Copper-Catalyzed Direct sp2C-H Silylation of Arylamides Using Disilanes

Article abstract of DOI:10.1021/acs.orglett.1c01129

A copper-catalyzed method for direct intermolecular ortho-silylation of benzamides has been developed that affords organosilane products in moderate to high yields. The key features include: (i) use of commercially available disilanes as a silicon source with 8-aminoquinoline as a bidentate directing group, (ii) use of earth-abundant first-row transition metal, (iii) operationally simple conditions without the need of an inert atmosphere, and (iv) tolerance of a wide range of functional groups. The practicality and effectiveness of this method have been demonstrated by a gram-scale experiment. This strategy, therefore, constitutes a convenient way of constructing C-Si bonds useful for synthetic organic chemistry.

Full text of DOI:10.1021/acs.orglett.1c01129

pubs.acs.org/OrgLett
Letter
Copper-Catalyzed Direct sp2 C−H Silylation of Arylamides Using
Disilanes
Writhabrata Sarkar,* Aniket Mishra, Arup Bhowmik, and Indubhusan Deb*
Cite This: Org. Lett. 2021, 23, 4521−4526
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: A copper-catalyzed method for direct intermolecular ortho-silylation of benzamides has been developed that affords
organosilane products in moderate to high yields. The key features include: (i) use of commercially available disilanes as a silicon
source with 8-aminoquinoline as a bidentate directing group, (ii) use of earth-abundant first-row transition metal, (iii) operationally
simple conditions without the need of an inert atmosphere, and (iv) tolerance of a wide range of functional groups. The practicality
and effectiveness of this method have been demonstrated by a gram-scale experiment. This strategy, therefore, constitutes a
convenient way of constructing C−Si bonds useful for synthetic organic chemistry.
Scheme 1. Transition-Metal-Catalyzed C−H Silylation
he C−Si bond possesses unique physical, chemical, and
Tbioactive properties, and the development of methods for
its formation is therefore indispensable in synthetic organic
chemistry. The organosilicon compounds are valuable building
blocks and have numerous applications in organic chemistry.1
Besides, these have found potential uses in the fields of
material science, polymer chemistry,2 and pharmaceutical
industries3a growing number of reports in medicinal
chemistry deal with the incorporation of silicon groups in
diverse drug candidates.4 In consequence, significant efforts
have been made in recent years for the strategic installation of
silyl groups into organic frameworks. Among these, the
synthesis of organosilanes through transition-metal-catalyzed
direct C−H bond functionalizations, as compared to tradi-
tional approaches of silylation reactions5 and transition-metal-
free techniques,6 has emerged as the most sought-after
protocol from the viewpoints of atom economy and high
efficiency.7−12 The high abundance, low cost, and environ-
mentally benign nature of silicon have in addition allowed the
development of catalytic silylation methods via C−H bond
activation. In the past decades, several advances have been
made in this field for the silylation of C(sp2)−H as well as
C(sp3)−H variants using Ru,7 Rh,8 Ir,9 Sc,10 and Pt11 as
transition metal catalysts (Scheme 1a).
have made splendid breakthroughs in both regioselective meta
and para C−H silylation techniques with the help of intricately
designed directing templates suitable for C−H bond
activation.12g,h In 2019, Yang et al. developed another
approach for meta C−H silylation to access silicon-containing
1,1′-biaryl-2-acetamides employing palladium catalysis.12i
Kuninobu and Kanai reported the first Pd-catalyzed
silylation of carboxamides with disilanes as silicon sources,
applying a directing group strategy (Scheme 1b).12a Following
this pioneering work, Zhang and Shi’s groups developed
elegant procedures for the silylation of aliphatic β-C(sp3)−H
bonds,12c,d which were then impressively extended to distal γ-
C(sp3)−H silylation by Maiti and co-workers.12e Maiti and Liu
Received: April 1, 2021
Published: May 13, 2021
https://doi.org/10.1021/acs.orglett.1c01129
© 2021 American Chemical Society
Org. Lett. 2021, 23, 4521−4526
4521

Organic Letters
pubs.acs.org/OrgLett
Letter
a
Table 1. Optimization of Reaction Conditions
b
entry
catalyst
additive
oxidant
solvent
yield of 3a (%)
1
2
3
4
5
6
7
8
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
CuBr2
-
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2SO4
NMO
Mn(OAc)2·4H2O
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
-
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
27
nr
51
29
19
nr
34
nr
nr
8
CsF
MgSO4
Na2SO4
CaSO4
K2CO3
MgSO4
MgSO4
MgSO4
MgSO4
MgSO4
MgSO4
MgSO4
MgSO4
MgSO4
MgSO4
MgSO4
MgSO4
MgSO4
9
10
11
12
13
14
15
16
17
18
19
CuF2
CuO
7
nr
70
72
69
74
nr
nr
c
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
-
c d
,
c de
,
,
c df
,
,
c
c d
,
Cu(OAc)2
Cu(OAc)2
c df g
h
,
, ,
Ag2CO3
88 (86)
a
Unless otherwise mentioned, 1a (0.1 mmol), 2a (2.0 equiv), catalyst (20 mol %), additive (2.0 equiv), oxidant (1.5 equiv), and solvent (1.0 mL)
b
c
d
e
f
g
at 120 °C under N2 atmosphere for 21 h. Isolated yield. 2a (10.0 equiv). Catalyst (10 mol %). 140 °C. Under air atmosphere. Reaction run
for 36 h. Yield for 0.2 mmol scale. nr: no reaction.
