Enantiopure building blocks for the synthesis of 3-methyl-2-alkanols. Diastereoselective methylmetal addition to a chiral 2-methylaldehyde followed by lipase catalysed esterification

Article abstract of DOI:10.1016/j.tetasy.2004.07.049

The racemic synthetic building block (2R*,3R*)-3-methyl-4- (phenylsulfanyl)butan-2-ol (2R*,3R*)-2 was obtained in a high diastereomeric ratio [95:5, (2R*,3R*)/(2R*,3S*)-ratio] by Lewis acid catalysed dimethylzinc addition to racemic 2-methyl-3- (phenylsul

Full text of DOI:10.1016/j.tetasy.2004.07.049

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 2907–2915
Enantiopure building blocks for the synthesis of
3-methyl-2-alkanols. Diastereoselective methylmetal addition to a
chiral 2-methylaldehyde followed by lipase catalysed esterification
Michael Larsson, Jimmy Andersson, Rong Liu and Hans-Erik Hogberg*
¨
Department of Natural and Environmental Sciences, Mid Sweden University, S-851 70 Sundsvall, Sweden
Received 3 June 2004; accepted 8 July 2004
Abstract—The racemic synthetic building block (2R*,3R*)-3-methyl-4-(phenylsulfanyl)butan-2-ol (2R*,3R*)-2 was obtained in a
high diastereomeric ratio [95:5, (2R*,3R*)/(2R*,3S*)-ratio] by Lewis acid catalysed dimethylzinc addition to racemic 2-methyl-3-
(phenylsulfanyl)propanal (rac-1). Two consecutive acylations with vinyl acetate catalysed by Chirazyme L-2 (immobilised Candida
antarctica lipase B, CAL-B) led to preferential esterification of three of the four stereoisomers leaving (2S,3S)-3-methyl-4-(phenyl-
sulfanyl)butan-2-ol (2S,3S)-2 of 98:2 dr and 98% ee. The stereoisomerically impure acetate of (2R,3R)-3-methyl-4-(phenylsulfa-
nyl)butan-2-ol (2R,3R)-2, obtained in the first CAL-B-catalysed acylation step, was hydrolysed and reesterified using CAL-A
(immobilised Novozyme SP 525) as the catalyst, which left (2R,3R)-3-methyl-4-(phenylsulfanyl)butan-2-ol (2R,3R)-2 of 98:2 dr
and 99% ee as the remaining substrate. The individual enantiomers of 2-methyl-3-(phenylsulfanyl)propanal 1 were prepared from
readily available (S)- and (R)-3-hydroxy-2-methylpropanoic acid methyl ester and reacted with dimethylzinc to give both enantio-
mers of (2R*,3R*)-3-methyl-4-(phenylsulfanyl)butan-2-ol (2R, 3R)- or (2S,3S)-2 of both high dr and ee. These products were puri-
fied by lipase catalysed acylation to give the enantiomerically and diastereomerically highly pure enantiomers (>99.5:0.5 dr, >99.9%
ee). Pure (2S,3S)-3-methyl-4-(phenylsulfanyl)butan-2-ol (2S,3S)-2 was transformed into a potential pheromone precursor isolated
from some pine sawflies of the genus Gilpinia, (2S,3R)-3-methylpentadecan-2-ol in 54% yield over eight steps.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
isomerically pure intermediate containing a suitable
group Y, which subsequently can be removed. Because
sulfur containing groups are easy to remove, they are
attractive to use as Y-groups. If the Y group is phenyl-
sulfanyl (Y = PhS), the neighbouring methylene carbon
can be transformed into an electrophilic one by conver-
sion of the PhS group into a good leaving group,
whereas if it is phenylsulfonyl (Y = PhSO2) the same
carbon can be rendered nucleophilic by deprotonation.
Many natural products such as antibiotics1 and some
pheromones2 contain the stereoisomerically pure
3-methyl-2-butanol moiety I attached to various sub-
stituents in the 4-position (Scheme 1). A number of
approaches exist for the synthesis of compounds
containing this moiety.1–3 One way of incorporating this
moiety in a synthetic target can be to alkylate a stereo-
We have recently studied the diastereoselectivity in
alkylmetal additions to some chiral racemic 2-methylal-
dehydes and found that titanium tetrachloride catalysed
dimethylzinc addition to racemic 2-methyl-3-(phenyl-
sulfanyl)propanal rac-1 (Scheme 2) furnished race-
mic (2R*,3R*)-3-methyl-4-(phenylsulfanyl)-2-butanol
Scheme 1. General outline describing the incorporation of the stereo-
isomerically pure 3-methyl-2-butanol moiety I in a synthetic target.
Reagents and conditions: (a) diastereoselective addition of a methyl-
metal reagent; (b) enzyme catalysed resolution; (c) transformation of
group X (optional); (d) alkylation; (e) removal of Y-group.
(2R*,3R*)-2 in
a high diastereomeric ratio (dr),
[(2R*,3R*)/(2R*,3S*)-ratio: ꢀ95:5].4 The predominance
of (2R*,3R*)-2 is probably due to a cyclic transition
state.4 Thus we have easy access to a synthetic interme-
diate for the preparation of targets of type I in which a
suitable group Y (Scheme 1) is already incorporated.
*
Corresponding author. Tel.: +46 60148704; fax: +46 60148802;
e-mail: hans-erik.hogberg@mh.se
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.07.049

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M. Larsson et al. / Tetrahedron: Asymmetry 15 (2004) 2907–2915
2.1. Resolution of racemic (2R*,3R*)-2
We screened various lipases in order to achieve resolu-
tion and diastereomeric separation of racemic
(2R*,3R*)-2 (80:20 dr). Regarding selectivity in position
3, Ohtsuka et al.6 have earlier shown, that a diastereo-
meric mixture of (2R,3R)- and (2R,3S)-2 can be sepa-
rated by using CAL-A-catalysed (Novozyme SP 525)
esterification and hydrolysis. Regarding selectivity at
position 2, we found that Candida Antarctica lipase B
(Chirazyme L-2, CAL-B) showed the highest selectivity
among the lipases tested. Hence, racemic (2R*,3R*)-2
(95:5 dr) was treated with vinyl acetate in the presence
of CAL-B in n-heptane over molecular sieves (Scheme
2). Under these conditions, the diastereomers of 2 with
(2R)-configuration reacted considerably faster than
(2S)-2. At 49% conversion the E-value was >500 and a
mixture of (2S)-isomers of 2 was recovered as the
remaining substrate with an unchanged dr and a (2S/
2R)-ratio of >99:1 along with the acetate of (2R,3R)-2
(94:6 dr, 2R/2S-ratio: 99:1).
