Synthetic studies on and mechanistic insight into [W(CO) 5(L)]-catalyzed stereoselective construction of functionalized bicyclo[5.3.0]decane frameworks

Article abstract of DOI:10.1002/chem.201001003

Stereoselective preparation of a variety of synthetically useful functionalized bicyclo[5.3.0]decane derivatives was achieved by tandem cyclization of 3-siloxy-1,3,9-triene-7-yne derivatives based on the electrophilic activation of alkynes catalyzed by [W(CO)₅(L)], The reaction proceeded smoothly under photoirradiation, and various substrates were cyclized to give the corresponding bicyclic compounds with up to four chiral centers stereospecifically. Reactions of siloxydienes with a silyl substituent as an equivalent of a hydroxyl group also proceeded with wide generality to afford silyl-substituted bicyclo[5.3.0]decanes, which were highly useful as synthetic intermediates. Stereochemical studies concerning the silyl enol ether moiety suggested that two types of reaction path way for the formation of seven-membered rings were present. The reaction of (Z)-enol silyl ethers proceeded through Cope rearrangement of cis-divinylcyclopropane intermediates, and that of (E)-enol silyl ethers by 1,4-addition of the dienyl tungsten species at the position δ to the metal atom. In the reactions of siloxydiene derivatives with silyl substituents, all possible diastereomers could be synthesized stereoselectively by changing the geometry of the silyl enol ether and enyne moieties.

Full text of DOI:10.1002/chem.201001003

FULL PAPER
DOI: 10.1002/chem.201001003
Synthetic Studies on and Mechanistic Insight into [W(CO)5(L)]-Catalyzed
Stereoselective Construction of Functionalized Bicyclo
Frameworks
ACHTUNGTREN[NUNG 5.3.0]decane
Yuji Onizawa, Masahiro Hara, Takuya Hashimoto, Hiroyuki Kusama, and
Nobuharu Iwasawa*[a]
Abstract: Stereoselective preparation
of a variety of synthetically useful func-
tionalized bicycloACHTUNGTRENNUNG[5.3.0]decane deriva-
tives was achieved by tandem cycliza-
tion of 3-siloxy-1,3,9-triene-7-yne deriv-
atives based on the electrophilic activa-
with a silyl substituent as an equivalent
of a hydroxyl group also proceeded
with wide generality to afford silyl-sub-
way for the formation of seven-mem-
bered rings were present. The reaction
of (Z)-enol silyl ethers proceeded
through Cope rearrangement of cis-di-
vinylcyclopropane intermediates, and
that of (E)-enol silyl ethers by 1,4-addi-
tion of the dienyl tungsten species at
the position d to the metal atom. In the
reactions of siloxydiene derivatives
with silyl substituents, all possible dia-
stereomers could be synthesized stereo-
selectively by changing the geometry of
the silyl enol ether and enyne moieties.
stituted bicycloACTHNGUTER[NNUG 5.3.0]decanes, which
were highly useful as synthetic inter-
mediates. Stereochemical studies con-
cerning the silyl enol ether moiety sug-
gested that two types of reaction path-
tion
of
alkynes
catalyzed
by
[W(CO)5(L)]. The reaction proceeded
smoothly under photoirradiation, and
various substrates were cyclized to give
the corresponding bicyclic compounds
with up to four chiral centers stereo-
specifically. Reactions of siloxydienes
Keywords: cyclization
·
enynes
·
·
polycycles
tungsten
· synthetic methods
Introduction
cyclopropanes to give bicycloACTHNGUETRNNU[G 5.3.0]decanes, developed by
Wender et al.,[4] while Trost et al. reported the same type of
reaction using Ru catalysts under milder conditions.[5]
Wender et al. further applied this reaction to the total syn-
thesis of natural products such as aphanamol[4c] and dictam-
nol,[4d] but it still remains difficult to stereoselectively intro-
Several thousand sesquiterpenes have been isolated from
natural sources, and about 1000 of them have a bicyclo-
ACHTUNGTRENNUNG[5.3.0]decane framework, most of which have important bio-
logical activity.[1] Therefore, development of novel method-
ologies for efficient and stereoselective synthesis of bicyclo-
duce desired substituents into the bicyclo
at chosen positions.
We recently reported rhenium(I)-catalyzed tandem cycli-
zation of 3-siloxy-1,3-diene-7-ynes to give bicyclo-
[3.3.0]octane derivatives 2 based on the geminal carbo-func-
ACHTUNGTREN[NUGN 5.3.0]decane core
ACHTUNGTRENNUNG[5.3.0]decane derivatives is of great importance in synthetic
chemistry.
Many methods have already been reported for the synthe-
1
sis of the bicyclo
[5.3.0]decane framework,[2,3] but efficient
ACHTUNGTRENNUNG
methods from easily available starting materials are quite
limited. An example is Rh-catalyzed intramolecular [5+2]
cycloaddition reactions of alkynyl, alkenyl, and allenyl vinyl-
tionalization strategy (Scheme 1).[6] Thus, treatment of ace-
tylenic dienol silyl ethers 1 with rhenium carbonyl com-
plexes gave zwitterionic intermediates B by 5-endo nucleo-
philic cyclization of the enol silyl ether part to
electrophilically activated h2-alkyne complexes A. The re-
sulting alkenyl rhenium moiety performed an intramolecular
attack on the a,b-unsaturated silyloxonium moiety at the
position b to the metal atom to generate bicyclic unstabi-
lized carbene complexes C. Finally, the unstabilized carbene
complexes underwent 1,2-hydrogen migration to give
[a] Dr. Y. Onizawa, M. Hara, T. Hashimoto, Dr. H. Kusama,
Prof. Dr. N. Iwasawa
Department of Chemistry, Tokyo Institute of Technology
2-12-1-E1-2 O-okayama, Meguro-ku, Tokyo 152-8551 (Japan)
Fax : (+81)3-5734-2931
E-mail: niwasawa@chem.titech.ac.jp
bicycloACHTNUTRGNE[NUG 3.3.0]octane derivatives 2 with regeneration of the
reactive metal species. This reaction enables successive for-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201001003.
Chem. Eur. J. 2010, 16, 10785 – 10796
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10785

bicyclo
sors.
Based on the above considerations, we examined various
aspects of the reactions of 3-siloxy-1,3,9-triene-7-ynes for
ACHTUNGTREN[NUGN 5.3.0]decane derivatives from simple acyclic precur-
the stereoselective construction of bicycloACTHNURTGNEU[GN 5.3.0]decane
framework.[10] Herein, we report a full account of this work,
including the scope, synthetic application, and mechanistic
aspects of this reaction.
Results and Discussion
Scheme 1. ReI-catalyzed tandem cyclization of 3-siloxy-1,3-diene-7-ynes.
MS=molecular sieves, TIPS=iPr3Si.
Development of tungsten-catalyzed stereoselective construc-
tion of bicycloACTHUNTGRNEUNG[5.3.0]decane frameworks from 3-siloxy-1,3,9-
triene-7-yne derivatives: Preparation of 3-siloxy-1,3,9-triene-
7-yne (3a) is shown in Scheme 3. Addition reaction of alkyl
mation of two carbon–carbon bonds on the same alkyne
carbon atom and provides synthetically useful bicyclic com-
pounds from easily available acyclic substrates in a single
operation.
During this study, we thought of applying this tandem cyc-
lization protocol to vinylogous substrates (Scheme 2). We
expected that treatment of 3-siloxy-1,3,9-triene-7-ynes 3
Scheme 3. Preparation of 3a. TMS=SiMe3.
lithium 5 with cinnamaldehyde 4a gave allylic alcohol 6a.
Then, removal of the TMS protecting group at the alkyne
terminus followed by oxidation of the allylic alcohol moiety
provided enone 8a, which was treated with TIPSOTf in the
presence of NEt3 to afford siloxydiene 9a with a (Z)-enol
silyl ether moiety as a single geometrical isomer. Finally, the
enyne was successfully prepared by Sonogashira coupling of
terminal alkyne 9a with (E)-1-bromoprop-1-ene to give si-
loxydiene 3a as a mixture of geometrical isomers (Z/E=
95:5). A small amount of (E)-enol silyl ether was produced
by isomerization during purification by column chromatog-
raphy on silica gel.
Dimethyl malonate derivative 14a-Z was prepared as
shown in Scheme 4. Benzalacetone (10a) was converted to
a-bromo ketone 12a by bromination of silyl enol ether 11a.
Then, alkylation of dimethyl prop-2-ynylmalonate with a-
bromo ketone 12a gave alkenyl ketone 13a, which was con-
verted to enyne 14a-Z with a siloxydiene moiety as a single
geometrical isomer by the same procedure as that described
above. A variety of substrates could be prepared by employ-
ing a,b-unsaturated ketones as starting materials and alken-
yl halides as coupling partners of the final step.
Scheme 2. Possible reaction pathways, including seven-membered ring
formation in tandem cyclization of 3-siloxy-1,3,9-triene-7-yne derivatives.
with an appropriate electrophilic metal reagent would give
zwitterionic intermediates D with a dienyl metal moiety by
a similar 5-endo cyclization. Addition to the a,b-unsaturated
silyloxonium moiety at the position b to the metal atom
would give similar bicyclo
vinyl substituent, but we expected it might be possible to
obtain synthetically useful bicyclo[5.3.0]decane derivatives
ACHTUNGTRNE[NUNG 3.3.0]octane derivatives with a
AHCTUNGTRENNUNG
by addition of the dienyl metal moiety at the position d to
the metal atom.[7] Alternatively, the alkenyl metallic species
might add directly to the silyloxonium carbon atom at the
position b to the metal atom to afford divinylcyclopropane
intermediates E, which would undergo Cope rearrangement
to give the same bicyclo
N
According to the previously established protocol for the
[ReCl(CO)4(L)]-catalyzed geminal carbo-functionalization
of 3-siloxy-1,3-diene-7-ynes for the preparation of bicyclo-
tion of such reactions would open up a new avenue to effi-
cient and stereoselective preparation of highly useful
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Construction of Functionalized BicycloACTHNUTRGNE[NUG 5.3.0]decane Frameworks
FULL PAPER
Table 1. Screening of catalysts and optimization of reaction conditions.
