Copper-Catalyzed Perfluoroalkylthiolation of Alkynes with Perfluoroalkanesulfenamides

Article abstract of DOI:10.1002/chem.201601338

Copper-catalyzed direct perfluoroalkylthiolation of alkynes by using the corresponding perfluoroalkanesulfenamide reagent is reported. The selective mono- and bis-perfluoroalkylthiolation of alkynes can be conducted under very mild conditions (no base, room temperature) in very good to excellent yields. This approach, which uses a low toxicity, inexpensive copper catalyst that incorporates a commercially available ligand, is applied in the absence of any additional base. Preliminary mechanistic investigations shed some light on the nature of the unprecedented reactivity observed.

Full text of DOI:10.1002/chem.201601338

DOI: 10.1002/chem.201601338
Full Paper
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Synthetic Methods
Copper-Catalyzed Perfluoroalkylthiolation of Alkynes with
Perfluoroalkanesulfenamides
Anis Tlili,*[a] Sꢀbastien Alazet,[a] Quentin Glenadel,[a] and Thierry Billard*[a, b]
Abstract: Copper-catalyzed direct perfluoroalkylthiolation of
alkynes by using the corresponding perfluoroalkanesulfena-
mide reagent is reported. The selective mono- and bis-per-
fluoroalkylthiolation of alkynes can be conducted under very
mild conditions (no base, room temperature) in very good
to excellent yields. This approach, which uses a low toxicity,
inexpensive copper catalyst that incorporates a commercially
available ligand, is applied in the absence of any additional
base. Preliminary mechanistic investigations shed some light
on the nature of the unprecedented reactivity observed.
generation of the SCF3 moiety in situ.[8] We reported a direct
approach to trifluoromethylthiolation by using either shelf-
stable trifluoromethanesulfenamide reagents in the presence
of Grignard derivatives or lithium alkynides generated in situ
with a catalytic amount of base.[9] The groups of Shen[7c,10] and
Rueping[11] developed different strategies by employing cata-
lytic or stoichiometric amounts of a copper–ligand complex in
the presence of a base and a shelf-stable trifluoromethylthio-
lating reagent (Scheme 1a). Thermal activation was necessary;
the reactions were performed at temperatures up to 808C.
Moreover, Qing and co-workers[12] demonstrated that an elec-
trophilic reagent could be obtained in situ by mixing AgSCF3
with N-chlorosuccinimide (NCS); alkynes underwent trifluoro-
methylthiolation at room temperature in the presence this re-
agent and a base (Scheme 1b).
Introduction
In the past few years, direct incorporation of an SCF3 moiety
has been extensively studied due to the intrinsic properties it
imparts to a compound, especially high lipophilicity.[1] In this
context, a plethora of methods have emerged, many of which
already show high potential and constitute a powerful tool for
organic synthesis.[2] The key to advances in trifluoromethylthio-
lation reactions is the design and development of new reac-
tants, which can be categorized into two types. On the one
hand, nucleophilic SCF3 donors that mainly consist of s-
bonded metal SCF3 derivatives[2g] (AgSCF3 and CuSCF3[4]) are
[3]
most commonly used. It should be noted that ammonium de-
rivatives are also attractive sources of SCF3,[4l,5] though their
usefulness in trifluoromethylthiolation reactions is less ex-
plored. On the other hand, discrete electrophilic reagents have
been designed to overcome the shortcomings encountered in
reactions for which an electrophilic SCF3 reagent is required.
More specifically, these efforts aim to circumvent the necessity
to operate under inconvenient conditions and/or with highly
toxic reagents[6] such as CF3SCl or CF3SSCF3.
Although these previous strategies are valuable, basic condi-
tions and/or heating can constitute a drawback for some sensi-
Both types of reagent have proven their efficiency in numer-
ous syntheses, and several elegant procedures have been pub-
lished recently.[2g,h,7] Among the studied reactions, the direct
formation of a C(sp)ÀSCF3 bond by using well-defined trifluoro-
methylthiolating reagents gave rise to renewed interest. In this
context different approaches have been evaluated, including
[a] Dr. A. Tlili, S. Alazet, Q. Glenadel, Dr. T. Billard
Institute of Chemistry and Biochemistry (ICBMS - UMR CNRS 5246)
Univ Lyon, Universitꢀ Claude Bernard-Lyon 1, CNRS
43 Bd du 11 novembre 1918, 69622 Villeurbanne (France)
E-mail: anis.tlili@univ-lyon1.fr
thierry.billard@univ-lyon1.fr
Homepage: www.FMI-Lyon.fr
[b] Dr. T. Billard
CERMEP - in vivo imaging, Groupement Hospitalier Est
59 Bd Pinel, 69003 Lyon (France)
Supporting information for this article is available on the WWW under:
http://dx.doi.org/10.1002/chem.201601338.
