Influence of the sulfinyl group on the chemoselectivity and π-facial selectivity of diels-alder reactions of (S)-2-(p Tolylsulfinyl)-1,4-benzoquinone

Article abstract of DOI:10.1021/jo951438y

Diels-Alder reactions of (S)-2-(p-tolylsulfmyl)-1,4-benzoquinone (1a) with cyclic (cyclopentadiene and cyelohexadiene) and acyclic dienes (1-[(trimethylsilyl)oxy]-1,3-butadiene and trans-piperylene) under different thermal and Lewis acid conditions are reported. Chemoselectivity (reactions on C₂-C₃ versus C₅-C₆ double bonds) is mainly related to the cyclic (on C₅-C₆) or acyclic (on C₂-C₃) structure of the diene. The high π-facial selectivity observed could be controlled by choosing adequate experimental conditions.

Full text of DOI:10.1021/jo951438y

J . Org. Chem. 1996, 61, 503-509
503
In flu en ce of th e Su lfin yl Gr ou p on th e Ch em oselectivity a n d
π-F a cia l Selectivity of Diels-Ald er Rea ction s of
(S)-2-(p-Tolylsu lfin yl)-1,4-ben zoqu in on e
M. Carmen Carren˜o,* J ose´ L. Garc´ıa Ruano,* Miguel A. Toledo, and Antonio Urbano
Departamento de Quı´mica Orga´nica (C-I), Universidad Auto´noma, Cantoblanco, 28049 Madrid, Spain
Cynthia Z. Remor and Valter Stefani
Instituto de Quı´mica/ UFRGS, Porto Alegre (RS), Brazil
J ean Fischer
Laboratoire de Cristallochimie, UA 424, Universite´ Louis Pasteur, 67070 Strasbourg, France
Received August 3, 1995X
Diels-Alder reactions of (S)-2-(p-tolylsulfinyl)-1,4-benzoquinone (1a ) with cyclic (cyclopentadiene
and cyclohexadiene) and acyclic dienes (1-[(trimethylsilyl)oxy]-1,3-butadiene and trans-piperylene)
under different thermal and Lewis acid conditions are reported. Chemoselectivity (reactions on
C2-C3 versus C5-C6 double bonds) is mainly related to the cyclic (on C5-C6) or acyclic (on C2-C3)
structure of the diene. The high π-facial selectivity observed could be controlled by choosing
adequate experimental conditions.
In tr od u ction
In a previous paper,1 we reported the preliminary
results obtained in the study of the Diels-Alder cycload-
ditions of (S)-2-(p-tolylsulfinyl)-1,4-benzoquinone (1a )
(Figure 1), mainly focused on reactions with cyclopenta-
diene. Unexpectedly, the cycloadditions took place on the
unsubstituted C5-C6 double bond in a high π-facial
diastereoselective manner (up to 82% of de). Diels-Alder
reactions of (S)-3-chloro- (1b) and (S)-3-ethyl-2-(p-tolyl-
sulfinyl)-1,4-benzoquinone (1c) (Figure 1) with cyclopen-
tadiene and 2,3-dimethylbutadiene in the presence of
ZnBr2 took place on the C5-C6 bond with diastereoiso-
meric excesses ranging from 40 to 72%.2 With the goal
of using sulfinylquinones as chiral starting materials in
the synthesis of optically enriched polycyclic systems, we
later studied the behavior of several sulfinylnaphtho-
quinones 2a -c (Figure 1) in asymmetric Diels-Alder
F igu r e 1.
cycloadditions.3 This study revealed that the sulfinyl
group was able to control both regiochemistry and π-facial
diastereoselectivity of cycloadditions on the dienophilic
double bond. This result was not unexpected, taking into
account the close disposition of the sulfinyl group and
the reactive double bond in these substrates. Recent
studies concerning Diels-Alder reactions of naphthaz-
arin thio derivatives4 evidenced a strong influence of the
sulfur substituent on the ring selectivity of cycloadditions
with several dienes. Moreover, in the case of sulfinyl-
naphthazarin 3 (Figure 1), cycloaddition with cyclopen-
tadiene in the presence of BF3‚OEt2 on the unsubstituted
dienophilic double bond of tautomer 3B proceeded with
a significant (70:30) π-facial diastereoselectivity despite
the remoteness of the chiral sulfur with respect to the
reactive double bond.
All these facts, as well as our interest in synthetic
aplications of sulfinylquinones,5 suggested the conven-
ience of undertaking a complete study of the behavior of
benzoquinone 1a as dienophile in order to know the
influence of the sulfinyl group on the reactivity and
diastereoselectivity of the two dienophilic double bonds
present in the quinonic structure. In this paper, we
report the results obtained in the Diels-Alder reactions
of 1a with cyclic and acyclic dienes carried out in different
solvents and temperatures and in the presence of several
Lewis acids.
Resu lts a n d Discu ssion
Enantiomerically pure (S)-2-(p-tolylsulfinyl)-1,4-ben-
zoquinone (1a ) was synthesized as previously described.6
The reaction of 1a with cyclopentadiene under thermal
conditions afforded a mixture of only two adducts 4a and
4b (n ) 1 in Scheme 1), out of the eight possible
diastereoisomers. Both adducts resulted from the endo
approach of the diene on the two diastereotopic faces of
X Abstract published in Advance ACS Abstracts, December 15, 1995.
(1) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Urbano, A. Tetrahedron Lett.
1989, 30, 4003.
(2) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Toledo, M. A.; Urbano, A.
Tetrahedron Lett. 1994, 35, 9759.
(3) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Urbano, A. J . Org. Chem.
1992, 57, 6870.
(4) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Urbano, A. Tetrahedron Lett.
1994, 35, 3789.
(5) For a review on synthetic aplications of sulfoxides see: Carren˜o,
M. C. Chem. Rev. 1995, 95, 1717.
(6) (a) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Mata, J . M.; Urbano, A.
