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A versatile method of synthesis of anilines and cyclohexenones
Tetrahedron Letters,Vol.28,No.4,pp Printed in Great Britain
A VERSATILE
397-400,1987
METHOD OF SYNTHESIS
Edmond Differding,
oo40-4039/87 $3.00 + .oo Pergamon Journals Ltd.
OF ANILINES
Oscar Vandevelde,
AND CYCLOHEXENONES
Bertrand
Roekens,
Tran Trieu Van and Leon Ghosez*
Laboratoire Universite
de Chimie Organique
Catholique
de Louvain,
Place L. Pasteur,
B-1348 LOUVAIN-LA-NEUVE,
Sumnary
: Allylic
alkenyl
ketenimines
cyanides
We
have
previously
of carbazoles
route
toward
reactions
polysubstituted
N-silylated
report4,
we found
presence
of lithium
dienophiles
with complete
on
capacity
the
with
olefinic
with
anilines
which
of
vinyl
important
give
by desilylation
ketenimines offer
synthetic
react
as
approach
convergent
of a vinyl
offered
to
a versatile
a highly
reaction
potentially
are
followed
to
regioselectivity.
dienophiles
Diels-Alder
an acetylene
chloride
synthesis
ketenimine3.
a convergent
The
synthetic
intermediates.
We now
of this goal.
alkenyl
since they
triisopropylsilyl
anilines
an intramolecular
ketenimine
report the realization
purpose
by
1
BELGIUM
132. More recently we have also described
involving
of a vinyl
reported
Their
silylated
of _1 with acetylenic
of substituted
dienes'.
toward cyclohexenones
reaction
readily
_1. The reaction
leads to the formation
nucleophilic
are
de Synthese,
ketenimines
are potential
that the reaction diisopropylamide
(Scheme 11. The use of a bulkier
appeared
precursors
to be the
of primary
of ally1 cyanide yielded
silylating
most
anilines.
appropriate
with t-butyldimethyl
a mixture
of vinyl
reagents
In contrast
ketenimine
agent such as triisopropyl
chlorosilano
CN
LDA-THF , -78’C
2
RzR4SiCl
c
1:
R’=
R *= H ,
b:
R’=
R*= H
t:
R’=
Ph ,
_d:
R’= H ,
R3 = Me
,
R4= t-Bu
R*= H , R*=
Me,
+
2
46%
23 %
77%
Cl %
R3 = R4 = i-pr
70%
0%
R3=
81%
0 %
, R3= R4= i-pr
R4= Scheme 397
i-pr 1
2a
complete;
+
1
in the
-la and nitrile
chlorosilane
R’ 1.
for this
with a previous
398
suppressed
the formation
N-silylated
alkenyl
With allylic the nitrogen
This protocol
of -2.
bearing
a substituent
atom even with t-butyldimethyl
CN
Ph
1.
LDA -THF,
2.
t- BuMe2SiCL
Compound -lb readily
cyclzdded spontaneous
accompanied
by
of synthesis
of
occured
at
Ph7
C=C=N-S
i Me2t-
BU
(\
by bulb-to-bulb
to naphtoquinone oxidation
crude mixture with KF in refluxing
exclusively
(Scheme 2).
2
la-e were purified
was
method
at C-2, silylation
chlorosilane
_78’C
Scheme Vinyl ketenimines
an efficient
lb-d. --
ketenimines
cyanides
provided
of
methanol
distillation
at room temperature the
dehydroaromatic
and stored at -20°C5.
(Scheme 3). adduct.
The reaction
Treatment
of the
gave compound -3 in 61 % yield5.
c 3
Scheme
Cycloadditions silylation
with
of _1 with acetylenic
KF
in refluxing
mixture
of -lb and methyl
adducts
with
a solution
chromatography
yielded
/N C’
X
was
of KF (3 equiv.)
the corresponding
3
esters yielded
methanol
propiolate
(Scheme
heated
A
KF-MeOH,
4,
substituted
Table
1). Typically
for 4 hrs at 150°C.
in refluxing
methanol
aniline derivative
anilines5 an
Treatment
7
0Si
q
( i-PrSSi
4 Scheme
4
of the crude by flash
(Table 1, entry 5) in 84% yield.
