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Reaction of β-phenylthioalkyltitanium reagents with carbonyl compounds
Tetrahedron Letters,Vo1.26,No.43,pp Printed in Great Britain
5313-5316,1985
REACTION OFfl-PHENYLTHIOALKYLTITANIUM
0040-4039/85 $3.00 + .OO 01985 Pergamon Press Ltd.
REAGENTS
WITH CARBONYL COMPOUNDS Takeshi TAKEDA*, Toshio TSUCHIDA, Ichiro NAKAGAWA, Shinji OGAWA, and Tooru FUJIWARA Department of Industrial Chemistry, Faculty of Technology, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184 (3-Phenylthioalkyltitanium reagent prepared by the hydrotitanation of alkenyl sulfide using triethylsilane and titanium tetrachloride is found to react with aromatic aldehyde ord,&unsaturated ketone to give the corresponding r-hydroxyalkyl sulfide or b-phenylthio ketone, respectively. much
Recently,
attention
have
been paid on the synthetic utility of
alkyltitanium reagents because of their stereo and functional group selectivity observed in the reaction with carbonyl compounds 1) . In the fide
(L) with
gave
paper 2) , we showed that the reduction of alkenyl sul-
previous
triethylsilane
in the
&phenylthioalkyltitanium
usual
"&thio
presence
compound
of titanium tetrachloride
(2) which is regarded as an un-
carbanion". This report summarizes the results of the study on
the reaction of the titanium reagent (2) with aldehydes and ketones. First, the
the
titanium
reaction
reagent
2-butene
(1) was
f-hydroxy
sulfide
addition similar were
of
zinc
manner,
performed
of 2 with
aromatic aldehyde was examined.
(2) prepared by the hydrotitanation of
allowed
to react
with
benzaldehyde
at
-78
"C,
the
(2) was produced in 70% yield. Further it was found that bromide the
and
increased
reactions the
the
yield
of the product (2).
In a
of 2 with several substituted benzaldehydes
corresponding adducts (3) were obtained in good to
moderate yields (Eq-1, Table-l).
ArCHO/Zrf3r2 -78”
1 I
When
2-phenylthio-
J
-L
5313
5314
Reaction of the titanium reagents (2)
Table 1.
with aromatic aldehydes. a) Alkenyl Sufide
ArCHO
o-
'_' CHO
b) Yield (%I
Time (h)
7oC)
l-5
77 73 72 78 ____________________~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
SPh l/d%/
a) All
described
ketones.
Ratio
1: 1.1:
fide
'_' CHO
1.5
53
‘_’ o-
CHO
1
47=)
" Q-
CHO
1
55
the reactions were carried out by a similar procedure
to that
1.1:
for
the
reaction
of l_/ Et3SiH/
withd,@unsaturated
TiC14/
ZnBr2/
ArCHO
=
b) All the products were identified
1.2: 1.2.
by IR and NMR spectra.
hyde
o-
c) In the absence of ZnBr2.
On the other hand, unsuccessful result was obtained when aliphatic aldeor aromatic ketone was employed. In such a case, unreacted alkyl sulwas
alkenyl
isolated sulfide.
as a major product along with a small amount of starting It was also confirmed that aliphatic ketone was unreactive
in the reaction of 2 under a similar reaction conditions.
RITRz +R3-dR4 CHC~
TiCL,
2
2 2
R4
(eq-2)
5315
Reaction of the titanium reagents (2)
Table 2.
with d&unsaturated Alkenyl Sulfide
R3
SPh
R4
ketones
Temp (OC1
Time
Yieldb)
(h)
(%I
Ph
CH3
-78
2
76')
H
CH3
-48
4
52 (10)')
CH3
CH3(CH2J7
-48
4
63')
-18
3
72')
-(CH2j3-
,‘”
;;’3
-48 -78
4 3
32 7oc)(31)')
CH3
CH3KH2),
-48
4
66c)
Ph
Ph
-78
3.5
77c) 45 (2l)d)
3
SPh Ott &p';l al All text,
reactions
:
70
-KH2j3-
-78
5
62')
-KH2j3-
-78
4
64c)
CH3
-48
4
48 (25)')
CH3(CH2)7
-48
4
53c)
CH3 were
performed with a same procedure as described in the
unless otherwise noted.
spectra. 5.
I::
H
E::,,,,,,
c) 1.05
equiv
b) All products were identified by IR and NMR of d,&unsaturated ketone were used. a) Yield of
e) Alkenyl sulfide was treated with Et3SiH/TiC14 for 1 h.
