Cu(I)-catalyzed coupling reactions of fluorinated imidoyl halides with terminal alkynes: Convenient synthesis of fluorinated alkynyl imines

Article abstract of DOI:10.1016/j.jfluchem.2011.01.003

The first example of coupling reactions of fluorinated imidoyl halides with terminal alkynes catalyzed by CuI is presented. Each reaction needed no ligand, and fluorinated alkynyl imines were obtained with excellent yields.

Full text of DOI:10.1016/j.jfluchem.2011.01.003

Journal of Fluorine Chemistry 132 (2011) 196–201
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Cu(I)-catalyzed coupling reactions of fluorinated imidoyl halides with
terminal alkynes: Convenient synthesis of fluorinated alkynyl imines
Shan Li a, Jiangtao Zhu a, Haibo Xie a, Zixian Chen b, Yongming Wu a,
*
a Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
b Department of Chemistry, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China
A R T I C L E I N F O
A B S T R A C T
Article history:
The first example of coupling reactions of fluorinated imidoyl halides with terminal alkynes catalyzed by
CuI is presented. Each reaction needed no ligand, and fluorinated alkynyl imines were obtained with
excellent yields.
Received 12 October 2010
Received in revised form 24 December 2010
Accepted 6 January 2011
ß 2011 Elsevier B.V. All rights reserved.
Available online 13 January 2011
Keywords:
Copper
Cross-coupling
Fluorinated imidoyl halides
Fluorinated alkynyl imines
1. Introduction
because of the unique physical and biological properties
imparted by fluorine [8]. In search for new CF2-containing
Alkynyl imines are versatile intermediates, which are used to
synthesize many different kinds of heterocycles, such as pyrroles
[1], quinolines [2], pyridines [3], and others [4]. Furthermore, they
can also react with conjugated diene to give bicyclic compounds
[5] (Scheme 1).
Up to now, many procedures have been developed to
construct the skeleton of alkynyl imines, such as the reactions
of alkynes with isonitriles, amides, or others [6]. Among them, the
most useful method is the cross coupling reaction of imidoyl
reactive synthetic intermediates, our group has focused devel-
oping new methods for the synthesis of BrCF2-containing
compounds from bromodifluoroacetimidoyl halides [9]. Several
years ago, we reported a method for synthesis of fluorinated
alkynyl imines via coupling reaction of bromodifluoroacetimi-
doyl iodide with terminal alkynes catalyzed by Pd/Cu system
(Eq. (1)) [10]. Herein, we wish to present the result of our further
study on this reaction which shows that the transformation can
be completed by Cu(I) salt catalyst only.
R1
R1
Pd(PPh3)2Cl2/CuI
+
R2
N
N
(1)
Et3N, r.t.
BrF2C
BrF2C
I
R2
50-90%
halides with terminal alkynes catalyzed by Pd(PPh3)2Cl2 and CuI
system [7]. Recently, synthetic and medicinal chemists have been
paying more and more attention to fluorinated compounds
2. Results and discussion
It is reported that terminal alkynes can react with aryl halides in
the presence of some Lewis acids [11–13]. Therefore, ZnBr2, and
CuI were tested in this transformation. Extensive research
indicated that when CuI was used as catalyst, K3PO4 as base,
* Corresponding author. Tel.: +86 21 54925190; fax: +86 21 64166128.
E-mail address: ymwu@sioc.ac.cn (Y. Wu).
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.01.003

S. Li et al. / Journal of Fluorine Chemistry 132 (2011) 196–201
197
R2
N
4, 5, 7, 9, 15, 16, 19, and 21) or weak electron-withdrawing groups
(Table 1, Entries 3, 6, 8, 10, 11, 12, 14, 17, 18, 19, 20, and 22) on the
benzene ring of imidoyl halides were compatible with the former
giving better yields. But in the case of imidoyl halides with strong
electron-withdrawing groups (NO2, F, and CF3) on the benzene
ring, the imidoyl chlorides shall be used as starting materials, since
the corresponding imidoyl iodides is not stable in this reaction
system, in such case, stoichiometric amount of CuI is needed
(Table 1, Entries 3, 6, 8, 12, 18, and 20). The effect of terminal
alkynes was also examined. It was found that phenylacetylene had
the strongest reactivity, while 1-hexyne had less in this
transformation. It is interesting to note that when ethylnyltri-
methylsilane was used as alkyne substrate, N,N0-(1,6-dibromo-
1,1,6,6-tetrafluorhex-3-yne-2,5-diylidene) dianiline was obtained
as sole product. In this case, the trimethylsilyl group in the
preliminary product of alkynyl imine was desilylated by K3PO4 and
formed a new terminal alkyne which was subjected to the reaction
with another equivalent of imidoyl halide.
H
R1
R1
R
N
N
R'
R2
R
R'
N
R
Ar
R1
R1
N
R2
O
N
R2
Ph
R
N
Ph
Ph
R'
R1
R2'
N
Ar
The reaction was applied to the synthesis of trifluoromethy-
lated alkynyl imines. Compared with bromodifluoromethylated
imidoyl halides, the corresponding trifluoromethylated imidoyl
halides showed weaker reactivity, and stoichiometric amount of
CuI was needed (Table 2).
Scheme 1. Heterocycles that synthesized from alkynyl imines.
and CH3CN as solvent, fluorinated alkynyl imines could be
obtained with excellent yields at 50 8C.
Next the scope and generality of this reaction are surveyed with
different bromodifluoroacetimidoyl halides and terminal alkynes,
and the results are listed in Table 1. Most of the imidoyl halides
reacted with terminal alkynes smoothly to give the desired
products in good to excellent yields. A variety of imidoyl halides
with different substituents on the benzene ring were employed in
this transformation. Electron-donating groups (Table 1, Entries 2,
There are two possible routes to form alkynyl imines from
imidoyl halides and terminal alkynes. The first one is the so-called
addition–elimination pathway. In such case, copper alkynide
attacks imidoyl halides followed by elimination of chloride anion
to form the final product. A controlled experiment indicated that,
complex results were obtained when NaH was used as base to
produce alkynide which was allowed to react with imidoyl halides
Table 1
The CuI-catalyzed coupling reaction of fluorinated imidoyl halides with terminal alkynesa.
