Stereocontrol in organic synthesis using silicon-containing compounds. A synthesis of the (±)-Prelog-Djerassi lactone

Article abstract of DOI:10.1039/a804270e

Each of the relative stereochemical relationships present in the Prelog-Djerassi lactone 34 was set up by a stereocontrolled reaction based on the presence of a silyl group. These were the enolate protonation 3→4 of a β-silyl ester, the enolate alkylation 11→12 of a β-silyl ester, silyl-to-hydroxy conversion with retention of configuration 13→14, and stereospecifically anti protodesilylation of the allylsilanes 26 and 27 giving largely the alkene 28. These allylsilanes had themselves been prepared in a stereocontrolled, convergent synthesis from the allylic acetates 24 and 25, providing thereby a general solution to the controlled synthesis of a new stereogenic centre relative to a resident centre without regard to their distance apart, except insofar as it influences a necessary separation of diastereoisomers (18 and 19 in this case). Using the opposite double bond geometries, the allylic acetates 29 and 30 gave the complementary pair of allylsilanes 31 and 32, which underwent stereospecifically anti protodesilylation to give largely the alkene 33 diastereoisomeric to 28 at C-6. The alkenes 28 and 33 were converted into the Prelog-Djerassi lactonic acid 34 and its C-6 epimer 35, respectively.

Full text of DOI:10.1039/a804270e

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Stereocontrol in organic synthesis using silicon-containing
compounds. A synthesis of the ( )-Prelog–Djerassi lactone
Hak-Fun Chow and Ian Fleming*
Department of Chemistry, Lensfield Road, Cambridge, UK CB2 1EW
Each of the relative stereochemical relationships present in the Prelog–Djerassi lactone 34 was set up by a
stereocontrolled reaction based on the presence of a silyl group. These were the enolate protonation 3→4
of a â-silyl ester, the enolate alkylation 11→12 of a â-silyl ester, silyl-to-hydroxy conversion with retention
of configuration 13→14, and stereospecifically anti protodesilylation of the allylsilanes 26 and 27 giving
largely the alkene 28. These allylsilanes had themselves been prepared in a stereocontrolled, convergent
synthesis from the allylic acetates 24 and 25, providing thereby a general solution to the controlled
synthesis of a new stereogenic centre relative to a resident centre without regard to their distance apart,
except insofar as it influences a necessary separation of diastereoisomers (18 and 19 in this case). Using
the opposite double bond geometries, the allylic acetates 29 and 30 gave the complementary pair of
allylsilanes 31 and 32, which underwent stereospecifically anti protodesilylation to give largely the alkene
33 diastereoisomeric to 28 at C-6. The alkenes 28 and 33 were converted into the Prelog–Djerassi lactonic
acid 34 and its C-6 epimer 35, respectively.
CO2R
Introduction
The Prelog–Djerassi lactone 34 has been a favourite synthetic
target on which to test and demonstrate new methods of stereo-
1 a R = Et
i, ii, iii, iv
i, iv
b
R = Me
control. The subject has been comprehensively reviewed from
the first synthesis in 1963 up to 1990,1 and new syntheses con-
tinue to appear.2 We now report our own synthesis, already
published in preliminary form,3 in which we used the stereo-
chemistry of electrophilic attack on a double bond adjacent to
a silicon-bearing stereogenic centre to control all the relative
stereochemistry in this molecule. In this synthesis, we used three
of the methods listed in the first paper of this series:4 succes-
sively the protonation and alkylation of enolates carrying an
adjacent silyl group,5 silyl-to-hydroxy conversion,6 and the anti
SE2Ј reaction of allylsilanes.7 The synthesis is notable for the
last of these reactions, which we used to control the relative
stereochemistry of two centres having a 1,3 relationship with-
out using rings or cyclic transition structures in any way.
Furthermore, each of the stereochemistry-determining reac-
tions that we used could have been redesigned to give the oppos-
ite stereochemistry, making our route capable, in principle, of
being used for the synthesis of any of the diastereoisomers. To
illustrate this point we used the last to set up the opposite
relative stereochemistry.
OSiMe3
OSiMe3
OMe
OEt
2
6
67%
v, vi
73%
v, vi
OMe
OMe
CO2Et
CO2Me
MeO
MeO
3
7
57%
57%
vii, ii
vii, viii
OMe SiMe2Ph
CO2Et
OMe SiMe2Ph
CO2Me
MeO
MeO
4
8
82%
70%
Results and discussion
ix, x, xi
ix, x, xi
We began (Scheme 1) by using discoveries that we had made in
our work on silyl enol ethers. In particular, we had established,
following a lead from Mukaiyama,8 that silyl dienol ethers
react with electrophiles as d4-synthons predominantly at the
γ-position,9 in contrast to lithium dienolates, which react as d2-
synthons predominantly at the α-position. We also established
some of the features that encouraged γ-attack, including the
observation that relatively well-stabilised cationic electrophiles
were most likely to behave well in this sense.10 The reaction that
we actually used was the combination of the silyl dienol ether 2
and the cation derived from trimethyl orthoformate in the pres-
ence of a catalytic amount of zinc bromide. In practice, we
obtained the product 3 of γ-attack in 57% yield together with
the product of α-attack in 14% yield. This was not as high a
degree of γ-selectivity (80:20) as we had expected from our
experience with highly stabilised electrophiles.10 Nevertheless,
O
O
2
2
O
O
SiMe2Ph
9
47%
3
SiMe2Ph
47%
3
5
Scheme 1 Reagents: i, LDA, HMPA; ii, MeI; iii, LDA, THF; iv, Me3-
SiCl; v, (MeO)3CH, ZnBr2 cat.; vi, separate from α product by distil-
lation; vii, (PhMe2Si)2CuLi, THF; viii, NH4Cl, H2O; ix, TsOH, Me2CO;
x, NaBH4, MeOH; xi, HCl
the products were easy to separate by fractional distillation, and
the starting materials cheap, so we did not try the methods that
we had developed for improving the degree of γ-selectivity, such
as using a diisopropylmethyl ester9 in place of the ethyl ester or
J. Chem. Soc., Perkin Trans. 1, 1998
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a triarylsilyl dienol ether10 in place of the trimethylsilyl dienol
ether. The silyl dienol ether 2 was derived from ethyl crotonate
1a by methylation of the lithium dienolate at the α-position,11
followed by the preparation of the silyl dienol ether, so that
we actually used successively the capacities of lithium and
silyl dienolates to be d2- and d4-synthons, respectively. We also
carried out a γ-selective reaction with the silyl dienol ether 6
without the C-2 methyl group. The selectivity for γ-attack
was slightly less (70:30), but again we easily separated the
α,β-unsaturated ester 7 by fractional distillation from the
product of α-attack in 57% yield.
OMe SiMe2Ph
CO2Et
OMe SiMe2Ph
i, ii
MeO
MeO
OSiMe2But
4
10
94%
iii, iv, v
SiMe2Ph
MeO2C
OSiMe2But
vi, vii
11
68%
SiMe2Ph
Conjugate addition of the silylcuprate reagent to the α,β-
unsaturated ester 3 and protonation of the resultant enolate
gave selectively (92:8) the product 4 with the silyl and methyl
groups syn, as we expected from our exploratory work on this
type of reaction.5 We have used this same reaction sequence in
another context, and obtained closely similar results, which we
have already reported in full.12 To make absolutely sure of the
relative stereochemistry, we also prepared the methyl ester 8
with the opposite relative stereochemistry, by methylation of
the enolate derived from the ester 7, which was selective (83:17)
in favour of the isomer with the silyl and methyl groups anti.
With each of the esters 4 and 8, we hydrolysed the acetal,
reduced the aldehyde group with sodium borohydride, and
made the diastereoisomeric δ-lactones 5 and 9, respectively, by
treatment with hydrochloric acid. The double quartets from the
MeO2C
4
2
3
OSiMe2But
i, viii
SiMe2Ph
12
97%
TsO
OSiMe2But
ix, x
13 81%
OH
OH
TsO
xi
14 54%
O
O
1
TsO
protons on C-2 in the H NMR spectra were identifiable for
xii
both lactones, and showed a diagnostic coupling constant to
the proton on C-3 of 11 Hz in the case of the isomer 5 and 7 Hz
in the case of the isomer 9.
O
O
15 91%
NC
It was now necessary to mask the carboxylic ester function,
in order to distinguish it from the ester we needed to set up on
the other side of the silyl group. We chose to do this safely, but
somewhat inelegantly, by reducing it to the alcohol and protect-
ing it as the tert-butyldimethylsilyl ether 10 (Scheme 2), at
which stage we were able to separate it from the small amount
of its diastereoisomer. Hydrolysis of the acetal, oxidation of
the aldehyde and esterification gave the methyl ester 11. We
methylated the ester using the lithium enolate and obtained
only one diastereoisomer 12, in happy contrast to our expect-
ation (85:15)5 based on having an isopropyl group as the
carbon substituent on the stereogenic centre. We now had two
of the stereochemical relationships safely in hand, and the scene
was set for the more critical operation of controlling the stereo-
chemistry at C-6 relative to the existing centres at C-2, C-3 and
C-4.
First we had to introduce the necessary carbon atoms and
appropriate functionality (Scheme 2). We reduced the ester, and
made the toluene-p-sulfonate 13 of the alcohol. At this stage we
chose to carry out the silyl-to-hydroxy conversion 13→14 using
our earlier protocol based on protodesilylation of the phenyl
group and oxidation with peracid. Although the protodesilyl-
ation appeared to work well (97% crude), the second step did
not (54% overall). Both steps have since been improved,6,13 and
no doubt better overall yields could be obtained today. The
advantage of carrying out the silyl-to-hydroxy conversion at
this stage was that it allowed us to tie down both hydroxy
groups as the acetal 15. We then displaced the sulfonate group
with cyanide ion to give the crystalline nitrile 16, and treated
this with the methyl Grignard reagent to obtain the ketone 17.
The ketone carbon, C-6 in 17, is too remote from the influ-
ence of the resident stereogenic centre on C-4, let alone from
those on C-3 and C-2, to expect a high level of open-chain
stereocontrol in any reactions on the ketone group. We even
returned to this subject with an elaborate study of what factors
might allow direct 1,3 control in open-chain systems.14 In the
present context, it is a rather artificial problem, since methods
for controlling C-6 in the Prelog–Djerassi lactone late in the
synthesis are easy in this specific case. However, we wanted to
use our methods of open-chain stereocontrol as a demon-
xiii
O
O
16 99%
O
4
2
3
6
17 94%
Scheme 2 Reagents: i, LiAlH4; ii, ButMe2SiCl; iii, TsOH, Me2CO; iv,
AgNO3, KOH; v, CH2N2; vi, LDA, THF; vii, MeI; viii, TsCl, Py; ix,
BF3ؒ2AcOH; x, MCPBA, KF, DMF; xi, TsOH, Me2C(OMe)2; xii,
NaCN, HMPA; xiii, MeMgI
stration that a carefully placed silyl group could be used in
general to solve the problem of setting up a new stereogenic centre
when it is remote from the influence of resident centres. Our solu-
tion is not even limited to 1,3 relationships, although it is most
likely to work best there, given that it involves a separation of
diastereoisomers that is most likely to be easy when they have
their stereocentres not too far apart.
In the event, the lack of 1,3 control was immediately appar-
ent when we found that the ketone 17 reacted with phenyl-
ethynyllithium with no selectivity—the two diastereoisomers 18
and 19 were obtained in essentially equal amounts (Scheme 3).
This did not matter in the slightest to us; all that was needed
was a means to separate them, which fortunately proved to be
easy by column chromatography or by preparative HPLC. We
did not know which isomer was which, but simply chose
arbitrarily the slow running isomer, which later proved to be
the isomer 18. We acetylated the alcohol and reduced the
triple bond to the cis double bond, to give the allylic acetate
20. The stereospecifically anti SN2Ј displacement of the acetate
group using the phenyldimethylsilylcuprate reagent gave a
pair of allylsilanes 21 and 22 in equal amounts, as expected
from our earlier work.15 The fact that we had a mixture was of
no consequence, since both isomers, differing in two stereo-
chemical features, were matched to give the same product
in a stereospecifically anti SE2Ј reaction. However, when we
tried protodesilylation with our favourite acid, the boron
trifluoride–acetic acid complex, a different reaction took place
with surprising ease. The product was the pyran 23, in which a
2652
J. Chem. Soc., Perkin Trans. 1, 1998

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Ph
O
O
Ph
O
O
O
O
O
HO
OH
17
18
24
26
19
i
i, ii, iii
i, iv, ii
Ph
O
O
Ph
O
O
Ph
OAc OAc
OAc OAc
6
6
HO
OH
OAc
AcO
Ph
18
19 46%
45%
ii, iii
82%
v
25
79%
v
O
O
Ph
SiMe2Ph
OAc OAc
OAc OAc
AcO
Ph
7
6
Ph
PhMe2Si
6
+
7
20 64%
iv
27
86% (50:50) from 24
Ph
SiMe2Ph
O
O
O
O
54% (60:40 or 40:60) from 25
Ph
PhMe2Si
+
vi
OAc OAc
21
22
88%
6
Ph
v
Ph
28 86% (83:17 at C-6)
O
OH
Scheme 4 Reagents: i, TsOH, PyHOTs, HO(CH2)2OH; ii, Ac2O, Et3N,
DMAP; iii, H2, Lindlar’s catalyst; iv, LiAlH4; v, (PhMe2Si)2CuLi; vi,
BF3ؒ2AcOH
23 70%
bond reacted more slowly than that with a cis double bond 24,
something which we had not noticed before. To make the reac-
tion with the trans isomer work at all well, we had to dilute the
THF with diethyl ether, and even so the yield was less impressive
than we have been used to for reactions with tertiary allylic
acetates. Fortunately, the regiochemistry was entirely reliable,
with the silyl group attaching itself to the secondary not the
tertiary end of the allylic system.15,17 Once again there was no
need to separate the two allylsilanes, protodesilylation of the
mixture can be expected to take place in a stereospecifically anti
SE2Ј reaction giving mainly the alkene 28. The degree of stereo-
specificity, while high, was somewhat compromised, with the
selectivity at C-6 only 83:17 in favour of the isomer 28. We
believe that the incomplete stereospecificity is caused by proton-
ation taking place some of the time on C-7, to give a C-6 cation.
