Intermolecular C-H Silylation of Arenes and Heteroarenes with HSiEt3 under Operationally Diverse Conditions: Neat/Stoichiometric and Acceptor/Acceptorless

Article abstract of DOI:10.1021/acscatal.5b02806

Efficient protocols for Rh-catalyzed intermolecular C-H silylation of unactivated arenes and heteroarenes are disclosed. The silylations are catalyzed by a Rh-complex (2 mol %) derived in situ from commercially available Rh(nbd)₂BF₄ and (S,S)-i-Pr-BPE (L3) with Et₃SiH in the presence of hydrogen acceptor under either neat (excess of arene) or stoichiometric conditions. The regioselectivity is determined mainly by the steric bulk of the substituents and by the electronic effect as an ancillary factor. In addition, our preliminary result shows that the current protocol catalyzes the silylation of arenes in the absence of hydrogen acceptors.

Full text of DOI:10.1021/acscatal.5b02806

Letter
pubs.acs.org/acscatalysis
Intermolecular C−H Silylation of Arenes and Heteroarenes with
HSiEt3 under Operationally Diverse Conditions: Neat/Stoichiometric
and Acceptor/Acceptorless
Kang-sang Lee,* Dimitris Katsoulis, and Jongwook Choi*
Dow Corning Corporation, 2200 West Salzburg Road, Auburn, Michigan 48611, United States
S
* Supporting Information
ABSTRACT: Efficient protocols for Rh-catalyzed intermolecular C−H
silylation of unactivated arenes and heteroarenes are disclosed. The
silylations are catalyzed by a Rh-complex (2 mol %) derived in situ from
commercially available Rh(nbd)2BF4 and (S,S)-i-Pr-BPE (L3) with
Et3SiH in the presence of hydrogen acceptor under either neat (excess
of arene) or stoichiometric conditions. The regioselectivity is
determined mainly by the steric bulk of the substituents and by the electronic effect as an ancillary factor. In addition, our
preliminary result shows that the current protocol catalyzes the silylation of arenes in the absence of hydrogen acceptors.
KEYWORDS: C−H silylation, Rh-catalyzed silylation, intermolecular C−H silylation,
silylation of unactivated arenes and heteroarenes, C−H bond activation, acceptorless C−H silylation
evelopment of efficient and practical synthetic methods
for arylsilanes is an important research area in chemical
arenes and heteroarenes) in the intermolecular C−H silylation
with Et3SiH, which has an intrinsically different reactivity
compared to HMTS. For example, commonly used Ir systems
are efficient in the silylation of more activated polycyclic
arenes6k and heteroarenes7b but significantly less effective for
electron-rich and -neutral benzene derivatives.6k
Herein, we outline a highly efficient protocol of Rh-catalyzed
intermolecular dehydrogenative C−H silylation of both
unactivated arenes and heteroarenes. In the presence of
commercially available Et3SiH and cyclohexene, the reactions
can be run either in excess arene or in THF with arene as the
limiting reagent. Furthermore, with this protocol, certain types
of arenes and heteroarenes can undergo acceptorless silylations
to afford arylsilanes.
We began the investigation of the C−H silylation by
screening a number of in situ-generated Rh-bisphosphine
complexes to transform benzene to triethylphenylsilane (1).
Initially, an excess amount of benzene (1 mL) was used with
triethylsilane (1 mmol) as the limiting reagent. After screening
various alkenes, cyclohexene was identified as an efficient
hydrogen acceptor. As shown in Scheme 1, complexes derived
from diphenyl- or dialkylphosphinoethane (L1a−d) with 1 mol
% [Rh(coe)2Cl]2 afforded the desired product in low yield (2−
11%, entries 1−4). When i-Pr-DuPhos (L2) was used, the yield
of the silylation was increased (17%, entry 5). Using
[Rh(cod)OH]2 and Rh(cod)2OTf, C−H silylations afforded 1
in moderate yields (39% and 45%, respectively, entry 6 and 7).