R1
R1
CuI (10 mol%)
R2
+
N
N
K3PO4/CH3CN
50 oC
BrF2C
BrF2C
X
R2
Entry
R1
R2
n-Bu
X
Product/yield (%)b
1
H
I
3aa/90.9
3ba/93.1
3ca/86.4
3da/73.1
3ea/75.3
3fa/71.6
3gb/100.0
3cb/90.6
3eb/98.1
3hb/96.5
3ib/98.4
3jb/98.2
3ac/87.6
3kc/90.7
3ec/93.2
3bd/93.4
3kd/85.5
3cd/80.1
3id/61.4
3jd/73.8
3be/83.1d
3ke/90.4d
2
p-CH3
p-NO2
o-CH3
I
3
Clc
4
I
5
m-CH3
3,4-2F
p-OCH3
P–NO2
m-CH3
o-Br
I
6
Clc
7
Ph
I
8
Clc
9
I
10
11
12
13
14
15
16
17
18
19
20
21
22
I
m-Cl
I
p-CF3
H
Clc
COOCH3
I
P–Cl
I
m-CH3
p-CH3
p-Cl
I
CH2OCOCH3
I
I
P–NO2
m-Cl
Clc
I
p-CF3
p-CH3
p-Cl
Clc
Si(CH3)3
I
I
a
Reaction conditions: fluorinated imidoyl halides (1.0 mmol), alkynes (1.2 mmol), CuI (10 mol%), K3PO4 (1.2 mmol), CH3CN (3.0 ml), T = 50 8C.
Isolated yields.
b
c
CuI (1.0 equiv).
d
The production is N,N0-(1,10-dibromo-1,10,6,60-tetrafluorhex-3-yne-2,5-diylidene)dianiline.

198
S. Li et al. / Journal of Fluorine Chemistry 132 (2011) 196–201
Table 2
Synthesis of trifluoromethylated alkynyl iminesa,b
.
OCH3
NO2
NO2
N
N
N
N
F3C
F3C
F3C
F3C
Ph
nBu
nBu
3ma 91%c
Ph
3mb 93%c
3la 84%
3nb 62%
F3C
N
F3C
N
N
N
F3C
F3C
COOCH3
F3C
CH2OCOCH3
3pd 66%
F3C
3ob 94%c
CH2OCOCH3
3od 71%c
Ph
3pc 86%
aReaction conditions: fluorinated imidoyl halides (1.0 mmol), alkynes (1.2 mmol), CuI
(10 mol%), K3PO4 (1.2 mmol), CH3CN (3.0 ml), T = 50 8C.
bIsolated yields.
cCuI (1.0 equiv).
R2
performed by the Analytical Laboratory of Shanghai Institute of
+
base
Ar
Organic Chemistry. Mass spectra were recorded by EI methods.
Solvents were purchased from commercial sources and purified
before used by standard procedures. Unless otherwise specified, all
reactions were carried out under nitrogen in a Schlenk tube and
magnetic stirring. TLC analysis was performed on silica gel plates,
Flash column chromatography was carried out using 300–400
mesh silica gel at increased pressure and petroleum ether/ethyl
acetate combination was used as the eluent.
N
CuI
Rf
R2
3
Ar
N
R2
Cu
I
Rf
Cu
Ar
I
N
4.2. Typical procedure for the synthesis of fluorinated alkynyl imines
Rf
R2
Under N2, CuI (20 mg, 0.1 mmol), K3PO4 (254 mg, 1.2 mmol),
CH3CN (3.5 mL), imidoyl halides (1.0 mmol), and terminal alkynes
(1.2 mmol) were added to a Schenk tube successively. Then the
mixture was stirred at 50 8C. The reaction was monitored by TLC
until the corresponding spot of imidoyl halide was no longer
observable. When the reaction completed, the solvent was
removed under reduced pressure, and the residue was purified
by column chromatography on silica gel to give the desired
products.
A
Scheme 2. Proposed mechanism for the coupling reaction.
under the same conditions. Only after cooling the mixture to 0 8C,
the alkynyl imine was obtained in low yield. This result rules out
the possibility of the addition-elimination mechanism. The other
route is an oxidative addition-reductive elimination process as
shown in Scheme 2. Copper alkynide firstly inserted to C–I bond of
imidoyl iodide by oxidant addition to form intermediate A. After
reductive elimination, alkynyl imine 3 was formed (Scheme 2).
4.3. Spectroscopic data of fluorinated alkynyl imines
3. Conclusion
N-(1-bromo-1,1-difluorooct-3-yn-2-ylidene) aniline (3aa) [10].
Yellow oil; 1H NMR (300 Hz, CDCl3):
d
7.41–7.36 (m, 3H), 7.26–7.17
In conclusion, we have demonstrated that CuI is able to catalyze
the coupling reaction of fluorinated imidoyl halides with terminal
alkynes in the absence of Pd complex [14]. A novel, general, and
efficient method for the synthesis of fluorinated alkynyl imines has
been developed, which offers a new way for the synthesis of
fluorinated compounds.
(m, 2H), 2.35 (t, J = 6.9 Hz, 2H), 1.50–1.43 (m, 2H), 1.34–1.27 (m,
2H), 0.89–0.84 (t, J = 7.2 Hz, 3H). 19F NMR (282 Hz, CDCl3):
ꢀ55.10 (s). MS (EI) m/z (%): 313 (M+, 10.28), 184 (100).
