Abnormal behaviour of allenylsulfones under Lu's reaction conditions: Synthesis of enantiopure polyfunctionalised cyclopentenes

Article abstract of DOI:10.1002/chem.200903185

Formal [3+2] cycloadditions of 5-alkoxyfuran-2(5H)-ones 1 and 2 with allenylsulfones 3-5, promoted by different nucleophiles, afford 3-alkoxy5-arylsulfonyl-3,3 a,6,6 a-tetrahydro-1Hcyclopenta[c]furan-l-ones in good yields with complete control of both regio- and π-facial selectivity. The incorporation of a sulfinyl group on the furanone ring enhances the reactivity of the furanones and allows the synthesis of optically pure, bicyclic adducts in good yields. Allenylsulfones evolve through a different mechanism to that proposed for allenoates (Lu's reaction) and afford bicyclic adducts in which the sulfonyl group is joined to C-5. This has advantages on the stereochemical control of further reactions leading to enantiomerically pure polyfunctionalised cyclopentenes and cyclopentanes.

Full text of DOI:10.1002/chem.200903185

FULL PAPER
DOI: 10.1002/chem.200903185
Abnormal Behaviour of Allenylsulfones under Luꢀs Reaction Conditions:
Synthesis of Enantiopure Polyfunctionalised Cyclopentenes
Alberto NfflÇez, Jr., M. Rosario Martín,* Alberto Fraile, and JosØ L. García Ruano*[a]
Dedicated to Professor Saverio Florio on the occasion of his 70th birthday
Abstract: Formal [3+2] cycloadditions
of 5-alkoxyfuran-2(5H)-ones 1 and 2
with allenylsulfones 3–5, promoted by
different nucleophiles, afford 3-alkoxy-
5-arylsulfonyl-3,3a,6,6a-tetrahydro-1H-
furanone ring enhances the reactivity
of the furanones and allows the synthe-
sis of optically pure, bicyclic adducts in
good yields. Allenylsulfones evolve
through a different mechanism to that
proposed for allenoates (Luꢀs reaction)
and afford bicyclic adducts in which
the sulfonyl group is joined to C-5.
This has advantages on the stereo-
chemical control of further reactions
leading to enantiomerically pure poly-
functionalised cyclopentenes and cyclo-
pentanes.
cyclopenta[c]furan-1-ones
in
good
yields with complete control of both
regio- and p-facial selectivity. The in-
corporation of a sulfinyl group on the
Keywords: asymmetric synthesis ·
cycloaddition · lactones · polycycles
Introduction
ed in the synthesis of optically pure cyclopentanes because
of their rather modest stereoselectivity.
Cyclopentanes are common substructures present in a wide
array of natural and non-natural products.[1] One of the
most direct methods for obtaining five-membered cycles is
the [3+2] cycloaddition of olefins with 1,3-dipoles generated
by the conjugate addition of nucleophiles to allenes. In 1995,
Lu reported the first [3+2] cycloaddition of electron-defi-
cient olefins with the 1,3-dipoles generated from phosphines
and 2-butynoates or 2,3-butadienoates[2] to afford cyclopen-
tenes. Since this disclosure, cycloadditions of allenes to a
We have previously showed that the endocyclic character
of dipolarophilic double bonds significantly improves both
the reactivity and regioselectivity of 1,3-dipolar cycloaddi-
tions,[10] therefore, furan-2(5H)-ones exhibit much better be-
haviour than acyclic unsaturated esters. Moreover, the incor-
poration of a sulfinyl group at C-3 of the furanone ring rein-
forces these tendencies and also improves the endo/exo se-
lectivity.[11] All of these facts allowed the synthesis of enan-
tiomerically pure, functionalised cyclopentenes by treating
3-p-tolylsulfinyl-5-ethoxyfuran-2(5H)-ones with the 1,3-
dipole generated by conjugate addition of phosphines to 2,3-
buta- and 2,3-pentadienoates. Adducts obtained in these re-
actions bear an alkoxy carbonyl group at the C-4 position.[12]
The mechanistic proposal is that usually accepted for Luꢀs
reaction, depicted in Scheme 1[13] (in our reactions: X=H,
SOTol (Tol=tolyl)).
wide range of polarised C=X bonds (X=N,[3] O,[4] and C[5–7]
)
have been reported. Intramolecular processes work in a
highly regio- and stereoselective manner,[8] whereas the effi-
ciency of intermolecular processes is usually lower and
clearly dependent on the structure of the dipolarophile. De-
spite reports of the asymmetric version of Luꢀs intermolecu-
lar reaction,[9] these reactions have not been widely exploit-
This excellent behaviour of the sulfinylfuranones in [3+2]
cycloadditions, in general and more specifically with alle-
noates under Luꢀs reaction conditions, prompted us to study
their reactions with other electron-deficient allenes[14,15] to
widen the scope of these cycloadditions. We chose allenyl-
sulfones for these studies because of the presumably excel-
lent features of the resulting cyclopentenylsulfones as chiral
synthons in Michael additions[16] and cycloadditions.[11c,17]
Additionally, desulfonylation made us consider them as syn-
thetic equivalents of the allenes devoid of other functional
[a] A. NfflÇez, Jr., Dr. M. R. Martín, Dr. A. Fraile,
Prof. Dr. J. L. García Ruano
Departamento de Química Orgµnica
Universidad Autónoma de Madrid
Cantoblanco, 28049 Madrid (Spain)
Fax : (+34)914973966
E-mail: joseluis.garcia.ruano@uam.es
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200903185.
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5443

anism (Scheme 1). Experiments aimed at clarifying the
mechanistic evolution of the allenylsulfones and the trans-
formation of the resulting adducts into polysubstituted cy-
clopentanes are also reported.
Scheme 1. Mechanism of Luꢀs reaction applied to furan-2(5H)-ones and
allenoates.
groups, which are not susceptible to attack by the nucleo-
phile generating the dipole and thus, unreactive. We also de-
cided to explore the role of nucleophiles other than PPh3
for activation of the allene. In this sense, we have used
NaSO2Ar mainly because the arylsulfinate acts as a leaving
group in the last step of Luꢀs reaction.
Allenylsulfones have been successfully used as dieno-
philes[18] and dipolarophiles,[19] as well as in Pauson–Kahnd
reactions.[20] However, their behaviour as precursors of 1,3-
dipoles has scarcely been exploited. The first report on the
use of allenylsulfones as precursors of 1,3-dipoles was de-
scribed by Padwa et al.[21] Reactions with acrylonitrile or
methyl vinyl ketone, catalysed by ionic species (KCN,
NaNO2 or NaSO2Ph) in polar solvent (THF), were studied.
These reaction conditions are different to the standard ones
reported several years later for Luꢀs reactions (phosphines
as catalysts and benzene or toluene as solvent). The mecha-
nistic proposal suggested by Padwa et al.[21] (Scheme 2) is
Results and Discussion
Cycloaddition reactions: Initially we explored the reaction
of racemic furanone (Æ)-1 with p-tolylsulfonylallene (3)
under the best conditions reported for Luꢀs reaction of fura-
nones with allenoates (catalytic amount of PPh3, benzene as
the solvent and room temperature).[12] A mixture of (Æ)-6
and 7[22] and other unidentified products, presumably poly-
mers derived from 3, were obtained. Compounds (Æ)-6 and
7 were isolated and purified by column chromatography,
with low isolated yield for compound (Æ)-6 (Table 1,
Table 1. Reactions of furanone (Æ)-1 with sulfonyl allene 3.
Entry Conditions[a] Allene
[equiv]
Nu
t
Ratio of
Yield of 6
[%]
[equiv] [h] 1/6/7
1
2
3
4
5
6
A
A
A
B
C
C
2.0
2.0
2.5
1.5
1.5
1.5
0.3
0.2
0.2
0.4
0.7
0.3
1
5
54:27:19
45:38:17
30
40
50
15
64
63
24 34:53:13
14 65:20:15
1
3
26:69:5
25:71:4
[a] A: PPh3, benzene; B: p-TolSO2Na, THF; C: p-TolSO2Na, [18]crown-
6, benzene.
