Hydrolytic kinetic resolution of terminal mono- and bis-epoxides in the synthesis of insect pheromones

Article abstract of DOI:10.1016/S0957-4166(02)00175-1

Hydrolytic kinetic resolution (HKR) of functionalised epoxides using (salen)Co(OAc) complexes provides enantiomerically enriched epoxides and diols, which have been transformed into important insect sex pheromones. In this general approach, (-)-(R)- and (+)-(S)-10-methyldodecyl acetates from the smaller tea tortrix moth were obtained, as was (-)-(R)-10-methyltridecan-2-one from the southern corn rootworm. The (S)-epoxide obtained from undec-1-en-6-yne was transformed to (-)-(R)-(Z)-undec-6-en-2-ol (Nostrenol) from ant-lions. HKR of appropriate bisepoxides was also investigated, and transformations of the resulting bisepoxides and epoxydiols provided (-)-(1R,7R)-1,7-dimethylnonylpropanoate from corn rootworms, (-)-(6R,12R)-6,12-dimethylpentadecan-2-one from the female banded cucumber beetle, and (-)-(2S,11S)-2,11-diacetoxytridecane and (+)-(2S,12S)-2,12-diacetoxytridecane from female pea-midges.

Full text of DOI:10.1016/S0957-4166(02)00175-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 779–793
Hydrolytic kinetic resolution of terminal mono- and bis-epoxides
in the synthesis of insect pheromones: routes to (−)-(R)- and
(+)-(S)-10-methyldodecyl acetate, (−)-(R)-10-methyl-2-
tridecanone, (−)-(R)-(Z)-undec-6-en-2-ol (Nostrenol),
(−)-(1R,7R)-1,7-dimethylnonyl propanoate,
(−)-(6R,12R)-6,12-dimethylpentadecan-2-one,
(−)-(2S,11S)-2,11-diacetoxytridecane and
(+)-(2S,12S)-2,12-diacetoxytridecane
Sharon Chow and William Kitching*
Department of Chemistry, The University of Queensland, Brisbane 4072, Australia
Received 5 April 2002; accepted 11 April 2002
Abstract—Hydrolytic kinetic resolution (HKR) of functionalised epoxides using (salen)Co(OAc) complexes provides enantiomer-
ically enriched epoxides and diols, which have been transformed into important insect sex pheromones. In this general approach,
(−)-(R)- and (+)-(S)-10-methyldodecyl acetates from the smaller tea tortrix moth were obtained, as was (−)-(R)-10-methyltridecan-
2-one from the southern corn rootworm. The (S)-epoxide obtained from undec-1-en-6-yne was transformed to (−)-(R)-(Z)-undec-
6-en-2-ol (Nostrenol) from ant-lions. HKR of appropriate bisepoxides was also investigated, and transformations of the resulting
bisepoxides and epoxydiols provided (−)-(1R,7R)-1,7-dimethylnonylpropanoate from corn rootworms, (−)-(6R,12R)-6,12-
dimethylpentadecan-2-one from the female banded cucumber beetle, and (−)-(2S,11S)-2,11-diacetoxytridecane and (+)-(2S,12S)-
2,12-diacetoxytridecane from female pea-midges. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
suggested that a reliable route to epoxides and 1,2-diols
of high enantiomeric excesses (e.e.s) would expedite
acquisition of such semiochemicals. Jacobsen has intro-
duced procedures for the hydrolytic kinetic resolution
Many chiral insect semiochemicals have been identified
in the last 40 years,1 with the sense of chirality being a
crucial determinant of perception and induced
behaviour.2 The determination of the enantiomeric
composition by chromatographic methods or biological
assays,3 requires synthetic methods that deliver particu-
lar enantiomers of the suspected active component.
Quite commonly, insect semiochemicals, including sex
pheromones, incorporate a medium to long hydrocar-
bon chain with some oxygen functionality, often alkyl
branching, with a specific or strongly dominating chi-
rality and/or double bond configuration. These struc-
tural features, and the regio- and stereo-regularities
characterising nucleophilic opening of terminal epox-
ides, and displacement of sulfonate ester moieties,4
(HKR)
of
terminal
epoxides
which
utilise
(salen)Co(OAc) complexes,5 e.g. 1.
H
H
H2O
Co
N
O
N
O
But
tBu
OAc
But
tBu
(R,R)-1
Most reports of successful HKR relate to simple epox-
ides lacking other functionality. This situation is chang-
* Corresponding author. Tel.: +61-07-3365-3925; fax: +61-07-3365-
4299; e-mail: kitching@chemistry.uq.edu.au
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00175-1

780
S. Chow, W. Kitching / Tetrahedron: Asymmetry 13 (2002) 779–793
ing, and more varied, but still terminal epoxides may be
satisfactorily processed.6 We now wish to describe the
application of the HKR approach to a number of
functionalised terminal epoxides, and how the resulting
highly enantiomerically enriched epoxides and diols
may be transformed to a range of important insect
semiochemicals, by routes which are in the main, more
direct than those previously described. In situations
where acquisition of both enantiomers of an insect
component is desirable, the re-constitution of the diol
(from the HKR procedure) to the alternate epoxide
enantiomer, permits this.
Acetylation yielded the target compound (−)-(R)-acet-
ate 3, with [h]2D3 −5.4 (c 0.97, CHCl3). The (+)-(S)-iso-
mer was also acquired. Treatment of (S)-diol 8, from
the HKR step, with mesyl chloride (1 equiv.) selectively
esterified the primary alcohol, and upon exposure to
K2CO3/MeOH afforded epoxide 12 which was then
processed to benzyl ether 14 as outlined above. (The
alternate procedure for converting the diol to the epox-
ide, through the cyclic sulfate, may have led to a higher
yield, on the basis of our experience in closely related
systems.) Debenzylation was achieved by hydrogenoly-
sis (H2, Pd–C, 95%), and then acetylation provided
(+)-(S)-acetate 4, with [h]2D3 +5.3 (c 1.02, CHCl3). These
procedures are summarised below in Schemes 1 and 2.
Our specific rotation values compare favorably with
those reported, which ranged from +4.3 (80% e.e.) to
+5.6,9 +5.910 and +4.511 (all for CHCl3).
2. Results and discussion
2.1. Hydrolytic kinetic resolution of mono-epoxides
2.1.1. (−)-(R)- and (+)-(S)-10-Methyldodecyl acetate 3
and 4, respectively. Initially this general approach was
directed towards (R)-(−)- and (S)-(+)-10-methyldodecyl
acetate, 3 and 4, respectively, which are components of
the pheromone of the lesser tea tortrix moth, Adox-
ophes spp. (Lepidoptera: Tortricidea).7
O
i
ii
OBn
OBn
(CH2)7
5
(CH2)7
6
OH
O
OBn
OBn
(CH2)7
7
HO
(CH2)7
+
8
OH
iii
iv
OBn
(CH2)7
7
9
OAc
OAc
(CH2)7
3
v
OH
OBn
(CH2)7
(CH2)7
10
Steps
OH
(CH2)7
2
11
(CH2)7
4
vi
OAc
(CH2)7
3
The (R)-isomer 3 was slightly more bioactive than the
(S), 4.8 A number of syntheses of 3 and 4 have been
reported and representative approaches utilise chiral
auxiliaries, resolution of an intermediate, and organo-
borane chemistry.9–11 Our procedure commenced with
commercially available 10-undecenol 2, which as its
benzyl ether 5, was epoxidised with m-chloroperbenzoic
acid (m-CPBA) in dichloromethane (DCM). Epoxide 6,
as the substrate for HKR, was stirred with 0.5 mol% of
(R,R)-1 and 0.55 mol equiv. of H2O at room tempera-
ture (ꢀ22°C) for ca. 24 h. Chromatography on silica
easily separated (R)-epoxide 7 and (S)-diol 8 and with
excellent recoveries, 48 and 45%, respectively. Epoxide
7 (>98% e.e. by chiral HPLC) on treatment with
Me2CuLi afforded secondary alcohol 9 in high yield,
which was converted to the mesylate in the standard
way. Mesylate displacement was effected with an excess
of Me2CuLi in ether, and afforded predominantly ben-
zyl ether 10 of 10-methyldodecanol 11, of inverted
configuration, along with significant elimination prod-
ucts (ꢀ30%), which were difficult to suppress. Previous
studies have demonstrated that displacement of sec-
ondary sulfonate ester groups by simple alkyl cuprates
proceeds with inversion of configuration, and is accom-
panied by varying levels of elimination.4 An ozonolytic
method of debenzylation was adopted, as this would, in
addition to transforming the benzyl ether to the ben-
zoate ester, degrade the accompanying alkenes. Thus,
treatment of benzyl ether 10 and the accompanying
alkenes with ozone–Me2S, followed by flash chro-
matography, afforded the benzoate ester, which was
hydrolysed with K2CO3/MeOH to afford alcohol 11.
Scheme 1. Reagents and conditions: (i) m-CPBA, DCM; (ii)
0.5% equiv. (R,R)-1, 0.55 equiv. H2O; (iii) Me2CuLi, Et2O,
0°C; (iv) 1. MsCl, Et3N, 2. Me2CuLi, Et2O, 0°C; (v) 1. O3,
Me2S, 2. K2CO3, MeOH; (vi) Ac2O, Py.
OH
O
i
OBn
OBn
OH
(CH2)7
HO
(CH2)7
12
8
ii
iii
OBn
(CH2)7
13
iv
OBn
OAc
(CH2)7
14
(CH2)7
4
Scheme 2. Reagents and conditions: (i) 1. MsCl, Et3N, 2.
K2CO3, MeOH; (ii) Me2CuLi, Et2O, 0°C, (iii) 1. MsCl, Et3N,
2. Me2CuLi, Et2O, 0°C; (iv) 1. H2, Pd–C (10%), 2. Ac2O, Py.
2.1.2. (−)-(R)-10-Methyltridecan-2-one 15. Ketone 15 is
the sex pheromone of the southern corn rootworm
(Diabrotica undecimpunctata howardi ), and biological
evaluation of the enantiomers indicated that the (R)-
enantiomer was preferred by males.12 Previous synthe-
ses have relied on resolution,9 chiral pool starting
materials, ((R)-citronellyl acetate and (S)-3,7-dimethyl-
1,6-octadiene),13 and asymmetric induction in an
organocopper addition to the camphorsulfonamide
derived crotyl ester.14 Several of these procedures are

S. Chow, W. Kitching / Tetrahedron: Asymmetry 13 (2002) 779–793
781
somewhat lengthy, but the reported specific rotations
for the (R)-enantiomer ([h]D (CHCl3) of −1.7,9 −1.4,13
−1.64,15 and −1.6114) agree well. The lowest value (−1.4)
may be associated with some racemisation in a reduc-
tion step.13
latter in 43% yield (maximum of 50%). Regiospecific
reductive opening of (S)-epoxide 22 with NaBH4/EtOH
provided (R)-alcohol 24, which was converted to its
Mosher’s ester and assayed at >95% e.e. Alcohol 24,
protected as the tetrahydropyran-2%-yl (THP) ether, was
now ready for Ti-mediated Z-reduction, which was
conducted as described in detail elsewhere for
analogous systems.17 Treatment with Ti(OiPr)4 and
iPrMgBr in ether (−78“−40°C) followed by aqueous
quenching provided the Z-alkene. Removal of the THP
group led to the desired (−)-(R)-(Z)-enol 20, with [h]D23
−5.5 (c 0.70, CHCl3) which may be compared with the
reported value, hD −6.1 (neat).16 Our sample of Nos-
trenol was a single double bond isomer on the basis of
the 13C NMR spectrum, and its Z-configuration was
established by decoupling (of the allylic protons) and
O
O
Steps
OBn
(CH2)7
(CH2)5
15
7
In our approach, (R)-epoxide 7 was treated with
EtMgBr, in the presence of CuI, to provide the mono-
protected (S)-diol 16. The derived secondary mesylate
was then treated with an excess of Me2CuLi in ether to
afford the benzyl-protected (R)-10-methyltridecanol 17.
Installation of the methyl ketone moiety was achieved
by Wacker oxidation of the terminal alkene 18, in turn
generated by [2,3]-Wittig rearrangement of benzyl ether
17. In this way, (−)-(R)-ketone 15, with [h]2D2 −1.6 (c
0.7, CHCl3) was obtained in five steps (ꢀ10% overall
yield) from (R)-epoxide 7. This procedure is shown in
Scheme 3.
3
measurement of J6-7 (10.8 Hz), appropriate for the
Z-configuration.18 The Ti-mediated conversion of alky-
nes to Z-alkenes, in all cases we have scrutinised,
proceeds in
a highly selective Z-sense (>99.5%).
Although not undertaken, diol 23 from the HKR could
have been reconstituted to the (R)-epoxide and thence
to (+)-(S)-(Z)-undec-6-en-2-ol.
OH
O
i
OBn
(CH2)7
16
OBn
(CH2)7
C4H9
C4H9
O
i
7
ii
iii
21
19
OBn
(CH2)7
17
C4H9
OH
C4H9
O
ii
O
+
OH
iv
(CH2)6
18
(CH2)5
22
23
C4H9
C4H9
OH
15
iii
iv
22
Scheme 3. Reagents and conditions: (i) EtMgBr, CuI; (ii) 1.
MsCl, Et3N, 2. Me2CuLi, Et2O, 0°C; (iii) nBuLi, THF, −78°C;
(iv) PdCl2, CuCl, DMF–H2O, O2.
20
24
OH
Scheme 4. Reagents and conditions: (i) m-CPBA, DCM; (ii)
0.5% equiv. (S,S)-1, 0.55 equiv. H2O; (iii) NaBH4, EtOH; (iv)
1. DHP, H+, 2. Ti(OiPr)4, iPrMgBr, Et2O then H2O, 3.
MeOH, H+.
2.1.3. (−)-(R)-(Z)-Undec-6-en-2-ol (Nostrenol) 20.
Volatile secretions from three sympatric ant-lion spe-
cies, Euroleon nostras, Grocus bore and Myrmeleon
formicarius have been investigated, and (−)-(R)-(Z)-
undec-6-en-2-ol 20 (Nostrenol) of >99.9% e.e. was iden-
tified from the former two species.16 Previous synthesis
of the (S)-enantiomer (ent-20) utilised (S)-propylene
oxide, and a Mitsunobu inversion led to (R)-Nostrenol
20. Our approach sought to utilise HKR, and to
demonstrate further the utility of a Ti-based method for
stereospecific Z-reduction of an isolated yne to the
Z-ene moiety.
2.2. Hydrolytic kinetic resolution of bisepoxides
Terminal bisepoxides (e.g. 25) should be amenable to
the HKR protocol and thereby extend the synthetic
utility of this procedure. HKR of bisepoxide 25 should
afford unprocessed bisepoxide 26, epoxydiol 27 and
tetrol 28, all in high e.e. This outcome is shown below,
with the theoretical maximal proportions being 25% of
(S,S)-bisepoxide 26, 50% of (S,R)-epoxydiol 27, and
25% of (R,R)-tetrol 28.
O
O
(CH2)n
C4H9
C4H9
Steps
26
OH
OH
O
O HKR; Catalyst
eg (S,S)-1
O
20
19
(CH2)n
(CH2)n
OH
OH
OH
27
25
The procedure commenced with 1-hexyne, which on
deprotonation and alkenylation with 5-bromo-1-pen-
tene, furnished undec-1-en-6-yne 19 (Scheme 4). Treat-
ment with m-CPBA in DCM wrought highly
chemoselective alkene epoxidation to provide the
volatile epoxy-yne 21, the required HKR substrate. Use
of (S,S) catalyst and 0.55 equiv. of H2O in the standard
fashion provided (S)-epoxide 22 and (R)-diol 23, the
OH
HO
(CH2)n
28
The predominating epoxydiol (e.g. 27) may provide
bi-directional and selective functionalisation, whereas
the bisepoxide and tetrol (which may be reconstituted
to the enantiomeric bisepoxide) are capable of afford-

