Enantioselective Diels-Alder cycloadditions with (SS)-2-(p- tolylsulfinyl)-1,4-naphthoquinone: Efficient kinetic resolution of chiral racemic vinylcyclohexenes

Article abstract of DOI:10.1021/jo9811874

Chiral racemic vinylcyclohexenes 1a-m, bearing allylic and nonallylic oxygenated substituents on the cyclohexene ring, were submitted to Diels- Alder reactions with enantiomerically pure (SS)-(2-p-tolylsulfinyl)-1,4- naphthoquinone. The tandem cycloadditi

Full text of DOI:10.1021/jo9811874

8320
J . Org. Chem. 1998, 63, 8320-8330
En a n tioselective Diels-Ald er Cycloa d d ition s w ith
(SS)-2-(p-Tolylsu lfin yl)-1,4-n a p h th oqu in on e: Efficien t Kin etic
Resolu tion of Ch ir a l Ra cem ic Vin ylcycloh exen es
M. Carmen Carren˜o,* Antonio Urbano, and Claudio Di Vitta†
Departamento de Quı´mica Orga´nica (C-I), Universidad Auto´noma, Cantoblanco, 28049-Madrid, Spain
Received J une 18, 1998
Chiral racemic vinylcyclohexenes 1a -m , bearing allylic and nonallylic oxygenated substituents
on the cyclohexene ring, were submitted to Diels-Alder reactions with enantiomerically pure (SS)-
(2-p-tolylsulfinyl)-1,4-naphthoquinone. The tandem cycloaddition/pyrolytic sulfoxide elimination
led to the formation of enantiomerically enriched angularly tetracyclic quinones (+)-8a and (+)-
12, arising from the kinetic resolution of the racemic diene. Dienes 1a -c, bearing an alkoxy
substituent at the allylic position C-3, and 1d -g, with C-3 alkoxy and C-5 methyl groups, gave
exclusively quinones (+)-8a -g, resulting from the anti approach to the dienophile. A similar anti
selectivity occurred in cycloadditions of dienes 1i,j, with the alkoxy group situated at the allylic
position C-6. Nonallylic 4-substituted vinylcyclohexenes 1k -m evolved to ca. 75:25 mixtures of
(+)-anti-8k -m and (+)-syn-12k -m derivatives. In all cases, (SS)-(2-p-tolylsulfinyl)-1,4-naphtho-
quinone reacted from the less hindered face of the more reactive s-cis conformation, giving rise to
products in moderate to excellent enantiomeric excesses. Steric effects and torsional interactions
in the corresponding approaches account for the observed π-facial diastereoselectivities at both
partners.
In tr od u ction
studies, no general conclusions can be reached about the
factors responsible for the observed facial diastereose-
lection, making it necessary to consider each system
separately. The presence of a stereogenic center at the
allylic position of either the dienophile10 or the diene
partner11 also imparts sufficient perturbation to control
the π-facial diastereoselectivity. In such systems, theo-
retical and experimental work directed to rationalize the
Among the stereochemical features of asymmetric
Diels-Alder reactions, the π-facial diastereoselectivity
has attracted increasing attention from both synthetic
and theoretical points of view1 due to the well-established
efficiency of this process to generate up to four stereo-
genic centers in a controlled fashion. Many studies have
focused on π-facially perturbed dienes2 and dienophiles.3
The observed results have been rationalized in terms of
steric,4 electronic,5 or torsional6 effects, product stability,7
orbital interactions,8 or hyperconjugation.9 From these
(6) (a) Houk, K. N.; Li, Y.; Evanseck, J . P. Angew. Chem., Int. Ed.
Engl. 1992, 31, 682. (b) Brown, F. K.; Houk, K. N. J . Am. Chem. Soc.
1985, 107, 1971.
(7) (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.
(8) (a) Gleiter, R.; Paquette, L. A. Acc. Chem. Res. 1983, 16, 328.
(b) Ishida, M.; Beniya, Y.; Inagaki, S.; Kato, S. J . Am. Chem. Soc. 1990,
112, 8980.
(9) (a) Wen-Sheng, C.; Turro, N. J .; Srivastava, S.; Li, H.; Le Noble,
W. J . J . Am. Chem. Soc. 1988, 110, 7882. (b) Macaulay, J . B.; Fallis,
A. G. J . Am. Chem. Soc. 1990, 112, 1136. (c) Li, H.; le Noble, W. J .
Recl. Trav. Chim. Pays-Bas 1992, 115, 199.
(10) See ref 5a and the following: (a) Paquette, L. A.; Lin, H. S.;
Gunn, B. P.; Coghlan, M. J . J . Am. Chem. Soc. 1988, 110, 5818. (b)
Haller, J .; Niwayama, S.; Duh, H. Y.; Houk, K. N. J . Org. Chem. 1997,
62, 5728.
(11) For acyclic dienes, see refs 5a, 9b, and the following: (a)
Tripathy, R.; Franck, R. W.; Onan, K. D. J . Am. Chem. Soc. 1988, 110,
3257. (b) Trost, B. M.; Le, D. C. J . Org. Chem. 1989, 54, 2271. (c)
McDougal, P. G.; J ump, J . M.; Rojas, C.; Rico, J . G. Tetrahedron Lett.
1989, 30, 3897. (d) Kaila, N.; Franck, R. W.; Dannenberg, J . J . J . Org.
Chem. 1989, 54, 4206. (e) Barluenga, J .; Gonza´lez, F. J .; Fustero, S.;
Garc´ıa-Granda, S.; Pe´rez-Carren˜o, E. J . Org. Chem. 1991, 56, 4459.
(f) Bloch, R.; Chaptal-Gradoz, N. J . Org. Chem. 1994, 59, 4162. (g)
Adam, W.; Gla¨ser, J .; Peters, K.; Prein, M. J . Am. Chem. Soc. 1995,
117, 9190. For semicyclic dienes, see ref 9b and the following: (h)
Fisher, M. J .; Overman, L. E. J . Org. Chem. 1988, 53, 2630. (i) Fisher,
M. J .; Hehre, W. J .; Kahn, S. D.; Overman, L. E. J . Am. Chem. Soc.
1988, 110, 4625. (j) Datta, S. C.; Franck, R. W.; Triphaty, R.; Quigley,
G. J .; Huang, L.; Chen, S.; Sihaed, A. J . Am. Chem. Soc. 1990, 112,
8472. (k) Larsen, D. S.; O’Shea, M. D. J . Chem. Soc., Perkin Trans. 1
1995, 1019. (l) Lee, J .; Li, J . H.; Oya, S.; Snyder, J . K. J . Org. Chem.
1992, 57, 5301 and references therein. For cyclic dienes, see refs 4f,
5a, 9b, and the following: (m) Macaulay, J . B.; Fallis, A. G. J . Am.
Chem. Soc. 1988, 110, 4074. (n) Winterfeldt, E. Chem. Rev. 1993, 93,
827. (o) Letorneau, J . E.; Wellman, M. A.; Burnell, D. J . J . Org. Chem.
1997, 62, 7272 and references therein.
† On leave from Instituto de Qu´ımica da Universidade de Sa˜o Paulo,
Brazil.
(1) For general reviews on asymmetric Diels-Alder reactions, see:
(a) Oppolzer, W. Angew. Chem., Int. Ed. Engl. 1984, 23, 876. (b)
Paquette, L. A. In Asymmetric Synthesis; Morrison, J . D., Ed.; Academic
Press: New York, 1984; Vol. 3, pp 455-501. (c) Helmchem, G.; Karge,
R.; Weetman, J . In Modern Synthetic Methods; Scheffold, R., Ed.;
Springer-Verlag: New York, 1986; p 261. (d) Carruthers, W. In
Cycloaddition Reactions in Organic Synthesis; Pergamon Press: New
York, 1990; pp 61-72.
(2) (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., Paquette, L. A., Eds.;
Comprehensive Organic Synthesis; Pergamon Press: Oxford, U.K.,
1991; Vol. 5, Chapter 4.
(3) See, for instance: (a) Mehta, G.; Padma, S.; Pattabhi, V.;
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(b) Okamoto, I.; Ohwada, T.; Shudo, K. J . Org. Chem. 1996, 61, 3155.
(c) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Urbano, A.; Lo´pez-Solera, M.
I. J . Org. Chem. 1997, 62, 976.
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Ishihara, K.; Yamamoto, H. J . Am. Chem. Soc. 1994, 116, 1561. (d)
Mikami, K.; Motoyama, Y.; Terada, M. J . Am. Chem. Soc. 1994, 116,
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Org. Chem. 1998, 63, 105.
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10.1021/jo9811874 CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/16/1998

Efficient Kinetic Resolution of Chiral Racemic Vinylcyclohexenes
J . Org. Chem., Vol. 63, No. 23, 1998 8321
Sch em e 1
obtained results led to the conclusion that more than one
factor could be responsible for the observed selectivities.
Thus, efforts directed to better understanding the origin
of such facial diastereoselectivity are welcome.
Our previous work devoted to the use of enantiopure
(SS)-2-(p-tolylsulfinyl)-1,4-quinones as dienophiles12 had
shown a high ability of the sulfoxide to control the
regiochemistry, endo selectivity, and π-facial diastereo-
selectivity of its Diels-Alder cycloadditions with a wide
range of cyclic and acyclic dienes. We established the
tandem Diels-Alder reaction/pyrolytic sulfoxide elimina-
tion as a general one-pot strategy to enantiomerically
pure polycyclic dihydroquinones. More recently, looking
for an enantioselective approach to angucyclinones,13
we envisaged the ability of the sulfinyl group on the
quinonic framework to promote a double induction14 in
the cycloaddition process, leading to the efficient ki-
netic resolution of some chiral racemic vinylcyclohexenes.
The behavior of such kinds of semicyclic dienes contain-
ing a stereogenic allylic carbon have been extensively
studied9b,11h-l in cycloadditions with classical dieno-
philes.15 Major parts of these studies were carried out
by using racemic dienes due to the multistep syntheses
necessary to obtain them in optically pure form.15c
The good results we obtained prompted us to deeply
investigate such a double asymmetric induction process.
In this paper, we report the study of Diels-Alder reac-
tions of several chiral racemic vinylcyclohexenes with
enantiomerically pure (SS)-2-(p-tolylsulfinyl)-1,4-naph-
thoquinone and propose a rationalization for the observed
diastereoselectivity. Differently positioned stereogenic
centers on the diene moiety would allow evaluation of
the influence of proximal and remote substitution on the
face diastereoselection. With this aim, racemic semicyclic
dienes included in this study showed an oxygenated
substituent at allylic position C-3 (1a -g)13 or C-6 (1h -
j) and at nonallylic position C-4 (1k -m ) of the cyclohex-
ene moiety.16 Prior to the present study, no experimental
evidence was available concerning the role of a C-4 or
C-6 stereogenic center in the vinylcyclohexene framework
on π-facial diastereoselection. Besides the intrinsic
fundamental interest, these results have a potential
synthetic utility as a short and efficient route to enan-
tiomerically enriched, angularly fused tetracyclic quino-
nes related to the angucyclinone family of antibiotics.
