Pyrrolo[2,1-b]thiazole derivatives by asymmetric 1,3-dipolar reactions of thiazolium azomethine ylides to activated vinyl sulfoxides

Article abstract of DOI:10.1021/jo801705d

(Chemical Equation Presented) 1,3-Dipolar reactions of thiazolium azomethine ylides to enantiopure cyclic and acyclic vinyl sulfoxides provide an efficient access to polyfunctionalized pyrrolo[2,1-b][1,3]thiazoles in a highly regio- and stereoselective manner. Regioselectivity can be inverted by modifying the position of the sulfinyl group at the double bond of the sulfinylfuranones. The sulfoxide is the main controller of the endo selectivity of these processes as well as of the π-facial selectivity in reactions of (Z)-3-p- tolylsulfinylacrylonitriles. In contrast, the π-facial selectivity in reactions of 5-alkoxy-3-p-tolylsulfinyl furan-2(5H)-ones is mainly controlled by the configuration at C-5, affording the anti adducts with respect to the alkoxy group as the major or exclusive adducts.

Full text of DOI:10.1021/jo801705d

Pyrrolo[2,1-b]thiazole Derivatives by Asymmetric 1,3-Dipolar
Reactions of Thiazolium Azomethine Ylides to Activated Vinyl
Sulfoxides
Jose´ Luis Garc´ıa Ruano,* Alberto Fraile, M. Rosario Mart´ın,* Gema Gonza´lez, and
Cristina Fajardo
Departamento de Qu´ımica Orga´nica, UniVersidad Auto´noma de Madrid, Cantoblanco,
28049 Madrid, Spain
joseluis.garcia.ruano@uam.es
ReceiVed July 31, 2008
1,3-Dipolar reactions of thiazolium azomethine ylides to enantiopure cyclic and acyclic vinyl sulfoxides
provide an efficient access to polyfunctionalized pyrrolo[2,1-b][1,3]thiazoles in a highly regio- and
stereoselective manner. Regioselectivity can be inverted by modifying the position of the sulfinyl group
at the double bond of the sulfinylfuranones. The sulfoxide is the main controller of the endo selectivity
of these processes as well as of the π-facial selectivity in reactions of (Z)-3-p-tolylsulfinylacrylonitriles.
In contrast, the π-facial selectivity in reactions of 5-alkoxy-3-p-tolylsulfinyl furan-2(5H)-ones is mainly
controlled by the configuration at C-5, affording the anti adducts with respect to the alkoxy group as the
major or exclusive adducts.
Introduction
formation of thiazolidine intermediate through the reaction of
ꢀ-amino thiols (generally L-cysteine) with γ-formyl acid deriva-
tives or their corresponding acetals3d in the presence of stannous
chloride.
Additionally, polyhydropyrrolo[2,1-b]thiazoles, with no lac-
tam moiety in their skeleton, have interesting pharmacological
properties and have been successfully used as intermediates in
the synthesis of pyrrolidines, such as racemic R-allokainic4a and
kainic acids4b or 2S,4R-4-methylpyrrolidine-2,4-dicarboxylate.5
However, the antecedents of the asymmetric synthesis of
polyhydropyrrolo[2,1-b]thiazoles are scarce. Katritzky6 and
Beaupere7 obtained this system via a condensation reaction with
L-cysteine ester and D-monosaccharides as chiral reagents,
The interest in polyhydroderivatives of pyrrolo[2,1-b]thia-
zoles is related to the wide scope of their biological activities,
allowing their use as hepatoprotective, hypoglycemic (an-
tidiabetic), antibiotic, anticonvulsant, antiinflammatory, or
antileukemic agents, bactericides, or as dopaminergic neu-
rotransmissors in CNS in vivo and dipeptidyl peptidase IV
(DPP-IV) inhibitors.1
There is a rich history regarding the preparation and im-
portance of tetrahydropyrrolo[2,1-b]thiazol-5(6H)-one scaffolds.
There are reports of solution-2 and solid-phase3 syntheses of
derivatives of this bicyclic scaffold. The majority rely on the
(1) (a) Campbell, D. A.; Betancort, J. M.; Winn, D. T. US Patent US
2006009518, 2006. (b) Wagner, H.; Schoenafinger, K.; Jaehne, G.; Gaul, H.;
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Ushirogochi, H.; Sato, K.; Takasaki, T.; Venkatesan, A. M.; Mansour, T. S. US
Pat. US 2004132708, 2004; Chem. Abstr. 2004, 141, 550737. (d) Aicher, T. D.;
Cheon, S. H.; Nadelson, J.; Simpson, W. R. J.; Houlihan, W. J. Eur. Pat. EP
702015, 1996; Chem. Abstr. 1996, 124, 343285. (e) Suzuki, N.; Nakayama, A.;
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J. Am. Chem. Soc. 2007, 129, 7077–7088, and references cited therein. (b)
Nielsen, T. E.; Le Quement, S.; Meldal, M. Gu, X.; Ying, J.; Agnes, R. S.;
Navratilova, E.; Davis, P.; Stahl, G.; Porreca, F.; Yamamura, H. I. Org. Lett.
2005, 7, 3601–3604. (c) Hruby, V. J. Org. Lett. 2004, 6, 3285–3288. (d) Cayley,
A. N.; Cox, R. J.; Me´nard-Moyon, C.; Schmidt, J. P.; Taylor, R. J. K. Tetrahedron
Lett. 2007, 48, 6556–6560.
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8484 J. Org. Chem. 2008, 73, 8484–8490
10.1021/jo801705d CCC: $40.75 2008 American Chemical Society
Published on Web 10/08/2008

1,3-Dipolar Reactions of Thiazolium Azomethine Ylides
reported examples on asymmetric [3 + 2] cycloaddition of
azomethine ylides to chiral vinyl sulfoxides.
The reported results prompted us to investigate the behavior
of the arylsulfinylfuran-2(5H)-ones and 3-p-tolylsulfinylacry-
lonitriles as chiral dipolarophiles in their reactions with thia-
zolium ylides as a method for preparing tetrahydropyrrolo[2,1-
b]thiazole scaffolds. In this paper, we report the results obtained
in the reactions of thiazolium ylides14b and 2 (Figure 1) with
acyclic (3-5)17 and cyclic (618 and 719) vinyl sulfoxides, which
have provided a quick and efficient entry to a variety of optically
pure functionalized pyrrolo[2,1-b]thiazoles. These studies have
also improved our knowledge on the role of the sulfinyl group
in asymmetric 1,3-dipolar reactions and widened the scope of
vinyl sulfoxides as chiral dipolarophiles.