2
‘10
equimolecular
for 3 hrs followed
* Y
after monode-
399
Table 1
Entry
: Cycloadditions Diene -1
of 1 with Acetylenic
Esters
Aniline
Temp"C. X
4
Yield
Y
z-
R
%
A
b
150
(i-Pr)3Si
H
H
C02Me
89
6
b
150
(i-Pr)3Si
H
H
H
84
C
b
150
(i-Pr)3Si
H
H
Me
52
D
C
110
(i-Pr)3Si
H
Ph
C02Me
56
E
C
100
(i-PrIgSi
H
Ph
H
52
F
d
150
(i-Pr)3Si
Me
H
C02We
50
G
e
150
H
H
C02He
49
These
results
PhCH2
demonstrate
anilines with strict control of an ortho triisopropylsilyl it can be smoothly
a
practical,
pattern
method
to
prepare
of the aromatic
group in _4 does not represent
removed with trifluoroacetic
a drawback
substituted
ring. The presence
for the method
since
acid6 (Scheme 5).
CF3CO2”
CO2Me
CCL4,
R
Scheme We have also
convergent
of the substitution
A,
2hrs
5
studied the reactions
of -lb with moderately
2,
R=H,
92 %
5,
R = C02Me
, 94 ‘A
reactive
olefinic
dienophiles
(Scheme 6). A 3:l mixture the ir absorption
of the dienophile and -lb was heated at 150°C until disappearance of -1 at Q 2040 cm typical for -lb. Desilylation with KF in refluxing methanol
,Si(i-Pr* rN
,CO2Me
+
1. 15o’c
II
2.
R’
KF-MGOH
I!?
I 0
( i-Pr&Si
.,.*CO2Me a
Scheme
6
R
%I eb /
#
70 % 52%
400
gave
dehydroanilines
readily
hydrolysed
-7a and -7b in 70% and 58% yield, respectively. (1.2 N HCl-CC141 into cyclohexenones 5 and -8b.
In conclusion, and regiospecific
Acknowledgments
we have
synthesis
found
readily
of substituted
available anilines
reagents
Both
compounds
for a practical
were
convergent
and cyclohexenones.
:
This work has been
supported
by I.R.S.I.A.
(contract
44401, N.A.T.O.,
(fellowship
to E.D)
and U.C.B. Bioproducts.
References
and Notes
11
E. Sonveaux
2)
For
other
and L. Ghosez, examples
see
(1980); A. Dondoni, G, 3) 4) 5)
1982
J. Am. Chem. Sot., -95, 5417 (1973) T. Saegusa, Synthetic
: Y. Ito, N. Ohta,
Heterocycles,
-14, 1547 (1980); L. Capuero,
Cornnun., -10, 233 A. Willmes, Lieb. Ann.
(1980).
E. Differding
and L. Ghosez,
Tetrahedron
Lett., -26, 1647 (1985).
D.S. Watt, Synth. Comnun., _4, 127 (1974). 13 1 had mass spectra, ir, H and C NMR consistent
All new compounds
with the proposed
structures. 61
For
a review
"Silicon
on electrophile-induced
in Organic
7) Representative
into
of 4.82 ml (%0.06
propylamine
of LDA
mole) of ally1 cyanide
made from the
in 240 ml THF with
32.14 ml (0.132 mole)
added dropwise.
The reaction
reaction
52.8 ml of butyl
Yield
:
b)Cycloaddition
methyl
17.4 g (77.3%) of lb
of 0.5 g (1.3 mnole) was heated
with 0.232q
ofKFand
removal of the solvent, CH2C12 3360,
(1981).
lithium
ml
(0.132
mole)
of diiso-
(2.5 Ml in hexane.
chloride
in 50 ml
After
5
of THF were
was allowed to warm to room temperature.
After
(bulb to bulb, t" oven = 15O"C, 0,l
; IR (film, cm-') 2045; 'H NMR (CDC13), 6 : 1.1
(dxd, 2H), 5.86 (dxd,lH).
of vinylketenimine
in a oil
bath
1690, 1600,1585;
at
?O ml of methanol
’ H NMR (CDC13),6 9 September
and
0.118 ml
After
and refluxed
(1.33 mmole)
4 hrs the mixture
for three
hours.
by flash chromatography
of was
After
(silicagel,
MS: m/e 307 CM+); IR (film, cm-'): 3520,
: 1.1 (m, 21H), 3.78 (s, 3H1, 5.73 (broad s,
2H), 6.5 (t, lH), 7.33 (dxd, lH), 7.77 (dxd, 1HI.
in France
E
150°C.
the residue was purified
: hexane 1:2). Yield: 0.342 g (84%);
(Received
: E. Colvin,
of lb to methylpropiolate
propiolate
treated
see
London
in 30 ml THF was added at -78 "C
of triisopropylsilyl
mixture
and 1.15 (m, 42H), 4.76 and 4.82
A mixture
Butterworths,
of 18.45
removal of the solvent, the residue was distilled mbarl.
of arylsilanes,
10, p. 126-132,
of lb
a solution
minutes,
desilylation
Chap.
