T. Kurisaki et al. / Tetrahedron Letters 48 (2007) 1871–1874
1873
poor solvent and afforded 2 in 54% yield after 3 h (entry
2). However, both toluene and dichloromethane were
shown to be excellent solvents giving 2 in 92% yield
within 30 min (entry 3) and 93% yield within 15 min (en-
try 4), respectively, at 25 °C. Dichloroethane was also an
excellent solvent and afforded 2 in 95% yield after
15 min at 25 °C (entry 5). Reaction using 1 mol % of
Hg(OTf)2 in dichloromethane required 20 h to consume
the starting material and afforded 2 in 93% yield (entry
6). Reflux in dichloromethane was inadequate and
required 15 h to give 2 in 95% yield (entry 7). Reflux
in 1,2-dichloroethane, however, afforded 2 in 94% yield
after 1 h (entry 8). Reflux in toluene using 1 mol % cat-
alyst is more efficient to give 2 in 99% yield within
15 min (entry 9). Even 0.5 or 0.25 mol % of Hg(OTf)2
is enough to complete the reactions in toluene at reflux
temperature within acceptable reaction periods (entries
10 and 11). However, 0.1 mol % of catalyst did not af-
ford any product within an acceptable reaction period
(entry 12). We also examined the reaction using
1 mol % of HgCl2 and Hg(OAc)2 as catalysts, however,
the reaction did not take place at all (Scheme 1).
catalyst. Silicon protection used to be the course of some
trouble,16 and the case of TBS derivative 20 resulted
affording in 21 as low as 51% yield after 15 h reaction
using 1 mol % of catalyst. Phenyl substituted 22 as well
as methoxyphenyl substituted 24 afforded indole deriva-
tives 23 (96%) and 25 (92%), respectively, within 1 h. On
the other hand, the reaction of p-nitro phenyl substi-
tuted 26 was very slow as expected, and afforded 27 in
20% yield even after 24 h.
Therefore, we have established a novel Hg(OTf)2-
catalyzed indole synthesis with broad applicability and
high catalytic turnover under very mild reaction
conditions.
Acknowledgements
This study was financially supported by a Grant-in-
Aid from the Ministry of Education, Culture, Sports,
Science and Technology of the Japanese Government,
and a MEXT.HAITEKU, 2003–2007.
The reaction is initiated by p-complexation of the alkyne
with Hg(OTf)2 as shown in 3 (Scheme 2). Nucleophilic
attack of nitrogen leads intermediate 4 generating
TfOH. Protonation of 4 with the TfOH forms nitronium
ion 5, which undergoes demercuration to produce indole
2 and regenerating the catalyst Hg(OTf)2. The proton-
ation step leading to 5 should be the rate-limiting step.
Supplementary data
Spectroscopic data. Supplementary data associated with
this article can be found, in the online version, at
Next we examined the effect of the protecting group on
nitrogen (Scheme 3). 2-Ethynylaniline 6a afforded a
complex mixture by the reaction with 5 mol % of
Hg(OTf)2 in CH2Cl2 at room temperature for 3 h, and
7a was not detected at all. N-Acetyl derivative 6b also
did not afford indole 7b, and unidentified unstable com-
pounds were obtained. o-Nitrobenzenesulfonyl (o-Ns)
protected aniline 6c slowly reacted at room temperature
and afforded 7c in 78% yield after 24 h. While p-Ns pro-
tected 6d reacted instantaneously to give 7d in 89% yield
within 15 min,14 but still did not reach the result
obtained by Ts protected 1 (Table 1, entry 4). Thus we
chose Ts group as the protecting group on nitrogen.
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