Scheme 2. Mechanistic proposal suggested by Padwa.[21]
entry 1). Better results were obtained under the conditions
of entry 2, compound (Æ)-6 was isolated in 40% yield after
5 h, which could be slightly improved to 50% by the use
2.5 equiv of allene and an increase in the reaction time to
24 h (Table 1, entry 3). Complete transformation of the fura-
none was never achieved under these conditions, but unal-
tered (Æ)-1 could be recovered in all of the experiments.
similar to that postulated some years later for explaining the
course of Luꢀs reaction. Therefore, these processes must be
considered as the first reactions of allenyl sulfones with elec-
tron-deficient alkenes, catalysed by nucleophiles, affording
cyclopentenyl sulfones.
Herein, we report the results obtained from the highly
stereoselective reactions of furan-2(5H)-ones (Æ)-1 and 2
with allenylsulfones 3–5 in the presence different nucleophil-
ic catalysts, which yield the 5-sulfonyl-substituted adducts in-
stead of the 4-derivatives expected from Luꢀs reaction mech-
1
The H NMR signals corresponding to allene 3 could not be
detected in the crude reaction spectra, despite the fact that
3 was used in excess, which suggests that 3 intervenes in re-
actions not involving the furanone (see below).
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Synthesis of Enantiopure Cyclopentenes
FULL PAPER
Only one cycloadduct, (Æ)-6, was detected by 1H NMR
spectroscopy, which indicates that (Æ)-1 evolves with com-
plete control of the regio- and facial selectivity. The anti ar-
rangement between the cyclopentene ring and the OMe
group suggests that the orientation of the latter is responsi-
ble for the stereocontrol. After a detailed NMR study, we
concluded that compound (Æ)-6 has the sulfonyl group at
C-5 of the expected bicyclic system. Therefore, the obtained
adduct is an isomer of the expected product (the 4-sulfonyl-
substitututed analogue), predicted in accordance with the
mechanism depicted in Scheme 1. This evidenced abnormal
behaviour of the allenyl sulfone under the conditions of Lu.
Padwa et al. had proposed a similar mechanism to that of
Luꢀs reaction (see Scheme 2) after studying reactions of 3
with methyl vinyl ketone and acrylonitrile, under different
conditions to those used by Lu (THF as the solvent and
NaSO2Ar as the catalyst versus toluene or benzene as sol-
vent and PPh3 as the catalyst). We investigated the reaction
of (Æ)-1 with 3 under Padwaꢀs conditions. Compound (Æ)-6
was the only adduct, although it was obtained in poor yield
(15%). To carry out the reaction in a non-polar solvent such
as benzene, the addition of [18]crown-6 was required to in-
crease the solubility of p-TolSO2Na (Table 1, entries 5 and
6). Under these conditions, we observed that both conver-
sion of the dipolarophile (73%) and the yield of (Æ)-6
(64%) were substantially improved, even when the amount
of the allene 3 was reduced to 1.5 equiv and a sub-stoichio-
metric amount of p-TolSO2Na (0.3 or 0.7 equiv) was used.
We next studied the reactions of 3 with sulfinylfuranones
2a and 2b in the presence of PPh3. Reactions with 2a were
complete at room temperature in short periods of time
(Table 2, entries 1–3) and thus, indicate a substantial in-
crease in the reactivity of the furanone as a consequence of
the presence of the sulfinyl group. Consequently, the
amount of disulfone 7 formed in these reactions was smaller
than that obtained from reaction with 1 (Table 1). Adduct
8a was isolated as the only diastereoisomer in yields higher
than 65%. Reaction times were longer when the amount of
PPh3 was reduced (Table 2, entries 1 and 2) and the yield
was slightly improved when the amount of allene 3 was in-
creased (Table 2, entry 3). When p-TolSO2Na was used as
the catalyst, the reactions in THF were improved by the ad-
dition of [18]crown-6 (Table 2, entries 4 and 5). However,
the best results were observed in benzene/[18]crown-6
(Table 2, entries 6 and 7), with yields of 8a up to 90%. This
behaviour was similar to that observed for (Æ)-1. The use of
NaNO2 as a nucleophilic catalyst produced similar results to
those obtained with PPh3 (Table 2, entries 8 and 9), but
worse than those obtained with p-TolSO2Na. As in previous
cases, the addition of [18]crown-6 slightly improved the re-
sults.
Reaction of allene 3 with sulfinylfuranone 2b, catalysed
by PPh3, afforded the cycloadduct 8b only, which was easily
isolated by column chromatography in moderate yield
(42%), lower than that obtained for 8a (Table 2, entries 10
and 1).[23] Slightly higher yields of 8b were obtained by
using tolylsulfinate as the nucleophile in THF (Table 2,
entry 11) but, unexpectedly, worse results were obtained
when [18]crown-6 was added (Table 2, entry 12).
To check whether the use of NaSO2Ar as the catalyst (in-
stead of PPh3) also has advantages in normal Luꢀs reactions,
we studied the reaction of ethyl allenoate with 1 in benzene,
[18]crown-6 and p-TolSO2Na. The expected Luꢀs product A
is obtained as the only bicyclic compound (the yield is lower
than that obtained with PPh3) along with the monocyclic lac-
tones B and B’. The formation of these products can be jus-
tified as depicted in Scheme 3. Protonation of D generates
Table 2. Reactions of furanones 2a and 2b with allene 3, catalysed by
different nucleophiles.
Entry
Furanone
Allene
[equiv]
Nu
([equiv])
t
Product
ACHTUNGTRENUN(NG yield [%])
G
N
[h]
1
2
3
4
5
6
7
8
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
1.5
1.5
2.0
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
PPh3 (0.3)[a]
1
8a (68)[d]
PPh3 (0.4)[a]
0.5 8a (65), 7 (15)
1.5 8a (71), 7 (21)
7
1
0.5 8a (85)
0.5 8a (90)
2.5 8a (60)
1
1
2
1
PPh3 (0.4)[a]
TolSO2Na (0.4)[a]
TolSO2Na (0.2)[b]
TolSO2Na (0.4)[c]
TolSO2Na (0.7)[c]
NaNO2 (1.5)[a]
NaNO2 (0.7)[b]
PPh3 (0.3)[a]
8a (40)
8a (64), 7 (12)
Scheme 3. Reaction of ethyl allenoate and (Æ)-1 with NaSO2Tol as cata-
lyst.
9
8a (75)
8b (42)
8b (47)
8b (31)
B and B’, whereas elimination of the sulfonyl group from F
produces A. The higher stability of the a-sulfonylcarbanion
E with respect to the ester enolates in equilibrium (D and F
are both of similar stability) determines that the [1,2]-hydro-
gen migration was not particularly favoured, which decreas-
es the yield of Luꢀs product. Therefore, it is noteworthy that
10
11
12
TolSO2Na (0.4)[a]
TolSO2Na (0.7)[c]
[a] THF used as solvent. [b] THF used as solvent and [18]crown-6.
[c] Benzene used as solvent and [18]crown-6. [d] The crude reaction was
an 87:13 mixture of 8a and 7 (determined by H NMR spectroscopy).
1
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M. R. Martín, J. L. García Ruano et al.
intermediate D evolved through two paths of similar signifi-
cance (60:40), and in a different manner to that of inter-
mediate II shown in Scheme 4.
must be much faster than that of PPh3 or nitrite and, there-
fore, the catalytic cycle in Scheme 4 must be preferred for
the evolution for furanones.
Taking into account that disulfone 7 is obtained in varia-
ble amounts in many of these reactions, the formation of ad-
ducts (Æ)-6 and 8 with p-TolSO2Na as the catalyst could be
explained as indicated in Scheme 4 for adduct (Æ)-6. The
The reaction of 3 with PPh3 provided a complex mixture
in which the phosphine was recovered in 86% yield, where-
as the allenyl sulfone had completely disappeared (only 8%
of its isomeric propargyl sulfone was recovered). Among the
products, we could isolate bisulfone 7 (5%), propanetrisul-
fone (7%) and a significant amount (almost 40% of the ini-
tial mass of allene) of unidentified products, the NMR spec-
trum of which suggests a polymeric structure (Scheme 5).
Scheme 5. Transformation of allenylsulfone in the presence of PPh3.