Sch em e 2
position, were prepared according to previously reported
procedures.17 The methoxymethyloxy (OMOM) deriva-
tive 1c was obtained from 1a in 75% yield by reaction
with MOMCl and diisopropylethylamine (DIPEA). Start-
ing from alcohol 1d ,18 we synthesized semicyclic dienes
1e and 1f, with an oxygenated substituent at C-3 and a
methyl group in cis disposition at C-5. Treatment of 1d
with tert-butyldimethylsilyl chloride (TBSCl) and imida-
zole gave an 87% yield of 1e, and upon reaction with
MOMCl and DIPEA, diene 1f was obtained in 94% yield.
Compound 1g, bearing a OTBS substituent at C-3 and a
methyl group in a trans disposition at C-5, was obtained
from the cis alcohol 1d , which was submitted to Mit-
sunobu conditions19 to yield a mixture of trans and cis
alcohols, where the trans derivative was the major
component. After silylation of this mixture (TBSCl/
imidazole) and flash chromatography, diene trans-1g was
isolated pure in 45% yield.
Resu lts
Syn th esis of Dien es. Semicyclic dienes 1a and 1b
(Scheme 1), with oxygen substituents at the allylic C-3
(12) For an overview of our work, see: (a) Carren˜o, M. C. Chem.
Rev. 1995, 95, 1717. For more recent references, see ref 3c and the
following: (b) 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. (c) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Urbano, A.; Hoyos,
M. A. J . Org. Chem. 1996, 61, 2980. (d) Carren˜o, M. C.; Garc´ıa Ruano,
J . L.; Urbano, A. J . Org. Chem. 1996, 61, 6136. (e) Carren˜o, M. C.;
Garc´ıa Ruano, J . L.; Remor, C. Z.; Urbano, A. Tetrahedron Lett. 1997,
38, 9077.
The required vinylcyclohexenes 1h -j, with allylic
substitution at C-6, were prepared as outlined in Scheme
2. Starting from 2-bromo-2-cyclohexenone (2),20 Luche
reduction21 (NaBH4/CeCl3) afforded in quantitative yield
alcohol 3,22 which after coupling with vinylmagnesium
bromide in the presence of catalytic Pd(0), gave diene 1h
in 57% yield. Protection of this alcohol with either
(13) A part of the work was previously communicated; see: Carren˜o,
M. C.; Urbano, A.; Fischer, J . Angew. Chem., Int. Ed. Engl. 1997, 36,
1621.
(14) Masamune, S.; Choy, W.; Petersen, J . S.; Sita, L. R. Angew.
Chem., Int. Ed. Engl. 1985, 24, 1.
(16) For the sake of clarity, the numbering used for carbinols 1a ,
1d , 1k , and 1l was the same as for the corresponding ethers.
(17) Strekowski, L.; Kong, S.; Battiste, M. A. J . Org. Chem. 1988,
53, 901.
(18) Hecker, S. J .; Heathcock, C. H. J . Org. Chem. 1985, 50, 5159.
(19) Mitsunobu, O. Synthesis 1982, 1.
(20) Smith A. B., III; Brance, S. J .; Prilla, N. W.; Graciano, M. A. J .
Org. Chem. 1982, 47, 1855.
(21) Germal, A. L.; Luche, J . L. J . Am. Chem. Soc. 1981, 103, 5454.
(15) For recent references on synthetic applications, see: (a) Krohn,
K.; Khanbabaee, K. Angew. Chem., Int. Ed. Engl. 1994, 33, 99. (b) Kim,
K.; Sulikowski, G. Angew. Chem., Int. Ed. Engl. 1995, 34, 2396. (c)
Boyd, V. A.; Sulikowski, G. A. J . Am. Chem. Soc. 1995, 117, 8472. (d)
Larsen, D. S.; O’Shea, M. D.; Brooker, S. Chem. Commun. 1996, 203.
(e) Matsuo, G.; Miki, Y.; Nakata, M.; Matsumura, S.; Toshima, K.
Chem. Commun. 1996, 225.

8322 J . Org. Chem., Vol. 63, No. 23, 1998
Carren˜o et al.
Sch em e 3
determined directly from the crude reaction mixtures by
1H NMR analysis. The enantiomeric excesses for com-
pounds (+)-8a -m (Table 1) were measured from H NMR
1
studies on the corresponding Mosher esters31 or by using
chiral lanthanide shift reagents, which required the
preparation of each racemic derivative (()-8a -m , start-
ing from racemic naphthoquinone (()-7.29 In these
cycloadditions, we could recover unreacted dienes (-)-
1a -m in optically active form, but only in the case of
diene (-)-1b did we investigate its enantiomeric purity
(see below).
A Diels-Alder reaction between enantiopure naphtho-
quinone (+)-7 and racemic vinylcyclohexenol 1a (Scheme
4; Table 1, entry 1) afforded a mixture of two products
8a and 9, which could be separated by flash chromatog-
raphy. Compound (+)-8a 13 (28% yield) resulted from
spontaneous pyrolysis of the sulfoxide in the initial
adduct formed by attack of the dienophile on the face of
the diene anti to the hydroxy group. Anthraquinone 913
(51% yield) probably was derived from 8a in a fragmen-
tation process promoted by the free OH as already
observed for similar systems.11k,32 When the same cy-
cloaddition was carried out in water (Table 1, entry 2),
the reaction was faster, with compound (+)-8a now being
the only isolated product in 73% yield. The ee and
absolute configuration of (+)-8a could not be determined
at this stage due to its easy transformation into 9 under
the experimental conditions necessary to generate the
corresponding Mosher esters.31 To avoid the formation
of 9, we decided to prepare a more stable derivative of
(+)-8a . Thus, the treatment of (+)-8a with m-chloro-
peroxybenzoic acid (m-CPBA) afforded epoxide (+)-10a 13
in 90% yield, resulting from the exclusive attack of the
oxidant from the R-face (cis to H12b). The relative
configuration of (+)-10a was initially established by
comparison with a similar intermediate prepared by
Sulikowski15b in the total synthesis of antibiotic SF
2315A. The absolute configuration for (+)-8a and (+)-
10a was confirmed from the Mosher esters of the latter,13
which showed a 50% and a 20% ee for the cycloadditions
in CH2Cl2 and water, respectively.
TBSCl/imidazole or MOMCl/DIPEA led respectively to
derivatives 1i23 (89% yield) and 1j (80% yield).
Compounds 1k -m , bearing the oxygenated substituent
at the nonallylic C-4 position, were prepared as depicted
in Scheme 3. Thus, commercially available ketone 4 was
reduced under Luche conditions21 and further protected
as the OTBS derivative to afford 5 in 90% overall yield.
Deprotection of the ketal function was troublesome under
the usual acidic conditions, but after several trials, ketone
624 could be obtained by treatment of ketal 5 with
CeCl3‚7H2O and NaI in refluxing CH3CN25 in 90% yield.
Preparation of diene 1k was achieved in two steps and
77% overall yield from 6, after formation of the corre-
sponding enoltriflate by treatment with (Tf)2NPh and
potassium hexamethyldisilazide (KHMDS)26 and further
coupling with vinyltributyltin in the presence of catalytic
Pd(0).27 Desilylation of this OTBS derivative with 40%
HF in CH3CN28 afforded dienol 1l in 86% yield, which
after reaction with MOMCl and DIPEA, gave diene 1m
in near quantitative yield (Scheme 3).
Diels-Ald er Rea ction s. With the desired racemic
vinylcyclohexenes in hand, we began the study of Diels-
Alder cycloadditions choosing enantiomerically pure (SS)-
2-(p-tolylsulfinyl)-1,4-naphthoquinone (+)-729 as a model
of a chiral dienophile. The influence of an array of
different solvents and reaction conditions was studied.
The use of Lewis acids was prevented due to the fast
polymerization of the dienes. The best results were
achieved working in CH2Cl2 at room temperature. Under
these conditions, Diels-Alder reactions between quinone
(+)-7 and 2 equiv of racemic vinylcyclohexenes 1a -m
gave rise to the optically active cycloaddition/elimination
products (+)-anti-8a -m (Schemes 4-6) as the major or
exclusive diastereoisomer in moderate to excellent yields
(Table 1). The diastereoisomeric anti/syn30 ratios were
Cycloaddition of (+)-7 and the OTBS-substituted ra-
cemic diene 1b afforded compound (+)-8b13 as the
exclusive product in 75% isolated yield (Scheme 4, Table
1, entry 3). The ee of >97% observed for (+)-8b indicated
an excellent diastereoselection for the initial Diels-Alder
reaction and that a kinetic resolution of the racemic diene
had efficiently occurred. This assumption was confirmed
by recovering unchanged diene 1b13 in optically active
form {[R]20 ) -38 (c 1, CHCl3)}. Desilylation of recov-
D
ered (-)-1b with tetrabutylammonium fluoride (TBAF)
in THF yielded diene (-)-1a 13 {[R]20D ) -47 (c 1, CHCl3)}
whose Mosher esters showed a 75:25 enantiomeric ratio
and the (S) configuration for C-3 as indicated in Scheme
4. We also carried out the cycloaddition between (+)-7
and the racemic OMOM derivative 1c (Scheme 4). In
this case, compound (+)-8c was isolated in 61% yield as
a sole product, showing a 92% ee (Scheme 4; Table 1,
entry 4).
(22) (a) Sonnenberg, J .; Winstein, S. J . Org. Chem. 1962, 27, 748.
(b) Bentley, T. W.; Norman, S. J .; Kemmer, R.; Christl, M. Liebigs Ann.
Chem. 1995, 599.
(23) Adsuta, H.; Fujiwana, K.; Murai, A. Synlett 1997, 307.
(24) Parker, K. A.; Dermatakis, A. J . Org. Chem. 1997, 62, 6692.
(25) Marcantoni, F.; Nobili, F. J . Org. Chem. 1997, 62, 4183.
(26) Pal, K. Synthesis 1995, 1485.
(27) Lee, O.; Snyder, J . K. J . Org. Chem. 1990, 57, 4995.
(28) Newton, R. F.; Reynolds, D. P.; Finch, M. A. W.; Kelly, D. R.;
Roberts, S. M. Tetrahedron Lett. 1979, 3981.
(30) The nomenclature anti refers to adducts resulting from the
approach of the dienophile in the initial cycloaddition on the face of
the diene opposite to the OR function. The syn adducts proceed from
the approach on the face bearing the OR substituent.
(31) (a) Dale, J . A.; Mosher, H. S. J . Am. Chem. Soc. 1973, 95, 512.
(b) Dale, J . A.; Dull, D. L.; Mosher, H. S. J . Org. Chem. 1969, 34, 2543.
(32) Kim, K.; Reibenspies, J .; Sulikowski, G. J . Org. Chem. 1992,
57, 5557.
(29) Carren˜o, M. C.; Garc´ıa Ruano, J . L.; Urbano, A. Synthesis 1992,
651.

