Synthesis of the acyltetronic acid ionophore tetronasin (ICI M139603)

Article abstract of DOI:10.1039/a804170i

A synthetic strategy for the preparation of tetronasin 1, an acyltetronic acid ionophore demonstrating antibiotic, antiparasitic and growth promotion in ruminants is described. The key step involves a metal mediated cyclization reaction which creates two

Full text of DOI:10.1039/a804170i

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Synthesis of the acyltetronic acid ionophore tetronasin
(ICI M139603)
Steven V. Ley,*,a Dearg S. Brown,b J. Andrew Clase,a Antony J. Fairbanks,a
Ian C. Lennon,b Helen M. I. Osborn,a Elaine S. E. Stokes (née Owen)b and
David J. Wadsworthb
a Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge,
UK CB2 1EW
b Department of Chemistry, Imperial College of Science, Technology and Medicine, London,
UK SW7 2AY
A synthetic strategy for the preparation of tetronasin 1, an acyltetronic acid ionophore demonstrating
antibiotic, antiparasitic and growth promotion in ruminants is described. The key step involves a metal
mediated cyclization reaction which creates two rings and four new stereocentres in a highly efficient
manner. The configurations of three of these stereocentres are as required for the synthesis of tetronasin.
The remaining stereocentre is readily epimerised to the natural configuration at a later stage of the
synthesis.
Tetronasin (ICI M139603) 1, an acyltetronic acid ionophore
published work the tri-n-butyl stannyl group served as a suit-
able coupling component with acid chlorides under palladium
catalysed conditions.
27
29
The stabilised Wittig reagent 5 is a known three carbon build-
ing block.7 The synthesis of the remaining fragments 6, 7 and
8 are reported below, together with further coupling studies
leading to the synthesis of tetronasin 1 itself.
OH
19
26
17
21
13
11
25
30
O
O
H
H
H
H
18
OMe
28
The preparation of the phosphonate 6 could be readily
achieved from the alcohol 95f in a series of straightforward
steps (Scheme 2).
32
5
O–Na+
H
Tetronasin 1
3
33
34
Firstly 9 was converted to the corresponding tosylate 10
which was then coupled with the Grignard reagent derived from
5-bromopent-1-ene in the presence of Li2CuCl4 to afford the
olefin 11.8 This in turn was subjected to ozonolysis followed by
Lehnert modified Knoevenagel condensation9 of the resulting
aldehyde 12 with triethylphosphonoacetate to give 13 as a mix-
ture of the desired allyl and undesired vinyl isomers in a ratio of
4:1 in favour of the former isomer. Removal of the benzyl
protecting group improved this ratio to 200:1 in favour of the
allyl isomer, and subsequent treatment with TMSCl in the pres-
ence of triethylamine afforded the silyl protected phosphonate
6.
The keto phosphonate fragment 7 was also readily obtained
from the same initial chiral alcohol 9. Firstly, conversion10
to the corresponding bromide 15 was necessary and this was
followed by reaction of 15 with the dianion generated from
dimethyl 2-oxopropylphosphonate to give the required
coupling component 7 in 56% overall yield (Scheme 3).
For the synthesis of the remaining tetrahydrofuran aldehyde
fragment 8 we report two routes, both of which are efficient and
allow access to multigramme quantities of material. We have
previously published5f an earlier route to this material, but it is
less amenable to scale up and is therefore not reported here.
Consistent with our synthesis plan to use common building
blocks wherever possible, one route to 8 employs the chiral
alcohol 9, the use of which was reported earlier. Oxidation of 9
under Swern conditions11 followed by addition of (Z)-crotyl-
(ϩ)-diisopinocampheylborane12 and oxidative work-up gave 16
in which three of the required stereogenic centres are set up
in place (Scheme 4). After standard protection as the tert-
butyldimethylsilyl ether and hydroboration with 9-BBN, oxid-
ative work-up followed by a Swern oxidation gave the aldehyde
19. This was homologated to the allylic ester 20 by reaction with
31
O
O
O
produced by Streptomyces longisporoflavus,1 is of commercial
interest owing to its biological activity as an antibiotic,
antiparasitic and growth promotion agent in ruminants.2 It has
also attracted attention owing to its unusual structure1 and
properties3 and has been the subject of extensive biosynthetic4
and synthetic studies.5
In terms of total synthesis, tetronasin 1 presents a significant
challenge in that it contains twelve stereogenic centres, three
different heterocyclic ring systems, two stereodefined alkenes
and a triequatorially substituted cyclohexane unit. Further-
more, the acyltetronic acid group occurs in only a limited
number of natural products, consequently there are relatively
few methods available for its construction.
In the initial synthesis plan towards tetronasin 1 we propose
to adopt a conceptually interesting approach involving a metal
templated polyene cyclization reaction of an open chain pre-
cursor 2. It was hoped that metal chelation might encour-
age a favourable reacting conformation leading directly to an
advanced polycyclic species 3 which could be further processed
to 1 (Scheme 1). The required open chain precursor 2 in turn,
could be assembled from readily prepared building blocks 4–8
in a convergent fashion.
Results and discussion
In previous studies we had shown that the stannyl tetronic acid
fragment 4 was indeed an excellent precursor for acyltetronic
acids and had completed the synthesis of three natural prod-
ucts, carlosic acid, carolinic acid and agglomerin A.6 In this
J. Chem. Soc., Perkin Trans. 1, 1998
2259

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EtO320C
OTMS
PO(OEt)2
12
11
31
29
5
6
14
MeO23C
PO(OMe)2
32
13
17
6
4
BnO
O
18
PPh3
5
7
27
29
O
O
14
19
21
26
32
25
4
EtO2C
HO
O
3
H
H
O
31
OMe
11
28
33
2
OH
34
6
27
O
19
SnBu3
OMe
26
21
OHC
25
O
O
H
H
CO2Et
33
OMe
34
28
4
8
O
O
M
H
O
O
H
OH
MeO
O
EtO2C
O
O
H
H
H
H
OMe
3
OMe
H
O
O
O
OH
O
O
H
H
H
H
OMe
O–Na+
H
O
Tetronasin 1
O
O
Scheme 1
triethylphosphonoacetate under the Masamune–Roush condi-
tions13 and subsequently reduced with diisobutylaluminium
hydride in tetrahydrofuran in excellent overall yield.
The stage was now set to introduce the remaining two stereo-
genic centres via a Sharpless asymmetric oxidation procedure.14
Thus, reaction of 21 with titanium() isopropoxide, tert-
butylhydroperoxide and (ϩ)-diethyl tartrate gave the desired
epoxide 22 (Scheme 4).
Deprotection of 22 with tetra-n-butylammonium fluoride in
THF at 60 ЊC resulted in concomitant intramolecular epoxide
ring opening to provide the tetrahydrofuran 23 in 85% yield.
The remaining steps in the synthesis were relatively straight-
forward and proceeded in equally high yields. Selective tosyl-
ation of the primary hydroxy group in 23 to give 24 was achieved
by reaction with dibutyltin oxide15 followed by toluene-p-
sulfonyl chloride and triethylamine. This was then transformed
to 26 by reduction with Super Hydride (LiEt3BH) and sub-
sequent alkylation of the hydroxy group with methyl iodide and
potassium hydride. Finally, deprotection with hydrogen using
palladium on charcoal as catalyst, followed by oxidation with
tetra-n-propylammonium perruthenate (TPAP)16 gave the
required tetrahydrofuran aldehyde 8 (Scheme 4). This material
was identical in all respects to that which we had prepared by
the earlier route5f and to that obtained by natural product
degradation.5f
In the second route to aldehyde 8 (Scheme 5) we sought to
exploit additional synthetic methodology developed in our
laboratories17 for the formation of carbon᎐carbon bonds
2260
J. Chem. Soc., Perkin Trans. 1, 1998

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OBn
OBn OH
OBn
OBn
OBn
OBn
b)
a)
c)
b)
CHO
OH
16
OTBS
OR
9
17
11
12
9 R = H
a)
c)
10 R = Ts
d)
OH
CHO
30
EtO2C
PO(OEt)2
OBn
OR1
EtO2C
PO(OEt)2
OBn
12
OBn
TMSO
e)
d)
f)
OTBS
31
5
OTBS
OTBS
11
CO2Et
6
20
f)
19
18
13 R1 = Bn
14 R1 = H
6
e)
Scheme 2 Reagents: a) TsCl, pyridine, 88%; b) BrMg(CH2)3CH᎐CH2,
᎐
OBn
g)
Li2CuCl4, 93%; c) O3, Ϫ78 ЊC, PPh3, 71%; d) TiCl4, NMM, EtO2-
OBn
O
CCH2P(O)(OEt)2, 90%; e) Na, NH3, 77%; f) TMSCl, Et3N, 98%
OTBS
OTBS
22
OH
OH
21
a)
Br
OH
h)
BnO
BnO
9
15
OR
OBn
OBn
j)
O
O
b)
O
H
O
P(OMe)2
H
H
H
OH
OH
25
k)
23 R = H
24 R = Ts
29
i)
14
13
17
P(O)(OMe)2
27
BnO
O
18
m)
OR
19
7
26
21
25
OHC
Scheme 3 Reagents: a) NBS, PPh3, CH2Cl2, 89%; b) NaH, BunLi,
O
O
H
H
H
H
OMe
OMe
THF, 71%
28
26 R = Bn
27 R = H
8
adjacent to oxygen in cyclic ethers using 2-phenylsulfonyl
derivatives.
l)
Accordingly, the alcohol 285f was oxidised under Swern
conditions11 and the aldehyde thus formed treated with (E)-
crotyl-(Ϫ)-diisopinocampheylborane12 to afford the alkene 29
after work-up with diethanolamine.18 Deprotection of the silyl
ether with TBAF afforded diol 30 with three of the required five
stereogenic centres efficiently established. The diol 30 was next
converted to the nitrile 32 by selective 2-mesitylenesulfonylation
of the primary hydroxy group and displacement with sodium
cyanide in 67% overall yield for these first four steps. The nitrile
group in 32 was reduced with diisobutylaluminium hydride and
the intermediate lactol treated with phenylsulfinic acid, using
our previously established protocol,17 to afford the crystalline
sulfone 34 in good yield. Sulfone 34 was then reacted with
ethynylmagnesium bromide in the presence of zinc chloride at
room temperature to afford stereoselectively the trans-sub-
stituted tetrahydrofuran 35. This was then hydrolysed with
mercuric oxide and sulfuric acid19 to yield the corresponding
acetyl derivative 36 in 71% yield from the sulfone 34. Finally, the
carbonyl group in 36 was reduced with sodium borohydride in
methanol at room temperature to afford a mixture of diastereo-
meric alcohols 37a and 37b (3:2 37a:37b). Alternatively, reduc-
tion with L-Selectride20 in THF at Ϫ78 ЊC afforded exclusively
alcohol 37a which could be readily inverted to the required
isomer 37b using standard Mitsunobu21 reaction conditions.
Methylation of alcohol 37b followed by ozonolysis of ether 38
afforded the furan fragment 8. This second route to 8 is com-
plementary to the first sequence, it provides efficient access to
good quantities of 8, and, moreover, it employs methods
developed by our group.
Scheme 4 Reagents: a) i) DMSO, (COCl)2, CH2Cl2 then Et3N; ii) (ϩ)-
(Z)-crotyldiisopinocampheylborane, THF then NaOH, H2O2, 70%; b)
TBDMSOTf, Et3N, CH2Cl2, 100%; c) 9-BBN, THF then NaOH, H2O2,
95%; d) DMSO, (COCl)2, CH2Cl2 then Et3N, 85%; e) EtO2CCH2-
PO(OEt)2, LiCl, Pri2EtN, MeCN, 93%; f) DIBAL-H, THF, 97%;
g) -(ϩ)-diethyl tartrate, ButOOH, Ti(OPri)4, CH2Cl2, 80%; h) TBAF,
THF, 85%; i) Bu2SnO, MeOH, TsCl, Et3N, 94%; j) LiEt3BH, THF, 92%;
k) KH, THF then MeI, 90%; l) Pd/C, H2, MeOH, 95%; m) TPAP, NMO,
4 Å sieves, CH2Cl2, 93%
Now that all the key fragments as outlined in the initial plan
for the synthesis of tetronasin 1 were available, their coupling
and further processing could be investigated (Scheme 6).
Firstly we assembled the C-13 to C-26 unit by coupling the
central keto phosphonate 7 with the terminal aldehyde group of
the tetrahydrofuran fragment 8 using the previously described
Masamune–Roush conditions13 to give the enone product 39 in
a completely (E)-selective fashion with no detectable epimeriz-
ation of the sensitive stereogenic centre adjacent to the alde-
hyde functionality. Reduction of the enone 39 with Noyori’s
(S)-BINAL-H reagent22 proceeded well to give the alcohol 40
with excellent control of the newly formed stereogenic centre.
The minor amount of the unwanted diasteroisomer was readily
inverted to give more 40 using the Mitsunobu procedure21
followed by hydrolysis in the normal way. The stereochemical
outcome of this reduction reaction is in agreement with the
model predicted by Noyori22 and also confirmed by the fact that
it was later converted to the natural product itself. Following
protection of 40 as its tert-butyldimethylsilyl ether 41 and
J. Chem. Soc., Perkin Trans. 1, 1998
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methanol to give 48 as a pure product in excellent overall yield
(Scheme 6).
b)
a)
OH
HO
OTBDPS
Whilst compound 48 is a suitable material on the pathway to
natural product tetronasin 1 based on our original synthesis
plan, it also contains all the elements necessary to undergo a
metal mediated polyene cyclization in its own right. Namely,
the secondary hydroxy group is ideally placed to undergo a
conjugate addition to the acceptor dienic ester unit which, via
reequilibration of the resulting enolate, could undergo the
second cyclization by Michael addition to the terminal meth-
acrylate unit to assemble the cyclohexyl ring of the natural
product in one operation. This attractive option was thus
worthy of investigation in spite of the realization that we would
be setting a tough challenge in forming two new rings and creat-
ing four new stereogenic centres simultaneously. Nevertheless,
we felt confident that the natural conformation might lead to
favourable transition states and hence to the double cascade
cyclization reaction under appropriate conditions. Moreover,
for various reasons, the product of this process might be more
readily converted to tetronasin 1.
OTBDPS
OH
30
OH
28
29
c)
e)
OH
R
O
f)
H
OH
33
31 R = OSO2Ar
32 R = CN
d)
g)
SO2Ph
O
H
34
O
H
H
35
Although we investigated many conditions for this ambitious
concept we were pleased to find that treatment of 48 with
potassium hexamethyldisilazide in toluene at 0 ЊC gave a single
product 49 in 67% yield!
h)
i)
What should be noticed in this reaction is that we do form the
tetrahydropyran and cyclohexane rings with complete control,
but the configuration of the C-4 (tetronasin numbering) methyl
substituent is opposite to that found in tetronasin 1. The proof
of configuration of this C-4 centre follows from extensive
NMR investigation and later experiments. Other metal bases,
solvents and temperature conditions used in this reaction were
much less satisfactory, leading to either monocyclization or
decomposition. We also investigated methods to install the
correctly configured methyl substituent by later introduction
via alkylation or by epimerisation of the C-4 stereogenic centre
in 49 but without success.
O
H
O
H
H
H
H
OH
OH
O
36
37a
+
j)
O
H
O
H
H
OMe
37b
38
k)
27
In order to correct this stereochemical problem we devised
an alternative sequence which proved to be very satisfactory.
Firstly we found that the diester 49 could be selectively reduced
to the alcohol 51 using lithium borohydride in THF to give 51
in 58% yield together with some of the diol 50 (19%) and a little
(4%) recovered starting material (Scheme 7). Reaction of 51
with tert-butyldimethylsilyl triflate gave the protected derivative
52 which upon treatment with diisobutylaluminium hydride in
CH2Cl2 gave the differentiated diol 53 (79%). This could then be
oxidised to the aldehyde 54 using the Dess–Martin periodinane
reagent.23 Although aldehyde 54 could not be epimerised under
any base mediated conditions which we investigated, we found
that epimerisation to the required aldehyde 55 could be
achieved in 85% yield by simply refluxing the aldehyde 54 with
morpholine and catalytic toluene-p-sulfonic acid (Scheme 7).
This aldehyde 55 was identical in all respects to that prepared
by Yoshii5g as a late stage precursor in their synthesis of
tetronasin which involved reaction of 55 with N2CHCO2CH2-
COOCH3 in the presence of ZrCl4 to give the β-keto ester
derivative 56.5g This, upon Dieckmann cyclization and depro-
tection using conditions first developed by our group involving
tetra-n-butylammonium fluoride in THF,24 following work-up
as the sodium salt gave the acyltetronic acid natural product
tetronasin 1.
19
26
21
25
OHC
O
H
H
OMe
28
8
Scheme 5 Reagents: a) i) (COCl)2, DMSO, Et3N; ii) (E)-crotyl-(Ϫ)-
diisopinocampheylborane, THF, Ϫ85 ЊC; iii) NaOH (aq), H2O2; iv)
HN(CH2CH2OH)2, Et2O, 74%; b) TBAF, THF, 100%; c) Et3N, DMAP,
2,4,6-triisopropylbenzenesulfonyl chloride, 90%; d) NaCN, DMSO,
100%; e) DIBAL-H, PhMe, 94%; f) PhSO2H, CaCl2, CH2Cl2, 93%; g)
HC᎐CMgBr, ZnBr2, THF, 88%; h) yellow HgO, H2SO4 (aq), acetone,
81%; i) NaBH4, MeOH, 89% (37a:37b 3:2); j) i) NaH, THF; ii) MeI,
᎐
᎐
87%; k) i) O3; ii) Ph3P, 84%
removal of the benzyl group with sodium in ammonia at
Ϫ33 ЊC, the intermediate alcohol 42 was oxidised to the alde-
hyde 43 in 95% yield using catalytic TPAP16 and N-methyl-
morpholine-N-oxide as cooxidant. Coupling of 43 to the next
key fragment 6 in the proposed synthesis of 1 was best achieved
using lithium hexamethyldisilazide in THF at Ϫ78 ЊC to
deprotonate the ester phosphonate 6 which was then reacted
with 43 and worked-up by treatment with a pH 3 buffer to give
45 in its deprotected form in excellent yield and with excellent
stereochemical control. Many alternative conditions were
investigated for this coupling but were much less successful,
giving either mixtures of double bond isomers or causing
racemisation of the stereogenic centre next to the aldehyde
group in 43. Once again we found it most convenient to oxidise
the hydroxy group in 45 to the aldehyde 46 using the TPAP
reagent system which proceeded in 95% yield and with no
detectable scrambling of the sensitive stereogenic centres.
In summary we report above the concise formal synthesis of
tetronasin 1, an important ionophore antibiotic using some of
the methods and reagents developed in our laboratory.
Experimental
General experimental
Ether refers to diethyl ether and petrol refers to light petroleum
(bp 40–60 ЊC). Petrol was distilled and other solvents were dried
and distilled before use; ether and tetrahydrofuran from
Further homologation of 46 was achieved via a Wittig
reaction followed by silyl deprotection with Dowex-50W in
2262
J. Chem. Soc., Perkin Trans. 1, 1998