Procedures
a) Preparation A solution
Synthesis",
1986)
A VERSATILE
397-400,1987
METHOD OF SYNTHESIS
Edmond Differding,
oo40-4039/87 $3.00 + .oo Pergamon Journals Ltd.
OF ANILINES
Oscar Vandevelde,
AND CYCLOHEXENONES
Bertrand
Roekens,
Tran Trieu Van and Leon Ghosez*
Laboratoire Universite
de Chimie Organique
Catholique
de Louvain,
Place L. Pasteur,
B-1348 LOUVAIN-LA-NEUVE,
Sumnary
: Allylic
alkenyl
ketenimines
cyanides
We
have
previously
of carbazoles
route
toward
reactions
polysubstituted
N-silylated
report4,
we found
presence
of lithium
dienophiles
with complete
on
capacity
the
with
olefinic
with
anilines
which
of
vinyl
important
give
by desilylation
ketenimines offer
synthetic
react
as
approach
convergent
of a vinyl
offered
to
a versatile
a highly
reaction
potentially
are
followed
to
regioselectivity.
dienophiles
Diels-Alder
an acetylene
chloride
synthesis
ketenimine3.
a convergent
The
synthetic
intermediates.
We now
of this goal.
alkenyl
since they
triisopropylsilyl
anilines
an intramolecular
ketenimine
report the realization
purpose
by
1
BELGIUM
132. More recently we have also described
involving
of a vinyl
reported
Their
silylated
of _1 with acetylenic
of substituted
dienes'.
toward cyclohexenones
reaction
readily
_1. The reaction
leads to the formation
nucleophilic
are
de Synthese,
ketenimines
are potential
that the reaction diisopropylamide
(Scheme 11. The use of a bulkier
appeared
precursors
to be the
of primary
of ally1 cyanide yielded
silylating
most
anilines.
appropriate
with t-butyldimethyl
a mixture
of vinyl
reagents
In contrast
ketenimine
agent such as triisopropyl
chlorosilano
CN
LDA-THF , -78’C
2
RzR4SiCl
c
1:
R’=
R *= H ,
b:
R’=
R*= H
t:
R’=
Ph ,
_d:
R’= H ,
R3 = Me
,
R4= t-Bu
R*= H , R*=
Me,
+
2
46%
23 %
77%
Cl %
R3 = R4 = i-pr
70%
0%
R3=
81%
0 %
, R3= R4= i-pr
R4= Scheme 397
i-pr 1
2a
complete;
+
1
in the
-la and nitrile
chlorosilane
R’ 1.
for this
with a previous
398
suppressed
the formation
N-silylated
alkenyl
With allylic the nitrogen
This protocol
of -2.
bearing
a substituent
atom even with t-butyldimethyl
CN
Ph
1.
LDA -THF,
2.
t- BuMe2SiCL
Compound -lb readily
cyclzdded spontaneous
accompanied
by
of synthesis
of
occured
at
Ph7
C=C=N-S
i Me2t-
BU
(\
by bulb-to-bulb
to naphtoquinone oxidation
crude mixture with KF in refluxing
exclusively
(Scheme 2).
2
la-e were purified
was
method
at C-2, silylation
chlorosilane
_78’C
Scheme Vinyl ketenimines
an efficient
lb-d. --
ketenimines
cyanides
provided
of
methanol
distillation
at room temperature the
dehydroaromatic
and stored at -20°C5.
(Scheme 3). adduct.
The reaction
Treatment
of the
gave compound -3 in 61 % yield5.
c 3
Scheme
Cycloadditions silylation
with
of _1 with acetylenic
KF
in refluxing
mixture
of -lb and methyl
adducts
with
a solution
chromatography
yielded
/N C’
X
was
of KF (3 equiv.)
the corresponding
3
esters yielded
methanol
propiolate
(Scheme
heated
A
KF-MeOH,
4,
substituted
Table
1). Typically
for 4 hrs at 150°C.
in refluxing
methanol
aniline derivative
anilines5 an
Treatment
7
0Si
q
( i-PrSSi
4 Scheme
4
of the crude by flash
(Table 1, entry 5) in 84% yield.