Efficient Kinetic Resolution of Chiral Racemic Vinylcyclohexenes
J . Org. Chem., Vol. 63, No. 23, 1998 8323
Ta ble 1. Diels-Ald er Rea ction s of En a n tiop u r e Su lfin yln a p h th oqu in on e (+)-7 a n d 2 Equ iv of Ra cem ic
Vin ylcycloh exen es 1a -m in CH2Cl2 a t Room Tem p er a tu r ea
product
entry
diene
substituent position
t (h)
anti (%)
syn (%)
(0)
(0)
(0)
(0)
(0)
(0)
(0)
(0)
(0)
12h (28)
(0)
(0)
12l (40)
12k (24)
12m (25)
12m (30)
yield, %
enantiomers ratio
1
2c
3
1a
1a
1b
1c
1d
1d
1e
1f
1g
1h
1j
1i
1l
3-OH
3-OH
3-OTBS
3-OMOM
cis-3-OH-5-Me
cis-3-OH-5-Me
cis-3-OTBS-5-Me
cis-3-OMOM-5-Me
trans-3-OTBS-5-Me
6-OH
6-OMOM
6-OTBS
4-OH
4-OTBS
4-OMOM
4-OMOM
72
12
72
72
72
12
72
72
48
48
48
48
16
16
16
24
8a (100)
8a (100)
8b (100)
8c (100)
8d (100)
8d (100)
8e (100)
8f (100)
8g (100)
8h (72)
8j (100)
8i (100)
8l (60)
28
73
75
61
26
69
73
59
62
62f
61
57
55j
85l
49n
53q
75:25b
60:40b
>97:3d
96:4d
4
5
75:25b
60:40b
>97:3e
97:3d
6c
7
8
9
90:10d
88:12,g 75:25h
97:3d
10
11
12
13
14
15
16p
97:3i
89:11k
93:7m
1k
1m
1m
8k (76)
8m (75)
8m (70)
89:11o
93:7o
Data for entries 1-3 and 5-7 were taken from ref 13. Using Mosher esters. c Cycloaddition performed in water. Using Eu(tfc)3.
a
b
d
e Using Eu(tfc)3 on epoxide 10e. f Yield for the mixture of 8h and 12h . Ratio for 8h using Eu(tfc)3 on the mixture of 8j and 12j. Ratio
g
h
for 12h using Eu(tfc)3 on the mixture of 8j and 12j. iUsing Pr(hfc)3. j Overall yield after transformation into the mixture of OMOM derivatives
k
l
m
8m and 12m . Ratio for 8l using Eu(tfc)3 on compound 8m . Yield for the mixture of 8k and 12k . Ratio for 8k using Yb(hfc)3 on epoxide
n
p
q
14. 38% for 8m and 11% for 12m isolated yields. o Ratio for 8m using Eu(tfc)3. Cycloaddition performed at 0 °C. Isolated yield for 8m
37% and for 12m 16%.
Sch em e 4
Sch em e 5
racemic OTBS-substituted derivative 1e reacted with
quinone (+)-7 yielding exclusively compound (+)-8e13 in
73% yield (Scheme 4), whose epoxidation gave derivative
(+)-10e13 in 86% yield, showing an ee value greater than
97% (Table 1, entry 7). This high ee indicated a total
stereocontrol in both the Diels-Alder reaction and ep-
oxidation. Moreover, the absolute configuration of (+)-
10e had been confirmed by X-ray diffraction.13 Diels-
Alder reaction of (+)-7 and racemic OMOM derivative
1f yielded compound (+)-8f as a sole product in 59% yield,
showing a 94% ee (Scheme 4; Table 1, entry 8).
Diels-Alder cycloaddition between sulfinylquinone
(+)-7 and racemic diene 1g, bearing a OTBS group at
C-3 and a methyl substituent at C-5 in trans disposition,
afforded compound (+)-8g in 62% yield as the only
diastereoisomer (Scheme 4; Table 1, entry 9), showing
80% ee. The same reaction at 0 °C for 72 h gave similar
stereochemical results.
Reaction of (+)-7 with racemic dienol 1d , containing
an additional cis methyl group at C-5, afforded products
(+)-8d 13 and 1113 in 26% and 50% yields, respectively,
after flash chromatography (Scheme 4; Table 1, entry 5).
The same reaction in water (Table 1, entry 6) led only to
compound (+)-8d in 69% yield. The m-CPBA oxidation
of (+)-8d gave epoxide (+)-10d 13 in 82% yield, whose
Mosher esters allowed us to establish the absolute
configuration depicted in Scheme 4, showing 50% and
20% ee, respectively, for the products resulting from
cycloadditions performed in CH2Cl2 and water. The
We further focused our attention on the behavior of
semicyclic dienes with allylic substitution at C-6 of the
cyclohexene moiety. Thus, cycloaddition between dienol
1h and quinone (+)-7 (Scheme 5; Table 1, entry 10)
afforded in 62% yield of a 75:25 mixture of the two
compounds 8h (76% ee) and 12h (50% ee), which could
not be separated. These derivatives were respectively
formed from the anti and syn approaches of the diene on
the sulfinylquinonic framework. Their configurational
assignment could be established after transformation into
the corresponding unseparable mixture of OMOM de-

8324 J . Org. Chem., Vol. 63, No. 23, 1998
Carren˜o et al.
Sch em e 6
rivatives 8j and 12j (dimethoxymethane, P2O5)33 and by
comparison with the 1H NMR data of the same compound
(+)-anti-8j (61% yield, 94% ee), which resulted as the
exclusive product from the reaction of quinone (+)-7 and
racemic OMOM-substituted diene 1j (Scheme 5; Table
1, entry 11). Cycloaddition between the OTBS-protected
derivative 1i and (+)-7 (Scheme 5; Table 1, entry 12) led
exclusively to the anti diastereoisomer (+)-8i (57% yield,
94% ee).
Racemic vinylcyclohexenol 1l, bearing the free hydroxy
substituent at the nonallylic C-4 position of the cyclo-
hexene moiety, reacted with enantiopure sulfinylnaph-
thoquinone (+)-7 affording a 60:40 mixture of two prod-
ucts, 8l and 12l (Scheme 6; Table 1, entry 13), which after
purification by flash chromatography, were transformed
(dimethoxymethane, P2O5)33 into the corresponding mix-
ture of separable OMOM derivatives (+)-anti-8m (29%
yield, 78% ee) and (+)-syn-12m (26% yield). Enantio-
meric purity could not be determined using chiral shift
lanthanide reagents neither for (+)-12m nor for epoxide
(+)-13, obtained as the exclusive product in the m-CPBA
oxidation of the former (Scheme 6). The Diels-Alder
reaction of OTBS derivative 1k with (+)-7 afforded a 76:
24 mixture of diastereoisomers anti-8k and syn-12k in
85% yield (Scheme 6; Table 1, entry 14), from which the
major compound (+)-8k could be isolated by flash chro-
matography. Nevertheless, the impossibility of deter-
mining its enantiomeric excess by using chiral shift
lanthanide reagents prompted us to epoxidate (+)-8k (m-
CPBA, CH2Cl2), obtaining a 80:20 mixture of epoxides
(+)-14 and (+)-15 (Scheme 6), easily separated by flash
chromatography. These derivatives were respectively
formed from the attack of the oxidant on the lower and
upper face of the double bond of (+)-8k . Compound (+)-
14 showed a 86% ee (Table 1, entry 14), reflecting the
facial diastereoselectivity for the initial cycloaddition
between diene 1k and quinone (+)-7. Finally, a reaction
between quinone (+)-7 and OMOM derivative 1m af-
forded a separable 75:25 mixture of (+)-anti-8m (38%
yield, 78% ee) and (+)-syn-12m (11% yield), respectively
(Scheme 6; Table 1, entry 15). When the reaction was
performed at 0 °C, the anti/syn ratio was similar (70:30)
but a slightly better ee (86%) was determined for (+)-
8m (Table 1, entry 16).
F igu r e 1. Significant 1H NMR parameters used for configu-
rational assignments.
Con figu r a tion a l Assign m en ts. The relative stereo-
chemistry of tetracyclic derivatives (+)-anti-8 and (+)-
1
syn-12 could be established on the basis of their H NMR
1
data, in particular coupling constants and NOE and H-
1H NOESY experiments34 (Figure 1). In the case of
compounds (+)-anti-8a -g, H1 always appeared as a
doublet of triplets with both J 1,12b and J 1,2ax ranging from
9.2 to 9.9 Hz. These values are consistent with a relative
trans diaxial relationship between H1 and H2ax, and H1
and H12b, respectively (Figure 1).
The absolute configurations of compounds (+)-anti-
8a -g were established from the (R) absolute configura-
tion at C-3 determined from the Mosher esters of epoxides
(+)-10a and (+)-10d 13 and from the absolute stereochem-
istry shown by X-ray data for derivative (+)-10e.13
The relative stereochemistry of compounds (+)-anti-
1
8h -j was determined from a H-1H NOESY experiment
on the nonseparable mixture of compounds (+)-anti-8j
and (+)-syn-12j. We noticed that the NOEs depicted in
Figure 1 show the cis relationship between pseudoaxial
protons H12b, H2ax, and H4ax for (+)-syn-12j, whereas the
only evident NOE for derivative (+)-anti-8j was that
between pseudoaxial protons H12b and H2ax
.
For the configurational assignment of derivatives (+)-
anti-8k -m and (+)-syn-12k -m , selective irradiations
(34) NOE and 1H-1H NOESY experiments were performed in CDCl3
or C6D6 at 500 MHz.
(33) Fuji, K.; Nakano, S.; Fujita, E. Synthesis 1975, 276.

Efficient Kinetic Resolution of Chiral Racemic Vinylcyclohexenes
J . Org. Chem., Vol. 63, No. 23, 1998 8325
effected on (+)-syn-12m showed relevant NOE enhance-
ments ranging from 1.8 to 4.4% between the pseudoaxial
protons H12b, H2ax, and H4ax, whereas the only observed
NOE for derivative (+)-anti-8m occurred between H12b
and H4ax protons.
Finally, the relative configurations of the epoxides
prepared in this study were established on the basis of
the observed long-range coupling constant existent be-
tween H12b and H5 (J 12b,5 ) 1.6 Hz) for compounds (+)-
10a ,d ,e, 13, and 14, having the epoxide group directed
to the lower face of the dihydroquinone moiety (Figure
1). This coupling was not observed for derivative (+)-
15, where the epoxide ring is directed to the upper face
of the dihydroquinone framework.
Discu ssion
To rationalize the results achieved in such a double
asymmetric induction process,35 we must differentiate the
diastereofacial selectivities of both chiral partners. Thus,
the observed anti/syn selectivities reflect the π-facial
diastereoselection of the diene, whereas the resulting
enantiomeric excess for each of the (+)-8 and (+)-12
derivatives indicates the diastereofacial control and the
efficiency of the kinetic resolution exerted by the sulfoxide
group on the quinonic moiety.