The formation of 1,2,3-trisulfonylpropane clearly demon-
À
Scheme 4. Mechanistic proposal for reaction of allenylsulfones with fura-
nones, catalysed by p-Tol-SO2Na (Ts=tosyl).
strates that Tol-SO2 has been formed in the course of the
reaction, but the way in which this formation takes place is
not easily rationalised. One of the reviewers has suggested
that the formation of sulfinate from sulfonylallene in the
presence of PPh3 can explain this as shown in Scheme 6.
addition of a sulfinate anion to 3 generates the anionic spe-
cies I, which attacks furanone (Æ)-1 to give lactone enolate
II. Intermediate II can intramolecularly evolve into cyclo-
pentene III through a 5-endo-trig attack onto the activated
double bond, which is followed by elimination of one of the
sulfonyl groups. This mechanism also accounts for the for-
mation of bisulfone 7 (by protonation of I) and the fact that
Scheme 6. Possible explanation for the formation of TolSOÀ2 from (Æ)-1
À
only sub-stoichiometric amounts of the promoter (Tol-SO2 )
and PPh3.
are required (0.2 equiv are enough for the reaction to be
successful).
The stereochemistry of the resulting adducts is a conse-
This possibility has been investigated, however, we could
not isolate the phosphonium salts that support this hypothe-
sis. Additionally, a similar pathway could contribute to sulfo-
nyl scrambling when allenylsulfones are activated by arylsul-
finates possessing a different aryl group.
quence of the favoured approach of the anionic bisulfone I
À
to the less-hindered face of furanones (the OR group
blocks one face of the electrophile). The strong reactivity of
vinyl sulfones as Michael acceptors and the leaving-group
The ratio of adducts is not strictly the allene/sulfinate
ratio used in each case (Scheme 7). It is evident that the
À
ability of ArSO2 determine the course of the last two steps.
The fact that these reactions do not evolve through the
route proposed for Luꢀs reaction (Scheme 1) can be ex-
plained by assuming that prototropy involved in the trans-
formation of III into IV is much slower than the direct elim-
ination of the sulfonyl group from III. Alternatively, the last
two steps of the catalytic cycle (intramolecular Michael ad-
À
dition and elimination of ArSO2 ) take place simultaneous-
ly, which precludes the formation of IV and, therefore, its
conversion into the 4-sulfonyl adduct.
The formation of (Æ)-6, 7 and 8 when nucleophiles other
than sulfinates are used as catalysts requires more intricate
explanation. One plausible route would involve the forma-
À
tion of TolSO2 by reaction of allene 3 with the nucleophile
(PPh3 or NaNO2). Once formed, its reaction with allene 3
Scheme 7. Reactions of (Æ)-1 with Ar1SO2CH=CH2 and Ar2SO2.
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Synthesis of Enantiopure Cyclopentenes
FULL PAPER
adduct retaining the group present in the allene is predomi-
nant.[24]
forded optically pure 10a in 61% yield (Scheme 8). These
results provide evidence for the positive influence exerted
by the sulfinyl group on the reactivity of the alkene. The ste-
reoselectivity was complete in both cases, which suggests
that the configuration at C-5 of the furanone ring is respon-
sible for the complete p-facial selectivity observed in these
reactions. We have also studied the reaction between 4 and
2b. The results were unsuccessful, which can be understood
by taking into account the long reactions times required and
the easier route of decomposition for furanone 2b.[23]
Finally, we studied the behaviour of allene 5. Reactions
with (Æ)-1 did not give good results, regardless of the cata-
lyst used. With sulfinate as the promoter and THF as the
solvent, unaltered furanone 1 was recovered but allene 5
was isomerised into p-tolylsulfonyl-2-butyne. Reaction of 2a
with 5, catalysed by PPh3, gave a complex reaction mixture
after long reaction times. The starting allene (partially iso-
merised to the corresponding alkyne) could be recovered,
whereas the furanone 2a was decomposed. When the reac-
tion was catalysed by the sulfinate in benzene/[18]crown-6,
it afforded a separable 60:40 mixture of C-4 epimers, 11a-
endo and 11a-exo, after 30 min (Scheme 9). This reaction
time, shorter than that required for 4 (4 h, Scheme 8), re-
veals the higher reactivity of 5 (which is expected for steric
reasons).
With the aim of supporting the mechanistic proposal de-
picted in Scheme 4 we have performed several experiments.
Firstly, we generated anions of type I by reaction of vinylsul-
fones (7 or the 2-phenylsulfonyl derivative) with base and
checked if they reacted with (Æ)-1 and 2a to afford (Æ)-6
and 8a or the 4-phenylsulfonyl adducts. The results support
the hypothesis that anions of type I can be considered as re-
action intermediates. The yield obtained in this reaction was
lower than those achieved starting from allenylsulfone. The
reaction of I with its precursor, in competition with the reac-
tion of I with the furanones, can explain these results. The
proposed mechanism suggests that the use of arylsulfinates
that contain a different aryl group to that bore by the start-
ing allenylsulfone would produce a mixture of adducts, that
differ in the nature of arylsulfonyl group joined to C-5 and
this was also confirmed (see Scheme 7).
To date, there are only two antecedents of the reaction of
2-methyl-2,3-butadienoates and electron-deficient alkenes
catalysed by phosphines and none of them evolved through
a normal Luꢀs reaction mechanism. In 2007, Kwon and Tran
reported that reactions of these allenes with benzylidenema-
lonitrile undergo a [4+2] annulation process through a dif-
ferent mechanism.[25] This year, Yu and co-workers reported
the first example of the synthesis of cyclopentenes in moder-
ate yields by [3+2] annulation of a-alkyl-substituted alle-
noates with fumarates.[13,26] According to the mechanism
proposed in Scheme 4, we hypothesised that 1,1-disubstitut-
ed allenes such as 4,[25,27] which would be unable to inter-
vene in normal Luꢀs reactions (the proton required for pro-
totropy is non-existent, see Scheme 1), would react accord-
ing to this alternative mechanism to afford adducts with the
methyl group at C-4. We verified this hypothesis by studying
the reactions of 4 with (Æ)-1 and 2a (Scheme 8) under dif-
ferent conditions.
Scheme 9. Reaction of 1,3-disubstituted allene 5 with furanone 2a.
The fact that (Æ)-1 was not able to react with 5, despite
the fact that 5 is more reactive than 4, can be rationalised
by assuming that the isomerisation of 5 to the corresponding
alkyne (non-reactive) competes with the normal reaction
over long reaction times. The reaction of 5 with 2b was un-
successful, and the lactone decomposed.
The low endo selectivity observed in the reactions of 2a
with 5 contrasts with the exclusive formation of the endo
adduct observed in the reactions of 2a with allenoate.[12] In
this case, we postulated that intermediate VI-A was fav-
oured with respect to VI-B because the latter was destabi-
lised by the Me/SOTol interaction (see Scheme 10). Howev-
er, this situation would be identical for allenylsulfone 5 (V-B
will be destabilised with respect to V-A by the Me/SOTol in-
teraction), yet the endo-selectivity is very low. This suggests
that another interaction must be responsible for this behav-
iour. Taking into account the electrostatic attraction be-
tween the sulfinyl oxygen and P+, the distance between the
carbanionic centre and the activated double bond in the
transition states (TS) derived from VI-A and VI-B can
become short enough to determine that their steric differen-
ces (Me/SOTol versus H/SOTol) could be critical for the in-
Scheme 8. Reactions of 1,1-disubstituted allene 4 with furanones 1 and
2a.
The reaction of 4 with (Æ)-1 in benzene, with PPh3 as the
nucleophile, did not work but the use of sulfinate in ben-
zene/[18]crown-6 afforded racemic compound (Æ)-9 in 56%
yield after long reaction times (24 h). As expected, the reac-
tivity of 4 was lower than that of 3 because the methyl
group decreases the electrophilic character of the allene for
both steric and electronic reasons. Under the same condi-
tions, the reaction of 4 with 2a required 4 h for completion
(also a longer reaction time than that required for 3) and af-
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M. R. Martín, J. L. García Ruano et al.
dienophiles and dipolarophiles. The change in position of
the substituent (C-5), with respect to that observed in Luꢀs
reactions (C-4), must favour the stereochemical control of
reactions with nucleophiles.[30] The attacked position in the
sulfones depicted in Scheme 11 (C-4) is closer to the bridge
(therefore, more congested) than the position attacked in
Luꢀs adducts (C-5). We have studied the catalytic hydroge-
nation of sulfones (+)-12 and 14a-exo. The reaction is
highly stereoselective and preferentially yields the diastereo-
isomer resulting from the approach of the reagent to the
less-hindered convex face of the bicyclic structure
(Scheme 12).
