Hydrotrifluoromethylthiolation of Unactivated Alkenes and Alkynes with Trifluoromethanesulfonic Anhydride through Deoxygenative Reduction and Photoredox Radical Processes

Article abstract of DOI:10.1002/anie.201911323

An ongoing challenge in trifluoromethylthiolation reactions is the use of less expensive and easily available trifluoromethylthio sources. Herein, we disclose an unprecedented usage of trifluoromethanesulfonic anhydride (Tf₂O) as a radical trifluoromethylthiolating reagent. Hydrotrifluoromethylthiolation of unactivated alkenes and alkynes with Tf₂O in the presence of PMePh₂ and H₂O under visible-light photoredox catalysis gave the addition products. The trifluoromethylthio radical (^.SCF₃) was first formed from Tf₂O through a photoredox radical processes and deoxygenative reduction of PMePh₂, and H₂O serves as the H-atom donor for the hydrotrifluoromethylthiolation reaction. This reaction provides a new strategy for radical trifluoromethylthiolation.

Full text of DOI:10.1002/anie.201911323

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Hydrotrifluoromethylthiolation of Unactivated Alkenes
and Alkynes with Trifluoromethanesulfonic Anhydride
through Deoxygenative Reduction and Photoredox Radical
Processes
Authors: Feng-Ling Qing, Yao Ouyang, and Xiu-Hua Xu
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201911323
Angew. Chem. 10.1002/ange.201911323
Link to VoR: http://dx.doi.org/10.1002/anie.201911323
http://dx.doi.org/10.1002/ange.201911323

10.1002/anie.201911323
Angewandte Chemie International Edition
COMMUNICATION
Hydrotrifluoromethylthiolation of Unactivated Alkenes and
Alkynes with Trifluoromethanesulfonic Anhydride through
Deoxygenative Reduction and Photoredox Radical Processes
Yao Ouyang, Xiu-Hua Xu, and Feng-Ling Qing*
Abstract: An ongoing challenge in trifluoromethylthiolation reaction
is the use of less expensive and easily available trifluoromethylthio
sources. Herein we disclose an unprecedented usage of
basis of this work, we envisioned that Tf2O might be used as the
less expensive and easily available trifluoromethylthio source by
the combination of deoxygenative reduction, nucleophilic
activation, and photoredox catalysis. As shown in Scheme 1b,
the deoxygenative reduction of Tf2O with phosphines (PR3)
would afford intermediate A (F3CSOTf),[8] which then reacted
trifluoromethanesulfonic
anhydride
(Tf2O)
as
radical
trifluoromethylthiolating reagent. The hydrotrifluoromethylthiolation of
unactivated alkenes and alkynes with Tf2O in the presence of
PMePh2 and H2O under visible-light photoredox catalysis gave the
addition products. The trifluoromethylthio radical (･SCF3) was firstly
formed from Tf2O through photoredox radical processes and
deoxygenative reduction of PMePh2, and H2O served as the H-atom
donor for the hydrotrifluoromethylthiolation reaction. This reaction
provided a new strategy for radical trifluoromethylthiolation.
with
PR3
to
give
the
corresponding
trifluoromethylthiophosphonium salts B.[8c] According to our
experiences on visible-light-induced fluoroalkylation with
fluoroalkylphosphonium salts,[12] the single-electron-transfer
(SET) reduction of intermediate B by excited photocatalyst (PC*)
to SCF3 radical should be feasible. If this approach is successful,
it will represent an unprecedented application of Tf2O as
trifluoromethylthiolating reagent.
