Synthesis of enantioenriched methyl vic-dihydroxystearates

Article abstract of DOI:10.1055/s-1998-6084

Several enantioenriched methyl vic-dihydroxystearates 4 have been synthesized from methyl octadecenoates by enantioselective dihydroxylation in good yields (85-97%) and with satisfactory enantiomeric excess (ee 80-97%). The enantioenriched anti-9,10 dihydroxystearates (anti-4c) were prepared by HPLC separation of the corresponding dicamphanyl esters anti-6. Their ee was determined by HPLC of the corresponding diastereoisomeric carbamates 7, and their configuration was assigned by relation to a described compound or by applying the mnemonic device of Sharpless.

Full text of DOI:10.1055/s-1998-6084

PAPERS
1255
Synthesis of Enantioenriched Methyl vic-Dihydroxystearates
Mark Plate, Michael Overs, Hans J. Schäfer*
Organisch-Chemisches Institut der Universität Münster, Corrensstraße 40, D-48149 Münster, Germany
Fax: +49(251)8339772; E-mail: schafeh@uni-muenster.de
Received 30 September 1997
Abstract: Several enantioenriched methyl vic-dihydroxystearates
4 have been synthesized from methyl octadecenoates by enantio-
selective dihydroxylation in good yields (85–97%) and with satis-
factory enantiomeric excess (ee 80–97%). The enantioenriched
anti-9,10-dihydroxystearates (anti-4c) were prepared by HPLC
separation of the corresponding dicamphanyl esters anti-6. Their
ee was determined by HPLC of the corresponding diastereoiso-
meric carbamates 7, and their configuration was assigned by rela-
tion to a described compound or by applying the mnemonic
device of Sharpless.
Key words: enantioselective dihydroxylation, methyl vic-
dihydroxystearates, methyl octadecenoates, separation of diastereo-
isomers, Kolbe electrolysis
Scheme 2
Monolayers of chiral amphiphiles can spontaneously se-
parate into chiral domains.1 Most of the amphiphiles,
In the case of methyl oleate (5) the enantiomeric excess of
the dihydroxylation was very low, which has been reported
before for the dihydroxylation of nearly symmetrical cis-
olefins.7 The synthesis of enantioenriched methyl anti-
9,10-dihydroxystearates was then achieved by HPLC sep-
aration of the corresponding diastereoisomeric dicamph-
anyl esters anti-6 (Scheme 3). For this purpose methyl ole-
ate (5) was treated with OsO4 to yield the methyl anti-9,10-
dihydroxystearates (anti-4c).8 The diastereoisomers anti-6
were obtained by diesterification of anti-4c with (–)-cam-
phanic acid chloride, as described by Mohr and Rosini,9
followed by HPLC separation and partial hydrolysis to the
methyl anti-9,10-dihydroxystearates (–)-(9S,10S)-4c and
(+)-(9R,10R)-4c (Scheme 3, Table 2).
studied so far bear chiral polar head groups. We wanted to
explore how the monolayer behavior of methyl stearates
is influenced by stereogenic centers located at different
positions in the alkyl chain. For this purpose enantioen-
riched methyl vic-dihydroxystearates were prepared using
the Sharpless2 method for the enantioselective dihydroxy-
lation of olefins. The corresponding methyl octade-
cenoates were synthesized by Kolbe electrolysis3 or Wit-
tig reaction. Methyl octadec-17-enoate (3a) has been ob-
tained in 40% yield by coelectrolysis of one equivalent of
undec-10-enoic acid (2) with four equivalents of methyl
azelate (1)4 (Scheme 1) at platinum electrodes in methan-
ol in an undivided cell.5 Ethyl trans-octadec-2-enoate (3b)
was synthesized by a Wittig reaction from hexadecanal and
(ethoxycarbonylmethylene)triphenylphosphorane in 74%
yield.
