Halogenation of β-alkoxyvinyl polyhaloalkyl ketones: A convenient route for the synthesis of α-chloro- or α-bromo-β-alkoxyvinyl polyhaloalkyl ketones

Article abstract of DOI:10.1055/s-2001-11435

A number of α-chloro- and α-bromo-β-alkoxyvinyl polyhaloalkyl ketones 4 and 5 were synthesized in high yields by halogenation of β-alkoxyvinyl polyhaloalkyl ketones 1 with chlorine or bromine and further dehydrohalogenation of dihalo-intermediates 2 and 3 with pyridine. The Z configuration of ketones 4 and 5 was deduced from X-ray analysis and NMR spectra. Some typical nucleophilic reactions of the title compounds 4 and 5 with amines were carried out to check their reactivity.

Full text of DOI:10.1055/s-2001-11435

PAPER
431
Halogenation of -Alkoxyvinyl Polyhaloalkyl Ketones: A Convenient Route
for the Synthesis of -Chloro- or -Bromo- -alkoxyvinyl Polyhaloalkyl
Ketones
Igor I. Gerus,* Liliya M. Kacharova, Sergei I. Vdovenko
Institute of Bioorganic Chemistry, Ukrainian National Academy of Sciences, Str. Murmanskaya 1, Kiev, 02094, Ukraine
Fax +38(044)5732552; E-mail: igerus@alfacom.com
Received 19 July 2000; revised 12 September 2000
At the same time, the electrophilic halogenation of olefins
is widely used for the synthesis of various useful and ac-
cessible vinyl halide building blocks6 and for fluoro-con-
taining compounds as well.7 It is obvious that the
Abstract: A number of -chloro- and -bromo- -alkoxyvinyl poly-
haloalkyl ketones 4 and 5 were synthesized in high yields by halo-
genation of -alkoxyvinyl polyhaloalkyl ketones 1 with chlorine or
bromine and further dehydrohalogenation of dihalo-intermediates 2
and 3 with pyridine. The Z configuration of ketones 4 and 5 was de- halogenation of -alkoxyvinyl polyhaloalkyl ketones 1
duced from X-ray analysis and NMR spectra. Some typical nucleo-
philic reactions of the title compounds 4 and 5 with amines were
carried out to check their reactivity.
will give -chloro-, bromo-derivatives 4, 5 having the
large prospect of an application as fluorinated building
blocks. The -halo- -alkoxyvinyl alkyl ketones were syn-
Key words: enones, halogenation, electrophilic additions, elimina-
tions, aminations
thesized by alkylation of 2-halo-1,3-dicarbonyl com-
pounds with various reagents such as diazomethane,8
dimethyl sulfate8 or ethanol.9 The halogenation of
-alkoxyenones has not been used for the synthesis of cor-
The introduction of fluorine atoms and fluorinated groups
into organic molecules often confers significant and use-
ful changes in their chemical and physical properties.
Therefore, methods for the synthesis of fluorinated com-
pounds have received considerable interest in recent
years.1 Although direct fluorinating or polyfluoroalkylat-
ing methods are the most attractive and powerful new
tools for constructing fluorinated compounds, the fluoro-
containing building blocks are often the more convenient
starting reagents.2 Thus, fluorinated carbonyl and dicarbo-
nyl compounds are often used as starting materials to ob-
tain the desired fluoro-containing substances. Particularly
(E)- -alkoxyvinyl polyfluoroalkyl ketones 1 (that may be
considered as synthetic equivalent of 1,3-ketoaldehydes)
are accessible polyfluoroalkylated building blocks3 for the
synthesis of various fluorine-containing heterocycles,
enaminones, dyes, drugs and protective reagents for ami-
no group protection in peptide synthesis.4 The nucleo-
philic reactions of enone 1b were studied in much more
detail, but only few reports have been published on the re-
actions of fluorinated enones 1 with electrophiles.5
responding -haloderivatives. Two patents are available
on the halogenation10a of enone 1b by various reagents
and the application of -chloro- 4b and -bromo-deriva-
tives 5b for the synthesis10b of 3-trifluoromethyl-4-ha-
lopyrazoles as potential insecticides. However, only
limited 1H NMR spectra data of dihalo-intermediates 2b,
3b, and no data concerning the configuration of the trisub-
stituted C=C bond in -chloro-, bromo-derivatives 4b, 5b
are given in the patents.10a In this article, we describe the
halogenation of enones 1a d which contain various poly-
haloalkyl-groups, and the examination of the reactivity of
-chloro-, bromo-derivatives 4b, 5b in amination reac-
tions.
