Tetrahedron Letters
Pd(II)-catalyzed bromo- and chlorodecarboxylation of electron-rich
arenecarboxylic acids
⇑
Xuefeng Peng, Xiang-Feng Shao, Zhong-Quan Liu
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A bromo- and chlorodecarboxylation of various aromatic carboxylic acids catalyzed by Pd(II) has been
Received 29 January 2013
Revised 20 March 2013
Accepted 28 March 2013
Available online xxxx
developed in this work.
decarboxylative monohalogenation products under the typical reaction conditions.
A series of electron-rich arenecarboxylic acids gave the corresponding
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Palladium-catalysis
Decarboxylation
Bromination
Direct decarboxylative halogenation of carboxylic acid is a
useful strategy for the synthesis of halides in synthetic organic
chemistry.1 During the past decades, various methods had been
developed by Hunsdiecker,2 Barton,3 and Kochi.4 Although these
pioneering studies, along with their modifications, provide helpful
strategies for this type of reaction, most of these systems suffer
from some disadvantages such as previous preparation of carbox-
ylic metal salts and esters, overloading of heavy metal salts, etc.
Recently, Gandelman and co-workers5 reported a facile iodode-
carboxylation of carboxylic acids by using 1,3-diiodo-5,5-dimeth-
ylhydantoin under irradiative conditions. Additionally, a novel
decarboxylative halogenation of electron-rich aryl carboxylic acids
by using hypervalent iodine(III)–LiX in fluoroalcohol media was
explored by Miki and co-workers,6 where large amounts of
oxidants were used. Very recently, Li and co-workers reported a
very efficient Ag(I)-catalyzed decarboxylative chlorination of
aliphatic carboxylic acids.7 However, no desired products were
obtained by using aryl carboxylic acids in this system.
Therefore, more efficient catalyzed decarboxylative halogen-
ations are highly desirable. Herein, we wish to report a Pd(II)-
catalyzed bromo- and chlorodecarboxylation of aryl carboxylic
acids using CuBr2 and CuCl2 as the halogen sources (Scheme 1).
Initially, we chose 2,4-dimethoxybenzoic acid as the model
substrate to optimize suitable conditions for this reaction (Table
1). Three compounds 1a, 1a0, and 1a00 were isolated as the major
products. It was found that the catalyst, halogen sources, additives,
and the solvent critically affect the reaction efficiency. Tetrahydro-
furan (THF) is a better solvent than others such as 1,4-dioxane,
DMSO, etc (entries 1–3). Ligands such as 2-(dicyclohexylphos-
phino)-20,40,60-triisopropylbiphenyl (X-phos), N,N-dimethyl ethyl-
ene diamine (DMEDA), Ph3P, and DMSO were also examined
(entries 4–6). The Ag2CO3 was proved to be more efficient as the
additive than others (entry 7). The halogen sources CuBr2 and
CuCl2 were found to be better than others (entries 8–10). The
yields of the products decreased neither increase nor decrease of
the amounts of the additive (entries 11 and 12). The catalyst PdCl2
was more efficient than others such as Pd(OAc)2 and Pd(TFA)2
(entries 13–17). No products were obtained without any catalyst
R
COOM
R
COOX
R
X
Hunsdiecker
Kochi
Pb(OAc)2/LiX
R
COOH
R
X
O
N
Barton
R
R
COOH
R
X
I
R
O
S
I
N
1. hv
O
O
COOH
+
R
Gandelman
N
2. NaHSO3
I
X
COOH
3 eq. PhI(OAc)2
+
LiX
Miki
FG
FG
X
cat. Ag(I)/tBuOCl
R
COOH
COOH
R
Cl
C. Z. Li
X
cat. PdCl2
CuX2
(X=Br, Cl)
+
this work
FG
FG
⇑
Corresponding author. Tel./fax: +86 931 8912280.
Scheme 1. Overview of decarboxylative halogenation.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
Peng, Xuefeng