782
S. Chow, W. Kitching / Tetrahedron: Asymmetry 13 (2002) 779–793
O
O
ing C2-symmetric derivatives. Given the ease of acquir-
ing the starting racemic bisepoxides, examination of
their HKR in the context of synthesis of selected insect
sex pheromones was undertaken, particularly towards
components incorporating two distant stereogenic cen-
tres, and possibly additional functionality. At the time
this work was commenced, we were unaware of any
reports describing HKR of racemic bisepoxides, but
Yokota19 has described the asymmetric cyclisations of a
few meso bisepoxides, which exhibit quite high e.e.s. It
is worthy of emphasis that aliphatic, open-chain sys-
tems, with ‘non-interacting’ remote stereogenic centres,
are generally assembled by ‘coupling’ separately pre-
pared building blocks of appropriate chirality. The
HKR of bisepoxides provides an alternative to this
approach, and this is now demonstrated with the syn-
thesis of several insect pheromones incorporating two
remote stereogenic centres.
i
(CH2)3
(CH2)3
29
31
O
O
ii
(CH2)3
+
32
OH
OH
OH
O
+
HO
(CH2)3
OH
(CH2)3
OH
34
33
O
iii
iv
O
O
33
(CH2)3
35
OH
O
O
v
O
O
(CH2)3
(CH2)3
36
37
OCOEt
O
vi
vii
(CH2)3
30
(CH2)3
38
Scheme 5. Reagents and conditions: (i) m-CPBA, DCM; (ii)
1.0% equiv. (R,R)-1, 0.8 equiv. H2O; (iii) DMP, H+; (iv)
Me2CuLi, Et2O, 0°C; (v) 1. MsCl, Et3N, 2. Me2CuLi, Et2O,
0°C; (vi) 1. MeOH, H+, 2. MsCl, Et3N, 3. K2CO3, MeOH;
(vii) 1. NaBH4, EtOH, 2. (EtCO)2O, Py.
2.2.1. (−)-(1R,7R)-1,7-Dimethylnonyl propanoate 30.
Various isomers of 1,7-dimethylnonyl propanoate
exhibit attractancy for males of corn rootworms, with
western corn rootworm (Diabrotica virgifera virgifera)
and northern corn rootworm (D. barberi ) responding
strongly to the (1R,7R)-isomer.20 Previous syntheses of
the four stereoisomers were based on optical resolution
of key intermediates21 or connection of chiral pool-
derived units about a one-carbon linker.22 More
recently, Keinan23 synthesised all four isomers of this
propanoate system by exploiting the selectivity of an
alcohol dehydrogenase (TBADH) in reduction of
nonane-2,8-dione.
2.2.2. (−)-(6R,12R)-6,12-Dimethylpentadecan-2-one 36.
Ketone 39 is the female produced sex pheromone of the
banded cucumber beetle (Diabrotica balteata), the lar-
vae of which are serious pests of crops such as cucurbits
and sweet potatoes.24 The route to 39 commenced with
epoxy-acetonide 35 is shown in Scheme 6. Treatment of
the acetonide with EtMgBr-CuI provided secondary
alcohol 40, which through its mesylate was methylated
with Me2CuLi, to furnish 41. The released diol 42 was
converted to epoxide 43, treatment of which with but-3-
enyl magnesium bromide–CuI yielded hydroxyalkene
44. Application of the methylation routine (mesylation
and treatment with Me2CuLi) delivered terminal alkene
45, which under Wacker oxidation conditions was
transformed to the target pheromone 39, with [h]2D3 −0.4
(c 0.40, CHCl3). In Mori’s approach to these stereoiso-
mers, two fragments from citronellol were linked by
sulfone mediation, and the resulting (6R,12R)-isomer
exhibited [h]2D2 −0.5 (CHCl3).25 More recently, Enders
accessed this isomer by utilizing nucleophilic allylation
of an enantiopure p-allyl-tetracarbonyl iron complex, in
a longish procedure that ultimately involved linkage of
two chiral units by sulfone based coupling. The product
had [h]2D0 −0.5 (c 0.60, CHCl3) and was considered to be
>98% e.e.26
OCOEt
Steps
(CH2)3
29
(CH2)3
30
In our approach, bisepoxide 31 from 1,8-nonadiene 29
was treated with 1.0% equiv. of (R,R)-1 and 0.8 equiv.
of H2O and provided a mixture of bisepoxide 32,
epoxydiol 33 and tetrol 34. Flash column chromatogra-
phy permitted easy separation of these components
shown below in Scheme 5.
Epoxydiol 33 was converted to acetonide 35, which was
then treated with Me2CuLi in ether to provide sec-
ondary alcohol 36. Mesylation and further treatment
with Me2CuLi effected methylation with inversion, to
furnish acetonide 37. Deprotection released the diol,
which was reconstituted to epoxide 38 by selective
mesylation of the primary alcohol and cyclisation with
base (K2CO3 in MeOH). Reductive opening of epoxide
38 with NaBH4/EtOH, followed by esterification with
propanoic anhydride in pyridine, provided the target
pheromone, (−)-(1R,7R)-propanoate 30, with [h]2D3 −7.2
(c 0.70, CHCl3). Reported rotations are −8.023 and
−7.6.22
2.2.3. (−)-(2S,11S)-2,11-Diacetoxytridecane 47 and (+)-
(2S,12S)-2,12-diacetoxytridecane 49. The diesters 47
and 49 were two of the three active components iden-
tified by coupled gas chromatography–electroantennog-
raphy of extracts from the pheromone glands of female
pea midges, Contarinia pisi, which are serious pests of
commercial peas.27 As part of that investigation, Hilbur
and Francke27 described the syntheses of these systems
in both racemic and enantiomeric forms, and also of
the third component, 2-acetoxytridecane. The approach
to the optical isomers of these systems was based on
alkylation, at both ends of a central carbon chain, with

S. Chow, W. Kitching / Tetrahedron: Asymmetry 13 (2002) 779–793
783
i
O
O
Br
(CH2)6
Br
50
46
O
O
ii
(CH2)6
+
51
OH
OH
OH
O
OH
(CH2)6
OH
+
HO
(CH2)6
52
53
OH
O
iii
iv
O
52
(CH2)6
54
OR
OR
O
O
v
O
(CH2)6
56
(CH2)6
55 (R = p-ClPhCO)
OAc
OH
OAc
OH
vii
vi
(CH2)6
57
(CH2)6
47
Scheme 7. Reagents and conditions: (i) 1. Allyl MgBr, THF, 2.
m-CPBA, DCM; (ii) 1.0% equiv. (S,S)-1, 0.6 equiv. H2O; (iii)
1. DMP, H+, 2. CH3MgBr, CuI, Et2O, 0°C; (iv) Ph3P, p-
chlorobenzoic acid, DEAD, THF; (v) 1. MeOH, H+, 2. MsCl,
Et3N, 3. K2CO3, MeOH; (vi) LiAlH4, Et2O; (vii) Ac2O, Py.
Scheme 6. Reagents and conditions: (i) EtMgBr, CuI, Et2O,
0°C; (ii) 1. MsCl, Et3N, 2. Me2CuLi, Et2O, 0°C; (iii) MeOH,
H+; (iv) 1. MsCl, Et3N, 2. K2CO3, MeOH; (v)
H2CꢀCH(CH2)2MgBr, CuI, Et2O, 0°C; (vi) 1. MsCl, Et3N, 2.
Me2CuLi, Et2O, 0°C; (vii) PdCl2, CuCl, DMF–H2O, O2.
Bisepoxide 58, on treatment with NaBH4/EtOH, pro-
vided (2S,12S)-diol 61, which on acetylation furnished
the target (+)-(2S,12S)-diacetate 49, with [h]2D3 +1.8 (c
1.21, CHCl3). The reported value was [h]578 +2.0
(CHCl3).28 In a similar way, epoxydiol 59 and tetrol 60
could be converted to the (2R,12S)- and (2R,12R)-
stereoisomers, respectively, but this was not
undertaken.
(S)- or (R)-methyl oxirane, or with epichlorohydrin.27
It is seen that this procedure represents the general
approach to carbon chains carrying remote stereogenic
centres.
OAc
OAc
O
O
Steps
Steps
(CH2)6
47
(CH2)6
46
O
O
O
O
i
(CH2)7
58
(CH2)7
48
+
OAc
OAc
O
O
(CH2)7
OH
OH
OH
(CH2)7
O
49
48
HO
(CH2)7
60
OH
OH
(CH2)7
59
+
OAc
OAc
OH
OH
The HKR approach appeared to offer a straightfor-
ward alternative for accessing both 47 and 49. Thus,
bisepoxide 46 of dodeca-1,11-diene, acquired by double
allylation of 1,6-dibromohexane 50, was treated with
(S,S) catalyst and H2O as shown below in Scheme 7.
The necessary epoxydiol 52 was acquired in 26% iso-
lated yield. For the target (2S,11S)-47, stereochemical
inversion of the secondary alcohol resulting from initial
epoxide opening was necessary. Hence, the acetonide
from epoxydiol 52 was treated with MeMgBr–CuI to
provide 54, which under Mitsunobu conditions
afforded the inverted p-chlorobenzoate 55. Acetonide
removal, with Amberlite in MeOH, was followed by
re-formation of the epoxide from the 1,2-diol. The now
available epoxyester 56, on reduction with LiAlH4,
yielded (2S,11S)-diol 57 which was converted to the
required (−)-(2S,11S)-diacetate 47, with [h]2D3 −4.0 (c,
0.70, CHCl3). This compares favourably with the
reported rotation ([h]2D0 −4.3 (CHCl3)).28
iii
ii
(CH2)7
58
(CH2)7
61
49
Scheme 8. Reagents and conditions: (i) 1.0% equiv. (S,S)-1,
0.6 equiv. H2O; (ii) NaBH4, EtOH; (iii) Ac2O, Py.
3. Conclusion
The value of hydrolytic kinetic resolution in providing
a range of highly enantiomerically enriched terminal
mono- and bisepoxides has been demonstrated by the
efficient conversion of such epoxides to a range of
important insect sex pheromones.
4. Experimental
4.1. General
In a similar way, bisepoxide 48 of 1,12-tridecadiene was
processed with (R,R)-1 to provide the easily separated
components 58, 59 and 60, as shown below in Scheme
8.
NMR spectra were obtained with Bruker EM200,
AMX400 and AV400 spectrometers, using CDCl3 or
EtOH-d6 as solvent, and referenced to residual solvents
at lH 7.24 and lC 77.0, and lH 5.19 and lC 56.8,

