Site-Selective Silylation of Arenes Mediated by Thianthrene S-Oxide

Article abstract of DOI:10.1021/acs.orglett.0c02458

The thianthrene S-oxide (TTSO)-mediated site-selective silylation of arenes has been realized via a thianthrenation/Pd-catalyzed silylation sequence. This method features a broad substrate scope and wide functional group tolerance under mild conditions and allows the synthesis of a set of (hetero)arylsilanes with operationally simple manipulations. The application and generality of the approach were further demonstrated by the late-stage functionalization of marketed drugs. This reaction also represents the first example of a Pd-catalyzed silylation reaction of aryl sulfonium salts.

Full text of DOI:10.1021/acs.orglett.0c02458

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Letter
Site-Selective Silylation of Arenes Mediated by Thianthrene S‑Oxide
Yichen Wu, Yu-Hao Huang, Xiao-Yue Chen, and Peng Wang*
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ABSTRACT: The thianthrene S-oxide (TTSO)-mediated site-selective silyla-
tion of arenes has been realized via a thianthrenation/Pd-catalyzed silylation
sequence. This method features a broad substrate scope and wide functional
group tolerance under mild conditions and allows the synthesis of a set of
(hetero)arylsilanes with operationally simple manipulations. The application and
generality of the approach were further demonstrated by the late-stage
functionalization of marketed drugs. This reaction also represents the first
example of a Pd-catalyzed silylation reaction of aryl sulfonium salts.
rylsilanes are structurally important fragments not only
because of their presence in pharmaceuticals, biologically
Tanaka,5h and others5g since Curtis’s early report,5c in which
good site selectivity for the multisubstituted arene was
observed thanks to the subtle alteration of the steric properties
of both the catalyst and the substrate. However, those
processes are largely constrained by harsh conditions and
insufficient selectivity for the monosubstituted arene (Scheme
1a). The electrophilic substitution and radical approach for
undirected aromatic silylation by Oestreich,6c−f Ohki,6f
Tatsumi,6f Hou,6g Chang,6h Grubbs,7a Stoltz,7a Maruoka,7b
Zhang,7c and others normally provided selective silylated
products with electron-rich anilines, anisole, and heterocycles.
As such, the development of a general protocol for the site-
A
active molecules, and materials1 but also due to their appealing
applications as versatile synthons in organic synthesis.2 Very
recently, we also demonstrated that the Si-centered spirocycle
could be used as a charming platform for chiral ligand design
(Figure 1).3 In comparison with the traditional nucleophilic
Scheme 1. Site-Selective Silylation of Arenes
Figure 1. Arylsilanes in pharmaceuticals, materials, and ligands.
substitution of silicon electrophiles with air-sensitive aryl-metal
reagents (ArLi, ArMgX),4 the direct C−H silylation of simple
(hetero)arenes has been demonstrated as a powerful and
attractive method starting from readily available simple
materials.5−8 To date, several inspired strategies have been
developed to accomplish the (hetero)arylsilane construction,
including transition-metal-catalyzed C−H silylation,5 electro-
philic silylation,6 electrophilic radical silylation,7 and other
approach.8 Despite the noteworthy advances, one particularly
continuous challenge of those undirected aromatic C−H
silylations is the precise control of the site-selective installation
of a silyl group into the aromatics, especially for the
monosubstituted arenes and the electron-neutral simple arenes
in the absence of a directing group. For instance, a branch of
transition-metal-catalyzed dehydrogenative coupling of undir-
ected arenes with silanes has been demonstrated by Berry,5i
Hartwig,5j−l Ishiyama,5f Miyaura,5f Ishikawa,5p Murata,5n
Received: July 23, 2020
https://dx.doi.org/10.1021/acs.orglett.0c02458
© XXXX American Chemical Society
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A