The high lipophilicity and strong electron-withdrawing power of
trifluoromethylthio (SCF3) group have attracted great interest in
pharmaceutical and agrochemical designs.[1] Recently,
numerous methodologies have been developed for the
incorporation of a SCF3 group into organic skeletons.[2] The rapid
progress of this area is mostly due to the invention of a series of
easy-to-handle electrophilic trifluoromethylthiolating reagents.[3]
These reagents mainly include R2N-SCF3 reagents (i.e.,
trifluoromethanesulfenamide, N-SCF3-succinimide, N-SCF3-
phthalimide,
N-SCF3-saccharin),[4]
RO-SCF3
reagents
(trifluoromethanesulfenates),[5] and RSO2CF3 reagents (CF3SO2-
containing hypervalent iodonium ylide or diazo compound,[6]
CF3SO2Na,[7] CF3SO2Cl,[8] and CF3SO2NHNHBoc[9]). Among
these reagents, synthesis of R2N-SCF3 and RO-SCF3 reagents
from nucleophilic trifluoromethylthiolating or trifluoromethylating
reagents generally requires multi-step preparation. Normally,
RSO2CF3 reagents undergo intramolecular or intermolecular
deoxygenation to in situ generate the electrophilic species such
as CF3SOR’, CF3SCl, and CF3SSCF3 for trifluoromethylthiolation
of nucleophiles (Scheme 1a).
Very recently, we have found that trifluoromethanesulfonic
anhydride (Tf2O), a commonly used chemical and well-known as
electrophilic trifluoromethanesulfonylating reagent,[2e,10] was
used as an efficient radical trifluoromethylating reagent by
merging photoredox catalysis and pyridine activation.[11] On the
Scheme 1. Trifluoromethylthiolation with CF3SO2-containing reagents.
Hydrofunctionalization of alkenes is
a
fundamentally
important transformation in organic synthesis and medicinal
chemistry. Recently, this method has been extensively extended
to hydrotrifluoromethylation[13] and hydrodifluoroalkylation[14] of
alkenes for the preparation of fluoroalkylated alkanes. However,
the analogous hydrotrifluoromethylthiolation of alkenes is
significantly
less
developed,
despite
the
radical
[15b-i]
trifluoromethylthiolation of alkenes and alkynes with AgSCF3
or electrophilic trifluoromethylthiolating reagents[15j-l] has been
well investigated. In 1961, Harris and Stacey disclosed a
hydrotrifluoromethylthiolation of polyfluoroalkenes using toxic
and gaseous CF3SH (Scheme 2a).[16] Very recently, Shen and
Lu reported the Markovnikov hydrotrifluoromethylthiolation of
alkenes with electrophilic trifluoromethylthiolating reagents and
hydrogen radical sources (Scheme 2b).[17] As part of our ongoing
study on hydrofluoroalkylation reactions,[12a,13a,13i,14c-e] we
[a]
Y. Ouyang, Dr. X.-H. Xu, Prof. Dr. F.-L. Qing
Key Laboratory of Organofluorine Chemistry, Center for Excellence
in Molecular Synthesis, Shanghai Institute of Organic Chemistry,
University of Chinese Academy of Science, Chinese Academy of
Sciences, 345 Lingling Lu, Shanghai 200032, China
E-mail: flq@mail.sioc.ac.cn
[b]
Prof. Dr. F.-L. Qing
Key Laboratory of Science and Technology of Eco-Textiles, Ministry
of Education, College of Chemistry, Chemical Engineering and
Biotechnology, Donghua University, 2999 North Renmin Lu,
Shanghai 201620, China
demonstrate
herein
a
practical
anti-Markovnikov
hydrotrifluoromethylthiolation of alkenes with Tf2O through
deoxygenative reduction and photoredox radical processes
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201911323
Angewandte Chemie International Edition
COMMUNICATION
(Scheme 2c). This protocol is highlighted by the employment of
Tf2O and H2O as the SCF3 and H sources, respectively.
them, PMePh2 was optimal, affording 2a in 86% yield. Further
optimizing reaction conditions including adding an external base,
reducing the amount of PMePh2, and changing the ratio of Tf2O
to PMePh2 failed to improve the yield (see Supporting
Information). Notably, none of 2a was observed when CF3SO2Cl
was used as the SCF3 source (entry 12).
Scheme 2. Hydrotrifluoromethylthiolation of alkenes.
