Preparation of aromatic triazenes and their application in silver-mediated perfluoroalkylation reactions

Article abstract of DOI:10.1055/s-0033-1341249

Herein, the syntheses of various functionalized 1,3-diisopropyltriaz-1-enes is described. This simple transformation tolerates a vast number of functional groups (e.g., halides) and allows the syntheses of 1,3-diisopropyltriaz-1-enes starting from commercially available aniline derivatives. These substrates are suitable for a range of silver-mediated perfluoroalkylation reactions. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1341249

1448▌
PRACTICAL SYNTHETIC PROCEDURES
practical synthetic procedures
Preparation of Aromatic Triazenes and Their Application in Silver-Mediated
Perfluoroalkylation Reactions
Triazenes in Silver-Mediated Perfluoroalkylation Reactions
Andreas Hafner,a Christoph Hussal,a Stefan Bräse*a,b
a
Institute of Organic Chemistry, KIT-Campus South, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
Fax +49(721)60848581; E-mail: braese@kit.edu
b
Institute of Toxicology and Genetics, KIT, Campus-North, Hermann-von-Helmholtz Platz 1,
76344 Eggenstein-Leopoldshafen, Germany
PSP
Received: 02.04.2014; Accepted after revision: 04.04.2014
No273
Abstract: Herein, the syntheses of various functionalized 1,3-diisopropyltriaz-1-enes is described. This simple transformation tolerates a
vast number of functional groups (e.g., halides) and allows the syntheses of 1,3-diisopropyltriaz-1-enes starting from commercially avail-
able aniline derivatives. These substrates are suitable for a range of silver-mediated perfluoroalkylation reactions.
Key words: alkylation, triazene, perfluoroalkylation, silver , synthetic methods
Procedure 1
N
N
isoamyl nitrite (1.5 equiv)
BF3⋅OEt2 (1.5 equiv)
THF, –20 °C, 2 h
1)
2)
N
NH2
R
R
HN(i-Pr)2 (3.0 equiv)
pyridine–THF
–20 °C to 25 °C, 18 h
1
2
Procedure 2
N
N
N
N
N
N
N
N
N
AgF (4.0 equiv)
CF3
F3C
CF3
TMS-CF3 (2.0 equiv)
R
H
R
R
+
C6F14, 100 °C, 4 h
2
3
4
Procedure 3
COOMe
F
N
N
N
N
F
N
N
F
CF3
F
(4.0 equiv)
R
R
H
AgF (4.0 equiv)
100 °C, 16 h
COOMe
2
5
Scheme 1 General procedures for the preparation of functionalized aromatic triazenes and their application in silver-mediated perfluoroalkyl-
ation reactions
offer unique synthetic opportunities due to the fact that
they are easily converted into a range of functional
Introduction
For years, aromatic triazenes have been used as versatile groups, which makes them interesting building blocks for
compounds in organic chemistry.1 Triazenes, which can chemistry in solution1b,2 as well as on solid support.1a,3 In
be regarded as equivalents of protected diazonium salts, contrast to diazonium salts, aromatic triazenes can be iso-
lated, stored, and are suitable for further transformations
on the aromatic core. For example, metal-catalyzed cross-
SYNTHESIS 2014, 46, 1448–1454
Advanced online publication: 30.04.2014
DOI: 10.1055/s-0033-1341249; Art ID: ss-2014-z0222-psp
© Georg Thieme Verlag Stuttgart · New York
coupling reactions as well as metalation protocols are
known.2b,e More recently, we have reported a number of
silver-mediated perfluoroalkylation reactions of aromatic
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

PRACTICAL SYNTHETIC PROCEDURES
Triazenes in Silver-Mediated Perfluoroalkylation Reactions
1449
triazenes that proceed through simple CH substitution.4
These transformations tolerate a broad range of functional
groups, which, combined with the versatility of the tri-
azene functionality, make them suitable for the synthesis
of a variety of fluorinated aromatic building blocks. Here-
in, we present an optimized one-step synthesis of a range
of functionalized aromatic 1,3-diisopropyltriaz-1-enes
and provide new insights into their use in silver-mediated
perfluoroalkylation reactions (Scheme 1).
Table 1 Synthesis of Aromatic Triazenes 2 from Commercially
Available Aniline Derivatives 1 (continued)
Entry
2
Triazene
Yield (%)a
N
N
N
3
2c
71
Scope and Limitations
Cl
In general, aromatic triazenes can be obtained by two dif-
ferent routes. They can be synthesized from metalated
arenes, an azide and an electrophile, or by converting an-
ilines into diazonium salts, which can then be quenched
with an amine.1b Because various aniline derivatives are
commercial available, we focused on the second ap-
proach. Starting from functionalized anilines, we first
generated the corresponding diazonium salt by using
BF3·OEt2 and isoamyl nitrite, which was then reacted with
diisopropylamine to give the aromatic triazene.5 By using
this optimized procedure, it was possible to obtain a range
of functionalized aromatic triazenes (Table 1) in mostly
good to very good yields. It is noteworthy that this proce-
dure could be easily performed on a gram scale. As al-
ready mentioned, these triazenes are well-suited as
substrates for silver-mediated perfluoroalkylation reac-
tions.
N
N
N
4
2d
77
F
N
N
N
5
6
7
2e
2f
77
94
92
I
N
N
N
Table 1 Synthesis of Aromatic Triazenes 2 from Commercially
Available Aniline Derivatives 1
Cl
Entry
2
Triazene
Yield (%)a
N
N
N
N
2g
N
N
F
1
2a
74
N
N
I
N
8
2h
44
N
N
N
2
2b
76
COOEt
N
N
Br
N
9
2i
71
Br
Br
a Isolated yield.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1448–1454

1450
A. Hafner et al.
PRACTICAL SYNTHETIC PROCEDURES
Trifluoromethyl silver organyls can be easily prepared by When one ortho position was blocked by a previously in-
using (trifluoromethyl)trimethylsilane in the presence of troduced functional group, as in the case of 2e, the corre-
silver(I) fluoride.6 When heated, these species can be used sponding mono-ortho-trifluoromethylated product was
for the generation of trifluoromethyl radicals, which read- still formed as the major product, however the ortho,para-
ily react with aromatic triazenes through simple CH sub- di-trifluoromethylated byproduct could also be isolated.
stitution.4a We showed that these reactions proceed with Furthermore, we could extend this procedure to other per-
high ortho selectivity, especially when para-substituted fluoroalkylation reactions such as pentafluoroethylation,
aromatic triazenes were used (Table 2). In the case of tri- heptafluoropropylation, and ethoxycarbonydifluorometh-
azenes 2b, 2c, 2d and 2h, the corresponding mono-ortho- ylation, which also showed a high preference for the
trifluoromethylated and di-ortho-trifluoromethylated ortho-position.4b
product could be isolated together in very good yields.
