Selective oxidations of methyl ricinoleate: Diastereoselective epoxidation with titaniumIV catalysts

Article abstract of DOI:10.1007/s11746-998-0072-1

Conditions were developed for the selective epoxidation of the double bond of methyl ricinoleate (1) with ethylmethyldioxirane (EMDO) to give the homoallylic epoxyalcohol, methyl (Z)-9,10-oxido-12-hydroxyoctadecanoate (2) in high yields but in poor enantiomeric excess. The diastereomeric ratio for epoxyalcohol 2 was improved modestly when t-butyl-hydroperoxide, coupled with a titanium catalyst and a D-tartrate ligand, was used as oxidizing agent. Reaction of 1 with excess EMDO resulted in the concomitant epoxidation of the double bond and oxidation of the hydroxy group of 1 to give methyl (Z)-9,10-oxido-12-oxo-octadecanoate (4), along with methyl 8-(5-hexylfuran-2-yl)octanoate (5). Alternatively, ketoepoxide 4 was prepared by dioxirane oxidation of methyl 12-oxo-(Z)-9-octadecene (3) or by treating epoxyalcohol 2 with sodium hypochlorite. The ketoepoxide 4 is acid-labile and rearranges with loss of water to give furan 5 in high yield.

Full text of DOI:10.1007/s11746-998-0072-1

Selective Oxidations of Methyl Ricinoleate:
Diastereoselective Epoxidation with TitaniumIV Catalysts1
Thomas A. Foglia*, Philip E. Sonnet, Alberto Nunez, and Robert L. Dudley
ERRC, ARS, USDA, Wyndmoor, Pennsylvania 19038
ABSTRACT: Conditions were developed for the selective offer unique properties so they can be sold by oil producers
epoxidation of the double bond of methyl ricinoleate (1) with
ethylmethyldioxirane (EMDO) to give the homoallylic epoxyal-
cohol, methyl (Z)-9,10-oxido-12-hydroxyoctadecanoate (2) in
high yields but in poor enantiomeric excess. The diastereomeric
ratio for epoxyalcohol 2 was improved modestly when t-butyl-
as specialty chemicals.
In this study, we evaluated some oxidations of methyl rici-
noleate, 1, in particular its conversion to the epoxyketone, 4
(Fig. 1). The epoxyalcohol, 2, has been characterized previ-
ously as mentioned below; here, we relate information that
suggests the absolute configuration of the diastereomers
formed from the epoxidation of methyl ricinoleate. We also
describe a preparation of one of the diastereomers in 80%
enantiomeric excess (90:10 ratio).
hydroperoxide, coupled with a titanium catalyst and a
D-tar-
trate ligand, was used as oxidizing agent. Reaction of 1 with ex-
cess EMDO resulted in the concomitant epoxidation of the dou-
ble bond and oxidation of the hydroxy group of 1 to give methyl
(Z)-9,10-oxido-12-oxo-octadecanoate (4), along with methyl 8-
(5-hexylfuran-2-yl)octanoate (5). Alternatively, ketoepoxide 4
was prepared by dioxirane oxidation of methyl 12-oxo-(Z)-9-
octadecene (3) or by treating epoxyalcohol 2 with sodium
hypochlorite. The ketoepoxide 4 is acid-labile and rearranges
with loss of water to give furan 5 in high yield.
MATERIALS AND METHODS
All solvents, including 2-butanone, were of high-performance
liquid chromatography (HPLC) grade or better. Other chemi-
cals were reagent-grade and were purchased from Aldrich
Chemical Company (Milwaukee, WI). Methyl ricinoleate was
prepared from castor oil as described (6). Gas–liquid chroma-
tography (GLC) was performed with a Chrompack-Packard
Model 438A instrument (Avondale, PA) and a split (50:1)
capillary column injector. Helium was used as the carrier gas,
with a Supelcowax column (0.25 mm × 30 m) (Supelco Inc.,
Bellefonte, PA) operating at temperatures indicated below.
