Studies of diastereoselectivity in Diels-Alder reactions of (S)S-4a,5,8,8a-tetrahydro-5,8-methane-2-(p-tolylsulfinyl)-1,4-naphthoquinones with cyclopentadiene

Article abstract of DOI:10.1021/jo9521209

The title compounds 6 and 7 have proved to be adequate rigid models to evaluate the ability of the sulfinyl group to control the diastereoselectivity of the [4 + 2] cycloadditions of cyclopentadiene on the ene-dione moiety. The results of thermal and Lewi

Full text of DOI:10.1021/jo9521209

2980
J . Org. Chem. 1996, 61, 2980-2985
Stu d ies of Dia ster eoselectivity in Diels-Ald er Rea ction s of
(S)S-4a ,5,8,8a -Tetr a h yd r o-5,8-m eth a n e-2-(p-tolylsu lfin yl)-1,4-n a p h th o-
qu in on es w ith Cyclop en ta d ien e
M. Carmen Carren˜o,*,† J ose´ L. Garc´ıa Ruano,*,† Antonio Urbano,† and Miguel A. Hoyos‡
Departamento de Quı´mica Orga´nica (C-I) and Departamento de Geoqu´ımica (C-VI), Universidad
Auto´noma, Cantoblanco, 28049-Madrid, Spain
Received November 30, 1995X
The title compounds 6 and 7 have proved to be adequate rigid models to evaluate the ability of the
sulfinyl group to control the diastereoselectivity of the [4 + 2] cycloadditions of cyclopentadiene on
the ene-dione moiety. The results of thermal and Lewis acid-catalyzed reactions allowed us to
establish that both reactivity and endo/ exo selectivity were modulated by the presence of the sulfinyl
group, the endo-anti-endo or the exo-anti-endo bisadducts being obtained as major products
depending on experimental conditions. The role of the association between the SOTol group and
several Lewis acids (BF3‚OEt2, Eu(fod)3, ZnBr2), which shifted the conformational equilibrium around
the C-S bond, was used to explain the stereochemical course of the cycloadditions mainly controlled
by steric factors. The synthesis of the exo-anti-endo bisadduct 5 was described for the first time.
Sch em e 1
In tr od u ction
The stereoselectivities associated with [4 + 2] cycload-
ditions of strained bridged polycyclic molecules have been
the subject of several studies.1 From a synthetic point
of view the interest of the resulting molecules rests on
the access to polycyclic natural products2 that can be
made from these adducts, as well as new materials3
showing host-guest complexation properties.4 Fre-
quently, repetitive Diels-Alder reactions2-5 have been
the method of choice to the synthesis of some of these
precursors as in the case of p-benzoquinone-cyclopenta-
diene bisadduct 4 (Scheme 1), an intermediate in the syn-
thesis of garudane.6 As can be seen in Scheme 1, com-
pound 4 could arise from a second cycloaddition of cyclo-
pentadiene on endo-monoadduct 1. In this reaction four
bisadducts with different stereochemistry could result:
endo-anti-endo-2, exo-syn-endo-3, endo-syn-endo-4, and
exo-anti-endo-5. Nevertheless, the endo-anti-endo bisad-
duct 2 was the only one formed directly in the cycload-
dition of cyclopentadiene7 because the π-facial selectivity
was controlled by the norbornene moiety of 1 and the
endo/ exo selectivity directed by the endo-orientating
character of the carbonyl groups of the ene-dione system.
This result precluded the obtention of the other possible
diastereoisomers by direct Diels-Alder reaction on 1.
Two of them, 3 and 4, could be prepared by alternative
methods. So, the exo-syn-endo-bisadduct 3 was obtained7c
by isomerization in basic medium of the endo-anti-endo
bisadduct 2, and more recently,6b bisadducts 3 and 4 were
prepared in two four-step reaction sequences from monoad-
duct 1. To our knowledge up to date, the exo-anti-endo
diastereoisomer 5 has not been synthesized.
† Departamento de Qu´ımica Orga´nica.
‡ Departamento de Geoqu´ımica.
X Abstract published in Advance ACS Abstracts, April 1, 1996.
(1) (a) Mehta, G.; Padma, S.; Pattabhi, V.; Pramanik, A.; Chan-
drasekhar, J . J . Am. Chem. Soc. 1990, 112, 2942. (b) Mehta, G.;
Krishna-Reddy, S. H.; Padma, S. Tetrahedron 1991, 47, 7821. (c) Dols,
P. P. M. A.; Klunder, A. J . H.; Zwanenburg, B. Tetrahedron Lett. 1993,
34, 3181. (d) Williams, R. V.; Todime, M. M. R.; Enemark, P. J . Org.
Chem. 1993, 58, 6740. (e) Mataka, S.; Ma, J .; Thiemann, T.; Rudzin˜ski,
J . M.; Sawada, T.; Tashiro, M. Tetrahedron Lett. 1995, 36, 6105.
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D′Andrea, S. V.; Freeman, J . P.; Szmuszkovicz, J . J . Org. Chem. 1990,
55, 4356.