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27
21
29
19
OHC
26
17
13
a)
P(O)(OMe)2
+
25
BnO
O
O
18
H
H
BnO
O
O
OMe
7
H
H
8
28
OMe
39
b)
e)
d)
OHC
TBSO
HO
O
O
TBSO
H
H
H
BnO
RO
O
H
OMe
42
OMe
H
H
OMe
40 R = H
43
c)
41 R = TBS
f)
h)
EtO2C
EtO2C
O
OR
O
TBSO
TBSO
H
H
H
H
OMe
OMe
OHC
46
44 R = TMS
45 R = H
g)
i)
27
29
3
26
17
21
MeO2C
EtO2C
O
RO
H
H
31
OMe
11
28
6
47 R = TBS
48 R = H
j)
Scheme 6 Reagents: a) LiCl, DIPEA, MeCN, 67%; b) (S)-BINAL-H, 63%; c) TBSCl, imidazole, CH2Cl2, 98%; d) Na, NH3, 99%; e) TPAP, NMO,
4 Å sieves, 95%; f) LHMDS, 6, THF, 82%; g) acetate buffer (aq), 100%; h) TPAP, NMO, 4 Å sieves, CH2Cl2, 95%; i) MeO2C(Me)᎐PPh3, CHCl3,
᎐
100%; j) Dowex 50W, MeOH, 100%
sodium–benzophenone ketyl, dichloromethane from phos-
phorous pentoxide, toluene from sodium, acetonitrile from
calcium hydride, dimethylformamide from calcium hydride
below 50 ЊC and dimethyl sulfoxide from calcium hydride. Other
solvents were purified by standard procedures as necessary.
Analytical thin layer chromatography was performed using
pre-coated glass-backed plates (Merck Kieselgel 60 F254) and
visualised by ultra-violet light (254 nm), acidic ammonium
molybdate, basic potassium permanganate, acidic palladium
chloride or iodine as appropriate. The products were purified
by column chromatography on Merck silica gel 60 (Art. 9385
230–400 mesh) under pressure unless otherwise stated. Florisil
200–300 mesh (supplied by BDH) was used for florisil
chromatography.
ment or by MEDAC Services, Brunel University. Melting
points were performed on a Reichert hot stage apparatus and
are uncorrected.
(2R)-(؊)-3-(Benzyloxy)-2-methylpropan-1-ol 9
A
solution of (2R)-methyl 3-hydroxy-2-methylpropanoate
(100 g, 0.848 mol), dihydropyran (108 ml, 1.18 mol) and pyrid-
inium p-toluenesulfonate (12 g, 0.06 mol) in dichloromethane
(500 cm3) was stirred at room temperature for 16 hours. The
solution was poured into saturated aqueous NaHCO3 (100
cm3) and dichloromethane (300 cm3). The organic layer was
separated, washed with brine, dried (MgSO4), filtered and
evaporated to dryness. The product was used without any
further purification.
1H NMR spectra were recorded on Bruker AM-200, Bruker
WM-250, JEOL GSX-270, Bruker AM-400 or Bruker DRX-500
spectrometers using CDCl3 as solvent and residual CHCl3 as
reference unless otherwise stated. Mass spectra were obtained
on VG 7070B, VG 12-253, VG ZAB-E (SERC mass spec-
trometry service, Swansea), Kratos MS 890, Kratos MALDI-2
or Bruker Apex2 FT-ICR (4.7 T magnet) spectrometers.
MALDI spectra were recorded using 2,5-dihydroxybenzoic
acid as matrix. IR spectra were recorded on a Perkin-Elmer
983G spectrophotometer as liquid films or Nujol mulls. Optical
rotations were measured using an Optical Activity AA-1000
polarimeter. Elemental microanalyses were performed in the
microanalytical laboratories of Imperial College Chemistry
Department or of Cambridge University Chemistry Depart-
Lithium aluminium hydride (26.8 g, 0.71 mol) was suspended
in ether (300 cm3) and cooled to 0 ЊC. The crude ester in ether
(200 cm3) was added dropwise over 1 hour at 0 ЊC. The mixture
was allowed to warm to room temperature and stirred for a
further 4 hours. The reaction was cooled to 0 ЊC and quenched
by the careful addition of water (25 cm3), 2  aqueous sodium
hydroxide (25 cm3) and water (75 cm3). The resulting mixture
was stirred at room temperature for 30 minutes and filtered. The
solids were repeatedly washed with ether and the combined
filtrates evaporated to dryness, to yield the crude THP alcohol
(145 g, 0.83 mmol).
Potassium tert-butoxide (112 g, 1 mol) was dissolved in THF
(200 cm3) and cooled to 0 ЊC. A solution of the crude THP
alcohol (~145 g, 0.83 mmol) in THF (300 cm3) was added and
J. Chem. Soc., Perkin Trans. 1, 1998
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19
26
13
EtO2C
25
17
21
a)
MeO2C
O
EtO2C
O
HO
O
H
H
H
H
18
H
H
OMe
OMe
11
11
48
49
6
4
b)
H
CO2Me
OH
OR
O
O
H
H
H
H
O
O
OMe
H
H
c)
H
H
OMe
+
51 R = H
50
H
H
52 R = TBS
OH
CO2Me
d)
TBSO
TBSO
O
O
H
O
O
H
H
H
H
H
H
H
OMe
OMe
e)
53
4
54
H
H
CHO
OH
f)
TBSO
TBSO
O
O
O
O
H
H
H
H
H
H
H
H
OMe
OMe
55
56
4
H
H
O
CHO
CO2Me
O
O
OH
O
O
H
H
H
H
OMe
O–Na+
Tetronasin 1
H
O
O
O
Scheme 7 Reagents: a) KHMDS, toluene, 67%; b) LiBH4, THF, 19% of 50 and 58% of 51; c) TBSOTf, pyridine, THF, 91%; d) DIBAL-H,
CH2Cl2, 79%; e) periodinane, CH2Cl2, 88%; f) morpholine, p-TSA, CH2Cl2, 85%
stirred for 40 minutes at 0 ЊC. Benzyl bromide (106 cm3, 0.89
mol) was added slowly over 45 minutes, the mixture was
allowed to warm to room temperature and stirred for 16 hours.
The reaction was quenched by the addition of water (500 cm3),
then extracted with ether (4 × 150 cm3). The combined organic
layers were washed with brine, dried (MgSO4), filtered and
evaporated to dryness. The crude residue was dissolved in
methanol (400 cm3) and Amberlite-120 acidic ion-exchange
resin (200 g) added. The mixture was stirred vigorously at room
temperature for 16 hours, filtered and the resin washed several
times with methanol and ethyl acetate. The combined filtrates
were evaporated to dryness. Chromatography of the residue on
silica gel (50% ether–petrol) yielded the alcohol 9 (140 g, 90%)
as a pale yellow oil (Found: C, 73.05; H, 9.07. C11H16O2C
2264
J. Chem. Soc., Perkin Trans. 1, 1998

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requiresC,73.30;H, 8.95%);[α]D23 ϩ15(c3.8inCHCl3), {lit.25 [α]D23
Ϫ12.9 (c 3.44 in CHCl3, enantiomer)}; νmax(thin film)/cmϪ1 3404,
2957, 1494, 1362, 1309, 1096, 1040, 737 and 698; δH(270
MHz; CDCl3) 7.39–7.27 (5H, m, ArH), 4.52 (2H, s, CH2Ph),
3.64–3.59 (3H, m, 1-H2, 3-H), 3.46 (1H, dd, J 9.0 and 8.0, 3-H),
2.50 (br s, OH), 2.14–2.04 (1H, m, 2-H), 0.88 (3H, d, J 7.1,
2.0, 2-H2), 1.46 (7H, m, 3-H2, 4-H2, 5-H2 and 6-H), 0.92 (3H, d,
J 6.8, 6-Me); m/z (EI) 234 (Mϩ), 191 (Mϩ Ϫ C3H7) and 91
ϩ
(C7H7 ).
(2E,7R)-Diethyl 1-ethoxycarbonyl-8-benzyloxy-7-methylnon-2-
enylphosphonate 13a and (1E,7R)-diethyl 1-ethoxycarbonyl-8-
benzyloxy-7-methylnon-1-enylphosphonate 13b
ϩ
2-Me); m/z (EI) 180 (Mϩ), 162 (Mϩ Ϫ H2O), 91 (C7H7 ) and 89
(Mϩ Ϫ C7H7).
Aldehyde 12 (13.85 g, 59 mmol) was dissolved in THF (50 cm3)
and added to titanium tetrachloride (22.43 g, 118 mmol) in
THF (400 cm3) at 5 ЊC, followed by triethylphosphonoacetate
(11.7 cm3, 50 mmol), and N-methylmorpholine (26 cm3, 236
mmol). The mixture was stirred for 4.5 hours, water was then
added (100 cm3), stirred vigorously for 15 minutes, and the mix-
ture poured into ether (300 cm3). The organics were washed
with water, aqueous sodium hydrogen carbonate and brine,
then dried (MgSO4), filtered and concentrated in vacuo to give a
4:1 mixture of allylic to vinylic phosphonates. The residue was
purified by chromatography (SiO2, 20% acetone–petrol) to give
allylic and vinylic benzylphosphonates 13a and 13b (23.27 g,
90%) (Found: C, 62.88; H, 8.49. C23H37O6 requires C, 62.70; H,
8.47%); νmax(thin film)/cmϪ1 2978, 2930, 2857, 1733, 1617, 1451,
1389, 1368, 1257, 1147, 1097, 1027, 969, 740 and 699; δH(270
MHz; CDCl3) Allylic 13a: 7.35 (5H, m, PhH), 5.64 (2H, m, 2-H
and 3-H), 4.48 (2H, s, PhCH2O), 4.17 [6H, m, (OCH2Me) × 3],
3.30 (1H, m, 8-H1), 3.23 (1H, m, 8-H1), 2.06 (2H, m, 4-H2), 1.50
[14H, m, 5-H2, 6-H2, 7-H and (OCH2CH3) × 3], 0.91 (3H, d,
J 6.7, 7-Me); Vinylic 13b: 7.35 (5H, m, PhH), 7.10 (1H, dt, J
23.0 and 7.5, 2-H), 4.48 (2H, s, PhCH2O), 4.17 [6H, m,
(OCH2Me) × 3], 3.30 (1H, m, 8-H1), 3.23 (1H, m, 8-H1) 2.50
(2H, ddd, J 14.9, 7.5 and 3.1, 3-H2), 1.50 [16H, m, 4-H2, 5-H2,
6-H2, 7-H and (OCH2CH3) × 3], 0.90 (3H, d, J 6.7, 7-Me);
m/z (EI) 440 (Mϩ), 395 (Mϩ Ϫ OEt), 367 (Mϩ Ϫ OEt Ϫ C2H4),
(2S)-3-(Benzyloxy)-2-methyl-1-(toluene-p-sulfonyl)propane 10
The alcohol 9 (22.54 g, 125 mmol) was dissolved in pyridine
(200 cm3) and cooled to 0 ЊC, toluene-p-sulfonyl chloride (47.68
g, 250 mmol) was added portionwise and the reaction mixture
was then stirred for 48 hours. The mixture was concentrated
in vacuo and dissolved in ether (1000 cm3). The organics were
washed with aqueous sodium hydrogen carbonate, 1  hydro-
chloric acid, water and brine, then dried (MgSO4), filtered and
concentrated in vacuo. The residue was purified by chrom-
atography (SiO2, 20% ether–petrol) to give tosylate 10 (38.34 g,
88%) (Found: C, 65.04; H, 6.83. C18H22O4S requires C, 64.65;
H, 6.63%); [α]D20 ϩ34.8 (c 1.80 in CHCl3); νmax(thin film)/cmϪ1
3062, 3030, 2963, 2861, 1922, 1810, 1598, 1494, 1451, 1361,
1307, 1292, 1258, 1210, 1177, 1098, 1019, 978, 815, 792, 738,
699 and 666; δH(270 MHz; CDCl3) 7.78 (2H, d, J 8.5, OTsH),
7.29 (7H, m, Ph, OTs), 4.40 (2H, s, PhCH2O), 4.04 (1H, dd,
J 9.3 and 5.9, 1-H1), 3.99 (1H, dd, J 9.4 and 5.9, 1-H1), 3.34
(2H, m, 3-H2), 2.41 (3H, s, PhMe), 2.10 (1H, m, 2-H), 0.94 (3H,
d, J 6.8, 2-Me); m/z (EI) 334 (Mϩ), 243 (Mϩ Ϫ C7H7) and 91
ϩ
(C7H7 ).
(7R)-8-(Benzyloxy)-7-methyloct-1-ene 11
5-Bromopent-1-ene (23.47 g, 156 mmol) in THF (50 cm3) was
added via cannula to a mixture of magnesium turnings (4.6 g,
189 mmol) and 1,2-dibromoethane (1 drop). After the reaction
had commenced the mixture was heated under reflux for 1 hour.
After cooling, the Grignard reagent was added via cannula to
the tosylate 10 (36.81 g, 105 mmol) at Ϫ78 ЊC, followed by
lithium tetrachlorocuprate (8.02 cm3, 0.82 mmol), then allowed
to warm to room temperature and stirred overnight. The
mixture was poured into dilute sulfuric acid (125 cm3 of a 1 
aqueous solution) and ether (1500 cm3). The organic layer was
separated and washed with water and brine, then dried
(MgSO4), filtered and concentrated in vacuo. The residue was
purified by chromatography (SiO2, 1.5% ether–petrol) to give
alkene 11 (22.63 g, 93%) (Found: C, 82.59; H, 10.63. C16H24O
requires C, 82.70; H, 10.41%); [α]D20 Ϫ2.9 (neat); νmax(thin film)/
cmϪ1 3067, 3030, 2927, 2854, 1639, 1494, 1451, 1362, 1307,
1204, 1100, 1029, 993, 910, 734 and 697; δH(270 MHz; CDCl3)
7.31 (5H, m, PhH), 5.79 (1H, m, 2-H), 4.98 (2H, m, 1-H2), 4.49
(2H, s, PhCH2O), 3.32 (1H, dd, J 9.0 and 6.1, 8-H1), 3.26 (1H,
dd, J 9.0 and 6.6, 8-H1), 1.74 (1H, m, 7-H), 2.05 (2H, m, 3-H2),
1.28 (6H, m, 4-H2, 5-H2 and 6-H2), 0.92 (3H, d, J 6.6, 7-Me);
m/z (EI) 232 (Mϩ), 214 (Mϩ Ϫ H2O), 199 (Mϩ Ϫ H2O Ϫ Me),
ϩ
349 (Mϩ Ϫ OEt Ϫ C2H4 Ϫ H2O) and 91 (C7H7 ).
(2E,7R)-Diethyl 1-ethoxycarbonyl-8-hydroxy-7-methylnon-2-
enylphosphonate 14a and (1E,7R)-diethyl 1-ethoxycarbonyl-8-
hydroxy-7-methylnon-1-enylphosphonate 14b
Ammonia (200 cm3) was redistilled from sodium under an
argon atmosphere, a small amount of sodium added (200 mg)
and then the benzylphosphonate 13 (10.82 g, 24.6 mmol) was
added in ether (10 cm3). Sodium was added until the solution
remained slightly blue and the mixture was then stirred for 45
minutes. Solid ammonium chloride was added until the blue
colour dissipated. The ammonia was evaporated and ether (200
cm3) added. The organics were washed with water, and brine,
then dried (MgSO4), filtered and concentrated in vacuo. The
residue was purified by chromatography (SiO2, 40% acetone–
petrol) to give hydroxyphosphonates 14 (6.57 g, 77%) (Found: C,
54.55; H, 8.88. C16H30O6P requires C, 54.85; H, 8.92%); νmax
-
(thin film)/cmϪ1 3427, 2929, 1734, 1443, 1368, 1149, 1025 and
973; δH(270 MHz; CDCl3) Allylic 14a: 5.64 (2H, m, 2-H and
3-H), 4.18 [6H, m, (OCH2Me) × 3], 3.65 (1H, dd, J 23.9 and
8.8, 1-H), 3.43 (2H, m, 8-H2), 2.10 (2H, m, 4-H2), 1.67 (1H, br s,
OH), 1.27 [14H, m, 5-H2, 6-H2, 7-H and (OCH2CH3) × 3], 0.89
(3H, d, J 6.8, 7-Me); Vinylic 14b: δH(270 MHz; CDCl3) 7.10
(1H, dt, J 23.4 and 8.1, 2-H), 4.18 [6H, m, (OCH2Me) × 3], 3.43
(2H, m, 8-H2), 2.48 (2H, ddd, J 10.1, 8.1 and 3.2, 3-H2), 1.67
(1H, br s, OH), 1.27 [16H, m, 4-H2, 5-H2, 6-H2, 7-H and
(OCH2CH3) × 3], 0.89 (3H, d, J 6.8, 7-Me); m/z (EI) 350 (Mϩ),
320 (Mϩ Ϫ CH2O), 305 (Mϩ Ϫ OEt) and 277 (Mϩ Ϫ OEt Ϫ
C2H4).
ϩ
141 (Mϩ Ϫ C7H7) and 91 (C7H7 ).
(6R)-7-(Benzyloxy)-6-methylheptanal 12
Alkene 11 (21.14 g, 91 mmol) in dichloromethane (500 cm3) was
cooled to Ϫ78 ЊC, and ozone (50 l hϪ1, 115 V) passed through
until the reaction was complete by TLC. Triphenylphosphine
(23.86 g, 91 mmol) was added and the mixture then allowed to
warm to room temperature and stirred for 16 hours. The mix-
ture was concentrated in vacuo then triturated with petrol (100
cm3), filtered and the filtrate concentrated in vacuo. The residue
was purified by chromatography (SiO2, 20% ether–petrol) to
give aldehyde 12 (15.1 g, 71%) (Found: C, 82.59; H, 10.63.
(2E,7R)-Diethyl 1-ethoxycarbonyl-8-trimethylsilyloxy-7-methyl-
non-2-enylphosphonate 6 and (1E,7R)-diethyl 1-ethoxycarbonyl-
8-trimethylsilyloxy-7-methylnon-1-enylphosphonate
C16H24O requires C, 82.70; H, 10.41%); [α]D20 ϩ35.0 (neat); νmax
-
Triethylamine (4.5 cm3) and chlorotrimethylsilane (1.5 cm3)
were mixed in a dry centrifuge tube and centrifuged for 10 min-
utes. The solution (3 cm3) was added to the alcohol 14 (1.86 g,
5.3 mmol) in dichloromethane (20 cm3) at 0 ЊC. The mixture
was poured onto water (20 cm3) and extracted into dichloro-
(thin film)/cmϪ1 3067, 3030, 2926, 2858, 2717, 1726, 1497, 1453,
1410, 1389, 1364, 1206, 1099, 1029, 737, 698 and 644; δH(270
MHz; CDCl3) 9.75 (1H, t, J 2.0, 1-H), 7.35 (5H, m, PhH), 4.49
(2H, s, PhCH2O), 3.28 (2H, m, 7-H2), 2.41 (2H, dt, J 7.3 and
J. Chem. Soc., Perkin Trans. 1, 1998
2265

