Reaction of β-fluorinated vinamidinium salts with Grignard reagents and reducing agents - New facile and efficient route to fluorinated allylamines

Article abstract of DOI:10.1016/S0022-1139(01)00349-9

β-Fluorinated vinamidinium salts (1) readily reacted with a series of Grignard reagents in tetrahydrofuran, followed by the action of reducing agents at room temperature, to produce stereospecifically the corresponding fluorinated allylamines (4 and 5) in good to excellent yields.

Full text of DOI:10.1016/S0022-1139(01)00349-9

Journal of Fluorine Chemistry 108 /2001) 199±205
Reaction of b-¯uorinated vinamidinium salts with
Grignard reagents and reducing agents
New facile and ef®cient route to ¯uorinated allylamines
Hiroki Yamanakaa,*, Yasumasa Odania, Takashi Ishiharaa,
Tsutomu Konnoa, John T. Guptonb
aDepartment of Chemistry and Materials Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
bDepartment of Chemistry, The University of Richmond, Richmond, VA 23173, USA
Received 27 September 2000; received in revised form 9 January 2001; accepted 20 January 2001
Abstract
b-Fluorinated vinamidinium salts /1) readily reacted with a series of Grignard reagents in tetrahydrofuran, followed by the action of
reducing agents at room temperature, to produce stereospeci®cally the corresponding ¯uorinated allylamines /4 and 5) in good to excellent
yields. # 2001 Elsevier Science B.V. All rights reserved.
Keywords: Vinamidinium salts; Grignard reactions/reagents; Reduction; Enamines; Allylamines; Fluorine and compounds
1. Introduction
variety of Grignard reagents to give the corresponding a,b-
unsaturated aldehydes [25,26]. Herein we would like to
report the reactions of these b-¯uorinated vinamidinium
salts with Grignard reagents followed by treatment with
reducing agents. The results demonstrated that the reactions
constitute a new facile and ef®cient route to b-¯uorinated
allylic amines which are useful synthons for the synthesis of
various organo¯uorine compounds [27].
Vinamidinium /1,5-diazapentadienium) salts, vinylogs of
amidinium compounds, have widely been utilized in organic
synthesis since they have unique and versatile reactivities
[1]. Many types of vinamidinium salts appended with
various substituents have hitherto been developed and used
as potent three-carbon building blocks for the synthesis of
acyclic and cyclic organic compounds [1±14]. In contrast to
such extensive works, there are only a few reports on the
¯uorine-containing vinamidinium salts [13±17], which
should be useful synthons for synthesizing ¯uorinated com-
pounds of biological and material interest. In our continuing
studies in this area, we recently succeeded in preparing the
vinamidinium salts with ¯uorine substituents, such as ¯uoro
[18], tri¯uoromethyl [19] and poly¯uoroalkoxy [20] at the b
carbon. These salts were successfully applied to the synth-
esis of ¯uorinated heterocycles [19,21,22], b-aminoacro-
leins [23], dienamino carbonyl compounds and aromatic
compounds [24]. A focus of our research interest has been
addressed to studies for the scope and limitation of the
synthetic utility of these ¯uorine-containing vinamidinium
salts. Very recently, we have reported that b-¯uoro and b-
poly¯uoroalkoxy vinamidinium salts react smoothly with a
2. Results and discussion
We previously proposed a possible mechanism for the
reaction of 1,5-diaza-1,1,5,5-tetraethyl-3-¯uoro-1,3-penta-
dienium iodide /b-¯uoro vinamidinium salt) /1A) with
Grignard reagents, followed by acidic workup, leading to
the formation of a-¯uoro-a,b-unsaturated aldehydes 3 via an
intermediate enamine X [25] /Scheme 1). In fact, the
existence of the intermediate had strongly been suggested
by the 19F NMR spectra of the reaction mixtures in all cases,
where the resonance appeared as doublet of doublets
/J ˆ 31À34 and 10±31 Hz) at around À70 ppm /up®eld
from the external standard of CF3COOH). This peak shifted
to around À57 ppm corresponding to the ®nal product 3 by
the treatment with aqueous acid. Attempts to isolate this
intermediate before acidic workup were unsuccessful; X
was entirely converted to 3 during the isolation by column
* Corresponding author. Tel.: ‡81-75-724-7517; fax: ‡81-75-724-7580.
E-mail address: yamanaka@ipc.kit.ac.jp /H. Yamanaka).
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 / 0 1 ) 0 0 3 4 9 - 9

200
H. Yamanaka et al. / Journal of Fluorine Chemistry 108 52001) 199±205
Scheme 1.
Scheme 2.
chromatography /silica gel or aluminum oxide [activated,
basic]/hexane).
equiv. of diisobutylaluminum hydride /DIBAL) as the redu-
cing agent in THF at room temperature for 1 h and then with
water gave a-¯uorocinnamaldehyde 3a, a hydrolysis pro-
duct of the enamine, in 98% yield as sole product /Entry 1).
