Asymmetry induction on the [4C(4π)+3C(2π)] cycloaddition reaction of C2-functionalized furans: Influence of the chiral auxiliary nature

Article abstract of DOI:10.1016/S0040-4020(02)00452-0

The study of the π-facial diastereoselectivity in the [4+3] cycloaddition reaction of thirteen different chiral 2-substituted furans with oxyallyl cations, under sonochemical and/or thermal conditions, is presented. In almost all studied furans, a cis diastereoselectivity and a high endo diastereoselectivity is observed. Decreasing the distance between the closest stereocenter of the chiral auxiliary and the reactive C2-carbon of the furan ring, increases the π-facial diastereoselectivity, especially by using chiral furyl-sulfoxides.

Full text of DOI:10.1016/S0040-4020(02)00452-0

TETRAHEDRON
Pergamon
Tetrahedron 58 42002) 4769±4786
Asymmetry induction on the [4Cꢀ4p)13Cꢀ2p)] cycloaddition
reaction of C2-functionalized furans:
in¯uence of the chiral auxiliary nature
Angel M. MontanÄap and Pedro M. Grima
   Á
Departamento de Quõmica Organica, Universidad de Barcelona, c/Martõ i Franques 1-11, 08028 Barcelona, Spain
Received 17 December 2001; revised 8 March 2002; accepted 26April 2002
AbstractÐThe study of the p-facial diastereoselectivity in the [413] cycloaddition reaction of thirteen different chiral 2-substituted furans
with oxyallyl cations, under sonochemical and/or thermal conditions, is presented. In almost all studied furans, a cis diastereoselectivity and a
high endo diastereoselectivity is observed. Decreasing the distance between the closest stereocenter of the chiral auxiliary and the reactive
C2-carbon of the furan ring, increases the p-facial diastereoselectivity, especially by using chiral furyl-sulfoxides. q 2002 Elsevier Science
Ltd. All rights reserved.
1. Introduction
Many of the actual synthetic target molecules having
pharmacological interest are chiral, and due to the experi-
mental ®nding that usually only one of the two enantiomers
4eutomer) has the required biological activity, it is of great
importance to prepare enantiomerically pure compounds,
for economical and safety reasons. The [413] cycloaddition
reaction is generally used as one of the initial steps of the
synthetic pathways, and because the resulting bicyclic
cycloadduct has little conformational freedom, this reaction
is a very adequate step to induce asymmetry in the overall
synthetic process. In addition, in the [413] cycloaddition
reaction four stereocenters are simultaneously formed,
whose relative con®guration is determined by mechanistic
requirements of the reaction, resulting in a high stereo-
selectivity.
The [4C44p)13C42p)] cycloaddition reaction1 between C2-
functionalized furans and oxyallyl cations is an elegant and
ef®cient method to synthesize polyfunctionalized cyclo-
heptenes. These systems are added-value structures with
applications in the preparation of molecules with pharma-
cological and/or biological activity.1,2 These synthons facili-
tate the straightforward synthesis of molecules having a
seven-membered ring 4Fig. 1). Moreover, the oxidative
cleavage of the carbocycle is also a good method to synthe-
size, in a stereoselective manner, linear polysubstituted
synthons 4Fig. 1) that could be transformed into subunits
of biologically active natural products such as ionomycin,3
rifamycin4 and other antibiotic macrolides, which are
usually prepared by reiterated aldol reactions with dif®cult
stereocontrol.
Surprisingly, in the literature, there are only a few
Figure 1. Preparation of useful C7 synthons by [413] cycloaddition reactions.
Keywords: [413]-cycloaddition; oxyallyl cation; syn±anti; endo±exo; p-facial diastereoselectivity; chiral auxiliary; furan.
Corresponding author. Fax: 134-93-3397878; e-mail: ammontana@qo.ub.es
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020402)00452-0

4770
A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
Figure 2. Chiral precursors used in asymmetric [413] cycloadditions.
references to the preparation of enantio-enriched cyclo-
heptane synthons via [413] asymmetric cycloadditions
4Fig. 2). The ®rst reference to the use of chiral substrates
in [413] cycloadditions is due to Hoffmann5 who published
in 1988 an example of diastereoselective cycloaddition
using pinofuran as a chiral diene. In 1996, Lautens6
published a study on the induction of asymmetry in the
[413] cycloaddition reactions by using furfural derived
substrates such as chiral 2-41-hydroxy-1-alkyl)-furans. In
1997, Kende7 published his work on the enantioselectivity
of [413] cycloadditions induced by chiral 2-amino-allyl
cations. The ®rst mention of asymmetric induction in
[413] cycloaddition reaction using chiral acetals was
made by Harmata in 1997.8a In 1998, Hoffmann8b published
the ®rst of a series of works dealing with the asymmetry
induction in the [413] cycloaddition reaction by using
2-trialkylsilyloxy-1-alkoxy-allyl cations that have at C1 a
chiral alkoxy group. Finally, in 2001, Hsung9 published his
work on the use of chiral epoxyallenes as precursors of
chiral nitrogen-substituted oxyallyl cations and its use in
enantioselective [413] cycloadditions 4Fig. 2).
of different nature, depending on the synthetic necessi-
ties, which makes the approach versatile.
4b) The use of C2-functionalized furans results in the
formation of cycloadducts having a doubly functionalized
bridgehead, which facilitates the opening of the oxygen
bridge to afford 3,6-difunctionalized cycloheptanes with
controlled and de®ned relative stereochemistry 4Fig. 2).
This fact also facilitates the removal and recycling of the
chiral auxiliary.
4c) Our previous experience in the reactivity of achiral
C2-substituted furans10 allowed us to select the most
adequate diene as substrate in order to get the highest
cis/trans and endo/exo diastereoselectivities, in such a
way that we could obtain almost stereospeci®cally the
cis-endo diastereoisomeric cycloadducts. This facilitates
the study of the p-facial diastereoselectivity 4`enantio-
selectivity' after removal of the chiral auxiliary) because
it reduces the number of formed stereoisomers from eight
to two.
4d) This methodology allows working with both enantio-
mers of the chiral auxiliary in order to get stereo-
selectively one or other of the p-facial diastereomeric
cycloadducts.
On the basis of these precedents, we planned the study of the
induction of asymmetry in the [413] cycloaddition reaction
by using chiral furan derivatives. We introduced on C2 of
the furan ring a chiral substituent 4in most cases an easily
removable chiral auxiliary). We thought this alternative to
be promising due to the excellent diastereoselectivity
obtained by us in previous work on [413] cycloaddition
reactions of achiral C2-functionalized furans.10
2. Results and discussion
In the present work, we have synthesized and used as diene
substrates in [413] cycloaddition reactions 13 chiral
C2-functionalized furans, in order to study the in¯uence
of the distance between the reactive center, C2, of the
furan and the closest stereocenter from the chiral auxiliary.
In addition, the in¯uence on the stereoselectivity of the
nature of the organic function acting as a linker of the
furan and the chiral auxiliary was also studied 4Fig. 4).
This approach has, a priori, several advantages with respect
to other possible methodologies to induce enantioselectivity
in this reaction 4Fig. 3):
4a) First of all, the insertion of the chiral group to the
diene allows, without restrictions, the use of a wide
range of methodologies1,11 to generate oxyallyl cations
When achiral C2 substituted furans10 are used, it is possible
Figure 3. Advantages of the model of induction of asymmetry in the [413] cycloaddition reactions by using C2-functionalized furans.

A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
4771
to form up to four cycloadducts as racemic diastereo-
isomers, resulting from the coupling with a symmetrically
substituted oxyallyl cation. When using chiral furans, it is
possible to obtain up to eight diastereomeric cycloadducts
4Fig. 5), due to both faces of the chiral furan are diastereo-
topic 4Fig. 4).
Figure 4. Model of a chiral C2 functionalized furan 4the notation of the
faces depends on the CIP rules in each case).
2.1. In¯uence of the nature of furan dienes on the
stereoselectivity
We have synthesized 13 chiral furans by insertion of a chiral
group on C2 4Fig. 6). The design and selection of these
Figure 5. The eight possible diastereomers from the cycloaddition reaction between a symmetrically substituted oxyallyl cation and a C2-substituted chiral
furan.
Figure 6. Chiral furan derivatives prepared in the present work.

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A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
Figure 7. [413] Cycloaddition reaction of chiral furans under Hoffmann methodology.
chiral groups was based on the following criteria in order to
analyze their in¯uence on the stereodifferentiation of the
furan faces: 4a) the distance between the insertion and
reactive center of the furan derivative and the closest stereo-
center of the chiral auxiliary 4Fig. 4); 4b) the volume and
shape of the auxiliary; 4c) the stereoelectronic nature of the
organic function that acts as a linker between the furan ring
and the auxiliary, considering the geometry and the confor-
mational freedom that this function gives to the linker.
furans or for furans attached to chiral heteroatoms like in
the case of chiral sulfoxides 4Fig. 6).
2.2. Cycloaddition methodologies
Initially we used the cycloaddition methodology based on
the generation of the 2-oxyallyl cation by reduction of 2,4-
dibromo-3-pentanone with copper, in the presence of
sodium iodide, which was described by Hoffmann12
4Fig. 9). In previous studies,10 under these conditions, we
obtained high cis/trans and endo/exo diastereoselectivities.
The high cis stereoselectivity could be interpreted on the
basis of both the preferential adoption of the `W' con®gura-
tion by the oxyallyl cation and the concerted mechanism of
the cycloaddition reaction. The almost exclusive formation
of the endo isomers could be due to both the preferential
compact 4versus extended) approach and the adequate
design of the group attached to C2 of the furan substrates.10
Therefore, under these experimental conditions, it was
possible to get the cis-endo cycloadducts, almost stereo-
speci®cally.
The H±C2 of furan is easily removed by a strong base
4usually BuLi), which facilitates the preparation of these
C2 functionalized furans by attack of the resulting furyl
lithium on an electrophilic center of a chiral auxiliary
precursor. In most of the cases, we obtained these furan
derivatives in enantiopure form, however, in some experi-
ments, racemic furan derivatives were used due to the avail-
ability and low cost of racemic precursors. This fact does
not distort the study of the stereodifferentiation of both faces
of the diene by the chiral group 4p-facial diastereo-
selectivity), but only leads to the formation of the different
diastereoisomeric products in racemic form. On the other
hand, the values of p-facial diastereoselectivity detected by
usual non-chiroptical techniques are identical for both
enantiomers of the chiral auxiliary.
Because the aforementioned Hoffmann methodology
implies the use of strong and energetic reaction conditions,
we designed a new methodology that requires milder
reaction conditions,13 with the intention of raising both the
yield, by decreasing the formation of byproducts, and the
p-facial diastereoselectivity, by decreasing the conforma-
tional freedom of the reactants. In this new methodology,
we generated the oxyallyl cation by reduction of 2,4-diiodo-
3-pentanone with zinc±copper couple at lower temperatures
under ultrasound sonication.
One of the reasons to use C2-functionalized furans as
substrates is the possibility to open, in an easy and selective
manner, the oxygen bridge of the cycloadducts. Further, in
our study of the asymmetric induction, it is of interest to
analyze the effect of the distance between the ®rst stereo-
center of the chiral auxiliary and the reactive center, C2, of
the furan derivatives on the stereochemical outcome of the
[413] cycloaddition reaction. In the case of one-bond
distance, the atom directly attached to C2 of furan should
be a stereocenter. This is only possible for C2-alkylated
2.2.1. Diastereoselectivity under the Hoffmann metho-
dology. We have carried out cycloaddition reactions of 13
chiral furans 4Fig. 6) under the Hoffmann conditions 4Fig. 7)
Table 1. Results from the [413] cycloaddition reactions of chiral furans using Hoffmann methodology
Entry
Diene
Cycloadduct
Conversion 4%)
Yield 4%)
DSa cis/trans 4%)
DSa endo/exo 4%)
DSa p-facial 4%)
1
2
3
4
5
6
7
8
6
11
2
3
4
5
6
7
9
1
66
97
100
9687
92
97
83
80
66
69
60
57
55
54
74
66
100:0
100:0
100:0
97:3
89:11
95:5
94:6
51:49
50:50
49:51
1
1
1
20
21
22
23
7
8
9
100:0
76100:0
12
48:52
95:5
47:53
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
49:51
45:55
54:46
37:63
63:37
63:37
46:54
73:27
42
80
53
66
9
3
24
10
11
12
13
11
1
1
25
2
4
5
26
27
28
70
38
1
51b
a
DS: Diastereoselectivity.
Partially reduced to sul®de.
b

A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
4773
whose results are quoted in Table 1. We have chosen several
linking functions to attach the chiral auxiliary to C2 of
furan: carbonate, ester, thioether, sulfoxide and cycloalkyl
linkers. On the other hand, we have studied the in¯uence on
the p-facial diastereoselectivity of one to four bonds
distance between C2 of furan and the ®rst stereocenter of
the chiral auxiliary.
with the compact approach due to the presence of a bulky
group on C2 of the diene.
The observed p-facial diastereoselectivity could be ration-
alized on the basis of four factors: 4a) the distance from C2
offuran to the ®rst stereocenter of the chiral auxiliary, 4b) the
nature of the linker 4type of organic function), 4c) the size
and shape of the chiral auxiliary and 4d) the conformational
freedom of both the linker and the auxiliary group.
Table 1 shows that the yields are good in most cases. This
parameter has a direct relationship with the stereoelectronic
nature of the C2 substituent of furan. These results are
consistent with the empirical rules established on the basis
of our previous work:10 electron-donating groups 4entries
1±5 and 8) show the best results, followed by the cycloalkyl
derivatives 4entries 9±12). The furans having electron-with-
drawing groups, due to the negative inductive effect on the
furan ring, afford lower yields 4entry 7). These trends are
obviously modulated by the steric interactions of the sub-
stituents. Therefore, bulky groups hamper the approach of
the dienophile, decreasing the conversion of furans and the
yield of cycloadducts.
With respect to the effect of the distance on the stereo-
differentiation on the faces of the furan ring, we can observe
in Table 1 that for long distances the p-facial diastereo-
selectivity is low or null 4see entries 1±6, corresponding
to 4 or 3 bonds distance). Even though these results could
be expected we designed these `long distance' chiral dienes
in order to account for the possible dipolar interactions and
the formation of hydrogen bonds.
When the chiral auxiliary is separated from the furan by one
or two bonds 4see entries 9±12 and 8, respectively) the
p-facial diastereoselectivity increases. The relation between
the distance and the p-facial diastereoselectivity is not
linear and it depends on other factors as it is commented
below 4compare, for example, entries 9±11 from Table 2).
One effect that should be analyzed is the in¯uence of the
volume and shape of the groups attached to the closest
stereocenter 4Cp). This effect is more important when the
C2±Cp distance is shorter. Thus, when there is only one
bond distance, the increase of the size of substituents
attached to the stereocenter, Cp, raises the p-facial dia-
stereoselectivity 4compare entries 11 and 12). For long
distances, this substitution effect could be observed but to
a lesser extent: compare the different furyl esters from
entries 2±6or the three derivatives of 2-furyl-cyclohexanol
4entries 10 and 11 versus 9). Finally, another remarkable
effect to consider is the nature of the linking function.
Thus, comparing entries 2±7 from Table 2, we can observe
With respect to the cis/trans diastereoselectivity, it is
possible to observe that, independent of the structure of
the furan derivative, all obtained cycloadducts have a rela-
tive cis con®guration for the methyl groups attached to C2
and C4. This could be the consequence of the W con®gura-
tion adopted by the oxyallyl cation, which depends on the
reaction conditions and on the nature of the substituents of
the oxyallyl cation. In relation to the endo±exo diastereo-
selectivity, the results quoted in Table 2 con®rm the empiri-
cal rule observed in our previous work10 that establishes a
direct relationship between the size and bulkiness of the C2
substituent of furan and the endo/exo ratio of the diastereo-
isomeric cycloadducts. Thus, we observed the almost exclu-
sive formation of the endo diastereoisomer. This result
could be due to the fact that the extended approach leading
to the formation of the exo product is destabilized in relation
Table 2. Results from the [413] cycloaddition reactions using mild modi®ed reaction conditions
Entry
Diene
Xa
Mb
Th
Energy sourced
Conv. 4%)
Yield 4%)
DSe cis/trans 4%)
DSe endo/exo 4%)
DSe p-facial 4%)
1f
2
7
7
7
7
Br
I
I
Br
Br
I
Br
I
I
Br
I
Br
Br
Br
Br
I
Cu
Zn
Zn
Cu
Cu
Cu
Cu
Cu
Zn
Cu
Cu
Cu
Zn
Cu
Zn
Zn
Zn
60
0
20
20
60
0
60
0
0
HMS
HMS
HMS
HMS
HMS
US
HMS
US
US
83
41
60
50
66
55
69
37
56100
60
32
57
40
55
45
36100
47
42
100
100
100
53
100
66
85
100:0
70
100
38
100
51
100
100:0
100
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
45:55
45:55
45:55
45:55
37:63
37:63
63:37
65:35
3
4
5f
13
13
11
11
11
12
12
14
14
15
15
15
15
6
7f
8
9
5:35
6
10f
11
12f
13
14f
15
16
17
60
0
HMS
US
100:0
100:0
100:0
100:0
100:0
100:0
63:37
65:35
46:54
46:54
73:27
75:25
60
20
60
20
0
HMS
HMS
HMS
HMS
US
77:23
I
20
US
100:0
76:24
a
Dihaloketone 4Fig. 10).
Reducing metal.
Inner temperature.
b
c
d
e
f
Energy source: HMSˆheating and/or magnetic stirring. USˆultrasound.
DS: Diastereoselectivity.
Hoffmann conditions.

