Regio- and stereoselectivity in Diels-Alder reactions of 1,2-disubstituted dienes with enantiopure (SS)-(p-tolylsulfinyl)-1,4-benzoquinones

Article abstract of DOI:10.1016/S0957-4166(00)00365-7

Reactions of 1,2-disubstituted dienes 1-3 with enantiopure sulfinylquinones 4-6 occur with similar π-facial diastereoselectivities but reversed regiochemistry under thermal conditions and in the presence of ZnBr₂. After spontaneous elimination

Full text of DOI:10.1016/S0957-4166(00)00365-7

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 4279–4296
Regio- and stereoselectivity in Diels–Alder reactions of
1,2-disubstituted dienes with enantiopure
(SS)-(p-tolylsulfinyl)-1,4-benzoquinones
M. Carmen Carren˜o,* Jose´ L. Garc´ıa Ruano,* Cynthia Z. Remor† and Antonio Urbano
Departamento de Qu´ımica Orga´nica (C-I), Universidad Auto´noma, Cantoblanco, 28049 Madrid, Spain
Received 26 July 2000; accepted 13 September 2000
Abstract
Reactions of 1,2-disubstituted dienes 1–3 with enantiopure sulfinylquinones 4–6 occur with similar
p-facial diastereoselectivities but reversed regiochemistry under thermal conditions and in the presence of
ZnBr2. After spontaneous elimination of the sulfoxide, optically active polycyclic dihydroquinones are
formed with ees ranging from 36 to >97%. The regiochemistry of the process is controlled by the alkyl
substituent at C-1 in thermal reactions, whereas in the presence of ZnBr2 the oxygenated function at C-2
becomes the main controller. © 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
The successful application of Diels–Alder reactions in synthesis stems from the possibility of
controlling both the regio- and stereochemistry of the cycloaddition.1 All these selective features
have been exploited in the asymmetric version of the process.2 The regiochemical course can be
predicted taking into account the substitution on the dienophile and the diene partners. In the
latter, the relative position of the substituent allows the major formation of ortho adducts, when
it is situated at C-1, and para adducts, when this is at C-2, to be predicted. Such regioselectivity
can be improved in the presence of Lewis acids.3 When the diene bears two or more substituents,
the regiochemistry of the process is generally controlled by the C-1 substituent, but, when a
Lewis acid is added to the reaction medium, the regioselectivity can be inverted being strongly
dependent on the reaction conditions as well as the Lewis acid.4
* Corresponding authors. E-mail: carmen.carrenno@uam.es; joseluis.garcia.ruano@uam.es
†
On leave from Instituto de Qu´ımica da Universidade Federal do R´ıo Grande do Sul, Porto Alegre, Brazil.
0957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00365-7

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In the course of our work related to the asymmetric Diels–Alder reactions of (SS)-(p-tolyl-
sulfinyl)quinones,5 we have observed remarkable p-facial diastereoselectivities with a wide range
of cyclic,6 semicyclic7 and acyclic6a,b,8 dienes. We have also pointed out a different p-facial
diastereoselection in reactions of cyclic or acyclic dienes in the presence of Lewis acids or under
thermal conditions. The regiochemical outcome of these cycloadditions had been studied only
with 1-substituted cyclic and acyclic dienes,6a,b,9 but the behavior of more substituted dienes
remained unknown. In particular, 1,2-disubstituted derivatives are of great interest since they
open an easy access to highly substituted polycyclic compounds.10–12 Among them, the well
known 6-methoxy-1-vinyl-3,4-dihydronaphthalene (Dane’s diene) 1,13 with activating sub-
stituents at C-1 and C-2, is one of the most frequently used in the construction of steroidal
systems.11
In a preliminary communication14 we have shown that the regiochemical course of Diels–
Alder reactions of Dane’s diene 1 with sulfinylquinones could be controlled by changing the
reaction conditions (thermal or Lewis acid catalyst). We now report these results in full as well
as the study of the regiochemistry of asymmetric Diels–Alder reactions between 1,2-disubstituted
acyclic and cyclic dienes 2 and 3 and differently substituted enantiopure (p-tolylsulfinyl)-1,4-ben-
zoquinones (+)-4, (+)-5 and (+)-6. With such chiral dienophiles the regiochemical problem is
superimposed on the stereochemical one. We disclose here that the regioselectivity is influenced
by a remote substituent at C-5 of the 2-(p-tolylsulfinyl)-1,4-benzoquinone and show that the
regiochemical inversion achieved in the presence of Lewis acids allows easy access to enan-
tiomerically enriched regioisomeric polycyclic dihydroquinones.
2. Results
2.1. Synthesis of dienes
Dane’s diene 1 was prepared according to a previously reported procedure.15 The synthesis
of 3-(tert-butyldimethylsilyloxy)-1,3-pentadiene 2 was planned through the transformation
of commercially available ethyl vinyl ketone into the corresponding silylenol ether. After
several trials using conventional procedures,16 compound 2 could be obtained, as outlined in
Scheme 1, following the methodology described by Evans for a similar derivative,17 based on
the treatment of the ketone precursor with solid KHMDS and further trapping of the formed
enolate with tert-butyldimethylsilyl triflate. In the case of 1-methyl-2-(tert-butyldimethylsilyl-
oxy)-1,3-cyclohexadiene 3 the synthesis was easily achieved from reaction of the known
6-methyl-2-cyclohexen-1-one18 with lithium diisopropyl amine (LDA) and TBDMSOTf
(Scheme 1).
Scheme 1. (a) TBDMSOTf, KHMDS, THF, −78°C to rt, 1 h, 37%. (b) LDA, TBDMSOTf, THF, −20°C to rt, 2 h,
74%

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4281
2.2. Diels–Alder reactions
With the desired dienes in hand, we began the study of their Diels–Alder reactions with
enantiopure sulfinylquinones 4, 5 and 6 under thermal conditions and in the presence of ZnBr2.
In all cases the initial cycloaddition was followed by the pyrolytic elimination of the sulfoxide,
which occurs even at −78°C, to recover the quinone structure in the final polycyclic product. The
enantiomeric excesses of all optically active compounds obtained in these cycloadditions were
1
measured by H NMR using chiral lanthanide shift reagents, which required the preparation of
each racemic derivative from the corresponding racemic sulfinylquinone.
Initially, we carried out the cycloadditions between Dane’s diene 1 and enantiopure (SS)-2-(p-
tolylsulfinyl)-1,4-benzoquinone (+)-4.19 The results obtained are depicted in Scheme 2 and Table
1. Working with 1 mol of 1 in CH2Cl2 at −78°C (entry 1), we observed the formation of optically
active 8-methoxy-4b,5,6,12-tetrahydro-1,4-chrysenequinone (+)-7, resulting from the attack of
the diene on the C2ꢀC3 substituted double bond of 4 and elimination of the sulfoxide in the
initially formed cycloadduct. Nevertheless, derivative (+)-7 was not stable enough and evolved
during the isolation process into a mixture of (+)-7 and 8-methoxy-5,6-dihydro-1,4-chry-
senequinone 8, which could be separated after flash chromatography in 24 and 23% yield,
Scheme 2.
Table 1
Diels–Alder reactions of Dane’s diene 1 and enantiopure sulfinylquinones (+)-4 and (+)-5
Entry
Quinone
Lewis acid (equiv.)
T (°C)
t (h)
Products (% isolated yield)
Products (% ee)
1
2
3
4
5
(+)-4
(+)-4
(+)-5
(+)-5
(+)-5
–
−78
−20
−20
−20
−20
24
0.25
4
2
0.25
(+)-7 (23)
(−)-7 (20)
(+)-9 (43)
(+)-7 (80)
(−)-7 (36)
(+)-9 (80)
ZnBr2 (2)
–
ZnBr2 (2)
BF3·OEt2 (5)
(−)-11 (38)
(−)-11 (\97)
(+)-9+(−)-11a
b
a Obtained as a 25:75 mixture.
b Not determined.

