Catalytic cyclopropanation of ricinolic acid derivatives with diazomethane

Article abstract of DOI:10.1023/A:1012471011407

The reaction of ricinolic acid methyl ester with diazomethane in the presence of Co(BF₄)₂·6H₂O results in selective methylation of the hydroxy group. Methyl (2Z, 12R)-12-acetoxy-9-octadecenoate reacts with diazomethane in the presence of Pd(acac)₂, leading to formation of a mixture of cis-cyclopropanated (9S, 10S, 12/R)- and (9R, 10R, 12R)-diastereoisomers at a ratio of 3:2 (overall yield 73%). Under similar conditions methyl (9Z)-12-oxo-9-octadecenoate gives rise to optically inactive methyl cis-8-[2-(2-oxooctyl)-cyclopropyl]octanoate.

Full text of DOI:10.1023/A:1012471011407

Russian Journal of Organic Chemistry, Vol. 37, No. 5, 2001, pp. 608 611. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 5, 2001,
pp. 652 655.
Original Russian Text Copyright
2001 by Davletbakova, Maidanova, Baibulatova, Dokichev, Tomilov, Yunusov, Nefedov.
Catalytic Cyclopropanation of Ricinolic Acid Derivatives
with Diazomethane
1
1
1
1
A. M. Davletbakova , I. O. Maidanova , N. Z. Baibulatova , V. A. Dokichev ,
2
1
2
Yu. V. Tomilov , M. S. Yunusov , O. M. Nefedov
1
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
fax: (3472)356066; e-mail: chemorg@anrb.ru
2
Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
Received October 17, 1999
Abstract The reaction of ricinolic acid methyl ester with diazomethane in the presence of Co(BF4)2 6H O
2
results in selective methylation of the hydroxy group. Methyl (2Z,12R)-12-acetoxy-9-octadecenoate reacts
with diazomethane in the presence of Pd(acac) , leading to formation of a mixture of cis-cyclopropanated
2
(9S,10S,12R)- and (9R,10R,12R)-diastereoisomers at a ratio of 3: 2 (overall yield 73%). Under similar
conditions methyl (9Z)-12-oxo-9-octadecenoate gives rise to optically inactive methyl cis-8-[2-(2-oxooctyl)-
cyclopropyl]octanoate.
Due to its accessibility and the presence of a chiral
R-center in position 12, ricinolic acid [(9Z,12R)-12-
hydroxy-9-octadecenoic acid] is a promising synthon
for preparation of optically active polyfunctional
compounds [1, 2]. Ricinolic acid derivatives also
attract interest as suicidal lipoxygenase substrates [3].
Until present, there were almost no published data on
the synthesis of cyclopropane-containing ricinolic acid
derivatives. The procedure for Simmons Smit cyclo-
propanation of ricinolic acid methyl ester was reported
to occur with low regioselectivity; no data on optical
activity of the products were given [4, 5]. We pre-
viously found [6] that catalytic [1+2]-cycloaddition
of methylene species generated from diazomethane at
double C C bonds of unsaturated compounds is
a convenient method of synthesis of cyclopropanes.
diazomethane, catalyzed by copper and palladium
compounds. Methyl (9Z,12R)-12-methoxy-9-octa-
decenoate (II, [ ]2 = +8.33 ) was synthesized in
8
D
98% yield by reaction of ester I with 4-fold excess of
diazomethane in pentane at 20 C in the presence of
Co(BF ) 6H O as catalyst. The insertion of CH
4
2
2
2
group into the O H bond occurred with retention of
the optically active R-center (Scheme 1).
Under the selected conditions [substrate-to-CH N -
2
2
to-catalyst ratio 1:5:0.01; 0 C, Et O or CH Cl ;
2
2
2
catalyst = Cu(CF SO ) , Pd(OAc) , or Pd(acac) ],
3
3 2
2
2
the double C C bonds in olefins I and II were not
involved, despite vigorous decomposition of CH N .
2
2
Diastereofacial differentiation, resulting from
intramolecular asymmetric induction, was observed
only in the cyclopropanation of methyl (9Z,12R)-12-
acetoxy-9-octadecenoate (III) which reacted with
The present communication reports on the results
of our study of the reaction of methyl (9Z,12R)-12-
hydroxy-, (9Z,12R)-12-methoxy-, (9Z,12R)-12-acet-
oxy-, and (9Z)-12-oxo-9-octadecenoates I IV with
diazomethane in the presence of Pd(acac) . The prod-
2
ucts were methyl cis-(9S,10S,12R)-12-acetoxy-9,10-
methyleneoctadecanoate (Va) and cis-(9R,10R,12R)-
Scheme 1.