Scheme 1
The synthesis of chiral vicinal diols by enantioselective
dihydroxylation has been described for a variety of ole-
fins;2 however, to our knowledge this powerful conver-
sion has not yet been applied to the synthesis of chiral vic-
dihydroxy fatty acid esters. The enantioselective dihy-
droxylation of 3a,b and of commercially available methyl
trans-octadec-9-enoate (3c) led in excellent yield (85–
97%) and satisfactory to high enantiomeric excess (ee 84–
97%) to methyl vic-dihydroxystearates 4 (Scheme 2, Tab-
le 1). As reagents for the dihydroxylations commercially
available AD-Mix-α and AD-Mix-β were used.6
Scheme 3
To determine their enantiomeric purity, the dihydroxy es-
ters 4a, syn-4b and anti-4c were transformed into their dia-
stereoisomeric carbamates 7 by refluxing them in toluene
with (S)-1-phenylethyl isocyanate (Scheme 4). The crude

SYNTHESIS
Table 1. Enantioenriched Methyl vic-Dihydroxystearates 4 Prepared by Enantioselective Dihydroxylation of Unsaturated Methyl Esters 3
Papers
1256
Methyl
Octadecenoate
Reagent
vic-Dihydroxy
Stearate
Yield
(%)
[α]D20
ee
(%)
mp
(°C)
3a
3a
3b
3b
3c
3c
AD-Mix-α
AD-Mix-β
AD-Mix-α
AD-Mix-β
AD-Mix-α
AD-Mix-β
(+)-(17S)-4a
90
90
85
85
97
95
+0.4
(c = 2, CHCl3)
–0.4
(c = 2, CHCl3)
+8.0
(c = 2, CHCl3)
–8.0
(c = 2, CHCl3)
–21.3
(c = 1, MeOH)
+21.9
92a
84a
95a
91a
95b
97b
88
(–)-(17R)-4a
88
(+)-(2R,3S)-4b
(–)-(2S,3R)-4b
(–)-(9S,10S)-4c
(+)-(9R,10R)-4c
64
64
68–69
68–69
(c = 1, MeOH)
a By HPLC analysis of the corresponding diastereomeric carbamates 7 (Scheme 4) on a Merck LiChroSpher RP-18 ec column.
b By comparison with the specific rotation of (+)-(9R,10R)-4c [α]D20 22.5 (c = 1.2, MeOH) prepared from methyl ricinoleate.10
Table 2. Enantioenriched Methyl vic-Dihydroxystearates anti-4c Pre-
pared by HPLC Separation of the Dicamphanic Esters anti-6
In summary, unsaturated trans-fatty acid esters can be
enantioselectively dihydroxylated to vic-dihydroxy esters
in good yields and high enantiomeric excess by the Sharp-
less method.2 The methyl anti-9,10-dihydroxystearates
anti-4c have been prepared by HPLC separation of their
diastereoisomeric dicamphanoyl esters anti-6. Results on
the chiral discrimination of monolayers of (–)-(9S,10S)-4c
and (+)-(9R,10R)-4c as determined by Brewster angle mi-
croscopy on the Langmuir trough and the formation of
gels consisting of helical fibers as observed by atomic
force microscopy are reported elsewhere.11
Methyl
Dihydroxystearate (%)
Yielda [α]D20 b
eec
(%)
mp
(˚C)
(+)-(9R,10S)-4c
(–)-(9S,10R)-4c
77
79
+0.7
(c = 1, MeOH)
–0.9
80
99
106–107
106–107
(c = 1, MeOH)
a
For three steps: 5 → anti-4c.
Lit.10: (–)-(9S, 10R)-4c: –0.12 (c = 1.1, MeOH).
By HPLC analysis of the corresponding diastereomeric carbamates
b
c
7 (Scheme 4) on a Knauer Nucleosil 100-3 column.
