One-pot synthesis of bromodifluoroacetimidoyl halides and its Suzuki coupling reactions with aryl boronic acids

Article abstract of DOI:10.1016/j.jfluchem.2005.02.016

N-aryl bromodifluoroacetimidoyl halides were prepared by the reaction of bromodifluoroacetic acid, triphenyl phosphine, p-arylaniline and triethylamine in tetrachloromethane in good yields. Palladium-catalyzed cross-coupling reaction of N-aryl bromodifluoroimidoyl iodide with arylboronic acids was realized to afford bromodifuoromethyl ketimine in good yields.

Full text of DOI:10.1016/j.jfluchem.2005.02.016

Journal of Fluorine Chemistry 126 (2005) 791–795
www.elsevier.com/locate/fluor
One-pot synthesis of bromodifluoroacetimidoyl halides and its
Suzuki coupling reactions with aryl boronic acids
*
Yong-Ming Wu , Ya Li, Juan Deng
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Road, Shanghai 200032, China
Received 10 January 2005; received in revised form 26 February 2005; accepted 28 February 2005
Available online 19 April 2005
Abstract
N-aryl bromodifluoroacetimidoyl halides were prepared by the reaction of bromodifluoroacetic acid, triphenyl phosphine, p-arylaniline
and triethylamine in tetrachloromethane in good yields. Palladium-catalyzed cross-coupling reaction of N-aryl bromodifluoroimidoyl iodide
with arylboronic acids was realized to afford bromodifuoromethyl ketimine in good yields.
# 2005 Elsevier B.V. All rights reserved.
Keywords: Suzuki coupling reaction; Bromodifluoroacetimidoyl halide; Arylboronic acids; Imine
1. Introduction
N-arylbromodifluoroimidoyl halide is a versatile reactive
intermediate in the synthesis of CF2-containing compounds.
Herein, we wish to report a facile approach to bromodi-
fluoromethyl ketimine via palladium-catalyzed Suzuki
coupling reaction of bromodifuoroacetimidol halides with
arylboronic acids.
The Suzuki coupling reaction provides a general method
for the formation of carbon–carbon single bond. Palladium-
catalyzed cross-coupling reaction of arylboronic acids with
alkenyl or aryl halides and acid chlorides have been
developed for applications in natural and unnatural products
synthesis [1]. The coupling reactions between imidoyl
halides and boronic acids tend to be the unit structure of
imidoyl halide exsited in a cyclic aromatic compound [2].
However, to our best knowledge, the Suzuki coupling
reaction of alkyl or aryl imidoyl halides has not yet been
reported. This is probably due to the labile nature of alkyl or
aryl imidoyl halides, such as moisture sensitive [3].
2. Results and discussion
N-aryl bromodifluoroacetimidoyl halides were prepared
according to Uneyama’s One-pot procedure [7]. When the
mixture of bromodifluoroacetic acid, triphenyl phosphine, p-
methoxyaniline and triethylamine in tetrachloromethane
was refluxed for 5 h, the desired bromodifluoroacetimidoyl
chloride (1a) was isolated in 82% yield (Scheme 1). It was
worth to note that the carbon–bromine bond in bromodi-
fluoroacetic acid remained intact in the reaction conditions,
i.e.:
In recent years, the introduction of difluoromethylene
fragment into organic compounds has proved to be attractive
[4]. It has been argued that the difluoromethylene group
could be regarded as an isopolar–isosteric replacement
for oxygen [5]. Bromodifluoroacetate, chlorodifluomethyl
ketones and bromodifluoromethyl acetylene are widely used
as reagents to introduce a CF2 moiety into molecules [6]. In
search for new CF2-containing synthons, we have found that
* Corresponding author. Tel.: +86 21 54925190; fax: +86 21 64166128.
E-mail address: ymwu@mail.sioc.ac.cn (Y.-M. Wu).
Scheme 1. Preparation of bromodifluoroacetimidoyl chloride (1).