Scheme 1. Trifluoromethylthiolation of alkynes. LiHMDS=lithium bis(trime-
thylsilyl)azide, Ts=p-toluenesulfonyl.
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tive compounds. Even with our previous base-catalyzed meth-
od,[9b] highly base-sensitive substrates cannot be efficiently tri-
fluoromethylthiolated. In this context copper-catalyzed, base-
free transformations could constitute efficient alternatives. Fur-
thermore, extrapolations to higher fluorinated homologues
have never been performed.
Results and Discussion
We recently demonstrated direct access to a wide range of
perfluoroalkylthiolated compounds from perfluoroalkanesul-
fenamides.[7d,9a,b,13] We decided to investigate the copper-cata-
lyzed perfluoroalkylthiolation of alkynes, but first we studied
the copper-catalyzed trifluoromethylthiolation reaction.
A short series of optimization experiments revealed the best
reaction conditions to be copper iodide (10 mol%), 2,2’-bipyri-
dine L1 (20 mol%), alkyne (1 equiv), and trifluoromethanesulfe-
namide 2a (1.2 equiv). The reactions were performed at room
temperature for 20 h under an ambient atmosphere.
To demonstrate the applicability of the described trifluoro-
methylthiolation of alkynes, we focused on the scope and limi-
tations of the catalytic system. Therefore, a variety of different
alkynes (aliphatic and aromatic) were applied under the stan-
dard reaction conditions. As shown in Scheme 2, aryl acety-
lenes bearing electron-donating groups were trifluorome-
thylthiolated in very good to excellent yields (3a–b). Aliphatic
alkynes were also well tolerated in our protocol: very good
yields of 3k–m were obtained. More-challenging substrate 2n,
with an iodide group on a C(sp3) carbon atom, underwent the
transformation smoothly and 3n was obtained in excellent
yield.
Scheme 2. Copper-catalyzed trifluoromethylthiolation of alkynes with 2a.
Reaction conditions: alkyne 1 (0.5 mmol), 2a (0.6 mmol), CuI (10 mol%), L1
(20 mol%), CH3CN (1 mL), RT, 20 h. The yield of the isolated product is re-
ported (the yield determined by 19F NMR spectroscopy with PhOCF3 as an in-
ternal standard is given in parentheses). [a] L2 (20 mol%) was used instead
of L1.
When methyl 4-ethynylbenzoate (1d) was evaluated, a very
good yield of 80% was observed by 19F NMR spectroscopy. Ad-
ditionally, two new singlets were observed at dF =À39 and
À41 ppm. Remarkably, during purification of the product 3d
this byproduct was isolated and confirmed as alkene 4d (see
Scheme 3 below), which was formed by bis-trifluoromethyl-
thiolation of the corresponding alkyne. Furthermore, the pres-
ence of acetyl- or bromo-substituents on the arylacetylene
moiety decreased the efficiency of the coupling process: 3e
and 3 f were formed in only 38 and 48% yield, respectively,
under the standard conditions. Moreover, the formation of bis-
trifluoromethythiolated byproducts was also observed in
more-considerable quantities (up to 20%). This lack of selectivi-
ty could be resolved by changing the ligand to 1,10-phenan-
throline (L2). Consequently, less than 1% of the bis-trifluoro-
methylthiolation products were observed and products 3e and
3 f were formed selectively in higher yields (Scheme 2). Next,
more-challenging non-aromatic acetylene substrates were
studied. Propargylic substrates with a chelating oxygen atom
demonstrate that an even higher ratio of bis-/mono-trifluoro-
methylthiolated product was obtained under the standard
conditions. Once again, using L2 allowed for highly selective
formation of the terminal mono-trifluoromethylthiol products
in moderate yields (3g–i, Scheme 2). The presence of a coordi-
nating oxygen atom in the starting alkyne appears essential
for the double insertion of SCF3 because 3j was formed exclu-
sively without any trace of the bis-trifluoromethylthiolated
product.
