From an acyclic, polyunsaturated precursor to the polycyclic taxane ring system: The [4+2]/[2+2+2] and [2+2+2]/[4+2] cyclization strategies

Article abstract of DOI:10.1002/ejoc.200500762

A combination of a cobalt(I)-mediated cyclotrimerization and a [4+2] reaction is described as a new entry into the ABC core of taxanes. The [4+2]/[2+2+2] and the [2+2+2]/[4+2] pathways both lead to the expected ABC core of the title compound. Mechanistic

Full text of DOI:10.1002/ejoc.200500762

FULL PAPER
DOI: 10.1002/ejoc.200500762
From an Acyclic, Polyunsaturated Precursor to the Polycyclic Taxane Ring
System: The [4+2]/[2+2+2] and [2+2+2]/[4+2] Cyclization Strategies
Gaëlle Chouraqui,[a] Marc Petit,[a] Phannarath Phansavath,[a] Corinne Aubert,*[a] and
Max Malacria*[a]
Keywords: Cobalt / Cyclization / Cyclotrimerization / Silicon tethers / Taxane
A combination of a cobalt(
I
)-mediated cyclotrimerization and
position has a dramatic influence on the cyclization. For the
second sequence, we observe that the silicon group at the
terminal position of the double bond can alter the chemose-
lectivity of the cycloaddition. In addition, the use of a tempo-
rary silicon tether in the [2+2+2] cycloaddition provides a ra-
pid access to a highly elaborate molecule 38, which exhibits
latent functionality for further synthetic transformations.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
a [4+2] reaction is described as a new entry into the ABC
core of taxanes. The [4+2]/[2+2+2] and the [2+2+2]/[4+2]
pathways both lead to the expected ABC core of the title
compound. Mechanistic proposals are described to under-
stand the formation of the side products during the [2+2+2]
cycloaddition and to apply useful modifications of the highly
substituted unsaturated precursors. Indeed, we demonstrate,
for the first approach, that the substitution at the propargylic
be obtained from an intramolecular Diels–Alder reaction
of the substrate 2. The benzocyclobutene unit of 2 could
arise from the [2+2+2] cyclization of the three alkynes of
precursor 3. The link between both unsaturated moieties 4
and 5 could be either an alkylated or a silylated tether,
which should ensure the chemo- and regioselectivity of the
[2+2+2] cyclizations.
Introduction
In 1971 Wall and Wani discovered a novel diterpenoid,
taxol, and elucidated its unusual structure.[1] Shortly after
its isolation, Horwitz and colleagues described taxol as a
drug candidate that promotes the assembly of microtu-
bules.[2] These two events stimulated different academic and
industrial groups all around the world to synthesize taxol,
and an impressive range of synthetic designs was pro-
posed.[3] Interest in the total synthesis of taxol was triggered
by the inherent complexity of this tetracyclic compound,
which includes an eight-membered ring and a bridgehead
double bond. To date, six total syntheses have been re-
ported.[4]
In this context, we envisioned that a combination of a
[4+2] cycloaddition and a cobalt()-mediated [2+2+2] cycli-
zation, starting from easily prepared simple acyclic polyun-
saturated partners, would allow a rapid construction of the
tetracyclic skeleton of taxoids. Indeed, cobalt()-catalyzed
cyclotrimerizations offer many possibilities and tolerance
toward varied functional groups and their versatility in or-
ganic synthesis is an important feature that has already
been widely demonstrated.[5]
Scheme 1.
Our strategy is depicted retrosynthetically in Scheme 1.
We reasoned that compound 1, which presents an aryl C-
ring, an all carbon D-ring, and an additional E-ring, could
Moreover, we have recently disclosed that the use of tem-
porary silicon tethers (TST) is highly efficient in cobalt-cat-
alyzed cyclotrimerizations and allows the formation of pol-
ysubstituted arenes, after the displacement of the silicon
group.[6] Therefore, the functionalization of the aromatic C-
ring appears feasible with this TST methodology.
[a] Université Pierre et Marie Curie (Paris 6), Laboratoire de Chi-
mie Organique UMR 7611, Institut de Chimie Moléculaire, FR
2769, Tour 44-54, 2ème étage, Case 229,
4 place Jussieu, 75252 Paris Cedex 05, France
Fax: +33-1-4427-7360
Compound 1 could also be obtained by a reversed [4+2]/
[2+2+2] sequence. The [2+2+2] cyclization could allow a
E-mail: aubert@ccr.jussieu.fr
malacria@ccr.jussieu.fr
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simultaneous formation of the A-, B-, and C-rings from
compound 6, and the latter could be formed by an intermo-
lecular Diels–Alder reaction. The [4+2] reaction has already
been successfully used by different groups in the approach
to the taxane skeleton,[7] but never in combination with a
cobalt()-mediated [2+2+2] cyclization.
In this paper we will document and discuss these two
different approaches to the ABC core of taxanes that were
achieved in our laboratory, and, moreover, we will conclude
the section by applying our experience to the formation, the
[2+2+2] cyclization, and the opening of silylated tethers.[8]
Figure 1. ORTEP representation of complex 11.
Its formation probably follows the general pathway[11]
described in Scheme 4: after the coordination of the two
triple bonds, the oxidative coupling could lead to the co-
baltacyclopentadiene 12. This presumed metallacycle inter-
mediate would then prefer to isomerize to the complex 11
rather than to incorporate the appended alkyne unit. This
is probably for electronic reasons due to the presence of the
carbonyl group conjugated to the cyclopentadiene moiety.
Results and Discussion
[4+2]/[2+2+2] Approach[8a]
The cycloadduct 9 was obtained in 68% yield upon treat-
ment of compounds 7 and 8 with Et2O·BF3 in dichloro-
methane at 0 °C (Scheme 2).
Scheme 2.
It was then submitted to “classical” conditions of cyclo-
trimerization: 5 mol-% of dicarbonyl(η5-cyclopentadienyl)-
cobalt [CpCo(CO)2] in boiling xylenes, benzene, or toluene
under irradiation (light from projector lamp; ELW, 300 W,
50% of its power). Surprisingly, this did not afford the de-
sired pentacyclic compound 10. However, when a stoichio-
metric amount of cobalt complex was used, the 6,8,4-tricy-
clic cyclobutadienyl complex 11 was obtained in 32% yield
(Scheme 3). Its structure was established by an X-ray analy-
sis[9] (Figure 1).
Scheme 4.
We next investigated the cyclizations of the cyclohexa-
triynes 13 in which the carbonyl group at the propargylic
position has been replaced by a hydroxy or a methoxy
group. The results showed the dramatic influence of the
substitution in that position. Thus, with a hydroxy group
the reaction led only to the degradation of the starting ma-
terial. It appeared that we could take advantage of a pos-
sible gem-disubstitution effect[12] in the cyclization by using
an acetal group in that position, but despite intense efforts
we were unable to introduce this kind of substituent either
before, during, or after the [4+2] cycloaddition.
In contrast, in the case of a methoxy group we obtained
the tetracyclic structure 14b in 15–20% yield (Scheme 5),
thus confirming the validity of the [4+2]/[2+2+2] approach
Scheme 3.
Complex 11 is photolytically and thermally quite inert to the taxane framework. Of course, the yield of the CoI-
and stable under oxidative conditions as well. The forma- mediated [2+2+2] cyclization would have to be improved
tion of such cyclobutadienes has been previously observed but this strategy has shown that the cobalt() species is able
and is generally considered to arise when either coordina- to mediate the ring closure of strained polyunsaturated
tion or insertion of the third alkyne component is problem- compounds into an eight-membered ring, which is sterically
atic.[10]
even more congested.
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From an Acyclic, Polyunsaturated Precursor to the Polycyclic Taxane Ring System
FULL PAPER
group at the terminal position of the double bond and we
chose a silylated substituent (R = tBuMe2Si) for this pur-
pose. The presence of such a group was found to be very
efficient, since when 20 was exposed to the cobalt mediator
we were pleased to observe the formation of the corre-
sponding benzocyclobutene 21 in 92% yield (Scheme 8).
