Trifluoromethylthiolation of allylsilanes and silyl enol ethers with trifluoromethanesulfonyl hypervalent iodonium ylide under copper catalysis

Article abstract of DOI:10.1021/acs.orglett.5b00057

Electrophilic trifluoromethylthiolation of allylsilanes and silyl enol ethers with trifluoromethanesulfonyl hypervalent iodonium ylide has been conducted. In the presence of a catalytic amount of CuF₂, the reaction proceeded in modest to high y

Full text of DOI:10.1021/acs.orglett.5b00057

Letter
pubs.acs.org/OrgLett
Trifluoromethylthiolation of Allylsilanes and Silyl Enol Ethers with
Trifluoromethanesulfonyl Hypervalent Iodonium Ylide under Copper
Catalysis
Sadayuki Arimori, Masahiro Takada, and Norio Shibata*
Department of Frontier Materials, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan
S
* Supporting Information
ABSTRACT: Electrophilic trifluoromethylthiolation of allylsilanes
and silyl enol ethers with trifluoromethanesulfonyl hypervalent
iodonium ylide has been conducted. In the presence of a catalytic
amount of CuF2, the reaction proceeded in modest to high yields
under mild conditions.
rganofluorine compounds now constitute a major family
of pharmaceuticals and agrochemicals that have attracted
bis-SCF3 product was observed for the trifluoromethylthiola-
tion of silyl enol ethers 4.
O
considerable interest over several years in these markets.1
Among them, trifluoromethylthio (SCF3) compounds are
currently appealing and have been given special attention2
due to their impressive lipophilicity, which plays an important
role in transport across cell walls. Moreover, enhanced
lipophilicity of molecules is also beneficial in material science
due to the improvement of physical property.3 Thus, the
development of efficient methods for the synthesis of SCF3
compounds is of great importance.4 Shelf-stable electrophilic
trifluoromethylthiolation reagents such as SCF3-phthalimide,5
SCF3-anilines6 (1), SCF3-ether,7 and SCF3-saccharine8 have
been developed for this purpose. In 2013, we also disclosed a
new type of reagent, trifluoromethanesulfonyl hypervalent
iodonium ylide 2, for the same purpose.9 Our reagent 2 has a
fundamentally novel structure with a trifluoromethyl sulfonyl
(SO2CF3) moiety, instead of an essential SCF3 unit in regular
reagents. Besides, the SO2CF3 group directly connects to the
carbon atom in 2, while regular SCF3 reagents have a
connection between the heteroatom and the SCF3 group.
Hence the reaction mechanism of 2 for electrophilic
trifluoromethylthiolation is rather complex and unique,
although the utility of 2 is still limited to the trifluoromethylth-
iolation of enamines, indoles, and β-keto esters. As part of our
continuing interest in the potential use of 2, which stems from
its structural and mechanistic uniqueness, we expand herein the
further scope and utility of 2 for the trifluoromethylthiolation of
allylsilanes 3 and silyl enol ethers 4. Although the
trifluoromethylthiolation of 3 and 4 has been reported by
others, a different reagent (1a or 1b) using different conditions
is likely to be required, depending on the substrates, 310 or 4.11
Moreover, the trifluoromethylthiolation of 4 tends to give a
mixture of mono- and bis-SCF3 products. Reagent 2 is
advantageous in that a wide variety of cyclic and linear
allylsilanes 3 and silyl enol ethers 4 are nicely transformed into
corresponding SCF3-products 5 and 6 in good to high yields
under the same conditions of copper catalysis (Scheme 1). No
Scheme 1. Electrophilic Trifluoromethylthiolation of
Allylsilanes and Silyl Enol Ethers by 1a,b and 2
Trimethyl(2-phenylallyl)silane (3a) was selected as a model
substrate for the optimization of reaction conditions (Table 1).
We first attempted the trifluoromethylthiolation of 3a with 2
under the best conditions reported for enamines (20 mol %
CuCl in 1,4-dioxane at room temperature), but no reaction
proceeded (run 1). The combination of catalyst and solvent
was found to be very important after careful screening (runs 2−
11), and desired SCF3 product 5a was obtained in 80% yield
with CuF2 in NMP or DMAc (runs 5 and 7). Neither catalyst
additives nor a higher reaction temperature under the best
conditions (run 7) improved the yield of 5a (runs 12−16).
With these optimized conditions in hand (Table 1, run 7),
