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Enantioselective aldol reaction of chiral acyl thiazolidine thione derived boron enolates
0040-4039/85 $3.00 + .OO 01985 Pergamon Press Ltd.
Tetrahedron Letters,Vo1.26,No.40,pp 4855-4858,1985 Printed in Great Britain
EWNTIOSELECTIVE ALOOL REACTIOll OF CHIRAL ACYL THIAZOLIDIWE THIONE DERIVED BORON ENQLATES
Chi-Nung
Hsiao*
Stephen P. Ashburn and Marvin Department of Chemistry University of Notre Dame Notre Dame, IN 46556
J. Miller**
The compatability of an acyl thiazolidine thione as a chiral auxillary in boron enolate chemistry has been demonstrated by an enantioselective aldol condensation. The aldol products provide direct access to chiral e-lactams.
Processes
for the diastereoselective
bonds are becoming
increasingly
given to the development reactions2b'c'3*4 chiral
aminolysis.
of efficient
of chiral metal
auxillaries
enantioselective
carbon-carbon
The ability
all of these
important
chiral
6-lactam
We were especially
ester for subsequent mediated
recognition)7
reactions enolate
auxillary
la
would
acyl thiazolidine
emphasis
has been
and aldol reactions
promote
removed
should employ
efficient
by solvolysis
also be desirable.
thione derived
or
Herein we
boron enolate
for the synthesis
which
of an
* thione
thiones
for enantioselective
also serves as an effective
active
In fact we have previously acyl thiazolidine
versions
interested
from L-cysteine7 acylated
applied Mukaiyama's tin thiones 3c in a stereoselective
of tin enolate
in incorporating
The ready availability
of the corresponding
chiral auxillary
and can be easily
to the use of acyl thiazolidine
While chiral we were
acylated,
The use of the aldol product
of non chiral
itself.
1,3-thiazolidine-2-thione
alkylations2a
readily
the acyl thiazolidine
elaboration. 5
using chiral diamines,3a'b thione
bond formation
attracted
of a-lactams. 6
thiazolidine
available,
of carbon-carbon
Special
Ideally, such asymmetric
is also demonstrated.
because
formation
synthesis.I
stereoselective
of a chiral
aldol condensation
synthesis
in organic
to recycle the chiral
requirements.
aldol condensations
and enantioselective
enolates.
which are readily
report an aldol condensation meets
practical
chemistry
the chirality
of optically
and the reported
derivatives
made
have been reported into the
pure 4(R)-methoxycarbonyl-
ease of aminolysis
its consideration
(with chiral
for use as a
in aldol condensations very attractive. The high enantioselectivity of aldol boron enolates 2c also prompted us to study the previously unreported boron
of chiral
(3) of a chiral
acyl thiazolidine
thione
4855
(2).
4856
Scheme
1
1 ClC(CH,),CH3 Jf"" S
Pyridine,
0-B(nBu)2
1. (nBu)2BOTf Et
CH2C12
2. (iPr)2NEt
S
,SKN
2
-40° la R=C02CH3 lb R=H
H2NOCH2Ph
OCH3
W L
6
7
Figure
1
300 MHz 'HNMR of Eu(hfc)3)
(with 40 mole % of the methyl
region of a) optically S~NHAc
and b) racemic 7 (prepared the process
described
ester
active 7 by
in ref 6
and by use of the boron enolate C02H 8, PS-5
with lb)
a
b
4857
We therefore
decided
Indeed acylation provided
of
([aID20 = _64,5")7,8
la
the optically
active
Treatment
CH2C12)
under N2 for 5 min at 0 ' in CH2C12 (350 pl, 2.01 mmole)
at-0°C
was cooled
was added.
