Palladium-catalyzed silylation reaction between benzylic halides and silylboronate

Article abstract of DOI:10.1039/c6cc00713a

An efficient Pd-catalyzed silylation reaction of benzylic halides with silylboronate is reported. In this reaction, primary and secondary benzylic halides could react well with silylboronates to afford benzylic silanes. This reaction accommodates a broad substrate scope and proceeds smoothly under very mild reaction conditions. The corresponding products could be obtained in moderate to high yields and with stereospecificity.

Full text of DOI:10.1039/c6cc00713a

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DOI: 10.1039/C6CC00713A
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ARTICLE TYPE
Palladium-Catalyzed Silylation Reaction between Benzylic Halides
and Silylboronate
Zhi-Dao Huang,a Ran Ding,a Peng Wang,*c Yun-He Xu,*a and Teck-
Peng Loh a,b
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
45 Scheme 1. Different methodologies for benzylic silylation
reactions.
An efficient Pd-catalyzed silylation reaction of benzylic
halides with silyboranate is reported. In this reaction,
primary and secondary benzylic halides could react well with
10 silylboronates to afford benzylic silanes. This reaction
accomodates a broad substrate scope and proceeds smoothly
under very mild reaction conditions. The corresponding
products could be obtained in moderate to high yields and
with stereospecificity.
15 Organosilicon fragments are widely observed or used in
synthesis of bioactive molecules and organic materials.[1]
Therefore, the development of efficient methods for the synthesis
of various organosilcon compounds has attracted much attention
from organic chemists.[2] Accordingly, various noble transitionꢀ
20 metal catalyzed hydrosilylation of unsaturated carbonꢀcarbon
bonds using silanes have been well developed to afford
organosilicon compounds.[3] Recently, the methods of direct C-H
bond silylation reaction catalyzed by transitionꢀmetal catalysts
have emerged gradually as powerful tools for the construction of
25 CꢀSi bonds.[4] Therefore, useful organosilicon products could be
prepared via these practicable methods. However, among the
established methodologies, the preparation of benzylic silanes
still faces some challenges such as limited substrate scope and/or
harsh reaction conditions etc. Traditionally, the most popular
30 synthetic route to access this kind of products is reacting the
Grignard reagents with silyl halides (Scheme 1, (a)).[5] However,
substrates with functional groups such as carbonyls, cyano and
other strong electronꢀwithdrawing groups could not be tolerated
which greatly restricts its wide application in organic synthesis.
35 Another strategy to synthesize these products was conducted by
using palladium catalyst and disilanes (Scheme 1, (b)).[6]
However, only limited substrates have been examined at high
temperature. Recently, few examples on benzylic CꢀH bond
silylation reactions with the help of directing groups have also
40 been elegantly developed (Scheme 1, (c)).[7] Noticeably, He and
coꢀworkers reported the first Pdꢀcatalyzed silylation reaction
between aryl pivalates and silylboronate.[10b] In continuation of
our interest in development of CꢀSi bond formation,[8] herein we
would like to report a palladiumꢀcatalyzed
Table 1. Optimization of reaction conditions between 1-
50 (bromomethyl)naphthalene and silylboronate PhMe2SiBpin.[a]
SiPhMe2
Br
[Pd] (1 mol%)
[Ag] (1.0 equiv)
Me2PhSi-Bpin (1.2 equiv)
THF , N2 , rt , 24 h
1a
2a
entry
1b
2b
3b
4
[Pd]
Pd(PPh3)4
[Ag]
Ag2O
Ag2O
Ag2O
Ag2O
Ag2CO3
AgTFA
AgOAc
AgOAc
AgOAc
AgOAc
/
solvent
THF
THF
THF
THF
THF
THF
THF
THF
Et2O
DCM
THF
THF
THF
THF
yield (%)
93
64
trace
70
Pd(PPh3)2Cl2
Pd2(dba)3
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)2
Pd(PPh3)4
Pd(PPh3)2
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
/
5
42
6
trace
85d
75
78
52
7c
8e
9
10
11f
12g
13
14
27
Ag2O
Ag2O
/
85d
0
a Department of Chemistry, University of Science and Technology of China, Hefei, 230026, China.