Prolongation of the reaction time /24 h) produced the
desired allylamine, N,N-diethyl-2-¯uoro-3-pheny-2Z-pro-
penylamine /4a), in a low yield /10%) along with 3a /Entry
2). Furthermore, the use of an excess amount of DIBAL
increased the yield of 4a /Entries 3 and 4). The best result
was obtained from the reaction with 4.0 equiv. of DIBAL for
24 h, affording 4a in 90% yield without formation of 3a
/Entry 5). The quenching with 10% hydrochloric acid,
instead of water, gave a hydrochloride salt of the amine 4a.
Borane-THF complex was also employable as the redu-
cing agent. Thus, 1.0 equiv. of borane-THF complex gave 4a
in 67% /with 13% of 3a) for 3 h and in 97% yields /without
3a) for 24 h /Entries 6 and 7). Other reducing agents, such as
sodium borohydride and lithium aluminum hydride /1.0
equiv.), yielded a mixture of 3a and 4a even if the reactions
were carried out for 24 h /Entries 8 and 9).
In the present study, we planned to make further synthetic
use of this enamine intermediate before acidic workup,
assuming that the in situ reduction of the intermediate X
with hydride-reducing reagents would provide very useful
¯uorinated allylic amines.
We ®rst treated the reaction mixture, resulting from the
reaction of 1A with phenylmagnesium bromide 2a /2.2
equiv.) in tetrahydrofuran /THF) at room temperature for
3 h, with a variety of hydride-reducing agents under various
conditions /Scheme 2). The results are summarized in
Table 1. The treatment of the reaction mixture with 1.1
Table 1
Reaction of 1A with phenylmagnesium bromide /2a) and reducing agents
under various conditions
Entry
Reducing reagent /eq.)
Time /h)
Yielda/% of
4a
3a
We next examined the synthesis of various ¯uorinated
allylamines 4 according to the previous described metho-
dology. The vinamidinium salt 1Awas allowed to react with
a variety of Grignard reagents /2.2 equiv.) in THF at ambient
temperature for 3 h, followed by treatment with DIBAL /4.0
equiv.) or borane-THF complex /1.0 equiv.) at room tem-
perature for 24 h /Entries 5 and 7) /Scheme 3). The results
are summarized in Table 2. Both reducing agents could
participate nicely in the reactions using all Grignard reagents
1
2
3
4
5
6
7
8
9
DIBAL /1.0)
DIBAL /1.0)
DIBAL /3.0)
DIBAL /4.0)
DIBAL /4.0)
BH3ÁTHF /1.0)
BH3ÁTHF /1.0)
NaBH4 /1.0)
LiAlH4 /1.0)
1
24
24
3
0
10
79
51
90
67
97
24
57
98
79
19
48
0
24
3
13
0
24
24
24
55
42
a Determined by 19F NMR.

H. Yamanaka et al. / Journal of Fluorine Chemistry 108 52001) 199±205
201
Scheme 3.
Table 2
the allylamines 4 thus obtained were only one stereoisomer
having the Z con®guration, which was unambiguously
determined on the basis of the magnitudes of vicinal H±F
Results of the reaction of 1A with various Grignard reagents-reducing
agents
Entry
RMgX /2)
Reducing
agent
Yielda/% of 4
1
couplings in H and 19F NMR spectra [28].
We also synthesized poly¯uoroalkoxylated allylamines 5
by the reaction of DIBAL with the reaction mixture from
b-poly¯uoroalkoxylated vinamidinium salts 1B±D and
Grignard reagent 2a /Scheme 4). Thus, 1,5-diaza-1,1,5,5-
tetraethyl-3-/2,2,2-tri¯uoroethoxy)-1,3-pentadienium iodide
/b-tri¯uoroethoxy vinamidinium salt) /1B) was treated with
2.2 equiv. of phenylmagnesium bromide /2a) in THF at
room temperature for 3 h and then with 4.0 equiv. of DIBAL
at the same temperature for 24 h to afford N,N-diethyl-3-
phenyl-2-/2,2,2-tri¯uoroethoxy)-2Z-propenylamine /5Ba)
in 86% yield. The reaction with other vinamidinium salts
having 2,2,3,3,3-penta¯uoropropoxy /1C) and 2,2,3,3-tetra-
¯uoropropoxy group /1D) at the b carbon proceeded
smoothly to give the corresponding poly¯uoroalkoxylated
allylic amines /5Ca, 5Da) in good yields. The chain length
and number of ¯uorine of the poly¯uoroalkoxy group did
not affect the yields of the allylamines 5. The products 5
consisted of single isomers but their stereochemistry has yet
to be determined.
