Copper-catalyzed trifluoromethylselenolation of aryl and alkyl halides: The silver effect in transmetalation

Article abstract of DOI:10.1021/ol403406y

A catalytic trifluoromethylselenolation of aryl and alkyl halides by a Cu(I) catalyst has been developed. A key intermediate, [(phen)Cu(SeCF3)]2 (5) was successfully isolated and characterized by X-ray diffraction. The important role of silver in the tran

Full text of DOI:10.1021/ol403406y

Letter
pubs.acs.org/OrgLett
Copper-Catalyzed Trifluoromethylselenolation of Aryl and Alkyl
Halides: The Silver Effect in Transmetalation
Chaohuang Chen,†,∥ Chuanqi Hou,†,∥ Yuguang Wang,† T. S. Andy Hor,*,‡,§ and Zhiqiang Weng*,†
†Department of Chemistry, Fuzhou University, Fuzhou 350108, China
‡Institute of Materials Research & Engineering, A*Star, 3 Research Link, Singapore 117602
§Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543
S
* Supporting Information
ABSTRACT: A catalytic trifluoromethylselenolation of aryl
and alkyl halides by a Cu(I) catalyst has been developed. A key
intermediate, [(phen)Cu(SeCF3)]2 (5) was successfully
isolated and characterized by X-ray diffraction. The important
role of silver in the transmetalation process during the catalytic
cycle was elucidated. A wide range of trifluoromethylselanes have been prepared from readily available starting materials from a
method that tolerates various important functional groups.
he trifluoromethylthiolato group (−SCF3),1 an important
class of heteroatom-containing fluorinated molecules, has
diselenide and the trifluoromethylselenolation with iodoarenes
(Scheme 1).16 However, these existing methods suffer from
disadvantages of limited substrate scope by the use of
selenocyanates or diselenides and the use of specific reagents
such as CuSeCF3.12b
As part of our ongoing program in copper-catalyzed and
-mediated trifluoromethylation17 and trifluoromethylthiolation
chemistry18 and platinum-mediated synthesis of macrocyclic
diselenoethers,19 we recently reported a copper(I) trifluor-
omethylthiolate reagent (bpy)Cu(SCF3) prepared from the
reactions of Cu(II)F2 with Ruppert’s reagent (Me3SiCF3),
sulfur, and bipyridine ligand.20 This reagent reacted with a
variety of aryl and heteroaryl halides to produce aryl
trifluoromethyl thioethers in good yields.
T
attracted increasing interest in recent years due to their strong
electron-withdrawing effect2 and high lipophilicity.3 The
trifluoromethylseleno group (−SeCF3),4 containing a larger
selenium atom, has beneficial effects similar to those of the
trifluoromethylthio group.5 Much recent attention has been
devoted to the development of new methods for the
construction of C−SCF3 bonds.6−8 In contrast, trifluorome-
thylselenolation is much less developed (Scheme 1), presum-
Scheme 1. Methods for Preparation of
Trifluoromethylselenolate Compounds
Encouraged by these results, we next sought to extend our
research to develop a catalytic version of synthetic routes to the
preparation of their selenium analogs with a broad substrate
scope. In this contribution, we report a new Cu(I)-catalyzed
trifluoromethylselenolation of aryl and alkyl halides with readily
available starting materials.
We began with scouting experiments employing 4-
iodotoluene (1a) as a substrate to optimize the reaction
conditions. Treatment of 1a with CF3·SiMe3 and elemental
selenium in the presence of 20 mol % of CuI, 20 mol % of 1,10-
phenanthroline (phen), and KF (3 equiv) in 1.5 mL of
dimethylformamide (DMF) at 80 °C for 16 h led to p-
tolyl(trifluoromethyl)selane (2a) in 50% yield determined by
19F NMR (entry 1). In the absence of CuI and phen, no
product formation was observed (entry 2), thus showing that
the copper is necessary for the reaction to occur.
ably because selenium substances are normally extremely toxic,
instable against air and/or moisture,9 and exhibit a penetrating
odor.10 In view of their potential applications as intermediates
of fluorine-containing compounds11 in the pharmaceutical,
agricultural, and advanced materials industries, the develop-
ment of a convenient synthetic pathway is highly desirable.