Table 1. Optimization of reaction conditions[a]
Entry
Phosphine
H source
Additive
Yield (%)[b]
1
PPh3
1,4-CHD
Et3SiH
HOAc
H2O
—
0
2
PPh3
—
trace
4
3
PPh3
—
4
PPh3
—
8
5
PPh3
H2O
n-Bu4NCl
n-Bu4NPF6
n-C12H25SO3Na
n-Bu4NPF6
n-Bu4NPF6
n-Bu4NPF6
n-Bu4NPF6
n-Bu4NPF6
34
77
62
0
6
PPh3
H2O
7
PPh3
H2O
8
PEt3
H2O
9
P(OEt)3
PMe2Ph
PMePh2
PMePh2
H2O
51
7
10
11
12[c]
H2O
H2O
86
0
H2O
[a] Reaction conditions: 1a (0.2 mmol), (CF3SO2)2O (0.6 mmol), Ir(dF-ppy)3
(0.003 mmol), phosphine (0.6 mmol), H source (0.4 mmol), additive (0.4 mmol),
DCE (2.0 mL), LEDs, N2, rt, 24 h. [b] Yields determined by 19F NMR
spectroscopy using trifluoromethoxybenzene as an internal standard. [c]
CF3SO2Cl (0.6 mmol).
Scheme 3. Substrate scope of hydrotrifluoromethylthiolation of unactivated
alkenes. Reaction conditions: 1 (0.5 mmol), (CF3SO2)2O (1.5 mmol), PMePh2
(1.5 mmol), Ir(dF-ppy)3 (0.0075 mol), n-Bu4NPF6 (1.0 mmol), H2O (1.0 mmol),
DCE (5.0 mL), LEDs, N2, rt, 24 h, isolated yields. [a] Diastereomeric ratio
determined by 19F NMR analysis of the crude reaction mixture.
We commenced our investigation with the reaction of but-3-
enylbenzene (1a) and Tf2O in the presence of Ir(dF-ppy)3, PPh3,
and different H sources under visible-light irradiation (Table 1).
The common hydrogen radical sources, such as 1,4-
cyclohexadiene (1,4-CHD) and Et3SiH, were ineffective for this
reaction (entries 1 and 2). In contrast, the desired product 2a
was detected in low yields in the presence of a proton source,
HOAc or H2O (entries 3 and 4). Thus H2O was used as the
hydrogen source. We observed white precipitates in the reaction
mixture and consequently decided to add phase-transfer catalyst
(PTC) to accelerate this reaction. To our delight, the yield was
significantly improved to 77% when n-Bu4NPF6 was added
(entry 6). Other PTCs including n-Bu4NCl and n-C12H25SO3Na
also promoted this reaction, albeit in low yields (entries 5 and 7).
Subsequently, different phosphines including PEt3, P(OEt)3,
PMe2Ph, and PMePh2 were examined (entries 8-11). Among
Under the optimized reaction conditions, the substrate scope
was scrutinized (Scheme 3). Reactions with nonfunctionalized
alkenes
(1a-d)
proceeded
smoothly
to
afford
hydrotrifluoromethylthiolated products in high yields. A variety of
synthetically useful functional groups, such as ester (1e), ether
(1f,g), sulfonate (1h), amide (1i), halogen (1k-m), cyano (1n),
and sulfonamide (1o), were well tolerated. Alkenes bearing
heterocycles including pyridine (1p) and furan (1q) were also
compatible, furnishing the corresponding products in reasonable
yields. Furthermore, 1,2-disubstituted alkene (1r) delivered the
desired product in moderate yield, whereas 1,1-disubstituted
alkenes and activated alkenes (such as styrenes, enol ethers
and enamines) were not suitable substrates.
This article is protected by copyright. All rights reserved.