h
Despite the efficacy, all these methodologies make use of
various transition metal catalysts that suffer from drawbacks of
high cost, low earth abundance, and bioincompatibility.
reaction or poor yields (see SI, Table S1), establishing DMF as
the solvent of choice. In order to improve the yield, we
surveyed a series of additives in the reaction (entries 2−6).
Gratifyingly, the use of 2.0 equiv of MgSO4 permitted a
significant increase in the yield of the silylation product,
furnishing 3a in 51% yield (entry 3), probably due to its
property of absorbing water possibly formed in the reaction
medium.
Inevitably, this offers an intriguing opportunity for the
design of complementary catalytic silylation routes using a
more efficient, cost-effective, and earth-abundant catalyst.
Possessing tremendous potency in functionalizing directed
C−H bonds, the first-row transition metal copper has been
well explored by diverse research groups.13 Its catalytic
reactivity and effectiveness are commendable compared to
the higher transition metal catalysts, while its remarkable low
cost and high bench stability allow it to be used in both
catalytic as well as stoichiometric manners. In particular, a
copper catalyst employed in a catalytic rather than
stoichiometric fashion appears more attractive for this purpose.
Several research groups have extensively used 8-amino-
quinoline as a bidentate auxiliary for C−H bond functionaliza-
tions,14 though the technique is not yet established to the best
of our knowledge for copper-catalyzed or -mediated C−H
silylation. Carrying on with our continuing efforts to develop
new methodologies on directing group assisted transition-
metal-catalyzed C−H bond functionalization,15 we herein wish
to report that C(sp2)−H silylation of an amide is indeed
feasible using disilanes as a silicon source via a novel copper-
catalyzed 8-aminoquinoline-directed process (Scheme 1c).
We commenced the studies with 2-methyl-N-(quinolin-8-
yl)benzamide (1a) as the model substrate and hexamethyldi-
silane (HMDS, 2a) as the silylation partner. To our delight, the
use of 2.0 equiv of HMDS in the presence of 20 mol % of
Cu(OAc)2 catalyst and 1.5 equiv of Ag2CO3 in DMF delivered
the desired product 2-methyl-N-(quinolin-8-yl)-6-
(trimethylsilyl)benzamide (3a) in 27% yield (Table 1, entry
1). A detailed screening of various solvents revealed either no
So we turned our attention to examine the effect of different
oxidants (entries 7−9) and Cu catalysts (entries 10−12), but
no improvement in the yield was possible. However, when the
amount of HMDS was increased to 10.0 equiv, the yield of 3a
went up to 70% (entry 13). In addition, when the catalyst
loading was decreased from 20 to 10 mol %, the yield of the
silylated product was similar (entry 14), so we persisted with
10 mol % of Cu(OAc)2. On further screening of the reaction
conditions, it was observed that an elevated temperature of 140
°C caused a slight decrease in the yield (entry 15), but the use
of air atmosphere resulted in a marginal improvement (entry
16). Extending the reaction time to 36 h led to an increase in
the yield of the reaction to 88% (Table 1, entry 19), which also
proved to be our optimized reaction condition for the current
protocol. It was confirmed by performing the reaction on a 0.2
mmol scale, giving 3a in 86% yield. Control experiments
proved the crucial role of copper catalyst and silver oxidant
(entries 17−18) for the silylation, as the desired products were
not formed when these were excluded. The present method-
ology required an excess amount of disilanes as a reaction
partner, as was evident from known literature reports,12 which
also needed superstoichiometric amounts of disilanes for
effective silylation of unactivated C−H bonds. This might be
due to the lesser reactivity of a strong Si−Si bond since both
(PhMe2Si)2 and (Ph2MeSi)2 remained unreacted when they
4522
https://doi.org/10.1021/acs.orglett.1c01129
Org. Lett. 2021, 23, 4521−4526

Organic Letters
pubs.acs.org/OrgLett
Letter
were used for the substrate scope. The use of other additives
and ligands was not beneficial (see SI, Table S1). Similarly, the
use of the other bidentate-directing groups under standard
reaction conditions also proved unsuccessful (see SI, Table
S2). To illustrate the practicality of this catalytic process, a
gram-scale reaction was conducted under the standard
conditions using 1.0 g of 1a (3.8 mmol) with 2a to isolate
the silylated product 3a in an impressive 79% yield (see SI for
more details).
formed in 11% yield, showing the limitation of this method to
ortho-substituted benzamides. The reason behind this could be
the better chelating property of the substrate for facile C−H
activation when an ortho-substituent is present. Very
interestingly, aliphatic benzamide could also be successfully
silylated at the β-position under the optimized conditions,
although with a paltry yield (3ai, 13%). Many other substrates
were attempted under the present protocol, including the
naphthyl substrate, only meta-substituted benzamides, olefinic,
as well as other heterocyclic variants, but all of them either
gave low yields or did not furnish any silylation product (see
SI, Table S3).