N-(1-bromo-1,1-difluorooct-3-yn-2-ylidene)-4-methylaniline
d
(3ba) [10]. Yellow oil; 1H NMR (300 Hz, CDCl3):
d 7.11 (s, 4H), 2.32–
2.27 (m, 5H), 1.46–1.41 (m, 2H), 1.31–1.23 (m, 2H), 0.88 (t,
J = 7.2 Hz, 3H); 19F NMR (282 Hz, CDCl3):
(%): 327 (M+, 10), 198 (100).
d
ꢀ54.26 (s); MS (EI) m/z
4. Experimental
N-(1-bromo-1,1-difluorooct-3-yn-2-ylidene)-4-nitroaniline
(3ca) [10]. Brown oil; 1H NMR (300 Hz, CDCl3):
8.20 (d, J = 9.0 Hz,
4.1. General
d
2H), 7.09 (d, J = 9.0 Hz, 2H), 2.30–2.25 (t, J = 6.8 Hz, 2H), 1.40–1.35
(m, 2H), 1.22–1.14 (m, 2H), 0.76 (t, J = 7.4 Hz, 3H); 19F NMR
1H NMR spectra were recorded in CDCl3 on a Bruker AM-300
spectrometer (300 MHz) with TMS as internal standard. 19F NMR
spectra were taken on a Bruker AM-300 (282 MHz) spectrometer
using CFCl3 as external standard. 13C NMR spectra were taken a
Bruker AM-400 (100 MHz) spectrometer. IR spectra were obtained
with a Nicolet AV-360 spectrophotometer. Elemental analysis was
(282 Hz, CDCl3):
(100).
d
ꢀ56.16 (s); MS (EI) m/z (%): 358 (M+, 3), 229
N-(1-bromo-1,1-difluorooct-3-yn-2-ylidene)-2-methylaniline
(3da). Yellow oil; 1H NMR (300 Hz, CDCl3):
7.23–7.10 (m, 3H),
6.98 (dd, J1 = 7.8 Hz, J2 = 1.5 Hz, 1H), 2.30 (t, J = 6.0 Hz, 2H), 2.19 (s,
d

S. Li et al. / Journal of Fluorine Chemistry 132 (2011) 196–201
199
J = 7.2 Hz, 3H), 1.45–1.37 (m, 2H), 1.29–1.21 (m, 2H), 0.83 (t,
ꢀ62.16 (s, 3F); 13C NMR (100 Hz, CDCl3):
d
146.5, 142.0 (t,
J = 7.4 Hz, 3H); 19F NMR (282 Hz, CDCl3):
(100 Hz, CDCl3):
d
ꢀ54.52 (s); 13C NMR
JC,F = 28.3 Hz), 128.6, 127.0, 124.3, 121.9, 122.6 (q, JC,F = 270.4 Hz),
116.8, 115.3, 110.4 (t, JC,F = 306.5 Hz), 97.7, 74.0; MS (EI) m/z (%):
401 (M+, 2.7), 272 (100); IR (neat, cmꢀ1): 2200, 1606, 1593, 1485,
1440, 1324, 1128, 1065, 918, 859, 757, 687; HRMS: Calc. for
d
147.5, 145.7 (t, JC,F = 27.9 Hz), 131.3, 130.7,
127.1, 126.7, 119.1, 116.0 (t, JC,F = 306.5 Hz), 104.9, 71.6, 30.3, 22.5,
20.0, 18.4, 14.3; MS (EI) m/z (%): 329 (M+, 8), 198 (100); IR (neat,
cmꢀ1): 2960, 2213, 1620, 1484, 1461, 1450, 1228, 1156, 1130, 888,
821, 764; HRMS: Calc. for C15H16NF279Br: 327.0431. Found:
327.0434.
C
17H9NF581Br: 402.9822. Found: 402.9818.
Methyl 5-bromo-5,5-difluoro-4-(phenylimino)pent-2-ynoate
(3ac) [10]. Brown oil; 1H NMR (300 Hz, CDCl3):
d 7.37–7.34 (m,
N-(1-bromo-1,1-difluorooct-3-yn-2-ylidene)-3-methylaniline
2H), 7.30–7.19 (m, 3H), 3.74 (s, 3H); 19F NMR (282 Hz, CDCl3):
d
(3ea). Yellow oil; 1H NMR (300 Hz, CDCl3):
d
7.26 (m, 1H), 7.03 (m,
ꢀ55.06 (s); MS (EI) m/z (%): 315 (M+, 4), 77 (100).
3H), 2.40–2.32 (m, 5H), 1.50–1.43 (m, 2H), 1.35–1.27 (m, 2H), 0.86
Methyl 5-bromo-5,5-difluoro-4-(4-chlorophenylimino)pent-2-
(t, J = 7.1 Hz, 3H); 19F NMR (282 Hz, CDCl3):
(100 Hz, CDCl3):
d
ꢀ54.54 (s); 13C NMR
ynoate (3kc) [10]. Brown oil; 1H NMR (300 Hz, CDCl3):
d 7.36 (d,
d
148.2, 145.1 (t, JC,F = 27.7 Hz), 139.4, 129.4,
J = 9.0 Hz, 2H), 7.17 (d, J = 9.0 Hz, 2H), 3.77 (s, 3H); 19F NMR
128.5, 122.5, 118.8, 116.2 (t, JC,F = 306.5 Hz), 104.8, 71.9, 30.3, 22.6,
22.2, 20.0, 14.3; MS (EI) m/z (%): 327 (M+, 6), 198 (100); IR (neat,
cmꢀ1): 2960, 2212, 1599, 1483, 1464, 1253, 1158, 1116, 835, 785;
HRMS: Calc. for C15H16NF281Br: 329.0418. Found: 3290414.