10.1002/anie.201911323
Angewandte Chemie International Edition
COMMUNICATION
The hydrotrifluoromethylthiolation of alkynes was also
successful. As shown in Scheme 4, both terminal (3a-c) and
internal alkynes (3d,e) were transformed to the corresponding
vinyl trifluoromethyl thioethers in moderate yields as mixtures of
Z/E isomers. Notably, the hydrotrifluoromethylthiolation of
terminal alkynes with AgSCF3 has been reported by Cao and co-
of D2O (Scheme 5c). The exclusive formation of the deuterated
product [D]-2a unambiguously confirmed that water served as
the hydrogen source.
Based on the above experimental results and previously
reported works, a plausible reaction mechanism is depicted in
Scheme 6. Initially, the deoxygenative reduction of Tf2O (1.0
equiv) with PMePh2 (2.0 equiv) via several intermediates affords
F3CSOTf A,[8] which then undergoes nucleophilic attack by
PMePh2 (1.0 equiv) to furnish trifluoromethylthiophosphonium
intermediate B.[8c] It was noteworthy that 3.0 equiv. of PMePh2
and 1.0 equiv. of Tf2O should be required for the formation of
intermediate B, consequently, 2.0 equiv of O=PMePh2 should be
produced. But stoichiometric amount of Tf2O (3.0 euquiv) and
PMePh2 (3.0 equiv) was suitable for the reaction and the peak
area of O=PMePh2 in 31P NMR of the reaction mixture was
significantly smaller than that of intermediate B, this was due to
workers.[18]
hydrotrifluoromethylthiolation of internal alkynes.
Our
protocol
represents
the
first
the
formation
of
[Ph2MePOTf]+[OTf]-
and
[Ph2MePOPPh2Me]2+[OTf]-2 from the reaction of the in situ
generated O=PMePh2 with Tf2O (See Supporting Information).[20]
On the other hand, the irradiation of visible light excites IrIII(dF-
ppy)3 to IrIII(dF-ppy)3*. Then, a SET from IrIII(dF-ppy)3* [E1/2
(IrIII*/IrIV) = -1.23 V vs SCE in CH3CN][21] to intermediate B
generates SCF3 radical and IrIV(dF-ppy)3. This electron transfer
event was confirmed by Stern−Volmer fluorescence quenching
studies (see Supporting Information). The SET reduction of
IrIV(dF-ppy)3 [E1/2 (IrIV/IrIII) = +1.18 V vs SCE in CH3CN][21] with
Scheme 4. Substrate scope of hydrotrifluoromethylthiolation of alkynes.
Reaction conditions: 3 (0.5 mmol), (CF3SO2)2O (1.5 mmol), PMePh2 (1.5
mmol), Ir(dF-ppy)3 (0.0075 mol), n-Bu4NPF6 (1.0 mmol), H2O (1.0 mmol), DCE
(5.0 mL), LEDs, N2, rt, 24 h, isolated yields. [a] Z/E Ratio determined by 19F
NMR analysis of the crude reaction mixture.
ox
PMePh2 [E1/2 = +1.04 V vs SCE in CH3CN, see Supporting
Information][22] regenerates IrIII(dF-ppy)3 and finishes this
catalytic cycle.[23] Subsequently, the addition of SCF3 radical to
alkenes 1 forms radical intermediate C, which then is reduced by
PMePh2 to afford anion intermediate D. This SET reduction step
proceeds as part of a radical chain process, which was
supported by the reaction quantum yield (Φ) of 4.3 (see
Supporting Information). However, the SET reduction of
intermediate C with IrIII(dF-ppy)3* cannot be excluded.[24] Finally,
protonation
of
intermediate
D
furnishes
the
hydrotrifluoromethylthiolated products 2.
Scheme 5. Mechanistic experiments.
To gain insights into the reaction mechanism, several
experiments were performed. Firstly, the reaction of Tf2O and
PMePh2 led to the formation of an unknown species B. The 19F
NMR spectrum of B shows a doublet (J = 4.3 Hz) at δ = -29.8
ppm, whereas the 31P NMR spectrum of B reveals a resonance
at δ = 47.0 ppm as a quartet (J = 4.4 Hz). These data support
the formation of P─SCF3 bond.[19] Subsequently, the reaction of
1a with the in situ generated B under standard conditions
afforded 2a in 52% yield (Scheme 5a), which indicated that the
intermediate B might be the active SCF3 species in this reaction.
