Antimony pentachloride catalyzed Diels-Alder reactions: Improved regioselectivity in the synthesis of dialkyl naphthoquinones

Article abstract of DOI:10.1016/S0040-4039(00)01968-7

Improved regioselectivity in catalyzed Diels-Alder (DA) cycloadditions between non-symmetrical benzoquinones and mono-substituted butadienes is achieved by use of SbCl₅. After oxidation, good yields of dialkylnaphthoquinones are obtained. The g

Full text of DOI:10.1016/S0040-4039(00)01968-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 219–221
Antimony pentachloride catalyzed Diels–Alder reactions:
improved regioselectivity in the synthesis of dialkyl
naphthoquinones
Ruth Leandro Nunes and Lothar Wilhelm Bieber*
Departamento de Qu´ımica Fundamental, Universidade Federal de Pernambuco, Recife 50740-540, Brazil
Received 24 October 2000; accepted 7 November 2000
Abstract—Improved regioselectivity in catalyzed Diels–Alder (DA) cycloadditions between non-symmetrical benzoquinones and
mono-substituted butadienes is achieved by use of SbCl5. After oxidation, good yields of dialkylnaphthoquinones are obtained.
The greater steric demand in comparison to other Lewis acids (LAs) seems to favor the less hindered transition state. © 2000
Elsevier Science Ltd. All rights reserved.
1,4-Benzoquinones are important dienophiles for the
construction of polycyclic natural products. However,
when non-symmetrically substituted reactants are used,
low selectivity is often observed and the separation of the
isomers can be problematic. For example, the thermal
reaction of toluquinone 1a and piperylene 2a (Scheme 1)
produces, after oxidative work up, a mixture of the
naphthoquinones in a ratio of 3a:4a of 30:70.1 BF3
catalysis inverts the isomer ratio 3a:4a to 69:31, but
obtaining pure 3a by crystallization or chromatography
is extremely difficult and low yielding.2 2,5-Dimethyl-1,4-
naphthoquinone, 3a, was the starting material in our
synthesis of Mansonone F recently described.3 Although
3a can also be obtained by the oxidation of 1,5-dimethyl-
naphthalene, the high cost of the latter and the low yield
of the reaction prompted us to reexamine the alternative
Diels–Alder (DA) reaction.
The improved selectivity obtained by BF3 catalysis was
rationalized in terms of Frontier Molecular Orbital
Theory.2 The uncatalyzed reaction favors the regioiso-
mer 4a, due to electronic effects. When BF3 is used, it
complexes preferentially, not exclusively, on carbonyl-4
of 1a, leading to inverted electronic distribution, favor-
ing regioisomer 3a. Such preference is not yet com-
pletely understood, but it is possible to explain it based
on steric interactions between the Lewis acid (LA) and
the methyl group of 1a, since the basicity of the car-
bonyl groups should be quite similar. Consequently, it
can be expected that a larger LA could still improve the
selectivity. Amongst the simple, commercially available
LAs commonly used in synthesis, SbCl5 is probably the
bulkiest because of the high atomic radius and coord-
ination number of Sb. To our surprise, its use in DA
reactions described in the literature is restricted to LA
Scheme 1.
Keywords: antimony pentachloride; benzoquinones; regioselectivity; Diels–Alder reactions.
* Corresponding author. Fax: (55) 81 271-8442; e-mail: lothar.bieber@dqfex.ufpe.br
0040-4039/01/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01968-7