To understand the origin of the high enantioselectivity
observed in these reactions, we must focus on the be-
havior of enantiopure sulfinylquinones. For such dieno-
philes, experimentation suggested that the face selectiv-
ity induced by sulfoxide was mainly due to steric factors.
According to previous studies,12 the most favored endo
approach of a diene occurred from the face of the sul-
finylquinone containing the less sterically demanding
lone electron pair at sulfur in the more reactive s-cis
conformation (Figure 2). Thus, considering the (S)
absolute configuration induced at C12b in all derivatives
(+)-8 and (+)-12,36 the resulting enantiomers must arise
from the attack of the diene on the top face of (+)-7.
For the diene partner, the analysis of face diastereo-
selection must differentiate among systems bearing the
stereogenic centers at C-3 (1a -g), C-4 (1k -m ), or C-6
(1h -j). In the former case, our results are in agreement
with those reported by Franck11j and Larsen11k for
cycloadditions of similar 3-oxygenated vinylcyclohexene
derivatives, which indicated the major or exclusive
formation of the anti adduct as the result for the
preferred approach of the dienophile from the face of the
diene anti to the oxygenated function, with the exception
of the free hydroxy derivatives 1a and 1d . For such
dienes, the syn adduct was mainly formed in cycloaddi-
tions with maleimide in benzene, whereas the anti adduct
was the major product in polar solvents.11j With quinones
as dienophiles, only the anti diastereoisomer was formed.11k
These results showed a dependence of face selectivity on
both the solvent and the nature of the dienophile. In our
case, cycloadditions between sulfinylquinone (+)-7 and
hydroxy dienes 1a and 1d in CH2Cl2 (Table 1, entries 1
and 5) gave only anti derivatives (+)-8a and (+)-8d
together with anthraquinones 9 and 11 as the major
F igu r e 2. Favored approaches of semicyclic dienes 1a -m
in Diels-Alder reactions with enantiopure sulfinylnaphtho-
quinone (+)-7.
components of the crude mixtures. Since both types of
anti and syn diastereoisomeric adducts could evolve into
the corresponding anthraquinones, we could not establish
accurately the anti/syn selectivity for these cycloaddi-
tions. When the solvent is changed to water (Table 1,
entries 2 and 6), the exclusive formation of anti deriva-
tives (+)-8a and (+)-8d could be a consequence of the
postulated increased size of the OH group by hydrogen
bond association with the solvent, which favored the anti
approach of the dienophile.11j
The exclusive formation of anti diastereoisomers in the
reactions of 3-OTBS- or 3-OMOM-substituted vinylcy-
clohexenes 1b,c,e-g (Table 1, entries 3-4 and 7-9) is
also consistent with the steric approach control model
proposed to rationalize the observed π-facial diastereo-
selectivities. On the basis of previously reported
models,11j,k the major formation of anti adducts in cy-
cloadditions of dienes bearing a C-3 oxygenated substitu-
ent with several dienophiles could be justified on the endo
approach anti-A shown in Figure 2. Although steric
effects in such an approach are minimized,11j,k according
to Houk’s work, allylic substituents must be staggered
with respect to forming bonds in cycloaddition transition
states.6b,37 The torsional interaction existent in anti-A
(Figure 2) between the partially formed C-C bond and
the pseudoaxial C3-H allylic bond contributes to desta-
bilizing it.38 Thus, we propose anti-B (R1 ) H, MOM,
(35) We use this term in the conventional sense defined by Masam-
une (see ref 14), considering the kinetically favored reaction occurring
between homochiral dienophile (+)-7 and one of the enantiomers of
chiral racemic dienes 1a -m .
(36) The same (S) configuration is always produced by a chiral (SS)-
2-(p-tolylsulfinyl)-1,4-quinone upon reaction with (1E)-substituted
dienes (see refs 12b and 12e).
(37) (a) Caramella, P.; Rondan, N. G.; Paddon-Row: M. N.; Houk,
K. N. J . Am. Chem. Soc. 1981, 103, 2438. (b) Rondan, N. G.; Paddon-
Row, M. N.; Caramella, P.; Mareda, J .; Mueller, P. H.; Houk, K. N. J .
Am. Chem. Soc. 1982, 104, 4974. (c) Paddar-Row, M. N.; Rondan, N.
G.; Houk, K. N. J . Am. Chem. Soc. 1982, 104, 7162. (d) Houk, K. N.;
Moses, S. R.; Wu, Y. D.; Rondan, N. G.; J a¨ger, V.; Schohe, R.; Fronczek,
F. R. J . Am. Chem. Soc. 1984, 106, 3880.

8326 J . Org. Chem., Vol. 63, No. 23, 1998
Carren˜o et al.
TBS; R2 ) R3 ) H), with the oxygen substituent of the
cyclohexene ring in pseudoaxial disposition, which is
responsible for the preferred approach of the sulfi-
nylquinone (+)-7 to the C-3 substituted dienes 1a -c
(Table 1, entries 2-4). In such disposition, torsional
interactions are avoided and the interaction between the
sulfur substituent of the dienophile and the pseudoequa-
torial H3 of the diene is minimized. Taking into account
the existence of a (R1O/H) 1,3-parallel destabilizing
interaction39 in anti-B (Figure 2, R2 ) R3 ) H) and the
torsional strain existent in anti-A,40 we could estimate a
difference in the energy content of both transition states
of ca. 4 kcal/mol in favor of anti-B. In the case of cis-
3,5-disubstituted dienes 1d -f (Table 1, entries 6-8), a
similar approach of anti-B (Figure 2, R2 ) CH3, R3 ) H)
could account for the anti preference. In such situation,
both C-3 (OR1) and C-5 (R2 ) Me) cis pseudoaxial
substituents must increase the energy content of this
transition state by ca. 2.4 kcal/mol,41 a minor amount if
compared to the destabilization generated in anti-A,
arising from the above-mentioned torsional interaction.40
In the case of cycloaddition with trans-3,5-disubstituted
vinylcyclohexene 1g (Table 1, entry 9), the anti diaste-
reofacial selectivity could also be justified by the higher
Although the anti/syn ratios resulting from cycloaddi-
tions with nonallylic 4-oxygenated vinylcyclohexenes
1k -m were lower, similar steric and torsional effects
could account for the observed results (Table 1, entries
13-16). Thus, the steric interactions favoring the anti
over the syn approach correspond to those existent
between the pseudoaxial proton at C-4 [anti-E in Figure
2, (R) enantiomer reacting] versus the pseudoaxial OR
at C-4 [syn-F in Figure 2, (S) enantiomer reacting]42 with
one of the carbonyl groups of quinone (+)-7. In this case,
the energy differences between both approaches must be
smaller than those in the cases discussed above, accord-
ing to the lower selectivity achieved.
Thus, we interpret the kinetic resolution process by
arguing that the endo anti approaches B, C, and E,
represented in Figure 2, correspond to the evolution of
the matched pairs. The most favored situation resulted
from the anti cycloaddition of dienes bearing respectively
the configurations 3R (for 1a -c); 3R,5R (for 1d -f);
3R,5S (for 1g); 6S (for 1h -j); 4R (for 1k -m ) to the less
hindered face of quinone (+)-(SS)-7 reacting in the s-cis
conformation. This model is in full agreement with
recovering a major unreacted diene (-)-1b, showing the
3S absolute configuration. The degree of enantioselec-
tivity achieved in anti cycloadditions increased with the
volume of the OR protecting group (OTBS > OMOM .
OH). This fact is consistent with steric effects contribut-
ing to control both the anti/syn face diastereoselection
in the diene partner and the enantiofacial selectivity on
the sulfinyl dienophile. The slight decrease of optical
purity observed in the products resulting from reactions
of dienes 1g,h ,k -m (76-85% ee) could be attributed to
the higher reactivity of these systems if compared with
those of 1a -f (see reaction times in Table 1).
stability of anti-B (Figure 2, R1 ) TBS, R2 ) H, R3
)
CH3) bearing the C-5 substituent in the pseudoequatorial
arrangement. In all cases, the approach represented as
anti-B corresponds to the evolution of the matched pair,
where the reacting diene is the (3R) enantiomer. This
is in full agreement with the (3S) absolute configuration
of the recovered diene (-)-1b (see Scheme 4).
When the stereogenic center of the diene partner is
located at C-6, we observed again the preferred formation
of anti adducts (+)-8h -j, which were exclusive for OTBS
and OMOM derivatives 1j and 1i (Table 1, entries 11-
12) and major for the reaction of the hydroxy derivative
1h (Table 1, entry 10). We assume that approach anti-C
(Figure 2), with a staggered disposition of the pseu-
doequatorial C3-H and the forming C-C bonds, must
be favored. In such an anti approach, the small pseudo-
axial proton at C-6 is interacting with the naphtho-
quinone framework, with the (6S) enantiomer of dienes
1h -j reacting with quinone (+)-(SS)-7 being the favored
matched pair. When the size of the OR group was
decreased (for reaction with dienol 1h ), syn attack
occurred in a small proportion (28%) giving rise to
compound (+)-12h . Although the absolute configuration
of syn derivative 12h could not be unequivocally deter-
mined, in accord with the steric and torsional interactions
that govern these processes, we can propose approach
syn-D (Figure 2, R ) H), showing the OH group in a
pseudoaxial position, as the approach responsible for the
formation of syn-12h . Accordingly, the syn-matched pair
should result from the cycloaddition between quinone (+)-
(SS)-7 and the (6R) enantiomer of diene 1h .42
Con clu d in g Rem a r k s
Generation of up to three stereogenic centers in the
angular tetracyclic framework of derivatives (+)-8 and
(+)-12 is possible starting from enantiomerically pure
(SS)-2-(p-tolylsulfinyl)-1,4-naphthoquinone (+)-7 and sub-
stituted racemic vinylcyclohexenes 1a -m . The products
are formed in a one-pot Diels-Alder cycloaddition/
sulfoxide pyrolytic elimination sequence. The initial
cycloaddition occurs in a highly endo and π-facial dias-
tereoselective manner with an efficient resolution of the
diene partner. The matched pair results from the anti
approach to the oxygenated substituent of the diene. The
importance of steric factors as well as torsional strain in
the relative stability of the different approaches has been
highlighted. Besides the fundamental study, the re-
ported methodology provides a short enantioselective
approach to highly functionalized systems related to
angucyclinone antibiotics.
Exp er im en ta l Section
(38) Such torsional interactions are similar to those involving formed
bonds.
(39) A (OTMS/H) 1,3-parallel interaction is estimated to be 0.74 kcal/
mol in cyclohexane derivatives; see: Eliel, E. L.; Wilen, S. H Stereo-
chemistry of Organic Compounds; J ohn Wiley & Sons: New York, 1994;
p 696.
(40) The attack of a hydrogen atom on propene in a staggered
arrangement between one allylic C-H bond and the forming C‚‚‚H
bond was estimated by Houk to be favored by 5 kcal/mol over the
eclipsed one (see ref 37a).
