Communications
DOI: 10.1002/anie.200905824
Boronic Acids
Direct Conversion of Arylamines to Pinacol Boronates: A Metal-Free
Borylation Process**
Fanyang Mo, Yubo Jiang, Di Qiu, Yan Zhang, and Jianbo Wang*
Arylboronic acids or arylboronates have found widespread
efficient because of the generally low-yielding and tedious
separation procedures required. Moreover, metals that might
contaminate the final boron products and cause environ-
mental problems in large-scale production are inevitably
involved in these steps. In this context, the direct borylation of
arylamines to arylboronates would be highly desirable.
Herein, we describe a novel method for the synthesis of
arylboronates by the reaction of the diboron pinacol ester
B pin with arylamines in the presence of tert-butyl nitrite.
applications in transition-metal-catalyzed CÀC bond forming
reactions, as represented by the Suzuki–Miyaura cross-
[
1]
coupling reaction. These applications have created an
[2]
increasing demand for various boronic acids and esters.
The most commonly utilized method to prepare these boron
compounds is the reaction of aryl Grignard reagents or
aryllithium reagents with trialkyl borates followed by hydro-
[3]
lytic workup. This traditional approach, although still widely
used, suffers some obvious drawbacks such as rigorous
anhydrous conditions and narrow functional group compat-
ibility. In 1995, Miyaura and co-workers reported a Pd-
catalyzed cross coupling of arylbromides or iodides with a
2
2
The reaction is metal-free and can be carried out under air at
room temperature.
The Sandmeyer reaction is a classic reaction in which an
[12]
aromatic amino group is replaced with a halogen, as well as
[
4]
[13]
[14]
[15]
diboron pinacol (pin). The favorable tolerance of this
method to a variety of functional groups means that it is
now well-established as a complementary route to arylboro-
with other groups such as hydrogen, hydroxy, cyano,
and azido
[
16]
groups. Diazonium ions are the common
intermediates in these synthetically very useful transforma-
tions. In view of the diversity of transformations that occur via
diazonium ions, we hypothesized that it might be possible to
replace an aromatic amino group with a boron group under
Sandmeyer reaction conditions. To the best of our knowledge,
this type of transformation has not been reported to date.
After some initial attempts, it was concluded that tert-butyl
nitrite (tBuONO, 3) was a suitable diazotization agent for this
[5–8]
nates.
In addition to these two important methods, it
should be mentioned that great efforts have been made in
transition-metal-catalyzed direct borylation of aromatic CÀH
[9,10]
bonds.
Arylamines are cheap and abundant starting materials,
which are easily available from arenes through nitration and
subsequent reduction. The aromatic amino group can be
converted into various functional groups by the Sandmeyer
[
17]
transformation. Thus, a solution of aniline 1a, B pin 2, and
2
2
[
11]
reaction.
The standard procedure for converting aryl-
tBuONO 3 in acetonitrile was heated at 608C for 1 h. To our
delight, phenylboronate 4a was formed in 40% yield as
shown by GC–MS analysis (Table 1, entry 1). Encouraged by
this initial result, we further proceeded to optimize the
reaction conditions.
amines to arylboronic acids or boronates would need two
steps, namely a Sandmeyer reaction to convert the amino
group into a halogen group, followed by use of a Grignard
reagent or a Pd-catalyzed borylation. Although the two-step
procedure is highly reliable and widely used in organic
synthesis, the combination of these reactions in the conver-
sion of arylamines to arylboronates is usually not very
Initially, we explored the use of additives that could
promote this transformation. Possible additives include
KOAc (Table 1, entry 2), which may accelerate trans-boryla-
[4]
tion of B pin , and metal salts (Table 1, entries 3–6), which
2
2
may speed up the decomposition of the phenyldiazonium
[
*] F. Mo, D. Qiu, 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)
[11b]
ion.
However, the reaction was not significantly improved
I
II
by these additives. Notably, Cu and Cu salts, which are
commonly used in the classic Sandmeyer reaction, afforded
4
a in only 8% and 7% yields, respectively (Table 1,
Fax: (+86)10-6275-1708
E-mail: wangjb@pku.edu.cn
Homepage: http://www.chem.pku.edu.cn/physicalorganic/
home.htm
entries 3,4). In both cases, diphenylamine was the major
product. It was noted that use of Fe(OAc)2 significantly
improved the yield (Table 1, entry 6). As it is suggested that
the Sandmeyer reaction proceeds by a radical mecha-
Y. Jiang
[11b,18]
nism,
the radical initiators 2,2’-azobisisobutyronitrile
Department of Chemistry, Tongji University
Shanghai 200092 (China)
(AIBN) and benzoyl peroxide (BPO) were introduced into
the reaction mixture in subsequent experiments. It was indeed
observed that higher yields could be obtained in the presence
of these radical initiators (Table 1, entries 7–13). Further-
more, when BPO was used as an additive, the reaction could
be carried out at room temperature with improved yields,
although the reaction time was extended from 1 to 3 hours
[
**] The project is supported by the NSFC (grant no. 20832002,
20772003, 20821062) and the 973 Program (no. 2009CB825300).
The authors greatly appreciate with discussions and suggestions
from Profs. Norio Miyaura and Todd B. Marder.
1
846
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 1846 –1849