Domino Mukaiyama-Michael reactions in the synthesis of polycyclic systems

Article abstract of DOI:10.1016/j.tet.2005.11.059

Good results were obtained in the Mukaiyama-Michael reaction of the silyl enol ether of cyclohexanone with 2-methyl-2-cyclopentenone and carvone, with transfer of the silyl group to the receiving enone and with TrSbCl₆ as catalyst. A second Mukaiyama-Michael reaction of this new silyl enol ether with methyl vinyl ketone and cyclization of the resulting adduct leads to tricyclic compounds in one-pot domino sequences. The scope and limitations of this domino reaction have been investigated.

Full text of DOI:10.1016/j.tet.2005.11.059

Tetrahedron 62 (2006) 1717–1725
Domino Mukaiyama–Michael reactions in the synthesis
of polycyclic systems
a
Florence C. E. Saraber, Svetlana Dratch, Geke Bosselaar, Ben J. M. Jansen
b
a
a
`
and Aede de Groota,
*
aLaboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, 6703 HB Wageningen, The Netherlands
bInstitute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Kuprevich str. 5/2, 220141, Minsk, Belarus
Received 20 May 2005; accepted 24 November 2005
Available online 20 December 2005
Abstract—Good results were obtained in the Mukaiyama–Michael reaction of the silyl enol ether of cyclohexanone with 2-methyl-2-
cyclopentenone and carvone, with transfer of the silyl group to the receiving enone and with TrSbCl6 as catalyst. A second Mukaiyama–
Michael reaction of this new silyl enol ether with methyl vinyl ketone and cyclization of the resulting adduct leads to tricyclic compounds in
one-pot domino sequences. The scope and limitations of this domino reaction have been investigated.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
possible starting with cyclic silyl enol ethers and cyclic
enones using two consecutive Mukaiyama–Michael
reactions followed by a ring-closing 1,6-aldol cyclization.
To probe the feasibility of such an approach, first two
reaction sequences starting with a cyclohexanone-derived
silyl enol ether 1 in additions with carvone 2, as a chiral
receiving enone, and with 2-methyl-2-cyclopentenone 3
have been investigated. In both cases the intermediate
adducts 4 have been reacted further with methyl vinyl
ketone (MVK) 5 as the second enone (see Scheme 1). This
should lead to adducts 6, which can undergo an
intramolecular 1,6-aldol condensation with the carbonyl
group of the cyclohexanone moiety, which originates from
the first silyl enol ether, to give the tricyclic endproducts 7.
The usefulness of sequential Michael additions in domino
reactions has been demonstrated several times1–16 and also
the Lewis acid-promoted Michael addition of silyl enol
ethers to enones, originally devised by Mukaiyama et al. is a
valuable tool in this field.17,18 Recently it has been shown
that an enantiomerically pure trans-hydrindane derivative
can be synthesised using a double Mukaiyama–Michael
reaction,4,6 and also a highly substituted cyclohexene has
been obtained in a domino reaction using a double
Mukaiyama–Michael addition, followed by an intra-
molecular 1,6-aldol condensation.1 It is evident that the
intermediate enolate has to be preserved for such a
sequence, so that the second Mukaiyama–Michael addition
can take place. Transfer of the silyl group from the starting
silyl enol ether to the receiving enone is in this respect a
very convenient side reaction, which has been noticed early
on to occur in some Mukaiyama–Michael additions.10 This
newly formed silyl enol ether can be isolated but can also be
reacted further in one-pot in a second Mukaiyama–Michael
addition, potentially with a different enone, or with other
reagents.1–11
Variations in the starting silyl enol ether would open
possibilities for further transformations of the tricyclic
systems, which have potential as intermediates in the
synthesis of polycyclic natural products. With carvone as
the first receiving enone, stereochemical guiding of the
configuration around the rings will be possible. The use of
2-methyl-2-cyclopentenone as the first receiving enone
should give a tricyclic compound with possible use for the
synthesis of steroid skeletons.
Based on these premises, the enantioselective construction
of highly substituted polycyclic compounds should be
2. Results and discussion
Keywords: Mukaiyama–Michael addition; Domino reactions; Tricyclic
systems; Carvone.
To investigate the feasibility of the approach and to find the
optimal conditions and stoichiometry for the reaction
sequence mentioned in Scheme 1, several catalysts,
*
Corresponding author. Tel.: C31 317482370; fax: C31 317484914;
e-mail: aede.degroot@wur.nl
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.11.059

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F. C. E. Saraber et al. / Tetrahedron 62 (2006) 1717–1725
1718
O
2
O
5
OSiR3
O
O
O
OSiR3
O
OSiR3
O
H
H
H
H
7
HO
H
H
6
O
1
4
3
Scheme 1.
different addition orders, reaction temperatures and reagent
ratios were researched. Many Lewis acids have been used as
catalysts in Mukaiyama reactions but relatively few have
been reported to give also transfer of the silyl group.19–27 In
our reaction, SmI2, TMSNTf2, BuSn(OTf)2, TrClO4 and
TrSbCl6 were investigated and the trityl salts were found to
give the best results, as was expected from literature. Since
TrSbCl6 is commercially available and can be stored at
C4 8C without decomposition or loss of activity, this
catalyst was chosen for all the following reactions. While
the addition order of reagents and catalyst did not influence
in any way the reaction yield or product ratios, the reaction
temperature had to be kept low (K78 8C) to avoid
hydrolysis of the starting silyl enol ether. At temperatures
above K60 8C an increase in desilylated starting material
could clearly be detected on TLC. In the reaction of silyl
enol ether 1 with carvone it was found that the use of 1, 1.25
or 1.5 equiv of 1 led to yields of 72, 82 and 89%,
respectively, and therefore an excess of 1.5 equiv of silyl
enol ether was applied in all reactions performed thereafter.
From both reaction sequences only two isomers of the final
tricyclic products were isolated, and no other isomers were
detected (see Scheme 2). The intermediate second adducts
9a, 9b, 12a and 12b have never been isolated because they
reacted further to the tricyclic products under the applied
conditions. The relative stereochemistry of compounds 10a,
13a and 13b was determined by X-ray crystallography28 and
OSiR3
OSiR3
O
2
OSiR3
O
O
TrS bCl6
H
H
+
+
CH2Cl2
,–78 °C
H
H
1
8b
8a
minor
major
O
4
OSiR3
OSiR3
O
O
O
O
O
O
O
O
H
H
+
H
+
H
H
H
H
HO
HO
H
10a
major
9a
major
9b
minor
10b
minor
OSiR3
OSiR3
OSiR3
O
3
O
O
H
H
TrS bCl6
+
+
H
H
CH2Cl2
,
–78 °C
1
11a
11b
major
O
4
minor
O
4
OSiR3
OSiR3
O
O
O
O
O
O
O
O
H
H
H
H
+
H
H
H
HO
H
HO
12a
12b
13b
13a
Scheme 2.

