Diisobutylaluminum hydride-promoted cyclization of benzyl and phenylsilyl ethers bearing a 2-(trimethylsilyl)ethynyl group: syntheses of indenes and benzosiloles

Article abstract of DOI:10.1016/j.tetlet.2016.06.123

The reaction of o-[2-(trimethylsilyl)ethynyl]benzyl methyl ethers with diisobutylaluminum hydride (DIBAL-H) gave 2-(trimethylsilyl)indenes in good yields. This cyclization proceeds by regio- and stereoselective hydroalumination of the alkyne moiety followed by intramolecular nucleophilic substitution. o-[2-(Trimethylsilyl)ethynyl]phenylsilyl methyl ethers also underwent the DIBAL-H promoted-cyclization to be converted into 2-(trimethylsilyl)benzosiloles in good yields. This approach provides straightforward and efficient way to construct benzosiloles from readily available organosilanes.

Full text of DOI:10.1016/j.tetlet.2016.06.123

Accepted Manuscript
Diisobutylaluminum hydride-promoted cyclization of benzyl and phenylsilyl
ethers bearing a 2-(trimethylsilyl)ethynyl group: syntheses of indenes and ben-
zosiloles
Hidenori Kinoshita, Hiroki Fukumoto, Takayuki Tohjima, Katsukiyo Miura
PII:
S0040-4039(16)30802-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.06.123
TETL 47850
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
30 May 2016
22 June 2016
27 June 2016
Please cite this article as: Kinoshita, H., Fukumoto, H., Tohjima, T., Miura, K., Diisobutylaluminum hydride-
promoted cyclization of benzyl and phenylsilyl ethers bearing a 2-(trimethylsilyl)ethynyl group: syntheses of indenes
and benzosiloles, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.06.123
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Diisobutylaluminum hydride-promoted
cyclization of benzyl and phenylsilyl ethers
bearing a 2-(trimethylsilyl)ethynyl group:
syntheses of indenes and benzosiloles
Leave this area blank for abstract info.
Hidenori Kinoshita, Hiroki Fukumoto, Takayuki Tohjima, and Katsukiyo Miura*
R1 R2
X
OMe
R1
X
R1
X
R2
R2
OMe
DIBAL-H
SiMe3
Al
Octane

14 h
SiMe3
SiMe3
Al = Al(i-Bu)2
X = C, Si
X = C, Si

1
Tetrahedron Letters
Diisobutylaluminum hydride-promoted cyclization of benzyl and phenylsilyl ethers
bearing a 2-(trimethylsilyl)ethynyl group: syntheses of indenes and benzosiloles
Hidenori Kinoshita, Hiroki Fukumoto, Takayuki Tohjima, and Katsukiyo Miura
Department of Applied Chemistry, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakura-ku, Saitama 338-8570, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The reaction of o-[2-(trimethylsilyl)ethynyl]benzyl methyl ethers with diisobutylaluminum
hydride (DIBAL-H) gave 2-(trimethylsilyl)indenes in good yields. This cyclization proceeds by
regio- and stereoselective hydroalumination of the alkyne moiety followed by intramolecular
nucleophilic substitution. o-[2-(Trimethylsilyl)ethynyl]phenylsilyl methyl ethers also underwent
the DIBAL-H promoted-cyclization to be converted into 2-(trimethylsilyl)benzosiloles in good
yields. This approach provides straightforward and efficient way to construct benzosiloles from
readily available organosilanes.
Available online
Keywords:
Diisobutylaluminum hydride
Benzocyclization
Indene
2009 Elsevier Ltd. All rights reserved.
Benzosilole
R1 R2
Indene frequently appears as a key structural motif in
biologically active compounds,1 functional materials,2 and
organometallic catalysts.3 Benzo[b]silole, a sila-analog of indene,
is also an important motif to impart privileged optical and
electronic properties to organic materials.4 Much attention has
been focused so far on efficient construction of these benzo-fuzed
skeletons with regio-controlled introduction of substituents.5-8
R1
R1
Si
R2
DIBAL-H
X = C
DIBAL-H
X = Si
R2
X
OMe
SiMe3
SiMe3
SiMe3
1: X = C
5: X = Si
indenes
benzosiloles
Scheme 1. Syntheses of indenes and benzosiloles.