The solvents were purified and dried, if necessary. Analytical TLC:
Merck aluminium foils covered with silica gel 60 F254. Preparative
column chromatography: Merck silica gel 60 (70–230 mesh). Analy-
tical GLC: Hewlett–Packard 5890 series II with integrator HP 3396,
HP 5 (25 m × 0.25 mm) or HP 1 (25 m × 0.31 mm) capillary columns,
carrier gas: N2. Optical rotations: Perkin–Elmer P 241 polarimeter. IR
products were filtered over silica gel and the carbamates
were separated by HPLC to determine their diastereoiso-
meric excess (Tables 1 and 2). The absolute configuration
of the methyl 9,10-dihydroxystearates (–)-(9S,10S)-4c
and (+)-(9R,10R)-4c were assigned by comparison of
their specific optical rotations with the values reported by
Morris and Crouchman.10 They correspond to the config-
urations predicted by the mnemonic device proposed by
Sharpless.2 The absolute configuration of the methyl di-
hydroxystearates (+)-(17S)-4a, (–)-(17R)-4a, (+)-(2R,3S)-
4b and (–)-(2S,3R)-4b were assigned applying this mne-
monic device.
spectra: Bruker IFS 28 spectrophotometer. 1H NMR (300 MHz), 13
C
NMR (75 MHz) spectra: Bruker WM 300. MS: Varian Saturn II (Ion
trap), Finnigan MAT 8230 with Varian GC 3400 (EI, 70 eV) or Finni-
gan MAT 312 (direct inlet). HPLC: Shimadzu LC-10-HPLC-system
with Merck LiChroSpher RP-18 ec column, system of Knauer pump
64 with Knauer refractometer type 5178 and Knauer Nucleosil 100-5
(250 mm × 16 mm) or Nucleosil 100-3 (250 mm × 8 mm) columns.
Methyl Octadec-17-enoate (3a):
A solution of 1 (2.24 g, 12 mmol), 2 (553 mg, 3 mmol) and NaOMe
(80 mg, 1.5 mmol) in MeOH (40 mL) was electrolyzed at 40–45°C
with a current density of 200 mA/cm2 at platinum electrodes in an
undivided cell.5 To prevent passivation of the electrodes their polarity
was reversed every 30 s. After current consumption of 1 F/mol the
electrolysis was stopped, the cell was rinsed with MeOH (50 mL) and
petroleum ether (50 mL). To the combined organic layers was added
petroleum ether (100 mL) and they were then washed with 0.5 N HCl
(4 × 50 mL), dried (MgSO4) and evaporated in vacuo. The residue
was purified by flash chromatography (petroleum ether/Et2O 30:1).
Yield: 356 mg (40%); mp 25–27°C; Rf 0.23 (petroleum ether/Et2O
30:1).
Ethyl trans-Octadec-2-enoate (3b):
To a stirred solution of (ethoxycarbonylmethylene)triphenylphospho-
rane (5.57 g, 16 mmol) in toluene (150 mL) a solution of hexadecanal
(3.12 g, 13 mmol) in toluene (20 mL) was added at 60°C. The mixture
Scheme 4

SYNTHESIS
September 1998
1257
Table 3. Spectroscopic Dataa
Com-
pound
IR (KBr/film)
1H NMR (CDCl3/TMS)