1
070-4280/01/3705-0608$25.00 2001 MAIK Nauka/Interperiodica

CATALYTIC CYCLOPROPANATION OF RICINOLIC ACID DERIVATIVES
609
Scheme 2.
Catalyst
Yield, %
Ratio Va:Vb
Pd(acac)2
73
5
25
3:2
3:2
4:5
Pd(OAc)2
Cu(CF SO )
3
3 2
1
2-acetoxy-9,10-methyleneoctadecanoate (Vb) at
published in [2, 7, 8]. The Va:Vb isomer ratio was
a ratio of 3:2, which we failed to separate (Scheme 2).
The overall yield was 73%, [ ] = +16.1 . With
Pd(OAc) or Cu(CF SO ) as catalyst the yield of
compounds Va and Vb was reduced to 5 25%. Unlike
Pd(acac) and Pd(OAc) , Cu(CF SO ) favored pre-
dominant formation of isomer Vb.
determined from the 13C NMR spectra.
2
0
In order to prove that intramolecular asymmetric
induction originates from the chiral R-center in posi-
tion 12, compound I was oxidized according to Col-
lins [3] to obtain methyl (9Z)-12-oxo-9-octadecenoate
(IV) which was then treated with diazomethane in
D
2
3
3 2
2
2
3
3 2
the presence of Pd(acac) . We thus isolated 83% of
methyl cis-8-[2-(2-oxooctyl)cyclopropyl]octanoate
The structure of products Va and Vb was con-
firmed by spectral data. Most proton signals in the
H NMR spectra were unresolved multiplets located in
2
1
(
VI) (Scheme 3). According to the spectral and
chromatographic data, product VI was an individual
a narrow range. Two triplets at
0.33 and 0.29 ppm
3
optically inactive substance.
(
J = 6.3 Hz) with an overall intensity corresponding
to one proton belong to the cis-proton of the cyclo-
propane methylene group; the substituents in the
cyclopropane ring are arranged cis. Splitting of the
above signal is caused by diastereotopic effect. In the
two-dimensional H H COSY spectrum we observed
cross peaks resulting from spin spin coupling between
Our results show that the reactivity of the cis-C C
bond increases on introduction of a carbonyl or car-
boxy group into the homoallylic position. Probably,
such groups favor formation of intramolecular -com-
plexes of palladium with olefins III and IV. The
result is that their coordinating activity increases.
In keeping with the data of [6], just this factor is
responsible for the reactivity of unsaturated com-
pounds in cyclopropanation with diazomethane in the
presence of palladium catalysts.
1
1
the upfield triplets (
0.33 and 0.29 ppm) and
a three-proton multiplet in the region 0.5 0.7 ppm;
the latter corresponds to one trans- and two cis-
1
3
protons of the cyclopropane ring. The C NMR spec-
trum recorded with broad-band decoupling from
9
13
protons contained paired signals from the C C
atoms. The small difference in their chemical shifts
0.1 0.5 ppm) suggests that magnetic nonequiv-
EXPERIMENTAL
The H and 13C NMR spectra were taken on
1
(
C
alence of the corresponding nuclei is determined by
diastereotopicity rather than by cis/trans isomerism,
otherwise the difference between the chemical shifts
a Bruker AM-300 spectrometer in CDCl . The IR
3
spectra were recorded on a Specord M-80 instrument
from samples prepared as thin films. The mass spectra
(electron impact, 70 and 12 eV) were obtained on
an MKh-1300 spectrometer, batch inlet temperature
100 C. The products were analyzed on a Chrom-5
8
11
of -CH (C and C ) would be as large as 10 ppm.
2
The diastereoisomeric configurations were derived
from comparison of our spectral data with those
Scheme 3.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 5 2001

6
10
DAVLETBAKOVA et al.
chromatograph, flame-ionization detector, 1200
-mm column packed with 5% of SE-30 on Inerton
(7.5 mmol) of acetyl chloride in 2 ml of benzene.