2
‘10
equimolecular
for 3 hrs followed
* Y
after monode-
399
Table 1
Entry
: Cycloadditions Diene -1
of 1 with Acetylenic
Esters
Aniline
Temp"C. X
4
Yield
Y
z-
R
%
A
b
150
(i-Pr)3Si
H
H
C02Me
89
6
b
150
(i-Pr)3Si
H
H
H
84
C
b
150
(i-Pr)3Si
H
H
Me
52
D
C
110
(i-Pr)3Si
H
Ph
C02Me
56
E
C
100
(i-PrIgSi
H
Ph
H
52
F
d
150
(i-Pr)3Si
Me
H
C02We
50
G
e
150
H
H
C02He
49
These
results
PhCH2
demonstrate
anilines with strict control of an ortho triisopropylsilyl it can be smoothly
a
practical,
pattern
method
to
prepare
of the aromatic
group in _4 does not represent
removed with trifluoroacetic
a drawback
substituted
ring. The presence
for the method
since
acid6 (Scheme 5).
CF3CO2”
CO2Me
CCL4,
R
Scheme We have also
convergent
of the substitution
A,
2hrs
5
studied the reactions
of -lb with moderately
2,
R=H,
92 %
5,
R = C02Me
, 94 ‘A
reactive
olefinic
dienophiles
(Scheme 6). A 3:l mixture the ir absorption
of the dienophile and -lb was heated at 150°C until disappearance of -1 at Q 2040 cm typical for -lb. Desilylation with KF in refluxing methanol
,Si(i-Pr* rN
,CO2Me
+
1. 15o’c
II
2.
R’
KF-MGOH
I!?
I 0
( i-Pr&Si
.,.*CO2Me a
Scheme
6
R
%I eb /
#
70 % 52%
400
gave
dehydroanilines
readily
hydrolysed
-7a and -7b in 70% and 58% yield, respectively. (1.2 N HCl-CC141 into cyclohexenones 5 and -8b.
In conclusion, and regiospecific
Acknowledgments
we have
synthesis
found
readily
of substituted
available anilines
reagents
Both
compounds
for a practical
were
convergent
and cyclohexenones.
:
This work has been
supported
by I.R.S.I.A.
(contract
44401, N.A.T.O.,
(fellowship
to E.D)
and U.C.B. Bioproducts.
References
and Notes
11
E. Sonveaux
2)
For
other
and L. Ghosez, examples
see
(1980); A. Dondoni, G, 3) 4) 5)
1982
J. Am. Chem. Sot., -95, 5417 (1973) T. Saegusa, Synthetic
: Y. Ito, N. Ohta,
Heterocycles,
-14, 1547 (1980); L. Capuero,
Cornnun., -10, 233 A. Willmes, Lieb. Ann.
(1980).
E. Differding
and L. Ghosez,
Tetrahedron
Lett., -26, 1647 (1985).
D.S. Watt, Synth. Comnun., _4, 127 (1974). 13 1 had mass spectra, ir, H and C NMR consistent
All new compounds
with the proposed
structures. 61
For
a review
"Silicon
on electrophile-induced
in Organic
7) Representative
into
of 4.82 ml (%0.06
propylamine
of LDA
mole) of ally1 cyanide
made from the
in 240 ml THF with
32.14 ml (0.132 mole)
added dropwise.
The reaction
reaction
52.8 ml of butyl
Yield
:
b)Cycloaddition
methyl
17.4 g (77.3%) of lb
of 0.5 g (1.3 mnole) was heated
with 0.232q
ofKFand
removal of the solvent, CH2C12 3360,
(1981).
lithium
ml
(0.132
mole)
of diiso-
(2.5 Ml in hexane.
chloride
in 50 ml
After
5
of THF were
was allowed to warm to room temperature.
After
(bulb to bulb, t" oven = 15O"C, 0,l
; IR (film, cm-') 2045; 'H NMR (CDC13), 6 : 1.1
(dxd, 2H), 5.86 (dxd,lH).
of vinylketenimine
in a oil
bath
1690, 1600,1585;
at
?O ml of methanol
’ H NMR (CDC13),6 9 September
and
0.118 ml
After
and refluxed
(1.33 mmole)
4 hrs the mixture
for three
hours.
by flash chromatography
of was
After
(silicagel,
MS: m/e 307 CM+); IR (film, cm-'): 3520,
: 1.1 (m, 21H), 3.78 (s, 3H1, 5.73 (broad s,
2H), 6.5 (t, lH), 7.33 (dxd, lH), 7.77 (dxd, 1HI.
in France
E
150°C.
the residue was purified
: hexane 1:2). Yield: 0.342 g (84%);
(Received
: E. Colvin,
of lb to methylpropiolate
propiolate
treated
see
London
in 30 ml THF was added at -78 "C
of triisopropylsilyl
mixture
and 1.15 (m, 42H), 4.76 and 4.82
A mixture
Butterworths,
of 18.45
removal of the solvent, the residue was distilled mbarl.
of arylsilanes,
10, p. 126-132,
of lb
a solution
minutes,
desilylation
Chap.
Procedures
a) Preparation A solution
Synthesis",
1986)