Analytical thin-layer chromatography (TLC) was performed
on 0.25-mm silica gel 60 plates (5 × 20 cm), obtained from
Analtech (Newark, DE), or on silica gel ultraviolet (UV)
plates (2.5 × 10 cm) from Aldrich Chemical Company. HPLC
was carried out with a Spectra-Physics SP8800 pump (Moun-
tainview, CA), a Supelcosil LC-Si column (4.6 mm × 25 cm),
and a Spectra-Physics SP8480 UV detector, operated as de-
scribed below. Infrared (IR) spectra were recorded with a
Perkin-Elmer 1310 (Norwalk, CT) spectrophotometer with
1% solutions in either CCl4 or CHCl3. Nuclear magnetic res-
onance (NMR) spectra were obtained with a Varian Gemini
200 (Palo Alto, CA) spectrometer, operating at 200 MHz for
proton and at 50 MHz for carbon-13 nuclei. All spectra were
recorded in CDCl3 solvent, and chemical shifts are reported
as ppm (δ) from tetramethylsilane (TMS). Mass spectra (MS)
were obtained with a Hewlett-Packard (Wilmington, DE)
Model 5890 Series II gas chromatograph, equipped with a
capillary inlet system, a 30 m × 0.25 mm capillary column
coated with 0.25 µm 5% cross-linked phenyl methyl silicone
(HP-5MS), and an HP Model 5972 mass selective detector set
JAOCS 75, 601–607 (1998).
KEY WORDS: Dioxirane, epoxide, epoxyhydroxy ester, furan,
phase-transfer catalyst, t-butyl hydroperoxide, titanium.
Ricinoleic acid, (R)-12-hydroxy-(Z)-9-octadecenoic acid, is
the principal fatty acid (FA) of castor oil. Both the oil and the
acid have a number of important industrial uses that are based
primarily upon the unique presence of the hydroxyl group (1).
Utility of these materials is often enhanced by conversion of
the unsaturated alcohol structure to other reactive functional
groups. Although few other hydroxylated FA are readily
available, efforts to exploit novel FA (2–4) and to convert
common industrially available FA, such as oleic and linoleic
acids, to hydroxylated FA may change this picture (5–8). The
chemistry performed on ricinoleic acid and its derivatives
therefore can serve as examples of what might be done with
new hydroxylated FA. Parenthetically, the chirality of hy-
droxylated FA has been of less interest to the oleochemicals
industries; evidently, chemical configuration plays no demon-
strated role in the physical properties sought by these indus-
tries as targets for their products. However, the configura-
tional homogeneity resident in such chiral compounds may
1Presented in part at the 88th Annual Meeting, American Oil Chemists’ So-
ciety, Seattle, Washington, May 1997.
*To whom correspondence should be addressed at ERRC, ARS, USDA, 600
E. Mermaid Lane, Wyndmoor, PA 19038. E-mail: tfoglia@arserrc.gov.
Copyright © 1998 by AOCS Press
601
JAOCS, Vol. 75, no. 5 (1998)

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T.A. FOGLIA ET AL.
to scan from 50 to 600 m/z at 1.5 scans per second. The oven 2-butanone in a two-phase oxidation that was conducted ex-
temperature was programmed from 80 to 230°C at 10°C per actly as for compound 2. From 0.62 g (2.0 mmol) of 3 was
minute at a He carrier gas flow of 1 mL per minute and a split obtained 0.63 g (100%) of crystalline 4, mp 32.5–34.5°C
1
ratio of 50:1. Samples with free hydroxy groups were sily- (hexane); IR: 1740, 1715, 1260, 1195, and 1170 cm−1; H
lated at room temperature with N,O-bis(trimethylsilyl)trifluo- NMR, δ: 3.66 (3H, s, CH3O), 3.3 (1H, bm, CH-O), 3.0 (1H,
roacetamide (BSFTA) (Pierce, Rockford, IL).
m, CH–O), 2.62 (2H, d of d, O–CH–CH2C=O), 2.46 [2H, t,
Methyl (Z)-12-oxo-9-octadecenoate, 3. To a solution of CH2C(=O)–CH2], 2.30 (2H, t, CH2CO2CH3), 1.6 (4H, m,
methyl ricinoleate, 1 (3.13 g, 10.0 mmol) in 30 mL CH2Cl2 CH2CH2C=O), 1.2–1.5 (m, CH2), and 0.87 (3H, t, CH3CH2)
was added sodium acetate (2.5 g, 30 mmol) and pyridinium ppm; 13C NMR (diagnostic signals), δ: 208.4 and 174.2 ppm;
chlorochromate (3.24 g, 15 mmol). The mixture was stirred and MS, m/z: 326 (M), 295 (M − OCH3), 241 (M − C6H13)
overnight. Ether (150 mL) was added, and the supernatant was 213 (M − COC6H13), and 113 (COC6H13).
