Palladium catalyzed arylation of malonate accompanying in situ dealkoxycarbonylation

Article abstract of DOI:10.1039/b109418a

One-pot conversion of aryl halides into aryl acetates was achieved by the palladium catalyzed arylation of malonate accompanying in situ dealkoxycarbonylation of aryl malonates using Cs₂CO₃ as a base and as a catalyst.

Full text of DOI:10.1039/b109418a

Palladium catalyzed arylation of malonate accompanying in situ
dealkoxycarbonylation
Yoshinori Kondo,* Kiyofumi Inamoto, Masanobu Uchiyama and Takao Sakamoto
Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Aoba-ku, Sendai 980-8578,
Japan. E-mail: ykondo@mail.pharm.tohoku.ac.jp
Received (in Cambridge, UK) 18th October 2001, Accepted 7th November 2001
First published as an Advance Article on the web 6th December 2001
One-pot conversion of aryl halides into aryl acetates was
achieved by the palladium catalyzed arylation of malonate
accompanying in situ dealkoxycarbonylation of aryl mal-
Table 2
2 3
onates using Cs CO as a base and as a catalyst.
3
Introduction of an sp carbon side chain into an aromatic ring is
one of the important process in organic synthesis and many
works have been done using palladium catalyzed reactions.1
Various approaches have been studied for the synthesis of aryl
acetates using coupling reactions2 and very recently sig-
nificant progress has been made for direct introduction of an
acetic acid ester moiety into aromatic rings using palladium
X
Y
Z
Time/h
Yield (%)
–4
I
I
I
Br
Br
CH
CH
CH
CH
N
H
65
74
76
70
45
87
70
61
78
75
OMe
COOEt
H
5
catalyzed reactions. On the other hand, introduction of active
H
methylenes into aromatic rings has also been an important
6
subject and Hartwig et al. recently succeeded in the arylation of
t
malonate, however a strong base such as NaO Bu has been
7
used. In connection with our recent studies on chemoselective
dealkoxycarbonylation during the cross coupling reaction, the
reaction of iodobenzene with diethyl malonate was carried out
at an elevated temperature such as 120 °C using 10 equiv. of
Cs CO for 65 h, and ethyl phenylacetate was obtained in 87%
8
transformation of functionalized aromatic compounds, we
became interested in the introduction of an acetic acid moiety
under mild reaction conditions using a weaker base. During the
course of our recent studies on the coupling reaction of aryl
halides with diethyl malonate, it was found that diethyl
phenylmalonate undergoes a dealkoxycarbonylation reaction in
the presence of a weak inorganic base. Namely, when we
2
3
yield exclusively. Similarly, iodoanisole was reacted with the
malonate under the same reaction conditions, and 4-methox-
yphenyl acetate was obtained in 70% yield. Ethyl 4-iodo-
benzoate was also successfully reacted with the malonate under
the same reaction conditions, and the coupling–dealkoxy-
carbonylation proceeded smoothly to give the aryl acetate in
61% yield without forming any side reaction products. Aryl
bromides were also employed as substrates for this process. The
reaction of bromobenzene and 3-bromopyridine gave the
corresponding aryl acetates in 78% and 75% yields respectively
carried out the cross coupling reaction of iodobenzene with
t
diethyl malonate in the presence of Pd
Cs CO
2
(dba)
3
, Bu
3
P using
2
3
as a base in dimethoxyethane at 80 °C for 68 h, diethyl
phenylmalonate was obtained in 71% yield together with the
dealkoxycarbonylated product, ethyl phenylacetate in 11%
yield (Scheme 1).
(
Table 2).
A simple and chemoselective introduction of an acetic acid
moiety was accomplished by using the present Pd coupling–
dealkoxycarbonylation process and further applications of this
method for the facile functionalization of biologically active
molecules are underway.
This work was partly supported by the Grant-in Aid for
Scientific Research (No. 12672047 and No. 12557198) from the
Ministry of Education, Culture, Sports, Science, and Technol-
ogy, Japan.
Scheme 1
We focused our interest in this interesting dealkoxycarbony-
lation and diethyl phenylmalonate was treated with various
bases in dimethoxyethane at elevated temperatures. As shown
in Table 1, Cs CO was found to be the most effective catalyst
2 3
for the decarbonylative conversion. In order to complete the
Notes and references
1
2
3
R. F. Heck, Palladium Reagents in Organic Synthesis, New York,
Academic Press, 1985; J. Tsuji, Palladium Reagents and Catalysts,
Chichester, John Wiley & Sons Ltd., 1995.
J. F. Fauvarque and A. Justand, J. Organomet. Chem., 1979, 177, 273; F.
Orsini, F. Pelizzoni and L. M. Vallarino, J. Organomet. Chem., 1989,
Table 1
3
67, 375.
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Chem., 1991, 56, 261; R. Galarini, A. Musco, R. Pontellini and R. Santi,
J. Mol. Catal., 1992, 72, L11; F. Agnelli and G. A. Sulikowski,
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and H. Yamanaka, J. Chem. Soc., Perkin Trans. 1, 1994, 235; T.
Sakamoto, Y. Kondo, K. Masumoto and H. Yamanaka, Heterocycles,
1993, 39, 8807.
Base
Conditions
Yield (%)
a
Cs
Cs
2
CO
CO
3
80 °C, 66 h
120 °C, 70 h
120 °C, 67 h
120 °C, 70 h
15 (78)
a
2
3
83 (3)
a
K CO
2 3
62 (8)
a
NaH
0 (99)
a
4 M. Kosugi, I. Hagiwara, T. Sumiya and T. Migita, Bull. Chem. Soc. Jpn.,
984, 57, 242.
Recovery yields in parentheses.
1
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Chem. Commun., 2001, 2704–2705
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b109418a

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