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a b
,
selective silylation of simple arenes with a broad substrate
scope is still of compelling interest in the synthetic community
and the medicinal industry. Herein we provide a practical
approach for the site-selective silylation of simple arenes
mediated by thianthrene S-oxide (TTSO), which is suitable for
the late-stage functionalization of drug molecules and other
bioactive scaffolds under mild conditions. This process is
enabled by the site-selective thianthrenation and subsequent
Pd-catalyzed silylation reaction, providing site-selective sily-
lated arenes with wide functional group tolerance under mild
conditions in one pot by simple manipulations. To the best of
our knowledge, this reaction also represents the first example
of a Pd-catalyzed silylation reaction of aryl sulfonium salts.9
Recently, site-selective sulfonium salts formation has been
demonstrated as a versatile platform for the late-stage
functionalization of simple aromatics and complex bioactive
compounds thanks to the contributions by Ritter,10 Procter,11
and ourselves.12 Among those examples, electrophilic thian-
threnation is noteworthy due to the remarkable selectivity
given to electron-neutral monosubstituted arenes.10,12 How-
ever, those processes normally require the isolation of resulting
sulfonium salts9k,10 or the removal of the solvent and acid in
the sulfonium salts formation step.11,12a In addition, the
generality of this approach is not fully explored, and thus limits
the synthetic efficiency and application. Given the importance
of synthesizing arylsilanes from simple arenes in a highly site-
selective manner, we expected to develop a TTSO-mediated
site-selective silylation without extra manipulations in one pot
and further addressed the aforementioned limitations.
Scheme 2. Evaluation of Reaction Parameters
a
Reaction conditions: (a) 1a (0.1 mmol), TTSO (0.12 mmol), Tf2O
(0.12 mmol), DCM (0.5 mL), N2; −40 °C for 10 min, then rt for
another 10 min. (b) [Pd] (10.0 mol %), ligand (20.0 mol %), base
b
(3.0 equiv), PhMe2SiBPin (2.0 equiv), MeOH (0.5 mL). Yield was
1
determined by H NMR using CH2Br2 as the internal standard; only
c
para-silylated product was observed in crude 1H NMR. Using
d
e
Pd(PPh3)4 as a Pd source. Using K2CO3 as a base. Isolated yield on
f
a 0.2 mmol scale. Ligand (10.0 mol %).
a b
,
Scheme 3. Scope of Monosubstituted Arenes
Because the strong acidic conditions and special solvents
(normally DCM or CH3CN) are required in the thianthrena-
tion step, developing a synthetically simple process starting
from simple arenes without the isolation of sulfonium salts or
the removal of the unavoidable solvent and acid is challenging.
The known transition-metal-catalyzed or photocatalyzed
silylation reactions normally happened under alkaline con-
ditions. Hence both a suitable catalyst that has the capability of
tolerating the solvent or contaminants from the thianthrena-
tion step and the tuning of pH value of the reaction system
with a proper base are crucial to achieving the desired silylation
reaction. After a careful evaluation of the reaction parameters,
the target silylated toluene 2a was efficiently formed in a high
para-selective manner when K2CO3 was used as base in the Pd-
catalyzed thio-silylation step of toluene. This silylation also
proceeded well in the presence of Na2CO3, KHCO3, or K3PO4,
whereas other bases (Li2CO3, Cs2CO3, KOAc) resulted in
inferior yields (Scheme 2, entries 1−7). Various phosphine
ligands were also evaluated in the presence of Pd(OAc)2 as the
palladium source (entries 8−14). The results indicated that
electronic discrepancy on the phosphine ligand [P(p-Tol)3 or
P(p-FC6H4)3] affected the efficiency of this silylation. The
utilization of an alkyl-substituted phosphine ligand (PCy3 or
RuPhos) afforded 2a in a comparable yield. However,
increasing the steric hindrance on phosphine (tButylXPhos)
led to a virtual suppression, whereas the bidentate phosphine
(dppf) was less productive as well.
