Conversion of aromatic amino into trifluoromethyl groups through a Sandmeyer-type transformation

Article abstract of DOI:10.1055/s-0033-1338659

A novel strategy for aromatic trifluoromethylation by converting amino into trifluoromethyl groups via a Sandmeyer-type reaction is reported. The transformation involves diazotization of the aromatic amines with tert-butyl nitrite and hydrochloric acid to form aryldiazonium chlorides, followed by trifluoromethylation with trifluoromethylsilver at low temperature. Various readily available aromatic amines are smoothly converted under mild conditions. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0033-1338659

PRACTICAL SYNTHETIC PROCEDURES
▌2143
pCraoctincavl seynrthseitioc nprocoefdurAesromatic Amino into Trifluoromethyl Groups through a
Sandmeyer-Type Transformation
Conversion of Aromatic Amino into Trifluoromethyl Groups
Xi Wang, Yan Xu, Yujing Zhou, Yan Zhang, Jianbo Wang*
Beijing National Laboratory of Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, College of Chemistry, Peking University, Beijing 100871, P. R. of China
Fax +86(10)62751708; E-mail: wangjb@pku.edu.cn
PSP
Received: 18.03.2014; Accepted after revision: 12.06.2014
No277
Abstract: A novel strategy for aromatic trifluoromethylation by converting amino into trifluoromethyl groups via a Sandmeyer-type reac-
tion is reported. The transformation involves diazotization of the aromatic amines with tert-butyl nitrite and hydrochloric acid to form
aryldiazonium chlorides, followed by trifluoromethylation with trifluoromethylsilver at low temperature. Various readily available aromat-
ic amines are smoothly converted under mild conditions.
Key words: trifluoromethylation, aromatic amines, diazonium salts, silver, Sandmeyer reaction
EtCN
AgF
+
TMSCF3
[AgCF3]
+
TMSF
mixed at –78 °C
then warm to r.t.
aq HCl (2.0 equiv)
[AgCF3]
t-BuONO (1.1 equiv)
R
R
R
–
+
dropwise at –78 °C
then r.t., 1 h
0 °C, 15 min
NH2
N2Cl
CF3
1
2
3
Scheme 1 Procedure 1
friendly and mild trifluoromethylation methods using var-
ious trifluoromethylation reagents have been established
1
Introduction
Currently, trifluoromethylated arenes are receiving wide as the alternatives to Swarts-type reactions. A commonly
attention in the fields of pharmaceutical, agrochemical, applied method is the conversion of halogen4 or boron5
and material sciences. A considerable number of biologi-
cally active compounds contain the trifluoromethyl group,
as shown by the examples in Figure 1. The unique proper-
Me
H
O
N
N
ties of the trifluoromethyl group include high electroneg-
ativity, lipophilicity, and metabolic stability.1 However,
trifluoromethylated arenes do not exist in nature, which
accounts for the vital importance of exploring novel meth-
ods for incorporation of the trifluoromethyl group onto or-
ganic moieties.2
Me
HCl
CF3
F3C
O
fluoxetine (Prozac®)
fluridone
O
N
Cl
Large-scale industrial production of trifluoromethylated
aromatic building blocks relies on a Swarts-type reaction,
which involves exhaustive chlorination of a methyl group
at the benzylic position, followed by Cl/F exchange on the
resulting (trichloromethyl)arene with hydrogen fluoride;
however, Swarts-type transformations suffer drawbacks
such as the use of hazardous reagents, the generation of
environmentally harmful waste, and the harsh reaction
conditions.3 In the past decades, many environmentally
Br
O
CO2H
CF3
H
OH
F3C
NO2
Br
acifluorfen
O
fluorosalan
CF3
O
O
H
HN
Me2N
N
H
CF3
H
N
H
H
CF3
H
dutasteride (Avodart®)
fluometuron
SYNTHESIS 2014, 46, 2143–2148
Advanced online publication: 24.07.2014
DOI: 10.1055/s-0033-1338659; Art ID: ss-2014-z0188-psp
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
Figure 1 Examples of biologically active compounds containing the
trifluoromethyl group