When this occurs, the stereochemical information embedded in
the double bond geometry is lost, and a subsequent hydride
shift from C-7 can take place to either surface of the cation at
C-6, giving each of the alkenes 28 and 33. We have shown,
without the stereochemical detail, that this pathway is followed
in a more simple system.18 This failure completely to control the
stereochemistry at C-6 stimulated us subsequently to find a
solution, which we tested only in a model series.19 We have not,
unfortunately, had occasion to return to the specific case in this
paper. The solution is to introduce the methyl group in this step
instead of the proton. The acetylenic nucleophile would be used
to attack an aldehyde instead of a methyl ketone like 17, and
the allylsilanes corresponding to the pair 26 and 27, but lacking
the C-6 methyl group, would then be prepared using the same
convergent sequence. Subsequent reaction to achieve overall
a stereospecifically anti SE2Ј replacement of the silyl group
by a methyl group would avoid any pathways involving the
᎐
Scheme 3 Reagents: i, PhC᎐CLi; ii, Ac2O, Et3N; iii, H2, Lindlar’s
catalyst; iv, (PhMe2Si)2CuLi; v, BF3ؒ2AcOH
᎐
bond had been formed between two fully-substituted carbons,
as a consequence of the acetal group acting as an intra-
molecular electrophile. We assigned the stereochemistry at the
new centre on the basis that such reactions can be relied upon
to be anti. There have since been several reactions reported in
which allylsilanes react intramolecularly with acetals, and we
had seen one ourselves earlier,16 but we had not expected the
acetal to react in competition with the abundant protons. The
compounds involved in this dead end, from the acetate of the
propargyl alcohols 18 and 19 to the product 23, since they led
nowhere, were not fully characterised, but the 1H NMR spectra
were compelling. We now had to backtrack, in order to render
the hydroxy group protection inoffensive.
We hydrolysed the acetal group in each of the alcohols 18 and
19, and reduced the triple bonds in different ways. With the
slow-running isomer, derived from 18, we fully acetylated the
three hydroxy groups and again converted the triple to a cis
double bond to give the triacetate 24. With the fast-running
isomer, we reduced the propargyl alcohol with lithium alu-
minium hydride to give the trans allylic alcohol, and then
acetylated all three hydroxy groups to give the triacetate 25
(Scheme 4). These isomers now differ in two respects, double
bond geometry and the relative stereochemistry at C-6, and
therefore the stereospecifically anti SN2Ј displacement of the
allylic acetate groups using the phenyldimethylsilylcuprate
reagent gave the same pair of allylsilanes 26 and 27, which also
differ in two respects, and remain correlated. In detail, we found
that the reaction with the allyl acetate 25 having a trans double
J. Chem. Soc., Perkin Trans. 1, 1998
2653

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1
competitive formation of a tertiary cation, but posed the prob-
lem of what the methyl electrophile should be. What we tried,
with some success, was methylenation of allylsilanes,20 and sub-
sequent protodesilylation of the cyclopropylmethylsilanes.19
Two problems we encountered in this approach were the lack of
regioselectivity in the site of proton attack21 and the susceptibil-
ity of the product alkene to further protonation under the
acidic conditions necessary to open the cyclopropane ring.
More recently, Landais has had some success in solving both
problems using mercury() ions or electrophilic iodine in the
opening of the cyclopropylmethylsilanes.22 Between our work
and that of Landais, it is clear that the C-6 problem could be
solved.
recognisable as having the distinctive H NMR signals of the
minor product in the earlier series. The stereoselectivity was,
disappointingly, a little less (80:20).
The remaining steps were straightforward (Scheme 6). Ozon-
O
i, ii, iii,
iv, v, vi
OAc OAc
6
O
H
Ph
6
4
2
3
3
4
2
CO2H
28
34
28%
O
i, ii, iii,
iv, v, vi
OAc OAc
We have repeatedly made the claim that our methods are
stereochemically versatile, and can be adapted to the synthesis
of any diastereoisomer. In this case we proved our point to
some extent by actually carrying out the alternative sequence
(Scheme 5), starting with the same propargylic alcohols 18 and
6
O
H
Ph
6
4
2
3
3
4
2
CO2H
33
35
36%
Scheme 6 Reagents: i, O3; ii, Me2S, PyHOTs; iii, Jones; iv, K2CO3,
MeOH; v, TsOH; vi, PDC, DMF
Ph
O
O
Ph
O
O
olysis of the double bond of the alkene 28, oxidation of the
aldehyde group, hydrolysis of the acetate groups, lactonis-
ation, and oxidation of the free hydroxy group gave the Prelog–
Djerassi lactonic acid itself 34. Each of the intermediates
showed the presence of the minor diastereoisomer at C-6 in the
same proportion throughout, indicating that there had been
no epimerisation at C-6, although this was only true for the
ozonolysis step when the reductive work-up included pyridin-
ium toluenesulfonate as a buffer. The lactonic acid itself, how-
ever, could be separated from its diastereoisomer by recrystal-
lisation, and now proved to have properties matching (mp, IR,
1H and 13C NMR and MS) those reported in the literature.24–27
With several of the diastereoisomers known, there can be little
doubt about the structural assignment, and we at last knew
which isomer 18 or 19 we had been using for which sequence.
Repeating the sequence of six reactions on the mixture rich in
the C-6 isomer 33 again gave mixtures that remained in the
same proportion, but this time in favour throughout of the
minor isomer in the earlier series, and giving the known C-6
isomer 35 of the Prelog–Djerassi lactonic acid, having proper-
ties matching (IR, 1H and 13C NMR and MS) those reported in
the literature. This sequence confirmed that no epimerisation
had taken place at C-6, as we had deduced earlier, but without
rigorous proof.
HO
OH
18
29
31
19
i, ii, iii
i, iii, iv
Ph
OAc OAc
OAc OAc
AcO
OAc
Ph
Ph
53%
v
30
78%
v
SiMe2Ph
OAc OAc
OAc OAc
Ph
PhMe2Si
+
32
52% (71:29 or 29:71) from 29
82% (62:38 or 38:62) from 30
vi
OAc OAc
6
Experimental
Ph
The details of the preparation of the ester 4, and of the alcohol
derived from it by lithium aluminium hydride reduction, have
already been reported.12 The numbering used in the experi-
mental section is that following IUPAC rules and does not
correspond with the numbering used in the text, which is that
used for the Prelog–Djerassi lactonic acid. Except where other-
wise stated, ether refers to diethyl ether, light petroleum refers
to the fraction bp 40–60 ЊC, and 1H NMR spectra were
recorded at 90 MHz, except where otherwise stated. Chemical
shifts in 1H NMR spectra reported as using CH2Cl2 as an
internal standard assume a chemical shift of δ 5.33 relative to
Me4Si.
33 85% (80:20 at C-6)
Scheme 5 Reagents: i, TsOH, PyHOTs, HO(CH2)2OH; ii, LiAlH4; iii,
Ac2O, Et3N, DMAP; iv, H2, Lindlar’s catalyst; v, (PhMe2Si)2CuLi; vi,
BF3ؒ2AcOH
19. All that was required was that we reduce the triple bond to a
trans double bond where formerly we had made a cis, and to
a cis where formerly we had made a trans. In this way we made
the correlated pair of allylic acetates 29 and 30, and hence the
correlated pair of allylsilanes 31 and 32. The lower yield in the
sequence 18→29 is probably in the reduction step with lithium
aluminium hydride, where allene formation23 can occur,
although we did not meet this problem in the sequence 19→25.
The 1H NMR spectra, both of the allylic acetates 29 and 30 and
of the allylsilanes 31 and 32, showed distinctive signals that
identified them as different from the pairs of their isomers
obtained earlier (Scheme 4). Protodesilylation of the mixture of
allylsilanes 31 and 32 again gave predominantly the product 33
of a stereospecifically anti SE2Ј reaction, which was immediately
Methyl (E)-5,5-dimethoxypent-2-enoate 7
n-Butyllithium (1.6 mol dmϪ3 in hexane, 68.8 cm3, 110 mmol)
was added dropwise to a stirred solution of diisopropylamine
(11.1 g, 110 mmol) and HMPA (19.7 g, 110 mmol) in dry THF
(250 cm3) under nitrogen at Ϫ76 ЊC. After 30 min, methyl cro-
tonate (10.0 g, 100 mmol) in dry THF (25 cm3) was added over
20 min. The mixture was stirred at Ϫ76 ЊC for another 10 min
and then quenched with chlorotrimethylsilane (16.3 g, 150
2654
J. Chem. Soc., Perkin Trans. 1, 1998

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mmol). The solution was allowed to warm to room temperature
and, after stirring for 1.5 h, the solvent was evaporated under
reduced pressure in the absence of moisture. Dry pentane (250
cm3) was added and the precipitated HMPA–lithium chloride
complex was removed by filtration. Evaporation of the filtrate
under reduced pressure, followed by refiltration and fractional
distillation (15 cm Vigreux) gave the silyl ketene acetals 6 (12.56
g, 73%), bp 40–42 ЊC at 0.5 mmHg. The silyl ketene acetals were
stirred with trimethyl orthoformate (10.0 g, 94.2 mmol) and
powdered anhydrous zinc bromide (400 mg, 1.8 mmol) in dry
dichloromethane (100 cm3) at room temperature for 4 h. The
solvent was evaporated under reduced pressure and the residue
was distilled (15 cm Vigreux) to give methyl 2-(dimethoxy-
methyl)but-3-enoate (3.05 g, 24%), bp 40–45 ЊC at 0.05 mmHg,
and the conjugated ester 7 (7.24 g, 57%), bp 52–54 ЊC at 0.05
(2R*,3S*)-5-Hydroxy-2-methyl-3-dimethyl(phenyl)silyl-
pentanoic acid ä-lactone 9
The ester 8 (228 mg, 0.70 mmol, containing 17% of the
diastereoisomer) and anhydrous toluene-p-sulfonic acid (10
mg) in dry acetone (10 cm3) were kept at room temperature for
4 h. The solution was poured into saturated aqueous sodium
hydrogen carbonate (20 cm3) and extracted with ether (2 × 50
cm3). The combined ethereal extracts were evaporated under
reduced pressure to give the aldehyde; δH(CDCl3) 9.68 (1 H, t,
J 2, HC᎐O), 7.63–7.05 (5 H, m, Ph), 3.50 (3 H, s, CO Me), 2.76–
᎐
2
2.44 (3 H, m, CH2CHO and CHMe), 2.22–1.89 (1 H, m, HCSi),
0.98 (3 H, d, J 7, CHMe), 0.29 (3 H, s, SiMeAMeB) and 0.28
(3 H, s, SiMeAMeB). Powdered sodium borohydride (50 mg,
1.32 mmol) was added to the aldehyde in methanol (10 cm3) at
5 ЊC and the mixture was stirred at 5 ЊC for 30 min. The mixture
was acidified to pH 3 with hydrochloric acid (6 mol dmϪ3) and
poured into saturated aqueous sodium chloride (10 cm3) and
extracted with chloroform (4 × 25 cm3). The combined organic
layers were washed with saturated aqueous sodium hydrogen
carbonate (50 cm3), dried (MgSO4), filtered and evaporated
under reduced pressure. Chromatography (SiO2, 20 g, EtOAc–
light petroleum, 1:9) gave the lactone (82 mg, 47%); Rf(EtOAc–
mmHg; νmax(neat)/cmϪ1 2835 (acetal) and 1724 (C᎐O);
᎐
δ (CDCl ) 6.94 (1 H, dt, J 17 and 7, CH᎐CCO Me), 5.92 (1 H,
᎐
H
3
2
dt, J 17 and 2, C᎐CHCO Me), 4.49 [1 H, t, J 6, HC(OMe) ],
᎐
2
2
3.75 (3 H, s, CO2Me), 3.36 (6 H, s, 2 × OMe) and 2.53 (2 H, ddd,
J 7, 6 and 2, CH C᎐C); m/z 174 (1%, Mϩ), 173 (5, M Ϫ H), 143
᎐
2
(55, M Ϫ OMe) and 75 [100, HC(OMe)2] (Found: Mϩ Ϫ OMe,
143.0707. C8H14O4 requires M Ϫ OMe, 143.0708).
light petroleum, 1:9) 0.10; νmax(neat)/cmϪ1 1726 (C᎐O);
᎐
Methyl 5,5-dimethoxy-3-dimethyl(phenyl)silylpentanoate
δH(CDCl3; 250 MHz) 7.54–7.33 (5 H, m, Ph), 4.43 (1 H, ddd,
J 11.0, 5.6 and 2.9, CHAHBO), 4.26 (1 H, ddd, J 11.0, 11.0 and
4.6, CHAHBO), 2.87 (1 H, dq, J 7.4 and 6.8, CHCO), 2.02–1.60
(3 H, m, SiCHCH2), 1.22 (3 H, d, J 7.4, MeCH), 0.39 (3 H, s,
SiMeAMeB) and 0.36 (3 H, s, SiMeAMeB); m/z 248 (13%, Mϩ),
233 (27, M Ϫ Me) and 135 (100, SiMe2Ph) (Found: Mϩ,
248.1224. C14H20O2Si requires M, 248.1232).
Dimethyl(phenyl)silyllithium (30.0 cm3, 1.0 mol dmϪ3 in THF)
was added into a suspension of copper() cyanide (1.35 g, 15
mmol) in THF (20 cm3) under nitrogen at Ϫ10 ЊC. After 10
min, the solution was cooled to Ϫ23 ЊC and the unsaturated
ester 7 (2.41 g, 13.9 mmol) in dry THF (10.0 cm3) was added.
