COMMUNICATION
The acid-promoted reactions of phenyliodonium ylides with substituted
anilines and their applications to the synthesis of indoles†‡
Xianpei Wang, Bing Han, Junyan Wang and Wei Yu*
Received 3rd June 2010, Accepted 21st June 2010
First published as an Advance Article on the web 8th July 2010
DOI: 10.1039/c0ob00201a
The N-substituted anilines 1 react readily with phenyliodo-
nium ylides 2 derived from 1,3-dicarbonyl compounds in
the presence of a catalytic amount of BF3·Et2O, forming
the C–N coupling products 3, which are precursors for the
synthesis of indoles. On the basis of this result, the direct
synthesis of indoles from 1 and 2 under thermal conditions
and photochemical conditions was explored. The transfor-
mations could be achieved in a one-pot way under thermal
conditions or in a tandem manner under photochemical
conditions.
ylides in the presence of BF3·Et2O. Based on this result and the
literature work, the one-pot synthesis of indoles from anilines and
phenyliodonium ylides was explored. Here we wish to report the
results.
(1)
Phenyliodonium ylides derived from 1,3-dicarbonyl compounds
are useful synthetic intermediates.1 The reactions between
phenyliodonium ylides and transitional metals such as copper(I)
and Rh(II) constitute a convenient approach to the corresponding
carbenoids, which subsequently undertake C–H insertion or addi-
tion to alkenes.2 In contrast to this well-known use of phenyliodo-
nium ylides, their synthetic potential under metal-free conditions
is far less explored.3 We found recently that Lewis acids such as
BF3·Et2O could catalyze the reactions between phenyliodonium
ylides and electron-rich enamine esters, and the reactions could be
used to prepare polysubstituted pyrrole products.4 Further studies
demonstrated that anilines could also react with phenyliodonium
The reaction was firstly investigated by applying the previously
reported4 reaction conditions to N-methyl aniline. Using 0.1 equiv.
of BF3·Et2O as catalyst, N-methyl aniline 1a readily reacted with
phenyliodonium ylide 2a, giving rise to the C–N coupling product
3aa (eqn (1)). The reaction could be carried out in various solvents,
but the best result was obtained when CH3OH was used, in
which the reaction finished in 5 min., and 3aa was produced in
excellent yield. By comparison, only a trace amount of products
was generated in the absence of BF3·Et2O. The N-unsubstituted
aniline, on the other hand, reacted with 2a to generate the imine
product (eqn (2)).
State Key Laboratory of Applied Organic Chemistry, Lanzhou University,
Lanzhou, P. R. China; Fax: +86-931-8912582; Tel: +86-931-8912500.
E-mail: yuwei@lzu.edu.cn
† Electronic supplementary information (ESI) available: General ex-
perimental procedures and NMR spectra of products. See DOI:
10.1039/c0ob00201a
(2)
‡ General procedure for the reactions of 1 with 2: 13 mL of BF3·Et2O was
added to the mixture of 1 mmol 1 and 1 mmol 2 in 2 mL methanol, and
the mixture was stirred at room temperature for 5 min. The solvent was
then removed under reduced pressure, and the residual was treated with
silica gel chromatography to give the pure product 3. General procedure
for the one-pot synthesis of indoles under thermal conditions: A mixture of
1 mmol 1, 1 mmol 2, and 13 mL of BF3·Et2O in 3 mL toluene was stirred
in a 10 mL round bottom flask at room temperature for 30 min. Then
300 mg of AmberlystR 15 was added into the reaction mixture, followed
by fitting the flask with a condenser. The reaction mixture was then stirred
at reflux for 12 h. The solvent was removed under reduced pressure, and
the residual was subject to silica gel chromatography to give the indole
product.5c General procedure for the synthesis of indoles from 1 and 2 under
photochemical conditions: To a Pyrex tube containing a solution of 1 mmol
1 in 10 mL of benzene and 10 mL of methanol was added 1 mmol 2.
The solution was bubbled with argon for 15 min. Then 0.6 mL TFAA
was added in and the solution was irradiated with a 500 W medium-
pressure mercury lamp under argon atmosphere at room temperature for
12 h. After irradiation, the solvent was removed under reduced pressure,
and the residual was treated with silica gel chromatography to give the
product.
Following the brief screening of the reaction conditions, the
scope of the reaction was then examined. As shown in Table 1, a
variety of substituted anilines 1 reacted with phenyliodonium ylide
2 to generate 3. The yields varied depending on the substituents in
both 1 and 2. While the yields were generally good for substrates
1a–1f, and 1i, the reactions with alkoxy group-substituted anilines
gave the products in lower yields. (Table 1, entries 16–19). The
reason for this might be that oxidation of the electron-rich anilines
by phenyliodonium ylides led to decomposed products. On the
other hand, p-NO2-substituted N-methyl aniline was not reactive
to 2 under the reaction conditions.
Compounds 3 are useful synthetic intermediates as they could
be transformed to substituted indoles by way of the modified
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 3865–3867 | 3865
©
Wang, Xianpei