we examined diverse allylsilanes 3b−o to explore the substrate
scope of trifluoromethylthiolation (Scheme 2). It was found
that the reaction of linear 2-aryl-substituted allylsilanes 3b−i
proceeded smoothly, and corresponding SCF3 compounds 5b−
Received: January 7, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b00057
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
aryl groups (biphenyl, naphthyl) could be applied in the same
reaction conditions. Allylsilane 3j with a branched structure was
also converted into CF3S product 5j, although the yield was
only 32%. Cyclic allylsilanes 3k and 3l gave the desired
products 5k and 5l in 70% and 38% yield, respectively.
Allylsilanes having 2-thiophenyl 3m, alkenyl 3n, and alkynyl 3o
groups could be applied in the same reaction conditions
providing CF3S products 5m−o in good yields. The stereo-
chemistry of 3n was retained in 5n during the reaction.
The trifluoromethylthiolation of silyl enol ethers 4 with 2
was examined next. Under the same reaction conditions (Table
1, run 7), silyl enol ethers 4 were nicely trifluoromethylthio-
lated furnishing 6 in moderate to good yields (Scheme 3). The
Table 1. Optimization of Cu-Catalyzed
Trifluoromethylthiolation
a
b
run
CuX
additive (mol %)
solvent
yield (%)
1
2
3
4
5
CuCl
CuF2
CuF2
CuF2
CuF2
CuF2
CuF2
CuF2
CuF2
CuCl
CuOAc
CuF2
CuF2
CuF2
CuF2
CuF2
dioxane
dioxane
THF
0
0
23
34
80
52
80
5
DMF
NMP
c
6
NMP
Scheme 3. Scope of Cu-Catalyzed Trifluoromethylthiolation
7
DMAc
CH2Cl2
MeCN
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
ab
,
of Silyl Enol Ethers 4
8
9
0
10
11
12
13
14
15
2
62
50
65
74
68
61
PhNMe2 (20)
2,4,6-collidine (20)
CsF (10)
TBAF (10)
d
16
a
Reaction conditions: 3a (0.25 mmol), 2 (0.50 mmol), CuX (20 mol
b
%), solvent (1.25 mL), rt, 10 h, under N2 atmosphere. 19F-NMR
yields with PhF as an internal standard. Compound 2 (0.25 mmol)
was used. The reaction was carried out at 50 °C. TBAF =
c
d
tetrabutylammonium fluoride. NMP = N-methyl-2-pyrrolidone.
DMAc = N,N-dimethylacetamide
Scheme 2. Scope of Cu-Catalyzed Trifluoromethylthiolation
a b
,
of Allylsilanes 3
a
Reaction conditions: 4 (0.25 mmol), 2 (0.50 mmol), CuF2 (20 mol
b
%), DMAc (1.25 mL), rt, 10 h, under N2 atmosphere. Isolated yields.
The values in parentheses are 19F-NMR yields with PhF as an internal
standard.
naphthyl group, as well as electron-donating (OMe) and
electron-withdrawing (Cl, CF3, F) groups on the aromatic ring
of 4 did not affect the reaction much and proceeded well to give
6 in modest to good yields. Additionally, cyclic silyl enol ethers
4i,j were also compatible in this system. It should be noted that
mono-trifluoromethylthiolated products 6 were selectively
obtained in all cases, although a reported method11
predominantly gave bis-trifluoromethylthiolated products.
In conclusion, we have developed copper-catalyzed trifluor-
omethylthiolation reactions of various allylsilanes 3 and silyl
enol ethers 4 with 2 under mild conditions. The protocol of
this reaction is concise compared to previously reported
procedures10,11 and tolerates diverse substrates. The present
results expand the scope and utility of reagent 2, and further
application of 2 is now under investigation.
ASSOCIATED CONTENT
* Supporting Information
Experimental procedures and NMR spectra. This material is
available free of charge via the Internet at http://pubs.acs.org.
■
a
S
Reaction conditions: 3 (0.25 mmol), 2 (0.50 mmol), CuF2 (20 mol
b
%), DMAc (1.25 mL), rt, 10 h, under N2 atmosphere. Isolated yields.
c
NMP was used as a solvent.
AUTHOR INFORMATION
Corresponding Author
■
i were obtained in modest to high yields (41−82%). The
t
electron-donating groups (OMe, Bu), electron-withdrawing
groups (Cl, CF3, F) on the aryl group, and sterically demanding
*E-mail: nozshiba@nitech.ac.jp.
B
DOI: 10.1021/acs.orglett.5b00057
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was financially supported in part by the Platform
for Drug Discovery, Informatics, and Structural Life Science
from MEXT Japan, the Advanced Catalytic Transformation
(ACT-C) from the Japan Science and Technology (JST)
Agency, and Kobayashi International Foundation.
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DOI: 10.1021/acs.orglett.5b00057
Org. Lett. XXXX, XXX, XXX−XXX