.
Angewandte
Communications
CÀH Activation
À
Cobalt(II)-Catalyzed Csp H Alkynylation/Annulation with Terminal
2
Alkynes: Selective Access to 3-Methyleneisoindolin-1-one**
Lin-Bao Zhang, Xin-Qi Hao, Zhan-Jiang Liu, Xin-Xiang Zheng, Shou-Kun Zhang, Jun-
Long Niu,* and Mao-Ping Song*
[
7b]
Abstract: A highly efficient cobalt(II)-catalyzed alkynylation/
annulation of terminal alkynes assisted by an N,O-bidentate
directing group is described. This protocol is characterized by
wide substrate scope utilizing cheap cobalt catalysts, and offers
a new approach to 3-methyleneisoindolin-1-one, which can be
converted into an oxadiazine salt in one step. Moreover, the
directing group could be removed in three steps.
recently. However, the use of highly activated substrates or
expensive catalysts restricts its development in organic syn-
thesis chemistry. In contrast, Kanai, Matsunaga, and co-
workers have developed a cobalt-catalyzed non-oxidative
[8]
coupling of Csp
2
ÀH bonds with terminal alkynes. However,
the directed cobalt-catalyzed coupling of terminal alkynes
with simple arenes by a twofold CÀH bond cleavage remains
rare.
I
n the past decades, transition-metal-catalyzed CÀH bond
CÀH activation employing simple, but powerful bidentate
functionalization has emerged as a practical method for the
synthesis of value-added molecules because of its high
chelating auxiliaries, has become one of the hottest research
areas in organic synthetic methodology since the seminal
work of Daugulis and co-workers on the use of the 8-
aminoquinoline group in palladium-catalyzed CÀH arylation
[1]
efficiency and atom economy. Remarkable progress has
been made in this field and numerous examples have
demonstrated the success of such a strategy. In general, the
practical utility of these transformations relies on precious
[
9]
reactions. Subsequently, the conversion of the CÀH bond
into a new CÀX bond (X = C, N, O, halogen, S, B, Si) using
a similar bidentate chelation system has made great prog-
[2]
[3]
[4]
metal catalysts such as Rh, Pd, and Ru. As such, it would
be advantageous if more-abundant first-row metal catalysts
could emulate the reactivity of a noble-metal catalyst and
enable comparable catalytic efficacy. Recently, cobalt-cata-
lyzed organic reactions through CÀH bond activation have
[10]
ress. Among these transformations, the groups of Yu and
You independently described copper-mediated coupling reac-
tions of arenes with terminal alkynes using an amide oxazo-
line and 8-aminoquinoline directing group, respectively, in
[
7g,i]
attracted much attention because of low cost, low toxicity, and
2014.
method for cobalt(II)-catalyzed, aminoquinoline-directed
Csp
Notably, Daugulis and co-workers reported a new
[
5]
abundant reserves.
Meanwhile, terminal acetylene chemistry has developed
rapidly because of its occurrence in biologically active
2
ÀH bond coupling with terminal alkynes, and six-mem-
[11]
bered heterocycles, 2-isoquinolin-1-ones, were formed. In
this case, for the first time cobalt was used as the catalyst for
[
6]
molecules and functional materials. From the viewpoint of
atom and step economy, the direct coupling of CÀH bonds
oxidative Csp
2
ÀH coupling with terminal alkynes by hydro-
with terminal alkynes is more appealing than the traditional
Sonogashira coupling reaction because of obviating prefunc-
tionalization of the reactant. Following this strategy, several
arylation of alkynes. However, to the best of our knowledge,
there is no report on the cobalt-catalyzed direct alkynylation
of arenes by CÀH bond activation. Recently, we also
groups have reported directed coupling reactions of C
bonds with terminal alkynes. Su and co-workers reported
2
ÀH
developed a removable bidentate directing group derived
sp
[
7]
[12]
from 2-aminopyridine 1-oxide (PyO-amine). Owing to the
[7f]
[13]
the palladium-catalyzed alkynylation of heterocycles.
relatively acidic NH in 2-benzamidopyridine 1-oxide, the
Nevado and co-workers revealed the gold-catalyzed oxidative
N,O-bidentate auxiliary is also believed to facilitate the CÀH
coupling of arenes with terminal alkynes by the CÀH bond
activation, thus more easily generating a reactive CNOÀCo
[7c]
activation in 2010.
Copper- and nickel-catalyzed direct
intermediate. We speculated that the use of a PyO directing
group might lead to pharmaceutically relevant 3-methylenei-
soindolin-1-ones by cobalt-catalyzed CÀH alkynylation.
alkynylation of azoles and poly-fluoroarenes with terminal
alkynes has also been demonstrated by Miura and co-workers
While 3-methyleneisoindolin-1-ones are typically prepared
from the cyclization of aryl halides under harsh reaction
[14]
[
*] L.-B. Zhang, Dr. X.-Q. Hao, Z.-J. Liu, X.-X. Zheng, S.-K. Zhang,
Dr. J.-L. Niu, Prof. M.-P. Song
conditions, our approach offers a powerful alternative for
accessing these compounds in a direct manner. As part of our
interest in the field, we present here the cobalt-catalyzed
oxidative alkynylation/annulation of terminal alkynes using
an N,O-bidentate auxiliary.
The College of Chemistry and Molecular Engineering
Zhengzhou University
Kexue avenue 100, Zhengzhou 450001 (P. R. China)
E-mail: niujunlong@zzu.edu.cn
We initially focused our investigation on the cobalt-
catalyzed cross-coupling of 2-benzamidopyridine 1-oxide
(1a) with phenylacetylene (2a). To our delight, the desired
product, (Z)-2-(1-benzylidene-3-oxoisoindolin-2-yl)pyridine
1-oxide (3aa), was obtained in 28% yield in the presence of
[
**] We are grateful to the National Natural Science Foundation of China
No. 21272217) for financial support of this work.
(
1
0012
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 10012 –10015