2144
X. Wang et al.
PRACTICAL SYNTHETIC PROCEDURES
substituents into trifluoromethyl groups via palladium- the aniline derivatives with an electron-donating group at
catalyzed or copper-mediated/copper-catalyzed reactions. the para position underwent transformation to give prod-
Additionally, a direct approach to introducing a trifluoro- uct 3b–d in moderate yields (entries 2–4). In contrast, an-
methyl group is transition-metal-catalyzed or transition- iline and aromatic amine derivatives bearing an electron-
metal-free direct C–H aromatic trifluoromethylation withdrawing group at the para position were converted
based on a radical process.6,7
into the corresponding product 3a, 3f–k in good to excel-
lent yields (entries 1 and 6–11). Sensitive functional
groups are tolerated in this reaction, including unprotected
carboxylic, vinyl, alkynyl, pinacolatoboryl (Bpin), and
trimethylsilyl groups (3l–s, entries 12–19). meta-Substi-
tuted anilines show moderate reactivity (3t–w, entries 20–
23); notably, trifluoromethylation of the unprotected ben-
zylic alcohol substrate was successful (entry 23). The
transformation is not sensitive to steric hindrance since
ortho-substituted bulky isopropyl group and ester aniline
substrates were trifluoromethylated without a decrease in
the yield (3x, 3y; entries 24 and 25). In the case of the sub-
strate containing a pyridine moiety, the conversion afford-
ed a very low yield of the product 3zb (entry 28),
presumably due to strong coordination of the pyridine ni-
trogen to the trifluoromethylsilver or low solubility of the
corresponding diazonium salt in the acidic conditions.
The trifluoromethylation process can also be applied to
heteroaromatic amines derivatives, such as indoles and
benzofurans (3zc–zf, entries 29–32). Furthermore, it was
found that the trifluoromethylation reaction worked prop-
erly with di- and multisubstituted anilines, in generally
moderate to good yields (3zg–zr, entries 33–44). Among
these, the highly electron-rich 3,4,5-trimethoxyaniline is
compatible with the reaction conditions, giving the single
trifluoromethylation product 3zo in moderate yield (entry
41).
Although remarkable achievements have been made on
aromatic trifluoromethylation, most current methods still
suffer from some drawbacks, such as harsh reaction con-
ditions, limited functional group compatibility, and the
use of expensive trifluoromethylation reagents or transi-
tion-metal catalysts/ligands. Therefore, it is highly
desirable to develop new methods for aromatic trifluoro-
methylation.
To this end, we disclose herein a novel approach to aro-
matic Sandmeyer-type trifluoromethylation via the direct
conversion of an aromatic amino group into a trifluoro-
methyl group (Scheme 1).8,9
The trifluoromethyl group in trifluoromethylsilver com-
plex, [AgCF3], exhibits a strong σ-donor nature, making
the silver center more electron rich.2e Accordingly, we
speculated that trifluoromethylsilver could undergo oxi-
dative addition by the resultant aryldiazonium chloride 2
to form the high-valent silver intermediate A, from which
reductive elimination would construct the Caryl–CF3 bond
and form a silver chloride precipitate (Scheme 2).10
[AgCF3]
R
R
–
+
oxidative
addition
diazotization
NH2
N2Cl
1
2
In addition, it was found that conversion of an amino
group embedded in the estrone or tocopherol skeleton into
the corresponding trifluoromethyl group is smooth,
demonstrating the potential applicability of this novel
method in more complicated molecules (Figure 2).