With the optimized conditions in hand, we then probed the
substrate scope of benzamides (1) in order to check the
generality of the silylation protocol (Scheme 2). In general, the
Adopting the standard reaction conditions, we next pursued
the scope of other organosilicon sources. Using bulky silanes
like (Me2PhSi)2 or (MePh2Si)2 in place of (Me3Si)2, moderate
to good conversion was seen, affording the corresponding
silylation products 3ag and 3ah in 67% and 47% yields,
respectively. No desired product was isolated with (Ph3Si)2,
which may be due to additional steric hindrance (see SI, Table
S3).
Scheme 2. Scope of Arylamides (1) with Disilanes (2)
In order to shed light on the reaction mechanism and the
catalytic cycle, several control experiments were executed
(Scheme 3 and SI). A deuterium−proton exchange experiment
Scheme 3. Mechanistic Experiments
reactivity of amides para-substituted with electron-donating
and electron-withdrawing groups was slightly superior to that
of the meta-substituted ones. Functional groups like Me, OMe,
t
F, Cl, Br, CF3, and Bu were all well tolerated. Beginning with
was conducted under standard conditions using 1a in the
absence of HMDS 2a and quenching with excess CD3OD
(Scheme 3a), revealing no deuterium exchange in the
recovered starting material, which suggested that the C−H
bond cleavage step was irreversible. This conclusion was
reassured when the same experiment was performed with the
deuterated version 1a-d1 (92% D), even when external H
sources like excess H2O or CH3OH were used since no H-
incorporation was observed at the ortho C−H bond of the
recovered starting material (Scheme 3a) (SI for more details).
In addition, a pronounced substituent effect was observed with
electron-withdrawing group bearing substrates undergoing
reaction at a faster rate than the electron-donating ones at
both meta and para positions under the optimized reaction
conditions (Scheme 3b and 3c, respectively, and SI).
the meta-substituted amides of o-toluic acid (1b−1f) for this
transformation, we found that electron-donating groups such
as Me and OMe gave the desired products 3b and 3c in high
yields (73% and 78%, respectively). Even an electron-
withdrawing substituent like fluoro produced the silylated
product 3d in a very good yield (75%), though chloro and
bromo substituents furnished the products 3e and 3f only in
moderate yields (54% and 37%, respectively). The location of
variously substituted aryl groups (1g−1n) at this position
provided moderate to satisfactory yields of products ranging
from 36 to 50%. Among amides carrying substituents at the
para position (1o−1aa), those with different aryl groups also
showed good conversion and provided the products (3o−3aa)
to the extent of 43−82%.
Changing the ortho-methyl group of benzamide with phenyl,
ethyl, or isopropyl (1ab−1ad) continued to deliver adequate
yields. Notably, the current protocol also allowed the use of the
challenging heterocycle thiophene (substrate 1ae) albeit with a
poor yield (3ae, 15%). However, the unsubstituted benzamide
1af fared worse, with only monosilylated product 3af being
On the basis of the preceding experimental results and
previous literature reports,12−14 a reaction pathway is proposed
as in Scheme 4. In accordance with the known coordination
properties of Cu(II), benzamide 1a first generates the
intermediate A in the presence of CuX2 (X = acetate/
carbonate) with the aid of complexation by an N,N-bidentate
4523
https://doi.org/10.1021/acs.orglett.1c01129
Org. Lett. 2021, 23, 4521−4526

Organic Letters
pubs.acs.org/OrgLett
Letter
Jadavpur, Kolkata 700032, India; orcid.org/0000-0002-
9007-1042; Email: indubhusandeb@iicb.res.in
Scheme 4. Plausible Mechanism
Writhabrata Sarkar − Organic and Medicinal Chemistry
Division, CSIR-Indian Institute of Chemical Biology,
Jadavpur, Kolkata 700032, India; orcid.org/0000-0003-
3738-9892; Email: writhabrata92@gmail.com
Authors
Aniket Mishra − Organic and Medicinal Chemistry Division,
CSIR-Indian Institute of Chemical Biology, Jadavpur,
Kolkata 700032, India; orcid.org/0000-0003-3961-
159X
Arup Bhowmik − Organic and Medicinal Chemistry Division,
CSIR-Indian Institute of Chemical Biology, Jadavpur,
Kolkata 700032, India
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c01129
8-aminoquinoline directing group. This is followed by the
formation of the key intermediate metallacyclic complex B by
chelate-directed ortho C(sp2)−H activation via a concerted
metalation−deprotonation (CMD) process. Subsequently,
intermediate C is formed by a disproportionation/oxidation
pathway along with the insertion of the Si−Si bond and
simultaneous transfer of a trimethylsilyl group in the presence
of HMDS 2a,12a−c,f which finally undergoes reductive
elimination to give the corresponding silylated product 3a
upon hydrolysis and generates the CuI species. Reoxidation of
CuI to CuII by Ag2CO3 as the terminal oxidant further
continues the catalytic cycle. However, a detailed under-
standing of the mechanism remains to be achieved.
