Communications
DOI: 10.1002/anie.200906699
Gold Catalysis
Gold-Catalyzed Halogenation of Aromatics by N-Halosuccinimides**
Fanyang Mo, Jerry Mingtao Yan, Di Qiu, Fei Li, Yan Zhang, and Jianbo Wang*
Halogenation of aromatic compounds is one of the funda-
mental reactions in organic chemistry.[1] N-Bromo- , N-iodo- ,
and N-chlorosuccinimide (NBS, NIS, and NCS, respectively)
are highly useful halogenating reagents in laboratories in
terms of their ease of handling, as well as the generation of
relatively inert succinimide as the by-product. Various
halogenation systems usingh NXS (X = Br, I, or Cl) have
been developed,[2–4] but halogenating unactivated aromatics
Scheme 1. Halogenation through activation by catalysts. A=acid,
M=metal, and X=Br, I, Cl.
proceeds only in the presence of strong Lewis acids or
protonic acids.[3] Moreover, reaction conditions are in general
very harsh, such as high catalyst loadings,[3f,i] high reaction
temperatures,[3e] or considerably acidic solutions.[3c] Some of
these reported catalytic systems proceed under relatively
milder reaction conditions. For example, Tanemura et al.
reported a method for the halogenation of aromatic rings
using NXS in the presence of NH4NO3 or FeCl3 in MeCN.[3g]
The reaction works with unactivated aromatics, but the
catalyst loading is high (10–100% mol). Yamamoto et al.
reported halogenation with ZrCl4 as the catalyst, and
although the catalyst loading is low (5mol%) the substrate
scope is limited to electron-rich aromatic rings.[2q] Moreover,
benzylic halogenation occurs when halogenating alkyl-sub-
stituted benzene derivatives, which is also a general side
reaction in many other halogenation systems. In view of these
facts, we still consider it highly desirable to develop milder
and more efficient halogenation methods.
Gold-catalyzed transformations have been hot topics in
organic chemistry in recent years.[6] It has been documented
À
that gold(III) can electrophilically metallate CAr H bonds to
afford arylgold(III) species.[7,8] In 1931 Kharasch and Isbell
reported that AuCl3 could react with neat benzene to form a
phenylgold(III) complex, which could react with hydrogen
chloride to form phenyl chloride.[7a] More recently, He and co-
À
workers reported several AuCl3-catalyzed C C bond-forming
reactions, in which arylgold(III) species, generated through
direct metallation of electron-rich aromatics, are proposed as
the key intermediates.[8a–d] AuCl3-catalyzed C C bond-form-
À
ing reactions between electron-rich aromatics and alkynes, as
well as methyl vinyl ketone are reported by Reetz and
Sommer,[8e] and Hashmi et al.[8f,g] Although the mechanism of
these highly efficient AuCl3-catalyzed reactions is still
unclear, we were encouraged by these reports and decided
to explore the possibility of gold-catalyzed halogenation
based on the hypothetical dual activation mode as shown in
Scheme 1b. Herein we report a highly efficient and practical
AuCl3-catalyzed halogenation of aromatics with NXS.
The previous studies have focused on the activation of
NXS through complexation or protonation of the carbonyl
oxygen atom of NXS by acids to enhance the reactivity of the
halogenation process (Scheme 1a). We envisaged that a dual
activation of both the aromatic ring and NXS might greatly
enhance the reactivity (Scheme 1b). For this purpose, the
À
formation of a CAr M bond through direct metallation of a
Table 1: Bromination of benzene with NBS using various catalysts in
DCE.[a]
À
À
H
CAr H bond is required. In principle, the cleavage of a CAr
À
bond to form CAr M bond proceeds through oxidative
addition or electrophilic substitution mechanisms by metal
complexes having either low or high oxidation states,
respectively.[5]
Entry
Catalyst (mol%)
Yield [%][b]
1
2
3
4
5
6
7
8
9
10
AuCl3 (1)
FeCl3 (20)
FeBr3 (20)
BF3·OEt2 (20)
NH4NO3 (20)
ZrCl4 (20)
99
27
25
7
<1
5
0
<1
0
[*] F. Mo, J. M. Yan, D. Qiu, F. Li, Dr. Y. Zhang, Prof. Dr. J. Wang
Beijing National Laboratory of Molecular Sciences (BNLMS) and
Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, College of Chemistry
Peking University, Beijing 100871 (China)
Fax: (+86)10-6275-1708
Pd(OAc)2 (20)
AlCl3 (20)
E-mail: wangjb@pku.edu.cn
home.htm
HCl (20)[c]
H2SO4 (20)
25
[**] The project is supported by the NSFC (Grant No. 20832002,
20772003, 20821062), 973 Program (No. 2009CB825300).
[a] Reaction conditions: benzene (1 mmol), NBS (1 mmol), DCE (2 mL),
808C, 24 h. [b] Yields determined by using GC/MS methods with
n-dodecane as the internal standard. [c] 4.7m in dioxane. DCE=1,2-
dichloroethane, NBS=N-bromosuccinimide.
Supporting information for this article is available on the WWW
2028
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 2028 –2032