a
Reaction conditions: (a) 1 (0.2 mmol), TTSO (0.24 mmol), Tf2O
(0.24 mmol), DCM (1.0 mL), N2; −40 °C for 10 min, then rt for
another 10 min. (b) Pd(OAc)2 (10 mol %), PPh3 (20 mol %), K2CO3
b
(3.0 equiv), PhMe2SiBPin (2.0 equiv), MeOH (1.0 mL). Isolated
yield. DCM (0.2 mL) was used. K2CO3 (4.0 equiv) was used.
c
d
With the optimized conditions in hand, the generality of this
protocol was examined systematically. The silylation of various
electron-rich and electron-neutral monosubstituted arenes was
first explored, affording the desired silylated products with
outstanding para-selectivies (Scheme 3). The alkylated
benzene (1b,c) showed the same efficiency and regioselectivity
as toluene. Arenes with para-aryl (1d, s) also underwent the
site-selective silylation in high yields. Other monosubstituted
arenes with polar functional groups (1e, f), electron-rich
anisole (1g), (S)-2-oxiranylanisole (1h), difluoromethoxyben-
zene (1i), 1-bromo-4-phenoxybenzene (1r), and aniline
derivatives (1j−l) were all compatible to yield the correspond-
B
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ing silylated products in synthetic useful yields with out-
standing para-selectivities. The use of electron-deficient
fluorobenzene allowed for the formation of 2m in a good
yield, albeit a higher concentration of thianthrenation was
required. We were particularly pleased with the tolerance of
the native acid group in this process under modified reaction
conditions (1n, o). Moreover, the arenes containing
phthalimide moieties (1p, q) gave the corresponding products
in moderate to good yields.
is noteworthy that TTSO could be recycled in 92% total yield
upon the oxidation of the recovered thianthrene. (See the
Supporting Information.)
To further evaluate the generality and utility of this reaction
in medicinal research, the late-stage functionalization of
marketed drugs and complex structures was conducted. As
depicted in Scheme 5, site-selective silylations of protected
a b
,
Scheme 5. Late-Stage Functionalization
Next, the silylation of a diverse set of multisubstituted arenes
was conducted to check the breadth of this protocol. As
summarized in Scheme 4, experimental results indicated that
a b
,
Scheme 4. Scope of Multisubstituted Arenes
a
Reaction conditions: (a) 5 (0.2 mmol), TTSO (0.24 mmol), Tf2O
(0.24 mmol), DCM (1.0 mL), N2; −40 °C for 10 min, then rt for
another 10 min. (b) Pd(OAc)2 (10 mol %), PPh3 (20 mol %), K2CO3
b
(3.0 equiv), PhMe2SiBPin (2.0 equiv), MeOH (1.0 mL). Isolated
c
d
yield. DCM (0.2 mL) was used. −40 °C for 30 min, then rt for
e
another 1.0 h in the thianthrenation step. K2CO3 (4.0 equiv) was
used.
amino alcohol and amino acid and flurbiprofen, pyriproxyfen,
boscalid, and gemfibrozil derivatives provided the correspond-
ing silylated products in synthetic useful yields, which further
demonstrated the versatility of this protocol.
The scope of silane reagents was also evaluated (Scheme
6a). Although the triethylsilylation was achieved with 3m as
a
Reaction conditions: (a) 3 (0.2 mmol), TTSO (0.24 mmol), Tf2O
(0.24 mmol), DCM (1.0 mL), N2; −40 °C for 10 min, then rt for
another 10 min. (b) Pd(OAc)2 (10 mol %), PPh3 (20 mol %), K2CO3
b
(3.0 equiv), PhMe2SiBPin (2.0 equiv), MeOH (1.0 mL). Isolated
yield. K2CO3 (4.0 equiv) was used. Reaction was conducted on a
gram scale. −40 °C for 30 min, then rt for another 1.0 h in the
thianthrenation step..
c
d
e
Scheme 6. Scope of Silylating Reagents and Synthetic
Applications of Arylsilanes
the silyl group could be selectively installed at the most
electron-rich site due to the electrophilic nature of the sulfide
dication intermediate.12a For instance, substituted anisoles
with an ester (3c), nitro (3d), chloro (3g), or keto group (3i)
at different positions proceeded well, in which the silyl motifs
were all installed in the para position to the methoxyl group.
