Enantioselective preparation of (2R,3R)-(+)- and (2S,3S)-(-)-2,3-epoxy- 2-methylbutanoic acids and some derivatives

Article abstract of DOI:10.1016/S0957-4166(98)00025-1

(2R,3R)-(+)- and (2S,3S)-(-)-2,3-epoxy-2-methylbutanoic acids (epoxyangelic acids) were prepared from (Z)-2-methyl-2-butenoic acid using the Sharpless asymmetric epoxidation method in combination with the use of (- )- and (+)-menthol as chiral auxiliaries. Both substances, obtained in high enantiomeric excess, were characterized by spectroscopic and optical activity data. Their absolute configuration was determined by correlation with (R)- (+)-2-methyl-1,2-butanediol.

Full text of DOI:10.1016/S0957-4166(98)00025-1

Pergamon
Tetrahedron: Asymmetry 9 (1998) 757–764
Enantioselective preparation of (2R,3R)-(+)- and (2S,3S)-(−)-2,3-
epoxy-2-methylbutanoic acids and some derivatives
J. Martín Torres-Valencia, Carlos M. Cerda-García-Rojas and Pedro Joseph-Nathan ∗
Departamento de Química del Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, Apartado
14-740, Mexico, D.F., 07000 Mexico
Received 31 October 1997; accepted 11 December 1997
Abstract
(2R,3R)-(+)- and (2S,3S)-(−)-2,3-epoxy-2-methylbutanoic acids (epoxyangelic acids) were prepared from (Z)-
2-methyl-2-butenoic acid using the Sharpless asymmetric epoxidation method in combination with the use of (−)-
and (+)-menthol as chiral auxiliaries. Both substances, obtained in high enantiomeric excess, were characterized
by spectroscopic and optical activity data. Their absolute configuration was determined by correlation with (R)-
(+)-2-methyl-1,2-butanediol. © 1998 Elsevier Science Ltd. All rights reserved.
1. Introduction
A literature survey revealed that there are more than 170 natural products which contain either (2R,3R)-
or (2S,3S)-2,3-epoxy-2-methylbutanoic acid residues as part of their structures. Most of these substances
are sesquiterpene lactones such as germacranolides (approximately 70), guaianolides (nearly 25) and
eudesmanolides (almost 25). Even some kaurenes, coumarins, furanoeremophilanes, alkaloids and
longipinene derivatives have been found to contain this kind of ester group. The absolute configuration
of the epoxyangelate moiety has been elucidated only in a few cases by X-ray diffraction analysis.
However, the problem still remains unsolved for at least 150 of these substances, in spite of the fact
that some of them have relevant biological activity as tumor inhibitors,1,2 antibiotics,3 antipyretics4 or
antiinflammatory agents.5
The present paper describes the enantioselective preparation of both (2R,3R)- and (2S,3S)-2,3-epoxy-
2-methylbutanoic acids [(+)- and (−)-epoxyangelic acids] by means of the Sharpless asymmetric epox-
idation method6,7 combined with the use of (−)- and (+)-menthol as chiral auxiliaries. These results,
together with our previous report8 on the obtention of (2R,3S)- and (2S,3R)-2,3-epoxy-2-methylbutanoic
∗
Corresponding author. E-mail: pjoseph@soun.red.cinvestav.mx
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00025-1

758
J. M. Torres-Valencia et al. / Tetrahedron: Asymmetry 9 (1998) 757–764
acids [(−)- and (+)-epoxytiglic acids], provide preparation procedures to obtain the four stereoisomers
of 2,3-epoxy-2-methylbutanoic acid in high enantiomeric excess.