The mixture
allowed
to warm to 0°C over 20 min.
mixture
was stirred vigorously
0.28).
solution
Note that
solution
(CH3CN, 6h) provided
Cyclization
The chiral
auxillary
was most
thiazolidine
thione
(heptafluoropropyl distinguished
(lb,
of
for
(368 mg, 1.96
5 min at -78°C and then
solution
was added and the
1:l) analysis
Instead,
of the (Rf =
the CH2C12
on silica gel
aldol product
Saq (654 mg, 77%,
5a with 0-benzylhydroxylamine
la ([a]U2o = -63.4') was also recovered in 91% yield. diisopropyl
azodicarboxylate
in 67% yield.
Analysis
(TPP/DIAO)6*12
gave the
of the optical
The 300 MHz NMR of 7 was identical
purity
to that of
and by the same route shown in Scheme 1, but with non chiral
R = H).
However,
addition
hydroxymethylene)-cl-camphorate]
the racemic
46*Io
in
of diisopropyl
which was stirred
of only one new component
chromatographed
hydroxaminolysis
straightforward.
previously6
-40" to 0')
6aq ([a];' = -8.8", c = 3.7, CHC13) in 74% yield after
of 6 with triphenylphosphine
racemic 7 prepared
another
buffer
active erythro
B-lactam 7' ([a];' = + 21.9", c = 1.88, CHC13) of this compound
solution
TLC (EtOAc/hexanes,
formation
and directly
Direct
the hydroxamate
la.
(2.01 mL of a 1.0 M_ solution
workup was emp1oyed.I’
the optically
[a];' = -83", c = 3.9, CHC13).
with
CH2C12,
by slow addition
was stirred
pH 7 phosphate
no H202 or other oxidative concentrated
(pyridine,
to -78°C and aldehyde
at 0°C for 3 min.
2:l) to provide
chromatography.
Excess
at this point indicated
was separated,
(hexanes/EtOAc,
(20 mL) followed
gave a light yellow
The solution
in 3 mL of CH2C12)
crude product
chloride
chemistry
2aq ([ali' = -123.5" (c = 1.9, CHC13)) in 97%
2a (480 mg, 1.943 mmole) with (nBu)2BOTf
another 30 min at 0°C. mmole
of boron enolate
with butyrl
acyl derivative
yield.
ethyl amine
of
to test the compatability
and chiral
B-lactams
of 40 mole % of tris [3europium(III),
Eu(hfc)3,
(fig. 1) and indicated
clearly
that 7 was present
in at
least 93% ee. Thus, we have demonstrated is compatible
with boron enolate
which are also effective
active
that the readily chemistry
available
and provides
esters and allow the chiral
Studies of the scope of this type of aldol condensation preparation
of optically
pure carbapenems,
chiral
products
aqyl thiazolidine of significant
auxillary
and extensions
thione
optical
la
purity
la to be regenerated. of this process
like PS-5 813, and other natural
products
to the
are in
progress.
Acknowledgements: Lilly and Company. University
We gratefully
acknowledge
the support
The 300 MHz NMR was made available
of Notre Dame.
of this research
by grants
from the
by the NIH and Eli
NIH and the
4858
References *
and Notes
Fellow of the Alfred
Development
Award
P. Sloan Foundation
(1981-1985) Recipient
of an
1. Morrison, J. 0. "Asymmetric Synthesis,"
Vol. 3, Part B, 1984.
a) Evans, D. A. in ref. 1, Chapter
b) Evans, D. A.; Nelson,
2.
"Topics
NIH Research Career
(1983-1988).
in Stereochemistry,"
1.
Vol. 13, 1, 1982,
J. V.; Taber,
c) Evans, D. A.; Bartroli,
T. R. Shih, T.
J.;
L. J. Am. Chem. Sot. 1981, 103, 2127. 3.
a) Iwasawa,
N.; Mukaiyama,
Chem. Lett. 1983, 4. 5.
1799.
T. Chem. Lett.,E,
c) Mukaiyama,
Heathcock,
C. H. in ref. 1, Chapter
a) Fujita,
E.; Nagao, Y. Heterocycles,
K .; Miyasaka,
T.; Takao,
297.
