Functionalization of a Single C?F Bond of Trifluoromethylarenes Assisted by an ortho-Silyl Group Using a Trityl-Based All-in-One Reagent with Ytterbium Triflate Catalyst

Article abstract of DOI:10.1002/chem.202001315

Catalytic thiolation and azidation of a single C?F bond of trifluoromethylarenes were achieved assisted by an ortho-silyl group with all-in-one reagents to generate a trityl cation and nucleophiles. The reactions catalyzed by ytterbium triflate efficientl

Full text of DOI:10.1002/chem.202001315

A Journal of
Accepted Article
Title: Catalytic Functionalization of a Single C–F Bond of
Trifluoromethylarenes Assisted by an ortho-Silyl Group Using a
Trityl-Based All-in-One Reagent with Ytterbium Triflate Catalyst
Authors: Youngchan Kim, Kazuya Kanemoto, Ken Shimomori,
Takamitsu Hosoya, and Suguru Yoshida
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content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.202001315
Link to VoR: http://dx.doi.org/10.1002/chem.202001315
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10.1002/chem.202001315
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COMMUNICATION
Functionalization of a Single C–F Bond of Trifluoromethylarenes
Assisted by an ortho-Silyl Group Using a Trityl-Based All-in-One
Reagent with Ytterbium Triflate Catalyst
Youngchan Kim, Kazuya Kanemoto, Ken Shimomori, Takamitsu Hosoya, and Suguru Yoshida*
Abstract: Catalytic thiolation and azidation of a single C–F bond of
trifluoromethylarenes were achieved assisted by an ortho-silyl group
with all-in-one reagents to generate trityl cation and nucleophiles. The
reactions catalyzed by ytterbium triflate efficiently afforded a wide
variety of difluoromethylenes avoiding the further C–F bond cleavage,
by virtue of the mild conditions without the generation of a Brønsted
acid.
In this context, we have developed a novel transformation of
a
single C–F bond of benzotrifluorides with a latently
transformable ortho-silyl group (Figure 1B).[5] For instance, the
treatment of a mixture of benzotrifluoride 1 and allylsilane 2 with
triphenylmethylium
tetrafluoroborate
efficiently
provided
difluoromethylene 3 by allylation of a single C–F bond of the
trifluoromethyl group, via hydride abstraction from the hydrosilyl
group, followed by the C–F bond cleavage. Further transformation
including the Hiyama cross-coupling of the resulting fluorosilyl
group successfully afforded difluoromethylene 4.
The development of selective transformation of the trifluoromethyl
group is a significant and challenging issue since organofluorines
including difluoromethylenes have gained the attention of a wide
range of researchers in pharmaceutical sciences, agrochemistry,
and materials science.[1,2] In particular, recent successes on C–F
transformations of benzotrifluorides enabled the synthesis of
various difluoromethylenes by photocatalysis[3] or frustrated
Lewis-pair[4] in the last few years (Figure 1A).
To expand the synthetic utility of the selective transformation
of trifluoromethylarenes, we attempted a C–F thiolation of
benzotrifluoride 1a using thiol 5 as a nucleophile (Figure 2A). As
a result, although the C–F bond cleavage took place smoothly,
the desired aryl difluorobenzyl sulfide 6a was not obtained.
Instead, the resulting product was trithioorthoester 7 via the
further C–F bond cleavage, which would be caused by
tetrafluoroboric acid generated in situ.[6]
A
photocatalysis
alkene
F
F
R
CF3
Ph
F
F
F
F
–NTf2
Ph
N
Nu
2,4,6-triphenylpyridine
cat. B(C6F5)3
Me3SiNTf2
nucleophile
Ph
A
HS
OMe
5
SiMe3
B
4-MeO2CC6H4I
cat. Pd
(5.0 equiv)
Ph3CBF4
(1.2 equiv)
F
F
ArS SAr
SAr
2
Ph3CBF4
F
F
F
F
CF3
Ar1
Ar1
Ar1
Ag2O
CF3
SAr
+
H
H
F
F
F
CH2Cl2
HFIP
(1:1)
Ar2
CH2Cl2
HFIP
Si
Si
Si
Si
Si
4
Ph Ph
3
Ph Ph
Ph Ph
Ph Ph
Ph Ph
1
0 °C, 10 min
1a
6a
7
80%
not detected
B
Figure 1. Selective transformation of an aromatic trifluoromethyl group via C–F
bond cleavage. (A) Recently reported works. (B) Our previous work.