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F. J . Am. Chem. Soc. 1992, 114, 6630. (b) Cory, R. M.; McPhail, C. L.;
Dikmans, A. J . Tetrahedron Lett. 1993, 34, 7533. (c) Pollmann, M.;
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Kohnke, F. H.; Parisi, M.; Raymo, F. M.; Stoddart, J . F. Tetrahedron
Lett. 1994, 35, 4839. (e) Komatsu, K.; Nishinaga, T.; Takeuchi, K.;
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(4) Benkhoff, J .; Boese, R.; Kla¨rner, F. G.; Wigger, A. E. Tetrahedron
Lett. 1994, 35, 73.
Considering the well demonstrated ability of a sulfinyl
group situated on a dienophilic double bond to control
the diastereoselectivity of Diels-Alder reactions,8 we
reasoned that the incorporation of a sulfoxide on the ene-
(5) (a) Forman, M. A.; Dailey, W. P. J . Org. Chem. 1993, 58, 1501.
(b) Zhu, J .; Klunder, A. J . H.; Zwanenburg, B. Tetrahedron Lett. 1993,
34, 3335. (c) Chou, T. C.; J iang, T. S.; Hwang, J . T.; Lin, C. T.
Tetrahedron Lett. 1994, 35, 4165. (d) Chou, T. C.; Yang, M. S.; Lin, C.
T. J . Org. Chem. 1994, 59, 661. (e) Alder, R. W.; Allen, P. R.; Edwards,
L. S.; Fray, G. Y.; Fuller, K. E.; Gore, P. M.; Hext, N. M.; Perry, M. H.;
Thomas, A. R.; Turer, K. S. J . Chem. Soc., Perkin Trans. 1 1994, 3071.
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Mehta, G.; Padma, S. Tetrahedron 1991, 47, 7807.
(7) (a) Alder, K.; Stein, G. J ustus Liebigs Ann. Chem. 1933, 501,
247. (b) de Vries, L.; Heck, R.; Piccolini, R.; Winstein, S. Chem. Ind.
(London) 1959, 1416. (c) Cookson, R. C.; Hill, R. R.; Hudec, J . J . Chem.
Soc. 1964, 3043. (d) Brown, R.; Bruce, J . M.; Hudson, D. W., Mills, O.
S. J . Chem. Soc., Perkin Trans. 2 1974, 132.
(8) (a) Arai, Y.; Koizumi, T. Rev. Heteroatom Chem. 1992, 6, 202.
(b) Arai, Y.; Matsui, M.; Kontani, T.; Ohno, T.; Koizumi, T.; Shiro, M.
J . Chem. Soc., Perkin Trans. 1 1994, 25.
S0022-3263(95)02120-7 CCC: $12.00 © 1996 American Chemical Society

Diastereoselectivity of Diels-Alder Reactions
J . Org. Chem., Vol. 61, No. 9, 1996 2981
Sch em e 2
dione moiety of compound 1 could modify the behavior
of the new dienophile in the second cycloaddition of
cyclopentadiene. This would make bisadducts with dif-
ferent stereochemistry from that of the endo-anti-endo
usually obtained from monoadduct 1 accesible. In previ-
ous studies devoted to sulfinylbenzo-9 and naphthoquino-
nes10 as dienophiles, we showed that π-facial diastereo-
selectivity could be controlled by choosing the proper
Lewis acid catalyst. Further studies on sulfinyl male-
ates11 also revealed a strong influence of the catalyst on
the endo/ exo selectivity, mainly in the case of cyclic
dienes, making possible the major formation of exo-
adducts in some cases.11b The study of cycloadditions on
sulfinylene-diones 6 and 7, which shared the norbornene
moiety of 1 and the chiral sulfoxide, could bring light on
the role of the latter in controlling both the endo/ exo
selectivity and the π-facial diastereoselectivity of sulfinyl
dienophiles.
In this paper we report the results obtained from the
Diels-Alder reactions of 6 and 7 with cyclopentadiene
(Scheme 2) under thermal conditions and in the presence
of Lewis acids.
Resu lts a n d Discu ssion
Compounds 6 and 7 were prepared as previously
described9a,c from (S)-2-(p-tolylsulfinyl)-1,4-benzoquino-
ne12,13 and cyclopentadiene. The reaction of compound
6 with cyclopentadiene took place under very mild
conditions, -20 °C in CH2Cl2 (Scheme 2, Table 1, entry
1) to afford a 85:15 mixture of two bisadducts 8 and 9,
showing the endo and exo stereochemistry, respectively,
in the newly generated norbornenyl system. This result
was not unexpected taking into account the existence of
the norbornene moiety in the starting dienophile which
makes only the upper face of the ene-dione accesible to
the attack of the diene.7
Compound 7 produced at 0 °C a 90:10 mixture of
diastereoisomers 10 and 11 (Scheme 2, Table 1, entry
11) which again resulted from the endo and exo approach
of cyclopentadiene to the upper face of 7. These mild
conditions for cycloadditions of both dienophiles 6 and 7
contrasted with other results published on Diels-Alder
reactions of substituted norbornene-diones which only
reacted with cyclopentadiene at high pressures14 and
suggested that the sulfoxide group increased the reactiv-
ity of the dienophile. This effect was not evident in
Diels-Alder reactions of other sulfinyl dienophiles.15 All
derivatives 8-11 obtained in these reactions could be
isolated diastereoisomerically pure by flash chromatog-
raphy (see Experimental Section).
