In situ generation of PhI+CF3 and transition-metal-free oxidative sp2 C-H trifluoromethylation

Article abstract of DOI:10.1002/chem.201301585

These things are sent to tri us: The introduction of CF₃ units into organic molecules is important and requires the development of convenient trifluoromethylating reagents. Here, PhI⁺CF₃, an acyclic electrophilic "CF₃

Full text of DOI:10.1002/chem.201301585

COMMUNICATION
DOI: 10.1002/chem.201301585
+
2
À
In Situ Generation of PhI CF3 and Transition-Metal-Free Oxidative sp C H
Trifluoromethylation
Cong Xu, Jingxin Liu, Wenbo Ming, Yingjie Liu, Jun Liu, Mang Wang,* and Qun Liu*[a]
Chem. Eur. J. 2013, 00, 0 – 0
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Approximately 20–30% of modern pharmaceuticals and
agrochemicals contain fluorine atoms, because fluorinated
compounds are more difficult to oxidize, leading to in-
creased metabolic stability and bioavailability over their
non-fluorinated analogues.[1] As a consequence, rapidly in-
creasing efforts have focused on developing valuable strat-
egies, reagents, and catalysts for the incorporation of, for ex-
ample, CF3 into various organic structures through nucleo-
philic, electrophilic, and radical trifluoromethylations.[2a–f] In
this context, a major challenge is the development and uti-
lization of diverse CF3 sources.[2] for example, (trifluorome-
thyl)trimethylsilane (TMSCF3, Ruppert–Prakash reagent)
has been widely used to provide a nucleophilic CF3 species
in various transformations.[2a–f] On the other hand, Yagupol-
skii and co-workers described the first electrophilic perfluor-
Brønsted acids as activators.[7b] In addition, using Togniꢁs re-
agent 4a, a number of elegant transition-metal catalyzed tri-
fluoromethylations have been reported. Examples includes
Cu-catalyzed allylic trifluoromethylation of terminal ole-
fins,[7c,d] Re-catalyzed trifluoromethylation of (hetero)
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
vinyltrifluoroborates,[7g] and [Cu
ACTHNUGTRENNUG(MeCN)4]PF6-catalyzed ole-
finic trifluoromethylation of enamides.[7h] As an application
of Togniꢁs reagent 4b, the Cu-catalyzed trifluoromethylation
of arylboronate esters has also been described.[7i]
For the synthesis of perfluoroalkylating reagents 1a, aryl
perfluoroalkyl iodonium salts 1b were first prepared
through the condensation of bis(trifluoroacetoxy)iodoper-
fluoroalkanes with toluene in trifluoroacetic acid for three
days.[3,4a] However, (trifluoromethyl)aryliodonium salt 1b-
CF3 (Figure 1, 1b: when RF =CF3) has not yet been success-
fully prepared, since the corresponding synthetic intermedi-
À
À
oalkylation to construct S RF or Se RF bonds (RF =per
ACHTUNGTRENNUNG ACHTUNGTRENNUNG
ACHUTGTNRENNUGfluACHTUNGTERNoNUGN -
late based on aryl perfluoroalkyl iodonium salts 1a
(Figure 1) in 1978.[3] Since then, many synthetically useful
ates (CF3IACHTGUNTERNNU(G OCOCF3)2), CF3IF2, and CF3IO) have low stabili-
ty in comparison to their analogues having RF groups with
two or more carbons.[3,4a,8] Therefore, Togni and co-workers
prepared the cyclic hypervalent-iodine based tri
ACHUTGTNRENNUGfluACHTUNGTRENNUGoACHTUNGTRENNUNGroACHTUNGTRENNUNGmeth-
AHCTUNGTREUGNyNN lAHCNUTGERTNNUNGaACUTHNGTRENtNNUG ing reagents 4 through an alternative route in a straight-
forward three-step sequence from commercially available 2-
iodobenzoic acid or a 2-iodobenzylic alcohol using TMSCF3
as the CF3 source.[5] It is true that the preparation and the
use of a simple hypervalent iodo compound as a source of
electrophilic trifluoromethyl group has been a challenge to
organic chemists.[4a,8,9] Here, we report that the acyclic hy-
pervalent iodide trifluoromethylating species [PhICF3]+ de-
rived from 6a (Figure 1) can be detected by simple mixing
of PhIACHTNUGRTNEUNG
(OAc)2, TMSCF3 and KF and directly applied in sp2
À
C H trifluoromethylation reactions without any catalyst
under mild conditions.