In addition to its high (2R)-selectivity in esterification of
compound 2, CAL-B also showed a slight preference for
acylation of the (3R)-isomers. Thus, in order to remove
traces of the other isomers present in the recovered sub-
strate, slightly impure (2S,3S)-2 (ꢀ95:5 dr, 98% ee) was
once again subjected to CAL-B and vinyl acetate. Con-
versions over 13% did not further increase the purity of
the remaining substrate. Stopping at this conversion
gave (2S,3S)-2 [98:2 dr; 98% ee and 37% overall yield
from racemic (2R*,3R*)-2].
It is known that vinyl acetate esterifies (2R,3S)-2 twenty
times faster than (2R,3R)-2 catalysed by Novozyme SP
525.6 Therefore, the slightly isomerically impure acetate
of (2R,3R)-2 obtained from the first CAL-B-catalysed
esterification was hydrolysed. The resulting alcohol was
subjected to vinyl acetate and Novozyme SP 525. The
reaction was interrupted at 41% conversion yielding the
remaining substrate as highly pure (2R,3R)-2 [98:2 dr,
99% ee, overall yield from racemic (2R*,3R*)-2: 18%].
Scheme 2. Preparation of racemic (2R*,3R*)-2 and its enzyme
catalysed resolution and diastereoselective purification.
Enantiomerically pure (2R*,3R*)-2 could serve as a syn-
thetic intermediate for the preparation of several pine
sawfly sex pheromones, esters of alcohols with the gen-
2.2. Preparation of (2S,3S)- and (2R,3R)-2 and their
enzyme catalysed purification
eral structure
I (Scheme 1, R = dimethyl-n-alkyl,
methyl-n-alkyl, or n-alkyl). It has earlier been shown
that some racemic pine sawfly pheromones can be re-
solved by lipase catalysed acylation.2h We were inter-
ested in being able to control the stereochemistry at an
earlier stage in the synthetic sequence. Because second-
ary alcohols are generally easy to resolve by lipase cata-
lysed resolutions,5,6 we have studied such reactions with
the racemic secondary alcohol (2R*,3R*)-2 to see if the
products could be obtained in sufficiently high enantio-
meric and diastereomic excesses for our needs.
Although lipase catalysed reactions of the slightly dia-
stereomerically impure and racemic (2R*,3R*)-2 fur-
nished both (2S,3S)-2 and (2R,3R)-2 in quite high
diastereomeric ratios and enantiomeric excesses, we were
not satisfied with the isomeric purities of these samples,
which were too low to be useful for the preparation of
the desired highly pure single stereoisomers of pine saw-
fly pheromones. Clearly, alternative approaches to the
pure enantiomers (2S,3S)- and (2R,3R)-2 were needed.
We wanted to use lipases for the purification of already
enantiomerically and diastereomerically enriched 2.
2. Results and discussion
If we should have access to enantiomerically pure 2-
methyl-3-(phenylsulfanyl)propanal 1, we could, using
our diastereoselective dimethylzinc addition reaction,4
be able to prepare both (2S,3S)- and (2R,3R)-2 in quite
high isomeric purities, provided that no racemisation of
For the synthesis of pure (2S,3R)-isomers of pine
sawfly pheromones, we decided to study the lipase-
mediated resolution by transesterification of racemic
(2R*,3R*)-2.

M. Larsson et al. / Tetrahedron: Asymmetry 15 (2004) 2907–2915
2909
the aldehyde 1 would occur during the reaction se-
quence. Both enantiomers of the aldehyde 1 have previ-
ously been prepared.7 The method starting from methyl
3-hydroxy-2-methylpropanoate7b seemed most advanta-
geous as both enantiomers of this ester are commercially
available. Because reaction of enantiopure aldehyde
(S)-1 should provide a 95:5 mixture of (2S,3S)-2 and
(2R,3S)-2, the latter unwanted product should, due to
its more reactive (2R)-configuration, be easily removed
by lipase catalysed acylation. Even if the enantiomeric
purity of the aldehyde will be only 90% ee, the product
of dimethylzinc addition will contain 90.3% of (2S,3S)-
2, 4.7% of (2R,3S)-2, 4.7% (2R,3R)-2, and a very minute
amount of 0.3% of (2S,3R)-2. Whereas the two isomers
with the (2R)-configuration will easily be separated from
the major and desired isomer (2S,3S)-2 by enzyme-cata-
lysed esterification, the one with (2S,3R)-configuration
will be more difficult to remove completely. However,
in the suggested reaction sequence, the latter is produced
in an extremely small amount.
tion of 1 to 4 and analysis as its MTPA-ester (vide su-
pra). The solution of the aldehyde (S)-1 was reacted
with dimethylzinc in the presence of titanium tetrachlo-
ride to give the following mixture of stereoisomers of
compound 2: 91.5% of (2S,3S)-2; 7% of (2R,3S)-2;
1.4% of (2R,3R)-2; 0.1% of (2S,3R)-2 (Scheme 3).
The mixture of the four stereoisomers containing mainly
compound (2S,3S)-2 was subjected to purification by
CAL-B-catalysed esterification with vinyl acetate. After
9% conversion, the slow reacting alcohol (2S,3S)-2 was
recovered in a very high isomeric purity (>99.9:0.1 dr
and >99.9% ee) and in 90% yield based on the starting
mixture (Scheme 4). The overall yield was 61% based
Thus, the preparation of the building blocks (2S,3S)-2
or its enantiomer was conducted as follows (Scheme
3). First we wanted to prepare (S)-2-methyl-3-(phenyl-
sulfanyl)propanal (S)-1 from commercially available
methyl (R)-3-hydroxy-2-methylpropanoate (>99% ee
by GC analysis). However, we experienced difficulties
with the reproduction of the eeÕs obtained earlier.7b
Therefore, to ensure retention of configuration in the
reaction sequence leading to enantiomerically enriched
1, we used a modified method. Thus, methyl (R)-3-hyd-
roxy-2-methylpropanoate was treated with diphenyldi-
sulfide to give the corresponding thioether (S)-3 (>97%
ee by GC analysis). Reduction of this compound with
lithium aluminium hydride gave the alcohol (S)-4
1
(>97% ee by H NMR analysis on its corresponding
MTPA-ester, derived from (ꢁ)-MTPAC1). Swern oxi-
dation of the alcohol (S)-4 using oxalyl chloride in
DMSO and HunigÕs base (N-ethyldiisopropylamine)
¨
was followed by workup with aqueous KH2PO4 to en-
sure that no amine remained and that the pH was neu-
tral. This afforded the corresponding aldehyde (S)-1.