However, whatever conditions we used, we were unable to
hydrolyze the tetrahydropyranyl ether of 21.
Scheme 5.
[2+2+2]/[4+2] Approach
Alkylated Tether[8b]
At the same time we developed an alternative [2+2+2]/
[4+2] approach. The cyclization of compound 15a, substi-
tuted with a ketone at both the allylic and propargylic posi-
tions, led only to the decomposition of the latter. On the
contrary, precursor 15b, which has one hydroxy group at
that position, gave the expected benzocyclobutene 16b but
in low yield (18%). Surprisingly, the major product was a
1:1 mixture of diastereomeric complexes 17b (37%), arising
from the [2+2+2] reaction between two alkynes and the ter-
minal double bond (Scheme 6). The insertion of the last
triple bond into the cobaltacyclopentadiene is probably dis-
favored for geometric reasons compared to that of the
double bond. In addition, 30% of starting material 15b re-
mained unchanged. Attempts to avoid the participation of
the double bond in the cyclization by a temporary protec-
tion of the diene system failed.
Scheme 8. (a) 5 mol-% [CpCo(CO)2], xylenes, ∆, hν; (b) cat. PTSA,
MeOH, quantitative; (c) IBX, DMSO, room temp., 76%; (d) 1.
LDA, PhSeBr, THF, 2. NaIO4, NaHCO3, MeOH/H2O, 81%; (e)
Et2O·BF3, CHCl3, –78 °C, 95 %.
Under the same conditions, 22 led to a mixture of benzo-
cyclobutenes 23 and 24 in 50 and 37% yield, respectively.
Compound 24 presumably arises from a migration of the
double bond leading to an enol. Moreover, the formation
of 24 is not a problem because it can be easily converted
into the dienophilic enone. Thus, after oxidation of 23 and
selenation/oxidation/elimination of 24, the resulting enone
was treated with 5 equiv. of Et2O·BF3 in chloroform to af-
ford 25 in 95% yield as a single diastereomer of unidentified
stereochemical arrangement.
As far as the [4+2] cyclization is concerned, molecular
models reveal that only the endo approach is possible, and
according to the chemical shifts of the three methyl groups
(δ = 1.33, 1.12, 0.77 ppm), the conformation of the cycload-
duct is probably endo, as described by Shea.[13]
Scheme 6.
In summary, by circumventing the competitive reactions
we have been able to perform the two key steps of our strat-
egy in high yields and to show that a [2+2+2]/[4+2] ap-
proach is valid for the construction of the core of taxoids.
However, the additional alkylated E-ring is a limiting factor
for the functionalization of the aromatic C-ring. In relation
with our studies on the use of TST in the [2+2+2] cycliza-
tions, we turned our attention to a disposable silylated link
connecting the unsaturated moieties 4 and 5, which should
ensure both the success of the [2+2+2] cyclization and fur-
ther transformations of the cycloadducts.
Nevertheless, 16b was oxidized[7b] (BaMnO4/Celite in
benzene) and the [4+2] cyclization of 18 was performed in
presence of Et2O·BF3 at –40 °C in toluene, allowing the for-
mation of the pentacyclic structure 19 in an excellent 95%
yield (Scheme 7), thus validating the [2+2+2]/[4+2] ap-
proach to the taxane framework.
Silylated Tether
In order to overcome all the previously encountered
problems, namely the 1,3-migration of the double bond
Scheme 7.
In order to avoid the competitive [2+2+2] reaction of the during the cobalt-mediated cyclization and the problematic
enediyne moiety, we then decided to introduce a bulky hydrolysis of the THP ether at both the allylic and benzylic
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positions, we envisioned the preparation of a new polyun- clobutene, which, after opening of the silaketal, afforded
saturated precursor 33. The latter presents a diisopropylsi- the diol 34 in 88% over two steps (Scheme 10).
laketal group and no allylic double bond.
Similar to the preparation of 22, the starting material for
the synthesis is the dienyne 26,[8b] which was alkylated with
paraformaldehyde in 71% yield (Scheme 9).
Scheme 10. (a) 5 mol-% [CpCo(CO)2], xylenes, ∆, hν; (b) nBu4NF
(3 equiv.), THF, –78 to 0 °C; (c) nBuLi, THF, –78 °C, TsCl, –78 °C
to room temp.; (d) nBu4NF (1.2 equiv.), THF, reflux; (e) IBX,
DMSO, room temp.; (f) NaHMDS, THF, –40 °C, PhSeCl, –40 °C
to room temp.; (g) NaIO4, NaHCO3, MeOH/H2O; (h) Et2O·BF3
(5 equiv.), CHCl3, –50 °C.
After monotosylation of 34, tricyclic compound 35 was
obtained in 80% yield. Subsequent treatment with nBu4NF
in refluxing THF, followed by oxidation of the resulting
Scheme 9. (a) nBuLi, THF, –78 °C, (CH2O)n; (b) nBuLi, THF,
–78 °C, CH3CH2CHO, –78 °C to room temp.; (c) cat. PTSA, 3,4-
dihydro-2H-pyran, CH2Cl2; (d) nBu4NF, THF, 0 °C to room temp.;
(e) SO3·pyridine, DMSO, Et3N, CH2Cl2, 0 °C; (f) MeCOC(N2)-
P(O)(OMe)2 K2CO3, MeOH; (g) cat. PTSA, MeOH, room temp.;
(h) tBuPh2SiCl, Et3N, 4-DMAP, CH2Cl2, room temp.; (i) nBuLi,
–78 °C, THF, (CH2O)n, –78 °C to room temp.; (j) 1. Et3N, 4-
DMAP, CH2Cl2, room temp., ClSiiPr2H, 2. NBS, CH2Cl2, room
temp., 3. 27, Et3N, 4-DMAP, CH2Cl2, room temp.
alcohol with o-iodoxybenzoic acid (IBX) in DMSO, af-
forded ketone 36. Finally, the selenation/oxidation/elimi-
nation sequence described above provided the requisite en-
one 37. The latter was treated with 5 equiv. of Et2O·BF3 in
chloroform to afford the desired cycloadduct 38 in 65%
yield as a single diastereomer. According to the chemicals
shifts of the three methyl groups (δ = 1.24, 1.18, 0.70 ppm),
the conformation of the cycloadduct is endo.[13] This was
unambiguously confirmed by a single-crystal X-ray analy-
sis[9] (Figure 2).
At the same time tert-butyldimethyl(pent-4-ynyloxy)si-
lane (28) was alkylated with propanal in 76% yield and the
resulting alcohol was protected as a tetrahydropyranyl ether
(Scheme 9). After removal of the silylated group, the corre-
sponding alcohol was oxidized to the aldehyde 30 in 87%
yield over three steps. The transformation of 30 into the
terminal alkyne was achieved in 81% yield by using the
Ohira–Bestmann procedure.[14] Then, acid-catalyzed hy-
drolysis of the THP ether, further protection with a tert-
butyldiphenylsilyl group, and hydroxyalkylation with para-
formaldehyde furnished 32 in 66% yield over three steps.
Finally, the silylated tether was introduced according to our
Figure 2. ORTEP representation of the cycloadduct 38.
It should be noted that the cycloadduct undergoes a pro-
reported procedure for the preparation of unsymmetrical todesilylation at C-13 in situ. As the tert-butyldimethylsilyl
silaketals.[15] This sequence is based upon the reaction of group is not suitable for a Fleming-[16] or Tamao–Kumada-
the alcohol 32 with chlorodiisopropylsilane, transformation type[17] oxidation, this protodesilylation is not troublesome,
of the resulting alkoxysilane into the corresponding bro- and therefore an allylic oxidation leading to the alcohol pre-
mide by reaction with N-bromosuccinimide, and condensa- cursor of the lateral chain can be considered.[18]
tion of the bromide with the second alcohol 27. The re-
sulting silaketal 33 was obtained in 68% yield and is stable has been validated with success. The yields of the two key
to aqueous workup and chromatography on silica gel. steps of our strategy are very high either with the alkylated
Thus, the [2+2+2]/[4+2] approach to the core of taxoids
Treatment of 33 with 5 mol-% of [CpCo(CO)2] in boiling tether or the silylated one. The use of a temporary silicon
xylenes under irradiation led to the corresponding benzocy- tether greatly improves the reaction, and the transformation
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From an Acyclic, Polyunsaturated Precursor to the Polycyclic Taxane Ring System
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rie Curie. Low-resolution mass spectra (MS) and high-resolution
mass spectra (HRMS) were measured by the Service de spectromé-
trie de masse de l’ICSN-CNRS, Gif-sur-Yvette. IR spectra were
recorded with a Bruker Tensor 27 spectrometer. Absorbance fre-
quencies are given at maximum of intensity in cm–1.
of the aromatic C-ring of compound 38 can be now envi-
sioned.