F
F
C–S bond
R
formation and
regeneration of
the catalyst
S
Ph
F
an all-in-one reagent
for thiolation of 1
LA
S
Si
R’
Ph
R
Ph
Ph Ph
F
6
8
LA
S
equilibrium
F
Ph
C
R
LA
generation of
a trityl cation
and a thiolate
F
S
Si
Ph Ph
Ph
Ph
R’
R
II
I
[*]
Mr. Y. Kim, Dr. K. Kanemoto, Mr. K. Shimomori, Prof. Dr. T. Hosoya,
Assoc. Prof. Dr. S. Yoshida,
hydride
abstraction
CF3
Laboratory of Chemical Bioscience, Institute of Biomaterials and
Bioengineering, Tokyo Medical and Dental University (TMDU),
2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan)
E-mail: s-yoshida.cb@tmd.ac.jp
H
C–F bond
cleavage
Si
R’
Ph
Ph Ph
1
Ph
Ph
H
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
http ://dx.doi.org/10.1002/anie.xxxxxxxxx.
Figure 2. Approaches for C–F thiolation. (A) An attempt to prepare 6a. (B) A
working hypothesis of catalytic C–F thiolation of 1 using a trityl sulfide 8.
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10.1002/chem.202001315
Chemistry - A European Journal
COMMUNICATION
We then conceived a novel catalytic cycle without generating
tetrafluoroboric acid for the selective C–F thiolation of
benzotrifluoride 1a enabled by equilibrium generation of trityl
cation and a thiolate nucleophile (Figure 2B).[7] The cycle is
triggered by the C–S bond cleavage of trityl sulfide 8 with a Lewis
acid catalyst, leading to the equilibrium generation of
triphenylmethylium thiolate I. Then, intermediate I can facilitate
the hydride abstraction of 1a followed by the C–F bond cleavage,
generating the cationic intermediate II. Finally, the thiolation of II
by the thiolate provides sulfide 6 with the regeneration of the
Lewis acid catalyst. We anticipated that the mild reaction
conditions only using a trityl sulfide and a Lewis acid catalyst
would prevent the decomposition affording trithioorthoester 7 by
the further C–F bond cleavage of difluoromethylene 6.
Various benzotrifluorides 1 were successfully thiolated under
the Yb(OTf)3-catalyzed conditions (Figures 3A and 3B). The
catalytic C–F thiolation smoothly took place affording a wide
range of difluoromethylenes 6b–i from the corresponding
benzotrifluorides bearing a methoxy, aryl, heteroaryl, bromo, or
trifluoromethyl group. In addition, the reaction of electron-poor 5-
bromo-
or
4-trifluoromethyl-substituted
2-
(hydrosilyl)benzotrifluoride proceeded slowly to yield 6g or 6h,
respectively, in moderate yields. It is worth noting that the C–F
bond thiolation of the trifluoromethyl group adjacent to the
hydrosilyl group selectively underwent to provide 6f and 6h. The
C–F bond cleavage using a dimethylsilyl group also occurred to
furnish the desired sulfide 6i albeit in moderate yield.
Ph3CSR
8
After
a rigorous screening of the reaction conditions
A
particularly for the Lewis acid catalysts, we found that
ytterbium(III) triflate efficiently catalyzed the selective C–F
thiolation of benzotrifluoride 1a using trityl sulfide 8a (Table 1).