The following mechanism is anticipated for the formation
of the allylamines 4 and 5 /Scheme 5). The intermediate
enamine X resulting from the attack of Grignard reagent on
the a carbon of 1 may react with reducing agent through a
six-membered ring transition state Y, in which the reductive
deamination occurs via an SN20 like process to afford the
allylamine. This mechanism was veri®ed by the reaction
using a deuterated reducing agent. Thus, the reaction mix-
ture prepared from 1A and 2a was similarly treated with
borane-d3-THF complex to give the corresponding a-deut-
erated allylamine 6 in 87% yield /Scheme 6).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
PhMgBr /2a)
DJBAL
/4a)
/4b)
/4c)
/4d)
/4e)
/4f)
85
BH3ÁTHF
DIBAL
92
88
82
93
94
83
88
71
60
74
43
50
40
/5)b
p-CH3OC6H4MgBr /2b)
p-CH3C6H4MgBr /2c)
a-NaphthylMgBr /2d)
BuMgBr /2e)
BH3ÁTHF
DIBAL
BH3ÁTHF
DIBAL
BH3ÁTHF
DIBAL
BH3ÁTHF
DIBAL
C6H5CH2MgCl /2f)
i-PrMgBr /2g)
BH3ÁTHF
DIBAL
/4g)
/4h)
BH3ÁTHF
DIBAL
t-BuMgCl /2h)
a Isolated yields.
19F NMR yie1d.
b
except t-butylmagnesium chloride. Thus, DIBAL reacted
smoothly with the mixture from aromatic Grignard reagents
2a±d to give the corresponding arylated ¯uoroallylamines
4a±d in high yields /83±93%) /Entries 10, 12, 14 and 16).
Similarly, borane-THF complex led to satisfactory results
/82±94 yield) /Entries 11, 13, 15 and 17). The reaction of
both reducing agents with the mixture from primary and
secondary alkyl Grignard reagents 2e±g also gave the cor-
responding alkylated ¯uoroallylamine 4e±g in good to
moderate yields /Entries 18±23). However, tertiary alkyl
Grignard reagent, t-butylmagnesium chloride /2h), gave the
product 4h only in low NMR yield along with an unidenti-
®ed product, large amounts of the starting material 1A being
left unchanged /Entry 24). The low yield of 4h is mainly due
to low reactivity of 2h toward 1A [25]. In all these reactions,
The predominant formation of the Z-isomer may be
explained by an SN20 displacement of the diethylamino
group for the most stable conformer of the six-membered
Scheme 4.

202
H. Yamanaka et al. / Journal of Fluorine Chemistry 108 52001) 199±205
Scheme 5.
Scheme 6.
ring transition state Y. The conformer Y-1 should be more
stable than the other Y-2, which has a 1,3-allylic strain
/Scheme 7). Therefore, the reaction proceeds preferentially
via Y-2, leading to the Z isomer.
allylamines in good yields. This reaction can serve as a facile
and ef®cient route to the ¯uorinated allylamines, and also
substantiates the utility of these vinamidinium salts as
¯uorine-containing three-carbon building blocks in organic
¯uorine synthesis.
3. Conclusion
4. Experimental
In the present study, we have shown that b-¯uoro /1A) and
b-poly¯uoroalkoxy vinamidinium salts /1B±D) react with
Grignard reagents to generate the intermediate enamines,
which can be transformed by the action of reducing agents,
such as DIBAL and borane±THF complex, into ¯uorinated
4.1. Measurement and materials
Infrared spectra /IR) were measured in a liquid ®lm or
KBr disk method with a Shimadzu FTIR-8200PC spectro-
photometer. 1H and 13C NMR spectra were obtained with a
1
Bruker DRX500 /500 MHz for H and 125 MHz for 13C)
spectrometer in a chloroform-d /CDCl3) solution with tetra-
methylsilane /TMS) as an internal reference. A JEOL JNM
EX90 /84.10 MHz) spectrometer was used to measure 19F
NMR spectra in CDCl3 with trichloro¯uoromethane /CCl3F)
as an internal reference. 19F NMR yield was calculated from
the peak area ratio of a sample to benzotri¯uoride /BTF) as
an internal standard. Mass spectra /MS) and high resolution
mass spectra /HRMS) were taken on a Hitachi M-80B,
Shimadzu QP-1000 and/or JEOL JMS-700 mass spectro-
meter. Melting points were obtained on a Mettler FP5
melting point determination apparatus and are uncorrected.
The elemental analyses of the products gave satisfactory
results.
b-Fluoro /1A) and b-poly¯uoroalkoxy vinamidinium
salts 1B±D were prepared according to the method reported
by us [18,20]. All chemicals are of reagent grade and, if
Scheme 7.

