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Synthesis of asymmetric 1-amino-2-phenylcyclopropanecarboxylic acids by diastereoselective cyclopropanation of highly functionalized homochiral olefines
Tetrahedron Letters,Vo1.30,No.23,pp Printed in Great Britain
SYNTHESIS BY
OF
ASYMMETRIC
3101-3104,1989
l-AMINO-2-PHENYLCYCLOPROPANECARBOXYLIC
DIASI-EREOSELECTIVE
CYCLOPROPANATION HOMOCHIRAL
Ma Dolores
Fernandez,
Eldiberto
Instituto
de Quimica
Aba&aot
-
0040-4039/89 $3.00 + -00 Maxwell Pergamon Macmillan P~C
FUNCTIONALIZED
OLEFINES
Ma Pilar
de Frutos,
Fernindez-Alvarez,
Organica,
OF HIGHLY
ACIDS
Jose
and Manuel
L. Marco,
BernabC*
CSIC, Juan de la Cierva
3, 28006 Madrid,
Spain.
benzy.Liddened.iktiop.ipe~az.inine and c( -benzoykmLnotizomtihane @J.&J kiyh to good tinte4eomeC..c 4aLia ad crpkopqaazoLine de,tiuativecr which, on photo.tqnA and acid hydtloLqh.in 06 Me tre.nu&@ ~p.i~ocyc~op4opy~ compounder gave, cespectiviveeq, (+Iand i-l-1-amino-2-phevly&qcLop4opantca4boxqLk acidn.
c&nam~c
tfomockinad
e&tend
XQ.RCRukth
have attracted special interest l-amino-l-cyclopropanecarboxylic acids I-9 Although several procedures for the preparation of their documented biological activity. 6-16 class of aminoacids have been described, an inexpensive and general synthetic method
During
the
because of this
last
for producing
years,
enantiomeric
pure
forms
of these
compounds
is still
lacking.
We have reported a simple method to produce racemic (Z)- and (E)-l-amino-2-arylcyclo11 starting from inexpensive 4-arylidene-oxazolones. This still appeared propanecarboxylic acids, convenient syntons
approach were
cyclopropanation,
overall
yield
single usual
to
key step
treatment
of the
On the other gave
91% of the
photolytic cyclopropyl silica
treatment
modifications which
(>95 %) of
was
the
reacted
with
corresponding
spirocyclopropane
homochiral of the
acid
easily
(Sa),
cleavage
of the
ester
6 (Scheme
II).
diastereoisomers,
gel (3 % MeOH/CH2C12).
amino-2-phenylcyclopropanecarboxylic
which
pyrazoline were
separated
Acid hydrolysis acid
the
starting
asymmetric
3101
the
resulting
(Z)-oxazolone
on photolysis
in the
of
57% of
by medium
pressure
ester
mixture
70% with
the
(+)-lstarting
(-)-N-methylephedrine
diazomethane a
of
solid.
lb with
gave
and
2 I7 in an almost
of 4 yielded
from
of the
major
L-proline,
give 70% of an
319 which
Cycloaddition
of the
(Sb).
to
hydrolysis
isolated
mixture
with
(la)
pyrazoline
similar
resulting
of induce
gave diketopiperazine diazomethane
4. Acid
at pH =8 and recrystallization hand,
could
process.
I). This
90% of the
by precipitation
pertinent
substituents
( Z ) -2-methyl-4-benzylideneoxazolone
amino-2phenyl-cyclopropanecarboxylic L-proline
provided
homochiral
N-acetyl-phenyldehydroalanyl-L-proline
of 72%, (Scheme
diastereoisomer
include
in the
of
resulting
way produced
synthesis,
asymmetric
in order
the
Thus, cyclisation
for
made
as a
mixture column
and of
subsequent
both
possible
chromatography
7a (66 %) produced
65 % of (-)-l-
on
3102
SCHEME
I”’
1892o
rib 0
a,b
Ph
Ni
0
CH3
(a) r-t.;
NaOH; I9
(d)
S-Proline,
H20-acetone,
hv, benzene,
7 h.;
(e)
r.t. 12 h.; fb) 6N
HCl-HOAc,
SCHEME
(a>
(-)-N-~ethylephedrine,
benzene
6 h.; (c)
6N
HNa, THF, HCl-dioxane,
r-t, 2 h.;
100°C,
17 h.
