(SS)-2-(p-Tolylsulfinyl)norborneno-p-benzoquinones: A New Type of Facially Perturbed Enantiopure Quinones

Article abstract of DOI:10.1021/jo9618942

The syntheses and asymmetric Diels-Alder reactions of (SS)-2-(p-tolylsulfinyl)norborneno-p-benzoquinones 10 and 11 with cyclopentadiene are reported. The cycloadditions allowed the highly stereoselective obtention of the four possible endo adducts 12-15, optically pure synthetic equivalents of norborneno-p-benzoquinone-cyclopentadiene bisadducts. The detailed study of the ¹H-NMR spectra of the adducts pointed out the anisotropic effects exerted by the sulfinyl moiety on the spectroscopic behavior of these rigid systems. In all cases, the π-facial selectivities were fully controlled by the sulfinyl group being possible to reverse the diastereoselection in thermal conditions and in the presence of ZnBr². The stereoselective synthesis of the cage compound 5, precursor of garudane, was achieved from cycloadduct endo-syn-13.

Full text of DOI:10.1021/jo9618942

976
J . Org. Chem. 1997, 62, 976-981
(SS)-2-(p-Tolylsu lfin yl)n or bor n en o-p-ben zoqu in on es: A New Typ e
of F a cia lly P er tu r bed En a n tiop u r e Qu in on es
M. Carmen Carren˜o,*,† J ose´ L. Garc´ıa Ruano,*,† Antonio Urbano,† and
M. Isabel Lo´pez-Solera‡
Departamento de Quı´mica Orga´nica (C-I) and Departamento de Quı´mica Inorga´nica (C-VIII),
Universidad Auto´noma, Cantoblanco, 28049-Madrid, Spain
Received October 8, 1996X
The syntheses and asymmetric Diels-Alder reactions of (SS)-2-(p-tolylsulfinyl)norborneno-p-
benzoquinones 10 and 11 with cyclopentadiene are reported. The cycloadditions allowed the highly
stereoselective obtention of the four possible endo adducts 12-15, optically pure synthetic
equivalents of norborneno-p-benzoquinone-cyclopentadiene bisadducts. The detailed study of the
1H-NMR spectra of the adducts pointed out the anisotropic effects exerted by the sulfinyl moiety
on the spectroscopic behavior of these rigid systems. In all cases, the π-facial selectivities were
fully controlled by the sulfinyl group being possible to reverse the diastereoselection in thermal
conditions and in the presence of ZnBr2. The stereoselective synthesis of the cage compound 5,
precursor of garudane, was achieved from cycloadduct endo-syn-13.
Sch em e 1
In tr od u ction
π-Facial diastereoselectivities in Diels-Alder reactions
on π-facially perturbed dienes have been extensively
investigated in the past years.1 The observed results
have been rationalized in terms of steric2 or electronic3
effects, product stability,4 orbital interactions,5 torsional
effects,6 or hyperconjugation.7 In contrast, a few sys-
tematic experiments have been devoted to study the
response of facially perturbed dienophiles in cycloaddi-
tions with various dienes.8-13 Several groups have
studied the behavior of dienophiles fixed on a norborna-
diene skeleton and vinylogous systems. Thus, Edman
† Departamento de Qu´ımica Orga´nica.
‡ Departamento de Qu´ımica Inorga´nica.
X Abstract published in Advance ACS Abstracts, February 1, 1997.
(1) (a) Watson, W. H. Stereochemistry and Reactivity of Systems
Containing π Electrons; Verlag Chemie International: Deerfield beach,
FL, 1983. (b) Trost, B. M.; Fleming, I., Eds.; Paquette, L. A., Vol. Ed.
Comprehensive Organic Synthesis; Pergamon Press: Oxford, U.K.,
1991; Vol. 5, Chapter 4.
and Simmons synthesized bicyclo[2.2.1]hepta-2,5-diene-
2,3-carboxylic anhydride and observed an unexpected exo
selectivity in the Diels-Alder reactions.8 Houk et al.
studied the cycloadditions of 7-substituted norborna-
dienes with hexachlorocyclopentadiene9 and found the
selectivity to be dependent on the electronegativity of the
substituent. More recently, other sophisticated facially
perturbed dienophiles have been prepared and their
cycloadditions investigated.10 With respect to quinones,
Mehta and co-workers, following the work initiated by
Cookson et al.,11 reported a systematic investigation of
the reactions of norbornano- and norbornenobenzoquino-
ne 1 (Scheme 1) with several dienes finding a reversed
stereochemical outcome in both systems.12 The results
obtained were applied to the synthesis of the polycyclic
strained cage compound “garudane” 13 following the
synthetic sequence depicted in Scheme 1.
(2) (a) Burnell, D. J .; Valenta, Z. Can. J . Chem. 1991, 69, 179. (b)
Tsuji, T.; Ohkita, M.; Nishida, S. J . Org. Chem. 1991, 56, 997. (c)
Ishihara, K.; Yamamoto, H. J . Am. Chem. Soc. 1994, 116, 1561. (d)
Mikami, K.; Motoyama, Y.; Terada, M. J . Am. Chem. Soc. 1994, 116,
2812. (e) Corey, E. J .; Sarshar, S.; Lee, D. H. J . Am. Chem. Soc. 1994,
116, 12089.
(3) (a) Kahn, S. D.; Hehre, W. J . J . Am. Chem. Soc. 1987, 109, 663.
