aryl trifluoromethanesulfonates,8 and direct trifluoro-
methanesulfonylation of aromatic compounds.9
triflones with a base and without any use of organometallic
chemistry.
First, trifluoromethanesulfonylation of indole 3a or 3b
with Tf2O in CH2Cl2 was attempted under a conventional
FriedelꢀCrafts condition using AlCl3; however, complex
mixtures were obtained (Table 1, entries 1 and 2). In the
absence of an additive, indole 3a was converted to dimer 4a
in 63% yield, and indole triflone was not observed (entry 3).
Figure 1. Aryl triflones 1 and indole triflones 2.
Table 1. Optimization of Reaction Conditions
Recently, Taguchi and co-workers reported a unique
regioselective synthesis of poly substituted aryl triflones
through a self-promoting three-component reaction.10
A tremendous number of aryl triflones have been reported
in the literature; however, no synthetic studies have been
reported on indole triflones 2 except for two patents11
despite their potential importance related to pharama-
ceuticals and agrochemicals. In this paper, we describe a
general and high-yielding method for the synthesis of
indole triflones 2 by FriedelꢀCrafts trifluoromethanesul-
fonylation of indoles with a triflic anhydride (Tf2O)/2,4,
6-tri-tert-butylpyridine (TTBP) system. The use of a weak
base, TTBP, is indispensable to reduce undesirable dimeric
byproducts, while the complex mixture resulted from
conventional Lewis acids-mediated FriedelꢀCrafts acyla-
tion and sulfonylation.12,13 The reaction is quite insensitive
to the choice of solvent and therefore an environmentally
friendly solvent, Solkane 365/227, can be hypothetically
substituted for CH2Cl2 and CH3NO2 without any loss of
efficiency. Biindolyl triflones were also accessed for the
first time by simple treatment of the resulting indole
entry
3
additive
solvent
temperature yield (2/4, %)a
1
3a AlCl3
3b AlCl3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3NO2
toluene
0 °C to rt
0 °C to rt
0 °C to rt
0 °C to rt
0 to 40 °C
0 to 70 °C
0 to 100 °C
0 °C to rt
0 °C to rt
0 °C to rt
0 °C to rt
0 °C to rt
0 °C to rt
complex
complex
0/63
2
3
3a
3b
3b
3b
3b
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
4
20/60
24/48
45/0
5
6
7
35/0
8
3b NaHCO3 CH3CN
7/68
9
3b KOBut
3b Et3N
3b DBU
3b TTBP
3b TTBP
CH3CN
CH2Cl2
CH2Cl2
CH2Cl2
CH3NO2
complex
complex
complex
82/0
10
11
12
13
88/0
a Isolated yield by silica-gel column chromatography.
(8) (a) Charmant, J. P.; Dyke, A. M.; Lloyd-Jones, G. C. Chem.
€
When the N-methyl indole 3b was used as the substrate,
indole triflone 2b was obtained in 20% yield along with the
unwanted dimer 4b in 60% yield (Table 1, entry 4). En-
couraged by this result, reaction conditions were screened to
improve the yield of 2b. Since indole dimers are known to
undergo thermal depolymerisation to give corresponding
monomers,14 optimization of the reaction temperature
might be a key for success (entries 5ꢀ7). The yield of 2b
was slightly increased to 24% at 40 °C in CH2Cl2. When the
temperature was increased to 70 °C in CH3NO2, the desired
2b was obtained in 45% yield, while no dimer 4b was
obtained. At a higher reaction temperature (100 °C in
toluene), however, the yield of 2b was decreased to 35%. We
next examined the use of additives. Since indole dimers are
formed under dilute acid conditions,15 the addition of a base
could prevent the formation of an indole dimer. By the
addition of bases, such as NaHCO3, KOBut, Et3N or DBU,
the reaction worsened or became more complex (entries
8ꢀ11). To our delight, trifluoromethanesulfonylation of 3b
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