Regioselective and Stereoselective Transformations of Enantiopure p-Benzoquinone Equivalents

Article abstract of DOI:10.1002/(sici)1099-0690(199804)1998:4<643::aid-ejoc643>3.0.co;2-v

The selectivities of typical transformations of the p-benzoquinone Diels-Alder adduct 2 and its dihydro derivative 3 are shown to be highly dependent on the mechanistic path followed. To avoid ambiguities and to make sure of clearly defined regioselectivity, the monoketal 13 was examined and proven not only to be an excellent dienophile but, of course, also to lead to reliable regioselectivity in subsequent transformations. This led to the correction of an earlier provisional assignment of the alkylation products 11 and 12.

Full text of DOI:10.1002/(sici)1099-0690(199804)1998:4<643::aid-ejoc643>3.0.co;2-v

FULL PAPER
Regioselective and Stereoselective Transformations of Enantiopure
p-Benzoquinone Equivalents
Ina Gerstenbergera, Martin Hansena, Antony Mauvaisb, Rudolf Wartchowc and Ekkehard Winterfeldt*a
Institut für Organische Chemie der Universität Hannovera,
Schneiderberg 1 B, D-30167 Hannover, Germany
Fax: (internat.) ϩ 49(0)511/762-3011
E-mail: winterfeldt@mbox.oci.uni-hannover.de
b
´
Fondation Nationale Alfred Kastler de lЈAcademie des Sciences ,
´
2, rue Brulee, F-67000 Strasbourg, France
Fax: (internat.) ϩ 33(0)3/88222477
Institut für Anorganische Chemie der Universität Hannoverc,
Callinstraße 9, D-30167 Hannover, Germany
Fax: (internat.) ϩ 49(0)511/762-3006
Received October 9, 1997
Keywords: Cycloaddition / High pressure chemistry / Quinones / Cyclohexanones / Retro Diels-Alder process
The selectivities of typical transformations of the p-benzo-
quinone Diels-Alder adduct 2 and its dihydro derivative 3
are shown to be highly dependent on the mechanistic path
followed. To avoid ambiguities and to make sure of clearly
defined regioselectivity, the monoketal 13 was examined and
proven not only to be an excellent dienophile but, of course,
also to lead to reliable regioselectivity in subsequent trans-
formations. This led to the correction of an earlier provisional
assignment of the alkylation products 11 and 12.
Since Diels-Alder adduct 2 is formed smoothly and quan-
As shown in Table 1, a mixture of the monoalkylated
titatively from p-benzoquinone and the enantiopure cyclo- compounds 11 and 12 was obtained in this case and, bear-
pentadiene 1[1], we became interested in studying the re- ing in mind the aforementioned results on reduction and
gioselectivity of its transformations. Having observed a oxidation, we provisionally assigned structure 12 to the
quite remarkable regioselectivity with anhydride[2] and imi- main reaction product. Since the differences in the NMR
de[3] adducts, we expected 2 to show a similar behaviour data were, however, quite small, we decided to resolve any
and envisaged it as being an excellent source of enantiopure ambiguities by obtaining definitive experimental data. The
cyclohexenones (see below).
quinone mono ketal 13 emerged as the most obvious candi-
date for enabling regioselective transformations of the cor-
responding cycloadduct 14, and hence we studied the Diels-
Alder chemistry of this dienophile. As expected, the cyclo-
addition of diene 1b and quinone monoketal 13 provided
one single regioisomer (14) in quantitative yield. The struc-
ture of 14 was proven by an X-ray investigation (see Figure
1)[8]. Since adduct 14 was obtained quantitatively after 3
days at 6.5 kbar, the reaction rate is somewhat lower than
that observed with p-benzoquinone itself (1 d, 6.5 kbar)
(Scheme 3). However, adduct formation is considerably fas-
ter than with spiro ether 15 (2 weeks, 6.5 kbar), which illus-
trates the remarkable effect of a second electronegative
atom adjacent to the dienophile double bond. In contrast,
the carbocyclic spiro compound 17 did not give rise to any
cycloadducts at all, once again demonstrating the higher
spatial demand of a CH2 group, which is fully in line with
our earlier reports on kinetic resolution, as well as on the
differentiation of enantiotopic groups.
This was borne out by experiment. -Selectride reduction
of the dihydro compound 3, as well as of the epoxide 4,
proved to be completely regioselective with the carbonyl
group distant from the phenyl substituent again being at-
tacked preferentially (Scheme 1).
Subsequent pyrolysis furnished the enantiopure hydroxy-
cyclohexenones 7[1] and 8[4] cleanly and with ee’s Ͼ 98%.
If the regioselectivities of oxidations were to parallel
those of reductions, the enantiomer of 8 should be obtain-
able from diol 9, which can be obtained in a highly dia-
stereoselective manner by DIBAH reduction of adduct 2.
With this diol at hand, we were in a position to study the
regioselectivities of the oxidation processes. The best results
were obtained with the Bobbit reagent[5]. As is clear from
the formula 10, this space-demanding reagent indeed at-
tacked at the same position as found previously in the -
Selectride reduction (Scheme 2). On subsequent pyrolysis,
the enantiomer of 8 was formed as predicted[5]
Compared to these two operations, only modest regiose-
.
Although cycloadduct 14 already looked quite promising
lectivity was observed in the enolate alkylation of the di- as far as chemo-, regio-, and diastereoselectivity were con-
hydro derivative 3[5] (Table 1).
Eur. J. Org. Chem. 1998, 643Ϫ650
cerned, the first set of hydride reductions additionally re-
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643

I. Gerstenberger, M. Hansen, A. Mauvais, R. Wartchow, E. Winterfeldt
FULL PAPER
Scheme 1
Scheme 2
Figure 1. Structure of compound 14
Table 1. Regioselectivity of alkylation
reduced to the corresponding unsaturated diol 9, under the
same conditions ketal 14 underwent reduction of the double
bond to yield mixtures of the saturated ketone 18 and the
corresponding α-carbinol 20a. Exclusive formation of 20a
could only be achieved using an excess of the reducing
agent.
Similar treatment with a simple Grignard reagent, such
as that derived from bromoethane, afforded exclusively the
conjugate addition product 16b, which corresponds to alky-
lation products of type 11 (see below).
As expected, cuprate additions in the presence of trimeth-
vealed a quite remarkable directing effect of the ketal moi- ylsilyl chloride also gave rise to 1,4-adducts (e.g. 16c) and
ety. Whereas the p-benzoquinone adduct 2 was smoothly although exclusive conjugate addition is quite normal in
644
Eur. J. Org. Chem. 1998, 643Ϫ650

Regioselective and Stereoselective Transformations of Enantiopure p-Benzoquinone Equivalents
FULL PAPER
Scheme 3
This proves very clearly that our earlier assignment has
to be reversed and that, in contrast to -Selectride reduction
(nucleophilic attack), enolate formation with diketone 3
takes place preferentially at the carbonyl group adjacent to
the phenyl residue. We have no straightforward explanation
for this outcome and one may again speculate that com-
plexation of the electron-rich aromatic π-system at an early
stage of the interaction directs the proton-accepting species
towards this particular carbonyl group. On the other hand,
pyrolysis of 21 furnished an almost quantitative yield (97%)
of the enantiomerically pure (ee > 98%) hydroxy ketone
22a. Transformation of this material into the corresponding
silyl ether 22b led to the enantiomer of a chiral intermediate
involved in the synthesis of “manzamine A”, which was pre-
pared from shikimic acid by OvermanЈs group[6]. The con-
stitutional identity of the two compounds was proved with
the aid of a sample kindly provided by Professor Overman.