2. Results and discussion
The synthesis of (2R,3R)-(+)- and (2S,3S)-(−)-2,3-epoxy-2-methylbutanoic acids 14 and 15 was
carried out starting from (Z)-2-methyl-2-butenoic acid (angelic acid) 1 as shown in Schemes 1 and
2. Angelic acid 1 was esterified with (1R,2S,5R)-(−)-menthol to give ester 29 which was treated
with AD-mix-β and AD-mix-α reagents6 to provide diolesters 4 and 5, respectively. AD-mix-β and
AD-mix-α are reagents for asymmetric dihydroxylation which contain potassium osmate, potassium
ferricyanide, potassium carbonate and the chiral ligands dihydroquinidine 1,4-phthalazinediyl diether or
dihydroquinine 1,4-phthalazinediyl diether, correspondingly. Although the ligands are diastereoisomeric
entities, they essentially induce opposite stereoselectivities.6
Scheme 1.
When using AD-mix-β for the treatment of 2, a 90% diastereoselectivity (ds) towards ester 4 was
achieved, while when AD-mix-α was employed, only 78% diastereoselectivity towards ester 5 was

J. M. Torres-Valencia et al. / Tetrahedron: Asymmetry 9 (1998) 757–764
759
Scheme 2.
1
obtained. These values were ascertained from the H-NMR spectra of the reaction products measured at
300 MHz in CDCl3. The mixtures of compounds 4 and 5 were converted into epoxyangelate esters 8 and
9, respectively, by known procedures,7 which preserved the chiral centers and also the diastereoselectivity
values. Compound 8 was obtained with a diastereoselectivity of 98% after flash chromatography10 of the
diastereomeric mixture formed by 8 and 9 in a 9:1 ratio by elution with hexane:EtOAc (100:7). The
1
improvement in diastereoselectivity was carefully monitored by H-NMR. Compound 8 was subjected
to alkaline hydrolysis with NaOH in MeOH, leading to the respective sodium salt 12 and (−)-menthol.
The sodium salt 12 was neutralized with HCl in aqueous NH4Cl solution to give the corresponding
(2R,3R)-(+)-2,3-epoxy-2-methylbutanoic acid 14 as shown in Scheme 2.
Attempts to obtain ester 9 in high diastereomeric excess (d.e.), and thus prepare (2S,3S)-(−)-2,3-
epoxy-2-methylbutanoic acid 15, were unsuccessful. Even chromatographies of the mixture enriched
up to 78% of 9 gave unsatisfactory results. Presumably, the fact that ester 9 is not the first eluate of the
column hinders its purification. To overcome this difficulty, we decided to prepare the enantiomer of
compound 8, that is to say ester 10. This substance (10) will emerge from the column as the first eluate,
thus allowing its obtention in high diastereomeric excess as was the case for 8. Esterification of angelic
acid 1 with (1S,2R,5S)-(+)-menthol yielded ester 3 which was also treated with AD-mix-β and AD-mix-
α reagents6 affording diolesters 6 and 7. When AD-mix-α was employed, an 80% diastereoselectivity
(ds) towards ester 6 was obtained, and when AD-mix-β was used, an 84% diastereoselectivity towards
ester 7 was obtained, as was observed in the 1H-NMR spectra of the crude reaction products. The mixture
formed by 6 and 7 in an 8:2 ratio was converted to epoxyangelates 10 and 11 (see Scheme 1). As expected,
flash chromatography of this mixture afforded compound 10 with 98% diastereoselectivity. This value
was also obtained by 1H-NMR measurements. Ester 10 was hydrolyzed with NaOH in MeOH affording
the sodium salt 13 and (+)-menthol. Finally, the sodium salt 13 was neutralized to give the corresponding
(2S,3S)-(−)-2,3-epoxy-2-methylbutanoic acid 15.
In the reactions of (−)- and (+)-menthyl angelate esters (2 and 3) with AD-mix-β and AD-mix-α, the
(−)- and (+)-menthol moieties make small contributions to stereodifferentiation because there was only
a modest change in the diastereoselectivities, as can be seen in Scheme 1 for 5 (78%) versus 4 (90%) and
6 (80%) versus 7 (84%). Furthermore, epoxidation of 2 with m-chloroperbenzoic acid gave a mixture of
8 and 9 in a ca 1:1 ratio. However, the use of (−)- and (+)-menthol was well appreciated when measuring
diastereoselectivities by 1H-NMR as well as for the chromatographic purification of 8 and 10.