R
R
CF3
Ag
– AgCl
reductive
elimination
CF3
Cl
A
3
Moreover, reactions performed on a gram-scale afforded
the trifluoromethylated products with no obvious influ-
ence on the yields, as demonstrated by the 9-mmol scale
and 40-mmol scale trifluoromethylation of ethyl 4-amino-
benzoate (1i) with trifluoromethylsilver in 90% and 75%
Scheme 2 Proposed strategy for silver-mediated Sandmeyer-type
trifluoromethylation
2
Scope and Limitations
According to the modification of previous reports by Tyrra
and co-workers,11 trifluoromethylsilver complex12 can be
synthesized in approximately quantitative yield by the re-
action of silver fluoride and trimethyl(trifluoromethyl)si-
O
H
H
H
lane
(TMSCF3,
Ruppert–Prakash
reagent)
in
propionitrile.13,14 The aryldiazonium chloride was pre-
pared by reaction of the corresponding aniline with con-
centrated hydrochloric acid and tert-butyl nitrite (t-
BuONO) in propionitrile.15
F3C
3zs, 57%
CF3
O
Trifluoromethylation of aryldiazonium chlorides pro-
ceeded smoothly upon slow addition of freshly prepared
trifluoromethylsilver at –78 °C, to give the corresponding
trifluoromethylated arenes (Procedure 1).16 As shown in
Table 1, a wide range of structurally diverse aromatic
amines are appropriate as reaction substrates. Generally,
O
( )3
( )3
O
3zt, 72%
Figure 2 Conversion of amino groups embedded in the estrone and
tocopherol frameworks into trifluoromethyl groups
Synthesis 2014, 46, 2143–2148
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Conversion of Aromatic Amino into Trifluoromethyl Groups
2145
yield, respectively (Scheme 3, see Procedure 2 for de- methyl groups successively by using our previously re-
tails).
ported metal-free borylation method17 and the current
trifluoromethylation reaction (Scheme 4).
Finally, we have successfully converted the two amino
groups of benzene-1,4-diamine into Bpin and trifluoro-
Table 1 Trifluoromethylation of Various Aromatic Aminesa
aq HCl (2.0 equiv)
[AgCF3]
dropwise at –78 °C
t-BuONO (1.1 equiv)
R
R
R
+
–
0 °C, 15 min
N2Cl
NH2
CF3
then r.t., 1 h
1
2
3
Entry Product
Yieldb (%) Entry Product
Yieldb (%) Entry Product
Yieldb (%)
TMS
1
3a, 96c
16
3p, 97
31
3ze, 72
N
Ts
CF3
CF3
CF3
TIPS
TMS
n-C6H13
F3C
CO2Et
2
3b, 63
3c, 53
3d, 73
3e, 59
3f, 95c
17
18
19
20
21
3q, 83
3r, 90c
3s, 54
3t, 74
3u, 62
32
33
34
35
36
3zf, 55
3zg, 86
3zh, 61
3zi, 70
3zj, 84
O
CF3
CF3
O2N
O2N
O2N
BnO
3
CF3
Cl
CF3
CF3
CF3
Me
N
4
pinB
Ph
O
CF3
CF3
n-C6H13
S
OMe
5
6
CF3
CF3
CF3
NO2
Br
BnO
CF3
CF3
CF3
NO2
F
Cl
7
8
3g, 85c
3h, 90
3i, 80
22
23
24
25
26
3v, 43
3w, 70
3x, 83c
3y, 80
3z, 51
37
38
39
40
41
3zk, 81
3zl, 71
3zm, 83
3zn, 83
3zo, 47
AcHN
CF3
CF3
CF3
Cl
EtO3S
EtO2C
I
HOH2C
CF3
CF3
CF3
CO2Me
i-Pr
MeO
9
CF3
CF3
CF3
CO2Me
O
CO2Et
CF3
Ph
10
11
3j, 87
3k, 78
CF3
MeO2C
CF3
O
OMe
MeO
MeO
N
CF3
CF3
CF3
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2143–2148