Iib,
(b)
Ac20,
r-t. 48 h.;
100°C,
24 h.
(cf
CHZN2/benzene,
3 days,
1852o
(1)
CH2N2/C13CH,
-20°,
3.5 days.
(2)
hv,
3103
The chemical graphic
depicted
shifts
of
analysis
absolute
the
of
Further
configuration
diastereoisomers
deacetylated studies
4.
on the
of
of
compounds
compound
3 - 7
4, and
later
were
estimated
corroborated
‘H-NMR
from
by
X-ray
crystallo-
21
scope
and
limitations
of
the
method
are
under
way.
Acknowledgments The QuImica cicin
authors
Organica,
y Ciencia
wish
to
express
Universidad for
de
scholarships
their
appreciation
Zaragoza,
(M.D.F.
Spain,
and
to
for
M.P.F.)
helpful
and
C.
Prof.
Cativiela,
discussions;
DGICYT
Departamento
to
(Grant
Ministerio
PR
de
84-0089)
for
de Educa-
financial
support.
References 1.
(a)
2.
K.
and
notes
R. J. Breckenridge,
(b)
C. J. Suckling, Shiraishi,
BLoiae. Chem. 3.
Ang.gew. Chem.
K.
Konoma,
1979,
43,
C. Walsh,
R. A. Pascal,
1981,
7509.
20,
H.
R. Raines,
(b)
I. Arenal,
(a)
M. C. Pirrung,
_T. Am. Chem.
(b)
M. C. Pirrung,
G.
N. Kurokawa,
8.
K.
9.
M. Bernab6,
10.
11.
Cuevas,
Yamanoi,
Y. 0.
(a)
S. W. King,
1983,
Ohfune,
A.
Anger.
Chern.
Itit.
1985,
T&rahedaon
M. Adlington,
B. J.
Rawlings,
Tti4ahcd4on
Lti.
1988,
E.
M. Holt,
C.
C. H.
Stammer,
K. I. Varughese,
C. H.
Stammer,
&id.
(d)
L.
(a)
I. Arenal,
(b)
M. Holt,
M. Bernabe,
I. Arenal,
M. Bernab6,
M. L.
13.
C. Cativiela,
14.
T.
Wakamiya,
Y. Oda,
U.
Schijllkopf,
M. Hauptreif,
25,
192.
therein. P. Sakai,
Agtti.
C.
1988,
Mapelli,
Q&n.
M. Homma,
1979,
75,
Biochemtiint4y
977.
L&did. 1983,
79C,
65.
Iti.
Ed.
26,
Eq!L.
27,
C. H.
53,
1985,
24,
1044.
83. Le*;t.
1985,
26,
481.
537.
J.
Med.
ibid.
Chem.
1979,
J.
045.
1984,
49,
14,
Chem.
35. 1982,
47,
3270.
1634.
992.
Stammer,
J.
Chem.
E. Fernandez-Alvarez,
M. L. Izquierdo,
E. Fernindez-Alvarez,
S. Penad&,
Sot.
Chem.
S. Penad&,
Cotnmun. 1988, _7.
252.
tfti~0cyc-e.
607.
12.
Izquierdo,
references
Nishiyama,
A. Krantz,
H. Stammer,
M. Bland,
20,
N.
M. Gibello,
Em.
A. Bartolussi,
1983,
537 and
Te.&ahedton
E. Fernandez-Alvarez,
J. M. Riordan,
E.
5665.
105, 7207.
