Synthesis of the novel 1,7,9-trioxadispiro[4.1.5.2]-tetradecane ring system present in the spirolides

Article abstract of DOI:10.1016/S0040-4020(01)00272-1

A synthesis of bis-spiroacetal 13 which constitutes the bis-spiroacetal moiety of the complex marine biotoxins, spirolides 1 and 2 is described. The synthetic strategy adopted is based on assembly of a suitably protected acyclic hydroxyketone precursor. K

Full text of DOI:10.1016/S0040-4020(01)00272-1

TETRAHEDRON
Pergamon
Tetrahedron 57 62001) 4023±4034
Synthesis of the novel 1,7,9-trioxadispiro[4.1.5.2]-tetradecane
ring system present in the spirolides
Vittorio Caprio, Margaret A. Brimblep and Daniel P. Furkert
Department of Chemistry, University of Auckland, 23 Symonds Street, Auckland, New Zealand
Received 21 December 2000;revised 6 February 2001;accepted 22 February 2001
AbstractÐA synthesis of bis-spiroacetal 13 which constitutes the bis-spiroacetal moiety of the complex marine biotoxins, spirolides 1 and 2
is described. The synthetic strategy adopted is based on assembly of a suitably protected acyclic hydroxyketone precursor. Key intermediate
25 was synthesised as a mixture of diastereomers from 1,3-propanediol using an iterative Grignard addition/hydroboration strategy and
converted to cis-enone 28. Attempted acid catalysed cyclisation of 28 to a spiroacetal was unsuccessful, however, the analagous saturated
precursor 30 readily afforded spiroacetal 31. Oxidative cyclisation of 31 then gave bis-spiroacetal 32. In an alternative route, bis-spiroacetal
32 was synthesised by selective deprotection of diketone 34. Selective deprotection of acetylene 25 gave methoxyl acetal 36 which formed
unsaturated spiroacetal 37 upon semi-hydrogenation. Finally, oxidative cyclisation of bis-spiroacetal 37 afforded the target bis-spiroacetal
13. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
bis-spiroacetal moiety as well as a seven-membered spiro-
linked cyclic iminium group and are structurally related to
the pinnatoxins 3±6, which are potent calcium channel
activators and are responsible for outbreaks of shell®sh
poisoning in China and Japan.2,3 To date, there has been
no reported synthesis of the spirolides and the relative
and absolute stereochemistry of these molecules is yet
to be determined. However, Kishi et al. have reported a
total synthesis of pinnatoxin A 3 which allowed assign-
ment of the absolute stereochemistry of these molecules
6Fig. 1).4
Spirolides B 1 and D 2 were isolated in 1995 from the
digestive glands of mussels 6Mytilus edulis) and scallops
6Placopecten magellanicus) collected off the coast of
Nova Scotia.1 They cause potent and characteristic symp-
toms in the mouse bioassay 6LD100 250 mgkg21 i.p.) and
were discovered to be weak activators 61.7 mmol.dm23 of
type L calcium channels. However, their mode of action has
not been established and their toxicological properties are
still under investigation. These compounds contain a 6,5,5
Figure 1.
Keywords: spirocetals;spirolides;oxidative cyclisation.
Corresponding author. Fax: 164-9-3737422;e-mail: m.brimble@auckland.ac.nz
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020601)00272-1

4024
V. Caprio et al. / Tetrahedron 57 )2001) 4023±4034
Scheme 1.
The novel structure and potent biological activity of the
spirolides prompted us to embark on their synthesis. The
synthetic strategy we adopted hinged on formation of the
C27±C26 bond via alkylation of a pre-assembled spiro
imine 7 with a functionalised bis-spiroacetal 8 6Scheme
1). The ®nal C9±C10 bond is then constructed using a
Ni6II)-Cr6II)-mediated, Kishi±Nozaki coupling between
the vinyl iodide moiety at C9 and an aldehyde functionality
at C10.5a±c
Unsaturated bis-spiroacetal 12, which possesses all the
functionality required for conversion to key intermediate 8
is therefore our initial target. Given that our synthetic
strategy would aid the stereochemical assignment of the
natural products it was desired that our route to 12 be
suf®ciently ¯exible such that fragments of varying relative
and absolute stereochemistry be synthesised with relative
ease. In order to test the viability of the key bond forming
steps on a simple, model system we synthesised bis-spiro-
acetal 13 as a racemic mixture of diastereomers and the
results of this study are reported herein. It is envisaged
that these preliminary ®ndings will form the basis for
development of a synthetic programme directed towards
the synthesis of 12 in a stereocontrolled manner.
The retrosynthetic plan for the synthesis of 8 is based on
studies previously carried out in our research group on
related bicyclic spiroacetal systems. It is planned to intro-
duce the allyl side chain using a Lewis acid mediated
addition of a functionalised allyl stannane 10 to anomeric
acetate 9 6Scheme 2).6 Acetate 9 is available from hydration
of unsaturated bis-spiroacetal 11 which, in turn is synthe-
sised from alkene 12. Thus, epoxidation of 12 followed by
base induced rearrangement of the epoxide, using con-
ditions previously developed for an analogous bicyclic
system7provides a hydroxyl group at C12 required for
introduction of the necessary tertiary alcohol.
2. Results and discussion
Our approach to the synthesis of the bis-spiroacetal core
hinges on the cyclisation of a suitably protected, acyclic
hydroxy ketone precursor. We chose a synthetic route that
is based on the stepwise addition of small carbon fragments
Scheme 2.

V. Caprio et al. / Tetrahedron 57 )2001) 4023±4034
4025
Scheme 3. Reagents and conditions: 6i) TBDPSCl, Et3N, CH2Cl2, 258C, 12 h, 90%;6ii) DMSO/6COCl) 2, CH2Cl2, 2788C, 20 min, then Et3N, 2788C to 258C,
90%;6iii) Allylmagnesium bromide, Et 2O, 08C, 0.5 h, 94%;6iv) TBSCl, imidazole, DMAP, CH 2Cl2, 12 h, 81%;6v) BH 3.SMe2, THF, 08C to 258C, 3 h, then
NaOH/H2O2, 82%;6vi) DMSO/6COCl) 2, CH2Cl2, 2788C, 20 min, then Et3N, 2788C to 258C, 95%.
and is relatively simple in design yet incorporates a degree
of ¯exibility such that large quantities of intermediates of
varying stereochemistry could be easily obtained. Acetylene
25 is a key precursor to the unsaturated bis-spiroacetal 13
and was the initial focus of our synthetic efforts.
required was then introduced by addition of the lithium
acetylide of 1-tert-butyldimethylsilyloxy-3-butyne to alde-
hyde 24 affording alcohol 25 in 19% overall yield from
1,3-propanediol 14.
With large quantities of 25 in hand, we next investigated its
conversion to an acyclic precursor which could be trans-
formed into bis-spiroacetal 12. We ®rst attempted to syn-
thesise the desired 6,5,5 bis-spiroacetal ring system by
oxidative cyclisation of a suitable bicyclic 6,5 hydroxy-
alkylspiroacetal precursor. This methodology has been
used successfully for the synthesis of the 6,6,5 bis-spiro-
acetal moiety of epi-17-deoxy-6O-8)-salinomycin. A double
oxidative cyclisation strategy has also been used by Suarez
et al., to assemble related bis-spiroacetals.10,11
The synthesis of acetylene 25 uses aldehyde 20 as a key
intermediate, which in turn is prepared from 1,3-propane-
diol 6Scheme 3). Protection of diol 14 under mild conditions
using triethylamine and tert-butyldimethylsilyl chloride
followed by Swern oxidation gave protected aldehyde 16.8
Subsequent addition of allylmagnesium bromide gave
secondary alcohol 17 which was then protected as tert-
butyldimethylsilyl ether 18. Hydroboration of the terminal
alkene 18 afforded primary alcohol 19 which underwent
Swern oxidation to aldehyde 20.
Given that our ultimate goal was the synthesis of unsatu-
rated, bis-spiroacetal 13, semi-hydrogenation of the triple
bond in acetylene 25, which ultimately provides the double
bond at C11 in 13 was carried out. Acetylene 25 was
reduced to cis-alkene 26 over Lindlar catalyst then oxi-
dation of alcohol 26 was attempted using Dess±Martin
periodinane 6Scheme 5). Under these conditions how-
ever, isomerisation of the double bond occurred and only
The remaining seven carbons in acetylene 25 were intro-
duced in a similar fashion. Addition of allylmagnesium bro-
mide to aldehyde 20 gave secondary alcohol 21 which was
protected as triethylsilyl ether 22 6scheme 4). Hydroboration
followed by oxidation using Dess±Martin periodinane9
buffered with pyridine gave the nine carbon aldehyde 24
in good yield. The ®nal, unsaturated four carbon fragment
Scheme 4. Reagents and conditions: 6i) Allylmagnesium bromide, Et2O, 08C, 0.5 h, 90%;6ii) TESCl, 2,6-lutidine, CH 2Cl2, 258C, 12 h, 86%;6iii) BH 3.SMe2,
THF, 08C to 258C, 3 h, then NaOH/H2O2, 82%;6iv) Dess±Martin periodinane, pyridine, CH Cl2, 20 min, 73%;6v) 1- tert-butyldimethylsilyloxy-3-butyne,
2
nBuLi, THF, 2788C, 1 h, then 24, 2788 to 258C, 86%.

