Palladium(II)-catalyzed ring expansion of a 1-alkenyl cyclopentanol

Article abstract of DOI:10.1016/j.tetlet.2005.03.068

7,7-Dimethyl-2-methylenenorbornan-1-ol, a strained bicyclic 1-alkenyl cyclopentanol, undergoes Wagner-Meerwein rearrangement to fenchone under treatment with a catalytic amount of PdCl₂(PPh₃) ₂ in refluxing N-methylpyrrolidin-2-one. The described reaction constitutes the first example of the palladium(II)-catalyzed ring expansion of 1-alkenyl cyclopentanols to the corresponding cyclohexanones.

Full text of DOI:10.1016/j.tetlet.2005.03.068

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3509–3511
Palladium(II)-catalyzed ring expansion of a
1-alkenyl cyclopentanol
a,
Antonio Garcıa Martınez, Enrique Teso Vilar, Amelia Garcıa Fraile,
b
b
*
´
´
´
Santiago de la Moya Cereroa,* and Beatriz Lora Marotob
a
´ ´ ´
Departamento de Quımica Organica I, Facultad de Quımica, Universidad Complutense de Madrid,
Ciudad Universitaria s/n, 28040 Madrid, Spain
b
´ ´ ´
Departamento de Quımica Organica y Biologıa, Facultad de Ciencias, Universidad Nacional de Eudacion a Distancia,
Senda del Rey 9, 28040 Madrid, Spain
´
Received 25 February 2005; revised 9 March 2005; accepted 14 March 2005
Available online 1 April 2005
Abstract—7,7-Dimethyl-2-methylenenorbornan-1-ol, a strained bicyclic 1-alkenyl cyclopentanol, undergoes Wagner–Meerwein
rearrangement to fenchone under treatment with a catalytic amount of PdCl2(PPh3)2 in refluxing N-methylpyrrolidin-2-one. The
described reaction constitutes the first example of the palladium(II)-catalyzed ring expansion of 1-alkenyl cyclopentanols to the
corresponding cyclohexanones.
Ó 2005 Elsevier Ltd. All rights reserved.
Ring-expansion reactions have a great interest in syn-
thetic organic chemistry since they provide efficient tac-
tics for the preparation of biologically active natural
products and drugs.1 In this sense, the palladium(II)-
promoted ring-expansion reaction of 1-alkenyl or
1-alkynyl cyclobutanols to cyclopentanones is a well-
known process, which has been successfully used for
the construction of several interesting natural products
with frameworks based on five-membered rings.2 The
reaction takes place by an initial required formation of
an alkene or alkyne p-complex before migration of a
(generally secondary) carbon (Scheme 1).
these cases the reaction is generally initiated by a carbo-
palladation, using a Heck-type reaction with aryl
halides,3 or generating a p-allylpalladium intermediate
by different ways (including also Heck-type reactions).4
All this palladium-based ring-expansion methodology
can also be applied to other strained rings, such as the
three-membered ones.5 Thus, 1-alkenyl and 1-alkynyl
cyclopropanols have been expanded to the correspond-
ing cyclobutanones by treatment with palladium(II)5b,c
or palladium(0)5a,d catalysts. Unfortunately, the related
expansion of less strained five-membered rings are
unusual, with the exceptions of the NagaoÕs palla-
dium(0)-catalyzed ring expansion of 1-(1-methoxy-
allenyl)cyclopentanols, via p-allylpalladium intermediates,6a
and a more complex palladium(0)/phosphine-catalyzed
ring expansion of 1-acryloylcyclopentanols of the same
author.6b
Related 1-alkenyl or 1-alkynyl cyclobutanol expansions
can be also realized using palladium(0) catalysts. In
H
O
PdXL2
R
migration
R
+
HX
Our approach to find
a
palladium(II)-catalyzed
PdX2Cl2
ring-expansion reaction of 1-alkenyl cyclopentanols is
performed by the use of 7,7-dimethyl-2-methylenenorbor-
nan-1-ol (1a) or 3,3-dimethyl-2-methylenenorbornan-1-ol
(1b) as the starting 1-alkenyl cyclopentanols (Fig. 1),
since such strained 1-alkenyl cyclopentanols have been
demonstrated to exhibit a great tendency for undergoing
cationic Wagner–Meerwein rearrangement to the corre-
sponding cyclohexanones (2-norbornanones) under
Scheme 1. Palladium(II)-promoted ring expansion of 1-alkenyl or
1-akynyl cyclobutanols.
Keywords: Palladium catalysis; Ring expansion; Bicycles; Cyclo-
pentanols.
*
Corresponding authors. Tel.: +34 913945090; fax: +34 913944103;
e-mail: santmoya@quim.ucm.es
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.03.068