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F. C. E. Saraber et al. / Tetrahedron 62 (2006) 1717–1725
1719
for compound 10b this was done using COSY and NOESY
experiments (for the most important NOE interactions see
Fig. 1), as this compound could not be obtained in a
crystalline form. The position of the hydroxyl group was
determined using IR-concentration experiments, showing
an intramolecular H-bridge, between the hydroxy and the
acetyl group.
ether gave the best result in the reaction with carvone as the
receiving enone (see Table 1), but the consecutive reaction
with MVK gave a slightly better yield with the TMS enol
ether. The reaction sequence with the TES enol ether gave
only a moderate yield for the first addition step with
carvone, and the domino reaction sequence gave a very low
yield. This lower yield in the addition of the TES ether may
be caused by a small increase in steric hindrance. The TES
ether has less possibilities to minimize steric effects by
rotation around the Si–O bond in comparison with the
TBDMS ether. With 2-methyl-2-cyclopentenone as the
receiving enone, no differences in yields between the TMS
and TBDMS groups were found in the first step, but for the
second Mukaiyama–Michael addition the best results were
again obtained with the TMS enol ether. Apparently steric
hindrance from the bulky TBDMS group has a greater
influence in the second addition step, substantially lowering
the yield in the five-membered ring compounds.
O
H
O
H
H
O
H
H
With respect to the stereoselectivity in the first step, the
three silyl enol ethers all gave an addition to the enone of
carvone opposite to the isopropenyl group, with comparable
ratios of isomers in the cyclohexanone part of the molecules.
In the consecutive MVK addition step, the reaction with the
TBDMS enol ether led to the formation of only one isomer,
thus giving a much higher stereoselectivity than the reaction
with the TMS enol ether. The absence of steric hindrance in
the starting enol ether gives the bulky TBDMS group the
possibility to steer out of range, in this way not interfering
with the approach to the enone for addition. When
substituents are present in the neighbourhood of the enol
ether moiety, the TBDMS group can not freely rotate and
consequently its bulkiness interferes with the approach to
the second enone (MVK) and influences the stereoselectivity
of the reaction to a greater extent, which confirms the
findings of Heathcock et al.29,30
10b
Figure 1.
The formation of the obtained products in the reaction with
carvone can be explained by addition of the cyclohexanone
silyl enol ether 1 from the less hindered side of the enone,
opposite to the isopropenyl group. Epimeric mixtures of
adducts are formed that differ in configuration only at C2 of
the cyclohexanone moiety. The second addition of MVK 4
to the newly formed silyl enol ether takes place only with
the major epimer. Steric factors probably are the reason for
this difference but these factors are difficult to specify
further. During this research it became clear that even small
differences in steric hindrance can have significant influence
on the yields and products of these Mukaiyama additions
(see below). The second addition with MVK is not
completely stereoselective, and occurs predominantly
trans with respect to the cyclohexanone moiety. With
2-methyl-2-cyclopentenone as the receiving enone, diaster-
eomeric racemates are obtained with trans-positioned
substituents in the cyclopentanone part of the molecules.
In this case, both products from the first addition (11) react
further with MVK to afford tricyclic products.
In the TMS and in the TBDMS enol ether of the
intermediate, the 2S isomer 8a reacts much easier than the
2R isomer 8b, as no final or intermediate product derived
from the latter has been isolated.
In the Mukaiyama–Michael additions with 2-methyl-2-
cyclopentenone, the bulkiness of the TBDMS enol ether
already influences the stereoselectivity of the first
Mukaiyama reaction, improving the isomer ratio to 4:1 in
comparison with the almost 1:1 ratio for the TMS enol ether.
However, in the second Mukaiyama–Michael addition with
MVK, the higher stereoselectivity of the TBDMS enol ether
shown in the first addition has disappeared and a much
better selectivity was obtained with the TMS enol ether. A
conceivable explanation could be that the TBDMS isomer
11a reacts slower with MVK than isomer 11b, possibly due
Three silyl enol ethers with different steric effects (TMS,
TBDMS and TES) were tested under the conditions
mentioned above (1.5 equiv of silyl enol ether, 0.05 equiv
of TrSbCl6 as catalyst, at K78 8C). The reactions were
quenched after the first Mukaiyama–Michael addition and
then reacted further in a separate reaction with MVK, in
order to get an impression of the stereoselectivity of the
separate steps of the domino reaction. The TBDMS enol
Table 1
Enone
Silyl group
Yield first addition
(%)
Isomeric ratio
(a:b)
Yield second
addition (%)
Isomeric ratio
(a:b)
Yield domino
reaction (%)
2
2
2
3
3
TMS
89
94
46
85
83
2:1
2:1
3:2
6:5
4:1
49
45
—
5:1
45
38
5
61
32
TBDMS
TES
TMS
1 (10a)
—
4:1
TBDMS
—
2:1
All reactions have been carried out in duplicate.

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F. C. E. Saraber et al. / Tetrahedron 62 (2006) 1717–1725
1720
OTMS
OTMS
OTMS
OTMS
OTMS
OTMS
OTMS
MeO
MeO
14
15
16
17
18
19
20
Figure 2.
to the higher steric strain in the latter, in combination with
an easy desilylating side reaction in isomer 11a. These
factors could also explain the much lower yield for the
domino reaction with the TBDMS enol ether (see below),
pointing to a low-yielding second addition step. Interest-
ingly, the MVK addition in the TMS enol ether resembles
the one in the carvone route, having a strong preference for
isomer 11a of the intermediate, although in this case less
pronounced.
An additional reason to select compounds 17–19 was to
introduce functionality in the left ring, enabling further
conversion of the tricyclic skeleton. The use of silyl enol
ether 19 derived from (S)-(C)-carvone in an addition with
2-methyl-2-cyclopentenone as the receiving enone could
possibly lead to an enantioselective synthesis of a tricyclic
intermediate 22 that would enable completion of a steroid
skeleton 23 (see Scheme 3). (D-homo) steroids could
rapidly become accessible using silyl enol ether 20 derived
from 6-methoxy-1-tetralone, a compound that has already
been used extensively in steroid total synthesis.32–38
The reaction sequences were also performed as one-pot
procedures, in which the second enone (MVK) was added at
low temperature to the reaction mixture after completion of
the first Mukaiyama–Michael addition. Although this
domino reaction procedure31 did not usually increase the
overall yield dramatically, giving typically 40–50% of the
tricyclic products, it did simplify the total reaction process
considerably by taking out one complete purification step.
Although in the previous results with the cyclohexanone-
derived silyl enol ethers, the TBDMS enol ether gave the
best and most selective domino Mukaiyama–Michael
addition, this silyl group proved not always to be the best
choice. Sometimes the TBDMS enol ethers appeared
troublesome to obtain or the first addition reaction gave
no products. Therefore, the TMS enol ethers were used in all
reaction sequences, which were carried out under the
standart reaction conditions (1.5 equiv of silyl enol ether,
0.05 equiv of TrSbCl6 as catalyst, at K78 8C). However, the
overall results were disappointing.
Variation in the starting silyl enol ether would give an
impression about the scope and limitations of the
domino sequence and maybe open up possibilities for
enantioselective and short syntheses of steroids and
D-homosteroids. For this reason, silyl enol ethers derived
from cyclic ketones with more steric hindrance in the
molecule (compounds 14–17) or with a double bond or
benzene ring conjugated with the carbonyl group (com-
pounds 18 and 20) were investigated (see Fig. 2) in their
reactions with R-carvone as the first receiving enone and
with MVK as the second enone. Compounds 19 and 20 were
also reacted with 2-methyl-2-cyclopentenone as the first
receiving enone, followed by addition of MVK (see
Scheme 3).