In the presence of Rh(nbd)2BF4, however, the yield of the
desired product was significantly increased to 91% (80%
D
synthesis due to their utility as fundamental building blocks of
industrially important polymers and materials.1 Among the
methods of synthesis of arylsilanes, including reactions of halo-
or alkoxysilane with aryl-Grignard, or lithium reagents, the
transition-metal-catalyzed C−H silylation2 of unactivated
arenes is particularly attractive because it serves as a direct
and atom-economical pathway with better functional group
compatibility and with significantly less amount of chemical
waste (magnesium- or lithium salts). Since the pioneering work
by the Curtis group in 1982,3 a number of catalytic C−H
silylations have been disclosed. However, the protocols are
mostly limited to intramolecular silylations4 or require a
directing group.5 There are only a handful reports on
intermolecular C−H silylations of unactivated arenes without
directing groups.3,6,7 Even in those cases, the reactions demand
specialized silane agents requiring multistep synthesis (e.g., o-
bissilylbenzene6b−d,f or tetrafluorodialkyldisilanes6g,h), or show
relatively narrow substrate scopes (only arenes,6 or hetero-
arenes7), or suffer from low to moderate efficiency.
Recently, the seminal reports by the Hartwig group8
demonstrated that Rh and Ir systems can efficiently catalyze
the silylation with 1,1,1,3,5,5,5-heptamethyltrisiloxane
(HMTS)8b,c to afford arylsiloxanes [Aryl-SiMe(OSiMe3)2]
with a broad substrate scope of arenes including unreactive
arenes as well as heteroarenes under mild conditions. However,
the corresponding Rh and Ir systems have been demonstrated
with a limited silane scope (only with HMTS) and are not
compatible with Et3SiH for the intermolecular C−H
silylations.8e
Several reports described the C−H silylations with
Et3SiH.6a,e,k,7b,i,8a However, with our best knowledge, there is
no catalytic protocol showing a broad substrate scope (both
Received: December 10, 2015
Revised: January 26, 2016
© XXXX American Chemical Society
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Scheme 1. Dehydrogenative C−H Silylations of Benzene
Scheme 2. Dehydrogenative C−H Silylations of Various
a
a
with Et3SiH: Screening of [Rh] and Ligand
Arenes with Et3SiH
a
All reactions were performed with 2 mol % Rh salt based on
b
1
monomer under N2. Yields were determined by H NMR analysis,
and isolated yields are shown in parentheses. Hydrosilylation
c
byproducts (79%) and desired product (12%) were obtained when
3,3-dimethyl-1-butene was used instead of cyclohexene.
isolated yield, entry 8). After further screening of a similar type
of ligands, the complex derived from (S,S)-i-Pr-BPE (L3) and
Rh(nbd)2BF4 was found to be an efficient catalyst for the
silylation to furnish 1 quantitatively (>98% yield and 96%
isolated yield, entry 9). Reactions with L3 and [Rh(cod)OH]2
or Rh(cod)2OTf were not efficient in this silylation (entry 10
and 11).
a
All reactions were performed under N2. Yields were determined by
b
1H NMR analysis, and isolated yields are shown in parentheses. 2-
Methoxy-4-methyl-1-triethylsilylbenzene (18%) was isolated together
c
with 6. Four mol % Rh(nbd)2BF4 and 4.4 mol % L3 were used.
d
e
Disilylated product was obtained in 9% yield. 40h, Disilylated
product was obtained in 6% yield.
Under the optimal reaction conditions, various arenes were
tested for the dehydrogenative C−H silylation. As illustrated in
Scheme 2, reactions with electronically variable 1,2- or 1,3-
disubstituted arenes furnished the desired products at the less
sterically hindered m-positions in 81 → 98% yield (2−6) with
no benzylic silylation. Reactions with monosubstituted arenes
generally resulted in mixtures of meta- and para-silylation
products (7−11): compared to statistical ratio (m/p = 2/1),
para-silylation preferred with bulky t-butyl substituent (1/2 =
m/p, 7) and less selective silylation for toluene (1.1/1 = m/p,
8). For electronically different arenes, C−H silylations
proceeded favorably at an electron-rich carbon: 1/6 = m/p
for dimethylaniline, 9 and 2.4/1 = m/p for trifluorotoluene, 10.