4774
A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
that placing the ester function conjugated to the furan ring,
we restrict the conformational freedom of the system and
the diastereoselectivity raises 4up to 10%) with respect to
that of the ester functions non-conjugated to the aromatic
ring. The high conformational freedom is the responsible of
the observed medium to low p-facial diastereoselectivity,
which reaches in the most favorable case a value of
d.e.ˆ46%.
selectivity avoiding polymerization reactions of the oxyallyl
cation, electrophilic additions to the furan ring or partial
reductions of the cycloadducts. However, the conversion
of the furan substrates for a given reaction time is lower
than in the case of using the Hoffmann reaction conditions.
As in the case of the experiments carried out under the
Hoffmann reaction conditions 4Table 1), we obtained, with
the new milder conditions 4Table 2), complete cis/trans and
endo/exo diastereoselectivities, which con®rms that the
oxyallyl cations generated by both procedures adopts a
preferential W con®guration and that the process goes
through a concerted mechanism. With respect to the
p-facial diastereoselectivity, we observe a slight increase
in the stereodifferentiation of the furan faces in the case of
dienes 11, 12 and 15, while in the case of furans 7, 13 and 14
the p-facial diastereoselectivity is the same than that
observed in the experiments carried out under Hoffmann
conditions. This small improvement of 2±3% in the p-facial
diastereoselectivity could be interpreted on the basis of the
lower reaction temperature 4from 60 to 0±208C) that
reduces the conformational freedom at the level of the chiral
auxiliary. This allows a better stereodifferentiation of the
furan faces and it facilitates the approach of the oxyallyl
cation by the less hindered face of the furan ring.
The experiment involving the 2-4p-tolylsul®nyl)-furan
requires special mention. Under the Hoffmann experimental
conditions, it affords a higher diastereoselectivity than other
furans 4entry 13). However, the resulting cycloadducts
undergo a partial reduction 4up to 49%) of the sulfoxide
group to thioether, under the aforementioned conditions. It
is worth noting that the reduction of the sulfoxide group
takes place on the cycloadduct once it is formed and not
on the furan precursor, which has been demonstrated by
submitting 2-4p-tolylsul®nyl)-furan to the same reaction
conditions without the presence of 2,4-dibromo-3-penta-
none 4precursor of the 2-oxyallyl cation). In such cases,
the furan derivative remained unchanged after several
hours of reaction time. We can rationalize this result by
assuming a stabilizing resonance effect between the
sulfoxide group and the aromatic furan ring.
2.2.2. Study of the induction of asymmetry in the
cycloaddition reaction under mild modi®ed conditions.
Due to the high conformational freedom of furan derivatives
at the reaction temperature of the previous experiments and
the problem of partial reduction of the cycloadducts 4in the
case of sulfoxide group), we designed new experimental
conditions,13 4Fig. 8) based on the use of 2,4-diiodo-3-penta-
none, as precursor of the 1,3-dimethyl-2-oxy-allyl cation
and Zn or Zn±Cu couple as reducing agents, at lower
temperatures 40±208C), under ultrasound or magnetic
stirring. Under these new reaction conditions, we tried
those chiral furan derivatives that showed promising stereo-
differentiating properties under the Hoffmann reaction
conditions. In Table 2 we have showed, on a comparative
way, the experiments carried out under both reaction con-
ditions, the Hoffmann's and the new milder ones, and their
corresponding results 4yield and diastereoselectivities: cis/
trans, endo/exo and p-facial).
2.3. Assignment of the relative stereochemistry of
cycloadducts
When using a symmetric oxyallyl cation and a chiral furan
as diene, it is possible to obtain up to eight diastereoisomers
4homochiral if an enantiopure diene is used or racemic if the
diene is also racemic. See Fig. 5). The differentiation and
characterization of these diastereoisomers was carried out
by comparative analysis and correlation of their NMR spec-
tra obtained from samples of pure diastereoisomers or from
mixtures 4in different ratios) of them, when they were non-
separable by conventional methods. For this purpose, we
followed next protocol:14
1
4a) Unequivocal assignment of the H and 13C NMR
signals by 1D and 2D NMR experiments 4DEPT,
COSY 1H±1H, HETCOR 1H±13C, HMQC, HMBC,
TOCSY, etc.).
4b) Conformational analysis by MM3 computational
methods in order to ®nd the minimum energy conforma-
tion of each diastereoisomer.
4c) Comparative study of the NMR data from all
diastereomers. Analysis of signi®cant differences and
correlation studies.
Looking at Table 2 it is possible to observe that when using
the new experimental conditions, the yield is always higher
than that obtained by using the more energetic Hoffmann
reaction conditions 4entries in italics). The yield becomes
quantitative when NaI is not used as initiator. The higher
observed yields when using lower temperature in the
absence of NaI could be due to the increase in chemical
4d) Study of the con®guration-dependent stereoelectronic
effects responsible of signi®cant and diagnostic DJ 4Hz)
Figure 8. [413] Cycloaddition reaction under the mild modi®ed conditions.

A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
4775
Figure 9. endo Stereoselectivity in the [413] cycloaddition reactions of chiral furans 11±13.
and Dd 4ppm) among diastereomers in their minimum-
energy conformations.
on the nature of the chiral auxiliary. Thus, it is possible to
distinguish two cases:
4e) Assignment of the relative stereochemistry that should
have a consistency with all data and observations from
the previous studies.
4a) Cycloadducts with a chiral center far away from the
oxabicyclic system. In this case, the stereoelectronic
interaction of the chirality-inducing group with the rest
of the molecule is very low and the shielding and
deshielding effects are very dif®cult to rationalize. For
this reason, in many of these cases, it was not possible
to do the assignment of the stereochemistry 4i.e. endo
45R) or endo 45S)) of the cycloadducts. In these cases,
the endo diastereoisomers are identi®ed as endo A and
endo B 4without using the CIP notation). The notation A,
B corresponds to the order of elution of both diastereo-
isomers in gas chromatography 4Rt endo A,Rt endo B).
4b) Cycloadducts with a chiral center close to the oxa-
bicyclic system and with bulky groups near the ®rst
stereocenter 4products 24±28). In this case, it is possible
that the stereochemical assignment of each model
because the interaction of the auxiliary with the oxa-
bicyclic moiety of the molecule is more intense, which
allows a more reliable interpretation of the shielding and
deshielding effects in NMR spectra. On the other hand,
the conformational freedom is lower, in such a way that
the aforementioned effects could be rationalized on the
basis of the most stable conformation of one or other of
both `p-facial' diastereoisomers. These diastereoisomers
are named in this work as endo 45R) or endo 45S) depend-
ing upon the stereochemistry postulated in each case.
These are tentative reasonable assignments of the con-
®guration, which should be con®rmed by X-ray diffrac-
tion analyses when reliable crystals became available.
Up to this point, we were only able to establish the relative
stereochemistry. In most cases, we worked with enantiopure
chiral auxiliaries, and we should be able to determine the
absolute stereochemistry 4because we have as a stereo-
chemical marker the inserted chiral auxiliary of known
absolute stereochemistry). However, it was not possible to
get crystals suitable for X-ray diffraction studies.
The assignment of the relative cis/trans and endo/exo
stereochemistry was possible by the analysis of the
in¯uence exerted on the chemical shifts d 4ppm) by the
stereoelectronic effects 4coulomb interactions, shielding
and deshielding effects) among the substituents of the oxabi-
cycle,14 which is facilitated by the conformational rigidity of
the bicyclic system. These assignments are corroborated by
the comparative analysis of the coupling patterns between
vicinal hydrogens on all formed diastereoisomers. This
model of assignment has proven to be of general applica-
bility to all studied cycloadducts, irrespective of the nature
of the chiral auxiliary, because the in¯uence that the
auxiliary has on the chemical shifts of the hydrogens and
carbon atoms of the oxabicyclic moiety is very low
compared to the in¯uence among the atoms and other
substituents of the oxabicycle itself.
The assignment of stereochemistry to the diastereoisomers
4for example: endo 45R,10S) and endo 45S,10S)) resulting
from the attack through both faces of the furan ring 4p-facial
diastereoselectivity) cannot be carried out on the basis of a
unique model of general applicability. Each case should be
individually studied, because the variations of the chemicals
shifts of the involved hydrogens and carbon atoms depend
In the case of cycloadducts 24±26 derived from the trans-
cyclohexyloxy-furans 411±13), an exhaustive correlation
study of their spectroscopic properties and also molecular
modeling studies,15 based on MM3 computational methods,
permitted us to postulate that the diene±dienophile
Figure 10. endo Stereoselectivity in the [413] cycloaddition reaction of chiral furan 15.

4776
A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
approach takes place preferment by the C24Si) face of the
chiral furan derivative, through late transition states
4resembling the products). Thus, we obtained the stereo-
isomer endo 45Rp,10S) as the major one and the endo
45Sp,10S) as the minor one 4Fig. 9).
nitrile and propionitrile were distilled under nitrogen from
CaH2. Infrared spectra were recorded on a FT-IR NICOLET
510 spectrophotometer as thin ®lms or as solutions. NMR
spectra were carried out in deuterated chloroform at
200 MHz 4GEMINI-200), 300 MHz 4UNITY-300) and/or
500 MHz 4UNITY-500) for 1H NMR, and at 50 and
1
The NMR analysis of the cycloadducts derived from 2-4p-
tolylsul®nyl)-furan indicates the preferential approach
between the furan and the oxyallyl cation takes place by
the C24Re) face 4same face than in the previous case, but
the notation changes according to the CIP rules), leading to
the endo 45R,SS) diastereoisomer as the major one and to the
cycloadduct endo 45S,SS) as the minor one 4Fig. 10).
75.43 MHz for 13C NMR. For H NMR, tetramethylsilane
was used as internal standard. 13C NMR spectra were refer-
enced to the d 77.0 ppm resonance of chloroform. Mass
spectra were measured on a HEWLETT±PACKARD
5890 mass spectrometer using electron impact or/and
chemical ionization. Melting points were measured on a
GALLENKAMP equipment. GC analyses were performed
on HP-8790 gas chromatograph equipped with
a
HEWLETT±PACKARD cross-linked MePh±silicone
capillary column 4Lˆ25 m, Bˆ0.2 mm, qˆ0.25 mm)
using Helium as a carrier gas and a FID detector
4Tˆ2508C, Pressure 4H2)ˆ4.2 psi, Pressure 4air)ˆ2.1 psi).
GC analyses were carried out under different temperature/
time conditions, indicated at each compound as: initial
temperature 48C), initial time 4min), rate 48C/min), ®nal
temperature 48C), ®nal time 4min). Elementary analyses
were obtained with a FISIONS Na 1500 apparatus, analyz-
ing combustion gases by gas chromatography and using a
thermal conductivity detector. The optical activity analyses
were carried out on a PERKIN±ELMER 241 MC polari-
meter, at room temperature.
3. Conclusions
The results obtained from the experiments carried out
following both cycloaddition methodologies 4Hoffmann's
and the milder modi®ed one) allowed us to draw interesting
conclusions that represent a ®rst step in the induction of
asymmetry in the [413] cycloaddition reactions mediated
by chiral C2-functionalized furans. We have obtained in this
work excellent cis/trans and endo/exo diastereoselectivities
and from null to moderate 4d.e.ˆ30% from furans 11±13) or
promising 4d.e.ˆ54% in the case of furan 15) p-facial dia-
stereoselectivities. In addition, we have opened the possi-
bility, by designing the chiral auxiliary, of obtaining an
oxabicycle with endo 45R) or endo 45S) stereochemistry.
4.2. Synthesis of chiral furan derivatives
In addition, we observed that both, the length and functional
nature of the linker between the furan ring and the chiral
auxiliary and, the bulkiness, substitution pattern and shape
of the auxiliary group itself have high in¯uence on the
p-facial diastereoselectivity and a very low in¯uence on
the cis/trans and endo/exo diastereoselectivities. At the
same time, we appreciated the in¯uence of the conforma-
tional freedom of the diene-chiral auxiliary system on the
p-facial diastereoselectivity, effect that has important
consequences at low temperature.
4.2.1.
hexyloxy)-carbonyloxy]furan,16
ꢀ10R,20S,50R)-2-[ꢀ2-Isopropyl-5-methyl-1-cyclo-
ꢀ1). Under argon
atmosphere and at 2238C, g-crotonolactone 4388 mg,
4.57 mmol) was dissolved in dry acetonitrile 41 mL).
Then, at this temperature, freshly distilled 4from potassium
hydroxide) triethylamine 4554 mg, 5.48 mmol) was added.
The color of the reaction mixture changed from white to
pale red, then, a solution of 42)-menthyl-chloroformiate
41 g, 4.57 mmol) in dry acetonitrile 44 mL) was added drop-
wise. The reaction mixture was kept at 08C for 1 h, and then
it was stirred for additional 14 h at room temperature. The
product was isolated by distilling off the solvent and by
suspending the residue in dry diethyl ether 425 mL) and
®ltering out the formed NEt3H1Cl2. The organic layer
was washed with water 43£50 mL) and brine 41£50 mL),
dried over anh. MgSO4, ®ltered and concentrated to dryness.
The product was puri®ed by distillation under 8 mmHg and
at a temperature between 150 and 2008C, on a Kugelrohr
Now, we are actively working in our laboratory in order to
improve the conversion of substrates and the p-facial dia-
stereoselectivity in the [413] cycloaddition reactions of
chiral C2-functionalized furans on two fronts: 4a) working
at very low temperatures but using high frequency ultra-
sound as an energy source; 4b) modifying the structure of
the chiral auxiliary and the nature of the linker in order to
decrease the conformational freedom of the system. Simul-
taneously, we are trying to optimize the isolation and puri-
®cation methods of cycloadducts and to obtain crystals of
cycloadducts suitable for X-ray analysis.
apparatus, affording 1.032 g of
a
colorless oil
4Conv.ˆ100%, Yieldˆ64%). IR 4®lm, n, cm21): 2960,
2940, 2920, 1740 4CvO, st), 1600, 1570, 1410, 1210,
1
1160. H NMR 4200 MHz, CDCl3, d, ppm): 0.82 43H, d,
Jˆ6.9 Hz, H100), 0.92 43H, d, Jˆ7 Hz, H80 or H90), 0.94
43H, d, Jˆ6.4 Hz, H80 or H90), 1.15±1.25 42H, m, 1H30 and
1H60), 1.42±1.47 42H, m, H70 and H20), 1.68±1.72 42H, m,
H30 and H40), 1.95±2.04 41H, m, H50), 2.12±2.17 41H, m,
1H60), 4.61 41H, dt, J1ˆ10.8 Hz, J2ˆ4.5 Hz, H10), 5.87 41H,
dd, J1ˆ3.3 Hz, J2ˆ1.1 Hz, H3), 6.35 41H, dd, J1ˆ2.1 Hz,
J2ˆ3.4 Hz, H4), 7.05 41H, dd, J1ˆ2.2 Hz, J2ˆ1.1 Hz, H5).
13C NMR 450 MHz, CDCl3, d, ppm): 16.7 4C100), 20.6
and 22.0 4C90 and C80), 23.2 4C30), 26.1 4C500), 31.2 4C70),
33.9 4C40), 40.2 4C60), 46.8 4C20), 80.64C1 ), 92.0 4C3),
111.5 4C4), 136.6 4C5), 151.1 4CO3), 151.2 4C2). MS
4. Experimental
4.1. General methods
Unless otherwise noted, all reactions were conducted under
an atmosphere of dry argon in oven-dried glassware. All
solvents were puri®ed before use: ether, tetrahydrofuran,
benzene, hexane and pentane were distilled under nitrogen
from sodium/benzophenone. Methylene chloride, aceto-