N-(1-bromo-1,1-difluorooct-3-yn-2-ylidene)-3,4-difluoroani-
(282 Hz, CDCl3):
(100).
d
ꢀ55.22 (s); MS (EI) m/z (%): 349 (M+, 9), 220
Methyl 5-bromo-5,5-difluoro-4-(m-tolylimino)pent-2-ynoate
(3ec). Brown oil; 1H NMR (300 Hz, CDCl3):
7.21–7.13 (m, 3H),
d
7.02–6.99 (m, 1H), 3.72 (s, 3H), 2.18 (s, 3H); 19F NMR (282 Hz,
line (3fa) [10]. Yellow oil; 1H NMR (300 Hz, CDCl3):
d
7.23–7.12 (m,
CDCl3):
d
ꢀ54.37 (s); 13C NMR (100 Hz, CDCl3):
d 152.2, 145.0,
2H), 7.01–7.69 (m, 1H), 2.41 (t, J = 7.2 Hz, 2H), 1.58–1.48 (m, 2H),
1.39–1.26 (m, 2H), 0.92–0.87 (t, J = 7.2 Hz, 3H); 19F NMR (282 Hz,
140.9 (t, JC,F = 29.3 Hz), 131.8, 130.9, 128.3, 126.3, 117.9, 114.2 (t,
JC,F = 306.6 Hz), 87.0, 72.4, 53.5, 17.7; MS (EI) m/z (%): 329 (M+,
12.6), 200 (100); IR (neat, cmꢀ1): 2956, 1728, 1577, 1485, 1436,
1230, 1141, 1090, 754; HRMS: Calc. for C13H10NF2O2Br: 328.9868.
Found: 328.9863.
CDCl3):
d
ꢀ55.41 (s), ꢀ136.75–136.60 (m, 1F), ꢀ138.56–139.45 (m,
1F); MS (EI) m/z (%): 349 (M+, 5), 220 (100).
N-(1-bromo-1,1-difluoro-4-phenylbut-3-yn-2-ylidene)-4-
methoxyaniline (3gb) [10]. Yellow oil; 1H NMR (300 Hz, CDCl3):
d
5-Bromo-5,5-difluoro-4-(p-tolylimino)pent-2-ynyl acetate
7.56–7.48 (m, 4H), 7.46–7.26 (m, 3H), 6.96 (d, J = 8.70 Hz, 2H), 3.86
(s, 3H); 19F NMR (282 Hz, CDCl3):
(3bd). Yellow oil; 1H NMR (300 Hz, CDCl3):
d
7.13 (s, 4H), 4.72
(s, 2H), 2.30 (s, 3H), 2.01 (s, 3H); 19F NMR (282 Hz, CDCl3):
ꢀ54.56
(s); 13C NMR (100 Hz, CDCl3):
169.8, 143.9, 141.6 (t,
d
ꢀ53.736 (s); MS (EI) m/z (%):
d
363 (M+, 7), 234 (100); IR (neat, cmꢀ1): 3060, 2927, 2196, 1613,
1574, 1504, 1378, 1254, 1033, 839; Anal: Calc. for C17H12BrF2NO: C,
56.07; H, 3.32; N, 3.84. Found: C, 50.17; H, 3.58; N, 3.71.
N-(1-bromo-1,1-difluoro-4-phenylbut-3-yn-2-ylidene)-4-
d
JC,F = 28.3 Hz), 138.2, 129.5, 121.9, 114.5 (t, JC,F = 306.6 Hz), 94.5,
75.7, 51.7, 21.2, 20.4; MS (EI) m/z (%): 343 (M+, 9.9), 214 (100); IR
(neat, cmꢀ1): 2923, 2212, 1753, 1617, 1571, 1504, 1428, 1377,
1221, 1151, 1114, 1035, 881, 826; HRMS: Calc. for
nitroaniline (3cb) [10]. Yellow solid; 1H NMR (300 Hz, CDCl3):
d
8.26–8.23 (d, J = 8.7 Hz, 2H), 7.41–7.35 (m, 1H), 7.29–7.28 (m, 4H),
C
14H12NO2F279Br: 343.0017. Found: 343.0019.
7.22–7.20 (d, J = 8.7 Hz, 2H); 19F NMR (282 Hz, CDCl3):
(s); MS (EI) m/z (%): 378 (M+, 1), 249(100).
d
ꢀ55.22
5-Bromo-5,5-difluoro-4-(4-chlorophenylimino)pent-2-ynyl
acetate (3kd). Yellow oil; 1H NMR (300 Hz, CDCl3):
d 7.29 (d,
N-(1-bromo-1,1-difluoro-4-phenylbut-3-yn-2-ylidene)-3-
methylaniline (3eb). Yellow oil; 1H NMR (300 Hz, CDCl3):
7.42–
J = 8.4 Hz, 2H), 7.11 (d, J = 8.4 Hz, 2H), 4.71 (s, 2H), 2.01 (s, 3H); 19
F
d
d
NMR (282 Hz, CDCl3):
d
ꢀ55.16 (s); 13C NMR (100 Hz, CDCl3):
7.31 (m, 6H), 7.14–7.09 (m, 3H), 2.39 (s, 3H); 19F NMR (282 Hz,
169.7, 145.1, 143.4 (t, JC,F = 28.7 Hz), 133.3, 129.1, 122.8, 114.6 (t,
JC,F = 306.8 Hz), 95.7, 75.2, 51.5, 20.4; MS (EI) m/z (%): 365 (M+,
10.7), 234 (100); IR (neat, cmꢀ1): 2936, 2218, 1751, 1617, 1485,
1377, 1220, 1156, 1116, 1092, 1035, 880, 835, 800; HRMS: Calc. for
CDCl3):
d
ꢀ54.14 (s). 13C NMR (100 Hz, CDCl3):
d 146.6, 144.5 (t,
JC,F = 28.3 Hz), 132.7, 130.9, 130.8, 130.6, 128.6, 126.8, 125.9, 120.1,
118.5, 115.2 (t, JC,F = 306.7 Hz), 100.5, 78.7, 17.7; MS (EI) m/z (%):
349 (M+, 7.5), 218 (100); IR (neat, cmꢀ1): 3061, 2923, 2195, 1593,
1488, 1444, 1137, 1062, 939, 891, 816, 756, 687; HRMS: Calc. for
C
13H9NO2ClF279Br: 362.9475. Found: 362.9473.