H. Yamanaka et al. / Journal of Fluorine Chemistry 108 52001) 199±205
203
necessary, were puri®ed by a conventional manner before
use. Tetrahydrofuran /THF) was distilled with sodium ben-
zophenone kethyl and stored under argon. All reactions were
carried out under an atmosphere of argon.
22.1 Hz, 1F); IR /KBr) 2978 /m), 2932 /m), 2878 /m), 2939
/m), 2731 /s), 2658 /s), 2584 /m), 2492 /m), 2434 /m), 1689
/w); MS m/e /relative intensity) 237 /M , 31), 222 /12), 166
/12), 165 /100); HRMS /EI) found: m/z 237.1511; calculated
for C14H20FNO: M, 237.1529.
‡
4.2. Reaction of vinamidinium salts 1 with Grignard
reagents and reducing agents: synthesis of fluorinated
allylamines 4 and 5
7. N,N-diethyl-2-fluoro-3-&4-methylphenyl)-2Z-
propenylamine &4c)
The typical procedure is as follows. To a solution of the
vinamidinium salt 1A /0.328 g, 1.0 mmol) in THF /3 ml)
was gradually added 2.2 equiv. of phenylmagnesium bro-
mide in THF /2.3 ml) at 08C and then the mixture was stirred
at room temperature for 3 h under an atmosphere of argon.
DIBAL /1.0 M solution in hexane /4.0 ml)) was added to the
reaction mixture and the whole was stirred at room tem-
perature for 24 h. The reaction mixture was poured on ice-
water and then extracted with dichloromethane /20 ml  4).
The organic layers were washed with a brine /30 ml), dried
over anhydrous sodium sulfate, and concentrated in vacuo.
The residue was puri®ed by silica-gel column chromato-
graphy /hexane-benzene /50:50)) to give N,N-diethyl-2-
¯uoro-3-pheny-2Z-propenylamine /4a) /0.176 g, 85% yield)
as a colorless liquid. When the reaction mixture was treated
with 10% hydrochloric acid instead of ice-water, the hydro-
chloride salt of 4a was isolated as a white solid after column
chromatography /benzene and then ethanol).
1
M.p. 60±618C; H NMR /CDCl3) d 1.33 /t, J ˆ 7:3 Hz,
6H), 2.35 /s, 3H), 2.88 /dq, J ˆ 12:8, 7.3 Hz, 2H), 2.96 /dq,
J ˆ 12:8, 7.3 Hz, 2H), 3.66 /d, J ˆ 22:0 Hz, 2H), 5.78 /d,
J ˆ 38:5 Hz, 1H), 7.16 /d, J ˆ 8:3 Hz, 2H), 7.40 /d,
J ˆ 8:3 Hz, 2H); 13C NMR /CDCl3) d 9.38, 21.23, 54.33,
59.21 /d, J ˆ 25:5 Hz), 114.99 /d, J ˆ 8:2 Hz), 128.27,
128.83 /d, J ˆ 7:6 Hz), 129.12 /d, J ˆ 3:1 Hz), 138.21
/d, J ˆ 2:0 Hz), 152.11 /d, J ˆ 265:3 Hz); 19F NMR
/CDCl3) d À102.92 /dt, J ˆ 38:5, 22.0 Hz, 1F); IR /KBr)
2297 /m), 2978 /m), 2951 /m), 2889 /w), 2380 /vs), 2326
/vs), 2280 /vs), 1686 /m) cmÀ1; MS m/e /relative intensity)
‡
221 /M , 17), 206 /19), 192 /2), 150 /12), 149 /100), 129
/11), 86 /5), 58 /15). HRMS /EI) found: m/z 221.1572;
calculated for C14H20FN: M, 221.1580.
8. N,N-diethyl-2-fluoro-3-&4-methylphenyl)-2Z-
propenylamine hydrochloride &4cÁHCl)
The other reactions employing 1A, 1B±D, various
Grignard reagents, DIBAL and borane±THF complex were
carried out in the same way as cited above.
