Ruthenium-Catalyzed Site-Selective Trifluoromethylations and (Per)Fluoroalkylations of Anilines and Indoles

Article abstract of DOI:10.1002/chem.202001439

Introducing (per)fluoroalkyl groups into arenes continues to be an interesting, but challenging area in organofluorine chemistry. We herein report an ortho-selective C?H perfluoroalkylation including trifluoromethylations of anilines and indoles without the need of protecting groups using R_fI and R_fBr as commercially available reagents. The availability and price of the starting materials and the inherent selectivity make this novel methodology attractive for the synthesis of diverse (per)fluoroalkylated building blocks, for example, for bioactive compounds and materials.

Full text of DOI:10.1002/chem.202001439

A Journal of
Accepted Article
Title: Ruthenium-Catalyzed Site-Selective Trifluoromethylations and
(Per)Fluoroalkylations of Anilines and Indoles
Authors: Yang Li, Helfried Neumann, and Matthias Beller
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10.1002/chem.202001439
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Ruthenium-Catalyzed Site-Selective Trifluoromethylations and
(Per)Fluoroalkylations of Anilines and Indoles
Yang Li,[a b] Helfried Neumann,[a] and Matthias Beller*[a]
Abstract: Introducing (per)fluoroalkyl groups into arenes continues to
be an interesting, but challenging area in organofluorine chemistry.
We herein report a novel ortho-selective C-H perfluoroalkylation
including trifluoromethylations of anilines and indoles without the need
of protecting groups using RfI and RfBr as commercially available
reagents. The availability and price of the starting materials as well as
the inherent selectivity make this novel methodology attractive for the
synthesis of diverse (per)fluoroalkylated building blocks, e.g. for bio-
active compounds and materials.
knowledge, there have been no examples reported, which allow
introducing Rf groups with high site selectivity.
The
incorporation of (per)fluoroalkyl
moieties
into
(hetero)arenes has been demonstrated to significantly improve
their physical and biological properties for various applications.[1,2]
Hence, in recent years there is an increasing interest to prepare
such molecules by thermal[3, 4] and photochemical reactions,[5-7]
as well as others.[8-11] Despite these notable achievements, still
more practical and convenient methodologies are lacking and
there is a need using sophisticated reagents and/or tedious
purification due to selectivity problems. Indeed, regio- and
chemoselective functionalizations are of crucial importance,
because isolation of the resulting pure fluorinated isomers is often
very difficult. To avoid these problems, synthetic methods have
been developed for the synthesis of perfluoroalkyl arenes starting
from the corresponding aryl halides.10 However, the direct
preparation of the desired compounds from arenes via C-H
functionalization would be more desirable due to their availability
and process step economy.
Scheme 1. Selected methods for introducing trifluoromethyl and perfluoroalkyl
groups into arenes.
Recently, our group reported platinum-, nickel- and cobalt-
based catalysts for such reactions. However, in no case the
regioselectivity problem could be resolved. Hence, we continued
to search for more suitable transition metal catalysts. Following
this strategy, we used the reaction of 4-methoxyaniline (1a) and
n-C4F9I (2a) as a model system. In an initial screening of catalysts,
ruthenium carbene complexes revealed to be active. In general,
5 mol% of the catalyst and 2.0 equiv. of base (to trap HX) were
used in organic solvents at 100 °C for 12 h. As shown in Table 1,
optimization of reaction conditions, including pre-catalysts, bases,
and solvents gave the desired product 4-methoxy-2-
(perfluorobutyl)-aniline (3a) in >80% yield. 19F NMR investigations
after the reaction clearly demonstrated that only the mono-
substituted aniline 3a is formed. However, in the presence of an
excess of 2a, tiny amounts (<5%) of double perfluoroalkylation
products can be formed.
Among the different perfluoroalkylation reagents, especially the
corresponding halides RfX constitute valuable substrates. Since
the original work by Fuchikami and Ojima using perfluoroalkyl
halides in the presence of copper bronze,[12] several transition
metal-catalyzed perfluoroalkylations of arenes have been
reported.[13-15] However, in general products are obtained as
mixtures, which were often not even isolated and purified. In this
respect, the recent work of Zhao and co-workers is noteworthy,
who reported a para-selective perfluoroalkylation of anilides in the
presence of Mo(CO)6 as catalyst.[16]
18]
Based on our interest in perfluoroalkylation reactions,[17,
herein we present the first general and practical methodology for
highly ortho-selective, direct C-H perfluoroalkylation of anilines
under mild reaction conditions (Scheme 1). To the best of our
Among the different ruthenium salts and complexes applied, a
variety of defined metathesis catalysts proved to be effective for
this transformation. In line with this observation, adding 1,3-
bis(2,6-diisopropylphenyl)-imidazolium bromide as NHC carbene
ligand to simple ruthenium trichloride led to a reasonable active
catalyst system (Table 1, entries 8-9). Nevertheless,
commercially available Ru-1 provided the highest product yield.
