- Email: [email protected]
or Ge-masked dienolates
Tetrahedron Letters,Vo1.30,NoS26,pp Printed in Great Britain
REGIOSELECTIVE
3445-3448,1989 0040-4039/89 $3.00 + .oo Maxwell Pergamon Macmillan plc
SYNTHESIS OF EITHER a- OR y- AMINO ACID DERIVATIVES %-MASKED,
AND/OR Ge-MASKED
Yosbinori Yamamoto,*
VIA Li,
DIENOLATES
Satoshi Hatsuya, and Jun-ichi Yamada
Department of Chemistry,Faculty of Science, Tohoku University,
Sendai 980, Japan
Summary: Either the a- (3) or y-amino acid derivatives (4) can be prepared with very high regioselectivity by treating diethyl azodicarboxylate (DEAD) with (i) lithium dienolates themselves (2) in certain cases, (ii) Sn-masked dienolates (5), or (iii) Ge-masked dienolates (6). The amination reaction of lithium dienolates often produces a mixture of a- and y-amino acid derivatives (eq 1). For example,
treatment
azodicarboxylate)
of the lithium
dienolate
affords a 5 1% of the a-adduct
of p,fl-dimethylacryloyl
imide
with
DBAD(di-t-butyl
along with 42% of the y-isomer.’
R* a-amino acid derivatives 1
+
R2 y-amino acid derivatives
Regiocontrolled important
synthesis
biologically
highly regioselective azodicarboxylate)
has been required in our group, since such functional
active natural products,
like vinyl glycine,z
synthesis of either a- or y-amino acid derivatives
groups are frequently
statine,3 and anthopleurine.3
found in
We report that
is realized via the reaction of DEAD(diethy1
with certain lithium dienolates or with Sn- and Ge-masked dienolates.
First, we examined the reaction of the lithium dienolates (2) prepared by treatment of the corresponding (1) with LDA in HMPA-THF
or in THF alone (eq 2). The results are summarized
3445
in Table 1.
enoates
3446
R’yCQR
1) LDA (HMPA)
* 2) EtO&N=NCO,Et 1
EtO&N-NHCQEt
EtO&N-NHCQEt f
(2)
R’
C4R R2
R2
3
a-adduct
Table
1.
VaddM
4
Reaction of Lithium Dienolates with DEADa product ratio total isolated yield, %
a:y(E/Zofy) conditions
substrate
entry
1
#
CO*Me
(3:4)
A
1 : >99
@-99/l)
64
A
1 :>99
(>99/1)
71
2
Ph_A./-X
3
Y--’
cozizt
B
1 : IO (l/l)
78
4
Y- I
C02Et
A
1:5
(2/l)
75
B
1 : 3 (l/2)
87
B
4: 1 (l/1.5)
69
5
CO$Jle
CO*Et
6
aLithium
dienolates
HMPA (1.3 eq)-THF,
(2) were prepared -78”C, 30min.
as described
Condition
previously. 4 Condition
B; 1(2mmol),
LDA(l.l
A; I (2mmol),
solution, DEAD( 1.1 eq) in CH2Cl2 was added at -78°C and then the reaction was quenched ratio was determined
LDA( 1.1 eq) in
eq) in THF, -78’C, 30min. at 0°C.
To this
The isomer
by 270 MHz IH NMR. The product was isolated through a silica-gel column chromatography.
3447
6
5 Sn-masked Table 2. DEADa
dienolate
Ge-masked
dienolate
Lewis Acid Mediated Reaction of Sn- and Ge-Masked Dienolates with product ratio
entry
total isolated yield,
masked
Lewis
temp RX
a:y
diendate
acid
reaction time
(3 : 4) (E/z of v)
TiCI4
-78, 30min
1 : 4 (> 99/l)
85
ZnCl2
-7i3*
15: 1
80
2
0 40rnin
O/O
k02Et
3
ClSs&C02Et
b
-10, lOOmin
10: 1
28
4
Cl2S~Co~e
b
-10, 30min
10: 1
58
TiCId
-78-r- r. t. 2h
1 : >99 (3/l)
71
TiCI4
-78-5
1 : >99 (8/l)
88
1 : > 99 (6/l)
55
GeMe3
6
CO,Et
40min GeMe3
7
C02Me
TiCI.,
-78+0 30min
aTo a CH$l;! solution of DEAD(2 mmol), TiCb( 1 eq)-CH2C12 or ZnC12( 1 eq)-CH2C12 was added at -78°C except entries 3 and 4. The masked dienolates (1.2 eq) in CH$I12 were added and the reaction was quenched at the indicated temperature. bin entries 3 and 4, the lithium dienolates were trapped with 1.1 eq SK4 DEAD was added to thii mixture (in situ method).