The absolute configuration of the compounds depicted in Schemes 1 and 2 was determined by chemical
correlation of ester 8 with (R)-(+)-2-methyl-1,2-butanediol11 as follows. Treatment of 8 (ds=90%) with
LiAlH4 in THF gave (R)-(+)-2-methyl-1,2-butanediol with [α]D25=+7, c 1.30 in CHCl3, ee=80% (lit.11

760
J. M. Torres-Valencia et al. / Tetrahedron: Asymmetry 9 (1998) 757–764
[α]D20=+8.7, c 1.35 in CHCl3, ee=94%). This correlation is possible because the hydride, besides
reduction of the ester group to the alcohol, attacks at C-30 while C-20 retains its configuration. On the
other hand, epoxyacids 14 and 15 were treated with diazomethane to give the corresponding methyl esters
16 with [α]D25=+19, c 1.10 in CHCl3 and 17 with [α]D25=−19, c 1.30 in CHCl3. Methyl ester 16 has
already been described in the literature12 with [α]D25=+21, neat. Assignments of the 1H- and 13C-NMR
spectra for all compounds were confirmed by COSY and HETCOR experiments.
According to the results shown in this work, the following sequence can be proposed for the absolute
configuration assignment of the epoxyangelic acid moiety present in natural products:
(i) hydrolysis of the ester group in those compounds where the absolute configuration of the epoxyan-
gelate moiety is unknown;
(ii) esterification of the resulting alcohol with both enantiomers of the epoxyangelic acid, prepared as
described herein; and
(iii) comparison of the 1H-NMR spectra of both semi-synthetic samples with that of the original natural
product.
3. Experimental
1
1H, 13C, COSY-1H/1H, and HETCOR-NMR spectra: Varian XL-300 GS. H measured at 300 MHz,
13C at 75.4 MHz, TMS as internal standard, solvent CDCl3, unless otherwise stated. IR spectra:
Perkin–Elmer 16F PC FT-IR spectrophotometer. Mass spectra: Hewlett–Packard 5989-A, 70 and 20
eV. Specific rotations: Perkin–Elmer 241 polarimeter. Column chromatography (CC): Merck silica
gel, particle size: 0.040–0.063 mm (230–400 mesh ASTM). Angelic acid 1, was prepared from tiglic
acid following published procedures.13 Tiglic acid, (−)- and (+)-menthol were commercially available
(Aldrich).
3.1. (−)-Menthyl angelate 2
Angelic acid 113 (8.0 g) was treated with KOH (4.5 g) in MeOH (25 ml) on an ice–water bath. The
solvent was removed with an N2 stream and acetone was added to precipitate the salt which was filtered,
washed and dried on a vacuum oven. The resulting potassium angelate was treated with oxalyl chloride
(10 ml) in Et2O (70 ml) to give angeloyl chloride14 which was immediately added to a solution of (−)-
menthol (9.3 g) in CH2Cl2 (30 ml). The mixture was stirred at room temp. for 48 h. The solvent was
evaporated under vacuum and the residue was chromatographed on a silica gel column eluting with
hexane:CH2Cl2 (2:1, v/v) to afford 2 (13.8 g, 73%). Spectroscopic data were in agreement to those
reported.9
3.2. (+)-Menthyl angelate 3
Prepared as described for compound 2, but using angelic acid 113 (5.0 g) and (+)-menthol (5.8 g) to
afford 3 (8.9 g, 75%) as a colorless oil. [α]D25=+83 (c=1.22, CHCl3). Spectroscopic data were identical
to those of compound 2.

J. M. Torres-Valencia et al. / Tetrahedron: Asymmetry 9 (1998) 757–764
761
3.3. (−)-Menthyl (20R,30R)-20,30-dihydroxy-20-methylbutanoate 4
Compound 2 (4.0 g) was treated with AD-mix-β6 yielding compound 4 as a colorless oil (4.22 g, 92%).