poured onto a column of Florisil to filter out inorganics. Ether
Synthesis of 4 from the epoxyalcohol 2 was accomplished
(2 × 30 mL) was used to rinse the flask and was also added to with NaOCl as follows. The epoxyalcohol 2 (1.00 g, 3.05
the column. The combined eluents were freed of solvent by mmol) was stirred at room temperature in 6.6 mL of laundry
rotary evaporation. The residue was purified by flash chroma- bleach (5.25% NaOCl) that contained 2.1 mL of concentrated
tography on silica with 7% ethyl acetate-hexane (EA-H, acetic acid for 1.5 h. The mixture was chilled in ice, and a
25-mL fractions). Fractions were monitored by TLC (10% cold solution of sodium carbonate (3 g in 10 mL H2O) was
EA-H). Removal of solvent by rotary evaporation from the ap- added slowly to neutralize the mixture. The product was ob-
propriately combined fractions gave 2.57 g (82.6%) of the ke- tained by extraction with ether and, after the ethereal extract
toalkene, 3 (Rf = 0.55). An analytical sample was obtained by had been dried with anhydrous MgSO4, the solvent was re-
molecular distillation: bath temperature 155–180°C at 0.05 moved to give crystalline 4 (0.87 g, 87%).
mm of Hg. IR: 3030, 1735, and 1715 cm−1; 1H NMR, δ: 5.55
Methyl 8-(5-hexylfuran-2-yl)octanoate, 5. The keto-
(2H, m, HC=CH), 3.66 (3H, s, OCH3), 3.2 (2H, bd, epoxide 4 (50 µL) was dissolved in 1 mL tetrahydrofuran
HC=CH–CH2C=O), 2.41 (2H, t, CH2CH2C=O), 2.29 (2H, t, with 10 µL of 1.5M TiCl4 in CH2Cl2. After 1.5 h at room tem-
CH2CO2CH3), 2.0 (2H, m, CH2CH2CH=C), 1.6 (2H, m, perature, a TLC plate showed a single spot (Rf = 0.60) that
CH2CH2C=O), and 0.86 (3H, t, CH2CH3) ppm; 13C NMR (di- was characterized as the furan, 5. A sample was purified by
agnostic signals) δ 209.1, 174.2, 133.4, and 121.0 ppm; and flash chromatography (10% EA-H); IR: 1740 cm−1; 1H NMR,
MS, m/z: 310 (M), 279 (M − OCH3), and 113 (M − COC6H13). δ: 5.81 (2H, s, furanyl H), 3.64 (3H, s, OCH3), 2.53 [4H,
Methyl (R,Z)-9,10-oxido-12-hydroxyoctadecanoate, 2. t, CH2CH2C(O)=C], 2.28 (2H, t, CH2CO2CH3), 1.6 (2H, m,
This procedure is patterned after that reported by Curci and CH2CH2C=O), 1.2–1.4 (m, CH2), and 0.86 (3H, t, CH2CH3)
co-workers (9). Methyl ricinoleate (3.90 g, 12.5 mmol) was ppm; 13C NMR (diagnostic signals) δ: 174.2, 154.7, 154.5,
dissolved in 25 mL of 2-butanone. Sodium bicarbonate and 104.8 ppm; MS, m/z 310 (M), 277 (M − OCH3), 237,
(2.65 g, 3.1 mmol) and tetrabutylammonium bisulfate and 165.