Conclusion
[4+2]/[2+2+2] Approach: Characterization data for 7, 8, 9, and 11
have already been reported.[8a,8b]
In this paper we have shown new examples of the re-
markable synthetic potential of the combination of a co-
balt()-mediated [2+2+2] cyclization with a [4+2] cycload-
dition. More than just the formation of the skeleton of a
natural product, we have studied here the behavior of highly
functionalized unsaturated precursors in the presence of a
cobalt() mediator and their transformations into strained
polycyclic structures. In summary, the [4+2]/[2+2+2] ap-
proach to the taxane framework has been validated. It is
obvious that the yield of the CoI-mediated [2+2+2] cycliza-
tion has to be improved, but it is noteworthy that this ap-
proach has shown that cobalt species are able to mediate
the ring closure of polyunsaturated compounds 9 and 13b
into an eight-membered ring containing a bridgehead
double bond, which is sterically even more congested.
As for the [2+2+2]/[4+2] approach, the yields are good
to excellent, no matter whether the link is an alkylated
tether or a silylated one. The endo conformation of the
pentacyclic structure 38 was established by a single-crystal
X-ray analysis. In addition, the results have also described
the compatibility of our previously reported method for the
preparation of unsymmetrical silaketals with numerous and
varied unsaturations. Finally, the most rewarding aspect of
this approach was the ability to perform the cobalt-cata-
lyzed cyclization with a temporary silicon tether, which al-
lows a rapid entry to a compound (38) that has latent func-
tionality for further synthetic transformations. Indeed, an
allylic oxidation of C-13 to generate the corresponding
alcohol, which is a precursor of the lateral chain, combined
with an easy functionalization of the aromatic C-ring can
be envisioned to lead to several analogs. In addition, this
proposed strategy is a good opportunity for the preparation
of a taxane skeleton with an all-carbon D-ring whose bio-
logical activity has never been evaluated due to the lack of
methods of formation of such a ring.
1-(3-But-3-ynyl-2,2,4-trimethylcyclohex-3-enyl)hepta-2,6-diyn-1-ol
(13a): Cerium() chloride (0.180 g, 0.73 mmol) and then sodium
borohydride (0.028 g, 0.73 mmol) were added to a cooled (–78 °C)
solution of ketone 9 (0.205 g, 0.73 mmol) in methanol (3.6 mL).
The reaction mixture was then diluted with Et2O and hydrolyzed
with H2O. The organic layer was dried with magnesium sulfate,
filtered, and concentrated in vacuo. The residue was purified by
flash chromatography (PE/EE = 80:20) to give the alcohol 13a as
a mixture of diastereomers (de = 93%). Only the major isomer of
13a (0.196 g, 95%) was characterized. IR (neat): ν = 3500, 3300,
˜
2920, 2100, 1470, 1430, 1380, 1365, 1040, 640 cm–1 1H NMR
.
(400 MHz, CDCl3, 21 °C): δ = 1.03 [s, 3 H, C(CH3)2], 1.11 [s, 3 H,
C(CH3)2], 1.54 [dt, J = 10.9, 2.3 Hz, 1 H, CH2–CH–CH(OH)–],
1.65 (s, 3 H, CH3–C=), 1.68–1.77 (m, 1 H, CH2–CH), 1.83–1.87
(m, 1 H, CH2–CH), 2.00 (t, J = 2.5 Hz, 1 H, ϵCH), 2.03 [t, J =
2.5 Hz, 1 H, CϵC(CH2)2CϵCH], 2.02–2.08 (m, 2 H, CϵC–CH2–
CH2–CϵCH), 2.18–2.24 (m, 2 H, CH2–CϵCH), 2.25–2.34 (m, 2
H, CH2–CH2–CϵCH), 2.38–2.48 (m, 4 H, CϵC–CH2–CH2–
CϵCH, =C–CH2–), 4.58 (br. s, 1 H, CH–OH) ppm. 13C NMR
(100 MHz, CDCl3, 21 °C): δ = 18.7 (CH2), 18.8 (2 CH2), 19.3
(CH2), 20.1 (CH3), 22.9 (CH3), 27.5 (CH3), 28.1 (CH2), 32.1 (CH2),
38.1 (C), 51.2 (CH–OH), 62.8 (CH), 68.2 (C), 69.3 (C), 82.6 (CH),
82.7 (C), 83.3 (C), 84.6 (CH), 129.2 (C), 136.0 (C) ppm.
2-But-3-ynyl-4-(1-methoxyhepta-2,6-diynyl)-1,3,3-trimethylcyclo-
hexene (13b): At 0 °C, a solution of alcohol 13a (0.30 g, 1.06 mmol)
in THF (3 mL) was added dropwise to a suspension of sodium
hydride (60% in oil, 42.4 mg, 1.06 mmol) in THF (2 mL). After
being stirred at room temperature for 30 min, methyl iodide
(0.33 mL, 5.3 mmol) was added and the resulting mixture was
stirred for an additional hour. The solution was then diluted with
Et2O and washed with a saturated solution of ammonium chloride
and brine, dried with magnesium sulfate, filtered, and concentrated
in vacuo. The residue was purified by flash chromatography (PE/
EE = 90:10) to give the ether 13b (0.268 g, 85%) as a colorless oil.
IR (CH Cl ): ν = 3300, 2980, 2950, 2100, 1660, 1610, 1440, 1250,
˜
2
2
930 cm–1. 1H NMR (400 MHz, CDCl3, 21 °C): δ = 0.91 [s, 3 H,
C(CH3)2], 1.07 [s, 3 H, C(CH3)2], 1.53–1.56 [m, 1 H, CH2–CH–
CH(OMe)–], 1.63 (s, 3 H, CH3–C=), 1.80–2.06 [m, 4 H, =C–
(CH2)2], 1.97 (t, J = 2.5 Hz, 1 H, ϵCH), 2.00 [t, J = 2.5 Hz, 1 H,
CϵC(CH2)2CϵCH], 2.14–2.31 (m, 4 H, CH2–CH2–CϵCH), 2.37–
2.47 [m, 4 H, CϵC(CH2)2CϵCH], 3.32 (s, 3 H, CH3O), 4.04 (d, J
= 1.5 Hz, 1 H, –CH–OMe) ppm. 13C NMR (100 MHz, CDCl3,
21 °C): δ = 18.7 (2 CH2), 19.2 (CH2), 19.4 (CH2), 19.9 (CH3), 22.4
(CH3), 27.0 (CH3), 28.2 (CH2), 32.5 (CH2), 38.2 (C), 51.1 (CH),
56.1 (CH3O), 68.1 (CH), 69.2 (CH), 71.6 (CH), 81.0 (C), 82.4 (C),
83.1 (C), 84.5 (C), 128.5 (C), 135.9 (C) ppm.