The product was obtained with a d.e. of 90% showing [α]D25=−66 (c=2.58, CHCl3). IR (CHCl3) νmax
:
3572, 3524, 3044, 2960, 1716, 1456, 1376, 1254, 1178, 954, 914 cm−1. 1H-NMR δ: 4.74 (d/t, J=4.4/10.9
Hz, H-1), 1.47 (m, H-2), 1.70 (m, H-3eq), 1.71 (m, H-4), 1.50 (m, H-5), 2.01 (m, H-6eq), 1.01 (m, H-
6ax), 1.88 (d/sep, J=2.7/9.8 Hz, H-7), 0.75 (d, J=7.0 Hz, Me-8,9), 0.91 (d, J=6.9 Hz, Me-8,9), 0.92 (d,
J=6.5 Hz, Me-10), 3.81 (d/q, J=8.8/6.4 Hz, H-30), 1.14 (d, J=6.4 Hz, Me-40), 1.43 (s, Me-50), 2.26 (d,
J=8.8 Hz, OH at C-20), 3.45 (s, OH at C-30) ppm. 13C-NMR δ: 76.65 (C-1), 46.86 (C-2), 22.98 (C-3),
34.12 (C-4), 31.41 (C-5), 40.58 (C-6), 26.01 (C-7), 15.73 (C-8,9), 20.82 (C-8,9), 21.94 (C-10), 175.29
(C-10), 77.09 (C-2), 71.85 (C-30), 17.76 (C-40), 22.46 (C-50) ppm.
3.4. (−)-Menthyl (20S,30S)-2030-dihydroxy-20-methylbutanoate 5
Ester 2 (4.0 g) was treated with AD-mix-α6 yielding 5 as a colorless oil (4.15 g 91%). The product
was obtained with a d.e. of 78% showing [α]D25=−74 (c=2.75, CHCl3). IR (CHCl3) νmax: 3666, 3522,
3042, 2992, 1710, 1456, 1378, 1280, 1130, 1090, 958, 914 cm−1. 1H-NMR δ: 4.77 (d/t, J=4.4/10.9 Hz,
H-1), 1.46 (m, H-2), 1.71 (m, H-3eq), 1.70 (m, H-4), 1.50 (m, H-5), 2.01 (m, H-6eq), 1.01 (m, H-6ax),
1.87 (d/sep, J=2.6/9.8 Hz, H-7), 0.76 (d, J=6.9 Hz, Me-8,9), 0.91 (d, J=7.1 Hz, Me-8,9), 0.92 (d, J=6.6
Hz, Me-10), 3.82 (d/q, J=8.5/6.4 Hz, H-30), 1.16 (d, J=6.4 Hz, Me-40), 1.44 (s, Me-50), 2.33 (d, J=8.5
Hz, OH at C-20), 3.54 (s, OH at C-30) ppm. 13C-NMR δ: 76.53 (C-1), 47.01 (C-2), 23.13 (C-3), 34.14
(C-4), 31.43 (C-5), 40.55 (C-6), 26.14 (C-7), 15.90 (C-8,9), 20.80 (C-8,9), 21.95 (C-10), 175.19 (C-10),
76.98 (C-2), 72.03 (C-30), 17.66 (C-40), 22.45 (C-50) ppm.
3.5. (+)-Menthyl (20S,30S)-20,30-dihydroxy-20-methylbutanoate 6
Compound 3 (4.0 g) was treated with AD-mix-α6 giving ester 6 as a colorless oil (4.02 g, 88%). The
product was obtained with a d.e. of 80% showing [α]D25=+64 (c=2.45, CHCl3) and spectroscopic data
identical to those of ester 4.
3.6. (+)-Menthyl (20R,30R)-20,30-dihydroxy-20-methylbutanoate 7
Compound 3 (0.50 g) was treated with AD-mix-β6 to yield ester 7 as a colorless oil (0.51 g, 90%). The
product was obtained with a d.e. of 84% showing [α]D25=+69 (c=2.55, CHCl3) and spectroscopic data
identical to those of ester 5.