5316
Next, titanium the
d,@-unsaturated reagent
Michael
(2).
adduct
ketone
was subjected to the reaction with the
In contrast to the above result, it was found that
(4) was produced in good yield.
The selectivity of the
present reaction is excellent and the formation of 1,2-adduct was not observed (Eq-2). The
typical
d,(3-unsaturated ethylsilane mmol)
was
at -78
experimental ketone
(128 mg, added
'C and
is as follows; to a CH2C12 (4 ml) solution of tri1.1
mmol)
a CH2C12
the
procedure for the Michael reaction of 2 with and
solution
reaction
1-(phenylthio)cyclohexene of titanium
mixture
was
(191 mg, 1
tetrachloride (1.1 mm011
stirred
for 30 min. A CH2C12 (1
ml)
solution
of 2-dodecen-4-one (273 mg, 1.5 mmol) was added to the result-
ing
deep
solution
red
reaction same
mixture
temperature,
organic over
material
graphed
on
silica
warmed
the was
After
Na2S04.
of the
was
alkyltitanium reagent (2) at -78 'C and the up to -48 'C.
reaction
was
extracted
with
evaporation gel
After stirring for 4 h at the
quenched CH2C12
by addition of water. and
the
extract
The
was dried
of the solvent, the residue was chromato-
(AcOEt-hexane)
and 2-[2-(phenylthio)cyclohexyll-4-
dodecanone (4) (262 mg) was isolated in 70% yield. As
shown
thesized When
in good
methyl
amount 5 was
2, the various &-phenylthio
in Table vinyl
yields
apparently
by way offi-phenylthioalkyltitanium
ketone
of 1,5-diketone due
ketones (Q) can be syn-
was
employed
(5) was isolated as a by-product. to the
further
reagents (2).
as an acceptor, the considerable reaction
of the
The formation of initially formed
titanium enolate with methyl vinyl ketone. Further
study
on
the reaction of alkyltitanium compound (2) is now in
progress. References 1) M. T. Reetz, Top. Curr. Chem., 106, 1 (1982); B. Weidman and D. Seebach, Angew. Chem., 95, 12 (1983). 2) T. Takeda, T. Tsuchida, and T. Fujiwara, Chem. Lett., 1984, 1219. (Received in Japan 1 August 1985)
5313-5316,1985
REACTION OFfl-PHENYLTHIOALKYLTITANIUM
0040-4039/85 $3.00 + .OO 01985 Pergamon Press Ltd.
REAGENTS
WITH CARBONYL COMPOUNDS Takeshi TAKEDA*, Toshio TSUCHIDA, Ichiro NAKAGAWA, Shinji OGAWA, and Tooru FUJIWARA Department of Industrial Chemistry, Faculty of Technology, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184 (3-Phenylthioalkyltitanium reagent prepared by the hydrotitanation of alkenyl sulfide using triethylsilane and titanium tetrachloride is found to react with aromatic aldehyde ord,&unsaturated ketone to give the corresponding r-hydroxyalkyl sulfide or b-phenylthio ketone, respectively. much
Recently,
attention
have
been paid on the synthetic utility of
alkyltitanium reagents because of their stereo and functional group selectivity observed in the reaction with carbonyl compounds 1) . In the fide
(L) with
gave
paper 2) , we showed that the reduction of alkenyl sul-
previous
triethylsilane
in the
&phenylthioalkyltitanium
usual
"&thio
presence
compound
of titanium tetrachloride
(2) which is regarded as an un-
carbanion". This report summarizes the results of the study on
the reaction of the titanium reagent (2) with aldehydes and ketones. First, the
the
titanium
reaction
reagent
2-butene
(1) was
f-hydroxy
sulfide
addition similar were
of
zinc
manner,
performed
of 2 with
aromatic aldehyde was examined.
(2) prepared by the hydrotitanation of
allowed
to react
with
benzaldehyde
at
-78
"C,
the
(2) was produced in 70% yield. Further it was found that bromide the
and
increased
reactions the
the
yield
of the product (2).
In a
of 2 with several substituted benzaldehydes
corresponding adducts (3) were obtained in good to
moderate yields (Eq-1, Table-l).
ArCHO/Zrf3r2 -78”
1 I
When
2-phenylthio-
J
-L
5313
5314
Reaction of the titanium reagents (2)
Table 1.
with aromatic aldehydes. a) Alkenyl Sufide
ArCHO
o-
'_' CHO
b) Yield (%I
Time (h)
7oC)
l-5
77 73 72 78 ____________________~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
SPh l/d%/
a) All
described
ketones.
Ratio
1: 1.1:
fide
'_' CHO
1.5
53
‘_’ o-
CHO
1
47=)
" Q-
CHO
1
55
the reactions were carried out by a similar procedure
to that
1.1:
for
the
reaction
of l_/ Et3SiH/
withd,@unsaturated
TiC14/
ZnBr2/
ArCHO
=
b) All the products were identified
1.2: 1.2.
by IR and NMR spectra.
hyde
o-
c) In the absence of ZnBr2.
On the other hand, unsuccessful result was obtained when aliphatic aldeor aromatic ketone was employed. In such a case, unreacted alkyl sulwas
alkenyl
isolated sulfide.
as a major product along with a small amount of starting It was also confirmed that aliphatic ketone was unreactive
in the reaction of 2 under a similar reaction conditions.
RITRz +R3-dR4 CHC~
TiCL,
2
2 2
R4
(eq-2)
5315
Reaction of the titanium reagents (2)
Table 2.
with d&unsaturated Alkenyl Sulfide
R3
SPh
R4
ketones
Temp (OC1
Time
Yieldb)
(h)
(%I
Ph
CH3
-78
2
76')
H
CH3
-48
4
52 (10)')
CH3
CH3(CH2J7
-48
4
63')
-18
3
72')
-(CH2j3-
,‘”
;;’3
-48 -78
4 3
32 7oc)(31)')
CH3
CH3KH2),
-48
4
66c)
Ph
Ph
-78
3.5
77c) 45 (2l)d)
3
SPh Ott &p';l al All text,
reactions
:
70
-KH2j3-
-78
5
62')
-KH2j3-
-78
4
64c)
CH3
-48
4
48 (25)')
CH3(CH2)7
-48
4
53c)
CH3 were
performed with a same procedure as described in the
unless otherwise noted.
spectra. 5.
I::
H
E::,,,,,,
c) 1.05
equiv
b) All products were identified by IR and NMR of d,&unsaturated ketone were used. a) Yield of
e) Alkenyl sulfide was treated with Et3SiH/TiC14 for 1 h.
5316
Next, titanium the
d,@-unsaturated reagent
Michael
(2).
adduct
ketone
was subjected to the reaction with the
In contrast to the above result, it was found that
(4) was produced in good yield.
The selectivity of the
present reaction is excellent and the formation of 1,2-adduct was not observed (Eq-2). The
typical
d,(3-unsaturated ethylsilane mmol)
was
at -78
experimental ketone
(128 mg, added
'C and
is as follows; to a CH2C12 (4 ml) solution of tri1.1
mmol)
a CH2C12
the
procedure for the Michael reaction of 2 with and
solution
reaction
1-(phenylthio)cyclohexene of titanium
mixture
was
(191 mg, 1
tetrachloride (1.1 mm011
stirred
for 30 min. A CH2C12 (1
ml)
solution
of 2-dodecen-4-one (273 mg, 1.5 mmol) was added to the result-
ing
deep
solution
red
reaction same
mixture
temperature,
organic over
material
graphed
on
silica
warmed
the was
After
Na2S04.
of the
was
alkyltitanium reagent (2) at -78 'C and the up to -48 'C.
reaction
was
extracted
with
evaporation gel
After stirring for 4 h at the
quenched CH2C12
by addition of water. and
the
extract
The
was dried
of the solvent, the residue was chromato-
(AcOEt-hexane)
and 2-[2-(phenylthio)cyclohexyll-4-
dodecanone (4) (262 mg) was isolated in 70% yield. As
shown
thesized When
in good
methyl
amount 5 was
2, the various &-phenylthio
in Table vinyl
yields
apparently
by way offi-phenylthioalkyltitanium
ketone
of 1,5-diketone due
ketones (Q) can be syn-
was
employed
(5) was isolated as a by-product. to the
further
reagents (2).
as an acceptor, the considerable reaction
of the
The formation of initially formed
titanium enolate with methyl vinyl ketone. Further
study
on
the reaction of alkyltitanium compound (2) is now in
progress. References 1) M. T. Reetz, Top. Curr. Chem., 106, 1 (1982); B. Weidman and D. Seebach, Angew. Chem., 95, 12 (1983). 2) T. Takeda, T. Tsuchida, and T. Fujiwara, Chem. Lett., 1984, 1219. (Received in Japan 1 August 1985)