5-Bromo-5,5-difluoro-4-(4-nitrophenylimino)pent-2-ynyl ace-
C17H12NF2Br: 347.0118. Found: 347.0121.
tate (3cd). Yellow solid; 1H NMR (300 Hz, CDCl3):
d 8.21 (d,
N-(1-bromo-1,1-difluoro-4-phenylbut-3-yn-2-ylidene)-2-bro-
J = 8.7 Hz, 2H), 7.13 (d, J = 8.7 Hz, 2H), 4.67 (s, 2H), 1.97 (s, 3H); 19
F
d
moaniline (3hb). Yellow oil; 1H NMR (300 Hz, CDCl3):
d
7.57 (d,
NMR (282 Hz, CDCl3):
d
ꢀ55.83 (s); 13C NMR (100 Hz, CDCl3):
J = 8.7 Hz, 1H), 7.35–7.23 (m, 6H), 7.06–7.02 (m, 2H); 19F NMR
169.6, 152.6, 145.8 (t, JC,F = 29.0 Hz), 146.2, 124.8, 120.9, 114.2 (t,
JC,F = 306.8 Hz), 97.4, 74.5, 51.4, 20.3; MS (EI) m/z (%): 374 (M+), 43
(100); IR (neat, cmꢀ1): 3103, 2929, 2224, 1753, 1626, 1590, 1520,
1377, 1345, 1222, 1156, 1118, 1036, 884, 859; HRMS: Calc. for
(282 Hz, CDCl3):
d
ꢀ55.15 (s); 13C NMR (100 Hz, CDCl3):
d 146.8,
147.0 (t, JC,F = 28.7 Hz), 133.2, 132.8, 131.1, 128.7, 127.6, 127.5,
120.2, 119.7, 115.7, 114.6 (t, JC,F = 306.7 Hz), 102.0, 78.3; MS (EI) m/
z (%): 413 (M+, 9.7), 282 (100); IR (neat, cmꢀ1): 3062, 2200, 1615,
1593, 1498, 1464, 1443, 1146, 1067, 916, 754; HRMS: Calc. for
C16H9NF281Br2: 414.9025. Found: 414.9029.
C
13H9N2O4F281Br: 375.9699. Found: 375.9693.
5-Bromo-5,5-difluoro-4-(3-chlorophenylimino)pent-2-ynyl
acetate (3id). Yellow oil; 1H NMR (300 Hz, CDCl3):
d 7.29–7.24 (m,
N-(1-bromo-1,1-difluoro-4-phenylbut-3-yn-2-ylidene)-3-
1H), 7.19–7.13 (m, 2H), 7.01–6.98 (m, 1H), 4.71 (s, 2H), 2.01 (s, 3H);
chloroaniline (3ib). Yellow oil; 1H NMR (300 Hz, CDCl3):
d
7.37–
19F NMR (282 Hz, CDCl3):
d
ꢀ55.17 (s); 13C NMR (100 Hz, CDCl3):
d
7.06 (m, 9H); 19F NMR (282 Hz, CDCl3):
(100 Hz, CDCl3):
d
ꢀ54.97 (s); 13C NMR
169.7, 147.8, 144.1 (t, JC,F = 28.9 Hz), 134.5, 130.0, 127.3, 120.9,
119.5, 114.4 (t, JC,F = 306.7 Hz), 95.9, 75.0, 51.5, 20.4; MS (EI) m/z
(%): 363 (M+, 2.7), 43 (100); IR (neat, cmꢀ1): 2936, 2224, 1756,
1587, 1570, 1469, 1219, 1157, 1121, 907, 835; HRMS: Calc for
d
148.6, 145.4 (t, JC,F = 28.6 Hz), 134.4, 132.8,
131.1, 130.6, 128.7, 127.1, 121.2, 119.9, 119.7, 114.9 (t,
JC,F = 306.9 Hz), 101.7, 78.5; MS (EI) m/z (%): 367 (M+, 3.2), 238
(100); IR (neat, cmꢀ1): 3064, 2202, 1614, 1585, 1489, 1469, 1145,
1063, 923, 756, 686; HRMS: Calc. for C16H9NClF2Br: 366.9573.
Found: 366. 9575.
C
13H9NO2ClF281Br: 364.9455. Found: 364.9453.
5-Bromo-5,5-difluoro-4-(4-(trifluoromethyl)phenylimino)-
pent-2-ynyl acetate (3jd). Yellow oil; 1H NMR (300 Hz, CDCl3):
d
N-(1-bromo-1,1-difluoro-4-phenylbut-3-yn-2-ylidene)-4-tri-
7.67 (d, J = 7.8 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 4.75 (s, 2H), 2.03 (s,
fluoromethylaniline (3jb). Yellow oil; 1H NMR (300 Hz, CDCl3):
d
3H); 19F NMR (282 Hz, CDCl3):
d
ꢀ55.27 (s, 2F), ꢀ62.29 (s, 3F); 13
C
7.70 (d, J = 7.8 Hz, 2H), 7.46–7.41 (m, 2H), 7.36–7.34 (m, 3H), 7.30
(d, J = 7.8 Hz, 2H); 19F NMR (282 Hz, CDCl3):
ꢀ55.01 (s, 2F),
NMR (100 Hz, CDCl3): d 165.4, 145.8, 140.8 (t, JC,F = 28.2 Hz), 124.7
(q, JC,F = 32.3 Hz), 121.9, 120.0 (q, JC,F = 270.9 Hz), 116.5, 110.0 (t,
d

200
S. Li et al. / Journal of Fluorine Chemistry 132 (2011) 196–201
JC,F = 306.8 Hz), 92.1, 70.5, 47.2, 16.0; MS (EI) m/z (%): 397 (M+,
2.05), 268 (100); IR (neat, cmꢀ1): 2936, 2223, 1754, 1609, 1580,
1325, 1223, 1164, 1125, 1067, 883, 847; HRMS: Calc. for
1603, 1582, 1489, 1452, 1319, 1258, 1224, 1155, 1069, 758, 687;
HRMS: Calc. for C17H9NF6: 341.0646. Found: 341.0639.