Ta ble 1. Diels-Ald er r ea ction s of 6 a n d 7 w ith
cyclop en ta d ien e
time yield
entry dienophile T (°C) cat. (equiv)
(h)
(%)
8:9
10:11
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
6
6
6
6
6
6
6
6
6
6
7
7
7
7
7
7
-20
20
-
-
48
2
92 85:15
93 85:15
76 100:0
90 60:40
87 45:55
89 80:20
84 75:25
81 80:20
77 85:15
75 85:15
89
91
-
84
84
80
20a BF3‚OEt2 (2) 24
20
-20
-40
ZnBr2 (2)
ZnBr2 (2)
ZnBr2 (2)
0.08
1
2
3
2
2
2
20a Eu(fod)3 (1)
20a Eu(fod)3 (2)
20a Eu(fod)3 (3)
20a Eu(fod)3 (5)
0a
20
20
-
-
48
8
90:10
90:10
-
40:60
50:50
50:50
BF3‚OEt2 (2) 48
ZnBr2 (2)
-20
0.5
5
3
20a Eu(fod)3 (2)
20a Eu(fod)3 (3)
a
No reaction at -20 °C.
Once separated, the reductive elimination of the sulfi-
nyl group on the endo-anti-endo sulfinyl bisadduct 8 by
using SmI2 and t-BuOH in THF16 yielded a 85% of the
endo-anti-endo bisadduct 27 (Scheme 2). In the same
conditions, the exo-anti-endo sulfinyl bisadduct 9 afforded
the unknown exo-anti-endo cyclopentadiene-quinone bisad-
duct 5 (Scheme 2) in a 89% yield.
Configurational assignment of adducts 8-11 was based
on a simple chemical correlation with the known com-
pounds 126b,17 and 136b,17 (Scheme 2). The endo-anti-endo
configuration of 8 and 10 was confirmed by their evolu-
tion into 12 upon heating in EtOAc solution. The same
pyrolytic elimination on sulfoxides 9 and 11 afforded 13,
allowing us to assign the exo-anti-endo configuration to
these sulfinyl derivatives.
(9) (a) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Urbano, A. Tetrahedron
Lett. 1989, 30, 4003. (b) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Toledo,
M. A.; Urbano, A. Tetrahedron Lett. 1994, 35, 9759. (c) Carren˜o, M.
C.; Garc´ıa Ruano, J . L.; Toledo, M. A.; Urbano, A.; Remor, C. Z.; Stefani,
V.; Fischer, J . J . Org. Chem. 1996, 61, 503.
(10) (a) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Urbano, A. J . Org.
Chem. 1992, 57, 6870. (b) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Urbano,
A. Tetrahedron Lett. 1994, 35, 3789.
(11) (a) Alonso, I.; Carretero, J . C.; Garc´ıa Ruano, J . L. J . Org. Chem.
1994, 59, 1499 and references cited therein. (b) Carretero, J . C.; Garc´ıa
Ruano, J . L.; Mart´ın Cabrejas, L. M. Tetrahedron 1995, 51, 8323.
(12) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Mata, J . M.; Urbano, A.
Tetrahedron 1991, 47, 605.
(13) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Urbano, A. Synthesis 1992,
651.
(14) Srivastava, S.; Marchand, A. P.; Vidyasagar, V.; Flippen-
Anderson, J . L.; Gilardi, R.; George, C.; Zachwieja, Z.; le Noble, W. J .
J . Org. Chem. 1989, 54, 247.
(16) Takahashi, T.; Sugita, J .; Hirano, T.; Koizumi, T. Heterocycles
1994, 39, 305.
(17) Mehta, G.; Padma, S.; Karra, S. R.; Gopidas, K. R.; Cyr, D. R.;
Das, P. K.; George, M. V. J . Org. Chem. 1989, 54, 1342.
(15) Maignan, C.; Raphael, R. A. Tetrahedron Lett. 1983, 24, 3245.