784
S. Chow, W. Kitching / Tetrahedron: Asymmetry 13 (2002) 779–793
respectively. The mass spectra (MS) were recorded on a
Hewlett–Packard 5890A GC/Mass Detector at 70 eV.
High resolution mass spectrum was performed on a
Finnigan MAT 900XL spectrometer. Microanalyses
were performed on the Elemental Analyzer Model 1106
from Elemental Microanalysis Limited. Flash chro-
matography was carried out using Merck silica gel
(230–400 mesh). Optical rotations were measured at 589
nm using a 1 dm cell on a Perkin–Elmer 241MC
polarimeter.
(II) (0.20 g, 0.3 mmol) and acetic acid (23 mL) were
stirred in toluene (1 mL) under air for 1 h. The solvent
was removed in vacuo, and the dark brown residue was
dried under vacuum, and used directly in the kinetic
resolution.5b
HKR: Racemic epoxide 6 (3.0 g, 10.8 mmol), H2O (0.12
mL, 6.7 mmol) and (R,R)-1 (17.2 mg, 24.2 mmol) were
stirred at rt for 18 h. (R)-Epoxide 7 (1.4 g, 46%) and
(S)-diol 8 (1.4 g, 47%) were separated by flash chro-
matography. (R)-2-(9-Benzyloxy-nonyl)-oxirane 7: [h]D23
+3.9 (c 1.02, CHCl3). Spectral data were identical with
those of the racemate 6. The epoxide was analysed by
chiral HPLC using a Chiral OD cel column with a flow
rate of 1.0 mL/min and solvent system of 1% iso-
propanol/hexane. The e.e. was determined to be >98%.
(S)-11-Benzyloxy-undecane-1,2-diol 8: [h]2D3 +0.7 (c
1.10, CHCl3). 1H NMR (400 MHz, CDCl3): l 7.32–7.25
(m, 5H), 4.48 (s, 2H), 3.66 (m, 2H), 3.44 (t, 2H, J=6.68
Hz), 3.40 (dd, 1H, J=11.12, 7.76 Hz), 2.39 (br s, 2H),
1.59 (m, 2H), 1.40–1.23 (m, 14H). 13C NMR (100 MHz,
CDCl3): l 138.6, 128.3, 127.6, 127.4, 72.8, 72.2, 70.5,
66.7, 33.22, 29.7, 29.6, 29.44, 29.41, 29.39, 26.1, 25.5.
These data matched those reported.29 Anal. calcd for
C18H30O3 (%): C, 73.43; H, 10.27. Found: C, 73.26; H,
10.50%.
4.2. (−)-(R)- and (+)-(S)-10-Methyldodecyl acetate 3
and 4
1-Benzyloxy-undec-10-ene 5: Under an inert atmo-
sphere, sodium hydride (60% dispersion in mineral oil,
2.2 g, 55.0 mmol) was washed with hexane, followed by
the addition of THF (20 mL) and t-butylammonium
iodide (0.50 g, 1.4 mmol). After cooling to 0°C, neat
10-undecenol (4.9 g, 29.0 mmol) was added dropwise and
the suspension was stirred at room temperature (rt) for
30 min. Benzyl bromide (8.1 g, 47.5 mmol) was slowly
added to the above, and the mixture was stirred for 3.5
h. The reaction was quenched by careful addition of H2O,
followed by washing with H2O. The organic layer was
separated, dried over MgSO4, and concentrated. The
benzyl ether was distilled at 119–121°C/0.3 mmHg as a
slightly yellowish liquid (7.5 g, 98%). 1H NMR (400 MHz,
CDCl3): l 7.32–7.24 (m, 5H), 5.81 (ddt, 1H, J=17.00,
10.24, 6.72 Hz), 4.98 (dm, 1H, J=17.08 Hz), 4.92 (ddt,
1H, J=10.20, 2.32, 1.16 Hz), 4.49 (s, 2H), 3.45 (t, 2H,
J=6.68 Hz), 2.03 (qt, 2H, J=6.80, 1.36 Hz), 1.62–1.27
(m, 14H); 13C NMR (100 MHz, CDCl3): l 139.2, 138.7,
128.3, 127.6, 127.4, 114.1, 72.8, 70.5, 33.8, 29.8, 29.5,
29.44, 29.41, 29.1, 28.9, 26.2; MS EI m/z (rel. int.): 260
(M+, <1), 169 (<1), 151 (1), 109 (6), 107 (15), 91 (100),
69 (10), 55 (29), 41 (38). These data matched those
reported.29
(S)-12-Benzyloxy-dodecan-3-ol 9: Under an inert atmo-
sphere, CuI (0.58 g, 3.0 mmol) in dry ether (30 mL) was
cooled to 0°C. MeLi (ca. 0.5 M in ether, 10 mL) was
added slowly, and the initiation of cuprate formation
was indicated by a bright yellow colour. After the
addition, the clear solution was stirred for an extra 10
min. (R)-Epoxide 7 (0.31 g, 1.1 mmol) in dry ether (15
mL) was added dropwise at 0°C, and the resulting
bright yellow mixture was stirred for 1 h at the same
temperature. The reaction was diluted with ether and
quenched carefully with saturated NH4Cl while the
ethereal solution was still cold. The aqueous layer was
separated and re-extracted with ether. The combined
organic layers were washed with brine, dried (MgSO4),
and concentrated. The crude product was purified by
flash chromatography to provide a clear oil (0.32 g,
2-(9-Benzyloxy-nonyl)-oxirane 6: A solution of benzyl
ether 5 (5.0 g, 19.3 mmol) in DCM (50 mL) was cooled
to 0°C. m-CPBA was added in small portions, followed
by K2CO3 (0.67 g, 4.8 mmol). The reaction was stirred
at rt for 3 h. The mixture was filtered through a sintered
glass funnel, washed repeatedly with saturated NaHCO3,
dried (MgSO4) and concentrated. After flash chromatog-
raphy, the epoxide was obtained as a clear oil (4.1 g, 78%).
1H NMR (400 MHz, CDCl3): l 7.32–7.25 (m, 5H), 4.48
(s, 2H), 3.45 (t, 2H, J=6.64 Hz), 2.88 (m, 1H), 2.72 (dd,
1H, J=5.04, 4.00 Hz), 2.44 (dd, 1H, J=5.04, 2.72 Hz),
1.63–1.28 (m, 16H). 13C NMR (100 MHz, CDCl3): l
138.7, 128.3, 127.6, 127.4, 72.8, 70.5, 52.3, 47.0, 32.4, 29.7,
29.43 (2C), 29.39, 29.37, 26.1, 25.9. MS EI m/z (rel. int.):
276 (M+, <1), 185 (<1), 149 (1), 121 (1), 107 (39), 91 (100),
71 (10), 55 (20), 43 (11), 41 (30). Anal. calcd for C18H28O2
(%): C, 78.21; H, 10.21. Found: C, 78.41; H, 10.26%.
1
100%). [h]2D3 +6.0 (c 1.18, CHCl3). H NMR (400 MHz,
CDCl3): l 7.32–7.25 (m, 5H), 4.48 (s, 2H), 3.50 (m, 1H),
3.45 (t, 2H, J=6.64 Hz), 1.61–1.27 (m, 19H), 0.92 (t,
3H, J=7.44 Hz). 13C NMR (100 MHz, CDCl3): l
138.7, 128.3, 127.6, 127.4, 73.2, 72.8, 70.5, 36.9, 30.1,
29.7, 29.6, 29.51, 29.48, 29.41, 26.1, 25.6, 9.8. Anal.
calcd for C19H32O2 (%): C, 78.03; H, 11.03. Found: C,
77.66; H, 11.23%.
(R)-1-Benzyloxy-10-methyldodecane 10: Under an inert
atmosphere, benzyl ether 9 (0.30 g, 1.0 mmol) was
dissolved in DCM (5 mL), and Et3N (0.40 mL, 2.8
mmol) was added. Mesyl chloride (0.20 mL, 2.4 mmol)
was added dropwise to the cool (0°C) solution, and a
white precipitate was formed almost immediately. The
resulting mixture was stirred at rt for 2 h, and then
diluted with ether, and filtered. The filtrate was washed
with saturated NaHCO3, dried over MgSO4 and con-
Hydrolytic kinetic resolution (HKR) of 2-(9-benzyloxy-
nonyl)-oxirane 6
Preparation of the active catalyst: (R,R)-N,N%-Bis(3,5-di-
tert-butylsalicylidene)-1,2-cyclohexane-diamino cobalt-

S. Chow, W. Kitching / Tetrahedron: Asymmetry 13 (2002) 779–793
785
centrated. The crude mesylate was redissolved in anhy-
drous ether (15 mL). In a separate flask, Me2CuLi was
prepared by slow addition of MeLi (ca. 0.4 M in ether,
10.0 mL, 0.4 mmol) to a suspension of CuI (0.39 g, 2.1
mmol) in ether at 0°C. After the addition, the cuprate
was stirred for another 5 min before the crude mesylate
was added dropwise. The resulting bright yellow mix-
ture was stirred at 0°C for 2.5 h, followed by dilution
with ether and quenched carefully with saturated
NH4Cl. The aqueous layer was separated and re-
extracted with ether. The combined organic extract was
dried (MgSO4), and concentrated. Flash chromatogra-
phy afforded a mixture of the unsaturated benzyl ethers
and product 10 in a ratio of ca. 2:3. Benzyl ether 10: 1H
NMR (200 MHz, CDCl3): l 7.32–7.25 (m, 5H), 4.48 (s,
2H), 3.45 (t, 2H, J=6.60 Hz), 1.59–1.06 (m, 19H),
0.830 (t, 3H, J=6.84 Hz), 0.825 (d, 3H, J=6.10 Hz).
13C NMR (50 MHz, CDCl3): l 138.7, 128.3, 127.6,
127.5, 72.9, 70.5, 36.6, 34.4, 30.0, 29.7, 29.63, 29.59,
29.47, 27.1, 26.2, 19.2, 11.4. MS EI m/z (rel. int.): 290
(M+, <1), 199 (3), 108 (11), 92 (67), 91 (100), 69 (16), 57
(18), 55 (13), 41 (20). This ether 10 was then subjected
to ozonolysis.
aqueous CuSO4. The DCM solution was separated,
dried over MgSO4, and then concentrated. After flash
chromatography, the acetate was obtained in quantita-
1
tive yield. [h]2D3 −5.4 (c 0.97, CHCl3). H NMR (400
MHz, CDCl3): l 4.02 (t, 2H, J=6.76 Hz), 2.01 (s, 3H),
1.59 (q, 2H, J=6.91 Hz), 1.35–1.03 (m, 17H), 0.83 (t,
3H, J=7.20 Hz), 0.81 (d, 3H, J=6.40 Hz). 13C NMR
(100 MHz, CDCl3): l 171.2, 64.7, 36.6, 30.0, 29.6,
29.50, 29.48, 29.2, 28.6, 27.1, 25.9, 21.0, 19.2, 11.4. MS
EI m/z (rel. int.): 182 (M+−CH3CO2H/C4H12, <1), 153
(8), 125 7), 111 (10), 97 (35), 83 (34), 70 (47), 55 (47), 43
(10), 41 (48). These data matched those reported.9–11
(S)-2-(9-Benzyloxy-nonyl)-oxirane 12: (S,S)-Diol
8
(0.82 g, 2.8 mmol) was dissolved in DCM (8 mL) in an
inert atmosphere. Et3N (0.49 mL, 3.4 mmol) was added
and the solution was allowed to stir for 5 min before
cooling to 0°C. Mesyl chloride (0.3 mL, 3.3 mmol) was
added dropwise, and precipitation was observed almost
immediately. The resulting mixture was stirred at rt for
3 h. After diluting with ether, the precipitate was
filtered and washed with ether. The combined ethereal
solution was washed with saturated NaHCO3, dried
(MgSO4) and concentrated. The crude mesylate was
redissolved in MeOH (8 mL) and K2CO3 (0.8 g, 5.5
mmol) was added. The suspension was stirred at rt for
3 h, and after addition of H2O, was extracted with
DCM. The organic layers were dried over MgSO4, and
concentrated. (S)-Epoxide 12 was purified by flash
chromatography to give a clear oil (0.80 g, 46%). [h]D23
−4.2 (c 1.23, CHCl3). The spectral data were identical
to those of the racemic epoxy benzyl ether, 6, described
above.
(R)-10-Methyldodecanol 11
Ozonolysis: In an attempt to purify benzyl ether 10, the
mixture was subjected to ozonolysis. The benzyl ethers
were taken up in DCM, and treated with ozone at
−78°C until a pale blue colour persisted. The solution
was purged with O2 until the colour disappeared, and
then an excess of Me2S (0.5 mL) was added. The
solution was warmed to rt and stirred for 2 h. The
mixture was worked up by washing with H2O, and the
aqueous layer was re-extracted with DCM. The com-
bined organic layers were dried over MgSO4, and con-
centrated. After column chromatography, the benzoate
ester was isolated (0.14 g, 42% over two steps). MS EI
m/z (rel. int.): 304 (M+, 1), 206 (1), 123 (100), 105 (57),
77 (25), 70 (28), 57 (19), 55 (29), 41 (28). The ester was
then hydrolysed immediately.
(R)-12-Benzyloxy-dodecan-3-ol 13: The procedure fol-
lowed the protocol described in the formation of (S)-
hydroxyl benzyl ether 9. Treatment of epoxide 12 (0.20
g, 0.72 mmol) with Me2CuLi generated from CuI (0.45
g, 2.4 mmol) and MeLi (ca. 0.4 M in ether, 8.5 mL, 3.4
mmol) yielded the desired alcohol 13 as a clear oil (191
mg, 90%) [h]2D3 −5.0 (c 1.58, CHCl3). The spectral data
matched those for benzyl ether 9 described above.
Saponification: K2CO3 (92 mg, 0.67 mmol) was added
to a solution of the above benzoate (69 mg, 0.23 mmol)
in MeOH (1.5 mL), and the suspension was stirred at rt
for 2.5 h. H2O was then added, followed by extraction
with ether. The ethereal solution was washed with H2O
and brine, and dried over MgSO4. After removal of
solvent and flash chromatography, alcohol 11 was
(S)-1-Benzyloxy-10-methyldodecane 14: Following the
procedure for the formation of (R)-isomer 10, alcohol
13 (0.15 g, 0.50 mmol) was converted to the corre-
sponding mesylate by treatment with Et3N (0.30 mL,
2.1 mmol) and mesyl chloride (0.20 mL, 2.5 mmol). The
crude mesylate was then reacted with Me2CuLi, formed
from CuI (0.30 g, 1.6 mmol) and MeLi (ca. 0.4 M in
ether, 8.0 mL, 3.2 mmol) in anhydrous ether. Benzyl
ether 14 was isolated as a colourless oil (50 mg, 34%)
after removing the unsaturated component by oxymer-
curation and careful flash chromatography. The spec-
tral data were identical with those for 10.
1
obtained as a clear oil (30 mg, 67%). H NMR (400
MHz, CDCl3): l 3.62 (t, 2H, J=6.64 Hz), 1.54 (q, 2H,
J=6.84 Hz), 1.35–1.04 (m, 18H), 0.83 (t, 3H, J=7.20
Hz), 0.82 (d, 3H, J=6.36 Hz). 13C NMR (100 MHz,
CDCl3): l 63.1, 36.6, 34.4, 32.8, 30.0, 29.6 (2C), 29.5,
29.4, 27.1, 25.7, 19.2, 11.4. MS EI m/z (rel. int.): 153
(M+−C3H7, 4), 125 (12), 111 (14), 83 (60), 70 (80), 57
(65), 55 (92), 41 (100). These data matched those
reported.9
(+)-(S)-10-Methyldodecyl acetate 4
Debenzylation: A catalytic amount of Pd–C (10%, 2
mg) was added to benzyl ether 14 (16 mg, 55 mmol) in
EtOH (1.5 mL). The suspension was stirred at rt for 7.5
h under a balloon of H2. The mixture was filtered
(−)-(R)-10-Methyldodecyl acetate 3: An excess of acetic
anhydride (0.1 mL) and pyridine (0.1 mL) were added
to alcohol 11 (30 mg, 0.15 mmol) in DCM (2 mL). The
solution was stirred for 3.5 h, and then washed with