Melting points were obtained in open capillary tubes and
are uncorrected. 1H and 13C NMR spectra were recorded in
CDCl3 at 300 and 75 MHz, respectively. Diastereoisomeric
ratios were established by integration of well-separated signals
of both diastereomers in the crude reaction mixtures and are
listed in Table 1. All reactions were monitored by thin-layer
chromatography that was performed on precoated sheets of
(41) This value corresponds to the 1,3-syn-diaxial interaction be-
tween a CH3 and a OH group in a cyclohexane ring; see ref 39, p 707.
(42) This assumption could not be demonstrated since the major
evolution corresponded to the anti approach.

Efficient Kinetic Resolution of Chiral Racemic Vinylcyclohexenes
J . Org. Chem., Vol. 63, No. 23, 1998 8327
silica gel 60, and flash column chromatography was done with
silica gel 60 (230-400 mesh) from Macherey-Nagel. Eluting
solvents are indicated in the text. The apparatus for inert
atmosphere experiments was dried by flaming in a stream of
dry argon. CH2Cl2 was dried over P2O5. For routine workup,
hydrolysis was carried out with water, extractions with
CH2Cl2, and solvent drying with Na2SO4. Vinylcyclohexenes
1a ,17 1b,17 and 1d 18 were prepared according to previously
reported procedures.
Gen er a l P r oced u r e for th e Syn th esis of OMOM De-
r iva tives, Meth od A. To a solution of 4 mmol of the
corresponding alcohol in 8 mL of CH2Cl2 1.4 mL (11 mmol) of
DIPEA and 3.4 mL (42 mmol) of MOMCl were added. The
mixture was stirred at room temperature overnight and
hydrolyzed with a cold aqueous saturated solution of NaHCO3.
After workup and flash chromatography, the pure OMOM
derivative was obtained.
Gen er a l P r oced u r e for th e Syn th esis of OTBS Der iva -
tives, Meth od B. To a solution of 4.8 mmol of the corre-
sponding alcohol in 7 mL of DMF 0.86 g (5.7 mmol) of TBSCl
and 0.82 g (12 mmol) of imidazole were added. The mixture
was stirred at room temperature overnight, hydrolyzed with
an aqueous saturated solution of NH4Cl, and extracted with
ethyl ether. The organic layer was washed with a saturated
solution of NH4Cl and brine and dried with MgSO4. After
evaporation of the solvent and flash chromatography, the pure
OTBS derivative was obtained.
3-[(Meth oxym eth yl)oxy]-vin ylcycloh exen e (1c). 1c was
obtained from 1a 17 following method A (eluent: CH2Cl2/
hexane, 60:40) as a colorless oil (75% yield): 1H NMR δ 6.38
(dd, 1H, J ) 10.7 and 17.7 Hz), 5.78 (broad s, 1H), 5.12 (d,
1H, J ) 17.7 Hz), 5.03 (d, 1H, J ) 10.7 Hz), 4.70 (m, 2H), 4.22
(broad s, 1H), 3.40 (s, 3H), 2.2-1.5 (m, 6H); 13C NMR δ 139.05,
138.54, 128.73, 112.09, 94.66, 70.91, 54.66, 28.88, 23.41, 18.67.
2-Br om o-2-cycloh exen ol (3). To a solution of 1.75 g (10
mmol) of ketone 220 and 3.80 g (12 mmol) of CeCl3‚7H2O in 30
mL of MeOH 0.39 g (10 mmol) of solid NaBH4 were added in
small portions over 15 min. After the mixture was stirred at
room temperature for 15 min and the workup was completed,
crude alcohol 322 was obtained in quantitative yield and used
without further purification: 1H NMR δ 6.22 (t, 1H, J ) 4.0
Hz), 4.21 (m, 1H), 2.3-1.6 (m, 6H).
2-Vin yl-2-cycloh exen ol (1h ). To a mixture of 0.72 g (4.1
mmol) of compound 3 in 6 mL of THF, containing catalytic
amounts of Pd(PPh3)4, 10.2 mL (2.5 equiv) of a solution of 1.0
M vinylmagnesium bromide in THF was added. After being
refluxed for 4 h, the mixture was hydrolyzed with an aqueous
saturated solution of NH4Cl and extracted with ethyl ether.
After workup and flash chromatography (eluent: CH2Cl2),
compound 1h was obtained as a colorless oil (57%): 1H NMR
δ 6.29 (dd, 1H, J ) 10.7 and 18.0 Hz), 5.89 (m, 1H), 5.38 (d,
1H, J ) 18.0 Hz), 5.05 (d, 1H, J ) 10.7 Hz), 4.50 (m, 1H),
2.3-0.8 (m, 7H); 13C NMR δ 137.81, 137.40, 132.43, 111.41,
62.73, 30.86, 25.78, 16.81.
6-[(ter t-Bu t yld im et h ylsilyl)oxy]-1-vin ylcycloh exen e
(1i).23 1i was obtained from 1h following method B (eluent:
hexane/EtOAc 90:10) as a colorless oil (89% yield): 1H NMR
δ 6.26 (dd, 1H, J ) 10.7 and 17.7 Hz), 5.83 (m, 1H), 5.25 (d,
1H, J ) 17.7 Hz), 4.97 (d, 1H, J ) 10.7 Hz), 4.45 (m, 1H),
2.2-1.2 (m, 6H), 0.90 (s, 9H), 0.12 (s, 6H); 13C NMR δ 138.08
(2C), 130.57, 111.16, 64.26, 32.04, 25.96 (3C), 25.91, 18.18,
16.96, -4.07 (2C).
6-[(Meth oxym eth yl)oxy]-1-vin ylcycloh exen e (1j). 1j
was obtained from 1h following method A, after flash chro-
matography (eluent: hexane/EtOAc 50:50), as a colorless oil
(80% yield): 1H NMR δ 6.30 (dd, 1H, J ) 10.7 and 17.7 Hz),
5.95 (m, 1H), 5.34 (d, 1H, J ) 17.7 Hz), 5.01 (d, 1H, J ) 10.7
Hz), 4.82 and 4.67 (AB system, 2H, J ) 7.0 Hz), 4.38 (m, 1H),
3.41 (s, 3H), 2.3-1.4 (m, 6H); 13C NMR δ 137.55, 135.35,
132.36, 110.58, 95.07, 68.19, 55.25, 27.30, 25.32, 16.28.
8-[(ter t-Bu t yld im et h ylsilyl)oxy]-1,4-d ioxa sp ir o[4,5]-
d eca n e (5). 5 was obtained by reduction of commercially
available 1,4-cyclohexanedione monoethylene ketal (4) under
the same conditions employed for the preparation of alcohol 3
and further protection following method B, after flash chro-
matography, (eluent: hexane/EtOAc 90:10) as a colorless oil
(90% yield): 1H NMR δ 3.95 (s, 4H), 3.82 (m, 1H), 2.0-1.4 (m,
8H), 0.90 (s, 9H), 0.03 (s, 6H); 13C NMR δ 108.65, 67.46, 64.13,
32.02, 30.76, 25.75 (3C), 18.02, -3.39 (2C).
cis-3-[(ter t-Bu t yld im et h ylsilyl)oxy]-5-m et h yl-1-vin yl-
cycloh exen e (1e). 1e was obtained from 1d 18 following
method B (eluent: hexane) as a colorless oil (87% yield): 1H
NMR δ 6.35 (dd, 1H, J ) 10.7 and 17.5 Hz), 5.60 (m, 1H), 5.14
(d, 1H, J ) 17.5 Hz), 5.00 (d, 1H, J ) 10.7 Hz), 4.41 (m, 1H),
2.3-1.2 (m, 5H), 1.05 (d, 3H, J ) 6.2 Hz), 0.92 (s, 9H), 0.11
and 0.10 (2s, 6H); 13C NMR δ 139.10, 136.59, 133.10, 112.02,
69.09, 41.47, 32.37, 27.77, 25.89 (3C), 22.09, 18.20, -4.52,
-4.69; HRMS (EI) calcd for C15H28OSi 252.19094, found
252.19112.
cis-3-[(Meth oxym eth yl)oxy]-5-m eth yl-1-vin ylcycloh ex-
en e (1f). 1f was obtained from 1d 18 following method A
(eluent: CH2Cl2/hexane 60:40) as a colorless oil (94% yield):
1H NMR δ 6.36 (dd, 1H, J ) 10.8 and 17.7 Hz), 5.69 (broad s,
1H), 5.17 (d, 1H, J ) 17.7 Hz), 5.01 (d, 1H, J ) 10.8 Hz), 4.73
(m, 2H), 4.30 (broad s, 1H), 3.40 (s, 3H), 2.4-1.1 (m, 5H), 1.05
(d, 3H, J ) 6.0 Hz); 13C NMR δ 138.62, 137.13, 129.94, 111.81,
94.71, 73.38, 54.59, 37.95, 32.05, 27.29, 21.67.
4-[(ter t-Bu tyld im eth ylsilyl)oxy]-cycloh exa n on e (6). A
mixture of 1.9 g (7 mmol) of compound 5, 0.2 g (1.3 mmol) of
NaI, and 4.5 g (12 mmol) of CeCl3‚7H2O in 50 mL of CH3CN
was refluxed for 1 h. After solvent evaporation and flash
chromatography (eluent: hexane/EtOAc 90:10), pure ketone
624 was obtained as a colorless oil (81%): 1H NMR δ 4.15 (m,
1H), 2.8-1.8 (m, 8H), 0.92 (s, 9H), 0.09 (s, 6H).