Thus, in the presence of this precursor the influences of base
(Table 1, entries 10-14) and solvents (Table 1, entries 15-18)
including THF, MeCN, MePh and DMF were studied. Best results
(86% of 3a) were obtained using K2CO3 in 1,4-dioxane with an
increased amount of 2a (1.3 mmol; Table 1, entry 19).
[a]
[b]
Prof. Dr. Y. Li, Dr. H. Neumann, Prof. Dr. M. Beller
Leibniz-Institut für Katalyse e.V., Rostock
Albert-Einstein-Straße 29a, 18059 Rostock (Germany)
E-mail: Matthias.Beller@catalysis.de
Prof. Dr. Y. Li
School of Environmental and Chemical Engineering, Xi’an
Polytechnic University
No.19 Jinhua South Road, 710048, Xi’an (China)
Supporting information for this article is given via a link at the end of
the document.
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Obviously, the stoichiometry of the perfluoroalkylation reagent
and the choice of base (Table 1, entries 10-11) have the major
influence on the efficiency of this reaction. Thus, a control
known for several ruthenium complexes.19 The excellent
regioselectivity observed in the model reaction should be a result
of the coordination of aniline to the metal center, which
determines preferential formation of the ortho-perfluoroalkylated
product 2a. To understand this selectivity and the underlying
reaction mechanism, several control experiments were carried
out under standard conditions (see SI, Table S1). In contrast to
aniline, phenol and anisole do not react under identical conditions,
which highlights the importance of the amino group for this
transformation.
.
experiment using simple RuCl3 H2O (5% mol) in the presence of
the carbene ligand (10 mol%) and K2CO3 as base was performed
using 1.3 equiv. of RfI. Indeed, the desired product 3a is obtained
in 73% yield (Table 1, entry 20). As expected without the metal
catalyst, the background reaction occurred only to a negligible
extent (Table 1, entry 21).
Table 1. Ru-catalyzed perfluoroalkylation of 4-methoxyaniline. [a]
Entry
Catalyst
Base
Solvent
Yield
(%) [b]
6
1
2
RuCl3 •3H2O
[RuCl2(p-
Cymene)]2
Ru-1
NaHCO3
NaHCO3
1,4-dioxane
1,4-dioxane
19
3
4
5
6
7
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
KHCO3
K2CO3
Na2CO3
Na2HPO4
Et3N
K2CO3
K2CO3
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
THF
45
36
31
26
19
38
41
51
72
58
16
22
49
23
35
14
83 (79)e
73
Ru-2
Ru-3
Ru-4
Ru-5
8[c]
9[c]
10
11
12
13
14
15
16
17
18
19[d]
20
21
Ru-5
RuCl3 •3H2O
Ru-1
Ru-1
Ru-1
Ru-1
Ru-1
Ru-1
Ru-1
Ru-1
Ru-1
MeCN
MePh
DMF
K2CO3
K2CO3
K2CO3
K2CO3
Ru-1
1,4-dioxane
1,4-dioxane
1,4-dioxane
RuCl3 •3H2O
free
K2CO3
8
[a] Reaction conditions: 1a (1.0 mmol), 2 (1.2 mmol), catalyst (5 mol%), base
(2.0 mmol), solvent (2.0 mL), 100 oC, 12 h. [b] Determined by 19F NMR
analysis using (trifluoromethoxy)benzene as internal standard. [c] 7 mol%
NHC ligand was added. [d] 2 (1.3 mmol). [e] Isolated yield in brackets.
Structure of catalysts and ligands:
[a] Reaction conditions: aniline (1.0 mmol), n-C4F9I (1.3 mmol), Ru-1 (5 mol%),
K2CO3 (2.0 eq). and 1,4-dioxane (2.0 mL), 100 oC, 12 h. [b] Isolated yield. [c] n-
C4F9Br (1.5 mmol) used for the reaction in brackets.
