OMe)(cod)]2 (5 mol%)
Me4-phen (10 mol%)
norbornene (1.5 equiv)
[Ir(OMe)(cod)]2 (5 mol%)
Me4-phen (10 mol%)
norbornene (3 equiv)
O(THP)
SiTHP
=
+
H
SiTHP
Ar
H
Ar
SiTHP
+
H
Ar
H
H
SiTHP
SiTHP
Ar
SiTHP
iPr2O, 80 °C
iPr2O, 80 °C
Si
Me2
2
1b, 1.5 equiv
3
6
1b, 3 equiv
7
Time
/h
Run
1
Product, yield/%b
Run
1
2
Time/h
Product, yield/%b
1
6
92
7a, 47
7a, 60
6a
6a
H
H
SiTHP
H
H
H
2c
SiTHP
SiTHP
9
3
S
S
S
O
2b
2c
O
3f, 93
3g, 44
Br
Br
SiTHP
2
N
H
N
H
3
4
5
5
H
SiTHP
SiTHP
S
6b
7b, 88
7c, 98
H
SiTHP
3c
4
O
O
O
O
37
N
Ts
N
2d
Ts
3h, 29
3i, 93
H
H
H
SiTHP
SiTHP
S
S
6c
S
S
Dodec
Dodec
Br
5
Br
S
H2e
S
H
S
SiTHP
S
SiTHP
5
6
SiTHP
2
4
6d
6e
7d, 94
aUnless otherwise noted, a mixture of 2 (1 equiv), 1b (1.5 equiv),
[Ir(OMe)(cod)]2 (0.05 equiv), Me4-phen (0.1 equiv), norbornene
(1.5 equiv), and iPr2O (2 M) was heated at 80 °C. bIsolated yield. The
conditions using dtbpy (0.1 equiv), tBuCH=CH2 (1.5 equiv), and
toluene (2 M) were employed.
S
S
c
H
H
H
SiTHP
SiTHP
S
S
7e, 50
S
S
SiTHP
SiTHP
7d
H
S
5
S
N
6f
7f, 86
Various arenes 2 were used in the silylation using 1b, and the
results are summarized in Table 2. Benzofuran (2b) was silylated
at the C2 position to give 3f in 93% yield (Run 1). Indole (2c)
reacted to form the 2-silylated product 3g in 44% yield (Run 2). In
this case, the N-H bond did not interfere with the silylation, i.e.,
N-H silylation did not proceed. On the other hand, N-tosylated
indole (2d) provided 3-silylated one 3h in 29% yield under the
conditions using dtbpy and tBuCH=CH2 as a potent hydrogen
acceptor in toluene (Run 3).8 This C3-selectivity may be explained
by the steric repulsion between the tosyl group and the silyl
functionality, a metal migration from C2 to C3 after C-H
activation at the C2 position, or a change in the reaction
mechanism, as mentioned by Falck.6c 2-Brominated thiophene 2e
smoothly reacted with bromine intact to give the 5-silylated
product 3i in 93% yield, which seems to be a promising building
block and a monomer for 3-alkylated thiophene (Run 4).
The successful mono C-H silylation conditions were next
applied to the double silylation of thiophene-based functional
pseudo-monomers, and the results are summarized in Table 3. The
reaction of thiophene (6a) with 3 equiv of 1b proceeded via double
silylation to give 2,5-disilylthiophene 7a in 47% yield (Run 1). To
increase the yield of 7a, we further screened ligands and hydrogen
acceptors (SI, Table S2) and found that dtbpy and tBuCH=CH2
gave 7a in 60% yield although it took 92 h (Run 2).9 3-
Bromothiophene (6b) was silylated at the 2- and 5-positions to
give 7b in 88% yield without affecting bromine (Run 3). 3,4-
Ethylenedioxythiophene (6c) could be successfully converted to
2,5-bisHOMSi reagent 7c in 98% yield (Run 4).10 2,2¤-Bithiophene
(6d), thieno[3,2-b]thiophene (6e), and benzo[1,2-b:4,5-b¤]dithio-
phene (6f) provided the corresponding disilylated products 7d, 7e,
and 7f (Runs 5-7). In particular, gram-scale synthesis of 7f (1.76 g)
was readily achieved. 4,7-Bis(2-thienyl)benzothiadiazole (6g)11
smoothly gave 7g in 86% yield under the conditions using dtbpy
and tBuCH=CH2 (Run 8). Consequently, the double silylation
approach allows easy preparation of HOMSi-based monomers, and
S
S
N
N
N
8c
86
S
S
S
S
SiTHP
SiTHP
H
H
6g
7g, 86
aUnless otherwise noted, a mixture of 6 (1 equiv), 1b (3 equiv),
[Ir(OMe)(cod)]2 (0.05 equiv), Me4-phen (0.1 equiv), norbornene
(3 equiv), and iPr2O (2 M) was heated at 80 °C. bIsolated yield. The
conditions using dtbpy (0.1 equiv) and tBuCH=CH2 (3 equiv) were
employed. d6f (3.0 mmol, 569mg) and 1b (9.0 mmol, 2.26 g) were
used to give 7f (2.57 mmol, 1.76g).
c
thus the synthesis of π-conjugated polymers using the monomers
and dihaloarenes will be straightforwardly carried out in due course.
