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Synthesis of useful building blocks for monofluorinated compounds derived from trifluoroethene
Journal of Fluorine Chemistry, 29 (1985)
445-458
445
Received:January 30,1985;accepted: June 17,198s
SYNTHESIS
OF USEFUL
COMPOUNDS
DERIVED
BUILDING
FROM
Yoshimichi
NAKAYAMA,
Department
of Chemical
Technology,
Ookayama,
BLOCKS
FOR MONOFLUORINATED
TRIFLUOROETHENE
Tomoya
KITAZUME
Technology, Meguro-ku,
*
and Nobuo
Tokyo Tokyo
ISHIKAWA*
Institute
152
of
(Japan)
SUMMARY
A synthetic
approach
from the Friedel-Crafts
to monofluorinated
acylhalogenation
give chlorotrifluoroketones These
are converted
monofluorinated reduction
and thence
afford
trifluorovinyl
to phenylthio-adducts
a,&unsaturated
compounds
to
ketones.
and thence
phenylthioesters,
&fluoroallylic
starts
of trifluoroethene
which
by
alcohols.
INTRODUCTION
The chemistry for the purpose the exception
of fluoroolefins
of studying
of lithiation
chlorotrifluoroethene
their
of trifluoroethene
[2], only a few reports
on the synthetic
utility
the wide variety
of monofluorinated
as bioactive Friedel-Crafts Claisen-type
materials.
condensation
We recently
are useful
under
we describe
chlorotrifluoroalkanones which
of fluoroolefins
acylhalogenation
In this paper,
has been developed reactivity
building
have
outlined
focussed
[3-S] of interest
conditions
the conversion
and its 19-101.
of the derived
trifluorovinyl
for valuable
of
a convenient
of trifluoroethene
into alkyl blocks
[2] or
in the preparation
compounds
acidic
mainly
[l]. However,with
ketones
monofluorinated
compounds. 0022-1139/85/$3.30
0 Elsevier Sequoia/Printed in The Netherlands
446 RESULTS
AND DISCUSSION
Our preparation than
that reported
of alkyl by other
(la)
3,4,4-trifluoro-2-butanone diglyme
solution
trifluorovinyl
trifluorovinyl
to produce
The reaction
(2a).
-18 C, and the product
was
under
The material
dynamic
isolated under
vacuum.
done
to react
with a
methyl
proceeded
smoothly
at
by a trap to trap system is stable
for several
ketone
weeks
structure
enough
to be
in the ice-box
in Fig.
was
finally
of the NMR
The assignment
spectroscopy.
as shown
is simpler
4-chloro-
atmosphere.
The trifluorovinyl by NMR
isolated
and can be stored
a nitrogen
ketones Thus,
[9] was allowed
of triethylamine
ketone
[ll].
workers
established
signals
was
I.
Et3N ldiglyme RC(0)CHFCF2CI
>
RC(0)CF=CF2
(1)
(2)
.8ppmi
d. d. q. 22.OHz
9 4ppm(d. d-1
Fig. 1
The 'H and I9 F NMR spectra
In our continuing compounds blocks,
[8-101,
being
nucleophiles.
of
programme
trifluorovinyl
susceptible
(2a)
to synthesise compounds
to attack
monofluorinated
are useful
by a wide variety
building of
447
2-Phenylthio-1,2,2-trifluoroethyl were
prepared
by the Michael
trifluorovinyl but smoothly compounds
ketones produced
made
alkyl
addition in situ.
alkyl
of HF using
the well-established (Table
coupling
constants
PhSHlEt3N zw
RC(0)CF=CF2
(2)
(1)
).
RC(0)CHFCF2SPh
(3)
(3a)
:
R bp
(3b)
:
R bp
R
q
Me
; Y.
96
78-80°C/0.6
= Et
; Y.
9596%/0.7
% mmHg
90
in 93%
P, mmHg
(4a) and
was determined
for difluorovinyl
1).
RC(O)CHFCF$
system.
l-phenylthio-
thus obtained
The E/Z ratio of the products 88% (4b) yield. 19 F NMR, the identification being based on
compounds
vinyl
(4a) and
(4b) were
compounds,
a Et3N/i-PrOH
I-Phenylthio-1,2-difluoro-1-buten-3-one 1,2-difluoro-1-penten-3-one
(3a,3b) to
They are stable
the corresponding
by the elimination
ketones
of thiophenol
by
1
Yields
b
standard.
a
(nc)
(20/80)
(26/74) 81
67
67
("C/mHg)
(97)
using PhCF3 as an internal
II/89
70-73/21
32/68
Bp
(82)
E/Z ratio
IOl-105/0.5
69-72/48
(%ja
(°C/mHg)
91-95/0.2
Bp
(85)
Yield
30/70
27/13
E/Z ratio
in parentheses are determined by "F NMR signal intensities b Isolated by column chromatography.