The mixture was refluxed for 2 h, cooled, and washed
in succession with a saturated solution of NaHCO3
(3 5 ml) and with water (5 ml). The benzene layer
was separated, and the aqueous layer was extracted
with diethyl ether (3 3 ml). The combined extracts
5
N-AW DMCS (0.125 0.160 mm), carrier gas helium.
The optical rotations were measured on a Perkin
Elmer 241 MC spectropolarimeter. Compounds Va,
Vb, and VI were isolated by preparative gas liquid
chromatography using a Perkin Elmer F21 instru-
ment; 5000 8-mm column packed with 5% of SE-30
on Inerton N-AW; oven temperature 220 C.
were dried over MgSO and evaporated to isolate
4
2
0
2.2 g (98%) of ester III, [ ] = +21.05 . IR spec-
trum, , cm : 732, 760, 1024, 1184, 1244 (OAc),
372, 1449, 1460, 1740 (CO ), 2360, 2928. H NMR
D
1
1
1
Methyl (9Z)-12-oxo-9-octadecenoate (IV) was syn-
thesized by the procedure reported in [3].
2
spectrum, , ppm: 0.85 t (3H, CH , J = 7.9 Hz), 1.14
3
1
.67 m (20H, CH ), 1.90 1.98 m (4H, CH C ), 2.0 s
2 2
Methyl (9Z,12R)-12-hydroxy-9-octadecenoate (I).
A solution of 10 g of castor oil in 20 ml of toluene
was added dropwise to 100 ml of a 0.5% solution
of sodium methoxide in toluene. The mixture was
stirred for 10 min at 50 C, evaporated by half, and
neutralized with acetic acid. Water, 70 ml, was added,
ester I was extracted into petroleum ether (bp 40
(
3H, CH CO ), 2.28 t (2H, 2-H, J = 7.5 Hz), 3.65 s
3 2
(
5
3H, COOCH ), 4.85 m (1H, 12-H, J = 6.2 Hz), 5.25
3
1
3
.50 m (2H, CH CH, J = 7.2 Hz). C NMR spec-
1
8
trum,
, ppm: 14.08 q (C ), 21.28 q (COCH ),
C
3
1
7
3
14
22.59 t (C ), 24.93 t (C ), 25.37 t (C ), 27.30 t
(
3
5
1
1
3
4
5
6
7
15
C ), 29.10 t (C , C , C ), 29.15 t (C ), 29.50 t (C ),
6
0 C), and the extract was washed with water, dried
8
16
11
2
1.75 t (C ), 31.92 t (C ), 33.59 t (C ), 34.06 t (C ),
1.46 q (CO CH ), 73.98 d (C ), 124.23 d (C ),
32.61 d (C ), 170.83 s (CO), 174.29 s (C ). Mass
over Na SO , and evaporated. The residue was sub-
12
10
2
4
2
3
jected to column chromatography on silica gel L
100/160 m) with gradient elution by petroleum
ether diethyl ether (1 to 100% of the latter). We
9
1
(
+
spectrum: m/z 354 [M] .
2
0
Cyclopropanation of ester III with diazomethane
isolated 9.6 g (96%) of compound I, [ ] = +4.98 .
D
in the presence of Pd(acac) . a. To a mixture of
Methyl (9Z,12R)-12-methoxy-9-octadecenoate
II). To a mixture of 0.2 g (0.64 mmol) of ester I and
2
0
.5 g (1.4 mmol) of ester III and 4.3 mg (1 mol %)
(
of Pd(acac) in 2 ml of Et O we added dropwise
4
.36 mg (2 mol %) of Co(BF ) 6H O in 2 ml of
2
2
4
2
2
while stirring at 0 C a solution of 28 mmol of
diazomethane, prepared from 5.8 g (56 mmol) of
N-methyl-N-nitrosourea in 60 ml of diethyl ether.