After observing partial bis-trifluoromethylthiolation of aro-
matic and propargylic alkynes we attempted to develop a se-
lective bis-trifluoromethylthiolation procedure. We decided to
double the catalyst loading: CuI (20 mol%)/ligand (40 mol%).
In consideration of previous observations, L1 was applied as
the ligand to enable higher selectivity for the bis-trifluorome-
thylation. Indeed, a higher ratio of bis-/mono-trifluorome-
thylthiolation product was confirmed (Table 1, entry 2). Further
increasing the catalyst loading (CuI (30 mol%)/L1 (60 mol%)
eventually enabled full conversion and excellent selectivity for
the desired bis-trifluoromethylthiolated product 4g (Table 1,
entry 3). Nevertheless, the use of 2a (2.4 equiv) to overcome
the expected maximum yield of 60% based on 1g appeared
to be deleterious for the reaction.
These conditions were found to be generally applicable, and
the desired products were obtained with full selectivity to-
wards the Z isomer (Scheme 3). Under these conditions only
the bis-trifluoromethylthiolated products 4 were obtained;
some trace amounts of 3 (<1%) were observed in few cases.
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Table 1. Optimization of the bis-trifluoromethylthiolation of 1g.
Entry
CuI [mol%]
L1 [mol%]
3g [%][a]
4g [%][a]
1
2
3
10
20
30
20
40
60
36
6
<1
20[b] (33)[c]
40[b] (67)[c]
44[b] (73)[c]
[a] The yield was determined by 19F NMR spectroscopy with PhOCF3 as an
internal standard. [b] The yield relative to 1g. [c] The yield relative to 2a.
Scheme 4. Copper-catalyzed perfluoroalkylthiolation of alkynes with 2b–c.
Reaction conditions: alkyne 1 (0.5 mmol), 2 (0.6 mmol), CuI (10 mol%), L1
(20 mol%), CH3CN (1 mL), RT, 20 h. The yield of the isolated product is re-
ported (the yield determined by 19F NMR spectroscopy with PhOCF3 as an in-
ternal standard is given in parentheses). [a] L2 (20 mol%) was used instead
of L1.
Scheme 3. Copper-catalyzed selective bis-trifluoromethylthiolation of alkynes
with 2a. Reaction conditions: alkyne 1 (0.5 mmol), 2a (0.6 mmol), CuI
(30 mol%), L1 (60 mol%), CH3CN (1 mL), RT, 20 h. The yield of the isolated
product is reported (the yield determined by 19F NMR spectroscopy with
PhOCF3 as an internal standard is given in parentheses). [a] Yield reported
relative to 1. [b] Yield reported relative to 2a.
Figure 1. Bis-pentafluoroethylthiolation of alkynes with 2b. The yield of the
isolated product is reported (the yield determined by 19F NMR spectroscopy
with PhOCF3 as an internal standard is given in parentheses). [a] Yield report-
ed relative to 1. [b] Yield reported relative to 2b.
Subsequently, we extended the methodology to the incor-
poration of perfluoroalkylthiol groups into alkynes. For the first
time we demonstrate the copper-catalyzed coupling of penta-
fluoroethyl- (2b) and heptafluoropropylsulfenamides (2c) with
aromatic and aliphatic alkynes, and products 5 and 6 were iso-
lated in good-to-excellent yields (Scheme 4).
the presence of 2a. The formation of the desired product 3c
was observed in only about 15% yield compared with the ini-
tial result of 86%. These results seem to contradict a mecha-
nism that involves the initial formation of an acetylene–cop-
Notably, the corresponding bis-pentafluoroethylthiolation
could also be performed by using the previous conditions
(Table 1, entry 3); products 7g and 7i were obtained, again
with Z selectivity (Figure 1).
After observing the general activity of the reaction, we
turned our attention to the reaction mechanism. When the re-
action was carried out in the presence of a radical scavenger
2,2,6,6-tetramethylpiperidine N-oxide (TEMPO) or 1,4-benzoqui-
none (1 equiv) almost no changes in the reaction outcome
were observed (Scheme 5a).