Ph
i-Pr
9b (nc)
9c
Me
9a
(E/Z ratio)
R
(3)
(8) with NaBH4
98
96
Yield(%)
of RC(O)CHFCF2SPh
of RC(CH3)=CFC(0)SPh
Product No.
Reduction
4
(nc)
4b
TABLE
Me
(nc)
4a
Et
R
Product No.
Dehydrofluorination
TABLE
449
Preparation
of monofluorinated
ohenvlthioesters
(8)
The rearrangement in Scheme [3-61.
of carbinols
1 has been reported
In our building
of compounds to the
(4a) and
formation
a route
compounds,
which
monofluorinated
block
to carboxylic
by J. F. Normant system,we
(4b) with NaBH4
of vinylic
gave monofluorinated providing
a,B-unsaturated
found
proceeded
(5a, 5b). Acid
a,&unsaturated
phenylthioesters
to functionalized
monofluoroorganic
can serve as building
blocks
hydrolysis (6a,6b)
for bioactive
materials.
F
F 0
F
F
R1 Li
+
R,
R2
*d=
rI-
F
OH
R2
F R1 CO2H
-
+ Scheme
R2
1
0
F l)NaBH4/EtOH P
SPh
R
2)lN
SPh
HCI
N4\ F (Sa)
R
= Ms
; Y.
95
%
(5b)
R
= Et
; Y.
90
5,
0 .. R TSPh
J F (6)
(See
Table
3)
H2S04
shown
that the reduction
readily
carbinols
acids
and co-workers
ther thus
450
Grignard
reagents
compounds
monofluorinated appear
easily
attacked
(4) to give other
the carbonyl
carbinol
efficient
7 (Table
of type
carbinols
to the title materials
sulphuric
acid,
or heat,
1)1.5 SPh
2).
(8) with
proceeded
eq.
of
30
min
reactions
for the formation
The rearrangement
carbinols
of
for
The Grignard-type
phenylthioesters.
to be particularly
group
precursors
quite
of
of these
concentrated readily
(Table
3).
2)sat.NH4CI
R’MgX
O°C
/
F R’
c.
sph
H2S04
HO
SPh
-z
0
e R
(8) R
L
OH
R
NaBH4
+
F
(9)
Preoaration
of
B-fluorinated
As it is well synthetic
tools
fluorinated was
most
[12],and
carbon-carbon
alcohols
(9)
that allylic
alcohols
are useful
so we attempted
phenylthioester
efficient
the allylic
known
allvlic
group.
and it readily
alcohols double
(9) having bond
(Table
the reduction
For this purpose, reduced
a fluorine 4).
of the NaBH4
the thioester atom
carried
to form on the
451
RJ z 2 a, ‘2
0 0
:
a3 m
0 u-l
m m
co -9
d 0 z co QI
z
,”
t
co m
B al3% w 0
2 : ::
4s z
%
0
N
w”
0
N
&
0 L2 b
0
N
w”
ti
N
0
l-4
2 ?-I Q 4
w”
2 2 Tl d
x s !x 9 v-l
2 tn 4 VI
4 v X
H
P p:
f
ki m 2
2
H
P G
ii
P
g
2
E
4
ii
3
9 E 2 vI, 5 z 2 w 0
4 E %
’
:z a
m
a,??!
a
iti
3
3
ii
2
6
ki
2 u)
E
rl
3
z
5 G
?J 4J
iTi& f G vi II)
N
.i
4J
3
cl
s
2
2s
:: kis
?a
5 rd I-
4
2
;3
P
I
m a m m
3
Me
Me
Et
Et
(nc)
(nc)
(nc)
(nc)
8b
8c
8d
8e
8f (nc)
PhCF3
Yields
Me
8a (nc)
a
Et
6b (nc)
as an internal
in parentheses
Me
Me
Me
R
70 (75) 64 80 55 69
B A A A A
Et
Et
Ph
i-Pr
Ph
standard.
on the signal intensities of b Method A : A (130-150°C)
85
A
Et
;
19
(7)
Method
using
48/52
26/74
31/69
39/61
31/69
2/98
(8)
H2S04.
(6) or
2/98
of
E/Z ratio
B : cont.
F NMR signal
(75)
(71)
(95)
(79)
(95)
(82)
(70)
77
Me
H A
(89)
63
(8)
Yielda
B
b
(8) from carbinols
Method
(6) or
82
esters
B
H
R'
thiol
are based
of a,f3_unsaturated
6a (nc)
No.
Product
Preparation
TABLE
453
d-f s c v-l
;;;
X
6
z 5 l-7 E!
L 4 P3-
5 -
E
2
-2
-J m . c-4
I-
. F I c-4 . r-
u-l r . ?
F
I N . b
(d 9 c 2
P
B 6 3 z
m I
z
2 h t J 4 ;;1 2 8 2 !x B E 0-7 m 3 2
a 9 x
I
bh
bh
..
..
la I,
z
In
tr
!x
2 F
Fu -Fr
2 -E
N
m . z
cn . a\ w
c-4 N m
E
. m ID
P-l
bh .. Ln
. 2 In . In IL)
7
ym a
..
mCT 5 a‘ I.4 ‘s 25
II
II
y
bh
tlTT
B ol
a
m
E
4:
cl
II
m
a h-
3
: iz P-l co
4 m
II
II
2.
t9
5L In . z
a
a2 2
bh
..
** a
4J d
k -Er
‘m -r.u
r
cr . c-l m
.
;; w NI
a * 9 J ci i+ v) 0 crh q rlrd a ln 20 2% 2 -WA
d
454
x II
I
7
(9b)
(SC)
i-Pr
Ph
R
'H and "F
TABLE
= 23 Hz, JF_H
= 23 Hz, JF_H
= 23 Hz, JF_H
(Z, t : JF_H
(E, t : JF_H
(Z, t : JF_H
39.8
36.3
37.0
(6 ppm)
(9)
= 3.0 Hz)
= 3.0 Hz)
= 3.0 Hz)
= 2.4 Hz)
shift
= 23 Hz, JF_H
(neat)
Chemical
for RC(CH3)=CFCH20H
(E, t : JF_H
NMR
data
38.7
"F
NMR spectral
(CH2, d)
7.25
(CH2, d), 4.26 4.00
3.09
(CH3, d),
(CH2, d)
4.11
(Ar-H, s)
(OH, br)
(CH, sep)
(CH2, d)
(CH3, d)
3.00
1.96
(CH, d,sep),
4.09
(OH, br),
3.55 2.67
I.60
(CH3, dl,
(in CC141
1.05
'H NMR
456 EXPERIMENTAL
Methyl
trifluorovinyl
ketone
Into a solution
of 4-chloro-3,4,4-trifluoro-2-butanone
(la) (8.03 gr 50 mmol) with
an ice-water
50 mmol).
After
temperature,the temperature.
a dry-ice
in freshly
bath,
was added
the mixture whole
Methyl
was collected
under
acetone
(2a)
dried
diglyme
had been allowed
solution
was stirred
dynamic
in a trap cooled
to a solution
had been
was poured
dried
over
removed. 2-butanone
stirred
(5.51 g, 50 mmol)
with an ice-water
The separated
anhydrous
magnesium gave
sulfate
whole
was stirred
with diethyl anhydrous residue
ether,
magnesium
was added
was distilled
1-buten-3-one
with an ice-water
into water.
After
C/O.6
mmHg.
to a solution
bath.
of
layer
the solvent
in vacuo,giving
The
temperature,and
Oily material
and then the ethereal
in a yield
was
(3a) (7.02 g, 30 mmol)
for 30 min at room
sulfate.
was
(4a)(nc)
(3.03 g, 30 mmol)
was then poured
layer
and then the solvent
4-phenylthio-3,4,4-trifluoro-2-butanone
mixture
temperature,the
organic
of 96 % (11.2 g), bp 78-80
(50 ml) cooled
After
4-phenylthio-3,4,4-trifluoro-
1-Phenylthio-1,2-difluoro-1-buten-3-one
Triethylamine
in
bath.
for 30 min at room
into water.
in a yield
(30 ml)
of 4-chloro-3,4,4,-trifluoro-2-butanone
Distillation
in 2-propanol
85 %)
with
in dichloromethane
and thiophenol
(70 ml) cooled
whole
(5.30 g, yield
(3a)(nc)
(5.06 g, 50 mmol)
(la) (8.03 g, 50 mmol)
the mixture
for 30 min at that
ketone
vacuum
to room
bath.
Triethylamine
dichloromethane
(5.05 g,
to warm
trifluorovinyl
4-Phenylthio-3,4,4-trifluoro-2-butanone
was added
(30 ml) cooled
triethylamine
the
was extracted was dried
over
was removed,the
1-phenylthio-1,2-difluoro-
of 96 % (6.14 g), bp 91-95
C/O.2 mmHg.
457
I-Phenylthio-1,2-difluoro-3-hydroxy-I-butene
Into a suspension ml) cooled
of NaBH4(0.19
with an ice-water
bath,
g, 5 mmol)
(4a)(2.14
was stirred
for lh at that temperature,
with
ether,and solvent
was removed,
I-butene
solution
(yield
and
After
the mixture
the reaction
was extracted
layer was washed
was
with diethyl
with water.
by column
chromatography
of n-hexane-diethyl
(1:l)
ether
using
30 mmol) diethyl
of MeMgI
and magnesium ether
buten-3-one
quenched
with diethyl
the carbinol mixture
was stirred
saturated
over magnesium
NH4Cl ether,
sulfate.
was purified
solution
(4.51 g, yield:
for 30 min,
solution.
After
of conc.H2S04
acid
was
layer was
was removed,
chromatography ether
(IO ml)
and was then
Oily material
the solvent
using
the
(1:l) as an eluent
phenylthio
was added
triethylamine
sulfate.
After
by column
(1.57 g, yield:
the solvent
70 %).
(8a)
(2.44 g, 10 mmol).
(3.0 g, 30 mmol) solution.
the mixture
chromatography
ester
to I-phenylthio-1,2(7a)
to the mixture
of the precipitate,
was purified
dried
ether
and then the ethereal
of n-hexane-diethyl
(30 ml) was added
magnesium
in freshly
98 %).
1 min of stirring,
filtration
(4.26 g,
in dry diethyl
difluoro-3-hydroxy-3-methyl-1-butene
n-hexane
(7a)(nc)
l-phenylthio-1,2-difluoro-l-
by column
2-Fluoro-3-methyl-2-butenoic
One drop
from Me1
(0.8 g, 33 mg-atom)
(4a) (4.28 g, 20 mmol)
with
extracted
prepared
(50 ml), was added
at O-5 C. The mixture
eluent
a
95 %).
Into a solution
After
The
as an eluent
l-Phenylthio-l,2-difluoro-3-hydroxy-3-methyl-l-butene
dried
(IO
I-phenylthio-1,2-difluoro-3-hydroxy-
(5a) was purified
mixture
was added.
IN HCl. Oily material
then the ethereal
and ethanol
1-phenylthio-1,2-difluoro-l-
buten-3-one
quenched
g, 10 mmol)
(5a)(nc)
was dried
was removed, using
in
After over
the product
n-hexane
as an
458 Z-Fluorourenol
(9a)
Into a suspension ethanol
(10 ml) cooled
2-butenoic slowly.
with
acid phenylthio
After
an ice-water
Oily material
and then the ethereal the solvent
2-fluoroprenol
(0.45 g, 12 mmol)
ester
bath,2-fluoro-3-methyl-
(aa)(2.10
g, 10 mmol)
was added
was quenched
with
was extracted
with diethyl
ether
extract
had been
in
the mixture
2h of stirring,
HCl solution.
After
of NaBH4
was dried
removed,
over magnesium
distillation
1N
sulfate.
gave
(9a) (0.37 g, 36 %), bp 69-72OCf48
mmHg.
REFERENCES
1
See for example, Compounds,
2 3
M. Schlosser,
4
R. Sauvetre,
Fluorine
and J.
122.
C. Chuit
and J. F. Normant,
128.
R. Sauvetre,
and J. Villieras, 6
(1975)
D. Masure, (1978)
C. Chuit,
of Organic
(1976).
-34 (1978) 3. J. P. Foulon, D. Masure, R. Sauvetre
Synthesis,
Synthesis, 5
N.Y.,
Tetrahedron,
J. F. Normant, Villieras,
Chemistry
M, Hudlicky,
Wiley,
D. Masure,
J. Chem.
D. Masure,
R. Sauvetre,
Synthesis,
(1976)
Res.,
M. Baudry, (1977)
J. F. Normant
J. F. Normant
104.
and J. Villieras,
761.
7
D. E. Bergstrom,
8
-48 (1983) 1902. N. Ishikawa, A. Takaoka,
Chem.
9
N. Ishikawa,
K. Edamura,
S. Kubota,
Bull.
Sot. Jpn., -54 (1981) 832. N. Ishikawa, A. Takaoka, H. Iwakiri,
S. Kubota,
S. R. F.
10
Kagaruki, 11
H.'Iwakiri,
Chem.
I. L. Knunyants, Dyatkin,
12
M. W. Ng and J. J. Wong,
Lett.,
J. F. Stoddart,
Nauk.
SSSR,
Comprehensive Vol. 1, Pergamon
(1981)
Chem.,
107. Chem.
1107.
R. N. Sterlin,
Izv. Akad.
S. G. Wilkinson,
(1980)
Lett.,
J. Org.
L. N. Pinkina Ser. Khim., Organic Press,
and B. L. (1958)
Chemistry, Oxford,
296. ed. by
1979, p 579.
445-458
445
Received:January 30,1985;accepted: June 17,198s
SYNTHESIS
OF USEFUL
COMPOUNDS
DERIVED
BUILDING
FROM
Yoshimichi
NAKAYAMA,
Department
of Chemical
Technology,
Ookayama,
BLOCKS
FOR MONOFLUORINATED
TRIFLUOROETHENE
Tomoya
KITAZUME
Technology, Meguro-ku,
*
and Nobuo
Tokyo Tokyo
ISHIKAWA*
Institute
152
of
(Japan)
SUMMARY
A synthetic
approach
from the Friedel-Crafts
to monofluorinated
acylhalogenation
give chlorotrifluoroketones These
are converted
monofluorinated reduction
and thence
afford
trifluorovinyl
to phenylthio-adducts
a,&unsaturated
compounds
to
ketones.
and thence
phenylthioesters,
&fluoroallylic
starts
of trifluoroethene
which
by
alcohols.
INTRODUCTION
The chemistry for the purpose the exception
of fluoroolefins
of studying
of lithiation
chlorotrifluoroethene
their
of trifluoroethene
[2], only a few reports
on the synthetic
utility
the wide variety
of monofluorinated
as bioactive Friedel-Crafts Claisen-type
materials.
condensation
We recently
are useful
under
we describe
chlorotrifluoroalkanones which
of fluoroolefins
acylhalogenation
In this paper,
has been developed reactivity
building
have
outlined
focussed
[3-S] of interest
conditions
the conversion
and its 19-101.
of the derived
trifluorovinyl
for valuable
of
a convenient
of trifluoroethene
into alkyl blocks
[2] or
in the preparation
compounds
acidic
mainly
[l]. However,with
ketones
monofluorinated
compounds. 0022-1139/85/$3.30
0 Elsevier Sequoia/Printed in The Netherlands
446 RESULTS
AND DISCUSSION
Our preparation than
that reported
of alkyl by other
(la)
3,4,4-trifluoro-2-butanone diglyme
solution
trifluorovinyl
trifluorovinyl
to produce
The reaction
(2a).
-18 C, and the product
was
under
The material
dynamic
isolated under
vacuum.
done
to react
with a
methyl
proceeded
smoothly
at
by a trap to trap system is stable
for several
ketone
weeks
structure
enough
to be
in the ice-box
in Fig.
was
finally
of the NMR
The assignment
spectroscopy.
as shown
is simpler
4-chloro-
atmosphere.
The trifluorovinyl by NMR
isolated
and can be stored
a nitrogen
ketones Thus,
[9] was allowed
of triethylamine
ketone
[ll].
workers
established
signals
was
I.
Et3N ldiglyme RC(0)CHFCF2CI
>
RC(0)CF=CF2
(1)
(2)
.8ppmi
d. d. q. 22.OHz
9 4ppm(d. d-1
Fig. 1
The 'H and I9 F NMR spectra
In our continuing compounds blocks,
[8-101,
being
nucleophiles.
of
programme
trifluorovinyl
susceptible
(2a)
to synthesise compounds
to attack
monofluorinated
are useful
by a wide variety
building of
447
2-Phenylthio-1,2,2-trifluoroethyl were
prepared
by the Michael
trifluorovinyl but smoothly compounds
ketones produced
made
alkyl
addition in situ.
alkyl
of HF using
the well-established (Table
coupling
constants
PhSHlEt3N zw
RC(0)CF=CF2
(2)
(1)
).
RC(0)CHFCF2SPh
(3)
(3a)
:
R bp
(3b)
:
R bp
R
q
Me
; Y.
96
78-80°C/0.6
= Et
; Y.
9596%/0.7
% mmHg
90
in 93%
P, mmHg
(4a) and
was determined
for difluorovinyl
1).
RC(O)CHFCF$
system.
l-phenylthio-
thus obtained
The E/Z ratio of the products 88% (4b) yield. 19 F NMR, the identification being based on
compounds
vinyl
(4a) and
(4b) were
compounds,
a Et3N/i-PrOH
I-Phenylthio-1,2-difluoro-1-buten-3-one 1,2-difluoro-1-penten-3-one
(3a,3b) to
They are stable
the corresponding
by the elimination
ketones
of thiophenol
by
1
Yields
b
standard.
a
(nc)
(20/80)
(26/74) 81
67
67
("C/mHg)
(97)
using PhCF3 as an internal
II/89
70-73/21
32/68
Bp
(82)
E/Z ratio
IOl-105/0.5
69-72/48
(%ja
(°C/mHg)
91-95/0.2
Bp
(85)
Yield
30/70
27/13
E/Z ratio
in parentheses are determined by "F NMR signal intensities b Isolated by column chromatography.
Ph
i-Pr
9b (nc)
9c
Me
9a
(E/Z ratio)
R
(3)
(8) with NaBH4
98
96
Yield(%)
of RC(O)CHFCF2SPh
of RC(CH3)=CFC(0)SPh
Product No.
Reduction
4
(nc)
4b
TABLE
Me
(nc)
4a
Et
R
Product No.
Dehydrofluorination
TABLE
449
Preparation
of monofluorinated
ohenvlthioesters
(8)
The rearrangement in Scheme [3-61.
of carbinols
1 has been reported
In our building
of compounds to the
(4a) and
formation
a route
compounds,
which
monofluorinated
block
to carboxylic
by J. F. Normant system,we
(4b) with NaBH4
of vinylic
gave monofluorinated providing
a,B-unsaturated
found
proceeded
(5a, 5b). Acid
a,&unsaturated
phenylthioesters
to functionalized
monofluoroorganic
can serve as building
blocks
hydrolysis (6a,6b)
for bioactive
materials.
F
F 0
F
F
R1 Li
+
R,
R2
*d=
rI-
F
OH
R2
F R1 CO2H
-
+ Scheme
R2
1
0
F l)NaBH4/EtOH P
SPh
R
2)lN
SPh
HCI
N4\ F (Sa)
R
= Ms
; Y.
95
%
(5b)
R
= Et
; Y.
90
5,
0 .. R TSPh
J F (6)
(See
Table
3)
H2S04
shown
that the reduction
readily
carbinols
acids
and co-workers
ther thus
450
Grignard
reagents
compounds
monofluorinated appear
easily
attacked
(4) to give other
the carbonyl
carbinol
efficient
7 (Table
of type
carbinols
to the title materials
sulphuric
acid,
or heat,
1)1.5 SPh
2).
(8) with
proceeded
eq.
of
30
min
reactions
for the formation
The rearrangement
carbinols
of
for
The Grignard-type
phenylthioesters.
to be particularly
group
precursors
quite
of
of these
concentrated readily
(Table
3).
2)sat.NH4CI
R’MgX
O°C
/
F R’
c.
sph
H2S04
HO
SPh
-z
0
e R
(8) R
L
OH
R
NaBH4
+
F
(9)
Preoaration
of
B-fluorinated
As it is well synthetic
tools
fluorinated was
most
[12],and
carbon-carbon
alcohols
(9)
that allylic
alcohols
are useful
so we attempted
phenylthioester
efficient
the allylic
known
allvlic
group.
and it readily
alcohols double
(9) having bond
(Table
the reduction
For this purpose, reduced
a fluorine 4).
of the NaBH4
the thioester atom
carried
to form on the
451
RJ z 2 a, ‘2
0 0
:
a3 m
0 u-l
m m
co -9
d 0 z co QI
z
,”
t
co m
B al3% w 0
2 : ::
4s z
%
0
N
w”
0
N
&
0 L2 b
0
N
w”
ti
N
0
l-4
2 ?-I Q 4
w”
2 2 Tl d
x s !x 9 v-l
2 tn 4 VI
4 v X
H
P p:
f
ki m 2
2
H
P G
ii
P
g
2
E
4
ii
3
9 E 2 vI, 5 z 2 w 0
4 E %
’
:z a
m
a,??!
a
iti
3
3
ii
2
6
ki
2 u)
E
rl
3
z
5 G
?J 4J
iTi& f G vi II)
N
.i
4J
3
cl
s
2
2s
:: kis
?a
5 rd I-
4
2
;3
P
I
m a m m
3
Me
Me
Et
Et
(nc)
(nc)
(nc)
(nc)
8b
8c
8d
8e
8f (nc)
PhCF3
Yields
Me
8a (nc)
a
Et
6b (nc)
as an internal
in parentheses
Me
Me
Me
R
70 (75) 64 80 55 69
B A A A A
Et
Et
Ph
i-Pr
Ph
standard.
on the signal intensities of b Method A : A (130-150°C)
85
A
Et
;
19
(7)
Method
using
48/52
26/74
31/69
39/61
31/69
2/98
(8)
H2S04.
(6) or
2/98
of
E/Z ratio
B : cont.
F NMR signal
(75)
(71)
(95)
(79)
(95)
(82)
(70)
77
Me
H A
(89)
63
(8)
Yielda
B
b
(8) from carbinols
Method
(6) or
82
esters
B
H
R'
thiol
are based
of a,f3_unsaturated
6a (nc)
No.
Product
Preparation
TABLE
453
d-f s c v-l
;;;
X
6
z 5 l-7 E!
L 4 P3-
5 -
E
2
-2
-J m . c-4
I-
. F I c-4 . r-
u-l r . ?
F
I N . b
(d 9 c 2
P
B 6 3 z
m I
z
2 h t J 4 ;;1 2 8 2 !x B E 0-7 m 3 2
a 9 x
I
bh
bh
..
..
la I,
z
In
tr
!x
2 F
Fu -Fr
2 -E
N
m . z
cn . a\ w
c-4 N m
E
. m ID
P-l
bh .. Ln
. 2 In . In IL)
7
ym a
..
mCT 5 a‘ I.4 ‘s 25
II
II
y
bh
tlTT
B ol
a
m
E
4:
cl
II
m
a h-
3
: iz P-l co
4 m
II
II
2.
t9
5L In . z
a
a2 2
bh
..
** a
4J d
k -Er
‘m -r.u
r
cr . c-l m
.
;; w NI
a * 9 J ci i+ v) 0 crh q rlrd a ln 20 2% 2 -WA
d
454
x II
I
7
(9b)
(SC)
i-Pr
Ph
R
'H and "F
TABLE
= 23 Hz, JF_H
= 23 Hz, JF_H
= 23 Hz, JF_H
(Z, t : JF_H
(E, t : JF_H
(Z, t : JF_H
39.8
36.3
37.0
(6 ppm)
(9)
= 3.0 Hz)
= 3.0 Hz)
= 3.0 Hz)
= 2.4 Hz)
shift
= 23 Hz, JF_H
(neat)
Chemical
for RC(CH3)=CFCH20H
(E, t : JF_H
NMR
data
38.7
"F
NMR spectral
(CH2, d)
7.25
(CH2, d), 4.26 4.00
3.09
(CH3, d),
(CH2, d)
4.11
(Ar-H, s)
(OH, br)
(CH, sep)
(CH2, d)
(CH3, d)
3.00
1.96
(CH, d,sep),
4.09
(OH, br),
3.55 2.67
I.60
(CH3, dl,
(in CC141
1.05
'H NMR
456 EXPERIMENTAL
Methyl
trifluorovinyl
ketone
Into a solution
of 4-chloro-3,4,4-trifluoro-2-butanone
(la) (8.03 gr 50 mmol) with
an ice-water
50 mmol).
After
temperature,the temperature.
a dry-ice
in freshly
bath,
was added
the mixture whole
Methyl
was collected
under
acetone
(2a)
dried
diglyme
had been allowed
solution
was stirred
dynamic
in a trap cooled
to a solution
had been
was poured
dried
over
removed. 2-butanone
stirred
(5.51 g, 50 mmol)
with an ice-water
The separated
anhydrous
magnesium gave
sulfate
whole
was stirred
with diethyl anhydrous residue
ether,
magnesium
was added
was distilled
1-buten-3-one
with an ice-water
into water.
After
C/O.6
mmHg.
to a solution
bath.
of
layer
the solvent
in vacuo,giving
The
temperature,and
Oily material
and then the ethereal
in a yield
was
(3a) (7.02 g, 30 mmol)
for 30 min at room
sulfate.
was
(4a)(nc)
(3.03 g, 30 mmol)
was then poured
layer
and then the solvent
4-phenylthio-3,4,4-trifluoro-2-butanone
mixture
temperature,the
organic
of 96 % (11.2 g), bp 78-80
(50 ml) cooled
After
4-phenylthio-3,4,4-trifluoro-
1-Phenylthio-1,2-difluoro-1-buten-3-one
Triethylamine
in
bath.
for 30 min at room
into water.
in a yield
(30 ml)
of 4-chloro-3,4,4,-trifluoro-2-butanone
Distillation
in 2-propanol
85 %)
with
in dichloromethane
and thiophenol
(70 ml) cooled
whole
(5.30 g, yield
(3a)(nc)
(5.06 g, 50 mmol)
(la) (8.03 g, 50 mmol)
the mixture
for 30 min at that
ketone
vacuum
to room
bath.
Triethylamine
dichloromethane
(5.05 g,
to warm
trifluorovinyl
4-Phenylthio-3,4,4-trifluoro-2-butanone
was added
(30 ml) cooled
triethylamine
the
was extracted was dried
over
was removed,the
1-phenylthio-1,2-difluoro-
of 96 % (6.14 g), bp 91-95
C/O.2 mmHg.
457
I-Phenylthio-1,2-difluoro-3-hydroxy-I-butene
Into a suspension ml) cooled
of NaBH4(0.19
with an ice-water
bath,
g, 5 mmol)
(4a)(2.14
was stirred
for lh at that temperature,
with
ether,and solvent
was removed,
I-butene
solution
(yield
and
After
the mixture
the reaction
was extracted
layer was washed
was
with diethyl
with water.
by column
chromatography
of n-hexane-diethyl
(1:l)
ether
using
30 mmol) diethyl
of MeMgI
and magnesium ether
buten-3-one
quenched
with diethyl
the carbinol mixture
was stirred
saturated
over magnesium
NH4Cl ether,
sulfate.
was purified
solution
(4.51 g, yield:
for 30 min,
solution.
After
of conc.H2S04
acid
was
layer was
was removed,
chromatography ether
(IO ml)
and was then
Oily material
the solvent
using
the
(1:l) as an eluent
phenylthio
was added
triethylamine
sulfate.
After
by column
(1.57 g, yield:
the solvent
70 %).
(8a)
(2.44 g, 10 mmol).
(3.0 g, 30 mmol) solution.
the mixture
chromatography
ester
to I-phenylthio-1,2(7a)
to the mixture
of the precipitate,
was purified
dried
ether
and then the ethereal
of n-hexane-diethyl
(30 ml) was added
magnesium
in freshly
98 %).
1 min of stirring,
filtration
(4.26 g,
in dry diethyl
difluoro-3-hydroxy-3-methyl-1-butene
n-hexane
(7a)(nc)
l-phenylthio-1,2-difluoro-l-
by column
2-Fluoro-3-methyl-2-butenoic
One drop
from Me1
(0.8 g, 33 mg-atom)
(4a) (4.28 g, 20 mmol)
with
extracted
prepared
(50 ml), was added
at O-5 C. The mixture
eluent
a
95 %).
Into a solution
After
The
as an eluent
l-Phenylthio-l,2-difluoro-3-hydroxy-3-methyl-l-butene
dried
(IO
I-phenylthio-1,2-difluoro-3-hydroxy-
(5a) was purified
mixture
was added.
IN HCl. Oily material
then the ethereal
and ethanol
1-phenylthio-1,2-difluoro-l-
buten-3-one
quenched
g, 10 mmol)
(5a)(nc)
was dried
was removed, using
in
After over
the product
n-hexane
as an
458 Z-Fluorourenol
(9a)
Into a suspension ethanol
(10 ml) cooled
2-butenoic slowly.
with
acid phenylthio
After
an ice-water
Oily material
and then the ethereal the solvent
2-fluoroprenol
(0.45 g, 12 mmol)
ester
bath,2-fluoro-3-methyl-
(aa)(2.10
g, 10 mmol)
was added
was quenched
with
was extracted
with diethyl
ether
extract
had been
in
the mixture
2h of stirring,
HCl solution.
After
of NaBH4
was dried
removed,
over magnesium
distillation
1N
sulfate.
gave
(9a) (0.37 g, 36 %), bp 69-72OCf48
mmHg.
REFERENCES
1
See for example, Compounds,
2 3
M. Schlosser,
4
R. Sauvetre,
Fluorine
and J.
122.
C. Chuit
and J. F. Normant,
128.
R. Sauvetre,
and J. Villieras, 6
(1975)
D. Masure, (1978)
C. Chuit,
of Organic
(1976).
-34 (1978) 3. J. P. Foulon, D. Masure, R. Sauvetre
Synthesis,
Synthesis, 5
N.Y.,
Tetrahedron,
J. F. Normant, Villieras,
Chemistry
M, Hudlicky,
Wiley,
D. Masure,
J. Chem.
D. Masure,
R. Sauvetre,
Synthesis,
(1976)
Res.,
M. Baudry, (1977)
J. F. Normant
J. F. Normant
104.
and J. Villieras,
761.
7
D. E. Bergstrom,
8
-48 (1983) 1902. N. Ishikawa, A. Takaoka,
Chem.
9
N. Ishikawa,
K. Edamura,
S. Kubota,
Bull.
Sot. Jpn., -54 (1981) 832. N. Ishikawa, A. Takaoka, H. Iwakiri,
S. Kubota,
S. R. F.
10
Kagaruki, 11
H.'Iwakiri,
Chem.
I. L. Knunyants, Dyatkin,
12
M. W. Ng and J. J. Wong,
Lett.,
J. F. Stoddart,
Nauk.
SSSR,
Comprehensive Vol. 1, Pergamon
(1981)
Chem.,
107. Chem.
1107.
R. N. Sterlin,
Izv. Akad.
S. G. Wilkinson,
(1980)
Lett.,
J. Org.
L. N. Pinkina Ser. Khim., Organic Press,
and B. L. (1958)
Chemistry, Oxford,
296. ed. by
1979, p 579.