We have found that chlorine and bromine readily add to
the C=C bond of enones 1a d, and the mixture of diaste-
reomeric (m.d.) dichloro- 2a d and dibromoketones 3a
d are formed in quantitative yields (Scheme 1, Table 1).
Formation of the diastereomeric mixture is a result of both
syn- and anti-addition of halogens to (E)-enones 1, where
bromine gives predominantly anti-adducts and chlorine
gives syn-adducts.11
Scheme 1
Synthesis 2001, No. 3, 431–436 ISSN 0039-7881 © Thieme Stuttgart · New York

432
I. I. Gerus et al.
PAPER
Table 1 NMR Spectra, Physical Constants and Yield of Compounds- 2a e, 3a d, 8a, b
Compd
Isolated Yielda, Bp, C/mmHg Contents of
1H NMRb
%
or Mp, C
(solvent)
diaste-
reomers, %
-H, (d)
4.80
-H, (d)
5.77
JHH, Hz Other
45
55
6.8
7.4
1.25 (t, 3 H, J = 7.1, CH3), 3.65 and
4.00 (m, 2 H, CH2), 5.9 (t, 1 H, J =
53.5, CHF2)
1.32 (t, 3 H, J = 7.1, CH3), 3.70 and
4.04 (m, 2 H, CH2), 6.06 (t, 1 H, J =
53.5, CHF2)
c
2a
~100
4.93
5.83
80
20
4.79
4.93
5.77
5.86
7.8
8.3
1.23 (t, 3 H, J = 7.1, CH3), 3.63 and
4.00 (m, 2 H, CH2)
1.33 (t, 3 H, J = 7.0, CH3), 3.72 and
4.06 (m, 2 H, CH2)
2b
2c
2d
~100 (70)
~100 (87)
~100 (97)
34 35/19
80 81/0.5
78
22
5.15
5.31
5.79
5.87
8.4
8.5
1.20 (t, 3 H, J = 7.1, CH3), 3.60 and
3.99 (m, 2 H, CH2)
1.34 (t, 3 H, J = 7.1, CH3) 3.74 and 4.05
(m, 2 H, CH2)
50
50
4.68
4.76
5.76
5.86
6.3
5.8
1.23 (t, 3 H, J = 7.0, CH3), 3.62 and
3.96 (m, 2 H, CH2), 4.68 [sept, 1 H, J =
7.3, CH(CF3)2]
1.29 (t, 3 H, J = 7.1, CH3), 3.66 and
4.04 (m, 2 H, CH2), 4.73 [sept, 1 H, J =
7.3, CH(CF3)2]
23 25
(hexane)
50
50
4.44
4.48
5.70
5.71
4.9
6.5
2.39 (s, 3 H, COCH3), 3.58 (s, 3 H,
OCH3)
2.39 (s, 3 H, COCH3), 3.60 (s, 3 H,
OCH3)
c
2e
3a
~90
23
77
4.96
5.24
5.97
6.15
6.7
9.2
1.27 (t, 3 H, J = 7.1, CH3), 3.66 and
3.99 (m, 2 H, CH2), 6.10 (t, 1 H, J =
53.3, CHF2)
1.35 (t, 3 H, J = 7.1, CH3), 3.71 and
4.02 (m, 2 H, CH2), 6.08 (t, 1 H, J =
53.3, CHF2)
c
~100
20
80
4.91
5.21
6.01
6.12
7.9
9.4
1.25 (t, 3 H, J = 7.0, CH3), 3.64 and
3.98 (m, 2 H, CH2)
1.36 (t, 3 H, J = 7.0, CH3), 3.66 and
4.02 (m, 2 H, CH2)
3b
3c
~100 (80)
~97
36 37/1
30
70
5.27
5.56
6.05
6.17
8.5
9.2
1.21 (t, 3 H, J = 7.1, CH3), 3.60 and