Figure 1. Electrophilic RF/CF3 species.
Our initial observation of an electrophilic tri
ACHTUNGTENRfUNG luACTHUNGTRENNNGoU ACHTUNRTEGNGrNUN oACHTUNGTRENNUNGmethACHTUNGTRENNUNGyl-
electrophilic tri
flu
E
ro
E
yl
G
ACTUHNGTERNNUNaG ACHTUNGTREtNGNUN ion using 6a occurred during the investigation on the
methyl chalcogen salts 2 and oxonium salts 3 invented by
modification of the a-position of ketene dithioacetals.[10–12]
When we tested a-trifluoromethylation of the a-acetyl
ketene dithioacetal, 1-(1,3-dithiolan-2-ylidene) propan-2-one
(7a), the a-trifluoromethylated product, 3-(1,3-dithiolan-2-
ylidene)-4,4,4-trifluorobutan-2-one (8a), could be isolated in
52% yield simply by adding TMSCF3 (2.0 equiv) to a pre-
Umemoto and co-workers,[4] cyclic hypervalent iodine com-
pounds 4 developed by Togni and co-workers,[5] and tri
ACHTUNGTRENNUNGroACHTUNGTRENNUNG
Among these electrophilic trifluoromethylating reagents,
compounds 4 (Togniꢁs reagent) have proved to be quite effi-
cient.[5,7] They can not only react with soft nucleophiles such
as thiols, phenolates, phosphines, and active methylenes,[5]
but also proceed through O-trifluoromethylation of aliphatic
alcohols in the presence of catalytic amount of a zinc(II)
salt as an activator[7a] and N-trifluoromethylation of nitriles
in the presence of azoles through a Ritter-type reaction with
mixed mixture of 7a (0.5 mmol), PhIACTHNUTRGNENUG(OAc)2 (1.0 equiv), and
KF (2.0 equiv) in MeCN (3.0 mL) under N2 and then stirred
for 1.0 h at room temperature (Table 1, entry 1). Further
screening of oxidants showed that only hypervalent iodine
compounds could give the desired trifluoromethylated prod-
ucts (entries 1–8). Product 8a could be isolated in 88%
yield by increasing the amount of PhIACTHNUTRGENUN(G OAc)2 to 2.0 equiva-
lents (entry 9). Lower yields were obtained with increased
amounts of TMSCF3 and KF though the reactions were
completed in shorter time (entries 10 and 11). In addition,
DMF, CH2Cl2, and THF were less effective than MeCN in
the solvents tested (entries 12–14).
[a] C. Xu, J. Liu, W. Ming, Y. Liu, Dr. J. Liu, Prof. M. Wang, Prof. Q. Liu
Department of Chemistry, Northeast Normal University
Renmin Street 5268, 130024 Changchun (P.R. China)
Fax : (+86)431-85099759
E-mail: wangm452@nenu.edu.cn
CF3-containing olefins are important organic synthons.
liuqun@nenu.edu.cn
However, relatively less attention has been paid to construct
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201301585.
À
the vinylic C CF3 bond. Recently, with Togniꢁs reagent 4 as
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In Situ Generation of PhI+CF3
COMMUNICATION
Table 1. Screen of reaction conditions.[a]
Table 2. a-Trifluoromethylation of ketene dithioacetals 7.[a]
7
R’
R,R
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)3
Me
Et
Et
Et
Et
Time [h]
8
Yield [%][b]
TMSCF3
[equiv]
KF
[equiv]
Oxidant
ACHTUNGTRNE[NUNG equiv]
Solvent
Time
[h]
Yield
[%][b]
G
R
1
2
3
4
5
6
7
8
9
7b
7c
7d
7e
7 f
7g
7h
7i
COEt
COPh
COPh
COPh
CO2Et
CN
COMe
COMe
COMe
4-ClPh
4-FPh
U
0.5
5.0
0.5
0.5
2.0
2.0
0.5
0.5
0.5
0.5
0.5
0.5
8b
8c
8d
8e
8 f
8g
8h
8i
85
74
70
70
75
68
79
74
64
81
71
80
1
2
3
4
5
6
7
8
9
10
11
12
13
14
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
3.0
4.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
3.0
4.0
2.0
2.0
2.0
PIDA (1.0)
PIDA (1.0)
PIFA (1.0)
DMP (1.0)
AgOAc (1.0)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DMF
1.0
8.0
1.0
2.0
8.0
8.0
8.0
8.0
0.5
0.3
0.3
3.5
48
52 (21)
53 (10)
46 (19)
25 (67)
n.r.[c]
G
E
CuACTHNGUTREN(UNG OAc)2 (1.0)
BQ (1.0)
n.r.[c]
–
[d](86)
BPO (1.0)
PIDA (2.0)
PIDA (2.0)
PIDA (2.0)
PIDA (2.0)
PIDA (2.0)
PIDA (2.0)
n.r.[c]
88
7j
7k
7l
8j
8k
8l
10
11
12
78
68
36
37
7m
4-MeOPh
8m
[a] Reaction conditions:
(2.0 equiv), PhI(OAc)2 (2.0 equiv), MeCN (3.0 mL), N2, room tempera-
ture. [b] Isolated yield.