2982 J . Org. Chem., Vol. 61, No. 9, 1996
Ta ble 2. 1H-NMR Da ta for Com p ou n d s 8-11
δ (ppm), multiplicity, J (in Hz)
Carren˜o et al.
proton
8
9
10
11
H1
H2
H3
H4
3.34, m
3.38-3.21, m
6.48, dd, 3.2, 5.5
6.30, dd, 3.0, 5.5
3.62, m
3.39, m
3.2-3.4, m
6.58, dd, 2.9, 5.6
6.43, dd, 3.3, 5.6
3.66, m
6.49, dd, 2.8, 5.6
6.17, dd, 3.2, 5.6
3.39, m
6.56, t, 1.8
6.56, t, 1.8
3.67, m
H5
H6
H7
H8
H8a
H9a
H10a
H11a
H11b
H12a
H12b
CH3
3.14-3.08, m
4.71, dd, 2.8, 5.6
5.20, dd, 2.8, 5.6
3.14-3.08, m
2.76, m
3.21-3.38, m
4.48, dd, 2.8, 5.7
5.42, dd, 2.5,5.7
3.20, m
3.21-3.38, m
2.94, d, 1.6 (J 9a,11b
3.21-3.38, m
2.10, m
1.47, dq, 9.8, 1.6
1.18, 1.27, 2m
1.18, 1.27, 2m
2.34, s
3.10, m
3.4-3.2, m
5.72, dd, 3.0, 6.0
5.99, dd, 3.0, 6.0
3.44, m
2.85, m
3.54, d, 3.8 (J 9a,1
2.85, m
1.82, dt, 9.1, 1.5
1.4-1.2, m
1.4-1.2, m
1.4-1.2, m
2.42, s
4.59, dd, 3.0, 5.6
5.54, dd, 2.7, 5.6
3.4-3.2, m
3.4-3.2, m
3.63, d, 3.6 (J 9a,1
2.76, m
)
)
)
2.48, d, 1.5 (J 9a,11b
3.4-3.2, m
)
2.46, dt, 8.9, 1.7
1.43, dt, 8.9, 1.5
1.06, dt, 8.7, 1.5
1.19, dt, 8.7, 1.9
2.35, s
2.00, m
1.64, dq, 10.0, 1.5
1.18, 2dt, 8.9, 1.6
1.26, 2dt, 8.9, 1.6
2.37, s
AA′BB′tolyl system
7.40, 7.20
7.31, 7.17
7.69, 7.32
7.41, 7.24
3.6 and 3.8 Hz, respectively) not present in 9 and 11, is
also consistent with the proposed structures where the
dihedral angle between H9a and H1 is ca. 30° in the
former cases and ca. 90° in the latter.
Other important spectroscopic characteristics of both
kind of adducts are the chemical shift differences ob-
served in the exo adducts 9 and 11 for the olefinic H6
and H7 protons (∆δ ) 0.94 and 0.95 ppm, respectively),
which are larger than those showed for the endo deriva-
tives 8 and 10 (∆δ ) 0.49 and 0.27 ppm, respectively).
This fact must be a consequence of the anisotropic effect
of the aromatic ring of the p-tolyl group shielding mainly
H6 in the exo adducts (interactions between the sulfinylic
oxygen and H11a in 8 and 10 arrange the aromatic ring
almost equidistant from H6 and H7, see Figure 1). The
most significant parameter to assign the absolute con-
figuration of 9 and 11 is the chemical shift difference of
the H9a protons, which appears ca. 0.5 ppm more deshield-
ed in compound 9 as a consequence of the strong
deshielding effect of the sulfinylic oxygen.19 This effect
is also apparent from the δ values observed for H11a in
compounds 8 (2.46 ppm) and 10 (1.82 ppm).
F igu r e 1.
From the results collected in Table 1 several facts
stand out. In thermal conditions diastereoisomer 6 was
more reactive than 7. The latter compound did not react
at -20 °C and required longer reaction times than 6 to
achieve total conversion at room temperature (compare
entries 1 with 11 and 2 with 12 in Table 1).
The addition of BF3‚OEt2 to the reaction medium
produced unexpected changes in the behavior of both
dienophiles 6 and 7. Surprisingly, the reactivity of com-
pound 6 decreased with respect to the thermal process,
but the endo selectivity increased giving rise exclusively
to compound 8 (compare entries 2 and 3). No reaction
was observed from 7 and cyclopentadiene in the same
conditions (entry 13) or even at higher temperatures.
The most efficient catalyst for the cycloaddition was
shown to be ZnBr2 which produced the highest increase
of the reaction rate for both 6 and 7. In these conditions,
the relative reactivity of both dienophiles was inverted
making the reaction of 7 slightly faster than that of 6 at
-20 °C (entries 5 and 14). With respect to the endo/ exo
selectivity, the addition of ZnBr2 increased the ratio of
the exo adducts 9 and 11 which became the major
Moreover, the absolute configuration of compound 8
was shown to be [1S,4R,4aR,5R,8S,8aR,9aS,10aS,(S)S]
by X-ray diffraction (see supporting information).18
Once the absolute configuration of 8 was known, a
detailed comparative analysis of the 1H-NMR parameters
of compounds 8-11 enabled the unambiguous structural
assignments of 9, 10, and 11 (See Figure 1 and Table 2).
As can be seen, a similar spectroscopic behavior is
observed for 8 and 10, as a consequence of the similar
endo-anti-endo structure of both bisadducts. The spec-
troscopic data of 9 and 11 are also very similar.