Experimental Section
General Methods: All reactions were carried out under argon in
flame-dried glassware, with magnetic stirring and degassed, anhy-
drous solvents. All commercially available reagents were used with-
out further purification, unless otherwise noted. All solvents were
reagent grade and distilled under a positive pressure of dry nitrogen
before use. THF was distilled from sodium/benzophenone. Solid
reagents were dried in vacuo (0.5–0.1 Torr). Thin layer chromatog-
raphy (TLC) was performed on Merck 60 F254 silica gel. Merck
Geduran SI 60-Å silica gel (35–70 µm) was used for column
chromatography according to Still’s method. PE and EE refer to
petroleum ether and Et2O. Chemical shifts are given in ppm, refer-
enced to the residual proton resonances of the solvents (δ =
7.26 ppm for CDCl3; δ = 7.16 ppm for C6D6). Coupling constants
(J) are given in Hertz (Hz). Elemental analyses were performed by
the Service Régional de Microanalyse de l’Université Pierre et Ma-
Cycloadduct 14b: Dicarbonyl(cyclopentadienyl)cobalt()
(0.05 equiv.) was added to a boiling solution of 13b (0.10 g,
0.33 mmol) in xylenes (15 mL) degassed by three freeze-pump-thaw
cycles and was irradiated (light projector lamp: ELW, 300 W, 50%
of its power). The reaction was monitored by TLC and, after com-
pletion, the reaction mixture was concentrated in vacuo. The crude
mixture was purified by flash chromatography on silica (PE/EE =
90:10) to give 14b (0.16 g, 16%) as a yellow oil. IR (CH Cl ): ν =
˜
2
2
2970, 1700, 1450, 1370, 1090 cm–1. 1H NMR (400 MHz, CDCl3,
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21 °C): δ = 0.30 [s, 3 H, C(CH3)2], 0.99 [s, 3 H, C(CH3)2], 1.64 (s, dropwise to a cooled (0 °C) solution of the preceding compound
3 H, CH3–C=), 1.10–2.71 [m, 9 H, –CH–CH(OMe), =C–(CH2)2– (68.7 mmol) in THF (500 mL). The solution was warmed up to
CH, =C–(CH2)2–C=], 3.00 [t, J = 4.2 Hz, 2 H, CH2(cyclobutene)], room temperature and stirred until completion of the reaction
3.10 (s, 3 H, CH3O), 3.22–3.28 [m, 2 H, CH2(cyclobutene)], 3.77
(d, J = 8.6 Hz, 1 H, –CH–OMe), 6.84 (d, J = 7.3 Hz, 1 H, H arom), brine, dried with magnesium sulfate, filtered, and concentrated in
6.91 (d, J = 7.3 Hz, 1 H, H arom) ppm. 13C NMR (100 MHz,
vacuo. The crude oil was used without further purification in the
CDCl3, 21 °C): δ = 18.8 (CH3), 21.5 (CH2), 21.7 (CH3), 26.3 (CH3), next step. DMSO (87 mL, 1220.1 mmol), triethylamine (85 mL,
27.1 (CH2), 29.9 (CH2), 31.2 (CH2), 31.7 (CH2), 32.5 (CH2), 38.2 610.5 mmol) and the complex pyridine/SO3 (50.92 g, 366.3 mmol)
(C), 57.0 (CH3), 57.1 (CH), 84.4 (CH), 122.2 (CH), 126.0 (C), 130.4 were added to a cooled (0 °C) solution of the preceding alcohol
(TLC). The reaction mixture was extracted with Et2O, washed with
(CH), 137.7 (C), 140.3 (C), 140.4 (C), 144.3 (C), 144.9 (C) ppm.
(13.82 g, 61.1 mmol) in CH2Cl2 (110 mL). The mixture was stirred
at 0 °C until TLC indicated completion of the reaction. The solu-
tion was diluted with Et2O, washed with a saturated solution of
NH4Cl and brine, dried with magnesium sulfate, filtered, and con-
centrated in vacuo. The residue was purified by flash chromatog-
raphy (PE/EE = 85:15) to give the aldehyde 30 (13.33 g, 87% over
[2+2+2]/[4+2] Approach: Characterization data of compounds 15–
26 have already been reported.[8b]
6-[2-(tert-Butyldimethylsilyl)-1-methylvinyl]-7-methyloct-6-en-2-yn-
1-ol (27): nBuLi (2.3  solution in pentane, 1.8 mL, 4.20 mmol) was
added dropwise to a cooled (–78 °C) solution of compound 26
(1.17 g, 4.00 mmol) in THF (7 mL). After being stirred at this tem-
perature for 15 min, paraformaldehyde (0.12 mmol, 3.60 g) was
added. The solution was warmed to room temperature and stirred
until completion of the reaction (TLC). The solution was then di-
luted with Et2O and washed with a saturated solution of ammo-
nium chloride and brine, dried with magnesium sulfate, filtered,
and concentrated in vacuo. The residue was purified by flash
chromatography (PE/EE = 90:10) to give the alcohol 27 (0.83 g,
3 steps) as a mixture of two diastereomers. IR (neat): ν = 2940,
˜
1
2100, 1765, 930 cm–1. H NMR (400 MHz, CDCl3, 21 °C): 30a: δ
= 0.97 (m, 3 H, CH3–CH2), 1.50–1.82 [m, 8 H, 3×CH2(THP), Me–
CH2], 2.51 (m, 2 H, –CH2–CH2–), 2.63 (m, 2 H, –CH2–CH2–
CHO), 3.48 (m, 1 H, CH–OTHP), 3.77 [m, 1 H, CH–O(THP)],
4.28 [m, 1 H, CH–O(THP)], 4.90 (m, 1 H, O–CH–O), 9.75 (s, 1
H, –HC=O) ppm; 30b: δ = 0.93 (m, 3 H, CH3–CH2), 1.50–1.82 [m,
8 H, 3×CH2(THP), Me–CH2], 2.51 [m, 2 H, –CH2–CH2–], 2.63
(m, 2 H, –CH2–CH2–CHO), 3.48 (m, 1 H, CH–OTHP), 3.95 [m, 1
H, CH–O(THP)], 4.18 [m, 1 H, CH–O(THP)], 4.68 (m, 1 H, O–
CH–O), 9.75 (s, 1 H, –HC=O) ppm. 13C NMR (100 MHz, CDCl3,
21 °C): 30a: δ = 9.96 (CH3), 12.1 (CH2), 19.4 (CH2), 25.5 (CH2),
29.2 (CH2), 30.5 (CH2), 42.7 (CH2), 62.2 (CH2), 66.2 (CH–O), 68.5
(CH–O), 81.0 (Cϵ), 83.6 (Cϵ), 200.6 (–HC=O) ppm; 30b: δ = 9.55
(CH3), 12.2 (CH2), 19.4 (CH2), 25.4 (CH2), 28.7 (CH2), 30.5 (CH2),
42.7 (CH2), 62.4 (CH2), 66.2 (CH–O), 68.5 (CH–O), 80.0 (Cϵ),
82.8 (Cϵ), 200.4 (–HC=O) ppm.
71%) as a colorless oil. IR (neat): ν = 3300, 2980, 2950, 2100, 1660,
˜
1610, 1440, 1250, 930 cm–1. 1H NMR (400 MHz, CDCl3, 21 °C): δ
= 0.10 [s, 6 H, Si(CH3)2], 0.90 [s, 9 H, SiC(CH3)3], 1.65 [s, 3 H,
C=C(CH3)2], 1.69 [s, 3 H, C=C(CH3)2], 1.80 [s, 3 H, CH=C(CH3)–
], 2.21 (m, 2 H, CH2–Cϵ), 2.33 (m, 2 H, =C–CH2), 4.25 (m, 2 H,
CH2–OH), 5.08 (s, 1 H, HC=) ppm. 13C NMR (100 MHz, CDCl3,
21 °C): δ = 4.2 (2 CH3), 17.3 (C), 17.9 (CH2), 19.5 (CH3), 21.7 (2
CH3), 26.5(3 CH3), 30.1 (CH2), 51.2 (CH2OH), 65.9 (C), 78.1 (C),
124.8 (C), 125.1 (=CH), 139.3 (C), 155.6 (C) ppm. C18H32OSi
(292.53): calcd. C 73.90, H 11.03; found C 73.93, H 11.35.
