SCHEME 1. Syn th esis of th e Su bstitu ted
Qu in on es 2a , 2b, a n d 5
Acid -In d u ced Rea r r a n gem en t Rea ction s of
Red u ced Ben zoqu in on e Cyclop en ta d ien e
Cycloa d d u cts
Martin Eipert,† Ca¨cilia Maichle-Mo¨ssmer,‡ and
Martin E. Maier*,†
Universita¨t Tu¨bingen, Institut fu¨r Organische Chemie and
Institut fu¨r Anorganische Chemie, Auf der Morgenstelle 18,
D-72076 Tu¨bingen, Germany
martin.e.maier@uni-tuebingen.de
Received J uly 25, 2002
Abstr a ct: Several Diels-Alder adducts between benzo-
quinones and cyclopentadiene were reduced to the corre-
sponding diols 7a -c and 11. Treatment of these diols with
strong acid triggered a skeletal rearrangement reaction
resulting in compounds 8a -c and 12 that contain a 4,8-
methanoazulene substructure. In addition, a dyotropic-like
rearrangement of the tetracyclic lactone 13 to the spiro-
lactone 18 was observed. Five of the structures were sup-
ported by X-ray analysis.
(2c) was prepared by alkylation of hydroquinone with
benzyl alcohol in the presence of phosphoric acid, followed
by oxidation of the intermediate hydroquinone with silver
oxide.4 The quinone 5 that carries a propionic acid side
chain was prepared by oxidation of 3-(2-hydroxyphenyl)-
propionic acid (4) with bis(trifluoroacetoxy)iodobenzene
in an acetonitrile/water mixture. This route is much
shorter than the published one.5,6
Subsequently, the quinones 2a , 2b, and 2c were
subjected to a Diels-Alder reaction with cyclopentadiene
that led to the endo cycloadducts 6a ,7,8 6b, and 6c4 in
good yield (Scheme 2). To solubilize the quinones, the
reactions were performed in methanol. Typically, the
cycloaddition reactions were performed at room temper-
ature. As is known from related benzoquinone Diels-
Alder adducts, the sodium borohydride reduction leads
to the endo-diols. The diols 7a ,9,10 7b, and 7c could be
isolated, but the acid-induced rearrangement reaction
was usually done in the same flask. Thus, after the
reduction with sodium borohydride, concentrated sulfuric
acid was carefully added to the mixture. After stirring
overnight and extractive workup, TLC analysis indicated
the formation of several compounds. The most prominent
one was isolated by chromatography. Rearrangement of
7a needed around 30 h to be complete. In contrast, the
diols 7b and 7c rearranged much faster, being complete
after around 9 h.
Many natural products, particularly terpenes, illus-
trate in an impressive way how the combination of
cationic cyclization reactions and Wagner-Meerwein
shifts can generate a wide range of topologically different
structures. Cationic rearrangements are facilitated by
several factors such as ring strain, stereoelectronic ef-
fects, and proximity. As a case in point, one might quote
the skeletal reorganizations that are possible in the
camphor system.1 In connection with work on dearoma-
tized benzene derivatives such as cyclohexadienones and
quinone methides, we prepared Diels-Alder adducts
from benzoquinones and cyclopentadiene. It was discov-
ered that the diols that were obtained by hydride reduc-
tion of the cycloadducts entered into a cascade of cationic
rearrangement reactions leading to compounds with a
4,8-methanoazulene-9-ol substructure. In this paper, we
present the synthesis, structural elucidation, and a
mechanistic proposal for these rearrangements.
For this study, we employed four benzo-1,4-quinones
with an alkyl substituent in the 2-position. In addition,
benzoquinone was used. Alkylated quinones can be
prepared by alkylation of hydroquinonemethyl ethers
followed by oxidative ether cleavage. Another common
method involves the reaction of radicals with quinones
in the presence of an oxidant. Thus, methyl- and ethyl-
benzoquinones 2a and 2b were prepared by oxidative
decarboxylation of the corresponding carboxylic acids
with silver persulfate in the presence of benzoquinone.2,3
This way, the monoalkylated quinones were obtained in
reasonable yields (Scheme 1). Benzyl-1,4-hydrochinone
(4) Al-Hamdany, R.; Bruce, J . M.; Heatley, F.; Khalafy, J . J . Chem.
Soc., Perkin Trans. 2 1985, 1395-1400.
(5) Wegner, G.; Keyes, T. F., III; Nakabayashi, N.; Cassidy, H. G.
J . Org. Chem. 1969, 34, 2822-2826.
(6) Borchardt, R. T.; Cohen, L. A. J . Am. Chem. Soc. 1972, 94, 9175-
9182.
(7) Alder, K.; Flock, F. H.; Beumling, H. Chem. Ber. 1960, 93, 1896-
1899.
† Institut fu¨r Organische Chemie.
‡ Institut fu¨r Anorganische Chemie.
(1) Money, T. Nat. Prod. Rep. 1985, 253-289.
(2) J acobsen, N.; Torssell, K. Liebigs Ann. Chem. 1972, 763, 135-
147.
(3) J ockers, R.; Schmid, R. D.; Rieger, H.; Krohn, K. Liebigs Ann.
Chem. 1991, 315-321.
(8) Ichihara, A.; Kobayashi, M.; Oda, K.; Sakamura, S. Bull. Chem.
Soc. J pn. 1978, 51, 826-829.
(9) Shimizu, M.; Kamikubo, T.; Ogasawara, K. Heterocycles 1997,
41, 21-26.
(10) Wu, H.-J .; Chao, C.-S.; Lin, C.-C. J . Org. Chem. 1998, 63, 7687-
7693.
10.1021/jo026238i CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/01/2002
8692
J . Org. Chem. 2002, 67, 8692-8695