To develop the cyclization to indenes, we commenced the
optimization of reaction conditions using benzyl ether 1a as a
probe (Table 1). Considering coordination of the ethereal oxygen
to the Lewis acidic aluminum center, 2 equiv of DIBAL-H was
used initially. The reaction of 1a at 100 ºC for 14 h gave the
desired indene 2a and styrene 3a in 31% and 46% yields,
respectively (entry 1). An increased amount of DIBAL-H (3.0
equiv) improved the yield of 2a (entry 2). In these reactions,
DIBAL-H would activate the methoxy group as Lewis acid.
Therefore Et2AlCl (1.0 equiv), a stronger Lewis acid, was
employed as an additive to facilitate the cyclization. This attempt
succeeded in giving 2a in 89% isolated yield (entry 3). Neither
shortening the reaction time nor lowering the reaction
temperature was effective in the Et2AlCl-promoted cyclization
(entries 4-7). An increase in the volume of solvent brought about
a slightly better result (entry 8). Aluminum Lewis acids other
than Et2AlCl were tested for the cyclization of 1a. Me3Al and
Et3Al turned out to be effective promoters, while use of AlCl3
resulted in a complex mixture of products (entries 9-11). In the
presence of Et2AlCl, the excess amount of DIBAL-H did not
seem to be necessary to perform the cyclization efficiently.
Expectedly investigation of the amount of DIBAL-H revealed
that reduced amounts of DIBAL-H promoted the cyclization
Recently we have found that -silylated alkenylaluminums,
which can be easily prepared by hydroalumination of
alkynylsilanes with diisobutylaluminum hydride (DIBAL-H), are
useful for intramolecular C-C bond formation by
carboalumination across alkenes. Regio-controlled syntheses of
substituted benzenes, naphthalenes, and indenes have been
achieved by the DIBAL-H-promoted reaction.5k,9 On the other
hand, organoaluminum reagents function as nucleophiles for
substitution reactions on sp3-carbon and silicon centers having a
leaving group.10,11 This knowledge on organoaluminum
chemistry induced us to explore new methods for indene and
benzosilole syntheses by intramolecular substitution using -
silylated alkenylaluminums prepared from ethynylsilanes and
DIBAL-H (Scheme 1). Herein we report the details of the
DIBAL-H-promoted
cyclization
of
o-[2-
(trimethylsilyl)ethynyl]benzyl methyl ether
1
and o-[2-
(trimethylsilyl)ethynyl]phenylsilyl methyl ethers 5.
———
 Corresponding author. Tel.: +81-48-858-3514; fax: +81-48-858-3516; e-mail: kmiura@apc.saitama-u.ac.jp

2
Tetrahedron
effectively (entries 12 and 14-16). The reaction using 1.3 equiv
converted into the desired indene 2i in a moderate yield (entry 8),
the cyclization of trityl ether 1j to 2j resulted in failure (entry 9).
of DIBAL-H achieved the same isolated yield (91%) of 2a as that
by the reaction using 2 equiv of DIBAL-H (entry 14 vs. 8). The
reaction with the reduced amount of Et2AlCl (0.8 equiv) resulted
in a slightly decreased yield of 2a (entry 13). The reaction
conditions of entry 14 were adopted as the optimized conditions.