The enantiomeric purity of this was checked by reduc-
Scheme 4. Enzyme catalysed purification of (2S,3S)- and (2R,3R)-2
prepared from methyl (R)- or (S)-3-hydroxy-2-methylpropanoate.
Scheme 3. Synthesis of the building blocks (2S,3S)- and (2R,3R)-2. *Stereogenic centre of either (S)- or (R)-configuration. Reagents and conditions:
(a) (PhS)2, (n-Bu)3P, DMF, 0ꢁC, rt (95%); (b) LiAlH4, THF (96%); (c) (i) DMSO, oxalyl chloride, ꢁ78ꢁC. (ii) DIPEA, CH2Cl2, ꢁ78ꢁC. (iii)
Extractive workup with KH2PO4; (d) (i) CH2Cl2, ꢁ78ꢁC, TiCl4 (1.0equiv), 10min, Me 2Zn (1.0equiv) [75%, over steps (c) and (d)].

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M. Larsson et al. / Tetrahedron: Asymmetry 15 (2004) 2907–2915
Scheme 5. Synthesis of (2S,3R)-3-methylpentadecan-2-ol (2S,3R)-8 from the chiral building block (2S,3S)-2. Reagents and conditions:
(a) TBDMSCl, DMF, imidazole (99%); (b) m-CPBA, CH2Cl2 (88%); (c) (i) THF, DMPU, ꢁ40ꢁC, n-BuLi (2.1equiv), up to 0ꢁC, cool to ꢁ40ꢁC.
(ii) 1-Iodoundecane (1.2equiv), THF, up to 20ꢁC (96%); (d) 10% Na–Hg, MeOH, Na2HPO4, rt (94%); (e) (i) TBAF, THF, reflux. (ii) Acetyl
chloride, pyr, CH2Cl2 (84%); (f) (i) RaNi, EtOH, H2. (ii) KOH/MeOH, rt (82%).
on methyl (R)-3-hydroxy-2-methylpropanoate over five
steps.
tective group were removed with sodium amalgam
followed by tetrabutylammonium fluoride (TBAF),
respectively, to give (2S,3R)-8. In our hands, the so-
dium amalgam reaction yielded the alcohol (2S,3R)-8
contaminated with an elimination product (ꢂ15%).
NMR-analysis indicated that the double bond in this
undesired product was located between the 4- and 5-car-
bons. Therefore, it should be possible to remove this
without epimerisation, provided that the double bond
does not migrate towards the alcohol end of the com-
pound, which indeed can happen in some cases.11–15
However, acetylation of a chiral alcohol seems to pre-
vent such migrations.16 Therefore, the crude product
mixture was acylated and treated with Raney nickel in
ethanol under hydrogen. Alkaline hydrolysis followed
by chromatography gave, from sulfone (1S,2S)-7,
(65%) of the pure pheromone precursor alcohol
(2S,3R)-8 [>99:1 dr, >99% ee, and 54% total yield based
on (2S,3S)-2].
The crude enantiomer, (2R,3R)-2, was prepared in the
same manner from methyl (S)-3-hydroxy-2-methylprop-
anoate (>99% ee by GC analysis). The purities of the
intermediate products were (R)-3 (>98% ee by GC anal-
1
ysis) and (R)-4 and (R)-1 (both >94% ee by H NMR
analysis on its corresponding MTPA-ester, from (+)-
MTPAC1). Dimethylzinc addition, as described above,
furnished the following mixture of stereoisomers of
compound 2; 92% of (2R,3R)-2, 4.9% of (2S,3R)-2,
2.9% of (2S,3S)-2, and 0.2% of (2R,3S)-2 (Scheme 3).
This mixture of four stereoisomers, containing mainly
compound (2R,3R)-2, was subjected to purification by
CAL-B-catalysed esterification with vinyl acetate. The
reaction was interrupted at 88% conversion. Chromato-
graphic separation furnished the acetate of (2R,3R)-2.
Alkaline hydrolysis gave the alcohol (2R,3R)-2 in a dia-
stereomeric ratio of >99.5:0.5 and an enantiomeric pur-
ity of >99.9% in 74% yield based on the starting mixture
(Scheme 4). The overall yield was 43% based on methyl
(S)-3-hydroxy-2-methylpropanoate over six steps.
4. Conclusion
Combination of synthesis from an enantiopure starting
material, diastereoselective dimethylzinc addition, and
enzyme-catalysed purification of the products is a very
efficient way to produce some valuable enantiopure syn-
thetic intermediates. By Mitsunobu inversion or related
reactions, pure (2R,3S)- and (2S,3R)-2 will probably be
easily accessible from the pure (2S,3S)- and (2R,3R)-
ones, respectively. The synthetic utility of the building
block (2S,3S)-2 is demonstrated by its conversion into
the pheromone precursor alcohol (2S,3R)-8.
3. Synthesis of a potential pheromone precursor present in
Gilpinia spp
(2S,3R)-3-Methylpentadecan-2-ol, (2S,3R)-8 (Scheme 5)
is a probable pheromone precursor, that has been
isolated from females of the pine sawflies G. socia and
G. frutetorum.8 Based on the structures of other known
pine sawfly pheromones, the actual Gilpinia spp. phero-
mone is most likely either the acetate or propanoate of
(2S,3R)-8.9 Using the pure building block (2S,3S)-2 de-
scribed in section 2.2 as the starting point, we have syn-
thesised the alcohol (2S,3R)-8 using a route similar to
that described in our previous paper (Scheme 5).10
5. Experimental
5.1. General
Commercially available chemicals were used without
further purification unless otherwise stated. Chirazymeꢂ
L-2, carrier fixed, C2, (Lipase B, from Candida antarc-
Treatment of the alcohol (2S,3S)-2 with tert-butylchlo-
rodimethylsilane (TBDMSCl) gave the silyl ether
(1S,2S)-5 (Scheme 5). Oxidation of this with MCPBA
furnished the sulfone (1S,2S)-6. The carbanion derived
from this was alkylated with 1-iodoundecane to yield
(1S,2S)-7, whose phenylsulfone unit and TBDMS pro-
Note that, although the stereochemistry at position 3 is retained when
the sulfonyl group is removed, the designation of configuration at
position 3 changes from S to R due to the CIP-priority rules.