Regarding the mechanism, we propose the initial formation
of a perfluoroalkyl radical via a metal-catalyzed single electron
transfer process (SET) is occurring. Such SET processes are well
Scheme 2. Selective Ru-catalyzed perfluoroalkylation of anilines.
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In these latter cases the starting materials were retained in >98%.
Interestingly, the use of N,N-dimethylaniline led to a mixture of
perfluoroalkylated products, which could not be isolated in pure
form due to the similar physical properties of the regioisomers. To
isolate and/or identify any organometallic intermediate of the
catalytic cycle, the complex Ru-1 (0.1 mmol) was mixed with n-
To demonstrate the synthetic utility of our protocol on multi-g-
scale, the reaction of 4-methoxyaniline (10.0 mmol) with n-C4F9I
(13.0 mmol) was performed and gave the corresponding product
only in slightly lower yield (Scheme 3).
o
C4F9I (0.1 mmol) in 1,4-dioxane (1 mL) and stirred at 100 C for
several hours. Analysis of the crude mixture by 19F NMR revealed
unfortunately no obvious changes (see SI for more details).
Next, we were interested to explore the substrate scope of
anilines of this novel methodology. Thus, reactions of various
substituted anilines with n-C4F9I were examined. Based on the
optimization vide supra, the following conditions were applied:1.3
equiv. of 2, 5 mol% Ru-1, 2.0 equiv. of K2CO3 in 1,4-dioxane (2.0
mL) at 100 °C for 12 h under N2. Initially, we focused on the
functional group tolerance of the catalyst. For this purpose,
several electron-rich para-substituted anilines (-OMe, -SMe, -OEt,
OPh, -t-Bu, -OH) were reacted with n-C4F9I to afford smoothly the
corresponding products in good to excellent yields (Scheme 2, 3a-
3i). Apart from n-C4F9I, also using n-C4F9Br gave the target
compounds, albeit in somewhat lower yields. In addition, anilines
with electron-withdrawing groups (-Cl, -Br, -Ac) provided the
perfluoroalkylated products in moderate to good yields. Notably,
halide and ketone substituents on the aniline ring remained
untouched demonstrating the excellent chemo-selectivity of the
system. In general, the reactivity of the latter substrates is lower
than those of electron-rich anilines. Next, we investigated
reactions of aniline, 1-naphthylamine, 1,3-disubstituted, and
1,3,5-trisubstituted anilines. In all these cases, the control of
regioselectivity is significantly more challenging. Nevertheless,
using parent aniline 1j as substrate perfluoroalkylation occurred
specifically in the ortho-position giving 3j in 73% isolated yield.
Other isomers (<5%) could not be observed. Next, anilines with
meta-substitution pattern were tested in this process. Again, both
electron-rich (-OMe) and -withdrawing (-CN, -NO2) substrates
expressed good activities for the perfluoroalkylation reaction and
only one regioisomer was obtained (Scheme 2, 3l-3n). In addition,
anilines with two substituents, such as 3,5-dimethyl and 3,5-
dimethoxy can be conveniently employed in this reaction with high
site-selectivity (Scheme 2, 3o, 3p). Finally, when using 2,3-
dihydrobenzo[b][1,4]dioxin-6-amine 1q we obtained two ortho-
substituted regioisomers in 49 and 22% yield (Scheme 2, 3q, 3q’),
respectively. Similarly to the model system, also for these
substrates n-C4F9Br could be successfully used as perfluoroalkyl
source and the ortho-perfluoroalkylated anilines were obtained in
moderate to good yields (Scheme 2, 3k, 3l, 3p). In all these cases
the perfluoroalkylated products are easily obtained in pure form
due to the high selectivity of the process.
Scheme 4. Ru-catalyzed perfluoroalkylation of indoles.
Indoles are an important class of heterocyclic compounds.
Indeed, numerous natural products contain this electron-rich
scaffold. Thus, we explored the reactivity of 4a-c with 2a in this
process. We were pleasured to find that selective
perfluorobutylation occurred selectively at the C-2 position with or
without N protection (Scheme 4).
[a] Reaction conditions: aniline (1.0 mmol), n-C4F9I (3.0 mmol), Ru-1 (5 mol%),
K2CO3 (2.0 eq.) and 1,4-dioxane (2.0 mL), 100 oC, 12 h. [b] Isolated yield.