Since the antipode of diene 1 is, of course, also at hand
in our laboratory, the enantiomer of 22b can be prepared
as well.
In the light of the above results, it is clear that regioselec-
tive introduction of alkyl residues into adduct 14 can be
achieved in a predictable manner, either by employing the
aforementioned alkylation protocol or by means of a cu-
prate addition in the presence of a trialkylchlorosilane.
Finally, two standard double-bond transformations,
this case, the outcome of the hydride reduction and the
Grignard attack may well be due to a chelating effect of the epoxidation and cyclopropanation, were addressed, since
ketal group. In any event, 16c should, in principle, have these could also lead to useful enantiopure building blocks.
served quite well for the structural assignment of the alky- Epoxidation under nucleophilic conditions leading to 23a
lation products 11 and 12. It turned out, however, that ketal proceeded in high yield. Subsequent thermolysis of this
hydrolysis to give the corresponding diketones was ac- compound provided the enantiomerically pure epoxide 25,
companied by epimerization at the α-carbonyl carbon atom, which is well-equipped for various highly selective trans-
leading to an inseparable mixture of epimers.
formations (Scheme 5).
To simplify matters and to ensure the exclusive formation
Although -Selectride reduction of 23a furnished the α-
of a single β-alkylation product, we investigated the alky- hydroxy compound 23b in high yield (96%) and with excel-
lation of dihydro compound 18, which is readily obtained lent diastereoselectivity, all our efforts to prepare the corre-
from adduct 14 under the Luche conditions employing zinc sponding α-hydroxy- or α-acetoxycyclohexenone ketals
and nickel dichloride under sonification (Scheme 4).
from 23a or 23c by means of thermal retro reactions met
The usual deprotonation (LDA)/alkylation sequence af- with failure.
forded in each case one single alkylation product
In contrast to the simple p-benzoquinone adduct 2,
(19aϪ19d), indicating excellent regioselectivity and exclus- which had resisted all our efforts to introduce a cyclopro-
ive β-attack of the alkyl bromide. To avoid epimerization pane ring under various conditions, cyclopropanation of ke-
during ketal hydrolysis, as well as to generate the corre- tal 14 proved to be a very efficient process. Under Corey-
sponding enantiopure hydroxy ketones as potential chiral Chaykovsky conditions[7], the product of exclusive β-attack
building blocks, the hydride reduction of ketone 19b was (24) was obtained in 90% yield and proved to be a stable
investigated. Since hydride attack can only occur from the and easy to handle compound. The retro process occurred
convex β-side, the β-alkyl residue, stereoselectively intro- readily at 300°C and generated 90% of the enantiopure bi-
duced in the alkylation process, hinders this transformation. cycloheptane 27. Since attempted cyclopropanation of the
Sodium tetrahydridoborate, -Selectride or DIBAH either p-benzoquinone adduct 2 had failed, we were particularly
leave the molecule unchanged or induce decomposition un- pleased to find that ketal hydrolysis of 24a proceeded very
der more forcing conditions. Finally, using an excess of lith- efficiently (90%) to provide this particular diketone 26,
ium aluminium hydride at Ϫ49°C, a 99% yield of the pure which could not be generated directly.
α-hydroxy ketal 20 was obtained. The ketal could then be
A remarkable resistance of the keto group in 24a towards
hydrolyzed without any epimerization. The hydroxy ketone hydride reduction needs to be mentioned in relation to
21 prepared in this way could easily be reoxidized to dike- further chemical transformations of this cyclopropane de-
tone 11c, which proved to be identical in every respect to rivative. As in the case of the β-alkylation products
the major product of the alkylation reaction summarized in 19aϪ19d, reagents such as tetrahydridoborate, -Selectride
Table 1.
and DIBAH left the keto group untouched and again it
Eur. J. Org. Chem. 1998, 643Ϫ650
645

I. Gerstenberger, M. Hansen, A. Mauvais, R. Wartchow, E. Winterfeldt
FULL PAPER
Scheme 4
Scheme 5
646
Eur. J. Org. Chem. 1998, 643Ϫ650

Regioselective and Stereoselective Transformations of Enantiopure p-Benzoquinone Equivalents
FULL PAPER
Ϫ78°C. After stirring for 15 min, 2 equiv. of the alkylating reagent
was added. On completion of the reaction (TLC control), the mix-
ture was poured into an aqueous solution of ammonium chloride,
the phases were separated, and the aqueous phase was extracted
with diethyl ether. The organic phase was washed with brine, dried
with MgSO4, and the solvent was evaporated under reduced pres-
sure. The remaining oil was purified by flash chromatography (di-
ethyl ether/petroleum ether, 1:1) to yield 50Ϫ71% of the mixed
products 11/12aϪd. The spectroscopic data were taken from the
spectra of the mixtures.
needed treatment with lithium aluminium hydride to obtain
an 85% yield of the α-hydroxy compound 24b. Clearly, since
α-attack is, owing to the concave-convex conformation, im-
possible, any β-substituent adjacent to the carbonyl group
hinders nucleophilic attack.
In summary, it is concluded that the system of p-benzo-
quinone monoketal in combination with the chiral diene 1
not only leads to the formation of cycloadducts with excel-
lent regioselectivities, but that these cycloadducts addition-
ally undergo highly selective chemical transformations. In
the particular case of cyclopropanation, this reagent is cer-
tainly superior to the corresponding quinone adduct.
11a: IR (CHCl3): ν˜ ϭ 2940 cmϪ1, 2864, 1700, 1516, 1252, 1180,
1
1036, 908. Ϫ H NMR (CDCl3, 200 MHz): δ ϭ 0.74 (s, 3 H), 3.08
(d, J ϭ 9 Hz, 1 H), 3.82 (s, 3 H), 4.02 (d, J ϭ 9 Hz, 1 H), 6.10 (d,
J ϭ 6 Hz, 1 H), 6.21 (d, J ϭ 6 Hz, 1 H), 6.84Ϫ6.94 (m, 2 H),
7.03Ϫ7.14 (m, 2 H), 7.18Ϫ7.33 (m, 5 H). Ϫ MS (230°C); m/z (%):
439 (1.92) [Mϩ], 240 (100), 225 (39), 197 (34), 91 (75). Ϫ C30H32O3
(440.58): calcd. 440.2351; found 440.2339 (MS).
Thanks are due to the Volkswagen Foundation for support of this
work, the DFG (Deutsche Forschungsgemeinschaft) for providing
the high-pressure apparatus, and the Alexander von Humboldt
Foundation for a postdoctoral fellowship for A. M.
11b: IR (CHCl3): ν˜ ϭ 2928 cmϪ1, 2860, 1700, 1612, 1516, 1252,
1180. Ϫ H NMR (CDCl3, 200 MHz): δ ϭ 0.76 (s, 3 H), 3.09 (d,
1
Experimental Section
J ϭ 9 Hz, 1 H), 3.82 (s, 3 H), 3.98 (d, J ϭ 9 Hz, 1 H), 4.97Ϫ5.05
(m, 1 H), 5.08 (s, 1 H), 5.54Ϫ5.76 (m, 1 H), 6.12 (d, J ϭ 6 Hz, 1
H), 6.20 (d, J ϭ 6 Hz, 2 H), 6.84Ϫ6.96 (m, 2 H), 7.22Ϫ7.32 (m, 2
H). Ϫ MS (120°C); m/z (%): 390 (3) [Mϩ], 349 (2), 240 (100), 225
(43), 197 (38). Ϫ C26H30O3 (390.52): calcd. 390.2195; found
390.2202.