4026
V. Caprio et al. / Tetrahedron 57 )2001) 4023±4034
Ê
Scheme 5. Reagents and conditions: 6i) Lindlar catalyst, H2, THF, 258C, 4 h, 90%;6ii) TPAP, NMO, 4 A mol. sieves, CH2Cl2, 258C, 0.5 h, 83%;6iii) Dess±
Martin periodinane, pyridine, CH2Cl2, 258C, 1 h, 67%.
trans-enone 27 was isolated. Oxidation of alcohol 26 using
tetrapropylammonium perruthenate and NMO12a afforded
cis-enone 28 in high yield, however, these results raised
the possibility that cis±trans isomerism would occur upon
attempted deprotection of the silyl ether protecting groups
under acidic conditions, thereby preventing spirocyclisation
from taking place. We therefore decided to initially develop
our synthetic protocol on a saturated precursor.
stirring 30 in ethanol in the presence of pyridinium p-tolu-
enesulphonate affording the desired hydroxyspiroacetal 31
in good yield.13 Finally, irradiation of a solution of 31,
iodine and iodobenzene diacetate in cyclohexane led to
clean oxidative cyclisation to give saturated bis-spiroacetal
32 as an equimolar mixture of four diastereoisomers.
Bis-spiroacetal 32 could also be obtained in one step from
acyclic diketone 34. This spirocyclisation precursor was
easily prepared by reduction of hydroxyacetylene 25 over
palladium on carbon without sodium bicarbonate followed
by oxidation of the resulting diol. When sodium bicarbonate
was not present in the reduction step concomitant depro-
tection of the C8 triethylsilyl ether occurred 6Scheme 7).
Oxidation of diol 33 with excess TPAP/NMO gave diketone
The triple bond in 25 was removed over palladium on
carbon in the presence of sodium bicarbonate to give hydro-
xyalkane 29 6Scheme 6). Oxidation using tetrapropylammo-
nium perruthenate and NMO as co-oxidant then gave ketone
30. Selective deprotection of the triethyl silyl ether and tert-
butyldimethylsilyl ethers was successfully achieved by
Ê
Scheme 6. Reagents and conditions: 6i) Pd/C, EtOAc, 258C, 3 h, 96%;6ii) TPAP, NMO, 4 A mol. sieves, CH2Cl2, 258C, 0.5 h, 82%;6iii) PPTS, EtOH, 60 8C,
10 h, 67%;6iv) PhI6OAc) 2, I2, cyclohexane, hn, 0.5 h, 56%.

V. Caprio et al. / Tetrahedron 57 )2001) 4023±4034
4027
Ê
Scheme 7. Reagents and conditions: 6i) Pd/C, H2, EtOAc, 258C, 6 h, 69%;6ii) TPAP, NMO, 4 A mol. sieves, 258C, 1 h, 70%;6iii) PPTS, EtOH, 60 8C, 7 h,
50%.
34 which cyclised to bis-spiroacetal 32 in moderate yield
upon stirring with PPTS in ethanol.
circumventing any problems associated with cis±trans
isomerism. Towards this end, hydroxyalkyne 25 was
oxidised to ynone 35 which when treated with a catalytic
quantity of camphorsulfonic acid in methanol to give
methyl acetal 36 6Scheme 8). Semi-hydrogenation of
alkyne 36 over Lindlar catalyst followed by addition
of a catalytic amount of PPTS then effected clean
conversion to spiroacetal 37. Finally, oxidative cycli-
sation under standard conditions gave the desired unsatu-
rated bis-spiroacetal 13.
With the synthesis of saturated bis-spiroacetal 32 in hand,
our attention next focussed on introducing the key double
bond at C11 of unsaturated spiroacetal 12. Unfortunately,
treatment of cis-enone 28 with PPTS in ethanol led to
1
formation of a complex reaction mixture. The H NMR
spectrum of the crude reaction mixture indicated incorpo-
ration of an ethoxy group onto the 6,5 spiroacetal structure,
presumably via 1,4-addition of ethanol to the cis-enone
prior to cyclisation. Deprotection using HF.pyridine in
THF also resulted in the formation of a complex mixture
suggesting that some isomerism of the double bond takes
place under these conditions thereby preventing clean cycli-
sation to a spiroacetal.
Having established our synthetic methodology to construct
the novel 6,5,5 bis-spiroacetal ring system of the spirolides,
work is now being directed towards incorporating the C3
methyl group in enantiopure form. The work reported herein
has elucidated the pathway for the synthesis of this bis-
spiroacetal moiety of these complex natural products
making use of a key oxidative cyclisation. Moreover, the
precise nature of the functional group manipulations
required in combination with appropriate protecting group
strategies for construction of the key cyclisation precursors
has been demonstrated.
We reasoned that semi-hydrogenation of a suitable
hydroxy-ynone precursor would afford a masked cis-enone
which would then undergo spontaneous cyclisation upon
addition of a catalytic amount of acid. This would avoid
prolonged exposure of a cis-enone to acidic conditions
Ê
Scheme 8. Reagents and conditions: 6i) TPAP, NMO, 4 A mol. sieves, CH2Cl2, 258C, 30 min, 79%;6ii) CSA, MeOH, 25 8C, 1 h, 55%;6iii) Lindlar catalyst,
THF, 258C, 3 h., then PPTS, THF/CH2Cl2, 5 min, 79%;6iv) PhI6OAc) 2, I2, cyclohexane, hn, 258C, 1 h, 78%.

4028
V. Caprio et al. / Tetrahedron 57 )2001) 4023±4034
3. Experimental
dried 6MgSO4) and concentrated under reduced pressure to
give the title compound 66.5 g, 94%) as a colourless oil;
max6®lm)/cm21 3432 6br, s, OH), 3071 6m, CvC±H),
n
3.1. General details
2957, 2931 6s, CH), 1472, 1112; dH 6400 MHz;CDCl )
3
1.06 69H, s, But), 1.67±1.77 62H, m, 2-H), 2.28 62H, td,
J3,4ˆJ4,5 7.1, J4,6 1.0, 4-H), 3.78±3.92 62H, m, 1-H),
3.94±4.0061H, m, 3-H), 5.07±5.15 62H, m, 6-H), 5.61±
5.96 61H, m, 5-H), 7.26±7.45 66H, m, ArH), 7.66±7.75
All reactions were conducted in ¯ame-dried or oven-dried
glassware under a dry nitrogen atmosphere unless otherwise
noted. Tetrahydrofuran and diethyl ether were dried over
sodium/benzophenone and distilled prior to use. Cyclo-
hexane, ethyl acetate, dichloromethane and triethylamine
were distilled from calcium hydride and used immediately.
Flash chromatography was performed by using Merck
Kieselgel 60 6230±400 mesh) with the indicated solvents.
Thin layer chromatography 6tlc) was carried out on
precoated silica plates 6Merck Kieselgel 60F254) and com-
pounds were visualised by UV ¯uorescence or by staining
with alkaline potassium permanganate solution or vanillin
in methanolic sulfuric acid and heating. Infrared spectra
were recorded with a Perkin±Elmer Spectrum One
Fourier±Transform IR spectrometer as thin ®lms between
sodium chloride plates. Absorption maxima are expressed in
wavenumbers 6cm21) with the following abbreviations:
sˆstrong, mˆmedium, wˆweak and brˆbroad. 1H and
13C NMR spectra were obtained using a Bruker DRX-400
spectrometer operating at 400 MHz and 100 MHz respec-
tively. All chemical shifts are given in parts per million
6ppm) down®eld from tetramethylsilane as internal standard
61H) or relative to CDCl3 613C) and J values are given in Hz.
1H NMR data are tabulated as s, singlet;d, doublet;t, triplet;
64H, m, ArH); dC 6100 MHz;CDCl ) 19.0 6quat., But),
3
26.8 6CH3, But), 37.8 6CH2, C-2), 41.9 6CH2, C-4), 63.3
6CH2, C-1), 70.8 6CH, C-3), 117.4 6CH2, C-6), 127.7 6CH,
Ar-C), 129. 8 6CH, Ar-C), 133.0 6CH, C-5), 135.0 6quat.,
Ar-C), 135.5 6CH, Ar-C); m/z 6CI, NH3) 355 6MH1, 42%),
277 612) and 199 635);Found: MH 1, 355.2093. C22H30O2Si
requires MH, 355.2093.
3.1.3. 1--tert-Butyldiphenylsilyloxy)-3--tert-butyldimethyl-
silyloxy)hex-5-ene 18. A solution of 4-6dimethylamino)-
pyridine 60.35 g, 2.9 mmol), alcohol 17 66.4 g, 18.1
mmol), tert-butyldimethylsilyl chloride 64.1 g, 27.2 mmol)
and imidazole 61.8 g, 27.1 mmol) in dichloromethane
640 mL) was stirred at room temperature for 12 h. Saturated,
aqueous sodium bicarbonate was added 630 mL) and the
mixture extracted with dichloromethane 63£100 mL). The
combined organic extracts were dried 6MgSO4) and concen-
trated under reduced pressure. Puri®cation by ¯ash chroma-
tography using hexane: diethyl ether 69:1) as eluent,
afforded silyl ether 18 66.9 g, 81%) as a colourless oil;
max6®lm)/cm21 3135 6s, CvCH), 2927 6s, CH), 1641,
1
q, quartet, m, multiplet, br, broad. The H and 13C NMR
n
1589; dH 6400 MHz;CDCl 3) 0.04 63H, s, SiMe), 0.08
63H, s, SiMe), 0.90 69H, s, But), 1.09 69H, s, But), 1.70±
1.76 62H, m, 2-H), 2.21±2.28 62H, m, 4-H), 3.73±3.77 62H,
m, 1-H), 3.96±4.00 61H, m, 3-H), 5.02±5.0762H, m, 6-H),
5.80±5.87 61H, m, 5-H), 7.38±7.45 66H, m, ArH), 7.68±
spectra of compounds 12 and 21 to 37 are complicated by
the presence of a mixture of diastereomers. Resonances for
individual diastereomers are denoted by asterisks. High
resolution mass spectra were recorded using a VG70-SE
spectrometer operating at nominal accelerating voltage of
70 eV. Chemical ionisation 6CI) mass spectra were obtained
with ammonia as the reagent gas. Fast atom bombardment
6FAB) mass spectra were obtained with 3-nitrobenzyl
alcohol as the matrix.
7.71 64H, m, ArH); dC 6100 MHz;CDCl ) 24.7 6CH3,
3
SiMe), 24.4 6CH3, SiMe), 18.1 6quat., But), 19.2 6quat.,
But), 22.7 6CH3, But), 25.8 6CH3, But), 39.6 6CH2, C-2),
42.1 6CH2, C-4), 60.8 6CH2, C-1), 68.9 6CH, C-3), 116.8
6CH2, C-6), 127.8 6CH, Ar-C), 129.5 6CH, Ar-C), 134.0
6quat., Ar-C), 135.2 6CH, C-5), 135.6 6CH, Ar-C); m/z
6CI, NH3) 469 6MH1, 100%), 429 610), 411 69), 337 632)
and 196 625);Found: MH 1, 469.2954. C28H44O2Si2 requires
MH, 469.2958.
3.1.1. 1--tert-Butyldiphenylsilyloxy)propan-3-ol 15. Tri-
ethylamine 65.2 mL, 38.2 mmol) was added to a solution
of 1,3-propanediol 65.8 g, 76.4 mmol) and tert-butyldi-
phenylsilyl chloride 67.0 g, 25.5 mmol) in dichloromethane
650 mL) at room temperature. The mixture was stirred for
12 h then diluted with dichloromethane 6200 mL), washed
with water 63£80 mL), dried 6MgSO4) and concentrated
under reduced pressure. The crude product was puri®ed
by ¯ash column chromatography using hexane:diethyl
ether 67:3) as eluent to afford the title compound 15
67.2 g, 90%) as a colourless oil. All spectral data was consis-
tent with that reported in the literature.8
3.1.4. 4--tert-Butyldimethylsilyloxy)-6--tert-butyldiphenyl-
silyloxy)hexan-1-ol 19. A solution of borane-dimethyl
sul®de 64.8 mL of a 10 M solution in THF, 48 mmol) was
added to a solution of alkene 18 67.45 g, 15.9 mmol) in THF
6100 mL) at 08C. The reaction mixture was allowed to warm
to room temperature then stirred for 3 h. A solution of
sodium hydroxide 6200 mL of a 3 M solution) followed by
H2O2 6100 mL of a 35% w/w solution in H2O) was added at
08C and the mixture stirred overnight. Solvent was removed
under reduced pressure and the residue partitioned between
water 6100 mL) and ethyl acetate 6200 mL). The aqueous
layer was further extracted with ethyl acetate 62£150 mL)
and the combined organic extracts dried 6MgSO4) and
concentrated under reduced pressure. The crude product
was puri®ed by ¯ash chromatography using hexane: diethyl
ether 67: 3) as eluent to give the title compound 19 66.3 g,
82%) as a colourless oil; nmax6®lm)/cm21 3399 6br s, OH),
3071 6m, Ar-H), 2951 6s, CH), 1589, 1472; dH 6400 MHz;
CDCl3) 0.04 63H, s, SiMe), 0.06 63H, s, SiMe), 0.86 69H, s,
3.1.2. 1--tert-Butyldiphenylsilyloxy)hex-5-en-3-ol 17. A
solution of allyl bromide 66.7 mL, 43.2 mmol) in diethyl
ether 640 mL) was added to a slurry of magnesium turnings
64.7 g, 195.5 mmol) in diethyl ether 640 mL) dropwise.
After initiation of the reaction, the mixture was stirred for
0.5 h at room temperature and then transferred via cannula
to a solution of aldehyde 168 in diethyl ether 640 mL) at 08C.
The mixture was stirred at 08C for 0.5 h then warmed to
room temperature. Saturated, aqueous ammonium chloride
680 mL) was added and the mixture extracted with ethyl
acetate 63£100 mL). The combined organic extracts were