7
(0.5 mmol), TMSCF3 (2.0 equiv), KF
CH2Cl2
THF
AHCTUNGTRENNUNG
48
33
[a] Reaction conditions: 7a (0.5 mmol), solvent (3.0 mL), N2, room tem-
perature. [b] Isolated yield. Numbers in parentheses indicate the recovery
yield of 7a. [c] No reaction. [d] Complex. PIDA: phenyliodine diacetate;
PIFA: phenyliodine bis(trifluoroacetate); DMP=(1,1,1-triacetoxy)-1,1-
dihydro-1,2-benziodoxol-3ACTHNURTGNEU(GN 1H)-one; BQ=1,4-benzoquinone; BPO=
benzoyl peroxide; DMF=N,N-dimethyl formamide.
cause of its extreme instability.[14a] Soon after, they also de-
scribed another radical-cation mechanism for the trifluoro-
methylation of electron-rich arenes by using the combina-
tion of TMSCF3 with PhIACHTUNTGRENUNG(OAc)2 and K3PO4 under metal-
free conditions. However, 1,4-benzoquinone was required
for the transfer of the CF3 group.[14b]
the electrophilic trifluoromethylating reagent, transition-
metal catalyzed trifluoromethylation of potassium vinyltri-
Based on the knowledge of the nucleophilicity of the
a-carbon of ketene dithioacetals,[10,12] however, we favor an
electrophilic “CF3+” species for the trifluoromethylations
described in Table 2. To gain information about the true
active intermediate involved, an in situ, high resolution elec-
trospray ionization mass spectra (HRMS-ESI) study of the
fluoroborates (using 4a) and decarboxylative tri
ACHUTGTNRNEUGfN luCAHTUNGTRENNUNoG AHCTUNRTGENNrGUN oACTHUNGTRENmNUNG eth-
ACHTUNGTRENNUNGylACHTUNGTRENNUNGaACHTUNGTRENNUNGtion of a,b-unsaturated carboxylic acids (using 4b) were
reported to give the corresponding vinyl-CF3 com-
pounds.[7g,13] A little later, Loh and Feng developed for the
À
first time a method for the vinylic C CF3 bond formation by
reaction mixture of PhIACHTUNGTRENNU(G OAc)2, TMSCF3, and KF in MeCN
2
À
a Cu-catalyzed direct olefinic sp C H trifluoromethylation
were performed at room temperature. Samples were taken
5.0 min after mixing of the reagents and diluted with MeCN
prior to the injection into the mass spectrometer. It was
found that a peak at m/z=260.93330 can be regarded as
of enamides with 4a.[7h] Comparatively, the successful syn-
thesis of 8a, the useful CF3-containing synthons,[10,11] pro-
2
À
vides an alternative way to olefinic sp C H tri
fluor
E
E
yl-
G
tion under mild transition-metal-free conditions.
