Bi(OTf)3-catalyzed cycloisomerization of aryl-allenes

Article abstract of DOI:10.1021/ol3009667

Intramolecular hydroarylation of allenes was achieved under very mild conditions using bismuth(III) triflate as the catalyst. Efficient functionalization of activated and nonactivated aromatic nuclei led to C-C bond formation through a formal Ar-H activation. A tandem bis-hydroarylation of the allene moiety was also developed giving access to various interesting polycyclic structures.

Full text of DOI:10.1021/ol3009667

ORGANIC
LETTERS
2012
Vol. 14, No. 11
2750–2753
Bi(OTf)3-Catalyzed Cycloisomerization of
Aryl-Allenes
ꢀ
Gilles Lemiere, Bastien Cacciuttolo, Emilie Belhassen, and Elisabet Dunach*
~
ꢁ
Institut de Chimie de Nice, UMR 7272, Universite de Nice Sophia-Antipolis, CNRS,
Parc Valrose, 06108 Nice Cedex 2, France
dunach@unice.fr
Received April 14, 2012
ABSTRACT
Intramolecular hydroarylation of allenes was achieved under very mild conditions using bismuth(III) triflate as the catalyst. Efficient
functionalization of activated and nonactivated aromatic nuclei led to CꢀC bond formation through a formal ArꢀH activation. A tandem bis-
hydroarylation of the allene moiety was also developed giving access to various interesting polycyclic structures.
The development of catalytic, clean, efficient, and mild
synthetic methods to create CꢀC bonds remains one of the
most important topics in the field of organic chemistry.
In this context, catalytic FriedelꢀCrafts reactions have
gained particular attention.1 The hydroarylation, namely
theaddition ofanareneCꢀH bondacrossamultiplebond,
represents the most atom-economical means to function-
alize aromatic nuclei since theoretically no waste is pro-
duced during the reaction. Although the studies concern-
ing the catalytic hydroarylation of alkynes2 and alkenes3
have been well-undertaken, the extension to related allenes
has been less pursued.4 Allenes have gained increasing
attention during the past decades5 and numerous tran-
sition-metal-catalyzed cycloisomerizations6 and cyclo-
additions7 involving allenes have been developed and
enable access to valuable cyclic compounds usually
with good selectivities.
Hydroarylation of allenes has been mainly reported
using noble transition-metal catalysts based on gold8,6c
and platinum9 derivatives. This strategy has been elegantly
used as the key step in the total synthesis of natural
compounds with the functionalization of pyrrole10 and
indole11 derivatives. Despite their efficiency, these meth-
odologies suffer from the need to use only electron-rich
ꢁ
arenes. For instance, Gagne has recently described the
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r
10.1021/ol3009667
Published on Web 05/11/2012
2012 American Chemical Society