Scheme 10. Endo/exo selectivity in reactions of 2a with allenyl sulfone or
ethyl allenoate.
duction of complete endo selectivity. In contrast, the strong
destabilising interaction of SO2Ar/SOTol (from both a steric
and electronic point of view) will determine a longer dis-
tance between the carbanionic centre and the activated
double bond in the TS, resulting from V-A and V-B, thus
minimising the magnitude of the steric interactions Me/
SOTol and H/SOTol and reducing the stereoselectivity.
Transformation of the adducts: The synthetic usefulness of
the obtained adducts depends on their ready desulfurisation
reactions. Elimination of the sulfinyl group is important be-
cause it would allow optically pure sulfinyl furanones 2a
and 2b to be considered as more reactive, chiral synthetic
equivalents of racemic furanone (Æ)-1. Desulfinylation can
be easily performed with aluminium amalgam. We first stud-
ied reactions of stereoisomers 8a and 8b, which afforded
(+)-12 and (À)-12, respectively, in good yields (Scheme 11).
The enantiomeric relationship of these compounds reveals
that the starting sulfoxides exhibit the opposite configura-
tion at all of their stereogenic carbon atoms. The high opti-
cal purity of compounds (+)-12 and (À)-12, established by
chiral HPLC,[28] proves that these cycloadditions were com-
pletely stereoselective and that the configuration at the C-6a
was maintained in the desulfinylation process. Under similar
conditions, compounds 10a, 11a-exo and 11a-endo were
converted into enantiomerically pure compounds 13a,[29]
14a-exo and 14a-endo, with good yields and without affect-
ing the sulfonyl group (Scheme 11).
Scheme 12. Palladium-catalysed hydrogenation of compounds (+)-12 and
14a-exo.
It is noteworthy that the stereocontrol (>95% diastereo-
meric excess (de)) observed in the hydrogenation of the bi-
cyclic sulfones (+)-12 and 14a-exo, with the sulfonyl group
at C-5, is much higher than that obtained from analogous 4-
esters (64% de).[12] This difference confirms that the position
of the substituent in the bicyclic system (C-5 for sulfones
and C-4 for esters) affects the stereoselectivity and increases
the potential interest of adducts obtained from allenylsul-
fones.
To check whether sulfonylallenes can be considered as
synthetic equivalents of non-substituted allenes, it was nec-
essary to perform the reductive desulfonylation of the pri-
mary adducts. We treated 8a with some of the reagents re-
ported for the desulfonylation of vinylsulfones, such as Mg/
MeOH and sodium amalgam.[31] The first reagent did not
afford the expected results because of the opening of the
furanone ring by the MeOÀ anion. In contrast, compound
8a was cleanly transformed into 17a in 66% yield by treat-
It is of interest to consider the optically pure, bicyclic vi-
nylsulfones shown in Scheme 11 as chiral Michael acceptors,
Scheme 11. Selective reductive desulfinylation of primary adducts with aluminium amalgam.
5448
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Synthesis of Enantiopure Cyclopentenes
FULL PAPER
ment with 6% sodium amalgam in a 6:1 THF/MeOH mix-
ture (Scheme 13). Their bicyclic structure predicts a strong
control of the stereoselectivity in electrophilic additions and
sulfinyl derivatives) to afford bicyclic adducts in a complete-
ly regioselective manner, with total control of the p-facial
selectivity. The reaction mechanism is different to that pro-
posed for Luꢀs reactions and yields 5-sulfonyl substituted ad-
ducts (instead of the expected 4-substituted adducts), which
enables a-methyl sulfonylallenes to react. Desulfinylation
and desulfonylation of the adducts yielded interesting syn-
thons, the bicyclic structures of which efficiently control the
stereoselectivity of subsequent reactions and allow the syn-
thesis of optically pure, polyfunctionalised cyclopentyl deriv-
atives.
Experimental Section
General: 1H and 13C NMR spectra were recorded at 300 (1H) and
75.5 MHz [13C, APT (Attached Proton Test)] on a Bruker AC-300 spec-
trometer in CDCl3, if not otherwise specified. Chemical shifts (d) are re-
ported in ppm, coupling constants (J) in Hz. TLC were eluted on DC-
Alufolien 60 F254 (Merck) and were viewed under UV light at 254 nm
or after development with DNPH (2,4-dinitrophenylhydrazine and
H2SO4, solution in ethanol) or MOPS (10% molybdophosphoric acid, so-
lution in ethanol). Column chromatography was carried out on Merck
silica gel 60 (230–400 mesh ASTM). IR spectra were recorded on a
Bruker Vector 22 spectrometer as KBr pellets or as films between NaCl
plates. HRMS were collected on an Applied Biosystems QSTAR Pulsar I
(ESI) or a Waters VG AutoSpec (FAB). Melting points were recorded
on a Gallenkamp apparatus in open capillary tubes and are uncorrected.
Optical rotations were measured at room temperature (20–238C) on a
Perkin–Elmer 241 MC polarimeter (concentration in g/100 mL). Micro-
analyses were carried out on a LECO CHNS-932 in the Laboratory of
Elemental Analyses of SIDI, Universidad Autónoma de Madrid and
were in good agreement with the calculated values. Enantiomeric excess
(ee) was determined by HPLC, fitted with a Daicel Chiralpack AD
column.
Scheme 13. Desulfurisation of primary adducts with sodium amalgam.
cycloadditions characteristic of electron-rich alkenes. This
reaction involves consecutive desulfinylation and desulfony-
lation, which is indicated through the detection by TLC of
the desulfinylated compound (+)-12 as an intermediate. The
reaction was similarly successful when it was performed on
adducts 10a, 11a-endo, (Æ)-6 and (Æ)-9 to yield com-
pounds 18a, 19a-endo, (Æ)-20 and (Æ)-21, respectively
(Scheme 13).
The compounds shown in Schemes 11–13 can be consid-
ered as synthons of optically pure, masked a-formyl cyclo-
pentene- and cyclopentanecarboxylic acids.[32,33] To illustrate
this feature, we have transformed 16a-exo into highly func-
tionalised cyclopentane 22, which contains four contiguous
stereocentres (Scheme 14). We followed a mild, inexpensive
and efficient one-pot protocol, previously reported by us,
for the synthesis of acetals of 4-oxo-but-2-enoates from 5-al-
koxyfuran-2(5H)-ones.[34]
AHCTUNGTERG[NNUN 3+2] Cycloaddition reactions
Procedure A: A solution of triphenylphosphine (see Table 1 and 2) in
benzene (1.3 mL) was added to a stirred solution of furanone (Æ)-1, 2a
or 2b (0.26 mmol) and p-tolyl-1-allenyl sulfone 3 (see Table 1 and 2) in
benzene (1.3 mL), under positive pressure of argon, at room temperature.
After the time indicated in each case the solvent was removed under
vacuum and the crude reaction mixture was analysed by 1H NMR spec-
troscopy and immediately purified by flash column chromatography. The
eluent used for purification and the yield of the isolated product are indi-
cated in each case.
Procedure B: To a stirred solution of furanone (Æ)-1, 2a or 2b in THF
(0.1m) p-tolyl allenyl sulfone 3–5 (1.5 equiv) and anhydrous p-TolSO2Na
(0.3–0.7 equiv) were added at room temperature. The reaction was moni-
torised by TLC, the solvent was removed under vacuum and the crude
reaction was analysed by 1H NMR spectroscopy and immediately puri-
fied by flash column chromatography. The reaction time, the eluent used
for purification and the yield of the isolated product are indicated in
each case.