A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
4777
[GC±MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]: 301 410,
M1N2H7), 285 418, M111NH4), 284 4100, M1NH4).
Anal. calcd for C15H22O4: C, 67.63; H, 8.33. Found: C,
45, M1NH4±C4H3O1), 103 47, M2C4H3O1), 102 4100).
Anal. calcd for C8H10O4: C, 56.47; H, 5.92. Found: C,
56.38; H, 6.01%. GC 41008C, 1 min, 108C/min, 2508C,
1 min): Rtˆ5.74 min. TLC 4SiO2, hexane/ethyl acetate,
1:1): Rfˆ0.72.
23
67.49; H, 8.51%. [a]D ˆ243.2 4cˆ1.5, CHCl3). GC
41008C, 1 min, 108C/min, 2508C, 1 min): Rtˆ14.4 min.
TLC 4SiO2, hexane/ethyl acetate, 1:1): Rfˆ0.58.
4.3.3. ꢀ^)-2-Furyl 2-phenoxy-propanoate ꢀ4). The ester 4
was prepared following the previously described procedure,
starting from 4^)-2-phenoxypropanoyl chloride 4140 mg,
0.76mmol). The crude product was puri®ed by ball-to-
ball distillation, resulting in a colorless oil 4111 mg)
4Yieldˆ13%, Conv.ˆ100%). The low yield was due to a
partial thermal decomposition of the product during distilla-
tion. IR 4®lm, n, cm21): 3080, 2995, 2940, 1770 4CvO, st),
4.3. Synthesis of 2-furyl esters17
At 2238C and under argon atmosphere, g-crotonolactone
41 equiv.) was dissolved in dry acetonitrile 41 mL, distilled
from calcium hydride). Then, triethylamine 41.2 equiv.,
freshly distilled from potassium hydroxide) was added.
The mixture turned into a pale red color, then, a solution
of the acid chloride derivative 41 equiv., synthesized accord-
ing to the literature18), in dry acetonitrile, was added drop-
wise under ef®cient magnetic stirring. The reaction mixture
was maintained at 08C for 1 h, and then was stirred at room
temperature, until constant conversion. The crude mixture
was concentrated to dryness in a rotary evaporator, without
heating. Diethyl ether was added 425 mL) and the resulting
suspension ®ltered to remove NEt3H1Cl2. The organic
solution was washed with water 43£50 mL) and brine
41£50 mL), dried over anh. MgSO4 and concentrated to
dryness without heating. The product was puri®ed by distil-
lation in a Kugelrohr apparatus, under the conditions
adequate for each compound.
1
1600 4CvC, st), 1490, 1380, 1240, 1094, 970, 825. H
NMR 4200 MHz, CDCl3, d, ppm): 1.7643H, d, Jˆ6.7 Hz,
H3), 4.92 41H, q, Jˆ6.7 Hz, H2), 5.92 41H, dd, J1ˆ1.4 Hz,
J2ˆ2.3 Hz, H30), 6.36 41H, dd, J1ˆ2.3 Hz, J2ˆ2.4 Hz, H40),
6.85±6.95 43H, m, H200, H40 and H60), 7.15±7.30 42H, m,
H300 and H500), 7.35 41H, dd, J1ˆ2.4 Hz, J2ˆ1.4 Hz, H50).
13C NMR 450 MHz, CDCl3, d, ppm): 14.9 4C3), 78.3 4C2),
109 4C30, C40), 114.8 4C200, C600), 118.9 4C400), 129.4 4C300,
C500), 142.7 4C20, C50), 158.3 4C100), 170.1 4C1). MS [DIP-
EI, 70 eV, 1508C, m/z, 4%)]: 232 429, M), 165 424,
M2C4H3O), 149 425, M2C4H3O2), 155 451, M2C6H5),
83 4100, C4H3O21). Anal. calcd for C13H12O4: C, 67.23;
H, 5.21. Found: C, 67.30; H, 5.42%. GC 41008C, 1 min,
108C/min, 2508C, 1 min): Rtˆ21.1 min. TLC 4SiO2, hexane/
ethyl acetate, 1:1): Rfˆ0.6.
4.3.1. ꢀS)-2-Furyl 2-methyl-butanoate ꢀ2). Colorless oil
synthesized following the procedure described above, start-
ing from 4S)-2-methyl-butanoyl chloride 4432 mg,
3.58 mmol) and obtaining 168 mg 4Yieldˆ11%,
Conv.ˆ73%). IR 4®lm, n, cm21): 3160, 2973, 2940, 2880,
1780 4CvO, st), 1645, 1512, 1462, 1388, 1238, 1202, 1171,
1086, 1038. 1H NMR 4200 MHz, CDCl3, d, ppm): 0.97 43H,
t, Jˆ7.4 Hz, H4), 1.21 43H, d, Jˆ7 Hz, H5), 1.56±1.86 42H,
m, H3), 2.48 41H, dq, J1ˆ6.9 Hz, J2ˆ7 Hz, H2), 5.8641H,
dd, J1ˆ1.0 Hz, J2ˆ3.3 Hz, H30), 6.35 41H, dd, J1ˆ2.2 Hz,
J2ˆ3.3 Hz, H40), 7.05 41H, dd, J1ˆ2.2 Hz, J2ˆ1.0 Hz, H50).
13C NMR 450 MHz, CDCl3, d, ppm): 11.8 4C4), 16.3 4C5),
4.3.4. 2-Furyl ꢀS)-2-ꢀ4-isobutyl-1-phenyl)-propanoate
ꢀ5). It was prepared following the general procedure
described above, starting from 4S)-2-44-isobutyl-1-phenyl)-
propanoyl chloride 4950 mg, 4.01 mmol) obtaining 835 mg
of a crude oily product that was puri®ed by ball-to-ball
distillation 4Yieldˆ42%, Conv.ˆ100%). Distillation should
be carried out under very low pressure to avoid the thermal
decomposition of the product. IR 4®lm, n, cm21): 2956,
2927, 1775 4CvO, st), 1604, 1512, 1466, 1383, 1238,
1
1063, 1034, 1018. H NMR 4200 MHz, CDCl3, d, ppm):
0.9 46H, d, Jˆ6.6 Hz, H300 and H400), 1.59 43H, d,
Jˆ7.4 Hz, H3), 1.80±1.88 42H, m, H200), 2.45 42H, d,
Jˆ7.2 Hz, H100), 3.84 41H, q, Jˆ7 Hz, H2), 5.84 41H, d,
Jˆ3.4 Hz, H3000), 6.34 41H, dd, J1ˆ5.6Hz, J2ˆ3.4 Hz,
H4000), 7.02±7.10 43H, m, H30, H50 and H5000), 7.20±7.25
42H, m, H20 and H60). 13C NMR 450 MHz, CDCl3, d,
ppm): 16.5 4C3), 21.4 4C300, C400), 30.1 4C200), 38.9 4C2),
44.3 4C100), 109.3 4C3000, C4000), 128.7 4C20, C60), 129.8 4C30,
C50), 131.5 4C10), 140.2 4C40), 143.8 4C2000, C5000), 170.6
4C1). MS [DIP-EI, 70 eV, 1508C, m/z, 4%)]:273 41, M),
20644, M 2C4H3O), 161 424, M2111). Anal. calcd for
C17H20O3: C, 74.97; H, 7.40. Found: C, 74.89; H, 7.35%.
GC 41008C, 1 min, 108C/min, 2508C, 1 min): Rtˆ16.0 min.
TLC 4SiO2, hexane/ethyl acetate, 1:1): Rfˆ0.68.
0
26.64C3), 41.3 4C2), 92.64C3 0), 111.64C4 ), 135.7 4C50),
159.5 4C20), 173.0 4C1). MS [GC±MS4CI), NH3, 70 eV,
1508C, m/z, 4%)]: 221 49, M1N3H11), 204 445, M1N2H8),
186414, M 1NH4), 169 41, M11). Anal. calcd for C9H12O3:
C, 64.27; H, 7.19. Found: C, 64.11; H, 7.25%. GC 41008C,
1 min, 108C/min, 2508C, 1 min): Rtˆ5.76min. TLC 4SiO 2,
hexane/ethyl acetate, 1:1): Rfˆ0.66.
4.3.2. ꢀR)-2-Furyl 2-methoxy-propanoate ꢀ3). It was
synthesized following the aforementioned procedure, from
4S)-2-methoxypropanoyl chloride 4915 mg, 7.47 mmol),
obtaining the product as
a colorless oil 4230 mg,
Yieldˆ18%, Conv.ˆ68%). IR 4®lm, n, cm21): 3158,
3138, 2992, 2940, 2834, 1779 4CvO, st), 1611 4CvC,
st), 1512, 1485, 1458, 1385, 1238, 1157, 1124, 1094,
1
4.3.5. 2-Furyl ꢀ1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabi-
cyclo[2.2.1]heptane-1-carboxilate ꢀ6). It was prepared
following the aforementioned general procedure, starting
from commercially available 41S)-camphanic chloride
4483 mg, 2.23 mmol), obtaining 383 mg of the product, as
a colorless oil 4Yieldˆ52%, Conv.ˆ61%). IR 4®lm, n,
cm21): 3160, 2980, 2950, 2890, 1800 4CvO, st), 1750
1061, 1011, 951, 879, 725. H NMR 4200 MHz, CDCl3, d,
ppm): 1.55 43H, t, Jˆ7 Hz, H3), 3.47 43H, s, H4), 4.09 41H,
q, Jˆ7 Hz, H2), 5.93 41H, dd, J1ˆ1.0 Hz, J2ˆ3.1 Hz, H30),
6.36 41H, dd, J1ˆ2.2 Hz, J2ˆ3.2 Hz, H40), 7.0641H, dd,
J1ˆ2.2 Hz, J2ˆ1.0 Hz, H50). 13C NMR 450 MHz, CDCl3,
d, ppm): 18.3 4C3), 57.9 4C4), 75.9 4C2), 92.4 4C30),
111.2 4C40), 135.4 4C50), 150.5 4C20), 169 4C1). MS [GC±
MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]:171 41, M11), 122
1
4CvO, st), 1613, 1510, 1449, 1383, 1227, 1097, 933. H