Our grouphas been interestedinthe development ofnew
cycloisomerization processes catalyzed by triflate12 and
triflimide13 metal salts. Bismuth(III) triflate has recently
emerged as a suitable and relatively inexpensive catalyst
to catalyze various organic transformations14 including
FriedelꢀCrafts acylation,15 benzylation,16 and propargyla-
tion.17 Moreover, this metal salt could be successfully
employed as a π-Lewis acid to formally activate alkynes18
and alkenes.12d,e We envisioned that bismuth(III) triflate
could be an appropriate catalyst for the intramolecular
hydroarylation of allenic substrates bearing a tethered
activated and nonactivated aromatic ring.
In earlier studies, we noticed that nitromethane was an
excellent solvent to perform CꢀC double bond activation
with Bi(OTf)3.12e By treatment with 5 mol % of this
catalyst in nitromethane, the arene-allene 1a, featuring a
simple phenyl ring, was cleanly converted into tetralin 2a
after 30 min at room temperature with an excellent yield
of99% (Scheme 1). This result constitutes the first example
of a catalyzed intramolecular FriedelꢀCrafts allylation of
nonactivated phenyl rings, involving the participation of
an allene under very mild conditions. Moreover, it avoids
the use of noble metal complexes. Other metal triflates and
metal complexes were also screened with no improvement
of the efficiency.19 Interestingly, triflic acid did catalyze
this reaction with almost the same yield as Bi(OTf)3;
nevertheless we preferred exploring the scope and limita-
tions of this novel cycloisomerization with the Bi(III) salt,
since it gave generally better results. Moreover it is safer
and easier-to-handle than corrosive and toxic triflic acid.
We next examined the influence of the nature of the
linker by introducing an ether function. Oxygen-containing
heterocycles are of particular interest, and the develop-
ment of new reactions to access substituted and func-
tionalized chromanes, an important class of naturally
occurring and bioactive compounds,20 is highly sought
after. Satisfyingly, readily available phenol derivative 3a
was converted into the isobutenyl chromane 4a at room
temperature with an excellent yield of 93% (Table 1,
entry 3). In this case, the catalyst loading could be reduced
to only 1 mol % without a decrease in catalytic activity.
Allenic substrate 3b, easily obtained from vanillin and
bearing additional methyl ether and aldehyde functions
on the aromatic ring, was transformed into polysubstitu-
ted chromane 4b in good yield, despite the presence of
the aldehyde (entry 4). Chromane 4c with a 4-MeO sub-
stituent could be obtained from allene 3c with a low
catalyst loading of 1 mol % (entry 5). Gratifyingly, the
less electron-rich para-Cl derivative 3d underwent a clean
and efficient cyclization to 4d within a short reaction time
(entry 6). Interestingly, under the same reaction condi-
tions, chiral-racemic substrate 3e provided the bicyclic
compound 4e with the trans configuration, as the only
diastereoisomer (Table 1, entry 7). Tetrahydroquinoline 6
was also obtained from tosylamide 5, demonstrating good
functional group tolerance and the broad applicability of
this novel bismuth(III)-catalyzed transformation (entry 8).
In addition, the catalyst could be recovered quantitatively
byaqueousextractionand solvent evaporation and recyled
in a second run with no loss of catalytic activity.20
One interesting feature of this reaction is that the
products obtained after the cyclization still contain a
CꢀC double bond which can be further functionalized.
We wondered whether, at higher temperature, the same
Bi(OTf)3 catalyst could allow a subsequent hydroarylation
of the generated olefin, to produce appealing tricyclic
frameworks.
Scheme 1. Bi(OTf)3-Catalyzed Transformation of 1a
Gratifyingly, when the previous hydroarylation reaction
was performed at a higher temperature, i.e. at refluxing
nitromethane, arene-allene 1a was directly converted into
the tricyclic compound 9a in 98% yield (Table 2, entry 1).
This new tandem reaction was then extended to other
allenic substrates. Allene 1b bearing an i-Pr substituent
easily underwent the double cyclization to afford the
polycycle 9b (entry 2). The oxygen-containing tricyclic
product 10c could be obtained from 3c in 69% yield
(entry 3). The reactivity of the allenic precursor 1c linked
A subsequent exemplification of the reaction with arene-
substituted analogues of 1a was undertaken. Allene 1b
substituted in the para position with an i-Pr group under-
went smooth cyclization tothe corresponding carbobicycle
2b with an excellent yield (Table 1, entry 2).
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Org. Lett., Vol. 14, No. 11, 2012
2751

Table 1. Bi(III)-Catalyzed Cyclohydroarylation of Allenes
Table 2. Bi(III)-Catalyzed Tandem Intramolecular Cyclizations
a Reaction conditions: allenic substrate in CH3NO2 (0.2 M) at the
indicated temperature with 5 mol % of Bi(OTf)3. b Isolated yields.
Scheme 2. Selective Formation of 2d and 9d
a Reaction conditions: allenic substrate in CH3NO2 (0.2 M) at room
temperature with 5 mol % of Bi(OTf)3. b Isolated yields. c 1 mol % of
catalyst was used. d The reaction was conducted at reflux. e Only the
trans-diastereoisomer was obtained.
only 10 min at room temperature in almost quantitative
yield (Table 2, entry 5).
to a 2-naphthyl group was also investigated. In the pre-
sence of 5 mol % Bi(OTf)3 at room temperature, the
tandem reaction proceeded smoothly and afforded regio-
selectively the tetracyclic product 11c in 97% yield (entry 4).
The tetrahydropyrene structure was confirmed by X-ray
crystallographic analysis.19 Methyl ether derivative 1d
could be cleanly cyclized into tricyclic compound 9d in
Remarkably, when the reaction was conducted with
TfOH (5 mol %) under the same conditions, only the
olefin intermediate 2d was formed with an excellent yield
(Scheme 2). This result clearly points out a difference of
behavior between TfOH and bismuth(III) triflate for this
transformation. The few examples of gold(I)-catalyzed
intermolecular hydroarylation of allenes with electron-rich
arenes did not allow further participation of the remaining
pendant double bond.21 Remarkably, in the presence
of Bi(OTf)3, trisubstituted allene 12 reacted cleanly with
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Org. Lett., Vol. 14, No. 11, 2012