The Mukaiyama–Michael addition of silyl enol ethers
14–16 to carvone proceeded in modest yields varying
from 30 to 53%, but in all cases unseparable mixtures of
stereoisomers were obtained. The reaction with the methoxy
compound 17 did not proceed at all and the product from
dienolsilyl enol ether 18, proved to be unstable. The reaction
of the carvone derived silyl enol ether 19 with 2-methyl-2-
cyclopentenone led to product 21 in a reasonable 68% yield.
It was published before that addition of the TMS enol ether
O
O
OTMS
O
O
O
OTMS
O
H
H
H
TrSbCl6
H
H
H
OH
22
CH2Cl2,–78°C
O
68%
23
19
21
OTMS
O
O
O
O
O
H
H
H
OH
H
MeO
MeO
TrSbCl6
24
25
OTMS
CH2Cl2,–78°C
56%
O
OTMS
O
O
MeO
O
O
20
H
H
TrSbCl6
CH2Cl2 –78°C
,
H
OH
H
90%
MeO
MeO
26
27
Scheme 3.

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F. C. E. Saraber et al. / Tetrahedron 62 (2006) 1717–1725
1721
of 6-methoxytetralone 20 to carvone gave a 3:2 mixture of
stereoisomers 24 in 56% yield, and that the stereoselectivity
and the yield are dependent on the type of starting silyl enol
ether. It was found also that the addition of 20 to 2-methyl-
2-cyclopetenone gives a 2:1 mixtures of stereoisomers of 26
in 90% yield.39
evaporator. Column chromatography was performed with
Fluka silica gel mean pore size 60 (SiO2, 230–400 mesh)
with mixtures of distilled petroleum ether, boiling range 40–
60 8C (PE) and distilled ethyl acetate (EA) as eluents, unless
1
reported otherwise. H and 13C NMR experiments were,
unless otherwise stated, conducted on a Bruker AC-E 200, at
200 and 50 MHz, respectively, using CDCl3 or C6D6 as
solvents. Chemical shifts are reported in ppm (parts per
million) (d), referenced to residual CHCl3 or C6H6 as
internal standard, and coupling constants are expressed in
In the consecutive addition reactions with MVK small
amounts (24 and 14%) of tricyclic products were obtained
from the product mixtures of silyl enol ethers resulting from
14 and 15, respectively, but the stereochemistry of these
products could not be established unambiguously. No
reaction to tricyclic products was observed in all other
cases and mostly only the desilylated intermediate adducts
could be isolated. These results show again that the reaction
sequence is sensitive for steric effects and especially the
yields of the second addition reaction with MVK drop
dramatically when extra substituents are present in the
molecule.
1
Hz. H NMR multiplicities are mentioned as singlet (s),
doublet (d), triplet (t), quadruplet (q), broad singlet (br s),
multiplet (m), double doublet (dd), etc. Multiplicities of the
13C NMR signals were determined using the DEPT
technique and are mentioned as q (CH3), t (CH2), d (CH)
or s (C). When two isomers were detected and specific peaks
could be assigned in the spectra, the data referred to the
major isomer are marked as (M) and those of the minor
isomer as (m). When the isomers are equally present, the
data is presented as 14.35 and 17.87 (q). Melting points
were determined on a C. Reichert, Vienna, hot stage
apparatus, and are uncorrected. Infrared spectra were
recorded on a FT-IR Biorad FTS-7 spectrometer using
carbon tetrachloride (CCl4) or chloroform (CHCl3) as
solvents when a solution was used. Only the characteristic
absorptions were reported. The isomeric ratio of all the
crude products was determined using GC–MS detection at
70 eV on a Hewlett Packard 5890B series Mass Selective
Detector, coupled with a Hewlett Packard 5973 GC
provided with a DB-17 fused silica capillary column,
30 m!0.25 mm i.d., film thickness 0.25 mm with helium as
the carrier gas, programmed from 100–250 8C at a rate of
10 8C/min, followed by an isothermic period at 250 8C. MS
and HRMS data were obtained with a Finnigan MAT 95
spectrometer. The ratios m/e and relative intensities (%) are
indicated for significant peaks. Elemental analyses were
performed on a Carlo Erba 1106 elemental analyser. Optical
rotations were recorded on a Perkin-Elmer 241 polarimeter
at 20 8C in chloroform solutions and concentrations are
specified in units of g/100 ml.
The failure of the second addition with MVK in the silyl
enol ethers 21, 24 and 26 either could be caused by steric
hindrance and/or by electronic effects in the 1,6-aldol
cyclization due to electron delocalisation in the receiving
enones. It seems that the electronic effects are the most
important, as it appeared to be possible to react the
intermediates 24 and 26 with carbocation precursors in
irreversible reactions.40 When the first carbonyl group is
conjugated with a double bond or an aromatic system, the
positive polarisation of the C-atom of the carbonyl group is
less pronounced and hence this group is less reactive in aldol
cyclizations. However, also uncyclised products similar to
compound 6 never have been isolated. This can be explained
by the equilibrium of the MVK addition lying on the side of
the intermediates like 4. Only if ring closure takes place, the
equilibrium is shifted, finally to the tricyclic product. When
ring closure does not take place, MVK will leave the
molecule again and therefore almost no uncyclised products
like 6, or their desilylated equivalents, were found.
3. Experimental
3.2. General method for thermodynamic silylation
3.1. General procedure
3.2.1. (1-Cyclohexen-1-yloxy)(trimethyl)silane(1[TMS]).41
To a stirred solution of cyclohexanone (2.45 g, 25 mmol) in
CH3CN (100 ml) under nitrogen were added Et3N (5.56 ml,
40 mmol), TMSCl (4.32 g, 40 mmol) and NaI (6.00 g,
40 mmol), in this order. After overnight stirring at room
temperature,thereactionmixturewasdilutedwithPE(100 ml)
and the acetonitrile layer was extracted with PE (2!100 ml).
The combined organic layers were washed with a saturated
NaHCO3 solution(100 ml) andbrine(100 ml), dried(Na2SO4)
and evaporated under reduced pressure. The residue was
purified by bulb-to-bulb distillation (br pt 44 8C at 4 Torr) to
give 1[TMS] as a colourless liquid (3.32 g, 78%). IR (CCl4
sol) cmK1 2933, 1668, 1549, 1252; 1H NMR (CDCl3): K0.12
(s, 9H), 1.30–1.38 (m, 2H), 1.38–1.53 (m, 2H), 1.77–1.92 (m,
4H), 4.66–7.71 (m, 1H); 13C NMR (CDCl3): 0.3 (3q), 22.3 (t),
23.2 (t), 23.8 (t), 29.9 (t), 104.3 (d), 150.3 (s). HRMS: MC,
found 170.1123. C9H18OSi requires 170.1127. MS m/e (%):
170 (MC, 100), 169 (41), 155 (64), 142 (23), 127 (49), 75 (86),
73 (55). These data are in accordance with literature values.