V. Caprio et al. / Tetrahedron 57 )2001) 4023±4034
4029
But), 1.05 69H, s, But), 1.52±1.61 64H, m, 2-H, 3-H), 1.71±
1.76 62H, m, 5-H), 3.55±3.64 62H, m, 1-H), 3.67±3.78 62H,
m, 6-H), 3.96±3.99 61H, m, 4-H), 7.38±7.41 66H, m, ArH),
7.64±7.68 64H, m, ArH)); dC 6100 MHz;CDCl 3) 24.7
6CH3, SiMe), 24.5 6CH3, SiMe), 18.1 6quat., But), 19.2
6quat., But), 25.9 6CH3, But), 26.9 6CH3, But), 28.1 6CH2,
C-2), 33.6 6CH2, C-3), 39.3 6CH2, C-5), 60.2 6CH2, C-6),
63.1 6CH2, C-1), 69.0 6CH, C-4), 127.6 6CH, Ar-C), 129.6
6CH, Ar-C), 133.9 6quat., Ar-C), 135.6 6CH, Ar-C); m/z 6CI,
NH3) 487 6MH1, 46%), 297 630) and 277 6100);Found:
MH1, 487.3059. C28H46O3Si2 requires MH, 487.3064.
SiMe), 0.07 61.5H, s, SiMe*), 0.08 61.5H, s, SiMe*), 0.89
69H, s, But), 1.07 69H, s, But), 1.52±1.75 66H, m, 5-H, 6-H,
8-H), 2.15±2.32 62H, m, 3-H), 3.60±3.63 61H, m, 7-H),
3.69±3.79 62H, m, 9-H), 3.92±4.01 61H, m, 4-H), 5.11±
5.17 62H, m, 1-H), 5.79±5.89 61H, m, 2-H), 7.39±7.42
66H, m, ArH), 7.66±7.69 64H, m, ArH); dC 6100 MHz;
CDCl3) 24.6 6CH3, SiMe), 24.5 6CH3, SiMe), 24.4
6CH3, SiMe*), 18.1 6quat., But), 19.2 6quat., But), 25.9
6CH3, But), 26.9 6CH3, But), 31.9 6CH2, C-5), 32.2 6CH2,
C-5*), 32.8 6CH2, C-6), 33.4 6CH2, C-6*), 39.4 6CH2, C-8),
39.6 6CH2, C-8*), 41.9 6CH2, C-3), 42.0 6CH2, C-3*), 60.9
6CH2, C-9), 69.1 6CH, C-7), 69.3 6CH, C-7*), 70.7 6CH,
C-4), 71.0 6CH, C-4*), 117.7 6CH2, C-1), 117.9 6CH2,
C-1*), 127.6 6CH, Ar-C), 129.6 6CH, Ar-C), 133.9 6quat.,
Ar-C), 134.9 6CH, C-2), 135.2 6CH, C-2*), 135.6 6CH,
Ar-C); m/z 6CI, NH3) 527 6MH1, 35%), 337 633), 317
6100) and 121 676);Found: MH 1, 527.3370. C31H50O3Si2
requires MH, 527.3377.
3.1.5. 4--tert-Butyldimethylsilyloxy)-6--tert-butyldiphenyl-
silyloxy)hexanal 20. A solution of DMSO 62.0 mL, 27.4
mmol) in dichloromethane 640 mL) was added to a solution
of oxalyl chloride 61.14 mL, 14.3 mmol) in dichloro-
methane 640 mL), dropwise at 2788C. The mixture was
stirred for 20 min at 2788C, then alcohol 19 65.5 g,
11.4 mmol) in dichloromethane 640 mL) was added drop-
wise. The mixture was stirred for a further 20 min at this
temperature then triethylamine 69.4 mL, 68.4 mmol) was
added. The reaction was stirred for 10 min at 2788C then
warmed to room temperature. Saturated, aqueous sodium
bicarbonate 6100 mL) was added and the mixture extracted
with dichloromethane 62£200 mL). The combined organic
extracts were dried 6MgSO4), concentrated under reduced
pressure and the residue puri®ed by ¯ash chromatography
using hexane: diethyl ether 68:2) as eluent to give the title
compound 20 65.2 g, 95%) as a colourless oil; nmax6®lm)/
cm21 3071 6m, Ar-H), 2954, 2889 6s, CH), 1727 6s, CvO),
1472; dH 6400 MHz;CDCl 3) 0.04 63H, s, SiMe), 0.06 63H, s,
SiMe), 0.86 69H, s, But), 1.05 69H, s, But), 1.58±1.88 64H,
m, 3-H, 5-H), 2.44 62H, dt, J2,37.5, J2,11.5, 2-H), 3.68±3.74
62H, m, 6-H), 3.94±3.97 61H, m, 4-H), 7.36±7.45 66H, m,
ArH), 7.64±7.67 64H, m, ArH), 9.76 61H, t, J3,21.5, 1-H));
dC 6100 MHz;CDCl 3) 24.6 6CH3, SiMe), 18.0 6quat., But),
19.1 6quat., But), 25.8 6CH3, But), 26.9 6CH3, But), 29.1
6CH2, C-3), 39.56 6CH2, C-5), 39.61 6CH2, C-2), 60.6
6CH2, C-6), 68.3 6CH, C-4), 127.6 6CH, Ar-C), 129.6
6CH, Ar-C), 133.8 6quat., Ar-C), 135.6 6CH, Ar-C), 202.5
6CO, C-1); m/z 6CI, NH3) 485 6MH1, 36%), 471 625), 353
654), 196 636) and 91 656);Found: MH 1, 485.2906.
C28H44O3Si2 requires MH, 485.2907.
3.1.7. 7--tert-Butyldimethylsilyloxy)-9--tert-butyldiphenyl-
silyloxy)-4-triethylsilyloxynon-2-ene 22. 2,6-Lutidine
61.99 g, 18.5 mmol) was added to a solution of alcohol 21
64.9 g, 9.3 mmol) and triethylsilyl chloride 61.8 g, 12.0
mmol) in dichloromethane 620 mL) at room temperature.
The mixture was stirred for 12 h then brine 615 mL) was
added and the mixture extracted with dichloromethane
63£20 mL). The combined organic extracts were dried
6MgSO4) and concentrated under reduced pressure and the
residue puri®ed by ¯ash chromatography using hexane:
diethyl ether 69:1) as eluent to give the title compound 22
65.1 g, 86%) as a colourless oil and as a 1:1 mixture of
diastereomers; nmax6®lm)/cm21 3071 6m, Ar-H), 2954,
2857 6s, CH), 1610, 1472; dH 6400 MHz;CDCl 3) 0.01
63H, s, SiMe), 0.03 63H, s, SiMe), 0.58 66H, q, Jˆ7.8,
SiEt3), 0.85 69H, s, But), 0.95 69H, t, Jˆ7.8, SiEt3), 1.05
69H, s, But), 1.35±1.55 64H, m, 5-H, 6-H), 1.61±1.75 62H,
m, 8-H), 2.22±2.19 62H, m, 3-H), 3.64±3.75 63H, m, 7-H,
9-H), 3.84±3.87 61H, m, 4-H), 5.01±5.06 62H, m, 1-H), 5.82
61H, m, 2-H), 7.26±7.42 66H, m, ArH), 7.64±7.68 64H, m,
ArH); dC 6100 MHz;CDCl 3) 24.6 6CH3, SiMe), 24.4
6CH3, SiMe), 5.1 6CH2, SiEt3), 6.9 6CH3, SiEt3), 18.1
6quat., But), 19.2 6quat., But), 25.9 6CH3, But), 26.9 6CH3,
But), 32.4 6CH2, C-5), 33.0 6CH2, C-6), 33.1 6CH2, C-6*),
39.9 6CH2, C-8), 40.0 6CH2, C-8*), 42.0 6CH2, C-3), 61.0
6CH2, C-9), 69.4 6CH, C-7), 72.2 6CH, C-4), 116.7 6CH2,
C-1), 127.6 6CH, Ar-C), 129.5 6CH, Ar-C), 134.0 6quat.,
Ar-C), 135.3 6CH, C-2), 135.6 6CH, Ar-C); m/z 6FAB,
NBA) Found: MH1, 641.4233. C37H64O3Si3 requires MH,
641.4242.
3.1.6. 7--tert-Butyldimethylsilyloxy)-9--tert-butyldiphenyl-
silyloxy)non-1-en-4-ol 21. A solution of allyl bromide
63.7 mL, 43.2 mmol) in diethyl ether 635 mL) was added
to a slurry of magnesium turnings 62.6 g, 108.3 mmol) in
diethyl ether 635 mL) dropwise. After initiation of the reac-
tion, the mixture was stirred for 0.5 h at room temperature
and then transferred via cannula to a solution of aldehyde 20
65.2 g, 10.8 mmol) in diethyl ether 640 mL) at 08C. The
mixture was stirred at 08C for 0.5 h then warmed to room
temperature. Saturated, aqueous ammonium chloride
680 mL) was added and the mixture extracted with ethyl
acetate 63£100 mL). The combined organic extracts were
dried 6MgSO4), concentrated under reduced pressure and
the residue puri®ed by ¯ash chromatography using hexane:
diethyl ether 67:3) as eluent to give the title compound 21
65.0 g, 90%) as a colourless oil and as a 1:1 mixture of
diastereomers; nmax6®lm)/cm21 3413 6br s, OH), 3071 6m,
CvCH), 2929, 2856 6s, CH), 1641, 1589, 1462; dH
3.1.8. 7--tert-Butyldimethylsilyloxy)-9--tert-butyldiphenyl-
silyloxy)-4-triethylsilyloxynonan-1-ol 23. A solution of
borane-dimethyl sul®de 62.4 mL of a 10 M solution in
THF, 24.0 mmol) was added to a solution of alkene 22
65.10 g, 7.9 mmol) in THF 6400 mL) at 08C. The reaction
mixture was allowed to warm to room temperature and then
stirred for 3 h. A solution of sodium hydroxide 690 mL of a
3 M solution, 270 mmol) followed by H2O2 645 mL of a
35% w/w solution in H2O, 400 mmol) was added at 08C
and the mixture stirred overnight. Solvent was removed
under reduced pressure and the residue partitioned between
water 640 mL) and ethyl acetate 6100 mL). The aqueous
layer was further extracted with ethyl acetate 62£80 mL)
6400 MHz;CDCl ) 0.04 61.5H, s, SiMe), 0.06 61.5H, s,
3