2146
X. Wang et al.
PRACTICAL SYNTHETIC PROCEDURES
Table 1 Trifluoromethylation of Various Aromatic Aminesa (continued)
aq HCl (2.0 equiv)
t-BuONO (1.1 equiv)
[AgCF3]
R
R
R
+
–
0 °C, 15 min
dropwise at –78 °C
then r.t., 1 h
N2Cl
NH2
CF3
1
2
3
Entry Product
Yieldb (%) Entry Product
Yieldb (%) Entry Product
Yieldb (%)
Cl
CF3
HO2C
OMe
12
3l, 80c
27
28
3za, 52
42
3zp, 82
CF3
Cl
CF3
O
Ph
N
CF3
N
O
13
3m, 58
3n, 71
3zb, 10c
43
44
3zq, 93
3zr, 70
CF3
N
O
CF3
O
CF3
EtO2C
F3C
14
15
29
30
3zc, 65
3zd, 45
O
CF3
N
Ts
F3C
3o, 50c
N
CF3
Ts
a Reaction conditions: see Procedure 1 for details.
b Yield refers to the isolated product, unless otherwise noted.
c Yield is based on the 19F NMR spectrum with 4-F3COC6H4OMe as internal standard.
EtO2C
1) diazotization
2) [AgCF3]
EtO2C
Details of the reagents, preparation of starting materials, general an-
alytical information, and corresponding analytical data can be found
in the literature.16a
CF3
3i (1.76 g, 90%)
NH2
1i (9 mmol)
(40 mmol)
Typical experimental procedures for the various aromatic amine
substrates shown in Table 1 and the scaled-up trifluoromethylations
shown in Scheme 3 are described below.
(6.54 g, 75%)
Scheme 3 Gram-scale trifluoromethylation
Trifluoromethylation Procedure 1 (Table 1); General Proce-
dure16a
Bpin
Bpin
NH2
NH2
An oven-dried Schlenk tube (A) equipped with a magnetic stir bar
was charged with AgF (132.2 mg, 1.05 mmol, 3.5 equiv), sealed
with a septum, and degassed by alternating vacuum evacuation and
nitrogen backfill (three times) before freshly distilled EtCN (3 mL)
was added. To the resulting suspension, which was precooled to
–78 °C (dry ice–acetone bath), was added TMSCF3 (149.3 mg, 1.05
mmol, 3.5 equiv) by microsyringe. The mixture was allowed to
warm to r.t. and stirring was continued for an additional 15 min. In
due course, AgF solid dissolved and a gray, dark solution of [Ag-
CF3] formed. Another Schlenk tube (B) equipped with a magnetic
stir bar was charged with the aniline (ArNH2; 0.30 mmol, 1.0 equiv)
in freshly distilled EtCN (1.5 mL). To the resulting solution, which
was precooled to 0 °C (ice bath), aq HCl (12 M; 50.0 μL, 0.60
mmol, 2.0 equiv) was added; precipitate formed immediately. After
5 min stirring, t-BuONO (37.7 mg, 0.33 mmol, 1.1 equiv) was add-
t-BuONO (1.1 equiv)
1) diazotization
B2pin2 (1.1 equiv)
MeCN, 80 °C, 2 h
62%
2) [AgCF3]
62%
CF3
NH2
3zu
3zv
Scheme 4 Conversion of the two amino groups of benzene-1,4-di-
amine into Bpin and trifluoromethyl groups
3
Summary
A general and practical trifluoromethylation method has
been established. The reaction, which can be regarded as ed by microsyringe, and the mixture was allowed to stir at 0 °C for
15 min. The resulting suspension in Schlenk tube (B) was degassed
by alternating vacuum evacuation at –196 °C (liquid nitrogen), then
the solution was allowed to warm to r.t. under a nitrogen atmo-
sphere (three times), and finally cooled to –78 °C (dry ice–acetone
the trifluoromethylation variation of the Sandmeyer reac-
tion, proceeds under mild conditions with excellent func-
tional group compatibility. The aromatic amine substrates
are commonly used and readily available. Furthermore,
bath). The gray, dark solution of [AgCF3] in Schlenk tube (A),
the amino group can be conveniently protected and depro-
tected, rendering this strategy appropriate for late-stage
incorporation of a trifluoromethyl group onto an aromatic
moiety.
which was precooled to –78 °C (dry ice–acetone bath), was added
+
to Schlenk tube (B) (ArN2 Cl–) by syringe at –78 °C (dry ice–ace-
tone bath) over a period of 1 h. After the addition was complete, the
reaction mixture was stirred for 3 h at –78 °C (dry ice–acetone
Synthesis 2014, 46, 2143–2148
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Conversion of Aromatic Amino into Trifluoromethyl Groups
2147
bath), allowed to warm to r.t., and stirring was continued for an ad-
ditional 1 h. An off-white precipitate was observed, and the reaction
mixture was diluted with EtOAc (3 mL) and filtered through a short
silica gel column. The solvent was removed under reduced pressure
with a rotatory evaporator, and the crude residue was purified by sil-
ica gel column chromatography to give the desired trifluoromethyl-
ation product 3. The yields of products 3a, 3f, 3g, 3l, 3o, 3r, 3x, and
3zb are based on the 19F NMR spectra with 4-F3COC6H4OMe as in-
ternal standard. Analytical data for the representative product ethyl
4-(trifluoromethyl)benzoate (3i) are provided below. Data for other
products can be found in the literature.16a
(4.00 g, 31.5 mmol, 3.5 equiv), EtCN (30 mL), TMSCF3 (4.47 g,
31.5 mmol, 3.5 equiv); 150-mL Schlenk flask (B): ethyl 4-amino-
benzoate (1i; 1.49 g, 9.00 mmol, 1.0 equiv), EtCN (20 mL), aq HCl
(12 M; 1.5 mL, 18.0 mmol, 2.0 equiv), t-BuONO (1.13 g, 9.9 mmol,
1.1 equiv); workup: EtOAc (90 mL). The reaction afforded ethyl 4-
(trifluoromethyl)benzoate (3i); yield: 1.76 g (90%).
Experiment with 40 mmol of substrate 1i: the reaction was under-
taken using Procedure 2 with a 250-mL Schlenk flask (A): AgF
(17.63 g, 140.0 mmol, 3.5 equiv), EtCN (80 mL), TMSCF3 (19.89
g, 140.0 mmol, 3.5 equiv); 500-mL Schlenk flask (B): ethyl 4-ami-
nobenzoate (1i; 6.61 g, 40.0 mmol, 1.0 equiv), EtCN (60 mL), aq
HCl (12 M; 6.67 mL, 80.0 mmol, 2.0 equiv), t-BuONO (5.04 g, 44.0
mmol, 1.1 equiv); workup: EtOAc (200 mL). The reaction afforded
ethyl 4-(trifluoromethyl)benzoate (3i); yield: 6.54 g (75%).
Ethyl 4-(Trifluoromethyl)benzoate (3i)16a
Light yellow oil; yield: 52.5 mg (0.241 mmol, 80%); Rf = 0.60 (pe-
troleum ether–EtOAc, 20:1).
IR (film): 1723, 1326, 1276, 1128, 1101, 775, 704 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.16 (d, J = 8.2 Hz, 2 H), 7.70 (d,
J = 8.2 Hz, 2 H), 4.42 (q, J = 7.1 Hz, 2 H), 1.42 (t, J = 7.1 Hz, 3 H).
Acknowledgment
The project was supported by the National Basic Research Program
of China (973 Program, No. 2012CB821600) and the Natural Scien-
ce Foundation of China (Grants 21332002, 21272010, and
21172005).
13C NMR (101 MHz, CDCl3): δ = 165.4, 134.3 (q, J2 = 32.7 Hz),
133.7, 129.9, 125.3 (q, J3 = 3.7 Hz), 123.7 (q, J1 = 272.7 Hz), 61.5,
14.2.
19F NMR (470 MHz, CDCl3): δ = –63.3 (s, 3 F).
MS (EI, 70 eV): m/z (%) = 218 (17) [M+], 199 (16), 190 (36), 173
(100), 145 (83), 125 (17), 95 (20), 75 (19).
Supporting Information for this article is available online
at
http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000084.SunogIpimrfiantoSuIpg
n
fonirtat
ori
Trifluoromethylation Procedure 2 (Scheme 3)16a
A Schlenk flask (A) equipped with a magnetic stir bar was charged
with AgF (3.5 equiv), sealed with a septum, and degassed by alter-
nating vacuum evacuation and nitrogen backfill (three times) before
freshly distilled EtCN was added. To the resulting suspension,
which was precooled to –78 °C (dry ice–acetone bath), was added
TMSCF3 (3.5 equiv) by syringe. The mixture was allowed to warm
to r.t. and stirring was continued for an additional 30 min. In the due
course, AgF solid dissolved and a gray, dark solution of [AgCF3]
was formed. Another Schlenk flask (B) equipped with a magnetic
stir bar was charged with ethyl 4-aminobenzoate (1i, 1.0 equiv),
sealed with a septum, and degassed by alternating vacuum evacua-
tion and nitrogen backfill (three times) before freshly distilled EtCN
was added. To the resulting solution, which was precooled to 0 °C
(ice bath), aq HCl (12 M, 2.0 equiv) was added and the mixture was
stirred for 10 min. t-BuONO (1.1 equiv) was then added by syringe.
The mixture was allowed to stir at 0 °C for 30 min. The resulting
solution in Schlenk flask (B) was cooled to –78 °C (dry ice–acetone
bath). The gray, dark solution of [AgCF3] in Schlenk flask (A),
which was precooled to –78 °C (dry ice–acetone bath), was added
References
(1) (a) Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis,
Reactivity, Applications; Wiley-VCH: Weinheim, 2004.
(b) Müller, K.; Faeh, C.; Diederich, F. Science 2007, 317,
1881.
(2) For reviews, see: (a) Prakash, G. K. S.; Yudin, A. K. Chem.
Rev. 1997, 97, 757. (b) Shimizu, M.; Hiyama, T. Angew.
Chem. Int. Ed. 2005, 44, 214. (c) Schlosser, M. Angew.
Chem. Int. Ed. 2006, 45, 5432. (d) Ma, J.-A.; Cahard, D.
J. Fluorine Chem. 2007, 128, 975. (e) Ma, J.-A.; Cahard, D.
Chem. Rev. 2008, 108, PR1. (f) Tomashenko, O. A.;
Grushin, V. V. Chem. Rev. 2011, 111, 4475. (g) Besset, T.;
Schneider, C.; Cahard, D. Angew. Chem. Int. Ed. 2012, 51,
5048. (h) Macé, Y.; Magnier, E. Eur. J. Org. Chem. 2012,
2479. (i) Shibata, N.; Matsnev, A.; Cahard, D. Beilstein J.
Org. Chem. 2010, 6, 65. (j) Wu, X. F.; Neumann, H.; Beller,
M. Chem. Asian J. 2012, 7, 1744. (k) Studer, A. Angew.
Chem. Int. Ed. 2012, 51, 8950. (l) Liang, T.; Neumann, C.
N.; Ritter, T. Angew. Chem. Int. Ed. 2013, 52, 8214.
(3) Swarts, F. Bull. Soc. Chim. Belg. 1892, 24, 309.
(4) (a) McLoughlin, V. C. R.; Thrower, J. Tetrahedron 1969,
25, 5921. (b) Chen, Q.-Y.; Wu, S.-W. J. Chem. Soc., Chem.
Commun. 1989, 705. (c) Chen, Q.-Y.; Duan, J.-X. J. Chem.
Soc., Chem. Commun. 1993, 1389. (d) Oishi, M.; Kondo, H.;
Amii, H. Chem. Commun. 2009, 1909. (e) Cho, E. J.;
Senecal, T. D.; Kinzel, T.; Zhang, Y.; Watson, D. A.;
Buchwald, S. L. Science 2010, 328, 1679.