Methyl 5,5,5-trifluoro-4-(o-tolylimino)pent-2-ynoate (3pc).
C
14H9NO2F581Br: 398.9713. Found: 398.9716.
Yellow oil; 1H NMR (300 Hz, CDCl3):
d 7.26–7.20 (m, 3H), 7.13–
N,N0-(1,6-dibromo-1,1,6,6-tetrafluorhex-3-yne-2,5-diylide-
7.11 (m, 2H), 3.78 (s, 3H), 2.25 (s, 3H); 19F NMR (282 Hz, CDCl3):
d
ne)di(4-methylaniline) (3be). Yellow solid; 1H NMR (300 Hz,
ꢀ70.78 (s); 13C NMR (100 Hz, CDCl3):
d 152.9, 146.1, 137.0 (q,
CDCl3):
d
7.00 (m, 8H), 2.18 (s, 6H); 19F NMR (282 Hz, CDCl3):
d
JC,F = 39.5 Hz), 132.8, 131.7, 129.5, 127.1, 118.5 (q, JC,F = 276.1 Hz),
118.8, 87.4, 73.5, 54.3, 18.4; MS (EI) m/z (%): 269 (M+, 68.1), 91
(100); IR (neat, cmꢀ1): 3378, 2940, 1731, 1669, 1578, 1461, 1438,
1329, 1253, 1196, 1100, 755; HRMS: Calc. for C13H10NO2F3:
269.0669. Found: 269.0664.
ꢀ53.94 (s); 13C NMR (100 Hz, CDCl3):
d 143.7, 140.0, 139.8 (t,
JC,F = 28.3 Hz), 130.0, 122.6, 114.8 (t, JC,F = 306.6 Hz), 86.1, 21.7. MS
(EI) m/z (%): 518 (M+, 2.57), 91 (100); IR (neat, cmꢀ1): 2960, 1577,
1502, 1296, 1156, 1096, 929, 819; HRMS: Calc. for C20H14N2F4Br2:
515.9464. Found: 515.9460.
5,5,5-Trifluoro-4-(o-tolylimino)pent-2-ynyl acetate (3pd). Yel-
N,N0-(1,1-dibromo-1,1,6,6-tetrafluorhex-3-yne-2,5-diylide-
ne)di(4-chloroaniline) (3ke). Yellow solid; 1H NMR (300 Hz,
low oil; 1H NMR (300 Hz, CDCl3):
d 7.23 (m, 1H), 7.19–7.16 (m, 2H),
7.05 (m, 1H), 4.72 (s, 2H), 2.21 (s, 3H), 2.04 (s, 3H); 19F NMR
CDCl3):
NMR (282 Hz, CDCl3):
d
7.28 (d, J = 9.0 Hz, 4H), 7.10 (d, J = 9.0 Hz, 4H); 19F
(282 Hz, CDCl3):
d
ꢀ71.33 (s, 3F); 13C NMR (100 Hz, CDCl3):
d 170.5,
d
ꢀ54.77 (s); 13C NMR (100 Hz, CDCl3):
d
146.8, 139.1 (q, JC,F = 38.4 Hz), 131.5, 131.4, 128.2, 126.8, 119.0,
119.5 (q, JC,F = 275.8 Hz), 95.0, 76.5, 52.3, 21.2, 18.3; MS (EI) m/z
(%): 283 (M+, 64.1), 223 (100); IR (neat, cmꢀ1): 2923, 2224, 1755,
1630, 1485, 1429, 1377, 1333, 1205, 1145, 1035, 951, 767; HRMS:
Calc. for C14H12NO2F3: 283.0818. Found: 283.0820.
144.6, 141.4 (t, JC,F = 29.3 Hz), 135.1, 129.7, 123.3, 114.2 (t,
JC,F = 307.4 Hz), 85.7; MS (EI) m/z (%): 558 (M+, 6.0), 111 (100);
IR (neat, cmꢀ1): 1895, 1607, 1574, 1482, 1304, 1175, 1155, 1102,
926, 844; HRMS: Calc. for C18H8N2Cl2F481Br2: 559.8332. Found:
559.8326.
5,5,5-Trifluoro-4-(2-(trifluoromethyl)phenylimino)pent-2-
N-(1,1,1-trifluorooct-3-yn-2-ylidene)-4-methoxylaniline (3la).
ynyl acetate (3od). Yellow oil; 1H NMR (300 Hz, CDCl3):
d
7.71 (d,
Yellow oil; 1H NMR (300 Hz, CDCl3):
d 7.43 (d, J = 8.7 Hz, 2H), 6.91
J = 7.8 Hz, 1H), 7.56 (t, J = 7.7 Hz, 1H), 7.35(t, J = 7.5 Hz, 1H), 7.03 (d,
J = 8.1 Hz, 1H), 4.70 (s, 2H), 2.02 (s, 3H); 19F NMR (282 Hz, CDCl3):
d
(d, J = 8.7 Hz, 2H), 3.83 (s, 3H), 2.41 (t, J = 7.1 Hz, 2H), 1.57–1.50 (m,
2H), 1.42–1.35 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H); 19F NMR (282 Hz,
ꢀ60.93 (s, 3F), ꢀ71.95 (s, 3F); 13C NMR (100 Hz, CDCl3):
d 165.4,
CDCl3):
d
ꢀ71.37 (s); 13C NMR (100 Hz, CDCl3):
d
159.3, 140.0,
141.5, 137.2 (q, JC,F = 39.3 Hz), 128.2, 122.4, 122.3, 118.5 (q,
JC,F = 272.2 Hz), 117.0, 112.5 (q, JC,F = 31.0 Hz), 112.3, 92.0, 70.7,
47.0, 25.5; MS (EI) m/z (%): 337 (M+, 15.4), 277 (100); IR (neat,
cmꢀ1): 2936, 2226, 1757, 1633, 1603, 1452, 1320, 1208, 1142,
1036, 948, 774; HRMS: Calc. for C14H9NO2F6: 337.0536. Found:
337.0537.