Moreover, the reaction efficiency is highly dependent on the
electronic discrepancy (3d vs 3l). The selectivity of dialkyl
arenes (3a,b, 3h) also followed the electronic-dominated
characteristic, giving the targeted products in moderate to
good yields. Notably, native phenol (3e) was also compatible
with this process and had excellent site-selectivity. The
reaction with 1,4-disubstituted arenes afforded the correspond-
ing products with the silyl group located ortho to the most
electron-donating group (4j,k). The heterocycles, including
indoline (3m), 1,2,3,4-tetrahydroquinoline (3n), 3,4-dihydro-
2(1H)-quinolone (3o), and carbazole (3p), proceeded
smoothly under these aromatic C−H silylation conditions in
a highly regioselective manner. The scalability of this process
was investigated by employing Ts-protected indoline (3m) as
the model substrate, giving 5-silylated indoline in 83% yield. It
the model substrate under our standard conditions (65% yield;
see the Supporting Information), a higher yield was reached
when the 3m-derived sulfonium salt 7 was directly used.
Moreover, the tributylsilyl group was introduced with less
efficiency, probably due to the steric hindrance (8b). TMS
could also be installed in a high yield with a commercially
available silane source (Me3Si−SiMe3) under modified
Hiyama’s conditions (8c).13 Furthermore, transformations of
C
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Organosilicon molecules with medicinal applications. J. Med. Chem.
2013, 56, 388−405. (f) Sun, D.; Ren, Z.; Bryce, M. R.; Yan, S.
Arylsilanes and siloxanes as optoelectronic materials for organic light-
emitting diodes (OLEDs). J. Mater. Chem. C 2015, 3, 9496−9508.
(2) (a) The Chemistry of Organic Silicon Compounds; Patai, S.,
Rappoport, Z., Eds.; Wiley Interscience: New York, 1989. (b) Luh, T.-
Y.; Liu, S.-T. In The Chemistry of Organic Silicon Compounds;
Rappoport, Y. A. Z., Ed.; Wiley: Chichester, U.K., 2003; pp 1793−
1868. (c) Hatanaka, Y.; Fukushima, S.; Hiyama, T. Selective synthesis
of unsymmetrical biaryls via palladium-Catalyzed cross-coupling of
arylfluoro-silanes with aryl iodides. Chem. Lett. 1989, 18, 1711−1714.
(d) Ball, L. T.; Lloyd-Jones, G. C.; Russell, C. A. Gold-catalyzed direct
arylation. Science 2012, 337, 1644−1648. (e) Sore, H. F.; Galloway,
W. R. J. D.; Spring, D. R. Palladium-catalysed cross-coupling of
organosilicon reagents. Chem. Soc. Rev. 2012, 41, 1845−1866.
(f) Denmark, S. E.; Ambrosi, A. Why You really should consider
using Palladium-catalyzed cross-coupling of silanols and silanolates.
Org. Process Res. Dev. 2015, 19, 982−994. (g) Minami, Y.; Hiyama, T.
Designing cross-coupling reactions using aryl(trialkyl)silanes. Chem. -
Eur. J. 2019, 25, 391−399.
triethylsilylarene 8a were preformed, giving brominated
derivative 9 and homocoupling product 10 in good yields,
respectively (Scheme 6b).6g,14
In summary, the TTSO-mediated site-selective silylation of
simple arenes has been realized thanks to the superiority of Pd
catalysis and the subtle alteration of the pH value of the
reaction system with a base. The protocol features remarkable
site selectivity, wide functional group and heterocycle
tolerance, mild conditions, and operatically simple manipu-
lations.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c02458.
