Revealing Silylation of C(sp2)/C(sp3)–H Bonds in Arylphosphines by Ruthenium Catalysis

Article abstract of DOI:10.1002/anie.202003865

The first aromatic C?H silylation between arylphosphines and hydrosilanes enabled by a ruthenium complex has been developed. The excellent ortho-selectivity results from a four-membered metallacyclic intermediate involving phosphorus chelation. The develo

Full text of DOI:10.1002/anie.202003865

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Accepted Article
Title: Revealing Silylation of Csp2/sp3-H Bonds in Arylphosphines by
Ruthenium Catalysis
Authors: Zhuangzhi Shi
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202003865
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Angewandte Chemie International Edition
10.1002/anie.202003865
DOI: 10.1002/anie.200((will be filled in by the editorial staff))
C-H Silylation
2
3
Revealing Silylation of Csp /sp -H Bonds in Arylphosphines by Ruthenium
Catalysis
+
+
Jian Wen , Ben Dong , Jinjun Zhu, Yue Zhao, and Zhuangzhi Shi*
Dedicated to the 100th anniversary of the School of Chemistry and Chemical Engineering, Nanjing University
Abstract: The first aromatic C–H silylation between arylphosphines
and hydrosilanes enabled by ruthenium complex has been developed.
The excellent ortho-selectivity is resulted from a four-membered
metallacyclic intermediate involving phosphorus chelation. The
developed system can be extended to benzylic C–H silylation of
arylphosphines. Diverse silylated arylphosphines are produced,
exhibiting broad functional group compatibility. Further
functionalization of the products under mild conditions renders the
formed compounds useful building blocks.
Silicon-containing compounds exhibit great interest in the
fields of medicinal chemistry, advanced materials and complex
molecule synthesis.[1] Ortho-silylated arylphosphines possess
intriguing properties, which have been widely used for ligand
design and diverse chemical transformation.[2] Although the
modern organic synthesis has evolved rapidly, only two
practical routes for the construction of these compounds have
been explored so far, from the classic way on substitution of
silicon electrophiles with lithiated arylphosphines formed in-
situ[2] to
Scheme 1. Synthesis of ortho-silylated arylphosphines.
a
more recent method by lithium-di-1-
adamantylamide-mediated aryne insertion into Si−P reagents
Scheme 1a).[3] Both approaches are useful, but they are often
(
species could further react with silicon reagents to form ortho-
silylation products. To evaluate this hypothesis, we primary
conducted these reactions with equimolar amounts of
limited in scope and require pre-installation of functional
groups such as halides into substrates and the use of large
amounts of sensitive organometallic species. Therefore, the
development of a simple and general approach to synthesize
these compounds with excellent atom and step economy is still
in high demand.
[
2 3 3 3 3
RuCl (PPh ) ] or RuHCl(PPh ) complex and hydrosilane 2a
in THF at 100°C (Scheme 1c). To our delight, these reactions
afforded the desired silylation product 3aa in trace amounts, as
detected by GC-MS. Considering that the transformations
proceed with formal loss of hydrogen, norbornene (NBE) was
added as a hydrogen acceptor to the above systems. Both of the
reactions conducted with NBE indeed led to a higher, but
modest yield (~30%) of product 3aa. Based on the results, a
catalytic C-H silylation process was considered to access the
ortho-silylated arylphosphines.[7] Here, we report a Ru-
catalyzed dehydrogenative silylation between arylphosphines
and hydrosilanes chelation assisted by phosphorus atom.[8]
Coordiantion of arylphosphines with transition metals have
been found to form the strained ortho-metallated rings.[4] In
1
981, the Sabo group first reported that a Ph
complex could be generated by treatment of [RuCl
and [ZrMe (Cp)
] (Scheme 1b).[5] Later, Stolzenberg and
coworkers also demonstrated the formation of the same
complex from RuHCl(PPh
and olefin.[6] Inspired by these
previous results, we considered whether such metallated
2
P(o-C
6 4
H )Ru
2
(PPh
3 3
) ]
2
2
3 3
)
We started our studies by treatment of PPh
2a) as the model substrates (Table 1). After systematic
screening, we found that using 5.0 mol% of [RuCl (p-
,[9] 5.0 equiv of norbornene as the hydrogen acceptor
cymene)]
and 3.0 equiv of CyNH as an base at 100 °C under an argon
atmosphere in THF (0.5 M) provided the best results, affording
product 3aa in 79% yield (entry 1). Ruthenium complexes such
3 3 2 3 3
as (PPh ) RuCl and (PPh ) RuHCl showed better results for
this reaction (entries 2-3). However, they are not suitable as
catalysts because mixed products could form when using other
arylphosphines as substrates. Rhodium and iridium catalysts
failed to promote this transformation (entries 4-5). Other
3 3
(1a) and Et SiH
(
2
[
+]
[+]
[
[
]
Dr. J. Wen , Dr. B. Dong , J. Zhu, Dr. Y. Zhao, and Prof. Dr.