4030
V. Caprio et al. / Tetrahedron 57 )2001) 4023±4034
and the combined organic extracts dried 6MgSO4) and
concentrated under reduced pressure. The crude product
was puri®ed by ¯ash chromatography using hexane: diethyl
ether 67:3) as eluent to give the title compound 23 64.3 g,
82%) as a colourless oil and as a 1:1 mixture of diastereo-
mers; nmax6®lm)/cm21 3400 6br s, OH), 3072 6m, Ar-H),
2928 6s, CH), 1590, 1471; dH 6400 MHz;CDCl 3) 0.01
63H, s, SiMe), 0.03 63H, s, SiMe), 0.61 66H, q, Jˆ7.8,
SiEt3), 0.85 69H, s, But), 1.00 69H, t, Jˆ7.8, SiEt3), 1.05
69H, s, But), 1.17±1.43 610H, m, 2-H, 3-H, 5-H, 6-H, 8-H),
3.61±3.74 65H, m, 1-H, 7-H, 9-H), 3.85±3.9061H, m, 4-H),
7.37±7.40 66H, m, ArH), 7.64±7.67 64H, m, ArH); dC
organic extracts dried 6MgSO4) and concentrated under
reduced pressure. The residue was puri®ed by ¯ash chroma-
tography using hexane: diethyl ether 68:2) as eluent to give
the title compound 25 63.4 g, 86%) as a colourless oil and as
a 1:1:1:1 mixture of four diastereomers; nmax6®lm)/cm21
3435 6br, s, OH), 3050 6m, Ar-H), 2953, 2876 6s, CH),
2243 6w, triple bond) 1471, 1111; dH 6400 MHz;CDCl )
3
0.01 63H, s, SiMe), 0.02 63H, s, SiMe), 0.04 66H, s, SiMe),
0.62 66H, q, J7.8, SiEt3), 0.86 69H, s, But), 0.90 69H, s, But),
0.98 69H, t, Jˆ7.8, SiEt3), 1.06 69H, s, But), 1.35±1.75
610H, m, 6-H, 7-H, 9-H, 10-H, 12-H), 2.45 62H, t, J2,3 7.3,
2-H), 2.71 61H, br s, OH), 3.67±3.74 65H, m, 1-H, 11-H,
13-H), 3.87 61H, m, 8-H), 4.32±4.38 61H, m, 5-H), 7.36±
7.43 66H, m, ArH), 7.65±7.69 64H, m, ArH); dC 6100 MHz;
CDCl3) 25.3 6CH3, SiMe), 24.6 6CH3, SiMe), 24.4
6CH3,SiMe), 5.0 6CH2, SiEt3), 6.9 6CH3, SiEt3), 18.0
6quat., But), 18.3 6quat., But), 19.1 6quat., But), 23.1 6CH2,
C-2), 25.9 6CH3, But), 26.9 6CH3, But), 31.7 6CH2, C-6),
32.0 6CH2, C-6*), 32.3 6CH2, C-7), 32.6 6CH2, C-7*), 32.7
6CH2, C-7**), 33.0 6CH2, C-9), 33.1 6CH2, C-9*), 33.4
6CH2, C-10), 33.7 6CH2, C-10*), 39.9 6CH2, C-12), 60.9
6CH2, C-13), 61.9 6CH2, C-1), 62.3 6CH, C-5), 62.8 6CH,
C-5*), 69.3 6CH, C-11), 72.1 6CH2, C-8), 72.2 6CH2, C-8*),
81.9 6quat., C-4), 82.4 6quat., C-3), 127.6 6CH, Ar-C), 129.5
6CH, Ar-C), 134.0 6quat., Ar-C), 135.5 6CH, Ar-C); m/z
6FAB, NBA) Found: MH1, 841.5422. C47H84O5Si4 requires
MH, 841.5474.
6100 MHz;CDCl ) 24.6 6CH3, SiMe), 24.4 6CH3, SiMe),
3
5.0 6CH2, SiEt), 6.9 6CH3, SiEt), 18.1 6quat., But), 19.2
6quat., But), 25.9 6CH3, But), 26.9 6CH3, But), 28.2 6CH2,
C-2), 32.0 6CH2, C-5), 32.3 6CH2, C-5*), 33.0 6CH2, C-6),
33.4 6CH2, C-3), 33.5 6CH2, C-3*), 40.0 6CH2, C-8), 61.0
6CH2, C-9), 63.2 6CH, C-7), 69.3 6CH, C-1), 69.4 6CH,
C-1*), 72.3 6CH, C-4), 127.6 6CH, Ar-C), 129.5 6CH,
Ar-C), 134.0 6quat., Ar-C), 135.6 6CH, Ar-C); m/z 6FAB,
NBA) Found: MH1, 659.4341. C37H66O4Si3 requires MH,
659.4347.
3.1.9. 7--tert-Butyldimethylsilyloxy)-9--tert-butyldiphenyl-
silyloxy)-4-triethylsilyloxynonal 24. Dess±Martin periodi-
nane 63.8 g, 9.0 mmol) was added to a solution of alcohol
23 64.3 g, 6.5 mmol) and pyridine 61.4 g, 18.0 mmol) in
dichloromethane 680 mL) at room temperature. The mixture
was stirred for 2 h then ®ltered through a plug of Celitew.
The ®ltrate was concentrated under reduced pressure and the
crude product puri®ed by ¯ash chromatography using
hexane: diethyl ether 68: 2) as eluent to give the title
compound 24 63.13 g, 73%) as a colourless oil and as a
1:1 mixture of diastereomers; nmax6®lm)/cm21 3071 6m,
Ar-H), 2954, 2857 6s, CH), 1727 6s, CvO), 1589, 1472;
3.1.11. cis-1,11-Bis--tert-butyldimethylsilyloxy)-13--tert-
butyldiphenylsilyloxy)-8-triethylsilyloxytridec-3-en-5-ol
26. A mixture of acetylene 25 6250 mg, 0.30 mmol) and
Lindlar catalyst 620 mg) in THF 630 mL) was stirred
under an atmosphere of hydrogen for 4 h then ®ltered
through Celitew. The ®ltrate was concentrated under
reduced pressure to give the title compound 26 6230 mg,
90%) as a colourless oil and as a 1:1:1:1 mixture of four
diastereomers; nmax6®lm)/cm21 3436 6br, s, OH), 3050,
3071 6m, CvC±H), 2954, 2857 6s, CH), 1590, 1471,
1111; dH 6400 MHz;CDCl 3) 0.01 63H, s, SiMe), 0.04
63H, s, SiMe), 0.08 66H, s, SiMe), 0.61 66H, q, Jˆ7.8,
SiEt3), 0.86 69H, s, But), 0.91 69H, s, But), 0.96 69H, t,
Jˆ7.8, SiEt3), 1.06 69H, s, But), 1.27±1.71 610H, m, 6-H,
7-H, 9-H, 10-H, 12-H), 2.23±2.29 62H, m, 2-H), 3.58±3.74
65H, m, 1-H, 11-H, 13-H), 3.38±3.86 61H, m, 8-H), 4.31±
4.36 61H, m, 5-H), 5.50±5.60 62H, m, 3-H, 4-H), 7.35±7.42
66H, m, ArH), 7.65±7.6964H, m, ArH); dC 6100 MHz;
CDCl3) 25.5 6CH3, SiMe), 24.7 6CH3, SiMe), 24.5
6CH3, SiMe), 5.0 6CH2, SiEt3), 6.9 6CH3, SiEt3), 17.9
6quat., But), 18.2 6quat., But), 18.4 6quat., But), 25.9 6CH3,
But), 26.9 6CH3, But), 31.3 6CH2, C-7), 31.6 6CH2, C-12),
32.5 6CH2, C-9), 32.6 6CH2, C-9*), 32.9 6CH2, C-10), 33.2
6CH2, C-10*), 35.9 6CH2, C-7), 39.9 6CH2, C-12), 60.8
6CH2, C-13), 62.3 6CH2, C-1), 67.1 6CH, C-11), 67.3 6CH,
C-11*), 69.3 6CH, C-5), 72.4 6CH, C-8), 127.5 6CH, ArH),
128.3 6CH, C-3), 128.5 6CH, C-3*), 129.4 6CH, Ar-C),
133.9 6quat., Ar-C), 135.2 6CH, C-4), 135.3 6CH, C-4*),
135.4 6CH, Ar-C); m/z 6FAB, NBA) Found: MH1,
843.5611. C47H87O5Si4 requires MH, 843.5631.
dH 6400 MHz;CDCl ) 0.01 63H, s, SiMe), 0.04 63H, s,
3
SiMe), 0.56 66H, q, Jˆ7.9, SiEt3), 0.85 69H, s, But), 0.95
69H, t, Jˆ7.9, SiEt3), 1.05 69H, s, But), 1.33±1.85 68H, m,
3-H, 5-H, 6-H, 8-H), 2.46 62H, dt, J2,3 7.4, J2,1 1.5, 2-H),
3.66±3.72 63H, m, 7-H, 9-H), 3.83±3.88 61H, m, 4-H),
7.35±7.42 66H, m, ArH), 7.64±7.68 64H, m, ArH), 9.77
61H, t, Jˆ1.5, 1-H); dC 6100 MHz;CDCl ) 24.6 6CH3,
3
SiMe), 24.4 6CH3, SiMe), 5.1 6CH2, SiEt3), 6.9 6CH3,
SiEt3), 18.0 6quat., But), 19.2 6quat., But), 25.9 6CH3, But),
26.9 6CH3, But), 29.1 6CH2, C-2), 32.4 6CH2, C-5), 32.7
6CH2, C-6), 33.1 6CH2, C-3), 39.9 6CH2, C-8), 60.8 6CH2,
C-9), 60.9 6CH2, C-9*), 69.3 6CH, C-7), 71.4 6CH, C-4),
127.6 6CH, Ar-C), 129.5 6CH, Ar-C), 134.0 6quat., Ar-C),
135.6 6CH, Ar-C), 202.6 6CH, C-1); m/z 6FAB, NBA)
Found: MH1, 657.4174. C37H64O4Si3 requires MH,
657.4191.
3.1.10. 1,11-Bis--tert-butyldimethylsilyloxy)-13--tert-butyl-
diphenylsilyloxy)-8-triethylsilyloxytridec-3-yn-5-ol 25.
nButyllithium 64.4 mL of a 1.6 M solution in hexanes,
7.0 mmol) was added to a solution of 1-6tert-butyldimethyl-
silyloxy)but-3-yne 61.3 g, 7.0 mmol) in THF 620 mL) at
2788C. The mixture was stirred at 2788C for 1 h then
aldehyde 24 63.1 g, 4.7 mmol) in THF 65 mL) was added.
The mixture was stirred at 2788C for a further 1 h then
warmed to room temperature and saturated, aqueous ammo-
nium chloride 630 mL) was added. The mixture was
extracted with ethyl acetate 63£80 mL) and the combined
3.1.12. trans-1,11-Bis--tert-butyldimethylsilyloxy)-13--tert-
butyldiphenylsilyloxy)-8-triethylsilyloxytridec-3-en-5-one
27. Dess±Martin periodinane 660 mg, 0.12 mmol) was
added to a solution of alcohol 26 650 mg, 0.06 mmol) and