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respectively. When reactions were conducted at higher temperatures or with an excess of the
diene, variable mixtures of (+)-7, 8 and bisadducts resulting from a double cycloaddition process
were obtained. Tetracyclic quinone (+)-7 showed a specific rotation of [h]2D0=+94 (c 0.12,
CHCl3) and 80% enantiomeric purity [Yb(hfc)3]. The absolute configuration at C-4b, the
only stereogenic center of (+)-7, was assigned as (S) taking into account the behavior of
sulfinylquinones as dienophiles in cycloadditions with acyclic dienes under thermal conditions6a
which reacted from the less hindered face of the most reactive s-cis conformation shown in
Scheme 1.
The same reaction in the presence of ZnBr2 (Table 1, entry 2) afforded the corresponding
enantiomer (−)-7. After flash chromatography we isolated a 20% yield of (−)-7 and a 25% yield
of aromatic compound 8. Derivative 7 showed an optical rotation of [h]2D0=−46 (c 0.12, CHCl3)
indicating 36% enantiomeric purity. Comparison with the rotary power of (+)-7 allowed us
to assign the (R) absolute configuration to the major enantiomer of (−)-7. Since no substituent
remained in the quinone moiety, the formation of (−)-7 could be a consequence of a change in
the regiochemistry or in the p-facial diastereoselectivity of the process. According to literature
data related to the use of Dane’s diene,11 the former reason seemed more suitable, but our earlier
observation of a reversed p-facial selectivity of the Diels–Alder reactions with cyclic dienes in the
presence of ZnBr2 could point to the latter.6a,b,9
In order to ascertain the origin of the change in the specific rotation of 7 and determine the
exact regiochemistry of the cycloaddition process, we thought of using enantiopure (SS)-2-
methyl-5-(p-tolylsulfinyl)-1,4-benzoquinone (+)-520 as dienophile (Scheme 2 and Table 1). Under
thermal conditions (entry 3), the Diels–Alder reaction of Dane’s diene 1 and (+)-5 afforded only
one regioisomer, 8-methoxy-2-methyl-4b,5,6,12-tetrahydro-1,4-chrysenequinone (+)-9, resulting
from the spontaneous elimination of the sulfinyl group in the initially formed ortho-cycloadduct.
After flash chromatography, compound (+)-9 and aromatic derivative 8-methoxy-2-methyl-5,6-
dihydro-1,4-chrysenequinone 10 were isolated in 43 and 24% yield, respectively. This result
indicated that the alkyl substituent at C-1 of the diene directed the regiochemistry of the process
under thermal conditions. Quinone (+)-9 showed a specific rotation of [h]2D0=+134 (c 0.13,
CHCl3) with 80% enantiomeric purity [Yb(hfc)3] and the (S) absolute configuration at C-4b.
When the cycloaddition of diene 1 and sulfinylquinone (+)-5 was carried out in the presence
of ZnBr2 (Table 1, entry 4), we obtained 8-methoxy-3-methyl-4b,5,6,12-tetrahydro-1,4-chry-
senequinone (−)-11, resulting from the pyrolytic elimination of the sulfoxide in the exclusively
meta-adduct21 initially formed, whose structure showed the opposite regiochemistry to that of
(+)-9. After flash chromatography, compound (−)-11 and aromatic derivative 8-methoxy-3-
methyl-5,6-dihydro-1,4-chrysenequinone 12 were isolated in 38 and 22% yield, respectively.
Quinone (−)-11 showed a specific rotation of [h]2D0=−185 (c 0.21, CHCl3) with >97% enan-
tiomeric purity [Yb(hfc)3] and the (R) absolute configuration at C-4b.
The regiochemical result achieved in this case indicated that the p-methoxyphenyl substituent
at C-2 of Dane’s diene was directing the regiochemical course of the Diels–Alder reaction in the
presence of the Lewis acid and confirmed that the change observed in the specific rotation for
derivative 7 working under thermal or ZnBr2 catalyzed conditions was due to a change in the
regiochemistry and not in the p-facial diastereoselectivity of the process.
The inversion of regiochemistry in cycloadditions with Dane’s diene under Lewis acid
conditions was confirmed when the reaction of 1 and (+)-5 was performed in the presence of
BF3·OEt2 (Table 1, entry 5). In this case, a 25:75 mixture of regioisomers (+)-9 and (−)-11 was
obtained, (−)-11 being predominant. When this reaction was carried out with minor amounts of

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4283
BF3·OEt2 and/or lower temperatures, the ratio (+)-9:(−)-11 changed in favor of 9, showing a
decreasing association between the Lewis acid and the basic center of diene 1. Different
regiochemical outcome has been already observed for Diels–Alder reactions of substituted
benzoquinones with 1,2-disubstituted dienes in the presence of different Lewis acids and/or
solvents.4h
The structural assignment of derivatives 7 and 8 was based on a detailed analysis of their
spectroscopic parameters (see Section 5). Nevertheless, these spectroscopic data were not enough
for the structural assignment of regioisomeric 9 and 11 as well as for that of aromatic derivatives
10 and 12. Finally, the structural assignment of compound 9 was established from 13C–1H NMR
bidimensional correlations through one bond (HMQC) or multiple bonds (HMBC).22 Moreover,
the X-ray ORTEP of aromatic derivative 10 showed the relative disposition of methyl and
methoxy groups shown in Scheme 1 for this compound as well as for its precursor 9 and
confirmed the ortho regiochemistry of the initial cycloaddition.
Once the cycloadditions with Dane’s diene 1 were studied, we undertook the Diels–Alder
reactions between acyclic diene 2 and enantiopure sulfinylquinones (+)-4, (+)-5 and (+)-620 under
thermal and ZnBr2 catalyzed conditions. The results obtained are depicted in Scheme 3 and
Table 2. In all cases cycloadditions occurred through the sulfinyl substituted C2ꢀC3 double bond
of sulfinylquinones to afford the corresponding 5,8-dihydronaphthoquinones, which partially
aromatized to the corresponding naphthoquinones during the isolation process. When a
regioisomeric mixture of substituted 5,8-dihydronaphthoquinones was formed, the regioisomer
ratios were determined directly from the crude reaction mixtures by integration of well separated
1
signals in the H NMR spectra.
Scheme 3.
The reaction of diene 2 and sulfinylquinone (+)-4 under thermal conditions (Table 2, entry 1)
afforded racemic 6-(tert-butyldimethylsilyloxy)-5-methyl-5,8-dihydro-1,4-naphthoquinone 13.
Nevertheless, when the cycloaddition was performed in the presence of ZnBr2 (entry 2), we
isolated derivative (−)-13 in optically active form, [h]2D0=−49 (c 0.14, CHCl3), with 70%
enantiomeric excess [Pr(hfc)3].

