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Condensation of enol silyl ethers and dialkoxymethanes catalyzed by trimethylsilyl trifluoromethanesulfonate. Regiospecific synthesis of α-alkoxymethyl ketones
Tetrafiedron
Letters Vol. 21, pp 2527 - 2528 OPergamon Pm88 Ltd. 1980. Printed in Great
CONDENSATION
OF
TRIMETHYLSILYL
ENOL
SILYL
ETHERS
Britain
AND
DIALKOXYMETHANES
TRIFLUOROMETHANESULFONATE.
REGIOSPECWlC
a-ALKOXYMETHYL
S. Murata, Department
Summary:
A facile,
Recently ethers
Nagoya
regiospecific
catalyzed
however,
erythro-selective
OF
Chikusa,
Nagoya
464, Japan
ketones is. described.
aldol type condensation
trifluoromethanesulfonate
of enol silyl
(TMSOTf,
l).’
Un-
the original
procedure for this reaction could not utilize simple di3 substrates. Described herein is a modified recipe which allows
~~~ox~eth~e~
as acetal
facile
of mono-cu-alkoxymethyl
synthesis
SYNTHEZW
and R, Noyori
University,
by trimethylsilyl
BY
KETONES1
entry to ~-alkox~ethyl
we found an efficient,
and acetals
fortunately,
of Chemistry,
M. Suzuki,
CATALYZED
ketones.
0 cat.
OR4
TMSOTf
CH2(OR4)2 -(CH,),SiOR4 III If
IV
The condensation dlchloromethane nitrogen procedure
of enol silyl
containing
ethers
catalytic
(II) and dialkoxymethanes
amounts (5 -10
base such as 2,6-di-t_ybutylpyridine is illustrated
siloxycyclopentene dichloromethane
(7 mL)
solution
mL,
of I(2.2
3.1 mmol)
and V (63 mg,
at 12 “C.
10 h and quenched by addition of saturated
an oil (480 mg,
76% yield),
mixture
were
(VI).
was stirred
aqueous NaHC03
I-Trimethyldissolved
in dry
solution
at this temperature (5 mL).
by column chromatography
as eluant) afforded
&&-active
on silica
the desired benzyloxymethyl 4 bp 140 “C (bath temp) at 0.3 mmHg.
2527
The typical
To this was added 0.15 M dichloromethane
The mixture
(10 mL x 3) followed
ether/ether
0.33 mmol)
in
hindered
of 2-benzylox~ethylcyclopent~one.
under argon atmosphere.
0.33 mmol)
up with dichloromethane 3:1 petroleum
(VI or dicycLohexylmethylamine
by the preparation
(561 mg,
(III) was conducted
mol 70) of I and a sterieally
for work-
gel (15 g, ketones
as
2528
Table I.
Condensation of Enol Sityl Ethers and Di~kox~ethanes
enol silyl ether, Rl
R2
II
I
R3
d~alkox~ethane,
III
in Dichloromethane
conditions -
I, mol %
basea temp,
OC
% yield time,
h
of I&
(CH2j3
H
CH2~OCH2CSH&
10
V
12
10
76
fCH21,
H
C~~{~~~C6H~~~
10
VI
12
100
65
(CH2)4
H
CH2(OCH2C6H5)2
10
V
1X
12
87
(CH2)4
H
CH2(OCH3)2
5
V
16
10
48%
H-d
CH~~~H~~~H~}~
10
V
14
12
7g
CH2(OCH2CgH5)2
7
V
17
12
92
CH2(OCH2C&&
7
V
18
12
77
CH~CH~C~~)~ C6H5
H
H
C6H5
H
CH3
b - Isolated yield.
5 Ratio of I to base was 1:l.
NMR spectra as well as elemental analysis. fi 6-bethel-1
20% yield.