3.96 (m, 2 H, CH2)
1.36 (t, 3 H, J = 7.1, CH3), 3.73 and
4.02 (m, 2 H, CH2)
c
25
75
4.81
5.06
6.04
6.10
6.6
8.5
1.25 (t, 3 H, J = 7.1, CH3), 3.64 and
3.96 (m, 2 H, CH2), 4.61 [sept, 1 H,
J = 7.4, CH(CF3)2]
1.36 (t, 3 H, J = 7.0, CH3, 3.69 and 4.01
(m, 2 H, CH2), 4.51 [sept, 1 H,
J = 7.4, CH(CF3)2]
53 54
(hexane)
3d
~100 (98)
87
13
5.09s
5.15s
2.00 (s, 3 H, CH3), 3.54 (s, OCH3)
2.06 (s, 3 H, CH3), 3.61 (s, OCH3)
c
c
8a
8b
~90
~90
80
20
5.45
5.50
2.11 (s, 3 H, CH3), 3.54 (s, OCH3)
2.14 (s, 3 H, CH3), 3.55 (s, OCH3)
a All compounds gave satisfactory elemental analysis data: C 0.26; H 0.19; F 0.23.
b Chemical shifts , ppm, coupling constants J, Hz.
c 92 98% purity (1H NMR) after evaporation of the solvents in vacuum.
Synthesis 2001, No. 3, 431–436 ISSN 0039-7881 © Thieme Stuttgart · New York

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Halogenation of -Alkoxyvinyl Polyhaloalkyl Ketones
433
Ketones 2 and 3 were obtained in near quantitative yields A comparison of halogenation of fluorinated enone 1b
with 92 98% purity (1H NMR) after evaporation of the and the parent unfluorinated enone 1e was carried out by
solvents in vacuum. In spite of the patent data10a concern- 1H NMR (Scheme 2). It was found that chlorination of
ing the instability of dihaloketones 2b and 3b, we have (E)-4-methoxy-3-buten-2-one (1e) gives a mixture of di-
distilled ketones 2b, c, 3b, and ketones 2d, 3d were crys- astereomers 2e in quantitative yield as in the case of
tallized. The vacuum distillation of ketone 3b is accompa- enones 1a d. Unexpectedly, the bromination of enone 1e
nied by thermal dehydrobromination (at temperatures gives monobromoacetyl compound 6 in high yield, ac-
>50 C); 17% of -bromoenone 5b being formed. A more companied by only 3 4% of the dibromo-adduct. This re-
effective dehydrohalogenation of dihaloketones 2, 3 can sult differs dramatically from results of the bromination of
be carried out in the presence of base. Thus, treatment of enones 1a, d having an -hydrogen atom in acyl group,
dihaloketones 2, 3 with pyridine yielded the correspond- which form dibromo-adducts 3a, d only.