786
S. Chow, W. Kitching / Tetrahedron: Asymmetry 13 (2002) 779–793
through a plug of cotton wool, and the filtrate was
dried (MgSO4). Solvent removal yielded (S)-10-methyl-
dodecan-1-ol as a clear oil (10 mg, 95%), which was
acetylated without further purification. All spectral
data matched those for the (R)-alcohol 11 above.
in hexane, 0.2 mL, 2.5 mmol) was added and the yellow
solution was stirred at the same temperature for 30
min. The reaction was warmed to 0°C and quenched
with saturated NH4Cl (1 mL). The mixture was
extracted with ether, and the organic extracts were
combined, washed with saturated NH4Cl and brine,
separated, dried and concentrated, to afford the alkene.
1H NMR (200 MHz, CDCl3): l 5.80 (m, 1H), 4.93 (m,
2H), 2.02 (q, 2H, J=6.60 Hz), 1.36–1.02 (m, 17H), 0.85
(t, 3H, J=6.85 Hz), 0.83 (d, 3H, J=6.61 Hz). MS EI
m/z (rel. int.): 154 (M+−C3H6, <1), 153 (3), 111 (10), 97
(29), 84 (35), 83 (26), 69 (42), 55 (72), 43 (100), 41 (90).
These data matched those reported.9,14
Acetylation: (S)-Acetate 4 was prepared in the manner
described for (R)-acetate 3. The (S)-alcohol (9 mg, 45
mmol) was treated with an excess of pyridine and acetic
anhydride to yield the required acetate (10 mg, 94%),
with spectral data matching those for the (R)-acetate
described above. The spectral data matched those
reported.9–11 [h]D23 +5.3 (c 1.02, CHCl3).
(R)-(−)-10-Methyltridecan-2-one 15: Oxygen gas was
bubbled through a suspension of PdCl2 (2 mg, 6 mmol)
and CuCl (4 mg, 37 mmol) in DMF (0.5 mL) and H2O
(80 mL) for 30 min. Alkene 18 (5 mg, 3 mmol) in DMF
(80 mL) was added to the above and O2 was admitted
for a further 4 h, then stirred under a balloon of O2
overnight. The reaction was quenched by H2O (15 mL)
and extracted with ether. The organic extracts were
combined, washed with H2O, separated and dried
(MgSO4). After concentration and chromatography,
ketone 15 was furnished as a clear liquid (5 mg, 90%).
[h]2D3 −1.6 (c 0.70, CHCl3). 1H NMR (400 MHz,
CDCl3): l 2.39 (t, 2H, J=7.40 Hz), 2.11 (s, 3H),
1.56–1.03 (m, 17H), 0.85 (t, 3H, J=6.88 Hz), 0.81 (t,
3H, J=6.60 Hz). 13C NMR (100 MHz, CDCl3): l
209.4, 43.8, 39.9, 37.0, 32.4, 29.83, 29.8, 29.4, 29.1, 27.0,
23.9, 20.1, 19.6, 14.4. MS EI m/z (rel. int.): 212 (M+,
<1), 194 (1), 151 (1), 123 (2), 110 (4), 95 (4), 85 (7), 71
(22), 58 (58), 43 (100). These data matched those
reported.13–15
4.3. (−)-(R)-10-Methyltridecan-2-one 15
(S)-13-Benzyloxy-tridecan-4-ol 16: Under an inert
atmosphere, CuI (35 mg, 0.2 mmol) in anhydrous THF
(1 mL) was cooled to 0°C and ethyl magnesium bro-
mide, freshly prepared with Mg turnings (49 mg, 2.1
mmol) and ethyl bromide (0.12 mL, 1.5 mmol) in
anhydrous ether, was then added. The dark purple
mixture was stirred for 10 min, followed by the drop-
wise addition of (R)-epoxide 7 (0.11 g, 0.4 mmol), and
stirred at 0°C for 2 h. The reaction was warmed to rt
and quenched by slow addition of saturated NH4Cl,
followed by standard workup. Column chromatogra-
phy yielded mono-protected diol 16 (0.13 g, 75%). [h]D23
1
+1.0 (c 0.97, CHCl3). H NMR (400 MHz, CDCl3): l
7.33–7.25 (m, 5H), 4.48 (s, 2H), 3.57 (m, 1H), 3.44 (t,
2H, J=6.68 Hz), 1.63–1.27 (m, 21H), 0.91 (t, 3H,
J=7.12 Hz). 13C NMR (100 MHz, CDCl3): l 138.7,
128.3, 127.6, 127.4, 72.8, 71.7, 70.5, 39.7, 37.5, 29.8,
29.7, 29.54, 29.51, 29.4, 26.2, 25.6, 18.8. MS EI m/z
(rel. int.): 306 (M+, <1), 288 (7), 197 (2), 155 (1), 123
(3), 107 (24), 91 (100), 83 (6), 69 (6), 55 (22), 41 (12).
Anal. calcd for C20H34O2 (%): C, 78.38; H, 11.18.
Found: C, 78.52; H, 11.48%.
4.4. (−)-(R)-(Z)-Undec-6-en-2-ol 20
Undec-1-en-6-yne 19: MeLi (1.0 M in ether, 20 mL,
20.0 mmol) was added to a solution of hexyne (2.0 mL,
17.4 mmol) in dry THF (20 mL) at −43°C under an
inert atmosphere. After stirring for 30 min, freshly
distilled HMPA (5 mL) was added, followed by 5-
bromo-1-pentene (2.0 mL, 16.9 mmol) in anhydrous
THF (2.5 mL). The reaction was allowed to warm
slowly to rt, and stirred overnight. The solution was
diluted with hexane and washed with H2O. The
aqueous layer was re-extracted with hexane. The com-
bined organic extracts were washed with brine, sepa-
rated and dried (MgSO4). Removal of the solvent
yielded enyne 19 (1.61 g, 63%) as a clear liquid, and
(R)-1-Benzyloxy-10-methyltridecane 17: Reductive
methylation of alcohol 16 was performed in the manner
described earlier. The alcohol (70 mg, 0.2 mmol) was
mesylated with Et3N (83 mL, 0.6 mmol) and mesyl
chloride (56 mL, 0.7 mmol) in DCM. The crude mesyl-
ate was then displaced with Me2CuLi, prepared from
MeLi (ca. 0.3 M in ether, 4.0 mL, 1.2 mmol) and CuI
(0.10 g, 0.55 mmol) in anhydrous ether, to furnish the
alkyl benzyl ether 17 as a colourless oil (28 mg, 40%)
after flash chromatography. [h]2D3 −2.4 (c 0.90, CHCl3).
1H NMR (400 MHz, CDCl3): l 7.33–7.25 (m, 5H), 4.49
(s, 2H), 3.44 (t, 2H, J=6.68 Hz), 1.63–0.80 (m, 27H).
13C NMR (100 MHz, CDCl3): l 138.7, 128.3, 127.6,
127.4, 72.8, 70.5, 36.6, 34.4, 30.0, 29.7, 29.63, 29.60,
29.5 (2C), 27.1, 26.2, 19.2, 11.4. MS (EI m/z (rel. int.):
304 (M+, <1), 213 (3), 151 (1), 125 (4), 108 (11), 91
(100), 83 (14), 69 (15), 55 (15), 41 (28). Anal. calcd for
C21H36O (%): C, 82.83; H, 11.92. Found: C, 82.85; H,
12.08%.
1
used directly in the next reaction. H NMR (400 MHz,
CDCl3): l 5.78 (ddt, 1H, J=17.0, 10.2, 6.7 Hz), 5.01
(dq, 1H, J=17.2, 1.72 Hz), 4.95 (ddt, 1H, J=10.2, 2.2,
1.2 Hz), 2.13 (m, 6H), 1.55 (q, 2H, J=6.9 Hz), 1.42 (m,
4H), 0.88 (t, 3H, J=7.1 Hz). 13C NMR (100 MHz,
CDCl3): l 138.1, 114.9, 80.5, 79.7, 32.8, 31.2, 28.3, 21.9,
18.4, 18.2, 13.6.MS EI m/z (rel. int.): 135 (M+−CH3, 9),
108 (29), 93 (100), 91 (37), 79 (79), 67 (39), 55 (28), 54
(30), 41 (57). These data matched those reported.30
(R)-10-Methyltridecene 18: A solution of benzyl ether
17 (20 mg, 66 mmol) in dry THF (0.8 mL) was cooled
2-Non-4-ynyl-oxirane 21: m-CPBA (7.0 g, 20.3 mmol)
was added in small portions to enyne 19 (2.8 g, 18.3
mmol) in DCM (40 mL) at 0°C, followed by K2CO3
n
to −78°C under an inert atmosphere. BuLi (ca. 1.3 M