M. Larsson et al. / Tetrahedron: Asymmetry 15 (2004) 2907–2915
2911
tica, CAL-B) was obtained from Roche. Novozymeꢂ SP
525, (immobilised lipase A from Candida antarctica,
CAL-A) was a gift from Novo Nordisk. Lipases were
stored at 4ꢁC over dry silica gel. Me2Zn was purchased
as a 2.0M solution in toluene. Raney nickel (W-2 type)
and titanium tetrachloride were obtained from Fluka
and Baker, respectively. Et2O (LiAlH4), THF (K, ben-
zophenone), DMPU, CH2Cl2, DMF, DMSO and
DIPEA (CaH2) were distilled from the indicated
drying agents and stored under argon. (S)- and (R)-
3-hydroxy-2-methylpropanoic acid methyl ester were
5.3. Synthesis of (2R,3R)- and (2S,3S)-isomers of 2 from
rac-1
5.3.1. (2R*,3R*)-3-Methyl-4-(phenylsulfanyl)butan-2-ol
(2R*,3R*)-2. 2-Methyl-3-(phenylsulfanyl)propanal rac-1
(5.1g, 28.3mmol) was dissolved in distilled CH2Cl2
(200mL), stirred and cooled to ꢁ70ꢁC under Ar. Then
TiCl4 (3.4mL, 31mmol) was added dropwise via a syringe.
An orange viscous solution was obtained and this was
kept stirring at ꢁ70ꢁC. After 1h, Me2Zn (21mL, 2M in
toluene, 42mmol) was added dropwise, followed by
stirring at ꢁ70ꢁC. After stirring overnight and when the
temperature had reached 10ꢁC, water (90mL) was added
and the phases were separated. The aqueous phase was
extracted with Et2O (3 · 100mL) and the combined
organic extract was washed with NaHCO3 (2 · 100mL,
aq, satd), dried (Na2SO4), filtered and the solvent was
evaporated off. Purification by LC furnished a yellowish
oil (5.4g, 96%), 99% pure and 95:5 dr by GC.
purchased from Aldrich and Fluka, respectively,
25
D
½aŠ ¼ þ26:2 (c 2.3, MeOH) and ꢁ26.3 (c 2.0, MeOH),
respectively. Preparative liquid chromatography (LC)
was performed on straight phase silica gel (Merck 60,
230–400 mesh, 0.040–0.063mm) employing a gradient
technique using an increasing concentration (0–100%)
of distilled ethyl acetate in distilled cyclohexane as elu-
ent. The diastereomeric ratio (dr) of the alcohols 2 and
(2S,3R)-8 were determined by gas chromatography
(GC, capillary column, factor four, 30m, 0.32mm id,
df = 0.25lm, carrier gas N2, 10psi, split ratio 30:1).
The enantiomeric purity of (S)- and (R)-3-hydroxy-2-
methylpropanoic acid methyl ester and (S)- and (R)-2-
methyl-3-(phenylsulfanyl)propanoic acid methyl ester 3
were determined by GC (30m · 0.25mm id capillary col-
umn coated with b-dex 325, df = 0.25lm; carrier gas He
22psi, split ratio 30:1). Program for (S)- and (R)-3-hyd-
roxy-2-methylpropanoic acid methyl ester: 40ꢁC,
10min, 1 ꢁC/min, 150ꢁC). Retention times (min): 36.6
(R-enantiomer) and 40.2 (S-enantiomer) and for (S)-
and (R)-3: 10 0ꢁC, 30min, 1 ꢁC/min, 160ꢁC). Retention
times (min): 72.4 (S-enantiomer) and 72.7 (R-enantio-
5.3.2. (2R,3R)-3-Methyl-4-(phenylsulfanyl)butan-2-ol
(2R,3R)-2. Method 1. Chirazyme L-2 (CAL-B) (1.17g,
˚
65mg/mmol) and molecular sieves (3A) were added to a
solution of racemic (2R*,3R*)-2 (from Section 5.3.1,
95:5 dr, 3.51g, 17.9mmol) in heptane (30mL, 1.7mL/
mmol) and stirred for 2h at room temperature, followed
by addition of vinyl acetate (30mL, 0.33mol). After
reaching 49% conversion the mixture was filtered and
the solid collected was rinsed with n-heptane. The solvent
was evaporated off and the product, the acetate of crude
(2R,3R)-2, was separated from the remaining substrate
alcohol by LC, furnishing a colourless oil (2.0g, 47%),
>99% pure, 94:6 dr, and 98% ee by chiral GC.
mer). 3-Methyl-4-(phenylsulfanyl)butan-2-ol
2
was
transformed into its acetate (CH3COCl, pyridine,
CH2Cl2) and analysed by GC (capillary column, b-dex
120, 30m, 0.25mm id, df = 0.25lm, carrier gas He,
20psi, split 25/1, program: 70 ꢁC/4min, 4ꢁC/min,
125ꢁC/2min, 0.2ꢁC/min, 150ꢁC). Retention times
(min) of the four stereoisomers: 125.5 (2S,3R)-2, 126.3
(2S,3S)-2, 129.1 (2R,3S)-2, 130.1 (2R,3R)-2. Mass spec-
tra were recorded on a Saturn 2000 instrument, (EI-
mode) coupled to a Varian 3800 GC. NMR spectra were
recorded on a Bruker Avance 500 (500MHz 1H and
125.8MHz 13C) spectrometer using CDCl3 as solvent
and TMS as internal reference. Boiling points are uncor-
rected, and are given as air-bath temperatures (bath
The isolated acetate of slightly isomerically impure
(2R,3R)-2 (1.9g, 8.0mmol) was stirred with KOH/
MeOH (100mL, 2.4M) at room temperature overnight.
The reaction was quenched by the addition of water
(50mL) and Et2O (70mL). The aqueous phase was
extracted with Et2O (3 · 50mL) and the combined
Et2O-extract was washed with NaHCO3 (2 · 100mL,
aq, satd), dried (MgSO4), filtered and the solvent was
evaporated off furnishing an alcohol containing mainly
(2R,3R)-2 (1.4g, 87%), >99% (sum of isomers) by GC
contaminated byminor amounts of other isomers of 2.