J.
Chem.
15.
Sot.
M. McGeehan,
Cuevas,
An.
(b)
Elrod,
27,
D. Dikskit,
(c)
F.
42,
Sakamura,
E. Fernandez-Alvarez,
Ohfune,
R.
1988, K.
E. Fernandez-Alvarez,
M. Bernabe,
Y.
Enge.
M. Johnston,
5.
J. E. Baldwin,
1986,
1753.
M. Bernabe,
7.
Ed.
A. Ichibara,
(a)
0.
Int.
Sato,
4.
6.
Ttimhedmn
C. J_ Suckling,
I. Arenal, M. D. Diaz
M. Bernabe, de
Villegas,
H. Fujita,
T.
J. Dippel,
E. Fern&ndez-Alvarez, E.
Mel&ndez,
Shiba,
M. Nieger,
1985,
Ttiaahedaon
Tettahednon
Ttitahedeon
SynZhesA
LeM.
E. Egert,
1985,
1986,
42,
583.
1986,
27,
2143.
Anyew.
Chem.
773.
Iti.
40,
Ed.
215.
EngL. 1986,
3104
16.
U. Schijllkopf,
B. Hupfeld,
17.
H. Poisel,
18.
All new compounds 1 H-NMR parameters
U. Schmidt,
(m, 3H, proline); J = 8.0 Hz);
R. Gull,
Chm.
of selected
4: d (C13CD);
propane,
IR and
derivatives
2.30 (s, 3H, CH3);
cu. 3.68 (m,
2.67 (dd,
6.7 Hz); 1.90 (dd, 6H (CH3)2N);
proline);
ca. 2.2 (m,
, J = 7.0, J = 9.8 Hz); ca.3.56
cu. 7.2 (m, SH, arom.). ca. 7.25 (m,
lH,
NH);
2.30 (dd,
cu.7.3
(m,
7.0, J = 8.4 Hz); 1.94
J = 9.6,
and
1~1~
Compound J = 7.0,
of relevant
KdUeS
[a]“,” +570 (c 0.28, C13CH). Compound 4: mp 144T;
(c 0.69, (dec.);
(Received
[a]‘,’
will be reported in
(dd,
(d,
lH,
5b: 6 (D20); J = 9.8 Hz);
4.11 (dd, lH, proline,
compounds
analysis were
3: mp 171-3OC;
3H, CH3, 2.32
J= (s,
J = 9.3, J = 8.1 Hz); 6.00 arom.).
Compound
%Z 6
J = 6.0, J = 8.0 Hz); 2.29 cu. 2.83 (m,
lH,
J = 4.8
CH-CH3);
Hz);
6.17
(s,
lH,
cyclopropane,
J =
lH,
cyclopropane,
J =
of the
crude reaction mixtures.
as foIIows:
comnound
[a]:
(c 0.22, C13CH). Com-
-266’
5a: mp 201°C
(c 1.1,
C13CH).
7b: syrup;
not
-103O (C 0.76, H20).
(d,
1.80 (dd,
C13CH). Compound
1989)
cycle-
3.15 (dd,
Compound
UK 6 March
Com-
lH,
cyclopropane);
CH-Ph,
(c 1.1, Cl CH). 2s3 6: 63-5’C; [a) u +95’
soon elsewhere.
(dd,
J =
J = 6.5, J = 9.8 Hz);
0.98
lH,
cyclopropane,
6.00
H-NMR
-270°
H 0). Compound 225 \a] D -12.50 (c 4.3,
mp 199oC (dec.); Details
[e]g
7% 6 (Ci3CD);
J = 6.0, J = 9.6 Hz);
Melting
points
lH,
Hz);
20.
J = 7.8,
pyrazohne,
1.66 (dd, lH, cyclopropane,
lH, cyclopropane,
9.8, J = 8.4 Hz); CU. 7.3 (m, SH, arom.). Diastereomeric ratios were determined by 1
cu. 2.0
CH-Ph,
2.31
( m, 2H, proline);
cu. 7.3 (m, lSH,
19.
