Full Paper
Received: 25 March 2011
Revised: 12 June 2011
Accepted: 13 June 2011
Published online in Wiley Online Library: 10 August 2011
(wileyonlinelibrary.com) DOI 10.1002/aoc.1826
Facile synthesis of indenones by
cyclopalladated ferrocenylimine-catalyzed
annulation of internal alkynes
Junli Zhang, Fan Yang∗ and Yangjie Wu∗
An efficient and facile protocol for the annulation of o-halobenzaldehyde derivatives with diverse internal alkynes has been
developed using cyclopalladated ferrocenylimine as the catalyst, and the indenones as the products could be obtained in
moderate to good yields. It was found for the first time that the addition of benzoic acid could remarkably speed up the reaction
c
process. Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: annulation; palladium catalysis; internal alkynes; indenones
Introduction
and diphenylacetylene (Table 1). Initially, a series of bases
were screened, and K2CO3 was shown to be the better choice
(Table 1, entries 1–9). Then, a variety of solvents, including DMAc,
acetonitrile, DMF, HMPA, DMSO, H2O and THF were checked, and
the results revealed that DMF was the best solvent, giving the
product with a high yield of 85% (Table 1, entries 10–15). The
addition of PhCOOH played an important role for the successful
reaction. In the absence of PhCOOH, a relatively lower yield of
60% was observed even after a prolonged reaction time of 24 h
(Table 1, entry 16). Other palladium catalysts, such as 5 mol% of
PdCl2 and Pd(OAc)2, were also checked and did not exhibit higher
catalytic activity (Table 1, entries 17 and 18).
Under these optimized conditions, the scope of the sub-
strates was also surveyed (Table 2). This catalytic system has been
proven to be effective for electron-neutral 2-halobenzaldehydes
(e.g. o-iodobenzaldehyde, o-bromobenzaldehyde and o-
chlorobenzaldehyde), affording the corresponding products
in moderate to good yields (Table 2, entries 1–3). For o-
halobenzaldehydes containing electron-donating groups, the
corresponding products were obtained in a good yield using
LiCl as the additive (Table 2, entries 4 and 5), while the an-
nulation of o-halobenzaldehydes bearing electron-withdrawing
groups did not occur at all (Table 2, entry 6). This indicated that
the electronic factor played a crucial role in the successful reaction
of o-halobenzaldehydes (Table 2, entries 1–6). For asymmetri-
cal internal alkynes, the reactions exhibited high regioselectivity
with the more sterically hindered group in the 3-position of the
Indenones are a family of important synthetic intermediates for
the construction of various organic and bioorganic compounds.[1]
Among the diverse routes for the synthesis of carbocycles such
as indenones, the palladium-catalyzed annulation of internal
alkynes could be the most facile and efficient.[2] The forma-
tion of 2,3-diphenylindenone can be realized by annulation of
o-iodobenzaldehyde with diphenylacetylene, promoted by stoi-
chiometric amounts of palladium species, as first discovered by
Heck and coworkers in 1989.[3] Subsequently, Vicente and cowork-
ers also described a stoichiometric palladium-assisted synthesis
of indenols and indenones.[4] Remarkable work in this area was
done be Larock et al., who introduced the first catalytic protocol
for the efficient synthesis of indenones, which represents a new
synthetic strategy for indenones, albeit this catalytic system has
some limitations in scope of the substrates.[5]
On the other hand, palladacycles have become a family of
versatile catalysts and exhibited high catalytic ability in the C–C
and C–heteroatom forming reactions.[6] Na´jera et al. realized the
facile preparation of 2,3-diphenylindenone assisted by this kind
of palladacycle.[7] However, there are still a few examples of the
synthesis of carbocycles involving palladacycles as the catalysts.
Recently, we found that cyclopalladated ferrocenylimine could act
as the palladacyclic catalyst in a wide variety of useful and well-
known coupling processes, ranging from classical reactions such
as Heck, Suzuki, Sonogashira and Buchwald–Hartwig couplings
to cyanation, addition reactions of arylboronic acids and coupling
reactions involving terminal alkynes (Fig. 1).[8] Inspired by these
promising reports and our own works, our research interests have
focused on exploring the possibility of using cyclopalladated
ferrocenylimine as catalysts in the annulation of internal alkynes.
∗
Correspondence to: Yangjie Wu and Fan Yang, Department of Chemistry, Key
Laboratory of Chemical Biology and Organic Chemistry of Henan Province, Key
Laboratory of Applied Chemistry of Henan Universities, Zhengzhou University,
Zhengzhou 450052 People’s Republic of China.
E-mail: wyj@zzu.edu.cn; yangf@zzu.edu.cn
Results and Discussion
Department of Chemistry, Key Laboratory of Chemical Biology and Organic
Chemistry of Henan Province, Key Laboratory of Applied Chemistry of Henan
Universities, Zhengzhou University, Zhengzhou 450052 People’s Republic of
China
On the basis of previous reports, we investigated the effect of
bases and solvents on the reaction of 2-bromobenzaldehyde
c
Appl. Organometal. Chem. 2011, 25, 675–679
Copyright ꢀ 2011 John Wiley & Sons, Ltd.