Scheme 14. Ring opening of 16a-exo to afford a masked a-formyl cyclo-
pentanecarboxylate.
Structural and configurational assignments of all new
compounds were based on detailed NMR spectroscopy stud-
ies (including two-dimensional NOESY, COSY and HMQC
experiments). The absolute configuration of 15a was un-
equivocally established from X-ray diffraction of this com-
pound.[35] Details can be found in the Supporting Informa-
tion.
Procedure C: Allene (1.5 equiv), [18]crown-6 (0.3–0.7 equiv, see Tables 1
and 2) and anhydrous p-TolSO2Na (0.3–0.7 equiv) were added to a stirred
solution of furanone in benzene (0.1m) at room temperature. The reac-
tion was monitored by TLC, the solvent was removed under vacuum and
the crude reaction was analysed by 1H NMR spectroscopy, before purifi-
cation by flash column chromatography. The reaction time, the eluent
used in the purification and the yield of obtained product are indicated
in each case.
Conclusion
Compound (Æ)-6: Following procedure C with (Æ)-1, 3 and p-TolSO2Na
(0.3 equiv) were stirred for 3 h. Purification by column chromatography
1
Allenyl sulfones are activated by phosphines or sulfinates in
(hexane/ethyl acetate, 2:1) as a colourless oil (63%). H NMR (300 MHz,
their reactions with 5-alkoxyfuran-2(5H)-ones (and their 3-
CDCl3): d=7.73 and 7.34 (AA’BB’ system, 4H), 6.60 (m, 1H), 5.28 (s,
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5449

M. R. Martín, J. L. García Ruano et al.
1H), 3.59 (m, 1H), 3.49 (s, 3H), 3.37 (td, J=8.7, 1.9 Hz, 1H), 2.97 (ddt,
J=16.8, 8.7, 2.5 Hz, 1H), 2.85 (dq, J=16.8, 1.9 Hz, 1H), 2.44 ppm (s,
3H); 13C NMR (75 MHz, CDCl3): d=177.8 (C), 147.7 (C), 145.3 (C),
136.7 (CH), 135.1 (C), 130.1 (2”CH), 128.0 (2”CH), 105.4 (CH), 56.8
(CH3), 53.8 (CH), 41.3 (CH), 34.8 (CH2), 21.7 ppm (CH3); IR (film): n˜ =
1779, 1596, 1318, 1153, 943 cmÀ1; HRMS (EI): m/z calcd for C15H16O5S:
[M]+ 308.0718; found: 308.0719.
Isomers 11a were separated by column chromatography (hexane/ethyl
acetate, 2:1).
Compound 11a-endo: Major component, white solid (31%); Rf =0.30
(hexane/ethyl acetate 3:2); m.p. 102–1048C (with decomposition); [a]D20
=
+93.3 (c=1.6 in CHCl3); 1H NMR (300 MHz, CDCl3): d=7.62 and 7.33
(AA’BB’ system, 4H), 7.50 and 7.25 (AA’BB’ system, 4H), 6.30 (dd, J=
2.8, 1.9 Hz, 1H), 5.29 (d, J=2.2 Hz, 1H), 3.96 (m, 1H), 3.87 (m, 1H),
3.62 (m, 1H), 3.41 (m, 1H), 2.46 (s, 3H), 2.42 (s, 3H), 1.24 (t, J=7.1 Hz,
3H), 0.93 ppm (d, J=7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=169.1
(C), 150.1 (C), 145.3 (C), 143.3 (C), 135.8 (C), 135.4 (CH), 134.4 (C),
130.0 (2”CH), 129.6 (2”CH), 128.1 (2”CH), 126.2 (2”CH), 103.8
(CH), 76.3 (C), 66.1 (CH2), 54.1 (CH), 41.6 (CH), 21.7 (CH3), 21.5 (CH3),
15.7 (CH3), 14.8 ppm (CH3); IR (KBr): n˜ =1771, 1596, 1318, 1155,
939 cmÀ1; elemental analysis calcd (%) for C24H26O6S2: C 60.74, H 5.52, S
13.51; found: C 60.60, H 5.55, S 13.32.
Compound 8a: Following procedure A or C, with sulfinylfuranone 2a
and sulfonylallene 3, compound 8a was obtained after 1 and 0.5 h, re-
spectively. Isolation by column chromatography (hexane/dichlorome-
thane/diethyl ether, 4:2:1) gave a white solid (68%, procedure A; 85%,
procedure C). Compound 8a was also obtained from 2a and but-2-yn-1-
yl-4-methylphenyl sulfone after 2 h, following procedure C, in 60% yield.
M.p. 70–728C (with decomposition); [a]2D0 =+124.7 (c=0.60 in CHCl3);
1H NMR (300 MHz, CDCl3): d=7.66 and 7.33 (AA’BB’ system, 4H),
7.47 and 7.30 (AA’BB’ system, 4H), 6.48 (m, 1H), 5.45 (d, J=0.7 Hz,
1H), 4.03 (m, 1H), 3.91 (m, 1H), 3.68 (m, 1H), 3.20 (dt, J=16.8, 2.2 Hz,
1H), 2.51 (dt, J=16.8, 1.9 Hz, 1H), 2.44 (s, 3H), 2.43 (s, 3H), 1.28 ppm
(t, J=7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=171.9 (C), 146.3 (C),
145.5 (C), 143.3 (C), 135.3 (CH), 135.1 (C), 134.9 (C), 130.2 (CH), 129.6
(CH), 128.0 (CH), 125.8 (CH), 103.8 (CH), 72.7 (C), 66.0 (CH2), 55.6
(CH), 33.2 (CH2), 21.7 (CH3), 21.6 (CH3), 14.8 ppm (CH3); IR (KBr): n˜ =
1771, 1596, 1321, 1206, 1156, 935 cmÀ1; HRMS (FAB): m/z calcd for
C23H25O6S2: 461.1093 [M+H]+; found: 461.1110 [M+H]+.
Compound 11a-exo: Minor component, white solid (28%); Rf =0.20
(hexane/ethyl acetate 3:2); m.p. 136–1388C (with decomposition); [a]D20
=
1
+155.0 (c=1.0 in CHCl3); H NMR (300 MHz, CDCl3): d=7.69 and 7.34
(AA’BB’ system, 4H), 7.61 and 7.29 (AA’BB’ system, 4H), 6.57 (dd, J=
2.1, 0.9 Hz, 1H), 5.02 (d, J=0.8 Hz, 1H), 3.48 (m, 1H), 3.43 (td, J=2.1,
0.8 Hz, 1H), 3.23 (q, J=7.1 Hz, 2H), 2.44 (s, 3H), 2.41 (s, 3H), 1.73 (d,
J=7.0 Hz, 3H), 0.88 ppm (t, J=7.0 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d=170.8 (C), 151.6 (C), 145.5 (C), 143.5 (C), 135.6 (C), 135.5
(CH), 135.4 (C), 130.3 (2”CH), 129.8 (2”CH), 127.9 (2”CH), 127.3 (2”
CH), 103.9 (CH), 74.0 (C), 65.9 (CH2), 52.9 (CH), 47.3 (CH), 21.7 (CH3),
21.6 (CH3), 16.4 (CH3), 14.3 ppm (CH3); IR (KBr): n˜ =1754, 1321, 1153,
1086, 924 cmÀ1; MS (FAB): m/z: 475 [M+H]+; HRMS (FAB): m/z calcd
for C24H27O6S2: 475.1249 [M+H]; found: 475.1259 [M+H]+.