V. Caprio et al. / Tetrahedron 57 )2001) 4023±4034
4031
pyridine 619 mg, 0.24 mmol) in dichloromethane 61 mL) at
room temperature. The mixture was stirred for 1 h then
®ltered through a plug of Celitew. The ®ltrate was concen-
trated under reduced pressure and the residue puri®ed by
¯ash chromatography using hexane: diethyl ether 69: 1) as
eluent to give the title compound 27 633 mg, 67%) as a
colourless oil and as a 1:1 mixture of diastereomers;
carbon 612 mg) and sodium bicarbonate 60.15 g, 1.8 mmol)
in ethyl acetate 650 mL) was stirred under an atmosphere of
hydrogen at room temperature for 3 h. The mixture was then
®ltered through Celitew and the ®ltrate concentrated under
reduced pressure to give the title compound 29 60.48 g,
96%) as a colourless oil and a 1:1:1:1 mixture of four
diastereomers; nmax6®lm)/cm21 3440 6br, s, OH), 3071,
6m, Ar-H), 2930 6s, CH), 1471, 1428; dH 6400 MHz;
CDCl3) 0.03 63H, s, SiMe), 0.04 63H,s, SiMe), 0.07 66H,
s, SiMe), 0.60 66H, q, Jˆ7.8, SiEt3), 0.85 69H, s, But), 0.89
69H, s, But), 0.95 69H, t, Jˆ7.8, SiEt3), 1.05 69H, s, But),
1.30±1.73 616H, m, 2-H, 3-H, 4-H, 6-H, 7-H, 9-H, 10-H,
14-H), 3.60±3.73 66H, m, 1-H, 8-H, 11-H, 13-H), 3.85±3.86
61H, m, 5-H), 7.36±7.42 66H, m, ArH), 7.64±7.68 64H, m,
ArH); dC 6100 MHz;CDCl 3) 25.3 6CH3, SiMe), 24.6
6CH3, SiMe), 24.4 6CH3, SiMe), 5.1 6CH2, SiEt3), 7.0
6CH3, SiEt3), 18.1 6quat., But), 18.4 6quat., But), 19.2
6quat., But), 22.0 6CH2, C-3), 25.9 6CH3, But), 26.0 6CH3,
But), 26.9 6CH3, But), 32.3 6CH2, C-6), 32.6 6CH2, C-10),
32.9 6CH2, C-9), 33.4 6CH2, C-7), 37.2 6CH2, C-2), 37.3
6CH2, C-4), 39.9 6CH2, C-12), 61.0 6CH2, C-1), 63.2 6CH2,
C-13), 69.4 6CH, C-11), 71.8 6CH, C-8), 72.1 6CH, C-8*),
72.6 6CH, C-5), 127.6 6CH, Ar-C), 129.5 6CH, Ar-C), 134.0
6quat., Ar-C), 135.6 6CH, Ar-C); m/z 6FAB, NBA) Found:
MH1, 845.5750. C47H88O5Si4 requires MH, 845.5787.
n
CH), 1698, 6m, CvO), 1471, 1111; dH 6400 MHz;CDCl )
max6®lm)/cm21 3071, 3050 6m, CvCH), 3954, 2930 6s,
3
0.01 63H, s, SiMe), 0.02 63H, s, SiMe), 0.06 66H, s, SiMe),
0.60 66H, q, Jˆ7.8, SiEt3), 0.85 69H, s, But), 0.90 69H, s,
But), 0.94 69H, t, Jˆ7.8, SiEt3), 1.04 69H, s, But), 1.26±1.68
68H, m, 7-H, 9-H, 10-H, 12-H), 2.40±2.43 62H, m, 6-H),
2.41±2.60 62H, m, 2-H), 3.66±3.75 65H, m, 1-H, 11-H,
13-H), 3.83±3.86 61H, m, 8-H), 6.11 61H, dt, J4,3 16.0, J4,2
1.4, 4-H), 6.80 61H, dt, J3,4 16.0, J3,2 7.0, 3-H), 7.35±7.41
66H, m, ArH), 7.64±7.67 64H, m, ArH); dC 6100 MHz;
CDCl3) 25.3 6CH3, SiMe), 24.6 6CH3, SiMe), 24.4
6CH3, SiMe), 5.1 6CH2, SiEt), 7.0 6CH3, SiEt), 18.0 6quat.,
But), 19.2 6quat., But), 25.9 6CH3, But), 26.9 6CH3, But), 30.9
6CH2, C-2), 32.5 6CH2, C-9), 32.8 6CH2, C-7), 33.1 6CH2,
C-10), 35.6 6CH2, C-6), 35.9 6CH2, C-6*), 39.9 6CH2, C-12),
60.9 6CH2, C-13), 61.6 6CH2, C-1), 69.3 6CH, C-11), 71.6
6CH, C-8), 127.7 6CH, Ar-C), 129.5 6CH, Ar-C), 131.9 6CH,
C-4), 134.0 6quat., Ar-C), 135.5 6CH, Ar-C), 143.6 6CH,
C-3), 201.2 6quat., C-5); m/z 6FAB, NBA) Found: MH1,
841.5506. C47H84O5Si4 requires MH, 841.5474.
3.1.15. 1,11-Bis--tert-butyldimethylsilyloxy)-13--tert-butyl-
diphenylsilyloxy)-8-triethylsilyloxytridecan-5-one 30. Tetra-
n-propylammonium perruthenate 63.3 mg, 9.4£1023 mmol)
was added to a mixture of alcohol 29 680 mg, 0.095 mmol),
3.1.13. cis-1,11-Bis--tert-butyldimethylsilyloxy)-13--tert-
butyldiphenylsilyloxy)-8-triethylsilyloxytridec-3-en-5-
one 28. Tetra-n-propylammonium perruthenate 61 mg,
2.8£1023 mmol) was added to a mixture of alcohol 26
Ê
N-methylmorpholine-N-oxide 617 mg, 0.14 mmol) and 4 A
mol. sieves 620 mg) in dichloromethane 65 mL) at room
temperature. The mixture was stirred for 0.5 h then ®ltered
through a plug of silica gel. The ®ltrate was concentrated
under reduced pressure to give the title compound 30
666 mg, 82 %) as a colourless oil and as a 1:1 mixture of
diastereomers; nmax6®lm)/cm21 3071 6m, Ar-H), 2953 6s,
623 mg,
0.027 mmol),
N-methylmorpholine-N-oxide
Ê
65 mg, 0.045 mmol) and 4 A mol. sieves 65 mg) in dichloro-
methane 62 mL) at room temperature. The mixture was
stirred for 0.5 h, then ®ltered through a plug of silica gel.
The ®ltrate was concentrated under reduced pressure to give
the title compound 28 619 mg, 83%) as a colourless oil and
as a 1:1 mixture of diastereomers; nmax6®lm)/cm21 3071 6m,
CvCH), 2877, 2954 6s, CH), 1695 6m, CvO), 1472, 1111;
CH), 1715 6s, CvO), 1471, 1110; dH 6400 MHz;CDCl )
3
0.01 63H, s, SiMe), 0.02 63H, s, SiMe), 0.0566H, s, SiMe),
0.60 66H, q, Jˆ7.8, SiEt), 0.86 69H, s, But), 0.90 69H, s,
But), 0.95 69H, t, Jˆ7.8, SiEt), 1.05 69H, s, But), 1.32±1.68
612H, 2-H, 3-H, 7-H, 9-H, 10-H, 12-H), 2.37±2.49 64H, m,
4-H, 6-H), 3.52±3.71 65H, m, 1-H, 11-H, 13-H), 3.73±3.82
61H, m, 8-H), 7.34±7.42 66H, m, ArH), 7.64±7.68 64H, m,
ArH); dC 6100 MHz;CDCl 3) 25.4 6CH3, SiMe), 24.5
6CH3, SiMe), 24.4 6CH3, SiMe), 5.1 6CH2, SiEt3), 7.0
6CH3, SiEt3), 20.3 6CH2, C-3), 25.9 6CH3, But), 26.9 6CH3,
But), 30.5 6CH2, C-9), 32.2 6CH2, C-7), 32.4 6CH2, C-10),
32.9 6CH2, C-2), 38.3 6CH2, C-6), 39.9 6CH2, C-4), 42.6
6CH2, C-12), 60.9 6CH2, C-1), 62.8 6CH2, C-13), 69.3
6CH, C-11), 71.6 6CH, C-8), 127.6 6CH, Ar-C), 129.5
6CH, Ar-C), 134.0 6quat., Ar-C), 135.5 6CH, Ar-C), 211.0
6quat., C-5); m/z 6FAB, NBA) Found: MH1, 843.5644.
C47H86O5Si4 requires MH, 843.5631.
dH 6400 MHz;CDCl ) 0.01 63H, s, SiMe), 0.02 63H, s,
3
SiMe), 0.06 66H, s, SiMe), 0.60 66H, q, Jˆ7.8, SiEt3),
0.86 69H, s, But), 0.90 69H, s, But), 0.91 69H, t, Jˆ7.8,
SiEt3), 1.06 69H, s, But), 1.34±1.80 68H, m, 7-H, 9-H,
10H, 12-H), 2.52 62H, t, J6,5 7.6, 6-H), 2.82±2.87 62H, m,
2-H), 3.67±3.76 65H, m, 1-H, 11-H, 13-H), 3.84±3.88 61H,
m, 8-H), 6.19 62H, br s, 3-H, 4-H), 7.35±7-43 66H, m, ArH),
7.65±7.68 64H, m, ArH); dC 6100 MHz;CDCl 3) 25.4 6CH3,
SiMe), 24.7 6CH3, SiMe), 24.5 6CH3, SiMe), 5.0 6CH2,
SiEt3), 6.9 6CH3, SiEt3), 18.0 6quat., But), 19.1 6quat.,
But), 25.8 6CH3, But), 26.8 6CH3, But), 30.6 6CH2, C-2),
30.7 6CH2, C-2*), 32.3 6CH2, C-9), 32.5 6CH2, C-9*), 32.7
6CH2, C-7), 33.0 6CH2, C-10), 33.1 6CH2, C-10*), 35.9
6CH2, C-6), 39.8 6CH2, C-12), 60.9 6CH2, C-13), 62.2
6CH2, C-1), 69.3 6CH2, C-11), 72.4 6CH, C-8), 127.6 6CH,
Ar-C), 129.5 6CH, Ar-C), 131.9 6CH, C-4), 133.9 6quat.,
Ar-C), 135.5 6CH, Ar-C), 144.9 6CH, C-3), 200.3 6quat.,
C-5) 201.3 6quat., C-5*); m/z 6FAB, NBA) Found: MH1,
841.5431. C47H84O5Si4 requires MH, 841.5474.
3.1.16. 1--tert-Butyldiphenylsilyloxy)-5--1,6-dioxaspiro-
[4.5]dec-2-yl)pentan-3-ol 31. Pyridinium p-toluenesulpho-
nate 65 mg, 0.02 mmol) was added to a solution of ketone 25
650 mg, 0.06 mmol) in ethanol 60.5 mL). The solution was
heated to 608C and stirred for 10 h. Saturated, aqueous
sodium bicarbonate 61mL) was added and the mixture
extracted with diethyl ether 63£3 mL). The combined
organic extracts were dried 6K2CO3) and concentrated
3.1.14. 1,11-Bis--tert-butyldimethylsilyloxy)-13--tert-butyl-
diphenylsilyloxy)-8-triethylsilyloxytetradecan-5-ol 29. A
mixture of acetylene 25 60.5 g, 0.06 mmol), palladium on