Melting points: Gallenkamp MPD 350, uncorrected values. Ϫ
1
IR: Perkin-Elmer 581. Ϫ H and 13C NMR: Bruker AM 400; in-
ternal standard tetramethylsilane. Ϫ MS: Finnigan MAT 312; 70
eV. Ϫ Elemental analyses: Heraeus CHN rapid analyser. Ϫ Optical
rotations: Perkin-Elmer 241 polarimeter, 10-cm cell, 589 nm (Na-
D line), in solution.
11c: IR (CHCl ): ν ϭ 3308 cmϪ1, 2932, 2860, 1712, 1516, 1252,
1180, 908. Ϫ H NMR (CDCl3, 200 MHz): δ ϭ 0.77 (s, 3 H), 3.1
(d, J ϭ 9 Hz, 1 H), 3.80 (s, 3 H), 4.05 (d, J ϭ 9 Hz, 1 H), 6.14 (d,
J ϭ 6 Hz, 1 H), 6.22 (d, J ϭ 6 Hz, 1 H), 6.83Ϫ6.92 (m, 2 H),
7.10Ϫ7.24 (m, 2 H). Ϫ MS (130°C); m/z (%): 388 (2) [Mϩ], 348 (2),
240 (100), 225 (24), 197 (22). Ϫ C26H28O3 (388.51): calcd. 388.2030;
found 388.2038 (MS).
˜
3
2b: 2.0 g (8.52 mmol) of diene 1 and 900 mg (8.52 mmol) of
p-benzoquinone were dissolved in 3 ml of dichloromethane. The
resulting solution was sealed in a Teflon tube, which was pressur-
ized at 6.5 bar for 48 h. After evaporation of the solvent and purifi-
cation of the residue by flash chromatography (diethyl ether/petro-
leum ether, 2:1), 2.67 g (92%) of yellow crystals was obtained. Ϫ
M.p. 127°C. Ϫ [α]D ϭ Ϫ355.2 (c ϭ 0.88, CHCl3). Ϫ IR (CHCl3):
1
1
ν˜ ϭ 2936 cmϪ1, 1752, 1668, 1516, 1288, 1252, 1108. Ϫ H NMR
11d: IR (CHCl ): ν ϭ 2932 cmϪ1, 2864, 1700, 1516, 1252, 1180.
˜
3
(CDCl3, 200 MHz): δ ϭ 0.55 (br. d, J ϭ 12 Hz, 1 H), 0.82 (s, 3
H), 2.24 (br. d, J ϭ 12 Hz, 1 H), 3.14 (d, J ϭ 8 Hz, 1 H), 4.01 (d,
J ϭ 8 Hz, 1 H), 5.96 (d, J ϭ 6 Hz, 1 H), 6.10 (d, J ϭ 6 Hz, 1 H),
6.48 (d, J ϭ 10 Hz, 1 H), 6.56 (d, J ϭ 10 Hz, 1 H), 6.87Ϫ6.96 (m,
2 H), 7.28Ϫ7.39 (m, 2 H). Ϫ MS (80°C); m/z (%): 348 (9) [Mϩ],
240 (100), 225 (26), 197 (20), 165 (12), 108 (19), 82 (10). Ϫ
C23H24O3 (348.44): calcd. 348.1725; found 348.1711 (MS).
1
Ϫ H NMR (CDCl3, 200 MHz): δ ϭ 0.76 (s, 3 H), 1.05 (d, J ϭ 6
Hz, 1 H), 3.08 (d, J ϭ 9 Hz, 1 H), 3.81 (s, 3 H), 4.02 (d, J ϭ 9 Hz,
1 H), 6.14 (d, J ϭ 6 Hz, 1 H), 6.18 (d, J ϭ 6 Hz, 1 H), 6.86Ϫ6.94
(m, 2 H), 7.14Ϫ7.33 (m, 2 H). Ϫ MS (110°C); m/z (%): 364 (2)
[Mϩ], 240 (100), 225 (21), 197 (17), 124 (14).
12a: IR (CHCl3): ν˜ ϭ 2940 cmϪ1, 2864, 1700, 1516, 1252, 1180,
1
1036, 908. Ϫ H NMR (CDCl3, 200 MHz): δ ϭ 0.73 (s, 3 H), 3.16
3b: An emulsion of 300 mg (0.86 mmol) of adduct 2 in 3 ml of
acetic acid was treated with 225 mg (3.44 mmol, 5 equiv.) of zinc
dust under ultrasound conditions for 5 min. The zinc was then
filtered off, and the solution was diluted with water. After extrac-
tion with diethyl ether, the combined organic phases were washed
with 10% aq. KOH and brine. The extract was dried with MgSO4,
filtered, and the solvent was evaporated under reduced pressure to
yield 259.2 mg (86%) of a colourless solid. Ϫ M.p. 138°C. Ϫ [α]D ϭ
(d, J ϭ 9 Hz, 1 H), 3.80 (s, 3 H), 3.95 (d, J ϭ 9 Hz, 1 H), 6.00 (d,
J ϭ 6 Hz, 1 H), 6.28 (d, J ϭ 6 Hz, 1 H), 6.84Ϫ6.94 (m, 2 H),
7.03Ϫ7.14 (m, 2 H), 7.18Ϫ7.33 (m, 5 H). Ϫ MS (230°C); m/z (%):
439 (1.92) [Mϩ], 240 (100), 225 (39), 197 (34), 91 (75). Ϫ C30H32O3
(440.58): calcd. 440.2351; found 440.2339 (MS).
12b: IR (CHCl3): ν˜ ϭ 2928 cmϪ1, 2860, 1700, 1612, 1516, 1252,
1
1180. Ϫ H NMR (CDCl3, 200 MHz): δ ϭ 0.78 (s, 3 H), 3.16 (d,
158.9 (c ϭ 0.9, CHCl ). Ϫ IR (CHCl ): ν ϭ 3000 cmϪ1, 2936, 1752,
J ϭ 9 Hz, 1 H), 3.81 (s, 3 H), 3.97 (d, J ϭ 9 Hz, 1 H), 4.97Ϫ5.05
(m, 1 H), 5.08 (s, 1 H), 5.54Ϫ5.76 (m, 1 H), 5.98 (d, J ϭ 6 Hz, 1
H), 6.30 (d, J ϭ 6 Hz, 1 H), 6.84Ϫ6.96 (m, 2 H), 7.22Ϫ7.32 (m, 2
H). Ϫ MS (120°C); m/z (%): 390 (3) [Mϩ], 349 (2), 240 (100), 225
(43), 197 (38). Ϫ C26H30O3 (390.52): calcd. 390.2195; found
390.2202 (MS).
˜
3
3
1704, 1516, 1252, 1180, 1036. Ϫ 1H NMR (CDCl3, 200 MHz): δ ϭ
0.51 (d, J ϭ 12 Hz, 1 H), 0.75 (s, 3 H), 3.14 (d, J ϭ 9 Hz, 1 H),
3.81 (s, 3 H), 3.99 (d, J ϭ 9 Hz, 1 H), 6.04 (d, J ϭ 6 Hz, 1 H),
6.26 (d, J ϭ 6 Hz, 1 H), 6.89Ϫ6.91 (m, 2 H), 7.19Ϫ7.27 (m, 2 H).
Ϫ MS (120°C); m/z (%): 350 (2) [Mϩ], 240 (100), 225 (16), 197 (13),
165 (8), 121 (9), 91 (8). Ϫ C23H26O3 (350.46): calcd. 350.1882;
found 350.1881 (MS).