More recently, we demonstrated that highly fluorinated
olefins are also useful as perfluoroalkyl sources in this re-
action.4c By using commercially available methyl 2,3,3-
Table 2 Synthesis of Trifluoromethylated Aromatic Triazenes 3 and
trifluoroacrylate (MTA) as a highly fluorinated olefin, it
was possible to synthesize a range of functionalized
methoxycarbonyltetrafluoroethylated aromatic triazenes
(and anisoles). These reactions could be realized by gen-
eration of a perfluoroorgano silver species in situ by nu-
cleophilic regioselective addition of silver(I) fluoride
towards the fluorinated double bond of MTA. Herein, it
was important to work under solvent-free (neat) condi-
tions because side reactions such as the dimerization or
oligomerization of fluorinated olefins in the presence of
nucleophiles are suppressed. To the best of our knowl-
edge, this was the first example of the use of highly fluo-
rinated olefins in metal-mediated perfluoroalkylation of
aromatic substrates. Based on these results, it was possible
to upscale this procedure to >1 mmol scale with compara-
ble yields (Table 3). However, further optimization to en-
able a simpler setup by using atmospheric conditions
instead of an argon atmosphere resulted in reduced yields
(Table 3, entry 3). It is noteworthy that all the silver-
mediated perfluoroalkylation reactions tolerated a broad
range of functional groups including iodides, bromides,
chlorides, fluoride, nitriles, and ethoxycarbonyl groups.
4
Entry
Reactant 2 Product 3
Yield (%)a
N
N
N
1
2b
3b
69 (20)b
CF3
CF3
CF3
Br
N
N
N
2
2c
3c
67 (24)b
Cl
N
N
N
Because of the versatile transformation protocols avail-
able for the triazene moiety (e.g., transformation into fluo-
rides,3 iodides,2e or azides2d), these protocols should find
application in the synthesis of a range of fluorinated build-
ing blocks.
3
4
5
2d
2e
2h
3d
3e
3h
67 (26)b
60 (17)c
53 (19)b
F
In summary, we have reported an optimized protocol for
the synthesis of a range of functionalized aromatic 1,3-di-
isopropyltriaz-1-enes. Furthermore, in analogy to our pre-
vious work, we showed that these triazenes are suitable
substrates for silver-mediated perfluoroalkylation reac-
tions. These reactions, combined with the versatile syn-
thetic nature of the triazene synthon, allow the synthesis
of a range of fluorinated building blocks.
N
N
N
I
CF3
N
N
All reactions (Table 2, Table 3) were carried out under an argon at-
mosphere. All starting materials were purchased from commercial
suppliers and used without further purification unless otherwise
stated. Yields refer to isolated compounds estimated to be >95%
pure as determined by 1H NMR spectroscopic analysis. NMR spec-
tra were recorded on a Bruker AM 400, a Bruker Avance 300 or a
Bruker DRX 500 spectrometer as solutions. Chemical shifts are ex-
pressed in parts per million (ppm, ) downfield from tetramethyl-
silane and are referenced to residual solvent peaks. The signal
structure in 13C NMR was analyzed by DEPT. Electron impact (EI)
N
CF3
COOEt
a Isolated yield.
b Isolated yield of the di-ortho-trifluoromethylated product 4.
c Isolated yield of the di-ortho,para-trifluoromethylated product.
Synthesis 2014, 46, 1448–1454
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Triazenes in Silver-Mediated Perfluoroalkylation Reactions
1451
mL) at –20 °C. The solution was stirred and allowed to warm slowly
to r.t. for an additional 16 h. The reaction was then quenched with
sat. NH4Cl solution, the aqueous phase was extracted twice with
EtOAc and the organic layer was dried over MgSO4. The solvent
was removed in vacuum and the crude product was purified by flash
column chromatography (silica gel).
Table 3 Synthesis of Methoxycarbonylated Aromatic Triazenes 5
Entry
Reactant 2 Product 4
Yield (%)a
N
N
F
Silver-Mediated Trifluoromethylation of Aromatic Triazenes;
General Procedure 2 (GP2)
N
I
CF3
COOMe
A vial equipped with a septum and a stirring bar was charged with
AgF (1.60 mmol) and triazene (0.40 mmol). The reaction vessel
was closed, and perfluorohexane (1 mL) was added by using a sy-
ringe under an argon atmosphere. TMS-CF3 (0.80 mmol) was then
added and the suspension was heated to 100 °C. The reaction mix-
ture was stirred for 4 h, then the solution was cooled to r.t., EtOAc
was added and the solution was stirred for 5 min. The solution was
poured into a flask and silica gel was added. Finally, the solvent was
removed in vacuum and the crude product was purified by flash col-
umn chromatography (silica gel).
1
2a
4a
38
(1.2 mmol)
N
N
F
N
CF3
Silver-Mediated Methoxycarbonyltetrafluoroethylation of Aro-
matic Triazenes; General Procedure 3 (GP3)
2
2b
4b
46
COOMe
A vial equipped with a septum and a stirring bar was charged with
AgF (4.00 equiv) and triazene (1.00 equiv), the reaction vessel was
closed and methyl 2,3,3-trifluoroacrylate (MTA; 4.00 equiv) was
added by using a syringe under an argon atmosphere. The suspen-
sion was heated to 100 °C and stirred for 16 h at 100 °C. The solu-
tion was then cooled to r.t. and EtOAc was added. The solution was
poured into a flask and the vial was rinsed a further two times with
EtOAc. The solvent was removed from the combined washing un-
der vacuum and the crude product was purified by flash column
chromatography (silica gel).