4032
V. Caprio et al. / Tetrahedron 57 )2001) 4023±4034
under reduced pressure and the residue puri®ed by ¯ash
chromatography using hexane: diethyl ether 61:1) as eluent
to gave the title compound 30 620 mg, 67%) as a colourless
oil and as a 1:1:1:1 mixture of four diastereomers;
64 mg) in ethyl acetate 610 mL) was stirred under an atmos-
phere of hydrogen for 6 h. The mixture was then ®ltered
through Celitew and the ®ltrate concentrated under reduced
pressure. The residue was puri®ed by ¯ash chromatography
using hexane: diethyl ether 62: 8) as eluent to give the title
compound 33 661 mg, 69%) as a colourless oil and as a
1:1:1:1 mixture of four diastereomers; nmax6®lm)/cm21
3367 6br, s, OH), 3051, 3071 6m, Ar-H), 2953, 2857 6s,
CH), 1589, 1471; dH 6400 MHz;CDCl 3) 0.01 63H, s,
SiMe), 0.04 66H, s, SiMe), 0.05 63H, s, SiMe), 0.85 65H,
s, But), 0.86 64H, s, But*), 0.89 69H, s, But), 1.05 69H, s, But),
1.47±1.73 616H, m, 2-H, 3-H, 4-H, 6-H, 7-H, 9-H, 10-H,
12-H), 3.58±3.74 66H, m, 1-H, 5-H, 11-H, 13-H), 3.90±3.94
60.5 H, m, 8-H), 3.94±4.01 60.5H, m, 8-H*), 7.35±7.42 66H,
n
max6®lm)/cm21 3437 6br, s, OH), 3070 6m, Ar-H), 2941
6s, CH), 1589, 1427; dH 6400 MHz;CDCl ) 1.06 69H, s,
3
But), 1.46±2.10 616H, m, 2-H, 30-H, 40-H, 80-H, 90-H,
100-H), 3.38±3.71 61H, m, 3-H), 3.79±3.94 64H, m, 1-H,
70-H), 4.04±4.11 61H, m, 20-H), 7.37±7.45 66H, m, ArH),
7.67±7.69 64H, m, ArH); dC 6100 MHz;CDCl 3) 19.0 6quat.,
But), 20.3 6CH2, C-90), 22.6 6CH2, C-30), 25.6 6CH2, C-80),
26.8 6CH3, But), 29.7 6CH2, C-5), 30.1 6CH2, C-5*), 31.5
6CH2, C-4), 32.1 6CH2, C-4*), 34.0 6CH2, C-40), 34.2 6CH2,
C-40*), 37.5 6CH2, C-100), 38.5 6CH2, C-2), 38.7 6CH2,
C-2*), 61.5 6CH2, C-70), 63.0 6CH2, C-1), 70.9 6CH, C-3),
71.1 6CH, C-3*), 78.0 6CH, C-20), 80.9 6CH, C-20*), 105.4
6quat., C-50), 105.5, 6quat., C-50*), 106.7 6quat., C-50**),
106.8 6quat., C-50***), 127.7 6CH, Ar-C), 129.7 6CH,
m, ArH), 7.64±7.6764H, m, ArH); dC 6100 MHz;CDCl )
3
25.3 6CH3, SiMe), 24.6 6CH3, SiMe), 24.4 6CH3, SiMe),
18.1 6quat., But), 19.2 6quat., But), 22.0 6CH2, C-3), 25.9
6CH3, But), 26.0 6CH3, But), 26.9 6CH3, But), 31.6 6CH2,
C-9), 32.7 6CH2, C-10), 33.4 6CH2, C-2), 37.2 6CH2, C-6),
37.4 6CH2, C-7), 39.0 6CH2, C-4), 39.5 6CH2, C-12), 60.8,
6CH2, C-1), 60.9 6CH2, C-13), 69.3 6CH, C-11), 71.8 6CH,
C-5), 72.2 6CH, C-8), 127.6 6CH, Ar-C), 129.6 6CH, Ar-C),
133.9 6quat., Ar-C), 135.6 6CH, Ar-C); m/z 6FAB, NBA)
Found: MH1, 731.4930. C41H75O5Si3 requires MH,
731.4922.
Ar-C), 133.2 6quat., Ar-C), 135.5 6CH, Ar-C); m/z 482
6EI) 6M1, 1%), 425 634) and 407 615);Found: M
482.2844. C29H42O4Si requires M, 482.2852.
1
,
3.1.17. 2-{-2-tert-Butyldiphenylsilyloxy)ethyl}-1,6,8-tri-
oxadispiro[4.1.5.2]tetradecane 32. Iodine 692 mg, 0.18
mmol) was added to a solution of hydroxyspiroacetal 32
690 mg, 0.18 mmol) and iodobenzene diacetate 60.13 g,
0.41 mmol) in cyclohexane 65 mL). The mixture was
irradiated using a 40 W tungsten lamp for 0.5 h at room
temperature. Saturated, aqueous sodium bicarbonate
64 mL) was added and the reaction mixture extracted with
diethyl ether 63£10 mL). The combined organic extracts
were dried 6K2CO3) and concentrated under reduced
pressure and the residue puri®ed by ¯ash chromatography
using hexane: diethyl ether 69:1) as eluent to give the title
compound 32 650 mg, 56%) as a colourless oil and as a
1:1:1:1 mixture of four diastereomers; nmax6®lm)/cm21
3048 6m, Ar-H), 2941, 2857 6s, CH), 1472, 1427, 1111;
3.1.19. 1,11-Bis--tert-butyldimethylsilyloxy)-13--tert-butyl-
diphenylsilyloxy)tridecane-5,8-dione 34. Tetra-n-propyl-
ammonium perruthenate 66 mg, 1.6£1023 mmol) was
added to a mixture of diol 29 660 mg, 0.082 mmol),
Ê
N-methylmorpholine-N-oxide 630 mg, 0.24 mmol) and 4 A
mol. sieves 6200 mg) in dichloromethane 63 mL) at room
temperature. The mixture was stirred for 1 h then ®ltered
through a plug of ¯ash silica gel. The ®ltrate was concen-
trated under reduced pressure to give the title compound 34
642 mg, 70%) as a colourless oil; nmax6®lm)/cm21 3071 6m,
Ar-H), 2930 6s, CH), 1714 6s, CvO), 1471, 1428; dH
6400 MHz;CDCl 3) 0.01 63H, s, SiMe), 0.03 63H, s,
SiMe), 0.04 66H, s, SiMe), 0.85 69H, s, But), 0.89 69H, s,
But), 1.04 69H, s, But), 1.49±1.74 68H, m, 2-H, 3-H, 10-H,
12-H), 2.43±2.50 64H, m, 4-H, 9-H), 2.66 64H, m, 6-H,
7-H), 3.57±3.62 61H, m, 11-H), 3.69±3.72 62H, m, 1-H),
3.89±3.96 62H, m, 13-H), 7.37±7.42 66H, m, ArH), 7.64±
7.66 64H, m, ArH) dC 6100 MHz;CDCl 3) 25.3 6CH3,
SiMe), 24.7 6CH3, SiMe), 24.5 6CH3, SiMe), 18.0 6quat.,
But), 19.1 6quat., But), 20.2 6CH2, C-3), 22.3 6quat., But),
25.8 6CH3, But), 25.9 6CH3, But), 26.8 6CH3, But), 29.2
6CH2, C-10), 30.7 6CH2, C-2), 32.2 6CH2, C-9), 36.0 6CH2,
C-6), 36.9 6CH2, C-7), 38.2 6CH2, C-4), 42.5 6CH2-C-12),
59.5 6CH2, C-1, C-13), 68.3 6CH, C-11), 127.6, CH, Ar-C),
129.6 6CH, Ar-C), 133.9 6quat., Ar-C), 135.5 6CH, Ar-C),
209.3 62£CO, C-5, C-8); m/z 6FAB, NBA) Found: MH1,
727.4617. C41H70O5Si3 requires MH, 727.4609.
dH 6400 MHz;CDCl ) 1.05 69H, s, But), 1.55±2.11 616H,
3
m, 10-H, 3-H, 4-H, 10-H, 11-H, 12-H, 13-H, 14-H), 3.54±
3.62 61H, m, 20-H), 3.70±3.93 63H, m, 20-H, 9-H), 4.17±
4.36 61H, m, 2-H), 7.26±7.47 66H, m, ArH), 7.67±7.71 64H,
m, ArH); dC 6100 MHz;CDCl ) 19.0 6quat., But), 20.2
3
6CH2, C-11), 26.8 6CH3, But), 29.9 6CH2, C-3), 30.1 6CH2,
C-3*), 30.5 6CH2, C-3**), 30.9 6CH2, C-3***), 33.7 6CH2,
C-10), 34.1 6CH2, C-10*), 34.2 6CH2, C-10**), 34.5 6CH2,
C-10***), 34.7 6CH2, C-13), 35.1 6CH2, C-13*), 35.3 6CH2,
C-13**), 36.8 6CH2, C-14), 36.9 6CH2, C-14*), 37.0 6CH2,
C-14***), 37.3 6CH2, C-4), 37.6 6CH2, C-4*), 37.8 6CH2,
C-4**), 38.1 6CH2, C-4***), 38.5 6CH2, C-12), 38.7 6CH2,
C-12*), 40.2 6CH2, C-20), 40.4 6CH2, C-20*), 61.2 6CH2,
C-10), 61.4 6CH2, C-10*), 62.0 6CH2, C-9), 62.1 6CH2,
C-9*), 75.7 6CH, C-2), 76.0 6CH, C-2*), 77.0 6CH2,
C-2**), 77.3 6CH2, C-2***), 105.6 6quat., C-7), 105.7
6quat., C-7*), 105.8 6quat., C-7**), 105.9 6quat., C-7***),
115.1 6quat., C-5), 115.3 6quat., C-5*), 115.4 6quat., C-5**),
115.5 6quat., C-5***), 127.6 6CH, Ar-C), 129.5 6CH, Ar-C),
3.1.20. 2--1-tert-Butyldiphenylsilyloxethyl-2-)-1,6,8-trioxa-
dispiro[4.1.5.2]tetradecane 32. Pyridinium p-toluene-
sulphonate 65 mg, 0.020 mmol) was added to a solution of
diketone 34 630 mg, 0.041 mmol) in ethanol 60.5 mL). The
mixture was stirred at 608C for 7 h. and then cooled to room
temperature and diluted with diethyl ether 61 mL).
Saturated, aqueous sodium bicarbonate 62 mL) was added
and the mixture extracted with diethyl ether 63£4 mL).
The combined organic extracts were dried 6K2CO3),
134.1 6quat., Ar-C), 136.7 6CH, Ar-C); m/z6EI) 480 6M1,
1
0.6%), 423 6100), 405 625) and 462 62.5);Found: M
480.2695. C29H40O4Si requires M, 480.2696.
,
3.1.18. 1,11-Bis--tert-butyldimethylsilyloxy)-13--tert-butyl-
diphenylsilyloxy)tridecane-5,8-diol 33. A mixture of
acetylene 25 60.10 g, 0.12 mmol) and palladium on carbon