Z. Shi
2
2
State Key Laboratory of Coordination Chemistry, Chemistry
and Biomedicine Innovation Center (ChemBIC) , School of
Chemistry and Chemical Engineering, Nanjing University,
Nanjing 210093 (China)
E-mail: shiz@nju.edu.cn
+] These authors contributed equally to this work.
Supporting information and the ORCID identification
number(s) for the author(s) for this article can be found under
http://www.angewandte.org.
1
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Angewandte Chemie International Edition
10.1002/anie.202003865
Table 1. Optimization of reaction conditions.[a]
phosphines
1
with hydrosilane 2f (Table 3). Aryl moieties in
triarylphosphines 1b-1f, with methyl (1b), methoxy (1c), F
1d), Cl (1e), and CF 1g) groups at the para position, were
(
3
(
compatiable, and the desired products 3bf-3ff were generated
in moderate to good yields. Treatment of meta-substituted
triarylphosphines 1g-1i in our catlytic system, C-H silylation
only occured at the less hindered C-H bonds. Phosphines 1j
and 1k, containing two different aryls for C-H silylation,
showed excellent selectivity for reaction of the sterically more
hindered ones. Diarylalkylphosphines bearing primary (1l) and
Yield of
Entry
Variation from the standard conditions
none
[b]
3
aa (%)
1
2
3
4
5
6
7
8
79
(PPh
3
)
3
RuCl
RuHCl instead of [RuCl
instead of [RuCl (p-cymene)]
[Ir(OMe)cod] instead of [RuCl (p-cymene)]
Using cyclohexene instead of NBE
Without CyNH
N instead of CyNH
2
instead of [RuCl
2
(p-cymene)]
2
82
(PPh
3
)
3
2
(p-cymene)]
2
85
secondary (1m, 1n) aliphatic substituents, exhibited the sole
[Rh(cod)Cl]
2
2
2
trace
0
selectivity at the aromatic C-H bonds. In addition,
heteroaromatic phosphines such as 1o could also be used for
such transformation. However, phosphine 1p with two ethyl
substituents displayed very low reactivity under the current
reaction conditions.
2
2
2
63
2
22
Et
3
2
55
[a]Reaction conditions: cat [TM] (10 mol %), 1a (0.3 mmol), 2a (1.5
mmol), NBE (1.5 mmol) and CyNH (0.9 mmol) in THF (0.6 mL) at
00 °C for 24 h, under argon. Isolated yields.
2
Table 3. Substrate scope of arylphosphines.[a]
[
b]
1
hydrogen acceptors, such as cyclohexene, were also effective,
albeit with a slightly lower yield (entry 6). It was confirmed
that the reaction became sluggish without the addition of the
base CyNH
conducted with other organic bases, such as Et
product 3aa was formed in a much lower yield (entry 8).
We first investigated a range of hydrosilane
phosphine 1a (Table 2). Hydrosilanes, including tributylsilane
2b), trihexylsilane 2c), diethylmethylsilane 2d and
2
(entry 7). Finally, when the reaction was
3
N, the desired
2
with
(
(
(
)
cyclohexyldimethylsilane (2e), could form the corresponding
silylation products 3ab-3ae in 51-72% yields. Among them,
the structure of 3ae was confirmed by X-ray diffraction
2
analysis. The sterically hindered silane HSiMe(OTMS) (2j)
has been applied in aromatic C–H silylation to achieve
excellent remote steric control using rhodium catalysis.[10] This
bulky hydrosilane did not hinder the phosphorus-directed
ortho-selective C-H silylation, affording desired product 3aj in
6
7% yield in the absence of the base.[11]
Table 2. Substrate scope of hydrosilanes.[a]
[a]Reaction conditions: [Ru(p-cymene)Cl
mmol), 2f (1.5 mmol), NBE (1.5 mmol) in THF (0.1 mL) at 100 °C
for 24 hours under argon; isolated yields. 36 h. THF (0.6 mL)
was used.
2 2
] (5.0 mol %), 1 (0.3
[a]Reaction conditions: [Ru(p-cymene)Cl
mmol), 2 (5.0 eqiuv), NBE (1.5 mmol) and CyNH
THF (0.6 mL) at 100 °C for 24 hours under argon; isolated yields.