136.6 (q, JC,F = 37.2 Hz), 124.3, 118.5 (q, JC,F = 275.4 Hz), 113.8,
103.2, 72.1, 55.4, 29.5, 21.8, 19.2, 13.4; MS (EI) m/z (%): 283 (M+,
49.8), 214 (100); IR (neat, cmꢀ1): 2961, 2936, 2211, 1615, 1579,
1504, 1466, 1252, 1195, 1138, 1034, 835; HRMS: Calc. for
C
15H16NOF3: 283.1182. Found: 283.1184.
N-(1,1,1-trifluorooct-3-yn-2-ylidene)-4-nitroaniline
(3ma).
Yellow oil; 1H NMR (300 Hz, CDCl3):
d
8.29 (d, J = 8.7 Hz, 2H),
Acknowledgement
7.19 (d, J = 8.7 Hz, 2H), 2.35 (t, J = 7.1 Hz, 2H), 1.47–1.42 (m, 2H),
1.28–1.21 (m, 2H), 0.83 (t, J = 7.2 Hz, 3H); 19F NMR (282 Hz, CDCl3):
We thank National Science Foundation of China (Nos. 20532040
and 20772145) for the financial support.
d
ꢀ72.19 (s); 13C NMR (100 Hz, CDCl3):
d 147.6, 140.1 (q,
JC,F = 38.0 Hz), 128.7, 127.0, 120.9, 118.5 (q, JC,F = 276.2 Hz),
103.8, 71.4, 29.4, 21.7, 19.1, 13.4; MS (EI) m/z (%): 298 (M+,
24.2), 229 (100); IR (neat, cmꢀ1): 2962, 2865, 2215, 1626, 1604,
1591, 1523, 1486, 1345, 1202, 1149, 862, 730; HRMS: Calc. for
References
[1] (a) A.W. Sromek, A.L. Rheingold, D.J. Wink, V. Gevorgyan, Synlett 14 (2006) 2325–
2328;
C
14H13N2O2F3: 298.0917. Found: 298.0929.
(b) A.V. Kel’in, A.W. Sromek, V. Gevorgyan, J. Am. Chem. Soc. 13 (2001) 2074–
2075.
[2] P.R. Lihar, M.S. Subhas, S. Roy, M.L. Kantam, Org. Biomol. Chem. 7 (2009) 85–93.
[3] (a) F. Sha, X. Huang, Angew. Chem. Int. Ed. 48 (2009) 3458–3461;
(b) I. Hachiya, Y. Minami, T. Aramaki, M. Shimizu, Eur. J. Org. Chem. 8 (2008)
1411–1417;
(c) I. Hachiya, S. Fukushima, M. Shimizu, Heterocycles 69 (2006) 43–48.
[4] (a) H.B. Yu, W.Y. Huang, J. Fluorine Chem. 87 (1998) 69–73;
(b) H.B. Yu, W.Y. Huang, Synlett 06 (1997) 679–680;
N-(1,1,1-trifluoro-4-phenylbut-3-yn-2-ylidene) aniline (3nb).
d
Yellow oil; 1H NMR (300 Hz, CDCl3): 7.47–7.30 (m, 10H); 19F NMR
(282 Hz, CDCl3):
d
ꢀ71.44 (s); 13C NMR (100 Hz, CDCl3):
d 147.6,
139.6 (q, JC,F = 38.7 Hz), 132.7, 130.9, 128.8, 128.7, 127.5, 121.4,
118.5 (q, JC,F = 276.2 Hz), 119.9, 100.0, 79.2; MS (EI) m/z (%): 273
(M+, 38.6), 204 (100); IR (neat, cmꢀ1): 3065, 2927, 2209, 1614,
1584, 1489, 1444, 1346, 1258, 1145, 1062, 757, 688; HRMS: Calc.
for C16H10NF3: 273.0767. Found: 273.0765.
(c) G. Bernard, H. van den Hoven, Alper, J. Am. Chem. Soc. 123 (2001) 10214–10220;
(d) L.Y. Ukhin, Z.I. Orlova, O.A. Tokarskaya, Dok. Akad. Nauk. SSSR 288 (1986) 897–
899 (Chem. Abstr., 106 (1986) 102150).
N-(1,1,1-trifluoro-4-phenylbut-3-yn-2-ylidene)-4-nitroaniline
(3mb). Yellow oil; 1H NMR (300 Hz, CDCl3):
d 8.34 (d, J = 8.7 Hz,
[5] R. Rahm, S. Espenlaub, U.R. Werz, G. Maas, Heteroatom Chem. 16 (2005) 437–446.
[6] (a) E. Barnea, C.J. Berthet, S.M. Eiseu, Organometallics 27 (2008) 3103–3112;
(b) Q.L. Dong, G.S. Liu, H.B. Zhou, L. Chen, Z.J. Yao, Tetrahedron Lett. 49 (2008)
1636–1640;
(c) Q. Kang, Z.A. Zhao, S.L. You, Org. Lett. 10 (2008) 2031–2034;
(d) H. Gerster, S. Espeulaub, G. Maas, Synthesis 13 (2006) 2251–2259.
[7] (a) K. Tamura, H. Mizukami, K. Maeda, H. Watanabe, K. Uneyama, J. Org. Chem. 58
(1993) 32–35;
(b) A. Isobe, J. Takagi, T. Katagiri, K. Uneyama, Org. Lett. 10 (2008) 2657–2659;
(c) F.L. Ge, Z.X. Wang, W. Wan, J. Hao, Synlett 3 (2007) 447–450;
(d) T. Kobayashi, T. Nakagawa, H. Amii, K. Uneyama, Org. Lett. 5 (2003) 4297–4300;
(e) H. Amii, Y. Kishikawa, K. Uneyama, Org. Lett. 3 (2001) 1109–1112;
(f) W.S. Huang, C.Y. Yuan, Z.Q. Wang, J. Fluorine Chem. 74 (1995) 247–250;
(g) K. Uneyama, H. Watanabe, Tetrahedron Lett. 32 (1991) 1459.