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methane (3 × 75 cm3). The organics were washed with water,
aqueous sodium hydrogen carbonate, and brine, then dried
(MgSO4), filtered and concentrated in vacuo. The residue was
purified by chromatography (SiO2, ether) to give silyloxyphos-
phonate 6 (2 g, 98%) (Found: C, 53.86; H, 9.41. C19H39O6PSi
requires C, 54.00; H, 9.30%); νmax(thin film)/cmϪ1 3433, 2926,
2855, 1723, 1461, 1388, 1369, 1251, 1028, 970, 876, 841, 797 and
748; δH(270 Hz; CDCl3) Allylic: 5.64 (2H, m, 2-H and 3-H), 4.18
[6H, m, (OCH2Me) × 3], 3.67 (1H, dd, J 23.6 and 9.2, 1-H),
3.35 (2H, m, 8-H2), 2.06 (2H, m, 4-H2), 1.30 (5H, m, 5-H2, 6-H2
and 7-H), 1.36 [9H, m, (OCH2CH3) × 3], 0.85 (3H, d, J 6.7,
7-Me); Vinylic: 7.10 (1H, dt, J 23.0 and 7.5, 2-H), 4.18 [6H, m,
(OCH2Me) × 3], 3.35 (2H, m, 8-H2), 2.46 (2H, ddd, J 15.0, 7.5
and 3.0, 3-H2), 1.30 (7H, m, 4-H2, 5-H2, 6-H2 and 7-H), 1.36
[9H, m, (OCH2CH3) × 3], 0.84 (3H, d, J 6.7, 7-Me); m/z
(EI) 422 (Mϩ), 407, 392, 377, 349, 335, 250, 224, 149, 103, 75
and 73.
allowed to warm to room temperature and diluted with ether
(600 cm3), washed with 2% aqueous KHSO4 (200 cm3),
water (200 cm3) and brine (200 cm3). The mixture was dried
(MgSO4), filtered and evaporated to dryness. The resulting
yellow oil was passed down a pad of florisil, eluting with
ether. The crude aldehyde was used without any further
purification.
cis-Butene (40 cm3) was condensed into a measuring cylinder
at Ϫ78 ЊC and transferred by cannula into a stirred solution of
potassium tert-butoxide (15.6 g, 0.14 mol) in THF (250 cm3) at
Ϫ78 ЊC. n-Butyllithium (2.5  in hexanes, 60 cm3, 0.14 mol) was
added dropwise and the mixture was warmed to Ϫ45 ЊC for 10
minutes. The solution was recooled to Ϫ78 ЊC, before adding
(ϩ)-B-methoxydiisopinocampheylborane (53 g, 0.16 mol) in
ether (100 cm3) by cannula. Stirring was continued for 45 min-
utes, then the mixture was cooled to Ϫ90 ЊC. Boron trifluoride–
diethyl ether (25 cm3, 0.2 mol) was added, followed immediately
by a pre-cooled (Ϫ78 ЊC) solution of the crude aldehyde in
ether (100 cm3). Stirring was continued at Ϫ90 ЊC for 16 hours.
The reaction mixture was allowed to warm to room tempera-
ture, 3  aqueous sodium hydroxide (250 cm3) added, then the
mixture heated to a gentle reflux before adding 30% aqueous
hydrogen peroxide (80 cm3) dropwise. The resulting mixture was
heated under reflux for 5 hours, cooled to room temperature
and the organic phase separated and washed with saturated
aqueous Na2SO3. The combined aqueous phases were extracted
with ethyl acetate (4 × 150 cm3) and the combined organic
layers were dried (MgSO4), filtered and evaporated to dryness.
Repeated chromatography of the residue on silica gel (10–20%
ether–petrol) yielded the alkene 16 (18 g, 70%) as a colourless
oil (Found: C, 77.15; H, 9.53. C15H22O2 requires C, 76.88; H,
9.46%); [α]D20 Ϫ21.4 (c 4.7 in MeOH) {lit.,26 [α]D20 Ϫ17.5 c 4.7 in
MeOH, (95:5 mixture)}; νmax(thin film)/cmϪ1 3478, 3029,
2960, 1636, 1498, 1206, 1028 and 698; δH(500 MHz; CDCl3)
7.39–7.27 (5H, m, ArH), 5.83 (1H, ddd, J 17.1, 10.6 and 7.3,
5-H), 5.05 (1H, dd, J 16.9 and 4.2, 6-H trans), 5.02 (1H, dd,
J 9.0 and 4.2, 6-H cis), 4.51 (2H, s, CH2Ph), 3.64 (1H, dd, J 9.1
and 4.2, 1-H), 3.48 (1H, dd, J 9.1 and 6.2, 1-H), 3.40 (1H, m,
3-H), 3.17 (1H, d, J 4.3, OH), 2.33 (1H, m, 4-H), 1.92–1.97
(1H, m, 2-H), 1.04 (3H, d, J 6.8, 4-Me), 0.96 (3H, d, J 7.0,
(S)-3-(Benzyloxy)-1-bromo-2-methylpropane 15
A solution of N-bromosuccinimide (19.75 g, 0.111 mol) in
dichloromethane (100 cm3) was added to the alcohol 9 (20 g,
0.110 mol) and triphenylphosphine (29.1 g, 0.110 mol) in
dichloromethane (200 cm3) at a rate sufficient to maintain the
internal temperature at 20 ЊC. The mixture was stirred for 1.5
hours then concentrated in vacuo. The residue was dissolved in
ether (450 cm3), washed with water, and brine, then dried
(MgSO4), filtered and concentrated in vacuo. The residue was
titurated with petrol, the solid filtered and the filtrate concen-
trated in vacuo. The residue was purified by chromatography
(SiO2, 5% ether–petrol) to give bromide 15 (24 g, 89%) as a
colourless oil (Found: C, 54.30; H, 6.22. C11H15OBr requires C,
54.43; H, 6.22%); [α]D20 ϩ12.3 (c 1.00 in EtOH); νmax(thin film)/
cmϪ1 2962, 2858, 1493, 1450, 1361, 1333, 1254, 1231, 1098,
1027, 736 and 697; δH(500 MHz; CDCl3) 7.34 (5H, m, PhH),
4.53 (2H, s, PhCH2O), 3.53 (2H, m, 1-H1, 3-H1), 3.43 (2H, m,
1-H1, 3-H1), 2.13 (1H, m, 2-H), 1.04 (3H, d, J 6.8, 2-Me).
(5R)-Dimethyl 6-(benzyloxy)-5-methyl-2-oxohexyl phosphonate
7
2-Me); m/z (EI) 235 (MHϩ), 234 (Mϩ), 179, 107 and 91 (C7H7 )
A solution of dimethyl (2-oxopropyl)phosphonate (18.02 g, 109
mmol) in THF (10 cm3) was added via cannula to sodium
hydride (4.55 g, 109 mmol, 60% dispersion in oil) and stirred for
1.5 hours. n-Butyllithium (43.4 cm3, 109 mmol) was added via
cannula and the mixture stirred for 20 minutes. Bromide 15 (24
g, 99 mmol) in THF (20 cm3) was added via cannula then stirred
for 45 minutes. The mixture was poured into 5% hydrochloric
acid solution (105 cm3) and ether (1050 cm3). The organic
layer was removed and washed with water, brine, and dried
(MgSO4), then concentrated in vacuo. The residue was purified
by chromatography (SiO2, ether then 40% acetone–petrol) to
give starting material (6.65 g) and keto phosphonate 7 (14.62 g,
71%) (Found: C, 57.34; H, 7.81. C16H25OPؒ1/2 H2O requires C,
56.97; H, 7.77%); [α]D20 Ϫ1.5 (c 2.67 in CHCl3); νmax(thin film)/
cmϪ1 3027, 2925, 2853, 2239, 1710, 1494, 1403, 1366, 1262,
1184, 1033, 813, 739 and 700; δH(500 MHz; CDCl3) 7.30 (5H,
m, PhH), 4.47 (2H, s, PhCH2O), 3.75 [6H, d, J 11.2, P(OMe)2],
3.28 (2H, d, J 5.5, 6-H2), 3.05 (2H, d, J 22.7, 1-H2), 2.63 (2H, m,
3-H2), 1.59 (3H, m, 4-H2, 5-H), m/z (EI) 324 (Mϩ), 219
[Mϩ Ϫ P(O)(OMe)2].
ϩ
[Found (CI, NH3) MHϩ 235.1698. C15H23O2 requires
235.1698].
(3S,4R,5S)-(؊)-6-(Benzyloxy)-4-(tert-butyldimethylsilyloxy)-
3,5-dimethylhex-1-ene 17
tert-Butyldimethylsilyl triflate (16 cm3, 68.6 mmol) was added
over 30 minutes to a solution of the alcohol 16 (14.6 g, 62.4
mmol) and triethylamine (26 cm3, 187 mmol) in dichloro-
methane (100 cm3), cooled to Ϫ30 ЊC. The mixture was then
stirred at Ϫ30 ЊC for a further 30 minutes, before being allowed
to warm to room temperature. The reaction mixture was
poured into saturated aqueous NaHCO3 (200 cm3), extracted
with ether (3 × 150 cm3) and the combined organic solvents
were dried (MgSO4), filtered, and evaporated to dryness.
Chromatography of the residue on silica gel (2% ether–petrol)
yielded the silyl ether 17 (22.9 g, 100%) as a colourless oil
(Found: C, 72.45; H, 10.50. C21H36O2Si requires C, 72.36; H,
10.41%); [α]D20 Ϫ18.2 (c 2 in CHCl3); νmax(thin film)/cmϪ1 3066,
3023, 2956, 2853, 1948, 1600, 1470, 1305, 1096, 911 and 774
cm1; δH(500 MHz; CDCl3) 7.33–7.27 (5H, m, ArH), 5.83–5.76
(1H, m, 2-H), 5.00–4.93 (2H, m, 1-H2), 4.46 (1H, d, J 16,
CH2Ph), 4.44 (1H, d, J 16, CH2Ph), 3.57 (1H, dd, J 9.2 and 4.8,
6-H), 3.50 (1H, t, J 5.1, 4-H), 3.26 (1H, dd, J 9.2 and 8.1, 6-H),
2.39–2.35 (1H, m, 3-H), 2.06–1.98 (1H, m, 5-H), 0.99 (3H, d,
J 4.9, 3-Me), 0.97 (3H, d, J 4.8, 5-Me), 0.88 (9H, s, But), 0.03
(6H, s, SiMe2); m/z (CI, NH3) 349 (MHϩ), 348 (Mϩ), 293
(2S,3R,4S)-(؊)-1-(Benzyloxy)-2,4-dimethylhex-5-en-3-ol 16
Dichloromethane (300 cm3) was cooled to Ϫ78 ЊC under an
argon atmosphere. DMSO (20 cm3, 0.28 mol) was added, fol-
lowed by the dropwise addition of oxalyl chloride (15 cm3, 0.17
mol). Stirring was continued for 10 minutes at Ϫ78 ЊC, then a
solution of the alcohol 9 (20 g, 0.11 mol) in dichloromethane
(100 cm3) was added by cannula. The mixture was stirred at
Ϫ78 ЊC for 1 hour, then triethylamine (40 cm3, 0.32 mol) was
added. After stirring at Ϫ78 ЊC for 15 minutes, the mixture was
ϩ
(Mϩ Ϫ C4H7), 291 (Mϩ Ϫ C4H9), 221, 199, 187 and 91 (C7H7 )
[Found (CI, NH3) MHϩ 349.2563. C21H37O2Si requires
349.2563].
2266
J. Chem. Soc., Perkin Trans. 1, 1998

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(3S,4R,5S)-(؊)-6-(Benzyloxy)-4-(tert-butyldimethylsilyloxy)-
3,5-dimethylhexan-1-ol 18
νmax(thin film)/cmϪ1 3029, 2930, 1718, 1649, 1459, 1256, 1096,
982 and 774; δH(500 MHz; CDCl3) 7.33–7.27 (5H, m, ArH),
6.95–6.87 (1H, m, 3-H), 5.78 (1H, dt, J 15.6 and 1.4, 2-H), 4.49
(1H, d, J 12.1, CH2Ph), 4.44 (1H, d, J 12.1, CH2Ph), 4.16 (2H,
q, J 7.2, 1Ј-H2), 3.53 (1H, dd, J 6.0 and 3.0, 6-H), 3.50 (1H, dd,
J 9.1 and 4.8, 8-H), 3.27 (1H, dd, J 9.1 and 7.3, 8-H), 2.31–2.26
(1H, m, 7-H), 2.11–2.06 (1H, m, 4-H), 2.02–1.93 (1H, m, 4-H),
1.85–1.77 (1H, m, 5-H), 1.28 (3H, t, J 7.1, 2Ј-Me), 0.97 (3H, d,
J 6.9, 7-Me), 0.89 (9H, s, But), 0.85 (3H, d, J 6.8, 5-Me), 0.04
(3H, s, SiMe), 0.03 (3H, s, SiMe); m/z (EI) 389 (Mϩ Ϫ C2H5O),
9-BBN (0.5  in THF, 344 cm3, 172 mmol) was added via
cannula to a solution of the alkene 17 (20 g, 57 mmol) in THF
(100 cm3), and the solution heated at reflux for 2 hours. The
mixture was cooled to 0 ЊC, water (20 cm3) added carefully,
followed by 2  NaOH (200 cm3) and 30% aqueous H2O2 (80
cm3). The reaction mixture was warmed to room temperature
and stirred for 1 hour, then the organic phase was separated,
and washed with saturated aqueous Na2SO3. The aqueous
layers were combined, saturated with K2CO3 and extracted with
ether (3 × 200 cm3). The combined organic solvents were dried
(MgSO4), filtered, and evaporated to dryness. Chromatography
of the residue on silica gel (40% ether–petrol) yielded the alco-
hol 18 (19.94 g, 95%) as a colourless oil (Found: C, 69.00; H,
10.53. C21H38O3Si requires C, 68.80; H, 10.45%); [α]D20 Ϫ11.4 (c
1.76 in CHCl3); νmax(neat)/cmϪ1 3379, 3063, 3030, 2954, 2244,
1493, 1379, 1203, 1095, 909 and 773; δH(500 MHz; CDCl3)
7.33–7.27 (5H, m, ArH), 4.47 (1H, d, J 12.1, CH2Ph), 4.44 (1H,
d, J 12.0, CH2Ph), 3.72–3.67 (1H, m, 1-H), 3.66–3.60 (1H, m,
1-H), 3.53–3.59 (2H, m, 4-H, 6-H), 3.29 (1H, dd, J 9.2 and 7.2,
6-H), 2.04–1.99 (1H, m, 5-H), 1.83–1.76 (1H, m, 2-H), 1.66
(1H, sept, J 6.5, 3-H), 1.59 (1H, t, J 5.5, OH), 1.46–1.39 (1H, m,
2-H), 0.97 (3H, d, J 7.0, 5-Me), 0.89 (3H, d, J 7.0, 3-Me), 0.88
(9H, s, But), 0.04 (3H, s, SiMe), 0.03 (3H, s, SiMe); m/z (EI) 309
ϩ
377 (Mϩ Ϫ C4H9), 293, 285, 187, 145 and 91 (C7H7 ) [Found
(EI) Mϩ Ϫ C4H9 377.2148. C21H33O4Si requires 377.2148].
(2E,5S,6R,7S)-(؊)-8-(Benzyloxy)-6-(tert-butyldimethyl-
silyloxy)-5,7-dimethyloct-2-en-1-ol 21
DIBAL-H (1.5  in toluene, 40 cm3, 58 mmol) was added to the
ester 20 (10.5 g, 24 mmol) in THF (100 cm3) at Ϫ78 ЊC. The
reaction mixture was stirred at Ϫ78 ЊC for 2 hours, then
quenched by the addition of water (2 cm3), maintained at
Ϫ78 ЊC for 15 minutes and saturated aqueous Na2SO4 was
added. The mixture was allowed to warm to room temperature
(CARE: exothermic at 20 ЊC, required recooling and stirred at
Ϫ40 ЊC for an additional 30 minutes), the resulting gel broken
up and solid Na2SO4 added. The mixture was filtered and the
solids rinsed several times with ethyl acetate. The combined
solvents were evaporated to dryness. Chromatography of the
residue on silica gel (30% ether–petrol) yielded the allylic
alcohol 21 (9.2 g, 97%) as a colourless oil (Found: C, 70.34; H,
10.37. C23H40O3Si requires C, 70.36; H, 10.27%); [α]D20 Ϫ6.2 (c 1.9
in CHCl3); νmax(thin film)/cmϪ1 3343, 3086, 3062, 3026, 2929,
2854, 1803, 1604, 1405, 1379, 1204, 1096, 1027 and 836; δH(500
MHz; CDCl3) 7.33–7.27 (5H, m, ArH), 5.64–5.62 (2H, m, 2-H,
3-H), 4.49 (1H, d, J 12.0, CH2Ph), 4.45 (1H, d, J 12.0, CH2Ph),
4.08–4.06 (2H, m, 1-H2), 3.56–3.52 (2H, m, 6-H, 8-H), 3.27
(1H, dd, J 9.2 and 7.4, 8-H), 2.18–2.11 (1H, m, 4-H), 2.01–1.96
(1H, m, 7-H), 1.95–1.88 (1H, m, 4-H), 1.73–1.65 (1H, m, 5-H),
1.23 (1H, t, J 5.9, OH), 0.96 (3H, d, J 7.0, 7-Me), 0.89 (9H, s,
But), 0.85 (3H, d, J 6.8, 5-Me), 0.04 (3H, s, SiMe), 0.03 (3H, s,
SiMe); m/z (EI) 392 (Mϩ), 335 (Mϩ Ϫ C4H9), 317 (Mϩ Ϫ C4H9-
ϩ
(Mϩ Ϫ C4H9), 293, 217, 201, 187 and 91 (C7H7 ) [Found (EI)
Mϩ Ϫ C4H9 309.1866. C17H29O3Si requires 309.1886].
(3S,4R,5S)-(؊)-6-(Benzyloxy)-4-(tert-butyldimethylsilyloxy)-
3,5-dimethylhexanal 19
Oxalyl chloride (6.84 cm3, 76.6 mmol) was added slowly to a
solution of dimethyl sulfoxide (11 cm3, 153 mmol) in dichloro-
methane (500 cm3) at Ϫ78 ЊC. The mixture was stirred at
Ϫ78 ЊC for 10 minutes, then the alcohol 18 (14 g, 38.3 mmol) in
dichloromethane (50 cm3) was added. After stirring at Ϫ78 ЊC
for 1 hour, triethylamine (27 cm3, 192 mmol) was added and the
temperature was maintained at Ϫ78 ЊC for 15 minutes before
allowing the mixture to warm to room temperature. The reac-
tion mixture was diluted with ether (600 cm3), the organic phase
separated, and washed with 2% aqueous KHSO4, dried
(MgSO4), filtered and evaporated to dryness. Chromatography
of the residue on silica gel (10% ether–petrol) yielded the alde-
hyde 19 (11.7 g, 85%) as a colourless oil; [α]D20 Ϫ2.9 (c 1.87 in
CHCl3); νmax(thin film)/cmϪ1 3029, 2954, 2882, 1723, 1459,
1380, 1252, 1095, 836 and 774; δH(500 MHz; CDCl3) 9.72 (1H,
t, J 1.8, 1-H), 7.33–7.27 (5H, m, ArH), 4.49 (1H, d, J 12.0,
CH2Ph), 4.44 (1H, d, J 12.0, CH2Ph), 3.56–3.52 (2H, m, 4-H,
6-H), 3.27 (1H, dd, J 9.1 and 7.1, 6-H), 2.55–2.50 (1H, m, 2-H),
2.33–2.27 (2H, m, 2-H, 5-H), 1.97–1.91 (1H, m, 3-H), 0.99 (3H,
d, J 7.0, 5-Me), 0.92 (3H, d, J 6.6, 3-Me), 0.88 (9H, s, But), 0.04
(3H, s, SiMe), 0.03 (3H, s, SiMe); m/z (EI) 365 (MHϩ), 307
(Mϩ Ϫ C4H9), 293 (Mϩ Ϫ C4H7O), 263, 215, 199, 149 and 91
ϩ
H2O), 293, 243, 187, 145, 115 and 91 (C7H7 ) [Found (EI) Mϩ
392.2747. C23H40O3Si requires 392.2747].
(2S,2ЈS,3ЈR,3S,4ЈS)-(؊)-2-[5Ј-(Benzyloxy)-3Ј-(tert-butyl-
dimethylsilyloxy)-2Ј,4Ј-dimethylpentyl]-3-(hydroxymethyl)-
oxirane 22
-(ϩ)-Diethyl tartrate (880 mg, 4.2 mmol) in dichloromethane
(10 cm3) was added to a slurry of activated powdered 4 Å
molecular sieves (1 g) in dichloromethane (50 cm3) at Ϫ20 ЊC,
followed by a solution of titanium() isopropoxide (1.1 cm3
in 2.0 cm3 of dichloromethane, 3.5 mmol). tert-Butylhydro-
peroxide (3.0  in isooctane, 19.8 cm3, 57.2 mmol) was added
dropwise and the reaction mixture was stirred at Ϫ20 ЊC for 30
minutes before the allylic alcohol 21 (11 g, 27.94 mmol, dried
over 4 Å molecular sieves) in dichloromethane (20 cm3) was
added. The reaction was stirred at Ϫ20 ЊC for 3.5 hours, then
quenched by the addition of citric acid monohydrate (300 mg)
dissolved in 10% acetone–ether (100 cm3). The mixture was
allowed to warm to room temperature, stirred for 20 minutes,
and then filtered through Celite, washed with dichloromethane
(3 × 100 cm3), and the combined organic solvents were evapor-
ated to dryness. Chromatography of the residue on silica gel
(40% ether–petrol) yielded the epoxide 22 (9.1 g, 80%) as a col-
ourless oil (Found: C, 67.39; H, 9.88. C23H40O4Si requires C,
67.60; H, 9.87%); [α]D20 Ϫ22.3 (c 1.4 in CHCl3); νmax(thin film)/
cmϪ1 3434, 2928, 1459, 1360, 1253, 1094, 903, 837 and 698;
δH(500 MHz; CDCl3) 7.33–7.27 (5H, m, ArH), 4.51 (1H, d,
J 12.0, CH2Ph), 4.46 (1H, d, J 12.0, CH2Ph), 3.86 (1H, ddd,
J 12.6, 5.7 and 2.7, 1Љ-H), 3.64 (1H, ddd, J 12.3, 8.1 and 4.9,
1Љ-H), 3.56–3.51 (2H, m, 5Ј-H2), 3.29 (1H, dd, J 9.1 and 7.4,
3Ј-H), 2.96–2.93 (1H, m, 2-H), 2.89–2.84 (1H, m, 3-H), 1.99–
ϩ
(C7H7 ) [Found (CI, NH3) MHϩ 365.2512. C21H37O3Si requires
365.2512].
(2E,5S,6R,7S)-(؊)-Ethyl 8-(benzyloxy)-6-(tert-butyldimethyl-
silyloxy)-5,7-dimethyloct-2-enoate 20
Triethylphosphonoacetate (9 cm3, 45 mmol) was added to a
suspension of lithium chloride (1.9 g, 45 mmol) in acetonitrile
(250 cm3), followed by diisopropylethylamine (8 cm3, 45 mmol).
The suspension was stirred for 15 minutes, then the aldehyde
19 (11.7 g, 32 mmol) in acetonitrile (50 cm3) was added. The
reaction mixture was stirred for 20 hours, then poured into
saturated aqueous NaHCO3 and ether. The organic phase was
separated and the aqueous phase extracted with ether (3 × 200
cm3). The combined organic extracts were dried (MgSO4), fil-
tered and evaporated to dryness. Chromatography of the resi-
due on silica gel (7% ether–petrol) yielded the ester 20 (12.95 g,
93%) as a colourless oil (Found: C, 69.03; H, 9.88. C25H42O4Si
requires C, 69.08; H, 9.74%); [α]D20 Ϫ6.0 (c 2.0 in CHCl3);
J. Chem. Soc., Perkin Trans. 1, 1998
2267