The mixture was stirred at Ϫ23 ЊC for 2 h and quenched with
saturated aqueous ammonium chloride (5 cm3). The mixture
was extracted with ether (3 × 50 cm3) and the combined ether-
eal extracts were washed with saturated aqueous ammonium
chloride (4 × 20 cm3), dried (MgSO4), filtered, evaporated
under reduced pressure and distilled to give the ester (3.66 g,
85%), bp 116–118 ЊC at 0.01 mmHg; νmax(neat)/cmϪ1 2831
(2R*,3R*)-5-Hydroxy-2-methyl-3-dimethyl(phenyl)silyl-
pentanoic acid ä-lactone 5
The ethyl ester 412 (150 mg, 0.44 mmol; containing 8% of its
diastereoisomer) similarly gave the lactone (48 mg, 47%);
Rf(EtOAc–light petroleum, 1:9) 0.10; νmax(neat)/cmϪ1 1726
(acetal) and 1734 (C᎐O); δ (CDCl ) 7.70–7.31 (5 H, m, Ph),
(C᎐O); δ (CCl ) 7.66–7.28 (5 H, m, Ph), 4.16 (2 H, t, J 6,
᎐
H 4
᎐
H
3
4.36 [1 H, t, J 5, HC(OMe)2], 3.62 (3 H, s, CO2Me), 3.25 (3 H, s,
OMe), 3.21 (3 H, s, OMe), 2.46–2.30 (2 H, m, CH2CO2Me),
1.91–1.36 (3 H, m, CH2CHSi) and 0.32 (6 H, s, SiMe2); m/z 310
(2%, Mϩ), 295 (12, M Ϫ Me), 278 (7, M Ϫ MeOH), 263 (10,
M Ϫ MeOH Ϫ Me), 247 (7, M Ϫ MeOH Ϫ OMe), 135 (57,
SiMe2Ph) and 75 [100, HC(OMe)2] (Found: Mϩ Ϫ Me,
295.1373. C16H26O4Si requires M Ϫ Me, 295.1366).
CH2O), 2.47 (1 H, dq, J 11 and 7, CHCO), 2.02–1.46 (3 H, m,
SiCHCH2), 1.15 (3 H, d, J 7, MeCH) and 0.45 (6 H, s, SiMe2);
m/z 248 (10%, Mϩ), 233 (29, M Ϫ Me) and 135 (100, SiMe2Ph)
(Found: Mϩ, 248.1249. C14H20O2Si requires M, 248.1232).
(3R*,4R*)-5-(tert-Butyldimethylsilyloxy)-4-methyl-3-dimethyl-
(phenyl)silylpentanal dimethyl acetal 10
A mixture of the alcohol12 (19.55 g, 66.0 mmol), tert-
butyldimethylsilyl chloride (10.50 g, 69.7 mmol) and imidazole
(10.00 g, 147 mmol) were stirred in dry DMF (100 cm3) under
nitrogen at 20 ЊC for 8 h. The solution was poured into water
(50 cm3) and extracted with ether–light petroleum (1:1, 4 × 100
cm3). The combined organic extracts were washed with water
(50 cm3), dried (MgSO4), filtered and evaporated under reduced
pressure. Chromatography (SiO2, 200 g, EtOAc–light petrol-
eum, 1:25) gave the silyl ether (27.06 g, 100%); Rf(EtOAc–light
petroleum, 1:25) 0.30; νmax(neat)/cmϪ1 2830 (acetal) and 1090
(C–O); δH(CCl4) 7.71–7.23 (5 H, m, Ph), 4.30 [1 H, t, J 5,
HC(OMe)2], 3.50–3.15 (2 H, m, CH2OSi), 3.20 (3 H, s, OMe),
3.12 (3 H, s, OMe), 1.95 (1 H, br m, CHMe), 1.79–1.53 (2 H, m,
CH2CHSi), 1.35 (1 H, br m, CHSi), 0.96 (3 H, d, J 7, CHMe),
0.94 (9 H, s, But), 0.40 (6 H, s, SiMe2Ph) and 0.02 (6 H, s,
SiMe2But); m/z 378 (1%, M Ϫ MeOH), 363 (50, M Ϫ
MeOH Ϫ Me), 321 (24, M Ϫ MeOH Ϫ But), 263 (22, M Ϫ
MeOH Ϫ SiButMe2), 135 (93, SiMe2Ph) and 75 [100,
HC(OMe)2] (Found: Mϩ Ϫ MeOH, 378.2412. C22H42O3Si2
requires M Ϫ MeOH, 378.2410).
Methyl (2R*,3S*)-5,5-dimethoxy-2-methyl-3-dimethyl(phenyl)-
silylpentanoate 8
Methyl 5,5-dimethoxy-3-dimethyl(phenyl)silylpentanoate (11.0
g, 35.5 mmol) in dry THF (100 cm3) was added dropwise to a
stirred solution of LDA [38.0 mmol, prepared from n-butyl-
lithium (1.6 mol dmϪ3 in hexane, 23.8 cm3) and diisoprop-
ylamine (4.05 g, 40.0 mmol) at Ϫ20 ЊC] in dry THF (200 cm3)
under nitrogen at Ϫ78 ЊC. After 10 min, methyl iodide (7.0 g,
49.3 mmol) was added and the mixture was stirred at room
temperature for 1 h, poured into saturated aqueous ammonium
chloride (50 cm3) and extracted with ether (3 × 50 cm3). The
combined organic extracts were washed with saturated aqueous
ammonium chloride (50 cm3), dried (MgSO4), filtered and
evaporated under reduced pressure to give the ester (11.25 g,
98%) as a mixture of inseparable diastereoisomers in a ratio of
84:16; νmax(neat)/cmϪ1 2831 (acetal) and 1729 (C᎐O); δ (CCl )
᎐
H
4
7.76–7.32 (5 H, m, Ph), 4.29 [1 H, t, J 5, HC(OMe)2], 3.68 (3 H,
s, CO2Me), 3.66 (s, CO2Me of minor diastereoisomer), 3.22
(3 H, s, OMe), 3.16 (3 H, s, OMe), 2.68 (1 H, dq, J 7 and 2.5,
CHCO), 1.82–1.50 (3 H, m, SiCHCH2), 1.21 (3 H, d, J 7,
MeCH of the minor diastereoisomer), 1.10 (3 H, d, J 7, MeCH)
and 0.40 (6 H, s, SiMe2); m/z 309 (2%, M Ϫ Me), 249 [5,
M Ϫ HC(OMe)2], 135 (57, SiMe2Ph) and 75 [100, HC(OMe)2]
(Found: Mϩ Ϫ Me, 309.1509. C17H28O4Si requires M Ϫ Me,
309.1522).
(3R*,4R*)-5-(tert-Butyldimethylsilyloxy)-4-methyl-3-dimethyl-
(phenyl)silylpentanal
The acetal 10 (28.41 g, 69.3 mmol) and anhydrous toluene-p-
sulfonic acid (20 mg) were stirred in anhydrous acetone (500
cm3) at 20 ЊC for 6 h. The solution was poured into saturated
J. Chem. Soc., Perkin Trans. 1, 1998
2655

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aqueous sodium hydrogen carbonate (20 cm3) and the solvent
evaporated under reduced pressure. The residue was dissolved
in ether (300 cm3) and washed with saturated aqueous sodium
hydrogen carbonate (50 cm3), dried (MgSO4), filtered and evap-
orated under reduced pressure to give a mixture of the acetal
and the aldehyde (NMR). This mixture was treated again in the
same way until no starting material remained. Chromatography
(SiO2, 200 g, EtOAc–light petroleum, 1:20) gave the aldehyde
97%); νmax(neat)/cmϪ1 1731 (C᎐O) and 1090 (C–O); δ (CCl )
᎐
H 4
7.73–7.29 (5 H, m, Ph), 3.62 (3 H, s, CO2Me), 3.53–3.12 (2 H,
m, CH2O), 2.75 (1 H, dq, J 7 and 4, CHCO2), 1.96 (1 H, br m,
CH2CHMe), 1.60 (1 H, br m, CHSi), 1.19 (3 H, d, J 7, MeCH-
CO2), 1.02 (3 H, d, J 7, CHMe), 0.93 (9 H, s, But), 0.47 (3 H, s,
SiMeAMeBPh), 0.42 (3 H, s, SiMeAMeBPh) and 0.03 (6 H, s,
SiMe2But); δC(CDCl3) 177.3 (C-1), 140.0, 134.0, 128.8, 127.8
(Ar), 68.0 (C-5), 51.4 (CO2Me), 39.4 (C-2), 35.9 (C-4), 32.1
(C-3), 26.0 (SiCMe3), 24.9 (SiCMe3), 18.0, 15.7 (2 × MeCH),
Ϫ0.7, Ϫ0.9 (SiMe2Ph) and Ϫ5.3 (SiMe2But); m/z 408 (1%, Mϩ),
393 (7, M Ϫ Me), 351 (71, M Ϫ But), 331 (6, M Ϫ Ph), 235 (64,
M Ϫ MeCHCH2OSiMe2But) and 135 (100, SiMe2Ph) (Found:
Mϩ Ϫ Me, 393.2307. C22H40O3Si2 requires M Ϫ Me, 393.2281).
(24.75 g, 98%); Rf(EtOAc–light petroleum, 1:20) 0.36; νmax
-
(neat)/cmϪ1 2710 (H–CO), 1723 (C᎐O) and 1092 (C–O);
᎐
δ (CCl ) 9.60 (1 H, t, J 2, HC᎐O), 7.64–7.27 (5 H, m, Ph), 3.52–
᎐
H
4
3.20 (2 H, m, CH2O), 2.53–2.34 (2 H, m, CH2CHO), 1.73 (1 H,
br m, CHMe), 1.29 (1 H, br m, CHSi), 0.93 (3 H, d, J 7,
CHMe), 0.91 (9 H, s, But), 0.37 (3 H, s, SiMeAMeBPh), 0.35 (3
H, s, SiMeAMeBPh) and Ϫ0.01 (6 H, s, SiMe2But); m/z 249
(<1%, M Ϫ SiMe2But), 248 (2, M Ϫ SiMe2But Ϫ H), 233 (8,
M Ϫ SiMe2But Ϫ H Ϫ Me) and 135 (100, SiMe2Ph) (Found:
Mϩ Ϫ SiMe2But Ϫ H, 248.1226. C20H36O2Si2 requires M Ϫ
SiMe2But Ϫ H, 248.1233).
(2R*,3R*,4R*)-5-(tert-Butyldimethylsilyloxy)-2,4-dimethyl-3-
dimethyl(phenyl)silylpentan-1-ol
The ester 12 (18.55 g, 45.5 mmol) in dry THF (100 cm3) was
added dropwise to a stirred suspension of lithium aluminium
hydride (1.60 g, 42.2 mmol) in THF (200 cm3) under nitrogen
at 0 ЊC. After 1.5 h, the mixture was poured into saturated
aqueous ammonium chloride (20 cm3) and extracted with ether
(3 × 100 cm3). The combined organic solvents were dried
(MgSO4), filtered and evaporated under reduced pressure.
Chromatography (SiO2, 150 g, EtOAc–light petroleum, 1:9)
gave the alcohol (16.80 g, 97%); Rf(EtOAc–light petroleum,
1:9) 0.10; νmax(neat)/cmϪ1 3600–3200 (O–H) and 1073 (C–O);
δH(CCl4) 7.73–7.25 (5 H, m, Ph), 3.50–2.95 (4 H, m, CH2OH
and CH2OSi), 2.59–2.32 (1 H, br, OH, exchangeable with D2O),
2.22–1.79 (2 H, m, 2 × CHMe), 1.65 (1 H, m, HCSi), 0.98 (3 H,
d, J 7, CHMe), 0.92 (9 H, s, SiBut), 0.86 (3 H, d, J 7, CHMe),
0.45 (3 H, s, SiMeAMeBPh), 0.38 (3 H, s, SiMeAMeBPh), 0.03
(3 H, s, SiMeAMeBBut) and 0.01 (3 H, s, SiMeAMeBBut); m/z
380 (<1%, Mϩ), 365 (<1, M Ϫ Me), 323 (1, M Ϫ But), 305 (2,
M Ϫ But Ϫ H2O), 248 (4, M Ϫ HOSiMe2But), 245 (4, M Ϫ
SiMe2Ph), 233 (2, M Ϫ HOSiMe2But Ϫ Me), 135 (100,
SiMe2Ph) and 115 (34, SiMe2But) (Found: Mϩ Ϫ But Ϫ H2O,
305.1763. C21H40O2Si2 requires M Ϫ But Ϫ H2O, 305.1757).
Methyl (3R*,4R*)-5-(tert-butyldimethylsilyloxy)-4-methyl-3-
dimethyl(phenyl)silylpentanoate 11
Potassium hydroxide (15.35 g, 274 mmol) in ethanol–water
(2:1, 370 cm3) was added dropwise to a stirred solution of silver
nitrate (25.50 g, 150 mmol) in water (100 cm3) at 0 ЊC. The
mixture was stirred in the dark for 10 min and the aldehyde
(24.75 g, 68.0 mmol) and potassium hydroxide (1 mol dmϪ3, 2
drops) in ethanol (300 cm3) were added over 15 min. The mix-
ture was stirred at 0 ЊC for 45 min and filtered. The filter cake
was washed with ether (3 × 100 cm3) and the filtrate was neu-
tralised with concentrated hydrochloric acid. The solvents were
evaporated off under reduced pressure and the residue was dis-
solved in ether (500 cm3). The aqueous layer was separated and
washed with ether (3 × 100 cm3). The combined ethereal layers
were dried (MgSO4), filtered and evaporated under reduced
pressure to give the acid as a pale yellow liquid; δH(CDCl3)
8.74–8.48 (1 H, br, CO2H, exchangeable with D2O), 7.75–7.31
(5 H, m, Ph), 3.66–3.19 (2 H, m, CH2O), 2.48 (2 H, d, J 6,
CH2CO2H), 1.87–1.14 (2 H, m, CHSi and CHMe), 0.97 (3 H, d,
J 7, CHMe), 0.91 (9 H, s, But), 0.39 (3 H, s, SiMeAMeBPh), 0.37
(3 H, s, SiMeAMeBPh) and 0.00 (6 H, s, SiMe2But). The acid was
dissolved immediately in ether (100 cm3) and mixed with an
excess of diazomethane. The resulting solution was kept at
room temperature for 15 min and the excess diazomethane was
destroyed by the addition of glacial acetic acid. The solvent was
evaporated off under reduced pressure. Chromatography (SiO2,
200 g, EtOAc–light petroleum, 1:25) gave the ester (18.47 g,
69%); Rf(EtOAc–light petroleum, 1:25) 0.37; νmax(neat)/cmϪ1
(2R*,3S*,4R*)-5-(tert-Butyldimethylsilyloxy)-2,4-dimethyl-3-
dimethyl(phenyl)silylpentyl toluene-p-sulfonate 13
The alcohol (17.02 g, 44.8 mmol) and toluene-p-sulfonyl chlor-
ide (9.53 g, 50.0 mmol) were kept in pyridine (50 cm3) under
nitrogen at 0 ЊC for 10 h. The mixture was poured into saturated
aqueous ammonium chloride (50 cm3). The mixture was
extracted with ether (4 × 75 cm3). The combined ethereal layers
were washed with water (50 cm3), dried (MgSO4), filtered and
evaporated under reduced pressure. Chromatography (SiO2,
200 g, EtOAc–light petroleum, 1:25) gave the tosylate (20.04 g,
1739 (C᎐O) and 1091 (C–O); δ (CDCl ) 7.66–7.26 (5 H, m, Ph),
84%); Rf 0.07; νmax(neat)/cmϪ1 1365, 1177 (S᎐O) and 1097
᎐
᎐
H
3
3.62 (3 H, s, CO2Me), 3.54–3.22 (2 H, m, CH2O), 2.37 (2 H, d,
J 7, CH2CO2Me), 1.70 (1 H, br m, CHMe), 1.30 (1 H, br m,
CHSi), 0.95 (3 H, d, J 7, CHMe), 0.91 (9 H, s, But), 0.37 (6 H, s,
SiMe2Ph) and Ϫ0.02 (6 H, s, SiMe2But); m/z 394 (1%, Mϩ), 379
(3, M Ϫ Me), 363 (2, M Ϫ OMe), 337 (55, M Ϫ But) and 135
(100, SiMe2Ph) (Found: Mϩ Ϫ Me, 379.2111. C21H38O3Si2
requires M Ϫ Me, 379.2125).