12c: IR (CHCl3): ν˜ ϭ 3308 cmϪ1, 2932, 2860, 1712, 1516, 1252,
1180, 908. Ϫ 1H NMR (CDCl3, 200 MHz): δ ϭ 0.77 (s, 3 H), 3.22
(d, J ϭ 9 Hz, 1 H), 3.82 (s, 3 H), 4.01 (d, J ϭ 9 Hz, 1 H), 5.94 (d,
11aϪd and 12aϪd. Ϫ General Procedure: A solution of 0.304 ml
(0.426 mmol) of n-butyllithium (1.6  in toluene) and 0.06 ml (0.43 J ϭ 6 Hz, 1 H), 6.34 (d, J ϭ 6 Hz, 1 H), 6.83Ϫ6.92 (m, 2 H),
mmol) of diisopropylamine in 1.5 ml of THF was stirred for 30
7.10Ϫ7.24 (m, 2 H). Ϫ MS (130°C); m/z (%): 388 (2) [Mϩ], 348 (2),
min at 0°C. Then, a cold solution (Ϫ78°C) of 50 mg (0.14 mmol) 240 (100), 225 (24), 197 (22). Ϫ C26H28O3 (388.51): calcd. 388.2030;
of the dihydro adduct 3 in 3 ml of THF was added dropwise at
found 388.2038 (MS).
Eur. J. Org. Chem. 1998, 643Ϫ650
647

I. Gerstenberger, M. Hansen, A. Mauvais, R. Wartchow, E. Winterfeldt
FULL PAPER
12d: IR (CHCl3): ν˜ ϭ 2932 cmϪ1, 2864, 1700, 1516, 1252, 1180. diluted with aqueous ammonium chloride solution and extracted
1
Ϫ H NMR (CDCl3, 200 MHz): δ ϭ 0.75 (s, 3 H), 1.09 (d, J ϭ 6
with diethyl ether. The organic phase was washed with brine, dried
Hz, 1 H), 3.19 (d, J ϭ 9 Hz, 1 H), 3.80 (s, 3 H), 3.97 (d, J ϭ 9 Hz, with MgSO4, and the solvent was evaporated under reduced pres-
1 H), 5.96 (d, J ϭ 6 Hz, 1 H), 6.31 (d, J ϭ 6 Hz, 1 H), 6.86Ϫ6.94 sure. The remaining oil was dissolved in 1.5 ml of acetic acid and
(m, 2 H), 7.14Ϫ7.33 (m, 2 H). Ϫ MS (110°C); m/z (%): 364 (2) stirred at room temperature for 30 min. Subsequently, the mixture
[Mϩ], 240 (100), 225 (21), 197 (17), 124 (14).
was diluted with saturated sodium hydrogen carbonate solution,
extracted with diethyl ether, and the combined extracts were dried
with MgSO4. The solvent was evaporated under reduced pressure
and the remaining oil was purified by flash chromatography (di-
ethyl ether/petroleum ether, 5:1) to yield 44.4 mg (86%) of a colour-
less oil. Ϫ [α]D ϭ Ϫ54.1 (c ϭ 0.425, CHCl3). Ϫ IR (CHCl3): ν˜ ϭ
14: 1.0 g (4.16 mmol) of diene 1 and 633 mg (4.16 mmol) of p-
benzoquinone monoketal were dissolved in 3 ml of dichlorometh-
ane. The resulting solution was sealed in a Teflon tube, which was
pressurized at 6.5 bar for 48 h. After evaporation of the solvent
and purification of the residue by flash chromatography (diethyl
ether/petroleum ether, 2:1), 1.41 g (86%) of white crystals was ob-
tained. Ϫ M.p. 132°C. Ϫ [α]D ϭ Ϫ128.4 (c ϭ 0.395, CHCl3). Ϫ IR
(CHCl3): ν˜ ϭ 2952 cmϪ1, 2928, 2892, 2864, 1668, 1516, 1248, 1180,
1
2932 cmϪ1, 2860, 1696, 1612, 1516, 1464, 1252, 1196, 1180. Ϫ H
NMR (CDCl3, 200 MHz): δ ϭ 0.42 (br. d, J ϭ 12 Hz, 1 H), 0.75
(s, 3 H), 0.96 (d, J ϭ 6 Hz, 1 H), 2.78 (d, J ϭ 10 Hz, 1 H), 3.73
(d, J ϭ 10 Hz, 1 H), 3.79 (s, 3 H), 3.95Ϫ4.07 (m, 4 H), 6.07 (d,
J ϭ 6 Hz, 1 H), 6.17 (d, J ϭ 6 Hz, 1 H), 6.80Ϫ6.89 (m, 2 H),
7.17Ϫ7.25 (m, 2 H). Ϫ MS (100°C); m/z (%): 408 (2) [Mϩ], 240
(100), 225 (12), 197 (12), 165 (6), 85 (24). Ϫ C28H32O4 (408.54):
calcd. 408.2301; found 408.2312 (MS).
1
1116, 964, 948, 824. Ϫ H NMR (CDCl3, 200 MHz): δ ϭ 0.46 (br.
d, J ϭ 12 Hz, 1 H), 0.80 (s, 3 H), 2.34 (br. d, J ϭ 12 Hz, 1 H),
2.83 (dd, J1 ϭ 9 Hz, J2 ϭ 1 Hz, 1 H), 3.80 (s, 3 H), 3.91Ϫ4.17 (m,
5 H), 5.89 (d, J ϭ 6 Hz, 1 H), 5.90 (d, J ϭ 10 Hz, 1 H), 6.03 (d,
J ϭ 6 Hz, 1 H), 6.32 (d, J ϭ 10 Hz, 1 H), 6.83Ϫ6.91 (m, 2 H),
7.26Ϫ7.34 (m, 2 H). Ϫ MS (110°C); m/z ϭ 392 (2) [Mϩ], 312 (2),
240 (100), 197 (7), 152 (6), 82 (4). Ϫ C25H28O4 (392.49): calcd.
392.1988; found 392.1987 (MS).
19aϪd. Ϫ General Procedure: A solution of 0.506 ml (0.76 mmol)
of n-butyllithium (1.6  in toluene) and 0.107 ml (0.76 mmol) of
diisopropylamine in 1.5 ml of THF was stirred for 30 min at 0°C.
A precooled solution of 150 mg (0.38 mmol) of the reduced mono-
ketal adduct 16a in 3 ml of HF was then added dropwise at Ϫ30°C.
After stirring for 15 min, 2 equiv. of the alkylating reagent was
added. The reaction mixture was slowly allowed to warm to 0°C
over a period of 2 h, and then poured into an aqueous ammonium
chloride solution. The phases were separated and the aqueous
phase was extracted with diethyl ether. The organic phase was
washed with brine, dried with MgSO4, and the solvent was evapo-
rated under reduced pressure. The remaining oil was purified by
flash chromatography (diethyl ether/petroleum ether, 1:1) to yield
50Ϫ84% of the products 19aϪd.
16a: A suspension of 500 mg (1.27 mmol) of the monoketal ad-
duct 14, 375 mg (1.85 mmol) of NiCl2 ·6 H2O and 625 mg (9.47
mmol) of zinc dust in 20 ml of glycol monoethyl ether and 2 ml of
water was subjected to ultrasonification for 3 h. The inorganic resi-
due was then filtered off and the filtrate was extracted with diethyl
ether. The organic phase was dried with MgSO4 and the solvent
was evaporated. The remaining oil was purified by flash chroma-
tography (diethyl ether/petroleum ether, 1:2) to yield 340 mg (67%)
of a colourless solid. Ϫ M.p. 144°C. Ϫ [α]D ϭ Ϫ36.1 (c ϭ 0.415,
CHCl3). Ϫ IR (KBr): ν˜ ϭ 2928 cmϪ1, 1709, 1615, 1515, 1230, 1182.