0022-1139/$ – see front matter # 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2005.02.016

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Y.-M. Wu et al. / Journal of Fluorine Chemistry 126 (2005) 791–795
Table 1
Synthesis of N-aryl-2,2,2-bromodifluoroacetimidoyl chlorides
Entry
Ar
Product
Yield (%)a
1
2
3
4
5
6
7
8
a
p-MeO-C6H4
p-Cl-C6H4
1a
1b
1c
1d
1e
1f
82
72
70
69
64
75
68
60
m-Me-p-Br-C6H4
C6H5
p-NO2-C6H4
o-Me-p-Br-C6H4
o-Cl-C6H4
1g
1h
o-Br-C6H4
Isolated yield.
By this method, other N-aryl substituted bromodifluor-
oacetimidoyl chlorides were also synthesized, the results are
summarized in Table 1. The configuration of the carbon–
nitrogen double bond was also studied. 19F NMR analysis
showed that only one of the two possible geometric isomers
was obtained. We tentatively assigned Z form for the
following reason: Fustero have calculated the energy of Z
and E form of trifluoroacetimidoyl chloride by an ab initio
smethod and found that the Z isomer was 5.6 kcal molÀ1
lower than the corresponding E form (Scheme 2). They
considered that trifluoroacetimidoyl chloride is existed in Z
form [8].
coupling product was obtained in 78% yield after 1.0 equiv.
Ag2O was added to the reaction mixture (Table 2, Entry 8).
Further studies indicated that 0.5 equiv. Ag2O was sufficient
for promoting this reaction (Table 2, Entry 9). When the
reaction was carried out with Ag2O and using Cs2CO3 as a
base, the yield was low though bromodifluoroacetimidoyl
iodide (2) was completely consumed (Table 2, Entries 10–
12). This might be due to the decomposition of 2 under the
reaction conditions.
The reactions of various boronic acids with 2 were
explored under the optimized reaction conditions, the results
are shown in Table 3. The cross-coupling reaction of 2 with
various arylboronicic acids proceeded smoothly with
satisfactory yields. It was found that different substituents
on benzene ring had a little effect on the result in this
reaction. However, o-substituted arylboronic acid gave the
coupling product in lower yield, obviously, this was due to
the steric hindrance. Because of the existing of carbon–
nitrogen double bond in products, two possible isomers Z
and E would be presented in the product, their ratio could be
determined by 19F NMR spectra. It is interesting to note that
when more steric arylboronic acids (e.g.: o- or m-
substituteed) were used as substrates, only one isomer
was obtained in their products (Table 3, Entries 5, 7 and 8).
From the view point of steric effects, this isomer could be
easily assigned to Z form. For other substrates, the major
isomer were also in Z form with the ratio from 3:2 to 50:1 of
Z and E form (Table 3).
Bromodifluoroacetimidoyl iodide (2) was prepared
almost in quantitative yields by displacement of the chlorine
in imidoyl chloride (1a) with iodide in a NaI–acetone system
(Scheme 3) [7].
With bromodifluoroimidoyl halides in hand, we then
studied Palladium-catalyzed Suzuki coupling reactions. As
the carbon–iodide bond was more reactive than carbon–
chloride bond [9], the coupling reaction of bromodifluor-
oimidoyl iodide (2) with arylboronic acid was first chosen as
a model reaction to opitimize the reaction conditions. The
reaction was first carried out in a mixture of bromodi-
fluoroacetimidoyl iodide (2), p-methoxyphenylboronic acid,
PdCl2(PPh3)2, K2CO3 and THF at 80 8C for 24 h, the desired
coupling product was not obtained at all (Table 2, Entry 1).
Different bases (KOH, KF or K2CO3) and different solvents
(Toluene, DMF or THF) were also tested in this reaction, all
the results were not satisfied (Table 2, Entries 2–7). The fact
that Ag2O dramatically enhanced the rate of some coupling
reaction encouraged us to use it to activate the reaction [10].
Fortunately, the reaction’s time was decreased to 8 h and the
When bromodifluoroacetimidoyl chloride (1a) under-
went similar reaction conditions, the reaction was sluggish.
After 24 h, 1a was almost consumed and the coupling
product was isolated in only 59% yield. One can envision
that prolonged reaction time resulted in the decomposition
of more starting material 1a.
Scheme 2.
Scheme 3. Preparation of bromodifluoroacetimidoyl iodide (2).

