COMMUNICATION
DOI: 10.1002/chem.201103438
Palladium-Catalyzed Intramolecular Decarboxylative Coupling of Arene
Carboxylic Acids/Esters with Aryl Bromides
Zengming Shen,*[a] Zhenjie Ni,[b] Song Mo,[b] Jing Wang,[b] and Yamin Zhu[a]
The transition-metal-catalyzed decarboxylation of aromat-
ic carboxylic acids has emerged as an exciting strategy in or-
ganic synthesis because it enables the formation of aryl–
metal intermediates by loss of CO2. This process can provide
uct. Since Nilsson reported the first example of transition-
metal-mediated decarboxylative biaryl coupling,[4] break-
throughs have been achieved by the groups of Goossen,[5]
Myers,[6] and others[7–11] in the development of decarboxyla-
tive cross-coupling reactions. Prominent examples include
the bimetallic Pd/Cu-catalyzed intermolecular decarboxyla-
tive coupling of benzoic acids with aryl halides, tosylates or
triflates by Goossen et al.,[5] the palladium-catalyzed decar-
boxylative Heck-type coupling of olefin and arene carboxyl-
ic acids by Myers et al. (for which stoichiometric quantities
of a Ag salt is often required),[6] and the Cu-catalyzed decar-
boxylative coupling of polyfluorobenzoates with aryl halides
by Liu et al.[7a]
To the best of our knowledge, however, the Pd-catalyzed
intramolecular decarboxylative arylation of benzoic acids
with aryl halides has not been well explored. Steglich and
co-workers have reported an intramolecular Heck-type cou-
pling between a tetrasubstituted pyrrole carboxylic acid and
a tethered aryl bromide in the synthesis of lamellarin L/G,
employing a stoichiometric amount of palladium.[12] Recent-
ly, Forgione et al. improved this stoichiometric palladium-
promoted intramolecular reaction to a catalytic system
under microwave irradiation at 1708C, but this reaction was
demonstrated for only two heteroaromatic acids.[9] As a con-
sequence, the development of a general intramolecular de-
carboxylative cross-coupling of benzoic acid with haloarenes
is still a target in organic synthesis. Herein, we wish to
report a concise and efficient protocol for the palladium-cat-
alyzed intramolecular arylation of arene carboxylic acids
with aryl halides through a decarboxylative cross-coupling
pathway under mild conditions [Eq. (3)].
À
unconventional alternatives to perform various types of C
À
C and C heteroatom bond-forming reactions relative to typ-
ical organometallic reagents.[1]
It is known that transition-metal-catalyzed cross-coupling
reactions with organometallic reagents as coupling partners
for the formation of unsymmetrical biaryl compounds, such
as the Suzuki–Miyaura coupling reaction [Eq. (1)], have
proven to be versatile and powerful methods.[2] However,
drawbacks to this reaction still exist, including the limited
commercial availability of some coupling partners or their
tedious preparation and the sensitivity of some organome-
tallic reagents. As an alternative approach, considerable at-
tention has been paid to the investigation of transition-
metal-catalyzed decarboxylative cross-coupling of arene car-
boxylic acids with aryl halides for the synthesis of biaryl
motifs [Eq. (2)].[1]
Carboxylic acids are desirable cross-coupling partners
owing to their prevalence in nature, ease of handling rela-
tive to organometallic reagents, high regioselectivity at the
À
carboxylic acid position relative to that of C H functionali-
zation,[3,10c,11] and the generation of CO2 as the waste prod-
[a] Prof. Dr. Z. Shen, Y. Zhu
School of Chemistry and Chemical Engineering
Shanghai Jiao Tong University
800 DongChuan Road, Shanghai, 200240 (P.R. China)
Fax : (+86)21-54741297
For our initial investigation of the intramolecular decar-
boxylative coupling, we chose the readily available 2-[(2-
bromobenzyl)oxy]benzoic acid 1a as
(Table 1). Inspired by the Goossen Pd/Cu catalyst system,
we first attempted a combination of Pd(OAc)2 (1 mol%)
a test substrate
[b] M. Sc. Z. Ni, S. Mo, J. Wang
Department of Chemistry, College of Life and Environment Sciences
Shanghai Normal University
AHCTUNGTRENNUNG
and CuI (3 mol%) as the catalyst with 1,10-phenanthroline
as the ligand and K2CO3 as the base in N-methylpyrrolidone
(NMP) at 1708C for 24 h. Pleasingly, a 36% yield of the de-
100 Guilin Road, Shanghai, 200234 (P.R. China)
Supporting information for this article is available on the WWW
Chem. Eur. J. 2012, 18, 4859 – 4865
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4859