A
distinguishing feature is the relative shielding of the H9a
proton in 9 (δ 2.94) and 11 (δ 2.48) compared to that of
8 (δ 3.63) and 10 (δ 3.54). This shielding is a character-
istic of the endo protons of the norbornenyl systems and
is a valuable tool to assign (in our case to confirm) the
exo-anti-endo configuration of 9 and 11. Moreover, the
long range coupling constant observed between H9a and
H
11b (J ) 1.6 and 1.5 Hz, respectively) in 9 and 11 is only
possible if the exo moiety is present. The coupling
constant between H9a and H1 observed in 8 and 10 (J )
(18) The authors have deposited atomic coordinates for 8 with the
Cambridge Crystallographic Data Centre. The coordinates can be
obtained, on request, from the Director, Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge, CB2 1EZ, U.K.
(19) (a) Foster, A. B.; Inch, T. D.; Qadir, M. H.; Weber, J . M. J . Chem.
Soc., Chem. Commun. 1968, 1086. (b) Cook, M. J . Kemia-Kemi 1976,
3, 16.

Diastereoselectivity of Diels-Alder Reactions
J . Org. Chem., Vol. 61, No. 9, 1996 2983
products at -20 °C (entries 5 and 14). When the
temperature decreased to -40 °C, the endo/ exo ratio
resulting from 6 was similar to that observed in the
absence of the Lewis acid (compare entries 6 and 1), but
the catalytic effect persisted. We could suggest a dif-
ficulty in the formation of the chelated species between
the dienophile and ZnBr2 at low temperatures9c to ac-
count for this result.
Finally, the effect of Eu(fod)3 on both reactivity and
selectivity of compound 6 was scarce (compare entries 2
and 7) even with increasing amounts of the catalyst
(entries 8-10). On the contrary, compound 7 reacted
more quickly than in thermal conditions yielding a higher
proportion of the exo adduct (compare entry 12 with 15
and 16).
The formation of exo adducts in the Diels-Alder
reactions of sulfinylene-diones 6 and 7 (Scheme 2 and
Table 1) must be a consequence of the presence of the
sulfoxide group in the ene-dione moiety which partially
compensates the endo-directing power of the carbonyl
groups of these dienophiles. A similar situation was
observed in cycloadditions with 2-sulfinylmaleates,11
whereas only endo adducts were formed in the reactions
of sulfinylquinones with cyclopentadiene.9,10 Thus, the
lack of the quinonic planar structure in 6 and 7 must be
responsible of the lower endo orientating character of
their carbonyl groups. On the other hand, the observed
π-facial selectivity in reactions of cyclopentadiene with
dienophiles 6 and 7 under different conditions must be
a consequence of their norbornene-dione rigid structure,
with the convex face only accessible to dienes.7,20 This
fact allowed us to clarify the role of the different Lewis
acids used in these cycloadditions.
The relative reactivity, as well as the selectivity
observed for these dienophiles, must be related with the
spatial arrangement of the substituents around the sulfur
atom. According to the well documented steric approach
control21 which governs the Diels-Alder reactions of
sulfinyl dienophiles, the attack of the diene must take
place from the face bearing the lone electron pair at
sulfur. Therefore, considering all the conformers around
the C-S bond, rotamers 6A and 7B, both displaying the
lone electron pair toward the convex face (Figure 2), must
be the only one able to evolve into the corresponding
adducts under thermal conditions. As can be seen, 6A
has the sulfinylic oxygen in s-cis arrangement with
respect to the dienophilic double bond, whereas this
disposition is adopted by the p-tolyl group in 7B. The
interactions of the s-cis substituent with the diene in both
endo and exo approaches, more severe in the case of 7B,
would explain the higher reactivity shown by compound
6 (Table 1). This result confirms the higher reactivity of
the conformations with the sulfinylic oxygen in s-cis
arrangement already proposed to explain other results
on sulfinyl dienophiles.10a On the other hand, the larger
endo/ exo selectivity exhibited by compound 7 could also
be explained by assuming that the increased size of the
substituent in s-cis arrangement (the p-tolyl group in 7B
is larger than oxygen in 6A) favors the endo approach of
cyclopentadiene with respect to the exo one. Nevertheless
F igu r e 2.
the reactivity-selectivity principle can also be invoked
to explain the higher selectivity of the less reactive
dienophile 7B.
A detailed analysis of the reactive species existing in
the presence of BF3‚OEt2 could account for the dimin-
ished reactivity observed in these conditions for cycload-
ditions on both sulfinylene-diones 6 and 7. Thus, the
acidic BF3‚OEt2 must be associated with the oxygens,
determining the complete shift of the conformational
equilibrium around the C-S bond toward the rotamers
6′A and 7′A (Figure 2) with the sulfinylic oxygen in s-cis
arrangement to minimize steric and electronic interac-
tions between oxygens. This association, which increases
the effective size of the sulfinylic oxygen and therefore
the interactions with the approaching diene in the
transition states, should be responsible of the unexpected
decrease of the reactivity of compound 6. This increased
size could also be related with the complete endo selectiv-
ity observed in this reaction, but the increase of the endo
orientating character of the carbonyl groups as a conse-
quence of the Lewis acid association cannot be ignored.