Br
(1.8 mmol)
N
N
N
Cl
3
2f
4f
39b (57)c
Products of Type 2
(E)-1-(4-Iodophenyl)-3,3-diisopropyltriaz-1-ene (2a)
Obtained after flash column chromatography (cyclohexane–EtOAc,
20:1).
CF3
MeOOC
F
(0.4 mmol)
Yield: 2.23 g (74%); orange solid; Rf = 0.70 (cyclohexane–EtOAc,
20:1).
N
N
IR (film): 3452 (vw), 3074 (vw), 2974 (m), 2931 (w), 2871 (vw),
1893 (vw), 1580 (vw), 1475 (m), 1423 (s), 1404 (m), 1389 (m),
1365 (m), 1298 (w), 1263 (vw), 1262 (s), 1195 (w), 1162 (m), 1100
(w), 1001 (w), 854 (vw), 827 (w), 749 (vw), 662 (vw), 577 (vw),
535 (vw), 470 (vw) cm–1.
N
Br
Br
4
2i
4i
35
1H NMR (400 MHz, CDCl3): δ = 1.31 (br s, 12 H, CH3), 4.00 (br s,
3
CF3
1 H, CH), 5.27 (br s, 1 H, CH), 7.18 (d, J = 8.6 Hz, 2 H, Ar-H-2,
MeOOC
Ar-H-6), 7.62 (d, 3J = 8.6 Hz, 2 H, Ar-H-3, Ar-H-5).
F
13C NMR (100 MHz, CDCl3): δ = 19.3 (+, br s, CH3), 23.8 (+, br s,
CH3), 46.0 (+, br s, CH), 48.8 (+, br s, CH), 88.4 (Cquat, C-4), 122.3
(+, CH-2, CH-6), 137.6 (+, CH-3, CH-5), 151.4 (Cquat, C-1).
(1.2 mmol)
a Isolated yield.
b Without argon atmosphere, para/ortho ratio 7.5:1.
MS (70 eV, EI): m/z (%) = 331 (32) [M+], 231 (40) [M+–C6H14N],
c Reaction performed under an argon atmosphere.
203 (100) [M+–C6H14N3].
HRMS (EI): m/z [M+] calcd for C12H18IN3: 331.0545; found:
331.0544.
mass spectrometry was performed by using a Finnigan MAT 95 (70
eV). Infrared spectroscopy (IR) was recorded on a FT-IR Bruker
alpha.
(E)-1-(4-Bromophenyl)-3,3-diisopropyltriaz-1-ene (2b)
Obtained after flash column chromatography (cyclohexane–EtOAc,
10:1).
Synthesis of Aromatic Triazenes; General Procedure 1 (GP1)
A flask equipped with a septum and a stirring bar was charged with
aniline derivative (2.00 g, 1.00 equiv). The flask was closed and
THF (5 mL) was added by using a syringe under an argon atmo-
sphere. The solution was cooled to –20 °C and BF3·OEt2
(1.50 equiv) was added. Isoamyl nitrite (1.50 equiv) was then slow-
ly added under vigorous stirring and the solution was stirred for 2 h
at this temperature. The precipitate was filtered off and washed with
ice-cold Et2O. Without further isolation, the precipitate was then
poured (with MeCN wash) into a freshly a prepared solution con-
taining i-Pr2NH (3.00 equiv) in a mixture of THF–pyridine (9:1, 10
Yield: 2.53 g (76%); red oil; Rf = 0.25 (cyclohexane–EtOAc, 10:1).
IR (film): 3448 (vw), 2975 (m), 2932 (vw), 2871 (vw), 1893 (vw),
1585 (vw), 1478 (vw), 1425 (m), 1404 (m), 1366 (m), 1296 (w),
1194 (w), 1161 (m), 1128 (w), 1099 (w), 1067 (w), 1031 (w), 1004
(w), 914 (vw), 855 (vw), 829 (w), 705 (vw), 670 (vw), 578 (vw),
554 (vw), 534 (vw), 474 (vw), 427 (vw) cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.31 (br s, 12 H, CH3), 4.00 (br s,
3
1 H, CH), 5.26 (br s, 1 H, CH), 7.28 (d, J = 8.6 Hz, 2 H, Ar-H-2,
Ar-H-6), 7.41 (d, 3J = 8.6 Hz, 2 H, Ar-H-3, Ar-H-5).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1448–1454

1452
A. Hafner et al.
PRACTICAL SYNTHETIC PROCEDURES
13C NMR (100 MHz, CDCl3): δ = 19.5 (+, br s, CH3), 23.8 (+, br s,
CH3), 46.0 (+, br s, CH), 48.9 (+, br s, CH), 117.6 (Cquat, C-4), 121.8
(+, CH-2, CH-6), 131.7 (+, CH-3, CH-5), 150.8 (Cquat, C-1).
3J = 8.1 Hz, 4J = 1.6 Hz, 1 H, Ar-H-6), 7.84 (dd, 3J = 7.8 Hz,
4J = 1.4 Hz, 1 H, Ar-H-3).
13C NMR (100 MHz, CDCl3): δ = 19.1 (+, CH3), 23.8 (+, CH3), 47.6
(+, CH), 49.8 (+, CH), 96.7 (Cquat, C-2), 117.3 (+, CH-6), 126.1 (+,
CH-4), 128.5 (+, CH-5), 139.0 (+, CH-3), 150.8 (Cquat, C-1).
MS (70 eV, EI): m/z (%) = 283 (24) [M+], 183 (38) [M+ – C6H14N],
155 (100) [M+ – C6H14N3].
HRMS (EI): m/z [M+] calcd for C12H18BrN3: 283.0684; found:
283.0683.
MS (70 eV, EI): m/z (%) = 331 (35) [M+], 231 (26) [M+ – C6H14N],
203 (100) [M+ – C6H14N3].
HRMS (EI): m/z [M+] calcd for C12H18IN3: 331.0545; found:
331.0544.