Relevant
(m, SH, arom.).
lH, cyclopropane,
Hz); 2.30
1.88 (dd,
cyclopropane,
ca.7.2
NH);
J = 8.0
15H, arom.).
(dd,
lH,
2H, proline);
3.08 (dd,
iH, cyclopropane,
cyclopropane,
(dd,
5.10 (dd, lH,
5a: 6 (D20)
Compound
J = 6.0, J=8.1
J = 4.2 Hz); 6.19 (s, broad,
(s, 6H, (CH3)2N);
3.66
data.
3: 6 (C13CD):
J = 7.0, J = 9.6 Hz); 3.03 (dd, lH, cyclopropane,
SH, arom.).
(C13CD); 1.01 (d, 3H, CH3, J = 6.8 Hz);
3.05 (dd,
Compound
lH, cyciopropane,
lH, cyclopropane,
compound
J= 9.0, J= 18.0 Hz);
ca. 2.82 (m, lH, Cff -CH3);
(d, lH, OCH-Ph,
21.
lH,
2.3 (m,
(m, 2H, proline);
lH, cyclopropane
J = 8.3, J= 9.6 Hz);
pound
or HRMS analytical
as follows:
cu.. 3.82 (m, 2H, proline);
lH, pyrazoline,
ca.2.0
elementary
were
ca.
lH, proline);
J = 7.0, J = 8.3 Hz); 1.80 (dd,
5%;
Ed. EngL. 1986, 25, 1754.
lti.
J = 6.5; J = 7.0 Hz); 2.33 (s, 3H, CH3); 2.60 (dd,
J = 7.9, J = 7.7 Hz);
broad,
&cm.
Be&. 1973, 106, 3408.
gave satisfactory
7.8, J = 18.0 Hz); 5.28 (dd, pound
AWE.
Compound
further
(dec.); 7a:
purified.
2: mn 163-
[o]~$ +105’ mp
119-22OC
Compound
5b:
SYNTHESIS BY
OF
ASYMMETRIC
3101-3104,1989
l-AMINO-2-PHENYLCYCLOPROPANECARBOXYLIC
DIASI-EREOSELECTIVE
CYCLOPROPANATION HOMOCHIRAL
Ma Dolores
Fernandez,
Eldiberto
Instituto
de Quimica
Aba&aot
-
0040-4039/89 $3.00 + -00 Maxwell Pergamon Macmillan P~C
FUNCTIONALIZED
OLEFINES
Ma Pilar
de Frutos,
Fernindez-Alvarez,
Organica,
OF HIGHLY
ACIDS
Jose
and Manuel
L. Marco,
BernabC*
CSIC, Juan de la Cierva
3, 28006 Madrid,
Spain.
benzy.Liddened.iktiop.ipe~az.inine and c( -benzoykmLnotizomtihane @J.&J kiyh to good tinte4eomeC..c 4aLia ad crpkopqaazoLine de,tiuativecr which, on photo.tqnA and acid hydtloLqh.in 06 Me tre.nu&@ ~p.i~ocyc~op4opy~ compounder gave, cespectiviveeq, (+Iand i-l-1-amino-2-phevly&qcLop4opantca4boxqLk acidn.
c&nam~c
tfomockinad
e&tend
XQ.RCRukth
have attracted special interest l-amino-l-cyclopropanecarboxylic acids I-9 Although several procedures for the preparation of their documented biological activity. 6-16 class of aminoacids have been described, an inexpensive and general synthetic method
During
the
because of this
last
for producing
years,
enantiomeric
pure
forms
of these
compounds
is still
lacking.