δ, J (Hz)
13C NMR (CDCl3/TMS)
δ
MS (70eV)
m/z (%)
ν (cm–1)
3a
3078, 2925,
2854, 1744,
1640, 1466,
1437, 1364,
1171, 1114,
994, 909, 721
1.18–1.40 (m, 24H, H-4–H-15), 1.60 (mc, 25.0 (C-3), 28.9, 29.1, 29.2, 29.5, 296 (M+, 10), 265 (M+-
2H, H-16), 2.02 (mc, 2H, H-3), 2.27 (t, 3J 29.6 (C-4–C-15), 33.8, 34.1 (C-2, CH3O, 60), 264 (M+-
= 7.6, 2H, H-2), 3.64 (s, 3H, OCH3), 4.90 C-16), 51.4 (OCH3), 114.1 (C-18), HOCH3, 100), 235 (3), 222
(ddt, 3Jcis = 10.1, 2Jgem = 2.2, 4Jallyl = 1.2, 139.2 (C-17), 174.3 (C-1)
(40), 180 (28), 152 (18), 111
(36), 97 (68), 87 (85), 83
(71), 74 (98), 69 (88), 55
(99), 43 (63), 41 (69)
1H, H-18a), 4.96 (ddt.3Jtrans = 17.0, 2Jgem
=
2.2, 4Jallyl = 1.4, 1H, H-18b), 5.78 (ddt, 3Jcis
= 10.1, 3Jtrans = 17.0, 3J = 6.7, 1H, H-17)
3b
3075, 2916,
2853, 1724,
1655, 1466,
1437, 1367,
1309, 1179,
1127, 1046,
980, 721
0.86 (t, 3J = 6.9, 3H, H-18), 1.18–1.35 (mc, 14.1, 14.3 (OCH2CH3, C-18), 22.7, 310 (M+, 16), 265 (M+-
26H, H-5–H-17), 1.43 (t, 3J = 7.1, 3H, 28.0, 29.2, 32.0, 32.2 (C-4–C-17), C2H5O, 28), 264 (M+-
4
OCH2CH3), 2.16 (ddt, Jallyl = 1.7, 3J = 60.0 (OCH2), 121.3 (C-2), 149.5 C2H5OH, 34), 222 (18), 155
3
3
7.2, J = 7.2, 2H, H-4), 4.16 (q, J = 7.1, (C-3), 166.8 (C-1)
(20), 141 (14), 127 (25), 101
(61), 88 (46), 83 (34), 69
(36), 57 (52), 55 (80), 43
(100), 41 (60)
3
2H, OCH2CH3), 5.78 (dt, Jtrans = 15.7,
4
3
Jallyl = 1.7, 1H, H-2), 6.94 (dt, J = 6.9,
3Jtrans = 15.7, 1H, H-3) lit.12
4a
3327, 2917,
2850, 1737,
1471, 1437,
1254, 1204,
1196, 1104,
719
1.15–1.36 (m, 24H, H-4–H-15), 1.42 (mc, 24.1, 24.8 (C-3, C-15), 28.2, 28.3, b459 (M+-CH3, 5), 443 (M+-
2H, H-3), 1.60 (mc, 2H, H-16), 2.28 (t, 3J 28.4, 28.7, 28.8, 28.9, 29.2, 29.4, OCH3, 4), 371 (M+-
= 7.6, 2H, H-2), 1.95 (sc, br, OH-17, OH- 29.7 (C-4–C-14), 32.6, 33.1 (C-2, CH2OSiMe3, 100), 147
18), 3.41 (dd, 3J = 7.5, 2Jgem = 10.8, 1H, H- C-16), 50.3 (OCH3), 65.9 (C-17), (26), 109 (12), 95 (20), 83
3
2
18a), 3.64 (dd, J = 3.1, Jgem = 10.8, 1H, 71.3 (C-18), 173.1 (C-1)
(22), 73 (58), 69 (24), 55
(28), 43 (16)
H-18b), 3.65 (s, 3H, OCH3), 3.70 (mc, 1H,
H-17)
syn-4b
3387, 3204,
2920, 2848,
1737, 1716,
1463, 1398,
1293, 1113,
0.86 (t, 3H, H-18), 1.16–1.30 (m, 26H, H- 14.1, 14.2 (C-18, OCH2CH3), 22.7 b473 (M+-CH3, 10), 415
5–H-17), 1.35 (t, 3J = 7.2, 3H, OCH2CH3), (C-17), 25.7, 25.8, 29.4, 29.6, 29.7 (M+-SiMe3, 5), 383 (5), 313
1.58 (mc, 2H, H-4), 1.98 (dc, 3J = 8.8, 1H, (C-5–C-15), 32.0 (C-16), 33.8 (C- (60), 248 (100), 176 (5), 147
OH-3), 3.07 (dc, 3J = 5.5, 1H, OH-2), 3.85 4), 62.1 (OCH2CH3), 72.6, 73.1 (C- (18), 83 (6), 73 (40), 69 (3),
(mc, 1H, H-3), 4.05 (dd, 3J = 5.5, 3J = 2.2, 2, C-3), 173.3 (C-1)