All reagents used were purchased from Aldrich or Acros,
except for carvone, which was donated by Quest, and used
without further purification unless otherwise stated. The
used solvents were freshly distilled, except for benzene,
˚
which was stored over mol sieves (4 A); dichloromethane
was distilled over calcium hydride and tetrahydrofuran
(THF) over sodium benzophenone ketyl. The glass
equipment used was dried overnight in an oven of 150 8C
and cooled down to room temperature under nitrogen.
Reactions under dry conditions were performed under a
steady flow of dry nitrogen or argon.
Reactions were monitored by thin-layer chromatography
(TLC) on Merck silica gel 60F254 plastic sheet plates and
compounds were visualized by potassium permanganate or
by acidic molybdate solution and subsequent heating.
Product solutions were dried over Na2SO4 or MgSO4 before
evaporation under reduced pressure using a rotary

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F. C. E. Saraber et al. / Tetrahedron 62 (2006) 1717–1725
1722
3.2.2. tert-Butyl(1-cyclohexen-1-yloxy)dimethylsilane
(1[TBDMS]).42 See method description of compound
1[TMS] for procedure and reaction scale. Yield: 83%, as a
clear oil (br pt 55 8C at 0.3 Torr). IR (CCl4 sol) cmK1: 2931,
1.85–2.11 (m, 5H), 2.12–2.50 (m, 4H), 2.86 (s, 1H), 4.69 (s,
2H); 13C NMR (CDCl3): K3.7 (2q), 14.4 (m) and 17.9 (M)
(q), 18.2 (s), 20.5 (M) and 20.7 (m) (q), 25.4 (t), 25.9 (3q),
27.2 (m) and 28.0 (M) (t), 28.7 (M) and 29.3 (m) (t), 32.7 (m)
and 33.6 (M) (t), 35.1 (m) and 35.3 (M) (t), 35.8 (m) and 36.1
(M) (d), 37.8 (M) and 39.3 (m) (d), 42.2 (m) and 42.4 (M) (t),
52.9 (m) and 56.4 (M) (d), 109.0 (t), 111.4 (m) and 112.6 (M)
(s), 145.0 (s), 148.7 (m) and 148.9 (M) (s), 212.6 (M) and
212.8 (m) (s). HRMS: MC, found 362.2652. C22H38O2Si
requires 362.2641. MS m/e (%): 362 (MC, 9), 305 (2), 155
(10), 75 (12), 73 (31).
1
2859, 1668, 1549, 1254; H NMR (CDCl3): 0.01 (s, 9H),
0.12 (s, 6H), 1.45–1.59 (m, 2H), 1.59–1.72 (m, 2H), 1.94–
2.08 (m, 4H), 4.85–4.90 (m, 1H); 13C NMR (CDCl3): K4.4
(q), K2.9 (q), 18.0 (s), 22.4 (t), 23.2 (t), 23.8 (t), 25.7 (q),
29.9 (t), 104.3 (d), 150.5 (s). HRMS: MC, found 212.1598.
C12H24OSi requires 212.1596. MS m/e (%): 212 (MC, 22),
75 (80), 73 (19). These data are in accordance with literature
values.
3.2.6. 2-{(5R)-5-Isopropenyl-2-methyl-3-[(triethyl-
silyl)oxy]-2-cyclohexen-1-yl}cyclohexanone (8[TES]).
See method description of compound 8[TMS] for procedure
and reaction scale. Yield: 46%, as a colourless oil (2
3.2.3. (1-Cyclohexen-1-yloxy)(triethyl)silane (1[TES]).43
See method description of compound 1[TMS] for procedure
and reaction scale. Yield: quantitative, as a colourless oil (br
pt 54 8C at 0.5 Torr). IR (CCl4 sol) cmK1: 2956, 2877, 1667,
1
isomers, 3:2). IR (film) cmK1: 2936, 1710, 1449, 1238; H
1
1550; H NMR (CDCl3): 0.60 (s, 9H), 0.60–0.88 (m, 6H),
NMR (C6D6): 0.64 (q, JZ7.9 Hz, 6H), 0.97 (t, JZ7.9 Hz,
9H), 1.53 (m) and 1.56 (M) (s, 3H), 1.70 (s, 3H), 1.45–1.71
(m, 5H), 1.88–2.12 (m, 4H), 2.26–2.45 (m, 4H), 2.89 (m,
1H), 4.70 (s, 2H); 13C NMR (C6D6): 5.9 (3t), 6.9 (3q), 14.9
(m) and 17.6 (M) (q), 20.4 (M) and 20.7 (m) (q), 25.2 (t),
26.9 (m) and 27.6 (M) (t), 28.6 (m) and 32.4 (M) (t), 29.2 (m)
and 33.7 (M) (t), 35.2 (m) and 35.5 (M) (t), 35.6 (m) and 36.1
(M) (d), 38.1 (M) and 39.5 (m) (d), 41.9 (t), 53.5 (m) and
56.1 (M) (d), 109.2 (t), 113.1 (s), 145.9 (s), 149.2 (m) and
149.6 (M) (s), 210.6 (M), 210.7 (m) (s). HRMS: MC, found
362.2648. C22H38O2Si requires 362.2641. MS m/e (%): 362
(MC, 26), 333 (9), 239 (12), 115 (13), 87 (24), 59 (11).
1.50–1.58 (m, 2H), 1.58–1.71 (m, 2H), 1.96–2.00 (m, 4H),
4.84–4.87 (m, 1H); 13C NMR (CDCl3): 5.0 (q), 5.8 (t), 6.4
(t), 6.5 (q), 6.8 (q), 23.8 (t), 29.8 (t), 41.5 (t), 41.9 (t), 103.9
(d), 150.4 (s). HRMS: MC, found 212.1598. C12H24OSi
requires 212.1596. MS m/e (%): 212 (MC, 23), 169 (18),
156 (12), 155 (17), 103 (47), 75 (43). These data are in
accordance with literature values.
3.2.4. 2-{(5R)-5-Isopropenyl-2-methyl-3[(trimethyl-
silyl)oxy]-2-cyclohexen-1-yl}cyclohexanone (8[TMS]).
(R)-(K)-Carvone (150 mg, 1 mmol) and 1[TMS] (255 mg,
1.50 mmol) were dissolved in dichloromethane (6 ml) and
stirred under nitrogen. The reaction mixture was cooled to
K78 8C. Trityl antimony hexachloride (TrSbCl6) (29 mg,
0.05 mmol) was added and the reaction was followed by
TLC. When all the carvone had reacted (1 h), the catalyst
was quenched by adding a few drops of pyridine, until the
yellow colour disappeared. The reaction mixture was
allowed to warm to room temperature and diluted with
dichloromethane (14 ml). The mixture was washed with a
saturated NaHCO3 solution (20 ml) and brine (20 ml), dried
(Na2SO4) and evaporated under reduced pressure. The
residue was purified on a short SiO2 column (PE/EtOAc/
pyridine 98:1:1) to give 8[TMS] (286 mg, 89%) as a
colourless oil composed of two isomers, which could not be
separated, in a ratio of 2:1 (GC). IR (film) cmK1: 2936,
1709, 1644, 1251; 1H NMR (CDCl3): 0.15 (s, 9H), 1.53 (s,
3H), 1.52–1.69 (m, 5H), 1.69 (s, 3H), 1.91–2.07 (m, 4H),
2.20–2.40 (m, 4H), 2.90–2.92 (m, 1H), 4.69 (s, 2H); 13C
NMR (CDCl3): 0.8 (3q), 17.5 (q), 20.5 (q), 25.4 (M) and
27.1 (m) (t), 27.9 (M) and 28.6 (m) (t), 29.2 (m) and 32.6 (M)
(t), 33.7 (t), 35.1 (t), 35.7 (d), 37.8 (M) and 39.2 (m) (d), 42.4
(t), 52.9 (m) and 56.3 (M) (d), 109.0 (t), 112.9 (s), 144.9 (s),
148.7 (m) and 148.9 (M) (s), 212.4 (s). HRMS: MC, found
320.2173. C19H32O2Si requires 320.2172. MS m/e (%): 320
(MC, 100), 181 (12), 75 (5), 73 (33).