M.p. 58 ꢀ 60ꢁC; 1H NMR /CDCl3) d 1.50 /t, J ˆ
7:25 Hz, 6H), 3.15 /s, 3H), 3.28 /q, J ˆ 7:25 Hz, 4H),
4.10 /d, J ˆ 20:0 Hz, 2H), 6.24 /d, J ˆ 39:01 Hz, 1H),
7:07 ꢀ 7:51 /m, 4H), 9.45±9.55 /m, 1H); 13C NMR
/CDCl3) d 9.3, 21.0, 47.4, 51.8 /d, J ˆ 27:48 Hz), 128
/d, J ˆ 2:26 Hz), 116.6 /d, J ˆ 5:66 Hz), 128.9 /d,
J ˆ 7:29 Hz), 129.1, 138.1 /d, J ˆ 1:76 Hz), 147.8 /d,
5. N,N-diethyl-2-fluoro-3-pheny-2Z-propenylamine &4a)
1H NMR /CDCl3) d 1.32 /t, J ˆ 7:3 Hz, 6H), 2.87 /dq,
J ˆ 13:0, 7.3 Hz, 2H), 2.94 /dq, J ˆ 13:0, 7.3 Hz, 2H), 3.64
/d, J ˆ 22:0 Hz, 2H), 5.81 /d, J ˆ 38:0 Hz, 1H), 7.25±7.37
/m, 3H), 7.49±7.53 /m, 2H); 13C NMR /CDCl3) d 9.20,
54.16, 59.08 /d, J ˆ 25:5 Hz), 114.94 /d, J ˆ 7:6 Hz),
128.03, 128.42, 128.79 /d, J ˆ 7:4 Hz), 131.87 /d,
J ˆ 3:1 Hz), 152.55 /d, J ˆ 266:5 Hz); 19F NMR /CDCl3)
d À101.87 /dt, J ˆ 38:0, 22.0 Hz, 1F); IR /neat) 3059 /w),
3004 /w), 2982 /m), 2943 /m), 2885 /w), 2388 /vs), 2284
J ˆ 262:8 Hz); 19F NMR /CDCl3)
d
À106.19 /dt,
J ˆ 39:01, 20.0 Hz, 1F); IR /KBr) 3340 /w), 2889 /w),
2384 /s), 1686 /m), 1450 /s), 1393 /s), 1366 /m), 1342
;
MS /EI) m/z /relative intensity) 221 /M , 22), 206 /19), 150
/s), 1157 /vs), 1110 /m), 1049 /s), 810 /s), 760 /m) cmÀ1
‡
/11), 149 /100), 129 /9), 86 /6); MS /SIMS) found:
‡
479.3021, calculated for C28H42 35Cl F2N2 /2M -35Cl):
479.3004.
‡
/m), 1685 /w) cmÀ1; MS m/e /relative intensity) 207 /M ,
21), 192 /30), 136 /11), 135 /100), 115 /18), 58 /20); HRMS
/EI) found: m/z 207.1407; calculated for C13H18FN: M,
207.1423.
9. N,N-diethyl-2-fluoro-3-&a-naphtyl)-2Z-
propenylamine &4d)
6. N,N-diethyl-2-fluoro-3-&4-methoxyphenyl)-2Z-
propenylamine &4b)
1H NMR /CDCl3) d 1.33 /t, J ˆ 7:3 Hz, 6H), 2.85±3.02
/m, 4H), 3.72 /d, J ˆ 21:5 Hz, 2H), 6.50 /d, J ˆ 35:5 Hz,
1H), 7.40±7.96 /m, 7H); 13C NMR /CDCl3) d 9.24, 54.26,
59.13 /d, J ˆ 26:0 Hz), 112.13 /d, J ˆ 9:7 Hz), 123.65,
125.23, 125.83, 126.43, 127.43 /d, J ˆ 8:3 Hz), 128.02,
128.22, 128.56 /d, J ˆ 6:8 Hz), 131.07, 133.45, 153.23
/d, J ˆ 265:2 Hz); 19F NMR /CDCl3) d À103.19 /dt,
1
M.p. 84±868C; H NMR /CDCl3) d 1.33 /t, J ˆ 7:2 Hz,
6H), 2.79±3.04 /m, 4H), 3.65 /d, J ˆ 22:1 Hz, 2H), 3.82 /s,
3H), 5.76 /d, J ˆ 38:5 Hz, 1H), 6.83±6.93 /m, 2H), 7.41±
7.51 /m, 2H); 19F NMR /CDCl3) d À104.88 /dt, J ˆ 38:5,

204
H. Yamanaka et al. / Journal of Fluorine Chemistry 108 52001) 199±205
J ˆ 35:5, 21.5 Hz, 1F); IR /neat) 3051 /vs), 2936 /s), 2873
/m), 2819 /m), 2630 /w), 1686 /m); MS m/z /relative
intensity) 257 /M , 23), 242 /11), 228 /6), 186 /21), 185
/100), 165 /31), 128 /60). HRMS m/z found: 257.1567;
calculated for C17H20FN: 257.1580.