Secondly, the radical probe experiments were carried out. The
standard reaction was completely inhibited in the presence of a
radical inhibitor 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO).
Furthermore, the reaction of diene 5 afforded the cyclized
product 6 in 70% yield (Scheme 5b). These results revealed that
a radical process was probably involved in this reaction. Finally,
a deuterium-labeling experiment was performed in the presence
Scheme 6. Proposed reaction mechanism.
This article is protected by copyright. All rights reserved.

10.1002/anie.201911323
Angewandte Chemie International Edition
COMMUNICATION
T. Radosevich, Angew. Chem. Int. Ed. 2019, 58, 2864; Angew. Chem.
2019, 131, 2890.
To conclude, we have reported an unprecedented
application of Tf2O as radical trifluoromethylthiolating reagent
through deoxygenative reduction and photoredox radical
processes. Using this strategy, the first practical anti-
Markovnikov hydrotrifluoromethylthiolation of unactivated
alkenes was achieved. A novel trifluoromethylthiophosphonium
salt for the formation of trifluoromethylthio radical was probably
involved in this reaction.
[9]
a) J.-Y. Guo, R.-H. Dai, W.-C. Xu, R.-X. Wu, S.-K. Tian, Chem.
Commun. 2018, 54, 8980; b) K. Lu, Q. Li, X. Xi, Y. Huang, Z. Gong, P.
Yu, X. Zhao, Org. Chem. Front. 2018, 5, 3088.
[10] a) J. B. Hendrickson, D. D. Sternbach, K. W. Bair, Acc. Chem. Res.
1977, 10, 306; b) B. A. Shainyan, L. L. Tolstikova, Chem.
Rev. 2013, 113, 699.
[11] Y. Ouyang, X.-H. Xu, F.-L. Qing, Angew. Chem. Int. Ed. 2018, 57,
6926; Angew. Chem. 2018, 130, 7042.
[12] a) Q.-Y. Lin, X.-H. Xu, K. Zhang, F.-L. Qing, Angew. Chem. Int. Ed.
2016, 55, 1479; Angew. Chem. 2016, 128, 1501; b) Q.-Y. Lin, Y. Ran,
X.-H. Xu, F.-L. Qing, Org. Lett. 2016, 18, 2419; c) N. B. Heine, A.
Studer, Org. Lett. 2017, 19, 4150.
Acknowledgements
National Natural Science Foundation of China (21332010,
21421002), the Strategic Priority Research Program of the
Chinese Academy of Sciences (XDB20000000), and Youth
Innovation Promotion Association CAS (No. 2016234) are
greatly acknowledged for funding this work.
[13] For selected examples, see: a) X. Wu, L. Chu, F.-L. Qing, Angew.
Chem. Int. Ed. 2013, 52, 2198; Angew. Chem. 2013, 125, 2254; b) S.
Mizuta, S. Verhoog, K. M. Engle, T. Khotavivattana, M. O’Duill, K.
Wheelhouse, G. Rassias, M. Médebielle, V. Gouverneur, J. Am. Chem.
Soc. 2013, 135, 2505; c) D. J. Wilger, N. J. Gesmundo, D. A. Nicewicz,
Chem. Sci. 2013, 4, 3160; d) P. Yu, J.-S. Lin, L. Li, S.-C. Zheng, Y.-P.
Xiong, L.-J. Zhao, B. Tan, X.-Y. Liu, Angew. Chem. Int. Ed. 2014, 53,
11890; Angew. Chem. 2014, 126, 12084; e) S. Choi, Y. J. Kim, S. M.