While no reaction occurred without Lewis acid catalyst (entry 1),
several Lewis acids promoted the thiolation of 1a (entries 2–5). In
particular, the treatment of 1a with 8a in the presence of 20 mol %
of ytterbium triflate in dichloromethane and HFIP successfully
provided the desired aryl difluorobenzyl sulfide 6a in high yield
(entry 5). Although decreasing the amount of ytterbium triflate to
5 mol % lowered the yield of 6a (entry 6), performing the reaction
at 0 °C resulted in producing 6a in good yield (entry 7). We also
found that HFIP was necessary for the thiolation possibly due to
the significant stabilization of cationic intermediates (entry 7 vs
entry 8).[8]
(2.0 equiv)
Yb(OTf)3
(5 mol %)
F
F
CF3
R
S
H
F
CH2Cl2, HFIP
(1/1)
0 °C, 80 min
Si
Si
Ph Ph
R
R
Ph Ph
1
6
Products by thiolation using 8a
(Ar = C6H4-4-OMe)
MeO
B
MeO
F
F
F
F
SAr
SAr
F
F
Ph3CS
OMe
Si
Si
Ph Ph
Ph Ph
8a
6b
75%
6c
69%
MeO2C
F3C
SAr
F
F
F F
F
F
S
SAr
SAr
F
F
F
Si
Ph Ph
Si
Si
Ph Ph
6e
70%
6f
67%
Ph Ph
6d
70%
Table 1. Optimization of the Reaction Conditions
MeO
F
F
F F
F
F
Br
SAr
F
SAr
F
SAr
Ph3CS
OMe
F
Si
F3C
Si
Si
8a
(2.0 equiv)
catalyst
(x mol %)
Ph Ph
6g
54%[a]
Ph Ph
6h
31%[b]
OMe
Me Me
F
F
6i
40%
CF3
S
H
Products by thiolation of 1a
F
C
CH2Cl2
HFIP
(1:1)
Si
Si
O
Me
Br
Ph Ph
Ph Ph
F
F
F F
OMe
F
F
temp., time
1a
6a
S
S
F
S
F
Si
Ph Ph
6j
Si
F
Si
Ph Ph
entry
catalyst
none
x
temp.
time (min)
yield (%)[a]
Ph Ph
6l
65%
6k
65%
49%
1
–
rt
10
10
10
10
10
10
80
80
n.d.[b]
18
F
F
F
F
F
F
F
F
S
S–n-C12H25
S
F
S
2
AlCl3
20
20
rt
S
F
Br
F
Si
Si
Si
F
Si
Ph Ph
6n
62%
3
BF3·OEt2
rt
42
Ph Ph
6p
not detected
Ph Ph
Ph Ph
6m
68%
6o
69%
4
(CH3CN)4CuBF4
Yb(OTf)3
20
20
5
rt
38
5
rt
76
Figure 3. C–F bond thiolation of benzotrifluorides 1. (A) General scheme. (B)
Results using various benzotrifluorides 1 using 8a. (C) Results using 1a with
various trityl sulfides 8. [a] The reaction was performed for 5.5 h. [b] The reaction
was performed using 20 mol % of Yb(OTf)3 for 3.5 h.
6
Yb(OTf)3
rt
49
7
Yb(OTf)3
5
0 °C
0 °C
69[c]
n.d.[b]
8[d]
Yb(OTf)3
5
Diverse trityl sulfides 8 participated in the C–F bond thiolation
of benzotrifluorides 1 (Figure 3C). Not only 4-tolylthio group but
also 4-(methoxycarbonyl)- and 4-bromophenythio groups were
[a] Yields based on 1H NMR analysis. [b] Not detected. [c] Isolated yield. [d] The
reaction was performed in dichloromethane.
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10.1002/chem.202001315
Chemistry - A European Journal
COMMUNICATION
applicable to the C–F thiolation to provide aryldifluoromethyl
sulfides 6j–l selectively, leaving various functional groups
untouched. Benzotrifluoride 1a could also be thiolated
uneventfully using bulky 2-bromophenyl trityl sulfide to afford 6m.
provide
11a–c
without damaging the arylthio and
difluoromethylene groups.[10]
Since a wide variety of aryl trityl sulfides and benzotrifluorides
could be prepared by the modular synthesis combining easily
available starting materials, the selective C–F thiolation allows for
the synthesis of diverse aryl difluorobenzyl sulfides from simple
modules. For example, we accomplished the synthesis of
benzotrifluoride 13 from 12a, trifluoromethylsilane, and
chlorodiphenylsilane, via the iodotrifluoromethylation of aryne
intermediate III (Figure 4B).[11,12] Aryl trityl sulfide 14 was also
prepared from simple modules, 12b, an aryl iodide, and
triphenylmethanethiol, via the C–H borylation followed by the
Suzuki–Miyaura cross-coupling reaction and subsequent addition
reaction using the thiol to aryne intermediate IV.[11,13] The
Yb(OTf)3-catalyzed C–F thiolation using 13 having two methoxy
groups at 3- and 4-positions and 14 proceeded efficiently through
the selective cleavage of one of three C–F bonds of
In
addition,
naphtyl-
and
heteroaryl-substituted
difluoromethylenes 6n and 6o were obtained by 2-naphtyl- and 2-
thienylthiolation, respectively. On the other hand, an attempt for
selective alkylthiolation of the C–F bond resulted in producing a
complex mixture, in which the desired sulfide 6p was not obtained.