CAL-A (Novozyme SP 525, 93mg, 1.1g/mmol) and
˚
molecular sieves (3A) were added to a solution of the
temperature/mbar) in a bulb-to-bulb (btb, Buchi-
¨
GKR-51) apparatus.
mixture containing mainly alcohol (2R,3R)-2 (85mg,
0.4mmol) in n-heptane (1.5mL, 3.7mL/mmol) and stir-
red for 2h, followed by the addition of vinyl acetate
(0.2mL, 2.2mmol). After 41% conversion, the mixture
was filtered and the solid collected was washed with n-
heptane. The solvent was evaporated off and the remain-
ing alcohol was separated from the ester product using
LC. The alcohol fractions were concentrated in vacuo
to give an oil [40mg, 42%, 18% overall from racemic
(2R*,3R*)-2], 99% pure by GC, 98:2 dr, and 99% ee by
chiral GC of its acetate.
5.2. General procedures for the lipase-catalysed reactions
Screening of lipases for different selectivity was made
using a diastereomeric mixture of 3-methyl-4-(phenyl-
sulfanyl)butan-2-ol [80:20 dr, (2R*,3R*)/(2R*,3S*)] a
˚
lipase and molecular sieves (3A) in n-heptane. The
reaction was started by the addition of vinyl acetate.
The reactions were performed on a shaking board at
25ꢁC. Samples were taken at intervals and filtered
through a pad of MgSO4 and rinsed with n-heptane be-
fore GC-analysis, which was used to assess the conver-
sion of the alcohol in relation to the amount of ester
produced.
5.3.3.
(2S,3S)-3-Methyl-4-(phenylsulfanyl)butan-2-ol
(2S,3S)-2. Method 1. A solution of the recovered alco-
hol substrate, (2S,3S)-2, obtained by LC from the first

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M. Larsson et al. / Tetrahedron: Asymmetry 15 (2004) 2907–2915
esterification step (Section 5.3.2) was concentrated
in vacuo to give a colourless oil (1.7g, 49%), 98% pure
by GC, 95:5 dr, and 98% ee by chiral GC of its acetate.
10.8Hz), 3.62 (1H, dd, J = 5.4 and 10.8Hz), 7.15–7.18
(1H, m), 7.26–7.29 (2H, m), 7.33–7.36 (2H, m). 13C
NMR: d 16.5, 35.5, 37.4, 66.8, 125.9, 128.9 (2C), 129.0
(2C), 136.8. MS (EI): m/z 182 (71) (M+), 164 (7), 151
(6), 135 (4), 123 (32), 110 (100).
This recovered substrate (1.53g, 7.81mmol) in heptane
(13mL, 1.7mL/mmol), Chirazyme L-2 (CAL-B, 0.25g,
˚
165mg/mmol) and molecular sieves (3A) were stirred
5.4.4. (R)-2-Methyl-3-(phenylsulfanyl)propan-1-ol (R)-
4. Similarly, (R)-3 (from Section 5.4.2, 1.2g,
5.71mmol) gave (R)-4 (1.0g, 98%), 99% pure by GC
for 2h, followed by the addition of vinyl acetate
(13mL, 140mmol). After 13% conversion the mixture
was filtered and the remaining solid was rinsed with n-
heptane. The solvent was evaporated off and the remain-
ing alcohol was separated from the ester produced by
LC. The fractions containing alcohol were concentrated
in vacuo to give an oil [1.2g, 76%, 37% overall yield
from racemic (2R*,3R*)-2], >99% pure by GC, 98:2
dr, and 98% ee by chiral GC of its acetate.
1
(>94% ee by H NMR analysis on its corresponding
MTPA-ester, from (+)-MTPAC1). Bp 160ꢁC/0.7mbar.
25
D
23
D
½aŠ ¼ ꢁ15:0 (c 2.4, CHCl3) {Lit.17 ½aŠ ¼ ꢁ13 (c 2.2,
1
CHCl3)}. H NMR, 13C NMR and MS (EI) spectral
data match those of the enantiomer (Section 5.4.3).
5.4.5.
(2S,3S)-3-Methyl-4-(phenylsulfanyl)butan-2-ol
(2S,3S)-2. A solution of DMSO (6.2mL, 86.9mmol)
in dry CH2Cl2 (50mL) was added to a stirred solution
of oxalyl chloride (6.0mL, 68.3mmol) in dry CH2Cl2
(60mL) at ꢁ78ꢁC under Ar, and the mixture was stirred
at the same temperature for 30min. The alcohol (S)-4
(from Section 5.4.3, 11.3g, 62.1mmol) in dry CH2Cl2
(80mL) was added dropwise to the mixture, and stirring
was continued at the same temperature for 2h. N-Ethyl-
diisopropylamine (54.1mL, 310mmol) was then added
and the reaction mixture allowed to slowly reach
ꢁ10ꢁC (4h). Water (150mL) was added, and the two
layers were separated. The aqueous phase was extracted
with CH2Cl2 (2 · 50mL). The combined organic phase
was washed repeatedly with portions (50mL) of a
KH2PO4-solution (1M, aq, pHꢀ5), until GC examina-
tion revealed that no residual base was present in the
organic phase. After additional washes with water
(100mL), brine (100mL) and drying over Na2SO4, the
organic phase was filtered and stored in CH2Cl2
(500mL) in the freezer. The (S)-2-methyl-3-(phenyl-
sulfanyl)propanal (S)-1 so obtained (>97% ee, deter-
mined through NaBH4-reduction of a sample to the
corresponding alcohol and analysis on its MTPA-ester
by 1H NMR as in Section 5.4.3) was brought to the next
step without further purification.