Ϫ 1H NMR (CDCl3, 200 MHz): δ ϭ 0.49 (br. d, J ϭ 13 Hz, 1 H),
0.76 (s, 3 H), 2.87 (d, J ϭ 10 Hz, 1 H), 3.78 (d, J ϭ 10 Hz, 1 H),
3.79 (s, 3 H), 3.90Ϫ4.07 (m, 4 H), 6.08 (d, J ϭ 6 Hz, 1 H), 6.12 (d,
J ϭ 6 Hz, 1 H), 6.81Ϫ6.89 (m, 2 H), 7.16Ϫ7.24 (m, 2 H). Ϫ MS
(100°C); m/z (%): 394 (3) [Mϩ], 240 (100), 225 (13). Ϫ C25H30O4
(394.51): calcd. 394.2144; found 394.2143 (MS).
19a: [α]D ϭ Ϫ9 (c ϭ 0.21, CHCl ). Ϫ IR (CHCl ): ν ϭ 2932
˜
3
3
cmϪ1, 2892, 2856, 1704, 1516, 1248, 1180. Ϫ 1H NMR (CDCl3,
200 MHz): δ ϭ 0.50 (d, J ϭ 13 Hz, 1 H), 0.77 (s, 3 H), 1.05 (d,
J ϭ 7 Hz, 3 H), 3.02 (d, J ϭ 10 Hz, 1 H), 3.80 (s, 3 H), 3.82 (d,
J ϭ 10 Hz, 1 H), 3.92Ϫ4.04 (m, 4 H), 6.03 (d, J ϭ 6 Hz, 1 H),
6.12 (d, J ϭ 6 Hz, 1 H), 6.81Ϫ6.90 (m, 2 H), 7.16Ϫ7.26 (m, 2 H).
Ϫ MS (135°C); m/z (%): 408 (2) [Mϩ], 240 (100), 225 (14), 197 (12).
Ϫ C26H32O4 (408.54): calcd. 408.2301; found 408.2290 (MS).
16b: To a solution of 100 mg (0.25 mmol) of the monoketal ad-
duct 14 in 3 ml of THF, 2 equiv. of ethylmagnesium bromide in
diethyl ether was added dropwise at 0°C. The mixture was stirred
for 4 h at this temperature, then diluted with an aqueous am-
monium chloride solution, and extracted with diethyl ether. The
organic phase was washed with brine, dried with MgSO4, and the
solvent was evaporated under reduced pressure. The remaining oil
was purified by flash chromatography (diethyl ether/petroleum
ether, 2:1) to yield 28 mg (26%) of a colourless oil. Ϫ IR (KBr):
ν˜ ϭ 2932 cmϪ1, 1704, 1614, 1516, 1251, 1181. Ϫ 1H NMR (CDCl3,
200 MHz): δ ϭ 0.47 (br. d, J ϭ 13 Hz, 1 H), 0.75 (s, 3 H), 2.80 (d,
J ϭ 10 Hz, 1 H), 3.71 (d, J ϭ 10 Hz, 1 H), 3.79 (s, 3 H), 3.90Ϫ4.06
(m, 4 H), 6.06 (d, J ϭ 6 Hz, 1 H), 6.16 (d, J ϭ 6 Hz, 1 H),
6.81Ϫ6.90 (m, 2 H), 7.15Ϫ7.25 (m, 2 H). Ϫ MS (95°C); m/z (%):
422 (2) [Mϩ], 395 (1), 241 (100), 225 (12), 198 (10), 165 (6). Ϫ
C27H34O4 (422.56): calcd. 422.2457; found 422.2464 (MS).
19b: M.p. 157°C. Ϫ [α]D ϭ 32.4 (c ϭ 0.105, CHCl3). Ϫ IR (KBr):
1
ν˜ ϭ 2930 cmϪ1, 1708, 1515, 1248, 1182. Ϫ H NMR (CDCl3, 200
MHz): δ ϭ 0.50 (br. d, J ϭ 13 Hz, 1 H), 0.77 (s, 3 H), 3.00 (d, J ϭ
10 Hz, 1 H), 3.75 (d, J ϭ 10 Hz, 1 H), 3.79 (s, 3 H), 3.90Ϫ4.02 (m,
4 H), 4.99 (dd, J1 ϭ 7 Hz, J2 ϭ 1 Hz, 1 H), 5.06 (s, 1 H), 5.59Ϫ5.78
(m, 1 H), 6.04 (d, J ϭ 6 Hz, 1 H), 6.10 (d, J ϭ 6 Hz, 1 H),
6.80Ϫ6.88 (m, 2 H), 7.14Ϫ7.22 (m, 2 H). Ϫ MS (140°C); m/z (%):
434 (5) [Mϩ], 406 (3), 377 (2), 240 (100), 225 (69), 197 (71). Ϫ
C28H34O4 (434.57): calcd. 434.2457; found 434.2454 (MS).
19c: M.p. 145°C. Ϫ [α]D ϭ 64 (c ϭ 0.5, CHCl3). Ϫ IR (CHCl3):
ν˜ ϭ 2924 cmϪ1, 2856, 1704, 1516, 1248, 1180. Ϫ 1H NMR (CDCl3,
200 MHz): δ ϭ 0.49 (br. d, J ϭ 13 Hz, 1 H), 0.69 (s, 3 H),
2.32Ϫ2.50 (m, 1 H), 2.68 (dd, J1 ϭ 14 Hz, J2 ϭ 9 Hz, 1 H), 2.92
(d, J ϭ 11 Hz, 1 H), 2.97 (dd, J1 ϭ 14 Hz, J2 ϭ 4 Hz, 1 H), 3.55
(d, J ϭ 11 Hz, 1 H), 3.81 (s, 3 H), 3.87Ϫ3.98 (m, 4 H), 6.04 (d,
J ϭ 6 Hz, 1 H), 6.09 (d, J ϭ 6 Hz, 1 H), 6.82Ϫ6.92 (m, 2 H),
7.05Ϫ7.32 (m, 7 H). Ϫ MS (130°C); m/z (%): 484 (3) [Mϩ], 467
(2), 406 (3), 240 (100), 225 (22), 197 (19). Ϫ C32H36O4 (484.63):
calcd. 484.2614; found 484.2615 (MS).
16c: To a stirred slurry of 22.7 mg (0.25 mmol) copper(I) cyanide
in 1 ml of diethyl ether at Ϫ20°C, 0.32 ml (0.25 mmol) of a meth-
yllithium solution was added slowly until the suspension became
homogeneous and colourless. The resulting dimethylcuprate solu-
tion was stirred at Ϫ30°C for 20 min and then added dropwise to
a solution of 50 mg (0.12 mmol) monoketal adduct 14 and 48 µl
(0.38 mmol) of trimethylsilyl chloride in 1 ml of diethyl ether and
19d: [α]D ϭ 34 (c ϭ 1.07, CHCl3). Ϫ IR (CHCl3): ν˜ ϭ 2932
1 ml of THF at Ϫ30°C. After 5 min, the reaction mixture was cmϪ1, 2856, 1704, 1612, 1516, 1248, 1180. Ϫ 1H NMR (CDCl3,
648
Eur. J. Org. Chem. 1998, 643Ϫ650

Regioselective and Stereoselective Transformations of Enantiopure p-Benzoquinone Equivalents
FULL PAPER
400 MHz): δ ϭ 0.52 (br. d, J ϭ 13 Hz, 1 H), 0.76 (s, 3 H), 1.55 (s, (m, 3 H), 2.50Ϫ2.65 (m, 2 H), 4.19Ϫ4.22 (m, 1 H), 5.04Ϫ5.10 (m,
3 H), 1.60 (s, 3 H), 1.69 (s, 3 H), 1.85Ϫ2.30 (m, 6 H), 3.00 (d, J ϭ 2 H), 5.65Ϫ5.70 (m, 1 H), 5.91 (ddd, J1 ϭ 10 Hz, J2 ϭ 2 Hz, J3 ϭ
11 Hz, 1 H), 3.75 (d, J ϭ 11 Hz, 1 H), 3.78 (s, 3 H), 3.88Ϫ4.02 (m, 1 Hz, 1 H), 6.78 (dd, J1 ϭ 10 Hz, J2 ϭ 2 Hz, 1 H). Ϫ MS (room
4 H), 5.02Ϫ5.12 (m, 2 H), 6.05 (s, 2 H), 6.80Ϫ6.87 (m, 2 H),
temperature); m/z (%): 267 (2) [Mϩ ϩ 1], 266 (2) [Mϩ], 209 (90),
7.11Ϫ7.19 (m, 2 H). Ϫ MS (130°C); m/z (%): 530 (3) [Mϩ], 502 167 (80), 135 (27). Ϫ C15H26O2Si (266.46): calcd. 266.1702; found
(1), 290 (36), 240 (100), 225 (39), 197 (38). Ϫ C35H46O4 (530.75): 266.1689 (MS).
calcd. 530.3408; found 530.3396 (MS).
11b: To a solution of 50 mg (0.127 mmol) of 20 in 2 ml of dry
20: An excess of LiAlH4 was refluxed in 3 ml of dry diethyl ether.
The suspension was then cooled to Ϫ40°C and a solution of 550
dichloromethane, a solution of 41 mg (0.19 mmol) of PCC and 3
mg (0.04 mmol) of sodium acetate in 5 ml of dichloromethane was
mg (1.27 mmol) of the adduct 18b in diethyl ether was added drop- added dropwise. The reaction mixture was stirred for 1.5 h at room
wise. After 15 min, the reaction mixture was diluted with an aque- temperature, and then filtered through silica gel to yield 25 mg
ous ammonium chloride solution and extracted with diethyl ether.
The organic phase was washed with brine and dried with MgSO4.
The solvent was evaporated to yield 550 mg (99%) of a colourless
oil. Ϫ [α]D ϭ Ϫ44.6 (c ϭ 0.56, CHCl3). Ϫ IR (CHCl3): ν˜ ϭ 3492
cmϪ1, 2928, 2856, 1512, 1248, 1224, 1180. Ϫ 1H NMR (CDCl3,
200 MHz): δ ϭ 0.45 (br. d, J ϭ 12 Hz, 1 H), 0.82 (s, 3 H), 2.50 (d,
J ϭ 10 Hz, 1 H), 3.41 (dd, J1 ϭ 10 Hz, J2 ϭ 5 Hz, 1 H), 3.80 (s,
3 H), 3.87Ϫ4.02 (m, 4 H), 3.94Ϫ5.13 (m, 2 H), 5.63Ϫ5.87 (m, 1
H), 5.93 (d, J ϭ 6 Hz, 1 H), 6.20 (d, J ϭ 6 Hz, 1 H), 6.83Ϫ6.91
(m, 2 H), 7.21Ϫ7.31 (m, 2 H). Ϫ MS (110°C); m/z (%): 436 (1)
[Mϩ], 240 (100), 225 (8), 197 (8). Ϫ C28H36O4 (436.59): calcd.
436.2614; found 436.2603 (MS).
(50%) of a colourless oil. For spectroscopic data, see above.
23a: A mixture of 255 mg (6.3 mmol) NaOH and 0.65 ml (6.3
mmol) of H2O2 (35% aqueous solution) was added to a solution
of 500 mg (1.27 mmol) of adduct 14 in 10 ml of THF at 0°C. On
completion of the reaction (TLC control), the mixture was ex-
tracted with dichloromethane. The organic phase was washed with
a 5% aqueous solution of FeSO4 and dried with MgSO4. The sol-
vent was evaporated under reduced pressure and the remaining oil
was purified by flash chromatography (diethyl ether/petroleum
ether, 5:1) to yield 415 mg (80%) of a colourless solid. Ϫ M.p.
194°C. Ϫ [α]D ϭ Ϫ12.9 (c ϭ 0.155). Ϫ IR (CHCl3): ν˜ ϭ 3392
1
cmϪ1, 2932, 1716, 1516, 1248, 948, 824. Ϫ H NMR (CDCl3, 200
21: To a solution of 550 mg (1.25 mmol) of the carbinol 20 in
10 ml of acetone, 2 ml of 6  HCl was added dropwise. The solution
MHz): δ ϭ 0.55 (br. d, J ϭ 13 Hz, 1 H), 0.75 (s, 3 H), 3.15 (d, J ϭ
11 Hz, 1 H), 3.29 (d, J ϭ 4 Hz, 1 H), 3.33 (d, J ϭ 4 Hz, 1 H), 3.79
was stirred at room temperature for 10 min, then diluted with (s, 3 H), 3.93Ϫ4.23 (m, 5 H), 6.01 (d, J ϭ 6 Hz, 1 H), 6.11 (d, J ϭ
water, and extracted with dichloromethane. The organic phase was 6 Hz, 1 H), 6.81Ϫ6.89 (m, 2 H), 7.08Ϫ7.17 (m, 2 H). Ϫ MS (80°C);
washed with a saturated sodium hydrogen carbonate solution and
m/z (%): 408 (16) [Mϩ], 380 (10), 240 (100), 225 (11), 197 (10). Ϫ
dried with MgSO4. The solvent was evaporated and the remaining C25H28O5 (408.49): calcd. 408.1937; found 408.1935 (MS).
oil was purified by flash chromatography (diethyl ether) to yield
23b: A solution of 150 mg (0.37 mmol) of epoxide 23a in 7 ml
283 mg (57%) of a colourless solid. Ϫ M.p. 53°C. Ϫ [α]D ϭ Ϫ76.4
of dry toluene was treated with 1.04 ml (0.73 mmol) of a solution
(c ϭ 0.56, CHCl3). Ϫ IR (CHCl3): ν˜ ϭ 3576 cmϪ1, 2928, 2860,
of -Selectride in toluene at 0°C. The reaction mixture was allowed
1
1696, 1512, 1248, 1180. Ϫ H NMR (CDCl3, 200 MHz): δ ϭ 0.45
to warm to room temperature over a period of 3 h, diluted with
(br. d, J ϭ 13 Hz, 1 H), 0.80 (s, 3 H), 2.76 (d, J ϭ 10 Hz, 1 H),
aqueous ammonium chloride solution, and extracted with diethyl
3.70 (dd, J1 ϭ 10 Hz, J2 ϭ 5 Hz, 1 H), 3.82 (s, 3 H), 4.16 (dd, J1 ϭ
ether. The combined organic phases were washed with brine, and
11 Hz, J2 ϭ 5 Hz, 1 H), 5.08 (s, 1 H), 5.15 (dd, J1 ϭ 4 Hz, J2 ϭ 1
the solvent was evaporated under reduced pressure. The remaining
Hz, 1 H), 5.67Ϫ5.90 (m, 1 H), 6.13 (d, J ϭ 6 Hz, 1 H), 6.27 (d,
oil was purified by flash chromatography (diethyl ether/petroleum
J ϭ 6 Hz, 1 H), 6.86Ϫ6.96 (m, 2 H), 7.21Ϫ7.30 (m, 2 H). Ϫ MS
ether, 5:1) to yield 145 mg (96%) of a colourless oil. Ϫ [α]D ϭ Ϫ65
(100°C); m/z (%): 392 (1) [Mϩ], 296 (10), 240 (100), 226 (14), 197
(c ϭ 0.415, CHCl3). Ϫ IR (KBr): ν˜ ϭ 3418 cmϪ1, 2927, 2859, 1515,
(15). Ϫ C26H32O3 (392.54): calcd. 392.2351; found 392.2340 (MS).