Scheme 5. Ru-catalyzed double-perfluoroalkylation of anilines.
During the initial optimization of this procedure, we found small
amounts of double perfluoroalkylation. Following this original
observation, we investigated the reaction of aniline 1a with a
larger excess of 2a. Surprisingly, the di-ortho-perfluoroalkylated
aniline 5a is obtained in 55% isolated yield using 3.0 equiv. of 2a.
As shown in Scheme 5, other anilines 1a-d, q presented similar
reactivity and gave the desired ortho/ortho-disubstituted
compounds in 53-66% isolated yield. It should be noted that such
2,6-difuctionalized anilines are otherwise very difficult to access.
Scheme 3. Gram-scale synthesis of 3a.
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Regarding the various perfluoroalkylation reactions, certainly
trifluoromethylation is the most important transformation,
especially for the synthesis of new bio-active compounds. Hence,
diverse state-of-the-art reagents for laboratory scale synthesis
including Umemoto´s,20 Togni´s,21 Langlois´,22 and Ruppert-
commercially available pre-catalyst Ru-1 various meta- and para-
substituted anilines, including mono- and disubstituted ones, gave
the corresponding products without the need for protecting groups
in high purity. The availability of the starting materials and the high
selectivity make the process attractive for the synthesis of all
kinds of perfluoroalkyl-substituted anilines, including trifluormethyl
derivatives.
23
Prakash´s reagent23 as well as CuCF3 were developed in the
past decades. However, due to their price and availability, the use
of these reagents on >kg-scale is highly problematic. In contrast,
CF3Br is available on multi-100 kg-scale and less expensive
compared to the above-mentioned reagents. Nevertheless, we
want to make clear that also this reagent has ozone depleting
properties, which are forbidden by the Montreal protocol. Hence,
appropriate safety measures should be taken. As shown in
Scheme 6, CF3Br allows for ortho-selective functionalization of
para-substituted anilines with acceptable yields (Scheme 6, 6a-
6f). Similarly, using Ru-1 other perfluoroalkyl iodides (C2F5I, C3F7I,
C6F13I, C8F17I, and C10F21I) reacted well with 4-methoxyaniline
(1a) to give the corresponding target compounds in moderate to
good yields and excellent selectivities (Scheme 6, 6g, 6h, 6i, 6j,
6k, 6l). In the context of building blocks for bio-active compounds,
it is worth mentioning that heptafluoroisopropyl iodide 2i afforded
the corresponding product in 63% yield (Scheme 6, 6i).
Experimental Section
Perfluoroalkylation of anilines with n-C4F9I: aniline (1.0 mmol), n-C4F9I (1.3
mmol), Ru-1 (5 mol%), K2CO3 (2.0 eq). and 1,4-dioxane (2.0 mL) were
added to a reaction tube. Then, the tube was degassed with argon three
times and heated at 100 °C for 12 h. After cooling to room temperature,
the solvent was removed under vacuum conditions, and the products were
purified through silica gel chromatography by using hexane and ethyl
acetate as the eluents.
Acknowledgements
We are grateful for the financial support from the BMBF and the
State of Mecklenburg-Western Pomerania, Germany. Y. L. would
like to thank the Chinese Scholarship Council, China for funding.
Keywords: anilines • ortho • perfluoroalkylation • Ru catalyst •
site-selective
[1] a) P. Kirsch, In Modern Fluoroorganic Chemistry, Wiley-VCH, Weinheim,
Germany, 1996.
b I. Ojima, Fluorine in Medicinal Chemistry and
Chemical Biology, Wiley-Blackwell: Chichester, UK; 2009.
[2] a) C. N. Neumann, T. Ritter, Angew. Chem. Int. Ed. 2015, 54, 3216-3218;
Angew. Chem. 2015, 127. 3261-3263; b) J. A. Ma, D. Cahard, Chem.
Rev. 2004, 104, 6119-6119.
[3]
a) A. B. Cowell, C. Tamborski, J. Fluorine Chem. 1981, 17, 345-356; b)
L. K. San, E. V. Bukovsky, I. V. Kuvychko, A. A. Popov, S. H. Strauss, O.
V. Boltalina, Chem. Eur. J. 2014, 20, 4373-4379.
[4]
a) Y. Macé, E. Magnier, Eur. J. Org. Chem. 2012, 2479-2494; b) T.
Kitazume, T. Ikeya, J. Org. Chem. 1988, 53, 2349-2350; c) D. Y.