We have reported a simple method to produce racemic (Z)- and (E)-l-amino-2-arylcyclo11 starting from inexpensive 4-arylidene-oxazolones. This still appeared propanecarboxylic acids, convenient syntons
approach were
cyclopropanation,
overall
yield
single usual
to
key step
treatment
of the
On the other gave
91% of the
photolytic cyclopropyl silica
treatment
modifications which
(>95 %) of
was
the
reacted
with
corresponding
spirocyclopropane
homochiral of the
acid
easily
(Sa),
cleavage
of the
ester
6 (Scheme
II).
diastereoisomers,
gel (3 % MeOH/CH2C12).
amino-2-phenylcyclopropanecarboxylic
which
pyrazoline were
separated
Acid hydrolysis acid
the
starting
asymmetric
3101
the
resulting
(Z)-oxazolone
on photolysis
in the
of
57% of
by medium
pressure
ester
mixture
70% with
the
(+)-lstarting
(-)-N-methylephedrine
diazomethane a
of
solid.
lb with
gave
and
2 I7 in an almost
of 4 yielded
from
of the
major
L-proline,
give 70% of an
319 which
Cycloaddition
of the
(Sb).
to
hydrolysis
isolated
mixture
with
(la)
pyrazoline
similar
resulting
of induce
gave diketopiperazine diazomethane
4. Acid
at pH =8 and recrystallization hand,
could
process.
I). This
90% of the
by precipitation
pertinent
substituents
( Z ) -2-methyl-4-benzylideneoxazolone
amino-2phenyl-cyclopropanecarboxylic L-proline
provided
homochiral
N-acetyl-phenyldehydroalanyl-L-proline
of 72%, (Scheme
diastereoisomer
include
in the
of
resulting
way produced
synthesis,
asymmetric
in order
the
Thus, cyclisation
for
made
as a
mixture column
and of
subsequent
both
possible
chromatography
7a (66 %) produced
65 % of (-)-l-
on
3102
SCHEME
I”’
1892o
rib 0
a,b
Ph
Ni
0
CH3
(a) r-t.;
NaOH; I9
(d)
S-Proline,
H20-acetone,
hv, benzene,
7 h.;
(e)
r.t. 12 h.; fb) 6N
HCl-HOAc,
SCHEME
(a>
(-)-N-~ethylephedrine,
benzene
6 h.; (c)
6N
HNa, THF, HCl-dioxane,
r-t, 2 h.;
100°C,
17 h.
Iib,
(b)
Ac20,
r-t. 48 h.;
100°C,
24 h.
(cf
CHZN2/benzene,
3 days,
1852o
(1)
CH2N2/C13CH,
-20°,
3.5 days.
(2)
hv,
3103
The chemical graphic
depicted
shifts
of
analysis
absolute
the
of
Further
configuration
diastereoisomers
deacetylated studies
4.
on the
of
of
compounds
compound
3 - 7
4, and
later
were
estimated
corroborated
‘H-NMR
from
by
X-ray
crystallo-
21
scope
and
limitations
of
the
method
are
under
way.
Acknowledgments The QuImica cicin
authors
Organica,
y Ciencia
wish
to
express
Universidad for
de
scholarships
their
appreciation
Zaragoza,
(M.D.F.
Spain,
and
to
for
M.P.F.)
helpful
and
C.
Prof.
Cativiela,
discussions;
DGICYT
Departamento
to
(Grant
Ministerio
PR
de
84-0089)
for
de Educa-
financial
support.
References 1.
(a)
2.
K.
and
notes
R. J. Breckenridge,
(b)
C. J. Suckling, Shiraishi,
BLoiae. Chem. 3.
Ang.gew. Chem.
K.
Konoma,
1979,
43,
C. Walsh,
R. A. Pascal,
1981,
7509.
20,
H.
R. Raines,
(b)
I. Arenal,
(a)
M. C. Pirrung,
_T. Am. Chem.
(b)
M. C. Pirrung,
G.
N. Kurokawa,
8.
K.
9.
M. Bernab6,
10.
11.