Compound 8b: Following general procedure A with sulfinylfuranone 2b
(0.19 mmol), sulfonylallene 3 (0.29 mmol) and PPh3 (0.06 mmol in 1 mL)
were stirred for 1 h. Isolation by column chromatography (hexane/di-
chloromethane/diethyl ether, 4:2:1) as a white solid (42%). M.p. 60–
628C (with decomposition); [a]2D0 =+115.8 (c=0.78 in CHCl3); 1H NMR
(300 MHz, CDCl3): d=7.76 and 7.36 (AA’BB’ system, 4H), 7.47 and 7.29
(AA’BB’ system, 4H), 6.57 (dt, J=2.5, 2.0 Hz, 1H), 5.11 (d, J=1.5 Hz,
1H), 3.70 (m, 1H), 3.40 (t, J=2.0 Hz, 2H), 3.26 (q, J=7.1 Hz, 2H), 2.45
(s, 3H), 2.40 (s, 3H), 0.84 ppm (t, J=7.1 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d=172.3 (C), 145.6 (2”C), 143.0 (C), 136.3 (CH), 134.8 (2”C),
130.3 (CH), 129.7 (CH), 128.1 (CH), 125.7 (CH3), 105.3 (CH), 75.7 (C),
65.8 (CH2), 51.7 (CH), 39.0 (CH2), 21.7 (CH3), 21.5 (CH3), 14.3 ppm
(CH3); IR (KBr): n˜ =1765, 1626, 1596, 1353, 1155, 1085, 929 cmÀ1; ele-
mental analysis calcd (%) for C23H24O6S2: C 59.98, H 5.25, S 13.92;
found: C 59.69, H 5.36, S 13.48.
General procedure for reductive desulfinylation with aluminium amal-
gam: Aluminium amalgam (obtained from the amount of aluminium
kitchen foil indicated in each case) was added in small portions to a vigo-
rously stirred 0.01m solution of sulfinylcycloadduct 8a, 8b, 10a, 11a-endo
or 11a-exo in a 9:1 mixture of THF/water. The reaction was monitored
by TLC and when the starting material was no longer observed the reac-
tion mixture was filtered through Celite and the solid was washed with
dichloromethane. The solvent was removed under reduced pressure and
the product was isolated by column chromatography with the eluent indi-
cated in each case.
Compound (+)-12: After following the general desulfination procedure
with cycloadduct 8a (0.15 mmol, 70 mg) and aluminium foil (277 mg),
isolation by column chromatography (hexane/ethyl acetate, 3:1) gave
(+)-12 as a white solid (93%). M.p. 110–1128C; [a]2D0 =+98.3 (c=0.88 in
CHCl3); 1H NMR (300 MHz, CDCl3): d=7.74 and 7.35 (AA’BB’ system,
4H), 6.61 (m, 1H), 5.38 (s, 1H), 3.86 (m, 1H), 3.67–3.56 (m, 2H), 3.39
(td, J=8.7, 1.9 Hz, 1H), 2.98 (ddt, J=16.8, 8.7, 2.5 Hz, 1H), 2.85 (dq, J=
16.8, 1.9 Hz, 1H), 2.44 (s, 3H) 1.23 ppm (t, J=7.0 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=177.9 (C), 147.6 (C), 145.3 (C), 136.8 (CH), 135.2
(C), 130.2 (CH), 128.1 (CH), 104.3 (CH), 65.4 (CH2), 53.9 (CH), 41.5
(CH), 34.8 (CH2), 21.7 (CH3), 14.8 ppm (CH3); IR (film): n˜ =1778, 1596,
1351, 1153, 940 cmÀ1; elemental analysis calcd (%) for C16H18O5S: C
59.61, H 5.63, S 9.95; found: C 59.66, H 5.63, S 9.96; HPLC (70:30
hexane/isopropyl alcohol, flow 1 mLminÀ1): ee=99.5%, retention time
(tR)=11.9 min.
Compound (Æ)-9: Following procedure C, furanone (Æ)-1, allene 4
(1.5 equiv), p-TolSO2Na (0.7 equiv) and [18]crown-6 (0.7 equiv) were
stirred for 24 h. Purification by column chromatography (hexane/ethyl
acetate, 2:1) gave 9 as a white solid (56%). M.p. 148–1508C; 1H NMR
(300 MHz, CDCl3): d=7.73 and 7.33 (AA’BB’ system, 4H), 5.26 (s, 1H),
3.50 (s, 3H), 3.44 (m, 1H), 3.18 (td, J=8.2, 2.3 Hz, 1H), 2.96 (m, 2H),
2.43 (s, 3H), 2.24 ppm (brs, 3H); 13C NMR (75 MHz, CDCl3): d=178.0
(C), 147.0 (C), 144.9 (C), 137.4 (C), 137.0 (C), 130.0 (2”CH), 127.4 (2”
CH), 104.7 (CH), 59.6 (CH), 56.7 (CH3), 38.4 (CH), 36.9 (CH2), 21.6
(CH3), 13.4 ppm (CH3); IR (KBr): n˜ =1774, 1632, 1319, 1149, 936 cmÀ1
;
elemental analysis calcd (%) for C16H18O5S: C 59.61, H 5.63, S 9.95;
found: C 59.63, H 5.66, S 9.91.
Compound 10a: Following procedure C, furanone 2a, allene
4
(1.5 equiv), p-TolSO2Na (0.7 equiv) and [18]crown-6 (0.7 equiv) were
stirred for 4 h. Purification by column chromatography (hexane/ethyl ace-
tate, 2:1) gave 10a as a white solid (61%). M.p. 135–1378C (with decom-
position); [a]2D0 =+108.5 (c=0.60 in CHCl3); 1H NMR (300 MHz,
CDCl3): d=7.64 (m, 2H), 7.47 (m, 2H), 7.32–7.27 (m, 4H), 5.42 (d, J=
1.0 Hz, 1H), 3.90 (m, 1H), 3.88 (m, 1H), 3.69 (m, 1H), 3.17 (m, 1H),
2.60 (m, 1H), 2.44 (s, 3H), 2.43 (s, 3H), 2.17 (brs, 3H), 1.28 ppm (t, J=
7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=172.1 (C), 146.2 (C), 145.0
(C), 143.2 (C), 136.9, (C) 136.1 (C), 135.2 (C), 130.1 (CH), 129.6 (CH),
127.4 (CH), 125.7 (CH), 103.3 (CH), 69.7 (C), 65.9 (CH2), 60.7 (CH),
35.6 (CH2), 21.6 (2”CH3), 14.9 (CH3), 13.4 ppm (CH3); IR (KBr): n˜ =
1774, 1638, 1596, 1322, 1154, 961 cmÀ1; elemental analysis calcd (%) for
C24H26O6S2: C 60.74, H 5.52, S 13.51; found: C 60.48, H 5.58, S 13.35.
Compound (À)-12: After following the general desulfination procedure
with cycloadduct 8b (0.13 mmol, 60 mg) and aluminium foil (300 mg),
isolation by column chromatography (hexane/ethyl acetate, 3:1) gave
(À)-12 as a white solid (70%). M.p. 106–1088C; [a]2D0 =À96.4 (c=0.70 in
CHCl3); elemental analysis calcd (%) for C16H18O5S: C 59.61, H 5.63, S
9.95; found: C 59.55, H 5.56, S 10.27; HPLC (70:30 hexane/isopropyl al-
cohol, flow 1 mLminÀ1): ee=99.5%, tR =9.5 min.
Compound 13a: After following the general desulfination procedure
with cycloadduct 10a (0.15 mmol, 70 mg) and aluminium foil (277 mg),
isolation by column chromatography (hexane/ethyl acetate, 3:1) gave 13a
as
a
white solid (80%). M.p. 110–1128C; [a]2D0 =+59.2 (c=0.60 in
CHCl3); 1H NMR (300 MHz, CDCl3): d=7.72 and 7.33 (AA’BB’ system,
4H), 5.36 (s, 1H), 3.85 (dq, J=9.4, 7.1 Hz, 1H), 3.62 (dq, J=9.4, 7.1 Hz,
1H), 3.44 (m, 1H), 3.20 (td, J=8.5, 2.1 Hz, 1H), 2.96 (m, 2H), 2.43 (s,
3H), 2.24 (brs, 3H), 1.23 ppm (t, J=7.1 Hz, 3H); 13C NMR (75 MHz,
Compound 11: Following procedure C, compound 2a, 5 (1.5 equiv), p-
TolSO2Na (0.7 equiv) and [18]crown-6 (0.7 equiv) were stirred for 30 min.