Mikhaylov, T. V. Gryaznova, Y. G. Budnikova, O. G. Sinyashin, Russ.
Chem. Bull. 2010, 59, 1918-1920; d) M. Médebielle, S. Fujii, K. Kato,
Tetrahedron 2000, 56, 2655-2664.
[5] a) D. -F. Jiang, C. Liu, Y. Guo, J. -C. Xiao, Q. -Y. Chen, Eur. J. Org. Chem.
2014, 28, 6303-6309; b) L. Cui, Y. Matusaki, N. Tada, T. Miura, B. Uno
and A. Itoh, Adv. Synth. Catal. 2013, 355, 2203-2207; c) M. Nappi, G.
Bergonzini and P. Melchiorre, Angew. Chem. Int. Ed. 2014, 53, 4921-
4925; Angew. Chem. 2014, 126, 5021-5025; d) N. J. Straathof, H. P.
Gemoets, X. Wang, J. C. Schouten, V. Hessel, T. Noel, ChemSusChem
2014, 7, 1612-1617; e) S. Barata-Vallejo, D. E. Yerien, A. Postigo, Eur.
J.Org. Chem. 2015, 7869-7875; f) C. -Y. He, J. -W. Gu, X. Zhang,
Tetrahedron Lett. 2017, 58, 3939-3941.
[a] Reaction conditions: 1 (1.0 mmol), RfX (1.3 mmol), Ru-1 (5 mol%), K2CO3
(2.0 eq). and 1,4-dioxane (2.0 mL), 100 oC 12 h. [b] 4 mL solution of CF3Br in
1,4-dioxane (0.06 mol/L) was used, and yield based on CF3Br.
[6]
a) J. W. Beatty, J. J. Douglas, R. Miller, R. C. McAtee, K. P. Cole, C. R.
J. Stephenson, Chem 2016, 1, 456-472; b) Y. Wang, J. Wang, G. X. Li,
G. He, G. Chen, Org. Lett. 2017, 19, 1442-1445; c) E. Torti, S. Protti, M.
Fagnoni, Chem. Commun. 2018, 54, 4144-4147; d) Y. Ouyang, X. H. Xu,
F. L. Qing, Angew. Chem. Int. Ed. 2018, 57, 6926-6929; Angew. Chem.
2018, 130, 7042-7045; e) D. E. Yerien, M. V. Cooke, M. C. García Vior,
S. Barata-Vallejo, A. Postigo, Org. Biomol. Chem. 2019, 17, 3741.
a) D. E. Yerien, R. Conde, S. Barata-Vallejo, B. Camps, B. Lantaño, A.
Postigo, RSC Adv. 2017, 7, 266-274; b) P. B. Arockiam, L. Guillemard,
J. Wencel-Delord, Adv. Synth. Catal. 2017, 359, 2571-2579; c) I. Ghosh,
Scheme 6. Substrate scope of trifluoromethyl and perfluoroalkyl halides.
In conclusion, we have developed an efficient and practical
ortho-selective mono- and di(per)fluoroalkylation methodology of
free anilines and indoles. In the presence of the stable and
[7]
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J. Khamrai, A. Savateev, N. Shlapakov, M. Antonietti, B. König, Science
2019, 365, 360-366.
d) J. Zheng, Z. Deng, Y. Zhang, S. Cui, Adv. Synth. Catal. 2016, 358,
746-751; e) L. -Z. Yu, Q. Xu, X. -Y. Tang, M. Shi, ACS Catal. 2016, 6,
526-531; f) N. Y. Yang, Z. L. Li, L. Ye, B. Tan, X. Y. Liu, Chem. Commun.
2016, 52, 9052-9055; g) K. Shen, Q. Wang, Org. Chem. Front. 2016, 3,
222-226; h) K. N. Lee, Z. Lei, C. A. Morales-Rivera, P. Liu, M. Y. Ngai,
Org. Biomol. Chem. 2016, 14, 5599-5605; i) Y. Kuninobu, M. Nishi, M.
Kanai, Org. Biomol. Chem. 2016, 14, 8092-8100; j) D. Katayev, J.
Vaclavik, F. Bruning, B. Commare, A. Togni, Chem. Commun. 2016, 52,
4049-4052; k) Y. L. Ji, J. J. Luo, J. H. Lin, J. C. Xiao, Y. C. Gu, Org. Lett.