1
In this case, the H NMR and GCMS analyses of the crude
product
indicated
that
1-diphenylmethyl-2-[(E)-2-
(trimethylsilyl)ethenyl]benzene was formed as the main product
by double reduction of the C-C triple bond and the benzylic C-O
bond. The reaction of 1j without Et2AlCl gave a complex
mixture. Surprisingly, the reaction of 1k gave naphthalene 4k
instead of the expected product 2k (entry 10). The formation of
4k is attributable to the Lewis acid-promoted elimination of
methanol from 1k followed by the DIBAL-H-promoted
cyclization of the resultant enyne, 1-cyclohexenyl-2-[2-
(trimethylsilyl)ethynyl]benzene. The latter step has already been
reported by this lab.13 When the reaction was conducted without
Et2AlCl, naphthalene 4k was obtained in 12% yield along with
trace amount of 2k. Benzyl ether 1l, bearing a chlorinated 1,2-
phenylene tether, was completely consumed under the standard
conditions. However, the desired cyclization to 2l was inefficient,
Table 1. Optimization of reaction conditions for indene
synthesis.a
Me
Me
OMe
SiMe3
Me
Lewis Acid
DIBAL-H
OMe
+
SiMe3
Octane
SiMe3
1a
2a
3a
DIBAL-H
(equiv)
2.0
Lewis
temp
time
(h)
14
18
14
8
yield (%)b
entry
Acid
–
(ºC)
100
100
100
100
100
80
2a
3a
(46)
(6)
0
1c
2c
(31)
(63)
89 (82)
(75)
(68)
(66)
(31)
91
and
(E)-1-[2-(trimethylsilyl)ethenyl]-4-chloro-2-
3.0
–
(methoxymethyl)benzene (3l) was formed in 31% yield as the
major byproduct. The reaction of naphthylmethyl ether 1m gave
benzo[e]indene 2m in 67% yield with a mixture of unidentified
products (entry 12).
3c
2.0
Et2AlCl
Et2AlCl
Et2AlCl
Et2AlCl
Et2AlCl
Et2AlCl
Et3Al
4c
2.0
(0)
(6)
(20)
(59)
0
5c
2.0
6
6c
2.0
6
Table 2. Synthesis of indenes.a
7c
2.0
50
6
R1
R2
Et2AlCl (1.0 equiv)
DIBAL-H (1.3 equiv)
R1
8
2.0
100
100
100
100
100
100
100
100
100
14
14
14
14
14
14
14
14
14
R2
OMe
R3
R3
SiMe3
9
2.0
82
0
Octane, 100 ºC, 14 h
10
11
12
13e
14
15
16
2.0
Me3Al
AlCl3
86
0
SiMe3
1
2
entry
1
substrate 1
product 2
yield (%)b
82
2.0
C. M.d
trace
0
OMe
1.5
Et2AlCl
Et2AlCl
Et2AlCl
Et2AlCl
Et2AlCl
90
1b
2b
2c
SiMe3
1.5
84
0
SiMe3
Et
1.3
91
0
Et
OMe
2
3
4
1c
1d
1e
89
96
92
1.2
88
0
SiMe3
SiMe3
SiMe3
1.0
73
0
SiMe3
t-Bu
Ph
Cl
aUnless otherwise noted, all reactions were carried out with 1a
t-Bu
OMe
2d
2e
(0.25 mmol), DIBAL-H (0.25-0.75 mmol), and a Lewis acid
(0.25 mmol) in octane (0.75 mL). Isolated yield. The yields
determined by H NMR analysis on the basis of an internal
standard (dibenzyl ether) are shown in parentheses. Octane (0.5
mL) was used. Complex mixture. Et2AlCl (0.20 mmol) was
used.
b
SiMe3
1
c
Ph
OMe
d
e
SiMe3
Cl
We next investigated the scope and limitations of the DIBAL-
H-promoted cyclization of benzyl ethers 1 (Table 2). Indene 2b
was obtained from 1b in 82% yield in spite of its volatility (entry
1). The reactions of 1c-f also afforded the corresponding 2-
(trimethylsilyl)indenes 2c-f in high yields (entries 2-5). In
contrast, the substrate 1g, bearing a p-methoxyphenyl group on
the benzylic carbon, was converted into a complex product
mixture, and the desired indene 2g was not detected (entry 6).