(0.40 g, 0.1 mmol) were added. To this stirred slurry (main-
Diastereoselective epoxidations of methyl ricinoleate. The
tained in the dark) was added dropwise a solution of Oxone™ following procedure was used to obtain the data listed in
(7.7 g, 12.5 mmol) in 50 mL water. Addition time was about Table 1. Freshly ground 3Å molecular sieves (0.25 g) were
15 min, and stirring was continued for another 45 min. A sec- placed into a nitrogen-purged round-bottom flask. Dry
ond equivalent of Oxone™ and sodium bicarbonate was
added, and stirring was continued in the dark for 1 h. The re-
action mixture was transferred to a separatory funnel, the lay-
ers were separated, and the aqueous phase was extracted with
ether (25 mL). The combined organic layers were then
TABLE 1
Diastereomer Ratios for Methyl (R,S)-9,10-Oxido-12-hydroxy-
octadecanoate with Different Epoxidizing Agents
Epoxidizing
agent
Diastereomeric
ratioa
washed with water (2 × 20 mL) and dried over anhydrous
MgSO4. The solvents were removed by rotary evaporation,
and the crude product was purified by silica flash chromatog-
raphy to give the epoxyalcohol 2 as a mobile liquid, 3.70 g
(89.4%). GLC analysis (260°C, isothermal) showed that 2
was a mixture of diastereomers with retention times of 19.9
and 20.4 min (ratio of 1:1); IR: 3640, 1740, and 1260 cm−1;
1H NMR, δ: 3.63 (3H, s, CH3O), 3.09 (1H, m, CH–OH), 2.9
(2H, bm, epoxy CHO), 2.27 (2H, t, J = 7.8 Hz, CH2CH2C=O),
2.0 (OH), 1.6 (m, CH2CH2C=O), 1.2–1.5 (m, CH2), and 0.85
m-Chloroperbenzoic acid
Ethylmethyldioxirane
60:40
45:55b
75:25
83:17
86:14c
78:22
90:10
87:13
t-BuOOH, TiIV(OiPr)4
t-BuOOH + TiIV(OC[CH3]2CH2CH2CH3)
t-BuOOH + TiIV(OiPr)4 +
t-BuOOH + TiIV(OiPr)4 +
t-BuOOH + TiIV(OiPr)4 +
t-BuOOH + TiIV(OiPr)4 +
D
-diethyl tartrate
L
-diethyl tartrate
D
-diisopropyl tartrate
-dicyclohexyl tartrate
D
aDiastereomeric ratio determined by gas–liquid chromatography (Supel-
cowax column) or high-performance liquid chromatography of (S)-α-
(3H, t, CH3CH2) ppm; MS, m/z: 385 (M − 15), 316 (M − methoxytrifluoromethyl phenylacetic acid esters (see the Materials and
Methods section).
C6H13), and 187 [M − (CH3)3SiOCHC6H13].
bData taken from Reference 3.
Methyl (Z)-9,10-oxido-12-oxooctadecanoate, 4. Synthesis
cReaction at −20°C gave 85:15 ratio. Abbreviation: TiIV(OiPr)4, titanium iso-
of 4 from ketoalkene 3 employed ethylmethyldioxirane and propoxide.
JAOCS, Vol. 75, no. 5 (1998)

EPOXIDATION OF METHYL RICINOLEATE
603
dichloromethane (10 mL), tartrate ester (0.45 mmol), and ti- mixtures of varying composition only indicated that differen-
tanium isopropoxide catalyst (0.4 mmol) were added sequen- tiation of the CO2CH3 groups was possible (δ = 0.01 ppm).
tially to the flask. The mixture was cooled to −20°C, and the This was of no help in assigning configuration of the epoxide
catalyst was aged at this temperature for 0.5 h. Methyl rici- rings.
noleate (3.0 mmol) and t-butylhydroperoxide (6.0 mmol)
were added, and the mixture was allowed to stand at room
temperature for 24 h. The mixture was transferred to a sepa-
RESULTS AND DISCUSSION
ratory funnel, and washed successively with equal volumes Oxidation of methyl ricinoleate. Oxidation of the secondary
of 0.1 M ferrous sulfate (to destroy residual peroxide) and alcohol group of methyl ricinoleate to a ketoalkene, 3 (Fig. 1),
water and dried with anhydrous MgSO4, and the solvent was has been reported with chromic acid (12,13). We found that
removed in vacuo. The crude epoxyalcohol 2 was purified by pyridinium chlorochromate–sodium acetate was a particu-
silica flash chromatography (20% EA-H) monitoring by TLC larly convenient laboratory reagent for preparing 3. Yields
(Rf = 0.40, 30% EA-H). GLC analysis of 2 obtained by this were higher, and product isolation was easier than previously
method was as described above.
reported (12).