T.; Iwasawa,
b) Stevens,
R. W.; Mukaiyama,
N.; Chem. Lett., 1982,
T.
1903.
2.
S.; Fujita,
1982,x,
537.
b)
Nagao,
E. Chem. Pharm. Bull.,
Y.; Seno, K.; Kawabata,
1984, 32, 2687 and references
therein. 6.
Jung, M.; Miller,
7.
a) Nagao, Y.; Yagi, M.; Ikede, T.; Fujita,
M. J. Tetrahedron
Lett.,
8.
Soai, K.; Ishizaki,
9.
Representative
characterization
1.65 (quintet,
J = 7.5 Hz, 2H), 2.90-3.75
Nagao, Y.; Ikede, T.; Yagi, M.; Fujita, M. Heterocycles,
1985, 26, 977. E. Tetrahedron
Lett.,
1982, 23, 201.
b)
E. J. Am. Chem. Sot., 1982, 104, 2079.
1984, 22, 2827.
data includes:
2a, oil, 'HNMR 6 0.95 (t. J = 7.5 HZ, 3H),
(m, 4H), 3.80 (s,
3H), 5.65 (dd, J = 7.5 HZ,
J = 7.5 Hz, 1H); IR (neat) 1750, 1700, 1210, 1150, 770 cm-l.
5a, oil, 'HNMR (300 MHz,
CDC13)
(m, lH), 2.05-2.22
6 0.99
(t, J = 8 Hz, 3H), 1.64-1.80
(m, lH),
1.86-2.00
2.75 (s, 2H), 3.25-3.36
(m, 2H), 3.69 (s, 3H), 3.82 (s, 3H), 4.03
4.87 (m, lH),
(dd, J= 8.5 Hz, J = 3 Hz, 1H);
cm -1.
5.67-5.70
6, oil, lHNMR (300 MHz, CDC13)
2.00 (m, lH),
(m, 3H),
2.05-2.20
6 0.95
2.70
(s,
(s, broad, 4H), 4.85 (s, 2H), 7.25-7.42 (broad),
7.5 Hz, 3H), 1.54-1.68 Hz. J = 14 Hz,
lH),
3.65
(s,
2H),
2.61
(dt,
3H),
3.72
(s, broad,
7, oil, 1HNMR
(m, 2H), 2.00 (dd, J = 8.7
2.58
(s,
(m, 5H), 8.84
(m, 2H). (m, 1H),
IR (neat) 3525, 1720 (broad)
(t, J = 8 Hz, 3H), 1.64-1.80
2H),
1730, 1660, 1200, 1010, 730 cm-l.
(s, 4H), 4.20
(m, lH), 1.86-
broad,
(s,
IR (neat) 3200-3600
1H);
(300 MHz, CDC13)
Hz, J = 14 HZ, lH),
J = 1.8 Hz, J = 6.6
lH), 4.00
2.37
Hz, lH),
6 0.97 (t, J =
(dd,
3.39
J= 3.9 (ddd.
J =
1.8 Hz, J = 3.9 Hz, J = 8.7 Hz, lH), 3.69 (s, 3H), 3.82 - 4.02 (m, 4H), 4.95 (s, 2H), 7.30-7.50
(m, 5H); IR (neat) 3750, 3050, 1770, 1750 cm-'.
10.
Kametani,
T.; Huang,
11.
Hydrogen
peroxide
isolation
S-P.; Nakayama,
(30%) was commonly
of aldol products
derived
A.; Honda, T. J. Org. Chem., used in the previously from boron enolates.
1982, 47,
reported
2328.
procedure
for
See: ref. 2c and references
therein. 12.
Miller,
M. J.; Mattingly,
P. G.; Morrison,
M. A.; Kerwin.
J.
F. Jr.
J.
Am. Chem. Sot.,
1980, 102, 7026. 13.