Y.-M. Wu et al. / Journal of Fluorine Chemistry 126 (2005) 791–795
793
Table 2
Effect of the bases and solvents on the Suzuki reaction of 2
Entry
Conditions
Time (h)
Time (h)a
1
2
3
4
5
6
7
8
9
PdCl2(PPh3)2, K2CO3, THF, 70 8C
PdCl2(PPh3)2, KOH, THF, 70 8C
PdCl2(PPh3)2, KF, THF, 70 8C
PdCl2(PPh3)2, K2CO3, DMF, 100 8C
PdCl2(PPh3)2, K2CO3, toluene, 100 8C
Pd(PPh3)4, K2CO3, toluene, 100 8C
PdCl2(PPh3)2, K2CO3/(0.5 equiv.) Cu2O, THF, 70 8C
PdCl2(PPh3)2, K2CO3/(1.0 equiv.) Ag2O, THF, 70 8C
PdCl2(PPh3)2, K2CO3/(0.5 equiv.) Ag2O, THF, 70 8C
PdCl2(PPh3)2, K2CO3/(0.5 equiv.) Ag2O, toluene, 100 8C
PdCl2(PPh3)2, Cs2CO3/(0.5 equiv.) Ag2O, THF, 70 8C
PdCl2(PPh3)2, Cs2CO3/(0.5 equiv.) Ag2O, Dioxane, 90 8C
12
24
24
24
22
24
24
8
0
22
–
–
16
–
30
78
81
73
4
12
18
20
6
10
11
12
a
22
Isolated yield.
Table 3
Palladium-catalyzed and Ag2O-assisted cross-coupling reaction of bromodifluoroacetimidoyl iodide (2) with various arylboronic acids
Entry
ArB(OH)2
Product
Isomer ratioa
Yield (%)b
1
2
3
4
5
6
7
8
a
p-MeO-C6H4B(OH)2
C6H5B(OH)2
3a
3b
3c
3d
3e
3f
4:1
5:1
81
79
63
73
73
72
61
46
p-MeS-C6H4B(OH)2
p-Ph-C6H4B(OH)2
m-Me-C6H4B(OH)2
p-CF3-C6H4B(OH)2
m-CF3-C6H4B(OH)2
o-MeO-C6H4B(OH)2
37:1
50:1
1:0
3:2
3g
3h
1:0
1:0
Ratio of Z:E, based on 19F NMR.
b
Isolated yield.
In summary, the palladium-catalyzed cross-coupling
all protons decoupled, and the chemical shifts are reported in
ppm downfield of SiMe4. Mass spectra were taken on a HP
5989a spectrometer, accurate mass measurements were
performed on Finnigan MAT instrument, and elemental
analysis were performed in this institute.
reaction of N-aryl bromodifluoroacetimidoyl iodides with
arylboronic acids was realized affording bromodifluoro-
methyl ketimine in good yield. This method efficiently and
nicely complements the existing methodology based on the
condensition reaction of ketone with arylamines.
3.1. General procedure for the synthesis of
bromodifluoroacetimidoyl chlorides
3. Experimental
PPh3 (48.1 g, 184 mmol), Et3N (10.4 ml, 61 mmol), CCl4
(50 ml), BrCF2COOH (10.7 g, 61 mmol) and p-anisidine
(8.7 g, 70 mmol) was added to a 250 ml three-necked flask.
After stirring for 5 h under refluxing, the solvent was
removed under reduced pressure, and the residue was
extracted with hexane (3Â 50 ml). The filtrate was
concentrated under reduced pressure and subsequent column
chromatography with 5% ethyl acetate in hexane as elucent
to afford 1a (14.9 g, 82%) as a yellow oil.
