Electrophilic Cyclization of Alkynes
SCHEME 1
Recently, we and others have developed efficient methods
for the synthesis of various carbo- and heterocyclic compounds
through electrophilic cyclization of appropriate ortho-function-
alized aromatic acetylenes.11 Relatively little work12 has been
carried out on the intramolecular electrophilic cyclization of
alkynes onto arenes to prepare polycyclic aromatics. Barluenga
has reported one example of the electrophilic carbocyclization
of 1,4-diphenyl-1-butyne to 1,2-dihydronaphthalene utilizing
expensive I(py)2BF4 (eq 1).12a The scope of this process has
yet to be investigated, but the conversion of such 1,2-
dihydronaphthalenes to naphthalenes is not always easy,13
especially when considerable functionality is present.
in excellent yields by the reaction of lithium acetylides and the
corresponding 2-arylacetaldehydes.15
We first examined the reaction of alkynol 1 with I2 and were
delighted to find that the desired 2-iodonaphthalene 2 was
formed exclusively in a 75% yield after 0.5 h when using 0.3
mmol of 1, 3 equiv of I2, and 2 equiv of NaHCO3 in MeCN at
ambient temperature (Table 1, entry 1). None of the 5-exo-dig
cyclization product was detected. Reducing the amount of I2 to
2 equiv resulted in an incomplete reaction after 48 h. The
addition of NaHCO3 did improve the yield in this reaction
(compare entries 1 and 2), although it is only a marginal effect.
To explore the scope of this chemistry, other electrophiles
have also been examined (entries 3-6). The reaction with ICl
was complete upon addition of the ICl and gave a higher yield
of product 2 than the reaction with I2 (entry 3). 2-Bromonaph-
thalenes can be obtained by using either Br2 or NBS as the
electrophile. An excellent 89% yield was provided by Br2 at
room temperature (entry 4). The reaction with NBS proceeded
only at a higher temperature (50 °C) and afforded a lower yield
of 3 (entry 5).
Cyclization with PhSeBr provided a 36% yield of 2-naphthyl
phenyl selenide, together with a 53% yield of the product of
simple addition of PhSeBr to the triple bond (entry 6).
Alkynes bearing an electron-rich aromatic ring and an acid-
sensitive heterocycle, such as a thiophenyl group, reacted well
with I2 to provide the desired 1,2-disubstituted iodonaphthalenes
in excellent yields (entries 7 and 10). None of the products of
direct substitution on the electron-rich aromatic ring in these
two examples were observed. Although the yield utilizing I2
was only moderate for substrate 7 (entry 8), presumably because
the ketone group decreases the electron-density of the aromatic
ring, the desired conversion could be significantly improved
by using ICl as the electrophile (entry 9). In the case of substrate
9, cyclization with 2 equiv of Br2 resulted in a 45% yield of
the monobrominated product 11 and a 36% yield of the dibromo
product 12, which bears an extra Br on the 5-position of the
thiophene (entry 11). The reaction with I2 proceeded smoothly
when a vinylic group was present on the alkyne terminus (entry
12). While only a 35% yield of 1-n-butyl-2-iodonaphthalene
was isolated from the reaction of 1-phenyl-3-octyn-2-ol and I2,
a higher 75% yield was again obtained when ICl was employed
(compare entries 13 and 14). An even better yield was obtained
from an alkyne bearing a secondary alkyl group on the alkyne
terminus (entry 15). The sterically hindered trimethylsilyl-
substituted alkyne 19 failed to give any cyclization product using
I2 (entry 16), but was cyclized without difficulty when treated
with ICl (entry 17). However, the only product observed was
1,2-diiodonaphthlene in which the trimethylsilyl group was
substituted by an iodine moiety. The synthesis of 1-ethoxy-2-
iodonaphthalene from the corresponding ethoxy-substituted
alkyne was not very successful using either I2 or ICl as
electrophiles under our standard reaction conditions (entries 17
and 18). Only low yields have been obtained. However, by
Herein, we report our results on the electrophilic cyclization
of arylalkynes to naphthalenes and naphthols. This chemistry
generally produces good to excellent yields of the desired arenes
under very mild reaction conditions, accommodates various
functional groups, and has been successfully extended to systems
containing heterocyclic rings.
Results and Discussion
We envisioned that hydroxydihydronaphthalenes might be
easily transformed to the corresponding naphthalenes through
acid-catalyzed dehydration.14 Thus, we chose to investigate the
cyclization of appropriate benzylic-substituted propargylic al-
cohols, such as 1 (Scheme 1). These alcohols are easily prepared
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J. Org. Chem, Vol. 71, No. 1, 2006 237