at -78°C and then
3448
In contmst to the lithium dienolate derived from the a&unsaturated amino acid derivatives
(4) either exclusively
imide,l the dienolates
(entries 1 and 2) or very predominantly
decreased in the presence of HMPA (cf. entry 3 and 4). An interesting the five membered
derivative
isomer preferentially
gave the y-isomer predominantly
(entries 5 and 6). No isomerizatlon
conditions, and thus the regioisomers However,
(entry 3). The y-selectivity
contrast was observed in the cyclic systems:
while the six membered
derivative produced the
took place between the a- and y-isomersunder
a-
the reaction
(3 and 4) are produced under kinetic control.
It is clear that certain y-amino acids are obtained with very high regioselectivity with DEAD.
from enoates gave the y-
the a-isomers
in entries
l-5 and the y-isomer
examined the Lewis acid mediated reaction of Sn- and Ge-masked
by simply treating dienolates
in entry 6 are not available.
We next
dienolates (eq 3), and the results are summarized
in Table 2. As expected, the y-Sn masked dienolates a-Ge masked dienolates
(6) produced
afforded the y-isomer predominantly method seems to be convenient
(5) gave the a-adducts with high regioselectivity
the y-adducts
exclusively
but the selectivity
(entries 2-4) and the
(entries 5-7). The well-known
was not so high (entryl,
(entries 3 and 4), since the isolation
silyl dienol ether
cf. entry 1 of Table 1). The in situ
of the masked enolate is no necessary
and
further use of Lewis acid is not required. It is known that the reaction produces
of azodicarboxylates
the amino acid derivatives
dienolates has not been achieved.
in high yields.
dienolates,
However,
or with ketene silyl acetals7~8
the regiocontrol
on the amination
reaction
of
The present results clearly indicate that either the a- or y-amino acid derivatives
can be prepared with very high regioselectivity cases, (2) Sn-masked
with lithium enolate&
by treating DEAD with (1) lithium dienolates
or (3) Ge-masked
dienolates.
We are now extending
themselves
in certain
this methodology
to the
synthesis of some useful y- and a-amino acids. References
and Notes
1)
D. A. Evans, T. C. Britton, R. L. Dorow, and J. F. Dellaria, Jr., Tetrahedron,
2)
J. N. Fitzner, Sahoo,
D. V. Pratt, and P. B. Hopkins,
ibid., 1984,25,
1984; and references
3)
I. Wagner and H. Musso,
4)
a) Y. Yamamoto,
5)
D. A. Evans, T. C. B&ton,
6)
L. A. Trimble and J. C. Vederas,
J. Chem. Sot., Chem. Commun.,
R. L. Dorow, and J. F. Dellaria,
C. Gennari, L. Colombo,
W. Oppolzer and R. Moretti, Japan
5525. and S. P.
19 8 7, 56 1. b) Ibid., 19 88,
1639.
7)
in
1988,44,
26, 1959; S. Hanessian
Angew. Chem., Int. Ed. Engl., 1983, 22, 8 16.
8)
(Received
Lett., 1985,
cited therein.
S. Hatsuya, and J. Yamada,
86. c) Ibid., 1988,
Tetrahedron
J. Am. Chem. Sot., 1986.
and G. Bertolini,
1989)
108,6397.
J. Am. Chem. Sot., 1986,
Helv. Chin-t. Acta, 1986,69,
17 March
J. Am. Chem. Sot., 1986,
1923.