The mixture was stirred for 2 h at 0 C until bright
yellow color disappeared and was left overnight at
room temperature. It was then passed through a layer
pentane we slowly added with stirring at 20 C a solu-
tion of 2.56 mmol of diazomethane prepared from
0
.53 g (5.12 mmol) of N-methyl-N-nitrosourea in 5 ml
of pentane. The mixture was kept for about 2 h until
bright yellow color disappeared. It was then filtered
and evaporated to obtain 0.2 g (98%) of ester II,
2
8
of Al O and evaporated to obtain 0.68 g of a mixture
[
]
= +8.33 (c = 1.4, CHCl ). IR spectrum,
,
2
3
D
3
1
containing, according to GLC data, 23% of unchanged
ester III and 73% of methyl cis-(9S,10S,12R)- and
cm : 750, 1125 (C O C), 1190, 1455, 1480, 1740
1
(
CO ), 2875, 2945. H NMR spectrum, , ppm: 0.83 t
2
cis-(9R,10R,12R)-12-acetoxy-9,10-methyleneocta-
(
3H, CH , J = 6.6 Hz), 1.12 1.45, 1.48 1.62 m (20H,
3
20
decanoates Va and Vb at a ratio of 3:2, [ ]D
=
CH ), 1.96 q (2H, CH C , J = 6.4 Hz), 2.18 t (2H,
2
2
1
+
16.7 (c = 1.4, CHCl ). IR spectrum, , cm : 845,
260 (OAc), 1750 (CO ), 2875, 2940, 2970. H NMR
CH C , J = 5.8 Hz), 2.35 t (2H, CH CO , J =
3
2
2
2
1
1
7
3
5
2
.6 Hz), 3.10 m (1H, 12-H), 3.26 s (3H, CH O),
2
3
spectrum, , ppm: 0.33, 0.29 d.t (1H, cis-CH in
cyclopropane ring, J = 6.3 Hz), 0.56 0.73 m (3H,
trans-CH in cyclopropane ring, cis-9-H, cis-10-H),
.60 s (3H, CO CH ), 5.45 m (2H, CH CH, J =
2
3
.8 Hz). 13C NMR spectrum, , ppm: 14.08 q (C ),
18
C
1
7
3
14
2.63 t (C ), 24.93 t (C ), 25.36 t (C ), 27.39 t
1
3
4
5
6
7
15
0.82 t (3H, CH , J = 6.0 Hz), 1.03 m and 1.11 1.40 m
3
(C ), 29.12 t (C , C , C ), 29.50 t (C ), 29.56 t (C ),
8
16
2
11
(18H, CH ), 1.44 1.72 m (6H, 8-H, 11-H, 13-H),
2
3
5
1
1.06 t (C ), 31.87 t (C ), 33.57 t (C ), 34.06 t (C ),
1
2
2.00 s (3H, COCH ), 2.22 t (2H, CH CO , J =
3
2
2
1.39 q (CO CH ), 56.54 q (CH O), 80.97 d (C ),
25.43 d (C ), 131.69 d (C ), 174.23 s (C ). Mass
2
3
3
7
.5 Hz), 3.60 s (3H, CO CH ), 4.81 4.95 m (1H,
1
0
9
1
2 3
+
CHOC O). Mass spectrum: m/z 368 [M] .
+
spectrum: m/z 326 [M] .
1
3
Diastereoisomer Va. C NMR spectrum, C,
Methyl (9Z,12R)-12-acetoxy-9-octadecenoate
1
0
ppm: 11.01 t (CH , cyclopropane), 11.91 d (C ),
1
(C ), 24.84 t (C ), 25.28 t (C ), 28.78 t (C ), 29.12 t
2
(
0
III). To a solution of 2 g (6.4 mmol) of ester I and
.6 g (7.5 mmol) of pyridine in 10 ml of benzene
we added with stirring and cooling to 0 C 0.6 g
1
8
9
3.96 q (C ), 15.44 d (C ), 21.16 q (COCH ), 22.50 t
3
1
7
3
14
8
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 5 2001

CATALYTIC CYCLOPROPANATION OF RICINOLIC ACID DERIVATIVES
611
4
5
6
7
11
(
(
5
1
C , C , C ), 29.19 t (C ), 29.30 t (C ), 29.90 t
cyclopropane ring); 0.82 t (3H, CH , J = 5.6 Hz);
3
1
5
16
13
2
1
7
.15 1.60 m (20H, CH ); 2.20 t (2H, CH CO , J =
C ), 31.67 t (C ), 33.14 t (C ), 33.94 t (C ),
2 2 2
1
2
.5 Hz); 2.30 2.40 m (4H, CH CO); 3.57 s (3H,
1.25 q (CO CH ), 74.91 d (C ), 170.68 s (CO),
74.06 s (C ).