Yamamoto,
K.; Shimauchi,
Y.; Ishikura,
(Received in USA 24 June 1985)
T. J. Antibiotics,
1980,
33,
796.
Tetrahedron Letters,Vo1.26,No.40,pp 4855-4858,1985 Printed in Great Britain
EWNTIOSELECTIVE ALOOL REACTIOll OF CHIRAL ACYL THIAZOLIDIWE THIONE DERIVED BORON ENQLATES
Chi-Nung
Hsiao*
Stephen P. Ashburn and Marvin Department of Chemistry University of Notre Dame Notre Dame, IN 46556
J. Miller**
The compatability of an acyl thiazolidine thione as a chiral auxillary in boron enolate chemistry has been demonstrated by an enantioselective aldol condensation. The aldol products provide direct access to chiral e-lactams.
Processes
for the diastereoselective
bonds are becoming
increasingly
given to the development reactions2b'c'3*4 chiral
aminolysis.
of efficient
of chiral metal
auxillaries
enantioselective
carbon-carbon
The ability
all of these
important
chiral
6-lactam
We were especially
ester for subsequent mediated
recognition)7
reactions enolate
auxillary
la
would
acyl thiazolidine
emphasis
has been
and aldol reactions
promote
removed
should employ
efficient
by solvolysis
also be desirable.
thione derived
or
Herein we
boron enolate
for the synthesis
which
of an
* thione
thiones
for enantioselective
also serves as an effective
active
In fact we have previously acyl thiazolidine
versions
interested
from L-cysteine7 acylated
applied Mukaiyama's tin thiones 3c in a stereoselective
of tin enolate
in incorporating
The ready availability
of the corresponding
chiral auxillary
and can be easily
to the use of acyl thiazolidine
While chiral we were
acylated,
The use of the aldol product
of non chiral
itself.
1,3-thiazolidine-2-thione
alkylations2a
readily
the acyl thiazolidine
elaboration. 5
using chiral diamines,3a'b thione
bond formation
attracted
of a-lactams. 6
thiazolidine
available,
of carbon-carbon
Special
Ideally, such asymmetric
is also demonstrated.
because
formation
synthesis.I
stereoselective
of a chiral
aldol condensation
synthesis
in organic
to recycle the chiral
requirements.
aldol condensations
and enantioselective
enolates.
which are readily
report an aldol condensation meets
practical
chemistry
the chirality
of optically
and the reported
derivatives
made
have been reported into the
pure 4(R)-methoxycarbonyl-
ease of aminolysis
its consideration
(with chiral
for use as a
in aldol condensations very attractive. The high enantioselectivity of aldol boron enolates 2c also prompted us to study the previously unreported boron
of chiral
(3) of a chiral
acyl thiazolidine
thione
4855
(2).
4856
Scheme
1
1 ClC(CH,),CH3 Jf"" S
Pyridine,
0-B(nBu)2
1. (nBu)2BOTf Et
CH2C12
2. (iPr)2NEt
S
,SKN
2
-40° la R=C02CH3 lb R=H
H2NOCH2Ph
OCH3
W L
6
7
Figure
1
300 MHz 'HNMR of Eu(hfc)3)
(with 40 mole % of the methyl
region of a) optically S~NHAc
and b) racemic 7 (prepared the process
described
ester
active 7 by
in ref 6
and by use of the boron enolate C02H 8, PS-5
with lb)
a
b
4857
We therefore
decided
Indeed acylation provided
of
([aID20 = _64,5")7,8
la
the optically
active
Treatment
CH2C12)
under N2 for 5 min at 0 ' in CH2C12 (350 pl, 2.01 mmole)
at-0°C
was cooled
was added.