S. Chow, W. Kitching / Tetrahedron: Asymmetry 13 (2002) 779–793
787
(ca. 0.3 g). The reaction was stirred at rt for 4 h before
being filtered. The filtrate was washed repeatedly with
saturated NaHCO3 and brine, separated, dried
(MgSO4) and concentrated. Column chromatography
afforded epoxide 21 (0.78 g, 29%). 1H NMR (400 MHz,
CDCl3): l 2.90 (m, 1H), 2.73 (dd, 1H, J=5.04, 4.04
Hz), 2.46 (dd, 1H, J=5.04, 2.72 Hz), 2.19 (m, 2H), 2.11
(m, 2H), 1.62 (m, 4H), 1.39 (m, 4H), 0.88 (t, 3H,
J=7.20 Hz). 13C NMR (100 MHz, CDCl3): l 80.9,
79.3, 51.9, 47.0, 31.5, 31.2, 25.5, 21.9, 18.5, 18.3, 13.6.
MS EI m/z (rel. int.): 151 (M+−CH3, 2), 123 (36), 109
(12), 93 (70), 91 (53), 79 (100), 55 (60). This volatile
epoxide was immediately subjected to HKR.
24 (18 mg, 0.11 mmol) and a catalytic amount of
DMAP were dissolved in DCM (1 mL), and Et3N (0.20
mL, 1.4 mmol) was then added. The (S)-MTPA solu-
tion was syringed into the above and stirred for 1 h.
The reaction was diluted with DCM, washed with HCl
(1 M) and NaOH (2 M), and the organic phase was
dried (MgSO4), concentrated and purified by flash chro-
matography to afford the Mosher’s ester as a viscous
1
oil (30 mg, 73%), and H NMR analysis indicated an
1
e.e. of 95%. H NMR (400 MHz, CDCl3): l 7.52 (m,
2H), 7.38 (m, 3H), 5.16 (s, 1H, J=6.46 Hz), 3.54 (q,
3H, J=1.16 Hz), 2.09 (m, 4H), 1.69 (m, 2H), 1.38 (m,
6H), 1.33 (d, 3H, J=6.24 Hz), 0.88 (t, 3H, J=7.16 Hz).
13C NMR (100 MHz, CDCl3): l 166.1, 132.5, 129.5,
128.3, 127.2 (q, J=1.3 Hz), 120.5 (q, J=287.9 Hz), 84.4
(q, J=27.2 Hz), 80.8, 79.1, 73.6, 55.4 (q, J=1.3 Hz),
34.6, 31.2, 24.5, 21.2, 19.8, 18.4, 13.6. MS EI m/z (rel.
int.): 342 (M+−C3H6, 2), 189 (100), 119 (11), 109 (29),
95 (88), 81 (37), 67 (36), 55 (31), 41 (20).
HKR: Racemic epoxide 21 (0.55 g, 3.3 mmol), H2O (47
mL, 2.6 mmol) and (S,S)-Jacobsen catalyst (16 mg, 22.2
mmol) were stirred at rt for 25 h. The mixture was
separated by flash chromatography to give (S)-epoxide
22 and (R)-diol 23 (0.25 g, 43%), where the epoxide was
used immediately. For the ease of characterisation, diol
23 (0.22 g, 1.2 mmol) was converted to the correspond-
ing acetonide in the usual manner. The diol was treated
with an excess of dimethoxypropane (DMP) and a
catalytic amount of p-TsOH in DCM to provide the
acetonide as a clear oil (0.25 g, 84%) after column
(−)-(R)-(Z)-Undec-6-en-2-ol (Nostrenol) 20
Protection of secondary alcohol 24: Dihydropyran (70
mL, 0.77 mmol) was added dropwise to a solution of
alcohol 24 (50 mg, 0.30 mmol) and a catalytic amount
of p-TsOH in DCM (0.5 mL). The solution was stirred
for 2 h. The reaction was diluted with ether and washed
with saturated NaHCO3. The aqueous layer was re-
extracted with ether and the combined organic extracts
were dried (MgSO4) and concentrated. Flash chromato-
graphic purification provided the THP ether as a
chromatography.
(R)-2,2-Dimethyl-4-non-4-ynyl-
1
[1,3]dioxolane: [h]2D3 −12.7 (c 1.42, CHCl3). H NMR
(400 MHz, CDCl3): l 4.07 (m, 1H), 4.02 (dd, 1H,
J=7.68, 5.96 Hz), 3.50 (t, 1H, J=7.32 Hz), 2.14 (m,
6H), 1.50 (m, 6H), 1.39 (s, 3H), 1.33 (s, 3H), 0.88 (t,
3H, J=7.16 Hz). 13C NMR (100 MHz, CDCl3): l
108.7, 80.8, 79.4, 75.7, 69.4, 32.7, 31.2, 26.9, 25.7, 25.3,
21.9, 18.7, 18.4, 13.6. MS (EI m/z (%)): 224 (M+, <1),
209 (27), 167 (11), 107 (21), 93 (23), 79 (29), 72 (27), 67
(20), 55 (16), 43 (100). Anal. calcd for C14H24O2 (%): C,
74.95; H, 10.78. Found: C, 75.00; H, 11.12%.
1
colourless liquid (two isomers, 63 mg, 84%). H NMR
(400 MHz, CDCl3): l 4.68 (m, 1H), 4.62 (m, 1H), 3.89
(m, 2H), 3.76 (m, 2H), 3.47 (m, 2H), 2.13 (m, 8H),
1.84–1.37 (m, 28H), 1.20 (d, 3H, J=6.28 Hz), 1.10 (d,
3H, J=6.16 Hz), 0.883 (t, 3H, J=7.20 Hz), 0.881 (t,
3H, J=7.12 Hz). 13C NMR (100 MHz, CDCl3): l 98.6,
95.4, 80.4, 80.2, 79.9, 79.7, 73.4, 70.5, 62.7, 62.3, 38.3,
36.5, 35.5, 31.13. 31.12, 31.1 (2C), 25.39, 25.36, 25.0,
21.8 (2C), 21.4, 20.0, 19.6, 19.0, 18.8, 18.7 18.32, 18.30,
13.5 (2C). MS EI m/z (rel. int.): 252 (M+, <1), 209 (1),
195 (2), 179 (5), 151 (3), 109 (14), 95 (41), 85 (100), 67
(26), 41 (29); 209 (M+−C4H9), 195 (2), 179 (2), 151 (3),
109 (14), 95 (37), 85 (100), 67 (24), 41 (25). This THP
ether was then reduced.
(R)-Undec-6-yn-2-ol 24: NaBH4 (0.18 g, 4.8 mmol) was
added to (S)-epoxide 22 in EtOH (5 mL), and the
mixture was refluxed for 2 h. After diluting with ether
and quenching with saturated NH4Cl, the mixture was
filtered. The precipitate was washed thoroughly with
ether. The ether layer was washed with H2O, and the
aqueous layer was re-extracted with DCM. The com-
bined organic phases were dried (MgSO4), concentrated
under reduced pressure and purified by flash chro-
matography to yield alcohol 24 (0.20 g, 73% over two
TiII-based reduction of THP ether of alkyne 24: Pre-
dried Mg turnings (0.76 g, 31.1 mmol) were dry-stirred
for 20 min under nitrogen, and anhydrous ether (5 mL)
was added. A few drops of neat 2-bromopropane (2.4
mL, 25.4 mmol) were added until the Grignard forma-
tion commenced. The remaining bromopropane was
diluted with ether (10 mL), while being added to the
Mg mixture at such a rate as to maintain gentle reflux-
ing. Occasional cooling in a water-ice bath was neces-
sary. After the addition was completed, the mixture was
stirred for 30 min. Anhydrous ether was added to give
1
steps). [h]2D3 −8.0 (c 0.84, CHCl3). H NMR (400 MHz,
CDCl3): l 3.80 (s, 1H, J=6.16 Hz), 2.14 (m, 4H),
1.38–1.55 (m, 10H), 1.18 (d, 3H, J=6.16 Hz), 0.88 (t,
3H, J=7.16 Hz). 13C NMR (100 MHz, CDCl3): l 80.7,
79.8, 67.7, 38.4, 31.2, 25.3, 23.5, 21.9, 18.7, 18.4, 13.6.
MS EI m/z (rel. int.): 153 (M+−CH3, 11), 111 (51), 97
(16), 93 (89), 79 (100), 67 (63), 54 (36), 45 (66), 41 (56).
Anal. calcd for C11H20O (%): C, 78.51; H, 11.98.
Found: C, 77.96; H, 12.28%.
i
Mosher’s ester of (R)-undec-6-yn-2-ol 24: Under an
inert atmosphere, oxalyl chloride (0.57 M in DCM,
0.60 mL, 0.34 mmol) was added to (S)-MTPA (88 mg,
0.38 mmol) in dry DCM (0.5 mL). A drop of DMF was
added, and after gas evolution ceased, the solution was
stirred for a further 35 min. In a separate flask, alcohol
20 mL of a ꢀ1.2 M PrMgBr solution. To the THP
protected alkyne (63 mg, 0.25 mmol) in ether, was
added freshly distilled Ti(OiPr)4 (0.15 mL, 0.51 mmol)
in ether (15 mL) under an inert atmosphere. The solu-
i
tion was cooled to −78°C, and PrMgBr (ca. 1.2 M in
ether, 1.1 mL, 1.3 mmol) was added dropwise to give a

788
S. Chow, W. Kitching / Tetrahedron: Asymmetry 13 (2002) 779–793
bright yellow solution. The mixture was warmed to
−43°C for 2 h, and H2O (1 mL) was then added to the
dark brown reaction mixture, followed by warming to
rt overnight. The reaction was quenched with saturated
NH4Cl, and the organic layer was separated, and the
aqueous layer was re-extracted with ether. The com-
bined extracts were dried (MgSO4) and concentrated to
yield a pale yellow oil (two diastereomers). MS EI m/z
(rel. int.): 254 (M+, <1), 170 (<1), 152 (1), 110 (8), 97
(11), 85 (100), 67 (15), 55 (25), 41 (22); 170 (<1), 152
(1), 110 (4), 97 (12), 85 (100), 67 (12), 55 (21), 41 (20).
with a catalytic amount of p-TsOH. The reaction was
stirred overnight, concentrated, and then chro-
matographed to yield the bisacetonide of 34 as a clear
1
oil (0.61 g, 83%). [h]2D3 +25.1 (c 1.88, CHCl3). H NMR
(400 MHz, CDCl3): l 4.03 (m, 2H), 3.98 (t, 2H, J=7.40
Hz), 3.45 (t, 2H, J=7.16 Hz), 1.60–1.24 (m, 10H), 1.36
(d, 6H, J=0.40 Hz), 1.30 (d, 6H, J=0.48 Hz). 13C
NMR (100 MHz, CDCl3): l 108.6, 76.0, 69.4, 33.5,
29.58, 26.9, 25.7, 25.6. MS EI m/z (rel. int.): 257
(M+−CH3, 74), 199 (2), 139 (6), 121 (14), 101 (13), 81
(19), 72 (39), 59 (18), 43 (100). Anal. calcd for C15H28O4
(%): C, 66.14; H, 10.36. Found: C, 66.02; H, 10.60%.
THP deprotection: The above oil was dissolved in
MeOH (2 mL) and a catalytic amount of p-TsOH was
added. The solution was stirred for 1.5 h, and then
worked up by addition of aqueous NaHCO3, followed
by extraction with DCM. The combined organic layers
were dried (MgSO4), concentrated and flash chro-
matographed to furnish enol 20 in 54% yield over two
(4S,5%R%) - 2,2 - Dimethyl - 4 - (5 - oxiranyl - pentyl) - [1,3]-
dioxolane 35: Epoxydiol 33 (0.56 g, 3.2 mmol), DMP
(1.4 mL) and a few crystals of p-TsOH in DCM (5 mL)
were stirred overnight. After concentration and column
purification, the acetonide was furnished as a clear oil
1
(0.54 g, 78%). [h]D23 +21.9 (c 1.15, CHCl3). H NMR
1
steps. [h]2D3 −5.5 (c 0.78, CHCl3). H NMR (400 MHz,
(400 MHz, CDCl3): l 4.03 (m, 1H), 3.99 (t, 1H, J=7.44
Hz), 3.46 (t, 1H, J=7.16 Hz), 2.86 (m, 1H), 2.71 (dd,
1H, J=5.00, 4.00 Hz), 2.42 (dd, 1H, J=5.04, 2.27 Hz),
1.61–1.26 (m, 10H), 1.37 (d, 3H, J=0.40 Hz), 1.32 (d,
3H, J=0.48 Hz). 13C NMR (100 MHz, CDCl3): l
108.6, 76.0, 69.5, 52.3, 47.0, 33.5, 32.3, 29.4, 26.9, 25.8,
25.70, 25.66. MS EI m/z (rel. int.): 199 (M+−CH3, 43),
121 (2), 101 (8), 93 (17), 81 (11), 79 (18), 72 (31), 57
(10), 43 (100). Anal. calcd for C12H22O3 (%): C, 67.26;
H, 10.35. Found: C, 67.47; H, 10.52%.
CDCl3): l 5.34 (m, 2H), 3.77 (m, 1H), 2.03 (m, 4H),
1.45–1.29 (m, 9H), 1.17 (d, 3H, J=6.16 Hz), 0.87 (t,
3H, J=7.08 Hz). 13C NMR (100 MHz, CDCl3): l
130.3, 129.3, 68.1, 38.9, 31.9, 27.1, 26.9, 25.9, 23.5, 22.3,
14.0. MS EI m/z (rel. int.): 170 (M+, 2), 155 (1), 152 (1),
110 (9), 95 (16), 81 (45), 71 (49), 67 (61), 54 (84), 41
(100). These data matched those reported.16
4.5. (1R,7R)-1,7-Dimethylnonyl propanoate 30
(3S,8S)-8-(2,2-Dimethyl-[1,3]dioxolan-4-yl)-octan-3-ol
36: This epoxide opening by Me2CuLi was undertaken
with the procedure described earlier. Epoxyacetonide 35
(0.45 g, 2.1 mmol) was reacted with Me2CuLi (from
CuI (0.98 g, 5.1 mmol) and MeLi (ca. 0.4 M in ether, 26
mL, 10.4 mmol)) in anhydrous ether at 0°C. The pure
hydroxyacetonide was obtained as a clear oil (0.48 g,
1,5-Bisoxiranyl-pentane 31: At 0°C, m-CPBA (70%,
14.8 g, 60.0 mmol) was added in portions to 1,8-nona-
diene (3.0 g, 17.8 mmol) in DCM (60 mL). The suspen-
sion was stirred at rt overnight. After standard workup
and purification, bisepoxide 31 was obtained as a clear
1
oil (1.9 g, 51%). H NMR (400 MHz, CDCl3): l 2.88
1
(m, 2H), 2.72 (dd, 2H, J=5.00, 4.00 Hz), 2.44 (dd, 2H,
J=5.04, 2.76 Hz), 1.58–1.40 (m, 10H). 13C NMR (100
MHz, CDCl3): l 52.3, 47.0, 32.3, 29.2, 25.8. MS EI
m/z (rel. int.): 137 (M+−H3O+, 1), 123 (3), 97 (18), 95
(14), 83 (19), 79 (29), 71 (47), 67 (61), 55 (55), 41 (100).
These data matched those reported.31
98%) after flash chromatography. H NMR (400 MHz,
CDCl3): l 4.04 (m, 1H), 4.00 (m, 1H), 3.49 (m, 1H),
3.47 (t, 1H, J=7.16 Hz), 1.63–1.27 (m, 13H), 1.38 (s,
3H), 1.32 (s, 3H), 0.91 (t, 3H, J=7.44 Hz). 13C NMR
(100 MHz, CDCl3): l 108.6, 76.1, 73.2, 60.5, 36.8, 33.5,
30.2, 29.7, 26.9, 25.7, 25.5, 9.8. MS EI m/z (rel. int.):
215 (M+−CH3, 47), 197 (1), 137 (7), 101 (10), 95 (55), 81
(51), 67 (35), 39 (54), 43 (100). Anal. calcd for C13H26O3
(%): C, 67.79; H, 11.38. Found: C, 67.97; H, 11.68%.
HKR: Bisepoxide 31 (4.0 g, 25.6 mmol), (R,R)-1 (0.18
g, 0.3 mmol) and H2O (0.38 mL, 21.1 mmol) were
stirred for 19 h. The products were separated by flash
chromatography to afford bisepoxide 32 (1.2 g, 24%),
epoxydiol 33 (2.1 g, 46%) and presumably tetrol 34
(0.52 g, 15%). (1R,5R)-1,5-Bisoxiranyl-pentane 32: [h]D23
+20.7 (c 1.03, CHCl3). The spectral data matched the
racemate reported above and those reported.32 (2R,8S)-
8-Oxiranyl-octane-1,2-diol 33: 1H NMR (400 MHz,
CDCl3): l 3.67 (m, 1H), 3.61 (dd, 1H, J=11.04, 3.08
Hz), 3.40 (dd, 1H, J=11.04, 7.60 Hz), 2.88 (m, 1H),
2.72 (dd, 1H, J=4.96, 4.04 Hz), 2.44 (dd, 1H, J=4.96,
2.76 Hz), 1.96 (br s, 2H), 1.55–1.36 (m, 10H). 13C NMR
(100 MHz, CDCl3): l 72.1, 66.8, 52.4, 50.7, 47.1, 32.9,
32.2, 29.2, 25.8, 25.3. This diol was protected as the
acetonide, 35, and fully characterised. For the ease of
characterisation, tetrol 34 was directly converted to its
bisacetonide by treatment of an excess of 2,2-
dimethoxypropane (DMP) (2 mL) in DCM (10 mL)
(4S,6%R%)-2,2-Dimethyl-4-(6-methyl-octyl)-[1,3]dioxo-
lane 37: This reductive methylation was performed in
the manner described earlier. Alcohol 36 (0.42 g, 1.7
mmol) was mesylated firstly with Et3N (0.75 mL, 5.2
mmol) and mesyl chloride (0.34 mL, 4.2 mmol) (3.5
mL) in DCM, followed by treatment with Me2CuLi in
ether, prepared from CuI (0.59 g, 3.1 mmol) and MeLi
(ca. 0.3 M in ether, 20 mL, 6.0 mmol) in the standard
way. Flash chromatography afforded a clear liquid
(0.35 g, 70%), of which contained ca. 15% of the
1
unsaturated acetonide from elimination. H NMR (400
MHz, CDCl3): l 4.04 (m, 1H), 4.00 (m, 1H), 3.48 (t,
1H, J=7.24 Hz), 1.62–1.08 (m, 13H), 1.38 (s, 3H), 1.33
(s, 3H), 0.83 (t, 3H, J=7.24 Hz), 0.81 (d, 3H, J=6.40
Hz). 13C NMR (100 MHz, CDCl3): l 108.6, 76.2, 69.5,
36.5, 34.4, 33.6, 30.0, 29.7, 29.5, 27.0, 25.79, 25.75, 19.2,