1
1251, 1181. Ϫ H NMR (CDCl3, 200 MHz): δ ϭ 0.51 (br. d, J ϭ
22a: 88 mg (0.3 mmol) of 20 was heated to 200°C under high-
vacuum conditions and vapour-pyrolyzed at 350°C. The products
were eluted from the cold-trap with dichloromethane and sub-
13 Hz, 1 H), 0.81 (s, 3 H), 2.47 (d, J ϭ 2 Hz, 1 H), 2.64 (d, J ϭ
10 Hz, 1 H), 3.17Ϫ3.26 (m, 2 H), 3.60 (dd, J1 ϭ 10 Hz, J2 ϭ 2 Hz,
2 H), 3.81 (s, 3 H), 3.89Ϫ4.20 (m, 4 H), 6.05 (d, J ϭ 6 Hz, 1 H),
sequently separated by flash chromatography (diethyl ether/petro- 6.17 (d, J ϭ 6 Hz, 1 H), 6.85Ϫ6.95 (m, 2 H), 7.23Ϫ7.34 (m, 2 H).
leum ether, 1:4) to yield 34 mg (97%) of a colourless oil. Ϫ [α]D
ϭ
Ϫ MS (120°C); m/z (%): 410 (3) [Mϩ], 392 (1), 381 (2), 365 (2),
46.6 (c ϭ 0.15, CHCl3). Ϫ IR (CHCl3): ν˜ ϭ 3616 cmϪ1, 3592, 2980, 240 (100), 225 (99), 197 (10). Ϫ C25H30O5 (410.51): calcd. 410.2093;
2908, 2848, 1680, 1228, 1160. Ϫ 1H NMR (CDCl3, 200 MHz): δ ϭ found 410.2095 (MS).
2.09Ϫ2.30 (m, 3 H), 2.62Ϫ3.41 (m, 2 H), 4.31 (br. s, 1 H), 5.11 (s,
23c: To a mixture of 55 mg (0.134 mmol) of 23b and 33 mg (0.27
1 H), 5.14Ϫ5.22 (m, 1 H), 5.72Ϫ5.91 (m, 1 H), 5.98 (ddd, J1 ϭ 10
mmol) of DMAP, dissolved in 3 ml of dichloromethane, 0.02 ml
Hz, J2 ϭ 2 Hz, J3 ϭ 1 Hz, 1 H), 6.90 (dd, J1 ϭ 10 Hz, J2 ϭ 2 Hz,
(0.205 mmol) of acetic anhydride was added dropwise. After stir-
1 H). Ϫ MS (room temperature); m/z (%): 152 (1) [Mϩ], 134 (5),
ring for 1 h at room temperature, the reaction mixture was diluted
110 (51), 150 (3).
with water and extracted with diethyl ether. The organic phase was
22b: A mixture of 30 mg (0.20 mmol) of 22a, 35.6 mg (0.24
mmol) of tert-butyldimethylsilyl chloride and 30 mg (0.433 mmol)
washed with aqueous citric acid solution and then with aqueous
sodium hydrogen carbonate solution. The ethereal solution was
of imidazole in 2 ml of dry DMF was stirred for 2 d at room dried with MgSO4 and the solvent was evaporated under reduced
temperature. The reaction mixture was then diluted with water and pressure to yield 62 mg (100%) of a colourless oil. Ϫ [α]D ϭ Ϫ45.8
extracted with a mixture of diethyl ether and petroleum ether. The (c ϭ 0.325, CHCl3). Ϫ IR (CHCl3): ν˜ ϭ 2928 cmϪ1, 2856, 1736,
1
organic phase was washed with water and brine, and dried with
1512, 1228, 1180. Ϫ H NMR (200 MHz, CDCl3): δ ϭ 0.52 (br. d,
MgSO4. The solvent was evaporated to yield 42 mg (80%) of a J ϭ 13 Hz, 1 H), 0.83 (s, 3 H), 2.17 (s, 3 H), 2.62 (d, J ϭ 9 Hz, 1
colourless oil. Ϫ [α]D ϭ 232.5° (c ϭ 0.15, CHCl3). Ϫ IR (CHCl3): H), 3.31Ϫ3.13 (m, 1 H), 3.59 (dd, J1 ϭ 9 Hz, J2 ϭ 2 Hz, 1 H),
ν˜ ϭ 2956 cmϪ1, 2932, 2856, 1680, 1256, 1100. Ϫ 1H NMR (CDCl3, 3.82 (s, 3 H), 3.84Ϫ4.19 (m, 4 H), 5.19 (d, J ϭ 4 Hz, 1 H), 6.06 (d,
400 MHz): δ ϭ 0.13 (s, 3 H), 0.14 (s, 3 H), 0.93 (s, 9 H), 1.90Ϫ2.20
J ϭ 6 Hz, 1 H), 6.17 (d, J ϭ 6 Hz, 1 H), 6.87Ϫ6.96 (m, 2 H),
Eur. J. Org. Chem. 1998, 643Ϫ650
649

I. Gerstenberger, M. Hansen, A. Mauvais, R. Wartchow, E. Winterfeldt
FULL PAPER
7.25Ϫ7.36 (m, 2 H). Ϫ MS (150°C); m/z (%) 452 (2) [Mϩ], 437 (1), H), 6.33 (dd, J1 ϭ 10 Hz, J2 ϭ 3 Hz, 1 H). Ϫ MS (100°C); m/z
410 (1), 392 (2), 240 (100), 225 (6), 197 (4).
(%): 169 (57) [Mϩ ϩ 1], 168 (11) [Mϩ], 139 (20), 126 (76). Ϫ
C8H8O4 (168.15): calcd. 168.0423; found 168.0419 (MS).
24a: 48.8 mg (1.02 mmol) of an NaH dispersion was washed with
petroleum ether and dried under reduced pressure. 121 mg (1.02
mmol) of trimethyloxosulfonium chloride and 4 ml of DMSO were
then added. After stirring for 20 min at room temperature, a solu-
tion of 200 mg (0.51 mmol) of adduct 14 in 10 ml of DMSO was
added dropwise and stirring was continued for a further 2 h at
room temperature. The reaction mixture was then diluted with
water, the aqueous phase was extracted with diethyl ether, and the
combined organic phases were washed with water. The ethereal
solution was dried with MgSO4 and the solvent was evaporated
under reduced pressure to yield 185 mg (89%) of a colourless solid.
Ϫ M.p. 192°C. Ϫ [α]D ϭ Ϫ12.2 (c ϭ 0.45, CHCl3). Ϫ IR (CHCl3):
ν˜ ؍ 3052 cmϪ1, 2932, 2892, 1692, 1612, 1516, 1248, 1180, 1120,
1040. Ϫ 1H NMR (CDCl3, 200 MHz): δ ϭ 0.53 (br. d, J ϭ 13 Hz,
1 H), 0.72 (s, 3 H), 3.02 (d, J ϭ 11 Hz, 1 H), 3.82 (d, J ϭ 11 Hz,
1 H), 3.88 (s, 3 H), 4.01Ϫ4.12 (m, 4 H), 6.06 (d, J ϭ 6 Hz, 1 H),
6.11 (d, J ϭ 6 Hz, 1 H), 6.78Ϫ6.87 (m, 2 H), 7.07Ϫ7.15 (m, 2 H).
Ϫ MS (80°C); m/z (%): 406 (4) [Mϩ], 240 (100), 225 (23), 165 (17),
86 (34). Ϫ C26H30O4 (406.52): calcd. 406.2144; found 406.2105
(MS).
