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Reactions of (α,α-disubstituted-phenacyl) and (carbethoxy-disubstituted-methyl)triphenylphosphonium halides with grignard reagents
Tetrahedron Letters No.1, pp. 23-24, 1969. Pergamon Press.
REACTIONS
0P (d,d-DISHBSTITUTED-PHENACYL)
METHYL)TRIPHENYLPHOSPHONIUM Teruaki Mukaiyama, Laboratory
HALIDES
Ryuichiro
of Organic
Printed in Great Britain.
AND (cARBETHoXY-DISUBSTITCTBD-
WITH GRIGNARD
REAGENTS
Yoda and Isao Kuwajima
Chemistry,
Tokyo Institute
of Technology
(Received in Japan 25 October 1968; received in UK for publication19 November 1968)
It was found that various ketones were obtained by the reaction disubstituted-phenacyljtriphenylphosphonium Thus,
isobutyrophenone
obtained
halides
(57$), triphenylphosphine
by the reaction
between
and 2-phenyl
acid.
propiophenone
(66s) and diphenyl
2 moles of phenylmagnesium
bromide
iodide 1) , with subsequent
(d,d.-dimethylphenacyl)triphenylphosphonium with dilute hydrochloric
In a similar way, cyclohexyl
reagents.
(65%) were and 1 mole of treatment
phenyl ketone(45$)
(49%) were formed from the corresponding
substituted-phenacyl)triphenylphosphonium
of (o
(I) with Grignard
iodides and Grignard
(d.,d-di-
reagents.
+ R' 8 -Y
-
ii'+
R&X2 -MgX1X2
(I) R&ZX2
(C6H5)3P
l
+ R 3-R3 + [
$f??2J
(Y=C6H5)
(III) The reaction the nucleophilic
probably
proceeds
through the intermediate
attack of R- derived
from Grignard
reagent
(II), produced by on the phosphorus
atom of the (d,d-disubstituted-phenacyl)triphenylphosphonium nucleophilic
attack
of another Grignard
triphenylphosphine, converted
the reaction
including
symmetrical
by replacing
formate.
or bialkyl
and unsymmetrical benzoyl
chloride
(III), which
is
to the synthesis
dialkyl ketones,
of various
ketones
and also alkyl aryl
in the above reaction
by ethyl chloro-
Isopropylidenetriphenylphosphorane
prepared _in situ in tetrahydroamount of ethyl chloroformate and the mixture
to stand for a few hours.
then added, and the mixture homogeneous
brown
solution.
heated
Three moles of n-propylmagnesium to reflux
(58%) and triphenylphosphine n-hexyl-,isopropyl cyclohexyl
bromide was
for about 5 hours to obtain a
The product mixture was treated with dilute hydro-
chloric acid and the organic layer distilled
listed
The (II) yields
(eq 1).
was further extended
furan was mixed with an equimolar allowed
and the intermediate
to the ketone upon hydrolysis
Next, ketones
biaryl
halide.
reagent on the intermediate
to obtain isopropyl n-propyl
(549'). By this method,
cyclohexyl-,
ethyl cyclohexyl-,
ketones were synthesizea
n-propyl
on fairly good yieids.
in TABLE I. 23
ketone
isopropyl n-butyl-, isopropyl cyclohexyl-and
n-hexyl
These results are
TABLE I REACTIONS OF (~,~(-DISIJBSTITDTED-PHENACYI)TRIPHENYDPH~SPH~NIUM IODIDBS (I;~'=I,
Y=c6H5)
mD (CARBETH~XY-DISUBSTITUTED-METHYL)TRIPHENYLPHOSPH~NIUMCHLORIDES (I;X1=c1,Y=OC2H5) WITH GRIGNARD REAGENTS \ Yield, Mp of the 2,4dinitrophenyl- (C,H5)3P R 4 -R3 Bp, "c/mmHg hy drazone, “C Ketone
R' R2 4 x'=I,Y=C6H5 CH3
CH3
R3MgX2
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
-CH2-(CH2)3-ZH2-CH2-(CH2j3-CH2-CH2-(CH2)3-CH2-
93-96) **
49
-CH2-(CH2)3-CH2-
3
62/2
57
CH3
CH3 CgH5 x'=Cl,Y=OC2H5 CH
Yield,* z
n-C3H7MgBr n-C4H9MgBr g6,,,gBr
0
66
161 161
63
65 -
45 49
195 - 196 150 -151
43
48
106 -107/1
40
59
56
130/760
94 - 97
54
oil oil
53
-
40
48
46
60
161
65
146 - 149 107 - 110 oil
67 41
44 -
45
31
53
63/I 4
45
77/a
70
83/g 96-l
65
146 -
00/l
0
C6H5MgBr C2H5MgBr n-C3H7MgBr
62
76/J 1
47
97/l
n-C6H13MgBr
45
80/l
1
149
* Total yield from alkyltriphenylphosphonium halides used for preparation of the corresponding alkylidenetriphenylphosphoranes. **Isolated by column chromatography. These reactions would proceed through the intermediate (III) and (IV) as sketched below (eq 2). R-' (III) + R &x2 -Mgx2Y
,0Mgx2
R&=c\B3
1 (
Y=OC2H5)
(2)
(IV) This method as described thus represents a simple and versatile method for the preparation of various ketones. Reference 1.