108,6394,
108,6395.
REGIOSELECTIVE
3445-3448,1989 0040-4039/89 $3.00 + .oo Maxwell Pergamon Macmillan plc
SYNTHESIS OF EITHER a- OR y- AMINO ACID DERIVATIVES %-MASKED,
AND/OR Ge-MASKED
Yosbinori Yamamoto,*
VIA Li,
DIENOLATES
Satoshi Hatsuya, and Jun-ichi Yamada
Department of Chemistry,Faculty of Science, Tohoku University,
Sendai 980, Japan
Summary: Either the a- (3) or y-amino acid derivatives (4) can be prepared with very high regioselectivity by treating diethyl azodicarboxylate (DEAD) with (i) lithium dienolates themselves (2) in certain cases, (ii) Sn-masked dienolates (5), or (iii) Ge-masked dienolates (6). The amination reaction of lithium dienolates often produces a mixture of a- and y-amino acid derivatives (eq 1). For example,
treatment
azodicarboxylate)
of the lithium
dienolate
affords a 5 1% of the a-adduct
of p,fl-dimethylacryloyl
imide
with
DBAD(di-t-butyl
along with 42% of the y-isomer.’
R* a-amino acid derivatives 1
+
R2 y-amino acid derivatives
Regiocontrolled important
synthesis
biologically
highly regioselective azodicarboxylate)
has been required in our group, since such functional
active natural products,
like vinyl glycine,z
synthesis of either a- or y-amino acid derivatives
groups are frequently
statine,3 and anthopleurine.3
found in
We report that
is realized via the reaction of DEAD(diethy1
with certain lithium dienolates or with Sn- and Ge-masked dienolates.
First, we examined the reaction of the lithium dienolates (2) prepared by treatment of the corresponding (1) with LDA in HMPA-THF
or in THF alone (eq 2). The results are summarized
3445
in Table 1.
enoates
3446
R’yCQR
1) LDA (HMPA)
* 2) EtO&N=NCO,Et 1
EtO&N-NHCQEt
EtO&N-NHCQEt f
(2)
R’
C4R R2
R2
3
a-adduct
Table
1.
VaddM
4
Reaction of Lithium Dienolates with DEADa product ratio total isolated yield, %
a:y(E/Zofy) conditions
substrate
entry
1
#
CO*Me
(3:4)
A
1 : >99
@-99/l)
64
A
1 :>99
(>99/1)
71
2
Ph_A./-X
3
Y--’
cozizt
B
1 : IO (l/l)
78
4
Y- I
C02Et
A
1:5
(2/l)
75
B
1 : 3 (l/2)
87
B
4: 1 (l/1.5)
69
5
CO$Jle
CO*Et
6
aLithium
dienolates
HMPA (1.3 eq)-THF,
(2) were prepared -78”C, 30min.
as described
Condition
previously. 4 Condition
B; 1(2mmol),
LDA(l.l
A; I (2mmol),
solution, DEAD( 1.1 eq) in CH2Cl2 was added at -78°C and then the reaction was quenched ratio was determined
LDA( 1.1 eq) in
eq) in THF, -78’C, 30min. at 0°C.
To this
The isomer
by 270 MHz IH NMR. The product was isolated through a silica-gel column chromatography.
3447
6
5 Sn-masked Table 2. DEADa
dienolate
Ge-masked
dienolate
Lewis Acid Mediated Reaction of Sn- and Ge-Masked Dienolates with product ratio
entry
total isolated yield,
masked
Lewis
temp RX
a:y
diendate
acid
reaction time
(3 : 4) (E/z of v)
TiCI4
-78, 30min
1 : 4 (> 99/l)
85
ZnCl2
-7i3*
15: 1
80
2
0 40rnin
O/O
k02Et
3
ClSs&C02Et
b
-10, lOOmin
10: 1
28
4
Cl2S~Co~e
b
-10, 30min
10: 1
58
TiCId
-78-r- r. t. 2h
1 : >99 (3/l)
71
TiCI4
-78-5
1 : >99 (8/l)
88
1 : > 99 (6/l)
55
GeMe3
6
CO,Et
40min GeMe3
7
C02Me
TiCI.,
-78+0 30min
aTo a CH$l;! solution of DEAD(2 mmol), TiCb( 1 eq)-CH2C12 or ZnC12( 1 eq)-CH2C12 was added at -78°C except entries 3 and 4. The masked dienolates (1.2 eq) in CH$I12 were added and the reaction was quenched at the indicated temperature. bin entries 3 and 4, the lithium dienolates were trapped with 1.1 eq SK4 DEAD was added to thii mixture (in situ method).