3-(Tetrahydropyran-2-yloxy)nona-4,8-diyne (31): K2CO3 (16.42 g,
118.8 mmol) and a solution of dimethyl (1-diazo-2-oxopropyl)-
phosphonate (13.70 g, 71.3 mmol) in MeOH (120 mL) were added
to a solution of 30 (59.4 mmol, 1.0 equiv.) in MeOH (330 mL) and
the mixture was stirred at room temperature for 6 h. The solution
was diluted with Et2O, washed with a saturated solution of NH4Cl
followed with brine, dried with magnesium sulfate, filtered, and
concentrated in vacuo. The crude oil was purified by flash
chromatography (PE/EE = 98:2) to give compound 31 (10.65 g,
81 %) as a mixture of two diastereomers. 1H NMR (400 MHz,
CDCl3, 21 °C): 31a: δ = 0.98 (t, J = 7.6 Hz, 3 H, CH3–CH2), 1.15–
1.70 [m, 8 H, 3×CH2(THP), Me–CH2], 1.97–1.98 (m, 1 H, ϵCH),
2.34–2.42 [m, 4 H, ϵC–(CH2)2–Cϵ], 3.46–3.49 (m, 1 H, CH–
OTHP), 3.76 [br. t, J = 9.0 Hz, 1 H, CH–O(THP)], 4.29 [dt, J =
6.6, 1.6 Hz, 1 H, CH–O(THP)], 4.94 (br. s, 1 H, O–CH–O) ppm;
31b: δ = 0.96 (t, J = 7.6 Hz, 3 H, CH3–CH2), 1.70–1.15 [m, 8 H,
3×CH2(THP), Me–CH2], 1.97–1.98 (m, 1 H, ϵCH), 2.34–2.42 [m,
4 H, ϵC–(CH2)2–Cϵ], 3.46–3.49 (m, 1 H, CH–OTHP), 3.97 [br. t,
J = 9.0 Hz, 1 H, CH–O(THP)], 4.19 [dt, J = 6.2, 1.6 Hz, 1 H, CH–
O(THP)], 4.70 (br. s, 1 H, O–CH–O) ppm. 13C NMR (100 MHz,
CDCl3, 21 °C): 31a: δ = 10.2 (CH3), 19.2 (2 CH2), 19.7 (CH2),
25.9 (CH2), 29.4 (CH2), 30.8 (CH2), 62.5 (CH2), 66.6 (CH–O), 69.5
(ϵCH), 80.4 (–Cϵ), 82.9 (–Cϵ), 84.0 (–Cϵ), 95.6 (O–CH–O) ppm;
31b: δ = 9.8 (CH3), 19.3 (2 CH2), 19.5 (CH2), 25.7 (CH2), 29.1
(CH2), 30.8 (CH2), 62.5 (CH2), 66.7 (CH–O), 69.6 (–CϵCH), 81.3
(–Cϵ), 83.0 (–Cϵ), 83.3 (–Cϵ), 98.0 (O–CH–O) ppm.
8-(tert-Butyldimethylsilyloxy)oct-4-yn-3-ol (29): nBuLi (2.3  solu-
tion in pentane, 43.0 mL, 99.0 mmol) was added dropwise to a co-
oled (–78 °C) solution of 5-(tert-butyldimethylsilyloxy)pent-4-
yne[19] (17.85 g, 90.0 mmol) in THF (138 mL). After being stirred
at this temperature for 20 min, propanal (7.1 mL, 99.0 mmol) was
added. The solution was warmed up to room temperature and
stirred until completion of the reaction (TLC). The solution was
then diluted with Et2O and washed with a saturated solution of
ammonium chloride and brine, dried with magnesium sulfate, fil-
tered, and concentrated in vacuo. The crude oil was purified by
flash chromatography on silica gel (PE/EE = 90:10) and gave 29
(17.63 g, 76%) as a yellow oil. IR (neat): ν = 3500, 2850, 2100,
˜
1450, 1395, 1110, 860 cm–1. 1H NMR (400 MHz, CDCl3, 21 °C): δ
= 0.05 [s, 6 H, Si(CH3)2], 0.89 [s, 9 H, SiC(CH3)3], 0.98 (m, 3 H,
CH3–CH2), 1.65–1.73 (m, 4 H, Me–CH2, CH2–CH2–CH2), 2.28
(m, 2 H, CH2–CH2–CH2), 3.68 (t, J = 3.6 Hz, 2 H, –CH2OSi), 4.28
(br. s, 1 H, CHOH) ppm. 13C NMR (100 MHz, CDCl3, 21 °C): δ
= –5.0 (2 CH3), 9.8 (CH3), 18.7 (C), 15.4 (CH2), 26.3 (3 CH3), 31.5
(CH2), 32.0 (CH2), 61.9 (CH2–O), 64.2 (CH–OH), 81.6 (C), 85.2
(C) ppm.
6-(Tetrahydropyran-2-yloxy)oct-4-ynal (30): 3,4-Dihydro-2H-pyran
(6.6 mL, 72.1 mmol) and p-toluenesulfonic acid (PTSA) (130 mg,
0.7 mmol) were added to a solution of 29 (68.63 mmol) in CH2Cl2
(69 mL). The mixture was stirred until completion of the reaction
(TLC). The solution was extracted with Et2O, washed with a satu-
rated solution of NaHCO3 and brine, dried with magnesium sul-
fate, filtered, and concentrated in vacuo. The crude oil was used
without further purification in the next step. Tetrabutylammonium
fluoride (1  solution in THF, 75.5 mL, 75.5 mmol) was added
8-(tert-Butyldiphenylsilyloxy)deca-9–2,6-diyn-1-ol (32): PTSA
(92 mg, 0.5 mmol) was added to a solution of 31 (10.65 g,
48.3 mmol) in MeOH (84 mL). The mixture was stirred at room
temperature until completion of the reaction (TLC). The solution
was diluted with Et2O, washed with a saturated solution of
1418
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 1413–1421

From an Acyclic, Polyunsaturated Precursor to the Polycyclic Taxane Ring System
FULL PAPER
NaHCO3 and brine, dried with magnesium sulfate, filtered, and
concentrated in vacuo. The crude mixture was used without further
freeze-pump-thaw cycles and was irradiated (light projector lamp:
ELW, 300 W, 50% of its power). The reaction was monitored by
purification in the next step. Triethylamine (6.8 mL, 49.3 mmol), 4- TLC, and after completion, the reaction mixture was concentrated
(dimethylamino)pyridine (4-DMAP) (547 mg, 4.5 mmol), and tert-
butyldiphenylsilyl chloride (12.3 mL, 47.0 mmol) were added to a
solution of the preceding alcohol (0.61 g, 44.8 mmol) in CH2Cl2
(100 mL). The mixture was stirred at room temperature until TLC
indicated completion of the reaction. The solution was diluted with
Et2O, washed with a saturated solution of NH4Cl and brine, dried
with magnesium sulfate, filtered, and concentrated in vacuo. The
crude oil was used without further purification in the next step.
nBuLi (2.2  solution in pentane, 19.1 mL, 41.4 mmol) was added
dropwise to a cooled (–78 °C) solution of the preceding compound
(14.76 g, 39.4 mmol) in THF (60 mL). After being stirred at this
temperature for 20 min, paraformaldehyde (3.55 g, 118.2 mmol)
was added. The solution was warmed up to room temperature and
stirred until completion of the reaction (TLC). The solution was
then diluted with Et2O, washed with a saturated solution of ammo-
nium chloride and brine, dried with magnesium sulfate, filtered,
and concentrated in vacuo. The crude oil was purified by flash
chromatography on silica gel (PE/EE = 90:10) to give 32 (12.87 g,
in vacuo. The crude mixture was filtered through a Celite pad and
used without further purification in the next step. Tetrabutylammo-
nium fluoride (1  solution in THF, 4.17 mL, 4.17 mmol) was
added dropwise to a cooled (–78 °C) solution of the preceding com-
pound in THF (16 mL). The solution was warmed to 0 °C and
stirred until completion of the reaction (TLC). The solution was
then diluted with Et2O, washed with a saturated solution of ammo-
nium chloride and brine, dried with magnesium sulfate, filtered,
and concentrated in vacuo. The crude oil was purified by flash
chromatography to give compound 34 (875 mg, 88% over 2 steps)
as a yellow oil. IR (ATR): ν = 3329, 2927, 2857, 1742, 1599, 1055,
˜
1
823, 700 cm–1. H NMR (200 MHz, CDCl3, 21 °C): δ = 0.13 [s, 6
H, Si(CH3)2tBu], 0.94 [m, 11 H, SiC(CH3)3Me2, CH2], 1.07 [m, 12
H, SiC(CH3)3Ph2, CH3], 1.44 [s, 3 H, =C(CH3)2], 1.62 [s, 3 H,
=C(CH3)2], 1.75 [s, 3 H, =C(CH3)2], 2.00 (m, 2 H, CH2–CH2), 2.34
(m, 2 H, CH2–CH2), 3.15 [m, 2 H, CH2(cyclobutene)], 3.38 [m, 3
H, CH2(cyclobutene), CH–OSi], 4.17 (br. s, 4 H, 2×CH2OH), 5.09
(br. s, 1 H, –CH=), 7.44–7.09 [m, 8 H, 2×4 H(Ph)], 7.69 [d, J =
6.8 Hz, 2 H, 2×1 H(Ph)]. HRMS calcd. for C44H64O3Si2 [MNH4+]:
66% over 3 steps) as a colorless oil. IR (neat): ν = 3329, 2931,
˜
2857, 2100, 1427, 1109, 1006, 821, 700, 611 cm–1 1H NMR 714.4738; found 714.4755.