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1.95 (1H, m, 4Ј-H), 1.90–1.86 (1H, m, 2Ј-H), 1.70–1.63 (2H, m,
OH, 1Ј-H), 1.40 (1H, ddd, J 15.6, 9.9 and 5.7, 1Ј-H), 0.97 (3H,
d, J 7.0, 4Ј-Me), 0.93 (3H, d, J 6.8, 2Ј-Me), 0.88 (9H, s, But),
0.03 (6H, s, SiMe2); m/z (EI) 351 (Mϩ Ϫ C4H9), 293
requires C, 73.34; H, 9.41%); [α]D20 Ϫ7.5 (c 1.4 in CHCl3); νmax
-
(thin film)/cmϪ1 3389, 2962, 2929, 2872, 1450 and 1072; δH(500
MHz; CDCl3) 7.31–7.17 (5H, m, ArH), 4.52 (1H, d, J 12.2,
CH2Ph), 4.42 (1H, d, J 11.7, CH2Ph), 3.93–3.80 (2H, m, 1-H,
2Ј-H), 3.63–3.52 (2H, m, 2Љ-H, 5Ј-H), 3.36 (1H, dd, J 8.8 and
6.8, 2Љ-H), 2.25–2.20 (1H, m, 4Ј-H), 1.98 (1H, ddd, J 16.1, 9.8
and 6.4, 3Ј-Hb), 1.84 (1H, d, J 2.9, OH), 1.80–1.74 (1H, m,
1Љ-H), 1.50 (1H, dd, J 11.7 and 5.9, 3Ј-Ha), 1.01 (3H, d, J 6.4,
1-Me), 0.88 (3H, d, J 6.4, 1Љ-Me), 0.85 (3H, d, J 6.8, 4Ј-Me); m/z
(EI) 279 (MHϩ), 278 (Mϩ), 235, 233 (Mϩ Ϫ C2H5O), 191, 187
ϩ
(Mϩ Ϫ C6H15Si), 259, 215, 199 and 91 (C7H7 ) [Found (EI)
Mϩ Ϫ C4H9 351.1992. C19H31O4Si requires 351.1992].
(1S,1ЉS,2ЈR,4ЈS,5ЈR)-(؊)-1-[Tetrahydro-5Ј-(2Љ-benzyloxy-1Љ-
methylethyl)-4Ј-methylfuran-2Ј-yl]ethane-1,2-diol 23
TBAF (40 cm3, 1  in THF) was added to a solution of the
epoxide 22 (9.0 g, 22 mmol) in THF (40 cm3). The mixture was
heated at 60 ЊC for 4 hours, cooled to room temperature, diluted
with dichloromethane (200 cm3) and washed with brine (50
cm3). The organic phase was dried (MgSO4), filtered and evap-
orated to dryness. Chromatography of the residue on silica gel
(75% ethyl acetate–petrol) yielded the diol 23 (5.5 g, 85%) as a
colourless oil (Found: C, 69.27; H, 8.92. C17H26O4 requires C,
69.36; H, 8.90%); [α]D20 Ϫ5.0 (c 1.2 in CHCl3); νmax(thin film)/
cmϪ1 3290, 2919, 2833, 1449, 1361, 1282 and 1102; δH(270
MHz; CDCl3) 7.34–7.26 (5H, m, ArH), 4.53 (1H, d, J 12.0,
CH2Ph), 4.49 (1H, d, J 12.2, CH2Ph), 4.11–4.04 (1H, m, 2Ј-H),
3.68–3.63 (4H, m, 1-H, 2-H2, 5Ј-H), 3.61 (1H, dd, J 8.5 and 3.6,
2Љ-H), 3.43 (1H, dd, J 8.8 and 6.6, 2Љ-H), 2.32–2.17 (3H, m,
2 × OH, 4Ј-H), 1.99–1.95 (1H, m, 3Ј-Hb), 1.85–1.82 (1H, m, 1Љ-
H), 1.73 (1H, dd, J 12.5 and 6.6, 3Ј-Ha), 0.95 (3H, d, J 7.1, 1Љ-
Me), 0.91 (3H, d, J 7.1, 4Ј-Me); m/z (EI) 295 (MHϩ), 294 (Mϩ),
ϩ
(Mϩ Ϫ C7H7), 129 and 91 (C7H7 ) [Found (EI) MHϩ 279.1960.
C17H27O3 requires 279.1960].
(1ЈS,1ЉS,2R,3S,5R)-(؊)-Tetrahydro-5-(1Ј-methoxyethyl)-3-
methyl-2-(2Љ-benzyloxy-1Љ-methylethyl)furan 26
The secondary alcohol 25 (3.5 g, 12.5 mmol), in THF (30 cm3),
was added to a suspension of KH (30 g of a 35% dispersion in
oil, 26 mmol), in THF (20 cm3) at 0 ЊC. After 15 minutes,
methyl iodide (4 cm3, 64 mmol) was added and the mixture was
allowed to warm to room temperature. Stirring was continued
for 3 hours, before quenching with methanol (20 cm3). The mix-
ture was diluted with dichloromethane (300 cm3), washed with
brine (2 × 25 cm3), the organic solvents were dried (MgSO4),
filtered and evaporated to dryness. Chromatography of the
residue on silica gel (10% ether–petrol) yielded the methyl ether
26 (3.3 g, 90%) as a colourless oil (Found: C, 73.80; H, 9.67.
C18H28O3 requires C, 73.93; H, 9.65%); [α]D20 Ϫ7.5 (c 1.3 in
CHCl3); νmax(thin film)/cmϪ1 3027, 2964, 2928, 2874, 2014,
1493, 1450, 1370 and 1240; δH(270 MHz; CDCl3) 7.39–7.24
(5H, m, ArH), 4.58 (1H, d, J 12.0, CH2Ph), 4.49 (1H, d, J 11.9,
CH2Ph), 3.98 (1H, ddd, J 11.7, 6.6 and 5.1, 5-H), 3.7 (1H, dd,
J 9.0 and 3.2, 2Љ-H), 3.58 (1H, dd, J 10.3 and 3.7, 2-H), 3.37
(3H, s, OMe), 3.40–3.27 (2H, m, 1Ј-H, 2Љ-H), 2.24–2.20 (1H,
m, 3-H), 1.97–1.95 (1H, m, 4-Hb), 1.87–1.82 (1H, m, 1Љ-H),
1.66 (1H, dd, J 12.5 and 6.8, 4-Ha), 1.10 (3H, d, J 6.4, 1Ј-Me),
0.96 (3H, d, J 6.6, 1Љ-Me), 0.90 (3H, d, J 6.8, 3-Me); m/z
(EI) 293 (MHϩ), 292 (Mϩ), 260 (Mϩ Ϫ MeOH), 242, 233
ϩ
263, 257, 245, 233 and 91 (C7H7 ) [Found (EI) MHϩ 295.1910.
C17H27O4 requires 295.1909].
(1S,1ЉS,2ЈR,4ЈS,5ЈR)-(؊)-1-[Tetrahydro-5Ј-(2Љ-benzyloxy-1Љ-
methylethyl)-4Ј-methylfuran-2Ј-yl]-2-(toluene-p-sulfonyloxy)-
ethanol 24
Dibutyltin oxide (2.4 g, 10 mmol) was added to a solution of
the diol 23 (2.7 g, 9.2 mmol) in methanol (50 cm3) and the
resulting mixture was heated at reflux for 45 minutes. After
cooling to room temperature, triethylamine (10 cm3, 32 mmol)
and toluene-p-sulfonyl chloride (11.8 g, 61 mmol) were added
sequentially. The mixture was stirred at room temperature for
15 minutes, poured into saturated aqueous NaHCO3 and
extracted with dichloromethane (3 × 100 cm3). The combined
organic solvents were dried (MgSO4), filtered and evaporated to
dryness. Chromatography of the residue on silica gel (35–60%
ether–petrol) yielded the tosylate 24 (3.9 g, 94%) as a colourless
oil; [α]D20 Ϫ19.3 (c 0.94 in CHCl3); νmax(thin film)/cmϪ1 3383,
2961, 1596, 1450, 1357, 1188 and 1176; δH(500 MHz; CDCl3)
7.78 (2H, d, J 8.3, ArH), 7.35–7.26 (7H, m, ArH), 4.54 (1H, d,
J 12.1, CH2Ph), 4.44 (1H, d, J 12.1, CH2Ph), 4.19 (1H, dd,
J 10.4 and 3.3, 2-H), 3.99 (1H, dd, J 10.4 and 6.8, 2-H), 3.93
(1H, ddd, J 15.9, 9.3 and 6.7, 2Ј-H), 3.77–3.72 (1H, m, 1-H),
3.57 (1H, dd, J 8.9 and 3.3, 2Љ-H), 3.53 (1H, dd, J 10.4 and 4.0,
5Ј-H), 3.34 (1H, dd, J 8.9 and 7.1, 2Љ-H), 2.44 (3H, s, MeAr),
2.29–2.23 (1H, m, 4Ј-H), 2.16 (1H, br s, OH), 1.97 (1H, ddd,
J 15.8, 9.4 and 6.5, 3Ј-Hb), 1.77–1.81 (1H, m, 1Љ-H), 1.73 (1H,
dd, J 12.5 and 6.5, 3Ј-Ha), 0.94 (3H, d, J 6.7, 1Љ-Me), 0.87 (3H,
d, J 7.1, 4Ј-Me); m/z (EI) 449 (MHϩ), 448 (Mϩ), 357 (Mϩ Ϫ C7-
ϩ
(Mϩ Ϫ C3H7O), 201 (Mϩ Ϫ C7H7) and 91 (C7H7 ) [Found (EI)
MHϩ 293.2117. C18H29O3 requires 293.2117].
(1ЉS,2S,2ЈR,3ЈS,5ЈR)-(؉)-2-[Tetrahydro-5Ј-(1Љ-methoxyethyl)-
3Ј-methylfuran-2Ј-yl]-2-methylethanol 27
10% Palladium on carbon (300 mg) was added to the benzyl
ether 26 (1.6 g, 5.5 mmol) in methanol (20 cm3), under an argon
atmosphere, the mixture degassed and then stirred under a
hydrogen atmosphere for 16 hours. The flask was flushed with
argon, the catalyst removed by filtration, and the solvent evap-
orated to dryness. Chromatography of the residue on silica gel
(60% ether–petrol) yielded the alcohol 27 (1.06 g, 95%) as a low
melting solid (Found: C, 65.02; H, 10.75. C11H23O3 requires C,
65.31; H, 10.96%); [α]D20 ϩ39.0 (c 0.9 in CHCl3); νmax(thin
film)/cmϪ1 3452, 2965, 2877, 1459, 1374, 1150, 1090, 1009,
965, 894 and 800; δH(500 MHz; CDCl3) 3.99 (1H, ddd, J 9.6,
6.6 and 4.9, 5Ј-H), 3.64 (1H, dd, J 10.1 and 4.0, 1-H), 3.61–
3.53 (3H, m, 1-H, 2Ј-H, OH), 3.38 (3H, s, OMe), 3.37–3.32
(1H, m, 1Љ-H), 2.32–2.27 (1H, m, 3Ј-H), 1.97 (1H, ddd,
J 12.5, 9.5 and 6.5, 4Ј-Hb), 1.88–1.82 (1H, m, 2-H), 1.65 (1H,
dd, J 12.5 and 6.6, 4Ј-Ha), 1.09 (3H, d, J 6.4, 1Љ-Me), 0.92
(3H, d, J 7.1, 2-Me), 0.77 (3H, d, J 6.8, 3Ј-Me); m/z (EI) 203
(MHϩ), 202 (Mϩ), 170 (Mϩ Ϫ MeOH), 143 [Mϩ Ϫ CH(Me)-
OMe] and 59 (C3H7Oϩ) [Found (EI) MHϩ 203.1647. C11H23O3
requires 203.1647; Found (EI) Mϩ 202.1569. C11H22O3 requires
202.1569].
ϩ
H7), 342, 299, 245 and 91 (C7H7 ) [Found (EI) MHϩ 449.2000.
C24H33O6S requires 449.2000].
(1S,1ЉS,2ЈR,4ЈS,5ЈR)-(؊)-1-[Tetrahydro-5Ј-(2Љ-benzyloxy-1Љ-
methylethyl)-4Ј-methylfuran-2Ј-yl]ethanol 25
A solution of the tosylate 24 (3.9 g, 8.71 mmol) in THF (20
cm3) was added dropwise to Super Hydride (40 cm3, 1  in
THF) at 0 ЊC. The mixture was stirred at room temperature for
6 hours and then quenched by careful addition of brine (50
cm3). The solution was concentrated to half the original volume
and diluted with dichloromethane (250 cm3). The organic phase
was washed with brine (2 × 50 cm3), dried (MgSO4), filtered
and evaporated to dryness. Chromatography of the residue on
silica gel (50–60% ether–petrol) yielded the alcohol 25 (2.23 g,
92%) as a colourless oil (Found: C, 73.28; H, 9.40. C17H26O3
(2S,3S,4S)-2,4-Dimethyl-1-[(1,1-dimethylethyl)diphenyl-
silyloxy]hex-5-en-3-ol 29
DMSO (3.4 cm3, 3.75 g, 48 mmol) in dry dichloromethane (10
cm3) was added dropwise to a stirred solution of oxalyl chloride
(12 cm3, 24 mmol, 2.0  in dichloromethane) in dry dichloro-
2268
J. Chem. Soc., Perkin Trans. 1, 1998