V. Caprio et al. / Tetrahedron 57 )2001) 4023±4034
4033
concentrated under reduced pressure and the residue puri-
®ed by ¯ash chromatography to give the title compound 32
610 mg, 50%) as a colourless oil and as a 1:1:1:1 mixture of
four diastereomers.
6CH2, C-500*), 61.5 6CH2, C-500**), 63.4 6CH2, C-1), 64.0
6CH2, C-1*) 70.7 6CH, C-300), 71.1 6CH, C-300*), 72.3 6CH,
C-300**), 72.8 6CH, C-300***), 79.8 6CH, C-50), 81.5 6quat.,
C-4), 81.6 6quat., C-3), 91.1 6quat., C-20), 127.6 6CH, Ar-C),
129.8 6CH, Ar-C), 134.2 6quat., Ar-C), 135.6 6CH, Ar-C);
m/z 6FAB, NBA) 479 6M-OMe) 67%), 421 67) and 401 68).
All spectral data was consistent with that obtained above.
3.1.21. 1,11-Bis--tert-butyldimethylsilyloxy)-13--tert-butyl-
diphenylsilyloxy)-8-triethylsilyloxytridec-3-yn-5-one 35.
Tetra-n-propylammonium perruthenate 613 mg, 0.036
mmol) was added to a mixture of alcohol 25 6200 mg,
0.24 mmol), N-methylmorpholine-N-oxide 636 mg, 0.31
3.1.23. 1--tert-Butyldiphenylsilyloxy)-5--1,6-dioxaspiro-
[4.5]dec-9-en-2-yl)-pentan-3-ol 37. A mixture of acetylene
36 620 mg, 0.039 mol) and Lindlar catalyst 62 mg) in THF
61 mL) was stirred under an atmosphere of hydrogen at
room temperature for 3 h. The mixture was then diluted
with dichloromethane 62 mL) and pyridinium p-toluene-
sulphonate 63 mg) was added. The mixture was stirred for
5 min. Two drops of triethylamine were added and the
mixture ®ltered through Celitew and concentrated under
reduced pressure. The residue was puri®ed by ¯ash chroma-
tography using diethyl ether: hexane 62: 3) as eluent to give
the title compound 37 615 mg, 79%) as a colourless oil and a
1:1:1:1 mixture of four diastereoisomers; nmax6®lm)/cm21
3435 6br, s, OH), 3054 6m, Ar-H), 2950, 2858 6s, CH),
Ê
mmol) and 4 A mol. sieves 650 mg) in dichloromethane
66 mL) at room temperature. The reaction mixture was
stirred for 0.5 h then ®ltered through a plug of silica gel.
The ®ltrate was concentrated under reduced pressure to give
the title compound 35 6160 mg, 80%) as a colourless oil and
as a 1:1 mixture of diastereomers; nmax6®lm)/cm21 3050,
3071 6m, Ar-H), 2954, 2930 6s, CH), 2215 6w, triple
bond), 1676 6s, CvO), 1472; dH 6400 MHz;CDCl ) 0.01
3
63H, s, SiMe), 0.03 63H, s, SiMe), 0.08 66H, s, SiMe), 0.60
66H, q, Jˆ7.8, SiEt3), 0.85 69H, s, But), 0.90 69H, s, But),
0.96 69H, t, Jˆ7.8, SiEt3) 1.04 69H, s, But), 1.38±1.80 68H,
m, 7-H, 9-H, 10-H, 12-H), 2.56±2.61 64H, m, 2-H, 6-H),
3.65±3.87 66H, m, 1-H, 8-H, 11-H, 13-H), 7.35±7.42 66H,
1111; dH 6400 MHz;CDCl ) 1.06 69H, s, But), 1.54±2.31
3
612H, m, 2-H, 4-H, 5-H, 30-H, 40-H, 80-H), 3.38 61H, br s,
OH), 3.63±3.98 65H, m, 1-H, 3-H, 70-H), 4.05±4.21 61H, m,
20-H), 5.58±5.65 61H, m, 100-H), 5.93±6.04 61H, m, 90-H),
7.36±7.44 66H, m, ArH), 7.67±7.69 64H, m, ArH); dC
6100 MHz;CDCl 3) 19.0 6quat., But), 24.5 6CH2, C-4),
30.2 6CH2, C-30), 30.3 6CH2, C-30*), 30.6 6CH2, C-5), 31.8
6CH2, C-80), 33.7 6CH2, C-4), 34.0 6CH2, C-4*), 34.2 6CH2,
C-4**), 37.3 6CH2, C-40), 38.6 6CH2, C-2), 58.7 6CH2, C-1),
59.2 6CH2, C-1*), 63.2 6CH2, C-70), 63.4 6CH2, C-70*), 71,3
6CH, C-3), 71.5 6CH, C-3*), 80.1 6CH, C-20), 81.0 6CH,
C-20*), 102.4 6quat., C-50), 127.7 6CH, Ar-C), 128.5 6CH,
C-9), 128.9 6CH, C-100), 129.6 6CH, ArC), 133.1 6quat.,
ArC), 135.5 6CH, ArC); m/z 6CI, NH3) 481 6MH1, 21%)
and 463 6100);Found: MH 1, 481.2779. C29H40O4Si requires
MH, 481.2774.
m, ArH), 7.64±7.6764H, m, ArH); dC 6100 MHz;CDCl )
3
25,3 6CH3, SiMe), 24.6 6CH3, SiMe), 24.4 6CH3, SiMe),
5.1 6CH2, SiEt3), 7.0 6CH3, SiEt3), 18.0 6quat., But), 18.3
6CH3, But), 19.2 6CH3, But), 23.4 6CH2, C-2), 25.9 6CH3,
But), 26.9 6CH3, But), 30.7 6CH2, C-9), 30.8 6CH2, C-9*),
32.4 6CH2, C-7), 32.7 6CH2, C-7*), 32.8 6CH2, C-10), 33.1
6CH2, C-10*), 39.9 6CH2, C-6), 41.2 6CH2, C-12), 60.8
6CH2, C-1), 60.9 6CH2, C-13), 69.2 6CH, C-11), 71.3 6CH,
C-8), 81.6 6quat., C-4), 90.8 6quat., C-3), 127.6 6CH, ArC),
129.5 6CH, Ar-C), 134.0 6quat., Ar-C), 135.5 6CH, Ar-C),
187.9 6quat., C-5); m/z 6FAB, NBA) Found: MH1,
839.5323. C47H83O5Si4 requires MH, 839.5318.
3.1.22.
4-{5-[5--tert-Butyldiphenylsilyloxy)-3-hydroxy-
3.1.24. 2-{2--tert-Butyldiphenylsilyloxy)ethyl}-1,6,8-trioxa-
dispiro[4.1.5.2]tetradec-11-ene 13. A mixture of hydroxy-
spiroacetal 37 645 mg, 0.094 mmol), iodine 649 mg,
0.19 mmol) and iodobenzene diacetate 663 mg, 0.20
mmol) in cyclohexane 65 mL) was irradiated with a 40 W
tungsten lamp at room temperature for 1 h. Saturated,
aqueous sodium thiosulphate 64 mL) was added and the
mixture extracted with diethyl ether 63£10 mL). The
combined organic extracts were washed with saturated,
aqueous sodium bicarbonate 65 mL), dried 6K2CO3) and
concentrated under reduced pressure. The residue was puri-
®ed by ¯ash chromatography using hexane: diethyl ether
68:2) as eluent to give the title compound 12 635 mg, 78
%) as a colourless oil and a 1:1:1:1 mixture of diastereo-
isomers; nmax6®lm)/cm21 3070 6m, Ar-H), 2958, 2857 6s,
pentyl]-2-methoxytetrahydrofuran-2-yl}but-3-yn-1-ol 36.
Camphorsulphonic acid 62.5 mg, 0.010 mmol) was added to
ketone 35 650 mg, 0.060 mmol) in methanol 60.5 mL) at
room temperature. The mixture was stirred for 1 h then
neutralised by the addition of triethylamine 62 drops). The
mixture was concentrated under reduced pressure and
puri®ed by ¯ash column chromatography using diethyl
ether as eluent to give the title compound 36 617 mg,
55%) as a colourless oil and as a 1:1:1:1 mixture of dia-
stereoisomers; nmax6®lm)/cm21 2931 6s, CH), 2115 6w,
triple bond), 1112; dH 6400 MHz;CDCl 3)1.05 69H, s,
But), 1.59±1.78 610H, m, 30-H, 40-H, 100-H, 200H, 400-H),
2.49±2.54 62H, m, 2-H), 3.35 60.5 H, s, OMe), 3.35 60.5
H, s, OMe*), 3.35 60.5 H, s, OMe**), 3.36 60.5 H, s,
OMe***), 3.49 61H, s, OMe****), 3.69-3.91 65H, m, 1-H,
300-H, 500-H), 4.04±4.26 61H, m, 50-H), 7.37±7.46 66H, m,
ArH), 7.64±7.68 64H, m, ArH); dC 6100 MHz;CDCl 3) 19.0
6quat., But), 22.9 6CH2, C-2), 23.4 6CH2, C-2*), 25.3 6CH2,
C-40) 26.9 6CH3, But), 29.7 6CH2, C-100), 31.0 6CH2, C-200),
31.5 6CH2, C-200*), 31.7 6CH2, C-200**), 31.9 6CH2,
C-200***), 33.4 6CH2, C-30), 33.6 6CH2, C-30*), 34.4 6CH2,
C-30**), 34.6 6CH2, C-30***), 38.1 6CH2, C-400), 38.2 6CH2,
C-400*), 384 6CH2, C-400**), 39.3 6CH2, C-400***), 42.1
6CH3, OMe), 42.6 6CH3, OMe), 60.2 6CH2, C-500), 60.8
CH), 1111; dH 6400 MHz;CDCl ) 1.05 69H, s, But), 1.52±
3
2.29 612H, m, 10-H, 3-H, 4-H, 10-H, 13-H, 14-H), 3.71±3.97
64H, m, 2-H, 90-H), 4.11±4.33 61H, m, 1-H), 5.55±5.68 61H,
m, 11-H), 5.91±6.01 61H, m, 12-H), 7.36±7.45 66H, m,
ArH), 7.67±7.69 64H, m, ArH); dC 6100 MHz;CDCl
)
3
19.1 6quat., But), 24.3 6CH2, C-3), 29.7 6CH2, C-13), 29.9
6CH2, C-13*), 30.6 6CH2, C-13*), 34.4 6CH2, C-14), 34.5
6CH2, C-14*), 34.6 6CH2, C-14**), 35.0 6CH2, C-14***),
36.3 6CH2, C-10), 36.6 6CH2, C-10*), 36.7 6CH2, C-10**),
36.8 6CH2, C-10***), 37.3 6CH2, C-4), 37.6 6CH2, C-4*),

