COMMUNICATION
Construction of aryl-substituted triquinanes through the interrupted
Nazarov reactionw
Curtis J. Rieder, Ryan J. Fradette and F. G. West*
Received (in College Park, MD, USA) 16th January 2008, Accepted 7th February 2008
First published as an Advance Article on the web 25th February 2008
DOI: 10.1039/b800800k
The first examples of intermolecular trapping of Nazarov
cyclopentenyl cation intermediates by simple arenes to furnish
a-arylcyclopentanones are described.
of cyclopentenyl cation to the 5-position of the furan ring of
3a, and this product could be suppressed by increasing the
ratio of furan to 1a to 10 : 1. It was not possible to determine
the relative configurations of the two triquinane units of 4a,
given the large distance separating the two moieties.
The Nazarov cyclization is a well established method for
construction of substituted cyclopentanoid ring systems.1 Re-
cently, we have shown that the electrophilic 2-oxidocyclo-
pentenyl cation intermediate is subject to capture by a variety
of pendent nucleophilic traps.2 We have been especially inter-
ested in trapping by arenes, as this process furnishes
a-arylcyclopentanones from simple reactants. The intramole-
cular version of the reaction is effective, producing complex
fused or bridged tricyclic systems from either dienone3 or
dichlorocyclopropane4 precursors containing pendent arene
traps. However, the corresponding bimolecular process could
not be observed with dienone substrates that had been success-
fully captured intermolecularly by a variety of other traps.5
Here we describe the first successful examples of intermolecu-
lar arylation of the Nazarov intermediate, using bicyclic
dienone precursors and a variety of electron-rich arene traps.
Initial studies focused on dicyclopentenyl ketone 1a. This
substrate had previously been shown to undergo a variety of
productive intermolecular trapping processes; in particular, its
efficient [3þ2] trapping by allylsilanes5b to furnish bridged/
fused tetracyclic adducts was encouraging. With this in mind,
we set out to explore the corresponding [4þ3] trapping,5c using
one equivalent of furan (Scheme 1). To our surprise, none of
the expected cyclooctene product 2a was obtained. Instead, a
mixture of furyltriquinanes 3a and 4a was isolated in good
yield. Spectral analysis of 3a confirmed the installation of a 2-
furyl substituent at one of the bridgehead positions a to the
cyclopentanone carbonyl group, consistent with electrophilic
aromatic addition of the cyclopentenyl cation intermediate.
The relative stereochemistry of 3a was inferred from the
known conrotatory electrocyclization mechanism together
with the precedent for preferential nucleophilic trapping5b to
form cis ring-fusions. Likewise, protonation of the enolate
formed after nucleophilic capture is expected to proceed with
high or complete selectivity for the more stable cis-fused ring
system. Product 4a arises from addition of a second equivalent
Using the optimized conditions, 1a was subjected to trap-
ping experiments using a variety of simple arene traps
(Table 1). Bridgehead arylated triquinanes 3b–d were obtained
in very good yields. Notably, 1,3-dimethoxybenzene was an
effective trap, demonstrating that this new reactivity is not
limited to heteroaromatic nucleophiles. However, no nucleo-
philic capture was observed with the less electron-rich anisole;
instead, the simple Nazarov elimination product 5 was ob-
tained (entry 5). The cis ring-fusion stereochemistry for 3a–d
was confirmed by 2D TROESY experiments, which indicated
correlations between aryl protons and the neighboring bridge-
head methines (see ESIw for details).
Next, other dienones were examined. Efficient trapping of
1a by electron-rich arenes suggested that in those cases the
simple eliminative termination step was slow enough to allow
bimolecular electrophilic aromatic substitution to compete
effectively. It is possible that elimination is conformationally
impeded in the rigid, polycyclic intermediate cation. With this
in mind, we chose to examine the homologous dienone 1b,
which could be prepared by addition of 1-lithiocyclopentene to
cyclohexenecarboxaldehyde, followed by Dess–Martin
oxidation.
Treatment of 1b with furan under the optimized conditions
noted above furnished two adducts in good yield, but which
Department of Chemistry, University of Alberta, E3-43 Gunning-
Lemieux Chemistry Centre, Edmonton, AB, Canada T6G 2G2.
E-mail: frederick.west@ualberta.ca; Fax: þ1 780-492-8231;
Tel: þ1 780-492-8187
w Electronic supplementary information (ESI) available: Experimental
procedures and spectral data for all new compounds. See DOI:
10.1039/b800800k
Scheme 1 Nucleophilic trapping of 1a by furan.
ꢀc
This journal is The Royal Society of Chemistry 2008
1572 | Chem. Commun., 2008, 1572–1574
Rieder, Curtis J.