[8] (a) J.T. Welch, S. Eswarakrishnan, Fluorine in Bioorganic Chemistry, Wiley, New
York, 1991;
2H), 7.49–7.44 (m, 1H), 7.37–7.36 (m, 4H), 7.30 (d, J = 8.7 Hz, 2H);
19F NMR (282 Hz, CDCl3):
d
ꢀ71.65 (s); 13C NMR (100 Hz, CDCl3):
d
153.4, 146.0, 142.5 (q, JC,F = 39.4 Hz), 132.9, 131.6, 128.8, 124.8,
121.1, 119.0, 118.0 (q, JC,F = 276.2 Hz), 102.7, 78.3; MS (EI) m/z (%):
318 (M+, 36.8), 249 (100); IR (neat, cmꢀ1): 3104, 2201, 1614, 1592,
1508, 1489, 1195, 1145, 1065, 872, 762, 687; HRMS: Calc. for
C
16H9N2O2F3: 318.0617. Found: 318.0616.
N-(1,1,1-trifluoro-4-phenylbut-3-yn-2-ylidene)-2-(trifluoro-
methyl) aniline (3ob). Yellow oil; 1H NMR (300 Hz, CDCl3):
d
7.73
(d, J = 7.8 Hz, 1H), 7.59 (t, J = 7.4 Hz, 1H), 7.44–7.27 (m, 6H), 7.13 (d,
J = 8.7 Hz, 1H); 19F NMR (282 Hz, CDCl3):
ꢀ60.84 (s, 3F), ꢀ71.69
(s, 3F); 13C NMR (100 Hz, CDCl3):
142.4, 138.4 (q, JC,F = 39.7 Hz),
d
(b) T. Katagiri, Y. Fujiwara, S. Takahashi, K. Uneyama, J. Fluorine Chem. 126 (2005)
1134–1139;
(c) L.W. Hertel, J.S. Kroin, J.W. Tustin, J. Org. Chem. 53 (1998) 2406–2409;
(d) A. Suzuki, M. Mae, H. Amii, K. Uneyama, J. Org. Chem. 69 (2004) 5132–5134;
(e) S. Fustero, A. Bartolome´, Org. Lett. 5 (2003) 2523–2526;
d
128.6, 128.1, 127.0, 124.5, 122.4, 122.0, 118.5 (q, JC,F = 272.2 Hz),
117.3 (q, JC,F = 31.0 Hz), 115.4, 115.1, 112.6, 97.8, 74.3; MS (EI) m/z
(%): 341 (M+, 27.9), 272 (100); IR (neat, cmꢀ1): 3064, 2194, 1621,

S. Li et al. / Journal of Fluorine Chemistry 132 (2011) 196–201
201
(f) K. Uneyama, Organofluorine Chemistry, Blackwell Publishing, Oxford, UK,
2006;
(c) M. Juricek, P. Kasak, M. Stach, M. Putala, Tetrahedron Lett. 48 (2007) 8869–
8873;
(g) P. Kirsh, Modern Fluoroorganic Chemistry, Wiley-VCH Verlag, Weinheim,
2004;
(d) S.F. Vasilevsky, O.L. Krivenko, V.R. Gorelik, I.V. Alabugin, Tetrahedron 64
(2008) 8807–8814;
(h) J.-P. Be´gue´, D. Bonnet-Delpon, Bioorganic and Medicinal Chemistry of
Fluorine, Wiley, Hoboken, 2008.
(e) C.C. Lee, M.K. Leung, G.H. Lee, Y.H. Liu, S.M. Peng, J. Org. Chem. 71 (2006)
8417–8423.
[9] (a) Y.M. Wu, Y. Li, J. Deng, J. Fluorine Chem. 126 (2005) 791–795;
(b) Y.M. Wu, M. Zhang, Y.Q. Li, J. Fluorine Chem. 127 (2006) 1168–1174;
(c) Y. Li, J. Deng, Y.M. Wu, Tetrahedron Lett. 46 (2005) 5357–5360;
(d) Y.M. Wu, Y. Li, J. Deng, J. Fluorine Chem. 127 (2006) 223–228;
(e) J.T. Zhu, H.B. Xie, Z.X. Chen, S. Li, Y.M. Wu, Chem. Commun. (2009) 2338–2340.
[10] Y.M. Wu, M. Zhang, Y.Q. Li, J Fluorine Chem. 127 (2006) 218–222.
[11] (a) Y.K. Lee, J.M. Lee, N.J. Kim, Tetrahedron 61 (2005) 8705–8710;
(b) C.J. Woltermann, H. Shechter, Helv. Chim. Acta 88 (2005) 354–369.
[12] (a) A. Biffis, C. Tubaro, E. Scattolin, M. Basata, G. Papini, C. Santini, E. Alvarez, S.
Conejero, Dalton Trans. 35 (2009) 7223–7229;
[13] (a) A. Corma, C.G. Arellano, M. Iglesias, S.P. Ferreras, M. Iglesias, F. Sanchez,
Synlett 11 (2007) 1771–1774;
(b) C.G. Arellano, A. Abad, A. Corma, H. Garcia, M. Iglesias, F. Sanchez, Angew.
Chem. Int. Ed. 46 (2007) 1536–1538;
(c) C.G. Arellano, A. Corma, M. Iglesias, F. Sanchez, Chem. Commun. 14 (2005)
1990–1993.
[14] (a) M. Oishi, H. Kondo, H. Amii, Chem. Common (2009) 1909–1911;
(b) J. Zhu, W. Zhang, L. Zhang, J. Liu, J. Zheng, J. Hu, J. Org. Chem. 75 (2010) 5505–
5512;
(c) L.-L. Chu, F.-L. Qing, J. Am. Chem. Soc. 132 (2010) 7262–7263;
(d) L.-L. Chu, F.-L. Qing, Org. Lett. 12 (2010) 5060–5063.
(b) A. Meetsma, J.H. Teuben, B. Hessen, Organometallics 27 (2008) 5672–5683;