(C–O); δH(CCl4) 7.74 (2 H, d, J 8, ArH o to S), 7.25–7.12 (7 H,
m, other ArH), 3.95–3.56 (2 H, m, CH2OTs), 3.30–3.10 (2 H,
m, CH2OSi), 2.48 (3 H, s, MeAr), 2.30–1.20 (3 H, m, CHCH-
SiCH), 0.95 (3 H, d, J 7, CHMe), 0.91 (3 H, d, J 7, CHMe), 0.85
(9 H, s, But), 0.38 (3 H, s, SiMeAMeBPh), 0.34 (3 H, s, SiMeA-
MeBPh) and Ϫ0.04 (6 H, s, SiMe2But); m/z 477 (1%, M Ϫ But),
171 (46, TolSO3), 135 (100, SiMe2Ph), 115 (23, SiMe2But) and
91 (27, C7H7) (Found: Mϩ Ϫ But, 477.1945. C28H46O4SSi2
requires M Ϫ But, 477.1951).
Methyl (2R*,3S*,4R*)-5-(tert-butyldimethylsilyloxy)-2,4-
dimethyl-3-dimethyl(phenyl)silylpentanoate 12
The ester 11 (18.47 g, 46.9 mmol) in dry THF (100 cm3) was
added dropwise to a stirred solution of LDA (50.0 mmol) in dry
THF (300 cm3) under nitrogen at Ϫ78 ЊC, and the solution was
stirred for 10 min. Methyl iodide (8.50 g, 59.9 mmol) was added
and the mixture was allowed to warm to room temperature
over 2 h. The mixture was poured into saturated aqueous
ammonium chloride (50 cm3), the organic layer was separated
and the aqueous layer was washed with ether (3 × 50 cm3). The
combined organic extracts were washed with saturated aqueous
ammonium chloride (50 cm3), dried (MgSO4), filtered and
evaporated under reduced pressure to give the ester (18.55 g,
(2R*,3S*,4R*)-2,4-Dimethyl-5-(toluene-p-sulfonyloxy)pentane-
1,3-diol 14
Boron trifluoride–acetic acid complex (20.0 cm3) and the
phenylsilane 13 (16.29 g, 30.5 mmol) were kept in dry dichloro-
methane (300 cm3) under nitrogen at 20 ЊC for 2 h. The mixture
was neutralised by the addition of powdered sodium hydrogen
carbonate, poured into water (100 cm3) and extracted with
dichloromethane (2 × 50 cm3). The combined organic extracts
were dried (NaHCO3), filtered and evaporated under reduced
pressure to give the fluorosilane (10.75 g, 97%); δH(CCl4) 7.82 (2
H, d, J 8, ArH o to S), 7.40 (2 H, d, J 8, other ArH), 4.14–3.49
2656
J. Chem. Soc., Perkin Trans. 1, 1998

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(4 H, m, CH2OTs and CH2OH), 2.49 (3 H, s, MeAr), 2.40–1.80
(4 H, m, OH and CHCHSiCH), 0.97 (3 H, d, J 7, CHMe),
0.95 (3 H, d, J 7, CHMe), 0.17 (6 H, d, J 4, SiMe2F). This
compound was then kept with anhydrous potassium fluoride
(4.43 g, 76.3 mmol) and m-chloroperbenzoic acid (16.84 g, 97.6
mmol) in dry DMF (170 cm3) under nitrogen at room temper-
ature for 7 h and then poured into water (150 cm3). The solu-
tion was extracted with ether (5 × 75 cm3) and the combined
ethereal solvents were washed with saturated aqueous sodium
bisulfite (2 × 50 cm3) and with saturated aqueous sodium
hydrogen carbonate (2 × 75 cm3), dried (MgSO4), filtered and
evaporated under reduced pressure. Chromatography (SiO2,
150 g, EtOAc–light petroleum, 4:3) gave the diol (4.98 g, 54%);
Rf(EtOAc–light petroleum, 4:3) 0.31; νmax(neat)/cmϪ1 3600–
combined ethereal solvents were dried (MgSO4), filtered and
evaporated under reduced pressure to give the ketone (3.03 g,
94%); νmax(neat)/cmϪ1 1710 (C᎐O); δ (CDCl ) 4.12 (1 H, dd,
᎐
H
3
J 12 and 3, CHAHBO), 3.64 (1 H, dd, J 12 and 2, CHAHBO),
3.55 (1 H, dd, J 9 and 1.5, CH–O), 2.87–2.29 (2 H, m, CH2C–
O), 2.14 (3 H, s, Ac), 1.95–1.20 (2 H, m, 2 × CHMe), 1.40 (3 H,
s, CMeAMeB), 1.34 (3 H, s, CMeAMeB), 1.08 (3 H, d, J 7,
CHMe) and 0.85 (3 H, d, J 7, CHMe); m/z 199 (8%, M Ϫ Me),
59 (80, Me2COH) and 43 (100, Ac) (Found: Mϩ Ϫ Me,
199.1339. C12H22O3 requires M Ϫ Me, 199.1334).
(3R*,5S*,6S*,7S*)-6,8-Dihydroxy-6,8-O-isopropylidene-3,5,7-
trimethyl-1-phenyloct-1-yn-3-ol 18 and (3R*,5R*,6R*,7R*)-
6,8-dihydroxy-6,8-O-isopropylidene-3,5,7-trimethyl-1-phenyloct-
1-yn-3-ol 19
3200 (O–H), 1356, 1176 (S᎐O) and 1097 (C–O); δ (CDCl ) 7.90
᎐
H
3
(2 H, d, J 9, ArH o to S), 7.42 (2 H, d, J 9, other ArH), 4.40–
4.02 (2 H, m, CH2OTs), 3.87–3.54 (3 H, m, CH2OH and
CHOH), 2.77 (2 H, br, 2 OH, exchangeable with D2O), 2.47
(3 H, s, MeAr), 2.10–1.63 (2 H, m, 2 × CHMe) and 0.90 (6 H, d,
J 7, 2 × CHMe); m/z 243 (<1%, M Ϫ MeCHCH2OH), 172 (19,
MeC6H4SO3H), 91 (63, C7H7), 71 (76, M Ϫ MeCHCH2OH Ϫ
TsOH) and 58 (100, C3H6O) (Found: Mϩ Ϫ MeCHCH2OH,
243.0701. C14H22O5S requires M Ϫ C3H7O, 243.0691).
n-Butyllithium (1.6 mol dmϪ3 in hexane, 4.0 cm3, 6.4 mmol) was
added dropwise to a stirred solution of phenylacetylene (0.80 g,
7.83 mmol) in dry ether (20 cm3) under nitrogen at 0 ЊC. The
mixture was stirred at 0 ЊC for 20 min and the ketone 17 (1.10 g,
5.14 mmol) in dry ether (10 cm3) was added over 5 min. The
solution was stirred at 0 ЊC for 30 min and quenched with sat-
urated aqueous ammonium chloride (20 cm3). The mixture was
extracted with ether (3 × 50 cm3) and the combined organic
extracts were dried (MgSO4), filtered and evaporated under
reduced pressure to give a mixture of the alcohols. They were
separated by HPLC to give the faster running alcohol 19 (747
mg, 46%); Rf(EtOAc–light petroleum, 1:7) 0.22; tR (EtOAc–
light petroleum, 1:6, solvent flow rate 6.72 cm3 minϪ1) 12.7 min;
(2R*,3S*,4R*)-3,5-Dihydroxy-3,5-O-isopropylidene-2,4-
dimethylpent-1-yl toluene-p-sulfonate 15
The diol 14 (4.20 g, 13.91 mmol) and toluene-p-sulfonic acid (2
crystals) in 2,2-dimethoxypropane (20 cm3) were stirred at room
temperature for 15 min. The mixture was diluted with ether
(100 cm3) and washed with saturated aqueous sodium hydrogen
carbonate (20 cm3). The organic layer was dried (MgSO4), fil-
tered and evaporated under reduced pressure to give the acet-
onide (4.33 g, 91%); Rf(EtOAc–light petroleum, 4:3) 0.81;
νmax(neat)/cmϪ1 3600–3200 (O–H) and 2240 (C᎐C); δ (CDCl ;
᎐
᎐
H
3
250 MHz) 7.50–7.27 (5 H, m, Ph), 4.28–4.12 (1 H, br, OH,
exchangeable with D2O), 4.09 (1 H, dd, J 11.6 and 2.6, CHA-
HBO), 3.63 (1 H, dd, J 11.6 and 1.3, CHAHBO), 3.56 (1 H, dd,
J 9.9 and 2.2, CHO), 2.16 (1 H, dd, J 14.3 and 5.0, CHAHB-
COH), 1.96–1.78 (1 H, m, CHMe), 1.72 (1 H, dd, J 14.3 and
4.1, CHAHBCOH), 1.67–1.58 (1 H, m, CHMe), 1.56 (3 H, s,
MeCOH), 1.47 (3 H, s, CMeAMeB), 1.43 (3 H, s, CMeAMeB),
1.09 (3 H, d, J 6.8, CHMe) and 0.97 (3 H, d, J 7.1, CHMe);
δC(CDCl3) 131.6, 128.1, 127.8, 123.4 (Ar), 99.1 (CMe2), 94.9
(C-1), 82.1 (C-2), 76.8 (C-6), 67.3 (C-3), 66.9 (C-8), 48.2 (C-4),
30.9, 29.6 (C-5 and C-7), 30.1, 29.5, 19.0, 17.2 and 10.2; m/z 316
νmax(neat)/cmϪ1 1361 and 1178 (S᎐O); δ (CDCl ) 7.95 (2 H, d,
᎐
H
3
J 8, ArH o to S), 7.39 (2 H, d, J 8, other ArH), 4.30–3.89 (3 H,
m, CH2OTs and CHAHBO), 3.82–3.48 (2 H, m, HCO and
CHAHBO), 2.40 (3 H, s, MeAr), 2.00–1.32 (2 H, m, 2 × CHMe),
1.29 (3 H, s, CMeAMeB), 1.27 (3H, s, CMeAMeB), 1.00 (3 H, d,
J 7, CHMe) and 0.86 (3 H, d, J 7, CHMe); m/z 327 (29%,
M Ϫ Me), 173 (22, TolSO3H2), 155 (22, Ts), 95 (35), 91 (42,
C7H7) and 59 (100, Me2COH) (Found: Mϩ Ϫ Me, 327.1275.
C17H26O5S requires M Ϫ Me, 327.1266).
ϩ
᎐
(7%, M ), 301 (5, M Ϫ Me), 145 (28, PhC᎐CCMeOH), 129 (22)
᎐
and 59 (100, Me2COH) (Found: Mϩ, 316.2033. C20H28O3
requires M, 316.2038), and the slower running alcohol 18 (731
mg, 45%); Rf(EtOAc–light petroleum, 1:7) 0.19; tR (EtOAc–
light petroleum, 1:6, solvent flow rate 6.72 cm3 minϪ1) 16.1 min;
(3R*,4R*,5R*)-4,6-Dihydroxy-4,6-O-isopropylidene-3,5-
dimethylhexanenitrile 16
νmax(neat)/cmϪ1 3600–3200 (O–H) and 2232 (C᎐C); δ (CDCl ;
᎐
The tosylate 15 (5.19 g, 15.2 mmol) was stirred with sodium
cyanide (0.80 g, 16.3 mmol) in dry HMPA (40 cm3) under nitro-
gen at 40 ЊC for 18 h. The mixture was poured into saturated
aqueous ammonium chloride (40 cm3) and extracted with ether
(3 × 75 cm3). The combined organic extracts were washed with
water (50 cm3), dried (MgSO4), filtered and evaporated under
reduced pressure to give the nitrile (2.95 g, 99%) as needles, mp
᎐
H
3
250 MHz) 7.50–7.28 (5 H, m, Ph), 5.33–5.25 (1 H, br, OH,
exchangeable with D2O), 4.09 (1 H, dd, J 11.6 and 2.5, CHA-
HBO), 3.64 (1 H, dd, J 11.6 and 1.5, CHAHBO), 3.59 (1 H, dd,
J 10.6 and 2.1, CH-O), 2.33–1.60 (4 H, m, CH2CHMe and
CHMe), 1.56 (3 H, s, MeCOH), 1.48 (3 H, s, CMeAMeB), 1.45
(3 H, s, CMeAMeB), 1.12 (3 H, d, J 6.7, CHMe) and 0.98 (3 H,
d, J 7.0, CHMe); δC(CDCl3) 131.6, 128.1, 127.8, 123.5 (Ar),
99.2 (CMe2), 93.6 (C-1), 82.8 (C-2), 77.5 (C-6), 67.3 (C-3), 66.9
(C-8), 50.3 (C-4), 32.4, 30.3 (C-5 and C-7), 31.3, 29.3, 19.0, 18.0
65–67 ЊC (from Et2O); νmax(KBr)/cmϪ1 2247 (C᎐N); δ (CDCl )
᎐
᎐
H
3
4.12 (1 H, dd, J 12 and 3, CHAHBO), 3.68 (1 H, dd, J 8 and 2,
CHO), 3.62 (1 H, dd, J 12 and 2, CHAHBO), 2.46 (2 H, d, J 6,
CH2CN), 2.10–1.20 (2 H, m, 2 × CHMe), 1.42 (3 H, s,
CMeAMeB), 1.36 (3 H, s, CMeAMeB), 1.03 (3 H, d, J 7, CHMe)
and 1.00 (3 H, d, J 7, CHMe); m/z 182 (14%, M Ϫ Me) and 59
(100, Me2COH) (Found: C, 67.2; H, 9.50; N, 7.35%; Mϩ Ϫ Me,
182.1177. C11H19NO2 requires C, 67.0; H, 9.70; N, 7.10%;
M Ϫ Me, 182.1181).