26: To a solution of 22 mg (0.05 mmol) of 25 in 6 ml of acetone,
1 ml of 6  HCl was added dropwise. The mixture was stirred at
room temperature for 1.5 h, diluted with water, and extracted with
dichloromethane. The organic phase was washed with a saturated
sodium hydrogen carbonate solution and dried with MgSO4. The
solvent was evaporated and the remaining oil was purified by flash
chromatography (diethyl ether) to yield 17.5 mg (89%) of a colour-
less solid. Ϫ M.p. 176°C. Ϫ [α]D ϭ Ϫ45.2 (c ϭ 0.155, CHCl3). Ϫ
IR (CHCl3): ν˜ ϭ 3000 cmϪ1, 2928, 2860, 1692, 1612, 1516, 1248,
1
1228, 1180. Ϫ H NMR (CDCl3, 200 MHz): δ ϭ 0.50 (d, J ϭ 13
Hz, 1 H), 0.72 (s, 3 H), 2.03 (dd, J1 ϭ 10 Hz, J2 ϭ 5 Hz, 1 H),
2.18 (dd, J1 ϭ 10 Hz, J2 ϭ 5 Hz, 2 H), 3.10 (d, J ϭ 10 Hz, 1 H),
3.80 (s, 3 H), 4.01 (d, J ϭ 10 Hz, 1 H), 6.05 (d, J ϭ 6 Hz, 1 H),
6.10 (d, J ϭ 6 Hz, 1 H), 6.82Ϫ6.92 (m, 2 H), 7.08Ϫ7.21 (m, 2 H).
Ϫ MS (150°C); m/z (%): 362 (1) [Mϩ], 240 (100), 225 (20), 197 (22),
165 (11). Ϫ C24H26O3 (362.47): calcd. 362.1882; found 362.1880
(MS).
27: 100 mg (0.246 mmol) of 24 was heated to 225°C under high-
vacuum conditions. Vapour pyrolysis took place at 350°C. The
products were eluted from the cold-trap with dichloromethane and
subsequently separated by flash chromatography (diethyl ether/
petroleum ether, 1:2) to yield 37 mg (90%) of a colourless oil. Ϫ
24b: An excess of LiAlH4 was refluxed for 30 min in 2 ml of dry
diethyl ether. The suspension was then cooled to Ϫ40°C and a
solution of 50 mg (0.123 mmol) of 24a in 2 ml of a 1:1 mixture of
diethyl ether and THF was added dropwise. After 10 min, the reac-
tion mixture was diluted with an aqueous ammonium chloride
solution and extracted with diethyl ether. The organic phase was
washed with brine and dried with MgSO4. The solvent was evapo-
rated to yield 43 mg (85%) of a colourless solid. Ϫ M.p. 181°C. Ϫ
[α]D ϭ Ϫ97 (c ϭ 0.17, CHCl3) Ϫ IR (CHCl3): ν˜ ϭ 3000 cmϪ1
,
1
2956, 2928, 2892, 1680, 1604, 1508, 1192, 1152, 1120. Ϫ H NMR
(CDCl3, 200 MHz): δ ϭ 1.07Ϫ1.17 (m, 1 H), 1.29Ϫ1.38 (m, 1 H),
1.92Ϫ2.11 (m, 2 H), 4.05Ϫ4.22 (m, 4 H), 5.84 (dd, J1 ϭ 10 Hz,
J2 ϭ 1.5 Hz, 1 H), 6.20 (dd, J1 ϭ 10 Hz, J2 ϭ 2 Hz, 1 H). Ϫ MS
(room temperature); m/z (%): 166 (85) [Mϩ], 138 (82), 112 (97), 78
(95), 66 (100). Ϫ C9H10O3 (166.18): calcd. 166.0630; found
166.0633 (MS).
[α]D ϭ Ϫ62.6 (c ϭ 0.225, CHCl ). Ϫ IR (KBr): ν ϭ 3527 cmϪ1
,
˜
3
2932, 2862, 1618, 1516, 1259, 1241, 1180, 1129. Ϫ 1H NMR
(CDCl3, 400 MHz): δ ϭ 0.48 (br. d, J ϭ 13 Hz, 1 H), 0.77 (s, 3
H), 1.91 (br. d, J ϭ 13 Hz, 1 H), 2.05 (ddd, J1 ϭ 13 Hz, J2 ϭ 13
Hz, J3 ϭ 4 Hz, 1 H), 2.35 (dd, J1 ϭ 13 Hz, J2 ϭ 13 Hz, 2 H), 2.89
(dd, J1 ϭ 11 Hz, J2 ϭ 5 Hz, 1 H), 3.80 (s, 3 H), 3.92 (d, J ϭ 11
Hz, 1 H), 4.00Ϫ4.31 (m, 4 H), 4.20Ϫ4.30 (m, 1 H), 5.89 (d, J ϭ 6
Hz, 1 H), 6.16 (d, J ϭ 6 Hz, 1 H), 6.83Ϫ6.88 (m, 2 H), 7.17Ϫ7.24
(m, 2 H). Ϫ MS (100°C); m/z (%): 408 (3) [Mϩ], 392 (2), 374 (1),
240 (100), 225 (18), 197 (15). Ϫ C26H32O4 (408.54): calcd. 408.2301;
found 408.2298 (MS).
[1]
R. Brünjes, U. Tilstam, E. Winterfeldt, Chem. Ber. 1991, 124,
1677Ϫ1678.
[2]
M. Beckmann, H. Hildebrandt, E. Winterfeldt, Chem. Ber.
1991, 124, 2505Ϫ2509.
[3]
M. Dockner, T.Meyer, P. Nemes, M. G. Otten, E. Winterfeldt,
Bull. Soc. Chem. Belg. 1994, 103, 379Ϫ387.
[4]
A. Mauvais, E. Winterfeldt, Tetrahedron 1993, 49, 5817Ϫ5822.
[5]
`
P. Riviere, A. Mauvais, E. Winterfeldt, Tetrahedron Asymm.
1994, 5, 1831Ϫ1846.
[6]
[7]
[8]
25: 185 mg (0.45 mmol) of 24 was heated to 250°C under high-
vacuum conditions and vapour-pyrolyzed at 350°C. The products
were eluted from the cold-trap with dichloromethane and sub-
sequently separated by flash chromatography (diethyl ether/petro-
T. M. Kamenecka, L. E. Overman, Tetrahedron Lett. 1994,
35, 4279Ϫ4282.
E. J. Corey, M. Chaykowsky, J. Am. Chem. Soc. 1965, 87,
1353Ϫ1364.
Crystallographic data for the structure reported in this paper
have been deposited with the Cambridge Crystallographic Data
Centre as no. CCDC-101024. Copies of the data can be ob-
tained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax: (int. code) ϩ 44(1223)336-033,
e-mail: deposit@ccdc.cam.ac.uk].
leum ether, 1:4) to yield 47 mg (62%) of a colourless oil. Ϫ [α]D
ϭ
Ϫ40 (c ϭ 0.06, CHCl3). Ϫ IR (CHCl3): ν˜ ϭ 2988 cmϪ1, 2960, 2628,
1
1696, 1512, 1264, 908, 816. Ϫ H NMR (CDCl3, 200 MHz): δ ϭ
3.49 (dd, J1 ϭ 4 Hz, J2 ϭ 2 Hz, 1 H), 3.59 (dd, J1 ϭ 4 Hz, J2 ϭ 3
Hz, 1 H), 4.11Ϫ4.27 (m, 4 H), 5.99 (dd, J1 ϭ 10 Hz, J2 ϭ 2 Hz, 1
[97306]
650
Eur. J. Org. Chem. 1998, 643Ϫ650