respectively, in the presence of 10 mol % of Pd(OAc)2.
Further optimization work showed that 5 mol % of Pd(OAc)2
and 2 equiv of Et3N are necessary to achieve decent yields
of naphthalene 2 in this palladium-catalyzed annulation
chemistry. We have also explored the effect on the reaction
yield of other variables, such as the ligand, certain additives,
and various amounts of the alkyne. The optimal reaction
conditions thus far developed employ 0.25 mol of aryl halide
1, 2 equiv of diphenylacetylene, 5 mol % of Pd(OAc)2, 10
mol % of PPh3, and 2 equiv of Et3N as a base in 3 mL of
DMF stirred at 80 °C, which affords an 86% yield of
naphthalene 2 (Table 1, entry 1).
2-pentyne, were allowed to react with aryl halide 1. Presum-
ably, the problem here is the difficulty in adding the hindered
vinylic palladium intermediate across the relatively hindered
internal alkene to place three bulky substituents in contiguous
positions on the resulting carbocyclic ring (Scheme 2).
Scheme 2
By using our optimal reaction conditions, the scope of the
annulation process has been explored using a variety of
substrates carefully selected in order to establish the general-
ity of the process and its applicability to commonly
encountered synthetic problems (Table 1). While the reaction
of aryl halide 1 and diphenylacetylene afforded naphthalene
2 in 86% yield (entry 1), only a 61% yield of naphthalene 3
was obtained from the reaction of aryl halide 1 and di(p-
methoxyphenyl)acetylene (entry 2). The decrease in the yield
of the reaction indicates that electron-rich diarylacetylenes
disfavor the annulation chemistry. However, when an
electron-deficient diarylacetylene, such as di(p-ethoxycar-
bonylphenyl)acetylene was allowed to react with aryl halide
1, an 83% yield of naphthalene 4 was obtained (entry 3),
comparable to the yield obtained from the reaction of aryl
halide 1 and diphenylacetylene (entry 1). When 4-octyne, a
dialkylacetylene, was allowed to react with aryl halide 1, a
60% yield of naphthalene 5 was obtained (entry 4).
Compound 10 was prepared to test if the annulation
process also works well with aryl bromides. The reaction of
aryl bromide 10 and diphenylacetylene afforded naphthalene
2 in 75% yield (entry 7). Although this yield is lower than
the yield from the reaction of aryl iodide 1 and diphenyl-
acetylene (entry 1), this result is still encouraging, because
we now can use aryl bromides instead of aryl iodides. When
nitriles 11 and 13, which are E/Z isomers, were allowed to
react with 4-octyne, they both reached completion in 7 h
and afforded very similar yields (entries 8 and 9). This result
indicates that the geometry of the carbon-carbon double
bond has little effect on this annulation process. The reaction
of aryl halide 14, bearing two methoxy groups on the
aromatic ring, and diphenylacetylene afforded naphthalene
15 in 71% yield (entry 10). Compared to the parent system
(entry 1), this reaction required a longer reaction time and
resulted in a slightly lower yield. When aryl halide 14 was
allowed to react with ethyl phenylpropiolate, two regio-
isomers 16 (73%) and 17 (8% yield) were isolated (entry
11). Comparing this result with that from the reaction of aryl
halide 1 and ethyl phenylpropiolate (entry 6), it is clear that
the introduction of electron-rich substituents, such as meth-
oxy groups, onto the benzene moiety increases the regio-
selectivity in this annulation process.
This reaction does not require the presence of a strong
electron-withdrawing functional group, such as an ester or
nitrile, although these substrates are particularly easy to
prepare. The phenyl-substituted aryl iodide 18 has been found
to react well with 2-butyne-1,4-diol to produce naphthalene
19 in 73% yield (entry 12). This result confirms our suspicion
that the earlier problem with alkynols had more to do with
transesterification of the ester group than any inherent
problems with the alcohol functionality.
A mechanism for the reaction of aryl halide 1 and
diphenylacetylene is proposed in Scheme 3. First of all, Pd(0)
oxidatively inserts into the carbon-iodide bond of the aryl
iodide to generate an arylpalladium species. Addition of the
arylpalladium species to the carbon-carbon triple bond,
followed by an intramolecular cis-addition to the carbon-
carbon double bond generates an alkylpalladium species 20.
Intermediate 20 can undergo â-hydride elimination to form
intermediate 21, which subsequently isomerizes to naphtha-
lene 2. Alternatively, the intermediate 20 may undergo
reversible palladium hydride elimination to an alkene
To test the regioselectivity of this annulation process,
1-phenylpropyne was allowed to react with aryl halide 1,
and a 53:47 mixture of two regioisomers 6 and 7 was
obtained in a 75% overall yield (entry 5). According to our
previous work, the bulkiness of the substituents on the
acetylene plays a major role in determining the regioselec-
tivity of alkyne insertion. The arylpalladium intermediate is
more likely to add to the less hindered end of the carbon-
carbon triple bond.2-10 In this naphthalene synthesis, the
regioselectivity appears to be significantly lower than we
have normally observed in the annulation of unsymmetrical
alkynes. Similarly, the reaction of aryl halide 1 and ethyl
phenylpropiolate afforded a 76:24 mixture of two regio-
isomers 8 and 9 (entry 6). In this case, the major product 8
results from aryl addition to the 3-position of the propiolate.
Electronic effects appear to play a major role here. As in
most Heck reactions, the aryl group of the Pd intermediate
is more likely to add to the end of the carbon-carbon
multiple bond furthest removed from the electron-withdraw-
ing ester moiety, which results in naphthalene 8 as the major
product.
The reactions of aryl iodide 1 and 2-butyne-1,4-diol and
3-phenyl-2-propyn-1-ol failed to afford any recognizable
product. It appears that the problem may be transesterification
of the ester group by the acetylenic alcohols. No recognizable
naphthalene products could be obtained when bulky sym-
metrical or unsymmetrical alkynes, such as di-tert-butyl-
acetylene, phenyl(trimethylsilyl)acetylene and 4,4-dimethyl-
Org. Lett., Vol. 4, No. 15, 2002
2507
Huang, Qinhua