4-[(ter t-Bu t yld im et h ylsilyl)oxy]-1-vin ylcycloh exen e
(1k ). To a stirred suspension of 0.73 g (3.2 mmol) of compound
6 and 1.7 g (4.8 mmol) of N-phenyltrifluoromethanesulfonimide
in 5 mL of THF and 5 mL of toluene at -78 °C under argon
0.96 g (4.8 mmol) of solid KHMDS was added. After 4 h at
-78 °C, the mixture was quenched with H2O, extracted with
ethyl ether, dried over MgSO4, and purified by flash chroma-
tography (eluent: hexane/EtOAc 90:10) to afford the corre-
sponding enol triflate as a colorless oil (95% yield). To a stirred
solution of 0.86 g (2.4 mmol) of the above obtained enol triflate
in 5 mL of THF, containing 0.42 g (10 mmol) of LiCl and 0.05
g of Pd(PPh3)4, 0.70 mL (2.4 mmol) of vinyltributylstannane
was added under argon. The mixture was refluxed for 7 h,
cooled to room temperature, diluted with hexane, and washed
with 10% aqueous NH4OH solution, H2O, and brine. After
drying of the organic layer with Na2SO4, evaporation of the
solvent, and purification of the residue by flash chromatogra-
phy (eluent: hexane), compound 1k was obtained as a colorless
oil (77% yield): 1H NMR δ 6.38 (dd, 1H, J ) 10.7 and 17.8
Hz), 5.64 (m, 1H), 5.07 (d, 1H, J ) 17.8 Hz), 4.93 (d, 1H, J )
10.7 Hz), 3.90 (m, 1H), 2.5-1.5 (m, 6H), 0.90 (s, 9H), 0.09 (s,
6H); 13C NMR δ 139.27, 135.55, 127.10, 110.48, 67.98, 35.60,
31.45, 25.89 (3C), 22.72, 18.20, -3.58 (2C).
tr a n s-3-[(ter t-Bu t yld im et h ylsilyl)oxy]-5-m et h yl-1-vi-
n ylcycloh exen e (1g). To a mixture of 0.85 g (6.2 mmol) of
alcohol cis-1d ,18 1.5 g (12.3 mmol) of benzoic acid, and 3.2 g
(12.3 mmol) of Ph3P in 85 mL of THF 2.1 g (12.3 mmol) of
ethyl azodicarboxylate was slowly added. After 24 h at room
temperature, the solvent was evaporated and the residue was
purified by flash chromatography (eluent: hexane/EtOAc 95:
5) to afford a mixture of the corresponding benzoic esters,
which was dissolved in 10 mL of MeOH and hydrolyzed with
4 mL of 5% aqueous NaOH solution. After extraction with
ether, drying with MgSO4, and evaporation of the solvent, the
crude mixture of trans and cis alcohols was obtained and
transformed into the corresponding OTBS derivatives follow-
ing method B. After flash chromatography (eluent: hexane),
compound trans-1g was obtained as a colorless oil (45%
yield): 1H NMR δ 6.36 (dd, 1H, J ) 11.3 and 17.2 Hz), 5.68
(m, 1H), 5.20 (d, 1H, J ) 17.2 Hz), 5.01 (d, 1H, J ) 11.3 Hz),
4.32 (dd, 1H, J ) 4.3 and 8.0 Hz), 2.4-1.2 (m, 5H), 1.00 (d,
3H, J ) 6.5 Hz), 0.90 (s, 9H), 0.08 (s, 6H); 13C NMR δ 139.64,
137.74, 129.99, 112.31, 65.56, 40.30, 32.43, 25.97 (3C), 23.48,
21.59, 18.30, -3.67, -3.82; HRMS (EI) calcd for C15H28OSi
252.19094, found 252.19080.

8328 J . Org. Chem., Vol. 63, No. 23, 1998
Carren˜o et al.
4-Vin yl-3-cycloh exen ol (1l). To a solution of 0.52 g (2.2
mmol) of 1k in 20 mL of CH3CN 0.2 mL of a 40% aqueous HF
solution was added at room temperature. The mixture was
stirred for 20 min and diluted with CH2Cl2. After workup and
flash chromatography (eluent: CH2Cl2), alcohol 1l was ob-
tained as a colorless oil (91%): 1H NMR δ 6.35 (dd, 1H, J )
10.9 and 17.0 Hz), 5.64 (m, 1H), 5.08 (d, 1H, J ) 17.0 Hz),
4.94 (d, 1H, J ) 10.9 Hz), 3.98 (m, 1H), 2.5-1.6 (m, 7H); 13C
NMR δ 139.50, 136.01, 126.59, 111.28, 67.32, 35.19, 30.95,
22.31.
4-[(Meth oxym eth yl)oxy]-1-vin ylcycloh exen e (1m ). 1m
was obtained from 1l following method A, after flash chroma-
tography (eluent: CH2Cl2), as a colorless oil (95% yield): 1H
NMR δ 6.34 (dd, 1H, J ) 10.8 and 17.6 Hz), 5.64 (m, 1H), 5.06
(d, 1H, J ) 17.6 Hz), 4.93 (d, 1H, J ) 10.8 Hz), 4.72 and 4.71
(AB system, 2H, J ) 7.0 Hz), 3.85 (m, 1H), 3.38 (s, 3H), 2.7-
1.6 (m, 6H); 13C NMR δ 139.11, 135.72, 126.36, 110.68, 94.77,
71.98, 55.23, 32.44, 27.87, 22.11.
Gen er al P r ocedu r e for Diels-Alder Reaction s, Meth od
C. To a solution of (SS)-2-(p-tolylsulfinyl)-1,4-naphthoquinone
(+)-729 (0.15 g, 0.5 mmol) in 5 mL of dry CH2Cl2 under argon
the corresponding racemic diene 1a -m (1.0 mmol, 2 equiv)
was added. After the time required in each case (see Table 1
for reaction conditions) and evaporation of the solvent, crude
dihydroanthraquinones anti-(+)-8a-m and/or syn-(+)-12h ,k-m
were obtained and purified by crystallization or flash chro-
matography. Physical and spectroscopic data for (+)-8b and
(+)-8e were previously reported.13
4-(9′,10′-Dih ydr oan th r acen -2′-yl)-3-m eth ylbu tan al (11).11k
11 was obtained from 1a following method C, after flash
chromatography (eluent: CH2Cl2/EtOAc 95:5), in 51% yield:
1H NMR δ 9.75 (t, 1H, J ) 2.0 Hz), 8.29 (m, 2H), 8.23 (d, 1H,
J ) 7.9 Hz), 8.08 (d, 1H, J ) 1.8 Hz), 7.79 (m, 2H), 7.59 (dd,
1H, J ) 1.8 and 7.9 Hz), 2.83 and 2.67 (2dd, 2H, J ) 6.2 and
13.2 Hz, J ) 7.1 and 13.2 Hz), 2.6-2.2 (m, 3H), 0.99 (d, 3H, J
) 6.5 Hz).
(1R,3R,12bS)-1-[(ter t-Bu tyld im eth ylsilyl)oxy]-3-m eth -
yl-1,2,3,4,6,12b -h exa h yd r ob en z[a ]a n t h r a cen -7,12-d ion e
(8e).13 8e was obtained from 1e following method C, after
flash chromatography (eluent: hexane/EtOAc 95:5), in 73%
yield.
(1R ,3R ,12b S )-1-[(M e t h o x y m e t h y l)o x y ]-3-m e t h y l-
1,2,3,4,6,12b-h exa h yd r oben z[a ]a n th r a cen -7,12-d ion e (8f).
8f was obtained from 1f following method C, after flash
chromatography (eluent: hexane/EtOAc 80:20), in 59% yield:
mp 114-116 °C (MeOH); [R]20D ) +130 (c 0.6, CHCl3); 1H NMR
δ 8.08 (m, 2H), 7.69 (m, 2H), 5.59 (t, 1H, J ) 3.7 Hz), 4.51 and
4.33 (AB system, 2H, J ) 7.1 Hz), 3.73 (ddd, 1H, J ) 4.1, 5.4,
and 9.9 Hz), 3.40 and 3.11 (ddt, 1H, J ) 1.7, 25.0 and 3.9 Hz,
m, 1H), 3.32 (dt, 1H, J ) 3.6 and 9.9 Hz), 3.03 (s, 3H), 2.4-
1.4 (m, 5H), 1.02 (d, 3H, J ) 6.0 Hz); 13C NMR δ 184.56, 184.38,
144.32, 141.66, 136.53, 133.54, 133.18, 132.89, 131.83, 126.30,
126.08, 115.82, 94.82, 81.17, 55.28, 42.88, 42.62, 41.92, 33.36,
25.49, 21.90. Anal. Calcd for C21H22O4: C, 74.54; H, 6.55.
Found: C, 74.18; H, 6.87.
(1R,3S,12bS)-1-[(ter t-Bu tyld im eth ylsilyl)oxy]-3-m eth -
yl-1,2,3,4,6,12b -h exa h yd r ob en z[a ]a n t h r a cen -7,12-d ion e
(8g). 8g was obtained from 1g following method C, after flash
chromatography (eluent: hexane/EtOAc 90:10), in 62% yield:
mp 125-126 °C (MeOH); [R]20D ) +78 (c 0.2, CHCl3); 1H NMR
δ 8.06 (m, 2H), 7.70 (m, 2H), 5.55 (m, 1H), 3.71 (dt, 1H, J )
9.6 and 4.3 Hz), 3.56 (dt, 1H, J ) 3.7 and 9.6 Hz), 3.42 and
3.17 (ddt, 1H, J ) 2.0, 24.3, and 4.0 Hz, ddt, 1H, J ) 2.3, 24.3,
and 4.6 Hz), 2.4-1.7 (m, 5H), 0.96 (d, 3H, J ) 7.3 Hz), 0.72 (s,
9H), -0.14 and -0.37 (2s, 6H); 13C NMR δ 184.51, 184.12,
144.94, 141.17, 134.26, 133.37, 133.00, 131.80, 126.56, 126.11,
125.97, 117.47, 73.76, 45.40, 43.11, 40.35, 28.56, 25.54, 25.29
(3C), 18.74, 17.85, -3.27, -3.35. Anal. Calcd for C25H32O3Si:
C, 73.49; H, 7.90. Found: C, 73.11; H, 8.23.
(4S,12b S)-4-Hyd r oxy-1,2,3,4,6,12b-h exa h yd r oben z[a ]-
a n t h r a cen -7,12-d ion e (8h ) a n d (4R,12b S)-4-H yd r oxy-
1,2,3,4,6,12b-h exah ydr oben z[a ]an th r acen -7,12-dion e (12h ).
8h and 12h were obtained from 1h following method C, after
flash chromatography (eluent: hexane/EtOAc 65:35), in 62%
yield as an unseparable 72:28 mixture. The following data
correspond to the major compound 8h : 1H NMR δ 8.07 (m,
2H), 7.70 (m, 2H), 5.71 (dt, 1H, J ) 1.1 and 3.3 Hz), 4.42 (t,
1H, J ) 2.7 Hz), 3.90 (m, 1H), 3.25 (m, 2H), 2.4-1.0 (m, 7H);
13C NMR δ 184.76, 184.14, 144.72, 141.05, 139.66, 133.52,
133.80, 132.41, 131.85, 126.31, 126.01, 116.00, 72.90, 35.13,
34.77, 32.94, 24.92, 21.16; HRMS (EI) (from the mixture) calcd
for C18H16O3 280.10994, found 280.10989.
(4S,12bS)-4-[(Meth oxym eth yl)oxy]-1,2,3,4,6,12b-h exah y-
d r oben z[a ]a n th r a cen -7,12-d ion e (8j) a n d (4R,12bS)-4-
[(Met h oxym et h yl)oxy]-1,2,3,4,6,12b -h exa h yd r ob en z[a ]-
a n th r a cen -7,12-d ion e (12j). To a solution of 78 mg (0.28
mmol) of a mixture of 8h and 12h in 3 mL of dry CHCl3 2.0 g
(26 mmol) of dimethoxymethane and 0.2 g (1.4 mmol) of P2O5
were added at room temperature, and the mixture was stirred
for 1 h. The mixture was poured into 25 mL of a cold aqueous
saturated solution of NaHCO3, extracted with ethyl ether, and
dried over MgSO4. After evaporation of the solvent and flash
chromatography (eluent: hexane/EtOAc 70:30), the mixture
of 8j and 12j was obtained in 71% yield.