Experimental procedures, complete characterization
1
data, and copies of H and 13C NMR spectra (PDF)
(3) Chang, X.; Ma, P.-L.; Chen, H.-C.; Li, C.-Y.; Wang, P.
Asymmetric synthesis and application of chiral spirosilabiindanes.
Angew. Chem., Int. Ed. 2020, 59, 8937.
AUTHOR INFORMATION
Corresponding Author
■
̌
(4) Bazant, V.; Chvalovsky, V.; Rathousky, J. Organosilicon
Peng Wang − State Key Laboratory of Organometallic
Chemistry, Center for Excellence in Molecular Synthesis and
CAS Key Laboratory of Energy Regulation Materials, Shanghai
Institute of Organic Chemistry, CAS, Shanghai 200032, China;
orcid.org/0000-0002-6442-3008; Email: pengwang@
sioc.ac.cn
Compounds; Academic Press: New York, 1965.
(5) For reviews on the transition-metal-catalyzed C−H silylation of
arenes, see: (a) Richter, S. C.; Oestreich, M. Emerging strategies for
C−H silylation. Trends Chem. 2020, 2, 13−27. (b) Cheng, C.;
Hartwig, J. F. Catalytic silylation of unactivated C−H bonds. Chem.
Rev. 2015, 115, 8946−8975. For selected examples with Ir catalysis,
see: (c) Gustavson, W. A.; Epstein, P. S.; Curtis, M. D. Homogeneous
activation of the carbon-hydrogen bond. Formation of phenyl-
siloxanes from benzene and silicon hydrides. Organometallics 1982,
1, 884−885. (d) Ishiyama, T.; Sato, K.; Nishio, Y.; Miyaura, N. Direct
synthesis of aryl halosilanes through Iridium(I)-catalyzed Aromatic
C−H silylation by disilanes. Angew. Chem., Int. Ed. 2003, 42, 5346−
5348. (e) 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. (f) Ishiyama, T.; Saiki, T.;
Kishida, E.; Sasaki, I.; Ito, H.; Miyaura, N. Aromatic C−H silylation of
arenes with 1-hydrosilatrane catalyzed by an iridium(I)/2,9-dimethyl
phenanthroline(dmphen) complex. Org. Biomol. Chem. 2013, 11,
8162−8165. (g) Lu, B.; Falck, J. R. Efficient Iridium-catalyzed C−H
functionalization/silylation of heteroarenes. Angew. Chem., Int. Ed.
2008, 47, 7508−7510. (h) 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. Rh catalysis: (i) Ezbiansky, K.;
Djurovich, P. I.; LaForest, M.; Sinning, D. J.; Zayes, R.; Berry, D. H.
Catalytic C−H bond functionalization: synthesis of arylsilanes by
dehydrogenative transfer coupling of arenes and triethylsilane.
Organometallics 1998, 17, 1455−1457. (j) Cheng, C.; Hartwig, J. F.
Rhodium-catalyzed intermolecular C−H silylation of arenes with high
steric regiocontrol. Science 2014, 343, 853−857. (k) Cheng, C.;
Hartwig, J. F. Mechanism of the Rhodium-catalyzed silylation of arene
C−H bonds. J. Am. Chem. Soc. 2014, 136, 12064−12072. (l) Karmel,
C.; Chen, Z.; Hartwig, J. F. Iridium-catalyzed silylation of C−H bonds
in unactivated arenes: A sterically encumbered phenanthroline ligand
accelerates catalysis. J. Am. Chem. Soc. 2019, 141, 7063−7072. Pt
catalysis: (m) Williams, N. A.; Uchimaru, Y.; Tanaka, M. Platinum
catalysed regioselective ortho-silylation of benzylideneamines via
intramolecular C−H activation. J. Chem. Soc., Chem. Commun.