4034
V. Caprio et al. / Tetrahedron 57 )2001) 4023±4034
38.4 6CH2, C-10), 38.6 6CH2, C-10*), 39.6 6CH2, C-10**),
40.3 6CH2, C-10***), 58.9 6CH2, C-20), 59.1 6CH2, C-20*),
59.2 6CH2, C-20**), 59.3 6CH2, C-20***), 61.1 6CH2, C-9),
61.8 6CH2, C-9*), 76.0 6CH, C-2), 76.1 6CH, C-2*), 77.1
6CH, C-2**), 77.3 6CH, C-2***), 102.8 6quat., C-5), 115.2
6quat., C-5*), 127.5 6CH, Ar-C), 127.9 6CH, C-11), 128.3
6CH, C-11*), 128.9 6CH, C-11**), 129.4 6CH, Ar-C), 129.6
6CH, C-12), 129.9 6CH, C-12*), 133.9 6quat., Ar-C), 135.5
6CH, Ar-C); m/z 6EI) 479 6M1, 2%) and 461 6100);Found:
MH1, 479.2608. C29H39O4Si requires MH, 479.2618.
6b) Zheng, S. Z.;Huang, F. L.;Chen, S. C.;Tan, X. F.;Zuo,
J. B.;Peng, J.;Xie, R. W. Chin. J. Mar. Drugs 1990, 33, 33.
4. McCauley, J. A.;Nagasawa, K.;Lander, P. A.;Mischke, S. G.;
Semones, M. A.;Kishi, Y. J. Am. Chem. Soc. 1998, 120, 7647.
5. 6a) Jin, H.;Uenishi, J.;Christ, W. J.;Kishi, Y. J. Am. Chem.
Soc. 1986, 108, 5644. 6b) Tukai, K.;Tagashira, M.;Kuroda,
T.;Oshima, K.;Utimoto, K.;Nozaki, H. J. Am. Chem. Soc.
1986, 108, 6048. 6c) Stamos, D. P.;Sheng, X. C.;Chen, S. S.;
Kishi, Y. Tetrahedron Lett. 1997, 38, 6355.
6. Brimble, M. A.;Fares, F.;Turner, P. J. Chem. Soc., Perkin
Trans. 1 1998, 677.
7. Brimble, M. A.;Furneaux, R. H.;Johnston, A. D. J. Org.
Chem. 1998, 63, 417.
Acknowledgements
8. Holmes, A. B.;Hughes, A. B.;Smith, A. L. J. Chem. Soc.
Perkin Trans. 1 1993, 633.
The authors thank the University of Auckland Research
Committee for ®nancial support 6V. C.).
9. 6a) Dess, D. B.;Martin, J. C. J. Am. Chem. Soc. 1991, 113,
7277. 6b) Ireland, R. E.;Liu, L. J. Org. Chem. 1993, 58, 2899.
6c) Frigerio, M.;Santagostino, M.;Sputore, S. J. Org. Chem.
1999, 64, 4537.
10. 6a) Brimble, M. A.;Williams, G. M. J. Org. Chem. 1992, 43,
1035. 6b) Allen, P. R.;Brimble, M. A.;Fares, F. A. J. Chem.
Soc., Perkin Trans. 1998, 1, 2403.
References
1. Hu, T.;Curtis, J. M.;Oshima, Y.;Quillam, M. A.;Walter,
J. A.;Watson-Wright, W.;Watson-Wright, J. L. C. J. Chem.
Soc., Chem. Commun. 1995, 2159.
Â
11. 6a) Dorta, R. L.;Martin, A.;Suarez, E.;Prange
Tetrahedron: Assymetry 1996, 7, 1907. 6b) Dorta, R. L.;
, T.
Â
Martin, A.;Salazar, J. A.;Suarez, E.;Prange , T. J. Org.
Chem. 1998, 63, 2251. 6c) Martin, A.;Salazar, J. A.;Suarez,
E. J. Org. Chem. 1996, 61, 3999.
2. 6a) Uemura, D.;Chuo, T.;Haino, T.;Nagatsu, A.;Fukuzawa,
S.;Zheng, S.;Chen, H. J. Am. Chem. Soc. 1995, 117, 1155.
6b) Chuo, T.;Kamo, O.;Uemura, D. Tetrahedron Lett. 1996,
37, 402.
12. 6a) Grif®th, W. P.;Ley, S. V.;Whitcombe, G. P.;White, A. D.
J. Chem. Soc., Chem. Commun. 1987, 1625. 6b) Grif®th, W. P.;
Ley, S. V. Aldrichemica Acta 1990, 23, 13.
3. 6a) Otofuji, T.;Ogo, A.;Koishi, J.;Matsuo, K.;Tokiwa, H.;
Yasumoto, T.;Nishihara, K.;Yamamoto, E.;Saisho, M.;
Kurihara, Y.;Hayashida, K. Food Sanit. Res. 1981, 31, 76.
13. Prakash, C.;Saleh, S.;Blair, I. Tetrahedron Lett. 1989, 30, 19.