3.7. (−)-Menthyl (20R,30R)-20,30-epoxy-2-methylbutanoate 8
Ester 4 (4.0 g) with a d.e. of 90% was converted to 8 by known procedures.7 The product was obtained
as a colorless oil (2.20 g, 59%) with the same d.e. as the starting material. Flash chromatography using
hexane:EtOAc (100:7, v/v) as eluent yielded compound 8 with a d.e. of 98%. This sample showed
[α]D20=−39 (c=2.90, CHCl3). IR (CHCl3) νmax: 3040, 1730, 1452, 1270, 1152, 1084, 980 cm−1. EIMS
m/z (%): [M+1]+ 255 (1), 155 (1), 139 (31), 138 (57), 123 (18), 116 (94), 95 (43), 83 (100), 81 (45), 72
(10), 71 (19), 69 (42), 57 (32), 43 (89), 41 (46). 1H-NMR δ: 4.80 (d/t, J=4.4/10.9 Hz, H-1), 1.50 (m, H-2),
1.62 (m, H-3eq), 1.71 (m, H-4), 1.46 (m, H-5), 1.98 (m, H-6eq), 1.03 (m, H-6ax), 1.87 (d/sep, J=2.7/7.0
Hz, H-7), 0.75 (d, J=7.0 Hz, Me-8,9), 0.91 (d, J=7.0 Hz, Me-8,9), 0.90 (d, J=7.1 Hz, Me-10), 3.04 (q,

762
J. M. Torres-Valencia et al. / Tetrahedron: Asymmetry 9 (1998) 757–764
J=5.5 Hz, H-30), 1.32 (d, J=5.5 Hz, Me-40), 1.55 (s, Me-50) ppm. 13C-NMR δ: 75.52 (C-1), 46.85 (C-
2), 23.41 (C-3), 34.19 (C-4), 31.43 (C-5), 40.89 (C-6), 26.27 (C-7), 16.20 (C-8.9), 20.63 (C-8,9), 21.96
(C-10), 169.48 (C-10), 59.86 (C-2), 59.76 (C-30), 13.80 (C-40), 19.29 (C-50) ppm.
3.8. (−)-Menthyl (20S,30S)-20,30-epoxy-2-methylbutanoate 9
Ester 5 (4.0 g) with a d.e. of 78% was converted to epoxyester 9 by known procedures.7 The product
was obtained as a colorless oil (2.31 g, 62%) with a d.e. of 78% showing [α]D25=−59 (c=1.40, CHCl3).
IR (CHCl3) νmax: 3040, 2924, 1734, 1454, 1268, 1170, 778 cm−1. EIMS m/z (%): [M+1]+ 255 (1), 138
1
(36), 116 (54), 95 (29), 83 (84), 95 (29), 57 (33), 55 (63), 43 (100), 41 (54). H-NMR δ: 4.76 (d/t,
J=4.4/10.8 Hz, H-1), 1.50 (m, H-2), 1.67 (m, H-3eq), 1.70 (m, H-4), 1.46 (m, H-5), 1.98 (m, H-6eq),
1.01 (m, H-6ax), 1.92 (d/sep, J=2.9/7.5 Hz, H-7), 0.76 (d, J=6.8 Hz, Me-8,9), 0.92 (d, J=7.0 Hz, Me-
8,9), 0.91 (d, J=6.4 Hz, Me-10), 3.03 (q, J=5.4 Hz, H-30), 1.32 (d, J=5.4 Hz, Me-40), 1.56 (s, Me-50)
ppm. 13C-NMR δ: 75.61 (C-1), 46.88 (C-2), 23.10 (C-3), 34.19 (C-4), 31.40 (C-5), 40.85 (C-6), 26.14
(C-7), 15.92 (C-8,9), 20.94 (C-8,9), 21.98 (C-10), 169.40 (C-10), 59.66 (C-2), 59.77 (C-30), 13.81 (C-40),
19.31 (C-50) ppm.
3.9. (+)-Menthyl (20S,30S)-20,30-epoxy-2-methylbutanoate 10
Ester 6 (4.0 g) with a d.e. of 80% was converted to epoxyester 10 by known procedures.7 The
product was obtained as a colorless oil (2.26 g, 61%) with a d.e. of 80%. Flash chromatography using
hexane:EtOAc (100:7, v/v) as the eluent yielded 10 with a d.e. of 98% showing [α]D25=+40 (c=1.29,
CHCl3). Spectroscopic data were identical to those of 8.