For instance, Langlois, Billard, and co-workers reported the
nucleophilic trifluoromethylation of selenocyanates or disele-
nides with trifluoromethyl trimethylsilane,12 trifluoroacetalde-
hyde,13 or trifluoromethane14 to form phenyl trifluoromethyl
selenide; Dolbier and co-workers published an atom-economic
procedure for the preparation of trifluoromethyl selenoethers
by the reaction of tetrakis(dimethylamino)ethylene (TDAE)
and CF3I with diphenyl diselenide;15 Yagupolskii and co-
workers described the synthesis of trifluoromethylselenocopper
from the reaction of copper power with bis(trifluoromethyl)
These preliminary results encouraged us to further explore
the precise reaction conditions. We then started to examine the
use of a number of additives for their ability to promote this
Received: November 24, 2013
Published: December 27, 2013
© 2013 American Chemical Society
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Organic Letters
Letter
transformation. Silver reagents have recently proven to behave
as efficient promoters for trifluoromethylation,17a,21 trifluor-
omethylthiolation,7a and trifluoromethoxylation.22 Formation
of 2a increased substantially to 87% when 0.5 equiv of Ag2CO3
was added as additive (entry 3). The significantly increased
yield of product in the presence of Ag2CO3 clearly shows the
importance of the silver effect in this reaction. No reaction
occurred in the presence of Ag2CO3 alone (entry 4), suggesting
that both the Cu catalyst and silver additive are required for the
reaction.
withdrawing and electron-donating groups, affording the
corresponding products 2e−i in 64−91% yields. Intriguingly,
Cl-containing substrate underwent trifluoromethylselenolation
to produce 2j in 84% yield, leaving the C−Cl bond intact,
which is attractive for further transformation. The substrates
containing important heterocyclic groups such as pyridine and
thiophene were also successful, affording the products 2k and
2l in 53% and 68% yields, respectively.
Encouraged by the success in the catalytic trifluoromethylse-
lenolation of aryl iodides, we next attempted to extend the
substrate scope to alkyl halides. As shown in Scheme 3, a great
Changing the copper salts also influenced the result. CuSCN
and Cu(OTf)2 provided slightly lower yields of the products
(entry 6 and 7), whereas the use of CuBr instead of CuI
dramatically slowed the reaction (entry 5). After screening a
variety of bidentate or monodentate nitrogen ligands, we found
that using Me2phen, TMEDA, or 2,6-lutidine unfortunately
gave unsatisfactory results (entries 8−11). Surprisingly, bpy,
which is a useful ligand for copper-mediated trifluoromethylth-
iolation,20 is not effective for catalytic trifluoromethylselenola-
tion of aryl iodides (entry 9). Variation of the silver salts
showed that Ag2CO3 is superior to other silver reagents. Use of
AgNO3, AgF, and AgOTf resulted in a sluggish reaction with
poor yields of products because of several side reactions (e.g.,
trifluoromethylation) (entries 12−14). The choice of solvent
has a significant impact on the efficiency of the reactions;
employing DMSO, NMP, CH3CN, CH2Cl2, diglyme, THF, or
toluene leads to marked diminished yields (entries 15−22).
Lowering or increasing the reaction temperature or reducing
the reaction time to 8 h significantly decreased the product
yields (entries 23−25).