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methane (40 cm3) at Ϫ60 ЊC under argon. The solution was
stirred at Ϫ60 ЊC for 10 minutes then a solution of alcohol 285f
(6.57 g, 20 mmol) in dry dichloromethane (40 cm3) was added
dropwise via a cannula. After stirring at Ϫ60 ЊC for a further 20
minutes, triethylamine (6.7 cm3, 4.86 g, 48 mmol) was added
and the mixture was allowed to warm to room temperature.
The reaction mixture was quenched with excess 1% w/v
aqueous KHSO4 and extracted with dichloromethane. The
combined extracts were dried (Na2SO4) and concentrated in
vacuo to give crude (S)-3-[(1,1-dimethylethyl)diphenylsilyloxy]-
2-methylpropanal.
cm3, 5.87 g, 58 mmol) and 4-(dimethylamino)pyridine (122 mg,
1 mmol) in dry dichloromethane (240 cm3) was stirred at room
temperature under argon for 5 days. The reaction was quenched
with 1  HCl and extracted with dichloromethane. The com-
bined extracts were dried (MgSO4) and concentrated in vacuo.
Purification by column chromatography on silica gel (10–50%
ether–petrol) afforded sulfonate 31 (17.8 g, 90%) as a colourless
oil (Found: C, 67.12; H, 9.60. C23H38O4S requires C, 67.28; H,
9.33%); [α]D20 ϩ12.7 (c 1.08 in CHCl3); νmax(thin film)/cmϪ1 3556,
2962, 1636, 1599, 1559, 1459, 1424, 1374, 1345, 1178, 967, 810
and 665; δH(270 MHz; CDCl3) 7.18 (2H, s, m-H), 5.67 (1H, ddd,
J 17.7, 9.7 and 8.7, 5-H), 5.17–5.07 (2H, m, 6-H), 4.16 (2H,
sept, J 6.7, o-CH), 4.14 (1H, dd, J 9.5 and 7.7, 1-H), 3.96 (1H,
dd, J 9.5 and 6.5, 1-H), 3.39 (1H, dt, J 8.9 and 3.0, 3-H), 2.91
(1H, sept, J 6.7, p-CH), 2.33–2.07 (2H, m, 2-H, 4-H), 1.67 (1H,
dd, J 3.0 and 1.0, OH), 1.26 (18H, d, J 6.7, CMe2), 0.94 (3H, d,
J 6.8, CH3), 0.91 (3H, d, J 6.8, CH3); m/z (EI) 410 (Mϩ, 5%),
355, 284, 267, 251, 218, 202 and 187.
Condensed trans-but-2-ene (7 cm3) was added to a solution
of freshly sublimed potassium tert-butoxide (2.8 g, 25 mmol)
in dry THF (25 cm3) at Ϫ78 ЊC. n-Butyllithium (10 cm3, 2.5 
in hexanes, 25 mmol) was added dropwise at Ϫ78 ЊC, the
solution stirred at Ϫ45 ЊC for 10 minutes, recooled to Ϫ78 ЊC
and a solution of (Ϫ)-B-methoxydiisopinocamphenylborane
(9.49 g, 30 mmol) in dry ether (30 cm3) added. After stirring
at Ϫ78 ЊC for 45 minutes boron trifluoride–diethyl ether (4.43
cm3, 5.11 g, 36 mmol) was added, the mixture cooled to
Ϫ85 ЊC and a solution of the crude (S)-3-[(1,1-dimethylethyl)-
diphenylsilyloxy]-2-methylpropanal in ether (40 cm3) was
added. The mixture was stirred at Ϫ85 ЊC for a further 20
hours, allowed to warm to room temperature and then 3 
aqueous NaOH (18 cm3) and 30% aqueous hydrogen peroxide
(7.5 cm3) were added. The reaction mixture was heated at reflux
for 1 hour, cooled and carefully quenched with saturated aque-
ous Na2SO3. Saturated aqueous NaCl was added and the solu-
tion extracted with ether. The combined extracts were dried
(MgSO4), concentrated in vacuo and dissolved in dry ether (100
cm3). Diethanolamine (3.2 cm3, 3.47 g, 33 mmol) was added
to this solution and the mixture stirred for 16 hours under
argon. The mixture was filtered and the filtrate concentrated
in vacuo. Purification by column chromatography on silica gel
(10–25% ether–petrol) afforded alcohol 29 (5.69 g, 74%) as
a colourless oil (Found: C, 75.61; H, 9.16. C24H34O2Si
requires C, 75.34; H, 8.96%); [α]D20 ϩ8.2 (c 1.02 in CHCl3);
νmax(thin film)/cmϪ1 3506, 3070, 2960, 2930, 2858, 1638, 1589,
1461, 1427, 1388, 1112, 998, 823, 740 and 703; δH(270 MHz;
CDCl3) 7.48–7.35 (6H, m, m-H, p-H), 7.07–7.63 (4H, m, o-H),
5.82 (1H, ddd, J 17.8, 9.5 and 8.3, 5-H), 5.13–5.05 (2H, m, 6-H),
3.73–3.71 (2H, m, 1-H), 3.58 (1H, dt, J 8.3 and 2.6, 3-H), 2.40
(1H, d, J 2.6, OH), 2.33–2.23 (1H, m, 4-H), 1.88–1.75 (1H, m,
2-H), 1.06 (9H, s, But), 0.95 (3H, d, J 6.8, CH3), 0.94 (3H, d, J
6.8, CH3); m/z (EI) 325 (Mϩ Ϫ But, 14%), 269, 229, 199 and 109.
(3S,4R,5S)-4-Hydroxy-3,5-dimethylhept-6-enenitrile 32
A mixture of sulfonate 31 (14.4 g, 35 mmol) and sodium cyan-
ide (2.06 g, 42 mmol) in dry DMSO (35 cm3) was heated at
65 ЊC under argon for 2 hours.27 The mixture was cooled, trans-
ferred to a silica gel chromatography column and purified by
flash column chromatography (1% methanol in 50% ether–
petrol) to afford nitrile 32 (5.36 g, 100%) as a colourless oil
(Found: C, 70.59; H, 9.96; N, 8.98. C9H15NO requires C, 70.55;
H, 9.87; N, 9.14%); [α]D20 ϩ24.8 (c 1.05 in CHCl3); νmax(thin film)/
cmϪ1 3474, 3075, 2970, 2247, 1630, 1459, 1419, 1381, 1101, 984
and 919; δH(270 MHz; CDCl3) 5.68 (1H, ddd, J 17.6, 9.7 and
8.7, 6-H), 5.16 (1H, dd, J 17.6 and 1.7, 7-H), 5.15 (1H, dd, J 9.7
and 1.7, 7-H), 3.32 (1H, dt, J 8.5 and 2.9, 4-H), 2.48 (1H, dd,
J 16.7 and 7.0, 2-H), 2.38 (1H, dd, J 16.7 and 7.0, 2-H), 2.21
(1H, tq, J 8.7 and 7.0, 5-H), 2.09 (1H, sext d, J 7.0 and 2.9,
3-H), 1.81 (1H, dd, J 2.9 and 1.0, OH), 1.02 (3H, d, J 7.0, CH3),
0.98 (3H, d, J 7.0, CH3); m/z (EI) 98 (Mϩ Ϫ C4H9, 62%) and 56.
(1ЈS,2RS,4S,5R)-Tetrahydro-4-methyl-5-(1Ј-methylprop-2Ј-
enyl)furan-2-ol 33
Diisobutylaluminium hydride (4.0 cm3, 1.5  in toluene, 6
mmol) was added dropwise to a stirred solution of nitrile 32
(306 mg, 2 mmol) in dry toluene (6 cm3) at Ϫ78 ЊC under argon.
The reaction was stirred at Ϫ78 ЊC for 2 hours, quenched with
ethyl acetate (2 cm3) and allowed to warm to room temperature.
The reaction was acidified with 2  HCl (6 cm3) and stirred for a
further 1 hour. The two phase mixture was saturated with solid
NaCl, the layers separated, and the aqueous layer extracted
with dichloromethane. The organic fractions were combined,
dried (Na2SO4) and concentrated in vacuo. Purification by
column chromatography using Florisil (40% ether–petrol)
afforded lactol 33 (294 mg, 94%) (20:80 mixture of anomers) as
a colourless oil (Found: C, 69.36; H, 10.56. C9H16O2 requires C,
69.19; H, 10.32%); νmax(thin film)/cmϪ1 3413, 2966, 1628, 1453,
1293, 1073, 998 and 911; δH(500 MHz; CDCl3) 5.89 (0.2H, ddd,
J 17.3, 10.2 and 7.5, minor 19-H), 5.85 (0.8H, ddd, J 17.3, 10.0
and 7.7, major 19-H), 5.57 (0.8H, dt, J 5.7 and 3.5, major 24-H),
5.43–5.40 (0.2H, m, minor 24-H), 5.09 (0.2H, dt, J 17.3 and 1.3,
minor 18-H), 5.08 (0.8H, ddd, J 17.3, 1.6 and 1.0, major 18-H),
5.04 (0.2H, dd, J 10.2 and 1.5, minor 18-H), 5.02 (0.8H, dd,
J 10.0 and 1.3, major 18-H), 3.86 (0.8H, dd, J 9.3 and 4.6, major
21-H), 3.58 (0.2H, dd, J 9.5 and 4.6, minor 21-H), 3.23–3.15
(0.2H, br s, minor OH), 3.07–2.97 (0.8H, br s, major OH), 2.45–
2.37 (0.2H, m, minor 22-H), 2.35 (0.2H, ddd, J 7.1, 4.6 and 2.5,
minor 23-H), 2.34 (0.2H, ddd, J 7.1, 4.6 and 2.5, minor 23-H),
2.33–2.25 (1H, m, minor/major 20-H), 2.25–2.15 (0.8H, m,
major 22-H), 1.98 (0.8H, ddd, J 13.5, 7.1 and 4.0, major 23-H),
1.90 (0.8H, ddd, J 13.5, 5.7 and 2.6, major 23-H), 1.12 (0.6H, d,
J 7.1, minor 22-CH3), 0.98 (3H, d, J 6.8, minor/major 20-CH3),
0.91 (2.4H, d, J 7.1, major 22-CH3); m/z (EI) 139 (Mϩ Ϫ OH,
100%), 95, 85 and 55.
(2S,3S,4S)-2,4-Dimethylhex-5-ene-1,3-diol 30
Tetrabutylammonium fluoride (3.3 cm3, 1  in THF, 3.3
mmol) was added in one portion to a stirred solution of silyl
ether 29 (1.15 g, 3 mmol) in dry THF (1.5 cm3) at room
temperature under argon. The mixture was stirred at room
temperature for 3 hours, transferred to a silica gel chroma-
tography column and purified by flash column chroma-
tography (1% methanol in 5–60% ether–petrol) to afford diol
30 (0.43 g, 100%) as a white solid (Found: C, 66.61; H, 11.35.
C8H16O2 requires C, 66.63; H, 11.18%); mp 43–44 ЊC; [α]D20
ϩ8.0 (c 1.00 in CHCl3); νmax(CHCl3)/cmϪ1 3437, 2970, 1636,
1459, 1380, 1240, 1099, 1025, 1002, 971, 925 and 681; δH(270
MHz; CDCl3) 5.70 (1H, ddd, J 16.5, 10.9 and 8.8, 5-H),
5.20–5.10 (2H, m, 6-H), 3.74 (1H, dd, J 10.7 and 4.3, 1-H),
3.68 (1H, dd, J 10.7 and 5.5, 1-H), 3.49 (1H, dd, J 8.8 and
1.6, 3-H), 2.59 (1H, br s, OH), 2.25 (1H, tq, J 8.8 and 6.8,
4-H), 2.17 (1H, br s, OH), 1.90–1.80 (1H, m, 2-H), 0.96 (3H,
d, J 6.8, CH3), 0.95 (3H, d, J 7.1, CH3); m/z (EI) (Mϩ Ϫ
HOCH2, 2%), 109, 89, 71 and 56.
(2S,3S,4S)-(3-Hydroxy-2,4-dimethylhex-5-enyl) 2Ј,4Ј,6Ј-tris-
(1-methylethyl)benzenesulfonate 31
A mixture of diol 30 (6.92 g, 48 mmol), 2,4,6-triisopropyl-
benzenesulfonyl chloride (16.1 g, 53 mmol), triethylamine (8.1
J. Chem. Soc., Perkin Trans. 1, 1998
2269

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(1ЈS,2R,3S,5RS)-Tetrahydro-3-methyl-2-(1Ј-methylprop-2Ј-
enyl)-5-(phenylsulfonyl)furan 34†
ddd, J 17.3, 1.7 and 1.2, 18-H), 5.05 (1H, ddd, J 10.3, 1.7 and
0.8, 18-H), 4.42 (1H, t, J 8.5, 24-H), 3.62 (1H, dd, J 9.5 and 4.2,
21-H), 2.40–1.90 (4H, m, 20-H, 22-H, 23-H), 2.19 (3H, s, 26-H),
0.98 (3H, d, J 6.6, CH3), 0.96 (3H, d, J 6.8, CH3); m/z (EI) 182
(Mϩ, 23%), 149, 139, 95 and 55 [Found (EI) Mϩ 182.1307.
C11H18O2 requires 182.1307].
A mixture of lactol 33 (0.52 g, 3.3 mmol), benzenesulfonic acid
(1.41 g, 9.9 mmol) and anhydrous calcium chloride (1.10 g, 9.9
mmol) in dry dichloromethane (8 cm3) was stirred at room
temperature under argon for 14 hours. The reaction was
quenched with excess water and extracted with dichloro-
methane. The combined extracts were washed with saturated
aqueous NaHCO3, dried (Na2SO4) and concentrated in vacuo.
Purification by column chromatography on silica gel (25%
ether–petrol) afforded sulfone 34 (0.86 g, 93%) (5R:5S 7:93) as
a white solid (Found: C, 64.12; H, 7.03. C15H20O3S requires C,
64.62; H, 7.19%); mp 84–87 ЊC; νmax(CHCl3)/cmϪ1 2970, 1638,
1447, 1308, 1287, 1148, 1073 and 687; δH(270 MHz; CDCl3)
7.95–7.90 (2H, m, 5R/5S o-H), 7.67–7.63 (1H, m, 5R/5S p-H),
7.67–7.53 (2H, m, 5R/5S m-H), 5.84 (0.93H, ddd, J 17.3, 10.3
and 7.1, 5S 19-H), 5.83 (0.07H, ddd, J 17.3, 10.3 and 7.1, 19-H),
5.05 (1H, dt, J 17.3 and 1.3, 5R/5S 18-H), 5.02 (0.93H, dt, J 10.3
and 1.3, 5S 18-H), 4.97 (0.07H, dt, J 10.3 and 0.8, 5R 18-H),
4.91 (0.93H, t, J 7.5, 5S 24-H), 4.74 (0.07H, d, J 9.2, 5.0, 5R
24-H), 3.97 (0.93H, dd, J 9.9 and 4.1, 5S 21-H), 3.60 (0.07H,
dd, J 9.2 and 5.4, 5R 21-H), 2.80 (0.93H, dt, J 13.9 and 7.0, 5S
23-H), 2.52 (0.07H, ddd, J 14.1, 9.1 and 7.8, 5R 23-H), 2.50–
2.37 (1H, m, 5R/5S 22-H), 2.29 (0.07H, ddd, J 14.1, 5.0 and 2.9,
5R 23-H), 2.30–2.20 (1H, m, 5R/5S 20-H), 2.07 (0.93H, ddd,
J 13.7, 7.8 and 1.2, 5S 23-H), 1.06 (0.21H, d, J 7.1, 5R, 22-CH3),
0.96 (3H, d, J 6.8, 5R/5S 20-CH3), 0.92 (2.79H, d, J 7.0, 5S
22-CH3); m/z (EI) 139 (Mϩ Ϫ PhSO2, 14%), 125, 110, 83 and 55.
(1R,1ЉS,2ЈR,4ЈS,5ЈR)-1-[Tetrahydro-4Ј-methyl-5Ј-(1Љ-methyl-
prop-2-enyl)furan-2-yl]ethanol 37a and (1S,1ЉS,2ЈR,4ЈS,5ЈR)-1-
[tetrahydro-4Ј-methyl-5Ј-(1Љ-methylprop-2Љ-enyl)furan-2-yl]-
ethanol 37b
Sodium borohydride (11.3 mg, 0.3 mmol) was added to a stirred
solution of ketone 36 (5.5 mg, 0.03 mmol) in methanol (0.6
cm3) at room temperature. The mixture was stirred for 30 min-
utes, quenched with 1  HCl and concentrated in vacuo. The
aqueous layer was extracted with dichloromethane and then the
combined extracts were dried (Na2SO4), filtered and concen-
trated in vacuo. Purification by column chromatography on
silica gel (1% methanol in 15% ether–petrol) afforded the
(1R,1ЉS,2ЈR,4ЈS,5ЈR)-alcohol 37a (3.1 mg, 56%) as a colourless
gum [α]D20 Ϫ13.3 (c 1.00 in CHCl3); νmax(thin film)/cmϪ1 3448,
2986, 1635, 1453, 1379, 1261, 1085, 1010, 965 and 909; δH(500
MHz; CDCl3) 5.92 (1H, ddd, J 17.3, 10.4 and 6.9, 19-H), 5.07
(1H, dt, J 17.3 and 1.4, 18-H), 5.00 (1H, dt, J 10.4 and 1.3,
18-H), 3.81 (1H, q, J 7.7, 24-H), 3.53–3.50 (1H, m, 25-H), 3.49
(1H, dd, J 9.7 and 4.0, 21-H), 2.58 (1H, d, J 2.0, OH), 2.33–2.25
(2H, m, 20-H, 22-H), 1.70 (2H, dd, J 7.7 and 3.9, 23-H), 1.08
(3H, d, J 6.3, CH3), 0.95 (6H, d, J 6.8, CH3); m/z (EI) 129
ϩ
(Mϩ Ϫ C4H7, 100%), 121, 111 and 95 [Found (CI) MNH4
202.1807. C11H24NO2 requires 202.1807].
(1ЈS,2R,3S,5R)-Tetrahydro-5-ethynyl-3-methyl-2-(1Ј-methyl-
prop-2Ј-enyl)furan 35
Further elution (1% methanol in 20% ether–petrol) afforded
the (1S,1ЉS,2ЈR,4ЈS,5ЈR)-alcohol 37b (2.0 mg, 36%) as a colour-
less gum [α]D20 ϩ5.0 (c 1.00 in CHCl3); νmax(thin film)/cmϪ1 3429,
2965, 1635, 1459, 1379, 1076, 1033, 1010 and 907; δH(500 MHz;
CDCl3) 5.92 (1H, ddd, J 17.3, 10.3 and 7.2, 19-H), 5.08 (1H, dt,
J 17.3 and 1.4, 18-H), 5.01 (1H, ddd, J 10.3, 1.7 and 0.9, 18-H),
4.03–3.97 (2H, m, 24-H, 25-H), 3.58 (1H, dd, J 9.7 and 4.0, 21-
H), 2.33–2.25 (2H, m, 20-H, 22-H), 2.07 (1H, ddd, J 12.2, 9.5
and 6.5, 23-H), 1.94 (1H, s, OH), 1.57 (1H, ddd, J 12.2, 6.2 and
1.2, 23-H), 1.07 (3H, d, J 6.4, CH3), 0.96 (3H, d, J 6.9, CH3),
0.95 (3H, d, J 6.7, CH3); m/z (EI) 129 (Mϩ Ϫ C4H7, 100%), 121,
111 and 95 [Found (CI) MNH4ϩ 202.1807. C11H24NO2 requires
202.1807].
Anhydrous zinc bromide (1.2 cm3, 1.2 mmol, 1  solution in
THF) was added to a stirred solution of ethynylmagnesium
bromide (10 cm3, 2.0 mmol, 0.2  solution in THF) and the
mixture was stirred at room temperature under argon for 30
minutes. Solid sulfone 34 (0.14 g, 0.5 mmol) was added and the
solution stirred for 19 hours. The reaction was quenched with
saturated aqueous 1  HCl and extracted with ether. The com-
bined extracts were dried (MgSO4) and concentrated in vacuo.
Purification by column chromatography on silica gel (4–5%
ether–petrol) afforded acetylene 35 (72 mg, 88%) (5R:5S >
20:1) as a colourless oil [α]D20 ϩ30.9 (c 1.00 in CHCl3); νmax(thin
film)/cmϪ1 3928, 2967, 2878, 1636, 1455, 1381, 1335, 1072, 1008,
962, 912; δH(270 MHz; CDCl3) 5.91 (1H, ddd, J 17.3, 10.2 and
7.3, 19-H), 5.08 (1H, ddd, J 17.3, 1.8 and 1.2, 18-H), 5.02 (1H,
ddd, J 10.2, 1.8 and 0.8, 18-H), 4.73 (1H, td, J 7.3 and 2.2,
24-H), 3.73 (1H, dd, J 9.3 and 4.6, 21-H), 2.41 (1H, d, J 2.2,
26-H), 2.40–2.23 (2H, m, 20-H, 22-H), 2.20 (1H, dt, J 12.5 and
7.1, 23-H), 2.00 (1H, ddd, J 12.5, 7.6 and 2.4, 23-H), 0.98 (3H,
d, J 6.6, CH3), 0.93 (3H, d, J 7.1, CH3); m/z (EI) 164 (Mϩ, 0.3%)
and 109 {Found (EI) Mϩ 164.1150. C11H16O requires 164.1201;
Found (EI) [M Ϫ C4H7]ϩ 109.0653. C7H9O requires 109.0653}.
(1R,1ЉS,2ЈR,4ЈS,5ЈR)-1-[Tetrahydro-4Ј-methyl-5Ј-(1Љ-methyl-
prop-2Љ-enyl)furan-2Ј-yl]ethanol 37a
L-Selectride (1.2 cm3, 1.0  solution in THF, 2.1 mmol) was
added to a solution of ketone 36 (191 mg, 1.05 mmol) in THF
(3.2 cm3) under argon at Ϫ78 ЊC and the mixture stirred at this
temperature for 3 hours. The reaction was allowed to warm to
room temperature, quenched with 1  HCl and extracted with
dichloromethane. The combined extracts were dried (Na2SO4),
filtered and concentrated in vacuo. Purification by column
chromatography on silica gel (1% methanol in 15% ether–
petrol) afforded the (1R,1ЉS,2ЈR,4ЈS,5ЈR)-alcohol 37a (141 mg,
73%) as a colourless gum with analytical data identical to that
reported previously.
(1ЉS,2ЈR,4ЈS,5ЈR)-1-[Tetrahydro-4Ј-methyl-5Ј-(1Љ-methylprop-
2Љ-enyl)furan-2Јyl]ethan-1-one 36
A solution of acetylene 35 (66 mg, 0.4 mmol) in acetone (4 cm3)
was added to a solution of yellow mercuric() oxide (50 mg) in
0.75  sulfuric acid (2.0 cm3) at 60 ЊC.19 The reaction was stirred
at 60 ЊC for 12 minutes, cooled to 0 ЊC and quenched with 1 
HCl (10 cm3). The mixture was extracted with dichloro-
methane, the combined extracts dried (MgSO4) and concen-
trated in vacuo. Purification by column chromatography on
silica gel (10% ether–petrol) afforded ketone 36 (59 mg, 81%) as
a light yellow oil. [α]D20 ϩ41 (c 1.00 in CHCl3); νmax(thin film)/cmϪ1
2967, 1713, 1636, 1453, 1353, 1087, 1006 and 909; δH(270 MHz;
CDCl3) 5.94 (1H, ddd, J 17.3, 10.3 and 7.2, 19-H), 5.12 (1H,
Tetrahydro-5-(1Ј-methoxyethyl)-3-methyl-2-(1Љ-methylprop-2Љ-
enyl)furan 38
Sodium hydride (60% dispersion in oil, 38.4 mg, 1.6 mmol) was
added to a stirred solution of alcohol 37b (29.5 mg, 0.16 mmol)
in dry THF (4.8 cm3) at room temperature under argon. After
15 minutes iodomethane (0.15 cm3, 341 mg, 2.4 mmol) was
added and the mixture was stirred at room temperature for a
further 4 hours. The reaction was quenched with saturated
aqueous NH4Cl and extracted with dichloromethane. The
combined extracts were dried (MgSO4), filtered and concen-
trated in vacuo. Purification by column chromatography on
silica gel (15% ether–petrol) afforded methyl ether 38 (27.3 mg,
† For compounds 8, 34–55 the NMR assignments follow the atom
numbering of Tetronasin 1.
2270
J. Chem. Soc., Perkin Trans. 1, 1998