S. Chow, W. Kitching / Tetrahedron: Asymmetry 13 (2002) 779–793
789
11.4. MS EI m/z (rel. int.): 213 (M+−CH3, 64), 171 (1),
141 (1), 111 (9), 97 (39), 83 (45), 72 (34), 55 (42), 43
(100). This material was then taken on to epoxide 38.
(15), 70 (21), 57 (27), 45 (100), 41 (34). These data
matched those reported.21–23
Esterification: The above alcohol (20 mg, 0.12 mmol),
propionic anhydride (0.1 mL), pyridine (0.1 mL) and a
catalytic amount of DMAP in DCM (0.3 mL) were
stirred for 3.5 h. The reaction was diluted with ether,
washed with saturated CuSO4 and dried over MgSO4.
Removal of solvent followed by flash chromatography
yielded propanoate 30 as a clear oil (21 mg, 79%). [h]D23
(2S,6%R%)-2-(6-Methyl-octyl)-oxirane 38
Acetonide deprotection: Amberlite IR120 (ca. 0.2 g) was
added to acetonide 37 (0.29 g, 1.3 mmol) in MeOH (2
mL). The mixture was stirred overnight. The beads
were filtered off and washed thoroughly with DCM,
and the filtrate was dried (MgSO4) and concentrated.
After flash chromatography, the diol was obtained as a
clear oil (0.18 g, 76%), still containing the 15% unsatu-
1
−7.2 (c 0.70, CHCl3). H NMR (400 MHz, CDCl3): l
4.91 (tq, 1H, J=7.00, 6.16 Hz), 2.31 (q, 2H, J=7.56
Hz), 1.61–1.08 (m, 13H), 1.21 (d, 3H, J=6.16 Hz), 1.15
(t, 3H, J=7.60 Hz), 0.86 (t, 3H, J=7.04 Hz), 0.85 (d,
3H, J=6.28 Hz). 13C NMR (100 MHz, CDCl3): l
174.2, 70.8, 36.5, 36.0, 34.4, 29.8, 28.0, 27.0, 25.4, 20.0,
19.2, 11.4, 9.2. MS EI m/z (rel. int.): 154 (2), 125 (15),
101 (10), 83 (13), 75 (11), 70 (30), 57 (100), 43 (21), 41
(29). These data matched those reported.21–23
1
rated product from the previous step. H NMR (400
MHz, CDCl3): l 3.69 (m, 2H), 3.42 (dd, 1H, J=10.92
and 7.52), 1.98–1.08 (m, 15H), 0.83 (t, 3H, J=7.12 Hz),
0.81 (d, 3H, J=6.32 Hz). 13C NMR (100 MHz, CDCl3):
l 72.3, 66.7, 36.5, 34.3, 30.0, 29.4 (2C), 27.0, 25.6, 19.2,
11.4. This diol was then processed to epoxide 38.
4.6. (6R,12R)-6,12-Dimethylpentadecan-2-one 39
Epoxide reconstitution: Under an inert atmosphere,
Et3N (0.19 mL, 1.3 mmol) was added to the diol (0.18
g, 1.0 mmol) in anhydrous DCM (2.5 mL). The solu-
tion was cooled to 0°C and mesyl chloride (82 mL, 1.0
mmol) was added, and the mixture was stirred at 0°C
for 2 h. The reaction was concentrated, diluted with
ether and filtered. The crude mesylate was obtained
from the usual workup, and redissolved in MeOH (3
mL). Anhydrous K2CO3 (0.41 g, 3.0 mmol) was added
to this and the reaction was stirred for 2 h. The solid
was filtered off, followed by dilution with H2O and
extraction with DCM. The organic extracts were com-
bined and dried (MgSO4). After concentration and
column purification, the volatile epoxide 38 was
(4S,9S)-9-(2,2-Dimethyl-[1,3]dioxolan-4-yl)-nonan-4-ol
40: Under an inert atmosphere, freshly prepared
EtMgBr (from Mg turnings (0.66 g, 27.1 mmol) and
EtBr (1.8 mL, 23.1 mmol) in anhydrous THF (15 mL))
was added to CuI (0.18 g, 0.9 mmol) in dry THF (10
mL) at 0°C. After stirring for 5 min, epoxy-acetonide
35 (1.5 g, 7.0 mmol) in dry THF (5 mL) was added
dropwise to the mixture and stirred at 0°C for 3 h. The
reaction was quenched carefully with saturated NH4Cl,
followed by the usual workup and column purification
1
to furnish alcohol 40 as a clear oil (1.6 g, 91%). H
NMR (200 MHz, CDCl3): l 4.01 (m, 2H), 3.50 (m, 2H),
1.85–1.25 (m, 15H), 1.39 (s, 3H), 1.34 (s, 3H), 0.90 (t,
3H, J=6.84 Hz). 13C NMR (50 MHz, CDCl3): l 108.6,
76.1, 71.5, 69.5, 39.6, 37.3, 33.5, 29.6, 26.9, 25.7 (2C),
25.5, 18.8, 14.1. MS EI m/z (rel. int.): 229 (M+−CH3,
19), 211 (1), 169 (1), 125 (4), 109 (17), 95 (35), 72 (28),
55 (45), 43 (100). This was subjected to reductive
methylation.
1
obtained as a clear oil (43 mg, 27%). H NMR (200
MHz, CDCl3): l 2.88 (m, 1H), 2.73 (dd, 1H, J=5.12,
4.20 Hz), 2.45 (dd, 1H, J=4.88, 2.68 Hz), 1.52–1.08 (m,
13H), 0.83 (t, 3H, J=7.12 Hz), 0.81 (d, 3H, J=6.40
Hz). 13C NMR (50 MHz, CDCl3): l 52.4, 47.2, 36.5,
34.3, 32.5, 29.8, 29.5, 27.0, 26.0, 19.2, 11.4. MS EI m/z
(rel. int.): 123 (M+−C3H7, 5), 109 (20), 95 (16), 81 (32),
70 (42), 55 (74), 41 (100). These data matched those
reported.32
(4S,6%R%)-2,2-Dimethyl-4-(6-methyl-nonyl)-[1,3]dioxo-
lane 41: The detailed procedure of this reductive methyl-
ation was described earlier. Alcohol 40 (1.1 g, 4.5
mmol) was firstly mesylated by reacting with Et3N (2.8
mL, 19.0 mmol) and mesyl chloride (0.85 mL, 10.3
mmol), followed by reacting with Me2CuLi (freshly
prepared from CuI (2.2 g, 11.3 mmol) and MeLi (ca.0.4
M in ether, 56 mL, 22.4 mmol)) to afford acetonide 41
as a clear oil (0.35 g, 41%) after flash chromatography.
[h]2D3 −15.2 (c 1.20, CHCl3). 1H NMR (200 MHz,
CDCl3): l 4.02 (m, 2H), 3.49 (m, 1H), 1.57–1.08 (m,
15H), 1.39 (s, 3H), 1.34 (s, 3H), 0.85 (t, 3H, J=6.82
Hz), 0.80 (d, 3H, J=3.90 Hz). 13C NMR (50 MHz,
CDCl3): l 108.5, 76.2, 69.5, 39.4, 36.9, 33.6, 32.4, 30.0,
27.0, 26.9, 25.79, 25.77, 20.1, 19.6, 14.4. MS EI m/z
(rel. int.): 227 (M+−CH3, 21), 141 (1), 123 (1), 97 (21),
83 (22), 72 (23), 55 (20), 43 (100), 41 (30). Anal. calcd
for C15H30O2 (%): C, 74.32; H, 12.47. Found: C, 74.56;
H, 12.86%.
(1R,7R)-1,7-Dimethylnonyl propanoate 30
Epoxide opening: NaBH4 (20 mg, 0.53 mmol) and epox-
ide 38 (25 mg, 0.15 mmol) in EtOH (1.5 mL) were
refluxed for 1.75 h. The reaction was cooled to rt and
quenched with saturated NH4Cl. The mixture was
filtered, and the precipitate was washed with ether. The
filtrate was concentrated and extracted with DCM. The
organic extracts were combined and dried (MgSO4).
The alcohol was isolated as a clear oil (23 mg, 92%)
after the removal of solvent and flash chromatography.
[h]2D3 −13.3 (c 1.00, CHCl3). 1H NMR (200 MHz,
CDCl3): l 3.76 (q, 1H, J=6.10 Hz), 1.42–1.05 (m,
14H), 1.16 (d, 3H, J=6.10 Hz), 0.83 (t, 3H, J=6.82
Hz), 0.80 (d, 3H, J=6.40 Hz). 13C NMR (50 MHz,
CDCl3): l 68.2, 39.4, 36.5, 34.4, 30.0, 29.5, 27.0, 25.8,
23.5, 19.2, 11.4. MS EI m/z (rel. int.): 125 (7), 97 (6), 83
(2S,8R)-8-Methylundecan-1,2-diol 42: Amberlite IR120
(ca. 60 mg) and acetonide 41 (0.30 g, 1.2 mmol) in