Some examples
All products were identified by IR and lH
5 Cyclohexanone dimethyl acetal was obtained in e A mixture of cis and trans isomers,
-t~methylsilox~yclo~exen~.
are given in Table I,
Thus this procedure offers a method for the
controlled, re~os~c~fi~ i~roduction of a single alkox~ethyl sub~i~ent to the Q position of 5 Henzyl protective group in the products is readily removed by catalytic ketones . hydrogenolysis.
For instance,
when a mixture of 2-benzyloxymethylcyclopentanone
and 5%
Pd/C catalyst in 15:l ethanol~acetic acid was stirred at 1% “C for 10 hunder atmosp~ri~ pressure
of hydrogen,
2-hydroxymethylcyclopentanone
was obtained in 97% yield.
methyl and alkoxymethyl ketones are masked forms of Lu-methylene ketones, 5a, 6 synthetic intermediates,
REFERFNCES 1, Tri~~ylsilyl Noyori,
Triflates
Tetrahedron
2. S. Murata,
M. Suzuki, and R. Noyori,
4.43
and M, Sasaki,
Tetrahedron
6. C. Stork and M. Isobe,
Part VI: T. Tsunoda,
M, Suzuki, and R.
Chem.
Lett,,
993,
J. Am.
Chem.
(Received in Japan 7 March 1980)
Sot.,
Soco, 91,
3.5% (d, 2, g=
(s, 5, C6H5). see (a) T.
Shono, I. Nis~~c~,
T.
_101, 984 (1979); (b) I, Paterson and I.
995 (1979).
Chem.
in press.
(m, 7, CH and CH2),
via enol silyl ethers,
J. Am.
Sot.,
of both enol silyl ethers and acetals.
(a, 2, C6H5C_Hz), 7.23
5. For related he~erometh~ations
Fleming,
J. Am.
(C=O); NMR (CC14) 6 1,6--2.5
Hz, C6H5CH20CI122’,
Komamura,
VII.
in press.
3. Attempted reaction resulted in recovery 4. IR (neat) 1738 cm-l
AND NOTES
in Organic Synthesis. Lett,,
Hydroxy-
well-known useful
6260 (1975).
3.5
Letters Vol. 21, pp 2527 - 2528 OPergamon Pm88 Ltd. 1980. Printed in Great
CONDENSATION
OF
TRIMETHYLSILYL
ENOL
SILYL
ETHERS
Britain
AND
DIALKOXYMETHANES
TRIFLUOROMETHANESULFONATE.
REGIOSPECWlC
a-ALKOXYMETHYL
S. Murata, Department
Summary:
A facile,
Recently ethers
Nagoya
regiospecific
catalyzed
however,
erythro-selective
OF
Chikusa,
Nagoya
464, Japan
ketones is. described.
aldol type condensation
trifluoromethanesulfonate
of enol silyl
(TMSOTf,
l).’
Un-
the original
procedure for this reaction could not utilize simple di3 substrates. Described herein is a modified recipe which allows
~~~ox~eth~e~
as acetal
facile
of mono-cu-alkoxymethyl
synthesis
SYNTHEZW
and R, Noyori
University,
by trimethylsilyl
BY
KETONES1
entry to ~-alkox~ethyl
we found an efficient,
and acetals
fortunately,
of Chemistry,
M. Suzuki,
CATALYZED
ketones.
0 cat.
OR4
TMSOTf
CH2(OR4)2 -(CH,),SiOR4 III If
IV
The condensation dlchloromethane nitrogen procedure
of enol silyl
containing
ethers
catalytic
(II) and dialkoxymethanes
amounts (5 -10
base such as 2,6-di-t_ybutylpyridine is illustrated
siloxycyclopentene dichloromethane
(7 mL)
solution
mL,
of I(2.2
3.1 mmol)
and V (63 mg,
at 12 “C.