The reaction conditions identified for the direct sp C H
[PhI
(OAc)2. Notably, a peak at m/z=272.93822 was observed
and assigned to [PhICF3]+ (Calculated: 272.93825), which is
generated from the oxidation of TMSCF3 by PhI(OAc)2 in
(OAc)2-K]+ (Calculated: 260.93336) derived from PhI-
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
trifluoromethylation of 7a (Table 1, entry 9) were thus eval-
uated for the synthesis of a-trifluoromethylated ketene di-
thioacetals 8 from a range of ketene dithioacetals 7. Clearly,
the mild conditions were compatible with 7 bearing R’ sub-
stituents of electron-withdrawing acetyl, benzoyl, ethoxycar-
bonyl, and cyano groups (Table 2, entries 1–7). Acyclic
ketene dithioacetals 7i and j were also suitable substrates
(entries 8 and 9). Additionally, substrates 7 having aromatic
R’ groups also afforded the desired products 8 in good
yields (entries 10–12).
AHCTUNGTRENNUNG
the presence of KF (also see the Supporting Information)
and more likely to be the key species in our trifluoromethy-
lations. Although the mechanistic details of the a-trifluoro-
methylation of 7 are not very clear at the moment, an elec-
trophilic pathway is proposed (Scheme 1) based on the suc-
cessful observation of iodonium 9 by HRMS analysis.
Initially, PhI
ACHUTGTNERN(NUG CF3)ACHTUNGTREN(NGUN OAc) (6a) is generated from the reac-
tion of PhI
AHCTUNGTRENNUNG
More recently, Qing proposed a single-electron-transfer
mechanism involving a radical-cation intermediate captured
by “CF3 ” for their Cu-catalyzed oxidative allylic trifluoro-
and quickly transforms to phenyl(trifluoromethyl)iodonium
(9; Scheme 1). Thereby, the nucleophilic attack of the
a-carbon of an ketene dithioacetal 7 at cation 9 leads to
À
methylation of terminal alkenes by using TMSCF3 as CF3
thionium intermediate I.[7a,10,12] The formation of C CF3
À
source and PhI
N
bond through reductive elimination of PhI from intermedi-
ate I followed by abstraction of the acidic proton of II along
with the release of HOAc gives trifluoromethylated ketene
dithioacetals 8.[10–12,16]
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M. Wang, Q. Liu et al.
and KF, respectively, to 4.0 equivalents. Similarly, 3-tri
ACHTUNGTRENNUNGfluACHTUNGTRENNUNGo-
A
R
ACHTUNGTRENNUNG
good yields (Scheme 2). Long reaction times proved to
make the reaction complex.
Scheme 1. Proposed mechanism for the electrophilic trifluoromethylation
of ketene dithioacetals 7.
In fact, iodonium cation 9’ [Eq. (1)], the equivalent of 9
À
generated from Togniꢁs reagent by cleavage of the I O
bond by a Lewis acid, has been speculated to act as an
active “CF3+” species in the electrophilic trifluoromethyla-
tions of alkenes.[7h,13,15] The zinc dicarboxylato complex
based on 9’ was also detected by ESI-MS spectrum in
Togniꢁs work.[7a] Comparatively, PhI
N
ACHTUNGTREN(NUNG OAc) (6a) and
ACHTUNGTRENNUNG
“CF3+” source. No Lewis acid activator is required for the
acyclic 6a during the process (Scheme 1). As a comparison
to our strategy, the reaction of 7a (0.2 mmol) with Togniꢁs
reagent 4a or b (2.0 equiv) in MeCN (1.0 mL) was carried
out. No reaction was detectable by stirring the reaction mix-
Scheme 2. Synthesis of 3-trifluoromethyl indoles 11.
ture under N2 at room temperature for 3.0 h. Clearly, we
+
provide here a new and simple route to generate “CF3
species that complements Togniꢁs reagent.
”
As shown in Scheme 1, the 3-trifluoromethylation of in-
doles 11 likely involves a similar pathway, including the for-
mation of 9, nucleophilic attack of the nucleophilic C3 atom
À
of 10 at 9, and the formation of C3 CF3 bond with reductive
elimination of PhI followed by rearomatization to give 3-tri-
fluoromethyl indoles 11 (Scheme 2). Additional comparisons
were also run to evaluate the performance of Togniꢁs re-
agent in this process. However, upon treatment of either 1-
methyl indole, 1,3-dimethyl indole or 1,2-dimethyl indole
with either Togniꢁs reagent 4a or b (2.0 equiv), respectively,
under the identified conditions as above, no reactions were
observed at room temperature for 5.0 h in all cases.