ϩ
᎐
and 10.2; m/z 316 (16%, M ), 301 (5, M Ϫ Me), 145 (50, PhC᎐
᎐
CCMeOH), 129 (31) and 59 (100, Me2COH) (Found: Mϩ,
316.2053. C20H28O3 requires M, 316.2038).
(2R*,3R*,4R*,6S*)-2,4,6-Trimethyl-8-phenyloct-7-yne-1,3,6-
triol
The acetonide 18 (924 mg, 2.92 mmol), pyridinium tosylate (20
mg) and toluene-p-sulfonic acid (40 mg) in chloroform–ethyl
acetate–ethylene glycol (7:13:25, 45 cm3) were stirred under
nitrogen at room temperature for 24 h. The solution was poured
into saturated aqueous sodium hydrogen carbonate (20 cm3)
and extracted with chloroform (5 × 30 cm3). The combined
organic extracts were dried (NaHCO3), filtered and evaporated
under reduced pressure to give the triol (734 mg, 89%) as
needles, mp 119–120 ЊC (from CH2Cl2); Rf(EtOAc–light petrol-
(4R*,5R*,6R*)-5,7-Dihydroxy-5,7-O-isopropylidene-4,6-
dimethylheptan-2-one 17
The nitrile (2.97 g, 15.1 mmol) was refluxed at 37 ЊC in dry ether
(15 cm3) with methylmagnesium iodide (1 mol dmϪ3 in Et2O, 25
cm3, 25 mmol) under nitrogen for 5 h. The solution was poured
into cold saturated aqueous ammonium chloride (20 cm3) and
stirred for another 5 min. The organic solvent was separated
and the aqueous layer was washed with ether (2 × 50 cm3). The
J. Chem. Soc., Perkin Trans. 1, 1998
2657

View Article Online
eum, 2:1) 0.30; νmax(KBr)/cmϪ1 3600–3100 (O–H) and 2229
(1E,3R*,5R*,6R*,7R*)-3,6,8-Triacetoxy-3,5,7-trimethyl-1-
phenyloct-1-ene 25
᎐
(C᎐C); δ (CDCl ; 250 MHz) 7.47–7.18 (5 H, m, Ph), 5.31–4.31
᎐
H
3
(3 H, br, 3 × OH, exchangeable with D2O), 3.87–3.50 (3 H, m,
CH2OH and CHOH), 2.23 (1 H, br m, CHMe), 1.96 (1 H, dd,
J 14.6 and 6.7, CHAHBCOH), 1.83 (1 H, br m, CHMe), 1.73
(1 H, dd, J 14.6 and 1.4, CHAHBCOH), 1.59 (3 H, s, MeCOH),
0.94 (3 H, d, J 6.9, CHMe) and 0.93 (3 H, d, J 7.0, CHMe);
δC(CDCl3) 131.7, 128.2, 128.0, 123.2 (Ar), 93.4 (C-8), 83.5
(C-7), 79.0 (C-3), 67.8 (C-6), 67.7 (C-1), 50.1 (C-5), 36.2, 34.0,
31.7, 19.6 and 8.7; m/z 276 (1%, Mϩ), 258 (1, M Ϫ H2O), 199
This compound was prepared by a similar procedure to that
described for the acetylenic triols. The trans-triol (244 mg, 0.88
mmol) derived from 19 gave the trans-triacetate (210 mg, 59%);
Rf(EtOAc–light petroleum, 1:5) 0.20; νmax(neat)/cmϪ1 1738
(C᎐O); δ (CDCl ; 250 MHz) 7.40–7.19 (5 H, m, Ph), 6.51 (1 H,
᎐
H
3
d, J 16.3, PhCH᎐CH), 6.36 (1 H, d, J 16.3, PhCH᎐CH), 4.84
᎐
᎐
(1 H, dd, J 7.1 and 4.4, CHOAc), 3.93 (1 H, dd, J 11.0 and 7.0,
CHAHBOAc), 3.83 (1 H, dd, J 11.0 and 6.3, CHAHBOAc), 2.21–
1.77 (4 H, m, CH2CHMe and CHMe), 2.03 (3 H, s, Ac), 2.02 (3
H, s, Ac), 2.01 (3 H, s, Ac), 1.67 (3 H, s, MeCOAc), 0.99 (3 H, d,
J 6.7, CHMe) and 0.91 (3 H, d, J 7.0, CHMe); m/z 404 (1%,
Mϩ), 284 (9, M Ϫ 2 HOAc), 224 (66, M Ϫ 3 HOAc), 209 (36,
M Ϫ 3 HOAc Ϫ Me), 171 (48, M Ϫ HOAc Ϫ AcOCHCHMe-
᎐
᎐
(16, M Ϫ Ph), 145 (100, PhC᎐CCMeOH) and 129 (44, PhC᎐
᎐
᎐
CCO) (Found: C, 73.8; H, 8.70%; Mϩ, 276.1708. C17H24O3
requires C, 73.9; H, 8.75%; M, 276.1725).
(2R*,3R*,4R*,6R*)-2,4,6-Trimethyl-8-phenyloct-7-yne-1,3,6-
triol
CH OAc), 147 (100, PhCH᎐CHCMeOH), 131 (68, PhCH᎐
᎐
᎐
2
CHCO) and 91 (82, C7H7) (Found: Mϩ, 404.2185. C23H32O6
This compound was prepared by a similar procedure to that
described for its diastereoisomer. The acetonide 19 (936 mg,
2.96 mmol) gave the triol (687 mg, 84%) as needles, mp 102.5–
103.5 ЊC (from CHCl3); Rf(EtOAc–light petroleum, 2:1) 0.30;
requires M, 404.2199).
(1E,3R*,5S*,6S*,7S*)-3,6,8-Triacetoxy-3,5,7-trimethyl-1-
phenyloct-1-ene 29
νmax(KBr)/cmϪ1 3680–3100 (O–H) and 2240 (C᎐C); δ (CDCl ;
᎐
᎐
H
3
Similarly, the trans-triol (107 mg, 0.38 mmol) derived from 18
gave the trans-triacetate (92 mg, 59%); Rf(EtOAc–light petrol-
250 MHz) 7.50–7.23 (5 H, m, Ph), 5.50–4.00 (3 H, br, 3 × OH,
exchangeable with D2O), 3.85–3.53 (3 H, m, CH2OH and
CHOH), 2.24–1.72 (4 H, m, CH2CHMe and CHMe), 1.58
(3 H, s, MeCOH), 0.96 (3 H, d, J 6.8, MeCH) and 0.89 (3 H,
d, J 7.0, MeCH); δC(CDCl3) 131.7, 128.2, 128.1, 123.1
(Ar), 94.5 (C-8), 82.9 (C-7), 78.6 (C-3), 67.9 (C-1), 67.7
(C-6), 48.4 (C-5), 36.3, 33.0, 29.9, 19.0 and 8.8; m/z 276 (1%,
eum, 1:5) 0.20; νmax(neat)/cmϪ1 1742 (C᎐O); δ (CDCl ; 250
᎐
H
3
MHz) 7.40–7.21 (5 H, m, Ph), 6.51 (1 H, d, J 16.3, PhCH᎐CH),
᎐
6.32 (1 H, d, J 16.3, PhCH᎐CH), 4.85 (1 H, dd, J 7.3 and 4.3,
᎐
CHOAc), 3.93 (1 H, dd, J 11.0 and 7.0, CHAHBOAc), 3.86 (1 H,
dd, J 11.0 and 6.0, CHAHBOAc), 2.18–1.78 (4 H, m, CH2CHMe
and CHMe), 2.08 (3 H, s, Ac), 2.04 (3 H, s, Ac), 2.04 (3 H, s,
Ac), 1.66 (3 H, s, MeCOAc), 0.98 (3 H, d, J 6.7, CHMe) and
0.92 (3 H, d, J 6.8, CHMe); m/z 404 (1%, Mϩ), 284 (9, M Ϫ 2
HOAc), 224 (48, M Ϫ 3 HOAc), 209 (31, M Ϫ 3 HOAc Ϫ Me),
171 (62, M Ϫ HOAc Ϫ AcOCHCHMeCH2OAc), 147 (100,
ϩ
᎐
M ), 258 (1, M Ϫ H O), 199 (22, M Ϫ Ph), 145 (100, PhC᎐
᎐
2
᎐
CCMeOH) and 129 (29, PhC᎐CCO) (Found: C, 74.0; H,
᎐
8.95%; Mϩ, 276.1724. C17H24O3 requires C, 73.9; H 8.75%; M,
276.1725).
PhCH᎐CHCMeOH), 131 (47, PhCH᎐CHCO) and 91 (83,
᎐
᎐
C7H7) (Found: Mϩ, 404.2179. C23H32O6 requires M, 404.2199).
(3R*,5S*,6S*,7S*)-3,6,8-Triacetoxy-3,5,7-trimethyl-1-
phenyloct-1-yne
The triol (482 mg, 1.75 mmol) derived from 18, acetic anhydride
(900 mg, 8.78 mmol) and DMAP (60 mg, 0.49 mmol) in dry
triethylamine (10 cm3) were stirred under nitrogen at 0 ЊC for
6 h. The mixture was diluted with ether (100 cm3) and washed
with water (2 × 20 cm3). The ether layer was dried (MgSO4),
filtered and evaporated. Chromatography (SiO2, EtOAc–light
petroleum, 1:5) gave the triacetate (664 mg, 95%); Rf(EtOAc–
(3R*,5S*,6S*,7S*)-6,8-Dihydroxy-6,8-O-isopropylidene-3,5,7-
trimethyl-1-phenyloct-1-yn-3-yl acetate
Similarly, the acetonide 18 gave the acetate; δH(CDCl3) 7.57–
7.17 (5 H, m, Ph), 3.95 (1 H, dd, J 11 and 2, CHAHBO), 3.65–
3.30 (2 H, m, CHAHBO and CHO), 2.40–1.46 (4 H, m,
CH2CHMe and CHMe), 2.0 (3 H, s, Ac), 1.74 (3 H, s,
MeCOAc), 1.37 (3 H, s, CMeAMeB), 1.33 (3 H, s, CMeAMeB),
1.05 (3 H, d, J 7, CHMe) and 0.97 (3 H, d, J 7, CHMe).
light petroleum, 1:5) 0.20; νmax(neat)/cmϪ1 2240 (C᎐C) and
᎐
᎐
1738 (C᎐O); δ (CDCl ; 250 MHz) 7.48–7.38 (2 H, m, ArH o to
᎐
H
3
᎐
C᎐C), 7.35–7.25 (3 H, m, other ArH), 4.90 (1 H, dd, J 6.7 and
᎐
(1Z,3R*,5S*,6S*,7S*)-3,6,8-Triacetoxy-3,5,7-trimethyl-1-
phenyloct-1-ene 24
4.9, CHOAc), 3.99 (1 H, dd, J 11.2 and 6.9, CHAHBOAc), 3.93
(1 H, dd, J 11.2 and 6.1, CHAHBOAc), 2.28–2.10 (4 H, m,
CH2CHMe and CHMe), 2.09 (3 H, s, Ac), 2.05 (6 H, s, 2 × Ac),
1.79 (3 H, s, MeCOAc), 1.15 (3 H, d, J 6.8, CHMe) and 0.96
The triacetate (661 mg, 1.64 mmol) derived from 18 and quin-
oline (0.10 cm3) in absolute ethanol (10 cm3) were hydrogenated
over Lindlar’s catalyst (Aldrich, 150 mg) until 1 equivalent of
hydrogen had been absorbed. The solvent was evaporated
under reduced pressure. Chromatography (SiO2, EtOAc–light
petroleum, 1:5)gavethecis-triacetate(642mg, 97%);Rf(EtOAc–
(3 H, d, J 6.8, CHMe); m/z 402 (1%, Mϩ), 257 (15, M Ϫ
2ϩ
᎐
᎐
PhC᎐C Ϫ CO ), 201 (22, M ), 160 (100), 145 (47, PhC᎐
᎐
᎐
2
CCMeOH) and 105 (70) (Found: Mϩ, 402.2062. C23H30O6
light petroleum, 1:5) 0.20; νmax(neat)/cmϪ1 1738 (C᎐O);
requires M, 402.2042).