bDivision of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences,
Nanyang Technological University, Singapore 637371
Pd(PPh3)4
0
a All the reactions were carried out with 1a (1.0 equiv, 0.2 mmol), solvent (2
mL), yield was determined by 1H NMR using mesitylene as internal standard. b
55 The amounts of [Pd] was 5 mol%. c This condition was not suitable for the
other substrates. d Isolated yield. e NaOAc(1.0 equiv) was used as an additive. f
K2CO3(1.0 equiv) was added. g The amounts of [Pd] was 2 mol%.
cDepartment of Chemical Engineering and Technology, Tianshui Normal University, Tianshui,
741000, China.
E-Mail: xyh0709@ustc.edu.cn; w.p.david@139.com
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DOI: 10.1039/C6CC00713A
benzylic silylation reaction using easily available benzylic halides
and silyboranate[9] as starting materials.[10]
palladium catalyst (entry 13, Table 1) or silver oxide (entry 14,
15 Table 1).
At the beginning, 1ꢀ(bromomethyl)naphthalene 1a and
silylboronate PhMe2SiBpin were reacted with different palladium
catalysts (entries 1ꢀ3, Table 1), and it was found that Pd(PPh3)4
was highly efficient to provide the desired product in the presence
With the optimized reaction conditions in hand, various
benzylic halides were tested in this reaction. The results are
summarized in Table 2. It could be observed that in most cases
the benzylic bromide bearing either electronꢀdonating or electronꢀ
5
of silver oxide in THF solution (entry 4, Table 1). Further 20 withdrawing group all afforded the desired products in high
screening showed that changing of silver additives or solvents
could not afford better results (entries 5ꢀ10, Table 1). Finally, the
10 desired product 2a still could be obtained in high yield by
yields (entries 1ꢀ8, Table 2). Although only moderate yield of the
product 2m was obtained (entry 13, Table 2), the highly electronꢀ
deficient 1ꢀ(bromomethyl)ꢀ3,5ꢀdinitrobenzene 1m still could be
employed in this reaction. Moreover, it is worthy noting that
reducing the catalyst loading to 2 mol% (entry 12, Table 1).
Control experiments were carried out, and the results showed that 25 some groups such as acetal, ester and cyano etc, being sensitive
no any desired product could be detected in the absence of in traditional methods, could all be tolerated in this reaction
Table 2. Palladium-catalyzed silylation reaction of different benzylic halides.
F3C
F3C
SiMe2Ph
Br
SiMe2Ph
Br
13
1
1m
2m, 49%
1a
CF3
2a, 85%
CF3
SiMe2Ph
Br
14
15
SiMe2Ph
2b, 72%
Br
1n
2n, 51%
NC
2
3
NC
1b
1c
Br
SiMe2Ph
Br
Br
SiMe2Ph
1o
2o, 73%
MeO2C
MeO2C
Ac
2c, 81%
Br
SiMe2Ph
SiMe2Ph
16
17
18
1p
4
5
2p, 70%
Ac
2d, 62%
1d
1e
Me
Me
SiMe2Ph
Br
SiMe2Ph
2e, 79%
SiMe2Ph
2f, 81%
Br
1q
2q, 73%
AcO
AcO
Me
tBu
Me
tBu
Br
SiMe2Ph
Br
6
7
8
9
2r, 79%
1r
1f
SiMe2Ph
2s, 80%
SiMe2Ph
2t, 95%
Br
SiMe2Ph
2g, 59%
SiMe2Ph
Br
Br
1g
MeO
MeO
1s
MeO
MeO
19
20
Ph
Ph
Br
1h
1i
2h, 70%
1t
N
Boc
Cl
N
Boc
SiMe2Ph
SiMe2Ph
Br
2i, 63%
F
F
SiMe2Ph
Br
10
21
2j, 87%
1j
F
F
2u, 76%
1u
1v
SiMe2Ph
2k, 72%
Br
Br
11
12
SiMe2Ph
Cl
1k
Cl
Cl
SiMe2Ph
22
1l
2l, 82%
CF3
CF3
2v, 68%
30
All the reactions were carried out with 1 (1.0 equiv, 0.3 mmol), Pd(PPh3)4 (2.0 mol%), Ag2O (1.0 equiv), silylboronate (1.2 equiv) in THF (2 mL) under an
atmosphere of N2 at room temperature. For 1aꢀ1h, 1qꢀ1v, the reactions ran for 24 h. For 1iꢀ1p, the reactions ran for 36 h. All yields were isolated yields after silica
chromatography.