Kim, J. W. Yang, S. W. Kim, E. J. Cho, Nat. Commun. 2014, 5, 4881; f)
N. J. W. Straathof, S. E. Cramer, V. Hessel, T. Noël, Angew. Chem. Int.
Ed. 2016, 55, 15549; Angew. Chem. 2016, 128, 15778; g) G. H. Lonca,
D. Y. Ong, T. M. H. Tran, C. Tejo, S. Chiba, F. Gagosz, Angew. Chem.
Int. Ed. 2017, 56, 11440; Angew. Chem. 2017, 129, 11598; h) W.
Zhang, Z. Zou, Y. Wang, Y. Wang, Y. Liang, Z. Wu, Y. Zheng, Y. Pan,
Angew. Chem. Int. Ed. 2019, 58, 624; Angew. Chem. 2019, 131, 634; i)
J.-X. Xiang, Y. Ouyang, X.-H. Xu, F.-L. Qing, Angew. Chem. Int. Ed.
2019, 58, 10320; Angew. Chem. 2019, 131, 10426.
Keywords: trifluoromethanesulfonic anhydride • deoxygenation
• photoredox catalysis • radical • hydrotrifluoromethylthiolation
[1]
a) S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev.
2008, 37, 320; b) J. Wang, M. Sanchez-Rosello, J. L. Acena, C. del
Pozo, A. E. Sorochinsky, S. Fustero, V. A. Soloshonok, H. Liu, Chem.
Rev. 2014, 114, 2432; c) N. A. Meanwell, J. Med. Chem. 2018, 61,
5822.
[2]
For selected reviews, see: a) T. Liang, C. N. Neumann, T. Ritter,
Angew. Chem. Int. Ed. 2013, 52, 8214; Angew. Chem. 2013, 125, 8372;
b) L. Chu, F.-L. Qing, Acc. Chem. Res. 2014, 47, 1513; c) F. Toulgoat,
S. Alazet, T. Billard, Eur. J. Org. Chem. 2014, 2415; d) X. Shao, C. Xu,
L. Lu, Q. Shen, Acc. Chem. Res. 2015, 48, 1227; e) X.-H. Xu, K.
Matsuzaki, N. Shibata, Chem. Rev. 2015, 115, 731; f) X. Yang, T. Wu,
R. J. Phipps, F. D. Toste, Chem. Rev. 2015, 115, 826; g) S. Barata-
Vallejo, S. Bonesi, A. Postigo, Org. Biomol. Chem. 2016, 14, 7150; h) H.
Zheng, Y. Huang, Z. Weng, Tetrahedron Lett. 2016, 57, 1397.
a) H. Chachignon, D. Cahard, Chin. J. Chem. 2016, 34, 445; b) J.
Zhang, J.-D. Yang, H. Zheng, X.-S. Xue, H. Mayr, J.-P. Cheng, Angew.
Chem. Int. Ed. 2018, 57, 12690; Angew. Chem. 2018, 130, 12872.
a) A. Ferry, T. Billard, B. R. Langlois, E. Bacqué, Angew. Chem. Int. Ed.
2009, 48, 8551; Angew. Chem. 2009, 121, 8703; b) T. Bootwicha, X.
Liu, R. Pluta, I. Atodiresei, M. Rueping, Angew. Chem. Int. Ed. 2013, 52,
12856; Angew. Chem. 2013, 125, 13093; c) C. Xu, B. Ma, Q. Shen,
Angew. Chem. Int. Ed. 2014, 53, 9316; Angew. Chem. 2014, 126, 9470;
d) S. Alazet, L. Zimmer, T. Billard, Chem. Eur. J. 2014, 20, 8589; e) P.
Zhang, M. Li, X. S. Xue, C. Xu, Q. Zhao, Y. Liu, H. Y. Wang, Y. Guo, L.
Lu, Q. Shen, J. Org. Chem. 2016, 81, 7486.