Alternatively, a common pathway in the chemistry of alkynes
with copper is the formation of copper acetylide species,
which are known to react with an electrophile or a nucleophile
through an oxidative mechanism.[14] In this context, we investi-
gated the reactivity of (phenylethynyl)copper[15] (1.0 equiv) in
Scheme 5. Mechanistic investigations for the formation of 3c. Yields were
determined by 19F NMR spectroscopy with PhOCF3 as an internal standard.
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per(I) complex, especially when the presence of base is re-
quired to obtain this complex in situ (Scheme 5b).
termediate of type II was detected by NMR or mass spectros-
copy due to its high reactivity, however the volatile species
CF3SSCF3 was formed (Scheme 5c). This is in accordance with
the formation of II, which could react with 2a to form
CF3SSCF3.
Moreover, we used a deuterium-labeled alkyne ([D]1g) to
experimentally determine whether the bis-trifluoromethylthio-
lation reaction occurs exclusively via a two-step pathway, and
a hydrogen–deuterium exchange (around 50% hydrogen atom
incorporation) was detected in the final product (Scheme 6a).
Hence, two pathways appear plausible: the second trifluoro-
methylthiolation could occur from the mono-trifluoromethylth-
iolated product (3g) or from a copper–vinyl intermediate.
Further investigations focused on the nature of the bis-tri-
fluoromethylthiolation of alkynes. Exemplarily, the reaction was
performed with the SCF3-substituted alkyne 3g as the starting
material under the standard conditions. The second trifluoro-
methylthiolation occurred, but with a lower yield of 14%
(Scheme 6b).
Species II undergoes p complexation to the alkyne to form
intermediate III.[17] Intermediate III could yield a copper–vinyl
SCF3 intermediate IV. The mono-trifluoromethylthiolated prod-
uct 3 could then be obtained by b-hydride elimination in the
copper–vinyl intermediate IV.[18] If the intermediate is stabilized
by an electronic effect (the presence of an electron-withdraw-
ing group or a coordinating oxygen atom) a second trifluoro-
methylthiolation step provides a competing pathway. If this
second pathway is competitive, the cis copper–vinyl complex
IV can react with a second molecule of 2a. This, in turn, gener-
ates the desired bis-trifluoromethylthiolated product 4 with Z
selectivity. Also, after the formation of the alkyne 3, we rea-
soned that formation of a nucleophilic metal–vinyl intermedi-
ate V is plausible, but less reactive, and could yield the bis-
functionalized product.
Conclusion
We have disclosed an original strategy for the trifluorome-
thylthiolation of alkynes by the association of trifluorometha-
nesulfenamide and a commercially available copper reagent to
form a catalyst in situ. This new mode of reactivity has been
exploited for mono- and bis-trifluoromethylthiolation, as well
as perfluoroalkylthiolation, of alkynes. Preliminary mechanistic
studies suggest an unprecedented reaction pathway.
Scheme 6. Mechanistic investigations for the formation of 4g. Yields were
determined by 19F NMR spectroscopy with PhOCF3 as an internal standard.
These preliminary studies concerning the reaction mecha-
nism suggest that an unprecedented reaction pathway takes
place (Scheme 7). We hypothesize that the formation of a polar-
ized Cu–SCF3 species is crucial for the transformation. An oxi-
dative addition of copper(I) takes place and forms a new cop-
per(III) complex II.[14,16] When reagent 2a was mixed with a stoi-
chiometric amount of CuI in the absence of any alkyne, no in-
Experimental Section
Typical procedure
CuI (0.05 mmol, 10 mol% or 0.15 mmol, 30 mol%), ligand
L
(0.10 mmol, 20 mol% or 0.30 mmol, 60 mol%), alkyne 1 (0.5 mmol,
1.0 equiv), perfluoroalkanesulfenamide 2 (0.60 mmol, 1.2 equiv),
and MeCN (1 mL) were added to a flask equipped with a magnetic
stirrer bar. The reaction mixture was stirred for 20 h at RT. The con-
version of the starting material was monitored by 19F NMR spec-
troscopy with PhOCF3 as an internal standard. The reaction was
partitioned between pentane and water. The aqueous layer was
extracted with pentane and the combined organic layers were
washed with brine, dried over anhydrous Na2SO4, filtered, and con-
centrated to dryness under a moderate vacuum (800 mbar) at
408C. The crude residue was purified by flash column chromatog-
raphy to afford the desired product.