In summary, we have developed a practical and convenient
copper-catalyzed direct ortho-silylation of unactivated arenes
using disilanes as a silicon source, assisted by 8-aminoquinoline
as a directing group. The methodology is applicable to a broad
range of substrates carrying a wide array of functional groups
and is scalable. The strategy gives efficient access to structural
C−Si bonds fundamental in organic synthesis, with the help of
a cheap copper catalyst and inexpensive disilanes. Further
mechanistic studies and application of this C−H silylation
methodology are currently under investigation in our
laboratory.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
W.S. and A.M. thank CSIR, and A.B. thanks UGC for their
fellowships. I.D. thanks IICB and SERB-(CRG/2020/004792)
for research funds. We thank Mr. S. Kundu (IICB) and Mr. G.
Karmakar (IICB) for recording NMR and X-ray data, Mr. S.
Laha (IICB) and Mr. D. Bhattacharya (IICB) for recording
HRMS, the Central Instrumentation Facility (CIF-IICB) for
analytical support, and Dr. B. Acharya (IICB) for valuable
suggestions.
REFERENCES
■
(1) (a) Colvin, E. W. Silicon Reagents in Organic Synthesis; Academic
Press: London, 1988. (b) Langkopf, E.; Schinzer, D. Uses of Silicon
Containing Compounds in the Synthesis of Natural Products. Chem.
Rev. 1995, 95, 1375−1408. (c) Corey, J. Y.; Braddock-Wilking, J.
Reactions of Hydrosilanes with Transition-Metal Complexes:
Formation of Stable Transition-Metal Silyl Compounds. Chem. Rev.
1999, 99, 175−292. (d) Rappoport, Z.; Apeloig, Y., Eds. Chemistry of
Organosilicon Compounds; Wiley-VCH: New York, 2001; Vol. 3.
(e) Mochida, K.; Shimizu, M.; Hiyama, T. Palladium-Catalyzed
Intramolecular Coupling of 2-[(2-Pyrrolyl)silyl]aryl Triflates through
1,2-Silicon Migration. J. Am. Chem. Soc. 2009, 131, 8350−8351.
(f) Liang, Y.; Zhang, S.-G.; Xi, Z. F. Palladium-Catalyzed Synthesis of
Benzosilolo[2,3-b]indoles via Cleavage of a C(sp3)-Si Bond and
Consequent Intramolecular C(sp3)-Si Coupling. J. Am. Chem. Soc.
2011, 133, 9204−9207. (g) Nakao, Y.; Hiyama, T. Silicon-based cross
coupling reaction: an environmentally benign version. Chem. Soc. Rev.
2011, 40, 4893−4901.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c01129.
Additional screening data, mechanistic experimental
details, single-crystal X-ray structure of 3a, 3b, 3c, 3d,
1
3e, 3q, 3s, 3t, 3ac, and 3ag, and H and 13C NMR
(2) (a) Jung, S.-H.; Kim, H. K.; Kim, S.-H.; Kim, Y. H.; Jeoung, S.
C.; Kim, D. Palladium-Catalyzed Direct Synthesis, Photophysical
Properties, and Tunable Electroluminescence of Novel Silicon-Based
Alternating Copolymers. Macromolecules 2000, 33, 9277−9288.
(b) Kumagai, T.; Itsuno, S. Asymmetric Allylation Polymerization
of Bis(allylsilane) and Dialdehyde Containing Arylsilane Structure.
Macromolecules 2002, 35, 5323−5325. (c) Liu, X.-M.; He, C.; Huang,
J.; Xu, J. Highly Efficient Blue-Light-Emitting Glass-Forming
Molecules Based on Tetraarylmethane/Silane and Fluorene: Synthesis
and Thermal, Optical, and Electrochemical Properties. Chem. Mater.
2005, 17, 434−441. (d) You, Y.; An, C.-G.; Kim, J.-J; Park, S. Y. A
Deep Red Phosphorescent Ir(III) Complex for Use in Polymer Light-
Emitting Diodes: Role of Arylsilyl Substituents. J. Org. Chem. 2007,
72, 6241−6246.
spectra of all new compounds (PDF)
Accession Codes
CCDC 2054613−2054622 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
Indubhusan Deb − Organic and Medicinal Chemistry
Division, CSIR-Indian Institute of Chemical Biology,
(3) (a) Mortensen, M.; Husmann, R.; Veri, E.; Bolm, C. Synthesis
and applications of silicon-containing α-amino acids. Chem. Soc. Rev.