(5.0 mol %), 1a (0.3
(1.5 mmol) in
2 2
]
[
b]
[c]
2
[
b]
2
Without CyNH , in THF (0.1 mL).
The developed system was also found to display good
Given that the formed Ar-SiMe(OTMS)
functionalized under mild conditions, we next subjected various
2
motif can be easily
3
[12]
reactivity for Csp –H bonds (Table 4).
Emplyment of
SiH (2a
phosphine 1q bearing an ortho-methyl group with Et
3
)
2
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Angewandte Chemie International Edition
10.1002/anie.202003865
in our catalytic system, benzylic C-H silylation occurred
preferentially to afford 4qa in excellent yield. Upon reaction of
phosphine 1r with a bulky mesityl group, the mono-substituted
product 4ra was obtained with a small amount of disilylation
product 4ra' (4ra
:4ra' = 11:1). Other triarylphosphines 1s-1w
with different substituents, including F (1s), Cl (1t-1u), Br (1v
)
and COOMe (1w), underwent facile benzylic C-H silylation. In
the case of phosphine 1y with an ethyl group, the silylation
occured exclusively at the methyl group. Further investigation
showed that phosphine 1z containing three o-tolyl moieties
could only transfer into the desired product 4za in trace
amounts.
Table 4. Ru-catalyzed Csp ‒H silylation in arylphosphines.[a]
3
Scheme 2. Synthestic applications.
When stoichiometric amout of [RuCl
2
(p-cymene)]
2
was
allowed to react with Et SiH (2a) or PPh (
3
3
1a) in THF
at100 °C, two complexes, 11[14] and 12[15], were obtained
respectively (Scheme 3a). Further investigation demonstrated
that product 3aa could be generated by a catalytic amount of
complex 12 (Scheme 3b). These results indicate that the
catalyst [RuCl
2 2
(p-cymene)] first coordinates with phosphine to
form complex 12, which can undergo dehydrogenative
silylation with HSiEt (2a) using NBE as the hydrogen
3
acceptor[16] through the key four-membered ring intermediate.
[a]Reaction conditions: [Ru(p-cymene)Cl
mmol), 2a (1.5 mmol), NBE (1.5 mmol) and CyNH
(5.0 mol %), 1 (0.3
(3.0 equiv) in
2 2
]
2
THF (0.5 mL) at 100 °C for 24 hours under argon; isolated yields.
[
b]
1
Determined by H NMR.
To showcase the practical utility of this C-H silylation
process, further investigations were conducted (Scheme 2).
This silylation reaction was viable on the gram scale. To
demonstrate this potential, 3.0 mmol of phosphine 1a was
2
silylated with HSiMe(OTMS) (2j) under our established
conditions, affording product 3af in 73% yield, consistent with
the small-scale trial. With compound 3af in hand, some
synthetic transformations were also demonstrated (Scheme 2a).
Treatment of 3af with H
product in 78% yield. Pd-catalyzed Hiyama cross-coupling of
af with iodoarene furnished Buchwald-type phosphine in
2 2
O (30%) generated a hydroxylation
5
3
6
7
moderate yield. The silyl moiety at the benzylic position of
phosphines can also be further functionalized under mild
conditions (Scheme 2b). For example, the reaction of product
Scheme 3. Investigation of the possible intermediates.
4
qa with benzaldehyde (8) and TBAF could produce alcohol 9
in 60% yield. Moreover, ortho-silylated arylphosphines have
some special properties as ligands with transition metals. For
instance, coordination of ortho-silylated arylphosphine 3aa
with a gold salt could form complex 10 in good yield (Scheme
In summary, we have demonstrated an important advance
which could considerably broaden the ortho-selective C–H
silylation process to arylphosphines. [RuCl
2 2
(p-cymene)] can
2
c).[13]
serve as a unique catalyst in this transformation for the
2
3
silylation of Csp and Csp -H bonds with hydrosilanes. This
3
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Angewandte Chemie International Edition
10.1002/anie.202003865
J.-F. Yang, R.-H. Wang, Y.-X. Wang, W.-W. Yao, Q.-S. Liu, M. Ye,
Angew. Chem. Int. Ed. 2016, 55, 14116-14120; Angew. Chem. 2016,
method shows excellent atom and step economy, greatly
simplifying the construction the library of ortho-silylated
arylphosphines for research in chemistry. Diverse C-H
functionalization of arylphosphines and detailed mechanistic
investigation of this C-H silylation process are currently being
carried out in our group.
