Published on Web 03/29/2007
Intramolecular Anionic Diels-Alder Reactions of
1-Aryl-4-oxahepta-1,6-diyne Systems in DMSO
Takayuki Kudoh,† Tomoko Mori,† Mitsuhito Shirahama,† Masashi Yamada,†
Teruhiko Ishikawa,† Seiki Saito,*,† and Hisayoshi Kobayashi‡
Contribution from the Department of Medical and Bioengineering Science, Graduate School of
Natural Science and Technology, Okayama UniVersity, Tsushima, Okayama, Japan 700-8530,
and Department of Chemistry and Material Technology, Faculty of Engineering and Design,
Kyoto Institute of Technology, Matsugasaki, Kyoto, Japan 606-8585
Received September 7, 2006; E-mail: seisaito@biotech.okayama-u.ac.jp
Abstract: Base-promoted cycloaddition reactions of 1-aryl- or 1-aryl-7-substituted-4-oxahepta-1,6-diyne
systems in DMSO have proven to involve an anionic intramolecular Diels-Alder process taking place even
at room temperature in spite of the reaction suffering from temporary disruption of aromaticity. Although
initially formed R-arylallenide anion can be protonated by DMSO, it can be back to the allenide anion probably
because of a small acidity difference between R-arylallene and DMSO. The R-arylallenide anion in
combination with the R-aryl substituent can constitute an anionic diene structure that undergoes the
intramolecular Diels-Alder reaction involving the C(6)-yne part, a very fast process probably because of
the increased HOMO-1 level of the anionic diene, as shown by DFT calculations. Diversified substituted
naphthalenes, benzofurans, phenanthrenes, and quinolines, including biaryl architectures, are available
from 4-oxahepta-1,6-diynes in a highly expeditious way.
Introduction
On the other hand, for the base-promoted Diels-Alder
reaction, only limited reports concerned with two-representative
The power of Diels-Alder reactions1 has been highlighted
in transforming a simple combination of diene and dienophile
into cyclohexene rings in a myriad of contexts for 80 years after
its discovery.2 A lot of versions of the Diels-Alder reaction
have been explored to establish valuable and irreplaceable ways
for constructing complex molecules.3 In particular, the Lewis
acid-promoted Diels-Alder reaction, with dienophiles bearing
an electron-withdrawing group capable of making complexes
with Lewis acids, has provided diverse opportunities in organic
synthesis including asymmetric synthesis.4 An extraordinary rate
acceleration effected by the Lewis acid in the Diels-Alder
reaction5 can be rationalized as a result of lowering an energy-
level of dienophile LUMO by such a coordination of the Lewis
acid to the dienophile.6
systems have appeared so far. One typical example is that the
Diels-Alder reaction between 9(10H)-anthracenone (anthrone)
and N-methylmaleimide (NMM) extremely rapidly proceeds in
hydrogen bond acceptor solvents such as DMF, pyridine, or
triethylamine; in DMF, the reaction is complete within a few
minutes, affording an almost quantitative yield of adduct-1,
whereas in CDCl3 it affords only 14% of the adduct-1 after 68
h at 25 °C. These results were reasoned by a mechanism
involving highly reactive oxido diene provided through a base-
promoted enolization process as shown in Scheme 1, which they
referred to as catalytic oxyanion acceleration mechanism.7
Similar oxyanion acceleration systems involving a dienolate
available through kinetically favored deprotonation of cyclo-
hexenone with LDA was demonstrated to react with methyl
acrylate to give bicyclo[2.2.2]nonane framework (adduct-2) in
90% yield under the given reaction conditions, as shown in
Scheme 2.8 Although the reaction can be rationalized as a [4 +
2] cycloaddition process, a conceivable stepwise mechanism
involving domino Michael pathway was suggested on the basis
of the very mild conditions under which the reaction occurred.9
† Okayama University.
‡ Kyoto Institute of Technology.
(1) For reviews or monographs, see (a) Oppolzer, W. In ComprehensiVe
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Roush, W. R. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Flemming, I., Paquette, L. A., Eds.; Pergamon Press: Oxford, 1991; Vol.
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Tamura, Y.; Sasho, M.; Nakagawa, K.; Tsugoshi, T.; Kita, Y. J. Org. Chem.
1984, 49, 473-483. (f) Ihara, M.; Suzuki, M.; Fukumoto, K.; Kametani,
T. Kabuto, C. J. Am. Chem. Soc. 1988, 110, 1963-1964. (g) Marchand,
A. P.; Annapurna, P.; Watson, W. H.; Nagl, A. Chem. Commun. 1989,
281-282.
(5) Yates, P.; Eaton, P. J. Am. Chem. Soc. 1960, 82, 4436-4437.
(6) Houk, K. N.; Strozier, R. W. J. Am. Chem. Soc. 1973, 95, 4094-4096.
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10.1021/ja066485u CCC: $37.00 © 2007 American Chemical Society
J. AM. CHEM. SOC. 2007, 129, 4939-4947
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