As we can see in Figure 2, conformation 7′A has the bulky
p-tolyl group oriented toward the upper convex face,
precluding the diene approach and justifying the lack of
reactivity of this dienophile. This result reinforces the
steric approach control model suggested to explain the
diastereoselectivity of sulfinyl dienophiles21 and rules out
(20) (a) Martin, J . G.; Hill, R. K. Chem. Rev. 1961, 61, 537. (b) Hill,
R. K.; Newton, M. G.; Pantaleo, N. S.; Collins, K. M. J . Org. Chem.
1980, 45, 1593.
(21) (a) Koizumi, T.; Hakamada, I.; Yoshii, E. Tetrahedron Lett.
1984, 25, 87. (b) Koizumi, T.; Arai, Y.; Takayama, T. Tetrahedron Lett.
1987, 28, 3689. (c) Arai, Y.; Matsui, M.; Koizumi, T.; Shiro, M. J . Org.
Chem. 1991, 56, 1983.

2984 J . Org. Chem., Vol. 61, No. 9, 1996
Carren˜o et al.
Eluting solvents are indicated in the text. The apparatus for
inert atmosphere experiments were dried by flaming it in a
stream of dry argon. Cyclopentadiene was freshly distilled.
CH2Cl2 was dried over P2O5. ZnBr2 was flamed-dried in the
reaction flask, under a stream of dry argon, before use. For
routine workup, hydrolysis was carried out with water, extrac-
tions with CH2Cl2, and solvent drying with Na2SO4.
other models based on electronic interactions, which
suggested that the approach of the diene became favored
from the face supporting the p-tolyl group.22
The behavior of both dienophiles in the presence of
ZnBr2 suggested the formation of the chelated species 6′′B
and 7′′B (Figure 2).23 The higher reactivity of the latter
could be a consequence of the disposition of the lone
electron pair at sulfur toward the only accessible upper
face of the dienophile. On the other hand, this double
association with the Zn atom must distort the planarity
of the ene-dione system, decreasing the endo orienting
character of the carbonyl groups, which results in an
increase of the exo adduct proportion. This increase is
similar for both dienophiles.
Finally, the different influence of Eu(fod)3 on the
selectivity of 6 (8:9 ratio similar to that obtained in the
absence of catalyst) and 7 (50:50 mixture of 10 and 11
almost identical to that obtained in the presence of ZnBr2)
suggested that in the first case a mixture of the species
6′′′A and 6′′′B could be the reactive substrates for the
cyclopentadiene attack. Starting from 7 only the species
7′′′B could evolve into the bisadduct (in 7′′′A the arrange-
ment of the p-tolyl group would preclude the attack of
the diene), and thus the observed selectivity is similar
to that observed in the reaction in the presence of ZnBr2.
Gen er al P r ocedu r e for Diels-Alder Reaction s in Th er -
m a l Con d ition s. To a solution of 69a,c or 79a,c (100 mg, 0.3
mmol) in 5 mL of dry CH2Cl2 at the temperature indicated in
each case (see Table 1 for conditions) was added cyclopenta-
diene (200 mg, 3 mmol) under argon. After completion of the
reaction (see Table 1 for reaction times), the solvent was
evaporated at reduced pressure and the residue was chro-
matographed on silica gel (eluent CH2Cl2:acetone ) 40:1).
Gen er a l P r oced u r e for Diels-Ald er Rea ction s in th e
P r esen ce of Lew is Acid s. A solution of 69a,c or 79a,c (100 mg,
0.3 mmol) in 5 mL of dry CH2Cl2 was added to the appropiate
Lewis acid (see Table 1 for conditions) under argon, and the
mixture was stirred for 1 h at rt. After the solution was cooled
at the desired temperature (see Table 1 for conditions) cyclo-
pentadiene (40 mg, 0.6 mmol) was added. After completion
of the reaction (see Table 1 for reaction times) and workup,
the residue was chromatographed on silica gel (eluent CH2-
Cl2:acetone ) 40:1).
en d o-a n ti-en d o-[1S,4R,4a R,5R,8S,8a R,9a S,10a S,(S)S]-
1,4,4a ,5,8,8a ,9a ,10a -Oct a h yd r o-1,4:5,8-d im et h a n o-4a -(p -
tolylsu lfin yl)a n th r a cen e-9,10-d ion e (8). Compound 8 was
obtained from 6 under the experimental conditions and in the
ratios showed in Table 1 as a white solid: mp 145-146 °C
dec (hexane); [R]20 ) -17 (c 1, CHCl3); IR (KBr) 1670, 1250,
Con clu sion s
D
1195, 1080, 1045, 810; 13C-NMR δ 21.3, 44.7, 45.6, 47.5, 48.2,
49.1, 49.5, 51.7, 55.8, 57.5, 80.5, 128.0 (2C), 129.3 (2C), 134.6,
136.2, 136.7, 138.2, 139.0, 142.6, 209.3, 209.5. Anal. Calcd
for C23H22SO3: C, 73.02; H, 5.82. Found: C, 73.05; H, 6.20.