(b) Fotiadu, F.; Michel, F.; Buono, G. Tetrahedron Lett. 1990, 31, 4863.
(c) Roush, W.; Brown, B. B. J . Org. Chem. 1992, 57, 3380. (d) Cokson,
J . M.; Fong, S. T.; McDonald, D. Q.; Steel, P. J .Tetrahedron Lett. 1993,
34, 163. (e) Paquette, L. A.; Branan, B. M.; Rogers, R. D.; Bond, A. H.;
Lange, H.; Gleiter, H. J . Am. Chem. Soc. 1995, 117, 5992.
(4) (a) Avenati, M.; Vogel, P. Helv. Chim. Acta 1983, 66, 1279. (b)
Pinkerton, A. A.; Schwarzenbach, D.; Birbaum, J . L.; Carrupt, P. A.;
Schwager, L.; Vogel, P. Helv. Chim. Acta 1984, 67, 1136.
(5) (a) Gleiter, R.; Paquette, L. A. Acc. Chem. Res. 1983, 16, 328.
(b) Macaulay, J . B.; Fallis, A. G. J . Am. Chem. Soc. 1990, 112, 1136.
(c) Ishida, M.; Beniya, Y.; Inagaki, S.; Kato, S. J . Am. Chem. Soc. 1990,
112, 8980.
(6) (a) Houk, K. N.; Li, Y.; Evanseck, J . P. Angew. Chem., Int. Ed.
Engl. 1992, 31, 682. (b) Machiguchi, T.; Hasegawa, T.; Ishii, Y.;
Yamabe, S.; Minato, T. J . Am. Chem. Soc. 1993, 115, 11536. (c) Storer,
J . W.; Raimondi, L.; Houk, K. N. J . Am. Chem. Soc. 1994, 116, 9675.
(d) Houk, K. N.; Gonza´lez, J .; Li, Y. Acc. Chem. Res. 1995, 28, 81.
(7) (a) Cieplak, A. S. J . Am. Chem. Soc. 1981, 103, 4540. (b) Li, H.;
le Noble, W. J . Recl. Trav. Chim. Pays-Bas 1992, 115, 199.
(8) Edman, J . R.; Simmons, H. E. J . Org. Chem. 1968, 33, 3808.
(9) Mazocchi, P. H.; Stahly, B.; Dodd, J .; Rondan, N. G.; Domelsmith,
L. N.; Rozeboom, M. D.; Caramella, P.; Houk, K. N. J . Am. Chem. Soc.
1980, 102, 6482.
(11) (a) Cookson, R. C.; Hill, R. R.; Hudec, J . J . Chem. Soc. 1964,
3043. (b) Cookson, R. C.; Hill, R. R. J . Chem. Soc. 1963, 2023. (c)
Cookson, R. C.; Grundwell, E.; Hill, R. R.; Hudec, J . J . Chem. Soc.
1964, 3062.
(12) (a) 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. (b) Mehta,
G.; Padma, S.; Pattabhi, V.; Pramanik, A.; Chandrasekhar, J . J . Am.
Chem. Soc. 1990, 112, 2942.
(13) (a) Mehta, G.; Padma, S. J . Am. Chem. Soc. 1987, 109, 7230.
(b) Mehta, G.; Padma, S. Tetrahedron 1991, 47, 7807.
(14) (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.; Stefani, V.; Remor,
C. Z.; Fischer, J . J . Org. Chem. 1996, 61, 503.
(10) (a) Chou, T. C.; J iang, T. S.; Hwang, J . T.; Lin, C. T. Tetrahedron
Lett. 1994, 35, 4165. (b) Okamoto, I; Ohwada, T.; Shudo, K. J . Org.
Chem. 1996, 61, 3155.
S0022-3263(96)01894-4 CCC: $14.00 © 1997 American Chemical Society

(SS)-2-(p-Tolylsulfinyl)norborneno-p-benzoquinones
J . Org. Chem., Vol. 62, No. 4, 1997 977
Ta ble 1. Diels-Ald er Rea ction s of 10 a n d 11 w ith
Sch em e 2
Cyclop en ta d ien e
entry dienophile cat. (equiv) time (h) yield (%) 12:13 14:15
1
2
3
4
10
10
11
11
24
1
24
1
79
87
92
88
90:10
0:100
ZnBr2 (2)
ZnBr2 (2)
100:0
0:100
the cycloadducts obtained would be enantiomerically pure
synthetic equivalents of norborneno-p-benzoquinone-
cyclopentadiene bisadducts already used as key inter-
mediates in the synthesis of bridged polycyclic molecules
such as “garudane”.13
In this paper we describe the synthesis of sulfinylnor-
borneno-p-benzoquinones 10 and 11 and the results of
their cycloadditions with cyclopentadiene under thermal
conditions and in the presence of ZnBr2. We also report
the photochemical obtention of the cage compound 5 and
the synthetic efforts made toward the transformation of
cycloadduct 13 into a chiral substituted cage derivative
of 5.
Resu lts a n d Discu ssion
Enantiomerically pure p-tolylsulfinylnorborneno-p-
benzoquinones 10 and 11 were prepared in two steps
from the previously described derivatives 616 and 716 as
depicted in Scheme 2.
Thus, the treatment of 6 or 7 with K2CO3 in THF/H2O
afforded sulfinylnorbornenohydroquinones 8 (81% yield)
and 9 (84% yield), respectively. Upon oxidation of the
hydroquinone moiety with ceric ammonium nitrate (CAN)
in CH3CN/H2O, sulfinylnorborneno-p-benzoquinones 10
and 11 were obtained in 92% and 95% yield, respectively.