Entry Conditions
Additive
t
Yield [%]
[h] 17a 18a
1
2
3
4
G
–
–
–
–
–
–
–
34
17 12
3
6
2
13 78
38 40
2
4
–
–
–
–
3
–
–
4
Scheme 4. Preparation of 14a-Z. LDA=lithium diisopropylamide, NBS=
N-bromosuccinimide.
54
0
66
5
6[a]
7
ACHTUNGTRENNUNG
[3.3.0]octane derivatives,[6a] we first examined the reaction
[b]
8
NEt3
83
of enyne 3a with [ReCl(CO)5] (5 mol%) under photoirra-
diation (super-high-pressure Hg lamp) in toluene in the
presence of 4 ꢁ molecular sieves (Scheme 5). The starting
[a] 10 mol% of [W(CO)5ACTHNUTRGNE(NUG thf)] was used. [b] 10 mol%.
did not proceed to an appreciable degree at room tempera-
ture, heating the reaction mixture to 608C promoted the re-
action in good yield (Table 1, entry 6). Thus, photoirradia-
tion is not indispensable for the present reaction. When the
reaction was carried out in toluene under photoirradiation,
as little as 5 mol% of [W(CO)6] was sufficient to complete
the reaction within 2 h at room temperature (Table 1,
entry 5). In addition, by carrying out the same reaction in
the presence of NEt3 (10 mol%), the formation of small
amounts of unidentified compounds was suppressed and the
yield of 17a was further improved to 83% (Table 1,
entry 8). In these cases, a small amount (3–4% yield) of
Scheme 5. Initial studies on tandem cyclization of 3a.
material was consumed within 7 h, but the desired bicyclo-
A
bicycloACTHNGUTER[NNUG 3.3.0]octane derivative 18a was obtained, the forma-
A
tion of which is thought to be due to the reaction of the cor-
responding (E)-enol silyl ether isomer produced by photo-
isomerization (see below).
ative 16a (39% yield). We next examined the same reaction
employing [W(CO)6] (10 mol%) under the same reaction
conditions and found that the desired bicyclo
derivative 15a was obtained as a major product (38% yield)
accompanied by the bicyclo[3.3.0]octane derivative 16a
(19% yield).
Next, enyne 14a-Z with a geminal diester moiety in the
tether (C5 position) was employed (Table 1). While the rhe-
nium catalyst showed low catalytic activity (Table 1,
entry 1), the tungsten-catalyzed reaction proceeded smooth-
[5.3.0]decane
Having established that [W(CO)5(L)] efficiently catalyzes
formation of seven-membered rings, we examined the reac-
tion with several kinds of substrates bearing a (Z)-enol silyl
ether moiety (Table 2). Vinylic, mono-substituted, and dis-
ubstituted enynes were cyclized to afford the corresponding
AHCTUNGTRENNUNG
bicycloACHTNUTRGNE[NUG 5.3.0]decane derivative in good yield as a single ste-
reoisomer (Table 2, entries 1–3 and 6). Furthermore, enynes
with an acetal (Table 2, entry 4) and an ester (Table 2,
entry 5) moiety and of alkyl-substituted dienes (Table 2, en-
tries 7 and 8) also underwent seven-membered ring forma-
tion smoothly in good yield with only a catalytic amount of
[W(CO)6]. In these reactions, only a trace of bicyclo-
ly to give the desired bicycloACHTUNGERTN[NUNG 5.3.0]decane derivative 17a in
66% yield (bicyclo[3.3.0]octane derivative 18a: 3%;
AHCTUNGTRENNUNG
Table 1, entry 5). The product 17a was obtained as a single
diastereomer and the structure was confirmed by X-ray
analysis.
AHCTUNGTRENNUNG
Since stereoselective construction of the bicyclo-
A
clohexenyl group at the alkyne terminus or as part of the
diene moiety with a catalytic amount of [W(CO)6] also pro-
ceeded to give synthetically useful tricyclic compounds with
examined several other typical electrophilic transition-metal
catalysts for this reaction (Table 1). Whereas PtII and cation-
ic AuI catalysts[11] showed low catalytic activity (Table 1, en-
tries 2 and 4), neutral AuI complex showed moderate activi-
ty in toluene at 708C (Table 1, entry 3). Among the catalysts
examined, [W(CO)5(L)] was found to be the most suitable
catalyst for this reaction. Although the reaction with pre-
a
6–7–5 ring system in good yields stereoselectively
(Scheme 6).
Comparison of the reactions of (E)-propenyl derivative
14a-Z and (Z)-propenyl derivative 14g clearly indicates ste-
reospecificity of seven-membered ring formation. The reac-
tion of (E)-propenyl derivative 14a-Z afforded the desired
formed [W(CO)5ACHTUNGTRENNUNG(thf)] (10 mol%) without photoirradiation
Chem. Eur. J. 2010, 16, 10785 – 10796
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10787

N. Iwasawa et al.
Table 2. Generality of bicycloACTHNUGRTENUNG[5.3.0]decane syntheses from enynes 14, 19.
Thus, cis-divinylcyclopropane intermediates G would be
generated by direct and rapid addition of the alkenyl tung-
sten moiety to the silyloxonium carbon in zwitterionic inter-
mediate F, which was produced by 5-endo nucleophilic cycli-
zation of the (Z)-enol silyl ether part to the electrophilically
activated h2-alkyne complexes. Then, this cis-divinylcyclo-
propane intermediates undergo Cope rearrangement via
Entry
R
(R1, R2, R3)
[W(CO)6]
[mol%]
t
Yield
[%]
conformation H[12] in
bicyclo[5.3.0]decane derivatives (Scheme 8).
a stereospecific manner to give
N
[h]
AHCTUNGTRENNUNG
1[a]
2
Ph
10
5
3
2
63 (17b)
79 (17c)
3
5
5
3
78 (17d)
71 (17e)
4[a]
3.5
5[a]
6
20
5
5
3
57 (17 f)
80 (17g)
7
8
iPr
5
2
83 (20a)
61 (20b)
10
1.5
[a] In the absence of NEt3. [b] 17e was obtained as a 6:1 mixture of dia-
stereomers.
Scheme 8. Plausible mechanism and stereochemical aspect of the tandem
cyclization.
The different catalytic activities of several electrophilic
metal reagents, in particular, the reason why [W(CO)5(L)]
showed higher activity, could be explained as follows based
on the assumption that formation of the divinylcyclopropane
intermediate is a crucial step in this reaction. Thus, in zwit-
terionic intermediate F, the nucleophilicity of the alkenyl
metal species would be dependent on the nature of the
metal. While highly electrophilic metals such as PtII or cat-
ionic AuI showed almost no nucleophilicity as alkenyl metal
compounds, [W(CO)5(L)] showed the highest nucleophilicity
because this alkenyl tungsten is zero valent and therefore
anionic. Thus, [W(CO)5(L)] was the most suitable catalyst
for this reaction (see Table 1).
Scheme 6. Synthesis of tricyclic compounds.
bicyclic compound 17a as a single diastereomer, the relative
stereochemistry of which was cis between the phenyl and
methyl groups. On the contrary, that of the product 17g de-
rived from (Z)-propenyl derivative 14g was trans
(Scheme 7).
This stereoselectivity can be explained by the following
cis-divinylcyclopropane rearrangement pathway, the propos-
al of which is based on the fact that the reaction proceeded
Synthesis of functionalized bicyclo
works: Among many natural products containing the
bicyclo[5.3.0]decane skeleton, those with oxygen functionali-
ACHTUNGTREN[NUNG 5.3.0]decane frame-
AHCTUNGTRENNUNG
ty at the 4-position are common.[13] With the purpose of ex-
panding the synthetic utility of the present reaction, we next
examined the possibility of introducing an alkoxy substitu-
ent at the diene terminus; however, elimination of the
oxygen group after tandem cyclization predominated. We
then examined the use of an arylsilyl group at the diene ter-
minus as an equivalent of oxygen functionality.[14] When the
reaction of 3-siloxy-1,3,9-triene-7-ynes 25, with a Me2PhSi
group at the 1-position, was carried out under the same re-
action conditions as for Ph-substituted dienes, the expected
much faster than the previous bicycloACHTUNTRGNEUNG[3.3.0]octane synthesis.
Scheme 7. Stereospecificity of seven-membered ring formation.
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Construction of Functionalized BicycloACTHNUTRGNE[NUG 5.3.0]decane Frameworks
FULL PAPER
silyl-substituted bicycloACTHUNRGTNE[NUG 5.3.0]decane derivatives 26 were ob-
tained in moderate to excellent yield with perfect stereose-
lectivity (Table 3, entries 1 and 2). Again, the reaction pro-
Table 3. Generality of Me2PhSi-substituted bicyclo
sis.
ACHTUNGERTN[NUNG 5.3.0]decane synthe-
Entry
R1
R2
R3
t [h]
Yield [%]
1
2
3
4
H
Me
H
H
H
H
H
Me
H
Me3Si
H
H
H
H
Me
H
25a-Z
25b-Z
25c-Z
25d-Z
25e
1
54 (26a-a)
93 (26b)
90 (26c-a)
94 (26d-a)
54 (26e)
0.5
0.5
0.5
2
5
6[a]
H
EtO2C
25 f
0.5
66 (26 f)
[a] The reaction was performed with 40 mol% of [W(CO)6] in the ab-
sence of NEt3.