(4S,12bS)-4-[(ter t-Bu tyld im eth ylsilyl)oxy]-1,2,3,4,6,12b-
h exa h yd r oben z[a ]a n th r a cen -7,12-d ion e (8i). 8i was ob-
tained from 1i following method C, after flash chromatography
(eluent: hexane/EtOAc 90:10), in 57% yield: mp 99-101 °C
(MeOH); [R]20D ) +142 (c 0.5, CHCl3); 1H NMR δ 8.03 (m, 2H),
7.60 (m, 2H), 5.28 (t, 1H, J ) 3.4 Hz), 4.24 (t, 1H, J ) 2.9 Hz),
4.16 (dd, 1H, J ) 3.7 and 10.9 Hz), 3.22 and 3.06 (ddd, 1H, J
) 3.4, 5.5, and 24.5 Hz, ddd, 1H, J ) 3.2, 6.9, and 24.5 Hz),
(1R,12bS)-1-Hyd r oxy-1,2,3,4,6,12b-h exa h yd r oben z[a ]-
a n th r a cen -7,12-d ion e (8a ). 8a was obtained from 1a fol-
lowing method C, after flash chromatography, (eluent: CH2Cl2/
EtOAc 95:5) in 28% yield: mp 170-171 °C (MeOH); [R]20
)
D
+3.4 (c 0.25, CHCl3); 1H NMR (CDCl3 + D2O) δ 8.10 (m, 2H),
7.73 (m, 2H), 5.60 (m, 1H), 3.50 (ddd, 1H, J ) 4.1, 5.7, and 9.9
Hz), 3.32 (dt, 1H, J ) 3.9 and 9.9 Hz), 3.40 and 3.15 (2m, 2H),
2.4-1.2 (m, 6H); 13C NMR δ 187.09, 184.15, 142.94, 142.34,
136.63, 133.60, 133.39, 131.93, 131.66, 126.56, 125.93, 115.32,
76.89, 44.98, 37.54, 34.39, 25.78, 25.16; HRMS (EI) calcd for
C
18H16O3 280.10994, found 280.10925.
4-(9′,10′-Dih yd r oa n th r a cen -2′-yl)-bu ta n a l (9).11k 9 was
obtained from 1a following method C, after flash chromatog-
raphy (eluent: CH2Cl2/EtOAc 95:5), in 51% yield: 1H NMR δ
9.79 (t, 1H, J ) 1.5 Hz), 8.29 (m, 2H), 8.23 (d, 1H, J ) 7.9
Hz), 8.11 (d, 1H, J ) 1.8 Hz), 7.78 (m, 2H), 7.62 (dd, 1H, J )
1.8 and 7.9 Hz), 2.83 (m, 2H), 2.53 (dt, 2H, J ) 1.5 and 7.5
Hz), 2.04 (m, 2H).
(1R,12b S)-1-[(ter t-Bu t yld im et h ylsilyl)oxy]-1,2,3,4,6,-
12b-h exa h yd r oben z[a ]a n th r a cen -7,12-d ion e (8b).13 8b
was obtained from 1b following method C, after flash chro-
matography (eluent: hexane/EtOAc 90:10), in 75% yield.
(1R,12bS)-1-[(Meth oxym eth yl)oxy]-1,2,3,4,6,12b-h exah y-
d r oben z[a ]a n th r a cen -7,12-d ion e (8c). It was obtained
from 1c following method C, after flash chromatography
(eluent: hexane/EtOAc 70:30), in 61% yield: mp 148-150 °C
(MeOH); [R]20D ) +251 (c 0.6, CHCl3); 1H NMR δ 8.08 (m, 2H),
7.70 (m, 2H), 5.60 (m, 1H), 4.51 and 4.34 (AB system, 2H, J )
6.9 Hz), 3.78 (ddd, 1H, J ) 4.0, 5.5 and 9.8 Hz), 3.40 and 3.12
(ddt, 1H, J ) 1.8, 24.5, and 4.0 Hz m, 1H), 3.31 (dt, 1H, J )
4.0 and 9.8 Hz), 3.00 (s, 3H), 2.3-1.3 (m, 6H); 13C NMR δ
184.13, 183.98, 143.89, 141.36, 137.15, 133.24, 132.88, 132.65,
131.58, 126.00, 125.77, 115.39, 94.59, 81.73, 54.95, 42.90,
34.24, 33.17, 25.99, 25.13. Anal. Calcd for C20H20O4: C, 74.06;
H, 6.21. Found: C, 73.87; H, 6.60.
(1R,3R,12bS)-1-Hyd r oxy-3-m eth yl-1,2,3,4,6,12b-h exa h y-
d r oben z[a ]a n th r a cen -7,12-d ion e (8d ). 8d was obtained
from 1d following method C, after flash chromatography
(eluent: CH2Cl2/EtOAc 95:5), in 26% yield: mp 175-176 °C
(ethyl ether); [R]20 ) +56 (c 1, CHCl3); 1H NMR (CDCl3
+
D
D2O) δ 8.10 (m, 2H), 7.72 (m, 2H), 5.59 (m, 1H), 3.5-3.0 (m,
4H), 2.4-2.1 (m, 2H), 1.8-1.5 (m, 2H), 1.38 (dd, 1H, J ) 10.3
and 12.2 Hz), 1.03 (d, 3H, J ) 6.2 Hz); 13C NMR δ 187.34,
184.28, 143.11, 142.48, 135.93, 133.73, 133.50, 131.98, 131.79,
126.70, 126.07, 115.62, 76.23, 46.42, 44.56, 42.95, 32.93, 25.34,
21.75; HRMS (EI) calcd for
294.12521.
C19H18O3 294.12559, found

Efficient Kinetic Resolution of Chiral Racemic Vinylcyclohexenes
J . Org. Chem., Vol. 63, No. 23, 1998 8329
2.6-1.1 (m, 6H), 1.04 (s, 9H), 0.13 and 0.11 (2s, 6H); 13C NMR
δ 184.91, 184.29, 145.11, 141.25, 140.85, 133.45, 133.31,
132.51, 131.97, 126.29, 125.99, 113.83, 73.32, 36.37, 35.34,
33.06, 25.81, 24.88 (3C), 21.22, 18.12, -3.24, -3.63. Anal.
Calcd for C24H30O3Si: C, 73.06; H, 7.67. Found: C, 72.99; H,
7.91.
2 equiv) in 2 mL of CH2Cl2 was added. After 4 h at 0 °C, the
mixture was treated with a saturated solution of NaHCO3.
After workup and purification by crystallization or flash
cromatography, epoxides were obtained as yellow solids.
Physical and spectroscopic data for (+)-10e were previously
reported.13
(4S,12bS)-4-[(Meth oxym eth yl)oxy]-1,2,3,4,6,12b-h exah y-
d r oben z[a ]a n th r a cen -7,12-d ion e (8j). 8j was obtained from
1j following method C, after flash chromatography (eluent:
hexane/EtOAc 70:30), in 61% yield: mp 148-150 °C (MeOH);
[R]20D ) +224 (c 0.4, CHCl3); 1H NMR δ 8.07 (m, 2H), 7.70 (m,
2H), 5.73 (t, 1H, J ) 3.5 Hz), 4.64 and 4.55 (AB system, 2H,
J ) 6.5 Hz), 4.24 (t, 1H, J ) 2.9 Hz), 3.72 (ddd, 1H, J ) 3.5,
7.5, and 17.6), 3.38 (s, 3H), 3.34 and 3.18 (ddd, 1H, J ) 3.2,
6.0, and 24.5 Hz, ddd, 1H, J ) 3.5, 7.2, and 24.5 Hz), 2.4-1.1
(m, 6H); 13C NMR δ 184.77, 184.24, 144.74, 141.15, 137.13,
133.53, 133.40, 132.47, 131.92, 126.31, 126.06, 117.97, 93.29,
75.75, 55.27, 35.05, 33.41, 33.30, 25.01, 21.69; HRMS (EI) calcd
for C20H20O4 324.13616, found 324.13562.
(1R,4a S,5R,12bS)-4a ,5-Ep oxy-1-h yd r oxy-1,2,3,4,4a ,5,6,-
12b-octa h yd r oben z[a ]a n th r a cen -7,12-d ion e (10a ). 10a
was obtained from (+)-8a following method D, after flash
chromatography (eluent: CH2Cl2/EtOAc 90:10), in 90% yield:
1
mp 169-170 °C (ethyl ether); [R]20 ) +20 (c 1.5, CHCl3); H
D
NMR (CDCl3 + D2O) δ 8.05 (m, 2H), 7.68 (m, 2H), 3.56 and
2.80 (dt, 1H, J ) 20.4 and 1.5 Hz; dt, 1H, J ) 20.4 and 1.7
Hz), 3.51 (dq, 1H, J ) 10.2 and 1.4 Hz), 3.39 (dt, 1H, J ) 3.7
and 10.2 Hz), 3.26 (q, 1H, J ) 1.6 Hz), 2.3-1.3 (m, 6H); 13C
NMR δ 185.94, 184.06, 142.44, 139.46, 133.64, 133.46, 129.85,
129.54, 126.53, 126.07, 74.63, 61.16, 56.37, 44.45, 35.63, 32.78,
24.50, 21.14; HRMS (EI) calcd for C18H16O4 296.104 86, found
296.105 26.
(2R,12b S)-2-[(ter t-Bu t yld im et h ylsilyl)oxy]-1,2,3,4,6,-
12b-h exa h yd r oben z[a ]a n th r a cen -7,12-d ion e (8k ). 8k was
obtained from 1k following method C, after flash chromatog-
raphy (eluent: hexane/EtOAc 90:10), in 63% yield: mp 113-
115 °C (MeOH); [R]20D ) +104 (c 0.25, CHCl3); 1H NMR δ 8.07
(m, 2H), 7.68 (m, 2H), 5.50 (m, 1H), 4.18 (m, 1H), 3.96 (m,
1H), 3.22 (m, 2H), 2.7-1.2 (m, 6H), 1.00 (s, 9H), 0.22 and 0.11
(2s, 6H); 13C NMR δ 184.85, 183.97, 145.19, 141.90, 138.72,
133.31, 133.14, 132.56, 131.92, 126.28, 125.92, 112.87, 67.21,
42.00, 36.11, 31.85, 29.87, 25.88 (3C), 25.20, 18.18, -3.32,
(1R,3S,4a S,5R,12b S)-4a ,5-E p oxy-1-h yd r oxy-3-m et h yl-
1,2,3,4,4a ,5,6,12b -oct a h yd r ob en z[a ]a n t h r a cen -7,12-d i-
on e (10d ). 10d was obtained from (+)-8d following method
D, after flash chromatography (eluent: CH2Cl2/EtOAc 90:10),
in 82% yield: mp 225-226 °C (MeOH); [R]20 ) +18 (c 1.5,
D
CHCl3); 1H NMR (CDCl3 + D2O) δ 8.06 (m, 2H), 7.70 (m, 2H),
3.56 and 2.79 (dd, 1H, J ) 20.4 and 2.1 Hz, dt, 1H, J ) 20.4
and 1.5 Hz), 3.45 (m, 2H), 3.26 (m, 1H), 2.18 (m, 1H), 1.74 (m,
2H), 1.5-1.2 (m, 1H), 1.41 (dd, 1H, J ) 1.8 and 8.9 Hz), 1.05
(d, 3H, J ) 6.1 Hz); 13C NMR δ 186.24, 184.16, 142.55, 139.58,
133.80, 133.59, 131.86, 131.80, 126.69, 126.23, 73.96, 60.71,
56.52, 44.58, 43.95, 41.38, 28.33, 24.60, 21.57; HRMS (EI) calcd
for C19H18O4 310.12051, found 310.12061.