Derivatization of 2 with chiral reagents. The epoxyalco-
Epoxidation of the ricinoleate ester is likewise a known re-
hols, 2, were converted to esters with Mosher’s reagent (10), action and has been accomplished, for example, by mi-
(S)-α-methoxytrifluoromethyl-phenylacetic acid (MTPA). crowave irradiation of the ester with meta-chloroperbenzoic
The epoxy esters were purified by silica flash chromatogra- acid in methylene chloride (14). In our hands, this reagent and
phy, and 100 µL of 2 was stirred at room temperature in a so- the conventional procedure generated two diastereomeric
lution of 0.10 g each of MTPA and dicyclohexylurea in 5 mL epoxyalcohols in a ratio of 3:2. Earlier, we reported the reac-
CH2Cl2 with a trace of dimethylaminopyridine for several tions of dimethyldioxirane (DMDO) and ethylmethyldioxi-
hours. The solution was filtered and analyzed directly by rane (EMDO), generated with Oxone™, with methyl rici-
HPLC on a silica column with 15% ethyl acetate-hexane as noleate, as well as the ratios of the epoxidized alcohols that
mobile phase at a flow rate of 1 mL/min. The capacity factors were produced by these and other dioxiranes (15). Because
for the diastereomers were 1.94 and 2.04 (α = 1.05), respec- the dioxirane reaction procedure is simple and the reagents
tively. A larger preparation of acylated 2 was made for HPLC involved are quite inexpensive, we evaluated this reaction for
separation and isolation of the diastereomeric acylated esters preparing 2 as well as 4 in several complementary ways,
of 2. Minor differences were noted in the 1H NMR spectra of namely, (i) Oxone™ without the added ketone that is nor-
the diastereomers; the most dramatic is the chemical shift dif- mally used to generate a dioxirane, (ii) Oxone™-acetone-
ference for the α-OCH3 protons. For HPLC peak #1: 3.411 chloroform as a two-phase system to generate and use
ppm; for HPLC peak #2: 3.424. HPLC peak #2 corresponds DMDO, (iii) an acetone solution of DMDO prepared as de-
to the major diastereomer formed by epoxidation of methyl scribed by Crandall et al. (16), and (iv) Oxone™ in varying
ricinoleate.
(S)-1-(1-Naphthyl)ethyl isocyanate was used to prepare di- cosolvent and source of EMDO in a two-phase reaction.
astereomeric carbamates from 2 by means of the procedure Alkenes have been epoxidized directly by Oxone™, that
molar ratios to the homoallylic alcohol with 2-butanone as a
described by us with methyl ricinoleate (11). The products is, without the intermediacy of a dioxirane. For example,
1
were not separable by HPLC, and the H NMR spectra of treatment of cyclooctene with this reagent in aqueous
FIG. 1. Structural formulas for methyl ricinoleate (1), its oxidation products 2, 3, and 4 and
furan 5.
JAOCS, Vol. 75, no. 5 (1998)

604
T.A. FOGLIA ET AL.
methanol at room temperature for 4 h gave a 94% yield of appealing (22), but unfortunately it requires stringent condi-
crude epoxycyclooctane (17). The same conditions applied to tions. The alumina is dried at 400°C for 24 h, and a quartz
methyl ricinoleate gave less than 10% conversion to epoxyal- vessel is employed. Reactions of 2 with nonactivated alumina
cohol 2. The two-phase reaction of DMDO in chloroform in pyrex glassware were unsuccessful. However, the epoxyal-
gave results similar to those for EMDO in 2-butanone as sol- cohol 2 was converted in high yield to 4 with NaOCl in aque-
vent (vide infra), but the oxidant was used less efficiently. An ous acetic acid. Reactions of 2 with pyridinium chlorochro-
acetone solution of DMDO converted the homoallylic alco- mate in dimethyl sulfoxide produced mainly furan 5 and
hol 1 to its epoxide preferentially, but as the amount of minor amounts of epoxyketone 4. Additionally, the keto-
DMDO was increased, the epoxyketone 4 and furan 5 became alkene 3 was epoxidized to 4 with either meta-chloroperben-
significant products, as determined by GLC. For example, zoic acid or EMDO. The latter reaction was conducted in the
with as much as 14% of the original ester 1 remaining, manner described above for the epoxidation of 1 (see the Ma-
epoxyalcohol 2 accounted for 28% of the mixture, along with terials and Methods section).