The discouraged result seemed to be due to high electron-
donating ability of the p-methoxyphenyl group, which would
make the benzylic position fragile in the presence of Et2AlCl.
When the reaction was conducted without the Lewis acid
promoter, use of an increased amount of DIBAL-H gave the
demethylated form of 2g, that is phenol 2g', in 94% yield.12 The
cyclization of 1h, bearing a benzhydryl group, resulted in a low
yield of the corresponding indene 2h (entry 7). Elongation of the
reaction time improved the yield slightly. Tertiary alkyl ethers 1i-
k were also tested for the present cyclization. Although 1i was
1f
2f
5
95
OMe
SiMe3
SiMe3
OMe
OH
C.M.c,d
94e
1g
2g'
6
7
OMe
SiMe3
SiMe3
32f
1h
2h
OMe
53f,g
SiMe3
SiMe3

3
1c
2
2.0
2.0
1.5
1.3
1.2
1.3
1.3
1.3
1.3
1.3
100
100
100
100
100
80
14
40
49
72
70
83
85
87
80
74
19
12
13
19
6
Me
OMe
Me
Ph
Et
Et
8
9
1i
2i
2j
42 f
SiMe3
SiMe3
SiMe3
3
Ph
OMe
4
Ph
Ph
1j
trace
5
SiMe3
6
7
7
70
3
10
0
1k
2k
4k
OMe
8
65
0
SiMe3
SiMe3
9
60
0
10d
65
0
75f
aUnless otherwise noted, all reactions were carried out with 5a
(0.25 mmol) in octane (0.75 mL) for 14 h. bIsolated yield.
cEt2AlCl (0.25 mmol) was used. dThe reaction time was 7 h.
SiMe3
SiMe3
Cl
OMe
Cl
11
12
1l
2l
30f
SiMe3
OMe
67
1m
2m
SiMe3
Under the optimized conditions, silyl ethers 5b and 5c were
efficiently converted into the desired benzosiloles 6b and 6c
SiMe3
aUnless otherwise noted, all reactions were carried out with 1
(0.25 mmol), DIBAL-H (0.325 mmol), and Et2AlCl (0.25 mmol)
in octane (0.75 mL) at 100 ºC for 14 h. bIsolated yield. cComplex
(Scheme 3). Bissilylbenzene 5d underwent
a successful
bicyclization to 1,5-disila-s-indacene 6c in 63% yield.
d
e
mixture. DIBAL-H (0.575 mmol) was used. The amount of
DIBAL-H was increased to 0.825 mmol and Et2AlCl was not
used. fNMR yield. gThe reaction time was 28 h.
Ph
Ph
Ph
DIBAL-H
(1.3 equiv)
Ph
Ph
Si
Si
Ph
OMe
Si
SiMe3
Octane
65 ºC
14 h
SiMe3
5b
6b, 84%
Sonogashira
Coupling
Me
R
R
Br
Me
Si
Br
I
OMe
as above
BuLi, R2SiCl2
then
Si
SiMe3
OMe
SiMe3
SiMe3 MeOH
SiMe3
5
SiMe3
5c
6c, 89%
Scheme 2. Synthesis of silyl ethers 5.
Me3Si
Ph
Ph
Ph
Si
DIBAL-H
Ph
SiMe3
Si
(2.6 equiv)
OMe
Me3Si
Ph
MeO
Octane
65 ºC
14 h
We attempted to apply the present cyclization to the synthesis
of benzosiloles from silyl ethers 5, which could be easily
prepared from 1-bromo-2-iodobenzene in two steps (Scheme 2).
The reaction conditions were reexamined using 5a (R = Me)
(Table 4). Treatment of 5a with 2 equiv of DIBAL-H at 100 ºC
for 14 h gave benzosilole 6a in only 14% yield along with
reduction product 7a (Table 4, entry 1). Without Et2AlCl the
yield of 6a was improved to 40% although 7a was still detected
(entry 2). Since benzosilole 6a was efficiently reduced to 7a
almost quantitatively with 2 equiv of DIBAL-H for 24 h, the
amount of DIBAL-H was decreased. This attempt succeeded in
improving the yield of 6a (entries 3-5). The reaction with 1.3
equiv of DIBAL-H achieved a good yield of 6a (entry 4). After
further optimization of the reaction conditions (entries 6-10), it
was revealed that the reaction temperature was crucial for the
silole construction. When the reaction was conducted at 65 °C,
6a was obtained in 87% isolated yield without 7a (entry 8).
Si
Si
Ph
Ph
Ph
SiMe3
5d
6d,
63%
Scheme 3. Syntheses of benzosiloles.
In conclusion, we have succeeded in efficient synthesis of
silylated indenes by the DIBAL-H-promoted cyclization of o-[2-
(trimethylsilyl)ethynyl]benzyl ethers. This reaction is applicable
to the synthesis of benzosiloles using silyl ether analogs as
substrates. The scope and mechanistic aspects of the benzosilole
synthesis are now under investigation and will be reported in due
course.
References and notes
1.
2.
(a) Lee, B. H.; Choi, Y. L.; Shin, S.; Heo, J.-N. J. Org. Chem.
2011, 76, 6611. (b) Majetich, G.; Shimkus, J. M. J. Nat. Prod.
2010, 73, 284.
(a) Yang, J.; Lakshmikantham, M. V.;Cava, M. P.;Lorcy,D.;
Bethelot, J. R. J. Org. Chem. 2000, 65, 6739. (b) Shoaee, S.;
Subramaniyan, S.; Xin, H.; Keiderling, C.; Tuladhar, P. S.;
Jamieson, F.; Jenekhe, S. A.; Durrant, J. R. Adv. Funct.
Mater. 2013, 23, 3286. (c) Rocha, M. A.; Petersen, P. A. D.;
Teixeira-Neto, E.; Petrilli, H. M.; Leroux, F.; Taviot-Gueho, C.;
Constantino, V. R. L. RSC Adv. 2016, 6, 16419.
Table 3. Optimization of reaction conditions for benzosilole
synthesis.a
Me
Me
Me
Me
Si
Me
Me
DIBAL-H
Octane
OMe
Si
Si
+
SiMe3
SiMe3
SiMe3
5a
6a
7a
3.
4.
Glöckner, A.; Bauer, H.; Maekawa, M.; Bannenberg, T.; Daniliuc,
C. G.; Jones, P. G.; Sun, Y.; Sitzmann, H.; Tamm, M.; Walter, M.
D. Dalton Trans. 2012, 41, 6614. and references therein.
Yamaguchi, S.; Tamao, K. Silicon-containing Polymers: The
Science and Technology of their Synthesis and Applications, Eds.:
DIBAL-H
(equiv)
temp
(ºC)
yield (%)b
entry
6a
7a

4
Tetrahedron
Jones, R. G.; Ando, W.; Chojnowski, J., Kluwer Academic
Publishers, Dordrecht, 2000, pp. 461–498.
Am. Chem. Soc. 2008, 130, 4240. (d) Shimizu, M.; Hiyama, T.
Synlett 2012, 23, 973. (e) Onoe, M.; Baba, K.; Kim, Y.; Kita, Y.;
Tobisu, M.; Chatani, N. J. Am. Chem. Soc. 2012, 134, 19477. (f)
Liang, Y.; Geng, W.; Wei, J.; Xi, Z. Angew. Chem., Int. Ed. 2012,
51, 1934. (g) Meng, T.; Ouyang, K.; Xi, Z. RSC Adv., 2013, 3,
14273.
(a) Kinoshita, H.; Ishikawa, T.; Miura, K. Org. Lett, 2011, 13,
6192. (b) Kinoshita, H.; Tohjima, T.; Miura, K. Org. Lett, 2014,
16, 4762.
5.