4524
https://doi.org/10.1021/acs.orglett.1c01129
Org. Lett. 2021, 23, 4521−4526

Organic Letters
pubs.acs.org/OrgLett
Letter
2009, 38, 1002−1010. (b) Mita, T.; Chen, J.; Sugawara, M.; Sato, Y.
One-Pot Synthesis of α-Amino Acids from CO2 Using a Bismetal
Reagent with Si-B Bond. Org. Lett. 2012, 14, 6202−6205.
(c) Yonemoto-Kobayashi, M.; Inamoto, K.; Tanaka, Y.; Kondo, Y.
Carboxylation of alkynylsilanes with carbon dioxide mediated by
cesium fluoride in DMSO. Org. Biomol. Chem. 2013, 11, 3773−3775.
(4) (a) Showell, G. A.; Mills, J. S. Chemistry challengesin lead
optimization: silicon isosteres in drug discovery. Drug Discovery Today
2003, 8, 551−556. (b) Tacke, R.; Heinrich, T.; Bertermann, R.;
Burschka, C.; Hamacher, A.; Kassack, M. U. Sila-haloperidol: A
Silicon Analogue of the Dopamine (D2) Receptor Antagonist
Haloperidol. Organometallics 2004, 23, 4468−4477. (c) Barnes, M.
J.; Conroy, R.; Miller, D. J.; Mills, J. S.; Montana, J. G.; Pooni, P. K.;
Showell, G. A.; Walsh, L. M.; Warneck, J. B.H. Trimeyhylsilylpyr-
azoles as novel inhibitors of p38 MAP kinase: A new use of silicon
bioisosteresin medicinal chemistry. Bioorg. Med. Chem. Lett. 2007, 17,
354−357. (d) Franz, A. K.; Wilson, S. O. Organosilicon Molecules
with Medicinal Applications. J. Med. Chem. 2013, 56, 388−405.
(e) Sieburth, S. M.; Nittoli, T.; Mutahi, A. M.; Guo, L. Silanediols: A
New Class of Potent Protease Inhibitors. Angew. Chem., Int. Ed. 1998,
37, 812−814.
(5) (a) Lickiss, P. D.; Sykes, A. G. The synthesis of and structure of
organosilanes. Adv. Inorg. Chem. 1995, 42, 147−262. (b) Geng, F.;
Maleczka, R. E., Jr Synthesis of aryl and alkyl acylsilanes using
trimethyl(tributylstannyl)silane. Tetrahedron Lett. 1999, 40, 3113−
3114. (c) Murata, M.; Ishikura, M.; Nagata, M.; Watanabe, S.;
Masuda, Y. Rhodium(I)-Catalyzed Silylationof Aryl Halides with
Triethoxysilane: Practical Synthetic Route to Aryltriethoxysilanes.
Org. Lett. 2002, 4, 1843−1845. (d) Hayashi, S.; Hirano, K.; Yorimitsu,
H.; Oshima, K. Synthesis of (Arylalkenyl)silanes by Palladium-
Catalyzed Regiospecific and Stereoselective Allyl Transfer from Silyl-
Substituted Homoallyl Alcohols to Aryl Halides. J. Am. Chem. Soc.
2007, 129, 12650−12651. (e) Guo, H.; Chen, X.; Zhao, C.; He, W.
Suzuki-type cross coupling between aryl halides and silylboranes for
the synthesis of aryl silanes. Chem. Commun. 2015, 51, 17410−17412.
(6) For representative examples and reviews, see: (a) Tyagi, A.;
Yadav, N.; Khan, J.; Singh, S.; Kumar Hazra, C. Transition-Metal-Free
C-H Silylation. Asian J. Org. Chem. 2021, 10, 334−354. (b) Toutov,
A. A.; Liu, W.-B.; Betz, K. N.; Fedorov, A.; Stoltz, B. M.; Grubbs, R.
H. Silylation of C-H bonds in aromatic heterocycles by an Earth-
abundant metal catalyst. Nature 2015, 518, 80−84. (c) Ma, Y.; Wang,
B.; Zhang, L.; Hou, Z. Boron-Catalyzed Aromatic C-H Bond
Silylation with Hydrosilanes. J. Am. Chem. Soc. 2016, 138, 3663−
3666.
(7) For selected examples, see: (a) Kakiuchi, F.; Igi, K.; Matsumoto,
M.; Chatani, N.; Murai, S. Ruthenium-Catalyzed Dehydrogenative
Silylation of Aryloxazolines with Hydrosilanes via C-H Bond
Cleavage. Chem. Lett. 2001, 30, 422−423. (b) Kakiuchi, F.;
Tsuchiya, K.; Matsumoto, M.; Mizushima, E.; Chatani, N.