Scheme 9. Schematic representation on the origin of the stereoselectivity
in the reactions of mono-ester substrates 27.
ceeded stereospecifically concerning the geometry of the
enyne moiety (Table 3, entries 3 and 4). Furthermore, highly
functionalized bicycloACTHNUTRGNE[NUG 5.3.0]decanes with a TMS or an
ethoxycarbonyl group could also be synthesized stereoselec-
favorable conformer I cyclizes to afford zwitterionic inter-
mediate K-trans, which further undergoes cyclopropane for-
mation and Cope rearrangement stereospecifically to give
tively by this reaction (Table 3, entries 5 and 6).[15]
Next, we examined the reaction of substrates 27 with a
monoester substituent at the C5 position[16] to determine the
effect of substitution at this position on the efficiency and
the stereoselectivity of the reaction (Table 4). When the re-
bicycloACHTNUTRGNE[UNG 5.3.0]decane derivative 28 in a highly stereocon-
trolled manner (Scheme 9). The reactions of E and Z pro-
penyl derivatives 27b and 27c also proceeded with high dia-
stereoselectivity (10:1 to 20:1)[17] to give bicyclo
ACHTNUTRGNE[NUG 5.3.0]decane
derivatives 28b and 28c with four stereogenic centers at the
3-, 4-, 7-, and 8-positions in good yield, respectively
(Table 4, entries 2 and 3).
Table 4. Stereoselective reaction of mono-ester substituted substrates 27.
Interestingly, the reaction of silyl-substituted dienes (3b,
3c) with no substituent on the tether also gave the desired
seven-membered ring products (15b, 15c) in good yield
(Table 5). These results are noteworthy because the reaction
of phenyl-substituted diene 3a gave a mixture of bicyclo-
Entry
R1
R2
R3
X [mol%]
t [h]
Yield [%]
AHCTUNGTRENNUNG
1
2
3
Me
H
H
H
Me
H
H
H
Me
27a
27b
27c
20
5
5
4
4
10
88 (28a)
87 (28b)[a]
72 (28c)[b]
AHCTUNGTRENNUNG
(see Scheme 5).
The Me2PhSi substituent was successfully converted to a
hydroxyl group by Fleming–Tamao oxidation (Scheme 10).
[a] 10:1 mixture of diastereomers. [b] 20:1 mixture of diastereomers.
action of isopropenyl derivative 27a was carried out with
Table 5. Reactions of substrates having no substituent at the 5-position.
[W(CO)6] (20 mol%) and NEt3 (10 mol%) under photoirra-
diation, silyl-substituted bicyclo
with three stereogenic centers at the 4-, 7-, and 8-positions
was obtained in 88% yield as single diastereomer
ACHTUNGTNER[NUNG 5.3.0]decane derivative 28a
a
(Table 4, entry 1). This result shows that almost complete
asymmetric induction by the C5 chirality on the substrate
was achieved. The asymmetric induction can be explained as
follows: in the p-alkyne complexes, conformer I is expected
to be more favorable than J due to the 1,3-allylic strain be-
tween C3 and C5 (Scheme 9, C5: H vs. CO2Me). The more
Entry
R1
R2
X [mol%]
t [h]
Yield [%]
1
2
Me
H
H
Me
3b
3c
0
10
2
10
67 (15b)
70 (15c)
Chem. Eur. J. 2010, 16, 10785 – 10796
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10789

N. Iwasawa et al.
Scheme 10. Conversion of Me2PhSi to a hydroxyl group. TBAF=tetra-n-
butylammonium fluoride.
Scheme 11. Comparison of the reactions of Z and E isomers.
Treatment of 28b with TBAF/AcOH in THF gave a ketone
by hydrolysis of the silyl enol ether moiety. Then, stereose-
lective reduction of the ketone by NaBH4 followed by re-
duction of the ester group with LiAlH4 gave diol 30. The re-
sulting g-hydroxy phenyl silane moiety could be converted
to cyclic alkoxy silane 31 under mild conditions[18] by nucleo-
philic addition of the alkoxide anion to the phenyl silane
was found to be stereospecific concerning the geometry of
the silyl enol ether moiety.
This stereospecificity is also apparent in the following re-
action of E and Z propenyl derivatives 25c-E and 25d-E
with an (E)-enol silyl ether moiety. In this case, the reaction
was stereospecific concerning both the geometry of the silyl
enol ether moiety and of the enyne moiety although the
yield of 26c-b obtained from (E)-propenyl derivative 25c-E
was moderate due to formation of another bicyclo-
À
moiety followed by protonation of the Si Ph bond. The re-
action of alkoxy silane 31 under standard Fleming–Tamao
oxidation conditions successfully afforded desired oxygen-
ACHTUNGTREN[NUNG 3.3.0]octane derivative, namely, 33. Thus, it is possible to
functionalized bicyclo
centers.
[5.3.0]decane 32 with five stereogenic
prepare all four possible diastereomers stereoselectively by
changing the geometry of the silyl enol ether and enyne
moieties (Scheme 12).
Mechanistic study and further synthetic utility: To expand
the generality of the reaction and to obtain information on
the mechanism of this reaction, we further examined the re-
action of the geometrical isomers concerning the silyl enol
ether moiety. All substrates employed so far were Z isomers
prepared from the corresponding ketones by using TIPSOTf
and NEt3. The corresponding E isomers were prepared by
photoisomerization of Z isomers with a super-high-pressure
Hg lamp (>300 nm). Treatment of Z isomers in toluene
under photoirradiation gave a mixture of E and Z isomers
(E/Z=4:1 to 6:1), which could be easily separated by
column chromatography on silica gel to give pure E iso-
mers.[19] To compare the reactivity of these two isomers, we
As already mentioned, Z derivative 25-Z could give
bicycloACHTNUTRGNE[UNG 5.3.0]decane derivative 26-a through Cope rear-
rangement of cis-divinylcyclopropane intermediate N. On
the other hand, in the case of E derivative 25-E, trans-di-
vinylcyclopropane intermediate P would be formed initially
in a similar manner but can not undergo Cope rearrange-
ment (Scheme 13). It is expected that this trans-divinylcyclo-
first examined the reaction with preformed [W(CO)5ACTHNUTRGNE(NUG thf)]
to avoid photoisomerization of the silyl enol ether moiety
during the reaction (Scheme 11, conditions A). Thus, treat-
ment of Z derivative 25a-Z with a stoichiometric amount of
preformed [W(CO)
afforded the same bicyclo
(thf)] at room temperature for 15 min
[5.3.0]decane derivative 26a-a as
AHCTUNGTRENNUNG
obtained under photoirradiation without problems. On the
other hand, the same reaction employing E derivative 25a-
E required a much longer reaction time (20 h), and silyl-sub-
stituted bicycloACHTUNGTRENNUNG[5.3.0]decane derivative 26a-b, a diastereo-
mer of the product 26a-a, was obtained in good yield as a
single diastereomer. Furthermore, we found that when the
photoirradiation wavelength was limited to 365 nm, no
scrambling of the products occurred under catalytic photoir-
radiation conditions (conditions B).[20] Thus, the reaction
Scheme 12. Stereoselective synthesis of the four possible diastereomers.
10790
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Chem. Eur. J. 2010, 16, 10785 – 10796

Construction of Functionalized BicycloACTHNUTRGNE[NUG 5.3.0]decane Frameworks
FULL PAPER
Although a similar tandem
cyclization pathway is possible
for the (Z)-enol silyl ether de-
rivative, we believe the reaction
of the
Z
isomer proceeds
through the divinylcyclopro-
pane intermediate based on the
following results:
The first is the reaction in the
presence of methanol. Treat-
ment of 25a-Z with preformed
[W(CO)
of MeOH afforded bicyclo-
[5.3.0]decane derivative 26a-a
5ACHTUNGRTEN(NUNG thf)] in the presence
AHCTUNGTRENNUNG
in 66% without formation of
monocyclic product. On the
other hand, when the reaction
of the corresponding E isomer
25a-E was carried out under
the same conditions, monocyclic
Scheme 13. Proposed mechanisms for tandem cyclization of 3-siloxy-1,3,9-triene-7-yne derivatives bearing (Z)-
and (E)-enol silyl ethers.
propane intermediate P would be in equilibrium with zwit-
terionic intermediate O by an aldol/retro-aldol-type process.
In zwitterionic intermediate O, the rotational barrier around
À
the Ca Cb bond is thought to be very high due to the steric
hindrance between the TIPSO group and the neighboring
alkenyl group or geminal diester moiety, and this intermedi-
ate O is thought to be difficult to be converted to the con-
À
formational isomer M by rotation about the Ca Cb bond.
Scheme 14. 1,2-Addition versus 1,4-addition of intermediate O.
Thus, intermediate O slowly undergoes addition of the
dienyl tungsten compound to the a,b-unsaturated silyloxoni-
um moiety at the d position to the metal atom preferentially
to give carbene complex intermediate Q with a bicyclo-
ketone 34, the protonated product of the zwitterionic inter-
mediate produced by the first cyclization, was obtained in
A
41% yield accompanied by bicycloACTHUGNETRNNU[G 5.3.0]decane derivative
gration to afford the product 26-b with regeneration of the
catalyst. As already mentioned, in the zwitterionic inter-
mediate O, the conformation of the alkenyl substituent and
the unsaturated silyloxonium moiety is strictly fixed due to
steric hindrance, and thus the second cyclization proceeded
from this conformation with perfect selectivity to afford
26a-b (Scheme 15). These results support that seven-mem-
bered ring formation from (Z)-enol silyl ether proceeds in a
concerted manner (Cope rearrangement of cis-divinylcyclo-
propane), and that from its E counterpart in a stepwise
manner (direct addition to unsaturated silyloxonium moiety
at the d position of the zwitterionic intermediate).
bicyclo
stereospecifically.