-3.44. Anal. Calcd for
C24H30O3Si: C, 73.06; H, 7.67.
Found: C, 72.70; H, 8.06.
(2R ,12b S )-2-H yd r oxy-1,2,3,4,6,12b -h e xa h yd r ob e n z-
[a ]a n t h r a cen -7,12-d ion e (8l) a n d (2S,12bS)-2-Hyd r oxy-
1,2,3,4,6,12b-h exah ydr oben z[a ]an th r acen -7,12-dion e (12l).
8l and 12l were obtained from 1l following method C as a 60:
40 mixture in 65% yield. After flash chromatography (elu-
ent: hexane/EtOAc 70:30), a not completely pure little portion
of both alcohols was separated. 8l: 1H NMR δ 8.05 (m, 2H),
7.70 (m, 2H), 5.52 (m, 1H), 4.27 (m, 1H), 3.93 (m, 1H), 3.24
(m, 2H), 2.7-2.3 (m, 2H), 2.2-1.9 (m, 3H), 1.7-1.4 (m, 2H).
12l: 1H NMR δ 8.08 (m, 2H), 7.71 (m, 2H), 5.56 (m, 1H), 4.03
(tt, 1H, J ) 4.2 and 11.2 Hz), 3.45 (m, 1H), 3.26 (m, 2H), 2.7-
1.1 (m, 7H). The mixture of 8l and 12l was transformed into
the corresponding OMOM derivatives 8m and 12m , in 55%
yield after flash chromatography (eluent: hexane/EtOAc 85:
15), by using the above-mentioned procedure to obtain the
mixture of 8j and 12j.
(2R,12bS)-2-[(Meth oxym eth yl)oxy]-1,2,3,4,6,12b-h exah y-
d r oben z[a ]a n th r a cen -7,12-d ion e (8m ). 8m was obtained
from 1m following method C, after separation of the resulting
75:25 mixture of 8m and 12m by flash chromatography
(eluent: hexane/EtOAc 85:15), in 38% yield: mp 119-121 °C
(MeOH); [R]20D ) +313 (c 0.2, CHCl3); 1H NMR δ 8.07 (m, 2H),
7.70 (m, 2H), 5.52 (m, 1H), 4.95 and 4.81 (AB system, 2H, J )
7.0 Hz), 4.06 (m, 1H), 3.84 (m, 1H), 3.50 (s, 3H), 3.24 (m, 2H),
2.6-1.2 (m, 6H); 13C NMR δ 184.79, 184.20, 144.60, 142.12,
138.08, 133.48, 133.33, 132.50, 131.97, 126.22, 126.06, 113.22,
94.35, 70.84, 55.47, 38.32, 33.33, 32.10, 30.26, 25.22. Anal.
Calcd for C20H20O4: C, 74.06; H, 6.21. Found: C, 73.75; H,
6.54.
(1R,3S,4a S,5R,12bS)-1-[(ter t-Bu tyld im eth ylsilyl)oxy]-
4a ,5-ep oxy-3-m eth yl-1,2,3,4,4a ,5,6,12b-octa h yd r oben z[a ]-
a n th r a cen -7,12-d ion e (10e).13 10e was obtained from (+)-
8e following method D, after flash chromatography (eluent:
hexane/EtOAc 90:10) in 86% yield.
(2S,4a S,5R,12bR)-4a ,5-Ep oxy-2-[(m eth oxym eth yl)oxy]-
1,2,3,4,4a ,5,6,12b -oct a h yd r ob en z[a ]a n t h r a cen -7,12-d i-
on e (13). 13 was obtained from (+)-12m following method
D, after flash chromatography (eluent: hexane/EtOAc 65:35),
in 67% yield as an oil: [R]20 ) +209 (c 0.7, CHCl3); 1H NMR
D
δ 8.05 (m, 2H), 7.69 (m, 2H), 4.71 and 4.67 (AB system, 2H, J
) 7.0 Hz), 3.85 (tt, 1H, J ) 3.6 and 11.3 Hz), 3.54 (m, 1H),
3.36 (s, 3H), 3.32 (q, 1H, J ) 1.6 Hz), 3.52 and 2.80 (m, 1H,
dt, 1H, J ) 20.7 and 2.1 Hz), 2.5-1.1 (m, 6H); 13C NMR δ
184.43, 183.46, 143.43, 138.66, 133.62, 133.60, 132.03, 131.86,
126.36, 126.23, 94.97, 73.99, 61.02, 57.03, 55.33, 37.51, 34.36,
31.97, 31.32, 24.59; HRMS (EI) calcd for C20H20O5 340.131 07,
found 340.131 53.
(2R,4a S,5R,12bR)-2-[(ter t-Bu tyld im eth ylsilyl)oxy]-4a ,5-
e p oxy-1,2,3,4,4a ,5,6,12b -oct a h yd r ob e n z[a ]a n t h r a ce n -
7,12-d ion e (14). 14 was obtained from (+)-8k following
method D, after flash chromatography (eluent: hexane/EtOAc
90:10), in 56% yield: mp 199-201 °C (MeOH); [R]20 ) +184
D
(c 0.5, CHCl3); 1H NMR δ 8.06 (m, 2H), 7.68 (m, 2H), 4.17 (m,
1H), 3.97 (m, 1H), 3.51 and 2.78 (dd, 1H, J ) 1.8 and 19.9 Hz,
ddd, 1H, J ) 2.1 and 19.9 Hz), 3.28 (q, 1H, J ) 1.6 Hz), 2.6-
1.2 (m, 6H), 1.01 (s, 9H), 0.20 and 0.11 (2s, 6H); 13C NMR δ
184.64, 183.25, 144.93, 138.52, 133.45, 133.33, 132.22, 131.88,
126.34, 126.05, 65.54, 61.47, 57.26, 39.19, 33.08, 31.08, 27.89,
25.83, 24.74 (3C), 18.13, -3.25, -3.44. Anal. Calcd for
(2S,12bS)-2-[(Meth oxym eth yl)oxy]-1,2,3,4,6,12b-h exah y-
d r oben z[a ]a n th r a cen -7,12-d ion e (12m ). 12m was obtained
from 1m following method C, after separation of the resulting
75:25 mixture of 8m and 12m by flash chromatography
C
24H30O4Si: C, 70.21; H, 7.37. Found: C, 70.09; H, 7.74.
(2R,4a R,5S,12bR)-2-[(ter t-Bu tyld im eth ylsilyl)oxy]-4a ,5-
(eluent: hexane/EtOAc 85:15), in 11% yield as an oil: [R]20
e p oxy-1,2,3,4,4a ,5,6,12b -oct a h yd r ob e n z[a ]a n t h r a ce n -
7,12-d ion e (15). 15 was obtained from (+)-8k following
method D, after flash chromatography (eluent: hexane/EtOAc
90:10), in 11% yield: mp 140-141 °C (MeOH); [R]20D ) +22 (c
0.8, CHCl3); 1H NMR (C6D6) δ 8.06 (m, 2H), 7.68 (m, 2H), 4.13
(broad s, 1H), 3.69 (ddd, 1H, J ) 2.6, 2.8, and 11.8 Hz), 3.35
and 2.31 (ddd, 1H, J ) 1.5, 3.9, and 21.0 Hz, dt, 1H, J ) 21.0
and 2.8 Hz), 2.92 (dd, 1H, J ) 1.9 and 2.7 Hz), 2.91 (m, 1H),
2.39 (m, 1H), 2.1-0.9 (m, 4H), 1.20 (s, 9H), 0.41 and 0.21 (2s,
6H); 13C NMR δ 184.57 (2C), 144.27, 140.23, 133.42, 133.14,
133.09, 131.75, 126.19, 125.86, 66.82, 61.97, 59.35, 35.56,
D
) +181 (c 2.1, CHCl3); 1H NMR δ 8.07 (m, 2H), 7.70 (m, 2H),
5.54 (t, 1H, J ) 3.2 Hz), 4.73 and 4.68 (AB system, 2H, J )
6.7 Hz), 3.90 (tt, 1H, J ) 4.5 and 11.4 Hz), 3.40 (m, 1H), 3.38
(s, 3H), 3.24 (m, 2H), 2.7-1.1 (m, 6H); 13C NMR δ 184.65,
184.19, 143.64, 141.89, 136.61, 133.52, 133.41, 132.50, 132.05,
126.30, 126.08, 114.40, 94.69, 75.21, 55.27, 40.27, 35.45, 34.75,
32.66, 25.46.
Gen er a l P r oced u r e for Ep oxid a tion s, Meth od D. To
a solution of 0.15 mmol of the corresponding derivative in 3
mL of dry CH2Cl2 cooled at 0 °C m-CPBA (100 mg, 0.3 mmol,

8330 J . Org. Chem., Vol. 63, No. 23, 1998
Carren˜o et al.
31.51, 31.31, 28.67, 25.88, 25.07 (3C), 18.18, -3.27, -3.38.
Anal. Calcd for C24H30O4Si: C, 70.21; H, 7.37. Found: C,
70.09; H, 7.68.
Ack n ow led gm en t. We thank Direccio´n General de
Investigacio´n Cient´ıfica y Te´cnica (Grant PB95-0174)
for financial support. C.D.V. thanks FAPESP-Fundac¸a˜o
de Amparo a` Pesquisa do Estado de Sa˜o Paulo for a
postdoctoral fellowship.
Syn th esis of MTP A Ester s. MTPA ester synthesis was
performed according to the known procedure.31 To a solution
of the corresponding alcohol (0.04 mmol) and DMAP (10 mg,
0.08 mmol) in 3 mL of CH2Cl2 (R)- or (S)-MTPA-Cl (13 mL,
0.07 mmol) was added. The mixture was stirred overnight at
room temperature, and then the reaction was quenched as
follows. Water in the amount of 1 mL and 3 mL of Et2O were
added, and the reaction mixture was stirred for 15 min. The
solution was washed successively with 4 mL of 1 N HCl, 4 mL
of 1 N NaOH, and brine and dried over MgSO4. After
evaporation of the solvents, the resulting mixture of diaster-
eomeric esters was used directly for NMR analysis.
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra of compounds 1c,f,h ,j-m , 5, and 12m and 1H
NMR spectra of compounds 8l, 12l, and the mixture of 8j and
12j (21 pages). This material is contained in libraries on
microfiche, immediately 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.
J O9811874