epoxyketone 4 (32%) and furan 5 (28%). Reactions con-
The furan, 5, that was a byproduct of the DMDO and
ducted under conditions (iv) above gave a 35% conversion of EMDO oxidations was prepared synthetically from the acid-
1 to epoxyalcohol 2 with one equivalent of Oxone™, and labile epoxyketone 4. Earlier accounts describe procedures
94% with a 2:1 ratio of oxidant to homoallylic alcohol 1. Ad- that involve treatment of 4 with mercuric acetate in acetic
ditionally, the product contained about 3% each of 4 and start- acid with microwave heating (14), or with sodium azide and
ing material 1, along with a trace of 5. An 8:1 ratio of oxi- ammonium chloride in aqueous ethanol (23). Brief treatment
dant/substrate succeeded in depleting 1 completely, but the of 4 with either a catalytic amount of titanium tetrachloride
product mixture now was 49% 2, 33% 4, and 18% 5. Judging or a trace of perchloric acid in tetrahydrofuran gave furan 5
from the altered ratio of the diastereomers for this last oxida- via the dihydrofuran 6 almost exclusively (Fig. 2A). Evidence
tion, it appears that the epoxyalcohols served as precursors that 6 is the precursor to 5 was obtained from gas chromatog-
for the epoxyketone 4 and ultimately furan 5.
raphy–mass spectrometry. Direct analysis of 4 gave peaks
The relative reactivity of a secondary alcohol and a disub- whose mass spectra corresponded to compounds 5, 4, and 6,
stituted alkene has been investigated recently (18). Oxidation in this order. Presumably, compounds 5 and 6 arose from ther-
of unsaturated alcohols favors epoxidation, although alcohol mal rearrangement of 4. Prior treatment of ketoepoxide 4 with
structure and solvent composition can affect product distribu- BSTFA before GLC-MS, however, gave a single peak whose
tion. Epoxidation was the sole reaction observed by these au- fragmentation pattern matched that predicted for silylated 6
thors for a specific homoallylic alcohol. We briefly explored (Fig. 2B). Apparently, the acidity of the BSTFA reagent was
competitive oxidations of Z-5-decene and 2-decanol and ob- sufficient to cause ring-opening of ketoepoxide 4 to 6, which
served that the alkene was oxidized at least 20 times faster is silated by this reagent before it dehydrates to furan 5.
than the alcohol group. In sharp contrast, the less electrophilic
1-decene reacted at a rate comparable to that of 2-decanol.
Diastereoselective oxidations of methyl ricinoleate. The di-
astereoselectivity of epoxidation of chiral allylic alcohols with
The epoxidation of chiral allylic alcohols can give epoxy- DMDO has been discussed with other oxidants (20). Oxida-
alcohols with considerable diastereoselectivity when less polar tion of achiral allylic alcohols with induction of asymmetry by
solvents are used (19,20). This has been interpreted in terms titanium-based chiral catalysts has been developed by K.B.
of hydrogen bonding of the alcohol to the dioxirane. In all re- Sharpless (24,25). The mechanisms by which these diastere-
actions studied, the ketoalkene was not the major product.
oselective and steroselective epoxidations are accomplished
Briefly, we found that Oxone™-promoted oxidations of are such that the competing transition states are better differ-
methyl ricinoleate can be employed successfully for prepara- entiated by the “tighter” arrangements permitted by the loca-
tion of the epoxyalcohol 2 under the conditions (iv) described tion of the alcohol OH as part of an allylic structure. Although
above. The ketoalkene, 3, was not observed as a co-product the ricinoleic acid structure is homoallylic, we hoped that the
in any of our procedures. Although further oxidation of 2 to configurational purity of 1 (R-12-hydroxy), coupled with a
the epoxyketone 4 occurs, the process is complicated by chiral catalyst, might allow good π-diastereofacial selectivity.