13. N,N-diethyl-2-fluoro-4-methyl-2Z-pentenylam-
monium Iodide &2g)
‡
1H NMR /CDCl3) d 1.05 /d, J ˆ 7:25 Hz, 6H), 1.56 /t,
J ˆ 7:25 Hz, 6H), 2.83 /dq, J ˆ 7:25, 2.50 Hz, 1H), 3.28 /q,
J ˆ 7:25 Hz, 4H), 3.89 /d, J ˆ 19:50 Hz, 2H), 5.24 /dd,
J ˆ 37:30, 9.25 Hz, 1H); 13C NMR /CDCl3) d 9.56, 22.20,
24.38 /d, J ˆ 3:14 Hz), 48.04, 51.31 /d, J ˆ 28:17 Hz),
126.12 /d, J ˆ 12:32 Hz), 146.23 /d, J ˆ 250:87 Hz); 19F
NMR /CDCl3) d À112.28 /dt, J ˆ 37:30, 19.5 Hz, 1F); IR
/neat) 3402 /m), 3209 /w), 2927 /vs), 2873 /s), 2642 /s), 2484
/m), 1705 /m), 1616 /w), 1292 /s); HRMS /FAB) found:
m/z 475.2376; calculated for C20H42F2IN2: 2M-I, 475.2362.
10. N,N-diethyl-2-fluoro-2Z-heptenylamine
hydrochloride &4eÁHCl)
1H NMR /CDCl3) d 0.91 /t, J ˆ 7:00 Hz, 3H), 1.28±1.43
/m, 4H), 1.50 /t, J ˆ 7:50 Hz, 6H), 2.18 /dt, J ˆ 7:50,
6.75 Hz, 2H), 3.20 /q, J ˆ 7:50 Hz, 4H), 3.90 /d,
J ˆ 19:50 Hz, 2H), 5.31 /dt, J ˆ 36:00, 7.50 Hz, 1H),
9.55±9.65 /m, 1H); 13C NMR /CDCl3) d 9.38, 13.43,
21.93, 23.33 /d, J ˆ 4:52 Hz), 30.40, 30.43, 47.45 /d,
J ˆ 28:00 Hz), 118.36 /d, J ˆ 13:20 Hz), 148.30 /d,
14. N,N-diethyl-2-&2,2,2-trifluoroethoxy)-3-phenyl-2Z-
propenylamine &5Ba)
J ˆ 251:5 Hz); 19F NMR /CDCl3)
d
À111.67 /dt,
J ˆ 36:00, 7.50 Hz, 1F); IR /neat) 3420 /m), 295 /vs),
2932 /vs), 2862 /s), 2484 /s), 1705 /m), 1632 /w), 1466
/s), 1119 /w), 883 /w); HRMS /FAB) found: m/z 411.3308;
1H NMR /CDCl3) d 1.30 /t, J ˆ 7:00 Hz, 6H), 2.86±3.00
/m, 4H), 3.56 /s, 2H), 4.00 /q, J ˆ 8:60 Hz, 2H), 6.07 /s,
1H), 7.27 /m, 1H), 7.33 /m, 2H), 7.48 /m, 2H); 13C NMR
/CDCl3) d 9.07, 53.58, 60.53, 67.32 /q, J ˆ 35:07 Hz),
121.54, 123.01 /q, J ˆ 278:54 Hz), 127.97, 128.43,
129.01, 132.99, 148.22; 19F NMR /CDCl3) d À75.19 /t,
J ˆ 8:8 Hz, 3F); IR /neat) 3005 /w), 2982 /w), 2947 /w),
2392 /m), 2353 /m), 2284 /m), 1660 /w), 1450 /w), 1281
‡
calculated for C22H46 35ClF2N2 /2M -35Cl): 411.3317.
11. N,N-diethyl-2-fluoro-4-phenyl-2Z-butenylamine &4f)
‡
1H NMR /CDCl3) d 1.33 /t, J ˆ 7:3 Hz, 6H), 2.87 /dq,
J ˆ 12:8, 7.3 Hz, 2H), 2.94 /dq, J ˆ 12:8, 7.3 Hz, 2H), 3.52
/d, J ˆ 7:5 Hz, 2H), 3.58 /d, J ˆ 21:0 Hz, 2H), 5.21 /dt,
J ˆ 35:0, 7.5 Hz, 1H), 7.15±7.38 /m, 5H); 13C NMR
/CDCl3) d 9.31, 30.08 /d, J ˆ 5:2 Hz), 54.34, 58.11 /d,
J ˆ 26:4 Hz), 114.70 /d, J ˆ 14:8 Hz), 126.40, 128.40 /d,
J ˆ 52:9 Hz), 139.08, 152.50 /d, J ˆ 256:0 Hz); 19F NMR
/CDCl3) d À108.76 /dt, J ˆ 35:0, 21.0 Hz, 1F); IR /neat)
3063 /w), 3028 /w), 3005 /w), 2982 /m), 2943 /m), 2854
/w), 2388 /vs), 2284 /m), 1697 /w); MS m/e /relative
/m), 1165 /s); MS m/e /relative intensity) 287 /M , 26), 272
/37), 258 /4), 204 /4), 155 /15); HRMS m/z found: 287.1487;
calculated for C15H20F3NO: 287.1497. N,N-diethyl-2-
/2,2,3,3,3-penta¯uoropropoxy)-3-phenyl-2Z-propenylamine
/5Ca) 1H NMR /CDCl3) d 1.35 /t, J ˆ 7:0 Hz, 6H), 3.03 /q,
J ˆ 7:0 Hz, 4H), 3.7 /s, 2H), 4.27 /t, J ˆ 13:20 Hz, 2H), 6.15
/s,1H),7.07±7.55/m,5H);19FNMR/CDCl3)dÀ83.93/s,3F),
À124.25/t,J ˆ 13:20 Hz,2F);MSm/e/relativeintensity)337
‡
/M , 25), 322 /36), 246 /6), 115 /12); HRMS m/z found:
337.1462. Calculated for C16H20F5NO: 337.1465.
‡
intensity) 221 /M , 14), 207 /15), 206 /100), 149 /42),
129 /54), 128 /11), 103 /12), 91 /10), 58 /50); HRMS /EI)
found: m/z 221.1572; calculated for C14H20FN: 221.1580.
15. N,N-diethyl-2-&2,2,3,3,-tetrafluoropropoxy)-3-
phenyl-2Z-propenylamine &5Da)
12. N,N-diethy-2-fluoro-4-phenyl-2Z-butenylamine
hydrochloride &4fÁHCl)
1H NMR /CDCl3) d 1.32 /t, J ˆ 7:0 Hz, 6H), 3.02 /q,
J ˆ 7:0 Hz, 4H), 3.67 /s, 2H), 4.27 /m, 2 H), 5.93 /tt,
J ˆ 52:8, 6.1 Hz, 1H), 6.03 /s, 1H), 7.08±7.60 /m, 5H);
19F NMR /CDCl3) d À125.12 /m, 2F), À138.80 /dm,
M.p.66 ꢀ 68ꢁC; 1H MNR /CDCl3)
d
1.46 /t,
‡
J ˆ 7:25 Hz, 6H), 3.19 /q, J ˆ 7:25 Hz, 4H), 3.51 /d,
J ˆ 7:50 Hz, 2H), 3.92 /d, J ˆ 19:5 Hz, 2H), 5.54 /dt,
J ˆ 35:5, 7.5 Hz, 1H), 7:13 ꢀ 7:33 /m, 5H); 13C NMR
/CDCl3) d 9.4, 30.0 /d, J ˆ 4:36 Hz), 47.6, 50.4 /d,
J ˆ 27:7 Hz), 117.1 /d, J ˆ 13:1 Hz), 126.5, 128.0,
138.0, 148.7 /d, J ˆ 253:4 Hz); 19F NMR /CDCl3) d
À110.97 /dt, J ˆ 35:5, 19.5 Hz, 1F); IR /KBr) 3395 /w)
2974 /s), 2923 /s), 2492 /vs), 1705 /m), 1454 /s), 1392 /s),
1218 /w), 1164 /m), 975 /m), 949 /m), 934 /m), 829 /m), 737
/s), 702 /s) cmÀ1; MS /SIMS) found: 479.3009, calculated
J ˆ 52:8 Hz, 2F); MS m/e /relative intensity) 319 /M ,
22), 304 /36), 247 /100), 115 /12); HRMS m/z found:
319.1558. Calculated for C16H21F4NO: 319.1559.
16. N,N-diethyl-1-deuterio-2-fluoro-3-phenyl-2Z-
propenylamine &6)
1H NMR /CDCl3) d 1.32 /t, J ˆ 7:30 Hz, 6H), 2.87 /dq,
J ˆ 12:8, 7.3 Hz, 2H), 2.95 /dq, J ˆ 12:8, 7.3 Hz, 2H), 3.63
/d, J ˆ 21:5 Hz, 1H), 5.81 /d, J ˆ 38:0 Hz, 1H), 7.25±7.56
‡
for C28H4235ClF2N2 /2M -35Cl): 479.3004.

H. Yamanaka et al. / Journal of Fluorine Chemistry 108 52001) 199±205
205
/m, 5H); 13C NMR /CDCl3) d 9.28, 54.18, 58.80 /q,
J ˆ 22:3 Hz), 115.01 /d, J ˆ 7:8 Hz), 128.12, 128.51,
128.86 /d, J ˆ 7:8 Hz), 131.92 /d, J ˆ 2:4 Hz), 152.61
/d, J ˆ 266:5 Hz); 19F NMR /CDCl3) d À102.03 /dd,
J ˆ 38:0, 21.5 Hz, 1F); IR /neat) 3055 /m), 3001 /m),
2982 /m), 2943 /m), 2885 /w), 1790 /vs); MS m/e /relative
intensity) 208 /M , 20), 193 /30), 154 /26), 137 /11), 136
/100), 116 /17), 94 /38); HRNS m/z found: 208.1465.