2016, 18, 1000-1003.
[8]
a) N. Kamigata, T. Ohtsuka, T. Fukushima, M. Yoshida, T. Shimizu, J.
Chem. Soc. Perkin Trans. 1 1994, 1339-1346; b) N. Kamigata, T.
Ohtsuka, M. Yoshida, T. Shimizu, Synth. Commun. 1994, 24, 2049-2055;
c) N. Kamigata, T. Ohtsuka, T. Shimizu, Phosphorus Sulfur Silicon Relat.
Elem. 1994, 95-96, 491-492; c) R. N. Loy, M. S. Sanford, Org. Lett. 2011,
13, 2548-2551; d) X. -T. Huang, Z. -Y. Long, Q. -Y. Chen, J. Fluorine
Chem. 2001, 111, 107-113; e) C. Wakselman, M. Tordeux, J. Chem. Soc.
Chem. Commun. 1987, 22, 1701-1703; f) K. Natte, R. V. Jagadeesh, L.
He, J. Rabeah, J. Chen, C. Taeschler, S. Ellinger, F. Zaragoza, H.
Neumann, A. Brückner, M, Beller, Angew. Chem. Ed. Int. 2016, 55, 2782-
2786.
[21] a) Q. Y. Lin, X. H. Xu, F. L. Qing, J. Org. Chem. 2014, 79, 10434-10446;
b) C. Zhang, Adv. Synth. Catal. 2014, 356, 2895-2906; c) A. Maji, A.
Hazra, D. Maiti, Org. Lett. 2014, 16, 4524-4527; d) L. Li, X. Mu, W. Liu,
Y. Wang, Z. Mi, C. J. Li, J. Am. Chem. Soc. 2016, 138, 5809-5812; e) Q.
Lefebvre, N. Hoffmann, M. Rueping, Chem. Commun. 2016, 52, 2493-
2496; f) X. -H. Cao, X. Pan, P. -J. Zhou, J. -P. Zou, O. T. Asekun, Chem.
Commun. 2014, 50, 3359; g) Y. Ji, T. Brueckl, R. D. Baxter, Y. Fujiwara,
I. B. Seiple, S. Su, D. G. Blackmond, P. S. Baran, Proc. Natl. Acad. Sci.
USA, 2011, 108, 14411-14415.
[9]
a) I. Popov, S. Lindeman, O. Daugulis, J. Am. Chem. Soc. 2011, 133,
9286-9289; b) H. Morimoto, T. Tsubogo, N. D. Litvinas, J. F. Hartwig,
Angew. Chem. Int. Ed. 2011, 50, 3793-3798; Angew. Chem. 2011, 123,
3877-3882; c) M. G. Mormino, P. S. J. F. Hartwig, Org. Lett. 2014, 16,
1744-1747.
[10]
E. J. Cho, T. D. Senecal, T. Kinzel, Y. Zhang, D. A. Watson, S. L.
Buchwald, Science 2010, 328, 1679-1681.
[22] a) M. Nagase, Y. Kuninobu, M. Kanai, J. Am. Chem. Soc. 2016, 138,
6103-6106; b) R. P. Singh, J. n. M. Shreeve, Tetrahedron 2000, 56,
7613-7632; c) B. Bayarmagnai, C. Matheis, E. Risto, L. J. Gooβen, Adv.
Synth. Catal. 2014, 356, 2343-2348; d) H. Serizawa, K. Aikawa, K.
Mikami, Chem. Eur. J. 2013, 19, 17692-17697; e) Y. Li, F. Liang, Q. Li,
Y. C. Xu, Q. R. Wang, L. Jiang, Org. Lett. 2011, 13, 6082-6085; f) G. K.
S. Prakash, A. K. Yudin, Chem. Rev. 1997, 97, 757-786.
[11] a) D. Leifert, D. G. Artiukhin, J. Neugebauer, A. Galstyan, C. A. Strassert,
A. Studer, Chem. Commun. 2016, 52, 5997-6000; b) T. Shirai, M. Kanai
and Y. Kuninobu, Org. Lett. 2018, 20, 1593-1596; c) L. Wu, F. Wang, P.
Chen, G. Liu, J. Am. Chem. Soc. 2019, 141, 1887-1892.
[12] T. Fuchikami and I. Ojima, J. Fluorine Chem. 1983, 22, 541-556.