4778
A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
NMR 4200 MHz, CDCl3, d, ppm): 1.07 43H, s, H9), 1.14
43H, s, H10 or H11), 1.1643H, s, H10 or H11), 1.75±2.52
44H, m, H5 and H6), 5.99 41H, d, Jˆ2.1 Hz, H30), 6.39 41H,
t, Jˆ2.1 Hz, H40), 7.09 41H, d, Jˆ2.1 Hz, H50). 13C NMR
450 MHz, CDCl3, d, ppm): 9.2 4C9), 16.1 and 16.2 4C10 and
C11), 28.4 4C5), 30.2 4C6), 54.3 and 54.4 4C4 and C7), 90.0
4C1), 92.5 4C30), 110.7 4C40), 135.2 4C50), 160.1 4C20),
170.0 4C8), 176.7 4C3). MS [GC±MS4CI), NH3, 70 eV,
1508C, m/z, 4%)]: 299 411, M1N2H7), 282 457, M1NH4),
233 426), 216 4100), 181 411). Anal. calcd for C14H16O5: C,
ture for 13 h. The product was puri®ed by selective
extraction: adding diethyl ether 415 mL) and washing the
organic layer with water 43£30 mL). The organic layer
was concentrated to dryness affording pure product as a
pale yellow oil 4830 mg, Yieldˆ63%, Conv.ˆ80%). IR
4®lm, n, cm21): 3424 4H±O, st), 3110, 2934, 2859, 1540
4CvC, st), 1449, 1358, 1261, 1215, 1150, 1063, 1005, 960,
1
881, 742. H NMR 4200 MHz, CDCl3, d, ppm): 1.21±1.29
44H, m, H5 and H4), 1.61±1.73 42H, m, H3), 2.04±2.13
42H, m, H6), 2.53 41H, td, J1ˆ10.7 Hz, J2ˆ4 Hz, H2),
2.64 41H, br s, OH), 3.25 41H, td, J1ˆ9.8 Hz, J2ˆ4.4 Hz,
H1), 6.41 41H, dd, J1ˆ3.4 Hz, J2ˆ1.8 Hz, H40), 6.59 41H,
dd, J1ˆ3.4 Hz, J2ˆ1 Hz, H30), 7.53 41H, dd, J1ˆ1.8 Hz,
J2ˆ1 Hz, H50). 13C NMR 450 MHz, CDCl3, d, ppm): 24.4
4C5), 26.1 04C4), 32.5 4C3), 33.7 4C6), 56.7 4C2), 72.2 4C1),
23
63.63; H, 6.10. Found: C, 63.58; H, 6.15%. [a]D ˆ218.9
4cˆ0.8, CHCl3). GC 41008C, 1 min, 108C/min, 2508C,
1 min): Rtˆ15.9 min. TLC 4SiO2, hexane/ethyl acetate,
9:1): Rfˆ0.78.
0
0
4.3.6.
ꢀ1S,2R,5S)-1-ꢀ2-Isopropyl-5-methyl)-cyclohexyl
111.64C4 ), 119.64C3 ), 142.64C2 ), 146.2 4C50). MS
[GC±MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]: 233 49, M1
N2H7), 2164100, M 1NH4), 1996431, M 11). Anal. calcd
for C10H14O2S: C, 60.57; H, 7.12; S, 16.17%. Found: C,
60.49; H, 7.05; S, 16.11%. GC 4508C, 1 min, 108C/min,
2508C, 1 min): Rtˆ17.25 min. TLC 4SiO2, hexane/ethyl
acetate, 9:1): Rfˆ0.40.
2-furoate ꢀ7). Under nitrogen atmosphere, 2-furoyl chloride
41.72 g, 14 mmol) and triethylamine 41.1 mL, 8 mmol) were
dissolved in dry tetrahydrofuran 45 mL). Then, a catalytic
amount of DMAP 410 mg) was added at once. A solution of
41)-menthol 41.26g, 8 mmol) in dry tetrahydrofuran
47 mL) was added dropwise at room temperature. The
reaction was magnetically stirred for 7 h, up to constant
conversion by GC analysis. The formed triethylammonium
hydrochloride was separated by ®ltration, and the organic
layer percolated through a short column of aluminum oxide.
The product was ®nally puri®ed by ¯ash column chromato-
graphic 4SiO2, hexane/ethyl acetate), obtaining 1.91 g of a
colorless oil 4Yieldˆ89%, Conv.ˆ100%). IR 4®lm, n,
cm21): 3141, 2956, 2930, 2871, 1721 4CvO, st), 1582,
4.3.8.
ꢀ^)-trans-[2-ꢀ2-Furylthioxy)-1-cyclohexyloxy]
methyl diphenyl silane ꢀ9).20 Under nitrogen atmosphere
and at room temperature, 4^)-trans-2-42-furylthio)-cyclo-
hexan-1-ol 4480 mg, 2.22 mmol) and imidazole 4362 mg,
5.33 mmol) were dissolved in dry dimethylformamide
42 mL). Under stirring and at room temperature, diphenyl-
methylchlorosilane 4623 mg, 2.66 mmol) was added drop-
wise. Then, the reaction mixture was stirred for 1 h and then
water 410 mL) was added at once. The mixture was
extracted with hexane 44£30 mL). The organic layer was
washed with water 420 mL) and brine 420 mL). Finally, it
was dried over anh. Na2SO4 and the solvent evaporated to
dryness, obtaining pure product, as a pale yellow oil
4740 mg, Yieldˆ85%, Conv.ˆ100%). IR 4®lm, n, cm21):
3069, 3030, 2936, 2859, 1653, 1589, 1459, 1368, 1259,
1
1474, 1393, 1231, 1180, 1122, 1011, 960, 883, 764. H
NMR 4200 MHz, CDCl3, d, ppm): 0.8 43H, d, Jˆ7 Hz,
H100), 0.91 43H, d, Jˆ7 Hz, H80 or H90), 0.92 43H, d,
Jˆ6.4 Hz, H80 or H90), 1.08±1.14 42H, m, 1H30 and
0
1H60), 1.49±1.5642H, m, H7 and H20), 1.68±1.74 42H,
0
m, 1H30 and 1H40), 1.90±1.9641H, m, H5 ), 2.03±2.10
41H, m, 1H60), 4.92 41H, dt, J1ˆ10.8 Hz, J2ˆ4.4 Hz,
H10), 6.50 41H, dd, J1ˆ3.4 Hz, J2ˆ1.6Hz, H4), 7.15 41H,
dd, J1ˆ3.6Hz, J2ˆ0.8 Hz, H3), 7.57 41H, dd, J1ˆ1.8 Hz,
J2ˆ0.8 Hz, H5). 13C NMR 450 MHz, CDCl3, d, ppm): 16.4
1
1150, 1119, 1022, 1005, 904, 877. H NMR 4200 MHz,
CDCl3, d, ppm): 0.7 43H, s, Si±CH3.), 1.25±1.55 44H, m,
H5 and H4), 1.45±1.65 42H, m, H3), 1.87±1.96 42H, m,
H6), 2.95 41H, td, J1ˆ8.4 Hz, J2ˆ4 Hz, H2), 3.67 41H, td,
J1ˆ8.4 Hz, J2ˆ4 Hz, H1), 6.32 41H, dd, J1ˆ3.4 Hz,
J2ˆ1.8 Hz, H40), 6.38 41H, dd, J1ˆ3.4 Hz, J2ˆ0.8 Hz,
H30), 7.26±7.38 46H, m, Hmeta, Hpara), 7.44 1H, 4dd,
J1ˆ1.8 Hz, J2ˆ0.8 Hz, H50), 7.55±7.69 44H, m, Hortho).
13C NMR 450 MHz, CDCl3, d, ppm): 22.21 4Si±CH3),
23.3 4C5), 24.64C4), 30.9 4C3), 34.5 4C6), 54.3 4C2), 73.7
4C1), 111.2 4C40), 118.4 4C30), 127.7 4Cmeta), 129.64C para),
133.9 4Cortho), 134.5 4Cipso), 141.5 4C20), 145.5 4C50). MS
[GC±MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]: 429 427,
M1N2H7), 428 473, M1N2H6), 413 427, M1NH4), 412
472, M1NH3), 395 421, M11), 329 422, M), 317 451,
M2Ph), 295 48, C6H8OSiMePh2), 214 433, HOSiMePh2),
181 4100, M2OSiMePh2). Anal. calcd for C23H26O2SSi:
C, 70.01; H, 6.64; S, 8.13. Found: C, 70.12; H, 6.60; S,
8.09%. GC 4508C, 1 min, 108C/min, 2908C, 1 min):
Rtˆ31.3 min. TLC 4SiO2, hexane/ethyl acetate, 9:1):
Rfˆ0.5.
0
0
4C100), 20.6and 21.9 4C9 and C80), 23.64C3 ), 26.5 4C50),
31.3 4C70), 34.1 4C40), 40.9 4C60), 47.2 4C20), 74.8 4C10),
111.64C3), 117.4 4C4), 145.064C2), 149.9 4C5), 158.3
4C6). MS [GC±MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]:
285 45, M1N2H7), 268 4100, M1NH4), 251 47, M11).
Anal. calcd for C15H22O3: C, 71.97; H, 8.86. Found: C,
23
71.54; H, 8.72%. [a]D ˆ272.7 4cˆ4.3, CHCl3). GC
41008C, 1 min, 108C/min, 2508C, 1 min): Rtˆ19.7 min.
TLC 4SiO2, hexane/ethyl acetate, 9:1): Rfˆ0.5.
4.3.7. ꢀ^)-trans-2-ꢀ2-Furyl-thioxy)-cyclohexan-1-ol ꢀ8).19
Under nitrogen atmosphere, a 2.5 M BuLi solution in
hexane 42.7 mL, 6.73 mmol) was added dropwise at room
temperature to a solution of freshly distilled furan 4468 mg,
6.73 mmol) in diethyl ether 415 mL). The reaction mixture
was magnetically stirred for 2 h at room temperature and
then warmed at 358C for 30 min, observing the formation of
a pale yellow solid. Under nitrogen atmosphere, solid
sulphur 4216mg, 6.73 mmol) was added portion wise
during 15 min. The reaction mixture was stirred for 3 h at
room temperature. Then, it was cooled down to 08C, and
cyclohexene oxide 4667 mg, 6.73 mmol) was added drop-
wise during 30 min. The reaction was kept at room tempera-
4.3.9. ꢀ^)-trans-2-ꢀ2-Furyl)-cyclohexan-1-ol ꢀ10). Under
nitrogen atmosphere, a solution of 2.5 M BuLi in hexane
42.72 mL, 6.73 mmol) was diluted with dry diethyl ether

A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
4779
45 mL). At room temperature, freshly distilled furan
4468 mg, 6.73 mmol) was added dropwise. The mixture
was stirred at room temperature for 2 h and then warmed
up to 358C for an additional 1.5 h, observing the formation
of 2-furyl lithium as a pale yellow solid. Then, the reaction
mixture was cooled down to 08C and cyclohexene oxide
4667 mg, 6.73 mmol) was added dropwise along 30 min.
Finally, the reaction mixture was stirred overnight at room
temperature. The product was puri®ed by selective extrac-
tion: addition of water 4100 mL) and that extraction with
diethyl ether 43£30 mL). The organic layer was dried over
anh. Na2SO4, ®ltered and concentrated to dryness, obtaining
369 mg of pure product as a colorless oil 4Yieldˆ35%,
Conv.ˆ48%). IR 4®lm, n, cm21): 3411 4H±O, st), 3100,
4.3.11. ꢀ^)-trans-2-ꢀ2-Furyl)-cyclohexyl benzoate ꢀ12).
Under inert atmosphere, 4^)-trans-2-42-furyl)-cyclohexan-
1-ol 4500 mg, 3.01 mmol) was dissolved in dry pyridine
45 mL). Benzoyl chloride 40.365 mL, 3.08 mmol) was
added dropwise, at room temperature. The reaction was
magnetically stirred for 2 h. Then, the solvent was evapo-
rated and the residue re-dissolved in diethyl ether 425 mL).
The organic layer was washed with water 425 mL) and 3%
aqueous HCl 43£25 mL), dried and concentrated to dryness.
Finally the product was isolated as a colorless oil 4700 mg,
Yieldˆ86%, Conv.ˆ100%) by ¯ash column chromato-
graphy 4SiO2, hexane/ethyl acetate). IR 4®lm, n, cm21):
2938, 2863, 1717 4CvO), 1601, 1505, 1451, 1315, 1273,
1
1109, 1026, 951, 920, 802, 712, 600. H NMR 4200 MHz,
1
2932, 2859, 1593, 1451, 1150, 1061, 1011, 976, 922. H
CDCl3, d, ppm): 1.2±2.30 48H, m, H30, H40, H50, H60), 2.97
41H, dt, J1ˆ11.2 Hz, J2ˆ4.4 Hz, H20), 5.13 41H, dt,
J1ˆ10.2 Hz, J2ˆ4.4 Hz, H10), 6.03 41H, dd, J1ˆ3.0 Hz,
J2ˆ0.8 Hz, H300), 6.20 41H, dd, J1ˆ3.0 Hz, J2ˆ1.8 Hz,
H400), 7.23 41H, dd, J1ˆ1.8 Hz, J2ˆ0.8 Hz, H500), 7.40±
7.44 43H, m, H3, H5, H7), 7.95 42H, dd, J1ˆ5 Hz,
J2ˆ1.2 Hz, H6, H4). 13C NMR 450 MHz, CDCl3, d, ppm):
24.2 4C50), 24.9 4C40), 30.4 4C30), 31.7 4C60), 42.4 4C20),
75.2 4C10), 104.8 4C300), 109.9 4C400), 128.1 4C4, C6), 129.5
4C3, C7), 130.64C2), 132.16 4C5), 140.9 4C5 00), 156.4
4C200), 166.2 4C1). MS [GC±MS4CI), NH3, 70 eV, 1508C,
m/z, 4%)]: 288 4100, M1NH4), 271 43, M11), 166 41,
MH12PhCO), 149 410, M2PhCO2), 105 41, PhCO1).
Anal. calcd for C17H18O3: C, 75.53; H, 6.71. Found: C,
75.44; H, 6.92%. GC 41008C, 1 min, 108C/min, 2908C,
1 min): Rtˆ17.2 min. TLC 4SiO2, hexane/ethyl acetate,
9:1): Rfˆ0.45.
NMR 4200 MHz, CDCl3, d, ppm): 1.35±2.1 48H, m, H3,
H4, H5 and H6), 2.56 41H, ddd, J1ˆ10 Hz, J2ˆ3.6Hz,
J3ˆ13 Hz, H2), 3.60 41H, td, J1ˆ10 Hz, J2ˆ4.4 Hz, H1),
6.12 41H, dd, J1ˆ3.4 Hz, J2ˆ0.8 Hz, H30), 6.32 41H, dd,
J1ˆ3.4 Hz, J2ˆ2 Hz, H40), 7.34 41H, dd, J1ˆ2 Hz,
J2ˆ0.8 Hz, H50). 13C NMR 450 MHz, CDCl3, d, ppm):
24.5 4C5), 25.3 4C4), 29.9 4C3), 34.1 4C6), 45.7 4C2), 72.9
4C1), 105.3 4C30), 110.1 4C40), 141.3 4C50), 157.2 4C20). MS
[GC±MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]: 218 49,
M1N3H11), 201 4100, M1N2H7), 184 4100, M1NH4),
167 421, M11). Anal. calcd for C10H14O2: C, 72.26; H,
8.49. Found: C, 72.19; H, 8.53%. GC 4508C, 1 min, 108C/
min, 2908C, 1 min): Rtˆ13.74 min. TLC 4SiO2, hexane/
ethyl acetate, 9:1): Rfˆ0.17.
4.3.10.
ꢀ^)-trans-2-ꢀ2-Furyl)-1-methoxy-cyclohexane
ꢀ11). Under nitrogen atmosphere 4^)-trans-2-42-furyl)-
cyclohexan-1-ol 4500 mg, 3.01 mmol) was dissolved in
dry tetrahydrofuran 45 mL). A solution of 2.5 M BuLi in
hexane 41.88 mL, 3.01 mmol) is added dropwise, at room
temperature. The reaction mixture was stirred at room
temperature for 1 h. Then, MeI 40.20 mL, 3.2 mmol) was
added dropwise, and the reaction mixture was magnetically
stirred overnight. The solvent was evaporated and the
residue re-dissolved in diethyl ether 420 mL) and water
420 mL). The aqueous layer was extracted with diethyl
ether 44£20 mL). The organic layers were combined
together and dried over anh. MgSO4. Finally, the solvent
was distilled off obtaining a crude oil that was submitted
to ¯ash column chromatography 4SiO2, hexane/ethyl
acetate), which afforded 304 mg of pure product
4Yieldˆ56%, Conv.ˆ92%). IR 4®lm, n, cm21): 3116,
4.3.12. ꢀ^)-trans-[2-ꢀ2-Furyl)-1-cyclohexyloxy] methyl
diphenyl silane ꢀ13). Compound 13 was synthesized
following the general procedure described above, starting
from
4^)-trans-2-42-furyl)-cyclohexan-1-ol
4307 mg,
1.85 mmol), isolating the product, as a colorless oil
4548 mg, Yieldˆ83%, Conv.ˆ100%) by ¯ash column chro-
matography 4SiO2, hexane/ethyl acetate). IR 4®lm, n,
cm21): 3069, 3040, 2932, 2859, 1589, 1506, 1446, 1429,
1254, 1119, 1092, 926, 879, 831, 793. 1H NMR
4200 MHz, CDCl3, d, ppm): 0.39 43H, s, Si±CH3), 1.22±
1.26 42H, m, H4), 1.48±1.55 42H, m, H5), 1.65±1.68 42H,
m, H3), 1.85±1.91 42H, m, H6), 2.71±2.77 41H, m, H2),
3.80 41H, td, J1ˆ10 Hz, J2ˆ4.4 Hz, H1), 6.03 41H, dd,
J1ˆ3.4 Hz, J2ˆ0.8 Hz, H30), 6.30 41H, dd, J1ˆ3.4 Hz,
J2ˆ1.8 Hz, H40), 7.22±7.35 44H, m, Hmeta), 7.16±7.54
45H, m, Hortho and H50), 7.22±7.54 44H, m, Hpara). 13C
NMR 450 MHz, CDCl3, d, ppm): 3.0 4Si±CH3), 24.5 4C5),
25.3 4C4), 30.64C3), 35.8 4C6), 45.8 4C2), 74.5 4C1), 105.5
4C30), 110.0 4C40), 127.5 4Cmeta), 129.3 and 129.5 4Cpara),
134.3 and 134.4 4Cortho), 136.7 and 136.8 4Cipso), 140.4
4C50), 157.8 4C20). MS [GC±MS4CI), NH3, 70 eV, 1508C,
m/z, 4%)]: 380 4100, M1NH4), 363 421, M11), 214 429,
OSiMePh21NH4), 149 48, M2OSiMePh2). Anal. calcd for
C23H26O2Si: C, 76.20; H, 7.23. Found: C, 75.87; H, 7.12%.
GC 4508C, 1 min, 108C/min, 2908C, 1 min): Rtˆ27.3 min.
TLC 4SiO2, hexane/ethyl acetate, 9:1): Rfˆ0.67.
1
2934, 2859, 2822, 1597, 1506, 1451, 1091, 951, 796. H
NMR 4200 MHz, CDCl3, d, ppm): 1.18±2.20 48H, m, H3,
H4, H5 and H6), 2.80 41H, dt, J1ˆ10 Hz, J2ˆ4.4 Hz, H2),
3.12±3.5641H, m, H1), 3.18 43H, s, O CH3), 6.05 41H, dd,
J1ˆ3.1 Hz, J2ˆ0.8 Hz, H30), 6.30 41H, dd, J1ˆ3.1 Hz,
J2ˆ1.8 Hz, H40), 7.31 41H, dd, J1ˆ1.8 Hz, J2ˆ0.8 Hz,
H50). 13C NMR 450 MHz, CDCl3, d, ppm): 24.31 4C4),
25.19 4C5), 30.8 4C3), 30.9 4C6), 43.5 4C2), 56.6
4OCH3), 81.69 4C1), 104.5 4C30), 109.9 4C40), 140.4
4C50), 157.9 4C20). MS [GC±MS4CI), NH3, 70 eV,
1508C, m/z, 4%)]: 215 426, M1N2H7), 198 4100,
M1NH4), 181 410, M11), 180 41, M1). GC 41008C,
1 min, 108C/min, 2508C, 1 min): Rtˆ8.4 min. Anal. calcd
for C11H16O2: C, 73.30; H, 8.95. Found: C, 73.44; H,
8.90%. TLC 4SiO2, hexane/ethyl acetate): Rfˆ0.55 49:1),
0.62 48:2), 0.24 41:0).
4.3.13. ꢀS)-1-ꢀ2-Furyl)-ethyl benzoate ꢀ14). The ester 14
was synthesized following the previously described pro-
cedure, starting from 1-4S)-42-furyl)-ethanol 40.3 mL,
2.87 mmol). The product was obtained as a white solid