3.2.7. (3R)-9-Acetyl-8a-hydroxy-3-isopropenyl-10a-
methyldodecahydro-1(2H)-phenanthrenone
(10).
Mukaiyama–Michael addition of intermediate 8[TMS]
with MVK. A stirred solution of TrSbCl6 (29 mg,
0,05 mmol) in dichloromethane (10 ml) under nitrogen
was cooled to K78 8C. A solution of 8[TMS] (320 mg,
1 mmol) and methyl vinyl ketone (MVK, 0.17 ml, 2 mmol)
in dichloromethane (5 ml) was added dropwise over a
period of 2.5 h. The reaction mixture was stirred at K78 8C
for another 2 h and was then allowed to warm to room
temperature. Water (10 ml) was added and, after stirring for
a further 1 h, the reaction mixture was diluted with
dichloromethane (20 ml) and washed with a saturated
NaHCO3 solution (20 ml) and brine (20 ml). The organic
layer was dried (Na2SO4) and evaporated under reduced
pressure. The residue was purified by column chromato-
graphy (PE/EtOAc 9:1) to give two isomers 10a (122 mg,
crystals) and 10b (25 mg, colourless oil) in a total 49% yield
in a 5:1 ratio. Compound 10a was recrystallised from
pentane to give white needles.
Mukaiyama–Michael addition of intermediate 8[TBDMS]
with MVK. The reaction of 8[TBDMS] (362 mg, 1 mmol)
with MVK was carried out as described for 8[TMS].
Compound 10a (143 mg) was obtained as a single isomer in
45% yield as white crystals (needles) after recrystallisation
from pentane.
3.2.5. 2-{(5R)-3-{[tert-Butyl(dimethyl)silyl]oxy}-5-iso-
propenyl-2-methyl-2-cyclohexen-1-yl}cyclohexanone
(8[TBDMS]). See method description of compound
8[TMS] for procedure and reaction scale. Yield: 94%, as a
Domino Mukaiyama reaction of 1[TMS]. At room tem-
perature, (R)-(K)-carvone (450 mg, 3 mmol) was added to a
stirred solution of 1[TMS] (765 mg, 4.5 mmol) in dichloro-
methane (20 ml) under nitrogen. The solution was cooled to
K78 8C and TrSbCl6 was added (87 mg, 0.15 mmol). After
colourless oil (mixture of 2 isomers, 2:1). IR (film) cmK1
2932, 1710, 1678, 1449, 1254; H NMR (CDCl3): 0.11 (s,
6H), 0.88 (m) and 0.94 (M) (s, 9H), 1.52–1.72 (m, 5H), 1.51
(m) and 1.54 (M) (s, 3H), 1.69 (M) and 1.70 (m) (s, 3H),
:
1

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F. C. E. Saraber et al. / Tetrahedron 62 (2006) 1717–1725
1723
2.5 h of stirring at K78 8C MVK (0.5 ml, 6 mmol) was
added dropwise over a period of 3.5 h. The reaction mixture
was stirred for another 2 h at K78 8C, before slow warming
to room temperature overnight. No TLC control was done
during the reaction due to the sensitivity of the compounds
towards desilylation. Water (10 ml) was added and after
further stirring for 1 h the reaction mixture was diluted with
dichloromethane (20 ml). The organic layer was washed
with a saturated NaHCO3 solution (20 ml) and brine
(20 ml), dried (Na2SO4) and evaporated under reduced
pressure. The residue was purified by column chromatog-
raphy (PE/EA 20:1, with 1% pyridine) to give a total 45%
yield of 10a (119 mg) and 10b (24 mg) in a 5:1 ratio.
1211; 1H NMR (CDCl3): 0.01 (s, 9H), 1.24 (s, 3H),
1.11–2.38 (m, 13H), 2.86–3.09 (m, 1H); 13C NMR (CDCl3):
0.6 (3q), 10.1 (M) and 12.1 (m) (q), 22.9 (t), 24.9 (M) and
25.4 (m) (t), 26.5 (M) and 27.0 (m) (t), 27.2 (M) and 28.5 (m)
(t), 32.6 (m) and 33.2 (M) (t), 42.0 (m) and 42.2 (M) (t), 42.7
(m) and 43.2 (M) (d), 52.3 (M) and 54.8 (m) (d), 113.1 (M)
and 114.4 (m) (s), 147.7 (M) and 148.3 (m) (s), 211.9 (m)
and 212.8 (M) (s). MS m/e (%): 266 (MC, 2), 169 (100), 155
(3), 75 (11), 73 (66).
3.2.9. 2-(3-{[tert-Butyl(dimethyl)silyl]oxy}-2-methyl-2-
cyclopenten-1-yl)cyclohexanone (11[TBDMS]). See
method description of compound 11[TMS] for procedure
and reaction scale. Yield: 83%, as a colourless oil (2
isomers, 4:1). IR (CCl4 sol) cmK1: 2923, 2858, 1711, 1549,
Domino Mukaiyama reaction of 1[TBDMS]. The reaction
of 1[TBDMS] (954 mg, 4.5 mmol) was carried out as
described for 1[TMS]. Compound 10a (120 mg) was
obtained as a single isomer in 38% yield as white crystals
(needles) after recrystallisation from pentane.
1
1253; H NMR (CDCl3): 0.10 (s, 6H), 0.93 (s, 9H), 1.31–
1.52 (m, 5H), 1.54–1.70 (m, 2H), 1.79–2.53 (m, 9H), 3.09
(s, 1H); 13H NMR (CDCl3) K4.0 (2q), 10.1 (q), 18.1 (s),
22.9 (t), 25.1 (t), 25.7 (3q), 26.5 (t), 27.2 (t), 33.2 (t), 42.4 (t),
43.1 (d), 52.4 (d), 112.7 (s), 147.9 (s), 213.1 (s). HRMS:
MC, found 308.2178. C18H32O2Si requires 308.2172. MS
m/e (%): 308 (MC, 14), 75 (25), 73 (33).