790
S. Chow, W. Kitching / Tetrahedron: Asymmetry 13 (2002) 779–793
MeOH (20 mL) were stirred overnight, followed by
27.0, 26.4, 20.1, 19.7 (2C), 14.4. MS EI m/z (rel. int.):
238 (M+, <1), 210 (<1), 167 (1), 139 (3), 111 (10), 97
(47), 69 (43), 55 (93), 43 (100), 41 (82). These data
matched those reported.26
filtration and concentration. Flash chromatography
1
afforded diol 42 as a viscous oil (0.25 g, 100%). H
NMR (200 MHz, CDCl3): l 3.62–3.32 (m, 3H), 1.35–
1.03 (m, 17H), 0.84 (t, 3H, J=6.82 Hz), 0.80 (d, 3H,
J=4.14 Hz). 13C NMR (50 MHz, CDCl3): l 72.4, 66.7,
39.4, 37.0, 33.1, 32.4, 30.0, 27.0, 25.6, 20.1, 19.6, 14.4.
This diol was then converted to the epoxide, 43.
(6R,12R)-6,12-Dimethylpentadecan-2-one 39: A suspen-
sion of PdCl2 (9 mg, 32 mmol) and CuCl (13 mg, 0.13
mmol) in DMF/H2O (10:1, 0.66 mL) was purged with
O2 for 40 min. Alkene 45 (25 mg, 0.13 mmol) in DMF
(0.1 mL) was added and the brownish mixture was
bubbled with O2 for 4 h. The reaction was diluted with
H2O and extracted with DCM. The organic extracts
were combined, dried over MgSO4, and concentrated.
Column purification furnished 39 as a clear oil (20 mg,
(2S,6%R%)-2-(6-Methyl-nonyl)-oxirane 43: The proce-
dure for the epoxide reconstitution was described above
in detail. Diol 42 (0.26 g, 1.3 mmol) was mesylated with
Et3N (0.23 mL, 1.6 mmol) and mesyl chloride (0.11 mL,
1.3 mmol), followed by treatment with K2CO3 (0.37 g,
2.7 mmol) to furnish epoxide 43 as a clear liquid (0.11
1
74%). [h]2D3 −0.4 (c 0.40, CHCl3). H NMR (400 MHz,
1
g, 48%) after column chromatography. H NMR (400
CDCl3): l 2.38 (t, 2H, J=7.44 Hz), 2.11 (s, 3H),
1.55–1.05 (m, 20H), 0.86 (t, 3H, J=7.00 Hz), 0.82 (d,
3H, J=6.60 Hz), 0.81 (d, 3H, J=6.72 Hz). 13C NMR
(100 MHz, CDCl3): l 209.4, 44.1, 39.4, 37.1, 36.9, 36.5,
32.6, 32.5, 30.3, 29.8, 27.08, 27.05, 21.4, 20.1, 19.7, 19.5,
14.4. MS EI m/z (rel. int.): 239 (M+−CH3, 2), 236 (7),
211 (3), 165 (1), 152 (2), 123 (4), 110 (10), 85 (15), 71
(24), 58 (57), 43 (100), 41 (27). These data matched
those reported.25,26
MHz, CDCl3): l 2.89 (m, 1H), 2.73 (dd, 1H, J=5.00,
3.96 Hz), 2.45 (dd, 1H, J=5.00, 2.72 Hz), 1.51–1.18 (m,
15H), 0.86 (t, 3H, J=6.96 Hz), 0.81 (d, 3H, J=6.60
Hz). 13C NMR (100 MHz, CDCl3): l 52.3, 47.1, 39.3,
36.8, 32.4, 32.3, 39.7, 26.8, 25.9, 20.0, 19.5, 14.3. MS EI
m/z (rel. int.): 137 (M+−C3H7, 1), 123 (7), 109 (16), 95
(20), 81 (36), 69 (38), 55 (76), 43 (98), 41 (100). The
volatile epoxide was immediately reacted with the Grig-
nard reagent.
4.7. (2S,11S)-2,11-Diacetoxytridecane 47
(6S,12R)-12-Methylpentadec-1-en-6-ol 44: Under an
inert atmosphere, 3-butenyl magnesium bromide was
freshly prepared from Mg turnings (67 mg, 2.8 mmol)
and 4-bromo-1-butene (0.24 mL, 2.4 mmol) in anhy-
drous THF (3 mL). The Grignard solution was added
to another flask containing CuI (15 mg, 79 mmol) in
THF (0.5 mL) at 0°C. Epoxide 43 (0.11 g, 0.60 mmol)
in THF (1 mL) was added dropwise to the above, and
then stirred for 3 h at this temperature. The reaction
was carefully quenched by the addition of saturated
NH4Cl. Standard workup and flash chromatography
afforded the corresponding alcohol as a clear oil (48
1,8-Bisoxiranyl-octane 46. 1,11-Dodecadiene: Under an
inert atmosphere, 1,6-dibromohexane (4.0 g, 16.4
mmol) in anhydrous THF (15 mL) was cooled to 0°C
and allyl magnesium bromide (Aldrich, 1.0 M in ether,
93 mL, 93.0 mmol) was added slowly. The mixture was
stirred at rt for 2 days. The reaction was re-cooled to
0°C and carefully quenched with MeOH (10 mL). The
mixture was filtered, and the filtrate was washed with
saturated NH4Cl, H2O and brine. The organic solution
was dried (MgSO4), and the solvent was distilled off.
Flash chromatography afforded 1,11-dodecadiene as a
1
1
mg, 34%). [h]2D3 −0.1 (c 1.30, CHCl3). H NMR (400
clear liquid (2.0 g, 75%). H NMR (400 MHz, CDCl3):
MHz, CDCl3): l 5.78 (ddt, 1H, J=17.08, 10.24, 6.68
Hz), 4.99 (dq, 1H, J=17.12, 1.88 Hz), 4.92 (ddt, 1H,
J=10.2, 2.04, 1.20 Hz), 3.56 (m, 1H), 2.04 (m, 2H),
1.51–1.04 (m, 20H), 0.84 (t, 3H, J=6.96 Hz). 13C NMR
(100 MHz, CDCl3): l 138.7, 114.5, 71.8, 39.4, 37.5,
37.0, 36.8, 33.7, 32.4, 30.0, 27.0, 25.7, 24.9, 20.1, 19.6,
14.4. MS EI m/z (rel. int.): 222 (M+−H2O, 1), 194 (1),
151 (3), 123 (4), 97 (30), 81 (100), 69 (37), 57 (46), 43
(94). This alcohol was then converted to alkene 45.
l 5.80 (dt, 2H, J=10.20, 6.72 Hz), 4.98 (m, 2H), 4.91
(m, 2H), 2.05 (dq, 4H, J=6.80, 1.36 Hz), 1.42–1.25 (m,
12H). 13C NMR (100 MHz, CDCl3): l 139.2, 114.1,
33.8, 29.4, 29.1, 28.9. This diene was immediately epox-
idised.
Diepoxidation: Based on the procedure for the forma-
tion of 31, 1,11-dodecadiene (2.0 g, 12.0 mmol) was
treated with m-CPBA (50%, 13.5 g, 39.1 mmol) and
K2CO3 (1.3 g, 9.4 mmol) to give bisepoxide 46 as a
1
(6R,12R)-6,12-Dimethylpentadec-1-ene 45: By follow-
ing the standard procedure described previously, alco-
hol 44 (48 mg, 0.20 mmol) was treated with Et3N (0.17
mL, 1.2 mmol) and mesyl chloride (50 mL, 0.61 mmol),
followed by Me2CuLi (prepared from CuI (0.10 g, 0.53
mmol) and MeLi (ca. 1.4 M in ether, 0.7 mL, 0.98
mmol)) to give alkene 45 as a clear liquid (25 mg, 53%)
after flash chromatography. 1H NMR (400 MHz,
CDCl3): l 5.79 (dt, 1H, J=10.28, 6.68 Hz), 4.98 (dq,
1H, J=17.12, 1.60 Hz), 4.91 (dq, 1H, J=10.16, 1.24
Hz), 2.01 (m, 2H), 1.41–1.04 (m, 20H), 0.86 (t, 3H,
J=6.96 Hz), 0.82 (d, 3H, J=6.60 Hz), 0.81 (d, 3H,
J=6.56 Hz). 13C NMR (100 MHz, CDCl3): l 139.3,
114.1, 39.4, 37.1, 37.0, 36.5, 34.1, 32.7, 32.5, 30.4, 27.1,
clear oil (1.1 g, 45%) after flash chromatography. H
NMR (200 MHz, CDCl3): l 2.87 (m, 2H), 2.73 (dd, 2H,
J=4.88, 3.90 Hz), 2.44 (dd, 2H, J=4.88, 2.68 Hz),
1.49–1.23 (m, 16H). 13C NMR (100 MHz, CDCl3): l
52.4, 47.1, 32.4, 29.40, 29.36, 25.9. MS EI m/z (rel.
int.): 97 (14), 93 (16), 81 (28), 79 (28), 71 (53), 67 (57),
55 (69), 41 (100).
HKR: Racemic bisepoxide 46 (2.1 g, 10.4 mmol), H2O
(0.15 g, 8.3 mmol) and (S,S)-Jacobsen catalyst (89 mg,
12.5 mmol) were stirred at rt for 24 h. The (S,S)-bis-
epoxide 51 (0.64 g, 23%), (S)-epoxy-(R)-diol 52 (0.58 g,
26%) and (R,R)-tetrol 53 (0.27 g, 12%) were separated
by flash chromatography. (S,S)-Bisepoxide 51: [h]D23