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87%) as a colourless gum (Found: C, 72.80; H, 11.50. C12H22O2
requires C, 72.68; H, 11.18%); [α]D25 ϩ4.1 (c 1.02 in CHCl3); νmax
added dropwise and then stirred for 30 minutes, and cooled to
-
Ϫ100 ЊC. Enone 39 (2.78 g, 6.9 mmol) in THF (13 cm3) was
added slowly over 10 minutes and the mixture stirred at this
temperature for 16 hours. The reaction was quenched by the
sequential addition of methanol (6.6 cm3) followed by water
(6.6 cm3). The mixture was warmed to room temperature, then
solid sodium hydrogen carbonate added and the mixture stirred
for 1 hour and then filtered. The filtrate was poured into ether
(300 cm3) and the organic layer separated. The organics were
washed with water and brine, then dried (MgSO4), filtered and
concentrated in vacuo. The oil was triturated with petrol to
remove S-BINAL, filtered and the filtrate concentrated in
vacuo. The residue was purified by chromatography (SiO2, 50%
ether–petrol) to give S-alcohol 40 (1.75 g, 63%) (Found: C,
74.32; H, 10.12. C25H40O4 requires C, 74.22; H, 9.97%); [α]D20
ϩ2.6 (c 1.0 in CHCl3); νmax(thin film)/cmϪ1 3413, 3028, 2922,
1594, 1494, 1450, 1375, 1203, 1093, 862, 802, 735 and 697;
δH(500 MHz; CDCl3) 7.28 (5H, m, Ph), 5.84 (1H, dd, J 15.5 and
7.1, 19-H), 5.50 (1H, ddd, J 15.5, 7.3 and 1.0, 18-H), 4.48 (2H, s,
PhCH2O), 4.0 (2H, m, 24-H, 17H), 3.50 (1H, dd, J 9.6 and 4.1,
21-H), 3.31 (3H, s, 25-OMe), 3.38 (2H, m, 13-H1, 25-H), 3.22
(1H, m, 13-H1), 2.26 (2H, m, 20-H, 22-H), 1.90 (1H, m, 23-H1),
1.80 (1H, m, 14-H), 1.62 (1H, ddd, J 12.4, 7.0 and 1.3, 23-H1),
1.50 (3H, m, 15-H1, 16-H2), 1.08 (1H, m, 15-H1), 1.08 (3H, d,
J 6.6, 26-Me), 0.92 (9H, m, 27-Me, 28-Me, 29-Me); m/z 404
(Mϩ), 386 (Mϩ Ϫ H2O), 345 (Mϩ Ϫ OC3H7) and 143.
(thin film)/cmϪ1 2967, 1638, 1456, 1371, 1094, 1013, 909; δH(270
MHz; CDCl3) 5.93 (1H, ddd, J 17.3, 10.4 and 7.0, 19-H), 5.07
(1H, ddd, J 17.3, 1.7 and 1.2, 18-H), 4.99 (1H, ddd, J 10.4, 1.7
and 1.0, 18-H), 3.97 (1H, ddd, J 8.6, 7.1 and 4.5, 24-H), 3.54
(1H, dd, J 9.6 and 4.0, 21-H), 3.45–3.33 (1H, m, 25-H), 3.39
(3H, s, OMe), 2.33–2.17 (2H, m, 20-H, 22-H), 2.01 (1H, ddd,
J 12.4, 8.7 and 6.6, 23-H), 1.66 (1H, ddd, J 12.4, 7.0 and 1.3,
23-H), 1.08 (3H, d, J 6.4, 25-CH3), 0.95 (3H, d, J 6.8, CH3),
0.93 (3H, d, J 7.1, CH3); m/z (EI) 198 (Mϩ, 1%), 143, 95, 59
and 55.
(1ЉS,2R,2ЈR,3ЈS,5ЈR)-2-[Tetrahydro-5Ј-(1Љ-methoxyethyl)-3Ј-
methylfuran-2Ј-yl]propanal 8
Ozone was passed through a solution of alkene 38 (23.8 mg,
0.12 mmol) in dry dichloromethane (18 cm3) for 30 minutes at
Ϫ78 ЊC. The reaction mixture was then degassed for 15 minutes
and concentrated in vacuo to approximately 2–3 cm3. Tri-
phenylphosphine (47 mg, 0.18 mmol) was then added and the
solution stirred at room temperature under argon for 4 hours.
The reaction mixture was concentrated in vacuo and purified by
column chromatography on silica gel (10–25% ether–petrol) to
afford aldehyde 8 (20.1 mg, 84%) as a colourless gum (Found: C,
65.75; H, 10.16. C11H20O3 requires C, 65.97; H, 10.07%); [α]D20
Ϫ58.5 (c 1.00 in CHCl3); νmax(thin film)/cmϪ1 2968, 1724, 1459,
1371, 1092 and 1011; δH(270 MHz; CDCl3) 9.80 (1H, d, J 2.7,
19-H), 4.02 (1H, ddd, J 8.9, 6.7 and 4.5, 24-H), 3.88 (1H, dd,
J 10.2 and 4.1, 21-H), 3.40–3.30 (1H, m, 25-H), 3.36 (3H, s,
OMe), 2.53–2.40 (1H, m, 20-H), 2.40–2.27 (1H, m, 22-H), 2.02
(1H, ddd, J 12.4, 9.0 and 6.6, 23-H), 1.69 (1H, dd, J 12.4
and 6.8, 23-H), 1.08 (3H, d, J 6.4, 25-CH3), 1.00 (3H, d, J 7.1,
20-CH3), 0.94 (3H, d, J 7.1, 22-CH3); m/z (EI) 200 (Mϩ, 100%),
157, 111, 85, 83 and 59.
(3E,1ЉS,2S,2ЈR,3ЈS,5S,5ЈR,8R)-9-Benzyloxy-5-tert-butyl-
dimethylsilyloxy-8-methyl-2-[tetrahydro-5Ј-(1Љmethoxyethyl)-
3Ј-methylfuran-2Ј-yl]non-3-ene 41
(S)-Alcohol 40 (2.03 g, 5 mmol) was dissolved in DMF (40 cm3)
and added via cannula to a mixture of imidazole (444 mg, 7.5
mmol) and tert-butylchlorodimethylsilane. The reaction was
stirred for 16 hours, then poured into water (40 cm3) and ether
(250 cm3). The organic layer was separated, washed with water
and brine, then dried (MgSO4), filtered and concentrated in
vacuo. The residue was purified by chromatography (SiO2, 15%
acetone–petrol) to give the silyl ether 41 (2.54 g, 98%) (Found:
C, 71.86; H, 10.34. C31H54O4Si requires C, 71.76; H, 10.49%);
[α]D20 Ϫ10.8 (c 1.94 in CHCl3); νmax(thin film)/cmϪ1 2958, 2929,
2855, 1460, 1370, 1250, 1201, 1096, 968, 863, 836, 813, 776, 734,
697 and 663; δH(500 MHz; CDCl3) 7.29 (5H, m, Ph), 5.66 (1H,
ddd, J 15.6, 6.7 and 1.1, 19-H), 5.41 (1H, ddd, J 15.6, 6.9 and
1.1, 18-H), 4.48 (2H, s, PhCH2O), 4.02 (1H, m, 17-H), 3.94 (1H,
m, 24-H), 3.50 (1H, dd, J 9.4 and 4.1, 21-H), 3.36 (3H, s,
25-OMe), 3.32 (2H, m, 13-H2), 3.21 (1H, qd, J 9.0 and 7.0,
25-H), 2.22 (2H, m, 20-H, 22-H), 1.97 (1H, m, 23-H1), 1.74 (1H,
m, 14-H), 1.66 (1H, m, 23-H1), 1.47 (3H, m, 15-H1, 16-H2), 1.07
(3H, d, J 6.3, 26-Me), 1.06 (1H, m, 15-H1), 0.92 (9H, m, 27-Me,
28-Me, 29-Me), 0.82 (9H, s, Si-But), 0.06 (3H, s, SiMe), 0.04
(3H, s, SiMe); m/z 519 (Mϩ), 461 (Mϩ Ϫ OC3H7) and 143.
(3E,1ЉS,2S,2ЈR,3ЈS,5ЈR,8R)-9-Benzyloxy-8-methyl-2-[tetra-
hydro-5Ј-(1Љ-methoxyethyl)-3Ј-methylfuran-2Ј-yl]non-3-en-5-
one 39
Keto phosphonate 7 (1.97 g, 5.99 mmol) in acetonitrile (3 cm3)
was added to lithium chloride (254 mg, 5.99 mmol) in
acetonitrile (30 cm3) and stirred for 10 minutes. Diisopropyl-
ethylamine (870 µl, 4.99 mmol) was added, followed by alde-
hyde 8 (1.0 g, 4.99 mmol) via cannula, and the mixture stirred
for 16 hours. The mixture was poured into a mixture of 5%
aqueous ammonium chloride (60 cm3) and ether (350 cm3). The
organic layer was separated, washed with water, and brine, then
dried (MgSO4), filtered and concentrated in vacuo. The residue
was purified by chromatography (SiO2, 20% acetone–petrol) to
give enone 39 (0.95 g, 67%) (Found: C, 74.30; H, 9.73. C25H38O4
requires C, 74.59; H, 9.51%); [α]D23 Ϫ9.4 (c 1.12 in CHCl3); νmax
-
(thin film)/cmϪ1 3029, 2965, 2930, 2875, 1675, 1671, 1628, 1494,
1451, 1370, 1190, 1095, 1009, 930, 864, 802, 737 and 698; δH(270
MHz; CDCl3) 7.33 (5H, m, Ph), 6.92 (1H, dd, J 16.4 and 7.2,
19-H), 6.12 (1H, dd, J 16.4 and 0.9, 18-H), 4.48 (2H, s,
PhCH2O), 3.96 (1H, m, 24-H), 3.60 (1H, dd, J 9.6 and 4.1,
21-H), 3.34 (3H, m, 13-H2 and 25-H), 3.31 (3H, s, 25-OMe), 2.57
(2H, m, 20-H, 22-H), 2.50 (2H, m, 16-H2), 2.42 (1H, m, 23-H1),
1.78 (2H, m, 14-H, 15-H1), 1.68 (1H, ddd, J 12.5, 7.0 and 1.1,
23-H1), 1.48 (1H, m, 15-H1), 1.07 (3H, d, J 6.3, 26-Me), 1.00
(3H, d, J 6.8, 28-Me), 0.94 (6H, d, J 6.8, 27-Me, 29-Me); m/z
402 (Mϩ), 387 (Mϩ Ϫ Me), 343 (Mϩ Ϫ OC3H7), 143 and 91
(6E,1ЉS,2R,2ЈR,3ЈS,5S,5ЈR,8S)-5-tert-Butyldimethylsilyloxy-2-
methyl-8-[tetrahydro-5Ј-(1Љ-methoxyethyl)-3Ј-methylfuran-
2Ј-yl]non-6-en-1-ol 42
Sodium (1 g) was added to ammonia (125 cm3) at Ϫ78 ЊC. Silyl
ether 41 (1.6 g, 3.09 mmol) in ether (10 cm3) was then added,
and the reaction stirred for 48 hours by which time the blue
colouration had dissipated. The reaction was gradually warmed
to room temperature, the ammonia evaporated, and ether (500
cm3) added. The ether was washed with water and brine, then
dried (MgSO4), filtered and concentrated in vacuo. The residue
was purified by chromatography (SiO2, 50% ether–petrol) to
give alcohol 42 (1.31 g, 99%) (Found: C, 67.24; H, 11.29.
C24H48O4Si requires C, 67.24; H, 11.28%); [α]D20 Ϫ8.2 (c 1.16 in
CHCl3); νmax(thin film)/cmϪ1 3399, 2930, 1462, 1375, 1250,
1093, 835, 775 and 663; δH(500 MHz; CDCl3) 5.67 (1H, dd,
J 15.7 and 6.6, 19-H), 5.43 (1H, ddd, J 15.6, 6.8 and 1.1, 18-H),
4.05 (1H, m, 17-H), 3.96 (1H, m, 24-H), 3.51 (1H, dd, J 9.5 and
4.1, 21-H), 3.42 (2H, m, 13-H2), 3.37 (3H, s, 25-OMe), 3.33 (1H,
ϩ
(C7H7 ).
(3E,1ЉS,2S,2ЈR,3ЈS,5S,5ЈR,8R)-9-Benzyloxy-8-methyl-2-
[tetrahydro-5Ј-(1Љ-methoxyethyl)-3Ј-methylfuran-2Јyl]non-3-en-
5-ol 40
Methanol (6.9 cm3 of a 2.0  solution in THF, 13.8 mmol) was
added to lithium aluminium hydride (13.8 cm3 of a 1.0  solu-
tion in THF, 13.8 mmol) at room temperature. After 5 minutes
(S)-1,1Ј-binaphth-2-ol (S-BINAL) (3.94 g, 10 mmol) was
J. Chem. Soc., Perkin Trans. 1, 1998
2271