4780
A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
4561 mg, Yieldˆ91%, Conv.ˆ100%). Mp 47±488C 4ether).
IR 4KBr, n, cm21): 3100, 2985, 2935, 1717 4CvO, st),
1601, 1506, 1451, 1317, 1267, 1153, 1097, 1011, 926,
temperature adequate to each substrate, the diene
41.06mmol, 1 equiv.) was added at once. A solution of
freshly distilled 2,4-dibromo-3-pentanone 4260 mg,
1.06mmol, 1 equiv.) in dry acetonitrile 46mL) was added
dropwise. The reaction mixture was magnetically stirred
and controlled by GC up to constant conversion of the
diene. Water 45 mL) was then added to the reaction mixture
and the solid was ®ltered out by using a no. 4 ®lter plate. The
®ltrated liquid was extracted with dichloromethane
45£15 mL). The organic layers were combined together,
washed with diluted aqueous ammonia 42£25 mL) and
brine 42£25 mL), dried over anh. MgSO4, ®ltered and
concentrated to dryness. The cycloadducts were puri®ed
by ¯ash column chromatography on silica gel, using
mixtures of hexane and ethyl acetate of increasing polarity
as eluents.
1
742, 710. H NMR 4200 MHz, CDCl3, d, ppm): 1.71 43H,
d, Jˆ7 Hz, H20), 6.22 41H, q, Jˆ6.8 Hz, H10), 6.36 41H, dd,
J1ˆ3.4 Hz, J2ˆ1.8 Hz, H400), 6.41 41H, dd, J1ˆ3.4 Hz,
J2ˆ0.8 Hz, H300), 7.41 41H, dd, J1ˆ1.8 Hz, J2ˆ0.8 Hz,
H500), 7.42±7.50 42H, m, H4 and H6), 7.52±7.56 41H, m,
H5), 8.04±8.08 42H, m, H3 and H7). 13C NMR 450 MHz,
CDCl3, d, ppm): 18.3 4C20), 65.6 4C10), 107.8 4C300), 110.2
4C400), 128.2 4C4 and C6), 129.7 4C3 and C7), 130.5 4C2),
132.9 4C5), 142.5 4C500), 153.4 4C200), 165.7 4C1). MS [GC±
MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]: 251 42, M1N2H7),
234 420, M1NH4), 21641, M). Anal. calcd for C 13H12O3: C,
21
72.21; H, 5.59. Found: C, 72.04; H, 5.91%. [a]D ˆ51.4
4cˆ1.61%, CHCl3). GC 41008C, 1 min, 108C/min, 2508C,
1 min): Rtˆ12.64 min. TLC 4SiO2, hexane/ethyl acetate,
9:1): Rfˆ0.44.
Under modi®ed reaction conditions,13b zinc±copper couple
was used 4instead of copper bronze) and 2,4-diiode-3-penta-
none 4instead of 2,4-dibromo-3-pentanone). In addition, in
some experiments, sodium iodide was not used as an
initiator. No other changes were introduced in the reaction
procedure, so, the order of addition, the reaction conditions
and the method of isolation of the cycloadducts were
essentially the same.
4.3.14. ꢀS)-2-ꢀp-Tolylsul®nyl)-furan ꢀ15).21 Under argon
atmosphere, a solution of BuLi 1.6M in hexane 45.05 mL,
8.08 mmol) was diluted with diethyl ether 410 mL). At room
temperature, freshly distilled furan 40.60 mL, 8.08 mmol)
was added dropwise. The reaction mixture was stirred at
room temperature for 2 h and warmed up to 358C for one
additional hour. Then, a solution of anhydrous magnesium
bromide 4freshly prepared from magnesium and 1,2-
dibromo-ethane) 48.88 mmol) in diethyl ether 45 mL) was
added dropwise. The mixture was re¯uxed for 1 h and, the,
cooled down to 2788C. At this temperature, a solution of
In some experiments, ultrasound was used as a metal
`activator'. The reaction mixture was sonicated by using a
1/800 direct insertion probe from Branson 4EDP no 101-148-
062). The internal reaction temperature was measured by
using a ¯exible PT-100 temperature probe.13a
41R,2S,5R)-42)-menthyl
4SS)-p-toluensul®nate
42 g,
6.73 mmol) in dry diethyl ether 410 mL) was added. The
reaction mixture was stirred at 2788C for 2 h and, then,
overnight at room temperature. Saturated aqueous NH4Cl
solution 430 mL) was added and the organic layer separated,
dried over anh. magnesium sulfate and concentrated to
dryness, obtaining 1.08 g of a white solid 4Yieldˆ78%,
Conv.ˆ100%) that was puri®ed by ¯ash column chromato-
graphy 4SiO2, hexane/ethyl acetate). Mp 47±498C 4ether).
IR 4KBr, n, cm21): 3125±3005, 2945, 1653, 1555, 1491,
1458, 1373, 1308, 1207, 1171, 1136, 1084, 1043, 910, 811,
773. 1H NMR 4200 MHz, CDCl3, d, ppm): 2.41 43H, s, H70),
6.43 41H, dd, J1ˆ3.6Hz, J2ˆ1.8 Hz, H400), 6.78 41H, dd,
J1ˆ3.6Hz, J2ˆ1.0 Hz, H300), 7.31 42H, d, Jˆ8.2 Hz, H30
and H50), 7.52 41H, dd, J1ˆ1.8 Hz, J2ˆ1.0 Hz, H500), 7.58
42H, d, Jˆ8.4, H20 and H60). 13C NMR 450 MHz, CDCl3, d,
ppm): 21.4 4C70), 111.2 4C4), 115.8 4C3), 124.8 4C20 and
C60), 129.9 4C30 and C50), 138.7 4C40), 141.8 4C10), 147.1
4C5), 158.3 4C2). MS [GC±MS4CI), NH3, 70 eV, 1508C,
m/z, 4%)]: 224 4100, M1NH4), 207 454, M11). Anal.
calcd for C11H10SO2: C, 64.06; H, 4.89. Found: C, 63.53;
Some of the synthesized cycloadducts were obtained as
mixtures of endo 45R) and endo 45S) diastereomers, which
were non-separable by using typical chromatographic
methods 4not yet optimized). The NMR characterization
of these products was possible by analyzing mixtures of
them 4with different ratios), which allowed us to discrimi-
nate 4by 1D and 2D NMR experiments) the signals corre-
sponding to both diastereomers. However, in some cases,
the assignment of the signals was ambiguous. In these cases,
we present the corresponding chemical shifts labeled by 4p).
On the other hand, in some cycloadducts, it was not possible
to unequivocally assign the endo 45R) or endo 45S) absolute
stereochemistry to the diastereomers. In these cases, the
endo diastereoisomers were named as endo A and endo B
4without using an R, S notation), depending on the order of
elution in gas chromatography analysis 4RtA,RtB).
4.5. Characterization of cycloadducts
21
4.5.1.
ꢀ10R,20S,50R)-1-[ꢀ2-Isopropyl-5-methyl-1-cyclo-
H, 5.5%. [a]D ˆ83.65 4cˆ1.5, CHCl3). GC41) 41008C,
1 min, 108C/min, 2508C, 1 min): Rtˆ15.64 min. GC42)
41008C, 1 min, 58C/min, 2208C, 20 min): Rtˆ18.06min.
TLC 4SiO2, hexane/ethyl acetate, 9:1): Rfˆ0.02; 4SiO2,
hexane/ethyl acetate, 1:1): Rfˆ0.35.
hexyloxy)-carbonyloxy]-2,4-dimethyl-8-oxabicyclo[3.2.1]-
oct-6-en-3-one ꢀ16)
4.4. Cycloaddition procedures12;13
A suspension of copper bronze 4210 mg, 3.3 mmol) and
sodium iodide 4954 mg, 6.36 mmol) in dry acetonitrile
45 mL) was placed in a round bottomed ¯ask, ®tted with
magnetic stirring and under inert atmosphere. At the
Mixture of diastereoisomers endo A and endo B. Colorless

A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
4781
oil. IR 4®lm, n, cm21): 3090, 2955, 2869, 1759 4CvO, st),
1719 4CvO, st), 1458, 1377, 1339, 1249, 1157, 1053, 1024,
4C10), 131.96p and 131.90p 4C60), 134.5p and 134.4p 4C70),
175.0 4C1), 207.8 4C30). MS [GC±MS4CI), NH3, 70 eV,
1508C, m/z, 4%)]: 287 422, M1N2H8), 270 4100,
M1NH4), 253 44, M11), 151 477, M2C5H9O2). Anal.
calcd for C14H20O4: C, 65.66; H, 7.99. Found: C, 65.45;
H, 7.85%. GC 41008C, 1 min, 108C/min, 2508C, 15 min):
Rtˆ13.84 min. TLC 4SiO2, hexane/ethyl acetate, 1:1):
Rfˆ0.59.
1
970. H NMR 4500 MHz, CDCl3, d, ppm): endo A: 0.79
43H, d, Jˆ7.0 Hz, H100), 0.90 and 0.91 46H, d, Jˆ7.0 Hz,
H80 and H90), 0.98 43H, d, Jˆ7.0 Hz, H10), 1.09 43H, d,
Jˆ7.0 Hz, H9), 1.25±1.30 42H, m, 1H30 and 1H60), 1.41±
1.48 42H, m, H70 and H20), 1.62±1.70 42H, m, 1H30 and
1H40), 1.94±1.99 41H, m, H50), 2.06±2.13 41H, m, 1H6 0),
2.80 41H, dq, J1ˆ7.0 Hz, J2ˆ4.5 Hz, H4), 3.13 41H, q,
Jˆ6.9 Hz, H2), 4.53 41H, td, J1ˆ11.0 Hz, J2ˆ5.0 Hz,
H10), 4.98 41H, dd, J1ˆ4.5 Hz, J2ˆ2.0 Hz, H5), 6.31 41H,
dd, J1ˆ6.0 Hz, J2ˆ2.0 Hz, H6), 6.38 41H, d, Jˆ6.0 Hz, H7).
endo B: 0.80 43H, d, Jˆ7.0 Hz, H100), 0.90 and 0.92 46H, d,
Jˆ7.0 Hz, H80 and H90), 0.98 43H, d, Jˆ7.0 Hz, H10), 1.09
43H, d, Jˆ7.0 Hz, H9), 1.25±1.32 42H, m, 1H30 and 1H60),
1.38±1.44 42H, m, H70 and H20), 1.63±1.71 42H, m, 1H30
and 1H40), 1.92±2.00 41H, m, H50), 2.06±2.14 41H, m,
1H60), 2.80 41H, dq, J1ˆ7.0 Hz, J2ˆ4.50 Hz, H4), 3.12
41H, q, Jˆ6.9 Hz, H2), 4.53 41H, td, J1ˆ11.0 Hz,
J2ˆ5.0 Hz, H10), 4.98 41H, dd, J1ˆ4.50 Hz, J2ˆ2.0 Hz,
H5), 6.31 41H, dd, J1ˆ6.0 Hz, J2ˆ2.0 Hz, H6), 6.38 41H,
d, Jˆ6.0 Hz, H7). 13C NMR 475.45 MHz, CDCl3, d, ppm):
endo A: 8.84 4C9), 10.33 4C10), 16.18 4C100), 20.68 4C90 or
C80), 21.92 4C90 or C80), 23.40 4C30), 26.03 4C50), 31.40
4C70), 34.00 4C40), 40.53 4C60), 46.7 4C20), 48.12 4C4),
54.12 4C2), 79.08 4C5), 80.7 4C10), 110.81 4C1), 132.28
4C6), 133.42 4C7), 151.78 4CO3), 207.12 4C3). endo B:
8.82 4C9), 10.31 4C10), 16.38 4C100), 20.63 4C90 or C80),
21.89 4C90 or C80), 23.2 4C30), 26.14 4C50), 31.4 4C70), 34.0
4C40), 40.51 4C60), 46.7 4C20), 48.13 4C4), 54.17 4C2), 79.02
4C5), 80.7 4C10), 110.85 4C1), 132.21 4C6), 133.48 4C7),
151.78 4CO3), 207.15 4C3). MS [GC±MS4CI), NH3,
70 eV, 1508C, m/z, 4%)]: endo A: 368 4100, M1NH4),
351 47, M11). endo B: 368 4100, M1NH4), 351 412,
M11). Anal. calcd for C20H30O5: C, 68.55; H, 8.63.
Found: C, 68.32; H, 8.49%. GC 4508C, 1 min, 108C/min,
2508C, 15 min): endo A: Rtˆ23.59 min. endo B:
Rtˆ23.81 min.
Mixture of exo A and exo B diastereoisomers. Colourless
oil. IR 4®lm, n, cm21): 3100, 2980, 2935, 2890, 17564O±
CvO, st), 1717 4CvO, st), 1601 4CvC, st), 1458, 1250,
1
1221, 1150, 1100. H NMR 4200 MHz, CDCl3, d, ppm):
0.926p and 0.931p 43H, t, Jˆ7.4 Hz, H4), 1.20 43H, d,
Jˆ6.8 Hz, H5), 1.26 43H, d, Jˆ7.2 Hz, H100), 1.38 43H,
d, Jˆ7.4 Hz, H90), 1.65p±1.82p 42H, m, H3), 2.28 41H, q,
J1ˆ7.4 Hz, H40), 2.45 41H, tq, J1ˆ6.8 Hz, J2ˆ6.9 Hz, H2),
3.05 41H, q, Jˆ7.3 Hz, H20), 4.77 41H, d, Jˆ1.9 Hz, H50),
6.35 41H, dd, J1ˆ5.9 Hz, J2ˆ1.9 Hz, H60), 6.55 41H, d,
Jˆ5.9 Hz, H70). 13C NMR 475.45 MHz, CDCl3, d, ppm):
11.5p and 11.6p 4C90), 13.4 4C4), 16.4 4C5), 17.9 4C100),
26.6 4C3), 41.1p and 41.4p 4C2), 47.7 4C40), 53.3 4C20),
80.5 4C50), 96.1 4C10), 133.3 4C60), 134.7 4C70), 172.6
4C1), 212.2 4C30). MS [GC±MS4CI), NH3, 70 eV, 1508C,
m/z, 4%)]: 287 430, M1N2H8), 270 4100, M1NH4), 253 415,
M11), 151 480, M2C5H9O2). Anal. calcd for C14H20O4: C,
65.66; H, 7.99. Found: C, 65.56; H, 7.91%. GC 41008C,
1 min, 108C/min, 2508C, 15 min): Rtˆ13.64 min. TLC
4SiO2, hexane/ethyl acetate, 1:1): Rfˆ0.59.
4.5.3. 2,4-Dimethyl-3-oxo-8-oxabicyclo[3.2.1]oct-6-en-1-
yl ꢀ2R)-2-methoxy-propanoate ꢀ18)
4.5.2. 2,4-Dimethyl-3-oxo-8-oxabicyclo[3.2.1]oct-6-en-1-
yl ꢀ2S)-2-methyl-butanoate ꢀ17)
Mixture of diastereoisomers: endo A and endo B. Colorless
oil. IR 4®lm, n, cm21): 3110, 2984, 2940, 2880, 2840, 1769
4CvO, st), 1717 4CvO, st), 1599 4CvC, st), 1452, 1377,
Mixture of endo A and endo B diastereoisomers. Colorless
oil. IR 4®lm, n, cm21): 3110, 2973, 2938, 2880, 1755 4O±
CvO, st), 1717 4CvO, st), 1599 4CvC, st), 1460, 1377,
1
1339, 1246, 1148, 1128, 1080, 995. H NMR 4500 MHz,
1
CDCl3, d, ppm): endo A: 0.982 43H, d, Jˆ7.0 Hz, H100),
1.07 43H, d, Jˆ7.0 Hz, H90), 1.45 43H, d, Jˆ7.0 Hz, H3),
2.815 41H, dq, J1ˆ7.0 Hz, J2ˆ4.5 Hz, H40), 3.169 41H, q,
Jˆ7.0 Hz, H20), 3.404 4s, 3H, H4), 3.902 41H, q, Jˆ7.0 Hz,
H2), 4.975 41H, dd, J1ˆ4.5 Hz, J2ˆ2 Hz, H50), 6.325 41H,
dd, J1ˆ6.0 Hz, J2ˆ2.0 Hz, H60), 6.411 41H, d, Jˆ6.0 Hz,
H70). endo B: 0.98643H, d, Jˆ7.0 Hz, H100), 1.07 43H, d,
Jˆ7.0 Hz, H90), 1.45 43H,d, Jˆ7.0 Hz, H3), 2.805 41H, dq,
J1ˆ7.0 Hz, J2ˆ4.5 Hz, H40), 3.104 41H, q, Jˆ7.0 Hz, H20),
3.402 4s, 3H, H4), 3.90641H, q, Jˆ7.0 Hz, H2), 4.983 41H,
dd, J1ˆ4.5 Hz, J2ˆ2.0 Hz, H50), 6.320 41H, dd, J1ˆ6.0 Hz,
J2ˆ2.0 Hz, H60), 6.404 41H, d, Jˆ6.0 Hz, H70). 13C NMR
1339, 1254, 1221, 1150, 1080, 997. H NMR 4500 MHz,
CDCl3, d, ppm): 0.951p and 0.956p 43H, t, Jˆ7.5 Hz, H4),
0.95 43H, d, Jˆ7.0 Hz, H100), 1.05 43H, d, Jˆ6.9 Hz, H90),
1.159p and 1.162p 43H, d, Jˆ7.0 Hz, H5), 1.48±1.56p and
1.66±1.74p 42H, m, H3), 2.43p and 2.44p 41H, tq, J1ˆ6.8 Hz,
J2ˆ7.0 Hz, H2), 2.79 41H, dq, J1ˆ7.3 Hz, J2ˆ4.7 Hz, H40),
3.07p and 3.09p 41H, q, Jˆ6.9 Hz, H20), 4.94 41H, dd,
J1ˆ4.7 Hz, J2ˆ1.9 Hz, H50), 6.26 41H, dd, J1ˆ6.1 Hz,
J2ˆ1.9 Hz, H60), 6.40 41H, d, Jˆ6.1 Hz, H70). 13C NMR
475.45 MHz, CDCl3, d, ppm): 9.4 4C90), 10.76pand 10.59p
4C100), 12.0 4C4), 16.73p and 16.82 4C5), 27.04p and 26.98p
4C3), 41.9 4C2), 48.7 4C40), 54.8 4C20), 81.0 4C50), 110.1