FIGURE 1. Dipoles and dipolarophiles studied.
respectively. Another reported method involves the ring contrac-
tion of 7,5-fused bicyclic thiazolidinelactams.8
Retrosynthetic analysis of polyhydropyrrolo[2,1-b]thiazoles
shows the 1,3-dipolar addition of thiazolium ylides to alkenes
as the most direct route for their preparation. However, the
asymmetric addition of 1 (Figure 1) to 2-methylacrylate bearing
an Evans oxazolidinone as chiral auxiliary is the only reported
example.5,9,10 Although enantioselective catalysis afforded good
results in the synthesis of enantiomerically pure pyrrolidines
using azomethine ylides generated from imino ester,11 thiazo-
lium ylides, because of their strongly delocalized structure, are
not likely to join efficiently to the so far studied catalysts.
Therefore, the use of chiral dipolarophiles for the asymmetric
synthesis of polyhydropyrrolo[2,1-b]thiazoles maintains its in-
terest.
Results and Discussion
Unstable ylides 1 and 2 were generated from the correspond-
ing quaternary ammonium bromides with amine base in the
presence of the dipolarophile. Initially we studied the behavior
of these ylides with the acyclic sulfoxides. The reaction of
sulfinylacrylonitrile 3 with ylide 1 afforded pyrrole 9 (Scheme
1), resulting from desulfinylation and further opening of the
thiazole ring at the primary adduct.
Several years ago, we initiated a program focused on the
applicability of vinyl sulfoxides as dipolarophiles in asymmetric
1,3-dipolar reactions. In this field, the excellent features of the
arylsulfinylfuran-2(5H)-ones12 and 3-p-tolylsulfinylacryloni-
triles13 as chiral dipolarophiles have been evidenced in their
reactions with diazoalkanes, nitrones, nitrile oxides, and carbonyl
ylides. Otherwise, reactions of N-metalated azomethine ylides
with sulfinylacrylates14 and 2-sulfinylcyclopentenone15 also
provided an excellent access to the asymmetric synthesis of
pyrrolidine rings. These results, and those concerning the
cycloaddition of 3-oxopyridinium betaines,16 are so far the only
However, the primary adducts could be isolated starting from
ylide 2, which reacted with 3 in a completely stereoselective
and regioselective way, affording only compound 10 (Scheme
2) in almost quantitative yield. However, after chromatographic
purification, the isolated yield was only 50% because it was
not quite stable in solution due to its easy desulfinylation.
Reaction of 2 with 4 also produced 11 as the only adduct but
its lower reactivity, due to the higher steric hindrance, deter-
mined a conversion of 50% (the unreacted dipolarophile could
be recovered). Compound 11 was less prone to desulfinylation
than 10, and therefore, it could be obtained in 39% isolated
yield after purification (78% based on recovered starting
material). The reaction of the most sterically hindered sulfiny-
lacrylonitrile 5 with ylide 2 was not successful, although the
unaltered dipolarophile could be recovered after long period of
times (Scheme 2).
We decided to investigate the reactions of ylides 1 and 2
with cyclic dipolarophiles because of the presumably higher
stability of the resulting adducts, which are less prone to
desulfinylation. As a control experiment, initially we studied
the reaction of 5-methoxyfuran-2(5H)-one (8) with ylide 2 under
different conditions. It did not take place successfully (starting
material and other not identifiable products were recovered from
the reaction mixtures), which proves the moderate reactivity of
the ylides derived from the thiazolium salts, which are not able
to react with the nonactivated furanone. Fortunately, the in-
corporation of the sulfinyl group into the dipolarophile dramati-
cally increases the reactivity, and therefore, the reaction of
furanone 6a with ylide 1 in acetonitrile proceeded at room
temperature in 5 min, yielding the adduct anti-12a-endo only
(Scheme 3). It is the result of the attack of the dipole, in its
s-trans conformation (see Figure 2), to the opposite face to that
occupied by the OEt group and endo mode approach. After
(7) Marek, D.; Wadouachi, A.; Uzan, R.; Beaupere, D.; Nowogrocki, G.;
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(9) The antecedents of cycloaddition of thiazolium azomethine ylides to
racemic olefinic dipolarophiles are also scarce. Polyhydropyrrolo[2,1-b]thiazoles
are reported by Kraus and Tsuge in references 4a and 10, respectively. For a
recent example of formation of aromatic systems, see: (a) Berry, C. R.; Zificsak,
C. A.; Hlasta, D. Org. Lett. 2007, 9, 4099–4102.
(10) Tsuge, O.; Kanemasa, S.; Takenaka, S. Bull. Chem. Soc. Jpn. 1985, 58,
31373157 a, nd 3320-3336.
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1795–1798. (b) Zeng, W.; Zhou, Y. Tetrahedron Lett. 2007, 48, 4619–4622. (c)
Alemparte, C.; Blay, G.; Jørgensen, K. A. Org. Lett. 2005, 7, 4569–4572. (d)
Na´jera, C.; Retamosa, M. G.; Sansano, J. M. Org. Lett. 2007, 9, 4025–4028. (e)
Saito, S.; Tsubogo, T.; Kobayashi, S. J. Am. Chem. Soc. 2007, 129, 5364–5365,
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(12) (a) Garc´ıa Ruano, J. L.; Fraile, A.; Gonza´lez, G.; Mart´ın, M. R.;
Clemente, F. R.; Gordillo, R. J. Org. Chem. 2003, 68, 6522–6534. (b) Garc´ıa
Ruano, J. L.; Alonso, M.; Fraile, A.; Mart´ın, M. R.; Peromingo, M. T.; Tito, A.
J. Org. Chem. 2005, 70, 8942–8947. (c) Garc´ıa Ruano, J. L.; Bercial, F.; Fraile,
A.; Mart´ın, M. R. Synlett 2002, 73, 76. (d) Garc´ıa Ruano, J. L.; Fraile, A.; Mart´ın
Castro, A. M.; Mart´ın, M. R. J. Org. Chem. 2005, 70, 8825–8834. (e) Garc´ıa
Ruano, J. L.; Fraile, A.; Mart´ın, M. R.; Nu´n˜ez, A. J. Org. Chem. 2006, 71,
6536–6541. (f) Garc´ıa Ruano, J. L.; Bercial, F.; Gonza´lez, G.; Mart´ın Castro,
A. M.; Mart´ın, M. R. Tetrahedron: Asymmetry 2002, 13, 1993–2002.
(13) Garc´ıa Ruano, J. L.; Alonso de Diego, S. A.; Blanco, D.; Mart´ın Castro,
A. M.; Mart´ın, M. R.; Rodr´ıguez Ramos, J. H. Org. Lett. 2001, 3, 3173–3176.
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Rodr´ıguez, J. H.; Lo´pez Solera, M. I. J. Org. Chem. 1998, 63, 3324–3332.