1
28, 14322–14326; d) X. Qiu, M. Wang, Y. Zhao, Z. Shi, Angew.
Chem. Int. Ed. 2017, 56, 7233−7237; Angew. Chem. 2017, 129, 7339–
343; e) S. E. Wright, S. Richardson-Solorzano, T. N. Stewart, C. D.
7
Miller, K. C. Morris, C. J. A. Daley, T. B. Clark, Angew. Chem., Int.
Ed. 2019, 58, 2834−2838; Angew. Chem. 2019, 131, 2860–2864; f) A,
J. Borah, Z. Shi, J. Am. Chem. Soc. 2018, 140, 6062−6066; g) D.
Wang, B. Dong, Y. Wang, J. Qian, J. Zhu, Y. Zhao, Z. Shi, Nat.
Commun. 2019, 10, 3539−3548; h) J. Wen, D. Wang, J. Qian, D.
Wang, C. Zhu, Y. Zhao, Z. Shi, Angew. Chem. Int. Ed. 2019, 58,
Acknowledgments
2
078–2082; Angew. Chem. 2019, 131, 2100–2104; i) K. Fukuda, N.
We thank the “1000-Youth Talents Plan”, the “Innovation &
Entrepreneurship Talents Plan” of Jiangsu Province, and National
Natural Science Foundation of China (Grant 21972064) for their
financial supports.
Iwasawa, J. Takaya, Angew. Chem. Int. Ed. 2019, 58, 2850–2853;
Angew. Chem. 2019, 131, 2876–2879; j) Z. Zhang, T. Roisnel, P. H.
Dixneuf, J.-F. Soulé, Angew. Chem. Int. Ed. 2019, 58, 14110 –14114;
Angew. Chem. 2019, 131, 14248 –14252.
[
9] For reviews on [RuCl
B. Arockiam, C. Bruneau, P. H. Dixneuf, Chem. Rev. 2012, 112,
879–5918; b) L. Ackermann, Acc. Chem. Res. 2014, 46, 281–295; c)
S. S. Sarkar, W. Liu, S. I. Kozhushkov, L. Ackermann, Adv. Syn. Cat.
2 2
(p-cymene)] -catalyzed C-H activation, see: a) P.
5
Keywords: phosphorus ·C-H activation ·silylation ·site-
selectivity ·coordination
2
2
014, 356, 1461–1479; d) J. A. Leitch, C. G. Frost, Chem. Soc. Rev.
017, 46, 7145–7153; e) P. Nareddy, F. Jordan, M. Szostak, ACS
Catal. 2017, 7, 5721−5745; For some recent examples, see: f) P. B.
Arockiam, C. Fischmeister, C. Bruneau, P. H. Dixneuf, Angew. Chem.
Int. Ed. 2010, 49, 6629–6632; Angew. Chem. 2010, 122, 6779–6782;
g) J. Li, S. Warratz, D. Zell, S. De, I. Suman, E. Eloisa, L. Ackermann,
J. Am. Chem. Soc. 2015, 137, 13894−13901; h) F. Hu, M. Szostak,
Chem. Commun. 2016, 52, 9715-9718; i) F. Hu, M. Szostak, Org. Lett.
[
[
1] a) E. Langkopf, D. Schinzer, Chem. Rev. 1995, 95, 1375–1408; b) I.
Fleming, A. Barbero, D. Walter, Chem. Rev. 1997, 97, 2063–2192; c)
M. Suginome, Y. Ito, Chem. Rev. 2000, 100, 3221–3256; d) A.
Showell, J. S. Mills, Drug Discov. Today 2003, 8, 551–556; e) A. K.
Franz, S. O. Wilson, J. Med. Chem. 2013, 56, 388–405; f) M.
Mortensen, R. Husmann, E. Veri, C. Bolm, Chem. Soc. Rev. 2009, 38,
2
2
016, 18, 4186−4189; j) Q. Zhao, J. Zhang, M. Szostak, ACS Catal.
019, 9, 8171−8177.
1
002–1010.
2] a) A. Kawachi, T. Yoshioka, Y. Yamamoto, Organometallics 2006, 25,
[
[
10] C. Cheng, J. F. Hartwig, Science 2014, 343, 853–857.
2
11] Given that HSiMe(OTMS) can be employed without CyNH , we
2
6
390–2393; b) J. Takaya, N. Iwasawa, Organometallics 2009, 28,
636–6638; c) P. Gualco, S. Ladeira, K. Miqueu, A. Amgoune, D.
2
consider this additive can not only act the base but also activate other
hydrosilanes for C-H silylation.
Bourissou, Angew. Chem. Int. Ed. 2011, 50, 8320–8324; Angew.