H. J. Bestmann and B. Arnason, Chem. Ber. 2, -
1513 (1962).
REACTIONS
0P (d,d-DISHBSTITUTED-PHENACYL)
METHYL)TRIPHENYLPHOSPHONIUM Teruaki Mukaiyama, Laboratory
HALIDES
Ryuichiro
of Organic
Printed in Great Britain.
AND (cARBETHoXY-DISUBSTITCTBD-
WITH GRIGNARD
REAGENTS
Yoda and Isao Kuwajima
Chemistry,
Tokyo Institute
of Technology
(Received in Japan 25 October 1968; received in UK for publication19 November 1968)
It was found that various ketones were obtained by the reaction disubstituted-phenacyljtriphenylphosphonium Thus,
isobutyrophenone
obtained
halides
(57$), triphenylphosphine
by the reaction
between
and 2-phenyl
acid.
propiophenone
(66s) and diphenyl
2 moles of phenylmagnesium
bromide
iodide 1) , with subsequent
(d,d.-dimethylphenacyl)triphenylphosphonium with dilute hydrochloric
In a similar way, cyclohexyl
reagents.
(65%) were and 1 mole of treatment
phenyl ketone(45$)
(49%) were formed from the corresponding
substituted-phenacyl)triphenylphosphonium
of (o
(I) with Grignard
iodides and Grignard
(d.,d-di-
reagents.
+ R' 8 -Y
-
ii'+
R&X2 -MgX1X2
(I) R&ZX2
(C6H5)3P
l
+ R 3-R3 + [
$f??2J
(Y=C6H5)
(III) The reaction the nucleophilic
probably
proceeds
through the intermediate
attack of R- derived
from Grignard
reagent
(II), produced by on the phosphorus
atom of the (d,d-disubstituted-phenacyl)triphenylphosphonium nucleophilic
attack
of another Grignard
triphenylphosphine, converted
the reaction
including
symmetrical
by replacing
formate.
or bialkyl
and unsymmetrical benzoyl
chloride
(III), which
is
to the synthesis
dialkyl ketones,
of various
ketones
and also alkyl aryl
in the above reaction
by ethyl chloro-
Isopropylidenetriphenylphosphorane
prepared _in situ in tetrahydroamount of ethyl chloroformate and the mixture
to stand for a few hours.
then added, and the mixture homogeneous
brown
solution.
heated
Three moles of n-propylmagnesium to reflux
(58%) and triphenylphosphine n-hexyl-,isopropyl cyclohexyl
bromide was
for about 5 hours to obtain a
The product mixture was treated with dilute hydro-
chloric acid and the organic layer distilled
listed
The (II) yields
(eq 1).
was further extended
furan was mixed with an equimolar allowed
and the intermediate
to the ketone upon hydrolysis
Next, ketones
biaryl
halide.
reagent on the intermediate
to obtain isopropyl n-propyl
(549'). By this method,
cyclohexyl-,
ethyl cyclohexyl-,
ketones were synthesizea
n-propyl
on fairly good yieids.
in TABLE I. 23
ketone
isopropyl n-butyl-, isopropyl cyclohexyl-and
n-hexyl
These results are
TABLE I REACTIONS OF (~,~(-DISIJBSTITDTED-PHENACYI)TRIPHENYDPH~SPH~NIUM IODIDBS (I;~'=I,
Y=c6H5)
mD (CARBETH~XY-DISUBSTITUTED-METHYL)TRIPHENYLPHOSPH~NIUMCHLORIDES (I;X1=c1,Y=OC2H5) WITH GRIGNARD REAGENTS \ Yield, Mp of the 2,4dinitrophenyl- (C,H5)3P R 4 -R3 Bp, "c/mmHg hy drazone, “C Ketone
R' R2 4 x'=I,Y=C6H5 CH3
CH3
R3MgX2
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
-CH2-(CH2)3-ZH2-CH2-(CH2j3-CH2-CH2-(CH2)3-CH2-
93-96) **
49
-CH2-(CH2)3-CH2-
3
62/2
57
CH3
CH3 CgH5 x'=Cl,Y=OC2H5 CH
Yield,* z
n-C3H7MgBr n-C4H9MgBr g6,,,gBr
0
66
161 161
63
65 -
45 49
195 - 196 150 -151
43
48
106 -107/1
40
59
56
130/760
94 - 97
54
oil oil
53
-
40
48
46
60
161
65
146 - 149 107 - 110 oil
67 41
44 -
45
31
53
63/I 4
45
77/a
70
83/g 96-l
65
146 -
00/l
0
C6H5MgBr C2H5MgBr n-C3H7MgBr
62
76/J 1
47
97/l
n-C6H13MgBr
45
80/l
1
149
* Total yield from alkyltriphenylphosphonium halides used for preparation of the corresponding alkylidenetriphenylphosphoranes. **Isolated by column chromatography. These reactions would proceed through the intermediate (III) and (IV) as sketched below (eq 2). R-' (III) + R &x2 -Mgx2Y
,0Mgx2
R&=c\B3
1 (
Y=OC2H5)
(2)
(IV) This method as described thus represents a simple and versatile method for the preparation of various ketones. Reference 1.
H. J. Bestmann and B. Arnason, Chem. Ber. 2, -
1513 (1962).