S. Chow, W. Kitching / Tetrahedron: Asymmetry 13 (2002) 779–793
791
25.72, 25.70, 25.3, 9.6. MS EI m/z (rel. int.): 397 (36),
396 (29), 395 (100), 335 (6), 239 (8), 157 (20), 141 (31),
139 (85), 97 (22), 95 (31), 72 (40), 55 (37), 43 (100).
Anal. calcd for C23H35ClO4 (%): C, 67.22; H, 8.58.
Found: C, 67.22; H, 8.94%.
−16.4 (c 0.30, CHCl3). The spectral data matched these
for the racemic epoxide above. (2R,11S)-11-Oxiranyl-
undecane-1,2-diol 52: Anal. calcd for C12H24O3 (%): C,
66.63; H, 11.18. Found: C, 66.14; H, 11.47%. (R,R)-
1
Tetrol 53: [h]2D3 +31.9 (c 0.51, MeOH). H NMR (400
MHz, EtOH-d6): l 5.19 (s, 4H), 3.35 (m, 6H), 1.42–1.25
(m, 16H). 13C NMR (100 MHz, EtOH-d6): l 72.7, 67.0,
34.2, 30.6, 30.4, 26.4. Anal. calcd for C12H26O4 (%): C,
61.51; H, 11.18. Found: C, 61.80; H, 11.42%. Epoxydiol
52 was converted to the corresponding acetonide
derivative, which was also characterised. (4R,8S)-2,2-
(1S,9R)-4-Chloro-benzoic acid 1-ethyl-9-oxiranyl-nonyl
ester 56. Acetonide deprotection: Acetonide 55 (58 mg,
0.14 mmol) and Amberlite IR120 (ca. 20 mg) in MeOH
(4 mL) were stirred overnight. After filtration, concen-
tration and column purification, (1R,10R)-4-chloro-
benzoic acid 1-ethyl-10,11-dihydroxy-undecyl ester was
1
Dimethyl-4-(8-oxiranyl-octyl)-[1,3]dioxolane: H NMR
1
obtained as a clear oil (43 mg, 83%). H NMR (400
(400 MHz, CDCl3): l 4.01 (m, 2H), 3.47 (t, 1H, J=7.20
Hz), 2.88 (m, 1H), 2.73 (dd, 1H, J=5.04, 4.04 Hz), 2.44
(dd, 1H, J=5.04, 2.76 Hz), 1.59–1.27 (m, 19H), 1.38 (s,
3H), 1.33 (s, 3H). 13C NMR (100 MHz, CDCl3): l
108.6, 69.5, 52.4, 47.1, 33.6, 32.5, 29.6, 29.42, 29.38,
26.9, 25.9, 25.7. MS EI m/z (rel. int.): 241 (M+−CH3,
24), 225 (1), 149 (1), 135 (2), 121 (6), 107 (7), 95 (23), 81
(30), 72 (34), 55 (36), 43 (100). This epoxy-acetonide
was taken on to organocuprate reaction.
MHz, CDCl3): l 7.95 (m, 2H), 7.38 (m, 2H), 5.03 (q,
1H, J=6.64 Hz), 3.65 (2H, m), 3.45 (1H, m), 1.71–1.24
(m, 20H), 0.91 (t, 3H, J=7.44 Hz). 13C NMR (100
MHz, CDCl3): l 165.6, 139.1, 129.2, 128.6, 72.3, 66.8,
33.6, 33.1, 29.5, 29.4, 29.34, 29.32, 27.0, 25.4, 25.3, 15.2,
9.6. Anal. calcd for C20H31ClO4 (%): C, 64.76; H, 8.42.
Found: C, 64.25; H, 8.67%.
Reconstitution to the epoxide: Following the procedure
described earlier, the above diol (36 mg, 0.10 mmol)
was mesylated with Et3N (15 mL, 0.10 mmol) and mesyl
chloride (8.0 mL, 0.10 mmol) was added, then treated
with K2CO3 (29 mg, 0.21 mmol) to give epoxy-ester 56
as a clear oil (21 mg, 44%) after flash chromatography.
1H NMR (400 MHz, CDCl3): l 7.96 (m, 2H), 7.39 (m,
2H), 5.04 (q, 1H, J=5.64 Hz), 2.87 (m, 1H), 2.71 (dd,
1H, J=5.00, 3.96 Hz), 2.43 (dd, 1H, J=5.04, 2.72 Hz),
1.68–1.23 (m, 18H), 0.91 (t, 3H, J=7.44 Hz). 13C NMR
(100 MHz, CDCl3): l 165.5, 139.1, 130.9, 129.3, 128.6,
52.4, 47.1, 33.6, 32.5, 29.5, 29.41, 29.35, 27.0, 25.9, 25.3,
9.6. HRMS calcd for C20H29NaClO3 375.1703, found
375.1707 (M+Na)+.
(3R,11R)-11-(2,2-Dimethyl-[1,3]dioxolan-4-yl)-unde-
can-3-ol 54: Under an inert atmosphere, CuI (61 mg,
0.32 mmol) in dry THF (2 mL) was cooled to −40°C.
MeMgBr (Aldrich, 3.0 M in ether, 1.0 mL, 3.0 mmol)
was added and stirred for 10 min. The above epoxyacet-
onide (0.37 g, 1.5 mmol) in dry THF (3 mL) was added
by syringe to the cuprate, and then stirred for 3.5 h at
the same temperature. Saturated NH4Cl was added
carefully to quench the reaction. Standard workup and
purification afforded the alcohol as a clear oil (0.36 g,
1
91%). [h]2D3 −17.1 (c 1.59, CHCl3). H NMR (400 MHz,
CDCl3): l 4.01 (m, 2H), 3.49 (m, 1H), 3.46 (1H, t,
J=7.24 Hz), 1.59–1.27 (m, 19H), 1.38 (s, 3H), 1.33 (s,
3H), 0.92 (t, 3H, J=7.44 Hz). 13C NMR (100 MHz,
CDCl3): l 108.6, 73.3, 69.5, 36.9, 33.6, 30.1, 29.65,
29.62, 29.5, 29.4, 27.0, 25.7, 25.6, 9.9. MS EI m/z (rel.
int.): 257 (M+−CH3, 53), 239 (1), 185 (7), 149 (5), 123
(11), 109 (22), 95 (34), 81 (39), 59 (64), 43 (100). This
alcohol was subjected to the Mitsunobu reaction.
(2S,11S)-Tridecane-2,11-diol 57: Under an inert atmo-
sphere, epoxy ester 56 (15 mg, 0.05 mmol) in dry ether
(1 mL) was added to LiAlH4 (12 mg, 0.31 mmol) in
ether (1.5 mL) at 0°C. The mixture was refluxed for 2 h
and stirred overnight at rt. The reaction was diluted
with ether, and Na2SO4·10H2O (0.12 g) was carefully
added and stirred for another 2 h. The mixture was
filtered, dried (MgSO4) and concentrated to furnish diol
(1S,9R)-4-Chloro-benzoic acid 9-(2,2-dimethyl-[1,3]
dioxolan-4-yl)-1-ethyl-nonyl ester 55: Under an inert
atmosphere, alcohol 54 (0.25 g, 0.92 mmol), p-
chlorobenzoic acid (0.17 g, 1.1 mmol) and
triphenylphosphine (0.42 g, 1.6 mmol) in dry THF (10
mL) were cooled to 0°C. DEAD (0.14 mL, 1.1 mmol)
in THF (0.5 mL) was added dropwise, and the reaction
was stirred for 1 h at the same temperature. After
diluting with ether, and washed with H2O, the aqueous
layer was separated and re-extracted with ether. The
combined organic extracts were dried (MgSO4), concen-
trated, and purified by flash chromatography to furnish
the benzoate ester as a viscous oil (0.30 g, 80%). [h]D23
1
57 as a clear oil (9 mg, 79%). H NMR (400 MHz,
CDCl3): l 3.77 (s, 1H, J=6.00 Hz), 3.50 (m, 1H),
1.59–1.27 (m, 20H), 1.16 (d, 3H, J=6.20 Hz), 0.92 (t,
3H, J=7.44 Hz). 13C NMR (100 MHz, CDCl3): l 73.3,
68.2, 39.3, 36.9, 30.1, 29.7, 29.6, 29.5, 25.7, 25.6, 23.5,
9.9. These data matched those reported.27
(2S,11S)-2,11-Diacetoxytridecane 47: The above diol
(8.0 mg, 0.04 mmol), an excess of pyridine (ca. 0.1 mL)
and acetic anhydride (ca. 0.1 mL) and a catalytic
amount of DMAP in DCM (1 mL) were stirred for 2 h.
The reaction was diluted with ether, washed repetitively
with saturated CuSO4, and dried (MgSO4). After con-
centration and column purification, the title product
was yielded as a clear oil (7 mg, 68%). [h]2D3 −4.0 (c 0.70,
1
+9.2 (c 0.20, CHCl3). H NMR (400 MHz, CDCl3): l
7.96 (m, 2H), 7.38 (m, 2H), 5.03 (q, 1H, J=6.36 Hz),
4.02 (m, 2H), 3.46 (t, 1H, 7.08 Hz), 1.72–1.24 (m, 18H),
1.37 (s, 3H), 1.33 (s, 3H), 0.91 (t, 3H, J=7.40 Hz). 13C
NMR (100 MHz, CDCl3): l 165.5, 139.1, 131.9, 128.6,
128.5, 108.5, 69.5, 33.59, 33.55, 29.6, 29.5, 27.0, 26.9,
1
CHCl3). H NMR (400 MHz, CDCl3): l 4.86 (tq, 1H,
J=6.24, 6.00 Hz), 4.79 (tt, 1H, J=6.72, 5.80 Hz), 2.02

792
S. Chow, W. Kitching / Tetrahedron: Asymmetry 13 (2002) 779–793
(s, 3H), 2.00 (s, 3H), 1.57–1.24 (m, 18H), 1.18 (d, 3H,
J=6.28 Hz), 0.85 (t, 3H, J=7.40 Hz). 13C NMR (100
MHz, CDCl3): l 171.0, 170.8, 75.5, 71.1, 35.9, 33.6,
29.5, 29.42 (2C), 29.40, 26.9, 25.4, 25.3, 21.4, 21.3, 20.0,
9.6. MS EI m/z (rel. int.): 271 (M+−C2H5, <1), 229 (1),
151 (4), 124 (5), 110 (5), 101 (3), 95 (10), 87 (4), 82 (12),
69 (10), 68 (9), 55 (17), 43 (100), 41 (14). These data
matched those reported.27,28
30.42, 30.39, 26.4. Anal. calcd for C13H28O4 (%): C,
62.67; H, 11.36. Found: C, 62.38; H, 11.32%.
(2S,12S)-Tridecane-2,12-diol 61: Bisepoxide 58 (65 mg,
0.31 mmol) and NaBH4 (60 mg, 1.6 mmol) in EtOH
(3.5 mL) were refluxed for 3 h, followed by quenching
with saturated NH4Cl. The white precipitate was
filtered, and the filtrate was concentrated and extracted
with DCM. The organic extracts were combined, dried
(MgSO4), concentrated and column purified to afford
1
diol 61 (56 mg, 84%). [h]2D3 +11.1 (c 0.76, MeOH). H
4.8. (2S,12S)-2,12-Diacetoxytridecane 49
NMR (200 MHz, CDCl3): l 3.75 (m, 2H), 1.50–1.25 (m,
20H), 1.16 (d, 6H, J=6.34 Hz). 13C NMR (100 MHz,
CDCl3): l 68.2, 39.3, 29.59, 29.55, 29.47, 25.7, 23.5.
Anal. calcd for C13H28O2 (%): C, 72.17; H, 13.04.
Found: C, 72.21; H, 13.52. These data matched those
reported.27
1,9-Bisoxiranyl-nonane 48. Grignard reaction: Under an
inert atmosphere, allyl magnesium bromide (Aldrich,
1.0 M in ether, 30 mL, 30 mmol) was added to 1,7-
dibromoheptane (1.01 g, 3.9 mmol) in dry THF (30
mL) at 0°C. The mixture was stirred at rt for 2 days.
After a standard workup and column chromatography,
1,12-tridecadiene was afforded as a clear liquid (0.53 g,
(2S,12S)-2,12-Diacetoxytridecane 49: Diol 61 (44 mg,
0.20 mmol), an excess of pyridine (ꢀ0.2 mL) and acetic
anhydride (ꢀ0.2 mL) and a catalytic amount of
DMAP in DCM (2 mL) were stirred for 1.5 h. The
reaction was diluted with ether, washed with saturated
CuSO4, and dried (MgSO4). After concentration and
flash chromatography, the title product was yielded as a
1
75%). H NMR (400 MHz, CDCl3): l 5.80 (ddt, 2H,
J=17.08, 10.26, 6.60 Hz), 5.00 (m, 2H), 4.91 (m, 2H),
2.02 (q, 4H, J=5.62 Hz), 1.35 (m, 14H). 13C NMR (100
MHz, CDCl3): l 139.3, 114.1, 33.8, 29.54, 29.47, 29.1,
28.9. MS EI m/z (rel. int.): 152 (M+−C2H4, <1), 109 (6),
95 (16), 81 (31), 69 (18), 67 (38), 55 (71), 41 (100). This
diene was then epoxidised.
1
clear oil (60 mg, 98%). [h]2D3 +1.8 (c 1.21, CHCl3). H
NMR (200 MHz, CDCl3): l 4.86 (s, 2H, J=6.10 Hz),
2.00 (s, 6H), 1.62–1.23 (m, 18H), 1.18 (d, 6H, J=6.10
Hz). 13C NMR (50 MHz, CDCl3): l 170.8, 71.0, 35.9,
29.5, 29.4, 25.4, 21.4, 19.9. MS EI m/z (rel. int.): 257
(M+−C2H3O+, <1), 197 (1), 180 (3), 138 (4), 110 (5), 96
(9), 87 (9), 82 (10), 68 (10), 55 (17), 43 (100), 41 (14).
Anal. calcd for C17H32O4 (%): C, 62.67; H, 11.36.
Found: C, 62.38; H, 11.32%. These data matched those
reported.27,28
Diepoxidation: m-CPBA (50%, 3.1 g, 9.0 mmol) was
added in portions to 1,12-tridecadiene (0.52 g, 2.9
mmol) in DCM (10 mL) at 0°C, and followed by
K2CO3 (0.23 g, 1.7 mmol). The resulting suspension
was stirred at rt overnight. The solid was filtered and
the filtrate was washed thoroughly with saturated
NaHCO3, dried (MgSO4) and concentrated. After flash
chromatography, bisepoxide 48 was acquired as a clear
1
liquid (0.38 g, 61%). H NMR (200 MHz, CDCl3): l
2.88 (m, 2H), 2.72 (dd, 2H, J=5.12, 4.16 Hz), 2.44 (dd,
2H, J=4.88, 2.36 Hz), 1.48–1.26 (m, 18H). 13C NMR
(50 MHz, CDCl3): l 52.4, 47.1, 32.5, 29.5, 29.4, 25.9.
MS EI m/z (rel. int.): 109 (7), 95 (17), 81 (31), 71 (44),
67 (49), 55 (61), 43 (42), 41 (100). Anal. calcd for
C13H24O2 (%): C, 73.54; H, 11.39. Found: C, 73.79; H,
11.69%.
Acknowledgements
We are grateful to Professor Dr. W. Francke of the
University of Hamburg for the specific rotation data
for some compounds in the 2,11- and 2,12-diace-
toxytridecane sections.
HKR: Racemic bisepoxide 48 (0.36 g, 1.7 mmol), H2O
(25 mg, 1.4 mmol) and (R,R)-1 (14 mg, 19.7 mmol) were
stirred at rt for 24 h. (R,R)-Bisepoxide 58 (72 mg, 19%),
(R)-epoxy-(S)-diol 59 (170 mg, 45%) and (S,S)-tetrol
60 (35 mg, 9%) were separated by flash chromatogra-
phy. (1R,9R)-1,9-Bisoxiranyl-nonane 58: [h]2D3 +11.1 (c
1.16, CHCl3). The spectral data matched those for the
racemic epoxide reported above. (2S,12R)-12-Oxiranyl-
References
1. (a) For a semi-encyclopedic compilation for the period
1979–1989, see Mori, K. In The Total Synthesis of Natu-
ral Products; Simon, J. A., Ed.; John Wiley and Sons
Inc.: Brisbane, Australia, 1992; Vol. 9; (b) Mori, K. Adv.
Asymm. Synth. 1995, 1, 211–269 (JAI Press Inc.).
2. (a) Mori, K. Chirality 1998, 10, 578; (b) Mori, K. Chem.
Commun. Rev. 1997, 1153; (c) Mori, K. Eur. J. Org.
Chem. 1998, 1479.
1
dodecane-1,2-diol 59: [h]2D3 −11.5 (c 0.40, MeOH). H
NMR (200 MHz, CDCl3): l 3.68 (m, 2H), 3.39 (m, 1H),
2.89 (m, 1H), 2.74 (dd, 1H, J=5.12, 4.20 Hz), 2.44 (dd,
1H, J=4.88, 2.36 Hz), 1.47–1.26 (m, 20H). 13C NMR
(100 MHz, CDCl3): l 71.8, 65.6, 52.4, 47.1, 32.4, 29.6,
29.5, 29.43, 29.38, 29.36, 25.9, 25.0. Anal. calcd for
C13H26O3 (%): C, 67.79; H, 11.38. Found: C, 67.56; H,
11.52%. (2S,12S)-Tridecane-1,2,12,13-tetrol 60: [h]D23
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−26.1 (c 0.70, MeOH). H NMR (400 MHz, EtOH-d6):
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