Ru3(CO)12-Catalyzed Silylation of Benzylic C-H Bonds in Arylpyr-
idines and Arylpyrazoles with Hydrosilanes via C-H Bond Cleavage. J.
Am. Chem. Soc. 2004, 126, 12792−12793. (c) Ihara, H.; Suginome,
M. Easily Attachable and Detachable Agent for Arylboronic Acids in
Ruthenium-Catalyzed Aromatic C-H Silylation. J. Am. Chem. Soc.
2009, 131, 7502−7503. (d) Sakurai, T.; Matsuoka, Y.; Hanataka, T.;
Fukuyama, N.; Namikoshi, T.; Watanabe, S.; Murata, M. Ruthenium-
catalyzed Ortho-selective Aromatic C-H Silylation: Acceptorless
Dehydrogenative Coupling of Hydrosilanes. Chem. Lett. 2012, 41,
374−376.
(8) For selected examples, see: (a) Sakakura, T.; Tokunaga, Y.;
Sodeyama, T.; Tanaka, M. Catalytic C-H Activation. Silylation of
Arenes with Hydrosilane or Disilane by RhCl(CO)(PMe3)2 under
Irradiation. Chem. Lett. 1987, 16, 2375−2378. (b) Tobisu, M.; Ano,
Y.; Chatani, N. Rhodium-Catalyzed Silylation of Aromatic Carbon-
Hydrogen Bonds in 2-Arylpyridines with Disilane. Chem. - Asian J.
2008, 3, 1585−1591. (c) Kuninobu, Y.; Nakahara, T.; Takeshima, H.;
Takai, K. Rhodium-Catalyzed Intramolecular Silylation of Unac-
tivated C(sp3)-H Bonds. Org. Lett. 2013, 15, 426−428. (d) Cheng,
C.; Hartwig, J. F. Rhodium-Catalyzed Intermolecular C-H Silylation
of Arenes with High Steric Regiocontrol. Science 2014, 343, 853−857.
(9) For selected examples, see: (a) Ishiyama, T.; Sato, K.; Nishio, Y.;
Miyaura, N. Direct Synthesis of Aryl Halosilanes through Iridum(I)-
Catalyzed Aromatic C-H Silylation by Disilanes. Angew. Chem., Int.
Ed. 2003, 42, 5346−5348. (b) Saiki, T.; Nishio, Y.; Ishiyama, T.;
Miyaura, N. Improvements of Efficiency and Regioselectivity in the
Iridium(I)-Catalyzed Aromatic C-H Silylation of Arenes with
Fluorodisilanes. Organometallics 2006, 25, 6068−6073. (c) Simmons,
E. M.; Hartwig, J. F. Catalytic functionalization of unactivated primary
C-H bonds directed by an alcohol. Nature 2012, 483, 70−73.
(d) Choi, G.; Tsurugi, H.; Mashima, K. Hemilabile N-Xylyl-N′-
methylperimidine Carbene Iridium Complexes as Catalysts for C-H
Activation and Dehydrogenative Silylation: Dual Role of N-Xylyl
Moiety for ortho-C-H Bond Activation and Reductive Bond Cleavage.
J. Am. Chem. Soc. 2013, 135, 13149−13161. (e) Cheng, C.; Hartwig,
J. F. Iridium-Catalyzed Silylation of Aryl C-H Bonds. J. Am. Chem. Soc.
2015, 137, 592−595.
(10) Oyamada, J.; Nishiura, M.; Hou, Z. Scandium-Catalyzed
Silylation of Aromatic C-H Bonds. Angew. Chem., Int. Ed. 2011, 50,
10720−10723.
(11) For selected examples, see: (a) Uchimaru, Y.; El Sayed, A. M.
M.; Tanaka, M. Selective arylation of a silicon-hydrogen bond in o-
bis(dimethylsilyl)benzene via carbon-hydrogen bond activation of
arenes. Organometallics 1993, 12, 2065−2069. (b) Williams, N. A.;
Uchimaru, Y.; Tanaka, M. Platinum catalysed regioselective ortho-
silylation of benzyldeneamines via intramolecular C-H activation. J.
Chem. Soc., Chem. Commun. 1995, 1129−1130. (c) Tsukada, N.;
Hartwig, J. F. Intermolecular and Intramolecular, Platinum-Catalyzed,
Acceptorless Dehydrogenative Coupling of Hydrosilanes with Aryl
and Aliphatic Methyl C-H Bonds. J. Am. Chem. Soc. 2005, 127, 5022−
5023.