1,2-dimethoxybenzene at room temperature to form the
functionalized Indane 13 in 94% yield, through an inter-
molecular regioselective tandem FriedelꢀCrafts allyla-
tion/alkylation (Scheme 3).
CD3NO2. The resulting mixture failed to promote cycliza-
tion in the presence of allene 1a, which suggests that an
LBA-type catalysis is presumably involved.
Scheme 4. Mechanistic Aspects: Plausible Activation Modes of
the Allene by Metal Triflates
Scheme 3. Intermolecular Bi(OTf)3-Catalyzed Tandem Reac-
tions
Mechanistically, two general distinctive activation
modes of the allene can be proposed for these cycloisome-
rizations. The first one is a purely metallic-based pathway
in which the initial allene activation arises from a η1 or η2
sigma-type interaction between the electrophilic metal
center and the allene moiety as previously established for
gold catalysis (Scheme 4).22
Inconclusion wereporthere thatcommerciallyavailable
and nontoxic bismuth(III) triflate is a suitable catalyst to
successfully promote the hydroarylation of substituted
allenes under very mild conditions. This reaction is quite
general and has been used to synthesize carbocycles and
heterocycles without using noble metals and additional
ligands. Moreover, a new tandem reaction with a low
catalyst loading has been developed in both intra- and
intermolecular versions to form polycyclic structures.
Some mechanistic investigations are in progress in order
to devise appropriate enantioselective approaches to this
unprecedented transformation.
The second possibility would involve a Brønsted acid
catalysis. Many metal triflate mediated transformations
havebeendescribedproceedingvia proton transfer, but the
nature of the catalytic species is still under debate.23 Metal
cations such as Bi3þ and Al3þ in water exhibit strong acidic
properties because of the acidification through coordina-
tion of water molecules present in the “inner-sphere” of the
cation.24 Lewis acids are therefore prone to induce
Brønsted acidity by coordination of a protic species (e.g.,
RꢀOH) to the metal center in organic solvents,25 and some
elegant stoichiometric and catalytic enantioselective pro-
tonation systems have been designed based on the concept
of a Lewis acid assisted Brønsted acid (LBA).26 Bismuth(III)
triflate27 is generally obtained and used as its hydrate
form and therefore presents indubitably a strong induced
Brønsted acidity. By treatment of a stoichiometric amount
of commercial Bi(OTf)3, 2,6-di-tert-butylpyridine, a pro-
ton scavenger, was instantly and totally displaced to its
Acknowledgment. This work was supported by CNRS
and the University of Nice Sophia-Antipolis, France. We
acknowledge a scholarship of the French Ministry of
Research for B.C.
1
Supporting Information Available. Synthetic experi-
mental details, spectroscopic data of all new compounds,
and X-ray structure of 11c. This material is available free
of charge via Internet at http://pubs.acs.org.
pyridinium salt as indicated by H NMR monitoring in
(26) (a) Yamamoto, H.; Futatsugi, K. Angew. Chem., Int. Ed. 2005,
44, 1924. (b) Cheon, C. H.; Kanno, O.; Toste, F. D. J. Am. Chem. Soc.
2011, 133, 13248. (c) Kanno, O.; Kuriyama, W.; Wang, Z. J.; Toste,
F. D. Angew. Chem., Int. Ed. 2011, 50, 9919.
ꢁ
(27) Repichet, S.; Zwick, A.; Vendier, L.; Le Roux, C.; Dubac, J.
The authors declare no competing financial interest.
Tetrahedron Lett. 2002, 43, 993.
Org. Lett., Vol. 14, No. 11, 2012
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