Scheme 3. Copper(I)-Catalyzed Trifluoromethylselenolation
of Alkyl Bromides
a
Having established an efficient Cu-based catalytic system, the
scope of iodoarenes and heteroarenes was examined (Scheme
2). Various electronically and structurally diverse iodoarenes 1
were applied to this reaction.
p-Alkyl or aryl-substituted aryl iodides were treated with CF3·
SiMe3 and elemental selenium to give the corresponding
trifluoromethylselenolated products 2a−c in 70−83% yields. 1-
Iodonaphthalene furnished 2d in 75% yield. The reaction
proceeded smoothly with aryl iodides bearing both electron-
a
Reaction conditions: CuI (0.050 mmol), phen (0.050 mmol), alkyl
bromides (0.25 mmol), CF3SiMe3 (0.75 mmol), Se8 (0.50 mmol), KF
(0.75 mmol), Ag2CO3 (0.125 mmol), DMF (2.0 mL), 80 °C, 16 h, N2.
b
Isolated yields. Alkyl iodide.
variety of alkyl bromides can be converted into the
corresponding trifluoromethylselanes. Moreover, a range of
functional groups, such as nitrile (4e), amide (4f), ester (4g,
4h), thioether (4i), and ether (4j), were tolerated in this
reaction. Remarkably, secondary alkyl iodide and bromide
could also be employed as facile substrates that provided the
corresponding products (4k and 4l, respectively) in good
yields.
Scheme 2. Copper(I)-Catalyzed Trifluoromethylselenolation
of Aryl and Heteroaryl Iodides
a
To gain an insight into the mechanism of this transformation,
we have examined the reaction intermediates under stoichio-
metric conditions.
Treatment of Ag2CO3, Se8, and KF with CF3SiMe3 (3 equiv)
in DMF at 80 °C smoothly afforded the well-known silver(I)
trifluoromethylselenate AgSeCF3 (eq 1).4a,10,23 Interestingly,
a
Reaction conditions: CuI (0.050 mmol), phen (0.050 mmol), aryl
the trifluoromethylselenolation of the AgSeCF3 with aryl
iodides in the presence of phen did not proceed at all; In
contrast, the reaction of AgSeCF3 and CuI (1.0 equiv) with
iodides (0.25 mmol), CF3SiMe3 (0.75 mmol), Se8 (0.50 mmol), KF
(0.75 mmol), Ag2CO3 (0.125 mmol), DMF (2.0 mL), 80 °C 16 h, N2.
b
Isolated yields. With 30 mol % of CuI/phen.
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Organic Letters
Letter
phen (1.0 equiv) was found to give an dinuclear copper
trifluoromethylselenate intermediate [(phen)Cu(SeCF3)]2 (5)
(eq 2). The facile transmetalation of the −SeCF3 group from
silver to copper center explains the increased efficiency in silver
promoted copper-catalyzed trifluoromethylselenolation. Com-
plex 5 has been determined by X-ray crystallography (see the
Supporting Information).
the absence of Ag2CO3, albeit with reduced efficiency (Table 1,
entry 1).
On the basis of the results described above, a tentative
reaction pathway for this copper-catalyzed trifluoromethylsele-
nolation is shown in Scheme 4. The transmetalation of the in
Scheme 4. Proposed Reaction Pathway
We then evaluated the relevance of complex 5 as
intermediate in the copper-catalyzed trifluoromethylselenola-
tion of aryl halides. Reactions of 5 with 1 equiv of p-tolyl iodide
in DMF for 16 h formed the trifluoromethylselenolate product
p-tolyl(trifluoromethyl)selane in 85% yield (19F NMR) (eq 3).
This result is consistent with its catalytic version (87% yield;
Table 1, entry 3) suggesting the plausible intermediacy of 5 in
the catalytic cycle.
situ generated silver trifluoromethylselenate AgSeCF3 with
copper iodide to form the copper trifluoromethylselenate 5,
followed by the reaction of 5 with iodoarenes to release the
ArSeCF3 products and to regenerate copper iodide for the next
catalytic cycle.
To probe whether any radical intermediates are generated, a
radical clock probe, 1-(allyloxy)-2-iodobenzene 6,24 was used as
the substrate in the trifluoromethylselenolation (Scheme 5).