(E)-1-(4-Chlorophenyl)-3,3-diisopropyltriaz-1-ene (2c)
Obtained after flash column chromatography (cyclohexane–EtOAc,
10:1).
(E)-1-(2-Chlorophenyl)-3,3-diisopropyltriaz-1-ene (2f)
Obtained after flash column chromatography (cyclohexane–EtOAc,
25:1).
Yield: 2.66 g (71%); red oil; Rf = 0.57 (cyclohexane–EtOAc, 10:1).
IR (film): 2976 (s), 2933 (m), 2872 (w), 1892 (vw), 1647 (vw), 1483
(s), 1428 (s), 1401 (s), 1366 (s), 1297 (m), 1228 (vs), 1194 (m),
1161 (s), 1128 (m), 1088 (s), 1032 (m), 1008 (w), 915 (vw), 855
(vw), 833 (s), 708 (vw), 687 (vw), 633 (vw), 579 (vw), 565 (vw),
535 (w), 486 (w) cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.23 (br s, 12 H, CH3), 3.93 (br s,
1 H, CH), 5.19 (br s, 1 H, CH), 7.18–7.20 (m, 2 H, Ar-H-3, Ar-H-
5), 7.25–7.28 (m, 2 H, Ar-H-2, Ar-H-6).
Yield: 3.55 g (94%); red solid; Rf = 0.50 (cyclohexane–EtOAc,
20:1).
IR (ATR): 3067 (vw), 2974 (w), 2931 (w), 1582 (vw), 1467 (w),
1399 (s), 1368 (m), 1291 (w), 1261 (m), 1222 (m), 1195 (m), 1150
(m), 1128 (m), 1095 (m), 1055 (m), 1030 (m), 912 (w), 858 (w), 768
(m), 740 (m), 719 (w), 693 (w), 631 (w), 584 (w), 549 (m), 522 (m),
457 (w), 429 (w) cm–1.
13C NMR (100 MHz, CDCl3): δ = 19.5 (+, br s, CH3), 23.8 (+, br s,
CH3), 46.2 (+, br s, CH), 48.9 (+, br s, CH), 121.4 (+, CH-3, CH-5),
128.7 (+, CH-2, CH-6), 129.7 (Cquat, C-4), 150.3 (Cquat, C-1).
1H NMR (400 MHz, CDCl3): δ = 1.33–1.34 (m, 12 H, CH3), 4.04
(br s, 1 H, CH), 5.23 (br s, 1 H, CH), 7.02–7.06 (m, 1 H, Ar-H-5),
7.19–7.23 (m, 1 H, Ar-H-4), 7.39–7.41 (m, 1 H, Ar-H-6), 7.44–7.47
(m, 1 H, Ar-H-3).
13C NMR (100 MHz, CDCl3): δ = 19.0 (+, CH3), 23.7 (+, CH3), 47.0
(+, CH), 49.7 (+, CH), 118.2 (+, CH-6), 125.2 (+, CH-4), 126.9 (+,
CH-5), 129.1 (Cquat, C-2), 129.9 (+, CH-3), 147.9 (Cquat, C-1).
MS (70 eV, EI): m/z (%) = 239 (35) [M+], 139 (39) [M+ – C6H14N],
111 (100) [M+ – C6H14N3].
HRMS (EI): m/z [M+] calcd for C12H18ClN3: 239.1189; found:
239.1187.
MS (EI): m/z (%) = 241/239 (9/22) [M+], 141/139 (9/52) [M+ –
C6H14N], 113/111 (45/100) [M+ – C6H14N3], 100 (63) [C6H14N].
(E)-1-(4-fluorophenyl)-3,3-diisopropyltriaz-1-ene (2d)
Obtained after flash column chromatography (cyclohexane–EtOAc,
10:1).
HRMS (EI): m/z [M+] calcd for C12H18ClN3: 239.1189; found:
239.1188.
Yield: 3.08 g (77%); red oil; Rf = 0.67 (cyclohexane–EtOAc, 10:1).
(E)-1-(2-Fluorophenyl)-3,3-diisopropyltriaz-1-ene (2g)
Obtained after flash column chromatography (cyclohexane–EtOAc,
25:1).
IR (film): 3443 (vw), 2975 (w), 2934 (w), 1594 (vw), 1499 (m),
1468 (w), 1435 (m), 1405 (m), 1366 (w), 1297 (w), 1265 (w), 1215
(m), 1187 (w), 1142 (w), 1098 (w), 1032 (w), 915 (vw), 589 (vw),
838 (w), 804 (vw), 732 (vw), 639 (vw), 602 (vw), 537 (vw), 519
(vw), 408 (vw) cm–1.
Yield: 3.70 g (92%); orange solid; Rf = 0.63 (cyclohexane–EtOAc,
25:1).
1H NMR (400 MHz, CDCl3): δ = 1.23 (br s, 12 H, CH3), 4.02 (br s,
1 H, CH), 5.07 (br s, 1 H, CH), 6.90–6.95 (m, 2 H, Ar-H-3, Ar-H-
5), 7.28–7.32 (m, 2 H, Ar-H-2, Ar-H-6).
13C NMR (100 MHz, CDCl3): δ = 22.0 (+, br s, CH3), 47.7 (+, br s,
CH), 115.3 (+, d, 2J = 22.1 Hz, CH-3, CH-5), 121.3 (+, d,
3J = 8.0 Hz, CH-2, CH-6), 148.1 (Cquat, d, 4J = 2.9 Hz, C-1), 160.4
(Cquat, 2J = 242.4 Hz, C-4).
IR (ATR): 2976 (w), 2934 (w), 2872 (vw), 1582 (w), 1486 (m),
1454 (w), 1399 (m), 1369 (m), 1268 (m), 1233 (m), 1209 (m), 1182
(w), 1148 (m), 1103 (m), 1028 (m), 933 (w), 915 (w), 888 (w), 854
(vw), 817 (m), 748 (m), 731 (m), 632 (w), 589 (w), 564 (w), 529
(w), 504 (w), 471 (w), 426 (vw) cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.20–1.45 (m, 12 H, CH3), 4.02
(br s, 1 H, CH), 5.33 (br s, 1 H, CH), 7.01–7.12 (m, 3 H, Ar-H),
7.42–7.49 (m, 1 H, Ar-H-3).