[14] For selected examples, see: a) G. Ma, W. Wan, J. Li, Q. Hu, H. Jiang,
S. Zhu, J. Wang, J. Hao, Chem. Commun. 2014, 50, 9749; b) C. Yu, N.
Iqbal, S. Park, E. J. Cho, Chem. Commun. 2014, 50, 12884; c) Q.-Y.
Lin, X.-H. Xu, F.-L. Qing, Org. Biomol. Chem. 2015, 13, 8740; d) W. Yu,
X.-H. Xu, F.-L. Qing, Org. Lett. 2016, 18, 5130; e) B. Yang, X.-H. Xu,
F.-L. Qing, Org. Lett. 2016, 18, 5956; f) W. Huang, W. Chen, G. Wang,
J. Li, X. Cheng, G. Li, ACS Catal. 2016, 6, 7471; g) X. Nie, C. Cheng, G.
Zhu, Angew. Chem. Int. Ed. 2017, 56, 1898; Angew. Chem. 2017, 129,
1924; h) W. Shu, E. Merino, C. Nevado, ACS Catal. 2018, 8, 6401; i) H.
Wang, N. T. Jui, J. Am. Chem. Soc. 2018, 140, 163.
[3]
[4]
[15] For a review, see: a) A.-L. Barthelemy, E. Magnier, G. Dagousset,
Synthesis 2018, 50, 4765; for selected examples, see: b) K. Zhang, J.-
B. Liu, F.-L. Qing, Chem. Commun. 2014, 50, 14157; c) F. Yin, X.-S.
Wang, Org. Lett. 2014, 16, 1128; d) N. Fuentes, W. Kong, L.
Fernández-Sánchez, E. Merino, C. Nevado, J. Am. Chem. Soc. 2015,
137, 964; e) D.-P. Jin, P. Gao, D.-Q. Chen, S. Chen, J. Wang, X.-Y. Liu,
Y.-M. Liang, Org. Lett. 2016, 18, 3486; f) M. Ji, Z. Wu, J. Yu, X. Wan, C.
Zhu, Adv. Synth. Catal. 2017, 359, 1959; g) C.-H. Guo, D.-Q. Chen, S.
Chen, X.-Y. Liu, Adv. Synth. Catal. 2017, 359, 2901; h) H. Li, S. Liu, Y.
Huang, X.-H. Xu, F.-L. Qing, Chem. Commun. 2017, 53, 10136; i) S.
Pan, H. Li, Y. Huang, X.-H. Xu, F.-L. Qing, Org. Lett. 2017, 19, 3247; j)
R. Honeker, R. A. Garza-Sanchez, M. N. Hopkinson, F. Glorius, Chem.
Eur. J. 2016, 22, 4395; k) Y. Li, T. Koike, M. Akita, Asian J. Org. Chem.
2017, 6, 445; l) G. Dagousset, C. Simon, E. Anselmi, B. Tuccio, T.
Billard, E. Magnier, Chem. Eur. J. 2017, 23, 4282; for a theoretical
study on the generation of the SCF3 radical from electrophilic reagents,
see: m) M. Li, B. Zhou, X.-S. Xue, J.-P. Cheng, J. Org. Chem. 2017, 82,
8697.
[5]
a) X. Shao, X. Wang, T. Yang, L. Lu, Q. Shen, Angew. Chem. Int. Ed.
2013, 52, 3457; Angew. Chem. 2013, 125, 3541; b) E. V. Vinogradova,
P. Müller, S. L. Buchwald, Angew. Chem. Int. Ed. 2014, 53, 3125;
Angew. Chem. 2014, 126, 3189; c) X. Shao, C. Xu, L. Lu, Q. Shen, J.
Org. Chem. 2015, 80, 3012.
[6]
[7]
[8]
a) Y. D. Yang, A. Azuma, E. Tokunaga, M. Yamasaki, M. Shiro, N.
Shibata, J. Am. Chem. Soc. 2013, 135, 8782; b) Z. Huang, Y. D. Yang,
E. Tokunaga, N. Shibata, Org. Lett. 2015, 17, 1094; c) S. Arimori, M.
Takada, N. Shibata, Org. Lett. 2015, 17, 1063.
a) L. Jiang, J. Qian, W. Yi, G. Lu, C. Cai, W. Zhang, Angew. Chem. Int.