Compound 10a. Mp 68–72 8C (from pentane); IR (CCl4
sol) cmK1: 3488, 2937, 1707, 1252; 1H NMR (CDCl3):
1.01–1.22 (2H, m), 1.18 (3H, s), 1.22–1.48 (4H, m), 1.55–
1.84 (9H, m), 1.88–2.13 (2H, m), 2.19 (3H, s), 2.35–2.55
(2H, m), 2.64 (d, JZ6.7 Hz, 1H), 3.02 (dd, J1Z3.3 Hz, J2Z
9.9 Hz, 1H), 3.99 (OH), 4.65 (1H, s), 4.81 (1H, s); 13C NMR
(CDCl3): 19.9 (q), 22.3 (q), 23.8 (t), 25.7 (t), 26.4 (t), 26.9
(t), 31.6 (q), 31.9 (t), 33.6 (d), 38.8 (t), 40.5 (d), 41.1 (t), 45.6
(d), 47.4 (s), 48.2 (d), 72.1 (s), 112.5 (t), 146.6 (t), 214.6 (s),
215.4 (s). HRMS: MC, found 318.2203. C20H30O3 requires
318.2195. MS m/e (%): 318 (MC, 42), 248 (86), 221 (63),
204 (96), 179 (77), 161 (84), 151 (98), 98 (67).
3.2.10. 5-Acetyl-5a-hydroxy-3a-methyldodecahydro-3H-
cyclopenta[a]naphthalen-3-one (13). For general pro-
cedures and scale see the syntheses of 10. From 11[TMS]
a total yield of 161 mg (61%), of 13a and 13b was obtained
as white crystals in a 4:1 ratio, respectively. From
11[TBDMS] a total yield of 84 mg (32%) of 13a and 13b
was obtained in a 2:1 ratio, respectively.
Compound 13a. Mp 86–90 8C (from pentane); IR (CCl4
sol) cmK1: 3469, 2933, 2860, 1739, 1692, 1398, 1359,
1190; 1H NMR (CDCl3): 0.92 (s, 3H), 1.08–2.18 (m, 15H),
2.18 (s, 3H), 2.41 (dd, J1Z8.0 Hz, J2Z16.4 Hz, 1H), 2.61
(dd, J1Z5.1 Hz, J2Z11.5 Hz, 1H), 3.81 (s, 1H); 13C NMR
(CDCl3): 13.4 (q), 21.1 (2t), 23.4 (t), 25.7 (t), 31.3 (q), 31.8
(t), 35.7 (t), 37.0 (t), 42.8 (d), 42.9 (d), 47.2 (s), 53.7 (d),
72.0 (s), 215.9 (s), 219.5 (s). HRMS: MC, found 264.1724.
C16H24O3 requires 264.1725. MS m/e (%): 264 (MC, 2),
246 (9), 249 (8), 246 (10), 203 (18), 194 (54), 98 (100), 97
(92), 55 (18), 43 (15).
Compound 10b. IR (CCl4 sol) cmK1: 3488, 2937, 1707,
1252; H NMR (CDCl3): 1.14 (3H, s), 1.04–1.28 (2H, m),
1
1.32–1.85 (13H, m), 1.93–2.12 (2H, m), 2.17 (3H, s), 2.50–
2.62 (2H, m), 2.62–2.74 (2H, m), 3.67 (OH), 4.69 (1H, s),
4.80 (1H, s); 13C NMR (CDCl3): 16.9 (q), 20.7 (t), 21.5 (q),
23.7 (t), 25.3 (t), 26.1 (t), 31.4 (q), 32.1 (t), 36.3 (d), 37.5 (t),
39.4 (d), 40.7 (t), 42.8 (d), 47.2 (s), 53.3 (d), 70.8 (s), 112.0
(t), 146.8 (s), 215.7 (s), 215.9 (s). HRMS: MC, found
318.2203. C20H30O3 requires 318.2195. MS m/e (%): 318
(MC, 42), 248 (86), 221 (63), 204 (96), 179 (77), 161 (84),
151 (98), 98 (67).
1
Compound 13b. Mp 79–82 8C (from pentane); H NMR
(CDCl3): 1.05 (s, 3H), 1.05–1.55 (m, 5H), 1.64–1.93 (m,
9H), 2.12 (dd, J1Z8.5 Hz, J2Z19.1 Hz, 1H), 2.24 (s, 3H),
2.32–2.57 (m, 1H), 3.10 (dd, J1Z5.1 Hz, J2Z11.1 Hz, 1H),
4.19 (s, 1H); 13C NMR (CDCl3): 16.9 (q), 20.8 (t), 24.0 (t),
25.7 (t), 26.1 (t), 31.5 (q), 31.7 (t), 35.7 (t), 38.8 (t), 41.6 (d),
46.3 (2d), 46.6 (s), 73.1 (s), 215.4 (s), 219.0 (s). HRMS:
MC, found 264.1726. C16H24O3 requires 264.1725. MS m/e
(%): 264 (MC, 20), 249 (15), 246 (22), 221 (7), 203 (33),
194 (99), 98 (93). 97 (100), 43 (29).
3.2.8. 2-{2-Methyl-3-[(trimethylsilyl)oxy]-2-cyclopenten-1-
yl}cyclohexanone (11[TMS]). 2-Methyl-2-cyclopentenone
(384 mg, 4 mmol) and 1[TMS] (1.36 g, 8 mmol) were
dissolved in dichloromethane (25 ml) and stirred under
nitrogen. The reaction mixture was cooled to K78 8C. Trityl
antimony hexachloride (TrSbCl6) (58 mg, 0.05 mmol) was
added and the reaction was followed by TLC. When all the
carvone had reacted (1 h), the catalyst was quenched by
adding a few drops of pyridine, until the yellow colour
disappeared. The reaction mixture was allowed to warm to
room temperature and diluted with dichloromethane
(15 ml). The mixture was washed with saturated NaHCO3
solution (25 ml) and brine (25 ml), dried (Na2SO4) and
evaporated under reduced pressure. The residue was
purified on a short column (PE/EtOAc/pyridine 98:1:1) to
give 11[TMS] (906 mg, 85%) as a colourless oil composed
of two isomers, which could not be separated, in a ratio of
6:5. IR (film) cmK1: 2937, 2860, 1709, 1691, 1330, 1252,
3.2.11. {[(3S)-3-Isopropenyl-6-methyl-cyclohexa-1,5-die-
nyl]oxy}(trimethyl)silane (19[TMS]).44 A solution of
diisopropylamine (2.25 ml, 16 mmol) in THF (20 ml) was
cooled to K10 8C, and butyllithium (1.45 M in THF, 10 ml)
was added in one portion. The solution was allowed to warm
to 0 8C and stirred for 30 min, after which the solution was
cooled to K78 8C and a solution of (S)-(C)-carvone (2.0 g,
13.2 mmol) in THF (20 ml) was added dropwise over a
period of 30 min. The solution was kept at K78 8C and

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F. C. E. Saraber et al. / Tetrahedron 62 (2006) 1717–1725
1724
stirred for 20 min, followed by dropwise addition of TMSCl
(2.0 ml, 16 mmol) over a period of 10 min. The solution was
allowed to warm to room temperature over a period of 1 h
and poured in a cold solution of brine and NaHCO3 (10%).