35
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DOI: 10.1039/C6CC00713A
(entries 14, 15 and 16, Table 2). Importantly, the terminal alkene
and internal alkyne fragment on substrates remain intact in the
presence of palladium catalyst (entries 18 and 19, Table 2).
Finally, Bocꢀprotected 3ꢀ(bromomethyl)ꢀindole (entry 20, Table 2)
and secondary benzyl chloride (entries 20 and 21, Table 2) were
applied in this silylation reaction, the corresponding products
could all be isolated in good yields. Therefore, this method
provides a practical pathway to prepare benzyl silanes compared
to the traditional synthetic routes.
investigations of this strategy to carry out other organic
transformations are currently underway.
45
Acknowledgement
5
We are grateful for financial support by the National Science
Foundation for Young Scientists of China (No. 21202156) for the
funding of this research. The authors also thank Miss. Jun Kee
50 Cheng for her careful proofreading of the final manuscript.
10
Notes and references
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G. A. Showell and J. S. Mills, Drug Discov. Today, 2003, 8, 551; (c)
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Chemistry, Wiley: New York, 2000; (d) I. Ojima, Z.ꢀY. Li and J.ꢀW.
Zhu, In Chemistry of Organic Silicon Compounds, Z. Rappoport and
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[2] For selected books contained general methods for synthesis of
organosilcons, see: (a) E. W. Colvin, Silicon in Organic Synthesis;
Butterworth: London, 1981; (b) W. P. Weber, Silicon Reagents for
Organic Synthesis; SpringerꢀVerlag: New York, 1983.
After successful synthesis of various benzyl silane
compounds, we next turned our attention to explore the possible
15 mechanism of this catalytic silylation reaction. An enatioenriched
2ꢀ(chloro(phenyl)methyl)naphthalene was prepared and
3
[3] For selected books and reviews, see: (a) B. M. Trost and Z. T. Ball,
Synthesis 2005, 853; (b) B. Marciniec, H. Maciejewski, C. Pietraszuk
and P. Pawluc in Hydrosilylation: A Comprehensive Review on
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2011, 111, 863; (d) D. S. W. Lim and E. A. Anderson, Synthesis 2012,
983; (e) Y. Nakajima and S. Shimada, RSC Adv., 2015, 5, 20603.
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Wilson, R. Berg, P. Ryberg and J. F. Hartwig, J. Am. Chem. Soc.,
2015, 137, 6742.
subjected to this coupling reaction. It was found that the desired
silylation product 4 could be obtained in 67% yield and with
retention of substrate’s enantiopurity.
With this observed result, a plausible mechanistic pathway
was proposed as shown in Scheme 1. Firstly, the CꢀX bond could
be activated by Pd(0) catalyst and a Pd(II) intermediate I was
generated. Following, a palladium species (II)[11] could be formed
in the presence of silver oxide which would facilitate the
25 activation of SiꢀB bond and transmetallation process to give
intermediate IV. Finally, the desired product could be generated
after reductive elimination and released the Pd(0) catalyst to next
catalytic cycle.
20
[5] (a) G. Fraenkel, J. H. Duncan, K. Martin and J. Wang. J. Am. Chem.
Soc., 1999, 121, 10538; (b) G. Martin and F. S. Kipping, J. Chem.
Soc., 1909, 95, 302.
30 Scheme 2. Proposed mechanism for the Pdꢀcatalyzed silylation of
benzylic halides.
