LETTER
263
A Novel Method for Direct Construction of Indole Skeletons by Intra-
molecular Carbopalladation of Allenes Followed by Nucleophilic Substitution
Kunio Hiroi,* Yuko Hiratsuka, Kazuhiro Watanabe, Ikuko Abe, Fumiko Kato, Mayumi Hiroi
Department of Synthetic Organic Chemistry, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai,
Miyagi 981-8558, Japan
Fax +81-22-275-2013; E-mail: khiroi@tohoku-pharm.ac.jp
Received 24 November 2000
responding allenyl compounds. Desilylation of the allenes
Abstract: Upon treatment with a palladium catalyst, (o-iodoanili-
with tetrabutylammonium fluoride followed by mesyl-
ation gave 4a-c. N-Alkylation of 2-iodoaniline (5) with
4a-c was carried out in THF at 0 C using LDA as a base
to give allenyl substrates 6a-c.
noalkyl)allene compounds undergo intramolecular carbopallad-
ation of allenes followed by intramolecular amination of -allylpal-
ladium complexes to afford indole derivatives in fairly good yields.
Key words: allenes, arylations, indoles, palladium, substitutions
Methyl ketone 2b was prepared from 2a by the reaction
with methylmagnesium bromide followed by oxidation
with tetra-n-propylammonium perruthenate and N-meth-
ylmorpholine N-oxide. The same sequences with this me-
thyl ketone 2b as mentioned above gave 6d.
Allenyl compounds have received much attention so far
for providing three-carbon units and, in some cases, chiral
three-carbon synthons with axial chirality in organic syn-
thesis.1 Currently, in particular, much interest is being fo-
cused on the chemistry of allenes with palladium
catalysts.2
Similar sequences were carried out starting from 1c to
give allenes 6e-h.
Palladium-catalyzed reactions of allenes with iodoben-
zene and nucleophiles afforded products by , -function-
alization of the allenes.3,4 The palladium-catalyzed
reactions of allenes with 2-iodobenzylamine or (2-iodo-
benzyl)malonate effected carbopalladation of the allenes
followed by intramolecular nucleophilic substitutions to
give cyclized products, isoquinoline or tetraline deriva-
tives. Previously, we reported the stereospecificity of the
reactions with chiral allenes5 and also palladium-cata-
lyzed asymmetric , -functionalization of allenes with
chiral phosphine ligands.6
O
Me2(But)SiO (CH2)m
C
R
XO (CH2)n OH
1a X = H,
n = 4
2a R = H, m = 3
b
c
d
= Si(But)Me2,
= H,
= 4
= 5
= 5
b
c
d
= Me,
= H,
= Me,
= 3
= 4
= 4
= Si(But)Me2,
R1
R1
(CH2)m
OAc
MsO (CH2)m
Me2(But)SiO
R2
R2
Me
We wish to communicate herein a novel and facile synthe-
sis of tricyclic compounds by palladium-catalyzed reac-
tions of (2-iodophenyl)alkyl allenyl compounds bearing
nucleophilic functions at appropriate sites, which presents
a new entry to indole derivatives shown below.
4a
b
c
R
1 = H,
= H,
R
2 = H, m = 3
3a R1 = H,
R
2 = H, m = 3
= Me,
= 3
b
c
d
e
f
= H,
= Me,
= 3
= H,
= Ph,
= 3
= Me
= H,
= Me,
= 3
d
e
= Me,
= Me,
= H,
= 3
= 4
= 4
= 4
= 4
= 4
= 4
= 4
= H,
= H,
= H,
= Me,
= H,
= H,
= Me,
f
g
h
= Me,
= Me,
= Me,
= Ph,
= Me,
Me
H
N
R
R
NH2
I
(CH2)m
R2
4a-h
R1
N
N
I
5
6a-h
Scheme 1
Allenyl substrates were obtained starting from 1,4-bu-
tanediol (1a) and 1,5-pentanediol (1c). Monosilylation of
the diol 1a with t-butyldimethylchlorosilane and subse-
quent oxidation of 1b with the Swern oxidation method
followed by addition of ethynyl- and 1-propynylmagne-
sium bromide to the aldehyde 2a and acetylation gave
propargylic alcohol derivative 3a,b. The reactions of the
acetate 3a,b with methyl- or phenylmagnesium bromide
were carried out in the presence of CuBr to give the cor-
The palladium-catalyzed reactions of allenes 6a-h were
carried out at reflux in THF, MeCN, or DME in the pres-
ence of a palladium catalyst, Pd(dba)2 or Pd(OAc)2 (0.1
equiv.), phosphine ligand (0.2 equiv.), and triethylamine
(1.5 equiv.) to furnish cyclized indole products 7a-d and
8a-d in fairly good yields. The results are summarized in
the Table.
Synlett 2001 No. 2, 263–265 ISSN 0936-5214 © Thieme Stuttgart · New York
Hiroi