Prompted by knowing the performance of the in-situ gen-
erated electrophilic trifluoromethylating species 9[17] and by
emphasizing the simplicity of the methodology, the oxidative
Mu and co-workers reported that 3-trifluoromethyl indole
(11a) was isolated in 65% yield by treatment of indole
2
À
sp C H trifluoromethylation of indoles was then exam
A
in-
(10a) with PhI
methylpiper dine 1-oxyl), and CsF in the presence of Pd-
(OAc)2 (10 mol%) and a ligand in MeCN at room tempera-
ACHTUNGTRNE(NUNG OAc)2, TMSCF3, TEMPO (2,2,6,6-tetra-
ed.[2h,k,7e,f,14b,18,19] Fortunately, under identical conditions
A
E
N
ACHTUNGTRNENUNG ACHTNUREGTNNUNGiACTUHNGTRENNUGN
(Table 2) for 0.5 h, N-methyl indole gave the 2- and 3-tri-
fluoromethylated products in 8.0 and 20% isolated yields,
respectively. This result, together with the above observa-
tions, are in well accordance with the electrophilic character
of phenyl(trifluoromethyl)iodonium cation 9, since the 3-po-
sition of indole is the preferred site for electrophilic
attack.[20] To simplify the regioselectivity problem, 1,2-di-
methyl indole (10a) was selected as a model nucleophile. As
we expected, upon treatment of 10a under standard reaction
conditions for 10 min, 1,2-dimethyl-3-(trifluoromethyl)-
indole (11a) was obtained in 61% yield. The yield of 11a
was raised to 76% by increasing the amounts of TMSCF3
ACHTUNGTRENNUNG
ture for 6.0 h.19a They also found that Umemotoꢁs reagent
2[21] and Togniꢁs reagent 4a were inappropriate for the Pd-
catalyzed oxidative trifluoromethylation of indoles.[19a]
Therefore, the trifluoromethylation in our work provides
further support for the reactivity of the electrophilic iodoni-
um species 9 toward both nucleophilic vinyl and electron-
2
À
rich heteroaryl sp C H bonds under mild transition-metal-
free conditions.[22]
It has been shown that the cyclic hypervalent iodine com-
pounds 4 developed by Togni and co-workers in 2006 are
very useful electrophilic trifluoromethylating reagents. In
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In Situ Generation of PhI+CF3
COMMUNICATION
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ACHTUNGTRENfUNG luACHTUNGTRENNUNGoACHTUNGTRENNUNGroACHTUNGTRENNUNGmethACHTUNGTRENNUNGyl-
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+
2
À
PhI CF3, the direct sp C H trifluoromethylation of ketene
dithioacetals and indoles are successful in terms of the re-
gioselectivity, product yields, tolerance to a broad range of
functional groups. Additionally, these reactions can be car-
ried out at room temperature and do not require any cata-
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2
À
lyst. Critical to the success of the sp C H trifluoromethyla-
tion was the generation of “CF3+” source by a more conven-
ient route. Although the participation of PhI+CF3 as new
trifluoromethylating reagent in trifluoromethylations needs
to be developed, we expect that the results presented here
will provide a greater understanding of the performance of
the acyclic aryl(trifluoromethyl)iodonium compounds for in-
corporation of trifluoromethyl group into organic structures.
Investigations on more evidences for the generation of acy-
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Experimental Section
General procedure for the trifluoromethylation of ketene dithioacetals 7
(with the reaction of 7a as an example): To a 15 mL dried poly
ACHTUNGTRENtGNUN etraACHTUNGTREGfNNUN luACTHNUGTRENoNUNG -
A
E
N
ACHTUNGTRENNUNG
1.0 mmol) and 7a (80 mg, 0.5 mmol) in sequence. The glass vial was
transferred to glove box to add KF (58 mg, 1.0 mmol) and anhydrous
MeCN (3.0 mL) and then closed tightly. After taking the glass vial out of
the glove box, TMSCF3 (0.148 mL, 1.0 mmol) was immediately added
using a syringe. The resulting mixture was then stirred at room tempera-
ture and monitored by thin layer chromatography. After complete con-
sumption of substrates (within 0.5 h), the mixture was evaporated to
remove the solvent. The residue was purified through silica gel chroma-
tography (eluent=petroleum ether/ethyl acetate: 15:1, v/v), to give 8a
(100 mg, 88%) as a light yellow solid.
Acknowledgements
We gratefully acknowledge the National Natural Sciences Foundation of
China (21272034 and 21172031) and New Century Excellent Talents in
Chinese University (NCET-11–0613) for financial support.
Keywords: alkenes
· indoles · metal-free · synthetic
methods · trifluoromethylation
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Chem. Eur. J. 2013, 00, 0 – 0
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www.chemeurj.org
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M. Wang, Q. Liu et al.
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The N-directing effect was proposed for the easier transfer of the
CF3 unit into the 2-position of indoles. On the contrary, the tri
ACHTUNGTRENNUNGfluACHTUNGTRENNUNGo-
A
R
ACHTUNGTRNENUNG ACHTNUREGTNNUNGaACTUHNGTRENNUGN
indoles. It indicates that our reactions may undergo an alternative
route and is likely to involve a usual electrophilic-substitution reac-
tion in which the stronger nucleophilicity of the 3-site of indole is
preferentially attacked by the electrophilic “CF3+” species in the ab-
sence of catalyst.
[16] We also doped the trifluoromethylation reaction of 7a under the
identical reaction conditions with 2,2,6,6-tetramethyl-1-piperidin
ACHTUNGERTNyNUNG l-
ACHTUNGTRENNUNGoxy (TEMPO, 0.5 equiv), a well-known radical scavenger. The ex-
periments showed that 8a was obtained in 84% yield in 0.5 h,
nearly the same as described in Table 1, entry 9 (88%). However,
lower yield of 8a (30%) was afforded by increasing the amounts of
TEMPO to one equivalent. It may be due to the consumption of the
oxidant PhIACHTUNGTRENNUNG(OAc)2 for the formation of oxoammonium salt and hy-
droxylamine from TEMPO under acidic conditions. T. Vogler, A.
Studer, Synthesis 2008, 1979–1993.
[21] Umemotoꢁs reagent 2 can be used in PdII-catalyzed ortho trifluoro-
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[22] We also tested the trifluoromethylations of arenes by using the com-
[17] W. Liu, X. Huang, M.-J. Cheng, R. J. Nielsen, W. A. Goddard III,
J. T. Groves, Science 2012, 337, 1322–1325.
bination of TMSCF3 with PhIACTHNGUTERN(UNG OAc)2 and KF without any catalyst. It
was found that those arenes with more electron-rich group, for ex-
ample, 1,3,5-trimethoxybenzene, and 1,2,4-trimethoxybenzene could
gave the desired mono-trifluoromethylated products in good isolat-
ed yields (80% and 59%, respectively) within 1.0 h under the stand-
ard conditions.
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Ko, E. J. Cho, Tetrahedron Lett. 2012, 53, 2005–2008.
[20] In fact, we have been aware that most investigations on the tri
G
G
Received: April 25, 2013
A
E
E
U
N
Published online: && &&, 0000
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www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
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These are not the final page numbers!

In Situ Generation of PhI+CF3
COMMUNICATION
Synthetic Methods
C. Xu, J. Liu, W. Ming, Y. Liu, J. Liu,
M. Wang,* Q. Liu* .......... &&&& — &&&&
These things are sent to tri us: The
introduction of CF3 units into organic
molecules is important and requires
the development of convenient tri-
fluoromethylating reagents. Here,
PhI+CF3, an acyclic electrophilic
“CF3+” species, is described, including
its in situ generation from TMSCF3,
In Situ Generation of PhI+CF3 and
Transition-Metal-Free Oxidative sp2
À
PhIACTHNURTGNENUG(OAc)2, and KF and its direct
C H Trifluoromethylation
2
À
applications in sp C H trifluorome-
thylations under mild transition-metal-
free conditions (see scheme).
Trifluoromethylation
Useful electrophilic trifluoromethylating reagents based
on cyclic hypervalent iodine were developed by Togni in
2006. However, their simple acyclic analogues have not
yet been identified. In their Communication on page &
& ff., M. Wang, Q. Liu et al. describe an acyclic
“PhI+CF3” species, nearly 35 years after its conception as
an electrophilic trifluoromethylating reagent by Yagupol-
skii in 1978. The compound’s in situ generation and direct
2
À
applications in sp C H trifluoromethylations are
discussed.
Chem. Eur. J. 2013, 00, 0 – 0
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
7
&
ÞÞ
These are not the final page numbers!