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Synthesis of Enantiopure Cyclopentenes
FULL PAPER
CDCl3): d=178.1 (C), 147.1 (C), 144.9 (C), 137.3 (C), 137.0 (C), 130.0
(CH), 127.4 (CH), 103.6 (CH), 65.3 (CH2), 59.7 (CH), 38.6 (CH), 36.9
(CH2), 21.6 (CH3), 14.8 (CH3), 13.4 ppm (CH3); IR (KBr): n˜ =1777, 1632,
1318, 1148, 938 cmÀ1; elemental analysis calcd (%) for C17H20O5S: C
60.70, H 5.99, S 9.53; found: C 60.71, H 6.03, S 9.62.
monitored by TLC and sodium amalgam was sequentially added in small
portions until no starting material remained or the corresponding sulfinyl
compounds were observed. The reaction mixture was filtered through
Celite and the solid residue was washed with dichloromethane. The fil-
trates were combined and the solvent was removed under reduced pres-
sure.
Compound 14a-endo: After following the general desulfination proce-
dure with cycloadduct 11a-endo (0.15 mmol, 71 mg) and aluminium foil
(235 mg), isolation by column chromatography (hexane/ethyl acetate,
3:1) gave 14a-endo as a colourless, gummy solid (81%). [a]2D0 =+24.9
(c=1.9 in CHCl3); 1H NMR (300 MHz, CDCl3): d=7.74 and 7.34
(AA’BB’ system, 4H), 6.61 (m, 1H), 5.29 (d, J=1.4 Hz, 1H), 3.86 (m,
1H), 3.60 (m, 1H), 3.52 (m, 1H), 3.42–3.33 (m, 2H), 2.44 (s, 3H), 1.27
(d, J=6.8 Hz, 3H), 1.22 ppm (t, J=7.0 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d=174.4 (C), 151.0 (C), 145.0 (C), 137.9 (CH), 136.4 (C), 130.0
(CH), 128.0 (CH), 103.9 (CH), 65.4 (CH2), 52.5 (CH), 45.7 (CH), 41.4
(CH), 21.6 (CH3), 14.8 (CH3), 14.6 ppm (CH3); IR (film): n˜ =1776, 1597,
1315, 1052, 948 cmÀ1; HRMS (ESI): m/z calcd for C17H21O5S: 337.1104
[M+H]+; found: 337.1120 [M+H]+; m/z calcd for C17H20O5NaS: 359.0923
[M+Na]+; found: 359.0920 [M+Na]+.
Compound 17a: After following the general procedure above with 8a
(93 mg, 0.20 mmol), NH4Cl (1 g), methanol (3.3 mL) and 6% sodium
amalgam (1 g), purification by column chromatography (hexane/diethyl
ether, 6:1) gave 17a as a colourless oil (66%). [a]2D0 =+139.0 (c=0.30 in
CHCl3); 1H NMR (300 MHz, CDCl3): d=5.86 (dq, J=5.7, 2.2 Hz, 1H),
5.68 (dq, J=5.7, 2.1 Hz, 1H), 5.30 (s, 1H), 3.88 (m, 1H), 3.61 (m, 1H),
3.43 (m, 1H), 3.27 (td, J=7.2, 3.4 Hz, 1H), 2.75 (m, 2H), 1.24 ppm (t, J=
7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=180.4 (C), 133.2 (CH),
128.0 (CH), 105.9 (CH), 65.0 (CH2), 54.1 (CH), 41.0 (CH), 36.6 (CH2),
14.9 ppm (CH3); IR (film): n˜ =1777, 1646, 1351, 1240, 1113, 952,
931 cmÀ1; elemental analysis calcd (%) for C9H12O3: C 64.27, H 7.19;
found: C 64.31, H 7.21.
Compound 18a: After following the general procedure above with 10a
(60 mg, 0.13 mmol), NH4Cl (650 mg), MeOH (1.9 mL) and 6% sodium
amalgam (1.6 g), purification by column chromatography (hexane/diethyl
ether, 9:1) gave 18a as a colourless oil (63%). [a]2D0 =+45.3 (c=0.60 in
Compound 14a-exo: After following the general desulfination procedure
with cycloadduct 11a-exo (0.12 mmol, 58 mg) and aluminium foil
(80 mg), isolation by column chromatography (hexane/ethyl acetate, 3:1)
gave 14a-exo as a colourless, gummy solid (87%). [a]2D0 =+105.0 (c=1.4
in CHCl3); 1H NMR (300 MHz, CDCl3): d=7.71 and 7.33 (AA’BB’
system, 4H), 6.59 (brs, 1H), 5.36 (s, 1H), 3.84 (m, 1H), 3.65–3.55 (m,
2H), 3.13 (q, J=7.1 Hz, 1H), 2.97 (d, J=7.1 Hz, 1H), 2.43 (s, 3H), 1.31
(d, J=7.1 Hz, 3H), 1.22 ppm (t, J=7.1 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d=177.3 (C), 152.3 (C), 145.1 (C), 136.8 (CH), 135.8 (C), 130.1
(CH), 127.9 (CH), 104.0 (CH), 65.3 (CH2), 51.9 (CH), 50.1 (CH), 43.7
(CH), 21.7 (CH3), 20.4 (CH3), 14.8 ppm (CH3); IR (film): n˜ 1775, 1597,
1316, 1151, 945 cmÀ1; HRMS (ESI): m/z calcd for C17H21O5S: 337.1104
[M+H]+; found: 337.1121 [M+H]+; m/z calcd for C17H20O5NaS: 359.0923
[M+Na]+; found: 359.0917 [M+Na]+.
1
CHCl3); H NMR (300 MHz, CDCl3): d=5.42 (m, 1H), 5.33 (s, 1H), 3.88
(m, 1H), 3.62 (m, 1H), 3.24 (m, 2H), 2.67 (m, 2H), 1.78 (brs, 3H),
1.25 ppm (t, J=7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=180.6 (C),
136.3 (C), 127.1 (CH), 104.3 (CH), 64.9 (CH2), 56.7 (CH), 41.7 (CH),
35.9 (CH2), 14.9 (CH3), 14.3 ppm (CH3); IR (film): n˜ =1760, 1655, 1234,
1105, 928 cmÀ1; HRMS (ESI): m/z calcd for C10H15O3: 183.1015 [M+H]+;
found: 183.1026 [M+H]+; m/z calcd for C10H14O3Na: 205.0835 [M+Na]+;
found: 205.0838 [M+Na]+.
Compound 19a-endo: After following the general procedure above with
11a-endo (42 mg, 0.09 mmol), NH4Cl (450 mg), MeOH (1.3 mL) and 6%
sodium amalgam (1.2 g), purification by column chromatography
(hexane/diethyl ether, 6:1) gave 19a-endo as a colourless oil (61%).
Catalytic hydrogenation (15a): A solution of (+)-12 (0.17 mmol) in ethyl
acetate (3 mL) containing 10% Pd(C) (25 mg) was stirred under positive
pressure of hydrogen at room temperature for 1 h. The suspension was
filtered through Celite, the solid residue was washed with ethyl acetate
and the solvent was removed in vacuo. Compound 15a was recrystallised
from dichloromethane/diethyl ether as a white solid (92%). M.p. 198–
2008C; [a]2D0 =+80.8 (c=1.0 in CHCl3); 1H NMR (300 MHz, CDCl3): d=
7.76 and 7.36 (AA’BB’ system, 4H), 5.31 (d, J=0.7 Hz, 1H), 3.86 (m,
1H), 3.60 (m, 1H), 3.54 (m, 1H), 3.19 (m, 1H), 2.81 (m, 1H), 2.45 (s,
3H), 2.38 (m, 1H), 2.29 (m, 1H), 2.00 (dt, J=13.3, 10.2 Hz, 1H),
1.21 ppm (t, J=7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=177.9 (C),
145.2 (C), 134.8 (C), 130.0 (CH), 128.6 (CH), 106.0 (CH), 65.3 (CH2),
64.9 (CH), 47.0 (CH), 42.9 (CH), 30.3 (CH2), 29.7 (CH2), 21.6 (CH),
14.9 ppm (CH3); IR (KBr): n˜ =1756, 1322, 1142, 1043, 939 cmÀ1; elemen-
tal analysis calcd (%) for C16H20O5S: C 59.24, H 6.21, S 9.88; found: C
59.10, H 6.12, S 9.94.