Tetrahedron 1991, 47, 605. (b) Carren˜o, M. C.; Garc´ıa Ruano, J . L.;
Urbano, A. Synthesis 1992, 651.
0022-3263/96/1961-0503$12.00/0 © 1996 American Chemical Society

504 J . Org. Chem., Vol. 61, No. 2, 1996
Carren˜o et al.
Sch em e 1
Sch em e 2
F igu r e 2.
in 4b and at 5.85 and 4.82 ppm in 4a . The high shielding
observed for H7 (∆δ ) 1.31 ppm) in 4a is probably
produced by the aromatic ring of the p-tolyl group and is
only possible if the stereochemistry of adduct 4a is that
shown in Scheme 1 and Figure 2. Similar shielding
effects of remote aromatic rings have been already
described for one of the two adducts obtained in the
reaction of (R-hydroxybenzyl)-1,4-benzoquinone with cy-
clopentadiene.11
On the basis of the stereochemistry assigned to 4a and
4b, we tried to rationalize the stereochemical course of
the cycloadditions. Nevertheless, some problems related
to the stereochemical models (see later) suggested the
convenience of confirming this configurational assign-
ment. This was achieved by X-ray diffraction of 4b,12
whose solid state disposition (see the supporting informa-
tion) revealed the same relative stereochemistry to that
suggested by the 1H-NMR parameters as well as the s-cis
disposition of the sulfinylic oxygen and the C2-C3 double
bond as shown in Figure 2. Thus, the absolute configu-
ration [4aR,5R,8S,8aR,(S)S] could be unequivocally as-
signed to the adduct endo-4b and the [4aS,5S,8R,8aS,
(S)S] one to the diastereoisomer endo-4a .
The results obtained in the Diels-Alder reactions of
1a with cyclopentadiene under different thermal condi-
tions are collected in Table 2. In all cases, clean mixtures
of 4a and 4b were formed. As can be deduced from these
data, the stereoselectivity increased (always in favor of
4a ) and the reactivity decreased (longer reaction times)
when the temperature became lower. The polarity of the
solvents also had a significant effect on both reactivity
and diastereoselectivity of the reaction. We observed a
gradual decrease of the reaction times with the increasing
polarity of solvents.13 At -20 °C the highest reactivity
was observed in H2O/EtOH mixtures (entries 15 and 16),
while at rt the lowest reaction times corresponded to the
use of H2O (entry 17). The diastereoselectivity also
increased (again in favor of 4a ) with the polarity of the
solvent. Thus, the best diastereoisomeric excess (72%)
was obtained in EtOH at -20 °C (entry 14). Under these
conditions, the addition of H2O, even in little amount
(entries 15 and 16) increased the reactivity but decreased
the unsubstituted C5-C6 double bond of 1a and could be
readily separated diastereoisomerically pure after flash
chromatography.
The endo configuration of 4a and 4b was confirmed as
depicted in Scheme 2. The reaction of 2-(p-tolylthio)-1,4-
benzoquinone (5)7 with cyclopentadiene yielded adduct
6,8 whose controlled oxidation with m-CPBA afforded a
60:40 diastereoisomeric mixture of the corresponding
racemic sulfoxides (()-4a and (()-4b, their 1H-NMR
spectra being identical to those obtained for optically pure
compounds 4a and 4b. Therefore, both sulfoxides must
exhibit the same endo or exo configuration because they
derive from the same thioether. The endo configuration
of these compounds could be unequivocally established
by irradiation of 4b to yield 7 showing a cage structure.
This evolution is only possible for endo-adducts.9
The relative configuration of 4a and 4b was initially
1
established on the basis of their H-NMR parameters (see
Figure 2 and Table 1), taking into account the favored
s-cis conformation between the S-O and C2-C3 bonds10
and the known anisotropic effect of the p-tolyl group3,11
on the protons under its influence. So, the main differ-
ence between adducts 4a and 4b is the chemical shifts
of H6 and H7 olefinic protons which appear at 6.13 ppm
(7) Ukai, S.; Hirose, K. Bull. Soc. Chem. Pharm. 1968, 16, 195.
(8) Wilgus, H. S., III; Frauenglass, E.; Chiesa, P. P.; Nawn, G. H.;
Evans, F. J .; Gates, J . W., J r. Can. J . Chem. 1966, 44, 603.
(9) (a) Bruce, J . M. In Rodd′s Chemistry of Carbon Compounds;
Coffey, S., Ed.; Elsevier: Amsterdam, 1974; Vol. IIIB, p 8. (b) Filipescu,
N.; Menter, J . M. J . Chem. Soc. B 1969, 616. (c) Cookson, R. C.;
Crundwell, E.; Hill, R. R.; Hudec, J . J . Chem. Soc. 1964, 3062. (d) Linz,
G. S.; Zektzer, A. S. S.; Martin, G. E. J . Org. Chem. 1988, 53, 2647.
(10) (a) Kahn, S. D.; Hehre, W. J . Tetrahedron Lett. 1986, 27, 6041.
(b) Koizumi, T.; Arai, Y.; Takayama, H. Tetrahedron Lett. 1987, 28,
3689. (c) Solladie´, G.; Carren˜o, M. C. In Organic Sulfur Chemistry.
Synthetic Aspects; Page, P., Ed.; Academic Press: London, 1995; pp
1-47.
(12) The authors have deposited atomic coordinates for 4b 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, UK.
(11) Al-Hamdany, R.; Bruce, J . M.; Heatley, F.; Khalafy, J . J . Chem.
Soc., Perkin Trans. 2 1985, 1395.
(13) Pindur, U.; Lutz, G.; Otto, C. Chem. Rev. 1993, 93, 741.

