A facile synthetic method for chiral 1,2-epoxides and the total synthesis of chiral pheromone epoxides

Article abstract of DOI:10.1016/S0957-4166(99)00082-8

Chiral 1,2-epoxy-3-alkanol tosylates were successfully synthesized from alkynols in three steps using the Sharpless AD reaction as a key step in good yields. Two chiral insect pheromone epoxides were smoothly obtained from the corresponding key intermediate.

Full text of DOI:10.1016/S0957-4166(99)00082-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 10 (1999) 837–840
A facile synthetic method for chiral 1,2-epoxides and the total
synthesis of chiral pheromone epoxides
Zhi-Bo Zhang, Zhi-Min Wang,∗ Yu-Xiu Wang, Huan-Quan Liu, Gui-Xin Lei and Min Shi ∗
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, People’s Republic of China
Received 2 February 1999; accepted 1 March 1999
Abstract
Chiral 1,2-epoxy-3-alkanol tosylates were successfully synthesized from alkynols in three steps using the
Sharpless AD reaction as a key step in good yields. Two chiral insect pheromone epoxides were smoothly obtained
from the corresponding key intermediate. © 1999 Elsevier Science Ltd. All rights reserved.
Synthetic chemists always face a major challenge in the preparation of chiral compounds with high
enantiomeric excess. The need for pure enantiomers is particularly apparent in the field of insect
pheromone chemistry, since insect chemoreception can be highly stereoselective.1–3 Optically active
epoxides are an important class of natural products encountered as sex attractants of lepidopteran pests,4
and self-defensive substances against rice blast disease.5 The optically active 1,2-epoxy-3-alkanols are
key intermediates in the synthesis of these insect pheromones because they can be easily converted
into the corresponding optically active 2,3-epoxy-1-alkanols through the Payne rearrangement6 or into
optically active internal epoxides via an alkylative rearrangement of the corresponding p-toluenesulfonate
esters.7 In order to obtain chiral epoxides via these synthetic approaches, the most frequently used key
reaction until now has been the Sharpless AE reaction on the Z-allylic alcohols.7–9 Herein we wish to
report an alternative synthetic method for chiral 1,2-epoxy-3-alkanol tosylates using the Sharpless AD
reaction10 as the key reaction and the total synthesis of the insect sex pheromones, (6Z,9S,10R)-9,10-
epoxy-6-henicosene and (3Z,6Z,9S,10R)-9,10-epoxy-3,6-henicosadiene.
The Sharpless AD reaction on starting material 2, which has different long alkyl chains (prepared
by reduction of the corresponding alkynol 111 using LiAlH4 in THF), installed the two stereogenic
centers, with 96% ee.12 The resulting triol 3 was subsequently treated with NaH and Tos–Im13 in THF
to produce the key intermediate 4 in good yield (Scheme 1). To the best of our knowledge, this new
synthetic approach is the shortest and the most efficient among those reported in previous literature.7–9
Thus 1,2-epoxy-3-tosylates 4a–h with different length alkyl chains were obtained as colorless solids or
oils. Their total yields in three steps, specific rotations and melting points are summarized in Table 1. The
∗
Corresponding author. E-mail: mshi@pub.sioc.ac.cn
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00082-8

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Z.-B. Zhang et al. / Tetrahedron: Asymmetry 10 (1999) 837–840
chemical yields of 4a–h slightly increased with the increase in alkyl chain length. The specific rotation of
the key intermediate 4g was very close to that reported in the literature {lit.8 [α]D20 +8.3 (c 1, CHCl3)}.
Scheme 1.
Table 1
Yields and physical properties of the obtained 1,2-epoxy-3-tosylates (4a–h)
The synthesis of a sex pheromone of Phragmatobia fuliginosa is depicted in Scheme 2. The epoxide
4g was opened by 1-lithio-heptyne in the presence of BF3·Et2O to afford compound 5. Treatment
of compound 5 with K2CO3 in methanol gave another epoxide 6 in good yield. Catalytic hydroge-
nation of compound 6 over the Lindlar catalyst easily gave the target compound (6Z,9S,10R)-9,10-
epoxy-6-henicosene 7 in moderate yield. By the same synthetic procedures, another sex pheromone
(3Z,6Z,9S,10R)-9,10-epoxy-3,6-henicosadiene could be also obtained using 1-lithio-1,4-heptadiyne as
the epoxide opening reagent (Scheme 3).
The specific rotations of our synthetic compounds 7 and 10 were very close to those reported in
20
20
20
literature {7: [α]D +8.7 (c 0.97, CHCl3), lit.14 [α]D +9.4 (c 0.55, CHCl3). 10: [α]D +5.7 (c 0.97,
23
CCl4), lit.15 [α]D +5.9 (c 1.61, CCl4)}. Their spectral data were completely consistent with those
reported in the literature.14,15
In conclusion, we have developed an efficient and convenient procedure for the stereocontrolled syn-
thesis of the chiral 1,2-epoxy-3-tosylates (4a–h) from which two important chiral pheromone epoxides
have been successfully synthesized. This new synthetic approach using the Sharpless AD reaction will
certainly open a new and effective synthetic route to prepare highly stereoselective chemoreception insect

Z.-B. Zhang et al. / Tetrahedron: Asymmetry 10 (1999) 837–840
839
Scheme 2.
Scheme 3.
pheromones. In order to disclose the relationship between structure and biological activity, syntheses of
their pheromone analogs are in progress.
Acknowledgements
We thank the National Natural Sciences Foundation of China for financial support.
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