MS (70 eV, EI): m/z (%) = 223 (26) [M+], 123 (41) [M+ – C6H14N],
100 (12) [C6H4N], 95 (100) [M+ – C6H14N3].
13C NMR (100 MHz, CDCl3): δ = 19.3 (+, CH3), 23.9 (+, CH3), 46.1
(+, CH), 49.0 (+, CH), 116.1 (+, d, 2J = 20.0 Hz, CH-3), 119.0 (+,
HRMS (EI): m/z [M+] calcd for C12H18FN3: 223.1484; found:
223.1483.
d, 4J = 2.0 Hz, CH-5), 123.9 (+, d, 3J = 3.7 Hz, CH-6), 125.2 (+, d,
2
3J = 7.7 Hz, CH-4), 139.8 (Cquat, d, J = 7.4 Hz, C-1), 156.3 (Cquat
,
d, 1J = 248.5 Hz, C-2).
(E)-1-(2-Iodophenyl)-3,3-diisopropyltriaz-1-ene (2e)
Obtained after flash column chromatography (cyclohexane–EtOAc,
10:1).
19F NMR (367 MHz, CDCl3): δ = –128.59 (s, 1 F, Ar-F).
MS (EI): m/z (%) = 223 (23) [M+], 123 (68) [M+ – C6H14N], 100
(22) [C6H14N], 95 (100) [M+ – C6H14N3].
Yield: 2.34 g (77%); orange solid; Rf = 0.53 (cyclohexane–EtOAc,
10:1).
HRMS (EI): m/z [M+] calcd for C12H18FN3: 223.1485; found:
223.1485.
IR (ATR): 3059 (vw), 2970 (w), 2929 (vw), 1575 (vw), 1458 (w),
1435 (vw), 1397 (m), 1365 (m), 1285 (vw), 1256 (m), 1221 (m),
1192 (m), 1148 (m), 1128 (m), 1111 (w), 1092 (m), 1042 (vw), 1027
(m), 1010 (m), 852 (vw), 762 (w), 742 (m), 712 (w), 661 (vw), 626
(w), 582 (vw), 541 (m), 517 (w), 439 (vw), 411 (vw) cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.34 (br s, 6 H, CH3), 1.39 (br s,
6 H, CH3), 4.04 (br s, 1 H, CH), 5.19 (br s, 1 H, CH), 6.82 (ddd,
3J = 7.8 Hz, 3J = 7.1 Hz, 4J = 1.6 Hz, 1 H, Ar-H-4), 7.27 (ddd,
3J = 8.1 Hz, 3J = 7.1 Hz, 4J = 1.4 Hz, 1 H, Ar-H-5), 7.36 (dd,
(E)-1-(4-Ethoxycarbonylphenyl)-3,3-diisopropyltriaz-1-ene
(2h)
Obtained after flash column chromatography (cyclohexane–EtOAc,
10:1).
Yield: 1.49 g (44%); light-yellow solid; Rf = 0.40 (cyclohexane–
EtOAc, 10:1).
IR (ATR): 2972 (w), 1707 (m), 1601 (m), 1459 (w), 1409 (m), 1390
(m), 1365 (m), 1311 (w), 1266 (m), 1249 (m), 1225 (m), 1154 (m),
Synthesis 2014, 46, 1448–1454
© Georg Thieme Verlag Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Triazenes in Silver-Mediated Perfluoroalkylation Reactions
1453
1129 (m), 1096 (m), 1026 (m), 916 (w), 860 (m), 775 (m), 748 (w),
700 (m), 579 (w), 558 (m), 540 (m), 440 (w) cm–1.
Yield: 73 mg (53%); yellow oil; Rf = 0.19 (cyclohexane–EtOAc,
50:1). Analytical data were identical with those reported.4a
1H NMR (400 MHz, CDCl3): δ = 1.26 (br s, 6 H, CH3), 1.38 (t,
3J = 7.1 Hz, 3 H, CH2CH3), 1.39 (br s, 6 H, CH3), 4.02 (br s, 1 H,
CH), 4.35 (q, 3J = 7.1 Hz, 2 H, CH2), 5.34 (br s, 1 H, CH), 7.43 (d,
3J = 8.7 Hz, 2 H, Ar-H-2, Ar-H-6), 8.00 (d, 3J = 8.7 Hz, 2 H, Ar-H-
3, Ar-H-5).
Products of Type 4
(E)-1-[4-Bromo-2,6-(bistrifluoromethyl)phenyl]-3,3-diisoprop-
yltriaz-1-ene (4b)
Obtained after flash column chromatography (cyclohexane).
Yield: 33 mg (20%); yellow oil; Rf = 0.29 (cyclohexane).
13C NMR (100 MHz, CDCl3): δ = 14.4 (+, CH3), 19.3 (+, br s, CH3),
23.9 (+, br s, CH3), 46.3 (+, CH), 49.2 (+, CH), 60.5 (–, CH2), 119.8
(+, CH-2, CH-6), 126.2 (Cquat, C-4), 130.5 (+, CH-3, CH-5), 155.3
(Cquat, C-1), 166.8 (Cquat, CO).
IR (film): 3443 (vw), 3091 (vw), 2978 (w), 2936 (w), 1580 (w),
1412 (m), 1385 (w), 1369 (m), 1333 (m), 1294 (m), 1257 (m), 1233
(m), 1188 (m), 1146 (m), 1072 (w), 1032 (w), 893 (w), 861 (vw),
838 (w), 812 (vw), 769 (w), 695 (w), 680 (w), 654 (vw), 594 (vw),
542 (vw), 508 (vw) cm–1.
MS (70 eV, EI): m/z (%) = 277 (37) [M+], 177 (16) [M+ – C6H14N],
149 (100) [M+ – C6H14N3].
3
1H NMR (400 MHz, CDCl3): δ = 1.27 (d, J = 6.8 Hz, 6 H, CH3),
HRMS (EI): m/z [M+] calcd for C15H23O2N3: 277.1790; found:
277.1793.