Inspired by the direct silylation of alkenes,12 we applied the
present reaction to the synthesis of functionalized vinyl silanes
(eq 1). Styrene (8a) was silylated to give the corresponding
vinylsilane 9a with E-selectivity. Next, we chose a vinyl ether
as the starting material, which is a useful substrate for Lewis
acid-catalyzed aldol reaction13 and vinyl-O bond-cleaving cross-
coupling.14 We examined the silylation of isobutyl vinyl ether (8b)
as a representative substrate and successfully obtained alkoxy
vinyl HOMSi (9b) in 77% yield as a stereomixture (E/Z = 16:1).
[Ir(OMe)(cod)]2 (5 mol%)
O(THP)
Me4-phen (10 mol%)
norbornene (1.5 equiv)
R
+
H
SiTHP
R
iPr2O (2 M), 80 °C, 4-5 h
Si
8
1b, 1.5 equiv
Me2
9
ð1Þ
O(THP)
O(THP)
Ph
O
Si
Me2
Si
Me2
9a, 98% (E/Z = >20:1)
9b, 77% (E/Z = 16:1)
1066 | Chem. Lett. 2015, 44, 1065–1067 | doi:10.1246/cl.150359
© 2015 The Chemical Society of Japan

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OH
HO
TsOH·H2O (3 mol%)
S
7f
Si
Me2
Si
MeOH/CH2Cl2 (1.5/1)
rt, 16 h
Me2
S
10, 85%
3i (2.1 equiv)
Pd[P(o-tolyl)3]2 (5 mol%) MS 3A
Cs2CO3 (2.0 equivment)
dppf (5.3 mol%)
toluene/glyme (3/1)
50 °C, 20 h
3
CuBr·SMe2 (7.5 mol%)
Dodec
S
Dodec
S
S
S
SiTHP
SiTHP
11, 54%
Scheme 1. Deprotection/double cross-coupling.
Protected (hetero)aryl-HOMSi and alkenyl-HOMSi reagents
4
are easily deprotected to give coupling-active HOMSi reagents.
For example, treatment of THP-protected benzothienyl-HOMSi 3b
with p-toluenesulfonic acid in MeOH at room temperature
produced active benzothienyl-HOMSi in 92% yield (see the SI,
eq S1). Protected bisHOMSi 7f could also be deprotected in
MeOH and CH2Cl2 to give bisHOMSi 10 in 85% yield, which
proceeded via double cross-coupling3f with bulky 2-bromo-3-
dodecyl-5-silylthiophene 3i to successfully form 2,6-dithienylben-
zodithiophene bisHOMSi reagent 11 as a functionalized monomer
for solar cells (Scheme 1).15
In conclusion, we have demonstrated that the C-H silylation
of heteroarenes and terminal alkenes with hydrosilanes is the
convenient and straightforward tool for the synthesis of heteroaryl-
and alkenyl-HOMSi reagents. This method allows us to synthesize
various bisHOMSi reagents, which are useful as building blocks
toward π-conjugated functional molecules. The proper choice of
ligand and hydrogen acceptor is the key to successful silylation.
The produced organo-HOMSi reagents are immediately utilized in
cross-coupling with haloarenes.
5
6
7
It should be mentioned that unprotected H-HOMSi is hard to isolate.
For example, treatment of 1b with TsOH in methanol always forms 5.
Attempted silylation of 2a with H-SiMe2(2-LiOCH2)C6H4 generated
from 5 and LiAlH4 failed.
The standard conditions which employs [Ir(OMe)(cod)]2, Me4-phen,
and norbornene in iPr2O reduced yield of 3h.
8
9
Monosilylated thiophene could not be isolated, suggesting that the
monosilylated thiophene is much more reactive than thiophene.
This work has been supported financially by a Grant-in-Aids
for Scientific Research (S) (No. 21225005 to T.H.) and Young
Scientists (B) (No. 25870747 to Y.M.) from JSPS and Sumitomo
Chemical Foundation. Y.M. also acknowledges Asahi Glass
Foundation.
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Supporting Information is available electronically on J-STAGE.
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Chem. Lett. 2015, 44, 1065–1067 | doi:10.1246/cl.150359
© 2015 The Chemical Society of Japan | 1067