ing -chloro- 4a d and -bromoenones 5a d (Scheme 1,
Table 2). -Haloenones 4, 5 can also be obtained in “one
pot”, without isolation of dihaloketones 2, 3. Despite the
formation of a diastereomeric mixture of intermediate di-
haloketones 2, 3, the final -haloenones 4, 5 are obtained
as single isomers. The chemical shift of the -proton of
-haloenones 4a d and 5a d are observed in a narrow
range (about 8 ppm, Table 2), which gives evidence of
configurational homogeneity of these -haloenones at
C=C bond. The Z configuration of ketone 5d was deter-
mined by X-ray analysis (Figure). The fragment of a mol-
ecule of ketone 5d (from C4 to C7) has a planar structure,
where bromine and oxygen (O1) atoms are in the same
Scheme 2
plane. The carbonyl group and C=C bond exist in an s-E
conformation. IR spectra of -haloenones 4a d, 5a d
A similar difference between chlorination and bromina-
(Table 2) contain one broadened C=O band at 1710 1693
tion is observed in the halogenation of enones 7a, b bear-
cm 1 (two bands C=O in this region are observed only in
ing a methyl group at the -position of C=C bond with
the case of difluoroacetyl-containing haloenones 4a, 5a),
respect to the carbonyl group (Scheme 3). The chlorina-
and two bands at 1621 1615 cm-1 and 1596 1590 cm-1
tion of enones 7a, b gives in high yields a mixture of dias-
ascribed to C=C. The presence of two
absorption
C=C
tereomers 8a, b, which are dehydrochlorinated during
vacuum distillation forming -chloroenones 9a, b. In this
way, -chloroenone 9b is formed in good yield, but the
yield of -chloroenone 9a does not exceed 20%. -Chlo-
roenone 9a was obtained in good yield and of 90% purity,
upon treatment of dihaloketone 8a with pyridine. -Chlo-
roenones 9a, b were obtained in single thermostable
forms that allowed us to assign the Z configuration to
these compounds, analogously to -chloroenone 9
(R = Ph) in reference.8 At the same time, bromination of
enones 7a, b gave at once -monobromomethyl com-
pounds 10a, b in high yields, as a result of allylic bromi-
nation of the vinylic methyl position. However, the
products 10a, b contain a 5 10% admixture of -dibro-
momethyl compounds,12 inseparable by vacuum distilla-
tion.
bands can be explained by an equilibrium between s-E-
and s-Z-conformers of Z- -haloenones 4, 5. A more de-
tailed examination of conformational behavior of haloge-
nated enones is now underway.
Earlier, -halo- -alkoxyenones have been used as starting
compounds in the heterocyclization9,10b or the Favorskii-
rearrangement.8 We have chosen the amination to com-
pare the reactivity of -chloro- 4b and -bromo-contain-
ing enone 5b with their parent enone 1b. Previously, we
have shown that enones 1 reacted readily with ammonia,
and primary and secondary amines yielding the corre-
sponding -aminovinyl polyhaloalkyl ketones.3,4a In order
to compare the reactivity of enone 1b with -halo-con-
taining enones 4b and 5b we studied reactions of these
enones with methylamine and dimethylamine (Scheme 4,
Table 2).
Figure Molecular structure of -bromoenone 5d
Selected bond lengths (Å) and torsion angles (o): Br(1)-C(2) 1.866(6),
O(2)-C(1) 1.304(9), C(1)-C(2) 1.337(9), C(2)-C(3) 1.432(11), O(1)-
C(3) 1.229(8), C(7)-O(2)-C(1)-C(2) 179.1(8), O(2)-C(1)-C(2)-C(3)
179.0(7), C(1)-C(2)-C(3)-O(1) 178.4(7).
Synthesis 2001, No. 3, 431–436 ISSN 0039-7881 © Thieme Stuttgart · New York