+
over a period of 2 h to Schlenk flask (B) (4-EtO2CC6H4N2 Cl–) by
syringe. After the addition was complete, the reaction mixture was
stirred for 3 h at –78 °C (dry ice–acetone bath). The mixture was
then allowed to warm to r.t., and stirring was continued for an addi-
tional 1 h. An off-white precipitate was observed, and the reaction
mixture was diluted with EtOAc and filtered through a short silica
gel column. The solvent was removed under reduced pressure with
a rotatory evaporator, and the crude residue was purified by silica
gel column chromatography (petroleum ether–EtOAc, 50:1) to give
ethyl 4-(trifluoromethyl)benzoate (3i) as a light yellow oil.
Note: Rigorous degassing is not necessary for the reaction itself.
The degassing was performed for removing the extra HCl, which
corrodes the stainless steel needle of the syringe used for the subse-
quent addition of [AgCF3] solution. For several substrates, we also
carried out the reaction without degassing and comparable yields
were obtained, although the stainless steel needle of the syringe was
corroded in these cases. This problem can be avoided if the addition
of [AgCF3] solution is conducted with a plastic syringe. In large-
scale experiments, a glass funnel was used for adding the [AgCF3]
solution.
(5) (a) Chu, L.; Qing, F.-L. Org. Lett. 2010, 12, 5060.
(b) Senecal, T. D.; Parsons, A. T.; Buchwald, S. L. J. Org.
Chem. 2011, 76, 1174. (c) Liu, T.; Shen, Q. Org. Lett. 2011,
13, 2342. (d) Xu, J.; Luo, D.-F.; Xiao, B.; Liu, Z.-J.; Gong,
T.-J.; Fu, Y.; Liu, L. Chem. Commun. 2011, 47, 4300.
(e) Zhang, C.-P.; Cai, J.; Zhou, C.-B.; Wang, X.-P.; Zheng,
X.; Gu, Y.-C.; Xiao, J.-C. Chem. Commun. 2011, 47, 9516.
(f) Litvinas, N. D.; Fier, P. S.; Hartwig, J. F. Angew. Chem.
Int. Ed. 2012, 51, 536. (g) Novák, P.; Lishchynskyi, A.;
Grushin, V. V. Angew. Chem. Int. Ed. 2012, 51, 7767.
(h) Ye, Y.; Sanford, M. S. J. Am. Chem. Soc. 2012, 134,
9034.
Experiment with 9.0 mmol of substrate 1i: the reaction was under-
taken using Procedure 2 with a 100-mL Schlenk flask (A): AgF
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2143–2148

2148
X. Wang et al.
PRACTICAL SYNTHETIC PROCEDURES
(6) For recent reports, see: (a) Nagib, D. A.; MacMillan, D. W.
C. Nature 2011, 480, 224. (b) Ji, Y.; Brueckl, T.; Baxter, R.
D.; Fujiwara, Y.; Seiple, I. B.; Su, S.; Blackmond, D. G.;
Baran, P. S. Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 14411.
(c) Ye, Y.; Lee, S. H.; Sanford, M. S. Org. Lett. 2011, 13,
5464. (d) Fujiwara, Y.; Dixon, J. A.; O’Hara, F.; Funder, E.
D.; Dixon, D. D.; Rodriguez, R. A.; Baxter, R. D.; Herlé, B.;
Sach, N.; Collins, M. R.; Ishihara, Y.; Baran, P. S. Nature
2012, 492, 95. (e) Studer, A. Angew. Chem. Int. Ed. 2012,
51, 8950.
(7) For trifluoromethylation via transition-metal-catalyzed C–H
bond activation, see: (a) Wang, X.; Truesdale, L.; Yu, J.-Q.