OMe
A
F
F
F
n-Bu4NF
MeO
MeO
S
CH3CN, rt
9
98%
H
OMe
F
4-(MeO2C)C6H4I
cat. Pd(PPh3)4
Ag2O
OMe
S
F
F
trifluoromethyl
group.
Further
desilylprotonation
with
MeO
S
tetrabutylammonium fluoride successfully afforded sulfide 15.
Thus, the facile accessibility of o-hydrosilyl-substituted
benzotrifluorides and trityl sulfides from simple modules via aryne
intermediates would serve to prepare a wide variety of aryl
difluorobenzyl sulfides in a convergent manner.
OMe
THF, 70 °C
F
Si
Ph Ph
6b
10
60%
O
NXS
(X = Cl, Br, or I)
AgF
OMe
F
F
MeO
S
CH3CN, rt
X = Cl 11a 82%
Br 11b 88%
11c 90%
X
I
A
OMe
HS
OMe
B
MeO
MeO
SiMe3
OTf
Me3Si
TfO
5
ArS SAr
SAr
F
F
(4.0 equiv)
HBF4 (1.0 equiv)
SAr
12a
1. KF, 18-crown-6 2. n-BuLi;
Me3SiCF3
then, Ph2SiHCl;
12b
F
F
1. cat. Ir, B2pin2
[ref. 13]
2. cat. Pd
CH2Cl2, HFIP (1:1)
0 °C, 10 min
Si
Si
3. Ph3CSH
CsF; 88%
Ph Ph
84%
Ph Ph
;
Ph
I
55%
3,5-(F3C)2C6H3I;
89%
7
84%
6a
OMe
Yb(OTf)3
(x mol %)
MeO
MeO
CF3
B
Ph3C+
H
CF3
Ph3CS
OMe
Si
Ph3CS
Ph Ph
13
14
S
OMe
CH2Cl2, HFIP (1:1)
0 °C, 10 min
8a
Yb
CF3
1.5
1.0
1. cat. Yb
CH2Cl2, HFIP
0 °C, 80 min; 74%
2. n-Bu4NF
92%
Absorbance
at 408 nm
x
OMe
OMe
MeO
MeO
100
50
10
0
1.3921
0.7689
0.1199
0.0505
F
F
0.5
0
CF3
MeO
MeO
CF3
S
III
IV
15
300
350
400
450
500
CF3
CF3
Figure 5. Control experiments. (A) Acid-mediated C–F thiolation. (B) Absorption
spectra of a mixture between trityl sulfide 8a and ytteribium triflate (red line: x =
100; orange line: x = 50; green line: x = 10; blue line: x = 0).
Figure 4. Synthesis of various difluorobenzyl sulfides. (A) Transformations of
the fluorosilyl group of 6b. (B) Modular synthesis of 15.
We then achieved the derivatizations of the transformable
fluorosilyl group in the arylthiolated products (Figure 4A). For
instance, desilylprotonation of 6b using tetrabutylammonium
fluoride (TBAF) efficiently underwent to afford 9 in high yield
leaving the α,α-difluorobenzylthio moiety intact. Furthermore,
biphenyl derivative 10 was also synthesized by the Hiyama cross-
coupling with methyl 4-iodobenzoate in the presence of silver(I)
oxide as an activator.[9] Desilylhalogenations using N-
halosuccinimides (NXS, X = Cl, Br, and I) efficiently proceeded to
We then performed several experiments to investigate the
reaction mechanism of the catalytic C–F thiolation (Figure 5). To
reveal the key which avoided the further C–F bond cleavage of
aryldifluoromethyl sulfides, we attempted the reaction between 6a
and 5 in the presence of tetrafluoroboric acid (Figure 5A). As a
result, trithioorthoester 7 was obtained in high yield, indicating that
the resulting acid facilitated the double cleavage of the C–F bonds
of 6a and the catalytic system enabled the selective C–F bond
thiolation free from the generation of tetrafluoroboric acid.[14]
Cleavage of the C–S bond of trityl sulfides 8 catalyzed by
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10.1002/chem.202001315
Chemistry - A European Journal
COMMUNICATION
ytterbium triflate was confirmed by the UV absorption spectra of
the resulting trityl cation (Figure 5B). Indeed, characteristic
absorptions of trityl cation at 406 and 429 nm were observed
when trityl sulfide 8a was treated with 10–100 mol % of ytterbium
triflate in dichloromethane and HFIP, while trace absorptions were
detected by the analysis without ytterbium triflate. Additionally, the
intensity of the absorptions was increased according to the
amount of ytterbium triflate. The results clearly indicated that the
trityl cation was generated by the treatment of trityl sulfide 8a with
ytterbium triflate.