55 (4), 43 (3)
1034, 862, 724 1H, H-2), 4.28 (q, 3J
OCCH2CH3)
= 7.2, 2H,
syn-4c
anti-4c
anti-6c
3404, 2917,
2847, 1739
0.85 (t, 3H, H-18), 1.15–1.63 (m, 26H, H- 14.1 (C-18), 22.7, 24.9, 25.6, 25.7, b459 (M+-CH3, 4), 442 (6),
3–H-8, H-11–H-17), 2.07 (sc, 1H, OH), 29.0, 29.1, 29.3, 29.4, 29.6, 29.7, 332 (20), 259
2.08 (sc, 1H, OH), 2.27 (t, 2H, H-2), 3.36 31.9, 33.6, 33.7, 34.1 (C-2–C-8, C- (Me3SiOC8H15CO2Me+,
+
(mc, 2H, H-9–H-10), 3.64 (s, 3H, OCH3)
11–C-17), 51.4 (OCH3), 74.5 (C-9– 100), 215 (C9H18OSiMe3 ,
C-10), 174.3 (C-1); in agreement 62), 147 (10), 73 (20), 55
with lit.8
(10)
3277, 2916,
2849, 1736
0.86 (t, 3H, H-18), 1.20–1.65 (m, 26H, H- 14.1 (C-18), 22.7, 24.9, 25.9, 26.0,
3–H-8, H-11–H-17), 1.75 (sc, 2H, OH), 29.0, 29.1, 29.2, 29.4, 29.5, 29.7,
2.28 (t, 2H, H-2), 3.57 (mc, 2H, H-9–H- 31.2, 31.3, 31.9, 34.1 (t, C-2–C-8,
10), 3.64 (s, 3H, OCH3)
C-11–C-17), 51.5 (OCH3), 74.7 (C-
9–C-10), 175.9 (C-1); in agreement
with lit.8
3
2931, 2857,
1795, 1738,
1453, 1314,
1270, 1168,
1060, 1017,
992, 959, 932,
898, 739
0.85 (t, J = 6.8, 3H, H-18), 0.92, 0.99, 9.7, 14.1, 16.7 (C-18, C-8', C-9', C- 691 (M++H, 1), 659 (M+-
1.05, 1.08 (s, 18H, H-8', H-9', H-10'), 10'), 22.7, 24.9, 25.5, 25.6, 28.5, OCH3, 2), 644 (1), 617 (1),
1.20–1.40 (m, 20H, H-4–H-7, H-12–H- 29.0, 29.2, 29.4, 29.5, 31.0, 31.8, 493 (10), 448 (10), 311 (8),
17), 1.50–1.62 (m, 8H, H-8, H-11, H-3, 34.1, 51.5, 54.2, 54.4, 54.9, 55.0 294 (10), 263 (8), 164 (12),
camph.-H), 1.81–2.08 (m, 4H, camph.-H), (C-2–C-8, C-11–C-17, camph.- 153 (30), 136 (50), 125 (40),
2.29 (t, 3J = 7.6, 2H, H-2), 2.31–2.45 (m, CH2), 51.5 (OCH3), 65.9 (camph.- 109 (80), 97 (50), 83 (100),
2H, camph.-H), 3.64 (s, 3H, OCH3), 5.07– CH2), 75.2, 75.8 (C-9, C-10), 91.0, 55 (60), 41 (30)
5.12, 5.20–5.26 (m, 2H, H-9, H-10)
91.2 (C-1'), 167.4, 174.2, 178.2,
178.3 (camph.-C=O, C-1)
anti-7c
3335, 2924,
2852, 1734,
1685, 1528,
1466, 1248,
1075, 1029,
757, 699
0.87 (t, 3J = 6.8, 3H, H-18), 1.09–1.61 (m, 14.0 (C-18), 22.6, 24.8, 25.3, 29.0, 624 (M+, 1), 609 (M+-CH3,
32H, H-5', H-3–H-7, H-11–H-17), 2.27 (t, 29.2, 29.4, 29.5, 31.8, 34.0 (C-2–C- 1), 460 (20), 444 (8), 335
3J = 7.6, 2H, H-2), 3.58 (s, 3H, OCH3), 8, C-11–C-17, C-5'), 50.5 (C-4'), (6), 313 (4), 281 (6), 262
4.47 (mc, 6H, H-9, H-10, H-3', H-4'), 51.3 (OCH3), 75.1 (C-9, C-10), (2), 166 (40), 147 (40), 132
7.11–7.31 (m, 10H, Harom
)
125.9, 127.1, 128.5, 145.0 (Carom), (82), 105 (100), 77 (40), 55
155.4 (C-2'), 174.2 (C-1) (20)
a Satisfactory elemental analyses were obtained for all new compounds except for 3a (C: ± 0.06–0.30, H: ± 0.02–0.23, N: ± 0.15).