Cuevas,
Yamanoi,
Y. 0.
(a)
S. W. King,
1983,
Ohfune,
A.
Anger.
Chern.
Itit.
1985,
T&rahedaon
M. Adlington,
B. J.
Rawlings,
Tti4ahcd4on
Lti.
1988,
E.
M. Holt,
C.
C. H.
Stammer,
K. I. Varughese,
C. H.
Stammer,
&id.
(d)
L.
(a)
I. Arenal,
(b)
M. Holt,
M. Bernabe,
I. Arenal,
M. Bernab6,
M. L.
13.
C. Cativiela,
14.
T.
Wakamiya,
Y. Oda,
U.
Schijllkopf,
M. Hauptreif,
25,
192.
therein. P. Sakai,
Agtti.
C.
1988,
Mapelli,
Q&n.
M. Homma,
1979,
75,
Biochemtiint4y
977.
L&did. 1983,
79C,
65.
Iti.
Ed.
26,
Eq!L.
27,
C. H.
53,
1985,
24,
1044.
83. Le*;t.
1985,
26,
481.
537.
J.
Med.
ibid.
Chem.
1979,
J.
045.
1984,
49,
14,
Chem.
35. 1982,
47,
3270.
1634.
992.
Stammer,
J.
Chem.
E. Fernandez-Alvarez,
M. L. Izquierdo,
E. Fernindez-Alvarez,
S. Penad&,
Sot.
Chem.
S. Penad&,
Cotnmun. 1988, _7.
252.
tfti~0cyc-e.
607.
12.
Izquierdo,
references
Nishiyama,
A. Krantz,
H. Stammer,
M. Bland,
20,
N.
M. Gibello,
Em.
A. Bartolussi,
1983,
537 and
Te.&ahedton
E. Fernandez-Alvarez,
J. M. Riordan,
E.
5665.
105, 7207.
J.
Chem.
15.
Sot.
M. McGeehan,
Cuevas,
An.
(b)
Elrod,
27,
D. Dikskit,
(c)
F.
42,
Sakamura,
E. Fernandez-Alvarez,
Ohfune,
R.
1988, K.
E. Fernandez-Alvarez,
M. Bernabe,
Y.
Enge.
M. Johnston,
5.
J. E. Baldwin,
1986,
1753.
M. Bernabe,
7.
Ed.
A. Ichibara,
(a)
0.
Int.
Sato,
4.
6.
Ttimhedmn
C. J_ Suckling,
I. Arenal, M. D. Diaz
M. Bernabe, de
Villegas,
H. Fujita,
T.
J. Dippel,
E. Fern&ndez-Alvarez, E.
Mel&ndez,
Shiba,
M. Nieger,
1985,
Ttiaahedaon
Tettahednon
Ttitahedeon
SynZhesA
LeM.
E. Egert,
1985,
1986,
42,
583.
1986,
27,
2143.
Anyew.
Chem.
773.
Iti.
40,
Ed.
215.
EngL. 1986,
3104
16.
U. Schijllkopf,
B. Hupfeld,
17.
H. Poisel,
18.
All new compounds 1 H-NMR parameters
U. Schmidt,
(m, 3H, proline); J = 8.0 Hz);
R. Gull,
Chm.
of selected
4: d (C13CD);
propane,
IR and
derivatives
2.30 (s, 3H, CH3);
cu. 3.68 (m,
2.67 (dd,
6.7 Hz); 1.90 (dd, 6H (CH3)2N);
proline);
ca. 2.2 (m,
, J = 7.0, J = 9.8 Hz); ca.3.56
cu. 7.2 (m, SH, arom.). ca. 7.25 (m,
lH,
NH);
2.30 (dd,
cu.7.3
(m,
7.0, J = 8.4 Hz); 1.94
J = 9.6,
and
1~1~
Compound J = 7.0,
of relevant
KdUeS
[a]“,” +570 (c 0.28, C13CH). Compound 4: mp 144T;
(c 0.69, (dec.);
(Received
[a]‘,’
will be reported in
(dd,
(d,
lH,
5b: 6 (D20); J = 9.8 Hz);
4.11 (dd, lH, proline,
compounds
analysis were
3: mp 171-3OC;
3H, CH3, 2.32
J= (s,
J = 9.3, J = 8.1 Hz); 6.00 arom.).