3
3
1.31 (d, J = 6.6 Hz, 6 H, CH3), 4.02 (sept, J = 6.6 Hz, 1 H, CH),
5.13 (sept, 3J = 6.8 Hz, 1 H, CH), 7.92 (s, 2 H, Ar-H-3, Ar-H-5).
13C NMR (100 MHz, CDCl3): δ = 19.0 (+, CH3), 23.0 (+, CH3), 47.0
(+, CH), 50.0 (+, CH), 116.1 (Cquat, CBr), 122.7 (Cquat, q,
1J = 274.2 Hz, CF3), 125.9 (Cquat, q, 2J = 31.3 Hz, C-2, C-6), 133.2
(+, q, 3J = 5.7 Hz, CH-3, CH-5), 149.9 (Cquat, C-1).
(E)-1-(2,6-Bisbromophenyl)-3,3-diisopropyltriaz-1-ene (2i)
Obtained after flash column chromatography (cyclohexane–EtOAc,
10:1).
Yield: 2.06 g (71%); beige solid; Rf = 0.82 (cyclohexane–EtOAc,
19F NMR (367 MHz, CDCl3): δ = –58.8 (s, 6 F, CF3).
10:1).
MS (70 eV, EI): m/z (%) = 419 (36) [M+], 319 (24) [M+ – C6H14N],
IR (ATR): 2969 (w), 2928 (w), 1545 (w), 1467 (w), 1397 (m), 1360
(m), 1270 (m), 1225 (m), 1191 (m), 1157 (m), 1130 (m), 1096 (w),
1066 (w), 1028 (m), 783 (m), 766 (m), 713 (m), 655 (w), 585 (w),
546 (w), 519 (m) cm–1.
291 (95) [M+ – C6H14N3], 100 (100) [C6H14N].
HRMS (EI): m/z [M+] calcd for C14H16BrN3F6: 419.0431; found:
419.0434.
3
1H NMR (400 MHz, CDCl3): δ = 1.33 (d, J = 6.8 Hz, 6 H, CH3),
3
3
1.37 (d, J = 6.6 Hz, 6 H, CH3), 4.04 (sept, J = 6.6 Hz, 1 H, CH),
5.15 (sept, 3J = 6.8 Hz, 1 H, CH), 6.83 (t, 3J = 8.0 Hz, 1 H, Ar-H-4),
7.52 (d, 3J = 8.0 Hz, 2 H, Ar-H-3, Ar-H-5).
(E)-1-[4-Chloro-2,6-(bistrifluoromethyl)phenyl]-3,3-diisoprop-
yltriaz-1-ene (4c)
Obtained after flash column chromatography (cyclohexane).
13C NMR (100 MHz, CDCl3): δ = 19.1 (+, CH3), 23.7 (+, CH3), 46.7
(+, CH), 49.7 (+, CH), 118.1 (Cquat, C-2, C-6), 126.2 (+, CH-4),
132.2 (+, CH-3, CH-5), 148.9 (Cquat, C-1).
Yield: 36 mg (24%); yellow oil; Rf = 0.17 (cyclohexane).
IR (film): 2977 (w), 1580 (vw), 1405 (s), 1367 (m), 1335 (w), 1293
(m), 1253 (m), 1230 (m), 1185 (s), 1135 (s), 1072 (m), 1031 (m),
893 (m), 864 (w), 841 (w), 773 (w), 707 (w), 681 (m), 657 (w), 601
(w), 545 (w), 511 (w), 477 (w) cm–1.
MS (70 eV, EI): m/z (%) = 363 (24) [M+], 263 (40) [M+ – C6H14N],
235 (63) [M+ – C6H14N3], 100 (100) [C6H14N].
3
1H NMR (400 MHz, CDCl3): δ = 1.28 (d, J = 6.8 Hz, 6 H, CH3),
HRMS (EI): m/z [M+] calcd for C12H17Br2N3: 360.9789; found:
360.9792.
3
3
1.31 (d, J = 6.6 Hz, 6 H, CH3), 4.02 (sept, J = 6.6 Hz, 1 H, CH),
5.13 (sept, 3J = 6.8 Hz, 1 H, CH), 7.78 (s, 2 H, Ar-H).
Products of Type 3
13C NMR (100 MHz, CDCl3): δ = 19.0 (+, CH3), 23.0 (+, CH3), 47.0
(+, CH), 50.0 (+, CH), 122.8 (Cquat, q, J = 274.1 Hz, CF3), 125.6
1
(E)-1-[4-Bromo-2-(trifluoromethyl)phenyl]-3,3-diisopropyltri-
az-1-ene (3b)
Obtained after flash column chromatography (cyclohexane).
2
(Cquat, q, J = 31.3 Hz, C-2, C-6), 129.0 (Cquat, CBr), 130.3 (+, q,
3J = 5.5 Hz, CH-3, CH-5), 149.5 (Cquat, C-1).
Yield: 97 mg (69%); yellow oil; Rf = 0.47 (cyclohexane). Analytical
19F NMR (367 MHz, CDCl3): δ = –58.9 (s, 6 F, CF3).
data were identical with those reported.4a
MS (70 eV, EI): m/z (%) = 375 (60) [M+], 275 (13) [M+ – C6H14N],
247 (24) [M+ – C6H14N3], 100 (100) [C6H14N].
(E)-1-[4-Chloro-2-(trifluoromethyl)phenyl]-3,3-diisopropyltri-
az-1-ene (3c)
Obtained after flash column chromatography (cyclohexane).
HRMS (EI): m/z [M+] calcd for C14H16ClN3F6: 375.0937; found:
375.0939.
Yield: 82 mg (67%); yellow oil; Rf = 0.40 (cyclohexane). Analytical
(E)-1-[4-Fluoro-2,6-(bistrifluoromethyl)phenyl]-3,3-diisoprop-
yltriaz-1-ene (4d)
data were identical with those reported.4a
Obtained after flash column chromatography (cyclohexane).
(E)-1-[4-Fluoro-2-(trifluoromethyl)phenyl]-3,3-diisopropyltri-
az-1-ene (3d)
Obtained after flash column chromatography (cyclohexane).