b MS spectra of the bistrimethylsilyl ether.
c The 1H NMR, 13C NMR and mass spectra of the mixture and the isolated two diastereoisomers are identical.

SYNTHESIS
Papers
1258
was refluxed for 4 h and then allowed to cool. After removal of the
solvent and addition of petroleum ether (20 mL) the Ph3PO was fil-
tered off. The ether layer was evaporated in vacuum and the residue
purified by flash chromatography (petroleum ether/Et2O 30:1). Yield:
2.54 g (63%); mp 25–27°C; Rf 0.26 (petroleum ether/Et2O 30:1).
48 h. After evaporation in vacuo the product was filtered over silica
gel (Et2O) and the filtrate was concentrated in vacuo. By HPLC anal-
ysis of the diastereoisomeric carbamates 7 the enantiomeric excess of
the dihydroxy esters 4 was determined (Tables 1 and 2).
Enantioselective Dihydroxylation; General Procedure:2
This work was supported by the Minister of Agriculture and Forestry
(project: 93NR065-F-A), the DFG-Sonderforschungsbereich SFB
424(97) and the Fonds der Chemischen Industrie.
A mixture of t-BuOH (5 mL), water (5 mL), AD-Mix-α or AD-Mix-
β (1.4 g) and MeSO2NH2 (95 mg, 1 mmol) was stirred at r.t. until both
phases were clear and then cooled to 0°C. The unsaturated fatty ester
3 (1 mmol) was added and, after stirring for 24 h at 0°C, the reaction
was quenched by addition of Na2SO3 (1.5 g, 12 mmol). The mixture
was allowed to warm up and extracted with EtOAc (3 × 15 mL). The
organic layer was washed with 2 N NaOH (15 mL), dried (MgSO4)
and evaporated in vacuo. The dihydroxy esters 4 were purified by
flash chromatography (EtOAc/cyclohexane 5:2) (Table 1).
(1) Vollhardt, D.; Emmerich, G.; Gutberlet, T.; Fuhrhop, J.-H.
Langmuir 1996, 12, 5659.
Viswanathan, R.; Zasadzinski, J. A.; Schwartz, D. K. Nature
1994, 368, 440.
Eckhardt, C. J.; Peachey, N. M.; Swanson, D. R.; Takacs, J. M.;
Khan, M. A.; Gong, X.; Kim, J.-H.; Wang, J.; Uphaus, R. A.
Nature 1993, 362, 614.
Preparation of Methyl (–)-(9S,10R)- and (+)-(9R,10S)-9,10-Dihy-
droxystearate [(–)-(9S,10R)-4c, (+)-(9R,10S)-4c]:
Fuhrhop, J.-H.; Helfrich, W. Chem. Rev. 1993, 93, 1565.
(2) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem.
Rev. 1994, 94, 2483.
(3) Schäfer, H. J. Top. Curr. Chem. 1990, 152, 91.
(4) Noller, C. R.; Adams, R. J. Am. Chem. Soc. 1926, 48, 1074.