The mixture
allowed
to warm to 0°C over 20 min.
mixture
was stirred vigorously
0.28).
solution
Note that
solution
(CH3CN, 6h) provided
Cyclization
The chiral
auxillary
was most
thiazolidine
thione
(heptafluoropropyl distinguished
(lb,
of
for
(368 mg, 1.96
5 min at -78°C and then
solution
was added and the
1:l) analysis
Instead,
of the (Rf =
the CH2C12
on silica gel
aldol product
Saq (654 mg, 77%,
5a with 0-benzylhydroxylamine
la ([a]U2o = -63.4') was also recovered in 91% yield. diisopropyl
azodicarboxylate
in 67% yield.
Analysis
(TPP/DIAO)6*12
gave the
of the optical
The 300 MHz NMR of 7 was identical
purity
to that of
and by the same route shown in Scheme 1, but with non chiral
R = H).
However,
addition
hydroxymethylene)-cl-camphorate]
the racemic
46*Io
in
of diisopropyl
which was stirred
of only one new component
chromatographed
hydroxaminolysis
straightforward.
previously6
-40" to 0')
6aq ([a];' = -8.8", c = 3.7, CHC13) in 74% yield after
of 6 with triphenylphosphine
racemic 7 prepared
another
buffer
active erythro
B-lactam 7' ([a];' = + 21.9", c = 1.88, CHC13) of this compound
solution
TLC (EtOAc/hexanes,
formation
and directly
Direct
the hydroxamate
la.
(2.01 mL of a 1.0 M_ solution
workup was emp1oyed.I’
the optically
[a];' = -83", c = 3.9, CHC13).
with
CH2C12,
by slow addition
was stirred
pH 7 phosphate
no H202 or other oxidative concentrated
(pyridine,
to -78°C and aldehyde
at 0°C for 3 min.
2:l) to provide
chromatography.
Excess
at this point indicated
was separated,
(hexanes/EtOAc,
(20 mL) followed
gave a light yellow
The solution
in 3 mL of CH2C12)
crude product
chloride
chemistry
2aq ([ali' = -123.5" (c = 1.9, CHC13)) in 97%
2a (480 mg, 1.943 mmole) with (nBu)2BOTf
another 30 min at 0°C. mmole
of boron enolate
with butyrl
acyl derivative
yield.
ethyl amine
of
to test the compatability
and chiral
B-lactams
of 40 mole % of tris [3europium(III),
Eu(hfc)3,
(fig. 1) and indicated
clearly
that 7 was present
in at
least 93% ee. Thus, we have demonstrated is compatible
with boron enolate
which are also effective
active
that the readily chemistry
available
and provides
esters and allow the chiral
Studies of the scope of this type of aldol condensation preparation
of optically
pure carbapenems,
chiral
products
aqyl thiazolidine of significant
auxillary
and extensions
thione
optical
la
purity
la to be regenerated. of this process
like PS-5 813, and other natural
products
to the
are in
progress.
Acknowledgements: Lilly and Company. University
We gratefully
acknowledge
the support
The 300 MHz NMR was made available
of Notre Dame.
of this research
by grants
from the
by the NIH and Eli
NIH and the
4858
References *
and Notes
Fellow of the Alfred
Development
Award
P. Sloan Foundation
(1981-1985) Recipient
of an
1. Morrison, J. 0. "Asymmetric Synthesis,"
Vol. 3, Part B, 1984.
a) Evans, D. A. in ref. 1, Chapter
b) Evans, D. A.; Nelson,
2.
"Topics
NIH Research Career
(1983-1988).
in Stereochemistry,"
1.
Vol. 13, 1, 1982,
J. V.; Taber,
c) Evans, D. A.; Bartroli,
T. R. Shih, T.
J.;
L. J. Am. Chem. Sot. 1981, 103, 2127. 3.
a) Iwasawa,
N.; Mukaiyama,
Chem. Lett. 1983, 4. 5.
1799.
T. Chem. Lett.,E,
c) Mukaiyama,
Heathcock,
C. H. in ref. 1, Chapter
a) Fujita,
E.; Nagao, Y. Heterocycles,
K .; Miyasaka,
T.; Takao,
297.
T.; Iwasawa,
b) Stevens,
R. W.; Mukaiyama,
N.; Chem. Lett., 1982,
T.