.
(200 MHz, CDCl3, 21 °C): δ = 0.81 (t, J = 7.1 Hz, 3 H, CH3–CH2),
0.94 [br. s, 9 H, SiC(CH3)3], 1.54 (m, 2 H, Me–CH2–), 2.10 [m, 4
H, ϵC–(CH2)2–Cϵ], 4.07 (m, 2 H, CH2OH), 4.17 (m, 1 H, CH–
OSi), 7.25 [m, 6 H, 2×3 H(Ph)], 7.45–7.63 [m, 4 H, 2×2 H(Ph)]
ppm. 13C NMR (100 MHz, CDCl3, 21 °C): δ = 9.7 (CH3), 19.2
(CH2), 19.7 (C), 27.4 (3 CH3), 32.0 (2 CH2), 51.6 (CH2OH), 65.6
(CH), 79.6 (C), 82.9 (C), 83.8 (C), 85.1 (C), 127.7 (2 CH), 128.0 (2
CH), 129.9 (CH), 130.1 (CH), 134.5(2 C), 136.2 (2 CH), 136.4 (2
CH) ppm. C26H32O2Si (404.62): calcd. C 77.18, H 7.97; found C
77.33, H 8.20.
4-{3-[2-(tert-Butyldimethylsilyl)-1-methylvinyl]-4-methylpent-3-
enyl}-3-[1-(tert-butyldiphenylsilyloxy)propyl]-1,2,5,7-tetrahydro-6-oxa-
cyclobuta[e]indene (35): nBuLi (2.2  solution in pentane, 0.13 mL,
0.29 mmol) was added dropwise to a cooled (–78 °C) solution of
34 (100 mg, 0.14 mmol) in THF (3 mL). After being stirred at this
temperature for 30 min, tosyl chloride (27 mg, 0.14 mmol) was
added. The solution was warmed to room temperature and stirred
until completion of the reaction (TLC). The solution was then di-
luted with Et2O, washed with a saturated solution of ammonium
chloride and brine, dried with magnesium sulfate, filtered, and con-
Silaketal Tether 33: Triethylamine (0.4 mL, 2.93 mmol), 4-DMAP centrated in vacuo. The crude oil was purified by flash chromatog-
(26 mg, 0.21 mmol), and chlorodiisopropylsilane (0.50 mL,
2.93 mmol) were added to a solution of alcohol 32 (1.02 g,
2.51 mmol) in CH2Cl2 (25 mL). The mixture was stirred at room
temperature until completion of the reaction (TLC). This solution
was then transferred under argon with filtration into another flask,
and NBS (447 mg, 2.51 mmol) was added slowly. The resulting
mixture was stirred until completion of the reaction (TLC). Finally,
the preceding solution was added to a solution of alcohol 27
(613 mg, 2.09 mmol) in the presence of triethylamine (0.35 mL,
raphy on silica gel (PE/EE = 95:5) to give 35 (78 mg, 80%) as a
yellow oil. IR (neat): ν = 3030, 2920, 1625, 1462, 1054, 822,
˜
739 cm–1. 1H NMR (400 MHz, CDCl3, 21 °C): δ = 0.14 [s, 6 H,
Si(CH3)2tBu], 0.94 [br. s, 12 H, SiC(CH3)3Me2, CH3–CH2], 1.08
[br. s, 11 H, SiC(CH3)3Ph2, Me–CH2], 1.30 [s, 3 H, =C(CH3)2], 1.62
[s, 3 H, =C(CH3)2], 1.74 [s, 3 H, =C(CH3)], 1.88–2.08 (m, 4 H,
–CH2–CH2–), 3.06 [m, 2 H, CH2(cyclobutene)], 3.41 [m, 3 H,
CH2(cyclobutene), CH–OSi], 5.13–4.93 (m, 5 H, CH2–O–CH2,
CH=), 7.69–7.02 [m, 10 H, 2 × 5 H(Ph)] ppm. C44H62O2Si2
2.51 mmol) and 4-DMAP (26 mg, 0.21 mmol) in CH2Cl2 (25 mL). (679.13): calcd. C 77.82, H 9.20; found C 77.93, H 9.59.
The mixture was stirred at room temperature until completion of
the reaction (TLC). After concentration in vacuo, the residue was
purified by flash chromatography on silica gel (PE/EE = 99:1) to
1-(4-{3-[2-(tert-Butyldimethylsilyl)-1-methylvinyl]-4-methylpent-3-
enyl}-1,2,5,7-tetrahydro-6-oxacyclobuta[e]inden-3-yl)propan-1-one
(36): Tetrabutylammonium fluoride (1  solution in THF, 1.06 mL,
give 33 (1.15 g, 68%) as a yellow oil. IR (neat): ν = 3000, 2940,
˜
1.06 mmol) was added dropwise to a solution of 35 (601 mg,
0.88 mmol) in THF (11 mL). The solution was stirred and refluxed
until TLC indicated completion of the reaction. The reaction mix-
ture was extracted with Et2O, washed with a saturated solution of
ammonium chloride and brine, dried with magnesium sulfate, fil-
tered, and concentrated in vacuo. The crude oil was used without
further purification in the next step. IBX (474 mg, 1.77 mmol) was
added to a solution of the preceding compound in DMSO (9 mL).
The mixture was stirred until completion of the reaction (TLC).
The solution was washed with water, filtered through a Celite pad,
diluted with Et2O, washed with brine, dried with magnesium sul-
fate, filtered, and concentrated in vacuo. The crude oil was purified
by flash chromatography to give compound 36 (320 mg, 82% over
2320, 1590, 1050, 690 cm–1. 1H NMR (400 MHz, CDCl3, 21 °C): δ
= 0.12 [s, 6 H, Si(CH3)2tBu], 0.92 [s, 9 H, SiC(CH3)3], 0.99 (t, J =
6.0 Hz, 3 H, CH3–CH2), 1.10 [br. s, 23 H (9 H + 2×7 H), SiC-
(CH3)3, SiiPr2], 1.66 [s, 3 H, =C(CH3)2], 1.70 [s, 3 H, =C(CH3)2],
1.82 [s, 3 H, =C(CH3)–], 2.37–2.22 [m, 10 H, 5×CH2, =C–(CH2)2–
Cϵ, ϵC–(CH2)2–Cϵ, CH2–Me], 4.32 (t, J = 1.2 Hz, 1 H, CH–
OSiPh2tBu), 4.44 (br. s, 4 H, ϵC–CH2–OSiiPr2O–CH2–Cϵ), 5.11
(s, 1 H, –CH=), 7.38–7.45 [m, 6 H, 2×3 H(Ph)], 7.79–7.71 [m, 4
H, 2 × 2 H(Ph)]. HRMS calcd. for C50H76O3Si3 [MNH4+]:
826.5446; found 826.5455.