3.10. (+)-Menthyl (20R,30R)-20,30-epoxy-2-methylbutanoate 11
Ester 7 (4.0 g) with a d.e. of 84% was converted to epoxyester 11 by known procedures.7 The product
was obtained as a colorless oil (2.31 g, 62%) with a d.e. of 84% showing [α]D25=+62 (c=1.20, CHCl3).
Spectroscopic data were identical to those of 9.
3.11. Sodium (2R,3R)-(+)-2,3-epoxy-2-methylbutanoate 12
A solution of 8 with a d.e. of 98% (657 mg) in MeOH (11 ml) was stirred with NaOH (103 mg) for 12
h at room temperature. The solvent was removed with an N2 stream and acetone (10 ml) was added to
precipitate the sodium salt. The suspension was filtered and washed with acetone (10 ml) to provide 12
(263 mg, 74%). [α]D25=+62 (c=1.0, H2O). IR (KBr) νmax: 1615, 1450, 1078, 843, 790 cm−1. 1H-NMR
(D2O, HDO centered at 4.63 ppm) δ: 2.99 (q, J=5.5 Hz, H-3), 1.08 (d, J=5.5 Hz, Me-4), 1.33 (s, Me-5)
ppm. 13C-NMR (D2O, 1,4-dioxane as internal standard centered at 66.40 ppm) δ: 177.00 (C-1), 64.07
(C-2), 60.46 (C-3), 13.69 (Me-4), 18.92 (Me-5) ppm. The chiral auxiliary, (−)-menthol, was recovered
after evaporation of the solvent.
3.12. Sodium (2S,3S)-(−)-2,3-epoxy-2-methylbutanoate 13
A solution of 10 with a d.e. of 98% (550 mg) in MeOH (8 ml) was stirred with NaOH (96 mg) and
treated as described for the obtention of 12 to yield compound 13 (207 mg, 70%). [α]D25=−62 (c=1.0,
H2O). Spectral data were identical to those of 12.

J. M. Torres-Valencia et al. / Tetrahedron: Asymmetry 9 (1998) 757–764
763
3.13. (2R,3R)-(+)-2,3-Epoxy-2-methylbutanoic acid 14
A solution of sodium salt 12 (100 mg) in a saturated solution of NH4Cl (5 ml) was cooled on an
ice–water bath, neutralized with HCl 0.5 N and extracted with EtOAc (20 ml). The organic layer was
dried with Na2SO4 and evaporated at room temperature to yield 14 as a colorless oil (27 mg, 32%).
[α]D25=+30 (c=1.8, CHCl3). IR (CHCl3) νmax: 3672, 3494, 1736, 1380, 1268, 1102 cm−1. EIMS m/z
(%): [M+1]+ 117 (7), 99 (4), 88 (11), 72 (57), 71 (21), 45 (100), 43 (98), 41 (18). 1H-NMR δ: 3.16 (q,
J=5.5 Hz, H-3), 1.40 (d, J=5.5 Hz, Me-4), 1.61 (s, Me-5), 5.00 (br s, COOH) ppm; 13C-NMR δ: 172.65
(C-1), 60.39 (C-2), 60.94 (C-3), 13.66 (C-4), 18.45 (C-5) ppm.
3.14. (2S,3S)-(−)-2,3-Epoxy-2-methylbutanoic acid 15
A solution of sodium salt 13 (100 mg) in a saturated solution of NH4Cl (5 ml) was treated as described
for the obtention of 14 affording compound 15 as a colorless oil (25 mg, 30%). [α]D25=−29 (c=1.4,
CHCl3). Spectral data were identical to those of 14.