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m, 25-H), 2.23 (2H, m, 20-H, 22-H), 1.96 (1H, m, 23-H1), 1.68–
1.44 (7H, m, OH, 14-H, 15-H2, 16-H2, 23-H1), 1.08 (3H, d,
J 6.3, 26-Me), 0.93 (3H, d, J 6.8, 29-Me), 0.92 (3H, d, J 7.0,
28-Me), 0.89 (3H, d, J 6.7, 27-Me), 0.88 (9H, s, Si-But), 0.03
(6H, s, SiMe2); m/z 371 (Mϩ Ϫ But), 353, 341 (Mϩ Ϫ But Ϫ
2Me), 296, 281, 257 and 143.
colourless oil, together with unreacted aldehyde 43 (0.11 g,
17%). For triene 44 (Found: C, 67.53; H, 10.72. C39H74O6Si2
requires C, 67.38; H, 10.73%); νmax(thin film)/cmϪ1 2959, 2931,
2857, 1725, 1460, 1372, 1333, 1251, 1190, 1151, 1094, 963, 877,
839 and 776; δH(500 MHz; CDCl3) 6.35 [1H, d, J 10.6, 13-
H(E)], 5.98 (1H, d, J 15.9, 11-H), 5.65 (2H, m, 10-H, 19-H),
5.64 [1H, 11-H(E)], 5.46 [1H, d, J 10.3, 13-H(Z)], 5.38 (1H, dd,
J 15.6 and 8.9, 18-H), 4.26 [2H, q, J 7.1, OCH2Me(Z)], 4.20
[2H, q, J 7.1, OCH2Me(E)], 4.01 (1H, m, 17-H), 3.94 (1H, m,
24-H), 3.49 (2H, m, 5-H1 and 21-H), 3.43 (1H, m, 5-H1), 3.37
(3H, s, 25-OMe), 3.33 (1H, m, 25-H), 2.60 [1H, m, 14-H(E)],
2.45 [1H, m, 14-H(Z)], 2.23 (3H, m, 20-H, 9-H2), 2.04 (2H, m,
22-H), 1.97 (1H, m, 23-H1), 1.64 (2H, m, 23-H1, 6-H), 1.39 (2H,
m, 16-H2), 1.3–0.75 (15H, m, 7-H2, 8-H2, 15-H2, 27-Me, 28-Me
and OCH2CH3), 1.08 (3H, d, J 6.3, 26-Me), 0.98 (3H, d, J 6.6,
29-Me), 0.87 (9H, s, Si-But), 0.02 (3H, s, SiMe), 0.01 (3H, s,
SiMe); m/z 622 (Mϩ), 577 (Mϩ Ϫ OEt) and 143.
(6E,1ЉS,2R,2ЈR,3ЈS,5S,5ЈR,8S)-5-tert-Butyldimethylsilyloxy-2-
methyl-8-[tetrahydro-5Ј-(1Љ-methoxyethyl)-3Ј-methylfuran-2Ј-
yl]non-6-enal 43
(a) The alcohol 42 (25 mg, 0.087 mmol) was dissolved in dichlo-
romethane (2 cm3). N-methylmorpholine-N-oxide (12 mg, 0.087
mmol) and powdered 4 Å molecular sieves (100 mg) were added
followed by tetra-n-propylammonium perruthenate (5 mg). The
reaction was stirred for 25 minutes then filtered through a silica
pad, washing with ether (30 cm3). The combined washings
and filtrate were then concentrated in vacuo. The residue was
purified by chromatography (SiO2, 20% ether–petrol) to give
aldehyde 43 (24 mg, 95%).
(1ЈE,2Z,8E,1ٞS,2ЉR,3ЉS,4R,5ЉR,6ЈR,7S,10S)-Ethyl 7-tert-
butyldimethylsilyloxy-2-(7Ј-hydroxy-6Ј-methylhept-1Ј-enyl)-4-
methyl-10-[tetrahydro-5Љ-(1ٞ-methoxyethyl)-3Љ-methylfuran-
2Љyl]undeca-2,8-dienoate 45a and (1ЈE,2E,8E,1ٞS,2ЉR,3ЉS,4R,
5ЉR,6ЈR,7S,10S)-ethyl 7-tert-butyldimethylsilyloxy-2-(7Ј-
hydroxy-6Ј-methylhept-1Ј-enyl)-4-methyl-10-[tetrahydro-5Љ-(1ٞ-
methoxyethyl)-3Љ-methylfuran-2Љ-yl]undeca-2,8-dienoate 45b
Triene 44 (1.25 g, 1.81 mmol) was stirred in dry THF (100 cm3)
at room temperature under argon. Aqueous acetate buffer (50
cm3, pH 3, ~0.003  in acetate) and methanol (25 cm3) were then
added. After 1 h, ether (200 cm3) was added and the mixture
shaken. The organic extracts were separated and then washed
with water (150 cm3), and brine (150 cm3), dried (MgSO4),
filtered, the solvent removed in vacuo and the residue purified
by flash column chromatography (75% petrol–ethyl acetate) to
afford the alcohol 45 (1.12 g, quant.) as a colourless oil (Found:
C, 69.30; H, 10.70. C36H66O6Si requires C, 69.41; H, 10.68%);
νmax(thin film)/cmϪ1 3463, 2928, 1721, 1461, 1370, 1250, 1191,
1146, 1094, 964, 836 and 776; δH(500 MHz; CDCl3) 6.33 [1H, d,
J 10.3, 13-H(E)], 5.98 [1H, d, J 16.0, 11-H(Z)], 5.65 (2H, m,
10-H, 19-H), 5.47 [1H, d, J 10.3, 13-H(Z)], 5.38 (1H, ddd,
J 14.5, 6.7 and 1.1, 18-H), 4.25 [2H, q, J 7.1, OCH2Me(Z)], 4.23
[2H, q, J 7.1, OCH2Me(E)], 4.04 (1H, m, 17-H), 3.95 (1H, m,
24-H), 3.49 (1H, dd, J 9.5 and 4.1, 21-H), 3.42 (1H, dd, J 9.5
and 4.1, 5-H1), 3.38 (3H, s, 25-OMe), 3.34 (1H, dd, J 10.0 and
6.0, 5-H1), 3.33 (1H, m, 25-H), 2.60 [1H, m, 14-H(E)], 2.45 [1H,
m, 14-H(Z)], 2.22 (3H, m, 20-H, 9-H2), 2.17 (2H, m, 22-H,
23-H1), 1.65 (1H, ddd, J 12.5, 6.9 and 1.3, 23-H1), 1.60 (1H, m,
6-H), 1.5–1.25 (11H, m, 7-H2, 8-H2, 16-H2, 15-H2, OCH2CH3),
1.08 (3H, d, J 6.3, 26-Me), 0.98 (3H, d, J 6.6, 27-Me), 0.92 (6H,
d, J 6.9, 28-Me, 29-Me), 0.88 (3H, d, J 6.7, 6-Me), 0.87 (9H, s,
Si-But), 0.02 (6H, s, SiMe2).
(b) Oxalyl chloride (1.4 cm3, 2.0  solution in dichloro-
methane, 2.8 mmol) was cooled to Ϫ78 ЊC, then dimethyl
sulfoxide (398 µl, 5.6 mmol) added. The solution was stirred for
ten minutes then alcohol 42 (1 g, 2.33 mmol) was added via
cannula and stirred for a further 30 minutes. Triethylamine (1.56
cm3, 11.2 mmol) was added and the reaction kept at this tem-
perature for 10 minutes then allowed to warm to room temper-
ature over 30 minutes. The mixture was poured into water
(40 cm3) and extracted with dichloromethane (3 × 40 cm3). The
combined organic extracts were washed with water (2 × 20 cm3)
and brine (100 cm3), then dried (Na2SO4), filtered and concen-
trated in vacuo. The residue was purified by chromatography
(SiO2, 20% ether–petrol) to give aldehyde 43 (0.94 g, 95%).
Aldehyde 43: (Found: C, 67.31; H, 10.55. C24H46O4Si requires
C, 67.55; H, 10.87%); [α]D20 Ϫ8.2 (c 1.16 in CHCl3); νmax(thin
film)/cmϪ1 2960, 2930, 2855, 2706, 1725, 1458, 1371, 1251, 1190,
1094, 1069, 1007, 968, 836, 776 and 663; δH(500 MHz; CDCl3)
9.59 (1H, d, J 2.0, 13-H), 5.69 (1H, dd, J 15.7 and 6.6, 19-H),
5.41 (1H, ddd, J 15.6, 6.8 and 1.2, 18-H), 4.09 (1H, m, 17-H),
3.95 (1H, m, 24-H), 3.49 (1H, dd, J 9.6 and 4.1, 21-H), 3.38
(3H, s, 25-OMe), 3.30 (1H, m, 25-H), 2.30 (1H, m, 14-H), 2.25
(2H, m, 20-H, 22-H), 1.99 (1H, ddd, J 12.4, 8.9 and 6.7, 23-H1),
1.75 (1H, m, 15-H1), 1.62 (1H, ddd, J 12.4, 6.7 and 1.2, 23-H1),
1.49 (2H, m, 16-H2), 1.35 (1H, m, 15-H1), 1.08 (6H, m, 26-Me,
29-Me), 0.90 (6H, m, 27-Me, 28-Me), 0.85 (9H, s, Si-But), 0.01
(6H, s, SiMe2); m/z 426 (Mϩ) and 143.
(1ЈE,2Z,8E,1ٞS,2ЉR,3ЉS,4R,5ЉR,6ЈR,7S,10S)-Ethyl 7-tert-
butyldimethylsilyloxy-2-(7Ј-trimethylsilyloxy-6Ј-methylhept-1Ј-
enyl)-4-methyl-10-[tetrahydro-5Љ-(1ٞ-methoxyethyl)-3Љ-methyl-
furan-2Љ-yl]undeca-2,8-dienoate 44a and (1ЈE,2Z,8E,1ٞS,2ЉR,
3ЉS,4R,5ЉR,6ЈR,7S,10S)-ethyl 7-tert-butyldimethylsilyloxy-2-
(7Ј-trimethylsilyloxy-6Ј-methylhept-1Ј-enyl)-4-methyl-10-[tetra-
hydro-5Љ-(1ٞ-methoxyethyl)-3Љ-methylfuran-2Љ-yl]undeca-2,8-
dienoate 44b
(1ЈE,2Z,8E,1ٞS,2ЉR,3ЉS,4R,5ЉR,6ЈR,7S,10S)-Ethyl 7-tert-
butyldimethylsilyloxy-2-(7Ј-oxo-6Ј-methylhept-1Ј-enyl)-4-
methyl-10-[tetrahydro-5Љ-(1ٞ-methoxyethyl)-3Љ-methylfuran-
2Љ-yl]undeca-2,8-dienoate 46
(a) The alcohol 45 (72.3 mg, 0.03 mmol) was dissolved in
dichloromethane (15 cm3). N-Methylmorpholine-N-oxide (25
mg, 0.174 mmol) and powdered 4 Å molecular sieves (100 mg)
were added followed by tetra-n-propylammonium perruthenate
(10 mg). The reaction was stirred for 30 minutes then filtered
through a silica pad, washing exhaustively with ether (30 cm3).
The combined filtrate and washings were then concentrated
in vacuo. The residue was purified by chromatography (florisil,
25% ether–petrol) to give aldehyde 46 (68 mg, 95%).
(b) Oxalyl chloride (203 µl, 2.0  solution in dichlorometh-
ane, 0.406 mmol) was cooled to Ϫ78 ЊC, then dimethyl sulfoxide
(58 µl, 0.817 mmol) was added. The solution was stirred for 10
minutes then alcohol 45 (211 mg, 0.34 mmol) was added via
cannula and the resultant mixture stirred for a further 30 min-
utes. Triethylamine (226 µl, 1.63 mmol) was added, the mixture
Phosphonate 6 (0.98 g, 2.33 mmol, 1.5 equiv.) in THF (2 cm3)
was cooled to Ϫ78 ЊC under argon. Lithium bis(trimethylsilyl)-
amide (2.28 cm3, 1.0  in THF, 2.28 mmol, 1.47 equiv.) was
added dropwise and the solution allowed to warm to room
temperature over 30 minutes. The solution was cooled to Ϫ78 ЊC
for 10 minutes then aldehyde 43 (0.66 g, 1.55 mmol) in dry THF
(2 cm3) was added dropwise via syringe. After 10 minutes the
reaction mixture was allowed to warm to room temperature
over 1.5 hours and was then stirred for a further 15 hours. The
reaction was quenched by the addition of saturated aqueous
ammonium chloride (5 cm3), and extracted with ether (3 × 75
cm3). The organic layer was separated, washed with water and
brine, then dried (Na2SO4), filtered and concentrated in vacuo.
The residue was purified by chromatography (SiO2, 60% petrol–
ethyl acetate) to give triene 44 (0.73 g, 68%, 82% based on
recovered starting material, mixture of Z:E of 4.6:1) as a
2272
J. Chem. Soc., Perkin Trans. 1, 1998

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kept at this temperature for 10 minutes and then allowed to
warm to room temperature over 30 minutes. The mixture was
poured into water (5 cm3) and extracted with dichloromethane
(3 × 20 cm3). The organics were washed with water (2 × 10 cm3)
and brine (10 cm3), then dried (Na2SO4) filtered and concen-
trated in vacuo. The residue was purified by chromatography
(florisil, 20% ether–petrol) to give aldehyde 46 (183 mg, 98%)
νmax(thin film)/cmϪ1 2961, 2931, 1857, 1719, 1649, 1460, 1368,
1257, 1176, 1147, 1095, 1006, 984, 836 and 776; δH(500 MHz;
CDCl3) 9.61 (1H, d, J 1.9, 5-H), 6.35 [1H, d, J 10.6, 13-H(E)],
5.98 (1H, d, J 15.6, 11-H), 5.65 (2H, m, 10-H, 19-H), 5.48 [1H,
d, J 10.3, 13-H(Z)], 5.38 (1H, ddd, J 16.6, 7.2 and 1.0, 18-H),
4.25 [2H, q, J 7.1, OCH2Me(Z)], 4.20 [2H, q, J 7.1, OCH2-
Me(E)], 4.02 (1H, m, 17-H), 3.92 (1H, m, 24-H), 3.48 (1H, dd,
J 10.0 and 4.0, 21-H), 3.36 (3H, s, 25-OMe), 3.31 (1H, m, 25-
H), 2.48 (1H, m, 14-H), 2.34 (4H, m, 20-H, 22-H and 9-H2),
1.96 (1H, m, 23-H1), 1.70 (1H, m, 6-H), 1.65 (1H, m, 23-H1),
1.4–0.75 (11H, m, 7-H2, 8-H2, 15-H2, 16-H2, OCH2CH3),
1.08 (6H, 2 × d, J 7.1 and 7.2, 6-Me, 26-Me), 0.99 (3H, d, J 6.6,
29-Me), 0.92 (6H, m, 27-Me, 28-Me), 0.87 (9H, s, Si-But), 0.02
(3H, s, SiMe), 0.01 (3H, s, SiMe).
were concentrated in vacuo and the residue was purified by
chromatography (SiO2, 70% ether–petrol), to give alcohol 48
(134 mg, 100%) (Found: C, 70.09; H, 9.78. C34H56O7 requires C,
70.80; H, 9.79%); νmax(thin film)/cmϪ1 3436, 2963, 2930, 1713,
1646, 1452, 1378, 1248, 1189, 1093, 1015, 966 and 751; δH(500
MHz; CDCl3) 6.52 (1H, dd, J 10.0 and 1.4, 5-H), 6.35 [1H, d,
J 9.6, 13-H(E)], 5.95 (1H, d, J 15.7, 11-H), 5.70 (1H, dd, J 15.6
and 7.2, 19-H), 5.62 (1H, dt, J 15.7 and 6.7, 10-H), 5.50 (1H,
ddd, J 15.6, 7.1 and 0.9, 18-H), 5.48 [1H, d, J 9.7, 13-H(Z)],
4.26 [2H, q, J 7.1, OCH2Me(Z)], 4.20 [2H, q, J 7.2, OCH2-
MeH(E)], 4.01 (2H, m, 17-H, 24-H), 3.73 (3H, s, CO2Me), 3.52
(1H, dd, J 9.7 and 4.0, 21-H), 3.37 (3H, s, 25-OMe), 3.33 (1H,
m, 25-H), 2.57 (2H, m, 6-H, 14-H), 2.25 (2H, m, 20-H, 22-H),
2.05 (2H, m, 9-H2), 1.97 (1H, m, 23-H1), 1.83 (3H, d, J 1.4,
32-Me), 1.32 (9H, m, 7-H2, 8-H2, 15-H2, 16-H2, 23-H1), 1.31
(3H, t, J 7.1, OCH2CH3), 1.08 (3H, d, J 6.3, 26-Me), 1.00 (3H,
d, J 6.4, 31-Me), 0.99 (3H, d, J 6.6, 27-Me), 0.93 (3H, d, J 6.8,
28-Me or 29-Me), 0.92 (3H, d, J 6.9, 28-Me or 29-Me); m/z (CI)
ϩ
594 (MNH4 ), 576 (Mϩ), 559 (Mϩ Ϫ OH), 530, 513, 143 [Found
(CI) MNH4ϩ 594.4370. C34H60O7N requires 594.4369].
(2Z)-Ethyl 2-[(2R,3R,6S)-tetrahydro-3-methyl-6-{3-(1E)-
[(1ЈS,2R,3S,5R)-tetrahydro-5-(1Ј-methoxyethyl)-3-methylfuran-
2-yl]but-1-enyl}-2H-pyran-2-yl)-3-(1S,1ЈR,2S,3R)-[3-methyl-2-
(1Ј-methoxycarbonylethyl)cyclohexyl]prop-2-enoate 49
(a) The alcohol 48 (34.4 mg, 0.0596 mmol) was dissolved in
toluene (4 cm3) and cooled to 0 ЊC for 15 minutes in an ice bath.
Potassium bis(trimethylsilyl)amide (131 µl, 0.5  solution in
toluene, 0.065 mmol) was added quickly and the yellow solu-
tion stirred for 30 minutes. The reaction was quenched with a
dilute solution of acetic acid in toluene and concentrated in
vacuo. The residue was purified by chromatography (SiO2, 35%
ether–petrol), to give diester 49 (27 mg, 67%).
(2E,8E,10Z,16E,1ЉS,2ЈR,3ЈS,4R,5ЈR,12R,15S,18S)-Methyl
15-tert-butyldimethylsilyloxy-10-ethoxycarbonyl-18-[tetrahydro-
5Ј-(1Љ-methoxyethyl)-3Ј-methylfuran-2Ј-yl]-2,4,12-trimethyl-
nonadeca-2,8,10,16-tetraenoate 47a and (2E,8E,10E,16E,
1ЉS,2ЈR,3ЈS,4R, 5ЈR,12R,15S,18S)-methyl tert-butyldimethyl-
silyloxy-10-ethoxycarbonyl-18-[tetrahydro-5Ј-(1Љ-methoxy-
ethyl)-3-methylfuran-2Ј-yl]-2,4,12-trimethylnonadeca-2,8,10,16-
tetraenoate 47b
The aldehyde 46 (63 mg, 0.101 mmol) was dissolved in chloro-
form (10 cm3) and then 2-(methoxycarbonyl)ethylenetriphenyl-
phosphorane (200 mg, 0.555 mmol) was added. The reaction
was heated under reflux in the dark for 16 hours, concentrated
in vacuo and then dissolved in ether. The solution was filtered
through a small pad of silica washing with 50% ether–petrol
and the combined filtrates and washings concentrated in vacuo.
The residue was purified by chromatography (SiO2, 25% ether–
petrol) to give the tetraene-47 (70 mg, 100%) (Found: C, 69.43;
H, 10.10. C40H70O7Si requires C, 69.52; H, 10.22%); νmax(thin
film)/cmϪ1 2956, 2928, 2854, 1714, 1645, 1459, 1371, 1248, 1190,
1152, 1095, 964, 835, 776 and 750; δH(500 MHz; CDCl3) 6.65
(1H, dd, J 10.1 and 1.4, 5-H), 6.35 [1H, d, J 10.4, 13-H(E)], 5.95
(1H, d, J 15.7, 11-H), 5.64 (2H, m, 10-H, 19-H), 5.47 [1H, d,
J 10.3, 13-H(Z)], 5.38 (1H, dd, J 15.6 and 6.7, 18-H), 4.25 [2H,
q, J 7.1, OCH2Me(Z)], 4.20 [2H, q, J 7.1, OCH2Me(E)], 4.03
(1H, m, 17-H), 3.94 (1H, m, 24-H), 3.73 (3H, s, CO2Me), 3.49
(1H, dd, J 9.4 and 4.1, 21-H), 3.36 (3H, s, 25-OMe), 3.32 (1H,
m, 25-H), 2.47 (2H, m, 6-H, 14-H), 2.22 (2H, m, 20-H, 22-H),
2.06 (2H, m, 9-H2), 1.96 (1H, m, 23-H1), 1.83 (3H, d, J 1.5,
32-Me), 1.65 (1H, m, 23-H1), 1.5–1.2 (8H, m, 7-H2, 8-H2, 15-H2,
16-H2), 1.31 (3H, t, J 7.1, OCH2CH3), 1.08 (3H, d, J 6.3,
26-Me), 0.99 (3H, d, J 6.6, 31-Me), 0.98 (3H, d, J 6.6, 27-Me),
0.92 (6H, d, J 6.9, 28-Me, 29-Me), 0.87 (9H, s, OSi-But), 0.02
(3H, s, SiMe), 0.01 (3H, s, SiMe); m/z (CI) 708 (Mϩ ϩ NH4),
559 (Mϩ Ϫ TBDMS Ϫ Me), 513 (Mϩ Ϫ TBDMSO Ϫ OEt),
417, 388, 315, 143 [Found (CI) MNH4ϩ 708.5235. C40H74O7NSi
requires 708.5234].
(b) The alcohol 48 (10.5 mg, 0.0182 mmol) was dissolved in
toluene (1 cm3), HMPA (3 µl, 0.0182 mmol) was added and the
solution was cooled to 0 ЊC for 15 minutes in an ice bath. Potas-
sium bis(trimethylsilyl)amide (40 µl, 0.5  solution in toluene,
0.02 mmol) was added quickly and the yellow solution stirred
for 30 minutes. The reaction was quenched with a dilute solu-
tion of acetic acid in toluene and extracted with ether (3 × 20
cm3). The organics were washed with water and brine, then
dried (Na2SO4), filtered and concentrated in vacuo. The residue
was purified by chromatography (SiO2, 35% ether–petrol)
to give diester 49 (6.5 mg, 62%) (Found: C, 69.93; H, 9.46.
C34H56O7 requires C, 70.80; H, 9.79%); [α]D20 Ϫ22.5 (c 0.92 in
CHCl3); νmax(thin film)/cmϪ1 2923, 1725, 1451, 1371, 1205, 1095
and 1013; δH(500 MHz; CDCl3) 5.89 (1H, d, J 10.5, 11-H), 5.76
(1H, dd, J 15.9 and 6.3, 19-H), 5.50 (1H, dd, J 15.1 and 5.7,
18-H), 4.20 (2H, q, J 7.1, OCH2Me), 3.95 (1H, ddd, J 8.6, 7.0
and 5.0, 24-H), 3.82 (1H, m, 17-H), 3.77 (1H, d, J 9.8, 13-H),
3.66 (3H, s, CO2Me), 3.50 (1H, dd, J 9.5 and 4.1, 21-H), 3.38
(3H, s, 25-OMe), 3.34 (1H, qd, J 6.3 and 5.0, 25-H), 2.83 (1H,
dtd, J 11.0, 11.0 and 3.1, 10-H), 2.51 (1H, m, 4-H), 2.23 (2H, m,
20-H, 22-H), 1.96 (1H, ddd, J 12.4, 8.6 and 6.8, 23-H1), 1.83–
1.50 (8H, m, 15-H1, 5-H, 9-H1, 23-H1, 8-H1, 7-H1, 16-H1, 14-H),
1.38–1.00 (6H, m, 6-H, 7H1, 15-H1, 8-H1, 9-H1, 16-H1), 1.29
(3H, t, J 7.1, OCH2CH3), 1.08 (3H, d, J 6.9, 26-Me), 1.07 (3H,
d, J 6.9, 32-Me), 0.93 (3H, d, J 6.8, 27-Me or 28-Me), 0.92 (3H,
d, J 6.9, 27-Me or 28-Me), 0.75 (3H, d, J 7.5, 31-Me), 0.74 (3H,
d, J 6.6, 29-Me); δC(125.6 MHz; CDCl3) 177.59 (CO2Et), 167.59
(CO2CH3), 145.41 (11-C), 138.62 (12-C), 134.07 (19-C), 130.13
(18-C), 85.91 (21-C), 83.72 (13-C), 80.23 (24-C), 79.54 (25-C),
78.40 (17-C), 60.13 (OCH2CH3), 57.42 (25-OMe), 51.49
(CO2Me), 49.85 (5-C), 40.79 (10-C), 40.36 (4-C), 36.60 (20-C or
22-C), 36.09 (14-C), 35.82 (16-C), 35.29 (23-C), 35.23 (20-C or
22-C), 33.22 (9-C), 32.94 (15-C), 32.74 (6-C), 32.44 (7-C), 25.49
(8-C), 19.78 (31-C), 17.65 (29-C), 16.44 (27-C or 28-C), 15.94
(26-C), 14.27 (OCH2CH3), 13.51 (27-C or 28-C), 8.97 (32-C);
(2E,8E,10Z,16E,1ЉS,2ЈR,3ЈS,4R,5ЈR,12R,15S,18S)-Methyl
10-ethoxycarbonyl-15-hydroxy-18-[tetrahydro-5Ј-(1Љ-methoxy-
ethyl)-3Ј-methylfuran-2-yl]-2,4,12-trimethylnonadeca-2,8,10,16-
tetraenoate 48a and (2E,8E,10E,16E,1ЉS,2ЈR,3ЈS,4R,5ЈR,12R,
15S,18S)-methyl 10-ethoxycarbonyl-15-hydroxy-18-[tetrahydro-
5Ј-(1Љ-methoxyethyl)-3Ј-methylfuran-2Ј-yl]-2,4,12-trimethyl-
nonadeca-2,8,10,16-tetraenoate 48b
The tetraene 47 (366 mg, 0.53 mmol) was dissolved in methanol
(12 cm3) and Dowex-50W 400 mesh (4 mg) was added. The
reaction was stirred for 48 hours then the resin filtered off and
washed exhaustively with ether. The combined organic extracts
ϩ
m/z (EI) 594 (MNH4 ), 143 and 85 [Found (EI) Mϩ 576.4030.
C34H56O7 requires 576.4025].
J. Chem. Soc., Perkin Trans. 1, 1998
2273