5.4. Synthesis of (2S,3S)- and (2R,3R)-2 from methyl
(R)- and (S)-3-hydroxy-2-methylpropanoate
5.4.1. (S)-2-Methyl-3-(phenylsulfanyl)propanoic acid
methyl ester (S)-3. Tri-n-butylphosphine (22.5mL,
90.2mmol) was added to a mixture of methyl (R)-3-hyd-
roxy-2-methylpropanoate (8.9g, 75.2mmol) (>99% ee)
and diphenyl disulfide (19.7g, 90.2mmol) in DMF
(125mL) at 0ꢁC (cf. Ref. 7b). After stirring for 4h, at
which point the temperature had reached 20ꢁC, water
(50mL) and Et2O (150mL) were added and the phases
were separated. The aqueous phase was extracted with
Et2O (3 · 75mL) and the combined Et2O-extract was
washed with brine (50mL), dried (MgSO4), filtered
and the solvent was evaporated off. A colourless oil
(15.0g, 95%) was obtained after LC, 98% pure by GC
and with an enantiomeric excess of >97% (GC). Bp
25
D
180ꢁC/1.0mbar. ½aŠ ¼ ꢁ63:6 (c 1.6, CHCl3). 1H
NMR: d 1.27 (3H, d, J = 7.1Hz), 2.70(1H, app. sextet,
J = 7.0Hz), 2.93 (1H, dd, J = 7.0and 13.4Hz), 3.27 (1H,
dd, J = 7.1 and 13.4Hz), 3.66 (3H, s), 7.18–7.22 (1H, m),
7.26–7.31 (2H, m), 7.35–7.38 (2H, m). 13C NMR: d 16.7,
37.4, 39.7, 51.8, 126.5, 129.0(2C), 130.1, (2C), 135.7,
175.4. MS (EI): m/z 210 (100) (M+), 179 (8), 150(23),
123 (95), 109 (32).
TiCl4 (6.1mL, 55.9mmol) was added dropwise via a syr-
inge to the solution of the aldehyde (S)-1 (10.1g,
55.9mmol) in CH2Cl2 (900mL) at ꢁ78ꢁC. An orange
viscous solution was obtained and this was kept at
ꢁ78ꢁC. After stirring for 10min, Me2Zn (27.9mL, 2M
in toluene, 55.9mmol) was added dropwise followed
by stirring at ꢁ78ꢁC. After 35min, water (100mL)
was added and the mixture allowed to reach room
temperature, additional water (100mL) was added
and the two phases were separated. The aqueous phase
was extracted with CH2Cl2 (2 · 100mL) and the
combined organic phases were washed with brine
(100mL), dried (MgSO4), filtered and the solvent
was evaporated off, furnishing a yellowish oil (9.1g,
75%) after LC, 98% pure by GC, 93:07 dr and 97%
ee by chiral GC of its acetate.
5.4.2. (R)-2-Methyl-3-(phenylsulfanyl)propanoic acid
methyl ester (R)-3. Similarly, methyl (S)-3-hydroxy-2-
methylpropanoate (1.0g, 8.47mmol) (>99% ee) gave
(R)-3 (1.5g, 85%), >99% pure by GC and with an enan-
tiomeric excess of >98% (GC). Bp 180ꢁC/0.9mbar.
25
22
½aŠ ¼ þ61:3 (c 1.6, CHCl3) {lit.17 ½aŠ ¼ þ66:6 (c 1,
D
D
1
CHCl3)}. H NMR, 13C NMR and MS (EI) spectral
data match those of (S)-3.
5.4.3. (S)-2-Methyl-3-(phenylsulfanyl)propan-1-ol (S)-
4. The title compound was prepared following the
method described by Tashiro and Mori,18 (S)-3 (from
Section 5.4.1, 14.5g, 69.0mmol) gave 12.1g (96%) of
(S)-4, after LC, >99% pure by GC (>97% ee by 1H
NMR analysis on its corresponding MTPA-ester, de-
rived from (ꢁ)-MTPACl). Bp 170ꢁC/0.95mbar.
25
D
1
½aŠ ¼ þ15:3 (c 2.0, CHCl3). H NMR: d 1.04 (3H, d,
5.4.6.
(2S,3S)-2. Method 2.
(2S,3S)-3-Methyl-4-(phenylsulfanyl)butan-2-ol
sample of the alcohol
J = 6.9Hz), 1.77 (1H, br s, –OH), 1.90–1.99 (1H, m),
2.83 (1H, dd, J = 6.9 and 12.9Hz), 3.06 (1H, dd,
J = 6.4 and 12.9Hz), 3.59 (1H, dd, J = 6.1 and
A
(2S,3S)-2 (from Section 5.4.5, 6.5g, 33.2mmol) was
mixed with n-heptane (60mL, 1.8mL/mmol), CAL-B

M. Larsson et al. / Tetrahedron: Asymmetry 15 (2004) 2907–2915
2913
7.31–7.33 (2H, m). 13C NMR: d 4.7, 4.2, 15.5, 18.2,
20.5, 26.0 (3C), 36.8, 40.6, 71.5, 125.5, 128.5 (2C),
128.9 (2C), 137.6. MS (EI): m/z 309 (2) (M ꢁ H)+, 295
(8), 253 (100), 211 (7), 167 (35), 143 (12), 123 (10).
˚
(1.54g, 46.5mg/mmol), and mol. sieves (3A). Vinyl ace-
tate (60mL, 649mmol) was added and the reaction was
stopped at 9% conversion. LC furnished the unreacted
alcohol (2S,3S)-2 as an oil (5.9g, 90%) >99% pure by
GC, >99.9:0.1 dr and >99.9% ee by chiral GC of its ace-
25
D
tate. Bp 125ꢁC/0.35mbar. ½aŠ ¼ þ55:0 (c 1.8, CHCl3),
5.5.2. (1S,2S)-tert-Butyl-[1,2-dimethyl-3-(phenylsulfon-
yl)propoxy]-dimethylsilane
25
578
25
546
½aŠ ¼ þ57:3 (c 2.0, CHCl3) and ½aŠ ¼ þ65:3 (c 2.0,
(1S,2S)-6. m-Chloroper-
CHCl3). 1H NMR: d 1.03 (3H, d, J = 6.9Hz), 1.19
(3H, d, J = 6.3Hz), 1.66 (1H, s, –OH), 1.75–1.83 (1H,
m), 2.79 (1H, dd, J = 8.1 and 12.8Hz), 3.20(1H, dd,
J = 4.6 and 12.8Hz), 3.76 (1H, app. quint, J = 6.3Hz),
7.14–7.18 (1H, m), 7.25–7.29 (2H, m), 7.34–7.36 (2H,
m). 13C NMR: d 15.4, 20.4, 37.3, 40.2, 71.1, 125.8,
128.9 (4C), 137.0. MS (EI): m/z 196 (92) (M+), 179 (5),
163 (10), 149 (16), 123 (50), 110 (100).
benzoic acid (8.1g, 36.3mmol) was added to a solution
of (1S,2S)-5 from Section 5.5.1 (4.3g, 14.5mmol) in
CH2Cl2 (100mL) at 0ꢁC. After stirring overnight, NaH-
CO3 (75mL, aq, satd) and Et2O (150mL) were added
and the phases were separated. The aqueous phase was
extracted with Et2O (2 · 50mL) and the combined
Et2O-extract was washed with brine (50mL), dried
(MgSO4), filtered and the solvent was evaporated off.