Acknowledgements
The authors are grateful to the CNRS and the French Ministry
of Research for financial support. The French Fluorine Network
is also acknowledged for its support.
Keywords: copper
·
cross-coupling
·
fluorine
·
trifluoromethanesulfenamide · trifluoromethylthiolation
Scheme 7. Proposed mechanism for the formation of 3 and 4.
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[1] a) C. Hansch, A. Leo, S. H. Unger, K. H. Kim, D. Nikaitani, E. J. Lien, J. Med.
Chem. 1973, 16, 1207–1216; b) C. Hansch, A. Leo, D. H. Hoekman, Ex-
ploring QSAR.: Hydrophobic, electronic, and steric constants, American
Chemical Society, Washington DC, 1995; c) A. Leo, C. Hansch, D. Elkins,
Chem. Rev. 1971, 71, 525–616.
[2] a) V. N. Boiko, Beilstein J. Org. Chem. 2010, 6, 880–921; b) A. Tlili, T. Bill-
ard, Angew. Chem. Int. Ed. 2013, 52, 6818–6819; Angew. Chem. 2013,
125, 6952–6954; c) F. Toulgoat, S. Alazet, T. Billard, Eur. J. Org. Chem.
2014, 2415–2428; d) X.-H. Xu, K. Matsuzaki, N. Shibata, Chem. Rev.
2015, 115, 731–764; e) J.-H. Lin, Y.-L. Ji, J.-C. Xiao, Curr. Org. Chem.
2015, 19, 1541–1553; f) K. Zhang, X. Xu, F. Qing, Chin. J. Org. Chem.
2015, 35, 556–569; g) H. Zheng, Y. Huang, Z. Weng, Tetrahedron Lett.
2016, 57, 1397–1409; h) H. Chachignon, D. Cahard, Chin. J. Chem. 2016,
34, 445–454.
D. Naumann, Y. L. Yagupolskii, Tetrahedron Lett. 2004, 45, 6101–6104;
c) C. Matheis, V. Wagner, L. J. Goossen, Chem. Eur. J. 2016, 22, 79–82;
d) W. Tyrra, D. Naumann, B. Hoge, Y. L. Yagupolskii, J. Fluorine Chem.
2003, 119, 101–107; e) G. Yin, I. Kalvet, U. Englert, F. Schoenebeck, J.
Am. Chem. Soc. 2015, 137, 4164–4172; f) G. Yin, I. Kalvet, F. Schoene-
beck, Angew. Chem. Int. Ed. 2015, 54, 6809–6813; Angew. Chem. 2015,
127, 6913–6917; g) C.-P. Zhang, D. A. Vicic, Chem. Asian J. 2012, 7,
1756–1758; h) C.-P. Zhang, D. A. Vicic, J. Am. Chem. Soc. 2012, 134,
183–185.
[6] E. C. Stump, Chem. Eng. News 1967, 45, 44.
[7] a) Y.-D. Yang, A. Azuma, E. Tokunaga, M. Yamasaki, M. Shiro, N. Shibata,
J. Am. Chem. Soc. 2013, 135, 8782–8785; b) Q. Glenadel, S. Alazet, A.
Tlili, T. Billard, Chem. Eur. J. 2015, 21, 14694–14698; c) X. Shao, C. Xu, L.
Lu, Q. Shen, Acc. Chem. Res. 2015, 48, 1227–1236; d) Q. Glenadel, M.
Bordy, S. Alazet, A. Tlili, T. Billard, Asian J. Org. Chem. 2016, 5, 428–433.
[8] C. Chen, L. Chu, F.-L. Qing, J. Am. Chem. Soc. 2012, 134, 12454–12457.
[9] a) F. Baert, J. Colomb, T. Billard, Angew. Chem. Int. Ed. 2012, 51, 10382–
10385; Angew. Chem. 2012, 124, 10528–10531; b) S. Alazet, L. Zimmer,
T. Billard, Angew. Chem. Int. Ed. 2013, 52, 10814–10817; Angew. Chem.
2013, 125, 11014–11017; c) Q. Glenadel, S. Alazet, T. Billard, J. Fluorine
Chem. 2015, 179, 89–95.