[4-{3-[2-(tert-Butyldimethylsilyl)-1-methylvinyl]-4-methylpent-3-
enyl}-5-{1-(tert-butyldiphenylsilyloxy)propyl}-2-(hydroxymethyl)bi-
cyclo[4.2.0]octa-1,3,5-trien-3-yl]methanol (34): Dicarbonyl(cy-
clopentadienyl)cobalt() (0.05 equiv.) was added to a boiling solu-
tion of 33 (1.12 g, 1.39 mmol) in xylenes (75 mL) degassed by three
1
2 steps) as a yellow oil. H NMR (400 MHz, CDCl3, 21 °C): δ =
0.16 [s, 6 H, Si(CH3)2tBu] 0.95 [s, 9 H, SiC(CH3)3Me2], 1.20 (t, J
= 7.1 Hz, 3 H, CH3–CH2), 1.69 [s, 3 H, =C(CH3)2], 1.80 [s, 3 H,
Eur. J. Org. Chem. 2006, 1413–1421
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1419

G. Chouraqui, M. Petit, P. Phansavath, C. Aubert, M. Malacria
FULL PAPER
=C(CH3)2], 1.88 [s, 3 H, =C(CH3)], 2.30 (m, 2 H, CH2–CH2), 2.70 136.9 (C), 138.2 (C), 138.3 (C), 213.3 (C=O). HRMS calcd. for
(m, 2 H, CH2–CH2), 2.75 (q, J = 7.1 Hz, 2 H, Me–CH2–), 3.15 [m, C22H26O2 [MNa]: 345.1830; found 345.1855.
2 H, CH2(cyclobutene)], 3.41 [m, 2 H, CH2(cyclobutene)], 5.07 (br.
s, 4 H, CH2–O–CH2), 5.15 (s, 1 H, –CH=) ppm. 13C NMR
(100 MHz, CDCl3, 21 °C): δ = –4.1 (2 CH3), 8.2 (CH3), 17.4 (C),
Acknowledgments
19.5 (3 CH3), 21.8 (CH3), 22.0 (CH3), 26.7 (CH3), 28.0 [CH2–C(O)],
Financial support was provided by CNRS, MRES, and IUF
30.7 (CH2), 32.3 (CH2), 32.4 (CH2), 36.8 (CH2), 72.1 (CH2–O–),
(M. M. is a member of IUF). M. P. thanks Aventis-CNRS for a
72.8 (CH2–O–), 124.0, 124.7 (CH=C), 131.8 (C), 134.3 (C), 135.6
fellowship.
(C), 136.5 (C), 139.6 (C), 140.5 (C), 145.4 (C), 156.7 (C), 202.8
(C=O) ppm. HRMS calcd. for C28H42O2Si [MNa]: 461.2852; found
[1] M. C. Wani, H. L. Taylor, M. E. Wall, P. Coggon, A. T.
461.2850.
McPhail, J. Am. Chem. Soc. 1971, 93, 2325–2327.
[2] P. B. Schiff, J. Fant, S. B. Horwitz, Nature 1979, 277, 665–667.
1-(4-{3-[2-(tert-Butyldimethylsilyl)-1-methylvinyl]-4-methylpent-3-
[3] D. G. I. Kingston, Chem. Commun. 2001, 867–880 and perti-
[lxenyl}-1,2,5,7-tetrahydro-6-oxacyclobuta[e]inden-3-yl)propenone
nent references cited therein.
(37): NaHMDS (2  solution in THF, 0.5 mL, 0.95 mmol) was
[4] a) R. A. Holton, C. Somoza, H. B. Kim, F. Liang, R. J. Bi-
added dropwise to a cooled (–40 °C) solution of 36 (320 mg
0.73 mmol) in THF (8 mL). The solution was stirred at this tem-
perature for 1 h and then phenylselenyl chloride (209 mg,
1.09 mmol) was added. The mixture was warmed up to room tem-
perature and stirred until completion of the reaction (TLC). The
reaction mixture was extracted with Et2O, washed with water and
brine, dried with magnesium sulfate, filtered, and concentrated in
vacuo. The crude oil was used without further purification in the
next step. NaHCO3 (92 mg, 1.09 mmol) and NaIO4 (312 mg,
1.46 mmol) were added to a solution of the preceding compound
in MeOH (12 mL)/H2O (1.95 mL)/CH2Cl2 (1.5 mL). The mixture
was stirred until completion of the reaction (TLC). The solution
was diluted with Et2O, washed with water and brine, dried with
magnesium sulfate, filtered, and concentrated in vacuo. The crude
oil was purified by flash chromatography to give compound 37
ediger, P. D. Boatman, M. Shindo, C. C. Smith, S. Kim, H.
Nadizadeh, Y. Suzuki, C. Tao, P. Vu, S. Tang, P. Zhang, K. K.
Murthi, L. N. Gentile, J. H. Liu, J. Am. Chem. Soc. 1994, 116,
1597–1598, 1599–1600; b) K. C. Nicolaou, Z. Yang, J. J. Liu,
H. Ueno, P. G. Nantermet, R. K. Guy, C. F. Claiborne, J. Re-
naud, E. A. Couladouros, K. Paulvannan, E. J. Sorensen, Na-
ture 1994, 367, 630–634; c) J. J. Masters, J. T. Link, L. B. Sny-
der, W. B. Young, S. J. Danishefsky, Angew. Chem. Int. Ed.
Engl. 1995, 34, 1723–1726; d) P. A. Wender, N. F. Badham, S. P.
Conway, P. E. Floreancig, T. E. Glass, C. Gränicher, J. B.
Houze, J. Jänichen, D. Lee, D. G. Marquess, P. L. McGrane,
W. Meng, M. G. Natchus, H. Paulsen, D. B. Rawlins, J. Satkof-
sky, A. J. Shuker, J. C. Sutton, R. E. J. Taylor, K. Tomooka, J.
Am. Chem. Soc. 1997, 119, 2755–2756, 2757–2758; e) H. Kus-
ama, R. Hara, S. Kawahara, T. Nishimori, H. Kashima, N.
Nakamura, K. Morihira, I. Kuwajima, J. Am. Chem. Soc. 2000,
122, 3811–3820; f) T. Mukaiyama, I. Shiina, H. Iwadare, M.
Saitoh, T. Nishimura, N. Ohkawa, H. Sakoh, K. Nishimura,
Y. I. Tani, M. Hasegawa, K. Yamada, K. Saitoh, Chem. Eur.
J. 1999, 5, 121–160.
(202 mg, 63% over 2 steps) as a yellow oil. IR (ATR): ν = 2925,
˜
2853, 1668, 1607, 1246, 822, 759 cm–1 1H NMR (400 MHz,
.
CDCl3, 21 °C): δ = 0.00 [s, 6 H, Si(CH3)2tBu], 0.79 [s, 9 H,
SiC(CH3)3Me2], 1.51 [s, 3 H, =C(CH3)2], 1.59 [s, 3 H, =C(CH3)2],
1.70 [s, 3 H, =C(CH3)], 2.12 (m, 2 H, CH2–CH2), 2.40 (m, 2 H,
CH2–CH2), 3.00 [m, 2 H, CH2(cyclobutene)], 3.13 [m, 2 H, CH2(cy-
clobutene)], 4.92 (br. s, 4 H, CH2–O–CH2), 4.97 (s, 1 H, Si–CH=),
5.83 (dd, J = 10.6, 1.6 Hz, 1 H, H2C=CH), 6.08 (dd, J = 17.5,
1.6 Hz, 1 H, H2C=CH), 6.62 (dd, J = 17.4, 10.6 Hz, 1 H, H2C=CH)
ppm. 13C NMR (100 MHz, CDCl3, 21 °C): δ = –3.8 (2 CH3), 17.7
(C), 19.8 (CH3), 22.1 (CH3) 22.3 (CH3), 26.9 (3 CH3), 28.7 (CH2),
30.8 (CH2), 31.7 (CH2), 32.8 (CH2), 72.4 (CH2O–), 73.1 (CH2O–),
124.5 (C), 125.1 (CH), 130.9 (CH2), 132.1 (C), 135.2 (C), 136.0 (C),
136.5 (C), 137.5 (CH), 139.5 (C), 140.6 (C), 145.3 (C), 156.8 (C),
194.7 (C=O) ppm. HRMS calcd. for C28H40O2Si [MNa]: 459.2675;
found 461.2695.