Unless otherwise noted, solvents and reagents were
commercially available and used as received. 1H NMR
spectra were recorded on a Brucker AM-300 (300 MHz)
spectrometer with Me4Si as internal standard. 19F NMR
spectra were taken on Brucher AM-300 (282 MHz)
spectrometer with CFCl3 as external standard, downfield
shifts being designed as positive. The 13C NMR spectra were
measured at Brucker AM-300 (75 MHz) spectrometer with

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Y.-M. Wu et al. / Journal of Fluorine Chemistry 126 (2005) 791–795
3.1.1. N-( p-anisyl)-2-bromo-2,2-difluoroacetimidoyl
chloride (1a)
3.1.7. N-(o-chlorophenyl)-2-bromo-2,
2-difluoroacetimidoyl chloride (1g)
1
1
Yield: 68%, yellow oil. H NMR: d 7.49 (dd, J = 8.10,
1.20 Hz, 1H), 7.36 (td, J = 7.50, 1.50 Hz, 1H), 7.23 (td,
Yield: 82%, yellow oil. H NMR: d 7.30–7.33 (m, 2H),
6.95–6.98 (m, 2H), 3.85 (s, 3H). 19F NMR: d À53.17 (s). IR
(neat, cmÀ1): 3006, 2960, 2839, 2056, 1677, 1599, 1505,
1148, 985, 804, 630; m/z (EI): 299 (80), 297 (64), 218 (100),
168 (37). Calc. for C9H7BrClF2NO: C, 36.21; H, 2.36;
N, 4.69; F, 12.73. Found: C, 36.34; H, 2.42; N, 4.92; F,
13.09.
J = 7.50, 1.80 Hz, 1H), 6.97 (dd, J = 7.80, 1.80 Hz, 1H). 19
F
NMR: d À54.71 (s). IR (neat, cmÀ1): 3069, 1913, 1686,
1587, 1471, 1232, 1061, 868, 722. m/z (EI): 303 (23), 222
(25), 172 (100), 137 (22). Calc. for C8H4BrCl2F2N: C,
31.72; H, 1.33; N, 4.62. Found: C, 31.57; H, 1.81; N, 4.92.
3.1.2. N-( p-chlorophenyl)-2-bromo-2,
2-difluoroacetimidoyl chloride (1b)
3.1.8. N-(o-bromophenyl)-2-bromo-2,
2-difluoroacetimidoyl chloride (1h)
1
Yield: 72%, yellow oil. H NMR: d 7.42 (ddd, J = 8.70,
Yield: 60%, yellow oil. 1H NMR: d 7.64 (d, J = 8.10 Hz,
1H), 7.37 (t, J = 7.50 Hz, 1H), 7.15 (td, J = 7.50, 1.50 Hz,
1H), 6.93 (dd, J = 7.80, 1.50 Hz, 1H). 19F NMR: d À54.65
(s). IR (neat, cmÀ1): 3067, 1686, 1467, 1231, 1155, 999, 793,
717. m/z (EI): 347 (35), 312 (20), 218 (100), 155 (47).
HRMS (EI): M+, found 344.83670. C8H4Br2ClF2N requires
344.83850.
2.70, 1.80 Hz, 2H), 7.07 (ddd, J = 8.70, 1.80 Hz, 2H). 19F
NMR: d À54.26 (s). IR (neat, cmÀ1): 3093, 1890, 1680,
1486, 1233, 1094, 863, 790. m/z (EI): 303 (94), 268 (24), 222
(64), 172 (100). Calc. for C8H4BrCl2F2N: C, 31.72; H, 1.33;
N, 4.62. Found: C, 31.63; H, 1.55; N, 4.89.
3.1.3. N-( p-bromo-m-methylphenyl)-2-bromo-2,
2-difluoroacetimidoyl chloride (1c)
3.2. Procedure for the preparation of N-( p-Anisyl)-2-
bromo-2,2-difluoroace-timidoyl idide (2)
Yield: 70%, yellow oil. 1H NMR: d 7.59 (d, J = 8.70 Hz,
1H), 6.98 (d, J = 2.10 Hz, 1H), 6.82 (dd, J = 8.70, 2.70 Hz,
1H), 2.44 (s, 3H). 19F NMR: d À54.22 (s). IR (neat, cmÀ1):
2955, 1880, 1689, 1590, 1472, 1237, 1031, 831, 782. m/z
(EI): 361 (34), 282 (20), 232 (100), 166 (73), 89 (100). Calc.
for C9H6Br2ClF2N: C, 29.91; H, 1.67; N, 3.88. Found: C,
30.11; H, 1.71; N, 4.19.