4782
A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
475.45 MHz, CDCl3, d, ppm): endo A: 8.9 4C90), 10.3
4C100), 18.25 4C3), 48.2 4C40), 54.14 4C20), 57.764C4),
76.37 4C2), 80.698 4C50), 110.29 4C10), 132.28 4C60),
133.53 4C70), 170.9 4C1), 206.9 4C30). endo B: 8.9 4C90),
10.3 4C100), 18.39 4C3), 48.2 4C40), 54.33 4C20), 57.88 4C4),
76.57 4C2), 80.78 4C50), 110.15 4C10), 132.09 4C60), 133.44
4C70), 170.9 4C1), 206.9 4C30). MS [GC±MS4CI), NH3,
70 eV, 1508C, m/z, 4%)]:289 48, M1N2H7), 272 4100,
M1NH3), 255 44, M11). Anal. calcd for C13H18O5: C,
61.41; H, 7.13. Found: C, 59.96; H, 7.37%. GC 41008C,
1 min, 108C/min, 2508C, 15 min): endo A: Rtˆ13.82 min.
endo B: Rtˆ13.89 min.
4.5.4. 2,4-Dimethyl-3-oxo-8-oxabicyclo[3.2.1]oct-6-en-1-
yl ꢀ^)-2-phenoxy-propanoate ꢀ19)
1.80±1.88 41H, m, H200), 2.45 42H, d, Jˆ7.4 Hz, H100),
2.73±2.81 41H, m, H4000), 3.13 41H, q, Jˆ7.0 Hz, H2000),
3.75 41H, q, Jˆ7.0 Hz, H2), 4.95 41H, d, Jˆ4.7 Hz, H5000),
6.26 41H, s, H6000), 6.30 41H, s, H7000), 7.14±7.20 44H, m,
H20, H30 H50 and H60). endo B: 0.85 43H, d, Jˆ6.9 Hz,
H10000), 0.88 46H, d, Jˆ5.5 Hz, H300 and H400), 0.9643H,
d, Jˆ7.0 Hz, H9000), 1.50 43H, d, Jˆ7.0 Hz, H3), 1.81±
1.89 41H, m, H200), 2.45 42H, d, Jˆ7.4 Hz, H100), 2.72±
2.80 41H, m, H4000), 2.90 41H, q, Jˆ7.0 Hz, H2000), 3.75
41H, q, Jˆ7.0 Hz, H2), 4.95 41H, d, Jˆ4.7 Hz, H5000), 6.26
41H, s, H6000), 6.30 41H, s, H7000), 7.14±7.20 44H, m, H20,
H30, H50 and H60). 13C NMR 475.45 MHz, CDCl3, d, ppm):
endo A: 8.48 4C9000), 10.2 4C10000), 18.0 4C3), 22.2 4C300 and
C400), 30.11 4C200), 44.9 4C100), 45.5 4C4000), 48.17 4C2000),
54.4 4C2), 80.75 4C5000), 109.9 4C1000), 127.11 4C20 and
C60), 129.35 4C30 and C50), 132.0 4C6000), 133.7 4C7000),
137.1 4C40), 140.7 4C10), 172.4 4C1), 207.2 4C3000). endo
B: 8.364C9 000), 10.14 4C10000), 17.8 4C3), 22.5 4C300 and
C400), 30.11 4C200), 44.9 4C100), 45.5 4C4000), 48.08 4C2000),
Mixture of racemic diastereoisomers: endo A and endo B.
Colorless oil. IR 4®lm, n, cm21): 3110, 2984, 2940, 2880,
2840, 1769 4CvO, st), 1717 4CvO, st), 1599 4CvC, st),
1
1452, 1377, 1339, 1246, 1148, 1128, 1080, 995. H NMR
4300 MHz, CDCl3, d, ppm): 0.91 43H, d, Jˆ7.0 Hz, H100),
0.98p and 1.03p 43H, d, Jˆ7.0 Hz, H90), 1.67p and 1.68p 43H,
d, Jˆ6.9 Hz, H3), 2.75±2.83 41H, m, H40), 3.00p and 3.13p
41H, q, Jˆ7.0 Hz, H20), 4.75 41H, q, Jˆ7.0 Hz, H2), 4.97
41H, dd, J1ˆ4.5 Hz, J2ˆ1.5 Hz, H50), 6.31 41H, dd,
J1ˆ5.9 Hz, J2ˆ1.5 Hz, H60), 6.34 41H, d, Jˆ5.7 Hz, H70),
6.80±6.86 43H, m, H200, H400 and H600), 7.19±7.24 42H, m,
H300 and H500). 13C NMR 475.45 MHz, CDCl3, d, ppm): 8.6p
and 8.8p 4C90), 10.22p and 10.26p 4C100), 18.28p and 18.34p
4C3), 48.12p and 48.17p 4C40), 54.0p and 54.3p 4C20), 72.5p
and 72.8p 4C2), 80.7p and 80.9p 4C50), 115.2p and 115.1p
4C10), 116.2p and 116.5p 4C200 and C600), 121.1p and 121.7p
0
53.7 4C2), 80.32 4C5000), 109.5 4C1000), 127.064C2 and
C60), 129.31 4C30 and C50), 131.2 4C6000), 133.5 4C7000),
136.7 4C40), 140.7 4C10), 172.4 4C1), 207.2 4C3000). MS
[GC±MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]:375 425,
M1NH411), 374 4100, M1NH4), 307 42, M11), 30642,
M). Anal. calcd for C22H28O4: C, 74.12; H, 7.92%. Found:
C, 74.31; H, 7.54%. GC 41008C, 1 min, 108C/min, 2908C,
15 min): endo A: Rtˆ22.39. endo B: Rtˆ22.47. exo A:
Rtˆ21.08 min. Exo B: Rtˆ22.04 min.
4C400), 129.5 4C300 and C500), 132.2p and 132.7p 4C60), 133.0p
4.5.6. 2,4-Dimethyl-3-oxo-8-oxabicyclo[3.2.1]oct-6-en-1-
yl ꢀ1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]hep-
tan-1-carboxilate ꢀ21)
p
00
and 133.2 4C70), 1564C1 ), 170.0 4C1), 206.4 4C30). MS
[GC±MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]:368 451,
M1N3H10), 351 43, M1N2H7), 344 4100, M1NH4), 317
41, M11). Anal. calcd for C13H18O5: C, 61.41; H, 7.13.
Found: C, 60.99; H, 7.37%. GC 41008C, 1 min, 108C/min,
2908C, 15 min): Rtˆ21.84 and 21.95 min. exo isomers: GC
41008C, 1 min, 108C/min, 2908C, 15 min): Rtˆ21.65 and
21.71 min.
4.5.5. 2,4-Dimethyl-3-oxo-8-oxabicyclo[3.2.1]oct-6-en-1-
yl ꢀS)-2-ꢀp-Isobutyl-phenyl)-propanoate ꢀ20). Non-
separable mixture of diastereoisomers: endo A and endo
B. Colorless oil. IR 4®lm, n, cm21): 3100, 2957, 2871,
1761 4O±CvO, st), 1717 4CvO, st), 1512, 1458, 1377,
1339, 1254, 1144, 1080, 1057, 990, 970. 1H NMR
4300 MHz, CDCl3, d, ppm): endo A: 0.7643H, d,
Jˆ6.9 Hz, H10000), 0.88 46H, d, Jˆ5.5 Hz, H300 and H400),
0.9643H, d, Jˆ7 Hz, H9000), 1.53 43H, d, Jˆ7.0 Hz, H3),
Mixture of diastereoisomers: endo A and endo B. Colorless
oil. IR 4®lm, n, cm21): 3100, 2970, 2940, 1792 4CvO, st),
1750 4CvO, st), 1719 4CvO, st), 1456, 1376, 1341, 1256,
1151, 1053, 995. 1H NMR 4500 MHz, CDCl3, d, ppm): endo
A: 0.97 43H, d, Jˆ6.0 Hz, H100), 1.02 43H, s, H11 or H10),
1.0643H, s, H11 or H10), 1.08 43H, d, Jˆ7.0 Hz, H90), 1.10
43H, s, H9), 1.68±2.43 44H, m, H5 and H6), 2.76±2.84 41H,
m, H40), 3.11 41H, q, Jˆ7 Hz, H20), 4.98 41H, dd,