at -78°C and then
3448
In contmst to the lithium dienolate derived from the a&unsaturated amino acid derivatives
(4) either exclusively
imide,l the dienolates
(entries 1 and 2) or very predominantly
decreased in the presence of HMPA (cf. entry 3 and 4). An interesting the five membered
derivative
isomer preferentially
gave the y-isomer predominantly
(entries 5 and 6). No isomerizatlon
conditions, and thus the regioisomers However,
(entry 3). The y-selectivity
contrast was observed in the cyclic systems:
while the six membered
derivative produced the
took place between the a- and y-isomersunder
a-
the reaction
(3 and 4) are produced under kinetic control.
It is clear that certain y-amino acids are obtained with very high regioselectivity with DEAD.
from enoates gave the y-
the a-isomers
in entries
l-5 and the y-isomer
examined the Lewis acid mediated reaction of Sn- and Ge-masked
by simply treating dienolates
in entry 6 are not available.
We next
dienolates (eq 3), and the results are summarized
in Table 2. As expected, the y-Sn masked dienolates a-Ge masked dienolates
(6) produced
afforded the y-isomer predominantly method seems to be convenient
(5) gave the a-adducts with high regioselectivity
the y-adducts
exclusively
but the selectivity
(entries 2-4) and the
(entries 5-7). The well-known
was not so high (entryl,
(entries 3 and 4), since the isolation
silyl dienol ether
cf. entry 1 of Table 1). The in situ
of the masked enolate is no necessary
and
further use of Lewis acid is not required. It is known that the reaction produces
of azodicarboxylates
the amino acid derivatives
dienolates has not been achieved.
in high yields.
dienolates,
However,
or with ketene silyl acetals7~8
the regiocontrol
on the amination
reaction
of
The present results clearly indicate that either the a- or y-amino acid derivatives
can be prepared with very high regioselectivity cases, (2) Sn-masked
with lithium enolate&
by treating DEAD with (1) lithium dienolates
or (3) Ge-masked
dienolates.
We are now extending
themselves
in certain
this methodology
to the
synthesis of some useful y- and a-amino acids. References
and Notes
1)
D. A. Evans, T. C. Britton, R. L. Dorow, and J. F. Dellaria, Jr., Tetrahedron,
2)
J. N. Fitzner, Sahoo,
D. V. Pratt, and P. B. Hopkins,
ibid., 1984,25,
1984; and references
3)
I. Wagner and H. Musso,
4)
a) Y. Yamamoto,
5)
D. A. Evans, T. C. B&ton,
6)
L. A. Trimble and J. C. Vederas,
J. Chem. Sot., Chem. Commun.,
R. L. Dorow, and J. F. Dellaria,
C. Gennari, L. Colombo,
W. Oppolzer and R. Moretti, Japan
5525. and S. P.
19 8 7, 56 1. b) Ibid., 19 88,
1639.
7)
in
1988,44,
26, 1959; S. Hanessian
Angew. Chem., Int. Ed. Engl., 1983, 22, 8 16.
8)
(Received
Lett., 1985,
cited therein.
S. Hatsuya, and J. Yamada,
86. c) Ibid., 1988,
Tetrahedron
J. Am. Chem. Sot., 1986.
and G. Bertolini,
1989)
108,6397.
J. Am. Chem. Sot., 1986,
Helv. Chin-t. Acta, 1986,69,
17 March
J. Am. Chem. Sot., 1986,
1923.
108,6394,
108,6395.