1995, 1129−1130. (n) Murata, M.; Fukuyama, N.; Wada, J.-i.;
Watanabe, S.; Masuda, Y. Platinum-catalyzed Aromatic C−H
silylation of arenes with 1,1,1,3,5,5,5-heptamethyltrisiloxane. Chem.
Lett. 2007, 36, 910−911. Ni catalysis: (o) Elsby, M. R.; Liu, J.; Zhu,
S.; Hu, L.; Huang, G.; Johnson, S. A. Influence of N-heterocyclic
carbene steric bulk on selectivity in Nickel catalyzed C−H bond
Authors
Yichen Wu − State Key Laboratory of Organometallic
Chemistry, Center for Excellence in Molecular Synthesis,
Shanghai Institute of Organic Chemistry, CAS, Shanghai
200032, China
Yu-Hao Huang − State Key Laboratory of Organometallic
Chemistry, Center for Excellence in Molecular Synthesis,
Shanghai Institute of Organic Chemistry, CAS, Shanghai
200032, China
Xiao-Yue Chen − State Key Laboratory of Organometallic
Chemistry, Center for Excellence in Molecular Synthesis,
Shanghai Institute of Organic Chemistry, CAS, Shanghai
200032, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c02458
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the Shanghai Institute of Organic
Chemistry, State Key Laboratory of Organometallic Chemistry,
Shanghai Rising-Star Program (20QA1411400), and National
Natural Science Foundation of China (21821002) for financial
support.
REFERENCES
■
(1) (a) Silicon-Containing Polymers; Jones, R. G., Ando, W.,
Chojnowski, J., Eds.; Kluwer: Dordrecht, The Netherlands, 2000.
(b) Brook, M. Silicon in Organic, Organometallic and Polymer
Chemistry; Wiley: New York, 2000. (c) Zelisko, P. M. Bio-Inspired
Silicon-Based Materials; Springer: Dordrecht, The Netherlands, 2014.
(d) Showell, G. A.; Mills, J. S. Chemistry challenges in lead
optimization: silicon isosteres in drug discovery. Drug Discovery
Today 2003, 8, 551−556. (e) Franz, A. K.; Wilson, S. O.
D
https://dx.doi.org/10.1021/acs.orglett.0c02458
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
silylation, germylation, and stannylation. Organometallics 2019, 38,
436−450. (p) Ishikawa, M.; Okazaki, S.; Naka, A.; Sakamoto, H.
Nickel-catalyzed reactions of 3,4-benzo-1,1,2,2-tetraethyl-1,2-disilacy-
clobutene with aromatic compounds. Organometallics 1992, 11,
4135−4139. Pd catalysis: (q) Xu, Y.; Liu, X.; Chen, W.; Deng, G.;
Liang, Y.; Yang, Y. Palladium/norbornene chemistry: synthesis of
norbornene-containing arylsilanes involving double C−Si bond
formation. J. Org. Chem. 2018, 83, 13930−13939. (r) 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.
Otsuka, S.; Nogi, K.; Yorimitsu, H. Palladium-catalyzed borylation of
aryl sulfoniums with diborons. ACS Catal. 2018, 8, 579−583.
́
(i) Aukland, M. H.; Talbot, F. J. T.; Fernandez-Salas, J. A.; Ball,
M.; Pulis, A. P.; Procter, D. J. An interrupted Pummerer/Nickel-
catalysed cross-coupling sequence. Angew. Chem., Int. Ed. 2018, 57,
9785−9789. (j) Zhao, J.-N.; Kayumov, M.; Wang, D.-Y.; Zhang, A.
Transition-metal-free aryl−heteroatom bond formation via C−S bond
cleavage. Org. Lett. 2019, 21, 7303−7306. (k) Kafuta, K.; Korzun, A.;
̈
Bohm, M.; Golz, C.; Alcarazo, M. Synthesis, Structure, and Reactivity
of 5-(Aryl)dibenzothiophenium Triflates. Angew. Chem., Int. Ed. 2020,
59, 1950−1955.