᎐
δH(CDCl3; 250 MHz) 7.27–7.15 (5 H, m, Ph), 6.43 (1 H, d,
(3R*,5R*,6R*,7R*)-3,6,8-Triacetoxy-3,5,7-trimethyl-1-
phenyloct-1-yne
J 12.8, PhCH᎐CH), 5.67 (1 H, d, J 12.8, PhCH᎐CH), 4.78 (1 H,
᎐ ᎐
dd, J 7.7 and 4.1, CHOAc), 3.88 (1 H, dd, J 11.0 and 7.3,
CHAHBOAc), 3.77 (1 H, dd, J 11 and 6.1, CHAHBOAc), 2.20–
1.67 (4 H, m, CH2CHMe and CHMe), 2.00 (3 H, s, Ac), 1.99
(3 H, s, Ac), 1.53 (3 H, s, Ac), 1.48 (3 H, s, AcOCMe), 0.99 (3 H,
d, J 6.7, CHMe) and 0.88 (3 H, d, J 6.8, CHMe); m/z 404 (1%,
Mϩ), 344 (1, M Ϫ HOAc), 284 (5, M Ϫ 2 HOAc), 224 (35,
M Ϫ 3 HOAc), 209 (15, M Ϫ 3 HOAc Ϫ Me), 171 (33,
Similarly, the triol (169 mg, 0.61 mmol) derived from 19 gave
the triacetate (235 mg, 96%); Rf(EtOAc–light petroleum, 1:5)
0.20; νmax(neat)/cmϪ1 2237 (C᎐C) and 1740 (C᎐O); δ (CDCl )
᎐
᎐
᎐
H
3
᎐
7.46–7.40 (2 H, m, ArH o to C᎐C), 7.32–7.28 (3 H, m, other
᎐
ArH), 4.90 (1 H, dd, J 7.5 and 4.3, CHOAc), 3.97 (1 H, dd,
J 11.1 and 7.1, CHAHBOAc), 3.90 (1 H, dd, J 11.1 and 6.2,
CHAHBOAc), 2.33–2.14 (2 H, br m, 2 × CHMe), 2.05 (3 H, s,
Ac), 2.04 (3 H, s, Ac), 2.03 (3 H, s, Ac), 1.87 (2 H, d, J 5.2,
CH2COAc), 1.78 (3 H, s, MeCOAc), 1.13 (3 H, d, J 6.8, CHMe)
and 0.97 (3 H, d, J 6.8, CHMe); m/z 402 (2%, Mϩ), 257 (26,
M Ϫ HOAc Ϫ AcOCHCHMeCH2OAc), 147 (100, PhCH᎐
᎐
CHCMeOH), 131 (30, PhCH᎐CHCO) and 91 (32, C H )
᎐
7
7
(Found: Mϩ, 404.2185. C23H32O6 requires M, 404.2199).
M Ϫ PhC᎐C Ϫ CO ), 201 (30, M2ϩ), 160 (100), 145 (42, Ph-
᎐
(1Z,3R*,5R*,6R*,7R*)-3,6,8-Triacetoxy-3,5,7-trimethyl-1-
phenyloct-1-ene 30
᎐
᎐
2
ϩ
᎐
C᎐CCMeOH) and 105 (59) (Found: M , 402.2041. C H O
23 30
6
requires M, 402.2042).
Similarly, the triacetate (234 mg, 0.58 mmol) derived from 19
2658
J. Chem. Soc., Perkin Trans. 1, 1998

View Article Online
gave the cis-triacetate (228 mg, 97%); Rf(EtOAc–light petrol-
THF, 2.5 cm3, 2.5 mmol) was added dropwise to copper() cyan-
eum, 1:5) 0.20; νmax(neat)/cmϪ1 1738 (C᎐O); δ (CDCl ; 250
ide (113 mg, 1.25 mmol) under nitrogen at 0 ЊC and kept for 10
min. The cis-triacetate 24 (542 mg, 1.34 mmol) in dry THF (2.0
cm3) was added dropwise under nitrogen at Ϫ23 ЊC, and kept
for 2 h. Saturated aqueous ammonium chloride (25 cm3) was
added and the mixture extracted with ether (3 × 50 cm3). The
combined organic extracts were washed with saturated aqueous
ammonium chloride (3 × 50 cm3), dried (MgSO4), filtered and
evaporated under reduced pressure. Chromatography (SiO2, 25
g, EtOAc–light petroleum, 1:5) gave the allylsilanes contamin-
ated with dimethyl(phenyl)silanol, which was removed by evap-
oration (60 ЊC at 0.05 mmHg), to leave the allylsilanes (554 mg,
86%) as a 1:1 mixture; Rf(EtOAc–light petroleum, 1:10) 0.25;
᎐
H
3
MHz) 7.32–7.18 (5 H, m, Ph), 6.51 (1 H, d, J 12.8, PhCH᎐CH),
᎐
5.68 (1 H, d, J 12.8, PhCH᎐CH), 4.83 (1 H, dd, J 7.0 and 4.6,
᎐
CHOAc), 3.94 (1 H, dd, J 11.0 and 7.0, CHAHBOAc), 3.85 (1 H,
dd, J 11.0 and 6.1, CHAHBOAc), 2.05–1.64 (4 H, m, CH2CHMe
and CHMe), 2.05 (3 H, s, Ac), 2.04 (3 H, s, Ac), 1.57 (3 H,
MeCO2CMe), 1.53 (3 H, s, MeCO2CMe), 0.98 (3 H, d, J 6.7,
CHMe) and 0.93 (3 H, d, J 7.0, CHMe); m/z 404 (1%, Mϩ),
284 (6, M Ϫ 2 HOAc), 224 (37, M Ϫ 3 HOAc), 209 (20, M Ϫ
3 HOAc Ϫ Me), 171 (40, M Ϫ HOAc Ϫ AcOCHCHMeCH2-
OAc), 147 (100, PhCH᎐CHCMeOH), 131 (34, PhCH᎐CHCO)
᎐
᎐
and 91 (C7H7) (Found: Mϩ, 404.2185. C23H32O6 requires M,
404.2199).
νmax(neat)/cmϪ1 1738 (C᎐O) and 1245 (SiMe Ph); δ (CDCl ;
᎐
2
H
3
250 MHz) 7.36–6.89 (10 H, m, Ph and SiPh), 5.64 (1 H, d,
J 11.7, HC᎐C, one isomer), 5.55 (1 H, d, J 11.3, HC᎐C, one
isomer), 4.86–4.76 (1 H, m, HCOAc), 3.94–3.72 (2 H, m,
CH2OAc), 3.33 (1 H, d, J 11.2, SiCH, one isomer), 3.25 (1 H, d,
J 11.5, SiCH, one isomer), 2.14–1.63 (4 H, m, CH2CHMe and
CHMe), 2.02, 2.00, 1.95, 1.92 (total 6 H, 4 × s, Ac), 1.72 (3 H, s,
(1Z,3R*,5S*,6S*,7S*)-6,8-Dihydroxy-6,8-O-isopropylidene-
3,5,7-trimethyl-1-phenyloct-1-en-3-yl acetate 20
Similarly, the acetate derived from the acetonide 18 gave the cis-
᎐
᎐
alkene; δH(CDCl3) 7.30–7.20 (5 H, m, Ph), 6.39 (1 H, d, J 13,
PhCH᎐CH), 5.72 (1 H, d, J 13, PhCH᎐CH), 3.97 (1 H, dd, J 11
᎐
᎐
and 2, CHAHBO), 3.63–3.23 (2 H, m, CHAHBO and CHO),
2.19–1.56 (4 H, m, CH2CHMe and CHMe), 1.53 (3 H, s, Ac),
1.48 (3 H, s, MeCOAc), 1.33 (3 H, s, CMeAMeB), 1.28 (3 H, s,
CMeAMeB), 1.02 (3 H, d, J 7, CHMe) and 0.86 (3 H, d, J 7,
CHMe).
MeC᎐C, one isomer), 1.44 (3 H, s, MeC᎐C, one isomer), 0.90,
᎐
᎐
0.83, 0.75, 0.66 (total 6 H, 4 × d, J 6.8, 6.8, 6.4 and 6.7, respect-
ively, CHMe), 0.26, 0.24, 0.21 and 0.20 (total 6 H, 4 × s, SiMe2);
δC(CDCl3) 170.7, 170.5, 170.4, 143.2, 142.9, 137.4, 134.3, 133.6,
132.1, 129.0, 128.0, 127.8, 127.5, 125.9, 125.3, 124.5, 124.4,
77.2, 66.6, 43.6, 38.0, 37.4, 34.6, 34.2, 34.0, 33.6, 32.9, 24.6,
20.7, 16.2, 15.8, 10.9, 10.8, Ϫ4.0, Ϫ4.3, Ϫ4.6 and Ϫ4.7; m/z 480
(1 %, Mϩ), 286 (5, M Ϫ SiMe2Ph Ϫ OAc), 226 (6, M Ϫ SiMe2-
(2R*,3R*,4R*,6R*,7E)-2,4,6-Trimethyl-8-phenyloct-7-ene-
1,3,6-triol
The acetylenic triol (213 mg, 0.77 mol) derived from 19 and
lithium aluminium hydride (150 mg, 3.95 mmol) were refluxed
in dry ether (10 cm3) under nitrogen at 37 ЊC for 5 h. Saturated
aqueous ammonium chloride (5 cm3) was added and the mix-
ture was extracted with ether (3 × 30 cm3). The combined
organic layers were dried (MgSO4), filtered and evaporated
under reduced pressure to give the trans-triol (210 mg, 98%) as
an amorphous solid, mp 117–118 ЊC (from CH2Cl2); νmax(KBr)/
cmϪ1 3600–3150 (O–H); δH(CDCl3; 250 MHz) 7.56–7.21 (5 H,
PhOAc Ϫ HOAc), 184 (14), 171 (12), 145 (28, PhCH᎐
᎐
CHCMe ), 144 (90, PhCH᎐CHMeC᎐CH ), 135 (40, SiMe Ph),
᎐
᎐
2
2
2
129 (41) and 43 (100, Ac) (Found: Mϩ Ϫ SiMe2PhOAc,
286.1929. C29H40O4Si requires M Ϫ SiMe2PhOAc, 286.1932).
Method B. Dimethyl(phenyl)silyllithium (1.5 cm3 of a 1.0 mol
dmϪ3 in THF, 1.5 mmol) was added dropwise to a stirred sus-
pension of copper() cyanide (68 mg, 0.75 mmol) in dry ether (7
cm3) under nitrogen at 0 ЊC and kept for 10 min. The trans-
triacetate 25 (210 mg, 0.52 mmol) was added and the procedure
described for the epimeric cis-triacetate then gave, after chrom-
atography (SiO2, EtOAc–light petroleum, 1:5), the allylsilanes
26 and 27 (108 mg, 43%, 54% based on reacted starting
material) in a ratio of 2:3 (or 3:2), identical (IR and 1H NMR)
to the earlier sample, and the starting material 25 (42 mg, 20%).
m, Ph), 6.66 (1 H, d, J 17, PhCH᎐CH), 6.36 (1 H, d, J 17,
᎐
PhCH᎐CH), 4.92–4.53 (3 H, br, 3 OH, exchangeable with D O),
᎐
2
3.93–3.40 (3 H, m, CHOH and CH2OH), 2.32–1.52 (3 H, m,
CH2COH and CHMe), 1.37 (3 H, s, MeCOH), 1.33 (1 H,
m, CHMe), 0.96 (3 H, d, J 7, CHMe) and 0.88 (3 H, d, J 6,
CHMe); m/z 260 (35%, M Ϫ H2O), 245 (44, M Ϫ H2O Ϫ Me),
147 [100, PhCH᎐CHC(Me)OH], 131 (84, PhCH᎐CHCO) and
᎐
᎐
(1R*,2E,5R*,6R*,7R*)-6,8-Diacetoxy-3,5,7-trimethyl-1-
dimethyl(phenyl)silyl-1-phenyloct-2-ene 31 and (1R*,2Z,5S*,
6S*,7S*)-6,8-diacetoxy-3,5,7-trimethyl-1-dimethyl(phenyl)-
silyl-1-phenyloct-2-ene 32
91 (48, C7H7) (Found: Mϩ Ϫ H2O, 260.1777. C17H26O3 requires
M Ϫ H2O, 260.1777). This product was contaminated with the
cis-isomer (7%, NMR), which did not separate from it on
recrystallisation.
Method A. The cis-triacetate 30 (503 mg, 1.25 mmol) in dry
THF (2.0 cm3) was treated by method A above to give the
allylsilanes (490 mg, 82%) as a 5:3 or 3:5 mixture; Rf(EtOAc–
(2R*,3R*,4R*,6S*,7E)-2,4,6-Trimethyl-8-phenyloct-7-ene-
1,3,6-triol
Similarly, the acetylenic triol (102 mg, 0.37 mmol) derived from
18 gave the trans-triol (102 mg, 100%) as an amorphous solid,
mp 126.5–127.5 ЊC (from CH2Cl2); νmax(KBr)/cmϪ1 3600–3150
(O–H); δH(CDCl3) 7.67–7.14 (5 H, m, Ph), 6.69 (1 H, d, J 17,
light petroleum, 1:5) 0.44; νmax(neat)/cmϪ1 1738 (C᎐O) and
᎐
1244 (SiMe2Ph); δH(CDCl3; 250 MHz) 7.33–6.90 (10 H, m, Ph
and SiPh), 5.66 (1 H, d, J 11.4, HC᎐C, one isomer), 5.56 (1 H, d,
᎐
J 11.2, HC᎐C, one isomer), 4.84–4.78 (1 H, m, HCOAc), 3.95–
᎐
3.76 (2 H, m, CH2OAc), 3.32 (1 H, d, J 11.1, SiCH, one isomer),
3.28 (1 H, d, J 11.4, SiCH, one isomer), 2.20–1.52 (4 H, m,
CH2CHMe and CHMe), 2.04, 2.04, 2.03, 2.01 (6 H, 4 × s, Ac),
PhCH᎐CH), 6.27 (1 H, d, J 17, PhCH᎐CH), 5.43–4.03 (3 H, br,
᎐
᎐
3 OH, exchangeable with D2O), 3.92–3.48 (3 H, m, CHOH and
CH2OH), 2.22–1.55 (3 H, m, CH2COH and CHMe), 1.37 (1 H,
m, CHMe), 1.36 (3 H, s, MeCOH), 0.85 (3 H, d, J 7, CHMe)
and 0.81 (3 H, d, J 7, CHMe); m/z 260 (21%, M Ϫ H2O), 245
1.67 (3 H, s, MeC᎐C, one isomer), 1.41 (3 H, s, MeC᎐C, one
᎐
᎐
isomer), 0.91, 0.88, 0.70, 0.55 (6 H, 4 × d, J 7.0, 6.8, 6.4 and 6.4,
respectively, CHMe), 0.24, 0.22, 0.21 and 0.20 (6 H, 4 × s,
SiMe2); δC(CDCl3) 170.7, 170.4, 142.9, 134.3, 131.9, 128.9,
128.3, 128.0, 127.4, 126.1, 125.5, 124.4, 77.4, 77.3, 66.5, 42.7,
42.6, 37.8, 34.1, 34.9, 33.1, 32.9, 23.4, 20.7, 15.5, 15.2, 10.7,
Ϫ4.4 and Ϫ4.8; m/z 286 (<1%, M Ϫ SiMe2Ph Ϫ OAc), 226 (4,
(14, M Ϫ H O Ϫ Me), 147 [100, PhCH᎐CHC(Me)OH], 131
᎐
2
(62, PhCH᎐CHCO) and 91 (68, C H ) (Found: Mϩ Ϫ H O,
᎐
7
7
2
260.1771. C17H26O3 requires M Ϫ H2O, 260.1777). This product
was contaminated with the cis-isomer (10%), which did not
separate from it on recrystallisation.