434
I. I. Gerus et al.
PAPER
Table 2 Physical Constants, Yield, NMR and IR Spectra of Enones 4a d, 5a d, 6, 9a, b, 10a, b and Enaminones 11b, c, e, f
1
Compd
Bp, C/mmHg or Yielda,%
Mp, C (solvent)
NMRb
IR, cm
(CCl4)
1H
19F
-H
Other
C=O
C=C
4a
49 50
(hexane)
65
7.92 (s)
1.45 (t, 3 H, J = 7.1, CH3),
4.34 (q, 2 H, J = 7.1, CH2),
6.10 (t, 1 H, J = 53.6, CHF2)
120.30 (d, 53.6) 1711 w
1690 m
1624 s
1604 m
4b
4c
4d
83 84/10c
80
70
81
7.90
(br q, 0.8)
1.47 (t, 3 H, J = 7.2, CH3),
4.43 (q, 2 H, J = 7.2, CH2)
70.12 (d, 0.8)
1710 m
1701 m
1698 m
1619 s
1596 m
127 128/0.5
8.18 (s)
7.88 (s)
1.44 (t, 3 H, J = 7.0, CH3),
4.33 (q, 2 H, J = 7.0, CH2)
_
1618 m
1592 s
87 88
(hexane)
1.45 (t, 3 H, J = 6.9, CH3),
4.34 (q, 2 H, J = 6.9, CH2),
5.03 [sept, 1 H, J = 7.2,
CH(CF3)2]
63.9 (d, 7.2)
1621 w
1596 s
5a
45 46
(hexane)
68
8.07 (s)
1.46 (t, 3 H, J = 7.0, CH3),
4.37 (q, 2 H, J = 7.0, CH2),
6.10 (t, 1 H, J = 53.8, CHF2)
119.19 (d, 53.8) 1704 vw
1687 m
1617 s
1595 w
5b
5c
5d
103 105/19d
114 115/0.5
85
90
90
8.00 (br s)
8.36 (s)
1.49 (t, 3 H, J = 7.1, CH3),
4.43 (q, 2 H, 7.1, J = CH2)
69.52 (br s)
1708 m
1702 s
1693 m
1615 s
1590 w
1.45 (t, 3 H, J = 7.0, CH3),
4.30 (q, 2 H, J = 7.0, CH2)
1618 vs
1586 s
95 97
(hexane)
8.00 (s)
1.46 (t, 3 H, J = 7.1, CH3),
4.37 (q, 2 H, 7.2, J = CH2), 5.1
[sept, 1 H, J = 7.4, CH(CF3)2]
63.91 (d, 7.4)
1619 w
1592 s
6
(90)
5.99
(d, 8.9)
2.39 (s, CH2Br ), 3.59 (s, 3 H,
OCH3), 4.82 (d, 1 H, J = 8.8,
CH)
9a
9b
89 90/14
140 141/16
77 78/10
50
74
72
2.56 (s, 3 H, CH3), 4.00
(s, 3 H, OCH3 )
73.25 (s)
79.03 (s)
1696 m
1564 s
2.49 (s, 3 H, CH3), 3.98 (s, 3
H, OCH3)
10a
3.86 (s, 3 H, OCH3), 4.43 (s,
2 H, CH2Br), 5.72 (s, 1 H,
CH)
1714 m
1712 m
1593 vs
1595 vs
10b
116 119/0.5
82
3.86 (s, 3 H, OCH3), 4.46 (s,
2 H, CH2Br), 6.03 (s, 1 H,
CH)
11b
11c
11e
11f
93 95
(hexane)
55
70
70
43
7.68
(d, 13.7)
3.22 (d, 3 H, J = 4.9, NCH3),
5.93 (br s, 1 H, NH)
68.32 (s)
68.14 (s)
67.68 (s)
66.98 (s)
1678 vwe
1677 vwe
1684 m
1623 vse
1621 vse
104 106
(hexane)
7.71
(d, 14)
3.26 (d, 3 H, J = 5.2, NCH3),
5.97 (br s, 1 H, NH)
74 75/0.5
7.50 (s)
3.33 [s, 6 H, N(CH3)2]
1617 vs
1588 s
43 45
(hexane)
7.70 (s)
3.37 [br s, 6 H, N(CH3)2]
1679 w
1614 vs
1585 m
a All compounds gave satisfactory elemental analysis data: C 0.47; H 0.52; F 0.49.
b Chemical shifts , ppm., coupling constants J, Hz.
c Lit.10a Bp: 84 87/13 mbar.
d Lit.10a Bp: 100 102/21 mbar.
e In CDCl3.