(10) (a) Berger, F.; Plutschack, M. B.; Riegger, J.; Yu, W.; Speicher,
S.; Ho, M.; Frank, N.; Ritter, T. Site-selective and versatile aromatic
C−H functionalization by thianthrenation. Nature 2019, 567, 223−
̈
(6) (a) Bahr, S.; Oestreich, M. The electrophilic aromatic
substitution approach to C−H silylation and C−H borylation. Pure
́
̈
228. (b) Engl, P. S.; Haring, A. P.; Berger, F.; Berger, G.; Perez-
̈
Appl. Chem. 2018, 90, 723−731. (b) Bahr, S.; Oestreich, M.
́
Bitrian, A.; Ritter, T. C−N cross-couplings for site-selective late-stage
Electrophilic aromatic substitution with silicon electrophiles: catalytic
Friedel−Crafts C−H silylation. Angew. Chem., Int. Ed. 2017, 56, 52−
59. (c) Chen, Q.-A.; Klare, H. F. T.; Oestreich, M. Brønsted acid-
promoted formation of stabilized silylium ions for catalytic Friedel−
Crafts C−H silylation. J. Am. Chem. Soc. 2016, 138, 7868−7871.
(d) Yin, Q.; Klare, H. F. T.; Oestreich, M. Friedel−Crafts-type
intermolecular C−H silylation of electron-rich arenes initiated by
base-metal salts. Angew. Chem., Int. Ed. 2016, 55, 3204−3207.
(e) Omann, L.; Oestreich, M. A catalytic SEAr approach to
dibenzosiloles functionalized at both benzene cores. Angew. Chem.,
Int. Ed. 2015, 54, 10276−10279. (f) Klare, H. F. T.; Oestreich, M.;
Ito, J.-i.; Nishiyama, H.; Ohki, Y.; Tatsumi, K. Cooperative catalytic
activation of Si−H bonds by a polar Ru−S bond: regioselective low-
temperature C−H silylation of indoles under neutral conditions by a
Friedel−Crafts mechanism. J. Am. Chem. Soc. 2011, 133, 3312−3315.
(g) 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. (h) Zhang, J.; Park, S.; Chang, S. Catalytic access to
bridged Sila-N-heterocycles from piperidines via cascade sp3 and sp2
C−Si bond formation. J. Am. Chem. Soc. 2018, 140, 13209−13213.
(i) Xu, W.; Pek, J. H.; Yoshikai, N. Iron-catalyzed directed C−H
silylation of pivalophenone N−H imines. Asian J. Org. Chem. 2018, 7,
1351−1354.
diversification via aryl sulfonium salts. J. Am. Chem. Soc. 2019, 141,
13346−13351. (c) Ye, F.; Berger, F.; Jia, H.; Ford, J.; Wortman, A.;
Borgel, J.; Genicot, C.; Ritter, T. Aryl sulfonium salts for site-selective
̈
late-stage trifluoromethylation. Angew. Chem., Int. Ed. 2019, 58,
14615−14619. (d) Sang, R.; Korkis, S. E.; Su, W.; Ye, F.; Engl, P. S.;
Berger, F.; Ritter, T. Site-selective C−H oxygenation via aryl
sulfonium salts. Angew. Chem., Int. Ed. 2019, 58, 16161−16166.
(e) Li, J.; Chen, J.; Sang, R.; Ham, W.-S.; Plutschack, M. B.; Berger,
F.; Chabbra, S.; Schnegg, A.; Genicot, C.; Ritter, T. Photoredox
catalysis with aryl sulfonium salts enables site-selective late-stage
fluorination. Nat. Chem. 2020, 12, 56−62. (f) Alvarez, E. M.;
Plutschack, M. B.; Berger, F.; Ritter, T. Site-Selective C−H
Functionalization−Sulfination Sequence to Access Aryl Sulfonamides.
Org. Lett. 2020, 22, 4593−4596.