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R. L. Nunes, L. W. Bieber / Tetrahedron Letters 42 (2001) 219–221
strength studies and, together with others acids, as a
comparison standard for zeolite catalysts.4,5
the same conditions as entry 1. Entry 6 represents the
DA reaction between hexadiene 2b and 1a, catalyzed by
SbCl5, yielding a 95:05 ratio of 3b:4b. The same reac-
tion catalyzed by BF3 (entry 7) gave an 87:13 ratio of
3b:4b. This result indicates a preference for a less
hindered arrangement diene–dienophile–LA in the
transition state as the LA becomes larger. In compari-
son, the thermal reaction was completely unselective
(entry 8).
Variable conditions of temperature, solvent, concentra-
tion and ratio of reagents were tested. The best results
were achieved when a solution of 1a was treated with
10% of SbCl5, at −70°C (entry 1, Table 1), followed by
the addition of an excess of diene 2a. After completion
of the reaction, about 2 h, the mixture was isomerized
and oxidized, to eliminate the problem of endo/exo
stereoisomers, and furnished 3a and 4a in a ratio of
90:10, significantly better than the 70:30 obtained with
BF3 under similar conditions (entry 2); from this mix-
ture, pure 3a could be isolated by simple crystallization.
This result suggests that complexation on the less hin-
dered carbonyl-4 of 1a has increased with SbCl5. Entry
3 presents the uncatalyzed DA reaction and confirms
the results described in the literature.1,2 It is worth
mentioning that experiments were also carried out using
TiCl4 (entry 4), under the same conditions, giving a
38:62 ratio of 3a:4a, similar to the uncatalyzed reaction.
This unexpected effect of TiCl4 catalysis in DA reac-
tions has been observed in other cases and is not
completely understood.6 The adsorption effects of SiO2
in DA reactions were also tested in entry 5: although
the reaction rate was enhanced, we observed a 33:67
ratio of 3a:4a ratio, which is very similar to that for the
uncatalyzed reaction.
On the other hand, increasing the size of the substituent
in the quinone, as in 1c, the same single product was
obtained in the catalyzed and uncatalyzed reactions
(entries 9–11). Its structure 3c (‘meta’) was deduced by
1
a comparison of the H NMR data with known naph-
thoquinones of the same substitution pattern. Steric
demand in 1c is such that both catalysts were forced to
complex at the carbonyl-4, causing the exclusive forma-
tion of 3c. In the thermal reaction, it seems that steric
factors become more important than electronic ones,
since no trace of the ‘ortho’ product 4c was detected.
The SbCl5 catalyzed reaction between isoprene and 1a
did not result in better selectivity than the thermal
reaction and produced high amounts of polymeric
material.
In conclusion, the use of SbCl5 can enhance the regiose-
lectivity in DA reactions when steric and electronic
factors compete in the transition state. Our results
should encourage further applications in regioselective
LA-catalyzed reactions.
Since synthesis of 2,5-dimethyl-1,4-naphthoquinone, 3a,
could be improved by SbCl5 catalysis, we started inves-
tigations with similar diene/dienophile systems, under
Table 1. DA reactions in toluene of 1,4-dienes and -benzoquinones

R. L. Nunes, L. W. Bieber / Tetrahedron Letters 42 (2001) 219–221
221
Typical procedures
J=7.5 Hz), 5.95 (1H, q, J=1.5 Hz), 6.70 (1H, dd,
J=7.8, 1.8 Hz), 6.75 (1H, dd, J=7.8, 7.8 Hz), 7.69
(1H, dd, J=7.8, 1.8 Hz) ppm. 3c: yellow crystals; mp
86°C; l 1.18 (9H, s), 2.68 (3H, s), 6.60 (1H, s), 6.89
(1H, dd, J=7.5, 0.6 Hz), 6.97 (1H, dd, J=7.5, 7.5 Hz),
8.00 (1H, dd, J=7.5, 0.6 Hz) ppm.
Catalyzed reaction: A solution of 1 mmol of 1 in 5 mL
of toluene was treated with 0.1 mmol of LA, at −70°C,
followed by the slow addition of 4 mmol of 2. After 2
hours, at −70°C, 0.5 mL of HCl (1N) and 5 mL of cold
H2O were added. After extraction and evaporation of
toluene, the residue was dissolved in 5 mL of concen-
trated HOAc and refluxed for 30 min. A solution of 2
g of CrO3, in 5 mL of H2O, was slowly added at 70°C.
After 15 min, at 70°C, this mixture was poured over 10
g of ice. Crystals were formed in entries 1–5 and 9–11,
which were filtered and dried. In entries 6–8, the oily
product was extracted with hexane. These crude materi-
als were analyzed by GC (5% phenylmethylsilicone,
Acknowledgements
CNPq (Bras´ılia) and FACEPE (Recife) supported this
work.
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