(5) Schäfer, H. J. In Comprehensive Organic Synthesis, Vol. 3;
Trost, B. M.; Fleming, I.; Pattenden, G., Eds; Pergamon: Ox-
ford, 1991; p 633, figure 2.
To a solution of anti-4c (388 mg, 1.17 mmol) in pyridine (10 mL) a
solution of (–)-ω-camphanic acid chloride (1.3 g, 6.35 mmol) in
CH2Cl2 (10 mL) was added at 0°C. The mixture was allowed to warm
up and stirred at r.t. for 15 h. After addition of 2 N HCl (50 mL) and
water (30 mL) it was extracted with Et2O (3 × 30 mL). The organic
layer was washed with NaHCO3 (30 mL), dried (MgSO4) and evapo-
rated in vacuo. The residue was purified by flash chromatography
(petroleum ether/Et2O 1:1) to give anti-6. Yield: 660 mg (81%); Rf
0.35 (petroleum ether/Et2O 1:1).
(6) Aldrich Chemical Co.
(7) Wang, L.; Sharpless, K. B. J. Am. Chem. Soc. 1992, 114, 7568.
(8) Bus, J.; Sies, I.; Lie Ken Jie, M. S. F. Chem. Lipids 1976, 17,
501.
(9) Mohr, P.; Rösslein, L.; Tamm, C. Helv. Chim. Acta 1987, 70,
142.
Part of anti-6 was separated into the diastereoisomers (–)-
(9S,10R,1'S,1'S)-6 ([a]D20 –7.89 (c
= 3.0, MeOH)) and (–)-
(9R,10S,1'S,1'S)-6 ([a]D20 –14.96 (c = 3.0, MeOH)) by HPLC (Knauer
Nucleosil 100-5 column, cyclohexane/EtOAc, 6:1). The 1H, 13C
NMR spectra and MS of the mixture of the two diastereoisomers and
the separated diastereoisomers are identical and are given in Table 3.
Solutions of (–)-(9R,10S,1'S,1'S)-6 (132 mg, 0.92 mmol), KOH (260
mg, 4.64 mmol) in MeOH (10 mL) and of (9S,10R,1'S,4'R,1'S,4'R)-6
(125 mg, 0.87 mmol), KOH (250 mg, 4.46 mmol) in MeOH (10 mL)
were stirred for 30 min at r.t. After addition of water (10 mL) the
mixtures were neutralized with 2 N HCl and extracted with Et2O (3
× 10 mL). The organic layers were washed with NaHCO3 (10 mL),
dried (MgSO4) and evaporated to yield (+)-4c and (–)-4c (Table 2).
For the synthesis of (+)-4c and
Rosini, G.; Carloni, P.; Iapalucci, M. C.; Marotta, E. Tetrahe-
dron: Asymmetry 1990, 1, 751.
(10) Morris, L. J.; Crouchman, M. L. Lipids 1972, 7(6), 372: Diaster-
eoisomeric methyl (12R)-9,10,12-trihydroxystearates were pre-
pared by dihydroxylation of methyl (12R)-cis-12-hydroxy-
octadec-9-enoate with performic acid or KMnO4 and separated.
In the higher melting diastereoisomer the 10- and 12-hydroxy
groups are anti to each other. The trihydroxystearates were re-
lated to the optical pure methyl 9,10-dihydroxystearates after
selective removal of the 12-hydroxy group.
(–)-4c from methyl ricinoleate see lit.10
(11) Jacobi, S.; Chi, L. F.; Plate, M.; Overs, M.; Schäfer, H. J.;
Fuchs, H. Thin Solid Films, 1998, in press.
(12) For the 1H NMR of the methyl ester see: K.-C. Shih, R. J. An-
gelici, J. Org. Chem. 1996, 61, 7784.
Preparation of the Carbamates 7; General Procedure:
A solution of the dihydroxy ester 4 (1 mmol) and (S)-1-phenylethyl
isocyanate (0.28 mL, 2 mmol) in toluene (5 mL) was refluxed for