̌
̌
(11) Aukland, M. H.; Siauciulis, M.; West, A.; Perry, G. J. P.;
Procter, D. J. Metal-free photoredox-catalysed formal C−H/C−H
coupling of arenes enabled by interrupted Pummerer activation. Nat.
Catal. 2020, 3, 163−169.
(12) (a) Wu, J.; Wang, Z.; Chen, X.-Y.; Wu, Y.; Wang, D.; Peng, Q.;
Wang, P. Para-selective borylation of monosubstituted benzenes using
a transient mediator. Sci. China: Chem. 2020, 63, 336−340. (b) Chen,
X.-Y.; Nie, X.-X; Wu, Y.; Wang, P. Para-Selective arylation and
alkenylation of monosubstituted arenes using thianthrene S-oxide as a
transient mediator. Chem. Commun. 2020, 56, 5058−5061.
(13) Shirakawa, E.; Kurahashi, T.; Yoshida, H.; Hiyama, T.
Diphenylphosphinophenolate: a ligand for the palladium-catalyzed
silylation of aryl halides activating simultaneously both palladium and
silicon. Chem. Commun. 2000, 1895−1896.
(7) (a) 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.
(b) Sakamoto, R.; Nguyen, B.-N.; Maruoka, K. Transition-metal-free
direct C−H silylation of electron-deficient heteroarenes with
hydrosilanes via a radical mechanism. Asian J. Org. Chem. 2018, 7,
1085−1088. (c) Liu, S.; Pan, P.; Fan, H.; Li, H.; Wang, W.; Zhang, Y.
Photocatalytic C−H silylation of heteroarenes by using trialkylhy-
drosilanes. Chem. Sci. 2019, 10, 3817−3825.
(14) Shibata, M.; Ito, H.; Itami, K. Oxidative homocoupling reaction
of aryltrimethylsilanes by Pd/o-chloranil catalysis. Chem. Lett. 2017,
46, 1701−1704.
(8) Gu, Y.; Shen, Y.; Zarate, C.; Martin, R. A mild and direct site-
selective sp2 C−H silylation of (poly)azines. J. Am. Chem. Soc. 2019,
141, 127−132.
(9) For reviews on the transformations of sulfonium salts, see:
(a) Nenaidenko, V. G.; Balenkova, E. S. New synthetic capabilities of
sulfonium salts. Russ. J. Org. Chem. 2003, 39, 291−330. (b) Tian, Z.-
Y.; Hu, Y.-T.; Teng, H.-B.; Zhang, C.-P. Application of arylsulfonium
salts as arylation reagents. Tetrahedron Lett. 2018, 59, 299−309. For
selected examples, see: (c) Srogl, J.; Allred, G. D.; Liebeskind, L. S.
Sulfonium salts. Participants par excellence in metal-catalyzed
carbon−carbon bond-forming reactions. J. Am. Chem. Soc. 1997,
119, 12376−12377. (d) Zhang, S.; Marshall, D.; Liebeskind, L. S.
Efficient Pd-catalyzed heterobenzylic cross-coupling using sulfonium
salts as substrates and (PhO)3P as a supporting ligand. J. Org. Chem.
1999, 64, 2796−2804. (e) Cowper, P.; Jin, Y.; Turton, M. D.; Kociok-
̈
Kohn, G.; Lewis, S. E. Azulenesulfonium salts: accessible, stable, and
versatile reagents for cross-coupling. Angew. Chem., Int. Ed. 2016, 55,
2564−2568. (f) Wang, S.-M.; Wang, X.-Y.; Qin, H.-L.; Zhang, C.-P.
Palladium-catalyzed arylation of arylboronic acids with Yagupolskii−
Umemoto reagents. Chem. - Eur. J. 2016, 22, 6542−6546. (g) Minami,
H.; Nogi, K.; Yorimitsu, H. Palladium-catalyzed alkoxycarbonylation
of arylsulfoniums. Org. Lett. 2019, 21, 2518−2522. (h) Minami, H.;
E
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