For recent examples of indene syntheses, see: (a) Tran, D. N.;
Cramer, N.; Angew. Chem., Int. Ed. 2011, 50, 11098. (b) Zhou, F.;
Han, X.; Lu, X. J. Org. Chem. 2011, 76, 1491. (c) Sato, T.;
Onuma, T.; Nakamura, I.; Terada, M. Org. Lett. 2011, 13, 4992.
(d) Nun, P.; Gaillard, S.; Poater, A.; Cavallo, L.; Nolan, S. P. Org.
Biomol. Chem. 2011, 9, 101. (e) Usanov, D. L.; Yamamoto, H.
Org. Lett. 2012, 14, 414. (f) McGonigal, P. R.; de León, C.;
Wang, Y.; Homs, A.; Solorio-Alvarado, C. R.; Echavarren, A. M.
Angew. Chem., Int. Ed. 2012, 51, 13093. (g) Zhao, J.; Clark, D. A.
Org. Lett. 2012, 14, 1668. (h) Eom, D.; Park, S.; Park, Y.; Ryu, T.;
Lee, P. H. Org. Lett. 2012, 14, 5392. (i) Dethe, D. H.; Murhade,
G. Org. Lett. 2013, 15, 429. (j) Mondal, S.; Mohamed, R. K.;
Manoharan, M.; Phan, H.; Alabugin, I. V. Org. Lett. 2013, 15,
5650. (k) Becker, P.; Priebbenow, D. L.; Pirwerdjan, R.; Bolm, C.
Angew. Chem. Int. Ed. 2014, 53, 269. (l) Kinoshita, H.; Hirai, N.;
Miura, K. J. Org. Chem. 2014, 79, 8171.
9.
10. C-C bond formation for intermolecular nucleophilic substitution
of vinylaluminum speices toward epoxides, see: Zweifel, G.;
Miller, J. A. Organic Reactions, 1984, 32, 375.
11. C-Si bond formation: Kadikova, R. N.; Zosim, T. P., Dzhemilev,
U. M.; Ramazanov, I. R. J. Organomet. Chem. 2014, 763, 14.
12. Demethylation of methyl phenyl ethers with LiAlH4 was reported,
see: Carroll, J. F.; Kulkowit, S.; McKervey, M. A. J. Chem. Soc.,
Chem. Commun. 1980, 507.
13. DIBAL-H promoted synthesis of naphthalenes from o-
(trimethylsilylethynyl)styrenes, see: Kinoshita, H.; Yaguchi, K.;
Tohjima, T.; Hirai, N.; Miura, K. Tetrahedron Lett. 2016, 57,
2039.
6.
7.
8.
Synthesis of benzosiloles using AlCl3 and o-ethynylphenylsilyl
hydride has been reported by Yamamoto’s group, see: Sudo, T.;
Asao, N.; Yamamoto, Y. J. Org. Chem. 2000, 65, 8919.
KH-promoted synthesis of benzosiloles using o-ethynylphenylsilyl
hydride has been reported by Nakamura’s group, see: Ilies, L.;
Tsuji, H.; Nakamura, E. Org. Lett. 2009, 11, 3966.
Supplementary Material
Other examples of syntheses of benzosiloles, see: (a) Matsuda, T.;
Kadowaki, S.; Yamaguchi, Y.; Murakami, M. Chem. Commun.
2008, 2744. (b) Matsuda, T.; Yamaguchi, Y.; Murakami, M.
Synlett 2008, 561. (c) Ilies, L.; Tsuji, H.; Sato, Y.; Nakamura, E. J.
Supplementary data associated with this article can be found,
in the online version, at http://xxxxxxxxxxxxxxxxxxxxxxxxxxxx.
Highlights:
• DIBAL-H promotes the cyclization of o-
(silylethynyl)benzyl ethers to 2-silylindenes.
• Diethylaluminum chloride assists the DIBAL-H-
promoted cyclization.
• The DIBAL-H-promoted cyclization is applicable
to the synthesis of benzo[b]siloles.