[5.3.0]decane derivatives 26-b stereoselectively and
The second is the difference in reaction rate between Z
and E isomers. The reaction of Z isomer 25a-Z with an
Furthermore, formation of a considerable amount of
bicycloACHTUNGTRENNUNG[3.3.0]octane derivative 33 from (E)-propenyl deriva-
tive 25c-E (R1 =Me, R2 =H) could be explained as follows:
in zwitterionic intermediate O, attack of the dienyl tungsten
moiety on the a,b-unsaturated silyloxonium moiety (1,4-ad-
dition) at the position d to the metal atom is unfavorable
due to steric repulsion between silyl substituent and (E)-
propenyl group. Thus, intermediate O undergoes addition to
the silyloxonium moiety directly (1,2-addition) at the posi-
tion d to the metal atom to give bicycloACTHNUTRGNEUNG[3.3.0]octane deriva-
tive 33 (Scheme 14). This repulsion would be reduced when
Z propenyl derivative 25d-E (R1 =H, R2 =Me) is employed,
and only bicycloACHTUNGTRENNUNG[5.3.0]decane derivative 26d-b is obtained
in this case.
Scheme 15. Reactions in the presence of methanol.
Chem. Eur. J. 2010, 16, 10785 – 10796
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10791

N. Iwasawa et al.
equimolar amount of preformed [W(CO)
G
in a similar manner to that of the E isomer, which in fact
complete within 15 min, whereas that of E derivative 25a-E
was not the case (Scheme 18).
was not complete even after 20 h of stirring (Scheme 16).
Scheme 18. Possible reaction pathways in the reactions of isopropenyl de-
rivatives 25b.
Scheme 16. Difference in reaction rate between 25a-Z and 25a-E.
This large difference in reaction rate between the two iso-
mers also supports that these two reactions proceeded in a
different manner.
Finally, another intriguing result was obtained when we
examined the reaction of the E isomer of phenyl-substituted
diene. In contrast to the reaction of Z derivative 14a-Z,
The third is the difference in reactivity between (Z)- and
(E)-enol silyl ethers observed with isopropenyl derivatives
25b. Whereas the reaction of (Z)-enol silyl ether proceeded
which gave the same bicyclo
before without problem with a stoichiometric amount of
preformed [W(CO)5A(thf)] (6 h), the same reaction employ-
ing the E derivative 14a-E required a longer reaction time
(21 h) and gave bicyclo[3.3.0]octane derivative 18a as a
major product (70%) accompanied by tricyclic compound
35 (20%) without formation of bicyclo[5.3.0]decane deriva-
ACHTUNGTRNE[NUNG 5.3.0]decane derivative 17a as
CTHUNGTRENNUNG
smoothly to give desired bicyclo
ACHTUNGTNER[NUNG 5.3.0]decane 26b in excel-
lent yield, that of (E)-enol silyl ether was complicated and
AHCTUNGTRENNUNG
proceeded
without
bicyclo
G
formation
(Scheme 17).
ACHTUNGTRENNUNG
tive 17a. Furthermore, by carrying out the reaction in dieth-
yl ether under photoirradiation in the presence of triethyla-
mine, formation of 35 was completely suppressed and 18a
was obtained in good yield catalytically (Scheme 19).
Scheme 17. Difference in reactivity between isopropenyl derivatives 25b-
Z and 25b-E.
Scheme 19. Reactions of phenyl-substituted dienes 14a.
Probably, zwitterionic intermediate R generated by cycli-
zation of (E)-enol silyl ether only undergoes the second cyc-
lization step (seven-membered ring formation) with difficul-
ty because the propenyl group cannot conjugate with the al-
kenyl tungsten moiety due to steric repulsion between the
methyl group at the g position to the metal atom and the
tungsten pentacarbonyl moiety. The same situation must
exist in zwitterionic intermediate S generated from the Z
isomer, and if the reaction of the Z isomer proceeds through
this intermediate, then the reaction should become sluggish
The differences in reactivity between Ph- and Si-substitut-
ed dienes could be explained as follows (Scheme 20): As a
Ph substituent is less bulky than a PhMe2Si group, attack of
the alkenyl tungsten group on the a,b-unsaturated silyloxo-
nium moiety at the b position to the metal atom (kinetically
favored five-membered ring formation) is possible in the re-
action of the Ph-substituted compound to give carbene com-
plex intermediate U with a bicycloACTHUNTGRNEUNG[3.3.0]octane skeleton,
10792
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Chem. Eur. J. 2010, 16, 10785 – 10796

Construction of Functionalized BicycloACTHNUTRGNE[NUG 5.3.0]decane Frameworks
FULL PAPER
4 ꢁ MS After the mixture was photoirradiated (250 W super-high-pres-
sure Hg lamp) for 2 h at room temperature, the suspension was filtered,
and then the solvent was removed under reduced pressure to give crude
product, which was purified by PTLC (10% ethyl acetate in hexane) to
give 53 mg of 17a (0.104 mmol, 83%).
Compound 17a: White crystal (m.p. 111–1128C); IR (KBr): n˜ = 2953,
2866, 1751, 1732, 1656, 1451, 1264 cmÀ1 1H NMR (400 MHz in CDCl3):
;
d=1.01 (d, J=7.2 Hz, 3H), 1.07–1.11 (m, 18H), 1.17–1.26 (m, 3H), 3.00–
3.08 (m, 1H), 3.42–3.47 (m, 1H), 3.70 (s, 3H), 3.81 (s, 3H), 4.86 (brs,
1H), 5.09 (dd, J=8.0, 2.0 Hz, 1H), 5.12 (dd, J=3.2, 2.4 Hz, 1H), 6.05 (d,
J=5.4 Hz, 1H), 6.20 (d, J=5.4 Hz, 1H), 7.19–7.28 (m, 3H), 7.34 (d, J=
7.2 Hz, 2H); 13C NMR (100 MHz in CDCl3): d=13.3, 18.2, 20.1, 36.5,
49.7, 51.7, 52.3, 52.7, 70.7, 111.3, 126.1, 127.1, 128.3, 130.3, 132.4, 136.9,
141.3, 143.9, 149.2, 169.1, 170.3; elemental analysis (%) calcd for
C30H42O5Si: C 70.55, H 8.29; found: C 70.36, H 8.54.
Scheme 20. Reaction course of E isomer of phenyl-substituted diene 14a-
E.
Compound 17b: White solid (m.p. 92–968C); IR (KBr): n˜ = 2945, 2867,
1743, 1654, 1432, 1198 cmÀ1 1H NMR (500 MHz in CDCl3): d=1.10 (d,
;
J=7.5 Hz, 18H), 1.16–1.25 (m, 3H), 2.41 (dt, J=14.8, 7.0 Hz, 1H), 2.74–
2.80 (m, 1H), 3.73 (s, 3H), 3.76–3.80 (m, 1H), 3.81 (s, 3H), 4.84–4.87 (m,
1H), 5.04 (dd, J=7.5, 2.0 Hz, 1H), 5.49–5.52 (m, 1H), 6.02 (d, J=5.5 Hz,
1H), 6.18 (d, J=5.5 Hz, 1H), 7.19 (t, J=7.5 Hz, 1H), 7.26–7.30 (m, 2H),
7.34 (d, J=7.5 Hz, 2H); 13C NMR (125 MHz in CDCl3): d=13.2, 18.1,
18.2, 34.0, 42.6, 51.3, 52.3, 52.7, 70.3, 109.8, 121.9, 126.0, 127.9, 128.4,
131.9, 137.2, 144.9, 145.6, 150.3, 169.3, 170.4; elemental analysis (%)
calcd for C29H40O5Si: C 70.12, H 8.12; found: C 69.85, H 8.41
from which 1,2-hydrogen migration of Ha or insertion into
À
the neighboring benzylic C Hb bond occurred to afford bi-
cyclic and tricyclic products 18a and 35. By carrying out the
reaction in the presence of Et3N, deprotonation of carbene
complex intermediate U is promoted to give 18a selective-
ly.[21] Based on the above-mentioned experimental results,
we believe that there are two distinct reaction pathways de-
pending on the geometry of the silyl enol ether moiety in
this unique cyclization reaction.