Synthesis 2001, No. 3, 431–436 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Halogenation of -Alkoxyvinyl Polyhaloalkyl Ketones
435
and trifluoroacetyl groups), that may be explained by ster-
ic hindrance between the -halogen atom and the trifluo-
romethyl group in E-s-Z-isomer of enaminones 11b, c
with intramolecular hydrogen bond. Enaminones 11e, f
exist in the Z configuration, which is a common feature
for N,N-dialkylenaminones. A more complete investiga-
tion of the stereochemistry of enaminones 11b, c, e, f de-
pending on the nature of the substituent at -position is
now underway.
In summary, we have synthesized a number of useful flu-
oro-containing building blocks
-chloro-, bromo- -
alkoxyvinyl polyhaloalkyl ketones, by the halogenation of
accessible -alkoxyvinyl polyhaloalkyl ketones with
chlorine and bromine and further dehydrohalogenation of
dihalo-intermediates. Halogenation of Me-containing
enones 1e and 7a, b proceeds by two different routes:
chlorination gives dichloro-adducts with the assistance of
C=C bond, whereas the bromination results in bromina-
tion of the methyl group. It was shown that an amination
of these available and convenient fluorinated enones 4b,
5b differ insignificantly from enone 1b.
Starting materials were of the highest commercial quality and were
used without further purification. 19F NMR chemical shifts are re-
ported in ppm, negative upfield relative to internal CFCl3, 1H NMR
chemical shifts are reported in ppm, positive downfield relative to
internal TMS; spectra were recorded in CDCl3 at 282.24 MHz and
300 MHz (Varian VXR-300), respectively. GC analysis were ob-
tained using SE-30 (5%) column (3.3 m 3 mm) on Chrom-5 (Pra-
gue, Czechoslovakia) with FID and N2 as gas-carrier. Starting
enones were obtained by the reaction of the corresponding acid
chlorides with alkyl vinyl ethers: enones 1a, d,3 enone 1b, c,15
enone 7a, b.16 Enone 1e was purchased from Fluka.
Scheme 3
The reactions of enones 1b, 4b and 5b with a slight excess
of the amines in water proceeded with substitution of the
ethoxy group by an amino group yielding enaminones
11a f. Hence, the presence of halogen atoms at -position
of enones 4b and 5b does not cause serious changes in the
reaction route, but results in a decrease of yields from 85
95% for enaminones 11a, d (X = H)13 to 43% for enami-
none 11b and 55% for enaminone 11f. The 1H NMR spec-
tra of enaminones 11b, c, e, f (Table 2) show that they
exist only as one isomer in CDCl3 solution. Previous-
ly,13,14 we have published detailed investigations on the
stereochemistry of trifluoromethyl containing enamino-
nes 11a, d. A comparison of -H and NH chemical shifts
of enaminones 11a, b, c and their behavior with increas-
ing solvent polarity (Table 3) indicate the Z configuration
of enaminones 11b, c (E configuration between amino
4,5-Dichloro-5-ethoxy-1,1,1-trifluoro-2-trifluoromethylpentan-
3-one (2d); Typical Procedure for Dihaloketones 2, 3 and 6
To the solution of enone 1d (1.17 g, 4.7 mmol) in CCl4 (4 mL, for
6 in CDCl3) was added 0.5 M solution of chlorine in CCl4 (10 mL,
5 mmol) at 0 C with stirring. The reaction mixture was stirred for
1 h at 20 C, then the solvent was evaporated. The residue was dis-
tilled in vacuum or crystallized. Yields, physical constants and
NMR data are shown in Table 1.