(12) (a) Kanyiva, K. S.; Kuninobu, Y.; Kanai, M. Palladium-
Catalyzed Direct C-H Silylation and Germanylation of Benzamides
and Carboxamides. Org. Lett. 2014, 16, 1968−1971. (b) Chen, C.;
Guan, M.; Zhang, J.; Wen, Z.; Zhao, Y. Palladium-Catalyzed Oxalyl
Amide Directed Silylation and Germanylation of Amine Derivatives.
Org. Lett. 2015, 17, 3646−3649. (c) Pan, J.-L.; Li, Q.-Z.; Zhang, T.-Y.;
Hou, S.-H.; Kang, J.-C.; Zhang, S.-Y. Palladium-catalyzed direct
intermolecular silylation of remote unactivated C(sp3)-H bonds.
Chem. Commun. 2016, 52, 13151−13154. (d) Liu, Y.-J.; Liu, Y.-H.;
Zhang, Z.-Z.; Yan, S.-Y.; Chen, K.; Shi, B.-F. Divergent and
Stereoselective Synthesis of β-Silyl-α-Amino Acids through Palla-
dium-Catalyzed Intermolecular Silylation of Unactivated Primary and
Secondary C-H Bonds. Angew. Chem., Int. Ed. 2016, 55, 13859−
13862. (e) Deb, A.; Singh, S.; Seth, K.; Pimparkar, S.; Bhaskararao, B.;
Guin, S.; Sunoj, R. B.; Maiti, D. Experimental and Computational
Studies on Remote γ-C(sp3)-H Silylation and Germanylation of
Aliphatic Carboxamides. ACS Catal. 2017, 7, 8171−8175. (f) Pan, J.-
L.; Chen, C.; Ma, Z.-G.; Zhou, J.; Wang, L.-R.; Zhang, S.-Y.
Stereoselective Synthesis of Z-Vinylsilanes via Palladium-Catalyzed
Direct Intermolecular Silylation of C(sp2)-H Bonds. Org. Lett. 2017,
19, 5216−5219. (g) Modak, A.; Patra, T.; Chowdhury, R.; Raul, S.;
Maiti, D. Palladium-Catalyzed Remote meta-Selective C-H Bond
Silylation and Germanylation. Organometallics 2017, 36, 2418−2423.
(h) Maji, A.; Guin, S.; Feng, S.; Dahiya, A.; Singh, V. K.; Liu, P.;
Maiti, D. Experimental and Computational Exploration of para-
Selective Silylation with a Hydrogen-Bonded Template. Angew. Chem.,
Int. Ed. 2017, 56, 14903−14907. (i) Li, W.; Chen, W.; Zhou, B.; Xu,
Y.; Deng, G.; Liang, Y.; Yang, Y. NBE-Controlled Palladium-
Catalyzed Interannular Selective C-H Silylation: Access to Divergent
Silicon-Containing 1,1′-Biaryl-2-Acetamides. Org. Lett. 2019, 21,
2718−2722.
(13) For representative examples and reviews of copper-catalyzed or
-mediated C−H functionalizations, see: (a) Liu, J.; Chen, G.; Tan, Z.
Copper-Catalyzed or -Mediated C-H Bond Functionalizations
Assisted by Bidentate Directing Groups. Adv. Synth. Catal. 2016,
358, 1174−1194. (b) Rao, W.-H.; Shi, B.-F. Recent advances in
copper-mediated chelation-assisted functionalization of unactivated
4525
https://doi.org/10.1021/acs.orglett.1c01129
Org. Lett. 2021, 23, 4521−4526

Organic Letters
pubs.acs.org/OrgLett
Letter
C-H bonds. Org. Chem. Front. 2016, 3, 1028−1043. (c) Chen, X.;
Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. Cu(II)-Catalyzed Functional-
izations of Aryl C-H Bonds Using O2 as an Oxidant. J. Am. Chem. Soc.
2006, 128, 6790−6791. (d) Kitahara, M.; Umeda, N.; Hirano, K.;
Satoh, T.; Miura, M. Copper-Mediated Intermolecular Direct Biaryl
Coupling. J. Am. Chem. Soc. 2011, 133, 2160−2162. (e) Truong, T.;
Klimovica, K.; Daugulis, O. Copper-Catalyzed, Directing Group-
Assisted Fluorination of Arene and Heteroarene C-H Bonds. J. Am.
Chem. Soc. 2013, 135, 9342−9345. (f) Shang, M.; Sun, S.-Z.; Wang,
H.-L.; Laforteza, B. N.; Dai, H.-X.; Yu, J.-Q. Exceedingly Fast
Copper(II)-Promoted ortho C-H Trifluoromethylation of Arenes
using TMSCF3. Angew. Chem. 2014, 126, 10607−10610. (g) Wang,
S.; Guo, R.; Wang, G.; Chen, S.-Y.; Yu, X.-Q. Copper-catalyzed
phosphorylation of sp2 C-H bonds. Chem. Commun. 2014, 50,
12718−12721. (h) Shang, M.; Wang, H.-L.; Sun, S.-Z.; Dai, H.-X.;
Yu, J.-Q. Cu(II)-Mediated Ortho C-H Alkynylation of (Hetero)-
Arenes with Terminal Alkynes. J. Am. Chem. Soc. 2014, 136, 11590−
11593. (i) Li, L.; Zhang, S.-Y.; He, G.; Ai, Z.; Nack, W. A.; Chen, G.