[5] a) K. P. C. Vollhardt, Angew. Chem. Int. Ed. Engl. 1984, 23,
539–556; b) R. L. Hillard III, C. A. Parnell, K. P. C. Vollhardt,
Tetrahedron 1983, 39, 905–911; c) R. L. Funk, K. P. C.
Vollhardt, J. Am. Chem. Soc. 1980, 102, 5245–5253, 5253–5261;
d) S. H. Lecker, N. H. Nguyen, K. P. C. Vollhardt, J. Am.
Chem. Soc. 1986, 108, 856–858; e) P. Cruciani, R. Stammler,
C. Aubert, M. Malacria, J. Org. Chem. 1996, 61, 2699–2708.
[6] G. Chouraqui, M. Petit, C. Aubert, M. Malacria, Org. Lett.
2004, 6, 1519–1521.
[7] a) K. J. Shea, P. D. Davis, Angew. Chem. Int. Ed. Engl. 1983,
22, 419–420; b) K. J. Shea, J. W. Gilman, C. D. Haffner, T. K.
Dougherty, J. Am. Chem. Soc. 1986, 108, 4953–4956; c) K. J.
Shea, P. D. Davis, Angew. Chem. Suppl.1983, 564–570; d) R. W.
Jackson, R. G. Higby, J. W. Gilman, K. J. Shea, Tetrahedron
1992, 48, 7013–7032; e) R. W. Jackson, R. G. Higby, K. J. Shea,
Tetrahedron Lett. 1992, 33, 4695–4698; f) R. W. Jackson, K. J.
Shea, Tetrahedron Lett. 1994, 35, 1317–1320; g) R. V. Bonnert,
P. R. Jenkins, J. Chem. Soc., Chem. Commun. 1987, 1540–1541;
h) R. V. Bonnert, P. R. Jenkins, J. Chem. Soc., Perkin Trans. 1
1989, 413–418; i) J. S. Yadav, R. Ravishankar, Tetrahedron Lett.
1991, 32, 2629–2632; j) Y. K. Park, I. J. Kim, S. J. Danishefsky,
S. de Gala, Tetrahedron Lett. 1995, 36, 1019–1022; k) J. D.
Winkler, H. S. Kim, S. Kim, Tetrahedron Lett. 1995, 36, 687–
690; l) J. D. Winkler, J. M. Holland, D. A. Peters, J. Org. Chem.
1996, 61, 9074–9075; m) J. D. Winkler, H. S. Kim, S. Kim, K.
Ando, K. N. Houk, J. Org. Chem. 1997, 62, 2957–2962.
[8] For a preliminary account of this work, see: a) P. Phansavath,
C. Aubert, M. Malacria, Tetrahedron Lett. 1998, 39, 1561–
1564; b) M. Petit, G. Chouraqui, P. Phansavath, C. Aubert, M.
Malacria, Org. Lett. 2002, 4, 1027–1029.
Compound 38: Et2O·BF3 (48% in Et2O, 0.18 mL, 0.69 mmol) was
added to a cooled (–50 °C) solution of 37 (60 mg, 0.14 mmol) in
CHCl3 (10 mL). The mixture was stirred until completion of the
reaction (TLC). The solution was diluted with Et2O, washed with
NaHCO3 solution and brine, dried with magnesium sulfate, fil-
tered, and concentrated in vacuo. The crude oil was purified by
flash chromatography to give compound 38 (29 mg, 65%) as a
white solid. IR (ATR): ν = 744, 898, 1054, 1456, 1672, 2923 cm–1.
˜
1H NMR (200 MHz, CDCl3, 21 °C): δ = 0.70 [s, 3 H, (CH*3)C=C],
1.18 (s, 3 H, CH*3), 1.24 (s, 3 H, CH*3), 1.58 (m, 2 H, =C–CH2–
CH2), 1.99 (m, 2 H, =C–CH2–CH2), 2.24 (m, 2 H, CH2–CH2), 2.46
(m, 2 H, CH2–CH2–), 2.58 [d, J = 7.1 Hz, 1 H, –CH–C(O)], 3.01
[m, 4 H, CH2(cyclobutene)], 4.90 (s, 2 H, CH2–O), 4.97 (m, 2 H,
CH2–O) ppm. 13C NMR (50 MHz, CDCl3, 21 °C): δ = 19.3 (CH3),
23.8 (CH3), 23.8 (CH2), 26.5 (CH2), 26.8 (CH2), 27.3 (CH2), 27.4
(CH3), 28.7 (C), 28.9 (CH2), 29.5 (CH2), 61.8 (CH), 70.9 (CH2–O),
71.7 (CH2–O), 126.3 (C), 130.8 (C), 131.1 (C), 132.3 (C), 134.5 (C),
[9] CCDC-262002 (11) and -262001 (38) contain the supplemen-
tary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 1413–1421

From an Acyclic, Polyunsaturated Precursor to the Polycyclic Taxane Ring System
FULL PAPER
[10] a) R. Gleiter, D. Kratz, M. L. Ziegler, B. Nuber, Tetrahedron
Lett. 1990, 31, 6175–6178; b) C. A. Chang, J. J. A. King,
K. P. C. Vollhardt, J. Chem. Soc., Chem. Commun. 1981, 53–
55; c) C. A. Chang, C. G. Francisco, T. R. Gadek, J. A. King Jr,
E. D. Sternberg, K. P. C. Vollhardt, in Organic Synthesis Today
and Tomorrow, (Eds.: B. M. Trost, C. R. Hutchinson), Perga-
mon Press, Oxford, 1981, pp. 71–83; d) A. Bradley, W. B.
Motherwell, F. Ujjainwalla, Chem. Commun. 1999, 917–918; e)
J. H. Hardesty, J. B. Koerner, T. A. Albright, G. B. Lee, J. Am.
Chem. Soc. 1999, 121, 6055–6067.
[11] L. F. Veiros, G. Dazinger, K. Kirchner, M. J. Calhorda, R.
Schmid, Chem. Eur. J. 2004, 10, 5860–5870.
[12] a) R. M. Beesley, C. K. Ingold, J. F. Thorpe, J. Chem. Soc.
1915, 107, 1080–1106; b) M. E. Jung, Synlett 1999, 843–846.
[13] a) K. J. Shea, J. W. Gilman, Tetrahedron Lett. 1984, 25, 2451–
2454; b) B. R. Bear, S. M. Sparks, K. J. Shea, Angew. Chem.
Int. Ed. 2001, 40, 820–849.
[15] M. Petit, G. Chouraqui, C. Aubert, M. Malacria, Org. Lett.
2003, 5, 2037–2040.
[16] a) For a review on the oxidation of the carbon–silicon bond,
see: G. R. Jones, Y. Landais, Tetrahedron 1996, 52, 7500–7662;
b) I. Fleming, R. Henning, H. Plaut, J. Chem. Soc., Chem.
Commun. 1984, 29–31; c) I. Fleming, P. E. J. Sanderson, Tetra-
hedron Lett. 1987, 28, 4229–4232.
[17] a) K. Tamao, N. Ishida, M. Kumada, J. Org. Chem. 1983, 48,
2120–2122; b) K. Tamao, N. Ishida, T. Tanaka, M. Kumada,
Organometallics 1983, 2, 1694–1696; c) K. Tamao, N. Ishida,
J. Organomet. Chem. 1984, 269, C37–C39.
[18] K. C. Nicolaou, J.-J. Liu, Z. Yang, H. Ueno, E. J. Sorensen,
C. F. Claiborne, R. K. Guy, C.-K. Hwang, M. Nakada, P. G.
Nantermet, J. Am. Chem. Soc. 1995, 117, 634–644.
[19] J. A. Marshall, B. S. DeHoff, J. Org. Chem. 1986, 51, 863–872.
Received: October 4, 2005
Published Online: January 12, 2006
[14] a) S. Ohira, Synth. Commun. 1989, 19, 561; b) S. Müller, B.
Liepold, G. J. Roth, H. J. Bestmann, Synlett 1996, 521–522.
Eur. J. Org. Chem. 2006, 1413–1421
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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