A colourless oil (4.4g, 88%) was obtained after LC,
25
578
5.4.7.
(2R,3R)-3-Methyl-4-(phenylsulfanyl)butan-2-ol
98% pure by GC. Bp 230ꢁC/0.35mbar. ½aŠ ¼ þ16:0
25
(c 2.6, CHCl3) and ½aŠ ¼ þ18:1 (c 2.6, CHCl3) {lit.1b
(2R,3R)-2. In a similar way (see Section 5.4.5), (R)-4
(0.3g, 1.50mmol) gave the intermediate aldehyde (R)-
2-methyl-3-(phenylsulfanyl)propanal (R)-1, which was
immediately transformed into (2R,3R)-2 (0.2g, 70%),
99% pure by GC, 95:05 dr, and 94% ee by chiral GC
of its acetate.
546
22
D
½aŠ ¼ þ15:0 (c 0.225, CHCl3)}. 1H NMR: d ꢁ0.02
(3H, s), 0.00 (3H, s), 0.82 (9 H, s), 1.01 (3H, d,
J = 6.2Hz), 1.09 (3H, d, J = 6.8Hz), 1.96–2.03 (1H,
m), 2.82 (1H, dd, J = 9.2 and 14.4Hz), 3.33 (1H, dd,
J = 2.6 and 14.4Hz), 3.64 (1H, dq, J = 4.4 and 6.2Hz),
7.54–7.58 (2H, m), 7.62–7.66 (1H, m), 7.90–7.93 (2H,
m). 13C NMR: d ꢁ4.8, ꢁ4.1, 17.1, 18.1, 20.9, 25.9
(3C), 36.2, 58.5, 71.6, 128.0(2C), 129.4 (2C), 133.6,
140.2. MS (EI): m/z 343 (4) (M + H)+, 327 (9), 285
(100), 199 (13), 159 (11), 135 (28).
5.4.8.
(2R,3R)-2. Method 2.
(2R,3R)-2 from Section 5.4.7. (123mg, 0.63mmol) was
mixed with n-heptane (1.5mL, 2.4mL/mmol), CAL-B
˚
(33mg, 52mg/mmol), and mol. sieves (3A). Vinyl ace-
(2R,3R)-3-Methyl-4-(phenylsulfanyl)butan-2-ol
sample of the alcohol
A
tate (1.5mL, 16mmol) was added and the reaction was
stopped at 88% conversion. Workup and LC furnished
the acetate of (2R,3R)-2 (127mg, 85%), >99% pure by
GC (>99.5:0.5 dr and >99.9% ee by chiral GC). The ace-
tate of (2R,3R)-2 was hydrolysed (see Section 5.3.2) to
5.5.3. (1S,2S)-(3-Benzenesulfonyl-1,2-dimethyl-tetrade-
cyloxy)-tert-butyl-dimethylsilane (1S,2S)-7. To a mix-
ture of (1S,2S)-6 from Section 5.5.2. (0.6g, 1.75mmol)
and DMPU (2.1mL, 17.5mmol) in dry degassed THF
(15mL) a solution of n-BuLi (3.1mL, 3.68mmol,
1.2M) was added at ꢁ40ꢁC. After 1h the reaction was
allowed to reach 0ꢁC (10min), followed by cooling to
ꢁ40ꢁC. 1-Iodoundecane (0.5mL, 2.10mmol) in dry
degassed THF (1mL) was added dropwise and the
reaction was allowed to reach room temperature
overnight. The reaction was quenched with NH4Cl
(5mL, aq, satd) and EtOAc (20mL) and the phases were
separated. The aqueous phase was extracted with
EtOAc (4 · 25mL) and the combined organic extract
was washed with brine (25mL), dried (MgSO4), filtered
and the solvent was evaporated off. A colourless oil
(0.83g, 96%) was obtained after LC, 98% pure by GC
with a diastereomeric ratio of 89:11. Bp 300ꢁC/0.5mbar.
give the alcohol (2R,3R)-2 in 87% yield (74% overall
25
578
yield). Bp 150ꢁC/0.55mbar. ½aŠ ¼ ꢁ54:7 (c 3.0,
25
CHCl3) and ½aŠ ¼ ꢁ62:4 (c 3.0, CHCl3) {lit.6
546
20
1
½aŠ ¼ ꢁ49:5 (c 0.41, CHCl3)}. H NMR, 13C NMR
D
and MS (EI) spectral data match those of (2S,3S)-2.
5.5. Synthesis of a probable pheromone precursor,
(2S,3R)-8, from (2S,3S)-2
5.5.1. (1S,2S)-tert-Butyl-[1,2-dimethyl-3-(phenylsulfan-
yl)propoxy]-dimethylsilane (1S,2S)-5. tert-Butylchloro-
dimethylsilane (2.4g, 16.0mmol) was added to a
mixture of (2S,3S)-2 from Section 5.4.6 (2.9g,
14.5mmol) and imidazole (1.1g, 16.0mmol) in DMF
(25mL) at room temperature. After stirring overnight,
water (30mL) and Et2O (75mL) were added and the
phases were separated. The aqueous phase was extracted
with Et2O (1 · 50mL) and the combined Et2O extract
was washed with HCl (25mL, 1M, aq), brine (25mL),
dried (MgSO4), filtered and the solvent was evaporated
25
25
½aŠ ¼ þ7:8 (c 1.6, CHCl3) and ½aŠ ¼ þ8:8 (c
578
546
1
1.6, CHCl3). H NMR: d 0.00 (2.67H, s), 0.02 (2.67H,
s), 0.14 (0.33H, s), 0.20 (0.33H, s), 0.84 (8.01H, s),
0.88 (0.99H, s), 0.87–0.90 (3H, m), 0.97 (3H, d,
J = 7.0Hz), 1.04 (3H, d, J = 6.1Hz), 1.17–1.42 (18H,
m), 1.61–1.68 (1H, m), 1.81–1.91 (1H, m), 2.04–2.10
(1H, m), 3.47–3.50(0.89H, m), 3.57 (1H, dq, J = 6.1
and 7.0Hz), 4.40–4.46 (0.11H, m), 7.52–7.55 (2H, m),
7.60–7.63 (1H, m), 7.86–7.90 (2H, m). 13C NMR (aster-
isk denotes minor diastereomer peaks): d ꢁ4.66, ꢁ4.15*,
ꢁ3.61, ꢁ3.31*, 11.7*, 11.8, 14.3, 18.1, 18.2*, 21.9, 22.5*,
22.8, 24.3, 26.0(3C), 26.1*, 26.8*, 28.2*, 28.9*, 29.1,
29.2*, 29.4, 29.5, 29.6, 29.7 (2C), 29.7*, 30.2, 32.0,
39.7, 44.2*, 63.1*, 64.2, 70.4*, 71.2, 128.7 (2C), 129.0*,
129.1 (2C), 133.3*, 133.4, 139.7, 140.6*. MS (EI): m/z
497 (2) (M + H)+, 481 (11), 439 (100), 365 (79), 341
off.