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Table 2
Diels–Alder reactions of acyclic diene 2 and enantiopure sulfinylquinones (+)-4, (+)-5 and (+)-6 at −20°C
Entry
Quinone
Lewis acid
(equiv.)
t
(h)
Products
(ratio)
Products
(% isolated yield)
Products
(ee)
1
2
3
4
5
6
(+)-4
(+)-4
(+)-5
(+)-5
(+)-6
(+)-6
–
48
(9)-13
(−)-13
(+)-14 (50)+(−)-15 (50)
(+)-14 (0)+(−)-15 (100)
(+)-16 (80)+(−)-17 (20)
(+)-16 (0)+(−)-17 (100)
13 (32)
13 (36)
14 (25) 15 (22)
15 (42)
16 (40) 17 (10)
17 (62)
13 (0)
13 (70)
14 (78) 15 (72)
15 (72)
16 (\97) 17 (74)
17 (74)
ZnBr2 (2)
–
ZnBr2 (2)
–
ZnBr2 (2)
0.25
48
0.1
56
1
The regiochemistry of the process could be established after the cycloadditions of 2 with
substituted sulfinylquinones (+)-5 and (+)-6 (Scheme 3 and Table 2). Thus, the reaction
between 2 and (+)-5 under thermal conditions (Table 2, entry 3) afforded a 50:50 mixture of
regioisomeric 6-(tert-butyldimethylsilyloxy)-2,5-dimethyl-5,8-dihydro-1,4-naphthoquinone 14
and 7-(tert-butyldimethylsilyloxy)-2,8-dimethyl-5,8-dihydro-1,4-naphthoquinone 15 in optically
active form, which could be separated by flash chromatography. This result indicated that the
regiodirecting power of both the alkyl substituent at C-1 and the silyloxy group at C-2 was
very similar under these conditions and contrasted with the result obtained in the reaction of
the same quinone (+)-5 with Dane’s diene (Table 1, entry 3) where only one regioisomer was
formed under thermal conditions. Compound (+)-14 showed a specific rotation of [h]2D0=+28
(c 0.84, CHCl3) with 78% enantiomeric excess [Pr(hfc)3], whereas that of (−)-15 was [h]2D0=−29
(c 0.33, CHCl3) and 72% enantiomeric excess [Pr(hfc)3]. In the presence of ZnBr2 (Table 2,
entry 4), the reaction of 2 and (+)-5 afforded compound (−)-15 {[h]2D0=−29 (c 0.37, CHCl3),
72% ee} as the only regioisomer, proceeding from the meta-adduct initially formed. In this
case, the regiochemistry of the process was totally controlled by the oxygenated substituent at
C-2.
The structural assignment of regioisomers 14 and 15 was very difficult due to the very
similar spectroscopic parameters of both compounds (see Section 5). Nevertheless, the correct
structure of derivative 15 was confirmed from HMBC experiments22 which showed the regio-
chemistry indicated in Scheme 3. Taking into account this consideration, we assigned the
2,5,6-trisubstituted-5,8-dihydro-1,4-naphthoquinone structure to major derivatives obtained
under thermal conditions and the 2,7,8-trisubstitution for regioisomers formed in the presence
of ZnBr2.
When cycloaddition of acyclic diene 2 was performed with enantiopure (SS)-2-isopropyl-5-(p-
tolylsulfinyl)-1,4-benzoquinone (+)-620 under thermal conditions (Scheme 3, Table 2, entry 5), an
80:20 mixture of regioisomeric 6-(tert-butyldimethylsilyloxy)-2-isopropyl-5-methyl-5,8-dihydro-
1,4-naphthoquinone (+)-16 and 7-(tert-butyldimethylsilyloxy)-2-isopropyl-8-methyl-5,8-dihydro-
1,4-naphthoquinone (−)-17 was formed. Both dihydronaphthoquinones could be separated by
flash chromatography. Compound (+)-16 showed a specific rotation of [h]2D0=+49 (c 1.2, CHCl3)
with an enantiomeric excess >97% [Pr(hfc)3], whereas that of (−)-17 was [h]2D0=−47 (c 0.8,
CHCl3) with 74% enantiomeric excess [Pr(hfc)3]. The regioselectivity which resulted in this
reaction contrasted with that obtained in the cycloaddition between the same diene 2 and

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4285
sulfinylquinone (+)-5 under similar thermal conditions (50:50 mixture of regioisomers was
formed) and suggested that the presence of a remote methyl versus an isopropyl group at C-5
in quinones 5 and 6 was influencing the regiochemical course of the reaction. In the presence of
ZnBr2 (Table 2, entry 6), the reaction of 2 and (+)-6 gave rise to compound (−)-17 {[h]2D0=−46
(c 0.8, CHCl3), 74% ee} in a regioselective way showing again that, under these conditions, the
oxygenated substituent at C-2 is governing the regiochemistry of the reaction.
Finally, we carried out the Diels–Alder reactions between cyclic diene 3 and substituted
sulfinylquinones (+)-5 and (+)-6 (Scheme 4, Table 3). As can be seen, in all cases reactions took
place chemoselectively on the sulfinyl substituted double bond of quinones. Thermal cycloaddi-
tions did not occurr at −20°C being necessary to heat to room temperature as a consequence of
the lower reactivity of cyclic diene 3 with respect to that of dienes 1 and 2.
Scheme 4.
Table 3
Diels–Alder reactions of cyclic diene 3 and enantiopure sulfinylquinones (+)-5 and (+)-6
Entry Quinone Lewis acid
(equiv.)
T
t
Products
Products
(% isolated yield) (ee)
Products
(°C) (h) (ratio)
1
2
3
4
(+)-5
(+)-5
(+)-6
(+)-6
–
rt
−40
rt
48 (−)-18 (75) 19 (25)
5
18 (37)
18 (\97) 19 (78)a
ZnBr2 (2)
–
ZnBr2 (2)
18 (0) (+)-19 (10) 20b (90) 19 (7) 20 (56)
19 (78)
18 (−)-22 (93) 23 (7)
22 (30)
24 (48)
22 (84) 23 (82)c
−40
6
22 (0) 23 (0) 24b (100)
a Measured from the mixture of 18 and 19.
b Obtained as a 60:40 mixture of diastereoisomers.
c Measured from the mixture of 22 and 23.
So, the cycloaddition between quinone (+)-5 and diene 3 (entry 1) afforded a 75:25 mixture of
regioisomeric 6-(tert-butyldimethylsilyloxy)-5,8-ethane-2,5-dimethyl-5,8-dihydro-1,4-naphtho-
quinone 18 and 7-(tert-butyldimethylsilyloxy)-5,8-ethane-2,8-dimethyl-5,8-dihydro-1,4-naphtho-
quinone 19, from which only derivative (−)-18 could be isolated pure by flash chromatography.

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Compound 18 showed a specific rotation of [h]2D0=−67 (c 0.4, CHCl3) with an enantiomeric
excess >97% [Pr(hfc)3], whereas the enantiomeric excess of 19 was 78% [Pr(hfc)3] from the
mixture of 18 and 19. The higher regioselectivity achieved in this reaction contrasted with that
resulting in the cycloaddition of acyclic diene 2 with the same sulfinylquinone (+)-5 where no
regioselectivity was observed. This different behavior was striking since the substitution at C-1
and C-2 of dienes 2 and 3 was very similar.
When the reaction was conducted in the presence of ZnBr2 (entry 2), we observed the
formation of a 10:90 mixture of derivative 19, proceeding from the Diels–Alder reaction, and
5a-(tert-butyldimethylsilyloxy)-4,9a-dimethyl-1-(p-tolylsulfinyl)-5a,8,9,9a-tetrahydrodibenzo-
furan-2-ol 20, isolated and characterized as a 60:40 mixture of diastereoisomers. The formation
of these type of derivatives had been already pointed out by several authors in similar reactions
of enol ethers with activated quinones23 and could be explained from the nucleophilic attack of
the electron rich C-1 position of cyclic diene 3 to the more electron deficient C-3 position of
sulfinylquinone 5 to afford an intermediate such as 21 which, after aromatization and
intramolecular nucleophilic attack of the quinonic oxygen to the charge deficient carbon,
evolved to the corresponding diastereoisomers 20 (Scheme 4). Although the ratio of compound
19 resulting from the Diels–Alder reaction was very low (10%), its formation confirmed that in
the presence of the Lewis acid the regioselectivity is directed by the oxygenated substituent at
C-2 of diene 3 which gave rise to the formation of the meta-adduct. Derivative 19 showed a
specific rotation of [h]2D0=+23 (c 0.47, CHCl3) and 78% ee [Pr(hfc)3].
When cycloaddition was performed between cyclic diene 3 and enantiopure sulfinylquinone
(+)-6 under thermal conditions (Scheme 4, Table 3, entry 3), a 93:7 mixture of regioisomeric
6-(tert-butyldimethylsilyloxy)-5,8-ethane-2-isopropyl-5-methyl-5,8-dihydro-1,4-naphthoquinone
22 and 7-(tert-butyldimethylsilyloxy)-5,8-ethane-2-isopropyl-8-methyl-5,8-dihydro-1,4-naphtho-
quinone 23 was formed. From this mixture, only compound (−)-22 could be isolated pure by
flash chromatography. This regiochemical result indicated that the alkyl substituent at C-1 of
diene 3 was almost exclusively directing the regiochemistry of the process under these condi-
tions. Derivative 22 showed a specific rotation of [h]2D0=−51 (c 0.65, CHCl3) with 84%
enantiomeric excess [Pr(hfc)3], whereas the enantiomeric excess of 23 was 82% [Pr(hfc)3] from the
mixture of 22 and 23.
When the reaction of 3 and (+)-6 was conducted in the presence of ZnBr2 (entry 4), no
product deriving from the cycloaddition process was detected. We only isolated 5a-(tert-
butyldimethylsilyloxy)-4-isopropyl-9a-methyl-1-(p-tolylsulfinyl)-5a,8,9,9a-tetrahydrodibenzo-
furan-2-ol 24 as a 60:40 mixture of diastereoisomers formed through the cationic intermediate
25 in a similar way to that indicated for compound 20 (Scheme 4).
3. Discussion
To rationalize the results achieved in these reactions we must differentiate the regioselectivity
and the p-facial diastereoselectivity. The observed regioselectivity was in turn different when
reactions were carried out under thermal or Lewis acid catalyzed conditions.
Reactions of methyl substituted quinone 5 under thermal conditions led to the major
formation of ortho-adduct from cyclic diene 3 (Table 3, entry 1), which became exclusive from