The Diels-Alder reactions of dienophiles 10 and 11
with cyclopentadiene were carried out under thermal and
ZnBr2-catalyzed conditions; the results obtained are
collected in Scheme 2 and Table 1.
Our previous work devoted to the use of sulfinylbenzo-
14 and naphthoquinones15 as dienophiles had shown that
π-facial diastereoselectivities of their Diels-Alder cy-
cloadditions could be controlled by choosing the proper
Lewis acid catalyst. Further studies16 carried out on
(SS)-4a,5,8,8a-tetrahydro-5,8-methano-2-(p-tolylsulfinyl)-
1,4-naphthoquinones 6 and 7 (Scheme 2) revealed that
both reactivity and endo/ exo selectivity were modulated
by the presence of the sulfinyl group, whereas the π-facial
selectivity was imposed by the norbornene moiety which
hindered diene approach to the bottom face of the
dienophile.
Accordingly, we reasoned that the incorporation of a
sulfoxide in the norbornenoquinone framework of 1 could
substantially increase the π-facial diastereoselection in
the cycloadditions of sulfinyl derivatives 10 and 11
compared to that observed for 1. The study of these rigid
substrates, having both faces accessible, should cast light
on the role of the sulfoxide vs the norbornene moiety in
the control of the π-facial diastereoselection which had
not been evaluated in our previous models. Moreover,
As can be seen, the cycloaddition of benzoquinone
derivative 10 with cyclopentadiene in CH2Cl2 at -20 °C
afforded two diastereoisomeric adducts endo-anti-12 and
endo-syn-13 (Scheme 2) in a 90:10 ratio (Table 1, entry
1). Both adducts resulted from the endo approach of the
diene on the two diastereotopic faces of the dienophile.
In the same conditions, compound 11 evolved to give
cycloadduct endo-syn-14 as a sole diastereoisomer (Table
1, entry 3). In the presence of ZnBr2 the Diels-Alder
reactions of dienophiles 10 and 11 with cyclopentadiene
were faster than in thermal conditions (Table 1, entries
2 and 4) and afforded respectively adducts endo-syn-13
and endo-anti-15 with a total control of the π-facial
selectivity. All derivatives 12-15 obtained in these
reactions could be isolated diastereoisomerically pure by
flash chromatography (see Experimental Section).
Configurational assignment of adducts 12-15 was
based on a simple chemical correlation with the known
compounds 1612a and 1712a (Scheme 2). Thus, endo-anti
cycloadducts 12 and 15 evolved into compound 16 upon
heating in EtOAc solution, whereas the same pyrolytic
elimination on endo-syn sulfoxides 13 and 14 afforded
compound 17. These results allowed us to assign the
configurations showed in Scheme 2 to these sulfinyl
derivatives. Moreover, the absolute configuration of
(15) (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.
(16) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Urbano, A.; Hoyos, M. A.
J . Org. Chem. 1996, 61, 2980.

978 J . Org. Chem., Vol. 62, No. 4, 1997
Carren˜o et al.
The high π-facial diastereoselectivities observed in the
cycloadditions of these rigid sulfinylbenzoquinones con-
trast with those reported for similar reactions on nor-
bornenobenzoquinone 1 lacking the sulfoxide group. As
can be seen in Scheme 1, upon reaction with cyclopen-
tadiene, compound 1 gave rise to a 35:65 mixture of
adducts 2 and 3 (top to bottom approach).12,13 Thus, the
high stereoselectivities observed in the related sulfinyl-
substituted systems 10 and 11 reveal the overwhelming
role played by the sulfoxide group with respect to the
norbornene moiety in the control of the diene approach.
Our results are fully consistent with the stereochemical
model on the basis of steric grounds,19 already proposed
to explain similar asymmetric Diels-Alder reactions on
sulfinyl dienophiles. The endo approach of cyclopenta-
diene is favored from the less hindered face of the reactive
conformation of dienophiles 10 and 11, which bears the
lone electron pair at sulfur.20 In thermal conditions, such
a reactive conformation corresponds to a s-cis disposition
of the sulfinylic oxygen with respect to the dienophilic
double bond. When ZnBr2 is present in the reaction
medium, a chelate resulting from metal association with
both sulfinylic and carbonylic oxygens (s-trans disposi-
tion) should be responsible for the reversed diastereose-
lection observed.21 Moreover, a complete endo selectivity
resulted in reactions with quinones 10 and 11, whereas
only a moderate endo selectivity was found with the
nonplanar ene-diones 6 and 7.16 This different behavior
suggests that the lack of planarity of the latter is
responsible of the formation of the exo adduct. The
obtention of 10% of the diastereoisomer 13 in the reaction
of 10 with cyclopentadiene could be a consequence of the
interactions existing in the endo approach of cyclopen-
tadiene between the H2 and H3 olefinic protons of
cyclopentadiene and the methylene group of the norbor-
nadienyl moiety.
The accessibility of compounds 12-15 and their po-
tential as chiral synthons of norborneno-p-benzoquinone-
cyclopentadiene bisadducts prompted us to undertake
their transformation into chiral polycyclic strained de-
rivatives. Thus, compound 13 with an endo-syn structure
was submitted to treatment with TiCl3 in the conditions
reported by Mehta13 (see Scheme 1). In our case, reduc-
tion of the ene-dione moiety did not take place from the
exo face as expected. Instead, compound 18 (Scheme 3)
resulting from the pyrolysis of the sulfinyl group and
further reduction of the initially formed quinone was
obtained in 75% yield. We reasoned that the transfor-
mation of the sulfinyl group in a less labile group such a
thioether would avoid the undesirable loss of the sulfur
functionality maintaining the chirality in the molecule.
So, the treatment of sulfoxide 13 with trifluoroacetic
anhydride and sodium iodide in acetone at -40 °C,22
afforded the corresponding thioether 19 in 75% yield. In
this case, the reduction of the ene-dione moiety of 19 took
place in the same conditions as above to yield a 82% of
the corresponding endo-syn-endo compound 20 mantain-
ing the p-tolylthio group (Scheme 3).
F igu r e 1.
compound 12 was shown to be (1S,4R,4aR,5R,8S,9aS,
SS) by X-ray diffraction.17
Once known the absolute configuration of 12, a detailed
comparative analysis of the 1H-NMR parameters of
derivatives 12-15 enabled the unambiguous structural
assignments of 13, 14, and 15 (See Figure 1 and Table
2).
As can be seen, the endo structure of all bisadducts
could be assigned from the observed high chemical shifts
of H11a (δ 2.33, 2.11, 2.30, and 2.14) if compared to that
of H11b (δ 1.48, 1.65, 1.42, and 1.71) as a consequence of
the strong deshielding effect exerted by the sulfinylic
oxygen18 on H11a, already observed in similar systems.15a,16
Other important spectroscopic characteristics of both
kinds of adducts are the relative shielding observed in
the endo-anti adducts 12 and 15 for the H6 and H7 olefinic
protons (δ 6.1-6.3) with respect to that of the same
hydrogens (δ 6.60-6.66) in the endo-syn adducts 13 and
14. This fact must be a consequence of the anisotropic
effect exerted by the aromatic ring of the p-tolyl group
shielding H6 and H7 in the endo-anti adducts. A similar
effect is also evident from the shielding of H12a proton (δ
0.95 and 1.02) in the endo-syn adducts 13 and 14 if
compared with the chemical shifts of the same hydrogen
(δ 1.88 and 1.89) in the endo-anti adducts 12 and 15.
Once the endo-anti and endo-syn relative configurations
were known, the most significant parameter to assign
the absolute configuration of 12 and 13 is the chemical
shift difference observed for H9a protons imposed by the
rigid disposition of the sulfinyl group. Thus, H9a appears
0.59 ppm more deshielded in compound 12 than in 15 as
a consequence of the strong deshielding effect of the
proximal sulfinylic oxygen.18 The same effect can be
observed for adducts 13 and 14 where H9a appeared at
3.82 ppm in 14 and at 3.22 in 13 (∆δ 0.60). All these
data reinforce the anisotropic effects of the p-tolylsulfinyl
group already pointed out by us15a,16 to assign the
stereochemistry of these rigid systems.
With compound 20 in hand, a [2 + 2] cycloaddition
would afford the desired chiral cage compound. Never-
(19) (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.
(20) Kahn, S. D.; Hehre, W. J . Tetrahedron Lett. 1986, 27, 5509.
(21) For a more detailed description see refs 14c and 15a.
(22) Bravo, P.; Pregnolato, M.; Resnati, G. J . Org. Chem. 1992, 57,
2726.
(17) The authors have deposited atomic coordinates for 12 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.
(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.

(SS)-2-(p-Tolylsulfinyl)norborneno-p-benzoquinones
Ta ble 2. 1H-NMR Da ta for Com p ou n d s 12-15
δ (ppm), multiplicity, J (in Hz)
endo-syn-13 endo-syn-14
J . Org. Chem., Vol. 62, No. 4, 1997 979
proton
endo-anti-12
endo-anti-15
H1
H2
H3
H4
3.47, m
3.5-3.7, m
3.45, m
3.62, m
6.14-6.26, m
6.14-6.26, m
3.85, m
5.94, dd, 2.9, 5.4
5.99, dd, 3.3, 5.4
4.00, m
5.93, dd, 2.7, 5.5
5.98, dd, 2.7, 5.5
3.80, m
6.1-6.3, m
6.1-6.3, m
4.04, m
H5
H6
H7
H8
H9a
H11a
H11b
H12a
H12b
CH3
3.72, m
3.5-3.7, m
3.60, m
6.64, t, 1.9
6.64, t, 1.9
3.64, m
3.82, d, 3.8
2.30, dt, 9.1, 1.7
1.42, dt, 9.1, 1.6
1.02, dt, 7.1, 1.5
1.91, dt, 7.1, 1.5
2.32, s
3.73, m
6.14-6.26, m
6.14-6.26, m
3.72, m
3.80, d, 3.8
2.33, dt, 9.0, 1.6
1.48, dt, 9.0, 1.6
1.88, dt, 7.2, 1.5
2.05, dt, 7.2, 1.5
2.29, s
6.60, ddd, 0.3, 3.0, 5.0
6.66, ddd, 0.3, 3.0, 5.0
3.5-3.7, m
6.1-6.3, m
6.1-6.3, m
3.78, m
3.21, d, 3.8
2.14, dt, 9.6, 1.5
1.71, dt, 9.6, 1.5
1.89, dt, 7.2, 1.5
2.04, dt, 7.2, 1.5
2.33, s
3.22, d, 3.8
2.11, dt, 9.7, 1.5
1.65, dt, 9.7, 1.8
0.95, dt, 7.1, 1.6
1.87, dt, 7.1, 1.5
2.34, s
AA′BB′tolyl system
7.06, 7.17
7.24, 7.46
7.19, 7.37
7.10,7.28
Sch em e 3
Con clu sion s
We have described a highly stereoselective route to
compounds 12-15, enantiomerically pure synthetic
equivalents of norborneno-p-benzoquinone-cyclopenta-
diene bisadducts. The success of our approach relies on
the high π-facial diastereoselection achieved in the cy-
cloaddition on the sulfinyl substituted quinonic double
bond of 10 and 11 which can be inverted in the presence
of ZnBr2. The selectivity is exclusively controlled by the
sulfoxide group whose steric effects are essential to direct
the diene approach. The effect of the norbornene moiety
of the dienophile to direct such an approach is circum-
vented by the sulfinyl group. Finally, the results ob-
tained in the [2 + 2] internal cycloaddition of 20 and 21
showed that the presence of substituents R to the
carbonyl group inhibited the reaction which was only
possible after the loss of the sulfur substituent.
Exp er im en ta l Section
Melting points were obtained in open capillary tubes and
are uncorrected. 1H- and 13C-NMR spectra were recorded at
200.1 and 50.3 MHz in CDCl3. Diastereomeric adduct 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 12-15 are
collected in Table 2. All reactions were monitored by TLC 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. The apparatuses for inert atmosphere experiments
were dried by flaming in a stream of dry argon. Cyclopenta-
diene was freshly distilled. CH2Cl2 was dried over P2O5. ZnBr2
was flamed in the reaction flask, under a stream of dry argon,
before using. For routine workup, hydrolysis was carried out
with water, extractions with CH2Cl2, and solvent drying with
Na2SO4.
theless, the irradiation of endo-syn-endo-20 in 20%
acetone-benzene at rt for 24 h, produced the cage
compound 5 in 58% yield (Scheme 3), showing neither
sulfur function nor chirality. When the reaction was
stopped before completion, we could detect in the 1H-
NMR spectrum of the crude reaction the corresponding
intermediate endo-syn-endo-4 (see Scheme 1), lacking the
p-tolylthio group, in addition to the starting material and
final products, 20 and 5, respectively. This result showed
that the loss of the thioether group occurred prior to the
[2 + 2] cycloaddition.
(5S,8R,SS)-1,4-Dih ydr oxy-5,8-m eth an o-2-p-tolylsu lfin yl-
5,8-d ih yd r on a p h th a len e (8). To a solution of 6 (936 mg, 3
mmol) in 50 mL of THF was added K2CO3 (4.14 g, 30 mmol,
10 equiv) in 50 mL of H2O. After 1 h at rt, the reaction mixture
was hydrolyzed with 10% HCl and extracted with ethyl ether.
After workup and flash chromatography (eluent: ethyl ether)
compound 8 was obtained as a white solid (81% yield): mp
A second trial, starting from the corresponding endo-
syn-endo sulfone 21 obtained by oxidation of thioether
20 with 2 equiv of m-CPBA (Scheme 3) was also unsuc-
cessful. The irradiation of 21 in the same conditions as
above, yielded again the cage compound 5 in 60% yield,
resulting from the [2 + 2] cycloaddition but lacking the
sulfone function (Scheme 3). Similar problems had been
encountered on other R-substituted ketones structurally
related to 20 and 21 with Cl, Br, or Me groups which
yielded uncharacterizable materials upon irradiation.23
These results suggest that only R-unsubstituted ketones
are able to undergo efficient [2 + 2] photochemical ring
closure.
194-196 °C dec (hexane); [R]20 ) +160 (c 0.3, CHCl3); 1H-
D
NMR δ 2.11 and 2.21 (2H, 2dt, J ) 7.2 and 1.6 Hz), 2.38 (3H,
s), 4.05 and 4.15 (2H, 2m), 6.42 (1H, s), 6.75 and 6.82 (2H,
2dd J ) 3.0 and 5.0 Hz), 7.28 and 7.54 (4H, AA′BB′ system),
9.51 (1H, broad s); 13C-NMR δ 21.3, 46.5, 46.9, 69.3, 111.2,
121.3, 124.9 (2C), 130.0 (2C), 139.7, 141.7, 141.8, 142.2, 142.6,
143.8, 144.0, 145.4; Anal. Calcd for C18H16SO3: C, 69.23; H,
5.13. Found: C, 68.98; H, 4.93.
(5R,8S,SS)-1,4-Dih yd r oxy-5,8-m et h a n e-2-p -t olylsu lfi-
n yl-5,8-d ih yd r on a p h th a len e (9). Compound 9 was obtained
(23) Forman, M. A.; Dailey, W. P. J . Org. Chem. 1993, 58, 1501.

980 J . Org. Chem., Vol. 62, No. 4, 1997
Carren˜o et al.
from 7 as above (84% yield): mp 188-190 °C dec (hexane);
[R]20D ) +31 (c 1.3, CHCl3); 1H-NMR δ 2.15 and 2.21 (2H, 2dt,
J ) 7.2 and 1.6 Hz), 2.34 (3H, s), 4.06 and 4.15 (2H, 2m), 6.44
(1H, s), 6.67 and 6.74 (2H, 2dd, J ) 3.0 and 5.0 Hz), 7.22 and
7.49 (4H, AA′BB′ system), 9.35 (1H, broad s); 13C-NMR δ 21.3,
46.6, 46.9, 69.9, 111.3, 121.6, 124.8 (2C), 130.0 (2C), 139.7,
141.6, 141.8, 142.7, 143.7, 143.8, 143.9, 145.3. Anal. Calcd
for C18H16SO3: C, 69.23; H, 5.13. Found: C, 69.02; H, 5.20.