Chem. 2011, 123, 8470–8474; d) M. J. Bernal, O. Torres, M. Martın,
́
[
12] a) F. Kakiuchi, K. Tsuchiya, M. Matsumoto, E. Mizushima, N. Chatani,
J. Am. Chem. Soc. 2004, 126, 12792–12793; b) T. Mita, K. Michigami,
Y. Sato, Org. Lett. 2012, 14, 3462–3465; c) K. Kon, H. Suzuki, K.
Takada, Y. Kohari, T. Namikoshi, S. Watanabe, M. Murata,
ChemCatChem. 2016, 8, 2202–2205; d) W. Li, X. Huang, J. You,
Chem. Commun. 2014, 50, 888; b) K. Takada, T. Hanataka, T.
Namikoshi, S. Watanabe, M. Murata, Adv. Synth. Catal. 2015, 357,
E. Sola, J. Am. Chem. Soc. 2013, 135, 19008–19015; e) S. Wu, X. Li,
Z. Xiong, W. Xu, Y. Lu, H. Sun, Organometallics 2013, 32, 3227–
3
8
237; f) M. J. Bernal, M. Martin, E. Sola, Organometallics 2015, 34,
00–803; g) J. Li, M. Xue, Y. Bai, J. Peng, W. Xiao, App.
Organometal. Chem. 2016, 30, 905-910.
[
[
[
[
[
3]
4]
M. Mesgar, J. Nguyen-Le, O. Daugulis, J. Am. Chem. Soc. 2018, 140,
1
3703–13710.
2
229–2232.
F. Mohra, S. H. Privér, S. K. Bhargava, M. A. Bennett, Coord.
Chem. Rev. 2006, 250, 1851–1888.
[
[
[
[
13] M. Joost, P. Gualco, Y. Coppel, K. Miqueu, C. E. Kefalidis, L. Maron,
A. Amgoune, D. Bourissou, Angew. Chem. Int. Ed. 2014, 53, 747–751;
Angew. Chem. 2014, 126, 766–770.
5] S. Sabo, B. Chaudret, D. Gervais, R. Poilblanc, Nouv. J. Chim. 1981, 5,
97–598.
6] A. M. Stolzenberg, E. L. Muetterties. Organometallics 1985, 4, 1739–
742
5
14] a) P. I. Djurovich, P. J. Carroll, D. H. Berry, Organometallics, 1994,
1
2
3, 2551–2553; b) B. Chatterje, C. Gunanathan, Chem. Commun.
014, 50, 888–890.
1
7] For reviews on C–H silylation, see: a) L. Omann, C. D. F. Kꢀnigs, H.
F. T. Klare, M. Oestreich, Acc. Chem. Res. 2017, 50, 1258–1269; b) J.
F. Hartwig, Acc. Chem. Res. 2012, 45, 864–873; c) C. Cheng, J. F.
Hartwig, Chem. Rev. 2015, 115, 8946–8975.
8] For some recent P(III)-directed C-H activations, see: a) Z. Zhang, P. H.
Dixneuf , J.-F. Soulé, Chem. Commun. 2018, 54, 7265–7280; b) K. M.
Crawford, T. R. Ramseyer, C. J. A. Daley, T. B. Clark, Angew. Chem.
Int. Ed. 2014, 53, 7589−7593; Angew. Chem. 2014, 126, 7719–7723; c)
15] R. Menye-Biyogo, F. Delpech, A. Castel, H. Gornitzka, P. Rivière,
Angew. Chem. Int. Ed. 2003, 42, 5610–5612; Angew. Chem. 2003,
1
15, 5768 –5770.
16] a) C. Cheng, J. F. Hartwig, J. Am. Chem. Soc. 2014, 136, 12064−12072;
b) C. Karmel, Z. Chen, J. F. Hartwig, J. Am. Chem. Soc. 2019, 141,
[
7
063−7072.
4
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Entry for the Table of Contents (Please choose one layout)
Layout 2:
C-H Silylation
+
+
Jian Wen , Ben Dong , Jinjun Zhu, Yue
Zhao, and Zhuangzhi Shi* ___ Page –
Page
2
3
Revealing Silylation of Csp /sp -H
Bonds in Arylphosphines by Ruthenium
Catalysis
SiRuP: An efficient Ru-catalyzed system has been uncovered for ortho-selective
aromatic C-H silylation of arylphosphines with hydrosilanes chelation assisted by
phosphorus atom. When the arylphosphine contains an ortho-methyl group,
silylation takes place preferentially at the benzylic C–H bond.
5
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