Diels-Alder Reactions of (S)-2-(p-Tolylsulfinyl)-1,4-benzoquinone
Ta ble 1. 1H-NMR Da ta for Com p ou n d s 4a ,b, 8, 10, a n d 11a ,b
δ (ppm), multiplicity, J (in Hz)
10
J . Org. Chem., Vol. 61, No. 2, 1996 505
proton
4a
4b
8
11a
11b
7.30, s
H2 and/or H3
7.17, s
7.23, s
6.10, 6.04, AB system, 6.60, s 7.24, s
10.3
H5
H8
H6
H7
3.48, m
3.26, m
3.54, m
3.54, m
3.96, m
3.65, m
6.16, m
6.16, m
3.55, m 3.08, m
3.55, m 2.71, m
6.10, m 6.02, ddd, 1.4, 6.5, 7.6 6.25, m
6.10, m 5.21, ddd, 1.4, 6.6, 8.1 6.25, m
3.24, m
3.24, m
5.85, dd, 2.9, 5.6 6.13, t, 2.0
4.82, m
3.26, m
6.13, t, 2.0
3.23, 3.12, 2dd, 3.9, 8.5 3.20, d, 3.8
H4a and/or H8a
3.25, m 3.01, m
2.98, 2.85, 2dd,
2.4, 9.3
H9a
H9b
1.39, m
1.39, m
1.40, dt, 8.9, 2.0
1.57, dt, 8.9, 2.0
2.07, m
1.67, m
1.50, m
1.60, m
H9 and H10
CH3
1.64, 1.24, 2m
2.41
1.66, 1.36, 2m
2.38
2.41, s
2.38, s
2.37, s
AA′BB′tolylsystem 7.55, 7.29
7.62, 7.28
7.42, 7.25
7.55, 7.29
7.61, 7.27
Ta ble 2. Th er m a l Diels-Ald er Rea ction s of Su lfin ylben zoqu in on e 1a w ith Cyclic Dien es
entry
dienea
solvent
T (°C)
time (h)
yield (%)
4a :4b
11a :11b
de
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclohexadiene
cyclohexadiene
cyclohexadiene
cyclohexadiene
cyclohexadiene
benzene
80
rt
5
67
rt
0.5
2
2
0.5
5
24
1
16
12
10
10
10
1
76
81
85
80
82
86
90
95
92
91
92
92
91
95
90
92
91
91
94
96
92
94
50:50
57:43
60:40
60:40
67:33
69:31
69:31
71:29
74:26
75:25
75:25
75:25
80:20
86:14
81:19
78:22
70:30
0
14
20
20
34
38
38
42
48
50
50
50
60
72
62
56
40
56
66
78
68
60
benzene
benzene
THF
THF
THF
CH2Cl2
CH2Cl2
DMSO
-20
rt
-20
-20
-20
-20
-20
0
-20
-20
-20
rt
DMF
acetone
CH3CN
EtOH
EtOH
6
1
1
EtOH/H2O(19:1)
EtOH/H2O (9:1)
H2O
CH2Cl2
CH2Cl2
EtOH
0.5
24
480
360
336
2
rt
78:22
83:17
89:11
84:16
80:20
-20
-20
-20
rt
EtOH/H2O (9:1)
H2O
a
One equiv of cyclopentadiene and 5 equiv of cyclohexadiene.
Ta ble 3. Lew is Acid Rea ction s of Su lfin ylben zoqu in on e 1a in CH2Cl2 w ith Cyclic Dien es
entry
dienea
Lewis acid (equiv)
T (°C)
time (h)
4a :4b
8
9
11a :11b
yield (%)
de
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclopentadiene
cyclohexadiene
cyclohexadiene
cyclohexadiene
cyclohexadiene
cyclohexadiene
cyclohexadiene
cyclohexadiene
-20
rt
-20
rt
-20
40
rt
16
0.1
0.5
0.1
0.5
0.05
0.05
0.05
1
3
480
2
24
0.2
1
71:29
13:87
10:90
75:25
89:11
95
80
90
75
80
80
83
85
89
83
94
95
81
85
92
91
95
42
74
80
50
78
BF3‚OEt2 (5)
BF3‚OEt2 (5)
Eu(fod)3 (2)
Eu(fod)3 (2)
ZnBr2 (2)
ZnBr2 (2)
ZnBr2 (2)
ZnBr2 (2)
ZnBr2 (2)
60
60
40
36
3
40
20:20
30:30
26:38
41:56
0
-20
-78
-20
-20
-20
40
rt
0
-20
83:17
9 :91
66
82
80
16
14
12
8
BF3‚OEt2 (5)
Eu(fod)3 (2)
ZnBr2 (2)
ZnBr2 (2)
ZnBr2 (2)
90:10
42:58
43:57
44:56
46:54
6
24
ZnBr2 (2)
a
One equiv of cyclopentadiene and 5 equiv of cyclohexadiene.
the diastereoselectivity of the cycloaddition. These facts
demonstrated once again that Diels-Alder reactions are
not insensitive to solvent effects.14 Although the origin
of the phenomenon is not well understood, the strong
influence of the solvent on both rate and stereoselectivity
of cycloadditions is generally observed.15
ditions has also been evaluated. The results are sum-
marized in Scheme 1 and Table 3. As expected, Lewis
acid reactions were always faster than their thermal
analogues. In the presence of Eu(fod)3, cycloaddition took
place only on C5-C6 and the π-facial selectivity increased
with respect to that observed in the absence of Lewis acid,
the diastereoisomeric excess becoming up to 78% at -20
°C (compare entries 1 and 5 in Table 3). Compound 4a
The influence of several Lewis acids on these cycload-
(14) Blokzijl, W.; Engberts, N. J . Am. Chem. Soc. 1992, 114, 5440
and references cited therein.
(15) Breslow, R. Acc. Chem. Res. 1991, 24, 159.

506 J . Org. Chem., Vol. 61, No. 2, 1996
Carren˜o et al.
Sch em e 3
was the major adduct under these conditions. The use
of BF3‚OEt2 did not modify the chemoselectivity but
determined the total inversion of the π-facial selectivity
in favor of 4b (de 80%, entry 3).
When ZnBr2 was present in the reaction medium, the
results were highly temperature dependent. At 40 °C
(Table 3, entry 6), a mixture of a new adduct 8 and
different double adducts 9 was formed (Scheme 1).
Compound 8, obtained as the major product, was isolated
by flash chromatography and was characterized as the
adduct resulting in the endo approach of cyclopentadiene
on the substituted C2-C3 double bond. This result
revealed a dramatic change in the chemoselectivity of the
cycloaddition in the presence of ZnBr2. Moreover, this
approach yielded only one diastereoisomer. Compounds
9 were a mixture of the possible double adducts resulting
in a second Diels-Alder reaction of cyclopentadiene on
4a and 4b.16 At rt (entry 7), a 20:20:60 mixture of 4a ,
4b, and 8 was obtained when the reaction was quenched
inmediately with H2O (longer reaction times determined
the evolution of 4a and 4b into bis-adducts 9). The
increasing amount of ZnBr2 did not modify these results.
At lower temperatures (entries 8-10), the ratio of ad-
ducts 4a and 4b increased whereas that of 8 decreased,
being almost none at -78 °C (entry 10). When com-
pounds 4a and 4b were formed in the presence of ZnBr2,
low diastereoisomeric excesses were observed (entries
7-10).
A comparative study of the 1H-NMR parameters of
compound 8 and the endo-adduct 10 obtained in the
reaction between cyclopentadiene and 1,4-benzoquinone
(δ values are collected in Table 1) allowed the configu-
rational assignment of 8 depicted in Figure 2. The first
remarkable observation was the strong shielding shown
by protons H2 and H3 in 8 with respect to that of 10 (∆δ
) 0.50-0.56). This effect is probably due to the rigid
disposition of the sulfinyl group where the aromatic
p-tolyl ring must be oriented parallel to the C2-C3 double
bond of the tetrahydronaphthoquinone moiety, resulting
in the shielding of H2 and H3 protons in 8. This
disposition must be the most stable due to π-stacking3,17
interactions between the aromatic ring and the double
bond. In such a conformation, the sulfinylic oxygen is
located close to H5 and H9a protons if adduct 8 has the
endo configuration. The deshielding observed for both
protons in 8 if compared with 10 (∆δ ) 0.41 for H5 and
∆δ ) 0.57 for H9a) confirmed the proposed geometry, the
well-known anisotropic effect associated to the sulfinylic
oxygen18 being responsible for this variation.
can be seen, mixtures of adducts 11a and 11b (n ) 2 in
Scheme 1), both resulting in the endo attack of the diene
on the unsubstituted quinonic C5-C6 double bond, were
formed under thermal and Lewis acid conditions. The
similarity of the H-NMR parameters (see Figure 2 and
Table 1) of adducts 4 and 11 allowed us to establish the
configurational assignment of 11a and 11b.
1
The main differences between the behavior of both
cyclic dienes were those derived from the known lower
reactivity of cyclohexadiene which required larger reac-
tion times. As a consequence, the observed π-facial
selectivities were slightly higher than those of cyclopen-
tadiene under similar conditions. On the other hand, the
double adducts and that resulting from reaction of
cyclohexadiene on the sulfinyl-substituted C2-C3 double
bond were not detected, even in the presence of ZnBr2
under reflux of CH2Cl2. As in the case of reactions with
cyclopentadiene, a low π-facial diastereoselectivity re-
sulted when the reaction of cyclohexadiene ocurred on
C5-C6 in the presence of ZnBr2, in contrast to those
obtained under thermal or other Lewis acid conditions
(see Tables 2 and 3).
Finally, we studied the reactions of sulfinylquinone 1a
with acyclic dienes such as 1-[(trimethylsilyl)oxy]-1,3-
butadiene and trans-piperylene. The results are shown
in Scheme 3. With this kind of acyclic dienes, compound
1a underwent cycloaddition on the sulfinyl-substituted
C2-C3 double bond exclusively. The initially formed
adducts 12a ,b could not be detected even when reactions
were conducted at low temperatures due to the pyrolytic
elimination of the sulfinyl group which took place spon-
taneously giving rise to quinonic compounds 13a ,b. In
the case of the reaction with 1-[(trimethylsilyl)oxy]-1,3-
butadiene, compound 13a was stable enough to be
detected by 1H-NMR only at -20 °C but inmediately
underwent aromatisation into 1,4-naphthoquinone (14a )
when the temperature increased.
Adduct 8 was not able to react as dienophile in a second
cycloaddition with cyclopentadiene even in refluxing CH2-
Cl2 and in the presence of ZnBr2. This unreactivity must
be a consequence of the blocking of both dienophilic faces
of the C2-C3 double bond of 8 by the p-tolyl group (the
upper face) and by the rigid structure of the norbornenyl
moiety (the bottom face), as evidenced by inspection of
the system shown in Figure 2.
The results obtained in the reactions of 1a with
cyclohexadiene are summarized in Tables 2 and 3. As
(16) The composition of these mixtures, as well as the stereochemical
assignment of the bis-adducts and the study of the cycloadditions of
monoadducts 4a and 4b with cyclopentadiene in different conditions,
are currently being studied.
(17) J ones, G. D.; Chapman, B. J . Synthesis 1995, 475.
(18) (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.
In the case of reactions with trans-piperylene under
thermal conditions, dihydronaphthoquinone 13b could be

Diels-Alder Reactions of (S)-2-(p-Tolylsulfinyl)-1,4-benzoquinone
J . Org. Chem., Vol. 61, No. 2, 1996 507
Sch em e 4
isolated optically pure (ee > 97%) as was determined in
the presence of the chiral shift reagent Pr(hfc)3. The
same enantiomer of 13b was formed by using BF3‚OEt2,
ZnBr2, and Eu(fod)3 as Lewis acids. The reaction times
decreased in their presence, but the influence on the
π-facial diastereoselectivity was scarce as can be deduced
from the value and sign of the specific rotation of the
isolated samples shown in Scheme 3. On the other hand,
cycloadditions between sulfinylnaphthoquinones 2a -c
(see Figure 1) and cyclopentadiene had given the opposite
π-facial diastereoselection under thermal conditions and
in the presence of ZnBr2.3 In order to ascertain whether
these results were due to the different nature (cyclic or
acyclic) of the dienes or if the formation of the same
enantiomer with trans-piperylene in both conditions was
a consequence of the simultaneous inversion of the
π-facial selectivity and the regiochemistry of the process
taking place on the sulfinyl-substituted double bond in
the presence of ZnBr2, we carried out the reaction of (S)-
5-methoxy-2-(p-tolylsulfinyl)-1,4-naphthoquinone (2b) with
trans-piperylene under thermal and ZnBr2-catalyzed
conditions (Scheme 4).
As we can see, the results obtained from sulfinylnaph-
thoquinone 2b were identical to those resulting from
sulfinylbenzoquinone 1a . A sole regioisomer 16 resulting
from the pyrolysis of the initially formed ortho-adduct
15 was obtained in the reaction of 2b with trans-
piperylene under thermal conditions and in the presence
of ZnBr2. The enantiomeric purity of 16 could be
determined to be as high as 97% in the presence of the
chiral shift reagent Pr(hfc)3. From the specific rotations
shown in Scheme 4, we could state that the absolute
configuration of 16 formed in both conditions was the
same. As a consequence, the behavior of trans-piperylene
is different from that observed with cyclopentadiene
which had given the opposite π-face selectivity under both
conditions in the reaction with 2b.3
The different chemoselectivity observed in the cycload-
ditions of 1a with cyclic and acyclic dienes is surprising
if we consider the activation of the C2-C3 double bond
exerted by the sulfinyl group. A similar situation was
found in the Diels-Alder reactions of sulfinylnaphthaz-
arin 3 (Figure 1).4 This absence of cycloaddition on the
sulfinylic-substituted double bond with cyclic dienes could
F igu r e 3. Favored approaches of cyclic and acylic dienes in
Diels-Alder reactions of (S)-2-(p-tolylsulfinyl)-1,4-benzoquino-
ne.
be explained by assuming that the activating effect of
the SOTol group on C2-C3 is overridden by steric
interactions between the (CH2)n bridge of cyclic dienes
and the sulfinyl group, which develop in the transition
state giving rise to endo-adducts when sulfinylquinone
1a reacts from the expectedly more reactive s-cis confor-
mation (1A in Figure 3). This interaction must be more
severe when n ) 2 and does not exist with acyclic dienes
(1′A in Figure 3).
The only exception to this behavior corresponded to the
reactions of cyclopentadiene in the presence of ZnBr2
which mainly afforded adduct 8 upon reaction of the C2-
C3 bond (Scheme 1 and Table 3). Assuming the formation
of the chelated species 1B from 1a and ZnBr2 shown in
Figure 3, an increased reactivity of the substituted C2-
C3 double bond should be expected. Moreover, the
possible steric interactions between the methylene bridge
of cyclopentadiene and the sulfur function in the bottom
face approach of the diene must be lower in this confor-
mation due to the planarity of the chelate and the
disposition of the sulfur atom now included in a half-
chair. The effect of the temperature on the chemoselec-
tivity of these reactions (the ratio of 8 decreased with
the temperature) is not easy to rationalize, but we could
suggest that the formation of the chelate between 1a and
ZnBr2 is more difficult at low temperatures.
The origin of the high π-facial diastereoselectivity
observed in these cycloadditions is intriguing. The model
based on steric approach control already proposed to
rationalize the π-face diastereoselectivity of cycloaddi-
tions on differently substituted vinyl sulfoxides3,10b,c could
explain our results when cycloaddition of dienes took
place on the sulfinylic substituted double bond C2-C3.
Thus, assuming the formation of the chelated species 1B

508 J . Org. Chem., Vol. 61, No. 2, 1996
Carren˜o et al.
in the presence of ZnBr2 (Figure 3), cyclopentadiene
approach must be favored from the less hindered bottom
face where the lone pair at sulfur is located to yield
exclusively diastereoisomer 8. The same π-facial dias-
tereoselectivity observed in cycloadditions of trans-pip-
erylene with both sulfinylquinones 1a and 2b in thermal
and Lewis acid conditions suggested the existence of a
similar reactive conformation of the sulfinyl quinonic
system in all the cases. A detailed examination of the
possible situations allowed us to propose that, in thermal
conditions, 1′A (Figure 3) could be the reactive conforma-
tion responsible for the favored approach of acyclic dienes
from the less hindered top face of 1a to afford, after
pyrolytic elimination of the sulfoxide, dihydroquinones
13b and 16 with the (S) absolute configuration at the
new stereogenic center. This model agrees with those
proposed in the literature to explain the cycloadditions
of activated vinyl sulfoxides in thermal conditions10 but
implies a contradiction with the accepted model when
ZnBr2, able to form chelated species, is present. In our
case, if we analyze the interactions resulting in the less
hindered approach of trans-piperylene to a chelated
conformation such as 1′B (Figure 3) the close disposition
between the quinonic and sulfinylic oxygens and the
methyl group of the diene could determine a high energy
content of the resulting transition state. In such situa-
tion, a shift toward conformation 1′A with the zinc atom
attached to the sulfinylic oxygen in the s-cis disposition
could occur. The approach of the diene from the less
hindered top face of 1′A avoids the above-mentioned
destabilizing interactions, giving rise again to the same
enantiomer of 13b. Moreover, the results obtained by
us3 in the reaction of (S)-2-(p-tolylsulfinyl)-1,4-naphtho-
quinone (2a ) with 1-methoxy-1,3-cyclohexadiene support
this explanation. Under thermal conditions, the reaction
afforded, after pyrolysis of the initially formed adduct 17,
compound 18, whose optical rotation had the same sign
as that resulting in the reaction in the presence of ZnBr2
(Scheme 4).19 Since under similar conditions cyclohexa-
diene had given adducts of opposite π-facial selectivity,3
the behavior observed in the case of 1-methoxy-1,3-
cyclohexadiene (as well as trans-piperylene) should be a
consequence of the destabilization of the transition state
1′B due to the presence of the substituent at C-1 of the
diene.