A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
4783
J1ˆ2.5 Hz, J2ˆ2.0 Hz, H50), 6.33 41H, dd, J1ˆ6.0 Hz,
J2ˆ2.0 Hz, H60), 6.40 41H, d, Jˆ6.0 Hz, H70). endo B:
0.97 43H, d, Jˆ6.0 Hz, H100), 1.02 43H, s, H11 or H10),
1.0643H, s, H11 or H10), 1.07 43H, d, Jˆ7.0 Hz, H90), 1.10
43H, s, H9), 1.68±2.43 44H, m, H5 and H6), 2.75±2.86 41H,
m, H40), 3.09 41H, q, Jˆ7.0 Hz, H20), 4.98 41H, dd,
J1ˆ2.5 Hz, J2ˆ2.0 Hz, H50), 6.33 41H, dd, J1ˆ6.0 Hz,
J2ˆ2.0 Hz, H60), 6.40 41H, d, Jˆ6.0 Hz, H70). 13C NMR
475.45 MHz, CDCl3, d, ppm): endo A: 8.97 4C9), 9.6
4C90), 10.2 4C100), 16.0 4C10 or C11), 28.90 4C5), 29.6
4C10 or C11), 30.64 4C6), 48.2 4C40), 54.8 4C4), 54.3
4C20), 80.9 4C50), 90.73 4C1), 110.9 4C10), 132.4 4C60),
133.3 4C70), 165.5 4C8), 178.0 4C3), 206.60 4C30). endo
H90), 0.92 43H, d, Jˆ6.6 Hz, H80 or H90), 0.99 43H, d,
Jˆ7.0 Hz, H10), 1.01 43H, d, Jˆ6.8 Hz, H9), 1.04±1.09
42H, m, 1H30 and 1H60), 1.43±1.48 42H, m, H70 and H20),
1.68±1.73 42H, m, 1H30 and 1H40), 1.84±1.89 41H, m, H50),
2.04±2.10 41H, m, H60), 2.90 41H, dq, J1ˆ4.6Hz, J2ˆ7 Hz,
H4), 2.93 41H, q, Jˆ7.0 Hz, H2), 4.84 41H, td, J1ˆ4.4 Hz,
J2ˆ11 Hz, H10), 4.9641H, dd, J1ˆ4.8 Hz, J2ˆ1.8 Hz, H5),
6.36 41H, dd, J1ˆ5.8 Hz, J2ˆ1.8 Hz, H6), 6.47 41H, d,
Jˆ5.8 Hz, H7). 13C NMR 475.45 MHz, CDCl3, d, ppm):
8.3 4C9), 9.1 4C10), 14.8 4C100), 19.5 and 20.7 4C90 and
C80), 22.0 4C30), 24.9 4C50), 30.2 4C70), 32.9 4C40), 39.4
4C60), 45.5 4C20), 48.4 4C4), 51.5 4C2), 74.6, 4C10), 82.1
4C5), 89.5 4C1), 131.1 4C6), 133.0 4C7), 166.6 4C11),
0
B: 8.92 4C9), 9.64C9 ), 10.2 4C100), 16.0 4C10 or C11),
205.64C3). MS [GC±MS4CI), NH , 70 eV, 1508C, m/z,
3
28.87 4C5), 29.6 4C10 or C11), 30.60 4C6), 48.2 4C40),
54.8 4C4), 54.5 4C20), 80.9 4C50), 90.69 4C1), 110.9 4C10),
132.4 4C60), 133.3 4C70), 165.5 4C8), 178.0 4C3), 206.55
4C30). MS [GC±MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]:
384 45, M1N2H8), 366 466, M1NH3), 349 43, M11).
Anal. calcd for C19H24O6: C, 65.49; H, 6.95. Found: C,
65.30; H, 7.31%. GC 41008C, 1 min, 108C/min, 2908C,
15 min): endo A: Rtˆ22.52 min. endo B: Rtˆ22.63.
4%)]: 196447, M 2menthyl), 152 49, C9H12O21), 140 43),
138 414). Anal. calcd for C20H30O4: C, 71.82; H, 9.04.
23
Found: C, 71.69; H, 9.22%. [a]D ˆ13.5 4cˆ2.52,
CHCl3). GC 4508C, 1 min, 108C/min, 2008C, 15 min):
Rtˆ26.87 min. TLC 4SiO2, hexane/ethyl acetate, 9:1):
Rfˆ0.26.
4.5.8. ꢀ^)-ꢀ10Rp,20Rp)-1-[2-ꢀDiphenylmethylsilyloxy)-1-
cyclohexylthioxy]-2,4-dimethyl-8-oxabicyclo[3.2.1]oct-6-
en-3-one ꢀ23)
4.5.7. ꢀ10S,20R,50S)-2-Isopropyl-5-methyl-cyclohexyl 2,4-
dimethyl-3-oxo-8-oxabicyclo[3.2.1]oct-6-en-1-carboxilate
ꢀ22)
4^)-endo A. Colorless oil. IR 4®lm, n, cm21): 3069, 2938,
2900, 1717 4CvO, st), 1603, 1451, 1379, 1275, 1113, 1070,
1026, 958, 746, 713. 1H NMR 4300 MHz, CDCl3, d, ppm):
0.65 43H, s, Si±CH3), 0.94 43H, d, Jˆ7.2 Hz, H10), 1.05
43H, d, Jˆ7.2 Hz, H9), 1.40±1.69 44H, m, H50 and H30),
1.80±1.91 42H, m, H60), 2.22±2.40 42H, m, H40), 2.68 41H,
q, Jˆ7.2 Hz, H2), 2.74 41H, dq, J1ˆ4.8 Hz, J2ˆ7.2 Hz, H4),
2.99 41H, q, Jˆ4.2 Hz, H10), 4.06±4.11 41H, m, H2 0), 4.65
41H, dd, J1ˆ4.8 Hz, J2ˆ1.8 Hz, H5), 6.06 41H, d, Jˆ6.0 Hz,
H7), 6.20 41H, dd, J1ˆ6.0 Hz, J2ˆ1.8 Hz, H6), 7.34±7.41
48H, m, Hmeta, Hpara), 7.54±7.62 42H, m, Hortho). 13C NMR
475.45 MHz, CDCl3, d, ppm): 2.68 4Si±CH3), 10.38 4C9),
endo A. Colorless oil. IR 4®lm, n, cm21): 3105, 2957, 2873,
1743 4CvO, st), 1717 4CvO, st), 1456, 1379, 1335, 1248,
1159, 1134, 1070, 1034, 984. 1H NMR 4200 MHz, CDCl3, d,
ppm): 0.78 43H, d, Jˆ7.0 Hz, H100), 0.91 43H, d, Jˆ7.4 Hz,
H80 or H90), 0.92 43H, d, Jˆ6.2 Hz, H80 or H90), 0.98 43H, d,
Jˆ7.0 Hz, H10), 1.00 43H, d, Jˆ7.4 Hz, H9), 1.07±1.11
42H, m, 1H30 and 1H60), 1.49±1.52 42H, m, H70 and H20),
1.66±1.70 42H, m, 1H30 and 1H40), 1.90 41H, dq, J1ˆ2.7 Hz,
J2ˆ7 Hz, H50), 2.02±2.05 41H, m, 1H60), 2.89 41H, dq,
J1ˆ4.8 Hz, J2ˆ7.0 Hz, H4), 2.9641H, q, Jˆ7.0 Hz, H2),
4.84 41H, td, J1ˆ4.4 Hz, J2ˆ11 Hz, H10), 4.94 41H, dd,
J1ˆ4.8 Hz, J2ˆ1.4 Hz, H5), 6.37 41H, dd, J1ˆ6.2 Hz,
J2ˆ1.6Hz, H6), 6.45 41H, d, Jˆ6.2 Hz, H7). 13C NMR
450 MHz, CDCl3, d, ppm)0: 8.4 4C9), 9.2 4C10), 14.9
4C100), 19.6and 20.8 4C9 and C80), 22.1 4C300), 24.9
4C50), 30.3 4C70), 33.0 4C40), 39.5 4C60), 45.64C2 ), 48.5
4C4), 51.3 4C2), 74.8, 4C10), 82.3 4C5), 89.7 4C1), 131.4
4C6), 133.1 4C7), 166.8 4C11), 206.0 4C3). MS [GC±
MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]: 196846,
M2menthyl), 152 412, C9H12O21), 140 45), 138 422).
Anal. calcd for C20H30O4: C, 71.82; H, 9.04. Found: C,
0
10.93 4C10), 20.4 4C30), 22.64C5 ), 29.0 04C60), 30.0 4C40),
45.8 4C10), 49.64C4), 55.5 4C2), 71.9 4C2 ), 82.5 4C5), 97.3
4C1), 127.7 4Cmeta), 129.64C para), 134.3 4Cortho), 134.4 4C7),
135.6 4C6), 136.9 4Cipso), 207.64C3). MS [GC±MS4CI),
NH3, 70 eV, 1508C, m/z, 4%)]:496444, M 1NH4), 480 436,
M12), 479 4100, M11), 401 420, M2phenyl), 265 447,
M2OSiMePh2), 214 413, OSiMePh21). Anal. calcd for
C28H34O3SSi: C, 70.35; H, 7.16. Found: C, 70.21; H,
7.20%. GC 41008C, 2 min, 108C/min, 2008C, 15 min):
Rtˆ48.44 min. TLC 4SiO2, hexane/ethyl acetate, 9:1):
Rfˆ0.31.
4^)-endo B. Colorless oil. IR 4®lm, n, cm21): 3069, 2938,
2900, 1717 4CvO, st), 1603, 1451, 1379, 1275, 1113, 1070,
1026, 958, 746, 713. 1H NMR 4200 MHz, CDCl3, d, ppm):
0.68 43H, s, Si±CH3), 0.94 43H, d, Jˆ7.2 Hz, H10), 1.04
43H, d, Jˆ7.2 Hz, H9), 1.30±1.69 44H, m, H50 and H30),
1.7±1.94 42H, m, H60), 2.17±2.38 42H, m, H40), 2.71 41H, q,
Jˆ7.2 Hz, H2), 2.7641H, dq, J1ˆ4.8 Hz, J2ˆ7.2 Hz, H4),
2.83 41H, dt, J1ˆ4.2 Hz, J2ˆ7.5 Hz, H10), 3.75 41H, dt,
23
71.65; H, 9.12%. [a]D ˆ78.3 4cˆ2.25, CHCl3). GC
4508C, 1 min, 108C/min, 2008C, 15 min): Rtˆ26.62 min.
TLC 4SiO2, hexane/ethyl acetate, 9:1): Rfˆ0.30.
endo B: Colorless oil. IR 4®lm, n, cm21): 3105, 2957, 2875,
1735 4CvO, st), 1717 4CvO, st), 1456, 1379, 1248, 1134,
1068, 1034, 985. 1H NMR 4200 MHz, CDCl3, d, ppm): 0.77
43H, d, Jˆ7.0 Hz, H100), 0.90 43H, d, Jˆ6.8 Hz, H80 or

4784
A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
J1ˆ3.3 Hz, J2ˆ7.2 Hz, H20), 4.81 41H, dd, J1ˆ4.8 Hz,
J2ˆ1.8 Hz, H5), 5.9641H, d, Jˆ5.7 Hz, H7), 6.19 41H,
4C30), 45.5 4C10), 49.5 4C4), 51.64C2), 71.64C2 0), 82.1
4C5), 90.9 4C1), 126.7 4C7), 127.6 4Cmeta), 129.4 4Cpara),
134.3 4Cortho), 137.0 and 137.1 4Cipso), 139.3 4C6), 207.7
4C3). MS [GC±MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]:
464 420, M1NH4), 448 442, M12), 447 4100, M11), 369
438, M2Phenyl). Anal. calcd for C28H34O3Si: C, 75.29; H,
7.67. Found: C, 75.14; H, 7.71%. GC 4508C, 1 min, 108C/
min, 2908C, 15 min): Rtˆ36.05 min.
dd, J1ˆ6Hz, J2ˆ1.8 Hz, H6), 7.34±7.40 46H, m, Hmeta
,
Hpara), 7.56±7.65 44H, m, Hortho). 13C NMR 475.45 MHz,
CDCl3, d, ppm): 22.34 4Si±CH3), 10.364C9), 10.95
4C10), 22.2 4C30), 24.0 4C50), 32.1 4C60), 32.9 4C40), 47.6
0
4C10), 49.64C4), 55.64C2), 72.9 4C2 ), 82.3 4C5), 97.7 4C1),
127.7 4Cmeta), 129.7 4Cpara), 133.9 4C7), 134.4 4Cortho) 136.2
4C6), 136.7 4Cipso), 207.7 4C3). MS [GC±MS4CI), NH3,
70 eV, 1508C, m/z, 4%)]: 496450, M 1NH4), 480 426,
M12), 479 4100, M11), 401 435, M2phenyl), 265 460,
M2OSiMePh2). Anal. calcd for C28H34O3SSi: C, 70.25;
H, 7.16. Found: C, 70.18; H, 7.22%. GC 41008C, 2 min,
108C/min, 2008C, 15 min): Rtˆ49.25 min. TLC 4SiO2,
hexane/ethyl acetate, 9:1): Rfˆ0.29.
4.5.10. ꢀ^)-ꢀ10Rp,20Rp)-1-ꢀ2-Methoxy-cyclohex-1-yl)-2,4-
dimethyl-8-oxabicyclo[3.2.1]oct-6-en-3-one ꢀ25)
4.5.9. ꢀ^)-ꢀ10Rp,20Rp)-1-[2-ꢀDiphenylmethylsilyloxy)-1-
cyclohexyl]-2,4-dimethyl-8-oxabicyclo[3.2.1]oct-6-en-3-
one ꢀ24)
4^)-endo 45Sp,10Rp). Major diastereoisomer. Colorless oil.
IR 4®lm, n, cm21): 3105, 2984, 2870, 1718 4CvO, st),
1450, 1310, 1284, 1108, 1070, 1025, 976. 1H NMR
4200 MHz, CDCl3, d, ppm): 0.95 46H, d, Jˆ7.0 Hz, H9
and H10), 1.08±2.20 49H, m, H10, H60, H50, H40 and
H30), 2.62±2.76 42H, m, H2 and H4), 3.12 43H, s, H70),
3.15±3.25 41H, m, H20), 4.79 41H, dd, J1ˆ4.4 Hz,
J2ˆ1.4 Hz, H5), 5.93 41H, dd, J1ˆ6.2 Hz, J2ˆ1.4 Hz, H6),
6.30 41H, d, Jˆ6.2 Hz, H7). 13C NMR 450 MHz, CDCl3, d,
ppm): 9.0 4C9), 10.3 4C10), 24.2 4C50), 24.9 4C40), 25.7
4C60), 31.5 4C30), 44.4 4C10), 49.8 4C4), 51.4 4C2), 55.6
4C70), 78.7 4C20), 81.9 4C5), 90.9 4C1), 125.5 4C7), 138.5
4C6), 210.2 4C3). MS [GC±MS4CI), NH3, 70 eV, 1508C,
m/z, 4%)]: 282 417, M1NH4), 266 427, M12), 265 4100,
M11). Anal. calcd for C16H24O3: C, 72.69; H, 9.15%.
Found: C, 72.48; H, 9.02%. GC 41008C, 1 min, 108C/min,
2908C, 1 min): Rtˆ16.18 min. TLC 4SiO2, hexane/ethyl
acetate, 8:2): Rfˆ0.55.
4^)-endo 45Rp,10Rp). Major cycloadduct. Colorless oil. IR
4®lm, n, cm21): 3090, 3070, 2931, 2870, 1709 4CvO, st),
1653, 1559, 1541, 1456, 1.429, 1117, 1079, 995, 876, 827,
791. 1H NMR 4300 MHz, CDCl3, d, ppm): 0.70 43H, s, Si±
CH3), 0.87 43H, d, Jˆ6.9 Hz, H9), 0.93 43H, d, Jˆ7.2 Hz,
H10), 1.01±2.05 49H, m, H10, H30, H40, H50 and H60), 2.26
41H, dq, J1ˆ4.5 Hz, J2ˆ6.9 Hz, H4), 3.26 41H, q, Jˆ6.9 Hz,
H2), 4.14 41H, dt, J1ˆ10.2 Hz, J2ˆ3.3 Hz, H20), 4.74 41H,
dd, J1ˆ4.4 Hz, J2ˆ1.2 Hz, H5), 6.05 41H, dd, J1ˆ6Hz,
J2ˆ1.5 Hz, H6), 6.08 41H, d, Jˆ6Hz, H7), 7.30±7.45
46H, m, Hmeta, Hpara), 7.54±7.62 44H, m, Hortho). 13C NMR
475.45 MHz, CDCl3, d, ppm): 22.1 4Si±CH3), 9.9 4C9),
10.31 4C10), 24.4 4C50), 25.3 4C40), 26.8 4C60), 36.8
4C30), 44.5 4C10), 49.3 4C4), 53.7 4C2), 73.2 4C20), 82.2
4C5), 92.7 4C1), 127.7 4Cmeta), 129.64C para), 130.4 4C7),
134.32 and 134.35 4Cortho), 136.7 4Cipso), 137.0 4C6), 210.7
4C3). MS [GC±MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]: 464
411, M1NH4), 448 437, M12), 447 4100, M11), 369 420,
M2Phenyl), 214 43, M2OSiMePh2). Anal. calcd for
C28H34O3Si: C, 75.29; H, 7.67. Found: C, 75.19; H,
7.60%. GC 4508C, 1 min, 108C/min, 2908C, 15 min):
Rtˆ34.9 min.
4^)-endo 45Sp,10Rp): Colorless oil. IR 4®lm, n, cm21): 3090,
3070, 2931, 2870, 1709 4CvO, st), 1653, 1559, 1541, 1456,
1.429, 1117, 1079, 995, 876, 827, 791. 1H NMR 4200 MHz,
CDCl3, d, ppm): 0.60 43H, s, Si±CH3), 0.90 43H, d,
Jˆ7.2 Hz, H9), 0.92 43H, d, Jˆ7.0 Hz, H10), 1.01±2.05
49H, m, H10, H30, H40, H50 and H60), 2.66 41H, dq,
J1ˆ4.5 Hz, J2ˆ7.0 Hz, H4), 2.67 41H, q, Jˆ7.0 Hz, H2),
3.9641H, dt, J1ˆ8.7 Hz, J2ˆ4.5 Hz, H20), 4.67 41H, dd,
J1ˆ4.5 Hz, J2ˆ1.5 Hz, H5), 5.64 41H, dd, J1ˆ6.0 Hz,
J2ˆ1.5 Hz, H6), 6.12 41H, d, Jˆ6.0 Hz, H7), 7.30±7.45
46H, m, Hmeta, Hpara), 7.52±7.60 44H, m, Hortho). 13C NMR
475.45 MHz, CDCl3, d, ppm): 22.2 4Si±CH3), 9.0 4C9),
10.29 4C10), 24.2 4C50), 24.64C4 0), 25.2 4C60), 36.3
4^)-endo 45Rp,10Rp). Colorless oil. IR 4®lm, n, cm21): 3105,
2983, 2870, 1717 4CvO, st), 1451, 1310, 1280, 1111, 1070,
1024, 976. 1H NMR 4200 MHz, CDCl3, d, ppm): 0.95 43H,
d, Jˆ7.0 Hz, H9), 1.0 43H, d, Jˆ7.0 Hz, H10), 1.08±2.20
49H, m, H10, H60, H50, H40 and H30), 2.47 41H, dq,
J1ˆ7.0 Hz, J2ˆ4.8 Hz, H4), 2.74 41H, q, Jˆ7.0 Hz, H2),
3.24±3.33 41H, m, H20), 3.32 43H, s, H70), 4.80 41H, d,
Jˆ4.4 Hz, H5), 6.11 42H, s, H6 and H7). 13C NMR
450 MHz, CDCl3, d, ppm): 9.9 4C9), 10.4 4C10), 24.8
4C50), 25.5 4C40), 26.7 4C60), 31.2 4C30), 42.9 4C10), 49.6
0
4C4), 54.0 4C2), 55.64C7 ), 80.3 4C20), 82.3 4C5), 92.7 4C1),
130.5 4C7), 137.0 4C6), 211.4 4C3). MS [GC±MS4CI), NH3,
70 eV, 1508C, m/z, 4%)]:282 414, M1NH4), 266 424, M12),
265 4100, M11). Anal. calcd for C16H24O3: C, 72.69; H,
9.15. Found: C, 72.56; H, 9.21%. GC 41008C, 1 min, 108C/
min, 2908C, 1 min): Rtˆ16.24 min. TLC 4SiO2, hexane/
ethyl acetate, 8:2): Rfˆ0.60.
4.5.11. ꢀ^)-ꢀ10Rp,20Rp)-2-ꢀ2,4-Dimethyl-3-oxo-8-oxabicy-
clo[3.2.1]oct-6-en-1-yl)-cyclohexyl benzoate ꢀ26). 4^)-
endo 45Rp,10Rp). Major diastereoisomer. Colorless oil. IR
4®lm, n, cm21): 3100, 2936, 2863, 1717 4CvO, st), 1653,
1
1603, 1559, 1451, 1314, 1271, 1111, 1070, 1026, 976. H
NMR 4200 MHz, CDCl3, d, ppm): 0.8643H, d, Jˆ7.0 Hz,
H900), 0.99 43H, d, Jˆ7.0 Hz, H1000), 1.1±2.4 49H, m, H20,