(5S,8R,SS)-5,8-Meth a n o-2-p-tolylsu lfin yl-5,8-d ih yd r o-
1,4-n a p h th oqu in on e (10). An aqueous solution (50 mL) of
CAN (2.1 g, 4 mmol, 2 equiv) was added to a solution of 8 (624
mg, 2 mmol) in 50 mL of CH3CN and the mixture was stirred
for 2 h. After evaporation of the solvent and workup compound
10 was obtained as an orange solid (92% yield): mp 173-175
°C (ethyl ether); [R]20D ) +656 (c 0.25, CHCl3); 1H-NMR δ 2.33
(2H, m), 2.38 (3H, s), 4.03 and 4.09 (2H, 2m), 6.78 (2H, m),
7.23 (1H, s), 7.27 and 7.65 (4H, AA′BB′ system); 13C-NMR δ
21.4, 48.2, 48.4, 74.4, 125.7 (2C), 130.1 (2C), 131.3, 138.6, 142.1,
142.2, 142.6, 154.1, 160.8, 162.7, 179.9, 181.5. Anal. Calcd
for C18H14SO3: C, 69.66; H, 4.54. Found: C, 69.81; H, 4.39.
(5R,8S,SS)-5,8-Meth a n o-2-p-tolylsu lfin yl-5,8-d ih yd r o-
1,4-n a p h th oqu in on e (11). Compound 11 was obtained from
from 40 mg (0.1 mmol) of 12 (75% yield) or 15 (78% yield) by
refluxing in 5 mL of EtOAc for 24 h, evaporation of the solvent,
and flash chromatography (eluent: hexane/EtOAc 20:1): mp
1
245-246 °C (lit.12a mp 250 °C); H-NMR δ 2.24 (4H, m), 4.00
(4H, m), 6.84 (4H, t, J ) 1.5 Hz).
1r,4r,5r,8r-Tetr 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 (17). Compound 17 was obtained as above, from
13 (82% yield) or 14 (77% yield) as a yellow solid: mp 202-
1
203 °C (lit.12a mp 205 °C); H-NMR δ 2.28 (4H, m), 4.04 (4H,
m), 6.80 (4H, t, J ) 1.5 Hz).
1r,4r,5r,8r-Tetr a h yd r o-1,4:5,8-d im eth a n oa n th r a cen e-
9,10-d iol (18). To a stirred solution of endo-syn-13 (110 mg,
0.3 mmol) in 5 mL of acetone was added 10% aqueous TiCl3
solution dropwise until a pale purple color persisted. After
workup and flash chromatography (eluent: CH2Cl2/ethyl ether
90:10) compound 18 was obtained as a white solid (75%
yield): mp > 300 °C (CHCl3); 1H-NMR (acetone-d6) δ 2.04 and
2.11 (4H, 2dt, J ) 6.6 and 1.7 Hz), 2.97 (2H, broad s), 4.03
(4H, m), 6.68 (4H, t, J ) 1.9 Hz); 13C-NMR (acetone-d6) δ 47.36
(4C), 70.30 (2C), 134.38 (4C), 141.06 (2C), 143.49 (4C). Anal.
Calcd for C16H14O2: C, 80.66; H, 5.92. Found: C, 80.40; H,
6.19.
9 as above (95% yield): mp 168-170 °C (ethyl ether); [R]20
)
en do-syn -(1R,4S,4aS,5R,8S,9aR,SS)-1,4,4a,5,8,9a-Hexah y-
d r o-1,4:5,8-d im eth a n o-4a -p-tolylth ioa n th r a cen e-9,10-d i-
on e (19). Trifluoroacetic anhydride (212 µL, 1.5 mmol, 5
equiv) was added dropwise into a stirred suspension of the
sulfoxide endo-syn-13 (113 mg, 0.3 mmol) and sodium iodide
(134 mg, 9 mmol, 3 equiv) in 10 mL of acetone at -40 °C under
an argon atmosphere. The reaction mixture was stirred for 2
h at the same temperature, and an excess of saturated aqueous
Na2SO3 and Na2CO3 was added. Acetone was removed under
reduced pressure and the aqueous layer was extracted with
diethyl ether. After workup, the residue was flash chromato-
D
1
+506 (c 0.5, CHCl3); H-NMR δ 2.19 and 2.30 (2H, 2dt, J )
7.2 and 1.5 Hz), 2.39 (3H, s), 3.98 and 4.08 (2H, 2m), 6.86 (2H,
t, J ) 1.9 Hz), 7.21 (1H, s), 7.30 and 7.68 (4H, AA′BB′ system);
13C-NMR δ 21.2, 48.0, 48.1, 73.4, 125.6 (2C), 129.9 (2C), 130.9,
138.4, 142.1, 142.2, 142.4, 154.0, 160.7, 162.4, 179.8, 181.3.