1903.
2.
S.; Fujita,
1982,x,
537.
b)
Nagao,
E. Chem. Pharm. Bull.,
Y.; Seno, K.; Kawabata,
1984, 32, 2687 and references
therein. 6.
Jung, M.; Miller,
7.
a) Nagao, Y.; Yagi, M.; Ikede, T.; Fujita,
M. J. Tetrahedron
Lett.,
8.
Soai, K.; Ishizaki,
9.
Representative
characterization
1.65 (quintet,
J = 7.5 Hz, 2H), 2.90-3.75
Nagao, Y.; Ikede, T.; Yagi, M.; Fujita, M. Heterocycles,
1985, 26, 977. E. Tetrahedron
Lett.,
1982, 23, 201.
b)
E. J. Am. Chem. Sot., 1982, 104, 2079.
1984, 22, 2827.
data includes:
2a, oil, 'HNMR 6 0.95 (t. J = 7.5 HZ, 3H),
(m, 4H), 3.80 (s,
3H), 5.65 (dd, J = 7.5 HZ,
J = 7.5 Hz, 1H); IR (neat) 1750, 1700, 1210, 1150, 770 cm-l.
5a, oil, 'HNMR (300 MHz,
CDC13)
(m, lH), 2.05-2.22
6 0.99
(t, J = 8 Hz, 3H), 1.64-1.80
(m, lH),
1.86-2.00
2.75 (s, 2H), 3.25-3.36
(m, 2H), 3.69 (s, 3H), 3.82 (s, 3H), 4.03
4.87 (m, lH),
(dd, J= 8.5 Hz, J = 3 Hz, 1H);
cm -1.
5.67-5.70
6, oil, lHNMR (300 MHz, CDC13)
2.00 (m, lH),
(m, 3H),
2.05-2.20
6 0.95
2.70
(s,
(s, broad, 4H), 4.85 (s, 2H), 7.25-7.42 (broad),
7.5 Hz, 3H), 1.54-1.68 Hz. J = 14 Hz,
lH),
3.65
(s,
2H),
2.61
(dt,
3H),
3.72
(s, broad,
7, oil, 1HNMR
(m, 2H), 2.00 (dd, J = 8.7
2.58
(s,
(m, 5H), 8.84
(m, 2H). (m, 1H),
IR (neat) 3525, 1720 (broad)
(t, J = 8 Hz, 3H), 1.64-1.80
2H),
1730, 1660, 1200, 1010, 730 cm-l.
(s, 4H), 4.20
(m, lH), 1.86-
broad,
(s,
IR (neat) 3200-3600
1H);
(300 MHz, CDC13)
Hz, J = 14 HZ, lH),
J = 1.8 Hz, J = 6.6
lH), 4.00
2.37
Hz, lH),
6 0.97 (t, J =
(dd,
3.39
J= 3.9 (ddd.
J =
1.8 Hz, J = 3.9 Hz, J = 8.7 Hz, lH), 3.69 (s, 3H), 3.82 - 4.02 (m, 4H), 4.95 (s, 2H), 7.30-7.50
(m, 5H); IR (neat) 3750, 3050, 1770, 1750 cm-'.
10.
Kametani,
T.; Huang,
11.
Hydrogen
peroxide
isolation
S-P.; Nakayama,
(30%) was commonly
of aldol products
derived
A.; Honda, T. J. Org. Chem., used in the previously from boron enolates.
1982, 47,
reported
2328.
procedure
for
See: ref. 2c and references
therein. 12.
Miller,
M. J.; Mattingly,
P. G.; Morrison,
M. A.; Kerwin.
J.
F. Jr.
J.
Am. Chem. Sot.,
1980, 102, 7026. 13.
Yamamoto,
K.; Shimauchi,
Y.; Ishikura,
(Received in USA 24 June 1985)
T. J. Antibiotics,
1980,
33,
796.