Compound 17c: White solid; IR (KBr): n˜ = 2951, 2866, 1739, 1656,
1462, 1195 cmÀ1 1H NMR (500 MHz in CDCl3): d=1.08–1.11 (m, 18H),
;
1.17–1.26 (m, 3H), 1.25 (d, J=2.0 Hz, 3H), 2.18 (dd, J=13.8, 6.2 Hz,
1H), 2.93 (brd, J=13.8 Hz, 1H), 3.74 (s, 3H), 3.77–3.80 (m, 1H), 3.80 (s,
3H), 4.84 (brs, 1H), 5.01 (dd, J=7.4, 1.7 Hz, 1H), 5.98 (d, J=5.7 Hz,
1H), 6.42 (d, J=5.7 Hz, 1H), 7.19 (t, J=7.3 Hz, 1H), 7.25–7.30 (m, 2H),
7.36 (d, J=7.3 Hz, 2H); 13C NMR (125 MHz in CDCl3): d=13.3, 18.1,
18.2, 22.5, 41.3, 42.4, 51.3, 52.3, 52.7, 70.2, 109.2, 125.9, 127.8, 128.5, 129.5,
130.4, 133.8, 138.2, 143.9, 151.2, 169.5, 170.7; elemental analysis (%) calcd
for C30H42O5Si: C 70.55, H 8.29; found: C 70.34, H 8.29
Conclusion
We have developed [W(CO)5(L)]-catalyzed stereoselective
construction of the bicyclo
simple enynes with a siloxydiene moiety. A variety of func-
tionalized bicyclo[5.3.0]decanes can be prepared in a stereo-
ACHTUNGTNER[NUNG 5.3.0]decane framework from
Compound 17d: White solid (m.p. 104–1058C); IR (KBr): n˜ = 2950,
2867, 1747, 1655, 1467, 1209 cmÀ1 1H NMR (500 MHz, 330 K in CDCl3)
;
ACHTUNGTRENNUNG
d=0.94 (s, 3H), 1.06–1.10 (m, 18H), 1.17–1.26 (m, 3H), 1.28 (s, 3H),
3.25–3.29 (m, 1H), 3.66 (s, 3H), 3.81 (s, 3H), 4.78–4.81 (m, 1H), 4.99 (dd,
J=7.7, 2.3 Hz, 1H), 5.40 (d, J=3.0 Hz, 1H), 6.03 (d, J=5.5 Hz, 1H), 6.20
(d, J=5.5 Hz, 1H), 7.15–7.25 (m, 3H), 7.35 (d, J=7.0 Hz, 2H); 13C NMR
(125 MHz, 330 K in CDCl3) d=13.2, 18.1, 18.2, 28.1, 29.8, 37.3, 51.9, 52.1,
52.5, 55.2, 70.7, 109.6, 126.1, 127.3, 130.2, 131.9, 133.0, 138.4, 142.8, 143.4,
148.0, 169.1, 170.4; elemental analysis (%) calcd for C31H44O5Si: C 70.95,
H 8.45; found: C 70.69, H 8.34
selective and stereospecific manner. Furthermore, all diaste-
reomers could be synthesized stereoselectively simply by
changing the geometry of the silyl enol ether moiety and the
enyne moiety by using silyl-substituted dienes as the sub-
strate. Through stereochemical analyses, it was shown that
two mechanisms of seven-membered ring formation exist:
1) Cope rearrangement of the cis-divinylcyclopropane inter-
mediate generated from (Z)-enol silyl ether, and 2) addition
to a,b-unsaturated silyloxonium moiety at the d position of
the dienyltungsten moiety in the zwitterionic intermediate
from (E)-enol silyl ether. This reaction would provide a
powerful method for the synthesis of natural products with
Compound 17e-cis: White crystal (m.p. 129–1318C); IR (KBr): n˜
=
2949, 2868, 1748, 1654, 1459, 1197 cmÀ1 1H NMR (400 MHz in CDCl3):
;
d=1.06–1.11 (m, 18H), 1.17–1.26 (m, 3H), 3.20–3.27 (m, 1H), 3.27 (s,
3H), 3.39 (s, 3H), 3.70 (s, 3H), 3.78–3.83 (m, 1H), 3.81 (s, 3H), 4.12 (d,
J=9.6 Hz, 1H), 4.88 (brs, 1H), 5.10 (dd, J=8.2, 2.2 Hz, 1H), 5.23 (dd,
J=5.8, 3.0 Hz, 1H), 6.08 (d, J=5.6 Hz, 1H), 6.24 (d, J=5.6 Hz, 1H),
7.18–7.29 (m, 3H), 7.39 (d, J=6.8 Hz, 2H); 13C NMR (100 MHz in
CDCl3): d=13.3, 18.2, 18.3, 43.46, 43.53, 50.9, 51.6, 52.3, 52.8, 53.1, 70.9,
103.6, 111.3, 121.8, 126.3, 127.4, 130.4, 132.8, 136.7, 140.9, 145.1, 149.4,
169.0, 170.1; elemental analysis (%) calcd for C32H46O7Si: C 67.34, H
8.12; found: C 67.47, H 8.41
a bicycloACHTUNGTRENNUNG[5.3.0]decane framework.
Experimental Section
Compound 17e-trans: White solid (m.p. 133–1358C); IR (KBr): n˜
=
2922, 2866, 1742, 1656, 1459, 1200 cmÀ1 1H NMR (500 MHz in CDCl3):
;
General: General procedures and spectral data of the cyclization precur-
sors (3, 14, 19, 21, 23, 25, 27), stereochemical assignment of the tandem
cyclization products (15, 17, 20, 22, 24, 26, 28), and experimental proce-
dures for Scheme 10 are described in the Supporting Information.
d=1.07–1.12 (m, 18H), 1.19–1.26 (m, 3H), 2.70 (td, J=8.5, 4.2 Hz, 1H),
3.29 (s, 3H), 3.43 (s, 3H), 3.74 (s, 3H), 3.80 (s, 3H), 3.83–3.87 (m, 1H),
4.71 (d, J=8.5 Hz, 1H), 4.74.79 (m, 1H), 4.90 (dd, J=7.7, 2.1 Hz, 1H),
5.52 (dd, J=8.5, 3.0 Hz, 1H), 6.02 (d, J=5.5 Hz, 1H), 6.20 (d, J=5.5 Hz,
1H), 7.17–7.21 (m, 1H), 7.25–7.29 (m, 2H), 7.40 (d, J=7.2 Hz, 2H);
13C NMR (125 MHz in CDCl3): d=13.1, 18.16, 18.20, 43.5, 47.0, 52.2,
52.4, 52.7, 53.1, 53.9, 70.8, 103.6, 107.4, 121.1, 126.0, 127.9, 129.0, 132.2,
138.2, 144.7, 145.5, 149.2, 169.2, 170.3; elemental analysis (%) calcd for
C32H46O7Si: C 67.34, H 8.12; found: C 67.11, H 8.20
Tandem cyclization of trienynes bearing a (Z)-enol silyl ether moiety: A
typical procedure for the cyclization of enynes is described for the reac-
tion of 14a-Z as a substrate: 14a-Z (64 mg, 0.125 mmol) and NEt3
(1.8 mL, 0.013 mmol, 10 mol%) in degassed toluene (1.3 mL) were added
to a mixture of [W(CO)6] (2.3 mg, 0.0065 mmol, 5 mol%) and activated
Chem. Eur. J. 2010, 16, 10785 – 10796
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10793

N. Iwasawa et al.
Compound 17 f: Colorless oil; IR (neat): n˜ = 2949, 2868, 1745, 1656,
1464, 1264, 1168 cmÀ1 1H NMR (400 MHz in C6D6) d=0.99 (t, J=
in CD2Cl2) d=À3.5, À3.2, 13.5, 18.27, 18.32, 26.6, 27.9, 51.4, 52.4, 52.8,
70.5, 108.2, 124.6, 128.0, 129.2, 132.2, 134.1, 137.4, 139.1, 145.9, 148.2,
169.7, 170.9; elemental analysis (%) calcd for C31H46O5Si2: C 67.10, H
8.36; found: C 66.99, H 8.48.
;
7.2 Hz, 3H), 1.13–1.31 (m, 21H), 3.42 (s, 3H), 3.41–3.46 (m, 1H), 3.53 (s,
3H), 3.98 (dq, J=11.0, 7.2 Hz, 1H), 4.07 (dq, J=11.0, 7.2 Hz, 1H), 4.44–
4.49 (m, 1H), 5.06 (dd, J=7.6, 1.9 Hz, 1H), 5.21–5.23 (m, 1H), 5.32 (dd,
J=8.0, 2.9 Hz, 1H), 5.92 (d, J=5.5 Hz, 1H), 6.12 (d, J=5.5 Hz, 1H),
7.02–7.08 (m, 1H), 7.15–7.22 (m, 2H), 7.50–7.52 (m, 2H); 13C NMR
(100 MHz in CDCl3): d=13.1, 14.1, 18.0, 18.1, 45.2, 50.2, 51.8, 52.4, 52.7,
61.0, 70.3, 106.7, 118.3, 126.4, 128.0, 128.8, 133.5, 137.5, 143.6, 147.8,
150.4, 169.2, 170.0, 171.7; elemental analysis (%) calcd for C32H44O7Si: C
67.57, H 7.80; found: C 67.69, H 8.04
Compound 26b: Pale yellow solid; IR (KBr): n˜ = 2949, 2866, 1740, 1432,
1249 cmÀ1 1H NMR (500 MHz in CDCl3): d=0.29 (s, 3H), 0.35 (s, 3H),
;
0.99–1.03 (m, 18H), 1.04–1.11 (m, 3H), 1.71 (s, 3H), 1.98 (dd, J=14.8,
7.1 Hz, 1H), 2.02–2.07 (m, 1H), 2.69 (brd, J=14.8 Hz, 1H), 3.67 (s, 3H),
3.75 (s, 3H), 4.76 (brd, J=7.5 Hz, 1H), 4.91 (brs, 1H), 5.97 (d, J=
5.7 Hz, 1H), 6.44 (d, J=5.7 Hz, 1H), 7.32–7.36 (m, 3H), 7.52–7.54 (m,
2H); 13C NMR (125 MHz in CDCl3): d=À4.2, À3.6, 13.1, 18.0, 18.1, 22.3,
25.6, 34.6, 50.6, 52.1, 52.7, 69.4, 106.3, 127.7, 128.9, 130.4, 130.6, 133.77,
133.80, 138.5, 138.6, 149.1, 169.5, 170.9. HRMS (EI+) calcd for