(Z)-3-Bromo-4-ethoxy-1,1,1-trichlorobut-3-en-2-one (5c); Typi-
cal Procedure for -Haloenones 4, 5, 8 10
To the solution of enone 1c (2.61 g, 12 mmol) in CH2Cl2 (5 mL) was
added bromine (2.1 g, 13 mmol) at 0 C with the stirring. After 1 h,
pyridine (1.04 g, 13 mmol) was added to the reaction mixture (ex-
cept for 10) at 0 C with stirring. The reaction mixture was stirred
for 1 2 h at 20 C, H2O (50 mL) was added, and the aqueous phase
was extracted with hexane (3 10 mL). The combined organic lay-
ers were dried (MgSO4) and the solvent was evaporated. The resi-
due was distilled in vacuum or crystallized. Yields, physical
constants and NMR data are shown in Table 2.
3-Bromo-4-methylamino-1,1,1-trifluorobut-3-en-2-one (11c);
Typical Procedure for Enaminones 11a f
Enone 5b (1.06 g, 4.3 mmol) was added to the solution of RNH2
(0.19 g, 6 mmol) in H2O (1 mL) under stirring at 0 C. The mixture
was stirred for 1 2 h at r.t., the product was filtered, and crystallized
or distilled in vacuum. Yields, physical constants and NMR data are
shown in Table 2.
Scheme 4
Synthesis 2001, No. 3, 431–436 ISSN 0039-7881 © Thieme Stuttgart · New York

436
I. I. Gerus et al.
PAPER
Table 3 Selected 1H NMR Spectra Data ( , ppm) for Enaminones 11a c in Various Solvents
Compds
X
CDCl3
NH
CD3CN or (CD3)2CO
(CD3)2SO
NH
-CH
7.10
7.97
7.68
7.71
-CH
NH
-CH
7.45
7.90
7.99
8.01
(Z)-11a
(E)-11a
(Z)b-11b
(Z)b-11c
H
H
Cl
Br
10.17
5.98
5.93
5.97
7.29a
7.93a
10.09a
6.78a
10.05
8.64
8.46
8.32
8.02c
7.50c
a In CD3CN.
b E-Configuration between amino and trifluoroacetyl groups.
c In (CD3)2CO.
X-ray Crystallographic Data for Compound 5d
The crystals of -bromoenone 5d were obtained by crystallization
from hexane.
b) Nenaidenko, V. G.; Sanin, A. V.; Balenkova, E. S. Russ.
Chem. Rev. (Engl. Transl.) 1999, 68, 437.
(5) Hojo, M.; Masuda, R.; Okada, E. Synthesis 1990, 347.
(6) Miyaura, N.; Susuki, A. Chem. Rev. 1995, 95, 2457.
(7) Allain, L.; Bégué, J. -P.; Bonnet-Delpon, D.; Bouvet, D.
Synthesis 1998, 847;
Shi, G.; Huang, X. -H.; Hong, F. J. Org. Chem. 1996, 61,
3200.
(8) Verhé, R.; De Buyck, L.; De Kimpe, N.; De Rose, A.; Schamp
N. Bull. Soc. Chim. Belg. 1978, 87, 143.
C8H7BrF6O2, M = 329.05, monoclinic, a = 6.928(1), b = 15.893(3),
c = 10.902(2) Å, = 90.94(3), V = 1200.2(4) Å3, space group
3
1
P21/c, Z = 4, Dc = 1.82 g cm , = 5.37 mm , F(000) = 640, crys-
tal dimensions 0.28 0.30 0.40 mm. The intensities of 1636 re-
flections were measured on a Enraf-Nonius CAD4 diffractometer
(CuK -adiation, T = 293 K, 4 < < 600, 1478 unique reflections).
The structure was solved by direct methods17 and refined on F2 by
full-matrix least-squares techniques18 in anisotropic approximation
(1308 reflection with I > 2 (I), 155 variables, observations/
(9) Lipinski, C.A.; Blizniak, T. E.; Craig, R. H. J. Org. Chem.
1984, 49, 566.
(10) a) Heine, H. G.; Ooms, P. Eur. Patent 290903 (1988), Bayer
AG; Chem. Abstr. 1989, 110, P192254.
1
2
variables = 8.4, weighting scheme
w =
2(Fo )+(0.0727P)2+
1.0938P, where P = (Fo +2Fc2)/3). All hydrogen atoms were placed
geometrically and included in the final refinement with the fixed
positional and thermal parameters. Convergence was obtained at
2
b) Heine, H.-G.; Ooms, P.; Bielefeldt, D.; Becker, B.;
Behrenz, W. European Patent 290904, 1988; Bayer AG;
Chem. Abstr. 1989, 110, P135235.
R(F) = 0.056, Rw(F2) = 0.131, GOF = 1.054,
(min/max) =
(11) March, J. Advanced Organic Chemistry. Reactions,
Mechanisms and Structure; Wiley: New York, 1985.
(12) 1H NMR spectra (CDCl3) of (E)-5,5-dibromo-1,1,1-trifluoro-
4-methoxy-3-penten-2-one [ = 3.97 (s, 3H, OMe), 5.53 (s,
1H, CH=), 7.50 (s, 1H, CHBr2) and (E)-5,5-dibromo-1,1,1-
trichloro-4-methoxy-3-penten-2-one [ = 3.97 (s, 3H, OMe),
5.86 (s, 1H, CH=), 7.57 (s, 1H, CHBr2).
3
0.27/0.56 e Å . Atomic coordinates and further crystallographic
details have been deposited at the Cambridge Crystallographic Data
Centre, deposition number 146922, and copies of this data can be
obtained in application to CCDC, University Chemical Laboratory,
Lensfield Road, Cambridge CB2 1EW, UK (fax:+44 1223-336-
033; E-mail: deposit@ccdc.cam.ac.uk).
(13) Vdovenko, S. I.; Gerus, I. I.; Gorbunova, M. G. J. Chem. Soc.,
Perkin Trans. 2 1993, 559.
(14) Wojcik, J.; Domalewski, W.; Kamienska-Trela, K.; Stefaniak,
L.; Vdovenko, S. I.; Gerus, I. I.; Gorbunova, M. G. Magn.
Reson. Chem. 1993, 31, 808.
Acknowledgement
This work was supported by the International Association Founda-
tion (INTAS-UA-95-0095).
(15) Hojo, M.; Masuda, R.; Kokuryo, Y.; Shioda, H.; Matsuo, S.
Chem. Lett. 1976, 499.
(16) Hojo, M.; Masuda, R.; Sakaguchi, S.; Takagawa, H. Synthesis
1986, 1016.
(17) Sheldrick, G. M. SHELXS-86. Program for the Solution of
Crystal Structures, University of Göttingen, Göttingen,
Germany, 1986.
(18) Sheldrick, G. M. SHELXL-93. Program for the Refinement of
Crystal Structures, University of Göttingen, Göttingen,
Germany, 1993.
References
(1) Fluorine in Bioorganic Chemistry; Welch, J. T.,
Eswarakrishnan, S., Eds.; Wiley: New York, 1991.
Organofluorine Compounds in Medicinal Chemistry and
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Yagupolskii, L.M., Eds.; Elsevier: Amsterdam, 1993.
(2) Percy, J. M. Top. Curr. Chem. 1997, 193, 131.
Uneyama, K. J. Fluorine Chem. 1999, 69, 195.
(3) Gorbunova, M. G.; Gerus, I. I.; Kukhar, V. P. Synthesis 2000,
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Article Identifier:
1437-210X,E;2001,0,03,0431,0436,ftx,en;T00700SS.pdf
(4) a) Gerus, I. I.; Gorbunova, M. G.; Kukhar, V. P. J. Fluorine
Chem. 1994, 69, 195.
Synthesis 2001, No. 3, 431–436 ISSN 0039-7881 © Thieme Stuttgart · New York