[13]
a) X. Bao, L. Liu, J. Li and S. Fan, J. Org. Chem. 2018, 83, 463-468;
b) S. Zhang, H. Neumann, M. Beller, Chem. Eur. J. 2018, 24, 67-70; c)
K. Aikawa, Y. Nakamura, Y. Yokota, W. Toya and K. Mikami, Chem. Eur.
J. 2015, 21, 91-100; d) T. Knauber, F. Arikan, G. V. Röschenthaler and
L. J. Gooβen, Chem. Eur. J. 2011, 17, 2689-2697; e) M. Moreno-Mañas,
R. Pleixats, S. Villarroya, Synlett 1999, 12, 1996-1998.
[23] a) P. Novák, A. Lishchynskyi, V. V. Grushin, Angew. Chem. Int. Ed. 2012,
51, 7767-7770; Angew. Chem. 2012, 124, 7887-7890; b) A. Zanardi, M.
A. Novikov, E. Martin, J. Benet-Buchholz, V. V. Grushin, J. Am. Chem.
Soc. 2011, 133, 20901-20913.
[14] a) L. Strekowski, H. Lee, S. -Y. Lin, A. Cyarny, D. V. Derveer, J. Org.
Chem. 2000, 65, 7703-7706; b) K. A. McReynolds, R. S. Lewis, L. K. G.
Ackerman, G. G. Dubinina, W.W.Brennessel, D. A. Vicic, J. Fluorine
Chem. 2010, 131, 1108-1112; c) M. Oishi, H. Kondo and H. Amii, Chem.
Commun. 2009, 1909-1911; d) J. Monteiro, P. F. Carneiro, P. Elsner, D.
M. Roberge, P. G. M. Wuts, K. C. Kurjan, B. Gutmann, C. O. Kappe,
Chem. Eur. J. 2017, 23, 176-186.
[15] a) A. Hafner, A. Bihlmeier, M. Nieger, W. Klopper, S. Bräse, J. Org. Chem.
2013, 78, 7938-7948; b) R. N. Loy, M. S. Sanford, Org. Lett, 2011, 13,
2548-2551; c) N. D. Litvinas, P. S. Fier, J. H. Hartwig, Angew. Chem. Int.
Ed. 2012, 51, 536-539; Angew. Chem. 2012, 124, 551-554.
[16] C. Yuan, P. Dai, X. Bao, Y. Zhao, Org. Lett. 2019, 21,6481-6484.
[17] L. He, K. Natte, J. Rabeah, C. Taeschler, H. Neumann, A. Brückner, M.
Beller, Angew. Chem. Int. Ed. 2015, 54, 4320-4324; Angew. Chem. 2015,
127, 4394-4398.
[18]
S. Zhang, N. Rotta-Loria, F. Weniger, J. Rabeah, H. Neumann, C.
Taeschler, M. Beller, Chem. Commun. 2019, 55, 6723-6726.
[19] T. Koike, M. Akita, Visible-Light-Induced Redox Reactions by Ruthenium
Photoredox Catalyst. Topics in Organometallic Chemistry. 2015, 48,
371-395.
[20]
a) J. Jacquet, S. Blanchard, E. Derat, M. Desage-El Murr and L.
Fensterbank, Chem. Sci. 2016, 7, 2030-2036; b) G. Dagousset, A.
Carboni, E. Magnier and G. Masson, Org. Lett. 2014, 16, 4340-4343; c)
W. An, N. Ha, H. M. Lee, Y. R. Malpani, D. -H. Lee, Y.-S. Jung and S. B.
Han, Adv. Synth. Catal. 2015, 357, 3949-3960; d) R. Tomita, Y. Yasu, T.
Koike and M. Akita, Beilstein J. Org. Chem. 2014, 10, 1099-1106.
[20] a) M. Fu, L. Chen, Y. Jiang, Z. -X. Jiang, Z. Yang, Org. Lett. 2016, 18,
348-351; b) Z. He, P. Tan, J. Hu, Org. Lett. 2016, 18, 72-75; c) S. P. Pitre,
C. D. McTiernan, J. C. Scaiano, Acc. Chem. Res. 2016, 49, 1320-1330;
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10.1002/chem.202001439
Chemistry - A European Journal
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Yang Li, Helfried, Neumann, Matthias
Beller*
Page No. – Page No.
Ruthenium-Catalyzed Site-Selective
Trifluoromethylations and
(Per)fluoroalkylation of Anilines and
indoles
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