A mixture of 1a (1.49 g, 5 mmol) and NaI (2.25 g,
15 mmol) in 10 ml acetone was stirred under N2 atmosphere
at room temperature for 10 h. The mixture was washed with
saturated Na2S2O3 and extracted with Et2O (2Â 15 ml). The
extracts were dried with Mg2SO4 and concentrated under
reduced pressure. Flash column chromatography with
hexane as elucent gave 2 (1.91 g, 98%). Yield: 98%, yellow
oil. 1H NMR: d 6.96–7.04 (m, 4H), 3.86 (s, 3H). 19F NMR: d
À49.76 (s). IR (neat, cmÀ1): 2959, 2837, 1670, 1601, 1504,
1251, 965, 832, 734. m/z (EI): 389 (9), 262 (100), 183 (48),
133 (56). Calc. for C9H7BrF2INO: C, 27,72; H, 1.81, N,
3.59. Found: C, 27.69; H, 1.79; N, 3.88.
3.1.4. N-phenyl-2-bromo-2,2-difluoroacetimidoyl
chloride (1d)
1
Yield: 69%, yellow oil. H NMR: d 7.42–7.48 (m, 2H),
7.27–7.33 (m, 1H), 7.09–7.12 (m, 2H). 19F NMR: d À54.08
(s). IR (neat, cmÀ1): 3068, 3038, 2930, 1943, 1680, 1594,
1488, 1228, 1150, 859, 784. m/z (EI): 269 (21), 232 (9), 188
(24), 138 (67), 77 (100). Calc. for C8H5BrClF2N: C, 35.79;
H, 1.88; N, 5.22. Found: C, 35.59; H, 1.99; N, 5.39.
3.3. General procedure for the palladium-catalyzed
cross-coupling reaction of bromodifluoacetimidoyl
iodide (2) with arylboronic acids
3.1.5. N-phenyl-2-bromo-2,2-difluoroacetimidoyl
chloride (1e)
1
Yield: 64%, yellow oil. H NMR: d 8.34 (dd, J = 8.70,
A mixture of 2 (156 mg, 0.4 mmol), 4-methoxyl-boronic
acid (73 mg, 0.48 mmol), PdCl2(PPh3)2 (14 mmg,
0.02 mmol), K2CO3 (111 mg, 0.8 mmol) and Ag2O
(46 mg, 0.2 mmol) was stirred in THF at 70 8C under N2
atmosphere for 8 h. The mixture was filtered and the filtrate
was concentrated under reduced pressure. The residue was
purified by flash column chromatography with 2% ethyl
acetate in hexanes as elucent affording to 3a (120 mg, 81%).
1.80 Hz, 2H), 7.14 (dd, J = 8.70, 2.40 Hz, 2H). 19F NMR: d
À55.04 (s). IR (neat, cmÀ1): 3110, 3080, 2937, 2453, 1686,
1606, 1525, 1487, 1345, 1153, 875, 756. m/z (EI): 314 (24),
183 (100), 75 (54). Calc. for C8H4BrClF2N2O2: C, 30.65; H,
1.29; N, 8.94. Found: C, 30.81; H, 1.54; N, 9.26.
3.1.6. N-( p-bromo-o-methylphenyl)-2-bromo-2,
2-difluoroacetimidoyl chloride (1f)
1
Yield: 75%, yellow oil. H NMR:d 7.42 (s, 1H), 7.38
3.3.1. Bromodifluoromethyl-4-methoxyphenyl-keton-4-
methoxyphenylimine (3a)
(dd, J = 8.40, 2.10 Hz, 1H), 6.81 (d, J = 8.40 Hz, 1H), 2.17
(s, 3H). 19F NMR: d À54.19 (s). IR (neat, cmÀ1): 2930,
1687, 1586, 1479, 1235, 996, 839, 665. m/z (EI): 361 (100),
232 (33), 151 (41), 89 (79). Calc. for C9H6Br2ClF2N: C,
29.91; H, 1.67; N, 3.88. Found: C, 30.15; H, 1.82; N,
4.07.
Yield: 81%. Yellowish solid. Mp: 64–65 8C. 1H NMR: d
7.21 (d, J = 8.40 Hz, 2H), 6.84 (d, J = 9.00 Hz, 2H), 6.74 (s,
4H), 3.81 (s, 3H), 3.75 (s, 3 H). 19F NMR: d À52.97
(s):À57.31 (s) = 4:1. 13C NMR: d 160.65, 159.41 (t,
J = 24.4 Hz), 157.60, 139.90, 130.96, 130.74, 123.41,

Y.-M. Wu et al. / Journal of Fluorine Chemistry 126 (2005) 791–795
795
123.30, 122.61, 117.49 (t, J = 302.0 Hz), 114.06, 113.99,
55.32, 55.24. IR (film, cmÀ1): 3052, 2970, 2840, 1593, 1504,
1253, 1127, 989, 835, 656. m/z (EI): 369 (4), 240 (100), 77
(23). HRMS (EI): M+, found 369.0180. C16H14BrF2NO2
requires 369.0176.