In the case of fluorobenzene and anisole, regioselectivity was
complicated by the substituents; the silylation of fluorobenzene
afforded the ortho-silylated product as major (4/1 = o/m, 11),
presumably due to an inductive effect of the ortho-fluorine and
relatively small steric presence of the fluorine atom.9 For
anisole, all three regioisomers were obtained (1/3.5/1 = o/m/p,
12) and resulted likely from the directing effect of the methoxy
group. With heteroarenes such as 1-methylindole and
benzofuran, as well as pyrrole and furan, the Rh-catalyzed
silylation delivered the desired products in high yield (76 →
98% yield, 13−16). The reaction with thiophene was sluggish,
affording 17 in 37% yield.
Next, our system was further applied to the reactions where
arene was used as the limiting reagent in the case that arenes
are more complex and valuable. As shown in Scheme 3,
aryltriethylsilane 1, 2, and 7 were isolated in 54−78% yield with
use of 1 equiv of unactivated arene, 1.2 equiv of triethylsilane,
and 1 mL of THF. Reactions with 1-methylpyrrole and furan
furnished a mixture of mono- and bis-silylation product (75%
yield, mono/bis =1/0.8, 15), but in the presence of an excess
amount of Et3SiH, only the bis-silylation product was obtained
(97% yield, 18, Scheme 3). Pyridine-type heteroarenes were
converted to the corresponding silylated products (68% yield
for 20 and 71% yield for 21).10 Under the reaction conditions,
the silylations of fused-heteroarenes were highly efficient to
afford the desired products in 92−99% of isolated yield (13, 14,
22, and 23).
Furthermore, our preliminary result shows the feasibility of
C−H silylation in the absence of a hydrogen acceptor, which is
one step closer to a practical and cost-effective method that can
be used at an industrial scale. Under the same catalytic system,
but without cyclohexene, the C−H silylation of benzene and
fluorobenzene proceeded to afford the desired products 1 and
10 in 64% and 79% yield, respectively (Scheme 4). Notably,
this acceptorless protocol efficiently catalyzed the silylation of
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employing solvent. (2) Only one equivalent of arene can be
used in the case where arenes (especially heteroarenes) are
valuable and have complex structures requiring multiple step
synthesis. (3) As a preliminary result was shown, this protocol
is feasible for the acceptorless C−H silylation. The
regioselectivity of products is mainly affected by the steric
bulk of the substituents on the arenes and by the electronic
properties as a secondary factor.8b
Scheme 3. Dehydrogenative C−H Silylations of Various
a
Arenes in THF
Mechanistic studies of this C−H silylation as well as further
applications of the Rh-catalyzed system for various arenes and
silanes are underway. Together with the silylations of
HMTS,8b,c we believe, this protocol will enrich the research
area of the C−H silylation by demonstrating the silylations of
Et3SiH with a broad arene scope.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acscatal.5b02806.
■
S
Detailed experimental procedures, compound character-
ization data, and NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Authors
*E-mail: kangsang.lee@dowcorning.com.
*E-mail: jongwook.choi@dowcorning.com.
■
a
All reactions were performed under N2. Yields were obtained after
Notes
b
c
silica gel chromatography. 40h. Four mol % Rh(nbd)2BF4 and 4.4
mol % L3 were used. 2.2 equiv of Et3SiH was used.
d
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
Scheme 4. Dehydrogenative C−H Silylations of Various
■
a
We thank Dr. Zhanjie Li, Clark W. Swerdan, and Donald V.
Eldred for helping with the NMR data collection and Alix L.
Schmidt for initial catalyst screening.
Arenes without Hydrogen Acceptor
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