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4287
semicyclic Dane’s diene (Table 1, entry 3). No regioselectivity was observed when the reacting
diene was the acyclic butadiene derivative 2 (Table 2, entry 1). Considering the role played by
the coefficients of the atomic orbitals of the HOMO of C-1 and C-2 substituted dienes3 in the
control of the regioselectivity of Diels–Alder reactions, the formation of a mixture of ortho-(C-1
control) and meta-(C-2 control) adducts should be expected for dienes 1, 2, and 3, but this was
only the case for 2. If we consider the endo transition states giving rise to both regioisomers (TSI
and TSII in Fig. 1) we can observe a R (CH3)/R% destabilizing interaction in that leading to the
meta-adduct, meta-TSII, which does not exist in the ortho transition state ortho-TSI. Such steric
interaction must be stronger for the transition state resulting from Dane’s diene 1 where R% is
a bulky aromatic group and could explain the exclusive evolution through the ortho transition
state. When dienes 2 and 3 are reacting, such interaction is similar since in both cases R% is a
OTBDMS group. The major formation of the ortho-adduct from cyclic diene 3 must be a
consequence of a distorted geometry of the endo–meta transition state (meta-TSIII in Fig. 1) due
to the destabilizing interaction existent between the methylene bridges of the diene and the
sulfoxide group of the quinone which forces an out-of-plane disposition when the dienophile is
approaching. As a consequence, the R% substituent must be shifted to the bottom face (see Fig.
1) determining an increased R/R% (OTBDMS) interaction. The higher energy content of this
transition state would explain the preferred evolution through the more stable ortho transition
state leading to the major formation of 18.
Figure 1.
The results obtained in the reactions of dienes 2 and 3 with 5-isopropyl-(2-p-tolylsulfinyl)-1,4-
benzoquinone 6 reinforce the above explanation. The R (i-Pr)/R% interaction existing in the
meta-TSII transition state (Fig. 1) is now stronger and, as a consequence, the evolution through
the most stable ortho transition state is preferred for 2 (80:20 ratio of 16 and 17, Table 2, entry
5) and 3 (93:7 ratio of 22 and 23, Table 3, entry 3). In the latter, the distorted geometry of the
transition state resulting from the cyclic diene approach must also contribute to the preferred
formation of 22. The higher preference for ortho regioisomers from 5-isopropyl derivative with
respect to the similar reactions with 5-methyl-2-(p-tolylsulfinyl)-1,4-benzoquinone must be due
to the higher destabilization of the meta transition state when R=i-Pr with respect to R=Me.
The regiochemical course of reactions with unsubstituted 2-(p-tolylsulfinyl)-1,4-benzoquinone
4 can be deduced from the enantiomeric excess of the resulting compounds (+)-7 (80% ee, Table
1, entry 1) and 13 (racemic, Table 2, entry 1). The enantiomeric excess of (+)-7 is identical to
that observed for (+)-9 suggesting that both quinones 4 and 5 evolve with similar p-facial
diastereoselectivities under thermal conditions. Therefore, the regioselectivity must be almost

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identical for both quinones. Racemic 13 must result from the formation of an equimolecular
mixture of (+)-13 and (−)-13 resulting in a reaction with null regioselectivity in the same way
observed in the reaction of (+)-5 with diene 2. This result indicates that under thermal
conditions the regioselectivity of the process is scarcely modified when the R substituent of the
quinone is H or Me.
When ZnBr2 was present in the reaction medium, the exclusive formation of meta-adducts
both from methyl substituted quinone 5 (Table 1, entry 4; Table 2, entry 4 and Table 3, entry
2) and the isopropyl substituted dienophile 6 (Table 2, entry 6) was observed. These results
could be explained invoking the Frontier Orbital theory taking into account that the coordina-
tion of the Lewis acid to the OMe group of Dane’s diene 1 or the OTBDMS substituent of
dienes 2 and 3 must induce significant changes in the coefficients of their HOMO bringing
about the major C-2 regiocontrol. The efficiency of ZnBr2 in inverting the regiochemistry with
respect to thermal reactions is higher than that of BF3·OEt2 (see Table 1, entries 4 and 5).
Since the effect of both Lewis acids on the orbital coefficients must be similar, other effects
must be invoked to account for such differences. Considering the ability of the ZnBr2 to form
doubly associated species with sulfinyl benzoquinones,9 the ortho cycloaddition through the
chelated species ortho-ZnBr2 represented in Fig. 1 must be strongly disfavored due to the steric
congestion existing between the sulfinyl and carbonyl oxygens and the substituent at C-1 of
the diene, leading to the exclusive meta evolution of the process
According to the enantiomeric excesses of compounds obtained from quinones 5 and 6, the
p-facial diastereoselectivities of these reactions range from 72 to >97% being slightly higher
when the ortho-adducts are formed. The absolute configuration of the stereogenic centers
indicated in Schemes 1–3 for products resulting from thermal reactions must be a consequence
of the well-known5,6 preferred evolution of sulfinylquinones through the s-cis conformation
from the less hindered top face bearing the lone electron pair of the sulfoxide (Fig. 1). For
reactions carried out in the presence of ZnBr2, the absolute configuration of the stereogenic
centers existing in the final products could not be unequivocally established, but the enan-
tiomeric excesses determined ranged from 36 to 97%. While we do not have a convincing
explanation for the moderate to excellent p-facial diastereoselectivity observed under ZnBr2
catalyzed conditions, it is noteworthy that this Lewis acid was able to efficiently invert the
regioselectivity of these processes due to the cooperation of orbital factors and steric interac-
tions with the remote C-5 substituent of the sulfinyl benzoquinone.
4. Conclusion
The results presented show that the regioselectivity of Diels–Alder reactions of (S)-2-(p-
tolylsulfinyl)-1,4-benzoquinones 5 and 6 can be directed by the adequate choice of thermal or
ZnBr2 catalyzed conditions. Such possibility allows the stereoselective synthesis of two
regioisomers of tetrahydrochrysenequinones 9 and 11 from Dane’s diene as well as dihy-
dronaphthoquinones 14–17 from 3-tert-butyldimethylsilyloxy-1,3-pentadiene. When 2-tert-
butyldimethylsilyloxy-1-methyl-1,3-cyclohexadiene was used as the diene partner, the
competitive formation of dibenzofuran derivatives 20 and 24 in the presence of ZnBr2 pre-
vented the efficient synthesis of regioisomeric 5,8-ethano-5,8-dihydro-1,4-naphthoquinones 19
and 23.

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5. Experimental
5.1. General methods
Melting points were obtained in open capillary tubes and are uncorrected. IR spectra were
1
obtained as CHCl3 solutions and are given in cm−1. H and 13C NMR spectra were recorded in
CDCl3 at 300 and 75 MHz, respectively. Regioisomeric adducts ratios were established by
integration of well-separated signals in the crude reaction mixtures and are listed in Tables 1–3.
All reactions were monitored by thin layer chromatography that was performed on precoated
sheets of silica gel 60, and flash column chromatography was performed 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. Dry THF was
distilled from sodium/benzophenone ketyl. CH2Cl2 and CHCl3 were dried over P2O5. For
routine workup, hydrolysis was carried out with water, extractions with CH2Cl2, and solvent
dryness with Na2SO4.
5.2. (Z)-3-(tert-Butyldimethylsilyloxy)-1,3-pentadiene 2
To a solution of 1-penten-3-one (1.63 g, 20 mmol) and TBDMSOTf (5.5 ml, 24 mmol) in dry
THF (150 ml) at −78°C under argon, a suspension of KHMDS (4.0 g, 20 mmol) in dry THF
(60 ml) was slowly added and the reaction continued at −78°C for 30 min and at rt for 1 h. The
mixture was hydrolyzed with NaHCO3 and extracted with Et2O. The organic layer was washed
with NaCl and dried with MgSO4. The residue was purified by flash chromatography (eluent
1
hexane) to obtain pure 2 as a colorless oil in 37% yield; H NMR: l 6.20 (dd, 1H, J=17.1 and
10.7 Hz), 5.32 (dd, 1H, J=17.1 and 10.8 Hz), 4.96 (dd, 1H, J=10.7 and 10.8 Hz), 4.90 (q, 1H,
J=7.0 Hz), 1.69 (d, 3H, J=7.0 Hz), 1.02 (s, 9H), 0.12 (s, 6H); 13C NMR: l 149.4, 135.6, 111.6,
110.0, 26.0 (3C), 18.4, 11.8, −2.9, −3.6.
5.3. 2-(tert-Butyldimethylsilyloxy)-1-methyl-1,3-cyclohexadiene 3
To a solution of diisopropylamine (492 mg, 4.86 mmol) in dry THF (16 ml) at −25°C under
argon, n-BuLi 2.02 M (2.3 ml, 4.65 mmol) was added. After 30 min, 6-methyl-2-cyclohexenone18
(466 mg, 4.23 mmol) was added and the reaction continued for 30 min at the same temperature.
Then, TBDMSOTf (1.02 ml, 4.44 mmol) was added and after 1 h at rt the mixture was diluted
with pentane and extracted with NaHCO3. After workup, the residue was purified by flash
chromatography over silica gel previously neutralized with a 10% solution of triethylamine in
pentane and washed three times with pentane (eluent pentane) to obtain pure 3 as a colorless oil
1
in 74% yield; H NMR: l 5.68 (broad s, 2H), 2.10 (broad s, 4H), 1.67 (broad s, 3H), 0.96 (s,
9H), 0.95 (s, 6H); 13C NMR: l 142.0, 126.4, 125.2, 112.4, 28.7, 23.0, 25.8 (3C), 18.1, 16.1, −4.2
(2C); EI-MS: m/z (%) 224 (M+, 10), 183 (31), 109 (21), 75 (100), 73 (74); HRMS (EI) calcd for
C13H24OSi: 224.15964; found: 224.15826.
5.4. General procedure for thermal Diels–Alder reactions. Method A
To a solution of the (p-tolylsulfinyl)-1,4-benzoquinone (0.4 mmol) in 5 ml of dry CH2Cl2 at
the temperature indicated in each case (see Tables 1–3 for reaction conditions) under argon, the

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corresponding diene (0.4 mmol) was added. After the time required and evaporation of the solvent,
crude dihydroquinones were obtained and purified by flash chromatography.
5.5. General procedure for ZnBr2 catalyzed Diels–Alder reactions. Method B
To a vigorously stirred suspension of dry ZnBr2 (0.8 mmol) in dry CH2Cl2 under argon, the
(p-tolylsulfinyl)-1,4-benzoquinone (0.4 mmol) in 5 ml of dry CH2Cl2 was added. After 1 h at rt,
the mixture was cooled to −20°C and the corresponding diene (0.4 mmol) was added. After the
time required in each case (see Tables 1–3 for reaction conditions) and workup, crude
dihydroquinones were obtained and purified by flash chromatography.
5.6. (4bS)-8-Methoxy-4b,5,6,12-tetrahydro-1,4-chrysenequinone (+)-7
Compound (+)-7 was obtained from (SS)-2-(p-tolylsulfinyl)-1,4-benzoquinone19 (+)-4 and
Dane’s diene15 1 (1 M in benzene) following method A at −78°C for 24 h (eluent hexane:EtOAc
90:10) as an orange solid in 23% yield; mp 158–159°C; [h]2D0=+94 (c 0.12, CHCl3), ee=80%
1
[Yb(hfc)3]; H NMR: l 7.38 (d, 1H, J=8.5 Hz), 6.76 (dd, 1H, J=8.5 Hz, and 2.9 Hz), 6.75 (s,
2H), 6.65 (d, 1H, J=2.9 Hz), 5.97–5.90 (m, 1H), 3.80 (s, 3H), 3.53–3.40 (m, 1H), 3.32–2.83 (m,
4H), 2.51–2.40 (m, 1H), 1.70–1.50 (m, 1H); 13C NMR: l 187.1, 187.0, 159.1, 150.0, 141.8, 137.4,
137.0, 135.9, 134.7, 128.7, 125.3, 113.2, 113.0, 112.6, 55.2, 35.0, 31.5, 30.3, 28.5; IR wmax: 2980,
2880, 1645, 1595, 1125; EI-MS: m/z (%) 292 (M+, 27), 290 (100), 277 (11), 261 (17), 247 (20), 219
(11), 189 (17), 165 (17), 147 (12), 94 (7); HRMS (EI) calcd for C19H16O3: 292.10995; found:
292.11022.
5.7. (4bR)-8-Methoxy-4b,5,6,12-tetrahydro-1,4-chrysenequinone (−)-7
Compound (−)-7 was obtained from (SS)-2-(p-tolylsulfinyl)-1,4-benzoquinone (+)-4 and Dane’s
diene 1 (1 M in benzene) following method B for 15 min (eluent hexane:EtOAc 90:10) as an orange
solid in 20% yield; [h]2D0=−42 (c 0.12, CHCl3), ee=36% [Yb(hfc)3].
5.8. 8-Methoxy-5,6-dihydro-1,4-chrysenequinone 8
Compound 8 was obtained from (SS)-2-(p-tolylsulfinyl)-1,4-benzoquinone (+)-4 and Dane’s
diene 1 (1 M in benzene) following method A at −78°C for 24 h or following method B for 15
min (eluent hexane:EtOAc 90:10) as an orange solid in 23 and 25% yield, respectively; mp
187–188°C; 1H NMR: l 8.09 and 8.00 (AB system, 2H, J=8.2 Hz), 7.69 (d, 1H, J=8.6 Hz), 6.91
(s, 2H), 6.85 (dd, 1H, J=8.6 and 2.8 Hz), 6.83 (d, 1H, J=2.8 Hz), 3.87 (s, 3H), 3.53 and 2.83
(2dd, 4H, J=7.4, 7.0 Hz); 13C NMR: l 187.7, 184.9, 160.5, 141.6, 140.6, 139.8, 139.3, 140.0, 135.9,
131.2, 127.8, 126.2, 125.8, 125.3, 113.2, 113.0, 55.3, 28.5, 25.3; IR wmax: 3110, 2990, 2920, 1650,
1600, 1130; EI-MS: m/z (%) 290 (M+, 100), 277 (9), 261 (17), 247 (10), 231 (9), 219 (11), 189 (17),
165 (17), 147 (6), 101 (6). Anal. calcd for C19H14O3: C, 78.60; H, 4.86. Found: C, 78.78; H, 4.99.
5.9. Compound (4bS)-8-Methoxy-2-methyl-4b,5,6,12-tetrahydro-1,4-chrysenequinone (+)-9
Compound (+)-9 was obtained from (SS)-2-methyl-5-(p-tolylsulfinyl)-1,4-benzoquinone20 (+)-
5 and Dane’s diene 1 (1 M in benzene) following method A at −20°C for 4 h (eluent
hexane:EtOAc 95:5) as a red solid in 43% yield; mp 128–129°C; [h]2D0=+134 (c 0.13, CHCl3),