The reaction proceeded smoothly to produce the trifluor-
omethylselenolation product 7 in 80% yield (19F NMR). No
cyclized product, 3-methyl-2,3-dihydrobenzofuran 8, was
observed by GC/MS.
Additionally, we found that the reactive intermediate 5 can
also be obtained from the stoichiometric reaction of CuI with
Se8, KF, CF3SiMe3, and phen (eq 4). This result may explain
how catalytic trifluoromethylselenolation can be performed in
Next, the catalytic trifluoromethylselenolation of 3j was
carried out in the presence of a radical scavenger, cyclohexa-1,4-
a
Table 1. Optimization of Trifluoromethylselenolation Conditions
b
entry
[Cu]
CuI
ligand
phen
[Ag]
solvent
temp (°C)
time (h)
yield (%)
1
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
NMP
CH3CN
CH2Cl2
CH3OH
diglyme
THF
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
40
80
80
80
80
110
50
80
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
8
50
0
2
3
CuI
phen
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
AgNO3
AgF
87
0
4
5
CuBr
CuSCN
Cu(OTf)2
CuI
phen
46
75
77
<1
12
6
6
phen
7
phen
8
Me2phen
bpy
9
CuI
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
CuI
TMEDA
2,6-lutidine
phen
CuI
<1
13
31
17
38
39
6
CuI
CuI
phen
CuI
phen
AgOTf
CuI
phen
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
CuI
phen
CuI
phen
CuI
phen
0
CuI
phen
0
CuI
phen
38
13
<1
26
29
69
CuI
phen
CuI
phen
toluene
DMF
DMF
DMF
CuI
phen
CuI
phen
CuI
phen
a
Reaction conditions: 1a (0.10 mmol), Se8 (0.20 mmol), KF (0.3 mmol), CF3·SiMe3 (0.30 mmol), [Cu] (0.020 mmol), ligand (0.020 mmol), [Ag]
b
(0.10 mmol), solvent (1.5 mL), under N2 atmosphere. Yields were determined by 19F NMR spectroscopy with PhOCF3 as internal standard.
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Letter
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nitro, nitrile, methoxy, chloro, amide, ester, thioether, and
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ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and spectral data for products and
mechanistic study experiments. This material is available free of
charge via the Internet at http://pubs.acs.org.
(18) (a) Kong, D.; Jiang, Z.; Xin, S.; Bai, Z.; Yuan, Y.; Weng, Z.
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277−280.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: andyhor@imre.a-star.edu.sg.
*E-mail: zweng@fzu.edu.cn.
(20) Weng, Z.; He, W.; Chen, C.; Lee, R.; Tan, D.; Lai, Z.; Kong, D.;
Yuan, Y.; Huang, K.-W. Angew. Chem., Int. Ed. 2013, 52, 1548−1552.
(21) (a) Ye, Y.; Lee, S. H.; Sanford, M. S. Org. Lett. 2011, 13, 5464−
5467. (b) Wang, X.; Xu, Y.; Mo, F.; Ji, G.; Qiu, D.; Feng, J.; Ye, Y.;
Zhang, S.; Zhang, Y.; Wang, J. J. Am. Chem. Soc. 2013, 135, 10330−
10333. (c) Zeng, Y.; Zhang, L.; Zhao, Y.; Ni, C.; Zhao, J.; Hu, J. J. Am.
Chem. Soc. 2013, 135, 2955−2958.
Author Contributions
∥These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(22) Huang, C.; Liang, T.; Harada, S.; Lee, E.; Ritter, T. J. Am. Chem.
Soc. 2011, 133, 13308−13310.
This work was supported by National Natural Science
Foundation of China (21072030), the Research Fund for the
Doctoral Program of Higher Education of China (No.
20123514110003), the SRF for ROCS, SEM, China (2012-
1707), and Fuzhou University (022318, 022494).
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