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A. Garcıa Martınez et al. / Tetrahedron Letters 46 (2005) 3509–3511
3510
hindrance existing around the carbon–carbon double bond
OH
OH
of 1b exerted by the C(3)-gem-dimethyl group (cf. 1a
and 1b in Fig. 1), as well as the also high steric volume
of the palladium-species bearing phosphine ligands.
1b
1a
In summary, the first palladium(II)-catalyzed ring-
expansion reaction of a 1-alkenyl cyclopentanol has
been described. Further investigations on the possible
synthetic application of palladiated intermediate 4a for
the preparation of new enantiopure C(10)-substituted
fenchones,9 as well as on the possible extension of such
rearrangement to other related bicyclic alcohols, are in
progress.
Figure 1. Selected starting strained 1-alkenyl cyclopentanols.
stoichiometric treatment with adequate electrophiles.7
Additionally, both starting 1-alkenyl cyclopentanols 1a
and 1b can be easily obtained from fenchone and cam-
phor, respectively.7
We have found that 1-alkenyl cyclopentanol 1a is able to
undergo Wagner–Meerwein rearrangement to fenchone
(2a) after treatment with a catalytic amount of
PdCl2(PPh3)2 in refluxing N-methylpyrrolidin-2-one
(NMP) (Scheme 2), whereas analogue 1b remains
unalterated after the same palladium(II) treatment.8
Acknowledgements
´
We thank the Ministry of Ciencia y Tecnologıa and the
Ministry of Educacion y Ciencia of Spain (BQU2001-
´
1347-C02 and CTQ2004-07244-C02/BQU, respectively)
for the financial support of this work.
The rearrangement shown in Scheme 2 constitutes the
first example of a palladium(II)-catalyzed ring-expan-
sion reaction of a 1-alkenyl cyclopentanol to the corre-
sponding cyclohexanone (see catalytic cycle in Scheme
3). The unreactivity of 1b can be attributed to the diffi-
culty of such substrate to coordinate the palladium(II)
catalyst and to form the corresponding initial required
p-complex. This difficulty is due to the high steric
References and notes
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5% PdCl2(PPh3)2 / refluxing NMP
OH
ca. quantitative
O
1a
2a
Scheme 2. Palladium(II)-catalyzed ring-expansion reaction of 1-alken-
yl cyclopentanol 1a.
HCl
H
O
PdCl2L2
3a
O
PdL2
Cl
4a
1a
PdCl2L2
5. For example, see: (a) Aoki, S.; Fujimura, T.; Nakamura, E.;
Kuwajima, I. J. Am. Chem. Soc. 1988, 110, 3296; (b) Park,
S.-B.; Cha, J. K. Org. Lett. 2000, 2, 147; (c) Okumoto, H.;
Jinnai, T.; Shimizu, H.; Harada, Y.; Mishima, H.; Suzuki,
A. Synlett 2000, 629; (d) Trost, B. M.; Yasukata, T. J. Am.
Chem. Soc. 2001, 123, 7162.
HCl
2a
6. For example, see: (a) Nagao, Y.; Ueki, A.; Asano, K.;
Tanaka, S.; Sano, S.; Shiro, M. Org. Lett. 2002, 4, 455, and
Scheme 3. Catalytic cycle.

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3511
related references cited therein; (b) Nagao, Y.; Tanaka, S.;
Ueki, A.; Kumazawa, M.; Goto, S.; Ooi, T.; Sano, S.;
Shiro, M. Org. Lett. 2004, 6, 2133.
argon atmosphere. After that, the reaction mixture was
analyzed by GC/MS, showing the quantitative conversion
of 1a to 2a, as well as the unreactivity of 1b.
´
7. As a review, see: de la Moya Cerero, S.; Garcıa Martınez,
A.; Teso Vilar, E.; Garcıa Fraile, A.; Lora Maroto, B.
´
9. On the synthetic importance of enantiopure C(10)-substi-
´ ´
tuted fenchones, see: Garcıa Martınez, A.; Teso Vilar, E.;
´
´
Garcıa Fraile, A.; de la Moya Cerero, S.; Lora Maroto, B.
Tetrahedron: Asymmetry 2001, 12, 3325, and references
cited therein.
J. Org. Chem. 2003, 68, 1451.
8. A solution of 1a or 1b (0.100 mmol) and PdCl2(PPh3)2
(0.005 mmol) in NMP (1.5 mL) was refluxed for 6 h under