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1
ee=80% [Yb(hfc)3]; H NMR: l 7.38 (d, 1H, J=8.5 Hz), 6.74 (dd, 1H, J=8.5 and 2.4 Hz), 6.64
(d, 1H, J=2.4 Hz), 6.59 (q, 1H, J=1.6 Hz), 5.98–5.92 (m, 1H), 3.80 (s, 3H), 3.52–3.35 (m, 1H),
3.32–2.82 (m, 4H), 2.53–2.41 (m, 1H), 2.06 (d, 3H, J=1.6 Hz), 1.68–1.51 (m, 1H); 13C NMR:
l 187.6, 187.1, 159.1, 145.1, 141.6, 139.1, 137.4, 134.7, 132.8, 125.3, 113.3, 113.2, 112.5, 55.2,
34.9, 31.5, 30.3, 25.4, 15.6; IR wmax: 2990, 1640, 1600, 1130. Anal. calcd for C20H18O3: C, 78.40;
H, 5.93. Found: C, 78.51; H, 6.02.
5.10. 8-Methoxy-2-methyl-5,6-dihydro-1,4-chrysenequinone 10
Compound 10 was obtained from (SS)-2-methyl-5-(p-tolylsulfinyl)-1,4-benzoquinone (+)-5
and Dane’s diene 1 (1 M in benzene) following method A at −20°C for 4 h (eluent hex-
ane:EtOAc 95:5) as a red solid in 24% yield; mp 138–139°C (hexane); 1H NMR: l 8.08–7.95 (AB
system, 2H, J=8.2 Hz), 7.67 (d, 1H, J=8.6 Hz), 6.88 (dd, 1H, J=2.6 and 8.5 Hz), 6.81 (d, 1H,
J=2.6 Hz), 6.76 (q, 1H, J=1.4 Hz), 3.86 (s, 3H), 3.52 and 2.81 (2m, 4H), 2.14 (d, 3H, J=1.4
Hz); 13C NMR: l 187.8, 185.5, 160.4, 146.3, 141.3, 139.8, 137.5, 137.7, 131.5, 127.5, 126.2, 126.0,
126.0, 113.1, 113.0, 112.9, 55.4, 28.6, 25.3, 15.9; IR wmax: 3000, 2950, 1640, 1600, 1130. Anal.
calcd for C20H16O3: C, 78.92; H, 5.30. Found: C, 79.08; H, 5.21.
5.11. (4bR)-8-Methoxy-3-methyl-4b,5,6,12-tetrahydro-1,4-chrysenequinone (−)-11
Compound (−)-11 was obtained from (SS)-2-methyl-5-(p-tolylsulfinyl)-1,4-benzoquinone (+)-5
and Dane’s diene 1 (1 M in benzene) following method B for 2 h (eluent hexane:EtOAc 95:5)
as an orange solid in 38% yield; mp 114–115°C (hexane); [h]2D0=−185 (c 0.2, CHCl3), ee >97%
1
[Yb(hfc)3]; H NMR: l 7.37 (d, 1H, J=8.5 Hz), 6.75 (dd, 1H, J=8.5 Hz and 2.4 Hz), 6.65 (d,
1H, J=2.4 Hz), 6.59 (q, 1H, J=1.6 Hz), 5.98–5.92 (m, 1H), 3.80 (s, 3H), 3.54–3.37 (m, 1H),
3.31–2.81 (m, 4H), 2.51–2.35 (m, 1H), 2.07 (d, 3H, J=1.6 Hz), 1.69–1.50 (m, 1H); 13C NMR:
l 187.4, 187.2, 159.1, 146.0, 141.7, 139.1, 137.4, 134.8, 128.7, 128.7, 125.3, 113.1, 112.5, 111.3,
55.2, 35.0, 31.5, 30.31, 25.2, 15.8; IR wmax: 2990, 2940, 1650, 1600, 1130. Anal. calcd for
C20H18O3: C, 78.40; H, 5.93. Found: C, 78.28; H, 5.82.
5.12. 8-Methoxy-3-methyl-5,6-dihydro-1,4-chrysenequinone 12
Compound 12 was obtained from (SS)-2-methyl-5-(p-tolylsulfinyl)-1,4-benzoquinone (+)-5
and Dane’s diene 1 (1 M in benzene) following method B for 2 h (eluent hexane:EtOAc 95:5)
1
as a red solid in 22% yield; mp 181–182°C (hexane); H NMR: l 8.05 and 7.95 (AB system, 2H,
J=8.2 Hz), 7.67 (d, 1H, J=8.6 Hz), 6.89 (dd, 1H, J=8.6 and 2.7 Hz), 6.80 (d, 1H, J=2.7 Hz),
6.78 (q, 1H, J=1.6 Hz), 3.87 (s, 3H), 3.50 and 2.81 (2dd, 4H, J=7.0 and 7.5 Hz), 2.19 (d, 3H,
J=1.6 Hz); 13C NMR: l 188.2, 184.8, 160.4, 149.7, 141.2, 139.7, 137.6, 136.5, 134.3, 131.6, 130.1
127.6, 126.2, 126.0, 125.4, 112.9, 55.3, 28.6, 25.6, 16.9; IR wmax: 3020, 2920, 1655, 1610, 1130;
EI-MS: m/z (%) 304 (M+, 100), 275 (7), 261 (26), 202 (8), 163 (8), 149 (11); HRMS (EI) calcd
for C20H16O3: 304.10995; found: 304.10915.
5.13. (5R*)-6-(tert-Butyldimethylsilyloxy)-5-methyl-5,8-dihydro-1,4-naphthoquinone 13
Compound 13 was obtained from (SS)-2-(p-tolylsulfinyl)-1,4-benzoquinone (+)-4 and (Z)-3-
(tert-butyldimethylsilyloxy)-1,3-pentadiene 2 following method A at −20°C for 48 h (eluent