(18) Carretero, J, C.; Garc´ıa Ruano, J. L.; Yuste, F.; Lorente, A. Tetrahedron:
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J. Org. Chem. Vol. 73, No. 21, 2008 8485

Garc´ıa Ruano et al.
SCHEME 1. Reaction of Ylide 1 with Sulfinylacrylonitriles 3
SCHEME 2. Reaction of Ylide 2 with Sulfinylacrylonitriles
3-5
from 1. Only one adduct, anti-14a-endo, was obtained from
furanone 6a in 78% isolated yield (after chromatographic
separation), whereas a 75:25 mixture of two diastereoisomers,
anti-14b-endo and syn-14b-endo, which could not be separated,
was obtained from furanone 6b.
As all these reactions evolved in a completely regioselective
manner, the preparation of the adducts with the opposite
regiochemistry became an important challenge in order to
broaden the structural diversity of the pyrrolo[2,1-b]thiazole
derivatives. With this aim, we studied the reaction of menth-
yloxyfuranone 7, bearing the sulfinyl group at C-4, with ylide
2. Complex mixtures were obtained under conditions identical
to those employed for sulfinylfuranones 6. The use of different
bases, such as Et3N or TMP, did not improve the results. The
adducts could be obtained eventually when thiazolium ylide 2
was generated before adding 4-sulfinylfuranone, using a 1:1.6:
1.4 ratio of 7/2–HBr/TMP in acetonitrile at room temperature.
Under these conditions, we could identify in the 1H NMR
spectrum of the reaction crude a 93:7 mixture of two diastere-
oisomers, anti-15-endo and syn-15-endo (Scheme 6), which
could be purified but were not separated by chromatography.
The major diastereoisomer was isolated in its diastereomerically
pure form by precipitation from the mixture with AcOEt-hexane
(39%), and its structure was unequivocally determined by X-ray
analysis.20 This result gives evidence that the sulfinyl group is
mainly responsible for the regiochemistry of these reactions,
and it can be controlled by choosing the position where the
sulfinyl group is located at the dipolarophile.
Once the influence of the sulfur function on the regioselec-
tivity was known, we also studied the reaction of sulfone 7′19
with ylide 2. A 71:18:7:4 mixture of four adducts was obtained
(Scheme 6). Despite the lower stereoselectivity control exerted
by the sulfonyl group, the two major adducts could be purified
and identified as anti-15′-endo (61% isolated yield) and syn-
15′-endo (16% isolated yield).
Structural assignment of compounds 10-15 was made by
NMR experiments. The configurations of the pyrrolothiazoles
12a,b, 13, 14a,b, and 15 were assigned by assuming that the
configurations at C-5 of the starting furanones 6a, 6b, 7, and 7′
remained unaltered in the course of these reactions and that the
ylides reacted in their anti conformation,4b,10 which was
confirmed by X-ray analyses of the adducts obtained from
furanones 6 and 7 with isoquinolinium (unpublished results) or
thiazolium azomethine ylide, respectively. Stereochemical results
can be rationalized by assuming that dipoles 1 and 2 always
adopt the anti conformation (Figure 2) in order to avoid the
steric repulsion Me/CO2Et which destabilizes the syn rotamer.
Reactions with sulfinylacrylonitriles 3 and 4 evolved in a
completely π-facial and endo selective manner affording 10 and
SCHEME 3. Reaction of Thiazolium Ylide 1 with
Sulfinylfuran-2(5H)-one 6a and Subsequent Cyclization
purification by filtration on Florisil, anti-12a-endo was isolated
in 84% yield. Chromatographic purification sharply decreased
the yield because of the partial cyclization of anti-12a-endo into
a mixture of 13a1 and 13a2, resulting from the attack of the
OH to both faces of the double bond. When this reaction is
provoked by silica gel, a mixture of both compounds was
obtained in high yield (81%), which becomes quantitative by
addition of HCl to a solution of anti-12a-endo in chloroform.
After their chromatographic separation, 13a1 and 13a2 could
be isolated in 30% and 68% yield, respectively.
Under the same conditions, furanone 6b reacted with 1
affording an 86:14 mixture of anti-12b-endo and syn-12b-endo
(Scheme 4). These two diastereoisomers result from the ap-
proach of the ylide to each faces of the double bond at 6b in
their endo-mode, the major one being that resulting from the
anti approach to the alkoxy group. Chromatographic separation
of this mixture was not feasible due to their easy cyclization in
contact with the silica gel to the corresponding tetracyclic
compounds 13. When a chloroform solution of the mixture of
adducts was treated with a HCl solution, the cyclization took
place in almost quantitative yield and afforded a mixture of four
cyclized compounds, the major ones 13b1 and 13b2 (derived
from anti-12b-endo) being isolated in 32% and 48% yields,
respectively (Scheme 4).
(20) Crystallographic data (excluding structure factors) for anti-15-endo have
been deposited with the Cambridge Crystallographic Data Centre as suplementary
publication no. CCDC 695820. Copies of the data can be obtained, free of charge,
on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44(0)-
1223-366033 or e-mail: deposit@ccdc.cam.ac.uk].
As the primary adducts obtained in these reactions are prone
to cyclization, we investigated the reactions of 6a and 6b with
ylide 2. The results (Scheme 5) were similar to those obtained
8486 J. Org. Chem. Vol. 73, No. 21, 2008

1,3-Dipolar Reactions of Thiazolium Azomethine Ylides
FIGURE 2. Preferred stereochemistry for dipoles 1 and 2.
SCHEME 4. Reaction of Thiazolium Ylide 1 with
Sulfinylfuran-2(5H)-one 6b and Subsequent Cyclization
of these reactions because of its strong steric interactions with
the dipole in the exo-approaches (Figure 4). The justification
that the reactive conformation in these reactions is A (with the
p-tolyl group in anti relationship with respect to the carbonyl
oxygen) can be the electrostatic repulsion between the sulfinyl
oxygen and the negative end of the dipole, which would be
larger when this latter attacks the dipolarophile at its conforma-
tion B (lower distance).
The π-facial and endo selectivities observed in reactions of
compound 7 can be understood with a similar reasoning and
assuming that most stable conformation of 7 (depicted in
Scheme 6) is the most reactive.
In summary, we have studied the usefulness of different
activated vinyl sulfoxides as dipolarophiles in the highly ste-
reoselective synthesis of a variety of pyrrolo[2,1-b]thiazole
derivatives. The sufinyl group dramatically increased the dipo-
larophilic reactivity of the double bonds and had a crucial role
on the control of the regioselectivity and the stereoselectivity
(π-facial and endo-selectivity) of these processes.
11, respectively, as the only adducts. These results were
explained on the assumption of a complete shift of the con-
formational equilibrium at dipolarophiles toward the rotamer
that minimizes the dipolar repulsion between the S-O and C-N
bonds (Figure 3). The orientation of the tolyl group determines
a large difference in the steric hindrance of the two diaste-
reotopic faces (the bottom face is the sterically disfavored),
which results in the complete control of the π-facial selectivity.
Moreover, the electrostatic repulsion of the sulfinyl oxygen and
the ester group at the exo approach justifies the high endo
selectivity observed in these reactions (Figure 3).
The results obtained from sulfinyl furanones cannot be
explained so easily. The major or exclusive formation of the
anti adducts (with respect to the OEt group) indicates that the
influence of the configuration at C-5 is larger than that of
the sulfur one on the π-facial selectivity control. This is easily
understood taking into account the rigidity of C-5 and the
conformational flexibility around the C-S bond. The fact that
evolution of 6a is completely π-facial selective, whereas 6b
affords a mixture of two isomers resulting from the attack to
opposite faces, can be explained by assuming that the more
reactive conformation around the C-S bond is that exhibiting
the p-tolyl group in an anti-relationship with respect to the
carbonyl oxygen (A in Figure 4).21 It would orientate the sulfinyl
oxygen to the face which displays the OEt group in 6a but to
the opposite one in 6b. In the first case the orientation of both
chiral centers would be reinforced, thus explaining its complete
facial selectivity, whereas in 6b the orientation favored for C-5
and S would be different and therefore its evolution would be
less stereoselective (Figure 4). The orientation proposed for the
p-tolyl group would also account for the complete endo character
Experimental Section
Reaction of (Z)-3-p-Tolylsulfinylacrylonitriles 3-5 with Thia-
zolium Ylide.
General Procedure. To a stirred suspension of the corresponding
sulfinylacrilonitrile (0.16 mmol) and the corresponding salt (0.22
mmol) in dry acetonitrile (3 mL), under argon at room temperature,
was added DBU (0.19 mmol). After the time indicated in each case,
the solvent was evaporated in vacuo and the residue was dissolved
in dichloromethane and washed with water and brine. The aqueous
layers were extracted with dichloromethane several times. The
organic layers were dried (Na2SO4), filtered, and concentrated in
vacuo. The reaction time and the purification method are indicated
in each case.
Ethyl 4-Cyano-1-[4-hydroxy-1-methyl-2-[(4-methylphenyl)-
disulfanyl]but-1-en-1-yl]-1H-pyrrole-2-carboxylate (9). Com-
pound 9 was obtained as the major product following the general
procedure from (Z)-3-[(R)-p-tolylsulfinyl]propenonitrile (3) and the
thiazolium salt 1-HBr after 5 min of reaction. It was purified by
flash column chromatography (AcOEt-hexane, 1:3): yield 21%;
IR (neat) 3528, 2233, 1710, 1635, 1595, 1261, 1074 cm-1; 1H NMR
(CDCl3, 300 MHz) δ 7.27 and 7.20 (AA′BB′ system, 4H), 7.13 (d,
1H, J ) 1.5 Hz), 6.08 (d, 1H, J ) 1.5 Hz), 4.25 (t, 2H, J ) 7.1
Hz), 3.86 (m, 2H), 2.93 (m, 2H), 2.41 (s, 3H), 2.17 (s, 3H), 1.32
(t, 3H, J ) 7.1 Hz); 13C NMR (CDCl3, 75 MHz) δ 159.4 (CO),
139.5 (C), 137.4 (C), 134.0 (C), 132.7 (C), 132.0 (CH), 130.1 (CH),
123.8 (C), 119.8 (CH), 114.9 (CN), 94.1 (C), 61.3 (CH2), 60.9
(CH2), 33.9 (CH2), 21.8 (CH3), 21.2 (CH3), 14.2 (CH3); MS (FAB+)
403 (M + H, 31), 385 (12), 279 (32), 247 (100), 138 (19). By
treatment of alcohol with acetic anhydride acetyl derivative 9-Ac
was obtained: IR (neat) 2232, 1740, 1719, 1639, 1548, 1259 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 7.27 and 7.18 (AA′BB′ system,
4H), 7.11 (d, 1H, J ) 1.8 Hz), 6.21 (d, 1H, J ) 1.8 Hz), 4.27 (m,
2H), 4.19 (q, 2H, J ) 7.2 Hz), 3.02 (m, 2H), 2.39 (s, 3H), 2.15 (s,
3H), 2.10 (s, 3H), 1.30 (t, 3H, J ) 7.2 Hz); 13C NMR (CDCl3, 75
MHz) δ 171.0 (C), 158.6 (C), 139.3 (C), 137.5 (C), 132.7 (CH),
132.69 (C), 132.0 (C), 131.4 (CH), 130.1 (CH) 124.3 (C), 119.6
(CH), 115.0 (CN), 93.9 (C), 61.7 (CH2), 60.8 (CH2), 29.6 (CH2),
21.3 (CH3), 21.2 (CH3), 21.0 (CH3), 12.2 (CH3).
(21) Nevertheless, the electrostatic repulsion between the sulfinyl and carbonyl
oxygens suggests for 6a and 6b that rotamers B must be the most stable ones (it
has been supported by theoretical calculations in compounds of similar structure).
The reason justifying that the more reactive conformation with ylides is A (with
the p-tolyl group in anti relationship with respect to the carbonyl oxygen) can
be the electrostatic repulsion between the sulfinyl oxygen and the negative end
of the dipole, which would be larger when the latter attacks to the dipolarophile
at its conformation B.
J. Org. Chem. Vol. 73, No. 21, 2008 8487

Garc´ıa Ruano et al.
SCHEME 5. Reaction of Thiazolium Ylide 2 with Sulfinylfuran-2(5H)-ones 6
SCHEME 6. Cycloaddition of Ylide 2 to 4-Phenylsulfinylfuranone 7 and 4-Phenylsulfonylfuranone 7′
Ethyl [5S,6R,7S,7aS,(S)R]-2-[2-(Acetyloxy)ethyl]-7-cyano-3-
methyl-6-(p-tolylsulfinyl)-5,6,7,7a-tetrahydropyrrolo[2,1-b][1,3]-
thiazole-5-carboxylate (10). Compound 10 was obtained as the
sole compound following the general procedure from (Z)-3-[(R)-
p-tolylsulfinyl]propenonitrile (3) and the thiazolium salt 2-HBr
after 5 min of reaction. It was purified by flash column chroma-
tography (AcOEt-hexane, 1:3): yield 48%; white solid; mp
(Et2O-hexane) 104-105 °C; [R]D +197.4 (c 0.5, CHCl3); IR (KBr)
2241, 1734, 1296, 1084, 1053 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 7.65 and 7.34 (AA’BB′ system, 4H), 5.21 (d, 1H, J ) 5.6 Hz),
4.91 (d, 1H, J ) 5.6 Hz), 4.14 (t, 2H, J ) 6.6 Hz), 4.08 (m, 2H),
3.84 (dd, 1H, J ) 7.6 and 5.7 Hz), 3.33 (dd, 1H, J ) 7.6 and 5.8
Hz), 2.57 (m, 2H), 2.41 (s, 3H), 2.05 (s, 3H), 1.94 (s, 3H), 1.20 (t,
3H, J ) 7.1 Hz); 13C NMR (CDCl3, 75 MHz) δ 171.0 (C), 170.3
(C), 143.0 (C), 139.5 (C), 133.3 (C); 130.3 (CH), 124.6 (CH), 115.1
(CN), 104.1 (C), 70.1 (CH), 65.2 (CH), 62.6 (CH2), 62.2 (CH2),
60.9 (CH), 39.9 (CH), 27.0 (CH2), 21.5 (CH3), 21.0 (CH3), 13.9
(CH3), 12.4 (CH3). Anal. Calcd for C22H26N2O5S2: C, 57.12; H,
5.67; N, 6.06; S, 13.86. Found: C, 56.99; H, 5.50; N, 6.07; S, 14.12.
Ethyl [5S,6R,7S,7aS,(S)R]-2-[2-(Acetyloxy)ethyl]-7-butyl-7-
cyano-3-methyl-6-(p-tolylsulfinyl)-5,6,7,7a-tetrahydropyrrolo[2,1-
b][1,3]thiazole-5-carboxylate (11). Following the general procedure
from (Z)-2-n-butyl-3-[(R)-p-tolylsulfinyl]propenonitrile (4) and the
thiazolium salt 2-HBr, compound 11 was obtained as the sole
isomer along with starting material in a 50:50 ratio after 15 min of
reaction. It was purified by flash column chromatography (AcOEt-
1
hexane, 1:6): yield 39%; H NMR (CDCl3, 300 MHz) δ 7.52 and
7.31 (AA’BB′ system, 4H), 5.00 (d, 1H, J ) 5.5 Hz), 4.78 (s, 1H),
4.13 (t, 2H, J ) 6.6 Hz), 3.92 (m, 2H), 3.39 (d, 1H, J ) 5.5 Hz),
2.54 (m, 2H), 2.40 (s, 3H), 2.04 (s, 3H), 1.94 (s, 3H), 1.70-1.20
(m, 6H), 1.10 (t, 3H, J ) 7.1 Hz), 0.90 (t, 3H, J ) 7.1 Hz); 13C
NMR (CDCl3, 75 MHz) δ 171.0 (C), 170.5 (C), 142.4 (C), 139.0
(C), 133.4 (C), 130.1 (CH), 124.2 (CH), 117.3 (CN), 102.7 (C),
76.5 (CH), 71.1 (CH), 62.6 (CH2), 61.9 (CH2), 58.3 (CH), 53.0
(C), 36.7 (CH2), 27.4 (CH2), 27.1 (CH2), 22.6 (CH2), 21.4 (CH3),
21.0 (CH3), 13.8 (CH3), 13.6 (CH3), 12.0 (CH3).
Reaction of Furanones with Thiazolium Ylides.
General Procedure. To a stirred suspension of furanone (0.56
mmol) and azolium salt (0.68 mmol) in dry acetonitrile (15 mL),
under argon at room temperature, was added DBU (0.68 mmol).
After the time indicated in each case, the solvent was evaporated
in vacuo and the residue was dissolved in dichloromethane and
washed with water and brine. The aqueous layers were extrac-
ted with dichloromethane several times. The organic layers were
dried (Na2SO4), filtered, and concentrated in vacuo. The reaction
time and the purification method are indicated in each case.
Ethyl [5R,5aR,6S,8aS,8bS,(S)S]-6-Ethoxy-2-(2-hydroxyethyl)-
3-methyl-8a-p-tolylsulfinyl-8-oxo-5a,6,8a,8b-tetrahydro-5H,8H-
furo[3′,4′:3,4]pyrrolo[2,1-b][1,3]thiazole-5-carboxylate (anti-12a-
endo). Compound anti-12a-endo was obtained as the sole compound
following the general procedure from [5S,(S)S]-5-ethoxy-3-p-
tolylsulfinylfuran-2(5H)-one (6a) and thiazolium salt 1-HBr, after
5 min of reaction. It was purified by flash column chromatography
(acetone-hexane, 1:2) using Florisil as the stationary phase: yield
FIGURE 3. π-Facial and endo-selectivities in reactions of 3 and 4.
8488 J. Org. Chem. Vol. 73, No. 21, 2008

1,3-Dipolar Reactions of Thiazolium Azomethine Ylides
FIGURE 4. Rationalization of the π-facial and endo-selectivities of reactions of 6a and 6b.
84%; white solid; mp 117-119 °C dec; [R]D) +17.4 (c 0.5,
acetone); IR (KBr) 3692-3138, 3549, 1755, 1737, 1492, 1080,
following the general procedure from [5S,(S)S]-5-ethoxy-3-p-
tolylsulfinylfuran-2(5H)-one (6a) and thiazolium salt 2-HBr after
5 min of reaction. It was purified by flash column chromatography
(acetone-hexane, 1:3): yield 78%; white solid; mp 127-129 °C
dec; [R]D) +7.2 (c 0.75, CHCl3); IR (KBr) 1769, 1736, 1658, 1117,
1055 cm-1; 1H NMR (CDCl3, 300 MHz) δ 7.67 and 7.35 (AA’BB′
system, 4H), 5.43 (s, 1H), 5.37 (d, 1H, J ) 1.4 Hz), 4.47 (d, 1H,
J ) 2.5 Hz), 4.30 (m, 2H), 3.93 (t, 2H, J ) 6.6 Hz), 3.84 (m, 1H),
3.62 (m, 2H), 2.44 (s, 3H), 2.34 (t, 2H, J ) 6.6 Hz), 1.98 (s, 3H),
1.70 (s, 3H), 1.37 (t, 3H, J ) 7.1 Hz), 1.25 (t, 3H, J ) 7.1 Hz);
13C NMR (CDCl3, 75 MHz) δ 170.8 (C), 169.3 (C), 167.5 (C),
143.1 (C), 134.2 (C), 132.1 (C), 129.7 (CH), 126.3 (CH), 106.7
(C), 104.9 (CH), 74.0 (C), 71.7 (CH), 66.9 (CH), 65.7 (CH2), 62.4
(CH2), 62.3 (CH2), 53.2 (CH), 26.9 (CH2), 21.6 (CH3), 20.9 (CH3),
14.8 (CH3), 14.1 (CH3), 12.2 (CH3). Anal. Calcd for C25H31NO8S2:
C, 55.85; H, 5.81; N, 2.61; S, 11.93. Found: C, 55.85; H, 5.67; N,
2.52; S, 12.29.
1052 cm-1 1H NMR (acetone-d6, 300 MHz) δ 7.66 and 7.43
;
(AA′BB′ system, 4H), 5.64 (d, 1H, J ) 1.8 Hz), 5.29 (s, 1H), 4.89
(d, 1H, J ) 2.2 Hz), 4.18 (m, 2H), 3.75 (m, 2H), 3.60 (t, 1H, J )
2.0 Hz), 3.41 (m, 2H), 3.22 (t, 1H, J ) 6.0 Hz), 2.44 (s, 3H), 2.21
(m, 2H), 1.74 (s, 3H), 1.29 (t, 3H, J ) 7.1 Hz), 1.21 (t, 3H, J )
7.1 Hz); 13C NMR (acetone-d6, 75 MHz) δ 170.1 (C), 169.1 (C),
143.8 (C), 136.0 (C), 133.4 (C); 130.4 (CH), 127.2 (CH), 107.2
(C), 106.2 (CH), 75.7 (C), 72.6 (CH), 67.4 (CH), 66.2 (CH2), 62.2
(CH2), 61.3 (CH2), 53.9 (CH), 31.9 (CH2), 21.5 (CH3), 15.2 (CH3),
14.5 (CH3), 12.1 (CH3). Anal. Calcd for C23H29NO7S2: C, 55.74;
H, 5.90; N, 2.83; S, 12.94. Found: C, 55.75; H, 5.85; N, 2.77; S,
13.19.
Ethyl 6-Ethoxy-2-(2-hydroxyethyl)-3-methyl-8a-p-tolylsulf-
inyl-8-oxo-5a,6,8a,8b-tetrahydro-5H,8H-furo[3′,4′:3,4]pyrrolo[2,1-
b][1,3]thiazole-5-carboxylates (12b-endo). Compound 12b-endo
was obtained as a mixture of diastereoisomers anti-12b-endo and
syn-12b-endo in 86:14 ratio from [5R,(S)S]-5-ethoxy-3-p-tolyl-
sulfinylfuran-2(5H)-one (6b) and thiazolium salt with free OH 1,
after 5 min. It could not be purified by flash column chromatog-
raphy. The spectroscopic data were measured from the NMR spectra
of the crude mixture: colorless oil; IR (neat) 3711-3150, 1755,
Ethyl 6-Ethoxy-2-[(2-acetyloxy)ethyl]-3-methyl-8a-p-tolylsulf-
inyl-8-oxo-5a,6,8a,8b-tetrahydro-5H,8H-furo[3′,4′:3,4]pyrrolo[2,1-
b][1,3]thiazole-5-carboxylate (14b-endo). Compound 14b-endo
was obtained as a mixture of diastereoisomers anti-14b-endo and
syn-14b-endo in 75:25 ratio from [5R,(S)S]-5-ethoxy-3-p-tolyl-
sulfinylfuran-2(5H)-one (6b) and thiazolium salt 2-HBr after 5
min. They were purified by flash column chromatography
(acetone-hexane, 1:3), but they could not separated. Their spec-
troscopic data were measured from the NMR spectra of a 75:25
diastereoisomeric mixture: overall yield 75%; IR (neat) 1758, 1737,
1700, 1647, 1624, 1492, 1083, 1053 cm-1
.
1
[5S,5aS,6R,8aR,8bR,(S)S]-anti-12b-endo: H NMR (acetone-
d6, 300 MHz) δ 7.46 and 7.39 (AA′BB′ system, 4H), 5.59 (s, 1H),
5.36 (d, 1H, J ) 2.1 Hz), 4.94 (s, 1H), 4.23 (m, 2H), 3.54 (m, 2H),
3.31 (m, 3H), 2.41 (s, 3H), 2.34 (m, 2H), 1.78 (s, 3H), 1.32 (t, 3H,
J ) 7.1 Hz), 0.82 (t, 3H, J ) 7.1 Hz); 13C NMR (acetone-d6, 75
MHz) δ 169.8 (C), 169.1 (C), 143.6 (C), 137.1 (C), 133.6 (C),
130.5 (CH), 126.5 (CH), 106.7 (CH), 106.4 (C), 82.4 (C), 74.9
(CH), 67.7 (CH); 65.6 (CH2), 62.2 (CH2), 61.4 (CH2), 50.6 (CH),
31.9 (CH2), 21.4 (CH3), 15.0 (CH3), 14.5 (CH3), 12.1 (CH3).
[5R,5aR,6R,8aS,8bS,(S)S]-syn-12b-endo: 1H NMR (acetone-d6,
300 MHz) δ 7.66 (m, 2H), 5.68 (d, 1H, J ) 7.1 Hz), 5.24 (s, 1H),
5.00 (d, 1H, J ) 2.3 Hz), 4.05 (m, 2H), 2.44 (s, 3H), 1.70 (s, 3H),
1.23 (t, 3H, J ) 7.2 Hz), 1.09 (t, 3H, J ) 7.0 Hz).
1650, 1597, 1083, 1054 cm-1
.
[5S,5aS,6R,8aR,8bR,(S)S]-(anti-14b-endo): 1H NMR (CDCl3, 300
MHz) δ 7.49 and 7.28 (AA’BB’system, 4H), 5.75 (s, 1H), 4.99 (d,
1H, J ) 2.2 Hz), 4.50 (d, 1H, J ) 1.6 Hz), 4.32 (m, 2H), 4.06 (m,
2H), 3.31 (dd, 1H, J ) 2.2 and 1.6 Hz), 3.27 (m, 2H), 2.48 (m,
2H), 2.38 (s, 3H), 2.01 (s, 3H), 1.73 (s, 3H), 1.38 (t, 3H, J ) 7.1
Hz), 0.83 (t, 3H, J ) 7.1 Hz); 13C NMR (CDCl3, 75 MHz) δ 170.6
(C), 168.8 (C), 167.7 (C), 142.5 (C), 135.1 (C), 132.5 (C), 129.5
(CH), 125.6 (CH), 106.0 (C), 105.7 (CH), 81.4 (C), 74.1 (CH),
67.2 (CH), 65.0 (CH2), 62.2 (CH2), 62.1 (CH2), 49.4 (CH), 26.8
(CH2), 21.2 (CH3), 20.7 (CH3), 14.3 (CH3), 14.0 (CH3), 12.0 (CH3).
Ethyl [5R,5aR,6S,8aS,8bS,(S)S]-6-Ethoxy-2-[(2-acetyloxy)ethyl]-
3-methyl-8a-p-tolylsulfinyl-8-oxo-5a,6,8a,8b-tetrahydro-5H,8H-
furo[3′,4′:3,4]pyrrolo[2,1-b][1,3]thiazole-5-carboxylate (anti-14a-
endo). Compound anti-14a-endo was obtained as the sole compound
1
[5R,5aR,6R,8aS,8bS,(S)S]-(syn-14b-endo): H NMR (CDCl3,
300 MHz) δ 7.61 and 7.35 (AA’BB’system, 4H), 5.43 (d, 1H, J )
7.2 Hz), 5.26 (s, 1H), 5.00 (d, 1H, J ) 2.0 Hz), 4.17 (q, 2H, J )
J. Org. Chem. Vol. 73, No. 21, 2008 8489

Garc´ıa Ruano et al.
7.1 Hz), 3.96 (m, 2H), 3.87 (m, 1H), 3.78 (dd, 1H, J ) 7.2 and 2.0
Hz), 3.69 (m, 1H), 2.43 (s, 3H), 1.99 (s, 3H), 1.71 (s, 3H), 1.30 (t,
3H, J ) 7.2 Hz), 1.25 (t, 3H, J ) 7.1 Hz).
with the corresponding sulfoxide. After 1 min at room temperature,
complete transformation of sulfone was observed by TLC. The
spectroscopic signals corresponding to adducts anti-15′-endo and
syn-15′-endo and those of other two possible adducts were observed
in a ratio of 71:18:7:4 in the 1H NMR spectrum of the crude reaction
mixture. The products anti-15′-endo and syn-15′-endo were isolated
by column chromatography using hexane-ethyl acetate (4:1) as the
eluent.
Ethyl [8S,(S)S]-2-[2-(Acetyloxy)ethyl]-3-methyl-8-menthyloxy-
8a-(phenylsulfinyl)-6-oxo-5a,6,8a,8b-tetrahydro-5H,8H-furo[3′,4′:
3,4]pyrrolo[2,1-b][1,3]thiazole-5-carboxylate (15). To a stirred
solution of (S,S)-4-phenylsulfinylfuranone (7) (0.55 mmol) in dry
acetonitrile (8 mL), under argon at room temperature, was added
quickly a solution of ylide 2 (0.8 mmol) in dry acetonitrile (4 mL),
freshly prepared by addition of TMP (0.8 mmol) to a suspension
of thiazolium salt 2-HBr (0.9 mmol) in dry acetonitrile (4 mL).
After 5 min, dichloromethane was added to the reaction mixture,
and it was washed with water. The aqueous layers were extracted
with dichloromethane several times. The organic layers were dried
(Na2SO4), filtered, and concentrated in vacuo. The 1H NMR
spectrum shows a mixture of diastereoisomers anti-15-endo and
syn-15-endo in 93:7 ratio, along with the starting material 7 and
other compounds. Diastereoisomers 15 were purified by flash
column chromatography (AcOEt-hexane, 1:3).
anti-15′-endo (major): 61% isolated yield; white solid; mp
89-90 °C (recrystallized from diethyl ether-hexane); [R]20D -34.5
(c ) 0.5, CHCl3); IR (neat) 1781, 1737, 1656, 1585, 1449, 1370,
1
1223, 1147 cm-1; H NMR (CDCl3, 300 MHz) δ 7.88 (m, 2H),
7.66 (m, 1H), 7.53 (m, 2H), 6.33 (s, 1H), 6.04 (s, 1H), 4.88 (s,
1H), 4.35 (q, 2H, J ) 7.1 Hz), 4.23 (s, 1H), 4.06 (m, 2H), 3.40 (dt,
1H, J ) 10.8 and 4.3 Hz), 2.54 (m, 1H), 2.42 (m, 1H), 2.16 (m,
1H), 2.03 (s, 3H), 1.72-0.54 (m, 17H), 1.68 (s, 3H), 1.39 (t, 3H,
J ) 7.1 Hz); 13C NMR (CDCl3, 75 MHz) δ 172.9 (C), 170.9 (C),
168.6 (C), 139.0 (C), 134.1 (CH), 133.1 (C); 130.7 (CH), 128.5
(CH), 104.1 (CH), 104.0 (C), 82.3 (CH), 80.8 (CH), 73.6 (CH),
66.2 (CH), 62.8 (CH2), 62.2 (CH2), 50.9 (CH), 48.5 (CH), 42.2
(CH2), 34.0 (CH2), 31.7 (CH), 26.9 (CH2), 24.3 (CH), 22.6 (CH2),
22.0 (CH3), 21.3 (CH3), 20.9 (CH3), 15.8 (CH3), 14.1 (CH3), 11.6
(CH3). Anal. Calcd for C32H43NO9S2: C, 59.15; H, 6.67; N, 2.16;
S, 9.87. Found: C, 59.25; H, 6.69; N, 2.51; S, 9.61.
[5S,5aR,8S,8aR,8bR,(S)S]-anti-15-endo. Compound anti-15-
endo was obtained as the major cycloadduct. It was isolated by
precipitation of a mixture of isomers anti-15-endo and syn-15-endo
(86:14) from AcOEt-hexane: yield 39%; mp (AcOEt-hexane)
102-103 °C; [R]D -50.4 (c 0.5, CHCl3); IR (KBr) 1776, 1754,
1726, 1443, 1383, 1311, 1253, 1121, 1043 cm-1; 1H NMR (CDCl3,
300 MHz) δ 7.83 (m, 2H), 7.53 (m, 3H), 6.04 (s, 1H), 5.97 (s,
1H), 4.55 (d, 1H, J ) 1.7 Hz), 4.29-4.07 (m, 4H), 3.63 (dt, 1H,
J ) 10.8 and 4.1 Hz), 3.53 (d, 1H, J ) 1.7 Hz), 2.66 (m, 1H), 2.45
(m, 2H), 2.14 (m, 2H), 2.06 (s, 3H), 1.76-0.80 (m, 15 H), 1.67 (s,
3H), 1.34 (t, 3H, J ) 7.2 Hz); 13C NMR (CDCl3, 75 MHz) δ 172.8
(C), 170.8 (C), 168.6 (C), 140.9 (C), 133.5 (C); 131.9 (CH), 129.1
(CH), 126.8 (CH), 106.4 (CH), 103.6 (C), 85.0 (CH), 79.4 (C),
71.0 (CH), 65.7 (CH), 62.5 (CH2), 62.4 (CH2), 49.1 (CH), 48.5
(CH), 42.6 (CH2), 34.0 (CH2), 31.5 (CH), 27.2 (CH2), 25.0 (CH),
22.6 (CH2), 22.1 (CH3), 21.2 (CH3), 20.9 (CH3), 16.0 (CH3), 14.2
(CH3), 11.6 (CH3). Anal. Calcd for C32H43NO8S2: C, 60.64; H, 6.84;
N, 2.21; S, 10.12. Found: C, 60.32; H, 6.74; N, 2.19; S, 9.98.
[5R,5aS,8S,8aS,8bS,(S)S]-syn-15-endo. Compound syn-15-endo
was obtained as the minor cycloadduct. It could not be isolated
diastereoisomerically pure. The spectroscopic parameters were
obtained from the spectrum of a 25:75 mixture of anti-15-endo
syn-15′-endo (minor): 16%; 1H NMR (CDCl3, 300 MHz) δ 7.98
(m, 2H), 7.75 (m. 1H), 7.60 (m, 2H), 6.14 (s, 1H), 5.82 (s, 1H),
4.31-4.05 (m, 6H), 3.55 (dt, 1H, J ) 10.6 and 4.4 Hz), 2.67-0.78
(m, 20H), 2.03 (s, 3H), 1.74 (s, 3H), 1.31 (t, 3H, J ) 7.1 Hz); 13
C
NMR (CDCl3, 75 MHz) δ 171.0 (C), 170.8 (C), 170.2 (C), 135.9
(C), 135.1 (CH), 134.9 (C), 130.5 (CH), 129.3 (CH), 119.3 (C),
101.7 (CH), 83.8 (CH), 81.3 (C), 75.5 (CH), 67.3 (CH), 62.9 (CH2),
62.1 (CH2), 52.3 (CH), 47.9 (CH), 41.8 (CH2), 33.9 (CH2), 31.6
(CH), 26.7 (CH2), 24.8 (CH), 22.7 (CH2), 22.1 (CH3), 21.2 (CH3),
1
20.9 (CH3), 16.0 (CH3), 14.0 (CH3), 13.8 (CH3); H NMR (C6D6,
300 MHz) δ 7.93 (m, 2H), 6.91 (m, 3H), 6.33 (s, 1H), 5.99 (s,
1H), 4.54 (d, 1H, J ) 3.4 Hz), 4.29 (d, 1H, J ) 3.4 Hz), 3.86 (m,
2H), 3.48 (dt, 1H, J ) 10.6 and 4.5 Hz), 2.60-0.60 (m, 20H),
1.68 (s, 3H), 1.55 (s, 3H), 0.92 (t, 3H, J ) 7.1); 13C NMR (C6D6,
75 MHz) δ 171.1 (C), 170.5 (C), 170.3 (C), 136.7 (C), 136.3 (C),
135.0 (CH), 131.1 (CH), 129.3 (CH), 121.2 (C), 102.2 (CH), 84.4
(CH), 82.2 (C), 77.1 (CH), 68.3 (CH), 63.0 (CH2), 62.1 (CH2),
53.5 (CH), 48.8 (CH), 42.6 (CH2), 34.5 (CH2), 32.0 (CH), 27.3
(CH2), 25.5 (CH), 23.3 (CH2), 22.6 (CH3), 21.9 (CH3), 20.8 (CH3),
16.7 (CH3), 14.3 (CH3).
1
and syn-15-endo: H NMR (CDCl3, 300 MHz) δ 7.79 (m, 2H),
7.57 (m, 3H), 5.88 (s, 1H), 5.82 (s, 1H), 4.27-4.08 (m, 4H), 4.00
(d, 1H, J ) 3.6 Hz), 3.72 (d, 1H, J ) 3.6 Hz), 3.57 (td, 1H, J )
10.5 and 4.0 Hz), 2.72-0.75 (m, 20H), 2.05 (s, 3H), 1.73 (s, 3H),
1.30 (t, 3H, J ) 7.1 Hz); 13C NMR (CDCl3, 75 MHz) δ 171.9 (C),
170.8 (C), 170.7 (C), 138.2 (C), 136.3 (C), 132.6 (CH), 129.3 (CH),
126.3 (CH), 121.6 (C), 102.2 (CH), 84.1 (CH), 78.0 (C), 76.2 (CH),
67.4 (CH), 63.1 (CH2), 62.0 (CH2), 49.5 (CH), 47.9 (CH), 42.0
(CH2), 34.0 (CH2), 31.6 (CH), 26.8 (CH2), 25.1 (CH), 22.8 (CH2),
22.1 (CH3), 21.1 (CH3), 20.8 (CH3), 16.1 (CH3), 14.0 (CH3), 13.9
(CH3).
Acknowledgment. We thank the Spanish Government
(DGICYT, Grant No. CTQ2006-06741/BQU) and Comunidad
Auto´noma de Madrid (CCG07-UAM/PPQ-1849) for financial
support.
Supporting Information Available: Experimental proce-
dures and spectroscopic data for compounds 2-HBr and 13a1-
13b2, NMR spectra of all new compounds, and crystallographic
data for compound anti-15-endo (CIF). This material is available
free of charge via the Internet at http://pubs.acs.org.
Ethyl [8S,(S)S]-2-[2-(Acetyloxy)ethyl]-3-methyl-8-menthyloxy-
8a-(phenylsulfonyl)-6-oxo-5a,6,8a,8b-tetrahydro-5H,8H-furo[3′,4′:
3,4]pyrrolo[2,1-b][1,3]thiazole-5-carboxylates (15′). The com-
pounds were obtained from dipole 2 and [(S)S,5S)]-5-(l)-menthyloxy-
4-phenylsulfonylfuran-2(5H)-one (7′) following the procedure used
JO801705D
8490 J. Org. Chem. Vol. 73, No. 21, 2008