exo-a n ti-en do-[1R,4S,4aR,5R,8S,8aR,9aS,10aS,(S)S]-1,4,-
4a ,5,8,8a ,9a ,10a -Octa h yd r o-1,4:5,8-d im eth a n o-4a -(p-tolyl-
su lfin yl)a n th r a cen e-9,10-d ion e (9). Compound 9 was ob-
tained from 6 under the experimental conditions and in the
ratios showed in Table 1 as a white solid: mp 96-7 °C dec;
Our study showed that the presence of the sulfinyl
group on the ene-dione moiety of 1 can be used to modify
the reactivity and to alter the expected endo-selectivity
of their Diels-Alder reactions making it possible to
obtain, under very mild conditions, the endo-anti-endo-
bisadducts 8 and 10 as well as the exo-anti-endo-bisad-
ducts 9 and 11. These results reinforce the model based
on the steric approach control proposed to explain the
diastereoselective cycloadditions of sulfinyl dienophiles
and clarify the role of the different Lewis acids used in
these reactions. Moreover, the presence of the sulfoxide
in compounds 8-11 makes them enantiomerically pure
synthetic equivalents of p-benzoquinone-cyclopentadiene
bisadducts.
To our knowledge, the results presented here constitute
the first examples where the exo addition of cyclopenta-
diene becomes favored in these kind of dienophiles. In
addition, the desulfurization of sulfinyl bisadduct 9
allowed us to achieve the first synthesis of the unknown
endo-anti-exo cyclopentadiene-quinone bisadduct 5.
[R]20 ) -15 (c 1.5, CHCl3); IR (KBr) 1690, 1245, 1180, 1085,
D
1050; 13C-NMR δ 21.2, 45.0, 46.0, 46.1, 47.6, 48.4, 51.3, 51.5,
54.4, 57.2, 80.4, 128.0 (2C), 129.0 (2C), 132.7, 133.6, 137.0,
139.0, 139.1, 142.2, 208.5, 209.5. Anal. Calcd for C23H22SO3:
C, 73.02; H, 5.82. Found: C, 72.80; H, 6.03.
en d o-a n ti-en d o-[1R,4S,4a S,5S,8R,8a S,9a R,10a R,(S)S]-
1,4,4a ,5,8,8a ,9a ,10a -Oct a h yd r o-1,4:5,8-d im et h a n o-4a -(p -
t olylsu lfin yl)a n t h r a cen e-9,10-d ion e (10). Compound 10
was obtained from 7 under the experimental conditions and
in the ratios showed in Table 1 as an oil: [R]20 ) +51 (c 0.8,
D
CHCl3); IR (NaCl) 1685, 1235, 1210, 1040, 810; 13C-NMR δ
21.3, 46.8, 46.9, 47.7, 48.2, 50.4, 51.9, 53.3, 53.8, 54.8, 78.0,
126.5 (2C), 129.5 (2C), 135.8, 136.1, 136.5, 137.1, 140.3, 141.8,
209.0, 209.8. Anal. Calcd for C23H22SO3: C, 73.02; H, 5.82.
Found: C, 73.11; H, 6.11.
exo-a n ti-en do-[1S,4R,4aS,5S,8R,8aS,9aR,10aR,(S)S]-1,4,-
4a ,5,8,8a ,9a ,10a -Octa h yd r o-1,4:5,8-d im eth a n o-4a -(p-tolyl-
su lfin yl)a n th r a cen e-9,10-d ion e (11). Compound 11 was
obtained from 7 under the experimental conditions and in the
ratios showed in Table 1 as an oil: [R]20D ) -25 (c 0.5, CHCl3);
IR (NaCl) 1685, 1230, 1185, 1095, 1030; 13C-NMR δ 21.2, 44.7,
45.6, 46.6, 47.5, 51.4, 51.5, 53.7, 53.8, 55.9, 78.5, 126.2 (2C),
129.4 (2C), 134.5, 135.7, 136.2, 137.3, 139.5, 141.6, 205.4,
208.7. Anal. Calcd for C23H22SO3: C, 73.02; H, 5.82. Found:
C, 73.16; H, 5.69.
1r,4r,5r,8r,8a â,10a â-H e xa h yd r o-1,4:5,8-d im e t h a n o-
9,10-a n th r a qu in on e (12). Compound 12 was obtained as a
bright yellow solid from 40 mg (0.1 mmol) of 8 (75% yield) or
10 (78% yield) by refluxing in 5 mL of EtOAc for 24 h,
evaporation of the solvent, and flash chromatography (eluent
EtOAc:hexane ) 1:20): mp 153-4 °C (lit.6b,17 155 °C); 1H-NMR
δ 1.46 (2H, m), 2.18 (2H, m), 3.26 (2H, d, J ) 2.0 Hz), 3.46
(2H, m), 3.98 (2H, m), 5.79 (2H, t, J ) 2.0 Hz), 6.78 (2H, t, J
) 2.0 Hz).