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hexane:acetone 95:5) as a yellow oil in 32% yield; [h]2D0=0 (c 0.75, CHCl3); H NMR: l 6.72 (s,
2H), 4.81 (dd, 1H, J=3.0 and 4.0 Hz), 3.4–2.9 (m, 3H), 1.27 (d, 3H, J=6.8 Hz), 0.94 (s, 9H),
0.18 and 0.17 (2s, 6H); 13C NMR: l 187.1, 186.6, 152.0, 143.9, 139.3, 136.7, 130.1, 96.7, 33.3,
25.6 (3C), 24.7, 19.6, 18.0, −4.5 (2C).
1
5.14. (5S)-6-(tert-Butyldimethylsilyloxy)-5-methyl-5,8-dihydro-1,4-naphthoquinone (−)-13
Compound (−)-13 was obtained from (SS)-2-(p-tolylsulfinyl)-1,4-benzoquinone (+)-4 and
(Z)-3-(tert-butyldimethylsilyloxy)-1,3-pentadiene 2 following method B for 1.5 h (eluent hex-
ane:acetone 95:5) as a yellow oil in 36% yield; [h]2D0=−49 (c 0.18, CHCl3), ee=70% [Pr(hfc)3].
5.15. (5R)-6-(tert-Butyldimethylsilyloxy)-2,5-dimethyl-5,8-dihydro-1,4-naphthoquinone (+)-14
Compound (+)-14 was obtained from (SS)-2-methyl-5-(p-tolylsulfinyl)-1,4-benzoquinone (+)-5
and (Z)-3-(tert-butyldimethylsilyloxy)-1,3-pentadiene 2 following method A at −20°C for 48 h,
after separation of the 50:50 mixture of 14 and 15 (eluent CH2Cl2:hexane 50:50) as a yellow oil
1
in 32% yield; [h]2D0=+28 (c 0.84, CHCl3), ee=78% [Pr(hfc)3]; H NMR: l 6.55 (q, 1H, J=1.6
Hz), 4.80 (dd, 1H, J=2.2 and 4.7 Hz), 3.4–2.9 (m, 3H), 2.03 (d, 3H, J=1.6 Hz), 1.25 (d, 3H,
J=6.7 Hz), 0.94, (s, 9H), 0.17 and 0.16 (2s, 6H); 13C NMR: l 187.6, 186.7, 151.9, 145.2, 143.6,
139.1, 133.5, 97.0, 33.2, 25.6 (3C), 24.8, 19.7, 18.0, 15.7, −4.5 (2C); IR wmax: 2960, 2840, 2770,
1675, 1640, 1290, 1195, 855, 840; EI-MS: m/z (%) 318.2 (M+, 36), 303 (11), 259 (100), 233 (34),
217 (5.9), 69 (40); HRMS (EI) calcd for C18H26O3Si: 318.16512; found: 318.16548.
5.16. (8S)-7-(tert-Butyldimethylsilyloxy)-2,8-dimethyl-5,8-dihydro-1,4-naphthoquinone (−)-15
Compound (−)-15 was obtained from (SS)-2-methyl-5-(p-tolylsulfinyl)-1,4-benzoquinone (+)-5
and (Z)-3-(tert-butyldimethylsilyloxy)-1,3-pentadiene 2 following method A at −20°C for 48 h
after separation of the 50:50 mixture of 15 and 14, or following method B for 15 min (eluent
CH2Cl2:hexane 50:50) as a yellow oil, in 20% yield (method A) or 42% yield (method B);
1
[h]2D0=−29 (c=0.4, CHCl3), ee=72% [Pr(hfc)3]; H NMR: l 6.54 (q, 1H, J=1.6 Hz), 4.80 (dd,
1H, J=3.0 and 4.2 Hz), 3.4–2.9 (m, 3H), 2.05 (d, 3H, J=1.6 Hz), 1.25 (d, 3H, J=6.7 Hz), 0.94
(s, 9H), 0.17 and 0.16 (2s, 6H); 13C NMR: l 187.1, 187.0, 152.1, 145.8, 143.8, 139.2, 132.9, 97.0,
33.4, 25.7 (3C), 24.5, 19.6, 18.0, 15.8, −4.5 (2C); IR wmax: 2940, 2920, 2840, 1675, 1640, 1270,
1175, 880, 865; EI-MS: m/z (%) 318.2 (M+, 42), 303 (13), 259 (100), 233 (32), 69 (54); HRMS
(EI) calcd for C18H26O3Si: 318.16512; found: 318.16490.
5.17. (5R)-6-(tert-Butyldimethylsilyloxy)-2-isopropyl-5-methyl-5,8-dihydro-1,4-naphthoquinone
(+)-16
Compound (+)-16 was obtained from (SS)-2-isopropyl-5-(p-tolylsulfinyl)-1,4-benzoquinone20
(+)-6 and (Z)-3-(tert-butyldimethylsilyloxy)-1,3-pentadiene 2 following method A at −20°C for
56 h, after separation of the 80:20 mixture of 16 and 17 (eluent CH2Cl2:hexane 50:50) as a yellow
oil in 40% yield; [h]2D0=+49 (c 0.8, CHCl3), ee >97% [Pr(hfc)3]; H NMR: l 6.48 (d, 1H, J=1.2
1
Hz), 4.81 (dd, 1H, J=2.9 and 4.4 Hz), 3.4–2.9 (m, 4H), 1.26 (d, 3H, J=6.7 Hz), 1.13 and 1.11
(2d, 6H, J=7.0 Hz), 0.94 (s, 9H), 0.17 and 0.16 (2s, 6H); 13C NMR: l 187.2, 186.8, 154.3, 151.9,
143.1, 139.4, 130.4, 97.1, 33.1, 26.6, 25.6 (3C), 24.9, 21.4 (2C), 19.6, 18.0, −4.6 (2C).

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5.18. (8S)-7-(tert-Butyldimethylsilyloxy)-2-isopropyl-8-methyl-5,8-dihydro-1,4-naphthoquinone
(−)-17
Compound (−)-17 was obtained from (SS)-2-isopropyl-5-(p-tolylsulfinyl)-1,4-benzoquinone
(+)-6 and (Z)-3-(tert-butyldimethylsilyloxy)-1,3-pentadiene 2 following method A at −20°C for
56 h after separation of the 20:80 mixture of 17 and 16, or following method B for 1 h (eluent
CH2Cl2:hexane 50:50) as a yellow oil, in 10% yield (method A) or 62% yield (method B);
[h]2D0=−46 (c 0.8, CHCl3), ee=74% [Pr(hfc)3]; H NMR 6.47 (d, 1H, J=1.2 Hz), 4.78 (dd, 1H,
1
J=2.9 and 4.4 Hz), 3.4–2.9 (m, 4H), 1.26 (d, 3H, J=6.6 Hz), 1.12 (d, 6H, J=6.8 Hz), 0.94 (s,
9H), 0.18 and 0.16 (2s, 6H); 13C NMR 187.6, 186.3, 155.0, 152.1, 144.0, 138.5, 129.7, 96.8, 33.4,
26.6, 25.6 (3C), 24.5, 21.5, 21.4, 19.6, 18.0, −4.5 (2C).
5.19. (5S,8R)-6-(tert-Butyldimethylsilyloxy)-2,5-dimethyl-5,8-ethane-5,8-dihydro-1,4-naphtho-
quinone (−)-18
Compound (−)-18 was obtained from (SS)-2-methyl-5-(p-tolylsulfinyl)-1,4-benzoquinone (+)-5
and 2-(tert-butyldimethylsilyloxy)-1-methyl-1,3-cyclohexadiene 3 following method A at −20°C
for 24 h, after separation of the 75:25 mixture of 18 and 19 (eluent hexane:acetone 95:5) as a
1
yellow oil in 37% yield; [h]2D0=−67 (c 0.39, CHCl3), ee >97% [Pr(hfc)3]; H NMR: l 6.32 (q, 1H,
J=1.6 Hz), 5.13 (d, 1H, J=6.9 Hz), 4.13 (dt, 1H, J=6.9 and 2.4 Hz), 1.99 (d, 3H, J=1.6 Hz),
1.72 (s, 3H), 1.7–1.3 (m, 4H), 0.92 (s, 9H), 0.10 and 0.07 (2s, 6H); 13C NMR: l 185.4, 184.7,
160.7, 152.1, 147.1, 143.1, 133.8, 102.7, 46.9, 35.0, 32.8, 26.6, 25.7 (3C), 18.2, 17.4, 15.2, −3.2,
−3.6.
5.20. (5R,8S)-7-(tert-Butyldimethylsilyloxy)-2,8-dimethyl-5,8-ethane-5,8-dihydro-1,4-naphtho-
quinone (+)-19
Compound (+)-19 was obtained from (SS)-2-methyl-5-(p-tolylsulfinyl)-1,4-benzoquinone (+)-5
and 2-(tert-butyldimethylsilyloxy)-1-methyl-1,3-cyclohexadiene 3 following method B for 3 h
after separation of the 10:90 mixture of 19 and 20 as a yellow oil in 7% yield; [h]2D0=+23
1
(c=0.47, CHCl3), ee=78% [Pr(hfc)3]; H NMR: l 6.40 (q, 1H, J=1.6 Hz), 5.12 (d, 1H, J=6.9
Hz), 4.10 (dt, 1H, J=6.9 and 2.8 Hz), 1.99 (d, 3H, J=1.6 Hz), 1.74 (s, 3H), 1.68–1.34 (m, 4H),
0.92 (s, 9H), 0.11 and 0.08 (2s, 6H); 13C NMR: l 185.6, 184.3, 160.7, 152.1, 147.2, 146.1, 131.0,
102.5, 47.0, 32.4, 26.6, 25.7, 18.2, 17.6, 16.1, 3.6, 3.2; IR wmax: 2920, 2840, 1525, 1015, 990;
EI-MS: m/z (%) 316 (M+−28, 10), 259 (100), 225 (71), 167 (8), 149 (26), 84 (82).
5.21 5a-(tert-Butyldimethylsilyloxy)-4,9a-dimethyl-1-(p-tolylsulfinyl)-5a,8,9,9a-tetrahydro-
dibenzofuran-2-ol 20
Compound 20 was obtained from (SS)-2-methyl-5-(p-tolylsulfinyl)-1,4-benzoquinone (+)-5
and 2-(tert-butyldimethylsilyloxy)-1-methyl-1,3-cyclohexadiene 3 following method B for 3 h
after separation of the 90:10 mixture of 20 and 19 as an inseparable 60:40 mixture of
1
diastereoisomers in 56% yield; H NMR (major): l 9.75 (s, 1H, OH), 7.50 and 7.24 (AA%BB%
system, 4H), 6.59 (broad s, 1H), 6.1–5.6 (m, 2H), 2.38 (s, 3H), 2.2–1.8 (m, 2H), 1.6–1.2 (m, 2H),
1.16 (s, 3H), 0.78 (s, 9H), 0.21 and −0.06 (2s, 6H); (minor): l 9.98 (s, 1H), 7.60 and 7.28 (AA%BB%
system, 4H), 6.62 (broad s, 1H), 6.1–5.6 (m, 2H), 2.38 (s, 3H), 2.2–1.8 (m, 2H), 1.6–1.2 (m, 2H),