[10] a) X. Shao, X. Wang, T. Yang, L. Lu, Q. Shen, Angew. Chem. Int. Ed. 2013,
52, 3457–3460; Angew. Chem. 2013, 125, 3541–3544; b) C. Xu, B. Ma,
Q. Shen, Angew. Chem. Int. Ed. 2014, 53, 9316–9320; Angew. Chem.
2014, 126, 9470–9474; c) X. Shao, C. Xu, L. Lu, Q. Shen, J. Org. Chem.
2015, 80, 3012–3021.
[3] a) D. J. Adams, J. H. Clark, J. Org. Chem. 2000, 65, 1456–1460; b) M.
Jiang, F. Zhu, H. Xiang, X. Xu, L. Deng, C. Yang, Org. Biomol. Chem.
2015, 13, 6935–6939; c) P. Luo, Q. Ding, Y. Ping, J. Hu, Org. Biomol.
Chem. 2016, 14, 2924–2929; d) Y.-F. Qiu, X.-R. Song, M. Li, X.-Y. Zhu, A.-
Q. Wang, F. Yang, Y.-P. Han, H.-R. Zhang, D.-P. Jin, Y.-X. Li, Y.-M. Liang,
Org. Lett. 2016, 18, 1514–1517; e) P. Saravanan, P. Anbarasan, Adv.
Synth. Catal. 2015, 357, 3521–3528; f) G. Teverovskiy, D. S. Surry, S. L.
Buchwald, Angew. Chem. Int. Ed. 2011, 50, 7312–7314; Angew. Chem.
2011, 123, 7450–7452; g) K.-P. Wang, S. Y. Yun, P. Mamidipalli, D. Lee,
Chem. Sci. 2013, 4, 3205–3211; h) Q. Xiao, J. Sheng, Q. Ding, J. Wu, Eur.
J. Org. Chem. 2014, 217–221; i) F. Xie, Z. Zhang, X. Yu, G. Tang, X. Li,
Angew. Chem. Int. Ed. 2015, 54, 7405–7409; Angew. Chem. 2015, 127,
7513–7517; j) J. Xu, X. Mu, P. Chen, J. Ye, G. Liu, Org. Lett. 2014, 16,
3942–3945; k) W. Yin, Z. Wang, Y. Huang, Adv. Synth. Catal. 2014, 356,
2998–3006; l) Y. Zeng, J. Hu, Org. Lett. 2016, 18, 856–859.
[4] a) D. J. Adams, A. Goddard, J. H. Clark, D. J. Macquarrie, Chem. Commun.
2000, 987–988; b) E. Emer, J. Twilton, M. Tredwell, S. Calderwood, T. L.
Collier, B. Liꢀgault, M. Taillefer, V. Gouverneur, Org. Lett. 2014, 16, 6004–
6007; c) C. Hou, X. Lin, Y. Huang, Z. Chen, Z. Weng, Synthesis 2015, 47,
969–975; d) M. Hu, J. Rong, W. Miao, C. Ni, Y. Han, J. Hu, Org. Lett.
2014, 16, 2030–2033; e) Y. Huang, J. Ding, C. Wu, H. Zheng, Z. Weng, J.
Org. Chem. 2015, 80, 2912–2917; f) Y. Huang, X. He, H. Li, Z. Weng, Eur.
J. Org. Chem. 2014, 7324–7328; g) P. Kirsch, M. Lenges, D. Kꢂhne, K.-P.
Wanczek, Eur. J. Org. Chem. 2005, 797–802; h) Q. Lefebvre, E. Fava, P.
Nikolaienko, M. Rueping, Chem. Commun. 2014, 50, 6617–6619; i) Q.
Lin, L. Chen, Y. Huang, M. Rong, Y. Yuan, Z. Weng, Org. Biomol. Chem.
2014, 12, 5500–5508; j) P. Nikolaienko, R. Pluta, M. Rueping, Chem. Eur.
J. 2014, 20, 9867–9870; k) C. Rhode, J. Lemke, M. Lieb, N. Metzler-
Nolte, Synthesis 2009, 2015–2018; l) M. Rueping, N. Tolstoluzhsky, P. Ni-
kolaienko, Chem. Eur. J. 2013, 19, 14043–14046; m) J. Tan, G. Zhang, Y.
Ou, Y. Yuan, Z. Weng, Chin. J. Chem. 2013, 31, 921–926; n) X. Wang, Y.