In summary, we have developed catalytic single C–F bond
transformations of benzotrifluorides using the all-in-one reagents
for generation of trityl cation and nucleophiles. This
transformation allowed the preparation of
a
variety of
difluoromethylenes, avoiding the further C–F bond cleavage.
From the viewpoint of the significance of sulfides and triazoles as
bioactive compounds,[16] difluoromethylenes accessible by the C–
F transformations developed in this study would serve in the
pharmaceutical sciences.[17] Further studies to expand the scope
of the available difluoromethylene compounds and the
applications to the synthesis of analogs of bioactive molecules are
now in progress.
Based on the success of the selective C–F thiolation, we also
found the Yb(OTf)3-catalyzed defluoroazidation using trityl azide
(16) (Figure 6). For instance, treatment of 1a with 16 in the
presence of 20 mol % of ytterbium triflate in dichloromethane and
HFIP successfully provided difluorobenzyl azide 17a (Figure 6A).
Methoxy-substituted difluorobenzyl azide 17b was also prepared
under the conditions. When using a benzotrifluoride bearing a 4-
(trifluoromethyl)phenyl group, the C–F bond azidation selectively
took place at the trifluoromethyl group adjacent to the hydrosilyl
group to afford desired azide 17c. The copper-catalyzed azide–
alkyne cycloaddition (CuAAC) between α,α-difluorobenzyl azide
17b and 17α-ethynylestradiol (18) efficiently proceeded to furnish
1,2,3-triazole 19 quantitatively, leaving a variety of functional
groups intact. Considering the significance of the emerging click
chemistry in medicinal chemistry and chemical biology, the
selective C–F azidation would serve to synthesize a wide range
of 1,2,3-triazoles bearing a difluoromethylene group by the
CuAAC reaction (Figure 6B).[15]
Acknowledgements
This work was supported by JSPS KAKENHI Grant Numbers
JP19K05451 (C; S.Y.), JP18H02104 (B; T.H.), and JP18H04386
(Middle Molecular Strategy; T.H.); the Naito Foundation (S.Y.);
the Japan Agency for Medical Research and Development
(AMED) under Grant Numbers JP19am0101098 (Platform Project
for Supporting Drug Discovery and Life Science Research,
BINDS); and the Cooperative Research Project of Research
Center for Biomedical Engineering.
Keywords: C–F activation • fluorine • sulfide • azide • Lewis acid
[1]
(a) S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev.
2008, 37, 320. (b) E. P. Gillis, K. J. Eastman, M. D. Hill, D. J. Donnelly,
N. A. Meanwell, J. Med. Chem. 2015, 58, 8315. (c) X. Pan, H. Xia, J. Wu,
Org. Chem. Front. 2016, 3, 1163. (d) J. Rong, C. Ni, J. Hu, Asian J. Org.
Chem. 2017, 6, 139. (e) W. Zhang, Y. Wang, Tetrahedron Lett. 2018, 59,
1301. (f) E. Carbonnel, T. Poisson, P. Jubault, X. Pannecoucke, T.
Besset, Front. Chem. 2019, 7, 111.
A
Ph3CN3
16
(2.0 equiv)
Yb(OTf)3
(20 mol %)
F
F
CF3
N3
H
F
[2]
[3]
(a) F. Jaroschik, Chem. Eur. J. 2018, 24, 14572. (b) J.-D. Hamel, J.-F.
Paquin, Chem. Commun. 2018, 54, 10224.
CH2Cl2, HFIP
(1/1)
0 °C, 10 min
Si
Si
R
R
Ph Ph
Ph Ph
Selected recent examples: (a) K. Fuchibe, T. Akiyama, J. Am. Chem.