Calc. for C16H11BrF5NO: C, 47.08; H, 2.72; N, 3.43. Found:
C, 47.48; H, 2.78; N, 3.35.
3.3.7. Bromodifluoromethyl-3-trifluoromethylphenylketon-
4-methoxyphenylimine (3g)
Yield: 61%. Yellow oil. 1H NMR: d 7.67 (d, J = 7.20 Hz,
1H), 7.42-7.56 (m, 3H), 6.68–6.75 (m, 4H), 3.74 (s, 3H). 19
F
3.3.2. Bromodifluoromethyl-phenylketon-4-
NMR: d À53.45 (s, 2H), À63.15 (s, 3H). IR (film, cmÀ1):
2951, 2840, 1647, 1601, 1504, 1466, 1533, 1133, 1076, 840.
m/z (EI): 407 (9.22), 328 (7.98), 278 (100.00), 263 (3.59).
HRMS (MALDI): M+ + 1 found 408.0034. C16H12BrF5NO
408.0028;
methoxyphenylimine (3b)
Yield: 79%. Yellowish solid. Mp: 52–53 8C. 1H NMR: d
7.32–7.40 (m, 3H), 7.26–7.28 (m, 2H), 6.74 (d, J = 9.30 Hz,
2H), 6.70 (d, J = 9.30 Hz, 2H), 3.74 (s, 3H). 19F NMR: d
À50.37 (s):À57.60 (s) = 5:1; 13C NMR: d 159.55 (t,
J = 23.9 Hz), 157.82, 139.51, 130.88, 129.92, 129.28,
129.01, 128.64, 123.63, 123.52, 117.27 (t, J = 308.7 Hz),
113.93, 55.30. IR (film, cmÀ1): 3060, 2963, 2839, 2049,
1646, 1606, 1506, 1250, 1031,840. m/z (EI): 339 (9), 210
(100), 77 (24). HRMS (EI): M+, found 339.0055.
C19H12BrF2NO requires 339.0070.
3.3.8. Bromodifluoromethyl-2-methoxyphenylketon-4-
methoxyphenyliamine (3h)
Yield: 46%. Yellow oil. 1H NMR: d 7.33–7.39 (m, 1 H),
7.20 (d, J = 7.20 Hz, 1H), 6.93 (t, J = 7.20 Hz, 1H), 6.84 (d,
J = 8.70 Hz, 1H), 6.74–6.83 (m, 2H), 6.67–6.70 (m, 2H),
3.72 (s, 3H), 3.67 (s, 3H). 19F NMR: d À53.43 (d,
J = 265.1 Hz). IR (film, cmÀ1): 3004, 2838, 1650, 1599,
1504, 1490, 1464, 1249, 1112, 990, 836. m/z (EI): 369 (7),
240 (100.00); HRMS(MALDI): M+ + 1, found 370.0262.
C16H15BrF2NO2 requires 370.0249.
3.3.3. Bromodifluoromethyl-4-methylthiophenyl-keton-4-
methoxyphenylimine (3c)
Yield: 63%. Yellowish solid. Mp: 82–84 8C. 1H NMR: d
7.17 (s, 4H), 6.74 (s, 4 H), 3.75 (s, 3H), 2.48 (s, 3H). 19F
NMR: d À53.01 (s):57.31 (s) = 37:1. IR (film, cmÀ1): 3064,
2973, 2841, 1638, 1593, 1504, 1250, 1124, 837; m/z (EI):
385 (7), 256 (100), 241 (16). Calc. for C16H14BrF2NOS: C,
49.75; H, 3.65; N, 3.63. Found: C, 50.17; H, 3.70; N, 3.63.
Acknowledgment
The authors thank the National Natural Science
Foundation of China (NNSFC) (No. 20472104) for financial
support.