75 [6] (a) C. Eaborn, R. W. Grifꢀfiths and A. Pidcock, J. Organomet. Chem.,
1982, 225, 331; (b) H. Matsumoto, M. Kasahara, I. Matsubara, M.
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Organomet. Chem., 1983, 250, 99.
[7] (a) T. Ureshino, T. Yoshida, Y. Kuninobu and K. Takai, J. Am. Chem.
80
85
90
95
Soc., 2010, 132, 14324; (b) F. Kakiuchi, K. Tsuchiya, M. Matsumoto,
E. Mizushima and N. Chatani, J. Am. Chem. Soc., 2004, 126, 12792;
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1254; (b) Y.ꢀH. Xu, L.ꢀH. Wu, J. Wang and T.ꢀP. Loh, Chem.
Commun., 2014, 50, 7195; (c) M. Wang, Z.ꢀL. Liu, X. Zhang, P.ꢀP.
Tian, Y.ꢀH. Xu and T.ꢀP. Loh, J. Am. Chem. Soc., 2015, 137, 14830.
[9] Please see review paper on application of silyboranate reagents: (a) T.
Ohmura and M. Suginome, Bull. Chem. Soc. Jpn. 2009, 82, 29; (b) T.
Ohmura, J. Synth. Org. Chem. Jpn. 2013, 71, 804; (c) M. Oestreich,
E. Hartmann and M. Mewald, Chem. Rev. 2013, 113, 402. and
references cited therein; Other selective recent examples on silylation
reactions: (d) L. B. Delvos, D. J. Vyas and M. Oestreich, Angew.
Chem. Int. Ed., 2013, 52, 4650; (e) J. A. Calderone and W. L. Santos,
Angew. Chem. Int. Ed., 2014, 53, 4154; (f) Y. Tani, T. Fujihara, J.
Terao and Y. Tsuji, J. Am. Chem. Soc., 2014, 136, 17706; (g) A.
GarcíaꢀRubia, J. A. RomeroꢀRevilla, P. Mauleón, R. G. Arrayás and J.
C. Carretero, J. Am. Chem. Soc., 2015, 137, 6857; (h) Z.ꢀT. He, X.ꢀQ.
Tang, L.ꢀB. Xie, M. Cheng, P. Tian and G.ꢀQ. Lin, Angew. Chem. Int.
Conclusions
In conclusion, we have developed an efficient methodology
35 of palladiumꢀcatalyzed silylation reaction of benzylic halides.
Various benzyl silanes could be obtained in good yields by using
only 2 mol% of palladium catalyst at room temperature. The wide
scope of the functional groups tolerated in the substrates will
allow this method to be a general and powerful tool for synthesis
40 of benzyl silane compounds. Moreover, the retention of
enantiopurity in the enantioenriched substrate during
transformation could be achieved in this reaction. Further
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Ed., 2015, 54, 14815.
[10] (a) For a recent example of Ni/Cuꢀcatalyzed silylation reaction
between benzylic pivalates and silylboronate, please see: C. Zarate
and R. Martin, J. Am. Chem. Soc., 2014, 136, 2236. (b) For a recent
example of Pdꢀcatalyzed silylation reaction between aryl pivalates
and silylboronate, please see: H. Guo, X. Chen, C. Zhao and W. He,
Chem. Commun., 2015, 51, 17410. c) One example on copperꢀ
catalyzed silylation reaction of benzylic phosphate, please see: M.
Takeda, R. Shintani and T. Hayashi, J. Org. Chem. 2013, 78, 5007.
5
10 [11] (a) B. W. Glasspoole, K. Ghozati, J. W. Moir and C. M. Crudden,
Chem. Commun., 2012, 48, 1230; (b) B. M. Partridge, L. Chaussetꢀ
Boissarie, M. Burns, A. P. Pulis and V. K. Aggarwal, Angew. Chem.,
Int. Ed., 2012, 51, 11795; (c) B. P. Carrow and J. F. Hartwig, J. Am.
Chem. Soc., 2011, 133, 2116; (d) C. Amatore, A. Jutand and G. Le
15
Duc, Chem. Eur. J., 2011, 17, 2492.
4
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