Yield: 38 mg (26%); yellow oil; Rf = 0.23 (cyclohexane).
IR (film): 2977 (w), 1599 (vw), 1462 (m), 1408 (m), 1362 (m), 1297
(m), 1279 (w), 1244 (m), 1183 (m), 1135 (s), 1065 (w), 1031 (m),
949 (m), 887 (m), 836 (w), 780 (w), 727 (w), 688 (w), 662 (w), 619
(w), 551 (w), 520 (w), 430 (w) cm–1.
Yield: 78 mg (67%); slightly yellow oil; Rf = 0.49 (cyclohexane).
Analytical data were identical with those reported.4a
(E)-1-[2-Iodo-6-(trifluoromethyl)phenyl]-3,3-diisopropyltriaz-
1-ene (3e)
Obtained after flash column chromatography (cyclohexane).
3
1H NMR (400 MHz, CDCl3): δ = 1.26 (d, J = 6.8 Hz, 6 H, CH3),
3
3
1.31 (d, J = 6.6 Hz, 6 H, CH3), 4.01 (sept, J = 6.6 Hz, 1 H, CH),
5.13 (sept, 3J = 6.8 Hz, 1 H, CH), 7.53 (d, 1J = 8.4 Hz, 1 H, Ar-H-
Yield: 96 mg (60%); yellow oil; Rf = 0.10 (cyclohexane). Analytical
6).
data were identical with those reported.4a
13C NMR (100 MHz, CDCl3): δ = 19.0 (+, CH3), 23.0 (+, CH3), 46.8
(+, CH), 49.9 (+, CH), 117.5 (+, dq, 2J = 25.0 Hz, 3J = 5.6 Hz, CH-
(E)-1-[4-Ethoxycarbonyl-2-(trifluoromethyl)phenyl]-3,3-diiso-
propyltriaz-1-ene (3h)
Obtained after flash column chromatography (pentane to pentane–
Et2O, 50:1).
1
4
3, CH-5), 122.6 (Cquat, dq, J = 273.9 Hz, J = 2.4 Hz, CF3), 125.8
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1448–1454

1454
A. Hafner et al.
PRACTICAL SYNTHETIC PROCEDURES
Products of Type 5
(E)-Methyl 2-[2-(3,3-Diisopropyltriaz-1-en-1-yl)-5-iodophe-
nyl]-2,3,3,3-tetrafluoropropanoate (5a)
The reaction was conducted on 1.2 mmol scale and the product was
obtained after flash column chromatography (cyclohexane–EtOAc,
50:1).
2
3
(Cquat, dq, J = 31.6 Hz, J = 7.2 Hz, C-2, C-6), 147.4 (Cquat, C-1),
157.9 (Cquat, d, 1J = 245.4 Hz, C-4).
19F NMR (367 MHz, CDCl3): δ = –58.9 (s, 6 F, CF3), –116.7 (s, 1
F, CF).
MS (70 eV, EI): m/z (%) = 359 (49) [M+], 259 (16) [M+ – C6H14N],
231 (38) [M+ – C6H14N3], 100 (100) [C6H14N].
Yield: 221 mg (38%); yellow solid; Rf = 0.18 (cyclohexane–EtOAc,
HRMS (EI): m/z [M+] calcd for C14H16N3F7: 359.1232; found:
359.1229.
50:1). Analytical data were identical with those reported.4c
(E)-Methyl 2-[5-Bromo-2-(3,3-diisopropyltriaz-1-en-1-yl)phe-
nyl]-2,3,3,3-tetrafluoropropanoate (5b)
The reaction was conducted on 1.8 mmol scale and the product was
obtained after flash column chromatography (cyclohexane–EtOAc,
20:1).
(E)-1-[2-Iodo-4,6-(trifluoromethyl)phenyl]-3,3-diisopropyltri-
az-1-ene (4e)
Obtained after flash column chromatography (cyclohexane).
Yield: 32 mg (17%); yellow oil; Rf = 0.18 (cyclohexane).
Yield: 363 mg (46%); orange solid; Rf = 0.25 (cyclohexane–EtOAc,
IR (film): 2978 (m), 2936 (w), 1612 (w), 1468 (w), 1413 (m), 1384
(w), 1368 (m), 1332 (m), 1282 (m), 1266 (m), 1232 (m), 1210 (m),
1137 (s), 1094 (m), 1068 (w), 1030 (w), 900 (w), 866 (vw), 783
(vw), 764 (vw), 690 (w), 677 (w), 665 (vw), 544 (vw), 430 (vw) cm–1.
20:1). Analytical data were identical with those reported.4c
(E)-Methyl 2-[3-Chloro-4-(3,3-diisopropyltriaz-1-en-1-yl)phe-
nyl]-2,3,3,3-tetrafluoropropanoate (5f)
3
1H NMR (400 MHz, CDCl3): δ = 1.33 (d, J = 6.8 Hz, 6 H, CH3),
The reaction was conducted on 0.4 mmol scale according to GP3
but under atmospheric conditions instead of under an argon atmo-
sphere. The product was obtained as a 7.5:1 mixture of para- and
ortho-methoxycarbonyltetrafluoroethylated product after flash col-
umn chromatography (cyclohexane–EtOAc, 50:1).
3
3
1.37 (d, J = 6.6 Hz, 6 H, CH3), 4.07 (sept, J = 6.6 Hz, 1 H, CH),
3
5.18 (sept, J = 6.8 Hz, 1 H, CH), 7.87 (s, 1 H, Ar-H-5), 8.25 (s,
1 H, Ar-H-3).
13C NMR (100 MHz, CDCl3): δ = 19.1 (+, CH3), 23.4 (+, CH3), 47.4
(+, CH), 50.2 (+, CH), 94.3 (Cqu1at, C-2), 122.7 (Cquat, q,
1J = 272.4 Hz, CF3), 122.74 (Cquat, q, J = 274.1 Hz, CF3), 124.1–
Yield: 61 mg (39%); yellow oil; Rf = 0.15 (cyclohexane–EtOAc,
50:1). Analytical data were identical with those reported.4c
124.4 (+, m, CH-5), 123.2 (Cquat, q, 2J = 31.5 Hz, C-6), 127.4 (Cquat
q, 2J = 33.7 Hz, C-4), 139.54 (+, q, 3J = 3.5 Hz, CH-3), 154.8 (Cquat
C-1).