M Ϫ SiMe PhOAc Ϫ HOAc), 145 (14, PhCH᎐CHCMe ), 144
᎐
2
2
(1R*,2E,5S*,6S*,7S*)-6,8-Diacetoxy-3,5,7-trimethyl-1-
dimethyl(phenyl)silyl-1-phenyloct-2-ene 26 and (1R*,2Z,5R*,
6R*,7R*)-6,8-diacetoxy-3,5,7-trimethyl-1-dimethyl(phenyl)-
silyl-1-phenyloct-2-ene 27
(100, PhCH᎐CHMeC᎐CH ), 135 (27, SiMe Ph) and 129 (36)
᎐ ᎐
2 2
(Found: Mϩ Ϫ SiMe2PhOAc, 286.1928. C29H40O4Si requires
M Ϫ SiMe2PhOAc, 286.1932).
Method B. The trans-triacetate 29 (92 mg, 0.23 mmol) was
treated by method B above to give the allylsilanes 31 and 32 (46
Method A. Dimethyl(phenyl)silyllithium (1.0 mol dmϪ3 in
J. Chem. Soc., Perkin Trans. 1, 1998
2659

View Article Online
mg, 42%, 52% based on reacted starting material) in a ratio of
5:2 (or 2:5) identical (IR, H NMR) with the earlier sample,
and the starting material 29 (18 mg, 20%).
(2R*,4S*,5S*,6S*)-5,7-Diacetoxy-2,4,6-trimethylheptanal
1
Ozone and air were passed into the alkene 28 (338 mg, 0.98
mmol) in dry dichloromethane (10 cm3) and methanol (0.1 cm3)
at Ϫ78 ЊC until the solution turned blue. The reaction was
stirred at Ϫ78 ЊC for 15 min and the excess ozone was flushed
away with dry nitrogen. Dimethyl sulfide (2 cm3) and pyridin-
ium tosylate (20 mg) were added and the mixture was allowed
to warm to room temperature over 1 h and kept for 5 h. The
solvent was evaporated off under reduced pressure and the
residue was chromatographed (SiO2, 20 g, EtOAc–light petrol-
eum, 1:10) to give the aldehyde (144 mg, 58%); Rf(EtOAc–light
petroleum, 1:10) 0.07; νmax(neat)/cmϪ1 2716 (H–CO) and 1738
(1E,3R*,5S*,6S*,7S*)-6,8-Dihydroxy-6,8-O-isopropylidene-
3,5,7-trimethyl-1-dimethyl(phenyl)silyl-1-phenyloct-2-ene 21 and
(1Z,3R*,5S*,6S*,7S*)-6,8-dihydroxy-6,8-O-isopropylidene-
3,5,7-trimethyl-1-dimethyl(phenyl)silyl-1-phenyloct-2-ene 22
Similarly, the cis-allylic acetate 20 gave the mixture of
allylsilanes; δH(CDCl3) 7.48–6.86 (10 H, m, Ph and SiPh), 5.58
(1 H, m, CH᎐C), 4.00 (1 H, m, CH H O), 3.65–3.20 (2 H, m,
᎐
A
B
CHAHBO and CHO), 2.54 (1 H, m, CHSi), 1.78 and 1.50 (total
(C᎐O); δ (CDCl ; 250 MHz) 9.58 (1 H, d, J 1.5, CH᎐O), 4.85
᎐
᎐
H
3
of 3 H, s, MeC᎐), 2.08–1.40 (4 H, m, CH CHMe and CHMe),
᎐
2
(1 H, dd, J 6.8 and 4.3, HCOAc), 3.99–3.80 (2 H, m, CH2OAc),
1.38, 1.33 and 1.28 (total of 6 H, s, CMe2), 1.05, 1.00, 0.62 and
0.60 (total of 6 H, d, J 6, 2 × CHMe) and 0.25, 0.22 and 0.20
(total of 6 H, s, SiMe2).
2.56 (1 H, m, HCC᎐O), 2.25–1.67 (2 H, m, 2 × CHMe), 2.08
᎐
(3 H, s, Ac), 2.06 (3 H, s, Ac), 1.65–1.38 (2 H, m, CCH2C), 1.21
(3 H, d, J 6.9, MeCCHO), 0.93 (3 H, d, J 6.6, CHMe) and
0.92 (3 H, d, J 6.8, HCMe); m/z 229 (1%, M Ϫ Ac), 173 (30,
M Ϫ MeCHCH2CHMeCHO), 131 (47), 127 (36), 113 (46),
75 (100) and 71 (44, CH2CHMeCHO) (Found: Mϩ Ϫ Ac,
229.1444. C14H24O5 requires M Ϫ Ac, 229.1440).
(1E,3R*,5S*,6S*,7S*)-6,8-Diacetoxy-3,5,7-trimethyl-1-
phenyloct-1-ene 28
A mixture of the allylsilanes 26 and 27 (557 mg, 1.61 mmol) and
boron trifluoride–acetic acid complex (0.37 cm3) in dry di-
chloromethane (10 cm3) were stirred under nitrogen at 5 ЊC for
25 min. The mixture was poured into saturated aqueous sodium
hydrogen carbonate (20 cm3) and extracted with dichlorometh-
ane (2 × 50 cm3). The combined organic layers were washed
with saturated aqueous sodium hydrogen carbonate (25 cm3),
dried (MgSO4), filtered and evaporated under reduced pressure.
Chromatography (SiO2, EtOAc–light petroleum, 1:7) gave the
alkene (345 mg, 86%) as an 83:17 mixture with its epimer at C-6
33; Rf(EtOAc–light petroleum, 1:7) 0.28; νmax(neat)/cmϪ1 1738
(2R*,4R*,5R*,6R*)-5,7-Diacetoxy-2,4,6-trimethylheptanal
Similarly, the alkene 33 (385 mg, 1.11 mmol) gave the aldehyde
(194 mg, 64%); Rf(EtOAc–light petroleum, 1:10) 0.07;
νmax(neat)/cmϪ1 2715 (H–CO) and 1738 (C᎐O); δ (CDCl ; 250
᎐
H
3
MHz) 9.65 (1 H, d, J 1.5, CH᎐O), 4.87 (1 H, dd, J 7.4 and 4.3,
᎐
HCOAc), 3.99–3.82 (2 H, m, CH OAc), 2.51 (1 H, m, HCC᎐O),
᎐
2
2.25–1.70 (2 H, m, 2 × CHMe), 2.08 (3 H, s, Ac), 2.06 (3 H, s,
Ac), 1.65–1.38 (2 H, m, CCH2C), 1.16 (3 H, d, J 6.9, MeC-
CHO), 0.93 (3 H, d, J 6.9, CHMe) and 0.91 (3 H, d, J 6.7,
CHMe); m/z 229 (1%, M Ϫ Ac), 173 (45, M Ϫ MeCHCH2-
CHMeCHO), 131 (97), 127 (95), 113 (99), 75 (35) and 71
(100, CH2CHMeCHO) (Found: Mϩ Ϫ Ac, 229.1420. C14H24O5
requires M Ϫ Ac, 229.1440).
(C᎐O); δ (CDCl ; 250 MHz) 7.38–7.19 (5 H, m, Ph), 6.36
᎐
H
3
(1 H, d, J 15.9, PhCH᎐CH), 5.96 (1 H, dd, J 15.8 and 8.8,
᎐
PhCH᎐CH), 4.84 (1 H, dd, J 7.7 and 3.7, HCOAc), 3.97–3.76
᎐
(2 H, m, CH OAc), 2.40 (1 H, br m, C᎐CCH), 2.25–1.68 (2 H,
᎐
2
m, CHMe and CHMe), 2.08 (3 H, s, Ac), 2.03 (3 H, s, Ac),
1.45–1.16 (2 H, m, CCH C), 1.08 (3 H, d, J 6.7, MeCC᎐C), 0.90
᎐
2
(2R*,4S*,5S*,6S*)-5,7-Diacetoxy-2,4,6-trimethylheptanoic
acid
(3 H, d, J 6.5, CHMe) and 0.88 (3 H, d, J 6.7, CHMe); m/z 346
(12%, Mϩ), 286 (5, M Ϫ HOAc), 226 (7, M Ϫ 2 HOAc), 171
Jones reagent (0.9 mol dmϪ3, 2.0 cm3, 1.8 mmol) was added
dropwise to a stirred solution of the aldehyde (143 mg, 0.53
mmol) derived from 28 in acetone (2 cm3) at 0 ЊC and stirred at
5 ЊC for 15 min. The mixture was poured into saturated aque-
ous sodium bisulfite (3 cm3) and extracted with ether (3 × 25
cm3). The combined organic layers were dried (MgSO4), filtered
and evaporated under reduced pressure to give the acid (120
mg, 79%); Rf(EtOAc–light petroleum, 1:3) 0.12; νmax(neat)/
cmϪ1 3600–3000 (O–H), 1738 (ester C᎐O) and 1710 (acid C᎐O);
(15, PhCH᎐CHCMe᎐CHCHMe), 145 (33, PhCH᎐CHCMe ),
᎐
᎐
᎐
2
144 (91, PhCH᎐CHCMe=CH ), 131 (65, PhCH᎐CHCHMe),
᎐
᎐
2
91 (47, C7H7), 77 (5, Ph) and 43 (100, Ac) (Found: Mϩ,
346.2137. C21H30O4 requires M, 346.2144).
(1E,3R*,5R*,6R*,7R*)-6,8-Diacetoxy-3,5,7-trimethyl-1-
phenyloct-1-ene 33
Similarly, the allylsilanes 32 and 31 (628 mg, 1.31 mmol) gave
the alkene (386 mg, 85%) as an 80:20 mixture with its epimer at
C-6 28; Rf(EtOAc–light petroleum, 1:7) 0.28; νmax(neat)/cmϪ1
᎐
᎐
δH(CDCl3; 250 MHz) 10.8–10.6 (1 H, br, CO2H, exchangeable
with D2O), 4.85 (1 H, dd, J 6.9 and 4.3, HCOAc), 3.99–3.82
(2 H, m, CH2OAc), 2.55 (1 H, m, HCCO2H), 2.17 (1 H, m,
CHMe), 2.08 (3 H, s, Ac), 2.06 (3 H, s, Ac), 1.79 (1 H, m,
CHMe), 1.66–1.40 (2 H, m, CCH2C), 1.21 (3 H, d, J 6.8,
MeCHCO2H), 0.93 (3 H, d, J 6.7, HCMe) and 0.92 (3 H, d,
J 6.9, HCMe); m/z 229 (1%, M Ϫ OAc), 173 (39, M Ϫ MeCH-
CH2 Ϫ CHMeCO2H), 131 (75), 127 (100), 113 (88) and 71 (84)
(Found: Mϩ Ϫ OAc, 229.1447. C14H24O6 requires M Ϫ OAc,
229.1440).
1738 (C᎐O); δ (CDCl ; 250 MHz) 7.36–7.15 (5 H, m, Ph), 6.35
᎐
H
3
(1 H, d, J 15.9, PhCH᎐CH), 6.12 (1 H, dd, J 15.9 and 7.4,
᎐
PhCH᎐CH), 4.89 (1 H, dd, J 7.7 and 3.9, CHOAc), 3.99–3.81
᎐
(2 H, m, CH OAc), 2.40 (1 H, m, C᎐CCH), 2.30–1.75 (2 H, m,
᎐
2
CHMe and CHMe), 2.07 (3 H, s, Ac), 2.05 (3 H, s, Ac), 1.43–
1.16 (2 H, m, CCH C), 1.04 (3 H, d, J 6.7, MeCC᎐C), 0.93 (3 H,
᎐
2
d, J 6.9, CHMe) and 0.92 (3 H, d, J 6.7, CHMe); m/z 346 (<1%,
Mϩ), 286 (2, M Ϫ HOAc), 226 (6, M Ϫ 2 HOAc), 171 (14,
PhCH᎐CHCMe᎐CHCHMe), 145 (16, PhCH᎐CHCMe ), 144
᎐
᎐
᎐
2
(100, PhCH᎐CHCMe᎐CH ), 131 (37, PhCH᎐CHCHMe) and
᎐
᎐
᎐
2
(2R*,4R*,5R*,6R*)-5,7-Diacetoxy-2,4,6-trimethylheptanoic
acid
91 (20, C7H7) (Found: Mϩ, 346.2164. C21H30O4 requires M,
346.2144).