epoxide ring opening of 4 to furan 5. The ability of the hy- The earlier diastereomeric ratios for epoxyalcohol 2, obtained
droxyl group to direct a stereoselective epoxidation of 1 was by reactions of 1 with meta-chloroperbenzoic acid, DMDO,
not useful for obtaining epoxyalcohol 2 in high diastere- and other dioxiranes, are given in Table 1. A titanium (IV)-
omeric excess (de).
catalyzed epoxidation (titanium isopropoxide) with t-butyl hy-
Because a one-pot transformation from 1 to 4 was not ap- droperoxide as the oxidant led to a 3:1 ratio of diastereomeric
parent, we examined single-step conversions of 2 to 4, or of 3 epoxyalcohols (Table 1). When the alcohol ligand was re-
to 4 (Fig. 1). Oxidations of secondary alcohols to ketones placed with a tertiary alcohol (titanium t-amyloxide), the di-
abound (21), although many of the procedures introduce elec- astereomeric excess (de) rose to 76%. A rationalization for
trophiles that might cause the epoxide ring to accept the chirality transfer by a titanium catalyst is shown in Figure 3.
neighboring hydroxy group as a nucleophile in a competing The side chain, hexyl substituent, prefers the equatorial posi-
reaction that opens the ring. Posner’s use of trichloroacetalde- tion to avoid stearic interaction with a group attached to tita-
hyde and activated alumina in a hydride transfer reaction was nium that is oriented axially. We briefly examined Sharpless’
JAOCS, Vol. 75, no. 5 (1998)

EPOXIDATION OF METHYL RICINOLEATE
605
B
FIG. 2. (A) Proposed acid-catalyzed rearrangement pathway for ketoepoxide 4 to furan 5 through intermediate 6.
(B) Mass spectrum for silylated dihydrofuran intermediate 6.
methodologies of enhancing the diastereoselectivity of epoxi- ricinoleic acid derivatives, such as those represented by struc-
dation. -Diethyl tartrate as ligand did not significantly alter tures 2, 3, and 4 in this paper, are of interest because of their
the enantiomeric ratio of 2, but the -ester increased de to potential in several industrial applications. For example, ma-
72%. -Diisopropyl tartrate as a ligand gave 80% de (9:1 terials similar in structure to those obtained in this study have
ratio). Replacement of the isopropoxy groups on titanium by a applications as nondrying polymer coatings, polyol surfac-
chelate formed from a -, as opposed to an -tartrate ester lig- tants, drying oils, and as emulsifiers and emollients in per-
L
D
D
D
L
and, might be expected to enhance stereo selection according sonal care products (4). Oxone™ is an inexpensive source of
to this picture. Figure 3 also suggests that the oxygen is deliv- EMDO, which is becoming yet more useful as more conve-
ered preferentially to that face, leading to the 9S,10R configu- nient procedures for preparing it become available (26,27)
ration for epoxyalcohol 2.
and as alternate procedures for in-situ generation and use of
In summary, the oxidation of methyl ricinoleate 1 can be other dioxiranes are reported (28,29). The ability of the
conveniently conducted to produce selective oxidation of the 12-OH group of 1 to direct EMDO epoxidation in our trials
alkene or the alcohol structures to epoxyalcohol 2 or ke- was modest, but one can obtain a 9:1 ratio of diastereomeric
toalkene 3, respectively, as well as the concomitant oxidation epoxyalcohols by using t-butylhydroperoxide and a titanium
of both functional groups to ketoepoxide 4. Oxo and epoxy catalyst coupled with D-diisopropyl tartrate ligand.
JAOCS, Vol. 75, no. 5 (1998)

606
T.A. FOGLIA ET AL.
FIG. 3. Selective diastereomeric epoxidation of methyl ricinoleate with t-butylhydroperoxide
catalyzed by chiral titaniumIV complexes.
saturated Fatty Acids: Nucleophilic Additions to Methyl (E)-12-
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[Received May 5, 1997; accepted November 5, 1997]
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