C32H48O5Si2: 568.3040; found: 568.3053
Compound 17g: White solid (m.p. 85–878C); IR (KBr): n˜ = 2951, 2867,
1
1745, 1655, 1451, 1204 cmÀ1; H NMR (500 MHz in CDCl3): d=1.07–1.10
(m, 18H), 1.17–1.26 (m, 3H), 1.21 (d, J=7.1 Hz, 3H), 2.54–2.61 (m, 1H),
3.50–3.54 (m, 1H), 3.73 (s, 3H), 3.80 (s, 3H), 4.80–4.83 (m, 1H), 4.88 (dd,
J=5.2, 2.1 Hz, 1H), 5.59 (dd, J=7.4, 2.9 Hz, 1H), 6.01 (d, J=5.4 Hz,
1H), 6.16 (d, J=5.4 Hz, 1H), 7.16–7.21 (m, 1H), 7.25–7.29 (m, 2H), 7.34
(d, J=7.1 Hz, 2H); 13C NMR (100 MHz in CDCl3): d=13.3, 18.08, 18.10,
19.1, 38.5, 49.5, 51.4, 52.3, 52.7, 70.3, 107.2, 125.9, 127.1, 127.9, 128.6,
131.5, 138.0, 144.0, 145.8, 149.7, 169.3, 170.5; elemental analysis (%)
calcd for C30H42O5Si: C 70.55, H 8.29; found: C 70.30, H 8.21
Compound 26c-a: Pale yellow solid; IR (KBr): n˜ = 2946, 2865, 1748,
1727, 1431, 1267, 1175 cmÀ1 1H NMR (500 MHz, 363 K in [D8]toluene)
;
d=0.38 (s, 3H), 0.39 (s, 3H), 0.95 (d, J=7.2 Hz, 3H), 1.13–1.16 (m,
18H), 1.20–1.27 (m, 3H), 2.04 (dt, J=8.2, 3.0 Hz, 1H), 2.95–2.98 (m,
1H), 3.49 (s, 3H), 3.52 (s, 3H), 4.89–4.91 (m, 1H), 5.01 (dd, J=8.2,
2.2 Hz, 1H), 5.41 (dd, J=6.3, 3.0 Hz, 1H), 5.94 (d, J=5.6 Hz, 1H), 5.97
(d, J=5.6 Hz, 1H), 7.16–7.21 (m, 3H), 7.49–7.51 (m, 2H); 13C NMR
(125 MHz, 363 K in [D8]toluene) d=À1.4, À1.0, 13.9, 18.6, 18.7, 21.6,
35.2, 35.7, 51.7, 52.0, 52.5, 71.1, 109.8, 128.2, 129.1, 131.7, 132.9, 134.4,
137.3, 140.5, 143.9, 148.7, 169.3, 170.7. HRMS (EI+) Calcd for
C32H48O5Si2: 568.3040; found: 568.3026
Compound 20a: Pale yellow oil; IR (neat): n˜ = 2952, 2869, 1746, 1651,
1464, 1434, 1261 cmÀ1 1H NMR (500 MHz, 330 K in CDCl3): d=0.94 (d,
;
J=6.7 Hz, 3H), 0.95 (d, J=6.7 Hz, 3H), 0.99 (d, J=7.0 Hz, 3H), 1.09–
1.13 (m, 18H), 1.20–1.28 (m, 3H), 1.63–1.70 (m, 1H), 2.17–2.22 (m, 1H),
2.58–2.65 (m, 1H), 3.63 (s, 3H), 3.76 (s, 3H), 4.60–4.63 (m, 1H), 4.66
(brs, 1H), 5.61 (dd, J=7.0, 2.8 Hz, 1H), 5.97 (d, J=5.5 Hz, 1H), 6.16 (d,
J=5.5 Hz, 1H); 13C NMR (125 MHz, 330 K in CDCl3): d=13.2, 16.1,
18.1, 21.5, 21.9, 30.4, 33.6, 46.9, 50.9, 52.1, 52.4, 69.0, 107.2, 130.2, 131.3,
137.9, 142.7, 150.5, 169.6, 170.5; elemental analysis (%) calcd for
C27H44O5Si: C 68.02, H 9.30; found: C 67.80, H 9.51
Compound 26d-a: Pale yellow oil; IR (neat): n˜ = 2952, 2868, 1745, 1434,
1251 cmÀ1 1H NMR (400 MHz in CD2Cl2) d=0.29 (s, 3H), 0.31 (s, 3H),
;
1.02–1.18 (m, 21H), 1.21(d, J=6.8 Hz, 3H), 1.76–1.84 (m, 1H), 2.38–2.48
(m, 1H), 3.65 (s, 3H), 3.74 (s, 3H), 4.76 (d, J=8.0 Hz 1H), 4.74–4.78 (m,
1H), 5.30–5.32 (m, 1H), 5.90–5.98 (m, 2H), 6.17 (d, J=5.2 Hz, 1H),
7.30–7.38 (m, 3H), 7.48–7.55 (m, 2H); 13C NMR (100 MHz in CD2Cl2):
d=À3.6, À3.1, 13.3, 18.06, 18.09, 19.7, 31.2, 34.7, 52.1, 52.2, 52.5, 71.0,
106.2, 127.6, 128.4, 128.7, 131.7, 133.7, 137.8, 139.1, 143.98, 144.04, 169.2,
170.5; HRMS (EI+) calcd for C32H48O5Si2: 568.3040; found: 568.3054
Compound 20b: Pale yellow oil; IR (neat): n˜ = 2951, 2868, 1742, 1643,
1464, 1262 cmÀ1 1H NMR (500 MHz in CDCl3): d=0.93 (d, J=6.7 Hz,
;
3H), 0.95 (d, J=6.7 Hz, 3H), 1.03–1.08 (m, 18H), 1.14–1.21 (m, 3H),
1.57–1.63 (m, 1H), 1.78 (s, 3H), 1.94 (dd, J=16.5, 9.6 Hz, 1H), 2.23–2.30
(m, 1H), 2.45 (d, J=16.5 Hz,1H), 3.65 (s, 3H), 3.74 (s, 3H), 4.67 (d, J=
7.4 Hz, 1H), 4.77 (brs, 1H), 5.99 (d, J=5.7 Hz, 1H), 6.50 (d, J=5.7 Hz,
1H); 13C NMR (125 MHz in CDCl3): d=13.1, 17.9, 18.1, 20.7, 21.3, 22.5,
32.4, 37.1, 42.0, 49.9, 52.1, 52.8, 68.4, 106.8, 129.2, 130.2, 133.8, 138.2,
151.2, 169.4, 170.8; elemental analysis (%) calcd for C27H44O5Si: C 68.02,
H 9.30; found: C 68.07, H 9.50.
Compound 26e: Pale yellow oil; IR (neat): n˜ = 2951, 2868, 1744, 1631,
1464, 1252 cmÀ1; two conformers of 26e interconvert very slowly on the
NMR timescale, and sharp signals in the 1H NMR for both conformers
1
are noted in a ratio of 60:40 at room temperature; H NMR (500 MHz in
CD2Cl2): major conformer: d=0.04 (s, 9H), 0.36 (s, 6H), 1.01–1.22 (m,
21H), 1.88–1.91 (m, 1H), 2.72–2.75 (m, 1H), 3.56 (s, 3H), 3.72 (s, 3H),
4.92–4.96 (m, 2H), 5.82 (d, J=5.5 Hz, 1H), 5.88–5.91 (m, 1H), 6.17 (d,
J=5.5 Hz, 1H), 7.30–7.36 (m, 3H), 7.50–7.53 (m, 2H); minor conformer:
d=À0.15 (s, 9H), 0.27 (s, 3H), 0.36 (s, 3H), 1.01–1.22 (m, 21H), 2.14
(ddd, J=8.2, 3.9, 1.8 Hz, 1H), 2.37 (d, J=8.2 Hz, 1H), 3.64 (s, 3H), 3.74
(s, 3H), 4.85–4.88 (m, 1H), 5.10 (dd, J=8.2, 2.0 Hz, 1H), 5.76 (dd, J=
8.2, 2.9 Hz, 1H), 5.99 (d, J=5.5 Hz, 1H), 6.22 (d, J=5.5 Hz, 1H), 7.30–
7.36 (m, 3H), 7.50–7.53 (m, 2H); 13C NMR (125 MHz in CD2Cl2): d=
À3.4, À2.9, À2.5, À1.8, À1.2, À0.2, 12.6, 12.9, 17.57, 17.62, 17.65, 17.69,
25.6, 29.5, 30.7, 31.4, 51.3, 51.4, 51.7, 51.8, 51.9, 52.1, 68.2, 70.3, 103.3,
115.6, 125.9, 127.3, 127.4, 128.3, 128.4, 128.6, 130.9, 132.3, 133.6, 133.8,
136.1, 138.6, 138.7, 138.9, 139.9, 145.2, 147.0, 153.8, 169.1, 169.5, 170.2,
170.4; elemental analysis (%) calcd for C34H54O5Si3: C 65.13, H 8.68;
found: C 64.92, H 8.85.
Compound 22: White crystal (m.p. 161–1648C); IR (KBr): n˜ = 2934,
2864, 1737, 1655, 1459, 1210 cmÀ1 1H NMR (500 MHz, 330 K in CDCl3)
;
d=1.09–1.13 (m, 18H), 1.20–1.40 (m, 5H), 1.44–1.54 (m, 2H), 1.56–1.65
(m, 2H), 1.71–1.80 (m, 1H), 2.01–2.08 (m, 1H), 2.68–2.73 (m, 1H), 3.69
(s, 3H), 3.79 (s, 3H), 3.79–3.84 (m, 1H), 4.95 (brs, 1H), 5.09 (dd, J=8.0,
2.1 Hz, 1H), 6.03 (d, J=5.8 Hz, 1H), 6.55 (d, J=5.8 Hz, 1H), 7.18–7.22
(m, 1H), 7.25–7.29 (m, 2H), 7.33–7.36 (m, 2H); 13C NMR (125 MHz,
330 K in CDCl3) d=13.2, 18.22, 18.23, 23.5, 24.6, 27.5, 30.1, 45.6, 47.0,
51.2, 52.1, 52.5, 69.5, 107.8, 126.1, 127.7, 129.4, 130.6, 133.7, 136.4, 136.6,
142.6, 151.2, 169.5, 170.7; elemental analysis (%) calcd for C33H46O5Si: C
71.96, H 8.42; found: C 72.19, H 8.66.
Compound 24: White solid; IR (KBr): n˜ = 2926, 2866, 1743, 1646, 1434,
1260 cmÀ1
;
1H NMR (500 MHz in CDCl3): d=1.10–1.13 (m, 18H), 1.20–
Compound 26 f: Pale yellow oil; IR (neat): n˜ = 2950, 2867, 1743, 1651,
1.32 (m, 4H), 1.39–1.80 (m, 7H), 1.83 (dd, J=13.8, 5.1 Hz, 1H), 1.85 (d,
J=2.2 Hz, 3H), 2.18–2.23 (m, 1H), 2.66 (brd, J=12.1 Hz, 1H), 2.79 (d,
J=13.5 Hz, 1H), 3.64 (s, 3H), 3.78 (s, 3H), 4.92 (brs, 1H), 5.83 (d, J=
5.7 Hz, 1H), 6.49 (d, J=5.7 Hz, 1H); 13C NMR (125 MHz, 350 K in
[D6]benzene): d=14.2, 18.5, 18.9, 22.7, 27.3, 28.5, 32.4, 33.6, 39.4, 43.5,
51.5, 52.1, 53.5, 72.2, 124.5, 129.9, 131.1, 133.7, 138.9, 142.2, 169.1, 171.2;
elemental analysis (%) calcd for C28H44O5Si: C 68.81, H 9.07; found: C
68.60, H 8.78.