3.3.4. Bromodifluoromethy-4-phenylphenylketon-4-
methoxyphenylimine (3d)
Yield: 73%. Yellowish solid. Mp: 105–105 8C. 1H NMR:
d 7.56–7.61 (m, 4H), 7.34–7.48 (m, 5H), 6.71–6.80 (m, 4H);
19F NMR: d À53.17 (s):À57.29 (s) = 50:1. IR (film, cmÀ1):
3028, 2841, 1636, 1594, 1504, 1299, 1251, 1125, 835. m/z
(EI): 415 (17), 286 (100), Calc. for C21H16BrF2NO: C,
60.59; H, 3.87; N, 3.36. Found: C, 60.96; H, 3.95; N, 3.41.
References
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(d) P.G. Schultz, S. Ding, Org. lett. 5 (2003) 3587.
[2] (a) Y. Gong, W. He, Org Lett. 4 (2002) 3803;
(b) J.Q. Tan, J.H. Chang, M.Z. Deng, Chin. J. Chem. 22 (2004) 941.
[3] (a) I. Ugi, F. Beck, U. Fetzer, Chem. Ber. 95 (1962) 126;
(b) K. Tamura, H. Mizukami, K. Uneyama, J. Org. Chem. 58 (1993)
32.
3.3.5. Bromodifluoromethyl-3-methylphenylketon-4-
methoxyphenylimine (3e)
Yield: 73%. Yellowish solid. Mp: 65–66 8C. 1H NMR: d
7.20–7.22 (m, 2H), 6.75 (d, J = 8.70 Hz, 2H), 6.73(d,
J = 8.70 Hz, 4H), 3.74(s, 3H), 2.32(s, 3H). 19F NMR: d
À53.02 (s). IR (film, cmÀ1): 3024, 2966, 2839, 1637, 1593,
1504, 1251, 1126, 884, 659. m/z (EI): 353 (5), 224 (100).
Calc. for C16H14BrF2NO: C, 54.26; H, 3.98; N, 3.95. Found:
C, 54.33; H, 4.08; N, 4.04.
[4] (a) S. Fustero, J.F. Sanz-Cervera, Org. Lett. 5 (2003) 2523;
(b) A. Suzuki, M. Mae, K. Uneyama, J. Org. Chem. 69 (2004) 5132;
(c) G.Q. Shi, W.L. Cai, J. Org. Chem. 60 (1995) 6289.
[5] K.E. Stremler, C.D. Poulter, J. Am. Chem. Soc. 109 (1987) 5542.
[6] (a) D.J. Burton, Z.Y. Yang, Tetrahedron 48 (1992) 189;
(b) Z.Y. Yang, D.J. Burton, J. Org. Chem. 56 (1991) 5125.
[7] K. Tamura, H. Mizukami, K. Uneyama, J. Org. Chem. 58 (1993) 32.
[8] S. Fustero, A. Navarro, A. Asensio, Tetrahedron Lett. 38 (1997) 4891.
[9] H. Watanabe, Y. Hashizume, K. Uneyama, Tetrahedron Lett. 33 (1992)
4333.
3.3.6. Bromodifluoromethyl-4-trifluoromethylphenylketon-
4-methoxyphenylimine (3f)
Yield: 72%. Yellowish solid. Mp: 71–72 8C. 1H NMR: d
7.63 (d, J = 8.40 Hz, 2H), 7.42 (d, J = 8.40 Hz, 2H), 6.72 (s,
4H), 3.75 (s, 3H). 19F NMR: d À53.37 (s):À63.38 (s) = 2:3.
IR (film, cmÀ1): 3052, 2911, 2840, 1667, 1618, 1503, 1324,
1179, 998, 886. m/z (EI): 407 (1), 278 (14), 77 (18), 40 (100).
[10] (a) J. Uenishi, J.-M. Beau, R.W. Armstrong, Y. Kish, J. Am. Chem.
Soc. 109 (1987) 4756;
(b) J.C. Anderson, H. Namli, C.A. Roberts, Tetrahedron 53 (1997)
15123;
(c) K. Hirabayashi, J. Kawashima, Y. Nishihara, A. Mori, T. Hiyama,
Org. Lett. 1 (1999) 299.