Anal. Calcd for C18H14SO3: C, 69.66; H, 4.54. Found: C,
69.53; H, 4.65.
en d o-a n t i -(1S ,4R ,4a R ,5R ,8S ,9a S ,S S )-1,4,4a ,5,8,9a -
H e x a h y d r o -1,4:5,8-d im e t h a n o -4a -p -t o ly ls u lfin y la n -
th r a cen e-9,10-d ion e (12). To a solution of 10 (122 mg, 0.4
mmol) in 10 mL of dry CH2Cl2 at -20 °C was added cyclopen-
tadiene (100 µL, 1.6 mmol, 4 equiv) under argon. After 24 h,
the solvent was evaporated, the residue chromatographed on
silica gel (eluent: CH2Cl2/EtOAc 90:10), and compound 12 was
obtained as a yellow solid (79% yield): mp 131-132 °C (ethyl
graphed (eluent: ethyl ether/hexane 20:80) to give compound
1
19 as a yellow oil (75% yield): [R]20 -74 (c 0.6, CHCl3); H-
D
NMR δ 1.64 (dt, 1H, J ) 9.0 and 1.8 Hz), 1.84 (dt, 1H, J ) 7.2
and 1.6 Hz), 2.13 (dt, 1H, J ) 7.2 and 1.5 Hz), 2.23 (dt, 1H, J
) 9.0 and 1.5 Hz), 2.34 (s, 3H), 3.26 (m, 1H), 3.37 (d, 1H, J )
3.9 Hz), 3.50 (m, 1H), 3.8-3.9 (m, 2H), 5.85 (m, 2H), 6.69 and
6.74 (2ddd, 2H, J ) 0.8, 3.0, and 5.0 Hz), 7.20 and 7.33 (AA′BB′
system, 4H); 13C-NMR δ 21.1, 46.4, 47.9, 48.0, 48.7, 50.3, 60.5,
64.8, 70.7, 127.1, 129.7 (2C), 136.2, 136.4, 136.7 (2C), 139.9,
141.9, 142.3, 164.6, 167.8, 191.4, 193.8. Anal. Calcd for
C23H20SO2: C, 76.64; H, 5.59. Found: C, 76.54; H, 5.41.
en d o-syn -en d o-(1R ,4S ,4a S ,5R ,8S ,8a R ,9a R ,10a S ,SS )-
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 -
tolylth ioa n th r a cen e-9,10-d ion e (20). To a stirred solution
of compound 19 (110 mg, 0.3 mmol) in 5 mL of acetone was
added 10% aqueous TiCl3 solution dropwise until a pale purple
color persisted. After 30 min and workup compound 20 was
obtained as a white solid (82% yield): mp 154-156 °C (MeOH);
ether); [R]20 ) -37 (c 1, CHCl3); 13C-NMR δ 21.1, 45.4, 47.5,
D
47.8, 48.1, 48.2, 53.5, 73.4, 79.9, 124.8 (2C), 129.5 (2C), 136.9,
137.5, 138.7, 140.1, 141.4, 142.1, 164.9, 165.5, 190.8, 193.3.
Anal. Calcd for C23H20SO3: C, 73.38; H, 5.35. Found: C,
73.55; H, 5.41.
en do-syn -(1R,4S,4aS,5S,8R,9aR,SS)-1,4,4a,5,8,9a-Hexah y-
d r o-1,4:5,8-d im eth a n o-4a -p-tolylsu lfin yla n th r a cen e-9,10-
d ion e (14). Compound 14 was obtained from 11 as above as
a yellow oil (92% yield): [R]20 -22 (c 0.7, CHCl3); 13C-NMR δ
D
21.9, 45.7, 48.4, 48.6, 48.7, 48.8, 53.7, 72.2, 78.4, 125.9, 130.3,
137.5 (2C), 138.7, 139.3, 142.8 (2C), 143.0, 143.1, 165.8, 166.9,
191.7, 194.3. Anal. Calcd for C23H20SO3: C, 73.38; H, 5.35.
Found: C, 73.20; H, 5.19.
[R]20
+179 (c 0.3, CHCl3); 1H-NMR δ 1.30 (dt, 1H, J ) 8.6
en do-syn -(1R,4S,4aS,5R,8S,9aR,SS)-1,4,4a,5,8,9a-Hexah y-
d r o-1,4:5,8-d im eth a n o-4a -p-tolylsu lfin yla n th r a cen e-9,10-
d ion e (13). A solution of 10 (122 mg, 0.4 mmol) in 10 mL of
dry CH2Cl2 was added to ZnBr2 (180 mg, 0.8 mmol, 2 equiv)