1433, 1257 cmÀ1 1H NMR (400 MHz in CD2Cl2) d=0.33 (s, 3H), 0.36 (s,
;
3H), 0.92–1.15 (m, 21H), 1.20 (t, J=7.2 Hz, 3H), 2.45–2.51 (m, 1H), 3.08
(dd, J=9.0, 3.4 Hz, 1H), 3.65 (s, 3H), 3.73(s, 3H), 4.02 (dq, J=10.8,
AHCTUNGTRENNUNG
7.2 Hz, 1H), 4.12 (dq, J=10.8, 7.2 Hz, 1H), 4.73–4.79 (m, 2H), 5.76 (dd,
J=9.0, 3.0 Hz, 1H), 6.06 (d, J=5.6 Hz, 1H), 6.26 (d, J=5.6, 1H), 7.33–
7.39 (m, 3H), 7.52–7.57 (m, 2H); 13C NMR (100 MHz in CD2Cl2) d=
À3.4, À2.8, 13.5, 14.3, 18.4, 31.3, 43.4, 52.4, 52.7, 52.8, 61.1, 71.0, 106.0,
120.3, 128.1, 129.4, 134.0, 134.1, 137.4, 138.4, 145.8, 148.5, 169.3, 170.5,
173.2; HRMS (EI+) calcd for C32H48O5Si2: 626.3095; found: 626.3069
Compound 26a-a: Pale yellow oil; IR (neat): n˜ = 2949, 2867, 1744, 1645,
1464, 1433, 1248 cmÀ1
;
1H NMR (400 MHz [D6]benzene): d==0.34 (s,
Compound 28a: Pale yellow oil; IR (neat): n˜ = 2947, 2866, 1741, 1643,
3H), 0.35 (s, 3H), 1.16–1.28 (m, 21H), 1.86–1.92 (m, 1H), 2.00–2.08 (m,
1H), 2.46–2.54 (m, 1H), 3.45 (s, 6H), 4.99 (dd, J=7.8, 1.7 Hz, 1H), 5.05–
5.08 (m, 1H), 5.57–5.61 (m, 1H), 5.96 (d, J=5.6 Hz, 1H), 6.08 (d, J=
5.6 Hz, 1H), 7.20–7.27 (m, 3H), 7.48–7.51 (m, 2H); 13C NMR (100 MHz
1464, 1249, 1176 cmÀ1 1H NMR (400 MHz in CD2Cl2) d=0.29 (s, 3H),
;
0.31 (s, 3H), 0.99–1.19 (m, 21H), 1.68 (brs, 3H), 1.97 (dd, J=16.8,
11.0 Hz, 1H), 2.13–2.20 (m, 1H), 2.40 (d, J=16.8 Hz, 1H), 3.67 (s, 3H),
4.23–4.28 (m, 1H), 4.55–4.60 (m, 1H), 4.77 (dd, J=7.2, 2.0 Hz, 1H), 5.83
10794
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 10785 – 10796

Construction of Functionalized BicycloACTHNUTRGNE[NUG 5.3.0]decane Frameworks
FULL PAPER
(dd, J=5.6, 3.0 Hz, 1H), 6.35 (dd, J=5.6, 2.6 Hz, 1H), 7.33–7.36 (m,
3H), 7.51–7.55 (m, 2H); 13C NMR (125 MHz in CDCl3): d=À4.5, À4.4,
12.7, 17.9, 18.0, 21.9, 22.5, 34.1, 45.3, 51.9, 52.6, 103.3, 127.6, 128.6, 128.9,
129.6, 131.9, 133.9, 138.0, 138.5, 152.9, 174.5; elemental analysis (%)
calcd for C30H46O3Si2: C 70.53, H 9.08; found: C 70.32, H 9.34
which was purified by PTLC (7% ethyl acetate in hexane) to give 19 mg
of 26a-b (0.034 mmol, 76%).
Compound 26a-b: Pale yellow oil; IR (neat): n˜ = 2950, 2867, 1744, 1642,
1433, 1251, 1203 cmÀ1 1H NMR (400 MHz in CDCl3): d=0.27 (s, 3H),
;
0.29 (s, 3H), 0.96–1.13 (m, 21H), 1.96–2.02 (m, 1H), 2.15–2.21 (m, 1H),
2.25–2.33 (m, 1H), 3.61 (s, 3H), 3.75 (s, 3H), 4.68 (brs, 1H), 4.82–4.85
(m, 1H), 5.89 (d, J=5.6 Hz, 1H), 6.01–6.04 (m, 1H), 6.24 (d, J=5.6 Hz,
1H), 7.32–7.35 (m, 3H), 7.47–7.50 (m, 2H); 13C NMR (100 MHz in
CDCl3): d=À5.3, À4.4, 13.3, 18.0, 25.6, 27.4, 52.1, 52.6, 52.7, 70.5, 108.4,
126.7, 127.8, 129.1, 131.7, 134.0, 137.50, 137.55, 144.1, 148.1, 169.2, 170.4;
elemental analysis (%) calcd for C31H46O5Si2: C 67.10, H 8.36; found: C
66.86, H 8.46
Compound 28b: Compound 28b and the other diastereomer were ob-
tained as an inseparable mixture in a ratio of 10:1. Pale yellow oil; IR
(neat): n˜ = 2949, 2867, 1744, 1637, 1463, 1255 cmÀ1 1H NMR (500 MHz,
;
350 K in [D6]benzene): major isomer: d=0.320 (s, 3H), 0.322 (s, 3H),
0.98 (d, J=7.1 Hz, 3H), 1.09–1.11 (m, 18H), 1.13–1.20 (m, 3H), 2.32–2.36
(m, 1H), 2.67–2.74 (m, 1H), 3.43 (s, 3H), 4.41–4.43 (m, 1H), 4.88–4.90
(m, 1H), 4.94 (dd, J=8.0, 2.2 Hz, 1H), 5.37 (dd, J=5.6, 2.6 Hz, 1H),
5.86–5.88 (m, 2H), 7.17–7.23 (m, 3H), 7.48–7.51 (m, 2H); 13C NMR
(125 MHz, 350 K in [D8]dioxane): major isomer: d=À2.6, À2.5, 13.4,
18.19, 18.21, 19.8, 30.7, 34.1, 46.4, 51.5, 54.0, 103.7, 128.2, 129.3, 130.3,
131.4, 134.5, 135.7, 139.7, 144.8, 173.7 (1C missing); elemental analysis
(%) calcd for C30H46O3Si2: C 70.53, H 9.08; found: C 70.75, H 9.29
Compound 26c-b: White solid (m.p. 70–758C); IR (KBr): n˜
= 2952,
2865, 1740, 1725, 1638, 1429, 1246 cm<M->1 1H NMR (500 MHz in
;
CDCl3): d=0.36 (s, 6H), 1.01–1.10 (m, 21H), 1.14 (d, J=6.9 Hz, 3H),
1.78 (dd, J=8.3, 4.7 Hz, 1H), 2.58–2.62 (m, 1H), 3.59 (s, 3H), 3.74 (s,
3H), 4.39 (brs, 1H), 4.84 (dd, J=8.3, 2.3 Hz, 1H), 5.70 (dd, J=6.5,
2.9 Hz, 1H), 5.84 (d, J=5.5 Hz, 1H), 6.18 (d, J=5.5 Hz, 1H), 7.30–7.32
(m, 3H), 7.50–7.52 (m, 2H); 13C NMR (125 MHz in CDCl3): d=À3.1,
À2.1, 13.1, 18.0, 18.1, 23.9, 32.1, 32.9, 52.1, 52.4, 52.9, 68.6, 103.3, 127.6,
128.8, 129.9, 130.9, 133.8, 138.5, 139.3, 140.8, 149.1, 169.1, 170.1; elemental
analysis (%) calcd for C32H48O5Si2: C 67.56, H 8.50; found: C 67.30, H
8.72
Compound 28c: Compound 28c and the other diastereomer were ob-
tained as an inseparable mixture in a ratio of 20:1. Pale yellow oil; IR
(neat): n˜
= ;
2950, 2867, 1746, 1650, 1463, 1248, 1163 cmÀ1 1H NMR
(400 MHz in CDCl3): major isomer: d=0.23 (s, 3H), 0.24 (s, 3H), 1.01–
1.08 (m, 21H), 1.20 (d, J=7.1 Hz, 3H), 1.76–1.81 (m, 1H), 2.34–2.43 (m,
1H), 3.70 (s, 3H), 3.89–3.91 (m, 1H), 4.36–4.40 (m, 1H), 4.70 (dd, J=8.1,
1.7 Hz, 1H), 5.73–5.77 (m, 2H), 6.01 (dd, J=5.4, 2.7 Hz, 1H), 7.29–7.35
(m, 3H), 7.46–7.53 (m, 2H); 13C NMR (100 MHz in CDCl3): major
isomer: d=À3.5, À3.3, 13.0, 18.0, 19.6, 31.8, 33.4, 47.9, 51.8, 56.1, 103.4,
127.0, 127.6, 128.7, 130.8, 133.8, 136.5, 139.0, 145.0, 146.6, 174.0; elemen-
tal analysis (%) calcd for C30H46O3Si2: C 70.53, H 9.08; found: C 70.78, H
9.38.