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1.48 (s, 3H), 0.84 (s, 9H), 0.23 and −0.06 (2s, 6H); IR wmax: 3660, 2915, 1840, 1620, 1595, 1460,
1420, 1180, 1120; EI-MS: m/z (%) 484 (M+, 52), 468 (28), 427 (26), 411 (42), 345 (24), 287 (20),
149 (11), 91 (21), 75 (36); HRMS (EI) calcd for C27H36O4SSi: 484.72500; found: 484.72485.
5.22. (5S,8R)-6-(tert-Butyldimethylsilyloxy)-2-isopropyl-5-methyl-5,8-ethane-5,8-dihydro-1,4-
naphthoquinone (−)-22
Compound (−)-22 was obtained from (SS)-2-isopropyl-5-(p-tolylsulfinyl)-1,4-benzoquinone
(+)-6 and 2-(tert-butyldimethylsilyloxy)-1-methyl-1,3-cyclohexadiene 3 following method A at rt
for 18 h, after separation of the 94:6 mixture of 22 and 23 (eluent hexane:acetone 95:5) as a
yellow solid in 40% yield; mp 88–89°C (hexane:ethyl ether); [h]2D0=−51 (c 0.65, CHCl3), ee=84%
[Pr(hfc)3]; 1H NMR: l 6.24 (d, 1H, J=1.1 Hz), 5.14 (d, 1H, J=7.0 Hz), 4.14 (dt, 1H, J=7.0 and
2.2 Hz), 3.00 (dsept, 1H, J=1.1 and 7.0 Hz), 1.72 (s, 3H), 1.7–1.3 (m, 4H), 1.11 and 1.08 (2d,
6H, J=7.0 Hz), 0.92 (s, 9H), 0.10 and 0.08 (2s, 6H); 13C NMR: l 185.9, 184.0, 160.7, 152.4,
152.2, 146.7, 130.9, 102.7, 46.8, 35.0, 32.9, 26.6, 26.3, 25.7 (3C), 21.6, 21.4, 18.1, 17.4, 15.2, −3.2,
−3.7. Anal. calcd for C22H32O3Si: C, 70.93; H, 8.66. Found: C, 71.08; H, 8.82.
5.23. (5R,8S)-7-(tert-Butyldimethylsilyloxy)-2-isopropyl-8-methyl-5,8-ethane-5,8-dihydro-1,4-
naphthoquinone 23
Compound 23 was obtained from (SS)-2-isopropyl-5-(p-tolylsulfinyl)-1,4-benzoquinone (+)-6
and 2-(tert-butyldimethylsilyloxy)-1-methyl-1,3-cyclohexadiene 3 following method A at rt for
18 h, after purification of the 6:94 mixture of 23 and 22 (eluent hexane:acetone 95:5). The
1
following data for 23 were taken from a 22:78 mixture of 23 and 22; ee=82% [Pr(hfc)3]; H
NMR: l 6.33 (d, 1H, J=1.2 Hz), 5.14 (d, 1H, J=6.9 Hz), 4.13–4.07 (m, 1H), 3.01 (dsept, 1.2
and 7.0 Hz), 1.74 (s, 3H), 1.6–1.2 (m, 4H), 1.11 and 1.04 (2d, 6H, J=7.0 Hz), 0.93 (s, 9H), 0.10
and 0.09 (2s, 6H); 13C NMR: l 185.0, 184.8, 160.8, 155.2, 151.4, 147.5, 127.9, 102.8, 47.2, 35.1,
32.4, 30.9, 26.5, 25.6 (3C), 21.8, 21.6, 18.2, 17.6, −3.2, −3.6 (2C).
5.24. 5a-(tert-Butyldimethylsilyloxy)-4-isopropyl-9a-methyl-1-(p-tolylsulfinyl)-5a,8,9,9a-tetra-
hydrodibenzofuran-2-ol 24
Compound 24 was obtained from (SS)-2-isopropyl-5-(p-tolylsulfinyl)-1,4-benzoquinone (+)-6
and 2-(tert-butyldimethylsilyloxy)-1-methyl-1,3-cyclohexadiene 3 following method B for 4 h, as
1
an inseparable 60:40 mixture of diastereoisomers in 51% yield; H NMR (major): l 9.82 (s, 1H),
7.50 and 7.27 (AA%BB% system, 4H), 6.67 (s, 1H), 5.93 and 5.69 (2dt, 2H, J=10.0 and 4.1 Hz;
J=10.0 and 1.6 Hz), 3.04 (m, 1H), 2.40 (s, 3H), 2.2–1.9 (m, 2H), 1.8–1.4 (m, 2H), 1.20 and 1.16
(2d, 6H, J=7.0 Hz), 1.15 (s, 3H), 0.81 (s, 9H), 0.23 and 0.06 (2s, 6H); (minor): l 10.10 (s, 1H),
7.64 and 7.28 (AA%BB% system, 4H), 6.71 (s, 1H), 5.72 and 5.63 (2dt, 2H, J=10.0 and 4.1 Hz;
J=10.0 and 1.6 Hz), 3.04 (m, 1H), 2.41 (s, 3H), 2.2–1.9 (m, 2H), 1.8–1.4 (m, 2H), 1.48 (s, 3H),
1.21 and 1.17 (2d, 6H, J=7.0 Hz), 0.88 (s, 9H), 0.25 and 0.09 (2s, 6H).
Acknowledgements
We thank Direccio´n General de Investigacio´n Cient´ıfica y Te´cnica (grants PB98-0062 to MCC
and PB98-0078 to JLGR) for financial support. CZR thanks Ministerio de Educacio´n y Ciencia:
Programa de Cooperacio´n con Iberoame´rica for a fellowship.

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