Copper-Catalyzed Carboxamide-Directed Ortho Amination of Ani-
lines with Alkylamines at Room Temperature. Org. Lett. 2014, 16,
1764−1767. (j) Wang, Z.; Kuninobu, Y.; Kanai, M. Copper-Mediated
Direct C(sp3)-H and C(sp2)-H Acetoxylation. Org. Lett. 2014, 16,
4790−4793. (k) Mandal, A.; Sahoo, H.; Baidya, M. Copper-Catalyzed
8-Aminoquinoline-Directed Selenylation of Arene and Heteroarene
C-H Bonds. Org. Lett. 2016, 18, 3202−3205. (l) Gandeepan, P.;
Koeller, J.; Ackermann, L. Expedient C-H Chalcogenation of
Indolines and Indoles by Positional-Selective Copper Catalysis. ACS
Catal. 2017, 7, 1030−1034. For further examples, see SI of ref 5.
(14) For selected examples of 8-aminoquinoline-directed C−H
functionalizations, see: (a) Zaitsev, V. G.; Shabashov, D.; Daugulis, O.
Highly Regioselective Arylation of sp3 C-H Bonds Catalyzed by
Palladium Acetate. J. Am. Chem. Soc. 2005, 127, 13154−13155.
(b) Aihara, Y.; Chatani, N. Ruthenium-catalyzed direct arylation of C-
H bonds in aromatic amides containing a bidentate directing group:
significant electronic effects on arylation. Chem. Sci. 2013, 4, 664−
670. (c) Nishino, M.; Hirano, K.; Satoh, T.; Miura, M. Copper-
Mediated C-H/C-H Biaryl Coupling of Benzoic Acid Derivatives and
1,3-Azoles. Angew. Chem., Int. Ed. 2013, 52, 4457−4461. (d) Shibata,
K.; Chatani, N. Rhodium-Catalyzed Alkylation of C-H Bonds in
Aromatic Amides with α,β-Unsaturated Esters. Org. Lett. 2014, 16,
5148−5151. (e) Wang, Z.; Ni, J.; Kuninobu, Y.; Kanai, M. Copper-
Catalyzed Intramolecular C(sp3)-H and C(sp2)-H Amidation by
Oxidative Cyclization. Angew. Chem., Int. Ed. 2014, 53, 3496−3499.
(f) Grigorjeva, L.; Daugulis, O. Cobalt-Catalyzed, Aminoquinoline-
Directed C(sp2)-H Bond Alkenylation by Alkynes. Angew. Chem., Int.
Ed. 2014, 53, 10209−10212. (g) Matsubara, T.; Asako, S.; Ilies, L.;
Nakamura, E. Synthesis of Anthranilic Acid Derivatives through Iron-
Catalyzed Ortho Amination of Aromatic Carboxamides with N-
Chloroamines. J. Am. Chem. Soc. 2014, 136, 646−649. (h) Aihara, Y.;
Tobisu, M.; Fukumoto, Y.; Chatani, N. Ni(II)-Catalyzed Oxidative
Coupling between C(sp2)-H in Benzamides and C(sp3)-H in Toluene
Derivatives. J. Am. Chem. Soc. 2014, 136, 15509−15512. For more
examples, see SI of ref 6.
(15) (a) Sarkar, W.; Bhowmik, A.; Mishra, A.; Vats, T. K.; Deb, I.
Cobalt-Catalyzed Directed sp2 C-H Acetoxylation of Arenes Employ-
ing Mn(OAc)3.2H2O as Acetoxy Source. Adv. Synth. Catal. 2018, 360,
3228−3232. (b) Sarkar, W.; Mishra, A.; Bhowmik, A.; Deb, I.
Copper-Mediated Direct and Selective C-H Thiolation of Quinazo-
linones. Asian J. Org. Chem. 2019, 8, 819−822. (c) Mishra, A.; Vats,
T. K.; Deb, I. Ruthenium-Catalyzed Direct and Selective C-H
Cyanation of N-(Hetero)aryl-7-azaindoles. J. Org. Chem. 2016, 81,
6525−6534. (d) Sarkar, W.; Bhowmik, A.; Das, S.; Balaram Sulekha,
A.; Mishra, A.; Deb, I. Iridium-catalyzed direct C-H arylation of cyclic
N-sulfonyl ketimines with arylsiloxanes at ambient temperature. Org.
Biomol. Chem. 2020, 18, 7074−7078. For further examples, see SI of
ref 7.
4526
https://doi.org/10.1021/acs.orglett.1c01129
Org. Lett. 2021, 23, 4521−4526