tion. Considering the electronic repulsion between the
lone electron pair at sulfur and the π-cloud of the
quinonic system, a desymmetrization of the latter by
increasing the electron density of the face opposite to that
containing the lone electron pair could exist. In such
situation, the favored approach of the electron rich cyclic
diene from the electron poor face containing the lone pair
(Figure 3, 1C in the presence of BF3‚OEt2 to afford
adducts 4b and 11b as majors, and 1D in the presence
of Eu(fod)3 to give mainly adducts 4a and 11a ) could be
responsible for the high π-facial diastereoselectivity
observed. This desymmetrization is probably also as-
sociated to the frontier orbitals which control these
concerted reactions as well as other processes.21
Con clu sion s
We have shown the efficiency of the sulfinyl group to
control the π-facial diastereoselectivity of Diels-Alder
reactions on sulfinylquinones by choosing the adequate
experimental conditions. A high asymmetric induction
is noticed even in remote control when the sulfoxide is
not directly joined to the reactive double bond. To our
knowledge these are the first sulfinyl dienophiles where
the chiral auxiliary is acting from a remote point. The
chemoselectivity of reactions with ambident dienophile
1a is mainly dependent on the cyclic or acyclic nature of
dienes.
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 in CDCl3 at 200.1 and 50.3 MHz,
respectively. 1H-NMR data of compounds 4a , 4b, 8, 11a , and
11b are collected in Table 1. Diastereoisomeric adducts ratios
were established by integration of well-separated signals of
the diastereoisomers in the crude reaction mixtures and are
listed in Tables 2 and 3. All reactions were monitored by thin
layer chromatography that was performed on precoated sheets
of silica gel 60, and flash column chromatography was done
with silica gel 60 (230-400 mesh) of Macherey-Nagel. Eluting
solvents are indicated in the text. Apparatuses for inert
atmosphere experiments were dried by flaming in a stream of
dry argon. Cyclopentadiene was used freshly distilled. Dry
THF was distilled from sodium/benzophenone ketyl. CH2Cl2
was dried over P2O5. ZnBr2 was flamed in the reaction flask,
in a stream of dry argon before using. For routine workup,
hydrolysis was carried out with water, extractions with CH2-
Cl2, and solvent dryness with Na2SO4.
Gen er al P r ocedu r e for Diels-Alder Reaction s. Meth od
A. To a solution of (S)-2-(p-tolylsulfinyl)-1,4-benzoquinone
(1a )6 (100 mg, 0.4 mmol) in 5 mL of the dry solvent was added
the corresponding diene under argon (see Table 2 for reaction
conditions). After the consumption of all the quinone and
evaporation of the solvent, the resulting material was purified
by flash chromatography (CH2Cl2/acetone 40/1). Yields and
diastereoisomeric ratios of adducts are detailed in Table 2.
Gen er a l P r oced u r e for Lew is Acid Diels-Ald er Rea c-
tion s. Meth od B. A solution of 1a 6 (100 mg, 0.4 mmol) in 3
mL of dry CH2Cl2 was added to the appropiate Lewis acid in
2 mL of CH2Cl2 under argon (see Table 3 for reaction
When cycloadditions with cyclic dienes took place on
the unsubstituted C5-C6 double bond of 1a , a similar
steric approach control had been invoked by us to explain
the results obtained.1 Nevertheless, the high π-facial
diastereoselectivity observed in these reactions is difficult
to understand only on steric grounds considering the
distance existent between the sulfinyl group and the
reactive dienophilic double bond. Moreover, the diaste-
reoselectivity (70:30) which resulted in the reaction of the
3B tautomer of sulfinylnaphthazarin 3 (Figure 1) and
cyclopentadiene4 in the presence of BF3‚OEt2 is not
possible to explain invoking steric factors.20 Thus, taking
into account the delocalized nature of the π-orbitals in
the quinonic system which are involved in the [4 +
2]-cycloadditions, we propose a desymmetrization of the
π-cloud due to the presence of the stereogenic sulfur as
the responsible for the observed π-facial diastereoselec-
(20) The major adduct resulting in the reaction of the 3B tautomer
of sulfinylnaphthazarin 3 (see Figure 1) with cyclopentadiene in the
presence of BF3‚OEt2 had the same configuration in its stereogenic
centers that adduct 4b, as was demonstrated by X-ray diffraction:
unpublished results.
(19) In this reaction, carried out in the presence of ZnBr2, a mixture
of compound 16 and that resulting from the 1,4-addition of the diene
to the activated double bond was formed. After flash chromatography,
16 could be isolated and characterized (see ref 3 for physical and
spectral data of 16).
(21) (a) Liotta, C. L. Tetrahedron Lett. 1975, 16, 519. (b) Klein, J .
Tetrahedron Lett. 1973, 14, 4307. (c) Frenking, G.; Kohler, K. F.; Reetz,
M. T. Angew. Chem., Int. Ed. Engl. 1991, 30, 1146. (d) Fujita, M.;
Ishida, M.; Manako, K.; Sato, K.; Ogura, K. Tetrahedron Lett. 1993,
34, 645.