,
,
(E)-Methyl 2-[3,5-Dibromo-4-(3,3-diisopropyltriaz-1-en-1-
yl)phenyl]-2,3,3,3-tetrafluoropropanoate (5i)
The reaction was conducted on 1.2 mmol scale and the product was
obtained after flash column chromatography (cyclohexane–EtOAc,
50:1).
19F NMR (367 MHz, CDCl3): δ = –59.2 (s, 3 F, CF3-6), –62.2 (s, 3
F, CF3-4).
MS (70 eV, EI): m/z (%) = 467 (48) [M+], 367 (17) [M+ – C6H14N],
Yield: 220 mg (35%); white solid; Rf = 0.30 (cyclohexane–EtOAc,
339 (58) [M+ – C6H14N3], 212 (32) [M+ – C6H14IN3], 58 (100).
50:1). Analytical data were identical with those reported.4c
HRMS (EI): m/z [M+] calcd for C14H16IN3F6: 467.0293; found:
467.0291.
Acknowledgment
(E)-1-[4-Ethoxycarbonyl-2,6-(bistrifluoromethyl)phenyl]-3,3-
diisopropyltriaz-1-ene (4h)
Obtained after flash column chromatography (pentane to pentane–
Et2O, 50:1).
This work was supported by the Landesgraduiertenförderung
Baden-Württemberg (fellowship to A.H.).
Yield: 32 mg (19%); slightly yellow oil; Rf = 0.30 (cyclohexane–
EtOAc, 50:1).
References
(1) (a) Bräse, S. Acc. Chem. Res. 2004, 37, 805. (b) Kimball, D.
B.; Haley, M. M. Angew. Chem. Int. Ed. 2002, 41, 3338.
(c) Wang, C. M.; Huang, Y. Synlett 2013, 24, 145.
(2) (a) Wang, C. M.; Sun, H.; Fang, Y.; Huang, Y. Angew.
Chem. Int. Ed. 2013, 52, 5795. (b) Wang, C. M.; Chen, H.;
Wang, Z. F.; Chen, J. A.; Huang, Y. Angew. Chem. Int. Ed.
2012, 51, 7242. (c) Voica, A. F.; Mendoza, A.; Gutekunst,
W. R.; Fraga, J. O.; Baran, P. S. Nat. Chem. 2012, 4, 629.
(d) Liu, C. Y.; Knochel, P. J. Org. Chem. 2007, 72, 7106.
(e) Liu, C. Y.; Knochel, P. Org. Lett. 2005, 7, 2543.
(f) Hejesen, C.; Petersen, L. K.; Hansen, N. J. V.; Gothelf, K.
V. Org. Biomol. Chem. 2013, 11, 2493. (g) Fang, Y.; Wang,
C. M.; Su, S. Q.; Yu, H. Z.; Huang, Y. Org. Biomol. Chem.
2014, 12, 1061. (h) Hafner, A.; Bräse, S. Adv. Synth. Catal.
2013, 355, 996.
IR (film): 3439 (vw), 2980 (w), 2938 (w), 1727 (m), 1618 (m), 1581
(w), 1465 (w), 1415 (m), 1368 (m), 1308 (m), 1249 (m), 1191 (m),
1141 (m), 1099 (m), 1074 (m), 1030 (m), 930 (w), 885 (w), 858 (w),
835 (w), 768 (w), 693 (vw), 681 (w), 665 (vw), 595 (vw), 496
(vw) cm–1.
3
1H NMR (400 MHz, CDCl3): δ = 1.29 (d, J = 6.8 Hz, 6 H, CH3),
1.34 (d, 3J = 6.6 Hz, 6 H, CH3), 1.42 (t, 3J = 7.1 Hz, 3 H, CH2CH3),
4.05 (sept, 3J = 6.6 Hz, 1 H, CH), 4.42 (q, 3J = 7.1 Hz, 2 H,
CH2CH3), 5.16 (sept, 3J = 6.8 Hz, 1 H, CH), 8.47 (s, 2 H, Ar-H-3,
Ar-H-5).
13C NMR (100 MHz, CDCl3): δ = 14.3 (+, CH3), 19.0 (+, CH3), 23.0
(+, CH3), 47.4 (+, CH), 50.4 (+, CH), 61.6 (–, CH2), 123.3 (Cquat, q,
1J = 273.8 Hz, CF3), 124.3 (Cquat, q, 2J = 31.3 Hz, C-2, C-6), 125.6
(Cquat, C-4), 131.6 (+, q, 3J = 5.5 Hz, CH-3, CH-5), 154.2 (Cquat, C-
1), 164.6 (Cquat, CO).
(3) Dobele, M.; Vanderheiden, S.; Jung, N.; Brase, S. Angew.
Chem. Int. Ed. 2010, 49, 5986.
19F NMR (367 MHz, CDCl3): δ = –58.8 (s, 6 F, CF3).
(4) (a) Hafner, A.; Bräse, S. Angew. Chem. Int. Ed. 2012, 51,
3713. (b) Hafner, A.; Bihlmeier, A.; Nieger, M.; Klopper,
W.; Bräse, S. J. Org. Chem. 2013, 78, 7938. (c) Hafner, A.;
Feuerstein, T. J.; Bräse, S. Org. Lett. 2013, 15, 3468.
(5) Reingruber, R.; Vanderheiden, S.; Wagner, A.; Nieger, M.;
Muller, T.; Es-Sayed, M.; Brase, S. Eur. J. Org. Chem. 2008,
3314.
MS (70 eV, EI): m/z (%) = 413 (100) [M+], 313 (36) [M+ – C6H14N],
285 (84) [M+ – C6H14N3].
HRMS (EI): m/z [M+] calcd for C17H21O2N3F6: 413.1538; found:
413.1540.
(6) Tyrra, W.; Naumann, D. J. Fluorine Chem. 2004, 125, 823.
Synthesis 2014, 46, 1448–1454
© Georg Thieme Verlag Stuttgart · New York