The water-layer was extracted with petrol-ether, and the
combined organic layers were washed with brine, dried
(MgSO4) and evaporated. The crude product was purified by
bulb-to-bulb distillation yielding 2.76 g of 19[TMS] (94%) s
a colourless oil. IR (CCl4 sol) cmK1 2963, 1660, 1605,
(CDCl3): K0.01 (s, 9H), 1.28 (s, 3H), 1.51 (s, 3H), 1.54 (s,
3H), 1.15–2.68 (m, 9H), 4.59 (s, 2H), 6.38–6.44 (m, 1H);
13C NMR (CDCl3): 0.6 (3q), 10.7 (q), 15.6 (q), 18.8 (q),
22.9 (t), 30.3 (t), 32.6 (t), 45.1 (d), 46.2 (d), 50.0 (d), 113.0
(t), 114.8 (s), 136.1 (s), 142.0 (d), 146.1 (s), 146.5 (s), 200.3
(s). HRMS: MC, found 318.2017. C19H30O2Si requires
318.2015. MS m/e (%): 318 (MC, 9), 222 (15), 182 (6), 169
(100), 150 (5), 73 (34).
1
1550, 1451, 1375, 1253, 1214; H NMR (CDCl3): 0.18 (s,
3.2.15. 6-Methoxy-2-(2-methyl-3-trimethylsilanyloxy-
cyclopent-2-enyl)-3,4-dihydro-2H-naphthalen-1-one
(26). See method description of compound 11 for procedure
and reaction scale. Yield: 90%, as a colourless oil (2
isomers, 2:1). IR (CCl4 sol) cmK1: 2941, 2851, 1673, 1600,
1333, 1252; 1H NMR (CDCl3) d: 0.14 (M) and 0.18 (m) (s,
9H), 1.27 (M) and 1.50 (m) (s, 3H), 1.41–2.73 (m, 7H),
2.86–3.00 (dd, J1Z3.7 Hz, J2Z8.3 Hz, 2H), 3.40–3.55 (m)
and 3.55–3.65 (M) (m, 1H), 3.83 (s, 3H), 6.66 (d, JZ2.5 Hz,
1H), 6.81 (dd, J1Z2.5 Hz, J2Z8.7 Hz, 1H), 8.00 (m) and
8.01 (M) (d, JZ8.7 Hz, 1H); 13C NMR (CDCl3): d: 0.6 (3q),
10.3 (m) and 11.9 (M) (q), 22.4 (m) and 23.6 (M) (t), 22.9
(m) and 25.0 (M) (t), 29.8 (M) and 29.9 (m) (t), 32.9 (M) and
33.1 (m) (t), 43.3 (M) and 43.9 (m) (d), 49.7 (m) and 52.2
(M) (d), 55.4 (q), 112.4 (d), 113.0 (d), 114.4 (s), 126.5(M)
and 127.1 (m) (s), 129.7 (m) and 123.0 (M) (d), 146.5 (M)
and 146.8 (m) (s), 147.9 (m) and 148.1 (M) (s), 163.3 (s),
197.8 (M) and 199.0 (m) (s). HRMS: MC, found 344.1807.
C20H28O3Si requires 344.1808. MS m/e (%): 344 (MC, 9),
249 (8), 248 (34), 138 (8), 176 (36), 170 (15), 169 (100).
9H), 1.67 (s, 3H), 1.71 (s, 3H), 2.11 (m, 2H), 2.99 (m, 1H),
4.69 (m, 1H), 4.76 (m, 2H), 5.54 (m, 1H); 13C NMR
(CDCl3): 0.1 (3q), 17.3 (q), 20.5 (q), 28.6 (t), 41.8 (d), 105.7
(d), 109.9 (t), 123.0 (d), 131.8 (s), 148.4 (s), 149.8 (s).
HRMS: MC, found 222.1439. C13H22OSi requires
222.1440. MS m/e (%): 222 (100, MC), 207 (83), 181
(65), 165(62), 91 (24), 82 (17), 75 (21), 73 (79), 45 (16).
Data are in accordance with literature values.
3.2.12. [(6-Methoxy-3,4-dihydro-1-naphthalenyl)oxy]-
(trimethyl)silane (20[TMS]).45 See method description of
compound 1 for procedure and reaction scale. Yield: 92%,
as a colourless oil. IR (CCl4 sol) cmK1: 2958, 2835, 1683,
1
1639, 1607, 1252; H NMR d: 0.31 (s, 9H), 2.24–2.35 (m,
2H), 2.79 (t, JZ7.8 Hz, 2H), 3.83 (s, 3H), 5.12 (t, JZ
4.6 Hz, 1H), 6.74 (s, 1H), 6.76 (d, JZ8.6 Hz, 1H), 7.41 (d,
JZ8.2 Hz, 1H); 13C NMR d: 0.2 (3q), 22.2 (t), 28.7 (t), 55.1
(q), 102.9 (d), 110.7 (d), 113.2 (d), 123.1 (d), 126.6 (s),
138.9 (s), 147.9 (s), 158.9 (s). HRMS: MC, found 248.1229.
C14H20O2Si requires 248.1233. MS m/e (%): 248 (MC,
100), 247 (64), 233 (30), 217 (13), 73 (21). Data are in
accordance with literature values.
Acknowledgements
3.2.13. 2-{(1S,5R)-5-Isopropenyl-2-methyl-3-[(trimethyl-
silyl)oxy]-2-cyclohexen-1-yl}-6-methoxy-3,4-dihydro-
1(2H)-naphthalenone (24). See method description of
compound 8 for procedure and reaction scale. Yield: 56%,
as a mixture of 2 isomers (3:2), white crystals (mp 55–56 8C
from pentane). IR (CCl4) cmK1: 2939, 1680, 1602, 1252; 1H
NMR d: 0.15 and 0.19 (s, 9H), 1.39 and 1.58 (s, 3H), 1.68
and 1.73 (s, 3H), 1.45–2.65 (m, 7H), 2.75 (dt, J1Z13.0 Hz,
J2Z3.7 Hz, 1H), 2.91–2.93 (m, 2H), 3.23 and 3.35 (br s,
1H), 3.83 (s, 3H), 4.72–4.74 (m, 2H), 6.67 (br s, 1H), 6.80
(dd, J1Z8.7 Hz, J2Z2.5 Hz, 1H), 8.02 (d, JZ8.7 Hz, 1H);
13C NMR (isomer 1) d: 1.3 (3q), 11.9 (q), 21.4 (q), 25.5 (t),
27.2 (t), 28.1 (t), 34.4 (d), 40.6 (d), 42.2 (t), 46.6 (d), 55.4
(q), 77.0 (s), 111.7 (t), 112.3 (d), 113.4 (d), 125.9 (s), 129.9
(d), 145.6 (s), 146.7 (s), 163.5 (s), 198.9 (s), 213.8 (s);
(isomer 2) 1.9 (3q), 12.2 (q), 21.1 (q), 26.8 (t), 29.1 (t), 29.5
(t), 36.5 (d), 42.4 (d), 44.1 (t), 47.9 (d), 55.4 (q), 77.7 (s),
111.0 (t), 112.3 (d), 113.2 (d), 125.2 (s), 130.0 (d), 145.8 (s),
147.0 (s), 163.5 (s), 198.8 (s), 213.8 (s). HRMS: MC, found
398.2275. C24H34O3Si requires 398.2277. MS m/e (%): 398
(MC, 12), 329 (3), 248 (31), 223 (100), 222 (49), 176 (21),
73 (33).