A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
4785
q, Jˆ7.0 Hz, H200), 4.93 41H, dd, J1ˆ4.5 Hz, J2ˆ1.5 Hz,
H500), 5.59 41H, q, Jˆ7.0 Hz, H10), 6.18 41H, d, Jˆ6.0 Hz,
H700), 6.25 41H, dd, J1ˆ6.0 Hz, J2ˆ1.5 Hz, H600), 7.35±7.56
42H, m, H6and H4), 7.41±7.68 41H, m, H5), 8.02 42H, dd,
J1ˆ7.0 Hz, J2ˆ1.5 Hz, H3 and H7). 13C NMR 475.45 MHz,
CDCl3, d, ppm): 9.5 4C900), 10.42 4C1000), 14.2 4C20), 49.7
4C400), 52.0 4C200), 69.7, 4C10), 83.38 4C500), 91.7 4C100),
128.3 4C6and C4), 129.7 4C3 and C7), 130.1 4C2), 133.0
H30, H40, H50 and H60), 2.69 41H, dq, J1ˆ4.4 Hz,
J2ˆ7.0 Hz, H400), 2.71 41H, q, Jˆ7.0 Hz, H200), 4.7641H,
dd, J1ˆ4.4 Hz, J2ˆ1.8 Hz, H500), 5.28 41H, dt, J1ˆ10.4 Hz,
J2ˆ5.2 Hz, H10), 5.72 41H, dd, J1ˆ6.0 Hz, J2ˆ1.8 Hz,
H600), 6.10 41H, d, Jˆ6.0 Hz, H700), 7.33±7.57 43H, m,
H3, H5 and H7), 7.67 42H, dd, J1ˆ8.0 Hz, J2ˆ2.0 Hz, H4
00
4C5), 133.64C7 ), 133.7 4C600), 166.0 4C1), 208.3 4C300).
MS [GC±MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]: 335 47,
M1N2H4), 318 4100, M1NH4), 301 457, M11), 179 46,
M2C7H5O2), 122 45, C7H6O21). Anal. calcd for C18H20O4:
C, 71.97; H, 6.72. Found: C, 71.82; H, 6.65%. GC 41008C,
1 min, 28C/min, 2908C, 15 min): Rtˆ68.39 min.
13
and H6). C NMR 450 MHz, CDCl3, d, ppm): 9.1 4C900),
endo B. Colorless oil. IR 4®lm, n, cm21): 3105, 2940, 1717
4CvO, st), 1605, 1450, 1379, 1273, 1111, 1074, 1025, 957,
745, 710. 1H NMR 4200 MHz, CDCl3, d, ppm): 0.98 43H, d,
Jˆ7.0 Hz, H1000), 0.99 43H, d, Jˆ7.0 Hz, H900), 1.3643H, d,
Jˆ6.5 Hz, H20), 2.68 41H, q, Jˆ7.0 Hz, H200), 2.85 41H, dq,
J1ˆ4.9 Hz, J2ˆ7.0 Hz, H400), 4.99 41H, dd, J1ˆ4.5 Hz,
J2ˆ1.5 Hz, H500), 5.51 41H, q, Jˆ7.0 Hz, H10), 6.10 41H,
d, Jˆ6.0 Hz, H700), 6.33 41H, dd, J1ˆ6.0 Hz, J2ˆ1.5 Hz,
H600), 7.35±7.55 42H, m, H6and H4), 7.40±65 41H, m,
H5), 8.09 42H, dd, J1ˆ7.0 Hz, J2ˆ1.5 Hz, H3 and H7).
13C NMR 475.45 MHz, CDCl3, d, ppm): 9.2 4C900), 10.38
4C1000), 14.7 4C20), 49.5 4C400), 52.2 4C200), 69.6, 4C10),
83.44 4C500), 91.64C1 00), 128.4 4C4 and C6), 129.7 4C3
and C7), 130.1 4C2), 133.4 4C700), 133.2 4C5), 134.3
4C600), 165.8 4C1), 209.1 4C300). MS [GC±MS4CI), NH3,
70 eV, 1508C, m/z, 4%)]: 335 42, M1N2H4), 318 4100,
M1NH4), 301 417, M11). Anal. calcd for C18H20O4: C,
71.97; H, 6.72. Found: C, 71.83; H, 6.63%. GC 41008C,
1 min, 28C/min, 2908C, 15 min): Rtˆ68.62 min.
10.2 4C1000), 24.0 4C40), 24.8 4C50), 25.1 4C30), 32.4 4C60),
42.9 4C20), 49.7 4C400), 51.3 4C200), 72.3 4C10), 82.0 4C500),
90.3 4C100), 128.3 4C4 and C6), 128.7 4C5), 129.3 4C3 and
00
C7), 130.8 42), 132.64C7 ), 136.8 4C600), 165.1 4C1), 209.8
4C300). MS [GC±MS4CI), NH3, 70 eV, 1508C, m/z, 4%)]:
373 426, M1NH41H1), 372 4100, M1NH4), 355 48,
M11), 152 4M2ChexOCOPh). Anal. calcd for C22H26O4:
C, 74.55; H, 7.39. Found: C, 74.39; H, 7.30%. GC 41008C,
1 min, 108C/min, 2908C, 5 min): Rtˆ24.40 min. TLC 4SiO2,
hexane/ethyl acetate, 8:2): Rfˆ0.48.
4^)-endo 45Sp,10Rp). Colorless oil. IR 4®lm, n, cm21): 3100,
2936, 2863, 1717 4CvO, st), 1653, 1603, 1559, 1451, 1314,
1
1271, 1111, 1070, 1026, 976. H NMR 4200 MHz, CDCl3,
d, ppm): 0.87 43H, d, Jˆ7.0 Hz, H900), 1.11 43H, d,
Jˆ7.0 Hz, H1000), 1.1±2.4 49H, m, H20, H30, H40, H50 and
H60), 2.63 41H, dq, J1ˆ4.4 Hz, J2ˆ7.0 Hz, H400), 2.81 41H,
q, Jˆ7.0 Hz, H200), 4.81 41H, dd, J1ˆ4.4 Hz, J2ˆ1.8 Hz,
H500), 5.29±5.41 41H, m, H10), 6.10 41H, d, Jˆ6.2 Hz,
H700), 6.14 41H, d, Jˆ6.2 Hz, H600), 7.29±7.58 43H, m,
H3, H5 and H7), 8.00 42H, dd, J1ˆ8.0 Hz, J2ˆ1.2 Hz, H4
4.5.13. ꢀSS)-2,4-Dimethyl-1-ꢀp-tolylsul®nyl)-8-oxabicy-
clo[3.2.1]oct-6-en-3-one ꢀ28)
13
and H6). C NMR 450 MHz, CDCl3, d, ppm): 10.0 4C900),
10.2 4C1000), 23.9 4C40), 24.4 4C50), 25.0 4C30), 32.4 4C60),
0
00
41.64C2 ), 49.5 4C400), 53.64C2 ), 74.1 4C10), 82.4 4C500),
92.0 4C100), 128.4 4C4 and C6), 129.4 4C3 and C7), 131.3
4C5), 130.5 4C2), 132.9 4C700), 136.0 4C600), 165.4 4C1),
210.1 4C300). MS [GC±MS4CI), NH3, 70 eV, 1508C, m/z,
4%)]: 372 4100, M1NH4), 355 48, M11), 152 4M2Chex-
OCOPh). Anal. calcd for C22H26O4: C, 74.55; H, 7.39.
Found: C, 74.42; H, 7.32%. GC 41008C, 1 min, 108C/min,
2908C, 5 min): Rtˆ24.96min. TLC 4SiO 2, hexane/ethyl
acetate, 8:2): Rfˆ0.52.
endo 45R,SS). Major diastereoisomer. Colorless oil. IR 4®lm,
n, cm21): 3100, 2975, 2936, 1713 4CvO, st), 1653, 1597,
1559, 1495, 1456, 1379, 1157, 1086, 1057, 1040, 1016, 985.
1H NMR 4200 MHz, CDCl3, d, ppm): 0.93 43H, d, Jˆ7 Hz,
H10), 1.30 43H, d, Jˆ7 Hz, H9), 2.41 43H, s, H70), 2.81 41H,
dq, J1ˆ4.8 Hz, J2ˆ7.0 Hz, H4), 3.21 41H, q, Jˆ7.0 Hz, H2),
4.85 41H, dd, J1ˆ4.8 Hz, J2ˆ1.4 Hz, H5), 6.25 41H, d,
Jˆ6.0 Hz, H7), 6.30 41H, dd, J1ˆ6.0 Hz, J2ˆ1.4 Hz, H6),
7.30 42H, d, Jˆ8.2 Hz, H20 and H60), 7.53 41H, d, Jˆ8.2 Hz,
H30 and H50). 13C NMR 450 MHz, CDCl3, d, ppm): 9.4
4.5.12. ꢀ10R)-1-ꢀ2,4-Dimethyl-3-oxo-8-oxabicyclo[3.2.1]-
oct-6-en-1-yl)-ethyl benzoate ꢀ27). endo A. Colorless oil.
IR 4®lm, n, cm21): 3104, 2938, 2900, 1717 4CvO, st),
1603, 1451, 1379, 1275, 1113, 1070, 1026, 958, 746, 713.
1H NMR 4500 MHz, CDCl3, d, ppm): 0.98 43H, d, Jˆ7 Hz,
H1000), 1.08 43H, d, Jˆ7 Hz, H900), 1.49 43H, d, Jˆ6.5 Hz,
H20), 2.81 41H, dq, J1ˆ4.9 Hz, J2ˆ7.0 Hz, H400), 2.91 41H,

4786
A. M. MontanÄa, P. M. Grima / Tetrahedron 58 02002) 4769±4786
4C9), 10.1 4C10), 21.4 4C70), 49.3 4C4), 51.0 4C2), 83.6
4C5), 102.9 4C1), 126.2 4C20 and C60), 129.3 4C30 and
C50), 129.8 4C6), 134.4 4C40), 135.9 4C7), 142.0 4C10),
207.4 4C3). MS [GC±MS4CI), CH4, 70 eV, 1508C, m/z,
4%)]: 291 4100, M11), 207 45, M285), 151 429,
M2SOC7H7). Anal. calcd for C16H18O3S: C, 66.18; H,
York, 1997 pp 331±425. 4k) Sarhan, A. E. A. O. Curr. Org.
Chem. 2001, 5, 827±844.
2. 4a) MontanÄa, A. M.; Nicholas, K. M.; Khan, M. A. J. Org.
Chem. 1988, 53, 5193±5201. 4b) MontanÄa, A. M.; Nicholas,
K. M. J. Org. Chem. 1990, 55, 1569±1578. 4c) MontanÄa,
Â
A. M.; Fernandez, D. Tetrahedron Lett. 1999, 40, 6499±
 Á
6502. 4d) MontanÄa, A. M.; Fernandez, D.; Pages, R.; Filippou,
21
6.25%. Found: C, 66.03; H, 6.18%. [a]D ˆ211.0 4cˆ0.9,
È
A. C.; Kociok-Kohn, G. Tetrahedron 2000, 56, 425±439.
CHCl3). GC 41008C, 1 min, 108C/min, 2908C, 15 min):
Rtˆ18.52 min. TLC 4SiO2, hexane/ethyl acetate, 8:2):
Rfˆ0.1.
3. 4a) MontanÄa, A. M.; Garcia, F.; Grima, P. M. Tetrahedron
Lett. 1999, 40, 1375±1378. 4b) MontanÄa, A. M.; Garcia, F.;
Grima, P. M. Tetrahedron 1999, 55, 5483±5504.
4. Rama Rao, A. V.; Yadav, J. S.; Vidyasagar, V. Chem.
Commun. 1985, 55±56.
endo 45S,SS). Colorless oil. IR 4®lm, n, cm21): 3100, 2977,
2936, 1715 4CvO, st), 1597, 1493, 1456, 1379, 1456, 1086,
1043, 969, 812. 1H NMR 4200 MHz, CDCl3, d, ppm): 0.93
43H, d, Jˆ7 Hz, H9), 1.22 43H, d, Jˆ7.2 Hz, H10), 2.43
43H, s, H70), 2.5641H, q, Jˆ7.0 Hz, H2), 2.70 41H, dq,
J1ˆ4.8 Hz, J2ˆ7.2 Hz, H4), 4.98 41H, d, Jˆ4.8 Hz, H5),
6.47 41H, d, Jˆ6.2 Hz, H6), 6.50 41H, d, Jˆ6.2 Hz, H7),
7.32 42H, d, Jˆ8.0 Hz, H20 and H60), 7.59 41H, d, Jˆ8.0 Hz,
H30 and H50). 13C NMR 450 MHz, CDCl3, d, ppm): 9.7
4C9), 10.3 4C10), 21.5 4C70), 49.5 4C4), 52.3 4C2), 83.8
4C5), 103.2 4C1), 126.5 4C20 and C60), 129.5 4C30 and
C50), 130.4 4C6), 134.9 4C40), 136.7 4C7), 142.5 4C10),
206.4 4C3). MS [GC±MS4CI), CH4, 70 eV, 1508C, m/z,
4%)]: 291 4100, M11), 167 47), 152 43,
M2SOC7H71H1), 151 423, M2SOC7H7). Anal. calcd for
C16H18O3S: C, 66.18; H, 6.25. Found: C, 66.05; H, 6.29%.
È
5. Kover, A.; Hoffmann, H. M. R. Tetrahedron 1988, 44, 6831±
6840.
6. Lautens, M.; Aspiotis, R.; Colucci, J. J. Am. Chem. Soc. 1996,
118, 10930±10931.
7. Kende, A. S.; Huang, H. Tetrahedron Lett. 1997, 38, 3353±
3356.
8. 4a) Harmata, M.; Jones, D. E. J. Org. Chem. 1997, 62, 1578±
1579. 4b) Stark, C. B. W.; Eggert, U.; Hoffmann, H. M. R.
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Â
10. 4a) MontanÄa, A. M.; Ribes, S.; Grima, P. M.; Garcõa, F. Chem.
Lett. 1997, 9, 847±848. 4b) MontanÄa, A. M.; Ribes, S.; Grima,
P. M.; Garcia, F.; Solans, X.; Fontbardia, M. Tetrahedron
1997, 53, 11669±11684. 4c) MontanÄa, A. M.; Ribes, S.;
Grima, P. M.; Garcia, F. Acta Chem. Scand. 1998, 52, 453±
460.
23
[a]D ˆ41.9 4cˆ2.0, CHCl3). GC 41008C, 1 min, 108C/min,
2908C, 15 min): Rtˆ18.57 min. TLC 4SiO2, hexane/ethyl
acetate, 8:2): Rfˆ0.1.
11. 4a) Harmata, M. Recent Res. Dev. Org. Chem. 1997, 1, 523±
535. 4b) Lee, J. C.; Jin, S. J.; Cha, J. K. J. Org. Chem. 1998, 63,
2804±2813. 4c) Harmata, M.; Jones, D. E. J. Org. Chem. 1997,
62, 1578±1582. 4d) Harmata, M.; Elomari, S.; Barnes, C. J.
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Acknowledgements
Financial support was provided by the Spanish Ministry of
Education and Science 4MEC TXT-96/2227 and PB-98/
1236) and by the University of Barcelona 4UB-3VR-
1999). Also a fellowship to P. M. G. from the Catalonian
Research Council 4CIRIT) is gratefully acknowledged.
12. Ashcroft, M. R.; Hoffmann, H. M. R. Org. Synth. 1978, 58,
17±23.
13. 4a) MontanÄa, A. M.; Grima, P. M. J. Chem. Educ. 2000, 77,
754±757. 4b) MontanÄa, A. M.; Grima, P. M. Tetrahedron Lett.
2001, 42, 7809±7813.
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