Similarly, the aldehyde (140 mg, 0.51 mmol) derived from 33
gave the acid (125 mg, 85%); Rf(EtOAc–light petroleum, 1:3)
(2R*,3R*,5R*)-2-[(1R*)-1-(Hydroxymethyl)ethyl]-3,4,5,6-
tetrahydro-3,5,6,6-tetramethyl-5-[(E)-2-phenylethenyl]pyran 23
Similarly, the allylsilanes 21 and 22 gave the alkene; δH(CDCl3)
0.12; νmax(neat)/cmϪ1 3600–3000 (O–H), 1738 (ester C᎐O) and
᎐
1708 (acid C᎐O); δ (CDCl ; 250 MHz) 11.0–10.3 (1 H, br,
᎐
H
3
CO2H, exchangeable with D2O), 4.87 (1 H, dd, J 7.4 and 4.3,
HCOAc), 3.98–3.80 (2 H, m, CH2OAc), 2.51 (1 H, m,
HCCO2H), 2.24–2.11 (1 H, m, CHMe), 2.08 (3 H, s, Ac), 2.06
(3 H, s, Ac), 1.81 (1 H, m, CHMe), 1.66–1.40 (2 H, m, CCH2C),
1.15 (3 H, d, J 7.1, MeCHCO2H), 0.93 (3 H, d, J 7.1, CHMe)
and 0.91 (3 H, d, J 6.8, CHMe); m/z 229 (1%, M Ϫ OAc), 173
7.50–7.18 (5 H, m, Ph), 6.39 (1 H, d, J 16, PhCH᎐CH), 6.17
᎐
(1 H, d, J 16, PhCH᎐CH), 3.90–3.33 (3 H, m, CH O and CHO),
᎐
2
2.30–1.40 (5 H, m, CH2CHMe and CHMe and OH), 1.30 (3 H,
s, Me Me C), 1.26 (3 H, s, Me Me C), 1.17 (3 H, s, MeCC᎐C),
᎐
A
B
A
B
1.03 (3 H, d, J 7, CHMe) and 0.86 (3 H, d, J 7, CHMe).
2660
J. Chem. Soc., Perkin Trans. 1, 1998

View Article Online
[53, M Ϫ MeCHCH2CH(Me)CO2H], 131 (73), 127 (100), 113
(77) and 71 (65) (Found: Mϩ Ϫ OAc, 229.1423. C14H24O6
requires M Ϫ OAc, 229.1440).
(from Et2O–pentane) (lit., 92–93 ЊC28 and 100–102 ЊC30);
Rf(AcOH–Et2O–hexane, 1:66:33) 0.14; νmax(KBr)/cmϪ1 3700–
2400 (O–H), 1740 (ester C᎐O) and 1709 (acid C᎐O); δ (CDCl ;
᎐
᎐
H
3
250 MHz) 8.5–8.2 (1 H, br, CO2H, exchangeable with D2O),
4.55 (1 H, dd, J 10.1 and 2.8, HCO), 2.81–2.65 (2 H, m,
CHCO2C and CHCO2H), 1.99 (1 H, m, CH2CHCO), 1.80–1.68
(2 H, m, CCH2C), 1.24 (3 H, d, J 6.9, MeCCO2C), 1.23 (3 H,
d, J 7.2, MeCCO2H) and 1.04 (3 H, d, J 6.6, CH2CHMeCO);
δC(CDCl3) 178.0, 175.8, 82.8, 41.0, 35.1, 32.6, 28.9, 17.5, 16.6
and 9.1; m/z 200 (4%, Mϩ), 182 (5, M Ϫ H2O), 158 (11), 130
(52), 127 (84), 112 (17), 99 (50), 98 (40), 83 (33), 69 (39) and 56
(100), matching published data.27,28
(3R*,5S*,6S*)-6-[(1S*)-1-(Hydroxymethyl)ethyl]-3,4,5,6-
tetrahydro-3,5-dimethylpyran-2-one
Powdered potassium carbonate (200 mg) was stirred with the
above diacetate (103 mg, 0.36 mmol) in dry methanol (5 cm3)
at room temperature for 1 h. The mixture was filtered and the
filter cake was washed with ether (2 × 30 cm3). The combined
organic extracts were evaporated under reduced pressure. The
residue and toluene-p-sulfonic acid (10 mg) in dichloro-
methane (5 cm3) were stirred for 1 h, the mixture was diluted
with dichloromethane (50 cm3) and washed with saturated
aqueous sodium hydrogen carbonate (20 cm3). The organic
layer was dried (MgSO4), filtered and evaporated under reduced
pressure to give the lactone25 (50 mg, 75%); νmax(neat)/cmϪ1
Acknowledgements
We thank the Croucher Foundation for an award to H.-F. C.
3600–3200 (O–H) and 1726 (C᎐O); δ (CDCl ; 250 MHz) 4.26
᎐
H
3
References
(1 H, m, CHO), 3.78–3.53 (2 H, m, CH2OH), 2.82–2.63 (1 H, br,
OH, exchangeable with D2O), 2.51 (1 H, m, HCCO2), 2.07–1.86
(3 H, m, CCHAHBCH and CHCH2OH), 1.40 (1 H, q, J 13,
CCHAHBC), 1.27 (3 H, d, J 7.1, MeCCO2), 0.98 (3 H, d, J 6.3,
CHMe) and 0.88 (3 H, d, J 6.5, CHMe); m/z 169 (3%,
M Ϫ Me), 127 (82) and 56 (100, C3H4O) (Found: Mϩ Ϫ Me,
169.1233. C10H18O3 requires M Ϫ Me, 169.1229).
1 S. F. Martin and D. E. Guinn, Synthesis, 1991, 245.
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5 R. A. N. C. Crump, I. Fleming, J. H. M. Hill, D. Parker, N. L. Reddy
and D. Waterson, J. Chem. Soc., Perkin Trans. 1, 1992, 3277.
6 I. Fleming, R. Henning, D. C. Parker, H. E. Plaut and P. E. J.
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8 T. Mukaiyama and A. Ishida, Chem. Lett., 1975, 319, 1201 and
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9 I. Fleming, J. Goldhill and I. Paterson, Tetrahedron Lett., 1979, 3205
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1197.
(3R*,5R*,6R*)-6-[(1R*)-1-(Hydroxymethyl)ethyl]-3,4,5,6-
tetrahydro-3,5-dimethylpyran-2-one
Similarly, the diacetate (140 mg, 0.49 mmol) derived from 33
gave the lactone (76 mg, 84%); νmax(neat)/cmϪ1 3600–3200 (O–
H) and 1726 (C᎐O); δ (CDCl ; 250 MHz) 4.24 (1 H, dd, J 10.7
᎐
H
3
and 1.9, HCO), 3.77–3.59 (2 H, m, CH2OH), 2.69 (1 H, m,
HCCO2), 2.06–1.89 (2 H, m, 2 × CHMe), 1.71 (2 H, m,
CCH2C), 1.66–1.56 (1 H, br, OH, exchangeable with D2O), 1.23
(3 H, d, J 6.8, MeCCO2), 0.99 (3 H, d, J 6.6, CHMe) and 0.92
(3 H, d, J 6.6, CHMe); m/z 186 (<1%, Mϩ), 127 (78) and 56
(100, C3H4O) (Found: Mϩ, 186.1258. C10H18O3 requires M,
186.1256).
(3R*,5S*,6S*)-6-[(1R*)-1-Carboxyethyl]-3,4,5,6-tetrahydro-
3,5-dimethylpyran-2-one 34
13 I. Fleming, Chemtracts: Org. Chem., 1996, 9, 1; G. R. Jones and
Y. Landais, Tetrahedron, 1996, 37, 7599; K. Tamao, Adv. Silicon
Chem., JAI Press, Greenwich, CT, 1996, 3, 1.
14 A. Barbero, D. C. Blakemore, I. Fleming and R. N. Wesley, J. Chem.
Soc., Perkin Trans. 1, 1997, 1329.
15 I. Fleming and N. K. Terrett, J. Organomet. Chem., 1984, 264, 99.
16 I. Fleming and A. Pearce, J. Chem. Soc., Perkin Trans. 1, 1981, 251;
H.-F. Chow and I. Fleming, J. Chem. Soc., Perkin Trans. 1, 1984,
1815.
The alcohol (40 mg, 0.22 mmol) and pyridinium dichromate
(430 mg, 1.14 mmol) in dry DMF (2.0 cm3) were stirred at room
temperature for 10 h. The mixture was poured into saturated
aqueous sodium bisulfite (10 cm3) and acidified to pH 1 with
concentrated hydrochloric acid. Sodium chloride was added to
make a saturated solution, which was extracted with ether
(5 × 15 cm3). The combined organic layers were dried (MgSO4),
filtered and evaporated under reduced pressure. Chrom-
atography (SiO2, AcOH–Et2O–hexane, 1:66:33) gave the
Prelog–Djerassi ( )-lactonic acid (35 mg, 82%) as needles, mp
112–112.5 ЊC (from Et2O–pentane) (lit., 119–120 ЊC;24 110–
113 ЊC;25 114–115 ЊC;26 and 116–117 ЊC27); Rf(AcOH–Et2O–
hexane, 1:66:33) 0.14; νmax(KBr)/cmϪ1 3700–2400 (O–H), 1742
17 I. Fleming and D. Marchi, Synthesis, 1981, 560.
18 I. Fleming, D. Marchi and S. K. Patel, J. Chem. Soc., Perkin Trans.
1, 1981, 2518.
19 I. Fleming, P. E. J. Sanderson and N. K. Terrett, Synthesis, 1992, 69.
20 I. Fleming, N. J. Lawrence, A. K. Sarkar and A. P. Thomas, J. Chem.
Soc., Perkin Trans. 1, 1992, 3303.
21 For another example, see P. Mohr, Tetrahedron Lett., 1995, 36, 7221.
22 Y. Landais and L. Parra-Rapado, Tetrahedron Lett., 1996, 37, 1209;
see also R. Angelaud and Y. Landais, Tetrahedron Lett., 1997, 38,
8841; R. Angelaud, Y. Landais and L. Parra-Rapado, Tetrahedron
Lett., 1997, 38, 8845.
23 A. Claesson and L.-I. Olsson, J. Am. Chem. Soc., 1979, 101, 7302
and references therein; A. Burger, J.-P. Roussel, C. Hetru, J. A.
Hoffmann and B. Luu, Tetrahedron, 1989, 45, 155; J. K. Crandall,
D. J. Keyton and J. Kohne, J. Org. Chem., 1968, 33, 3655; L. G.
Damm, M. P. Hartshorn and J. Vaughan, Aust. J. Chem., 1976, 29,
1017; M. P. Hartshorn, R. S. Thompson and J. Vaughan, ibid., 1977,
30, 865; J. W. Blunt, M. P. Hartshorn, M. H. G. Munroe, L. T.
Soong, R. S. Thompson and J. Vaughan, J. Chem. Soc., Chem.
Commun., 1980, 820; C. J. Elsevier, J. Meijer, H. Westmijze,
P. Vermeer and L. A. Van Dijk, J. Chem. Soc., Chem. Commun.,
1982, 84 and references therein; I. Fleming, Y. Landais and P. R.
Raithby, J. Chem. Soc., Perkin Trans. 1, 1991, 715.
(ester C᎐O), 1710 (acid C᎐O), 1458, 1385, 1260, 1212, 1192 and
᎐
᎐
1098; δH(CDCl3; 250 MHz) 7.6–7.4 (1 H, br, CO2H, exchange-
able with D2O), 4.60 (1 H, dd, J 10.4 and 2.2, HCO), 2.77 (1 H,
dq, J 7.2 and 2.4, CHCO2H), 2.57 (1 H, m, CHCO2C), 2.04–
1.86 (2 H, m, CHAHBCHCO), 1.47 (1 H, t, J 12.6, CCHAHBC),
1.29 (3 H, d, J 7.0, MeCCO2C), 1.20 (3 H, d, J 7.3, MeCCO2H)
and 1.02 (3 H, d, J 6.2, CH2CHMeCO); δC(CDCl3) 176.6,
174.0, 86.2, 41.2, 37.5, 36.3, 31.1, 17.2, 17.0 and 8.6; m/z 200
(1%, Mϩ), 182 (1, M Ϫ H2O), 158 (7), 130 (53), 127 (97), 99
(75), 98 (45), 83 (48), 69 (62) and 56 (100), matching published
data.24–27,28,29
(3R*,5R*,6R*)-6-[(1S*)-1-Carboxyethyl]-3,4,5,6-tetrahydro-
3,5-dimethylpyran-2-one 35
Similarly, the alcohol (72 mg, 0.39 mmol) derived from 33 gave
the ( )-lactonic acid (62 mg, 80%) as prisms, mp 124–126 ЊC
24 S. Masamune, C. U. Kim, K. E. Wilson, G. O. Spessard, P.-E.
Georghiou and G. S. Bates, J. Am. Chem. Soc., 1975, 97, 3512.
25 J. D. White and Y. Fukuyama, J. Am. Chem. Soc., 1979, 101, 226.
26 G. Stork and V. Nair, J. Am. Chem. Soc., 1979, 101, 1315.
J. Chem. Soc., Perkin Trans. 1, 1998
2661

View Article Online
27 P. A. Bartlett and J. L. Adams, J. Am. Chem. Soc., 1981, 102, 337.
28 R. E. Ireland and J. P. Daub, J. Org. Chem., 1981, 46, 479.
Lett., 1981, 22, 3725; R. W. Hoffmann, H.-J. Zeiss, W. Ladner and
S. Tabche, Chem. Ber., 1982, 115, 2357; D. A. Evans and J. Bartroli,
Tetrahedron Lett., 1982, 23, 807.
29 P. A. Grieco, Y. Ohfune, Y. Yokoyama and W. Owens, J. Am. Chem.
Soc., 1979, 101, 4749; M. Isobe, Y. Ichikawa and T. Goto,
Tetrahedron Lett., 1981, 22, 4287; S. Masamune, Aldrichimica Acta,
1978, 11, 23; S. Masamune, M. Hirama, S. Mori, S. A. Ali and
D. S. Garvey, J. Am. Chem. Soc., 1981, 103, 1568; K. Maruyama,
Y. Ishihara and Y. Yamamoto, Tetrahedron Lett., 1981, 22, 4235;
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30 D. J. Morgans, Jr., Tetrahedron Lett., 1981, 22, 3721.
Paper 8/04270E
Received 5th June 1998
Accepted 25th June 1998
2662
J. Chem. Soc., Perkin Trans. 1, 1998