Compound 33: Colorless oil; IR (neat): n˜ = 2952, 2867, 1737, 1615, 1431,
1254 cmÀ1 1H NMR (500 MHz in CDCl3): d=0.28 (s, 3H), 0.36 (s, 3H),
;
0.84 (d, J=7.2 Hz, 3H), 1.10–1.17 (m, 18H), 1.21–1.28 (m, 3H), 3.29 (s,
3H), 3.36–3.40 (m, 1H), 3.70 (s, 3H), 4.52 (t, J=2.8 Hz, 1H), 5.24–5.26
(m, 1H), 5.88 (d, J=18.6 Hz, 1H), 6.11 (d, J=5.5 Hz, 1H), 6.20 (d, J=
18.6 Hz, 1H), 6.37 (d, J=5.5 Hz, 1H), 7.29–7.32 (m, 3H), 7.50–7.53 (m,
2H); 13C NMR (125 MHz in CDCl3): d=À2.8, À2.0, 13.6, 14.2, 18.4, 18.6,
51.6, 52.9, 55.0, 61.3, 64.2, 93.0, 121.8, 126.6, 127.6, 128.7, 129.6, 133.7,
138.6, 139.4, 145.2, 149.5, 169.5, 170.5; elemental analysis (%) calcd for
C32H48O5Si2: C 67.56, H 8.50; found: C 67.34, H 8.73
Compound 15a: Compounds 15a, 16a-a, and 16a-b were obtained as an
inseparable mixture in a ratio of 67:8:25. Pale yellow oil; IR (neat): n˜ =
2944, 2867, 1646, 1463, 1333, 1202 cmÀ1; elemental analysis (%) calcd for
C26H38OSi: C 79.12, H 9.70; found: C 78.89, H 9.82. 15a: 1H NMR
(500 MHz, 350 K in CD3CN) d=0.93 (d, J=7.1 Hz, 3H), 1.11–1.13 (m,
18H), 1.22–1.30 (m, 3H), 2.75 (dd, J=18.5, 9.0 Hz, 1H), 2.86–2.92 (m,
1H), 3.03–3.09 (m, 1H), 3.75–3.79 (m, 1H), 4.10–4.14 (m, 1H), 5.09 (dd,
J=7.1, 2.2 Hz, 1H), 5.17–5.20 (m, 1H), 6.01–6.05 (m, 2H), 7.16–7.20 (m,
1H), 7.24–7.28 (m, 4H); 13C NMR (125 MHz, 350 K in CD3CN): d=14.2,
18.8, 18.9, 37.7, 38.1, 44.7, 49.0, 109.3, 126.5, 127.4, 129.0, 130.8, 134.7,
136.0, 144.0, 148.7, 154.2.
Compound 26d-b: Pale yellow oil; IR (neat): n˜ = 2950, 2867, 1747, 1649,
1432, 1250 cmÀ1 1H NMR (500 MHz in CDCl3): d=0.31 (s, 3H), 0.32 (s,
;
3H), 1.01–1.08 (m, 18H), 1.09 (d, J=7.2 Hz, 3H), 1.10–1.15 (m, 3H),
2.26–2.29 (m, 1H), 2.48–2.53 (m, 1H), 3.58 (s, 3H), 3.76 (s, 3H), 4.54–
4.57 (m, 1H), 4.74 (dd, J=3.5, 1.4 Hz, 1H), 5.84 (d, J=5.5 Hz, 1H), 6.15
(dd, J=8.7, 3.1 Hz, 1H), 6.23 (d, J=5.5 Hz, 1H), 7.32–7.40 (m, 3H),
7.49–7.52 (m, 2H); 13C NMR (125 MHz in CDCl3): d=À3.62, À3.55,
13.3, 15.8, 18.00, 18.04, 30.0, 31.5, 52.0, 52.5, 53.9, 70.2, 103.9, 127.7, 129.0,
131.1, 133.4, 133.9, 138.0, 138.9, 141.4, 147.8, 169.1, 170.3; elemental anal-
ysis (%) calcd for C32H48O5Si2: C 67.56, H 8.50; found: C 67.32, H 8.70
Compound 15b: Pale yellow oil; IR (neat): n˜ = 2945, 2866, 1634, 1463,
1427, 1255 cmÀ1 1H NMR (500 MHz, 330 K in CDCl3) d=0.34 (s, 3H),
;
0.37 (s, 3H), 1.00 (d, J=7.2 Hz, 3H), 1.09–1.12 (m, 18H), 1.13–1.21 (m,
3H), 2.19–2.21 (m, 1H), 2.66 (dd, J=17.8, 9.0 Hz, 1H), 2.73–2.80 (m,
1H), 2.90–2.96 (m, 1H), 4.06–4.12 (m, 1H), 4.88 (dd, J=8.1, 2.0 Hz, 1H),
5.41 (dd, J=5.4, 3.1 Hz, 1H), 5.92–5.95 (m, 1H), 5.96–5.98 (m, 1H),
7.33–7.35 (m, 3H), 7.53–7.56 (m, 2H); 13C NMR (125 MHz, 330 K in
CDCl3) d=À2.5, À2.3, 12.9, 18.1, 20.3, 31.4, 34.0, 36.4, 43.6, 104.4, 127.6,
127.7, 128.7, 133.87, 133.94, 134.1, 139.7, 146.0, 153.4; elemental analysis
(%) calcd for C28H44OSi2: C 74.27, H 9.79; found: C 74.04, H 10.03
Acknowledgements
This research was partly supported by a Grant-in-Aid for Scientific Re-
search from the Ministry of Education, Culture, Sports, Science, and
Technology of Japan. Y.O. has been granted a Research Fellowship of
the Japan Society for the Promotion of Science for Young Scientists. We
would like to thank Professor Hidehiro Uekusa and Sachiyo Kubo for
performing X-ray analysis.
Compound 15c: Pale yellow oil; IR (neat): n˜ = 2945, 2866, 1662, 1464,
1248, 1171 cmÀ1 1H NMR (400 MHz in CDCl3): d=0.22 (s, 3H), 0.24, (s,
;
3H), 1.04–1.13 (m, 21H), 1.16 (d, J=7.1 Hz, 3H), 1.71–1.76 (m, 1H),
2.33–2.42 (m, 1H), 2.58–2.66 (m, 1H), 2.74–2.82 (m, 1H), 3.72–3.78 (m,
1H), 4.73 (dd, J=8.2, 1.7 Hz, 1H), 5.70 (dd, J=8.2, 3.1 Hz, 1H), 5.88–
5.93 (m, 1H), 5.96–6.00 (m, 1H), 7.30–7.33 (m, 3H), 7.47–7.52 (m, 2H);
13C NMR (100 MHz in CDCl3): d=À3.6, À3.2, 12.8, 18.2, 19.7, 31.7, 33.8,
39.1, 46.1, 103.3, 124.5, 127.5, 128.6, 133.7, 133.8, 135.1, 139.4, 146.5,
147.6; elemental analysis (%) calcd for C28H44OSi2: C 74.27, H 9.79;
found: C 74.03, H 9.80
[1] For recent reviews on natural products containing
a bicyclo-
AHCTUNGTRENNUNG
25, 1180; b) B. M. Fraga, Nat. Prod. Rep. 2006, 23, 943; c) B. M.
Fraga, Nat. Prod. Rep. 2005, 22, 465.
Tandem cyclization of trienynes bearing (E)-enol silyl ether moiety: A
typical procedure for the cyclization of enynes is described for 25a-E as
substrate: 25a-E (25 mg, 0.045 mmol) in degassed toluene (0.7 mL) was
added to a mixture of [W(CO)6] (1.6 mg, 0.0045 mmol, 10 mol%) and ac-
tivated 4 ꢁ molecular sieves. After the mixture was photoirradiated
(250 W super-high-pressure Hg lamp through 365 nm bandpass filter) for
10 h at room temperature, the suspension was filtered and then the sol-
vent was removed under reduced pressure to give the crude product,
[2] For reviews on the construction of natural products containing a
seven-membered ring, see: a) M. A. Battiste, P. M. Pelphrey, D. L.
Wright, Chem. Eur. J. 2006, 12, 3438; b) R. C. Hartley, S. T. Cald-
well, J. Chem. Soc. Perkin Trans. 1 2000, 477; c) M. Lautens, W.
Klute, W. Tam, Chem. Rev. 1996, 96, 49.
[3] For recent synthetic approaches toward the bicycloACTHNUTRGNE[UNG 5.3.0]decane
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[11] In the case of the cationic gold complex, the protonated product of
the first cyclization intermediate was obtained in 75% yield.
[12] This transition structure was supported by calculations: I. ꢄzkan, M.
Zora, J. Org. Chem. 2003, 68, 9635, and references therein. See also
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[4] a) P. A. Wender, H. Takahashi, B. Witulski, J. Am. Chem. Soc. 1995,
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[13] Guaianolides, which have a bicycloACTHNUGTRNEUNG[5.3.0]decane skeleton, are one of
the largest groups of naturally occurring sesquiterpene lactones.[1]
À
[14] For reviews on Fleming–Tamao oxidation of the C Si bond, see:
a) I. Fleming, R. Henning, D. C. Parker, H. E. Plaut, P. E. J. Sander-
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arrangement easily.[8e] For examples of the Cope rearrangement of
divinyl cyclopropanes with silyl substituents, see: a) K. Takeda, A.
Nakajima, M. Takeda, Y. Okamoto, T. Sato, E. Yoshii, T. Koizumi,
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[16] Mono-esters 27 were prepared from diesters 25 by Krapcho decar-
boxylation (see Supporting Information).
[8] The Cope rearrangement of divinylcyclopropane was first reported
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[17] The stereochemistry of minor isomers could not be determined, but
it is highly likely that diastereomers concerning C5 chirality were
produced, as the reaction should proceed stereospecifically with
regard to the geometry of the enyne moiety.
[18] With specific substrates such as g-hydroxy silanes, the phenyl group
on silicon can be removed through silicates under basic conditions,
see a) T. Harada, S. Imanaka, Y. Ohyama, Y. Matsuda, A. Oku, Tet-
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[19] See Supporting Information for details.
[20] The reaction of the E derivative was carried out under photoirradia-
tion at a longer wavelength (365 nm) to avoid photoisomerization of
the silyl enol ether moiety. [W(CO)5(L)] is known to be generated
by photoirradiation of [W(CO)6] around 350 nm: S. A. Trushin, W.
Fub, W. E. Schmid, Chem. Phys. 2000, 259, 313.
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Received: April 19, 2010
Published online: August 2, 2010
10796
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Chem. Eur. J. 2010, 16, 10785 – 10796