DOI: 10.1002/chem.201402487
Communication
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Synthetic Methods
An Easy Route to (Hetero)arylboronic Acids
William Erb, Akila Hellal, Mathieu Albini, Jacques Rouden, and Jꢀrꢁme Blanchet*[a]
Abstract: An unprecedented spontaneous reactivity be-
tween diazonium salts and diboronic acid has been un-
veiled, leading to a versatile arylboronic acid synthesis di-
rectly from (hetero)arylamines. This fast reaction (35 min
overall) tolerates a wide range of functional groups and is
carried out under very mild conditions. The radical nature
of the reaction mechanism has been investigated.
Arylboronic acids are important building blocks that have
found a widespread utility during the last two decades in vari-
ous palladium-, copper-, or nickel-catalyzed cross-coupling re-
actions (Suzuki–Miyaura and Chan–Lam couplings) and in the
Petasis borono-Mannich reaction.[1] The unique stability, low
toxicity, and easy handling of arylboronic acids make them an
Scheme 1. Borylations using aminoborane and diboron reagents.
appealing class of user- and environment-friendly building
blocks. Additionally, the catalytic properties[2] and biological ac-
tivities[3] of these compounds has received broad interest from
the scientific community.
et al.[8] and Pucheault et al.,[12] previous methodologies yield
a less-reactive pinacolate ester, which then requires an addi-
tional step to deliver the reactive boronic acid.[13] Moreover,
Since the isolation of the first boronic acid by Frankland and
Duppa in 1860[4] the preparation of boronic acids has attracted
a lot of attention because, unlike the analogous carboxylic
acids, boronic acids are abiotic compounds. For over a century,
the synthesis of boronic acids mainly relied on the trapping of
ArLi or ArMgX[2,5] with a trialkyl borate, followed by acidic hy-
drolysis. Although straightforward, this approach is limited by
poor functional-group tolerance, which results from the use of
strongly basic and nucleophilic organometallic species.
[8c]
the poor atom economy associated with the use of B2pin2
should lead to the investigation of its replacement with
a more simple boron source when possible. Interestingly,
when used as a halide surrogate,[14a] diazonium salts were
found to undergo borylation without the assistance of palladi-
um species, leading to the first examples of catalyst-free bory-
lation.[14b–c] Accordingly, the development of a new methodolo-
gy that is able to directly deliver boronic acids from simple
and inexpensive starting materials is attractive.
This area of research was rejuvenated with the seminal con-
tribution by Miyaura et al.,[6] introducing palladium-catalyzed
borylation of aryl halides with B2pin2 (pin=pinacol). This
method was later refined by Murata et al., Buchwald and Bill-
ingsley,[7] and Molander et al.[8] by using HBpin and B2(OH)4 as
boron reagents (Scheme 1). Although the substrate compatibil-
ity was broadened, the competitive formation of homocoupled
products needed to be dealt with. Recently, CÀH bond activa-
tion[9] and electrophilic borylation[10] have been reported. How-
ever, the steric or electronic bias required to govern the regio-
selectivity are still limiting factors.[11] It is important to point
out that with the exception of the methods by Molander
We have recently initiated a research program dedicated to
the design of original chiral Brønsted acids for asymmetric cat-
alysis.[15] One method involves a Suzuki arylation as the key
step to develop steric hindrance around the acidic site, but re-
quired large quantities of boronic acids. Because it is reasona-
ble to avoid cryogenic/anhydrous conditions and high-cost
palladium catalysts we reported thereafter a new methodolo-
gy, inspired by the recently reported palladium-catalyzed bory-
lation, using diboronic acid (B2(OH)4, 2). Our original plan was
to combine Molander’s strategy by using widely available Pd/C
species to promote the borylation of aryl diazonium salts.[16]
In the first attempt, diazonium salt 1a was introduced to
a methanol solution of diboronic acid 2, at room temperature
in the presence of palladium adsorbed on charcoal. A rapid
gas evolution was observed, attributed to a fast palladium oxi-
dative insertion.[17] However, a test reaction revealed a similar
reactivity in the absence of palladium species.[18] After only
a few minutes, the homogeneous reaction mixture turned to
[a] Dr. W. Erb, A. Hellal, M. Albini, Prof. J. Rouden, Dr. J. Blanchet
Laboratoire de Chimie Moleculaire et Thio-organique
ENSICAEN, Universite de Caen
6 boulevard du Marechal Juin, 14050 Caen (France)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402487.
Chem. Eur. J. 2014, 20, 1 – 6
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ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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