J. Am. Chem. Soc. 2010, 132, 3648. (b) Zhang, X.-G.; Dai,
H.-X.; Wasa, M.; Yu, J.-Q. J. Am. Chem. Soc. 2012, 134,
11948. (c) Hafner, A.; Bräse, S. Angew. Chem. Int. Ed. 2012,
51, 3713. (d) Zhang, L.-S.; Chen, K.; Chen, G.-H.; Li, B.-J.;
Luo, S.; Guo, Q.-Y.; Wei, J.-B.; Shi, Z.-J. Org. Lett. 2013,
15, 10.
(8) For recent reviews on arenediazonium salts, see: (a) Mo, F.;
Dong, G.; Zhang, Y.; Wang, J. Org. Biomol. Chem. 2013,
11, 1582. (b) Hari, D. P.; König, B. Angew. Chem. Int. Ed.
2013, 52, 4734.
(9) (a) Sandmeyer, T. Ber. Dtsch. Chem. Ges. 1884, 17, 1633.
(b) Sandmeyer, T. Ber. Dtsch. Chem. Ges. 1884, 17, 2650.
(c) Balz, G.; Schiemann, G. Ber. Dtsch. Chem. Ges. 1927,
60, 1186.
Harada, S.; Lee, E.; Ritter, T. J. Am. Chem. Soc. 2011, 133,
13308.
(11) Tyrra, W. E. J. Fluorine Chem. 2001, 112, 149.
(12) (a) Naumann, D.; Wessel, W.; Hahn, J.; Tyrra, W.
J. Organomet. Chem. 1997, 547, 79. (b) Eujen, R.; Hoge, B.;
Brauer, D. J. Inorg. Chem. 1997, 36, 1464. (c) Weng, Z.;
Lee, R.; Jia, W.; Yuan, Y.; Wang, W.; Feng, X.; Huang, K.-
W. Organometallics 2011, 30, 3229.
(13) Kremlev, M. M.; Mushta, A. I.; Tyrra, W.; Naumann, D.;
Fischer, H. T. M.; Yagupolskii, Y. L. J. Fluorine Chem.
2007, 128, 1385.
(14) (a) Ruppert, I.; Schlich, K.; Volbach, W. Tetrahedron Lett.
1984, 25, 2195. (b) Prakash, G. K. S.; Krishnamurti, R.;
Olah, G. A. J. Am. Chem. Soc. 1989, 111, 393. (c) Prakash,
G. K. S.; Jog, P. V.; Batamack, P. T. D.; Olah, G. A. Science
2012, 338, 1324.
(15) (a) Doyle, M. P.; Siegfried, B.; Dellaria, J. F. Jr. J. Org.
Chem. 1977, 42, 2426. (b) Doyle, M. P.; Dellaria, J. F. Jr.;
Siegfried, B.; Bishop, S. W. J. Org. Chem. 1977, 42, 3494.
(16) (a) 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. (b) Dai, J.-J.; Fang, C.; Xiao, B.; Yi, J.; Xu, J.;
Liu, Z.-J.; Lu, X.; Liu, L.; Fu, Y. J. Am. Chem. Soc. 2013,
135, 8436. (c) Danoun, G.; Bayarmagnai, B.; Grünberg, M.
F.; Gooßen, L. J. Angew. Chem. Int. Ed. 2013, 52, 7972.
(d) Browne, D. L. Angew. Chem. Int. Ed. 2014, 53, 1482.
(17) (a) Mo, F.; Jiang, Y.; Qiu, D.; Zhang, Y.; Wang, J. Angew.
Chem. Int. Ed. 2010, 49, 1846. (b) Qiu, D.; Jin, L.; Zheng,
Z.; Meng, H.; Mo, F.; Wang, X.; Zhang, Y.; Wang, J. J. Org.
Chem. 2013, 78, 1923.
(10) (a) Furuya, T.; Strom, A. E.; Ritter, T. J. Am. Chem. Soc.
2009, 131, 1662. (b) Tang, P.; Furuya, T.; Ritter, T. J. Am.
Chem. Soc. 2010, 132, 12150. (c) Huang, C.; Liang, T.;
Synthesis 2014, 46, 2143–2148
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