Diels-Alder Reactions of (S)-2-(p-Tolylsulfinyl)-1,4-benzoquinone
J . Org. Chem., Vol. 61, No. 2, 1996 509
conditions). The reaction was stirred for 1 h at rt, and then
the diene was added at the desired temperature. After the
time required and workup, the resulting material was purified
by flash chromatography (CH2Cl2/acetone 40/1). Yields and
diastereoisomeric ratios of adducts are detailed in Table 3.
en d o-[4a R,5S,8R,8a S,(S)S]-5,8-Meth a n o-2-(p-tolylsu lfi-
n yl)-4a ,5,8,8a -tetr a h yd r o-1,4-n a p h th oqu in on e (4a ). Com-
pound 4a was obtained as a yellow oil from 1a and cyclopen-
tadiene following methods A or B: [R]20D ) +276 (c 1, CHCl3);
13C-NMR δ 196.5, 196.0, 161.0, 142.6, 138.1, 136.4, 135.2,
134.0, 129.8, 125.9, 50.0, 49.7, 49.5, 49.4, 49.2, 21.4; IR (NaCl)
pound 11a was obtained from 1a and cyclohexadiene following
methods A or B as a yellow solid: mp 145-6 °C (methanol);
[R]20 ) +319 (c 1, CHCl3); 13C-NMR δ 197.0, 196.4, 161.3,
D
142.6, 138.0, 136.5, 133.4, 132.4, 129.9, 126.1, 50.5, 50.3, 36.3,
36.2, 24.7, 24.6, 21.5; IR (KBr) 1670, 1250, 1160, 1080, 1050.
Anal. Calcd for C19H18SO3: C, 69.94; H, 5.52; S, 9.82.
Found: C, 70.11; H, 5.37; S, 9.70.
en do-[4aS,5R,8S,8aR,(S)S]-5,8-Eth an o-2-(p-tolylsu lfin yl)-
4a ,5,8,8a -t et r a h yd r o-1,4-n a p h t h oq u in on e (11b ). Com-
pound 11b was obtained from 1a and cyclohexadiene following
methods A or B as a yellow solid: mp 161-2 °C (hexane); [R]20
D
) +367 (c 1, CHCl3); 13C-NMR δ 197.1, 195.8, 161.3, 142.7,
138.3, 137.0, 133.8, 133.3, 130.1, 125.8, 50.9, 50.1, 35.2, 34.9,
24.7, 24.3, 21.5; IR (KBr) 1660, 1250, 1170, 1080, 1050. Anal.
Calcd for C19H18SO3: C, 69.94; H, 5.52; S, 9.82. Found: C,
69.92; H, 5.68; S, 9.71.
1660, 1590, 1310, 1265, 1160, 1070, 810. Anal. Calcd for C18
-
H16SO3: C, 69.23; H, 5.13; S, 10.26. Found: C, 69.50; H, 5.47;
S, 9.89.
en d o-[4a S,5R,8S,8a R,(S)S]-5,8-Meth a n o-2-(p-tolylsu lfi-
n yl)-4a ,5,8,8a -tetr a h yd r o-1,4-n a p h th oqu in on e (4b). Com-
pound 4b was obtained from 1a and cyclopentadiene following
methods A or B as a yellow solid: mp 162-163 °C (hexane);
5-[(Tr im eth ylsilyl)oxy]-5,8-d ih yd r o-1,4-n a p h th oqu in -
on e (13a ). To a solution of 1a 6 (100 mg, 0.4 mmol) in 4 mL of
dry CH2Cl2 cooled at -20 °C was added 1-[(trimethylsilyl)-
oxy]-1,3-butadiene (90 µL, 0.5 mmol) under argon. After 8 h,
the solvent was evaporated at -20 °C at reduced pressure and
the resulting material was analyzed directly by 1H-NMR to
avoid the easy aromatization of 13a to 1,4-naphthoquinone
(14a ) at temperatures above -20 °C: 1H-NMR δ 6.73 (2H, s),
6.02 (1H, dt, J ) 10.1 and 3.1 Hz), 5.91 (1H, ddt, J ) 3.8, 10.1,
and 1.9 Hz), 5.23 (1H, q, J ) 3.8 Hz), 3.07 (2H, m), 0.39 (9H,
s).
(5S)-5,8-Dih yd r o-5-m eth yl-1,4-n a p h th oqu in on e (13b).
To a solution of 1a 6 (125 mg, 0.5 mmol) in 5 mL of dry CH2Cl2
was added trans-piperylene (200 µL, 2 mmol). After 48 h at
-20 °C, the solvent was evaporated and the resulting material
was purified by flash chromatography (CH2Cl2) to afford
[R]20 ) +472 (c 1, CHCl3); 13C-NMR δ 196.6, 195.7, 160.7,
D
142.5, 138.4, 137.0, 135.6, 135.2, 130.0, 125.7, 50.2, 49.4, 48.8,
48.6, 48.5, 21.3; IR (KBr) 1670, 1600, 1310, 1250, 1180, 1080,
1060, 810. Anal. Calcd for C18H16SO3: C, 69.23; H, 5.13; S,
10.26. Found: C, 69.25; H, 5.48; S, 10.02.
en d o-5,8-Meth a n o-2-(p-tolylth io)-4a ,5,8,8a -tetr a h yd r o-
1,4-n a p h th oqu in on e (6). A solution of 2-(p-tolylthio)-1,4-
benzoquinone (5)7 (100 mg, 0.34 mmol) and cyclopentadiene
(100 µL, 1.5 mmol) in 5 mL of CH2Cl2 was stirred at rt for 2 h.
The solvent was evaporated in vacuo and the residue purified
by crystallization in hexane to afford compound 6 (90% yield)
as a yellow solid: mp 150-152 °C (lit.8 144-154 °C); 1H-NMR
δ 7.30 and 7.23 (4H, AA'BB' system), 6.13 and 6.06 (2H, 2dd,
J ) 2.9 and 5.4 Hz), 5.81 (1H, s), 3.59 and 3.49 (2H, 2m), 3.34
and 3.16 (2H, 2dd, J ) 4.1 and 8.5 Hz), 2.39 (3H, s), 1.55 and
1.44 (2H, 2dt, J ) 8.8 and 1.8 Hz); 13C-NMR δ 195.9, 195.7,
160.4, 140.8, 135.7, 135.4, 134.7, 132.4, 131.0, 124.1, 49.2, 48.9,
48.7, 48.6, 48.5, 21.3.
compound 13b as a yellow solid (71% yield): mp 85-86 °C
1
(hexane); [R]20 ) +102 (c 0.5, CHCl3); H-NMR δ 6.72 (2H,
D
s), 5.79 (2H, m), 3.41 (1H, m), 3.25-2.85 (2H, m), 1.18 (3H, d,
J ) 7.0 Hz); 13C-NMR δ 187.2, 186.7, 144.1, 139.4, 136.7, 136.0,
129.9, 121.2, 28.8, 24.0, 21.8; IR (KBr) 1695, 1640, 1350, 1295.