Ed. 2015, 54, 14965; Angew. Chem. 2015, 127, 15178; b) Y. Yang, L.
Xu, S. Yu, X. Liu, Y. Zhang, D. A. Vicic, Chem. Eur. J. 2016, 22, 858; c)
J. Liu, X. Zhao, L. Jiang, W. Yi, Adv. Synth. Catal. 2018, 360, 4012.
a) H. Chachignon, M. Maeno, H. Kondo, N. Shibata, D. Cahard, Org.
Lett. 2016, 18, 2467; b) L. Jiang, T. Ding, W. Yi, X. Zeng, W. Zhang,
Org. Lett. 2018, 20, 2236; c) A. Ghosh, M. Lecomte, S.-H. Kim-Lee, A.
[16] J. F. Harris, Jr., F. W. Stacey, J. Am. Chem. Soc. 1961, 83, 840.
[17] a) T. Yang, L. Lu, Q. Shen, Chem. Commun. 2015, 51, 5479; b) X.
Shao, X. Hong, L. Lu, Q. Shen, Tetrahedron 2019, 75, 4156.
[18] W. Wu, W. Dai, X. Ji, S. Cao, Org. Lett. 2016, 18, 2918.
[19] a) A. Lopusiński, Phosphorus Sulfur Silicon Relat. Elem. 1989, 45, 137;
b) N. Santschi, A. Togni, J. Org. Chem. 2011, 76, 4189.
This article is protected by copyright. All rights reserved.

10.1002/anie.201911323
Angewandte Chemie International Edition
COMMUNICATION
[20] a) J. B. Hendrickson, S. M. Schwartzman, Tetrahedron Lett. 1975, 16,
177; b) J. B. Hendrickson, M. S. Hussoin, J. Org. Chem. 1989, 54, 1144.
[21] A. Singh, K. Teegardin, M. Kelly, K. S. Prasad, S. Krishnan, J. D.
Weaver, J. Organomet. Chem. 2015, 776, 51.
Gui, S.-S. Yan, G. Shen, D.-G. Yu, J. Am. Chem. Soc. 2018, 140,
17338.
[24] a) V. R. Yatham, Y. Shen, R. Martin, Angew. Chem. Int. Ed. 2017, 56,
10915; Angew. Chem. 2017, 129, 11055; b) J. Hou, A. Ee, H. Cao, H.-
W. Ong, J.-H. Xu, J. Wu, Angew. Chem. Int. Ed. 2018, 57, 17220;
Angew. Chem. 2018, 130, 17466.
[22] G. Pandey, D. Pooranchand, U. T. Bhalerao, Tetrahedron 1991, 47,
1745.
[23] a) C. K. Prier, D. A. Rankic, D. W. C. MacMillan, Chem. Rev. 2013, 113,
5322; b) L.-L. Liao, G.-M. Cao, J.-H. Ye, G.-Q. Sun, W.-J. Zhou, Y.-Y.
This article is protected by copyright. All rights reserved.

10.1002/anie.201911323
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Yao Ouyang, Xiu-Hua Xu, and Feng-
Ling Qing*
Page No. – Page No.
Hydrotrifluoromethylthiolation of
Unactivated Alkenes and Alkynes
with Trifluoromethanesulfonic
Anhydride through Deoxygenative
Reduction and Photoredox Radical
Processes
A practical anti-Markovnikov hydrotrifluoromethylthiolation of unactivated alkenes
using (CF3SO2)2O and H2O as the SCF3 and H sources was achieved through
deoxygenative reduction with PMePh2 and photoredox radical processes. This
reaction represents the first example of using (CF3SO2)2O as the
trifluoromethylthiolating reagent and provides a new strategy for radical
trifluoromethylthiolation.
This article is protected by copyright. All rights reserved.