View Article Online
(2R)-2-((1S,2S,6R)-6-Methyl-2-{3-hydroxy-2-[(2R,3R,6S)-
tetrahydro-3-methyl-6-(1E)-((2R,3S,5R)-3-{tetrahydro-5-[(R)-
1-methoxyethyl]-3-methylfuran-2-yl}but-1-enyl)-2H-pyran-2-
yl]prop-1-enyl}cyclohexyl)propanol 50 and (2R)-methyl 2-
((1S,2S,6R)-6-methyl-2-{3-hydroxy-2-[(2R,3R,6S)-tetrahydro-
3-methyl-6-(1E)-((2R,3S,5R)-3-{tetrahydro-5-[(1R)-1-methoxy-
ethyl]-3-methylfuran-2-yl}but-1-enyl)-2H-pyran-2-yl]prop-1-
enyl}cyclohexyl)propanoate 51
added and stirring was continued at this temperature. After 30
minutes methanol (0.5 cm3) was added and the reaction mixture
allowed to warm to room temperature. The solvent was
removed in vacuo and the residue purified by flash chrom-
atography (90% petrol–ethyl acetate) to give silyl ether 52 (11
mg, 91%) as a colourless oil; [α]D20 Ϫ38.1 (c 0.75 in CHCl3); νmax
-
(thin film)/cmϪ1 2927, 2855, 1735, 1462, 1378, 1254, 1205, 1064,
839 and 775; δH(500 MHz; CDCl3) 5.75 (1H, dd, J 15.9 and 6.9,
19-H), 5.52 (1H, dd, J 15.5 and 6.3, 18-H), 5.28 (1H, d, J 9.9,
11-H), 4.13 (1H, d, J 10.8, 30-H1), 4.06 (1H, d, J 10.7, 30-H1),
3.95 (1H, m, 24-H), 3.77 (1H, m, 17-H), 3.65 (3H, s, CO2Me),
3.51 (1H, dd, J 9.5 and 4.0, 21-H), 3.37 (3H, s, 25-OMe), 3.36
(1H, d, J 9.8, 13-H), 3.35 (1H, qd, J 6.7 and 5.1, 25-H), 2.65
(1H, m, 4-H), 2.31 (1H, m, 10-H), 2.2 (2H, m, 20-H, 22-H), 1.98
(1H, m, 23-H1), 1.80 (1H, m, 15-H1), 1.69 (1H, m, 5-H), 1.67–
1.12 (12H, m, 6-H, 7-H2, 8-H2, 9-H2, 14-H, 15-H1, 16-H2,
23-H1), 1.07 (3H, d, J 6.3, 26-Me), 1.02 (3H, d, J 7.1, 32-Me),
0.94 (3H, d, J 6.8, 28-Me), 0.91 (3H, d, J 7.0, 27-Me), 0.87 (9H,
s, Si-But), 0.74 (3H, d, J 6.6, 31-Me), 0.73 (3H, d, J 6.5, 29-Me),
Diester 49 (24 mg, 0.042 mmol) was stirred in dry THF (1 cm3)
at room temperature under argon. Lithium borohydride (0.2
cm3, 2.0  solution in THF, 0.4 mmol) was then added. After 60
hours methanol (5 cm3) was added, the reaction mixture stirred
for a further 10 minutes and solvent then removed in vacuo. The
crude residue was then co-evaporated with methanol (3 × 5
cm3) and purified by flash chromatography (85% petrol–ethyl
acetate) to give monomethyl ester 51 (13 mg, 58%) as a colour-
less oil together with some recovered starting material (1 mg,
4%) and more polar material identified as the di-reduced com-
pound 50 (4 mg, 19%). Monomethyl ester 51 [α]D20 Ϫ18.3 (c 0.3 in
CHCl3); νmax(thin film)/cmϪ1 3528, 2926, 1733, 1456, 1379,
1297, 1260, 1205, 1094, 1055, 1014, 911, 862 and 801; δH(500
MHz; CDCl3) 5.76 (1H, dd, J 15.8 and 6.5, 19-H), 5.51 (1H, dd,
J 15.8 and 5.9, 18-H), 5.26 (1H, d, J 10.0, 11-H), 4.18 (1H, dd,
J 11.7 and 8.9, 30-H1), 4.11 (1H, dd, J 11.9 and 2.2, 30-H2), 3.95
(1H, ddd, J 8.6, 6.9 and 4.8, 24-H), 3.79 (1H, m, 17-H), 3.66
(3H, s, CO2Me), 3.53 (1H, d, J 10.0, 13-H), 3.50 (1H, dd, J 9.6
and 4.2, 21-H), 3.37 (3H, s, 25-OMe), 3.33 (1H, qd, J 6.3 and
5.0, 25-H), 3.09 (1H, dd, J 8.8 and 2.1, OH), 2.73 (1H, m, 4-H),
2.23 (3H, m, 10-H, 20-H, 22-H), 1.97 (1H, ddd, J 12.4, 8.7 and
6.7, 23-H1), 1.86 (1H, m, 15-H1), 1.73 (1H, m, 5-H), 1.67–1.12
(12H, m, 6-H, 7-H2, 8-H2, 9-H2, 14-H, 15-H1, 16-H2, 23-H1),
1.08 (3H, d, J 6.7, 32-Me), 1.07 (3H, d, J 6.1, 26-Me), 0.92 (3H,
d, J 6.9, 28-Me), 0.91 (3H, d, J 7.1, 27-Me), 0.75 (3H, d, J 6.5,
ϩ
0.07 (3H, s, SiMe), 0.06 (3H, s, SiMe); m/z (CI) 666 (MNH4 ),
517 (Mϩ Ϫ TBDMSO), 143, 111, 85 and 59 [Found (CI)
MNH4ϩ 666.513. C38H72NO6Si requires 666.513].
(2R)-2-((1S,2S,6R)-6-Methyl-2-(3-tert-butyldimethylsilyloxy-2-
[(2R,3R,6S)-tetrahydro-3-methyl-6-(1E)-((2R,3S,5R)-3-{tetra-
hydro-5-[(R)-1-methoxyethyl]-3-methylfuran-2-yl}but-1-enyl)-
2H-pyran-2-yl]prop-1-enyl}cyclohexyl)propanol 53
Ester 52 (11.0 mg, 0.017 mmol) was stirred in dry dichloro-
methane (3 cm3) at Ϫ78 ЊC under argon. DIBAL-H (26 cm3
of a 1.0  solution in dichloromethane, 0.026 mmol) was then
added and the reaction mixture stirred at this temperature.
After 30 minutes saturated aqueous sodium potassium tartrate
(0.5 cm3) and methanol (0.5 cm3) were then added and the reac-
tion mixture allowed to warm to room temperature overnight.
Further dichloromethane (5 cm3) and water (5 cm3) were added
and the aqueous layer separated. The organic extracts were
dried (MgSO4), filtered, the solvent removed in vacuo and the
residue purified by flash chromatography (80% petrol–ethyl
acetate) to give alcohol 53 (8.3 mg, 79%) as a colourless oil; [α]D20
Ϫ27 (c 0.2 in CHCl3); νmax(thin film)/cmϪ1 3470 br (OH); δH(500
MHz; CDCl3) 5.62 (1H, dd, J 15.4 and 8.3, 19-H), 5.47 (1H, dd,
J 15.4 and 7.7, 18-H), 5.28 (1H, d, J 10.2, 11-H), 4.07 (2H, m,
30-H2), 3.99 (1H, ddd, J 9.9, 6.9 and 3.6, 24-H), 3.79 (1H, m,
17-H), 3.58 (1H, dd, J 10.0 and 4.0, 21-H), 3.52–3.45 (3H, m,
3-H2, 25-H), 3.40–3.38 (1H, m, 13-H), 3.38 (3H, s, 25-OMe),
2.29–2.18 (3H, m, 10-H, 20-H, 22-H), 2.12–2.06 (1H, m,
23-H1), 1.84 (1H, m, 4-H), 1.70–0.90 (14H, m), 1.02 (3H, d,
J 6.4, 26-Me), 0.91–0.88 (12H, 4 × d, 27-Me, 28-Me, 31-Me,
32-Me), 0.88 (9H, s, But), 0.76 (3H, d, J 6.5, 29-Me), 0.07, 0.06
(6H, 2 × s, Me2Si); m/z (FAB) 622 (MHϩ, 40%), 488 (50), 154
(75), 143 (100) [Found (FAB) MHϩ 621.492 50. C37H69O5Si
requires 621.49143].
ϩ
31-Me), 0.69 (3H, d, J 6.6, 29-Me); m/z (CI) 552 (MNH4 ), 535
(Mϩ ϩ H), 517 (Mϩ ϩ H Ϫ H2O), 143, 111, 85 and 59 [Found
(CI) MNH4ϩ 552.426. C32H58NO6 requires 552.426].
Diol 50 [α]D20 Ϫ4.94 (c 0.85 in CHCl3); νmax(thin film)/cmϪ1
3446, 2965, 2925, 2848, 1646, 1519, 1452, 1376, 1297, 1225,
1192, 1152, 1055, 1012, 908, 863 and 802; δH(500 MHz; CDCl3)
5.69 (1H, dd, J 15.7 and 7.4, 19-H), 5.48 (1H, dd, J 15.7 and 6.8,
18-H), 5.27 (1H, d, J 10.0, 11-H), 4.23 (1H, dd, J 11.8 and 8.1,
30-H1), 4.12 (1H, dd, J 11.4, 30-H1), 3.98 (1H, ddd, J 9.0, 6.9
and 4.2, 24-H), 3.80 (1H, m, 17-H), 3.54 (3H, m, 3-H2, 21-H),
3.53 (1H, d, J 10.0, 13-H), 3.40 (1H, m, 25-H), 3.38 (3H, s,
25-OMe), 2.94 (1H, d, J 8.1, 20-OH), 2.37 (1H, s, 3-OH), 2.27
(3H, m, 10-H, 6-H and 20-H), 2.02 (2H, m, 23-H1, 22-H), 1.87
(1H, m, 15-H1), 1.77 (4H, m, 14-H, 23-H1, 8-H1, 7-H1), 1.43
(3H, m, 16-H1, 4-H, 9-H1), 1.21 (2H, m, 8-H1, 15-H1, 16-H1),
1.05 (3H, d, J 6.4, 26-Me), 1.00 (2H, m, 9-H1, 7-H1), 0.92
(12H, m, 27-Me, 28-Me, 31-Me and 32-Me), 0.69 (3H, d, J 6.6,
29-Me); δC(125.6 MHz; CDCl3) 139.62 (11-C), 135.49 (19-C),
134.27 (12-C), 129.86 (18-C), 91.19 (13-C), 85.83 (21-C), 80.27
(24-C), 79.26 (25-C), 78.64 (17-C), 68.23 (3-C), 58.39 (30-C),
57.36 (25-OMe), 49.17 (5-C), 39.84 (10-C), 38.45 (22-C), 36.93
(20-C), 36.61 (7-C), 35.10 (6-C), 34.96 (23-C), 34.58 (9-C),
33.26 (4-C), 32.43 (14- or 15- or 16-C), 32.39 (14- or 15- or
16-C), 32.30 (14- or 15- or 16-C), 25.63 (8-C), 22.23 (31-C),
18.00 (29-C), 16.73 (27- or 28-C), 15.79 (26-C), 13.52 (27- or
28-C), 12.44 (32-C); m/z (CI) 507 (MHϩ), 489, 471 (Mϩ Ϫ
2H2O), 329, 234, 223, 183, 167, 143, 111, 85 and 41 [Found (CI)
Mϩ 507.405. C31H55O5 requires 507.405].
(2R)-2-((1S,2S,6R)-6-Methyl-2-(3-tert-butyldimethylsilyloxy-
2-[(2R,3R,6S)-tetrahydro-3-methyl-6-(1E)-((2R,3S,5R)-3-
{tetrahydro-5-[(R)-1-methoxyethyl]-3-methylfuran-2-yl)but-1-
enyl)-2H-pyran-2-yl]prop-1-enyl}cyclohexyl)propanal 54
Alcohol 53 (8.3 mg, 0.013 mmol) was stirred in dry dichloro-
methane (2 cm3) under argon at room temperature. Dess–
Martin periodinane (11.4 mg, 0.027 mmol) was then added.
After 20 minutes the solvent was then removed in vacuo and the
residue purified by flash chromatography (80% petrol–ethyl
acetate, 5:1) to give aldehyde 54 (7.3 mg, 88%) as a colourless
(2R)-Methyl 2-((1S,2S,6R)-6-methyl-2-(3-tert-butyldimethyl-
silyloxy-2-[(2R,3R,6S)-tetrahydro-3-methyl-6-(1E)-[(2R,3S,
5R)-3-{tetrahydro-5-[(R)-1-methoxyethyl]-3-methylfuran-2-
yl}but-1-enyl)-2H-pyran-2-yl]prop-1-enyl}cyclohexyl)propano-
ate 52
oil; [α]D20 Ϫ60 (c 0.14 in CHCl3); νmax(thin film)/cmϪ1 1721 (C᎐O);
᎐
δH(500 MHz; CDCl3) 9.71 (1H, s, 3-H), 5.74 (1H, dd, J 15.8 and
6.6, 19-H), 5.51 (1H, dd, J 15.8 and 6.0, 18-H), 5.24 (1H, d,
J 10.1, 11-H), 4.14 (1H, d, J 10.8, 30-H1), 4.06 (1H, d, J 10.8,
30-H1), 3.95 (1H, ddd, J 12.0, 7.0 and 4.9, 24-H), 3.77 (1H, br
dd, J 10.0 and 6.3, 17-H), 3.51 (1H, dd, J 9.5 and 4.0, 21-H),
3.36 (3H, s, 25-OMe), 3.36 (2H, m, 13-H, 25-H), 2.52 (1H, br q,
Alcohol 51 (10 mg, 0.019 mmol) and dry pyridine (6.2 cm3,
0.076 mmol) were stirred in dry THF (3 cm3) at Ϫ30 ЊC under
argon. tert-Butyldimethylsilyl triflate (9 cm3, 0.038 mmol) was
2274
J. Chem. Soc., Perkin Trans. 1, 1998

View Article Online
Tetrahedron Lett., 1996, 37, 3519; (b) G.-J. Boons, J. A. Clase, I. C.
J 6.6, 4-H), 2.43 (1H, dq, J 10.8 and 3.7, 10-H), 2.26–2.10 (2H,
m, 20-H, 22-H), 1.97 (1H, ddd, J 15.3, 8.5 and 7.0, 23-H1),
1.84–1.81 (2H, m), 1.70–1.10 (12H, m), 1.07 (3H, d, J 6.3, 26-
Me), 1.02 (3H, d, J 6.9, 32-Me), 0.93, 0.91 (6H, 2 × d, J 7.0, 6.8,
27-Me, 28-Me), 0.88 (9H, s, But), 0.74 (3H, d, J 6.5, 29-Me),
0.67 (3H, d, J 6.5, 31-Me), 0.07, 0.06 (6H, 2 × s, Me2Si); m/z
(electrospray): Found MNaϩ 641.460. C37H66NaO5Si requires:
641.458.
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Demitriadou, E. D. Laue, J. Staunton, G. A. F. Ritchie, A. Davies
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J. M. Bulsing, E. D. Laue, F. J. Leeper, J. Staunton, D. H. Davies,
G. A. F. Ritchie, A. Davies, A. B. Davies and R. P. Mabelis, J. Chem.
Soc., Chem. Commun., 1984, 1301; (i) D. M. Doddrell, E. D. Laue,
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Ritchie, J. Chem. Soc., Chem. Commun., 1984, 1302.
(2S)-2-((1S,2S,6R)-6-Methyl-2-(3-tert-butyldimethylsilyloxy-2-
[(2R,3R,6S)-tetrahydro-3-methyl-6-(1E)-((2R,3S,5R)-3-{tetra-
hydro-5-[(R)-1-methoxyethyl]-3-methylfuran-2-yl)but-1-enyl)-
2H-pyran-2-yl]prop-1-enyl}cyclohexyl)propanal 55
Aldehyde 54 (4.0 mg, 6.5 mmol) together with morpholine (0.5
equiv.) and toluene-p-sulfonic acid (0.1 equiv.) were stirred
together in dry dichloromethane (2 cm3) at reflux under argon.
After a period of 6 h the reaction mixture had boiled dry and
the heat source was removed. Further dichloromethane (3 cm3)
was added and at this point TLC analysis indicated complete
consumption of starting material and the formation of a single
product. The crude reaction mixture was washed with dilute
aqueous hydrochloric acid (1.0 , 3 cm3), water (2 cm3), dried
(MgSO4), filtered and the solvent removed in vacuo. The residue
was then purified by flash chromatography (90% petrol–ethyl
acetate) to give aldehyde 55 (3.4 mg, 85%) as a colourless oil; [α]D20
Ϫ34 (c 0.14 in CHCl3); νmax(thin film)/cmϪ1 1721 (C᎐O); δ (500
MHz; CDCl3) 9.68 (1H, s, 3-H), 5.71 (1H, dd, J 1.58 and 6.3,
19-H), 5.52 (1H, dd, J 15.8 and 5.4, 18-H), 5.04 (1H, d, J 10.4,
11-H), 4.15 (1H, d, J 11.2, 30-H1), 4.11 (1H, d, J 11.2, 30-H2),
3.95 (1H, m, 24-H), 3.76 (1H, m, 17-H), 3.52 (1H, dd, J 9.3 and
4.1, 21-H), 3.38 (3H, s, 25-OMe), 3.35 (1H, m, 25-H), 3.28 (1H,
d, J 9.9, 13-H), 2.50 (1H, br q, J 6.3, 4-H), 2.43 (1H, dq, J 10.4
and 3.0, 10-H), 2.27–2.20 (2H, m, 20-H, 22-H), 2.00–1.94 (1H,
m, 23-H), 1.83–1.11 (14H, m), 1.09 (3H, d, J 7.1, 32-Me), 1.08
(3H, d, J 6.1, 26-Me), 0.94 (3H, d, J 6.8), 0.92 (6H, d, J 6.7),
0.88 (9H, s, But), 0.71 (3H, d, J 6.5, 29-Me), 0.07, 0.06 (6H,
2 × s, Me2Si); m/z (MALDITOF) 527 (MNaϩ Ϫ TBDMS,
100%), 288 (90) [Found (electrospray) MNaϩ 641.459 68. C37-
H66NaO5Si requires 641.457 72].
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᎐
H
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Acknowledgements
We are grateful to Professor E. Yoshii for providing authentic
spectral data and experimental details for aldehyde 55. We also
gratefully acknowledge the SERC (now the EPSRC), the
Natural Sciences and Engineering Research Council of Canada
(J. A. C.), Sidney Sussex College, Cambridge (A. J. F.), Schering
Agrochemicals Ltd. (H. M. I. O.) as well as Pfizer Central
Research, the BP Endowment and the Novartis Research
Fellowship (S. V. L.) for funding this work.
15 S. David and S. Hanessain, Tetrahedron, 1985, 41, 643.
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Paper 8/04170I
Received 3rd June 1998
Accepted 17th June 1998
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