Compound
%Z 6
J = 6.0, J = 8.0 Hz); 2.29 cu. 2.83 (m,
lH,
J = 4.8
CH-CH3);
Hz);
6.17
(s,
lH,
cyclopropane,
J =
lH,
cyclopropane,
J =
of the
crude reaction mixtures.
as foIIows:
comnound
[a]:
(c 0.22, C13CH). Com-
-266’
5a: mp 201°C
(c 1.1,
C13CH).
7b: syrup;
not
-103O (C 0.76, H20).
(d,
1.80 (dd,
C13CH). Compound
1989)
cycle-
3.15 (dd,
Compound
UK 6 March
Com-
lH,
cyclopropane);
CH-Ph,
(c 1.1, Cl CH). 2s3 6: 63-5’C; [a) u +95’
soon elsewhere.
(dd,
J =
J = 6.5, J = 9.8 Hz);
0.98
lH,
cyclopropane,
6.00
H-NMR
-270°
H 0). Compound 225 \a] D -12.50 (c 4.3,
mp 199oC (dec.); Details
[e]g
7% 6 (Ci3CD);
J = 6.0, J = 9.6 Hz);
Melting
points
lH,
Hz);
20.
J = 7.8,
pyrazohne,
1.66 (dd, lH, cyclopropane,
lH, cyclopropane,
9.8, J = 8.4 Hz); CU. 7.3 (m, SH, arom.). Diastereomeric ratios were determined by 1
cu. 2.0
CH-Ph,
2.31
( m, 2H, proline);
cu. 7.3 (m, lSH,
19.
Relevant
(m, SH, arom.).
lH, cyclopropane,
Hz); 2.30
1.88 (dd,
cyclopropane,
ca.7.2
NH);
J = 8.0
15H, arom.).
(dd,
lH,
2H, proline);
3.08 (dd,
iH, cyclopropane,
cyclopropane,
(dd,
5.10 (dd, lH,
5a: 6 (D20)
Compound
J = 6.0, J=8.1
J = 4.2 Hz); 6.19 (s, broad,
(s, 6H, (CH3)2N);
3.66
data.
3: 6 (C13CD):
J = 7.0, J = 9.6 Hz); 3.03 (dd, lH, cyclopropane,
SH, arom.).
(C13CD); 1.01 (d, 3H, CH3, J = 6.8 Hz);
3.05 (dd,
Compound
lH, cyciopropane,
lH, cyclopropane,
compound
J= 9.0, J= 18.0 Hz);
ca. 2.82 (m, lH, Cff -CH3);
(d, lH, OCH-Ph,
21.
lH,
2.3 (m,
(m, 2H, proline);
lH, cyclopropane
J = 8.3, J= 9.6 Hz);
pound
or HRMS analytical
as follows:
cu.. 3.82 (m, 2H, proline);
lH, pyrazoline,
ca.2.0
elementary
were
ca.
lH, proline);
J = 7.0, J = 8.3 Hz); 1.80 (dd,
5%;
Ed. EngL. 1986, 25, 1754.
lti.
J = 6.5; J = 7.0 Hz); 2.33 (s, 3H, CH3); 2.60 (dd,
J = 7.9, J = 7.7 Hz);
broad,
&cm.
Be&. 1973, 106, 3408.
gave satisfactory
7.8, J = 18.0 Hz); 5.28 (dd, pound
AWE.
Compound
further
(dec.); 7a:
purified.
2: mn 163-
[o]~$ +105’ mp
119-22OC
Compound
5b: