Cyclic vinyl p-tolyl sulfilimines as chiral dienophiles: Diels-Alder reactions with furan and acyclic dienes

Article abstract of DOI:10.1021/jo016174w

The dienophilic behavior of the sulfilimine 2, synthesized from (Z)-3-p-tolylsulfinylacrylonitrile 1, in its Diels-Alder reactions with furan and acyclic dienes has been investigated. A complete π-facial selectivity for 2, opposite to that observed from its precursor 1, is the main feature of all these cycloadditions. Moreover, the high exo selectivity observed in reactions of 2 with furan (not observed for 1) contrasts with the almost complete endo selectivity with other cyclic and acyclic dienes. Additionally, the opposite regioselectivities obtained for 2 with Dane's diene and 1-substituted butadienes (not observed for 1) are also noteworthy. This behavior allows dienophiles 1 and 2 to be considered as complementary precursors from a synthetic point of view.

Full text of DOI:10.1021/jo016174w

J . Org. Chem. 2002, 67, 2919-2925
2919
Cyclic Vin yl p-Tolyl Su lfilim in es a s Ch ir a l Dien op h iles:
Diels-Ald er Rea ction s w ith F u r a n a n d Acyclic Dien es
J ose´ L. Garc´ıa Ruano,*,† Carlos Alemparte,† Fernando R. Clemente,‡
Lorena Gonza´lez Gutie´rrez,† Ruth Gordillo,‡ Ana M. Mart´ın Castro,† and
J esu´s H. Rodr´ıguez Ramos*,†
Departamento de Quı´mica Orga´nica, Universidad Auto´noma de Madrid, Cantoblanco, 28049 Madrid,
Spain, and Departamento de Quı´mica Orga´nica, Universidad de Extremadura, 06071 Badajoz, Spain
joseluis.garcia.ruano@uam.es
Received October 4, 2001
The dienophilic behavior of the sulfilimine 2, synthesized from (Z)-3-p-tolylsulfinylacrylonitrile 1,
in its Diels-Alder reactions with furan and acyclic dienes has been investigated. A complete π-facial
selectivity for 2, opposite to that observed from its precursor 1, is the main feature of all these
cycloadditions. Moreover, the high exo selectivity observed in reactions of 2 with furan (not observed
for 1) contrasts with the almost complete endo selectivity with other cyclic and acyclic dienes.
Additionally, the opposite regioselectivities obtained for 2 with Dane’s diene and 1-substituted
butadienes (not observed for 1) are also noteworthy. This behavior allows dienophiles 1 and 2 to be
considered as complementary precursors from a synthetic point of view.
In tr od u ction
asymmetric Diels-Alder reactions,4,1a we have recently
demonstrated that (Z)-3-p-tolylsulfinylacrylonitriles (1)
exhibit a complete π-facial selectivity and a very high
endo selectivity, both higher than those of their corre-
sponding acrylates, when they react with cyclopentadi-
ene.5 Moreover, the reactivity of the nitriles is clearly
higher than that of the esters, which could be demon-
strated in reactions with furan and acyclic dienes.6 As
compared with sulfinylacrylates, the higher reactivity
and endo selectivity of sulfinylacrylonitriles were at-
tributed to the linear structure of the nitrile, which avoids
any steric repulsion between CO2R and SOTol groups
distorting the planarity in the case of the ester and hence
decreasing both the reactivity and the endo selectivity.
The interest in asymmetric Diels-Alder reactions of
these sulfinylacrylonitriles, with better dienophilic fea-
tures than their esters counterparts, increased because
of the fact that the π-facial selectivity of their reactions
with cyclopentadiene can be completely reversed in the
presence of BF3‚OEt2 (Scheme 1).5 However, we did not
succeed in making use of this inversion with acyclic
dienes, because of their fast polymerization in the pres-
ence of the catalytic BF3‚OEt2.
The sulfinyl group has been shown to be one of the
most efficient chiral auxiliaries in asymmetric Diels-
Alder reactions,1 as a result of its ability to differentiate
the diastereotopic faces of the double bond of substituted
vinyl sulfoxides. Nevertheless, the reactions of vinyl
p-tolyl sulfoxide with cyclopentadiene exhibited a moder-
ate π-facial selectivity as well as a scarce endo selectiv-
ity,2 which indicated that the ability of the sulfinyl group
to control the stereochemical course of these reactions is
only apparent in the presence of other functional groups
that increase the dienophilic reactivity and restrict the
conformational equilibrium around the C-S bond. In this
sense, a large number of vinyl sulfoxides bearing electron-
withdrawing groups have been studied,1a alkyl (Z)-3-
arylsulfinylacrylates being the most widely used in
asymmetric synthesis.3 The alkoxycarbonyl group in
these compounds shifts the conformational equilibrium
around the C-S bond toward the rotamer with the
sulfinyl oxygen in an s-trans arrangement (thus control-
ling the π-facial selectivity) and enhances the weak endo
orientating character of the sulfinyl group.
In the course of our studies on the behavior of substi-
tuted activated vinyl sulfoxides as chiral dienophiles in
Fortunately, we found another way to invert the
π-facial selectivity of the reaction with cyclopentadiene,
consisting of the transformation of the starting nitrile
into the cyclic vinyl-p-tolylsulfilimine (2).7 As we can see
in Scheme 1, the spatial arrangement of the p-tolyl group
in compound 2 is identical to that of the intermediate
generated in the presence of BF3‚OEt2 and opposite to
that adopted by such a group in the most stable s-trans
* Fax: 3491 397 3966.
† Universidad Auto´noma de Madrid.
‡ Universidad de Extremadura.
(1) (a) Garc´ıa Ruano, J . L.; Cid, B. In Topics in Current Chemistry;
Page, P. C. B., Ed.; Springer: Berlin, 1999; Vol. 204, pp 1-127. (b)
Carren˜o, M. C. Chem. Rev. 1995, 95, 1717. (c) Solladie, G.; Carren˜o,
M. C. In Organosulphur Chemistry: Synthetic Aspects; Page, P. C. B.,
Ed.; Academic Press: New York, 1995; pp 1-47.
(2) Maignan, C.; Raphael, R. A. Tetrahedron 1983, 39, 3245.
(3) (a) Arai, Y.; Yamamoto, M.; Koizumi, T. Chem. Lett. 1986, 1225.
(b) Arai, Y.; Yamamoto, M.; Koizumi, T. Bull. Chem. Soc. J pn. 1988,
61, 467. (c) Takayama, H.; Iyobe, A.; Koizumi, T. J . Chem. Soc., Chem.
Commun. 1986, 771. (d) Arai, Y.; Hayashi, Y.; Matatoshi, Y.; Takaya-
ma, H.; Koizumi, T. J . Chem. Soc., Perkin Trans. 1 1988, 3133. (e)
Takayama, H.; Iyobe, A.; Koizumi, T. Chem. Pharm. Bull. 1987, 35,
433. (f) Takahashi, T.; Iyobe, A.; Arai, Y.; Koizumi, T. Synthesis 1989,
189. (g) Takahashi, T.; Katsubo, H.; Iyobe, A.; Namiki, T.; Koizumi, T.
J . Chem. Soc., Perkin Trans. 1 1990, 3065. (h) Takayama, H.; Hayashi,
K.; Koizumi, T. Tetrahedron 1993, 27, 5509.
(4) Garcia Ruano, J . L.; Carren˜o, M. C.; Carretero, J . C.; Mart´ın, L.
M.; Urbano, A. Pure Appl. Chem. 1996, 68, 925.
(5) Garc´ıa Ruano, J . L.; Esteban Gamboa, A.; Mart´ın Castro, A. M.;
Rodr´ıguez, J . H.; Lo´pez-Solera, M. I. J . Org. Chem. 1998, 63, 3324.
(6) Garc´ıa Ruano, J . L.; Alemparte, C.; Martı´n Castro, A. M.; Adams,
H.; Rodr´ıguez Ramos, J . H. J . Org. Chem. 2000, 65, 7938.
(7) Garc´ıa Ruano, J . L.; Esteban Gamboa, A.; Gonza´lez Gutie´rrez,
L.; Mart´ın Castro, A. M.; Rodr´ıguez Ramos, J . H.; Yuste, F. Org. Lett.
2000, 2, 733.
10.1021/jo016174w CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/28/2002

2920 J . Org. Chem., Vol. 67, No. 9, 2002
Garc´ıa Ruano et al.
Sch em e 1
stereoselectivity decreased. The best results were ob-
tained working at low temperature (-20 °C) when the
process was catalyzed by BF3‚OEt2 (entry 5). Under these
conditions, an almost complete conversion was observed,
as well as the formation of exo-3A as the major product,
which could be easily isolated diastereomerically pure in
85% yield. However, the stereoselectivity under these
catalytic conditions was lost on increasing the tempera-
ture (entry 6). Contrary to the cycloadditions of (Z)-
sulfinylacrylonitriles,6 the use of Me3AlCl in the reactions
of vinyl sulfilimines led to decomposition mixtures.
The behavior of vinyl-p-tolylsulfilimine 2 with acyclic
dienes such as (E)-1-methoxy-1,3-butadiene (4) and pip-
erylene (5) was also investigated. These dienes had
afforded high stereoselectivities and regioselectivities in
reactions with (Z)-sulfinylacrylonitrile 1,6 although in the
presence of BF3‚OEt2 as the catalyst no transformation
had been achieved (see above). The results are sum-
marized in Table 2.
Sch em e 2
The low solubility of 2 in both dienes made necessary
the use of CH2Cl2 as a solvent. All assays were performed
with 2 equiv of diene, although higher ammounts of diene
(up to 8 equiv) were also tried with identical results.
When the reactions were performed at atmospheric
pressure, even at high temperature (entry 4) or in the
presence of ZnBr2 as a catalyst (entries 1 and 6), the
degree of transformation was small in the best of the
cases, with substantial amounts of unaltered starting
material being recovered. The best results were achieved
by combining the use of high pressure and a catalyst
(entries 3 and 7). With (E)-1-methoxy-1,3-butadiene (4)
in the presence of ZnBr2 at 4 kbar the reaction evolved
with complete regio-, endo, and π-facial selectivities,
affording just one adduct endo-6A. Under the same
conditions, the reaction with piperylene (5) gave a
mixture of two regioisomers 7 (regioisomer 7A being
predominant), but once again the π-facial and the endo
selectivities of the process were complete.
conformation of the starting nitrile, which justifies the
stereochemical evolution of these new dienophiles.
On this assumption we reasoned that sulfilimines 2
could be used as a complementary dienophile to the
sulfinyl nitriles for the preparation of adducts derived
from furan and acyclic dienes exhibiting the opposite
configuration in all the chiral centers created in the
cycloaddition. Therefore, in this paper we report the
results obtained in these reactions conducted under
different conditions in order to expand the scope of
applicability of these new dienophiles, which are inter-
esting both from a synthetic and a theoretical point of
view.
Finally, reactions with 3,4-dihydro-6-methoxy-1-vinyl
naphthalene (8) (Dane’s diene)9 were also studied (Table
3). The interest of this diene, one of the most frequently
used in the construction of steroidal skeletons,10 is related
to the regioselectivity of their reactions, mainly with the
role of Lewis acid catalysts, which are able to invert it
in many cases.11 These reactions only take place at high
pressure (4 kbar), affording mixtures of two stereoiso-
mers, endo-9A and exo-9A, the former being clearly
Resu lts a n d Discu ssion
The synthesis of the optically pure vinyl-p-tolylsulfil-
imine 2 can be readily achieved in a short three-step
sequence involving sulfinylation of commercially avail-
able terminal alkynes,8 stereoselective conjugated addi-
tion of Et2AlCN to the resulting alkynyl sulfoxides,5 and
treatment of the obtained (Z)-sulfinylacrylonitrile 1 with
HBF4 and then quenching with methanol7 (Scheme 2).
The results obtained in the Diels-Alder cycloadditions
of 2 with furan under different conditions are collected
in Table 1. Refluxing 2 in an excess of furan, in the
absence of any cosolvent, for several days, afforded the
unaltered starting sulfilimine (entry 1). When the reac-
tion was conducted at high pressure, a mixture of two
adducts could be detected, but the major component of
the reaction mixture was the starting material (entry 2).
In the presence of 1.2 equiv of ZnBr2 as a catalyst at room
temperature a mixture of exo-3A (major) and endo-3B
(minor) adducts was obtained, although the reaction was
not complete (entry 3). No improvement was achieved
with the use of high pressures in the presence of ZnBr2
(entry 4), because the conversion was similar and the
(9) (a) Dane, E.; Schmitt, J . Liebigs Ann. Chem. 1938, 536, 196. (b)
Liebigs Ann. Chem 1939, 537, 246. (c) Robins, D. A.; Walker, J . J .
Chem. Soc. 1956, 3249.
(10) (a) Cole, J . E.; J ohnson, W. S.; Robin, P. A. J . Chem. Soc. 1962,
244. (b) Dickinson, R. A.; Kubela, R.; MacAlpine, G. A.; Stojanac, Z.;
Valenta, Z. Can. J . Chem. 1972, 50, 2377. (c) Das, J .; Kubela, R.;
MacAlpine, G. A.; Stojanac, Z.; Valenta, Z. Can. J . Chem. 1979, 57,
3308. (d) Quinkert, G.; Stark, H. Angew. Chem., Int. Ed. Engl. 1983,
22, 637. (e) Quinkert, G.; Grosso, M.; Bucher, A.; Bats, J . W.
Tetrahedron Lett. 1991, 32, 3357. (f) Takano, S.; Moriya, M.; Ogasawara,
K. Tetrahedron Lett. 1992, 33, 1909. (g) Quinkert, G.; Grosso, M.;
Bucher, A.; Bauch, M.; Doring, W.; Bats, J . W.; Durner, G. Tetrahedron
Lett. 1992, 33, 3617. (h) Alonso, I.; Carretero, J . C.; Garc´ıa Ruano, J .
L.; Mart´ın Cabrejas, L. M.; Lo´pez-Solera, I.; Raithby, R. Tetrahedron
Lett. 1994, 35, 9461. (i) Quinkert, G.; Grosso, M.; Do¨ring, A.; Do¨ring,
W.; Schenkel, R. I.; Bauch, M.; Dambacher, G. T.; Bats, J . W.;
Zimmermann, G.; Du¨rner, G. Helv. Chim. Acta 1995, 78, 1345. (j)
Sugahara, T.; Ogasawara, K. Tetrahedron Lett. 1996, 37, 7403. (k)
Schuster, T.; Kurz, M.; Go¨bel, M. W. J . Org. Chem. 2000, 65, 1697.
(11) (a) Tou, J . S.; Reusch, W. J . Org. Chem. 1980, 45, 5012. (b)
Arseniyadis, S.; Rodr´ıguez, R.; Spanavello, R.; Ca´mara, J .; Thompson,
A.; Guittet, E.; Ourisson, G. Tetrahedron 1992, 48, 1255. (c) Arseniya-
dis, S.; Rodr´ıguez, R.; Yashunsky, D. V.; Ca´mara, J .; Ourisson, G.
Tetrahedron Lett. 1994, 35, 4843 and refs 10b and 10e.
(8) (a) Kosugi, H.; Kitaoka, M.; Tagami, K.; Uda, H. Chem. Lett.
1985, 805. (b) Kosugi, H.; Kitaoka, M.; Tagami, K.; Takahashi, A.; Uda,
H. J . Org. Chem. 1987, 52, 1078.

Sulfilimines as Chiral Dienophiles
J . Org. Chem., Vol. 67, No. 9, 2002 2921
Ta ble 1. Diels-Ald er Rea ction s of 2 a n d F u r a n
isolated yield (%)
entry
Lewis acid
conditions
pressure
ratioa 2:exo-3:endo-3
exo-3A
endo-3B
1
2
3
4
5
6
reflux, 4 d
rt, 6 d
rt, 4 d
rt, 3 d
-20 °C, 5 d
reflux, 5 d
1 bar
4 kbar
1 bar
4 kbar
1 bar
1 bar
100: 0:0
80:17:3
19:74:7
22:55:23
2:94:4
b
ZnBr2
ZnBr2
69
85
<7
<4
b
c
BF3‚OEt2
BF3‚OEt2
c
4:49:47
a
b
From integration of well separated signals of the 1H NMR spectrum of the crude mixture. 1.2 equiv. c 2 equiv.
Ta ble 2. Diels-Ald er Rea ction s of 2 w ith Acyclic Dien es 4 a n d 5
isolated yield (%)
entry
diene
Lewis acida
ZnBr2
conditions
pressure
product
ratiob 2:A:B
A
B
1
2
3
4
5
6
7
4
4
4
5
5
5
5
rt, 14 d
rt, 10 d
rt, 3 d
reflux, 10 d
rt, 6 d
1 bar
6A
6A
6A
7A/7B
7A/7B
7A/7B
7A/7B
90:10:0
32:68:0
0:100: 0
100: 0:0
95:5:0
4 kbar
4 kbar
1 bar
4 kbar
1 bar
c
ZnBr2
89
ZnBr2
ZnBr2
rt, 28 d
rt, 3 d
43:50:7
0:87:13
b
4 kbar
84
11
a
b
1.2 equiv. From integration of well separated signals of the 1H NMR spectrum of the crude mixture c Not determined.
Ta ble 3. Diels-Ald er Rea ction s of 2 a n d Da n e’s Dien e
enophile 2, instead of the sulfur function, was mainly
responsible for the regioselectivity (see Table 2).
(8)
The stereochemistry of the adducts resulting from all
of these reactions was unequivocally established by
chemical correlation with compounds of known configu-
ration (Scheme 3). Thus, the major adducts obtained in
reactions with acyclic alkenes (endo-6A and endo-7A)
were correlated with the major adducts, endo-12 and
endo-13, obtained from sulfinylacrylonitrile 1, whose
optical purities were determined by NMR using Eu(hfc)3
as the LSR.6 Treatment of the adducts obtained from
sulfilimine with LiAlH4 in THF yielded the corresponding
sulfenyl carboxamides 10A and 11A. The same com-
pounds could be obtained from endo-12 and endo-13 by
hydrolysis of the cyano group with anchimeric assistance
of the sulfinyl oxygen.12 Specific rotation of the com-
pounds derived from both routes are identical but with
the opposite sign, thus demonstrating that they are
enantiomers. The stereochemistry of the minor regioiso-
mer 7B was assigned by asuming that the π-facial
selectivity and the endo selectivity are identical in both
regioisomeric approaches.
isolated yield (%)
entry acida conditions pressure 2:9A:9B endo-9A exo-9B
Lewis
ratiob
1
2
3
rt, 7 d
rt, 7 d
rt, 14 d
1 bar
100: 0:0
4 kbar 0:73:27
4 kbar 0:86:14
ZnBr2
70
84
5
7
a
b
1.2 equiv. From integration of well separated signals of the
1H NMR spectrum of the crude mixture.
predominant. In this reaction, the presence of the catalyst
decreased the stereoselectivity (compare entries 2 and 3
in Table 3), but the regioselectivity remained unaltered
and the yields were very high in any case. These results
demonstrate that the reactions of sulfilimine 2 with
Dane’s diene are completely regio- and π-facial selective,
and their endo selectivity is very high although not
complete. Concerning the regioselectivity, it seems to be
controlled by the sulfur function at the dienophile and
the substituent at C-1 at the diene whereas in reactions
with 1-substituted dienes the amide moiety at the di-
The endo or exo character of the resulting adducts (exo-
3A was isolated by chromatography, whereas diastereo-
merically pure endo-3B could not be isolated) was
1
determined by H NMR. The absolute configuration of
(12) Garc´ıa Ruano, J . L.; Mart´ın Castro, A. M.; Rodr´ıguez Ramos,
J . H. Tetrahedron Lett. 1996, 37, 4569.

2922 J . Org. Chem., Vol. 67, No. 9, 2002
Garc´ıa Ruano et al.
Sch em e 3
Sch em e 4
9B, obtained in less than a 5% yield, was tentatively
assigned as the exo isomer of 9A, resulting from cycload-
dition with the same π-facial selectivity.14
Upon establishing the configurational assignment of
all obtained adducts, we can summarize the main dif-
ferences between the dienophiles 1 and 2 in their
reactions with furan and acyclic dienes. The main dif-
ference is that both dienophiles evolve with the opposite
π-facial selectivity. In this sense, the control of this type
of selectivity is very efficient for both dienophiles but even
better for 2.16 This could be easily explained taking into
account that the relative spatial arrangement of the
p-tolyl group is opposite for both dienophiles (Scheme 6).
In this sense compounds 1 and 2 can be considered as
complementary.
compound exo-3A obtained as the major product from
these reactions was unequivocally assigned by chemical
correlation with the exo-adduct (exo-16) obtained as the
minor product from Diels-Alder reaction of (Z)-sulfiny-
lacrylonitrile with furan, which had been previously
described.6 In this case, the correlation was made by
using a slightly different sequence (Scheme 4). Thus,
adduct exo-3A was treated with LiAlH4-THF affording
exo-14, which was transformed into sulfenylnitrile 15
with the dehydrating reagent (Tf)2O-NEt3.13 The enan-
tiomer of this compound resulted from reduction with
PCl3-CH3CN of the adduct exo-16, one of the minor ones
obtained from (Z)-sulfinylacrylonitrile 1 (Scheme 4). The
configuration of the minor adduct endo-3A was assigned
by assuming that the π-facial selectivity is identical for
the endo and exo approaches.
Finally, the configurational assignment of the adducts
endo-9A and exo-9B also required their transformation
into the corresponding diastereomeric sulfenylcarboxa-
mides endo-17A and exo-17B with LiAlH4 (Scheme 5).
The reaction of the adduct 18, obtained from compound
1 with the Dane’s diene,6 with BF3‚OEt2 and NaI yielded
the carboxamide endo-19, whose 1H NMR spectrum is
different from those of 17A and 17B, as it must be
expected for regioisomers.14
Concerning the regioselectivity, two main differences
have been observed. First, the cyclic dienophile 2 exhibits
a regioselectivity with 1-substituted dienes 4 and 5,
where the amide function is the main controller, yielding
the ortho-adduct as predominant, opposite to the regi-
oselectivity obtained with Dane’s diene, which only
affords the meta-adduct (with respect to the substituent
at C-1). Second, this change in the regioselectivity was
not observed for compound 1, which reacted with all of
the dienes, yielding the ortho-adducts.6 The results
obtained with dienes 4 and 5 can be explained by
assuming that the electronic influence of the cyano and
amide groups in the regiochemistry must be higher than
that of the sulfur function, hence favoring the formation
of the ortho-adducts with respect to the former ones. As
this situation is analogous to reactions with Dane’s diene,
other factors, such as the steric interactions of Dane’s
diene with the s-trans oxygens at dienophiles, must be
responsible for the observed differences. As we can see
in Figure 2, such interactions of the carbonyl oxygen at
the dienophile 2 unstabilize the TS, yielding the ortho-
adduct (B in Figure 2), thus evolving preferentially
through the TS, which yields the meta-adduct (A in
Figure 2). On the contrary, in reactions of dienophile 1
the steric grounds reinforce the electronic tendency, since
the interactions of the diene with the s-trans sulfinyl
oxygen determine the higher stability of the transition
state favored by electronic grounds (B′ in Figure 2),
where such interactions are absent. As the steric interac-
tions must be less significant in reactions with 1-substi-
tuted dienes, they are not able to invert the orientation
imposed by the electronic factors. However, the formation
of a small amount of the regioisomer 7B in the reaction
The configuration of the major adduct 9A, resulting
from the endo approach of the diene to the less hindered
face of the dienophile, was unequivocally assigned by 1H
NMR analysis (NOE)15 (Figure 1). Configuration of minor
(13) Subhas Bose, D.; J ayalakshmi, B. Synthesis 1999, 64.
(14) Initially we thought that the minor cycloadduct 9B should be
the regioisomer of 9A with endo stereochemistry, as it happened with
piperylene. So, we transformed 9B and 18 into their corresponding
sulfenylcarboxamides, 17B and 19, with the hope that they would be
enantiomers, such as it had been demonstrated for the adducts derived
from furane, piperylene, and 1-methoxybutadiene. However, we could
check that the NMR spectra of the obtained carboxamides, 17B and
19, were different, proving that they were not enantiomers. This fact
suggested to us that 17A and 17B should be the adducts resulting
from the endo and exo approaches of Dane’s diene to the less hindered
face of the dienophile 2, but with the regiochemistry opposite to that
observed in the case of dienophile 1.
(15) Double pulsed field gradient echo-DPFGS (Bruker DRX-500).
(16) The reaction of 1 with acyclic dienes 4 and 5 yielded mixtures
of two endo-adducts (see ref 6).

Sulfilimines as Chiral Dienophiles
J . Org. Chem., Vol. 67, No. 9, 2002 2923
Sch em e 5
a mixture of diastereoisomers, which indicates that the
retro Diels-Alder reaction does not take place under such
conditions.
Dienophiles exhibiting kinetic exo-selectivity are not
too frequent, and this feature is usually associated with
secondary orbital overlap in the endo transition struc-
tures,17 solvent effects,18 or steric effects of the substit-
uents destabilizing the endo approach.19 Nevertheless,
in the case of dienophile 2 there do not exist such
substituents, which suggests that the electrostatic inter-
actions or the solvent effects must be responsible for the
observed behavior. To support some of these issues
accounting for the obtained results, some theoretical
calculations were performed (see the following article).
According to the obtained results, the incorporation of
the solvent to the transition state is able to account for
the highest stability of the exo-TS.
F igu r e 1. NOE values for adduct 9A.
Sch em e 6
As a conclusion, we can state that sulfilimine 2 exhibits
a reactivity that allows its complete reaction with furan
as well as with acyclic dienes. The π-facial selectivity is
complete in all of the studied reactions and controlled
by the orientation of the p-tolylsulfinyl group. The endo
selectivity is almost complete in most of the reactions
with acyclic dienes (only Dane’s diene affords a small
amount of the exo-isomer), but reactions with furan
evolved with a marked exo-selectivity, which is not a
consequence of a retro Diels-Alder process. Finally, the
regioselectivity is almost complete with all of the studied
dienes, but the orientation with 1-substituted butadienes
is the opposite to that with Dane’s diene. Taking into
account that the mentioned behavior is different in many
aspects to that found for sulfinylacrylonitrile 1, dieno-
philes 1 and 2 can be considered as complementary from
stereochemical and regiochemical points of view. Bearing
in mind that sulfilimines can be easily obtained from
sulfinylnitriles, this behavior is of great synthetic inter-
est.
F igu r e 2. Approaches accounting for the regiochemistry of
reactions with Dane’s diene.
with piperylene (see Table 2) could be indicative of a
small contribution of these steric effects.
The last issue that deserves to be commented is the
exo-selectivity observed in the reactions of the dienophile
2 with furan. Initially we thought that this result was a
consequence of a retro Diels-Alder process, which would
determine the formation of a mixture of adducts, the
thermodynamically most stable exo one being the major
component of the equilibrium. However, we could dem-
onstrate that this was not the case. Reactions conducted
in refluxing furan, conditions favoring that the thermo-
dynamic equilibrium was reached, afforded a 1:1 mixture
of the endo and exo adducts (entry 6, Table 1), which
suggests a similar stability for both. On the other hand,
when compounds exo-3A and endo-3B were indepen-
dently treated with furan under the conditions described
in entry 5 (Table 1), we could not detect the formation of
Exp er im en ta l Section
Gen er a l Meth od s. Dienes, except Dane’s diene, and Lewis
acids are commercially available and were used without
further purification. ZnBr2 was flamed-dried in the reaction
flask prior to use. Flash chromatography was performed with
silica gel 60 (230-400 mesh ASTM), and silica gel F254 plates
were used for preparative TLC. NMR spectra were determined
in CDCl3 solutions at 200 (or 300) and 50.3 (or 75.5) MHz for
1H and 13C NMR, respectively; J values are given in hertz.
(17) Woodward, R. B.; Hoffmann, R. J . Am. Chem. Soc. 1965, 87,
4388.
(18) Berson, J .; Hamlet, Z.; Mueller, W. J . J . Am. Chem. Soc. 1962,
84, 297.
(19) (a) Brown, F. K.; Houk, K. N.; Burnell, D. J .; Valenta, Z. J .
Org. Chem. 1987, 52, 3050. (b) Kakushima, M.; Scott, D. Can. J . Chem.
1979, 57, 1399. (c) Kakushima, M. Can. J . Chem. 1979, 57, 2564.

2924 J . Org. Chem., Vol. 67, No. 9, 2002
Garc´ıa Ruano et al.
Yields are shown in Tables 1-3. All described compounds were
over 97% pure by NMR analysis. Compound 1 was synthesized
and purified according to the procedure described in ref 5. To
verify the optical purity of 1 to be used as the substrate in
further reactions, it was necessary to check it by NMR using
Yb(hfc)3 as the LSR (substrate-LSR molar ratio 1:0.3).
Compound 2 was synthesized and purified according to
procedure described in ref 7. Its optical purity could not be
determined directly either by HPLC or NMR. However, a
>97% ee could be inferred by indirect methods.7 High-pressure
reactions were performed in 1.5 mL polyethylene sample vials.
Diels-Ald er Cycloa d d ition s of 2 w ith F u r a n . Meth od
i. Th er m a l Con d ition s. A solution of 2 (143 mg, 0.75 mmol)
in an excess of furan (2 mL, 27.5 mmol) was kept at room
temperature at 4 kbar. When the reaction was completed (4
days), the crude mixture was concentrated, and the residue
was purified by flash chromatography (acetone).
Meth od ii. In th e P r esen ce of Zn Br 2. To a solution of
ZnBr2 (270 mg, 1.2 mmol) in THF (0.4 mL), under argon at
room temperature, was added a solution of 2 (191 mg, 1.0
mmol) in CH2Cl2 (0.5 mL) and the mixture was stirred for 1
h. Then an excess of furan (2 mL, 27.5 mmol) was added. The
reaction mixture was stirred at room temperature for 4 days,
water (4 mL) was added, and the mixture was extracted with
CH2Cl2 (3 × 4 mL). The organic layer was dried (Na2SO4) and
concentrated. The residue was purified by flash chromatog-
raphy (acetone).
Meth od iii. In th e P r esen ce of BF 3‚OEt2. To a solution
of 2 (1.0 mmol) in refluxing CH2Cl2 (1 mL) under argon was
added BF3‚OEt2 (225 µL, 2 mmol). The reaction mixture was
stirred for 1 h, and then an excess of furan (2 mL, 27.5 mmol)
was added. The reaction mixture was stirred at -20 °C for 5
days, then poured into water (4 mL), and extracted with CH2-
Cl2 (3 × 4 mL). The organic layer was dried (Na2SO4) and
concentrated. The residue was purified by flash chromatog-
raphy (acetone).
(1S,3a R,4S,7a R)-4-Meth yl-1-(p-tolyl)-3a ,4,7,7a -tetr a h y-
d r o-3H-1,2-ben zisoth ia zol-3-on e (7A). Reaction of 2 with
piperylene (method ii) and further flash chromatographic
purification (acetone) afforded 7A in 84% yield. It was crystal-
lized from 1:1 hexanes-ethyl acetate (white solid): mp 154-
1
155 °C; [R]20 +84.2 (c 0.5, CHCl3); H NMR δ 7.46 and 7.30
D
(AA′BB′ system, 4H), 5.89 (dt, 1H, J ) 1.9 and 4.0 Hz), 5.75
(ddt, 1H, J ) 1.9, 3.8, and 8.6 Hz), 3.91 (ddd, 1H, J ) 4.6, 7.8,
and 8.3 Hz), 2.93 (dd, 1H, J ) 5.6 and 8.6 Hz), 2.72 (dt, 1H, J
) 4.7 and 17.5 Hz), 2.60 (dq, 1H, J ) 1.9 and 17.5 Hz), 2.51
(m, 1H), 2.37 (s, 3H), 1.39 (d, 3H, J ) 7.2 Hz); 13C NMR δ
188.4, 143.1, 135.9, 133.6, 130.5 (2C), 125.4 (2C), 123.0, 64.3,
44.2, 29.8, 25.4, 21.2, 16.0; HRMS (EI) 259.1037 (C15H18NOS
requires 259.1030). Anal. Calcd for C15H18NOS: C, 69.47; H,
6.61; N, 5.40; S, 12.34. Found: C, 69.19; H, 6.65; N, 5.19; S
12.14.
(1S,3a R,7R,7a R)-7-Meth yl-1-(p-tolyl)-3a ,4,7,7a -tetr a h y-
d r o-3H-1,2-ben zisoth ia zol-3-on e (7B). Reaction of 2 with
piperylene (method ii) and further flash chromatographic
purification (acetone) afforded 7B as a white solid in 11%
yield: mp 86-87 °C; [R]20 +2.2 (c 1.49, CHCl3) 1H NMR δ
D
7.42 and 7.31 (AA′BB′ system, 4H), 6.02 (ddd, 1H, J ) 3.2,
6.4, and 12.6 Hz), 5.72 (dt, 1H, J ) 3.2 and 9.4 Hz), 3.96 (ddd,
1H, J ) 0.8, 5.4, and 9.4 Hz), 3.17 (ddd, 1H, J ) 1.9, 7.5, and
9.4 Hz), 2.89 (ddd, 1H, J ) 1.6, 6.7, and 15.3 Hz), 2.65 (m,
1H), 2.39 (s, 3H), 2.10 (m, 1H), 1.45 (d, 3H, J ) 7.1 Hz); 13C
NMR δ 190.7, 143.1, 134.9, 131.3 (2C), 130.7, 130.2, 125.7 (2C),
73.8, 41.9, 30.6, 29.2, 25.8, 21.4, 17.9.
Diels-Ald er Cycloa d d ition s of 2 w ith Da n e’s Dien e.
Rea ction s a t High P r essu r e. Meth od i: Th er m a l Con d i-
tion s. To a solution of 2 (191 mg, 1.0 mmol) in CH2Cl2 (1 mL)
was added a 1 M solution of Dane’s diene (1.6 mL, 3 mmol) in
benzene. The mixture was kept at 4 kbar at room temperature
for 14 days. When the reaction was completed, the crude
mixture was concentrated, and the residue was purified by
flash chromatography.
Meth od ii: In th e P r esen ce of Zn Br 2. To a solution of
ZnBr2 (270 mg, 1.2 mmol) in THF (0.5 mL), under argon at
room temperature, was added a solution of 2 (191 mg, 1.0
mmol) in CH2Cl2 (1 mL). The reaction mixture was stirred for
1 h at room temperature. Then a 1 M solution of Dane’s diene
(1.6 mL, 3 mmol) in benzene was added, and the mixture was
kept at 4 kbar at room temperature for 7 days. When the
reaction was completed, water (4 mL) was added, and the
mixture was extracted with CH2Cl2 (3 × 5 mL). The organic
layer was dried (Na2SO4) and concentrated. The residue was
purified by flash chromatography.
(1S,1aR,3aR,11aR)-1a,3a,4,10,11,11a-Hexah ydr o-8-m eth -
oxy-1-(p-tolyl)-3H-1,2-p h en a n th r en e-isoth ia zol-3-on e (en -
d o-9A). Reaction of 2 with Dane’s diene (method i) afforded
endo-9A in 84% yield. It was crystallized from acetone (white
solid): mp 123-124 °C; [R]20D -141.3 (c 0.25, CHCl3); 1H NMR
δ 7.49 (d, 1H, J ) 8.7 Hz), 7.41 and 7.30 (AA′BB′ system, 4H),
6.76 (dd, 1H, J ) 2.4 and 8.7 Hz), 6.66 (d, 1H, J ) 2.6 Hz),
6.37 (dt, 1H, J ) 3.0 and 6.9 Hz), 4.15 (dd, 1H, J ) 4.7 and
9.7 Hz), 3.80 (s, 3H), 3.33 (t, 1H, J 7.5 Hz), 3.11 (dd, 1H, J )
7.5 and 15.0 Hz), 2.90-2.70 (m, 3H), 2.40 (s, 3H), 2.30-2.13
(m, 2H), 2.05 (dq, 1H, J ) 4.5 and 11.9 Hz); 13C NMR δ 190.4,
158.9, 143.2, 137.9, 135.6, 134.5, 130.8 (2C), 126.2, 125.8 (2C),
125.1, 120.4, 113.1, 112.8, 73.8, 55.2, 43.2, 36.8, 29.9, 27.2, 26.9,
21.4; HRMS (FAB) 378.1527 [M + H]+ (C23H23NO2S requires
378.1539).
(1S,1aS,3aS,11aR)-1a,3a,4,10,11,11a-Hexah ydr o-8-m eth -
oxy-1-(p-tolyl)-3H-1,2-p h en a n tr en e-isoth ia zol-3-on e (exo-
9B): It was obtained as the minor product (<5%) of the
reaction of 2 with Dane’s diene (method i) and could not be
completely purified. 1H NMR (from a mixture) δ 7.47 and 7.31
(AA′BB′, 4H), 7.41 (d, 1H, J ) 8.5 Hz), 6.67 (dd, 1H, J ) 2.6
and 8.7 Hz), 6.59 (d, 1H, J ) 2.6 Hz), 6.14 (m, 1H), 4.1 (ddd,
1H, J ) 2.7, 6.2, and 8.1 Hz), 3.70 (s, 3H), 3.14 (dd, 1H, J )
5.4 and 8.6 Hz), 2.96 (dd, 1H, J ) 2.8 and 6.9 Hz), 2.93 (dd,
1H, J ) 2.6 and 6.5 Hz), 2.88-2.68 (m, 4H), 2.4 (s, 3H), 1.97
(dq, 1H, J ) 4.0 and 12.5 Hz); 13C NMR δ 188.2, 158.9, 143.2,
139.6, 134.6, 130.7 (2C), 126.6, 125.6 (2C), 125.3, 124.8, 114.0,
112.8, 112.6, 65.4, 55.2, 44.0, 36.9, 30.9, 26.9, 23.5, 21.4.
Rea ction s of Cycloa d d u cts w ith LiAlH4. Gen er a l P r o-
ced u r e. A suspension of the adduct (1 mmol) and LiAlH4 (1
(1S)-1-(p-Tolyl)-3a ,4,7,7a -tetr a h yd r o-3H-4,7-ep oxy-1λ4-
1,2-ben zisoth ia zol-3-on e (exo-3A). It was crystallized from
CH2Cl2-acetone-hexane (white solid): yield 85%; mp 172-
173 °C; [R]20 +133.6 (c 0.5, CHCl3); 1H NMR δ 7.51 and 7.36
D
(AA′BB′ system, 4H), 6.62 (dd, 1H, J ) 1.6 and 5.9 Hz), 6.35
(dd, 1H, J ) 1.8 and 5.9 Hz), 5.55 (d, 1H, J ) 1.7 Hz), 5.42 (d,
1H, J ) 1.7 Hz), 3.68 (d, 1H, J ) 6.7 Hz), 3.23 (d, 1H, J ) 6.7
Hz), 2.36 (s, 3H); 13C NMR δ 185.4, 143.9, 140.2, 134.4 (2C),
131.0 (2C), 125.9 (2C), 83.4, 81.9, 71.0, 51.8, 21.5; HRMS (FAB)
260.0745 [M + H]+ (C14H14NO2S requires 260.0753).
Diels-Ald er Cycloa d d ition s of 2 w ith Acyclic Dien es.
Rea ction s a t High P r essu r e. Meth od i: Th er m a l Con d i-
tion s. A solution of 2 (191 mg, 1.0 mmol) and 4 mmol of the
corresponding diene in CH2Cl2 (1 mL) was kept at 4 kbar at
room temperature. When the reaction was completed, the
crude mixture was concentrated and the residue was purified
by flash chromatography.
Meth od ii: In th e P r esen ce of Zn Br 2. To a solution of
ZnBr2 (270 mg, 1.2 mmol) in THF (0.4 mL), under argon at
room temperature, was added a solution of 2 (191 mg, 1.0
mmol) in CH2Cl2 (1 mL). The reaction mixture was stirred for
1 h at room temperature. Then the corresponding diene (2
mmol of piperylene or 1-methoxybutadiene) was added, and
the mixture was kept at 4 kbar at room temperature. When
the reaction was completed, water (4 mL) was added, and the
mixture was extracted with CH2Cl2 (3 × 5 mL). The organic
layer was dried (Na2SO4) and concentrated.
(1S,3aR,4S,7aR)-4-Meth oxy-1-(p-tolyl)-3a,4,7,7a-tetr ah y-
d r o-3H-1,2-ben zisoth ia zol-3-on e (6A). Reaction of 2 with
methoxybutadiene (method ii) and further flash chromato-
graphic purification (acetone) afforded 6A as an oil in 89%
1
yield: [R]20 +127.7 (c 1.0, CHCl3); H NMR δ 7.48 and 7.25
D
(AA′BB′ system, 4H), 6.18 (ddt, 1H, J ) 0.5, 2.4, and 5.1 Hz),
5.89 (ddd, 1H, J ) 9.6, 3.2, and 5.5 Hz), 4.18 (dd, 1H, J ) 4.0
and 5.4 Hz), 3.73 (ddd, 1H, J ) 6.2, 8.6, and 9.8 Hz), 3.25 (s,
3H), 2.98 (dd, 1H, J ) 4.0 and 10.0 Hz), 2.79 (ddd, 1H, J )
3.0, 6.2, and 17.2 Hz), 2.62 (ddd, 1H, J ) 5.7, 8.6, and 17.2
Hz), 2.31 (s, 3H); 13C NMR δ 184.4, 143.5, 134.1, 130.5 (2C),
129.4, 128.5, 125.5 (2C), 70.8, 63.6, 56.8, 48.0, 24.1, 21.1;
HRMS (EI) 275.0972 (C15H18NOS requires 275.0980).

Sulfilimines as Chiral Dienophiles
J . Org. Chem., Vol. 67, No. 9, 2002 2925
mmol) in THF (2 mL) under argon was stirred for 5 min. Water
(2 mL) was added, and the mixture was extracted with AcOEt
(3 × 4 mL). The organic layer was dried (Na2SO4) and
evaporated.
Reaction of exo-9B with LiAlH4 and further chromatographic
purification (acetone) afforded 17B as an oil: [R]20D +89 (c 0.1,
CHCl3); 1H NMR δ 7.57 (d, 1H, J ) 8.9 Hz), 7.44 and 7.14
(AA′BB′ system, 4H), 6.72 (dd, 1H, J ) 2.7 and 8.9 Hz), 6.57
(d, 1H, J ) 3.0 Hz), 6.37-6.27 (m, 1H), 5.81 (bs, 1H), 5.58 (bs,
1H), 3.55 (dt, 1H, J ) 8.6 and 4.3 Hz), 3.29 (s, 3H), 2.96 (t,
1H, J ) 5.1 Hz), 2.86-2.76 (m, 2H), 2.72-2.62 (m, 2H), 2.61-
2.50 (m, 1H), 2.34 (s, 3H), 1.97-1.83 (m, 1H), 1.82-1.72 (m,
1H); 13C NMR δ 172.9, 158.7, 137.7, 133.2, 132.8 (2C), 130.5,
129.9 (2C), 125.9, 124.7, 116.4, 113.2, 112.9, 55.2, 49.7, 45.1,
38.9, 32.1, 30.6, 30.1, 26.7, 21.1; HRMS (FAB) 380.1684 [M +
H]+ (C23H25NO2S requires 380.1677).
Rea ction s of Cycloa d d u cts w ith BF 3‚OEt2/Na I. Gen -
er a l P r oced u r e. To a solution of cycloadduct (1 mmol) in CH2-
Cl2 (2 mL) was added BF3‚OEt2 (1.2 mmol), and the resulting
mixture was stirred at reflux for 1 h. Then it was cooled at
room temperature, and NaI (5 equiv) was added. The mixture
was stirred overnight. It was quenched with water (4 mL) and
extracted with CH2Cl2 (3 × 4 mL). The organic layer was
washed with Na2SO3 (4 mL), dried (Na2SO4), and concentrated.
(2R,3S)-3-[(p-Tolyl)su lfen yl]-7-oxa bicyclo[2.2.1]h ep t-5-
en e-8-ca r boxa m id e (14). Reaction of exo-3A with LiAlH4 and
further flash chromatographic purification (acetone) afforded
14. It was crystallized from CH2Cl2-acetone-hexane (white
solid): mp 152-153 °C; [R]20 +43.0 (c 1.78, CHCl3); 1H NMR
D
δ 7.36 and 7.15 (AA′BB′ system, 4H), 6.41 (dd, 1H, J ) 1.6
and 5.9 Hz), 6.37 (dd, 1H, J ) 1.6 and 5.9 Hz), 5.47 (bs, 2H),
5.17 (t, 1H, J ) 1.2 Hz), 4.93 (t, 1H, J ) 1.2 Hz), 3.33 (d, 1H,
J ) 8.3 Hz), 2.79 (dd, 1H, J ) 2.4 and 8.3 Hz) and 2.33 (s,
3H); 13C NMR δ 173.5, 139.6, 137.7, 136.5, 135.1, 132.0 (2C),
130.0 (2C), 84.2, 81.8, 50.3, 49.3, 21.1; HRMS (FAB) 262.0902
[M + H]+ (C14H16NO2S requires 262.0908).
(1R,2S,6R)-2-Meth oxy-6-[(p-tolyl)su lfen yl]cycloh ex-3-
en e-1-ca r boxa m id e [(+)-11A]. Reaction of 6A with LiAlH4
and further flash chromatographic purification (1:1 hexanes-
ethyl acetate) afforded (+)-11A. It was crystallized from 1:1
hexanes-ethyl acetate (white solid): mp 131-132 °C; [R]20
D
(1S,2R,6S)-2-Met h oxy-6-[(p-t olyl)su lfen yl]cycloh ex-3-
en e-1-ca r boxa m id e [(-)-11A]. Reaction of (1R,2R,6S)-2-
methoxy-6-[(R)-(p-tolyl)sulfinyl]-3-cyclohexene-1-carbonitrile (en-
do-13)6 with BF3‚OEt2 and NaI afforded (-)-11A. It was
purified by flash chromatography (1:1 hexanes-ethyl ac-
+85.5 (c 1.0, CHCl3); 1H NMR δ 7.36 and 7.09 (AA′BB′ system,
4H), 6.79 (bs, 1H), 6.10 (bs, 1H), 5.83 (bs, 2H), 4.06 (dd, 1H, J
) 1.2 and 3.4 Hz), 3.44 (ddd, 1H, J ) 3.4, 5.6 and 8.3 Hz),
3.43 (s, 3H), 3.18 (dd, 1H, J ) 3.4 and 5.2 Hz), 2.57-2.38 (m,
2H) and 2.3 (s, 3H); 13C NMR δ 172.8, 137.2 (2C), 132.4 (2C),
129.7 (2C), 129.0, 125.9, 75.8, 56.8, 47.9, 44.9, 31.3, 20.9;
HRMS (FAB) 278.1215 [M + H]+ (C15H19NO2S requires
278.1212). Anal. Calcd for C15H19NO2S: C, 64.95; H, 6.90; N,
5.05; S, 11.56. Found: C, 64.71; H, 6.95; N, 5.12; S 11.82.
(1R,2S,6R)-2-Met h yl-6-[(p -t olyl)su lfen yl]cycloh ex-3-
en e-1-ca r boxa m id e [(+)-10A]. Reaction of 7A with LiAlH4
and further flash chromatographic purification (1:1 hexanes-
ethyl acetate) afforded (+)-10A as an oil: [R]20D +130.4 (c 1.25,
etate): [R]20 -82.4 (c 1.0, CHCl3).
D
(1S,2R,6S)-2-Meth yl-6-[(p-tolyl)su lfen yl]cycloh ex-3-en e-
1-ca r boxa m id e [(-)-10A). Reaction of (1S,2R,6S)-2-methyl-
6-[(R)-(p-tolyl)sulfinyl]-3-cyclohexene-1-carbonitrile (endo-12)6
with BF3‚OEt2 and NaI afforded (-)-10A. It was purified by
flash chromatography (1:1 hexanes-ethyl acetate): [R]20
-125.9 (c 1.25, CHCl3).
D
(1S,2S,3S,4R)-3-[(p-Tolyl)su lfen yl]-7-oxa bicyclo[2.2.1]-
h ep t-5-en e-2-ca r bon itr ile [(+)-15]. To a solution of 14 (1
equiv) in CH2Cl2 (4 mL) under argon at 0 °C was added NEt3
(2 equiv). Then (Tf)2O (1.5 equiv)12 was added dropwise. The
mixture was stirred for 1 h at room temperature, quenched
with water (4 mL), and extracted with CH2Cl2 (3 × 4 mL).
The organic layer was dried (Na2SO4) and concentrated. It was
crystallized from 1:2 AcOEt-hexane (white solid): mp 105-
106 °C; [R]20D +117.4 (c 0.99, CHCl3); 1H NMR δ 7.42 and 7.15
(AA′BB′ system, 4H), 6.46 (dd, 1H, J ) 1.6 and 5.9 Hz), 6.40
(dd, 1H, J ) 1.6 and 5.3 Hz), 5.32 (s, 1H), 4.99 (s, 1H), 3.26 (d,
1H, J ) 7.5 Hz), 2.95 (d, 1H, J ) 7.5 Hz), 2.35 (s, 3H); 13C
NMR δ 138.2, 137.2, 135.2, 132.6 (2C), 130.4, 130.1 (2C), 118.4,
83.6, 82.5, 48.5, 36.4, 21.1; HRMS (FAB) 244.0796 [M + H]+
(C14H16NO2S requires 244.0800).
1
CHCl3); H NMR δ 7.37 and 7.09 (AA′BB′ system, 4H), 6.28
(bs, 1H), 5.83 (bs, 1H), 5.73 (ddd, 1H, J ) 1.8, 4.8, and 5.4
Hz), 5.49 (dd, 1H, J ) 1.8 and 10.1 Hz), 3.47 (ddd, 1H, J )
4.1, 6.5, and 10.3 Hz), 2.76 (t, 1H, J ) 4.8 Hz), 2.55-2.46 (m,
1H), 2.46-2.35 (m, 2H), 2.30 (s, 3H), 1.08 (d, 3H, J ) 7.3 Hz);
13C NMR δ 173.4, 137.2 (2C), 132.8 (2C), 130.0, 129.7 (2C),
125.8, 49.1, 45.4, 32.9, 28.9, 21.0, 17.7; HRMS (FAB) 262.1269
[M + H]+ (C15H19NOS requires 262.1266).
(1R,5R,6R)-5-Met h yl-6-[(p -t olyl)su lfen yl]cycloh ex-3-
en e-1-ca r boxa m id e (10B). Reaction of 7B with LiAlH4 and
further flash chromatographic purification (1:1 hexanes-ethyl
acetate) afforded 10B. It was crystallized from 1:1 hexanes-
ethyl acetate (white solid): mp 162-163 °C; [R]20 -50.5 (c
D
0.4, CHCl3); 1H NMR δ 7.38 and 7.06 (AA′BB′ system, 4H),
6.05 (bs, 1H), 5.82 (bs, 1H), 5.69 (ddd, 1H, J ) 2.4, 4.6, and
7.3 Hz), 5.43 (ddq, 1H, J ) 1.6, 3.8, and 9.9 Hz), 3.82-3.75
(m, 1H), 2.89 (ddd, 1H, J ) 2.4, 5.6, and 11.0 Hz), 2.82-2.70
(m, 1H), 2.62-2.42 (m, 1H), 2.29 (s, 3H), 2.38-2.21 (m, 1H),
1.14 (d, 3H, J ) 6.9 Hz); 13C NMR δ 175.8, 137.2, 133.4, 132.3,
131.9 (2C), 130.1 (2C), 124.9, 55.2, 46.7, 37.7, 25.4, 21.4, 18.8;
HRMS (EI) 261.1192 [M + H]+ (C15H19NOS requires 261.1187).
Anal. Calcd for C15H19NOS: C, 68.93; H, 7.33; N, 5.36; S, 12.27.
Found: C, 68.81; H, 7.37; N, 5.22; S, 12.27.
(1R,2R,3R,4S)-3-[(p-Tolyl)su lfen yl]-7-oxa bicyclo[2.2.1]-
h ep t-5-en e-2-ca r bon itr ile [(-)-15]. To a solution of (1R,2R,
3R,4S)-3-[(R)-(p-tolyl)sulfinyl]-7-oxabicyclo[2.2.1]hept-5-ene-2-
carbonitrile (exo-16)6 (1 mmol) in MeCN (4 mL) under argon
was added PCl3 (2 equiv). The reaction was stirred for 1 h at
room temperature, quenched with water (4 mL), and extracted
with CH2Cl2 (3 × 4 mL). The organic layer was dried (Na2-
SO4) and concentrated. It was crystallized from 1:2 AcOEt-
hexane (white solid): [R]20 -114.3 (c 0.99, CHCl3).
D
(1R,2R,10a R)-1,2,3,9,10,10a -H exa h yd r o-7-m et h oxy-1-
[(p -t olyl)su lfen yl]-p h en a n t h r en e-1-ca r b oxa m id e (17A).
Reaction of endo-9A with LiAlH4 and further flash chromato-
graphic purification (acetone) afforded 17A. It was crystallized
from acetone (white solid): mp 213-214 °C; [R]20D -78 (c 0.15,
Ack n ow led gm en t. Financial support from the Di-
reccio´n de Investigacio´n Cient´ıfica y Te´cnica CAICYT
(Projects BQU2000-0246, BQU2000-0248, and PB98-
0102) is gratefully acknowledged. C.A. thanks the
Spanish Ministerio de Educacio´n y Cultura for a fel-
lowship. R.G. thanks the J unta de Extremadura-Fondo
Social Europeo for a predoctoral fellowship. L.G.G.
thanks Consejo Nacional de Ciencia y Tecnolog´ıa (CON-
ACYT-Me´xico) for a fellowship.
1
DMSO-d6); H NMR (DMSO-d6, 50 °C) δ 7.61 (d, 1H, J ) 8.9
Hz), 7.35 and 7.07 (AA′BB′ system, 4H), 7.20 (bs, 1H), 6.81
(bs, 1H), 6.71 (dd, 1H, J ) 2.8 and 8.9 Hz), 6.61 (d, 1H, J )
2.0 Hz), 6.29 (t, 1H, J ) 2.0 Hz), 3.98 (t, 1H, J ) 2.4 Hz), 3.70
(s, 3H), 2.86-2.74 (m, 2H), 2.73-2.64 (m, 2H), 2.63-2.53 (m,
1H), 2.36-2.28 (m, 1H), 2.26 (s, 3H), 1.95-1.76 (m, 1H), 1.56-
1.44 (m, 1H); 13C NMR (DMSO-d6) δ 173.7, 158.2, 137.9, 135.8,
134.1, 131.9, 131.8 (2C), 129.6 (2C), 126.4, 124.6, 116.4, 113.3,
112.9, 55.2, 54.6, 44.4, 43.4, 29.9, 27.4, 24.9, 20.6; HRMS (FAB)
380.1684 [M + H]+ (C23H25NO2S requires 380.1677). Anal.
Calcd for C23H25NO2S: C, 72.79; H, 6.64; N, 3.69; S, 8.45.
Found: C, 72.48; H, 6.71; N, 3.71; S, 8.13.
Su p p or tin g In for m a tion Ava ila ble: IR and MS data and
copies of 1H NMR spectra of sulfilimines 3A, 6A, 7A, 7B, and
9A, of sulfenylcarboxamides 10A, 11A, 14, 17A, and 17B, and
of sulfenylcarbonitrile 15. This material is available free of
charge via the Internet at http://pubs.acs.org.
(1S,2S,10a R)-1,2,3,9,10,10a -H exa h yd r o-7-m et h oxy-1-
[(p -t olyl)su lfen yl]-p h en a n t h r en e-1-ca r b oxa m id e (17B).
J O016174W