The authors gratefully acknowledge financial support from
the Dutch Technology Foundation (Grant CW/STW-project
790.35.215) and from Organon International. The authors
thank B. van Lagen for NMR and IR spectroscopic data, and
M.A. Posthumus for mass spectroscopic measurements.
References and notes
¨
¨
1. Paulsen, H.; Antons, S.; Brandes, A.; Logers, M.; Muller,
S. N.; Naab, P.; Schmeck, C.; Schneider, S.; Stoltefuss, J.
Angew. Chem., Int. Ed. 1999, 38, 3373.
2. Hagiwara, H.; Yamada, Y.; Sakai, H.; Suzuki, T.; Ando, M.
Tetrahedron 1998, 54, 10999.
3. Prowotorow, I.; Stepanenko, W.; Wicha, J. Eur. J. Org. Chem.
2002, 2727.
4. Gorobets, E.; Urbanczyk-Lipkowska, Z.; Stepanenko, V.;
Wicha, J. Tetrahedron Lett. 2001, 42, 1135.
5. Gorobets, E.; Miftakhov, M. S.; Valeev, F. A. Russ. Chem.
Rev. 2000, 69, 1001.
3.2.14. (5S,6R)-5-Isopropenyl-2-methyl-6-(2-methyl-3-
trimethylsilanyloxy-cyclopent-2-enyl)-cyclohex-2-enone
(24). The reaction was carried out as described for
compound 11. The reaction was carried out several times
on a scale that varied from 100 mg to 1 g. The product was
obtained in an average of 68% yield as a colourless oil.
6. Stepanenko, W.; Wicha, J. Tetrahedron Lett. 1998, 39, 885.
7. Marczak, S.; Michalak, K.; Urbanczyk-Lipkowska, Z.; Wicha,
J. J. Org. Chem. 1998, 63, 2218.
8. Marczak, S.; Wicha, J. Tetrahedron Lett. 1993, 34, 6627.
9. Grzywacz, P.; Marczak, S.; Wicha, J. J. Org. Chem. 1997, 62,
5293.
1
IR (CCl4) cmK1: 2960, 2957, 2945, 1741, 1671; H NMR
10. Kobayashi, S.; Mukaiyama, T. Chem. Lett. 1986, 221.

`
F. C. E. Saraber et al. / Tetrahedron 62 (2006) 1717–1725
1725
¨
11. Hagiwara, H.; Okano, A.; Uda, H. J. Chem. Soc., Chem.
Commun. 1985, 1047.
29. Heathcock, C. H.; Norman, M. H.; Uhling, D. E. J. Am. Chem.
Soc. 1985, 107, 2797.
¨
30. Heathcock, C. H.; Uhling, D. E. J. Org. Chem. 1986, 51, 279.
12. Posner, G. H. Chem. Rev. 1986, 86, 831.
13. Posner, G. H.; Asirvatham, E. Tetrahedron Lett. 1986, 27, 663.
14. Posner, G. H.; Lu, S. B.; Asirvatham, E. Tetrahedron Lett.
1986, 27, 659.
31. This one-pot procedure is termed a domino reaction although
not all reagents are present in the reaction mixture from the
start. On the other hand, the reaction conditions remain the
same during the whole reaction time and for this reason, we
estimate this term appropriate for the situation.
32. Quinkert, G.; Grosso, M. d.; Bucher, A.; Bats, J. W.;
Du¨rner, G. Tetrahedron Lett. 1991, 32, 3357.
15. Posner, G. H.; Lu, S. B.; Asirvatham, E.; Silversmith, E. F.;
Shulman, E. M. J. Am. Chem. Soc. 1986, 108, 511.
16. Wakselman, C.; Mondon, M. Tetrahedron Lett. 1973, 14,
4285.
17. Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am. Chem. Soc.
1974, 96, 7503.
33. Posner, G. H.; Mallamo, J. P.; Black, A. Y. Tetrahedron 1981,
37, 3921.
18. Narasaka, K.; Soai, K.; Aikawa, Y.; Mukaiyama, T. Bull.
Chem. Soc. Jpn. 1976, 49, 779.
34. Nazarov, I. N.; Torgov, I. V.; Verkholetova, G. P. Dokl. Akad.
Nauk SSSR 1957, 112, 1067.
19. Kobayashi, S.; Murakami, M.; Mukaiyama, T. Chem. Lett.
1985, 953.
35. Mikami, K.; Takahashi, K.; Nakai, T. J. Am. Chem. Soc. 1990,
112, 4035.
36. Jung, M. E.; Halweg, K. M. Tetrahedron Lett. 1984, 25, 2121.
20. Kobayashi, S. Eur. J. Org. Chem. 1999, 15.
21. Cossy, J.; Lutz, F.; Alauze, V.; Meyer, C. Synlett 2002, 45.
22. Chen, J.; Otera, J. Tetrahedron 1997, 53, 14275.
23. Sato, T.; Wakahara, Y.; Otera, J.; Nozaki, H. Tetrahedron
1991, 47, 9773.
´
37. Gauthier, V.; Cazes, B.; Gore, J. Tetrahedron Lett. 1991, 32,
915.
38. Das, J.; Kubela, R.; MacAlpine, G. A.; Stojanac, Z.;
Valenta, Z. Can. J. Chem. 1979, 57, 3308.
`
39. Dratch, S.; Charnikhova, T.; Saraber, F. C. E.; Jansen, B. J. M.;
de Groot, A. Tetrahedron 2003, 59, 4287.
24. Bernardi, A.; Colombo, G.; Scolastico, C. Tetrahedron Lett.
1996, 37, 8921.
25. Grieco, P. A.; Cooke, R. J.; Henry, K. J.; VanderRoest, J. M.
Tetrahedron Lett. 1991, 32, 4665.
40. Grieco, P. A.; May, S. A.; Kaufman, M. D. Tetrahedron Lett.
1998, 39, 7047.
26. Harada, T.; Iwai, H.; Takatsuki, H.; Fujita, K. Org. Lett. 2001,
3, 2101.
41. Hydrio, J.; van de Weghe, P.; Collin, J. Synthesis 1997, 68.
42. Kopka, I.; Rathke, M. W. J. Org. Chem. 1981, 46, 3771.
43. Kruglaya, O. A.; Belousova, L. I.; Gendin, D. V.; Kalikhman,
I. D.; Vyazankin, N. S. J. Organomet. Chem. 1980, 201, 69.
44. Hong, S. P.; Lindsay, H. A.; Yaramasu, T.; Zhang, X.;
McIntosh, M. C. J. Org. Chem. 2002, 67, 2042.
27. Van de Weghe, P.; Collin, J. Tetrahedron Lett. 1993, 34, 3881.
28. Kooijman, H.; Saraber, F. C. E.; de Groot, A.; Spek, A. L. Acta
Crystallogr., Sect. E 2005, 61, 3921 for compound 10a.
Spek, A. L.; Menzer, S.; Meulemans, T.; de Groot, A. CCDC
227434 for compound 13b and CCDC227438 for compound
13a.
45. Cazeau, P.; Duboudin, F.; Moulines, F.; Babot, O.;
Dunogues, J. Tetrahedron 1987, 43, 2075.