Zhou, G. Ji, G. Wu, M. Li, Y. Zhang, J. Wang, Eur. J. Org. Chem. 2014,
2014, 3093–3096; o) Z. Wang, Q. Tu, Z. Weng, J. Organomet. Chem.
2014, 751, 830–834; p) Z. Weng, W. He, C. Chen, R. Lee, D. Tan, Z. Lai,
D. Kong, Y. Yuan, K.-W. Huang, Angew. Chem. Int. Ed. 2013, 52, 1548–
1552; Angew. Chem. 2013, 125, 1588–1592; q) P. Zhu, X. He, X. Chen, Y.
You, Y. Yuan, Z. Weng, Tetrahedron 2014, 70, 672–677; r) P. Nikolaienko,
T. Yildiz, M. Rueping, Eur. J. Org. Chem. 2016, 1091–1094.
[11] R. Pluta, P. Nikolaienko, M. Rueping, Angew. Chem. Int. Ed. 2014, 53,
1650–1653; Angew. Chem. 2014, 126, 1676–1679.
[12] S.-Q. Zhu, X.-H. Xu, F.-L. Qing, Eur. J. Org. Chem. 2014, 4453–4456.
[13] a) S. Alazet, T. Billard, Synlett 2015, 26, 76–78; b) S. Alazet, K. Ollivier, T.
Billard, Beilstein J. Org. Chem. 2013, 9, 2354–2357; c) Q. Glenadel, T. Bill-
ard, Chin. J. Chem. 2016, DOI:10.1002/cjoc.201500913.
[14] in Copper-Mediated Cross-Coupling Reactions (Eds.: E. Gwilherm, N. Blan-
chard), John Wiley & Sons, Inc., Hoboken, 2013.
[15] K. Jouvin, J. Heimburger, G. Evano, Chem. Sci. 2012, 3, 756–760.
[16] a) F. Monnier, M. Taillefer, Angew. Chem. Int. Ed. 2009, 48, 6954–6971;
Angew. Chem. 2009, 121, 7088–7105; b) G. Evano, N. Blanchard, M.
Toumi, Chem. Rev. 2008, 108, 3054–3131; c) E. Sperotto, G. P. M. van
Klink, G. van Koten, J. G. de Vries, Dalton Trans. 2010, 39, 10338–10351;
d) G. Lefꢃvre, G. Franc, A. Tlili, C. Adamo, M. Taillefer, I. Ciofini, A. Jutand,
Organometallics 2012, 31, 7694–7707; e) A. Casitas, X. Ribas in Copper-
Mediated Cross-Coupling Reactions (Eds.: E. Gwilherm, N. Blanchard),
John Wiley & Sons, Inc., Hoboken, 2013, pp. 239–251.
[17] a) F. Alonso, I. P. Beletskaya, M. Yus, Chem. Rev. 2004, 104, 3079–3160;
b) M. G. Suero, E. D. Bayle, B. S. L. Collins, M. J. Gaunt, J. Am. Chem. Soc.
2013, 135, 5332–5335.
[18] A. T. Lindhardt, T. M. Gøgsig, T. Skrydstrup, J. Org. Chem. 2009, 74, 135–
143.
Received: March 21, 2016
Revised: April 10, 2016
[5] a) D. J. Adams, J. H. Clark, P. A. Heath, L. B. Hansen, V. C. Sanders, S. J. Ta-
vener, J. Fluorine Chem. 2000, 101, 187–191; b) M. M. Kremlev, W. Tyrra,
Published online on && &&, 0000
Chem. Eur. J. 2016, 22, 1 – 6
www.chemeurj.org
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ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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&
These are not the final page numbers! ÞÞ

Full Paper
FULL PAPER
&
Synthetic Methods
A. Tlili,* S. Alazet, Q. Glenadel, T. Billard*
&& – &&
Copper-Catalyzed
Perfluoroalkylthiolation of Alkynes
with Perfluoroalkanesulfenamides
One or two? Selective mono- and bis-
perfluoroalkylthiolation of alkynes could
be performed with perfluoroalkanesulfe-
namides under copper-catalyzed base-
free conditions (see scheme). This origi-
nal approach seems to occur through
an unprecedented pathway.
&
&
Chem. Eur. J. 2016, 22, 1 – 6
www.chemeurj.org
6
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!