Calculated for C13H17DFN: 208.1485.
[10] A. Ehmann, R. Gompper, H. Hartmann, T.J.J. Muller, K. Polborn, R.
Schutz, Angew. Chem. Int. Ed. Engl. 33 /1994) 572.
[11] C. Payrastre, N. Obaya, Y. Madaule, J.G. Wolf, Tetrahedron Lett. 35
/1994) 3059.
[12] F.A. Cotton, L.M. Daniels, S.C. Haefner, C.A. Murillo, J. Chem.
Soc., Chem. Commun. /1996) 2507.
[13] I.W. Davies, J.-F. Marcoux, J. Wu, M. Palucki, E.G. Corley, M.A.
Robbins, N. Tsou, R.G. Ball, P. Dormer, R.D. Larsen, P.J. Reider, J.
Org. Chem. 65 /2000) 4571.
‡
[14] J.-F. Marcoux, E.G. Corley, K. Rossen, P. Pye, J. Wu, M.A. Robbins,
I.W. Davies, R.D. Larsen, P.J. Reider, Org. Lett. 2 /2000) 2339.
[15] C. Reichardt, K. Halbritter, Justus Liebigs Ann. Chem. 737 /1970)
99.
[16] C. Reichardt, K. Halbritter, Justus Liebigs Ann. Chem. /1975)
470.
Acknowledgements
[17] V.I. Saloutin, Z.E. Skryabina, Y.V. Burgart, O.N. Chupakhin, M.
Font-Altaba, X. Solans, M. Font-Bardia, J. Fluorine Chem. 69 /1994)
25.
The authors are grateful to Daikin Industries, Ltd. for the
kind donation of ¯uorochemicals.
[18] H. Yamanaka, S. Yamashita, T. Ishihara, Tetrahedron Lett. 33 /1992)
357.
[19] H. Yamanaka, T. Takekawa, K. Morita, T. Ishihara, Tetrahedron Lett.
37 /1996) 1829.
References
[20] K. Kase, M. Katayama, T. Ishihara, H. Yamanaka, G.T. Gupton,
Chem. Lett. /1997) 893.
[1] D. Lloyd, H. McNab, Angew. Chem. Int. Ed. Engl. 15 /1976) 459 and
references therein.
[21] X. Shi, T. Ishihara, H. Yamanaka, J.T. Gupton, Tetrahedron Lett. 36
/1995) 1527.
[2] C. Jutz, H.G. Lobering, K.H. Trinkl, Synthesis /1977) 326.
[3] F. Adams, R. Gompper, E. Kujath, Angew. Chem. Int. Ed. Engl. 28
/1989) 1060.
[22] K. Kase, M. Katayama, T. Ishihara, H. Yamanaka, J.T. Gupton, J.
Fluorine Chem. 90 /1998) 29.
[4] J.T. Gupton, J.E. Gall, S.W. Riesinger, S.Q. Smith, K.M. Bevirt, J.A.
Sikorski, M.L. Dahl, Z. Arnold, J. Heterocyclic Chem. 28 /1991)
1281.
[23] H. Yamanaka, S. Yamashita, T. Ishihara, Synlett /1993) 353.
[24] H. Yamanaka, K. Hisaki, K. Kase, T. Ishihara, J.T. Gupton,
Tetrahedron Lett. 39 /1998) 4355.
[5] S.A. Petrich, F.A. Hickes, D.R. Wilkinson, J.G. Tarrant, S.M. Bruno,
M. Vargas, K.N. Hosein, J.T. Gupton, J.A. Sikorski, Tetrahedron 51
/1995) 1575.
[25] H. Yamanaka, Y. Odani, T. Ishihara, J.T. Gupton, Tetrahedron Lett.
39 /1998) 6943.
[26] K. Kase, M. Katayama, T. Konno, T. Ishihara, H. Yamanaka, J.
Fluorine Chem. 104 /2000) 225.
[6] V. Nair, C.S. Cooper, Tetrahedron Lett. 21 /1980) 3155.
[7] V. Nair, C.S. Cooper, J. Org. Chem. 46 /1981) 4759.
[8] J.T. Gupton, D.A. Krolikowski, R.H. Yu, S.W. Riesinger, J.A.
Sikorski, J. Org. Chem. 55 /1990) 4735.
[27] A. Selmi, M.M. El Gaied, G. Alvernhe, J. Fluorine Chem. 72
/1995) 1.
[28] L.M. Jackman, S. Sternhell, Nuclear Magnetic Resonance Spectro-
scopy in Organic Chemistry, 2nd Edition, Pergamon Press, Sidney,
1969, p. 316.
[9] J.T. Gupton, S.W. Riesinger, A.S. Shah, J.E. Gall, K.M. Bevirt, J.
Org. Chem. 56 /1991) 976.