A colourless oil (4.5g, 99%) was obtained
after LC, 99% pure by GC. Bp 145ꢁC/0.3mbar.
25
25
½aŠ ¼ þ41:1 (c 2.0, CHCl3) and ½aŠ ¼ þ46:8 (c
578
546
21
D
1
2.0, CHCl3) {lit.1b ½aŠ ¼ þ39 (c 0.305, CHCl3)}. H
NMR: d 0.03 (3H, s), 0.05(3H, s), 0.88 (9H, s), 1.00
(3H, d, J = 6.8Hz), 1.11 (3H, d, J = 6.2Hz), 1.71–1.79
(1H, m), 2.62 (1H, dd, J = 9.1 and 12.8Hz), 3.20(1H,
dd, J = 4.4 and 12.8Hz), 3.75 (1H, app. quint,
J = 6.0Hz), 7.12–7.18 (1H, m), 7.23–7.27 (2H, m),

2914
M. Larsson et al. / Tetrahedron: Asymmetry 15 (2004) 2907–2915
(11), 297 (10), 217 (4), 199 (14), 159 (15), 135 (12), 103
(18).
125 (25), 111 (41), 97 (58), 83 (44), 69 (50), 57 (62), 45
(100).
5.5.4. (2S,3R)-3-Methylpentadecan-2-ol (2S,3R)-8.
A
Acknowledgements
solution of (1S,2S)-7 from Section 5.5.3 (0.3g,
0.60mmol) in dry MeOH (5mL) was added dropwise
to a prestirred mixture of 10% Na(Hg) (1.12g, 4.8mmol)
and dry Na2HPO4 (0.69g, 4.8mmol) at room tempera-
ture. After 1h, the mixture was diluted and filtered
through a pad of Celite/silica gel with Et2O (8 · 5mL).
The filtrate was washed with water (30mL), brine
(30mL), dried (MgSO4) and concentrated in vacuo. This
gave crude (1S,2R)-tert-butyl-(1,2-dimethyl-tetradecyl-
oxy)-dimethylsilane (0.2g, 94%) as a colourless oil; pur-
ity of >90% (GC), which was contaminated with an
elimination product (ꢂ15%). This crude product was
employed in the next step without any further purifica-
tion. TBAF (5.1mL, 5.06mmol, 1M in THF) was added
to the protected alcohol (0.16g, 0.44mmol) in THF
(5mL) at room temperature and the mixture was re-
fluxed overnight. The reaction was quenched by the
addition of water (10mL) and Et2O (20mL). The aque-
ous phase was extracted with Et2O (3 · 25mL) and the
combined Et2O-extract was washed with water
(25mL), brine (25mL), dried (MgSO4) and concentrated
in vacuo. A colourless oil (0.1g, 96%) was obtained after
LC. Acetyl chloride (1.5mL, 21mmol) and pyridine
(3mL) were added to a solution of this oil (68mg,
0.28mmol) in CH2Cl2 (5mL) and the solution was stir-
red overnight. The reaction was quenched by HCl
(25mL, 2M, aq) and Et2O (20mL). The aqueous phase
was extracted with Et2O (2 · 25mL) and the combined
Et2O-extract was washed with NaHCO3 (25mL), dried
(MgSO4) and concentrated in vacuo. A colourless oil
(0.07g, 88%) of (1S,2R)-1,2-dimethyltetradecyl acetate
was obtained as an oil after LC, 99% pure by GC (if
the ꢂ15% unsaturated product is included). This acetate
(0.35mg, 0.12mmol) in EtOH (1.5mL) was subjected to
a suspension of Raney nickel (W-2) in EtOH (3mL) and
stirred under H2 at room temperature overnight. The
catalyst was filtered off through a pad of Celite/silica
gel and the solids were rinsed with Et2O (7 · 10mL).
The filtrate was concentrated to give the saturated
(1S,2R)-1,2-dimethyltetradecyl acetate (0.03g, 86%).
This was subjected to alkaline hydrolysis with KOH/
MeOH (3mL, 2.4M) and stirred for 2h at room temper-
ature. Water (10mL) and Et2O (20mL) were added and
the phases were separated. The aqueous phase was
extracted with Et2O (4 · 15mL) and the combined
Et2O-extract was washed with brine (20mL), dried
(MgSO4), filtered and the solvent was evaporated off.
After LC the title compound was obtained as a colour-
less oil (0.02g, 95%) 99% pure by GC and <0.1% of the
corresponding (2S,3S)-isomer. Bp 160ꢁC/0.45mbar.
The authors thank Mid Sweden University, EU (Objec-
tive 1 the Region of South Forest Counties), and VIN-
NOVA for financial support. We also thank Novo
Nordisk for generous gifts of various lipases.
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25
25
½aŠ ¼ þ18:3 (c 2.2, n-hexane) and ½aŠ ¼ þ20:8 (c
578
546
20
D
1
2.2, n-hexane) {lit.19 ½aŠ ¼ þ16:0 (c 5, hexane)}. H
NMR: d 0.89 (3H, d, J = 6.8Hz), 0.88–0.92 (3H, m),
1.14 (3H, d, J = 6.3Hz), 1.28–1.54 (23H, m), 1.48 (1H,
s, –OH), 3.68 (1H, app. quint, J = 6.3Hz). 13C NMR:
d 14.1, 14.5, 19.3, 22.7, 27.3, 29.4, 29.7 (5C), 30.0,
32.0, 32.6, 40.1, 71.8. MS (EI): m/z 241 (4) (M ꢁ H)+,
227 (8), 194 (13), 181 (5), 166 (8), 152 (7), 139 (14),

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