Exp er im en ta l Section
Melting points were obtained in open capillary tubes and
are uncorrected. IR spectra are given in cm-1 1H- and 13C-
.
NMR spectra were recorded at 200.1 and 50.3 MHz in CDCl3.
Diastereomeric adducts ratios were established by integration
of well-separated signals of both diastereomers in the crude
reaction mixtures and are listed in Table 1. 1H-NMR data of
compounds 8-11 are collected in Table 2. All reactions were
monitored by TLC which was performed on precoated sheets
of silica gel 60, and flash column chromatography was carried
out with silica gel 60 (230-400 mesh) of Macherey-Nagel.
(22) (a) Kahn, S. D.; Hehre, W. J . Tetrahedron Lett. 1986, 27, 6041.
(b) Kahn, S. D.; Pau, C. F.; Overman, L. E.; Hehre, W. J . J . Am. Chem.
Soc. 1986, 108, 7381. (c) Kahn, S. D.; Hehre, W. J . J . Am. Chem. Soc.
1986, 108, 7399.
(23) The formation of these species must not be favored at -40 °C
which would explain the results obtained at this temperature (entry
6 in Table 1). This effect has been observed in other ZnBr2-catalyzed
cycloadditions of sulfinylquinones.9c,10a
1r,4r,5â,8â,8a r,10a r-H e xa h yd r o-1,4:5,8-d im e t h a n o-
9,10-a n t h r a qu in on e (13). Compound 13 was obtained as

Diastereoselectivity of Diels-Alder Reactions
J . Org. Chem., Vol. 61, No. 9, 1996 2985
above from 9 (82% yield) or 11 (80% yield) as a bright yellow
2.1 Hz), 3.40 (2H, m), 3.35 (2H, m), 3.23 (2H, br s), 2.12 (2H,
d, J ) 1.7 Hz), 1.54 (1H, dt, J ) 8.6 and 1.8 Hz), 1.39 (1H, dt,
J ) 8.6 and 1.5 Hz), 1.31 (1H, dquint, J ) 9.3 and 1.7 Hz),
1.21 (1H, dt, J ) 9.3 and 1.6 Hz); 13C-NMR δ 211.7 (2C), 137.2
(2C), 135.8 (2C), 53.6 (2C), 52.4 (2C), 50.4, 48.7 (2C), 47.6, 46.4
(2C). Anal. Calcd for C16H16O2: C, 80.00; H, 6.67. Found:
C, 79.91; H, 6.52.
1
solid: mp 150-2 °C (lit.6b,17 153-5 °C); H-NMR δ 1.48 (2H,
m), 2.10 (2H, m), 3.15 (2H, d, J ) 2.0 Hz), 3.48 (2H, m), 3.92
(2H, m), 6.00 (2H, t, J ) 2.0 Hz), 6.76 (2H, t, J ) 2.0 Hz).
en d o-a n ti-en d o-1,4,4a ,5,8,8a ,9a ,10a -Octa h yd r o-1,4:5,8-
d im eth a n oa n th r a cen e-9,10-d ion e (2). t-BuOH (200 µL, 2
mmol) was added to a solution of compound 8 (76 mg, 0.2
mmol) in dry THF (5 mL) at rt under argon. After being
stirred for 10 min, a 0.1 M solution of SmI2 in THF (10 mL, 1
mmol) was added, and the mixture was stirred for 15 min.
The reaction mixture was worked up with cold water and 5%
HCl and extracted with CH2Cl2. The organic layer was washed
with brine, dried over Na2SO4, and concentrated. The residue
was chromatographed on silica gel (eluent CH2Cl2:EtOAc )
98:2) to obtain 2 as a white solid (85% yield): mp 155-6 °C
Ack n ow led gm en t. We thank Direccio´n General de
Investigacio´n Cient´ıfica y Te´cnica (Grants PB92-0161
and PB92-0162) and Comunidad Auto´noma de Madrid
(Grant AE 244/95) for financial support.
Su p p or tin g In for m a tion Ava ila ble: An ORTEP drawing
and X-ray experimental data of 8 (2 pages). This material is
contained in libraries on microfiches, inmediately follows this
article in the microfilm version of the journal, and can be
ordered from ACS; see any current masthead page for ordering
information.
1
(methanol) (lit.7b 155-6 °C); H-NMR δ 6.17 (4H, t, J ) 2.0
Hz), 3.34 (4H, br s), 2.86 (4H, br s), 1.44 (2H, dt, J ) 8.6 and
1.8 Hz), 1.27 (2H, br d, J ) 8.6 Hz).
exo-a n ti-en d o-1,4,4a ,5,8,8a ,9a ,10a -Oct a h yd r o-1,4:5,8-
d im eth a n oa n th r a cen e-9,10-d ion e (5). Compound 5 was
obtained as above from 9 as a white solid (89% yield): mp
1
160-1 °C (methanol); H-NMR δ 6.20 and 6.19 (4H, 2t, J )
J O9521209