Soc. 2006, 128, 1434. (b) C. Douvris, O. V. Ozerov, Science 2008, 321,
1188. (c) J. Terao, M. Nakamura, N. Kambe, Chem. Comm. 2009, 6011.
(d) T. Stahl, H. F. T. Klare, M. Oestreich, J. Am. Chem. Soc. 2013, 135,
1248. (e) R. Doi, M. Ohashi, S. Ogoshi, Angew. Chem., Int. Ed. 2016, 55,
341; Angew. Chem. 2016, 128, 349. (f) K. Fuchibe, R. Oki, H. Hatta, J.
Ichikawa, Chem. Eur. J. 2018, 24, 17932. (g) H. Zeng, C. Zhu, H. Jiang,
Org. Lett. 2019, 21, 1130. (h) L. Tang, Z.-Y. Liu, W. She, C. Feng, Chem.
Sci. 2019, 10, 8701.
1
17
F3C
F
F
F F
F
F
MeO
N3
N3
N3
F
F
F
Si
Ph Ph
17a
62%
Si
Si
Ph Ph
Ph Ph
17b
68%
17c
66%
OH
B
H
H
[4]
For successful transformations of
a
single C–F bond of
trifluoromethylarenes, see: (a) D. Ferraris, C. Cox, R. Anand, T. Lectka,
J. Am. Chem. Soc. 1997, 119, 4319. (b) H. Amii, Y. Hatamoto, M. Seo,
K. Uneyama, J. Org. Chem. 2001, 66, 7216. (c) H. Dang, A. M. Whittaker,
G. Lalic, Chem. Sci. 2016, 7, 505. (d) I. Mallov, A. J. Ruddy, H. Zhu, S.
Grimme, D. W. Stephan, Chem. Eur. J. 2017, 23, 17692. (e) S. B. Munoz,
C. Ni, Z. Zhang, F. Wang, N. Shao, T. Mathew, G. A. Olah, G. K. S.
Prakash, Eur. J. Org. Chem. 2017, 2322. (f) K. Chen, N. Berg, R.
Gschwind, B. König, J. Am. Chem. Soc. 2017, 139, 18444. (g) H. Wang,
N. T. Jui, J. Am. Chem. Soc. 2018, 140, 163. (h) D. B. Vogt, C. P. Seath,
H. Wang, N. T. Jui, J. Am. Chem. Soc. 2019, 141, 13203. (i) C. Luo, J.
S. Bandar, J. Am. Chem. Soc. 2019, 141, 14120. (j) D. Mandal, R. Gupta,
A. K. Jaiswal, R. D. Young, J. Am. Chem. Soc. 2020, 142, 2572.
S. Yoshida, K. Shimomori, Y. Kim, T. Hosoya, Angew. Chem., Int. Ed.
2016, 55, 10406; Angew. Chem. 2016, 128, 10562.
H
OH
F
F
18
Me
HO
MeO
H
H
cat. Cu
N3
F
F
F
H
MeO
CH2Cl2, rt
Si
Ph Ph
19
quant.
N
Me
HO
N
N
17b
Si = Si(F)Ph2
Si
Figure 6. C–F azidation and further transformation. (A) C–F azidation of various
benzotrifluorides 1. (B) Derivatization through the copper-catalyzed azide–
alkyne cycloaddition.
[5]
[6]
When a base such as triethylamine was added in the reaction between
1a and 5, the desired sulfide 6a was not obtained.
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10.1002/chem.202001315
Chemistry - A European Journal
COMMUNICATION
[7]
[8]
[9]
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10.1002/chem.202001315
Chemistry - A European Journal
COMMUNICATION
COMMUNICATION
Y. Kim, K. Kanemoto, K. Shimomori, T.
Hosoya, S. Yoshida*
Page No. – Page No.
Catalytic Functionalization of a Single
C–F Bond of Trifluoromethylarenes
Assisted by an ortho-Silyl Group
Using a Trityl-Based All-in-One
Reagent with Ytterbium Triflate
Catalyst
Catalytic thiolation and azidation of a single C–F bond of trifluoromethylarenes
were achieved assisted by an ortho-silyl group with an all-in-one reagent for
generation of a trityl cation and nucleophile. The reactions catalyzed by ytterbium
triflate efficiently afforded a wide variety of difluoromethylenes avoiding the further
C–F bond cleavage, by virtue of the mild conditions without the generation of a
Brønsted acid.
This article is protected by copyright. All rights reserved.