Diastereoisomer Vb. 13C NMR spectrum, C,
2
2
3
1
3
1
CO CH ). C NMR spectrum,
(CH , cyclopropane ring), 10.88 d (C ), 13.90 q (C ),
15.20 d (C ), 22.37 t (C ), 23.64 t (C ), 24.79 t
(C ), 28.80 t (C ), 28.98 t (C ), 29.13 t (C ), 29.21 t
, ppm: 10.71 t
2
3
C
9
18
2
1
0
17
14
1
0
ppm: 10.80 t (CH , cyclopropane), 11.79 d (C ),
2
3
8
7
6
1
8
9
1
(
3.96 q (C ), 14.94 d (C ), 21.16 q (COCH ), 22.50 t
3
4
5
15
16
2
1
7
3
14
4
5
(
C , C ), 29.67 t (C ), 31.50 t (C ), 33.89 t (C ),
C ), 24.84 t (C ), 25.23 t (C ), 29.12 t (C , C ,
1
1
13
6
8
7
11
42.24 t (C ), 42.32 t (C ), 51.25 q (CO CH ),
2 3
C ), 28.67 t (C ), 29.19 t (C ), 29.30 t (C ), 29.90 t
1
12
1
5
16
13
2
174.06 s (C ), 211.36 s (C ). Mass spectrum: m/z
(
5
1
C ), 31.67 t (C ), 33.03 t (C ), 33.94 t (C ),
+
324 [M] .
1
2
1.25 q (CO CH ), 74.91 d (C ), 170.63 s (CO),
2 3
1
74.06 s (C ).
b. Following the above procedure, from 0.3 g
0.85 mmol) of compound III and an ether solution
of 4.25 mmol of diazomethane in the presence of
.9 mg (1 mol %) of Pd(OAc) we obtained 0.3 g of
REFERENCES
(
1. Jacobson, M., J. Org. Chem., 1960, vol. 25, no. 11,
p. 2074.
1
2
2. Klunder, J.M., Caron, M., Uchiyama, M., and Sharp-
less, K.B., J. Org. Chem., 1985, vol. 50, no. 6,
pp. 912 915.
a mixture containing (GLC) 5% of isomers Va and
Vb and 90% of unchanged ester III.
c. Following the above procedure, from 0.3 g
3
4
5
6
.
.
.
.
Zabolotskii, D.A. and Myagkova, G.I., Bioorg. Khim.,
991, no. 17, pp. 1129 1132.
(
4
0.85 mmol) of compound III, an ether solution of
.25 mmol of diazomethane, and 1.9 mg (1 mol %)
of Cu(CF SO ) in CH Cl we obtained 0.3 g of
1
Ansari, F.H. and Osman, S.M., Indian J. Chem., 1973,
vol. 11, no. 10, pp. 1053 1054.
3
3 2
2
2
a mixture containing (GLC) 25% of isomers Va and
Vb and 60% of unchanged ester III.
Methyl cis-12-oxo-9,10-methyleneoctadecanoic
acid (VI). Following the above procedure, from 0.3 g
Lie Ken Jie, M.S.F. and Lam, W.L.K., J. Chem. Soc.,
Chem. Commun., 1987, no. 19, pp. 1460 1461.
Tomilov, Yu.V., Dokichev, V.A., Dzhemilev, U.M.,
and Nefedov, O.M., Usp. Khim., 1993, vol. 62, no. 9,
pp. 847 886.
(
1
0.97 mmol) of ketone IV, an ether solution of
9.4 mmol of diazomethane, and 2.9 mg (1 mol %) of
Pd(acac) we obtained 0.38 g of a mixture containing
7
.
Mash, E.A. and Nelson, K.A., Tetrahedron, 1987,
vol. 43, no. 4, pp. 679 692.
2
1
(
1
(
GLC) 83% of ester VI. IR spectrum, , cm : 728,
024, 1168, 1364, 1432, 1460, 1712 (C O), 1736
CO ), 2856, 2928. H NMR spectrum, , ppm: 0.33
8. Mash, E.A., Hemperly, S.B., Nelson, K.A.,
Heidt, P.C., and Deusen, S.V., J. Org. Chem., 1990,
vol. 55, no. 7, pp. 2045 2055.
1
2
to 0.25 m, 0.51 0.52 m, and 0.88 1.10 m (4H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 5 2001