10 h and quenched by addition of saturated
an oil (480 mg,
76% yield),
mixture
were
(VI).
was stirred
aqueous NaHC03
I-Trimethyldissolved
in dry
solution
at this temperature (5 mL).
by column chromatography
as eluant) afforded
&&-active
on silica
the desired benzyloxymethyl 4 bp 140 “C (bath temp) at 0.3 mmHg.
2527
The typical
To this was added 0.15 M dichloromethane
The mixture
(10 mL x 3) followed
ether/ether
0.33 mmol)
in
hindered
of 2-benzylox~ethylcyclopent~one.
under argon atmosphere.
0.33 mmol)
up with dichloromethane 3:1 petroleum
(VI or dicycLohexylmethylamine
by the preparation
(561 mg,
(III) was conducted
mol 70) of I and a sterieally
for work-
gel (15 g, ketones
as
2528
Table I.
Condensation of Enol Sityl Ethers and Di~kox~ethanes
enol silyl ether, Rl
R2
II
I
R3
d~alkox~ethane,
III
in Dichloromethane
conditions -
I, mol %
basea temp,
OC
% yield time,
h
of I&
(CH2j3
H
CH2~OCH2CSH&
10
V
12
10
76
fCH21,
H
C~~{~~~C6H~~~
10
VI
12
100
65
(CH2)4
H
CH2(OCH2C6H5)2
10
V
1X
12
87
(CH2)4
H
CH2(OCH3)2
5
V
16
10
48%
H-d
CH~~~H~~~H~}~
10
V
14
12
7g
CH2(OCH2CgH5)2
7
V
17
12
92
CH2(OCH2C&&
7
V
18
12
77
CH~CH~C~~)~ C6H5
H
H
C6H5
H
CH3
b - Isolated yield.
5 Ratio of I to base was 1:l.
NMR spectra as well as elemental analysis. fi 6-bethel-1
20% yield.
Some examples
All products were identified by IR and lH
5 Cyclohexanone dimethyl acetal was obtained in e A mixture of cis and trans isomers,
-t~methylsilox~yclo~exen~.
are given in Table I,
Thus this procedure offers a method for the
controlled, re~os~c~fi~ i~roduction of a single alkox~ethyl sub~i~ent to the Q position of 5 Henzyl protective group in the products is readily removed by catalytic ketones . hydrogenolysis.
For instance,
when a mixture of 2-benzyloxymethylcyclopentanone
and 5%
Pd/C catalyst in 15:l ethanol~acetic acid was stirred at 1% “C for 10 hunder atmosp~ri~ pressure
of hydrogen,
2-hydroxymethylcyclopentanone
was obtained in 97% yield.
methyl and alkoxymethyl ketones are masked forms of Lu-methylene ketones, 5a, 6 synthetic intermediates,
REFERFNCES 1, Tri~~ylsilyl Noyori,
Triflates
Tetrahedron
2. S. Murata,
M. Suzuki, and R. Noyori,
4.43
and M, Sasaki,
Tetrahedron
6. C. Stork and M. Isobe,
Part VI: T. Tsunoda,
M, Suzuki, and R.
Chem.
Lett,,
993,
J. Am.
Chem.
(Received in Japan 7 March 1980)
Sot.,
Soco, 91,
3.5% (d, 2, g=
(s, 5, C6H5). see (a) T.
Shono, I. Nis~~c~,
T.
_101, 984 (1979); (b) I, Paterson and I.
995 (1979).
Chem.
in press.
(m, 7, CH and CH2),
via enol silyl ethers,
J. Am.
Sot.,
of both enol silyl ethers and acetals.
(a, 2, C6H5C_Hz), 7.23
5. For related he~erometh~ations
Fleming,
J. Am.
(C=O); NMR (CC14) 6 1,6--2.5
Hz, C6H5CH20CI122’,
Komamura,
VII.
in press.
3. Attempted reaction resulted in recovery 4. IR (neat) 1738 cm-l
AND NOTES
in Organic Synthesis. Lett,,
Hydroxy-
well-known useful
6260 (1975).
3.5