3.15. Methyl (2R,3R)-(+)-2,3-epoxy-2-methylbutanoate 16
Epoxyacid 14 (135 mg) was treated with an ethereal solution of diazomethane15 (20 ml) at room
temperature. After evaporation of the solvent, methyl ester 16 (24 mg, 16%) was obtained as a colorless
oil. [α]D25=+19 (c=1.1, CHCl3). IR (CHCl3) νmax: 3040, 1720, 1460, 1380, 1265, 1160 cm−1. EIMS
1
m/z (%): [M+1]+ 131 (1), 115 (1), 99 (1), 83 (2), 71 (10), 59 (93), 55 (8), 43 (100). H-NMR δ: 3.06
(q, J=5.4 Hz, H-3), 1.33 (d, J=5.4 Hz, Me-4), 1.57 (s, Me-5), 3.78 (s, MeO) ppm. 13C-NMR δ: 170.48
(C-1), 59.77 (C-2), 59.95 (C-3), 13.62 (C-4), 19.14 (C-5), 52.25 (MeO) ppm.
3.16. Methyl (2S,3S)-(−)-2,3-epoxy-2-methylbutanoate 17
Epoxyacid 15 (80 mg) was treated as described for 16 to yield methyl ester 17 (13 mg, 14%) as a
colorless oil. [α]D25=−19 (c=1.3, CHCl3). Spectroscopic data were identical to those of 16.
3.17. (2R)-(+)-2-Methyl-1,2-butanediol
A solution of 8 with a d.e. of 90% (250 mg) in THF (8 ml) was treated with LiAlH4 (150 mg) at
0°C. The mixture was stirred under reflux for 4 h, cooled to 0°C, treated with EtOAc, MeOH and H2O,
filtered and extracted with EtOAc. The organic layer was washed with H2O, dried with Na2SO4 and
evaporated. The product was chromatographed on silica gel. Elution with CH2Cl2:EtOAc (1:1) yielded
the title compound (72 mg, 71%). [α]D25=+7 (c 1.30, CHCl3). Spectroscopic data were identical to those
reported.11
Acknowledgements
Partial financial support from CoNaCyT (Mexico) is acknowledged.

764
J. M. Torres-Valencia et al. / Tetrahedron: Asymmetry 9 (1998) 757–764
References
1. Kimura, Y.; Okuda, H.; Baba, K.; Kozawa, M.; Arichi, S. Planta Med. 1987, 53, 521–525.
2. Kupchan, S. M.; Maruyama, M.; Hemingway, R. J.; Hemingway, J. C.; Shibuya, S.; Fujita, T. J. Org. Chem. 1973, 38,
2189–2196.
3. Kato, T.; Frei, B.; Heinrich, M.; Sticher, O. Planta Med. 1996, 62, 66–67.
4. Alam, M.; Susan, T.; Joy, S.; Kundu, A. B. Indian J. Exp. Biol. 1992, 30, 38–41.
5. Okuda, H. Chemical Abstracts 1989, 111: 160193d.
6. Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.; Hartung, J.; Jeong, K.-S.; Kwong, H.-L.; Morikawa, K.;
Wang, Z.-M.; Xu, D.; Zhang, X.-L. J. Org. Chem. 1992, 57, 2768–2771.
7. Kolb, H. C.; Sharpless, K. B. Tetrahedron 1992, 48, 10515–10530.
8. Torres-Valencia, J. M.; Cerda-García-Rojas, C. M.; Joseph-Nathan, P. Tetrahedron: Asymmetry 1995, 6, 1611–1616.
9. Miyashita, M.; Shiina, I.; Miyoshi, S.; Mukaiyama, T. Bull. Chem. Soc. Jpn 1993, 66, 1516–1527.
10. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923–2925.
11. Seebach, D.; Naef, R.; Calderari, G. Tetrahedron 1984, 40, 1313–1324.
12. Christensen, B.; Kjaer, A. Acta Chem. Scand. 1962, 16, 2466–2467.
13. Buckles, R. E.; Mock, G. V. J. Org. Chem. 1950, 15, 680–684.
14. Beeby, P. J. Tetrahedron Lett. 1977, 38, 3379–3382.
15. Arndt, F. Org. Syn. Coll. 1943, 2, 165.