Anal. Calcd for C11H10O2: C, 75.86; H, 5.75. Found: C, 75.74;
H, 5.89.
en d o-[4a R*,5S*,8R*,8a S*,(S)S*]-5,8-Met h a n o-2-(p -t olyl-
su lfin yl)-4a ,5,8,8a -t et r a h yd r o-1,4-n a p h t h oq u in on e (4a )
a n d en d o-[4a S*,5R*,8S*,8a R*,(S)S*]-5,8-m eth a n o-2-(p-tolyl-
su lfin yl)-4a ,5,8,8a -tetr a h yd r o-1,4-n a p h th oqu in on e (4b).
To a solution of 6 (15 mg, 0.05 mmol) in 1 mL of CH2Cl2 was
added m-CPBA (10 mg, 0.05 mmol) in 1 mL of CH2Cl2. After
1 h at rt, the mixture was treated with a saturated solution of
NaHCO3. Workup afforded a 60:40 diastereoisomeric mixture
of (()-4a and (()-4b. The 1H-NMR spectroscopic data of these
racemic adducts were identical with the optically actives 4a
and 4b.
(5S )-5,8-Dih yd r o-1-m e t h oxy-5-m e t h yl-9,10-a n t h r a -
qu in on e (16). To a solution of (S)-5-methoxy-2-(p-tolylsulfi-
nyl)-1,4-naphthoquinone (2b)6 (33 mg, 0.1 mmol) in 2 mL of
dry CH2Cl2 was added trans-piperylene (30 µL, 0.3 mmol, 3
equiv). After 16 h at rt, the solvent was evaporated and the
resulting material was purified by flash chromatography (CH2-
Cl2) to afford compound 16 as a yellow solid (78% yield): mp
138-40 °C (hexane); [R]20 ) +93 (c 0.15, CHCl3); 1H-NMR δ
D
(+)-1-(p -Tolylsu lfin yl)p e n t a cyclo[5.4.0.02,6.03,10.05,9]-
u n d eca n e-8,11-d ion e (7). A solution of 4b (100 mg, 0.32
mmol) in 50 mL of dry ethyl acetate was irradiated under
argon with an OSRAM HQL-125 W lamp. After 24 h, the
solvent was evaporated and the residue purified by flash
chromatography (EtOAc) to afford compound 7 as an oil (65%
7.72 (1H, dd, J ) 1.4 and 8.0 Hz), 7.65 (1H, t, J ) 8.0 Hz),
7.27 (1H, dd, J ) 1.4 and 8.0 Hz), 5.82 (2H, m), 4.01 (3H, s),
3.57 (1H, m), 3.43-2.97 (2H, m), 1.23 (3H, d, J ) 7.0 Hz); 13C-
NMR δ 184.1, 183.9, 159.3, 144.1, 143.2, 136.9, 134.8, 134.4,
129.7, 121.4, 119.0, 117.3, 56.3, 29.0, 24.6, 21.7; IR (KBr) 1651,
1585, 1472, 1290, 1057. Anal. Calcd for C16H14O3: C, 75.59;
H, 5.51. Found: C, 75.72; H, 5.48.
yield): [R]20 ) +30 (c 1, CHCl3); 1H-NMR δ 7.65 and 7.34
D
(4H, AA'BB' system), 3.72 (1H, m), 3.08 (1H, m), 2.93 (3H, m),
2.71 (2H, m), 2.42 (3H, s), 2.09 (1H, dt, J ) 11.5 and 1.5 Hz),
1.97 (1H, dt, J ) 11.5 and 1.3 Hz); 13C-NMR δ 209.3, 205.4,
142.4, 136.0, 129.9, 125.4, 68.3, 56.0, 54.9, 44.3, 44.0, 43.9, 40.8,
37.5, 21.5; IR (NaCl) 1590, 1540, 1440, 1230, 1190. Anal. Calcd
for C18H16SO3: C, 69.23; H, 5.13; S, 10.26. Found: C, 69.40;
H, 4.99; S, 9.91.
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 Ministerio de Educacio´n y Cien-
cia: Programa de Cooperacio´n con Iberoame´rica for
financial support.
en do-[4aS,5S,8R,8aR,(S)S]-5,8-Meth an o-4a-(p-tolylsu lfi-
n yl)-4a ,5,8,8a -tetr a h yd r o-1,4-n a p h th oqu in on e (8). Com-
pound 8 was obtained from 1a and cyclopentadiene following
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
spectra of compounds 8 and 13a and an ORTEP drawing and
X-ray experimental data for 4b (2 pages). This material is
contained in libraries on microfiche, inmediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
method B as a yellow oil which decomposes on standing: [R]20
D
) -148 (c 0.6, CHCl3); 13C-NMR δ 196.2, 190.9, 142.8, 141.4,
138.7, 137.7, 137.0, 135.5, 130.0, 124.7, 75.5, 50.4, 48.4 (2 C),
44.4, 21.2; IR (NaCl): 2990, 2390, 1660, 1590, 1280, 1180,
1080, 910.
en do-[4aR,5S,8R,8aS,(S)S]-5,8-Eth an o-2-(p-tolylsu lfin yl)-
4a ,5,8,8a -t et r a h yd r o-1,4-n a p h t h oq u in on e (11a ). Com-
J O951438Y