under argon and the mixture was stirred for 1 h at rt. After
the solution was cooled at -20 °C, cyclopentadiene (100 µL,
1.6 mmol, 4 equiv) was added and the reaction was continued
for 1 h. After workup, the residue was chromatographed on
silica gel (eluent: CH2Cl2/EtOAc 90:10) and compound 13
D
and 1.4 Hz), 1.41 (dt, 1H, J ) 8.6 and 1.9 Hz), 1.48 (dt, 1H, J
) 8.9 and 1.9 Hz), 2.11 (dt, 1H, J ) 8.9 and 1.4 Hz), 2.37 (s,
3H), 2.94 (m, 1H), 2.96 (dd, 1H, J ) 1.3 and 3.7 Hz), 3.29 (m,
3H, H1
), 3.47 (ddd, 1H, J ) 1.3, 3.5 and 11.7 Hz), 4.28 (dd,
1H, J ) 3.5 and 11.7 Hz), 5.70 (dd, 1H, J ) 3.0 and 5.6 Hz),
5.84 and 5.95 (2dd, 2H, J ) 3.3, and 5.7 Hz), 5.99 (dd, 1H, J
) 2.9 and 5.6 Hz), 7.18 and 7.32 (AA′BB′ system, 4H); 13C-
NMR δ 21.3, 43.9, 44.0, 44.4, 44.6, 46.9, 47.6, 50.0, 53.5, 61.6,
67.3, 126.9, 129.8 (2C), 135.8 (2C), 136.1, 136.2, 136.8, 138.4,
140.3, 203.7, 208.2. Anal. Calcd for C23H22SO2: C, 76.21; H,
6.11. Found: C, 75.98; H, 6.30.
obtained as a yellow oil (87% yield): [R]20 ) -195 (c 0.6,
D
CHCl3); 13C-NMR δ 21.3, 45.0, 47.8, 48.3, 48.4, 48.6, 53.2, 70.2,
78.2, 125.2, 129.9, 136.7 (2C), 137.1, 137.4, 142.3, 142.4 (2C),
142.7, 164.6, 168.5, 187.3, 192.3. Anal. Calcd for C23H20SO3:
C, 73.38; H, 5.35. Found: C, 73.26; H, 5.50.
en d o-syn -en d o-(1R ,4S ,4a S ,5R ,8S ,8a R ,9a R ,10a S ,SS )-
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 lfon yla n th r a cen e-9,10-d ion e (21). To a solution of
20 (108 mg, 0.3 mmol) in 5 mL of CH2Cl2 cooled at 0 °C,
m-CPBA (200 mg, 0.6 mmol, 2 equiv) in 5 mL of CH2Cl2 was
added. After the addition, the temperature was raised to rt
and the reaction was continued for 2 h. The mixture was then
treated with NaHCO3 saturated solution, and after workup,
the residue was purified by flash chromatography (eluent:
en d o-a n t i -(1S ,4R ,4a R ,5S ,8R ,9a S ,S S )-1,4,4a ,5,8,9a -
H e x a h y d r o -1,4:5,8-d im e t h a n o -4a -p -t o ly ls u lfin y la n -
th r a cen e-9,10-d ion e (15). Compound 15 was prepared from
11 as above as a yellow solid (88% yield): mp 125-126 °C
(ethyl ether); [R]20 ) -246 (c 0.5, CHCl3); 13C-NMR δ 21.1,
D
45.2, 47.5, 47.6, 48.8, 48.9, 53.3, 74.4, 77.4, 124.5 (2C), 129.7
(2C), 136.5, 137.0, 137.2, 140.0, 141.2, 142.1, 164.4, 167.4,
186.9, 191.7. Anal. Calcd for C23H20SO3: C, 73.38; H, 5.35.
Found: C, 73.55; H, 5.41.
ethyl ether/hexane 40:60) to afford compound 21 as a colorless
1
oil (62% yield): [R]20 +192° (c 0.5, CHCl3); H-NMR δ 1.25
D
1r,4r,5â,8â-Tetr 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 (16). Compound 16 was obtained as a yellow solid
(dt, 1H, J ) 9.3 and 1.7 Hz), 1.30 (dt, 1H, J ) 8.7 and 1.9 Hz),
1.38 (dt, 1H, J ) 8.7 and 1.9 Hz), 2.23 (dt, 1H, J ) 9.3 and 1.4

(SS)-2-(p-Tolylsulfinyl)norborneno-p-benzoquinones
J . Org. Chem., Vol. 62, No. 4, 1997 981
Hz), 2.48 (s, 3H), 2.97 (m, 1H), 3.33 (m, 1H), 3.36 (m, 1H),
3.47 (m, 1H), 3.55 (ddd, 1H, J ) 1.0, 3.7 and 11.6 Hz), 3.97
(dd, 1H, J ) 1.0 and 4.8 Hz), 4.03 (dd, 1H, J ) 3.7 and 11.6
Hz), 5.61 (dd, 1H, J ) 3.1 and 5.5 Hz), 5.77 (d, 1H, J ) 2.8
and 5.6 Hz), 5.96 (dd, 1H, J ) 2.8, and 5.6 Hz), 6.02 (dd, 1H,
J ) 2.8 and 5.5 Hz), 7.39 and 7.66 (AA′BB′ system, 4H); 13C-
NMR δ 21.7, 43.6, 44.5, 44.6, 45.1, 46.9, 50.1, 53.4, 54.1, 55.4,
83.8, 129.6 (2C), 129.8 (2C), 131.7, 135.7, 137.1, 137.6, 140.6,
145.7, 204.2, 207.7. Anal. Calcd for C23H22SO4: C, 70.03; H,
5.62. Found: C, 69.96; H, 5.49.
60% from 21): mp 245-246 °C (lit.13 mp 247-248 °C); 1H-
NMR δ 1.55 (4H, m), 2.68 (4H, m), 2.84 (4H, m), 3.08 (4H, m).
Ack n ow led gm en t. We thank Direccio´n General de
Investigacio´n Cient´ıfica y Te´cnica (Grants PB93-0257
and PB95-0174) and Comunidad Auto´noma de Madrid
(Grants AE 00144/94 and AE00244/95) for financial
support.
H e p t a cyclo[7.6.1.02,8.03,7.04,13.06,12.010,15]h e xa d e ca n e -
11,14-d ion e (5). A solution of compounds 20 (140 mg, 4 mmol)
or 21 (158 mg, 2 mmol) in 20% acetone-benzene (50 mL) 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 (eluent: EtOAc/hexane 40:60) to
afford compound 5 as a white solid (58% yield from 20 and
Su p p or tin g In for m a tion Ava ila ble: An ORTEP drawing
of 12 (1 page). This material is contained in libraries on
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J O9618942