1
[a]2D0 =+3.8 (c=0.40 in CHCl3); H NMR (300 MHz, CDCl3): d=5.71 (dt,
J=5.6, 2.0 Hz, 1H), 5.63 (dt, J=5.6, 2.2 Hz, 1H), 5.20 (d, J=1.1 Hz,
1H), 3.87 (dq, J=9.5, 7.0 Hz, 1H), 3.59 (dq, J=9.5, 7.0 Hz, 1H), 3.47 (m,
1H), 3.28 (dd, J=9.1, 8.0 Hz, 1H), 3.20 (m, 1H), 1.24 (t, J=7.0 Hz, 3H),
1.23 ppm (d, J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=176.6 (C),
139.4 (CH), 126.7 (CH), 105.6 (CH), 64.9 (CH2), 55.0 (CH), 44.5 (CH),
42.3 (CH), 16.0 (CH3), 14.9 ppm (CH3); IR (film): n˜ =1775, 1646, 1166,
1117, 950 cmÀ1; HRMS (ESI): m/z calcd for C10H15O3: 183.1015 [M+H]+;
found: 183.1022 [M+H]+; m/z calcd for C10H14O3Na: 205.0835 [M+Na]+;
found: 205.0837 [M+Na]+.
Compound (Æ)-20: After following the general procedure above with
(Æ)-6 (64 mg, 0.21 mmol), NH4Cl (1 g), methanol (3 mL) and 6% sodium
amalgam (1.8 g), purification by column chromatography (hexane/diethyl
ether, 6:1) gave (Æ)-20 as a colourless oil (60%). 1H NMR (300 MHz,
CDCl3): d=5.86 (dq, J=5.7, 2.2 Hz, 1H), 5.68 (dq, J=5.7, 2.1 Hz, 1H),
5.20 (s, 1H), 3.51 (s, 3H), 3.43 (m, 1H), 3.25 (td, J=7.2, 3.4 Hz, 1H),
2.75 ppm (m, 2H); 13C NMR (75 MHz, CDCl3): d=180.3 (C), 133.3
(CH), 127.9 (CH), 107.0 (CH), 56.5 (CH3), 54.0 (CH), 40.9 (CH),
36.6 ppm (CH2).
Compound 16a-exo: Following the above procedure, a solution of 14a-
exo (23 mg, 0.07 mmol) in ethyl acetate (1.5 mL) and 10% Pd(C) (10 mg)
was stirred for 2 h. Purification by column chromatography (hexane/ethyl
acetate, 2:1) gave 16a-exo as a white solid (85%). M.p. 138–1398C;
[a]2D0 =+48.8 (c=0.5 in CHCl3); 1H NMR (300 MHz, CDCl3): d=7.76
and 7.36 (AA’BB’ system, 4H), 5.24 (s, 1H), 3.83 (m, 1H), 3.57 (m, 1H),
3.16 (m, 1H), 2.85–2.63 (m, 3H,), 2.46 (s, 3H), 2.31 (m, 1H), 1.96 (m,
1H), 1.19 (t, J=7.2 Hz, 3H), 1.15 ppm (d, J=6.8 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=177.4 (C), 145.2 (C), 134.9 (C), 130.0 (CH), 128.7
(CH), 106.0 (CH), 71.6 (CH), 65.3 (CH2), 51.6 (CH), 45.4 (CH), 39.0
(CH), 31.3 (CH2), 21.6 (CH3), 21.2 (CH3), 14.8 ppm (CH3); IR (KBr): n˜ =
1771, 1598, 1301, 1284, 1146, 927 cmÀ1; elemental analysis calcd (%) for
C17H22O5S: C 60.33, H 6.55; found: C 60.30, H 6.58.
Compound (Æ)-21: After following the general procedure above with
(Æ)-9 (64 mg, 0.20 mmol), NH4Cl (1 g), methanol (3 mL) and 6% sodium
amalgam (1.8 g), purification by column chromatography (hexane/diethyl
ether, 6:1) gave (Æ)-21 as a colourless oil (60%). 1H NMR (300 MHz,
CDCl3): d=5.43 (m, 1H), 5.22 (s, 1H), 3.51 (s, 3H), 3.24 (m, 2H), 2.68
(m, 2H), 1.68 ppm (brs, 3H); 13C NMR (75 MHz, CDCl3): d=180.5,
136.2, 127.1, 105.5, 56.6, 56.5, 41.5, 35.8, 14.3 ppm.
Synthesis of acetal-ester 22: A solution of 16a-exo (17 mg, 0.05 mmol) in
methanol (2 mL) containing 1% sulfuric acid was allowed to stand for
24 h at room temperature. The reaction mixture was neutralised with
solid NaHCO3 (60 mg) and stirred for 30 min. The solid was filtered off
and the solvent was removed in vacuo. The crude ester acetal was puri-
fied by column chromatography (hexane/diethyl ether, 1:1) to give 22 as
General procedure for reductive desulfination and desulfonylation with
sodium amalgam: NH4Cl and 6% sodium amalgam (see individual en-
tries for quantities) were added in small portions to a 0.01m solution of
sulfone 8a, 10a, 11a-endo, (Æ)-6 or (Æ)-9 in anhydrous THF, cooled in
an ice bath. After the addition of the first amalgam portions, anhydrous
MeOH (see individual entries for volume) was added. The reaction was
a
colourless oil (82%). [a]2D0 =À26.5 (c=1.0 in CHCl2); 1H NMR
(300 MHz, CD2Cl2): d=7.76 and 7.39 (AA’BB’ system, 4H), 4.32 (d, J=
Chem. Eur. J. 2010, 16, 5443 – 5453
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M. R. Martín, J. L. García Ruano et al.
8.1 Hz, 1H), 3.63 (s, 3H), 3.26 (s, 3H), 3.20 (s, 3H), 3.08 (q, J=9.0 Hz,
1H), 2.69 (m, 1H), 2.51 (m, 2H), 2.45 (s, 3H), 2.13 (m, 1H), 1.94 (m,
1H), 1.03 ppm (d, J=6.6 Hz, 3H); 13C NMR (75 MHz, CD2Cl2): d=173.3
(C), 145.5 (C), 136.3 (C), 130.4 (CH), 129.1 (CH), 104.6 (CH), 69.8 (CH),
54.5 (CH3), 53.8 (CH), 53.7 (CH3), 52.0 (CH3) 43.2 (CH), 39.0 (CH), 30.2
(CH2), 21.9 (CH3), 19.8 ppm (CH3); IR (film): n˜ =1732, 1597, 1301, 1285,
1145, 1058 cmÀ1; HRMS (ESI): m/z calcd for C18H26O6SNa: 393.1342
[M+Na]+; found: 393.1356 [M+Na]+.
M. R. Martín, Tetrahedron Lett. 2004, 45, 4653–4656; for cycloaddi-
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j) J. L. García Ruano, A. Fraile, M. R. Martín, G. Gonzµlez, C. Fajar-
do, J. Org. Chem. 2008, 73, 8484–8490. For cycloaddition of carbon-
yl ylides, see: k) J. L. García Ruano, A. Fraile, M. R. Martín, A.
NuÇez, J. Org. Chem. 2006, 71, 6536–6541.
[12] J. L. García Ruano, A. NfflÇez, Jr., M. R. Martín, A. Fraile, J. Org.
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[13] Z-X. Yu, and co-workers suggest the intervention of water mole-
cules to explain the intramolecular [1,2]-proton shift indicated in
Scheme 1, see: Y. Liang, S. Liu, Z-X. Yu, Synlett 2009, 905–909, and
references therein.
Acknowledgements
We thank DGICYT (CTQ2009-12168/BQU) and Comunidad Autónoma
de Madrid (CCG08-UAM/PPQ-4151/08 and S2009/PPQ-1634) for finan-
cial support. We thank Universidad Autónoma de Madrid for a Predoc-
toral Fellowship to A.N.
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5452
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Chem. Eur. J. 2010, 16, 5443 – 5453

Synthesis of Enantiopure Cyclopentenes
FULL PAPER
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[35] CCDC-755291 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
Received: November 19, 2009
Published online: April 6, 2010
Chem. Eur. J. 2010, 16, 5443 – 5453
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5453